Tesis Final

Cover Page
The handle http://hdl.handle.net/1887/36019 holds various files of this Leiden University

dissertation.
Author: Malan, Daniel Francois
Title: Pinning down loosened prostheses : imaging and planning of percutaneous hip
rexation
Issue Date: 2015-10-29
Pinning down loosened prostheses:

Imaging and planning of
percutaneous hip refixation
Danil Franois Malan
About the cover:

A Roman marble Venus, circa 1st century CE. The figurines hip region is
overlaid with elements addressed in this thesis: a fluoroscopic X-ray view,
a three dimensional surface model of the pelvis and femur and a multi-material
finite element mesh.
These components are combined into a single
augmented reality visualization of patient-specific hip anatomy.
ISBN/EAN: 978-94-6203-944-5
Thesis layout & cover design by Danil Franois Malan.
Marble Venus statue on front cover Christies Images Limited, 2009.
Printed by CPI Whrmann Print Service.
Copyright 2015 by Danil Franois Malan, Leiden, the Netherlands.
All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without
permission in writing from the copyright owner.
Pinning down loosened prostheses:

Imaging and planning of
percutaneous hip refixation
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden,
op gezag van Rector Magnificus
Prof. mr. dr. Carel J.J.M. Stolker,
volgens besluit van het College voor Promoties
te verdedigen op 29 oktober 2015
klokke 11:15uur
door
Danil Franois Malan

geboren te Tygerberg, Zuid-Afrika
Promotiecommissie
Promotores:
Prof.dr. R.G.H.H Nelissen

Prof.dr.ir. E.R. Valstar
Copromotor:
Dr. C.P. Botha
Overige leden:
Prof.dr. J. Dankelman
Prof.dr.ir. B.P.F. Lelieveldt
Dr.ir. D. Janssen
This work was carried out in the ASCI graduate

school. ASCI dissertation series number 336.
Financial support for the publication of this thesis was kindly provided by:
Advanced School for Computing and Imaging (ASCI)
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)
Stichting Anna Fonds
Technologiestichting STW
dedicated to my father
Contents
1 Introduction and motivation
1.1 Aseptic prosthesis loosening: the clinical problem . . . . . . .
1.2 Existing options for treating aseptic hip prosthesis loosening
1.3 A new integrated planning and treatment approach . . . . . .
1.4 Contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1.5 Structure of this thesis . . . . . . . . . . . . . . . . . . . . . . . .
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2 Measuring femoral lesions despite CT metal artefacts

2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . .
2.2 Materials and Methods . . . . . . . . . . . . . . . . . .
2.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . .
2.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . .
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3 Percutaneous bone cement refixation of aseptically loose hip

prostheses: the effect of interface tissue removal on injected
cement volumes
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . .
3.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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4 CT density overestimation in enclosed regions and its implications on estimating bones mechanical properties
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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5 Voxel classification of periprosthetic tissues of the hip

5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . .
5.2 Method . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2.1 Image parameters . . . . . . . . . . . . . . . . .
5.2.2 Choosing image features . . . . . . . . . . . . .
5.2.3 Training the voxel classifiers . . . . . . . . . . .
5.3 Results & Discussion . . . . . . . . . . . . . . . . . . . .
5.4 Conclusion & Future work . . . . . . . . . . . . . . . .
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6 The addition of Graph Cuts to voxel classification for automated

segmentation of pathological periprosthetic hip anatomy
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.2.1 Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.2.2 Manual segmentation . . . . . . . . . . . . . . . . . . . . .
6.2.3 Performance metrics . . . . . . . . . . . . . . . . . . . . .
6.2.4 Computation of image features . . . . . . . . . . . . . . .
6.2.5 Classifier construction and feature selection . . . . . . .
6.2.6 Segmentation by maximum posterior probability . . . .
6.2.7 Segmentation by graph cuts . . . . . . . . . . . . . . . . .
6.2.8 Segmentation by single multilabel graph cut on classifier output . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.2.9 Segmentation by stepwise multilabel graph cut with
geometrical containment . . . . . . . . . . . . . . . . . . .
6.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.3.1 Feature and classifier selection . . . . . . . . . . . . . . .
6.3.2 Tissue segmentation . . . . . . . . . . . . . . . . . . . . . .
6.3.3 Computational cost . . . . . . . . . . . . . . . . . . . . . .
6.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7 Sparse particle-based multi-material volume meshing for
formal 3D meshes
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.2 Related Work . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.3 Algorithm . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.4 Implementation . . . . . . . . . . . . . . . . . . . . . . . . .
7.5 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.5.1 Bunny (binary image volume) . . . . . . . . . . .
7.5.2 Tooth dataset (multiple materials) . . . . . . . .
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7.5.3 Femur dataset (multiple materials, anisotropic scan) 104

7.6 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
7.7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
8 A fluoroscopy-based planning and guidance software tool
minimally invasive hip refixation by cement injection
8.1 Materials and Methods . . . . . . . . . . . . . . . . . . . . . .
8.1.1 Workflow . . . . . . . . . . . . . . . . . . . . . . . . .
8.1.2 Software User Interface . . . . . . . . . . . . . . . .
8.1.3 Algorithm . . . . . . . . . . . . . . . . . . . . . . . . .
8.1.4 Validation Experiment on cadaver specimens . . .
8.2 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.3 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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9 General Discussion
9.1 The effect of fibrous interface tissue before cement injection
9.2 Image capture and image processing . . . . . . . . . . . . . . .
9.3 Transforming medical images to 3D models of the hip . . . .
9.4 Planning and guiding a minimally invasive procedure . . . .
9.5 Perspectives on the Future . . . . . . . . . . . . . . . . . . . . .
9.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Bibliography
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Summary
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Samenvatting
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Curriculum Vitae
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Acknowledgments
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1
CHAPTER 1
Introduction and motivation
INTRODUCTION
1.1
Aseptic prosthesis loosening: the clinical problem
Human life expectancy has increased dramatically over the past century
[World Health Organization, 2014], which manifests in a quickly growing
population of elderly people across the whole world. As humans live longer,
more people suffer from painful hip or knee joints resulting from degenerative age-related diseases such as osteoarthritis and rheumatoid arthritis [Kurtz
et al., 2011, Kurtz et al., 2005, Merx et al., 2003]. The hip joint, being a relatively simple ball and socket, was the first joint for which, in the first half of
the twentieth century, an artificial replacement was developed to address the
clinical problems of its deterioration [Charnley, 1961]. Hip arthroplasty, the
procedure whereby the diseased joint is surgically replaced with an artificial
joint, is today considered one of the most successful surgical interventions in
existence [Gomez and Morcuende, 2005]. Literally millions of people worldwide already live with artificial hip implants, with approximately 1 million
additional hip replacement operations carried out annually.
Despite hip arthroplastys overwhelming success, some implanted prostheses
fail prematurely. A hip prosthesis could, and in principle should, last for more
than 20 years. Despite this goal, approximately 10% of hip prostheses fail
within ten years of placement [Thillemann et al., 2010]. When a prosthesis
fails, the standard approach is to replace it surgically with a new prosthesis
in what is called a revision procedure. Advances in materials and technique
have led to improved implant designs, yet the last decades have seen a slowly
decreasing trend in the age at which patients receive their first prosthesis.
Younger patients tend to lead more active lifestyles and live longer, increasing the probability of eventually needing revision. These factors combine in
such a way that the rate at which prostheses are revised have remained stable
over recent years [Kurtz et al., 2005]. Regardless of whether significant improvement in prosthesis durability could be implemented today, the millions
of already-implanted hip prostheses will result in hundreds of thousands of
prostheses failing over the coming decades.
A hip prosthesis may fail for one of several reasons, yet there is one clearly predominant cause for their long-term failure: aseptic loosening caused by periprosthetic osteolysis [Harris, 2001]. The Swedish Hip Arthroplasty Register
and Dutch Arthroplasty Register attribute approximately 70% of revisions to
aseptic loosening [Garellick et al., 2011, Swe, 2013, Dut, 2013].
The term "osteolysis" refers to a process in which bone is broken down. Specifically, osteolysis is the active breakdown and resorption of bone during a cascade of cytokine release by macrophages and activation of both osteoclasts
10
1.2
Existing options for treating aseptic hip prosthesis loosening
Prosthesis loosening is normally treated with open revision surgery where the
loose prosthesis is replaced with a new one. The peri-prosthetic bone defects
are either filled with a bigger metal implant or with allograft bone impaction
and a new implant [Nelissen et al., 1995]. This surgery is demanding, and
11
INTRODUCTION
It is our belief that timely detection and appropriate treatment of osteolysis may eventually postpone or even eliminate the need for replacement of
the affected hip prosthesis. Although the osteolytic process is generally selfpropagating and accelerated by the presence of increasing amounts of fibrous
interface tissue [Park et al., 2004, Purdue et al., 2007], some authors have
even hinted at reversal of the periprosthetic osteolytic area [Talmo et al.,
2006]. For routine treatment of periprosthetic osteolysis to become a practical reality, however, new technologies and techniques are needed.
CHAPTER 1
and osteoblasts. Osteolysis may act as a normal biological process of the

human body. Peri-prosthetic osteolysis, however, refers to a specific pathological process. A local inflammatory reaction is caused by wear products of
an implant, and is also mediated by the genotype of the patient. In other
words, people with a pro-inflammatory genotype may be more susceptible.
Periprosthetic osteolysis is characterized by the resorption of bone around
the prosthesis with subsequent formation of soft fibrous interface tissue in its
place. The mechanism by which periprosthetic osteolysis occurs is complex,
but the implication for implant stability is straightforward: the layer of interface tissue offers little mechanical stability and allows the prosthesis to move
relative to the surrounding bone. Aseptic osteolysis is an insidious problem as
it is asymptomatic at first and typically progresses [Agarwal, 2004]; eventually osteolysis manifests in hip dysfunction and pain. Osteolysis can however
be detected before it reaches a symptomatic or disabling level. The standard
method for early detection is by searching for radiolucent regions in X-ray
radiographs. If osteolysis is suspected, its extent can be further quantified in
three dimensions using either Computer Tomograpy (CT) or Magnetic Resonance (MR) [Cahir et al., 2007, Cahir and Toms, 2009]. It has been shown
that aseptic loosening may, however, be measured or predicted at a much
earlier stage. Early three-drimensional sub-millimetre prosthesis migration
may be detected using the RSA stereographic X-ray technique, and correlates
with later and more severe aseptic prosthesis loosening [Nieuwenhuijse et al.,
2012, Pijls et al., 2012].
may be prohibitively risky for older patients suffering from poor health.
Alternatives to revision surgery either consist of conservative treatment (i.e.
management of pain, without treating the cause), or new and experimental
techniques such as the one to which this thesis pertains.
This thesis focuses on a relatively new and experimental treatment option
where the aseptically loosening prosthesis is stabilised by injecting bone cement into the periprosthetic lytic zones surrounding the prosthesis. This
method was first pioneered by [de Poorter et al., 2008a] and has since been
adopted as an experimental treatment of last resort, also at other academic
hospitals [Raaijmaakers and Mulier, 2010]. De Poorter et al. examined genedirected enzyme therapy to selectively kill the peri-prosthetic interface tissue
prior to percutaneous cement injection. With or without prior gene directed
enzyme therapy, percutaneous cement injection has so far only been used to
treat patients who do not qualify for traditional revision surgery. The mean
age at the index operation, when a hip prosthesis is first placed, is 68 years
in the Netherlands [Dut, 2013]. When loosening occurs 1520 years after
the initial treatment, patients are at an advanced age with generally more comorbidity and additional surgical risks. The median patient age in a relevant
clinical trial was observed to exceed 80 years [de Poorter et al., 2008a]. Compared to traditional revision, a minimally invasive percutaneous procedure requires shorter hospital stay and can be performed at lower cost. The efficacy
of this treatment is not believed to yet be comparable to that of traditional
prosthesis replacement. However, the inherent advantage of less invasiveness
that results in less patient morbidity gives this approach the potential of being
applied to a wider population of patients suffering from aseptic loosening.
1.3
A new integrated planning and treatment approach
The work of this thesis forms part of a larger research project at our institution
which aims to develop minimally invasive prosthesis refixation to reach its full
potential.
The envisaged goal is a multi-faceted and integrated diagnostic, planning
and execution workflow that relies on medical imaging, planning and guidance software. Together with new purpose-designed surgical instruments this
should lead to safe and effective prosthesis refixation. Our envisaged integrated approach is illustrated schematically in Figure 1.1.
The goal of the image processing component is to analyse radiographic images of a patients hip. Image analysis allows each patients unique anatomy
to be identified and digitally encoded. The three dimensional distribution of
12
CHAPTER 1
INTRODUCTION
Figure 1.1 A schematic illustration of an integrated approach to minimally

invasive hip prosthesis refixation.
material in the periprosthetic region is determinedspecifically bone and fibrous interface tissue, existing bone cement and the 3D position of the metal
prosthesis. Technologies applicable to this step include automated image segmentation and tissue classification.
The modelling-and-simulation component uses the output of the image processing step to simulate the mechanical stability of the patients hip prosthesis.
Modelling allows different treatment options to be evaluated. Primary among
these choices is the desired location of cement to be percutaneously injected,
as this may strongly determine the longevity and effectiveness of refixation.
Technologies applicable to this step include three dimensional mesh building
and finite element modelling.
13
During the planning step, the outputs of the preceding steps are presented to
a medical professional. Medical images and simulation results are visualized
so that the professional may decide on a suitable approach for treating the
patient. Technical and/or treatment decisions may be based on the planning
softwares output. Technical decisions may include the way in which the fluoroscopic imager should be oriented to best view the procedure. Treatment
decisions may include the amount of cement that should be injected, and the
choice of where to inject the stabilizing cement. Technologies applicable to
this step include volume rendering, non-linear optimization, data visualization and interaction techniques.
The larger project to which this thesis belongs also set out to develop new
surgical tools. These tools will facilitate and/or enable new ways of removing periprosthetic interface tissue and of stabilizing cement to be injected.
Technologies applicable to this step may include miniaturized steerable instruments that make use of plasma coblation or water-jet cutting [Kraaij et al.,
2012, den Dunnen et al., 2013].
1.4
Contributions
In this thesis we examine how computer software can be used to assist a minimally invasive cement injection procedure intended to stabilize an aseptically
loose hip prosthesis. We develop several algorithms and proof-of-concept software tools that can aid in the analysis of a patients aseptically loose hip. Our
software may one day be used by a surgeon to plan a minimally invasive cement injection procedure, to guide him/her in its execution and allow insight
into the achieved outcome. Software is developed on the assumption that
a pre-operative CT image volume of the affected hip will be available, and
dovetails with the existing treatment workflow for such patients.
We develop new tissue segmentation techniques for determining the tissue
distribution adjacent to an aseptically loose (hip) prosthesis. Our approach
focuses on automated methods that are able to deal with CT images affected
by metal-induced image artefacts.
We improve upon an existing particle-based meshing algorithm that converts
a three dimensional (3D) multi-tissue segmented image volume into a tetrahedral mesh. We show that a mesh can be made sparser than was previously
possible, without sacrificing its geometric accuracy. This is important as a
mesh with a tractable number of elements may be used to perform finite element simulations of a prosthesiss stability.
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Structure of this thesis
The ordering of chapters in this thesis is aligned with the diagnosis-andplanning workflow illustrated in Figure 1.1. First we discuss imaging, then
image analysis, followed by model-building and finally pre-operative planning and per-operative guidance.
We start in Chapter 2 by investigating whether manual delineation of periprosthetic lesions is feasible, and the extent to which metal-induced image
artefacts interfere with this delineation. We then examine whether delineation is improved by standard techniques for metal artefact reduction.
Armed with the knowledge gained in the preceding chapter, we retrospectively examine CTs of patients that were treated via minimally invasive cement injection. In Chapter 3 we measure lesion and cement volumes in postoperative CTs of two patient groups. Both groups had aseptically loose hip
prostheses that were treated by minimally invasive cement injection at the
LUMC in Leiden.
In Chapter 4 we again look at the quality of CT images obtained in periprostheic regionsspecifically whether their image intensities are directly
suitable for deriving mechanical properties in finite element models.
In Chapters 5 and 6 we develop supervised machine learning pipelines that
can automatically segment the peri-prosthetic region in a CT image volume of
the hip. These pipelines are based on voxel classification and simultaneously
incorporates metal artefact reduction and unprocessed image data, gaining
advantages from both. With the addition of a multi-label graph cut algorithm
that enforces smoothness and geometrical containment relationships, tissue
segmentation of a high resolution CT volume is performed on a standard desktop computer.
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INTRODUCTION
1.5
CHAPTER 1
Lastly, we develop a software preoperative planning system for fluoroscopyguided minimally invasive cement injection. This system allows a simulated
fluoroscopic snapshots to be made that can guide a surgeon as a patientspecific step-by-step per-operative roadmap. Our software can also estimate
the percutaneously injected cement volume that reached the intended cement injection targetsinformation that would otherwise not be quantitatively known to a treating physician.
This thesis illustrates our techniques when they are applied to the femoral
side of a hip with aseptic prosthesis loosening. We propose that all of our
software and techniques may easily be adapted to be applicable to a loose
acetabular component, or in fact to any loosened orthopaedic implant.
In Chapter 7 we address the issue of creating 3D finite element meshes from

a segmented multi-material tissue map. Our algorithm attempts the creation of a conformal multi-material output mesh that has fewer elements
and/or lower geometric approximation errors than comparable Delaunaytriangulation-based methods.
In Chapter 8 we describe HipRFX, a software preoperative planning system
for fluoroscopy-guided minimally invasive cement injection. We report the
results of a cadaver experiment where HipRFX could be used in a realistic
pre-clinical setting to estimate injected cement volumes.
In Chapter 9 we conclude our work with a discussion and elaborate on possible future developments.
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2
CHAPTER 2
Measuring femoral lesions despite

CT metal artefacts
MEASURING
DESPITE
CT
Adapted from:
Skeletal Radiology,
Volume 41, Issue 5, pp 547555, May 2012.
doi: 10.1007/s00256-011-1223-2
17
ARTEFACTS
Daniel F. Malan, Charl P. Botha, Gert Kraaij,

Raoul M.S. Joemai, Huub J.L. van der Heide,
Rob G.H.H. Nelissen, Edward R. Valstar
Abstract
Objective
Computed tomography is the modality of choice for measuring osteolysis but
suffers from metal-induced artefacts obscuring periprosthetic tissues. Previous papers on metal artefact reduction (MAR) show qualitative improvements, but their algorithms have not found acceptance for clinical applications. We investigated to what extent metal artefacts interfere with the segmentation of lesions adjacent to a metal femoral implant and whether metal
artefact reduction improves the manual segmentation of such lesions.
Materials and methods
We manually created 27 periprosthetic lesions in 10 human cadaver femora.
We filled the lesions with a fibrotic interface tissue substitute. Each femur was
fitted with a polished tapered cobalt-chrome prosthesis and imaged twice
once with the metal, and once with a substitute resin prosthesis inserted.
Metal-affected CTs were processed using standard back-projection as well as
projection interpolation (PI) MAR. Two experienced users segmented all lesions and compared segmentation accuracy.
Results
We achieved accurate delineation of periprosthetic lesions in the metal-free
images. The presence of a metal implant led us to underestimate lesion
volume and introduced geometrical errors in segmentation boundaries. Although PI MAR reduced streak artefacts, it led to greater underestimation of
lesion volume and greater geometrical errors than without its application.
Conclusion
CT metal artefacts impair image segmentation. PI MAR can improve subjective image appearance but causes loss of detail and lower image contrast
adjacent to prostheses. Our experiments showed that PI MAR is counterproductive for manual segmentation of periprosthetic lesions and should be used
with care.
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2.1
Introduction
Aseptic loosening caused by osteolysis is one of the foremost problems limiting the survival of hip prostheses [Agarwal, 2004]. Plain radiographs (Fig.
2.1) are the default modality for evaluating osteolysis [Garcia-Cimbrelo et al.,
2007] but tend to underestimate lesion volume [Agarwal, 2004]. [Claus
et al., 2003] even refers to the lack of any relationship between the twodimensional lesion size and the actual three-dimensional lesion volume.
ARTEFACTS
19
CT
The aim of this study was to examine the extent to which the presence of a
metal hip prosthesis, and the subsequent application of PI MAR, affect the
segmentation of periprosthetic fibrous lesions. Does the presence of metal
DESPITE
In comparison, non-PI algorithms are computationally expensive and remain

confined to academic papers [Watzke and Kalender, 2004, Bal and Spies,
2006, Man et al., 2001, Lemmens et al., 2009, Wang et al., 2000]. Extended
CT scale techniques [Link et al., 2000] have been made redundant by the 16bit quantization used in modern scanners such as the Toshiba scanner used
in this study.
MEASURING
Although there still exists no general solution for removing metal-induced

artefacts [Hsieh, 2003], several approaches have been offered. [Glover and
Pelc, 1981] and [Kalender et al., 1987] first proposed replacing metal sinogram projections with interpolations of adjacent data referred to here as
projection interpolation (PI) metal artefact reduction (MAR). To our knowledge all MAR techniques that have found clinical application are based on
PI. A notable example is the algorithm [Watzke and Kalender, 2004] implemented on the Siemens SOMATOM from 1987 to 1990, and which is still undergoing further development [Liu et al., 2009]. Commercial software such
as ScanIP (Simpleware, Exeter, U.K.) offers PI as an image preprocessing tool.
These MAR techniques can lead to lowering of detail and cause unpredictable
secondary artefacts, such as that described by [Mahnken et al., 2003] as a
ground glass like fan-shaped artifact.
CHAPTER 2
In recent years CT has gained popularity for quantifying periprosthetic osteolysis. There seems to be consensus that CT has superior sensitivity and
measurement accuracy for the detection and measurement of osteolysis compared to traditional radiographs [Cahir et al., 2007, Looney et al., 2002, Puri
et al., 2002, Schwarz et al., 2003, Walde et al., 2005]. Unfortunately CT images suffer from metal-induced artefacts in the vicinity of metal prostheses
[Liu et al., 2009, Watzke and Kalender, 2004]. These most notably arise due
to beam hardening and photon starvation [Kalender, 2005, Lee et al., 2007].
Figure 2.1 In a clinical radiograph, osteolysis is indicated by radiolucent regions adjacent to the prosthesis (arrows) .
decrease the manual segmentation performance of such lesions? Does MAR

improve the manual segmentation compared to the metal-degraded CT images? To answer these questions we first compare the segmented lesion volumes to ground truthed volumes obtained by filling each lesion with water.
Second, we compare the segmentation boundaries between scans acquired
under optimal metal-free scanning to those found in metal-degraded images,
both before and after the application of MAR. Contrast and image intensity
gradients are measured across segmentation boundaries to help explain the
results. This enables us to either recommend or warn against MAR as a preprocessing step in assessing periprosthetic lesions.
20
2.2
Materials and Methods
CT Scan
S
MAR Image
age
reconstruction
Manu
Manual
nual lesion
segmentation
tati
(by GK))
CT Scan
S
ARTEFACTS
Measure lesion
volumes (fluid)
CT
Bisect
sect femur &
create lesions
Substitute metal
with resin
prosthesis
DESPITE
Place
e & remo
remove
cemented
nted
prosthesis
Insert fibrous
tissue & metal
prosthesis
pr
MEASURING
10 cadaver
femora
CHAPTER 2
Fig. 2.2 shows a flow chart of the complete experimental work flow. Ten human femora were retrieved post-mortem from seven donors. These comprised
three female and seven male femora with a mean age of 80.7 years (range
67-98). Dual energy X-ray absorptiometry (DXA) measurements performed
prior to preparation yielded a median T-score of 0.7 (average 1.4) within
a range of 4.9 to +1.1. A T-score of 1 or higher is considered normal,
whereas clinical osteoporosis is defined by a T-score of 2.5 or lower [Beers,
2006]. All femora were preserved in formalin and surrounding soft-tissue removed. We fitted each femur with a polished tapered cobalt-chrome Exeter
size 42-2 stem (Stryker, Limerick, Ireland). For fixation we used radiopaque
contrast-enhanced bone cement (Palacos, Biomet, Warsaw, IN, USA). The
prostheses were implanted under supervision of an experienced orthopedic
surgeon (H.J.L.vdH.) while using standard cemented implantation protocol.
Standard
rd FFBP
Image
Im
reconstruction
Manu
Manual
nual
al lesio
lesion
ion
segmentation
tati
(by FM)
Compare
e measurements
measur
(volume, Dice coefficient,
Hausdorff distances)
Figure 2.2 Flow chart of the experiments performed in this study.
21
To enable scanning each femur with and without the metal prosthesis, we
required removable prostheses. After each prosthesis was cemented it was
mechanically removed from the femur, leaving the remaining cement mantle
and femur intact (Figs. 2.3, 2.4). This was possible due to the Exeter prosthesiss smooth polished surface and tapered shape.
Figure 2.3 The removable Exeter prosthesis is shown partly dislodged from
one of the test femora.
Each femur was axially bisected so as to intersect the cement mantle. We subsequently created lesions both proximally and distally from the sawn-through
interface and at varying locations along the circumference (Fig. 2.4) using a
rotary burr (Dremel). In total, 27 cavities were created having a mean volume of 2.4 ml (range 1.1-5.0)ml. We measured lesion volumes by using a
22
CHAPTER 2
23
ARTEFACTS
During scanning each femur required an inserted prosthesis to hold the two
bisected halves in place. When the metal prosthesis was removed we used a
CT
Previous studies used water [Stamenkov et al., 2003], lean beef mince [Walde
et al., 2005, Weiland et al., 2005], or an unspecified soft-tissue equivalent
material to fill artificially created lesions [Claus et al., 2003]. In this study
we specifically chose radiologically compatible tissue to represent the fibrotic
zones. On four occasions, real periprosthetic fibrotic tissue was retrieved during hip implant revision surgery and its CT opacity measured ex vivo. These
tissues had a mean opacity of 72 Hounsfield Units (HU) with standard deviation of 10 HU. This differs substantially from water (mean 0 HU) and our
measurements for lean beef mince (mean 50 HU). After evaluating several
commercially available alternatives we chose chicken liver, which was considered sufficiently similar with a mean opacity of 77 HU and standard deviation
of 6 HU.
DESPITE
0.2ml graduated syringe to fill each cavity with water. The lesions were then
drained and filled with a fibrous tissue substitute.
MEASURING
Figure 2.4 Femoral lesions mechanically created anterior and posterior of the
cement mantle are shown with the prosthesis removed.
mould-cast resin substitute. The resin had a measured CT opacity of 150 HU,
placing it above the opacity of soft tissues and blood ('50 HU), but less than
bone (>300 HU) and much less than metal (>3,000 HU) [Mukherjee and Rajagopalan, 2007]. The resin prosthesiss low radiopacity did not significantly
contribute to beam hardening, the main source of metal-induced artefacts,
and therefore enabled us to acquire optimal images for CT ground truthing.
Scans were performed on a helical CT scanner (Aquilion 16, Toshiba Medical
Systems, Japan) at 135 kVp using a 200 mA tube current. The in-slice voxel
spacing was 0.44 0.44mm with a slice thickness of 0.5mm. Following the
advice of [Lee et al., 2007] and [Douglas-Akinwande et al., 2006], we chose
a standard smooth reconstruction filter (FC 12) to minimize metal artefacts.
For MAR we used the recent sinogram-interpolation method of [Veldkamp
et al., 2010]. This algorithm has a lot in common with the original method
of [Kalender et al., 1987] but uses raw sinogram data to interpolate metal
traces. Adding a fraction of the original metal signal to the interpolation has
a similar role as the nonzero confidence parameter of [Oehler et al., 2008]
and makes the implant visible in the final reconstruction.
Each of the 27 fibrotic lesions was independently and manually segmented
by each of two experienced users (F. M. and G.K.) using MITK, an interactive
segmentation software tool [Maleike et al., 2009]. F.M. and G.K. independently segmented the resin prosthesis volumes as well as the metal prosthesis
volumes with and without application of MAR. F.M. and G. K. segmented the
volumes sequentially and in randomized order, with 2 weeks separating their
segmentation work.
The volumes of the segmented lesions were compared to the physically measured ground-truthed fluid volumes. The metal-affected and MAR image segmentations were registered to their metal-free counterparts using a 3D iterative closest point (ICP) algorithm, correcting for translational and/or rotational offsets between scans. Geometric deviation in each segmented metal
or MAR volume was compared to the corresponding metal-free resin prosthesis volume. To avoid interobserver bias when comparing segmentations
performed with metal, MAR, or resin volumes, we always compared pairwise
segmentations of the same lesion on a per-user basis. Measurements by F.M.
and G.K. were treated as separate and not averaged.
The residual shape difference between each segmentation pair was computed
by their Hausdorff distance, mean Hausdorff distance, and Dice coefficient.
The Hausdorff distance is defined as the global maximum of all the minimum
distances between two surfaces. The mean Hausdorff distance is the mean
24
minimum distance between the two surfaces. The Dice coefficient is a ratio
2|AB|
between the volumes enclosed by the two surfaces, defined by c = |A|+|B| and
has a value in the range [0, 1] where 1 represents complete overlap between
volumes and 0 represents completely disjoint volumes. A perfectly matched
segmentation pair would have a zero Hausdorff distance and a Dice coefficient
of one, whereas a bad match will have a high Hausdorff distance and Dice
coefficient approaching zero. The Dice coefficient and Hausdorff distance are
well suited to evaluating differences in 3D segmentation such as in [van der
Lijn et al., 2008].
CT
ARTEFACTS
25
DESPITE
We did not assume normal distributions of the measured differences in volume, edge gradient magnitude, Michelson contrast, pairwise Hausdorff distances, or Dice coefficients. This decision was supported by the Shapiro-Wilk
test for normality, indicating that the hypothesis of normality should be rejected for several of the measurement pairs, as is also visually evidenced
in asymmetry in several of the measurement distributions (e.g. Figs. 2.6
and 2.8). Distributions of measurements and differences between measurement pairs are described by nonparametric measures such as median and
interquartile range. Rather than the Students t-test we therefore chose the
Wilcoxon signed rank test to compare measurements of the same quantities
under metal-free, metal-containing, and MAR acquisition. We furthermore
chose not to assume linear relationships between variables when testing for
correlation, choosing instead to use Spearmans rank correlation coefficient,
which serves as a nonparametric analogue to Pearsons correlation.
MEASURING
Image registration, distance metrics, and contrast metrics were computed

using the Insight Segmentation and Registration Toolkit (ITK), Visualization
Toolkit (VTK) and the Python programming language. All computations were
performed on the DeVIDE image processing and visualization platform [Botha
and Post, 2008].
CHAPTER 2
For each segmentation boundary we computed the median image gradient

magnitude, as well as the Michelson contrast between the inner and outer
region defined by this boundary. The Michelson contrast for each lesion is
I I in
where I in and I out represent the median image intensities
defined as Iout
out +I in
in a 1 mm wide region symmetrically located inward and outward of the
segmentation border.
2.3
Results
To answer whether the presence of metal degrades segmentation performance,

we compared segmentations performed on the metal-free ground-truthed images to those of metal-affected images. In metal-free image segmentations we
measured volumes that were not significantly different (P = 0.65) compared
to the physically measured fluid volumes (Fig. 2.5), while metal-containing
CT scans tended to significantly (P = 0.002) underestimate the physically
measured volumes. The Hausdorff distances, mean Hausdorff distances, and
Dice coefficients of metal-affected versus metal-free images show low dissimilarity albeit with several outliers (Figs. 2.6, 2.7, 2.8). Michelson contrast
across segmentation boundaries is significantly lower (P = 0.002) than for
metal-free scans (Fig. 2.9). Image gradient magnitudes on segmentation
boundaries also have a lower median value compared to metal-free images
(Fig. 2.10), although this difference is not significant (P = 0.811).
Parameter
Median difference
Significance
Volume
Hausdorff distance
Mean Hausdorff distance
Dice coefficient
Median edge contrast
Median edge gradient
-0.1 mm
-0.62 mm
-0.009 mm
0.0028
0.0046
-9 HU/mm
0.007
0.400
0.474
0.453
0.885
0.228
Table 2.1 Interobserver differences calculated pair wise over all lesions according to the Wilcoxon signed rank test. The only statistically significant difference
is a 0.1 ml bias in measured volume. (HU Hounsfield Units).
The second question is whether PI MAR improves segmentation performance

relative to unprocessed metal-degraded CT. Unexpectedly, we found that volumes measured after application of PI MAR were even smaller than those
measured in the metal-affected scans (Fig. 2.5), and significantly smaller
than the ground-truthed volumes (P < 0.001). We see that the MAR segmentations exhibit significantly larger geometrical deviations (P < 0.001 in all
three cases) from the ground-truthed results than unprocessed metal scans
(Figs. 2.6, 2.7, 2.8). Michelson contrast across segmentation boundaries
(Fig. 2.9) is significantly lower than for either resin scans (P < 0.001) or
unprocessed metal (P = 0.003).
26
2.00
1.00
.00
-1.00
CHAPTER 2
Measured Volume Difference (ml)
3.00
-2.00
-3.00
Resin vs Fluid
Metal vs Fluid
MAR vs Fluid
ARTEFACTS
27
CT
We found no significant correlation between the lesion size or DXA T-score

and any of the measured parameters using Spearmans rank correlation coefficient. Barring a statistically significant but small difference in segmentation
volume we found observations between the two independent observers to
agree well (Table 2.1).
DESPITE
Image gradient magnitudes on segmentation boundaries (Fig. 2.10) are significantly reduced compared to either metal-free ground-truthed or unprocessed metal scans (P < 0.001 in both cases).
MEASURING
Figure 2.5 Metal-free CT accurately estimates volume, whereas metal degradation causes volume underestimation. MAR causes even further volume underestimation.
Figure 2.6 Hausdorff distances compared to resin ground-truthed results

show maximum local segmentation boundary errors.
Average Hausdorff Distance (mm)
4.00
3.00
2.00
1.00
.00
metal
mar
Figure 2.7 Mean Hausdorff distances compared to resin ground-truthed results show average segmentation boundary errors.
28
CHAPTER 2
DESPITE
.8
CT
.7
ARTEFACTS
Michelson Contrast across

segmentation boundary
MEASURING
Figure 2.8 Dice coefficients compared to resin ground-truthed results show

volumetric agreement between segmentations.
.6
.5
.4
.3
.2
resin
metal
mar
Figure 2.9 The median Michelson contrast across each segmented lesions
boundary.
29
Edge Gradient Magnitude ( HU / mm )
800
600
400
200
resin
metal
mar
Figure 2.10 The median edge gradient magnitude across each segmented lesions boundary.
Figure 2.11 A CT slice showing fibrous-tissue lesions (arrows). A: with resin

prosthesis and B: metal prosthesis. C: after sinogram in-painting, metal artefacts
are reduced at the cost of a loss in periprosthetic detail.
30
2.4
Discussion
MEASURING
DESPITE
CT
ARTEFACTS
31
CHAPTER 2
We set out to determine whether the presence of a metal prosthesis and subsequent projection interpolation metal artefact reduction (PI MAR) affect the
segmentation of periprosthetic lesions resembling osteolysis. We compared
segmentation volume as well as geometrical deviation between segmentations performed with and without the presence of metal and after application
of PI MAR.
We believe that the observed trend of lowered segmentation performance due
to MAR is widely relevant to the diagnosis and quantification of periprosthetic
tissues from CT. Our experimental data were obtained under optimal scanning
conditions, with all soft-tissue removed from around the femora. In the clinical setting the image degrading effects of metal-induced beam hardening,
as well as secondary artefacts created by MAR, are likely to present a greater
obstacle to lesion detection and quantification than in the carefully controlled
environment described in this paper. Through inspection we believe that the
threshold we used for identifying metal prosthesis yielded a good segmentation of the metal boundary while still excluding all surrounding biological
tissue. Using a different threshold affects the delineation of the interpolation
region, and subsequently also the amount and the location of detail lost to
the MAR algorithm. A detail-retaining compromise could involve decreasing
the interpolation regions size at the cost of artefact suppression.
We found no tendency for manual CT-based segmentation to either over- or
underestimate lesion volume in the absence of metal hardware. When a metal
prosthesis was introduced, however, lesion volume was underestimated. This
agrees with [Walde et al., 2005] and [Leung et al., 2005] who found that CT
neither consistently underestimated nor overestimated lesion volume, and
[Stamenkov et al., 2003] who found that CT systematically underestimates
lesion volume in the presence of metal artefacts. We explain this tendency
by our measurements, which show that metal-induced artefacts cause lower
contrast across lesion boundaries, which negatively influences their visibility.
Contrary to expectation we found that lesion segmentation deteriorated even
further after application of PI MAR, with larger associated underestimation of
lesion volume and larger geometrical errors. PI MAR reduced image noise in
homogenous regions, but this was achieved at the cost of a substantial loss of
detail, evidenced by lowered edge gradients and image contrast across lesion
boundaries. [Kalender et al., 1987] mentioned that PI MAR works best for
objects with simple near-circular geometries, while [Watzke and Kalender,
2004] mentioned that PI MAR is well suited to larger implants consisting of
dense metal. This view is also echoed by [Liu et al., 2009] who wrote that
MAR improved image quality in scans of large prostheses, whereas it had a
negative effect on small metal objects due to image blurring. In this regard
we expected PI MAR to be of benefit since the Exeter prosthesis chosen for
this study meets the requirements mentioned above. Except for its smoother
appearance (Fig. 2.11C), there is little to recommend the application of PI
MAR above the original metal degraded image (Fig. 2.11B). Detail in the
MAR image is noticeably blurred especially in regions closest to the metal
prosthesis. This is supported by a measured lowering of edge contrast and
edge gradient magnitude after application of PI MAR (Figs. 2.9 and 2.10).
Papers showcasing MAR algorithms [Mahnken et al., 2003, Bal and Spies,
2006, Lemmens et al., 2009] emphasize starburst" artefacts by choosing display windows that create the impression that these artefacts completely obliterate all image detail in their path. This study suggests that a human operator
who has to manually delineate structures adjacent to a metal prosthesis might
obtain better segmentations from unfiltered artefact-containing images than
from images processed with PI MAR. This contrasts with the view that MAR
invariably improves the appearance and usefulness of metal-affected clinical
scans. However, in patients with bilateral prostheses, as often seen in practice,
the beam hardening shadow connecting the two prostheses is much more pronounced than in this single prosthesis experiment. In this scenario PI MAR
can improve the subjective appearance of radiographic cross sections by
equalizing the shadow regions [Watzke and Kalender, 2004, Lemmens et al.,
2009]. This improvement is often confirmed by radiologists subjective rating
[Liu et al., 2009]. For our application of measuring periprosthetic lesions,
however, there seems to be a net loss of quantifiable image information when
applying PI MAR.
CT, in the absence of metal artefacts, is an accurate and unbiased tool for measuring the volume and geometry of periprosthetic lesions. When adding the
presence of a metal prosthesis the result remains usable, albeit with degraded
image quality, increased difficulty in discerning structures, and a tendency to
underestimate lesion volume. Previous studies [Liu et al., 2009, Bal and Spies,
2006] investigating the merits of MAR used subjective rating scales to assess
image quality and limited quantitative measurements to mean CT number
and standard deviation within certain regions of interest. A strength of our
study is its quantitative evaluation of segmentation performance, albeit for a
small set of lesions.
A limitation of this study is the inclusion of only 27 fibrotic lesions from 10 hu32
2.5
Conclusion
MEASURING
DESPITE
Despite its popularity in the literature and superficial improvements to image appearance, projection interpolation metal artefact reduction (PI MAR)
was detrimental to the user-guided segmentation described in this paper. It
remains to be seen whether other image-based metal artefact reduction techniques can improve quantitative segmentation results of such periprosthetic
lesions.
CHAPTER 2
man cadaver femora, all using the same type of metal prosthesis and scanned
in the same CT scanner. We limited ourselves to evaluating a single software
PI MAR implementation, and independent segmentations were performed by
only two operators. Although the femora were harvested from older patients,
only two of the 10 samples had DXA T-scores suggesting osteoporosis, whereas
osteoporosis may be more common in patient populations. Our manually created lesions lacked the radio-dense sclerotic borders that may be found in
clinical practice [Bauer and Schils, 1999, Sofka, 2007]. The current clinical
significance of MAR algorithms is low, although it remains an active field of
research. We suggest that in addition to our general observations, validation
should be performed in any specific clinical setting whenever PI MAR is to be
considered.
CT
ARTEFACTS
33
35
OF INTERFACE TISSUE REMOVAL
Adapted from:
Skeletal Radiology,
Volume 43, Issue 11, pp 15371542, November 2014.
doi: 10.1007/s00256-014-1924-4
EFFECT
Daniel F. Malan, Edward R. Valstar, Rob G.H.H. Nelissen
CHAPTER 3
Percutaneous bone cement

refixation of aseptically loose hip
prostheses: the effect of interface
tissue removal on injected cement
volumes
Abstract
Objective
To quantify whether injected cement volumes differed between two groups
of patients who underwent experimental minimally invasive percutaneous
cement injection procedures to stabilize aseptically loose hip prostheses. One
patient group was preoperatively treated using gene-directed enzyme prodrug
therapy to remove fibrous interface tissue, while the other group received no
preoperative treatment. It was hypothesized that cement penetration may
have been inhibited by the presence of fibrous interface tissue in periprosthetic lesions.
We analyzed 17 patients (14 female, 3 male, ages 72-91, ASA categories 2-4)
who were treated at our institution. Osteolytic lesions and injected cement
were manually delineated using 3D CT image segmentation, and the deposition of injected cement was quantified.
Results
Patients who underwent preoperative gene-directed enzyme therapy to remove fibrous tissue exhibited larger injected cement volumes than those who
did not. The observed median increase in injected cement volume was 6.8
ml. Higher cement leakage volumes were also observed for this group.
Conclusion
We conclude that prior removal of periprosthetic fibrous interface tissue may
enable better cement flow and penetration. This might lead to better refixation of aseptically loosened prostheses.
36
3.1
Introduction
Standard treatment of symptomatic aseptic loosening of a hip prosthesis comprises revision of the loose components, with concomitant removal of the fibrous interface tissue that formed in the periprosthetic osteolytic bone lesions
[Bauer and Schils, 1999, Sundfeldt et al., 2006]. Worldwide, the rate of hip
prosthesis revision at 10 year follow-up is estimated at 12% [Labek et al.,
2011]. Revision rates are predicted to increase in the coming decades [Kurtz
et al., 2007].
3.2
Our candidate population consisted of twenty two patients at our hospital

who consecutively underwent hip stem refixation by means of percutaneous
bone cement injection. CT image data were collected retrospectively. Before
2006, CT imaging was not standard after cement injection at our hospital
37
The aim of this study was to quantify whether injected cement volumes differed between patients who underwent percutaneous cement injection only,
compared to those who also underwent pre-operative gene-directed enzyme
prodrug therapy to remove fibrous interface tissue.
EFFECT
The incompressible periprosthetic fibrous tissue is not removed during percutaneous cement injection and might impede sufficient cement flow. De
Poorter et al. investigated pre-operatively removing interface tissue by using a gene-directed enzyme prodrug therapy (GDEPT) approach [de Poorter
et al., 2005, de Poorter et al., 2008a]. However, it remained unclear whether
cement volumes following GDEPT differed from those cases where interface
tissue were left intact.
CHAPTER 3
Revision surgery has higher perioperative mortality and morbidity rates in

elderly and high-risk groups, with some authors reporting up to 51% postoperative complications in these patients [Strehle et al., 2000]. In the subset of
patients with significant comorbidity the risks of revision surgery might outweigh the benefits. Percutaneously injecting bone cement into the periprosthetic osteolytic lesions was demonstrated as an experimental alternative treatment for these symptomatic patients [de Poorter et al., 2005, de Poorter et al.,
2008a, Raaijmaakers and Mulier, 2010]. During this procedure one or more
hollow vertebroplasty needles are inserted under spinal anaesthesia, and vertebroplasty cement is injected into the periprosthetic space to stabilize and
fixate the loosened prosthesis [Raaijmaakers and Mulier, 2010, de Poorter
et al., 2008b].
and we consequently had to exclude patients for whom no post-operative

CT images were available. The study was performed under approval of the
Medical Ethics Committee (CME) of our institution.
Our study population comprised two groups that were treated consecutively,
not blinded, and over the course of several years. The twelve patients in
the GDEPT group had interface tissue treated with gene directed enzyme
therapy prior to cement injection as described by [de Poorter et al., 2008a,
de Poorter et al., 2008b]. Each had a single hip treated between 2004 and
2006. Of these patients five were excluded due to post-procedure CT image
volumes not being available, yielding a total of 7 GDEPT hips for our analysis.
The cement-only patients received no treatment before cement injection
and were treated between 2005 and 2011. One patient was excluded due
to no post-procedure CT being available. Of the remaining nine patients,
one patient was treated bilaterally. For this patient we included both hips
separately in the analyses, yielding a total of 10 cement-only hips.
Of the 17 hips investigated in this study 14 were from female patients, and
3 from male patients. The median age at operation of the patients was 82
years (range 72-91). All patients presented with invalidating hip pain, and
all were deemed unfit for traditional revision surgery. The American Society
of Anesthesiologists (ASA) classifications [Owens et al., 1978] of the patients
ranged from ASA-2 to ASA-4. There was no difference in the age distribution
between the cement-only and GDEPT groups.
Percutaneous bone cement injection was performed in all patients by the
method described by [de Poorter et al., 2008a, de Poorter, 2010, de Poorter
et al., 2008b] (Figs. 3.13.2). All procedures were performed under guidance
by the same orthopaedic surgeon and intervention radiologist. Patients underwent CT guided percutaneous injection of polymethyl-methacrylate
(PMMA) cement (Osteopal, Biomet; Disc-O-Tech, Disc-O-Tech Medical technologies, Herzeliya, Israel; Vertaplex, Stryker Orthopaedics, Michigan, USA)
via vertebroplasty needles of 3.2 x 100 mm (Biomet, Dordrecht, The Netherlands). Cement injection was performed under spinal anaesthesia and guided
fluoroscopically. Cement injection was halted either when the target lesion
was filled to the extent that additional cement flow leaked beyond the intended region (i.e. extra osseously), or when cement flow ceased due to being
high resistance at the injection cannula (Fig. 3.4). A post-operative CT scan
of the hip was made on the same day as the minimally invasive procedure.
38
CHAPTER 3
In a previously published cadaveric study examining periprosthetic femoral

lesions the interobserver variability of this volumetric segmentation method
was found to span an interquartile range (IQR) of 0.4ml, with a standard
deviation of 0.5 ml and a bias of 0.1ml [Malan et al., 2012b].
39
The extent of the pre-operative osteolytic zones and the injected cement volumes were measured in three dimensions using the acquired CT image volumes. The image volumes were created on a helical CT scanner (Toshiba
Aquilion, Toshiba Medical Systems, Japan) with slice thicknesses ranging
from 0.4 mm to 1.0 mm, and in-plane resolutions between 0.39 mm and 0.74
mm. Osteolytic lesions and cement volumes were manually segmented by an
expert user in a slice-by-slice fashion using the Medical Imaging Interaction
Toolkit (MITK 0.12.2), an interactive medical image segmentation software
tool [Maleike et al., 2009] (Fig. 3.5).
EFFECT
Figure 3.1 Cement being percutaneously injected into the periprosthetic space
via vertebroplasty needles
Figure 3.2 Cement flow was monitored using intra-operative fluoroscopy
Another study that applied this segmentation method to various periprosthetic tissues in clinical CT volumes reported a spatial volumetric interobserver agreement of between 90% and 95% (Median Dice Coefficient between
0.9 and 0.95) for segmentations performed by two subsequent human operators [Malan et al., 2012a].
Sub-volumes of injected cement that had leaked outside the desired target region, i.e. extra-osseously adjacent to the introduced cement injection needle
in the femur, were separately labelled. Pre-operative fibrous tissue regions
were determined as the union between residual periprosthetic radiolucent
zones and the regions occupied by newly injected cement excluding regions
of leaked cement.
40
CHAPTER 3
EFFECT
Using these segmented regions we computed the following values for each
patient:
Lesion volume: Volume of pre-operative radiolucent fibrous tissue lesions (ml)
Filling fraction: the percentage of pre-operative lesions that was filled
by injected cement (%)
Leakage fraction: the percentage of the total volume of injected cement
that leaked into undesired areas (%)
41
Figure 3.3 Cement flow was monitored using intra-operative fluoroscopy
Figure 3.4 Lateral view X-ray of a patients hip after cement injection. Of all
examined cases, this patient had the highest cement leakage percentage at 73%
leakage of the injected 11.95 ml. This patient was part of the GDEPT group.
Segmented volumes were measured in millilitres and each volume distribution characterized by its median, range and IQR. Outliers were defined as
being more than 1.5 IQRs outside the interval spanned by the first and third
quartiles. Results were analysed using IBM SPSS Statistics 20 for Microsoft
Windows (IBM Corporation, Armonk, NY, USA).
In comparing the observed differences between two sampled case series we
used the nonparametric Mann Whitney U-test for independent groups, as our
patients groups were small and we did not assume normal distribution of
our measured parameters. A p value of 0.05 was taken to be statistically
significant.
42
CHAPTER 3
Results
The cement-only groups radiolucent lesion volumes ranged from 13.8 ml to

36.2 ml (median 27.8 ml, IQR 18.8 ml). The GDEPT group had lesion volumes
ranging from 8.5 ml to 52.0 ml (median 20.9 ml, IQR 25 ml). These two
distributions (Fig. 3.6) were statistically indistinguishable as measured by
the Mann Whitney U-test (p = 0.96).
The injected cement volumes for the cement-only group ranged from 3.4 ml
to 13.0 ml (median 5.2 ml, IQR 4.1 ml). For the GDEPT group, the injected cement volumes ranged from 6.9 ml to 27.8 ml (median 12.0 ml, IQR 14.3 ml).
The observed difference in median injected cement volume was 6.8ml, which
is more than one order of magnitude larger than the interobserver variability
in the volume measurement technique as reported by [Malan et al., 2012b].
This difference in distributions was statistically significant (p=0.007), and is
shown in Fig. 3.7.
43
3.3
EFFECT
Figure 3.5 A single axial slice through the CT volume of the same patient as
in Fig. 3.4. In (a) the original image is shown. In (b) the regions of interest are
labelled: Remainder of interface tissue zone (gray), injected cement at desired
location (white), and leaked cement (hatched)
Figure 3.6 Volumes of osteolytic fibrous tissue for patients in the cement-only
and GDEPT groups
The cement filling percentages achieved for the cement-only group ranged
from 10.2% to 58.3% (median 20.7%, IQR 16.5%). The GDEPT groups
larger injected cement volumes also translated to higher cement filling fractions compared to the cement-only group. For the GDEPT group the cement
filling percentages ranged from 16.5% to 52.1% (median 33.6%, IQR 31.8%).
There was a single outlier in the cement-only group representing an exceptionally high filling percentage (58.3%) which occurred for the femur with
the smallest osteolytic lesion (13.8 ml) in this group (Fig. 3.8). Omitting this
outlier resulted in a statistically significant difference in filling percentages
between the cement-only and GDEPT-only groups (p = 0.05).
Without omission of the outlier in the cement-only group, the differences
in cement filling fractions between the two groups did not reach statistical
significance (p=0.16).
44
CHAPTER 3
45
For the cement-only group the percentage of the injected cement that leaked
out of the intended target (i.e. extra osseously) ranged between 0% and
40.1% (median 5.3%, IQR 35.6%). In comparison, the extra-femoral cement
leakage in the GDEPT group ranged from 0.2% to 73.1% (median 39.6%, IQR
64.8%), and is shown in Fig. 3.9. Omitting the measurement corresponding
to the outlier of Fig. 3.8, this difference was statistically significant (p=0.05).
With the outlier included, the difference between these distributions did not
reach statistical significance (p = 0.06).
EFFECT
Figure 3.7 Volumes of injected cement for patients in the cement-only and
GDEPT groups
Figure 3.8 Cement filling percentages of the osteolytic lesions for patients in
the cement-only and GDEPT groups
Figure 3.9 Cement leakage percentages for patients in the cement-only and
GDEPT groups
46
3.4
Discussion
EFFECT
47
CHAPTER 3
Refixation of aseptic loosened hip stems by percutaneous cement injection

can improve clinical outcomes for patients with loosened hip prostheses [de
Poorter et al., 2008b]. Cement injection may be performed either with or
without prior interface tissue treatment [Raaijmaakers and Mulier, 2010, de
Poorter, 2010]. The literature on this topic is limited. Earlier phase I-II
preclinical and clinical trials found that the adenoviral vector CTL102 and
the prodrug CB1954 were viable for removing interface tissue despite possible transient adverse side effects including fever, nausea and leukopenia [de
Poorter et al., 2008b]. This study examines whether differences in cementinjection outcomes between these two approaches were observed.
Our results indicate that pre-operative treatment of interface tissue enabled
more cement to be injected into the periprosthetic osteolytic lesions. This difference was statistically significant, even in our small sample population. The
larger injected cement volumes for the patients who underwent pre-operative
interface tissue removal was not correlated with the patients pre-operative lesion volume, as the distribution of the latter was the same for the cement-only
and GDEPT groups. With the exception of a single outlier, the larger injected
cement volumes in the GDEPT group also manifested in higher fractions of
cement filling of the target lesions. This greater degree of cement filling might
translate to better refixation of loosened prostheses [Andreykiv et al., 2012].
The disadvantage to the hypothesised improved refixation in the GDEPT group
may be side-effects caused by the treatment GDEPT itself, as well as adverse
effects caused by bone cement leaking into e.g. surrounding muscle tissue.
Given that elderly patients with aseptically loose hip prostheses present with
invalidating pain and severely limited mobility, the benefits of better refixation are seen to outweigh the increased risk of transient side effects or cement
leakage, which may cause temporary discomfort.
With the exception of a single outlier in the GDEPT group, the observed cement leakage percentages support the view that prior apoptosis-driven removal of fibrous interface tissue permits injected cement to flow more freely
in the periprosthetic space during the cement injection procedure both into
and out of osteolytic target regions. An interesting question is whether use of
more viscous cement is advisable where interface tissue has been sufficiently
eliminated. We speculate that the association between lower cement viscosity and cement leakage in percutaneous vertebroplasty [Nieuwenhuijse et al.,
2010] may also apply to the scenario of periprosthetic refixation by cement
injection.
Osteolysis is a progressive process and is propagated by the presence of interface tissue [Agarwal, 2004]. Failure to completely remove pre-existing interface tissue may lead to progression or recurrence of osteolysis [Park et al.,
2004]. A positive aspect of fibrous interface tissue removal that was not examined in this study is that fibrous tissue apoptosis and/or removal may reduce
the self-propagating progression of osteolysis. Biomechanical finite element
simulation has furthermore shown that interface tissue removal increases mechanical stability of the prosthesis [Andreykiv et al., 2012].
Limitations of this study include the small, consecutive, patient groups which
arose from the experimental nature of the interventions described. A phase III
study using the adenoviral vector CTL102 and prodrug CB1954, is currently
awaiting funding at our institution. All bone cement used in this study was
of comparable viscosity. The scope of our study excluded the research question of a possible relationship between cement leakage outside the femur and
cement viscosity.
3.5
Conclusion
We conclude that the pre-operative GDEPT treatment of fibrous interface tissue had a measurable effect on the efficacy of percutaneous cement injection
into the periprosthetic space. Only cement injection without fibrous tissue removal is currently possible in routine clinical practice due to a lack of available
tissue removal agents and methodologies. We encourage continued research
into minimally invasive methods for removing fibrous interface tissue prior to
refixation by cement injection.
Acknowledgements
The authors wish to thank Anika Hoogenstraaten who helped us retrieve and
organize historical clinical records at our hospital. We also acknowledge Dr
Arian van Erkel, radiologist who assisted in the treatment of several of the
patients described in this study. We also thank Samuel van de Velde who
contributed his expertise to this paper. This research was supported by a
grant from the Stichting Anna Fonds (Leiden, The Netherlands), as well as the
Dutch Technology Foundation STW, which is the applied science division of
the NWO and the Technology Programme of the Ministry of Economic Affairs
(project number LKG 7943).
48
4
CHAPTER 4
CT density overestimation in
enclosed regions and its
implications on estimating bones
mechanical properties
CT
49
DENSITY OVERESTIMATION
D.F. Malan, B.C. Stoel, J. Geleijns, E.R. Valstar
Abstract
We investigated how the density and strength of trabecular bone as measured
with computed tomography (CT) could be affected by being enclosed in cortical bone. To this end we measured the opacity of a low density CT phantom
enclosed in a sheath of high density contrast fluid. We found a clear correlation between increasing thickness of the radiopaque sheath and increase in
measured opacity within the enclosed phantom. This increase was not due to
partial volume effects or the scanners point spread function, but presumably
caused by beam hardening and the way the image reconstruction algorithm
deals with it. An increase was visible both with and without water submersion, and for all investigated reconstruction kernels. We then estimated what
the error in derived mechanical properties for finite element (FEM) models of
such bony structures may be. We estimate that the observed effect can lead
to inaccuracies exceeding 33% in derived mechanical strength of trabecular
bone. Recent skeletal FEM studies seem to insufficiently guard against this
issue.
Keywords Computed Tomography, beam hardening, Hounsfield, finite
element, density, cortical, trabecular, cancellous, bone
4.1
Introduction
The Finite Element Method (FEM) has proven itself a powerful tool in analysing
stress distribution in bone [Taylor et al., 1995, Weinans et al., 2000, Stolk
et al., 2002, Schileo et al., 2007]. FEM models need to accurately represent
both the geometry and mechanical properties of bone. One way of measuring
these properties is by X-ray computed tomography (CT).
CT measures the radiodensity of an object relative to water and air, quantified
according to the Hounsfield scale. We can relate the measured CT number of
each volume element, in Hounsfield Units (HU), to bone mineral ("ash") density, which in turn can be directly related to the bones mechanical properties.
Several recent studies have used this approach [Viceconti et al., 2004, Taddei
et al., 2006, Imai et al., 2008, Bessho et al., 2009].
Beam hardening artefacts, caused by radiodense materials, have been widely
described, and result in deviant CT numbers being reconstructed. These
artefacts may appear as a lowering of apparent attenuation coefficients, also
known as the "cupping" effect [Brooks and Chiro, 1976]. In the human body,
radiodense cortical bone often encloses lower density tissues such as trabec50
We used a solid cylindrical Perspex rod with a diameter of 20mm and length
150mm to represent low density trabecular bone. Perspex has a known CT
number of 122 5 HU [Brown et al., 2008], which is representative for trabecular bone found in elderly patients [Mosekilde et al., 1989]. We performed
all scans in a clinical CT scanner (Aquilion One, Toshiba Medical Systems,
Japan) using its 64-slice helical mode, operating at 120 kVp and 250 mAs.
The scan target consisted of the Perspex rod in isolation, as well as concentrically enclosed in one of four contrast fluid filled PVC pipes of increasing diameter. The contrast fluid consisted of a mix of water and Iomeprol (Iomeron
51
CT
4.2
CHAPTER 4
ular bone. CT opacities measured in these enclosed regions might therefore

also be affected by beam hardening.
Beam hardening artefacts can be reduced by enveloping the target in water
[Brooks and Chiro, 1976]. Computational beam hardening correction may
be applied by scanning a calibration phantom simultaneously with the target
in a process known as Quantitative CT (QCT).
While QCT using standard CT hardware is accurate in measuring vertebral
bone density [Zink et al., 1997], special dual energy CT is required to fully
correct for beam hardening caused by thicker cortical bone [de Casteele,
2004, DeLuca et al., 2009]. However, the use of standard CT to assign material properties to patient specific FEM models is widespread. Several recent
studies omit any mention of using QCT or beam hardening correction [Viceconti et al., 2004, Imai et al., 2008, Keyak and Skinner, 1993, Zannoni et al.,
1998]. [Taddei et al., 2006] submerged their CT target in water to suppress
beam hardening, but made no explicit mention of using QCT. [Bessho et al.,
2009] referred to QCT, but did not mention whether single or dual energy
was used.
[Tanck et al., 2010] examined the effect which the shape of the surrounding
"lower body model" has on volumetric bone mineral density measured within
femoral heads. They measured density values from water basin scans that
were on average 10.8% lower than in situ. Though recognizing that beam
hardening caused by surrounding structures contributes to this discrepancy,
they did not quantify the effect caused by the femurs cortical bone itself.
The goal of this investigation was to quantify how cortical bone would affect
the CT numbers measured in enclosed trabecular bone, and to provide an
indication on what the effect of resulting inaccuracies would be on the bones
derived mechanical properties.
400, Bracco Imaging, Konstanz, Germany) with an opacity of 1030 HU, which
is in the same range as normal human cortical bone [Mukherjee and Rajagopalan, 2007]. The wall thickness of each pipe was 3mm, with a mean
opacity of 380 HU. The four PVC pipes had inner diameters of 25mm, 33mm,
43mm and 68mm respectively. With the Perspex rod inserted this resulted in
concentric contrast fluid sheaths with thicknesses of 2.5mm, 6.5mm, 11.5mm
and 24mm respectively - see Fig. 4.1.
Figure 4.1 Schematic and axial view of one of the CT phantoms with A) The
Perspex rod, B) the contrast filled pipe, C) surrounding water or air. The darkened band between B and C is due to the lower-density construction of the inner
pipe wall.
For each parameter set the target was scanned suspended in air, and again
when submerged in a rectangular water bath measuring 240mm x 300 mm
x 380 mm. To ensure that our results were not determined by the choice of
reconstruction kernel, we used three substantially different reconstructions.
Both "smooth" and "sharp" kernels were chosen. On our scanner these kernels are labelled FC04, FC14 and FC30. FC30 is a "sharp" bone kernel used
as a standard kernel for clinical skeletal imaging. FC04 and FC14 are both
"smooth" kernels, the difference being that FC04 incorporates beam hardening correction, and FC14 does not. The Perspex rod was segmented from
the reconstructed images using the MITK toolkit [Maleike et al., 2009], and
its opacity distribution in each image analysed using the DeVIDE image processing platform [Botha and Post, 2008]. We consistently chose the bars
innermost cylindrical region, 10mm in diameter, as region of interest (ROI),
where we recorded the mean CT numbers and their 95% per-voxel confidence
intervals.
52
4.3
Results
Observed opacity in the ROI increased strongly as the surrounding thickness

of contrast fluid increased. This trend was observed for all three of the reconstruction kernels - see Fig. 4.2 and Fig. 4.3.
Observed CT opacity of "trabecular" rod versus
thickness of surrounding "cortical" layer (in air)
Kernel
FC 04
FC 14
FC 30
300
CHAPTER 4
200
100
CT
0
zero
2.5mm
6.5mm
11.5mm
24mm
Thickness of "cortical" layer
Figure 4.2 CT values measured in the enclosed Perspex rod (surrounded by

air). Average 2 plotted for each region of interest.
While the increase occurred with and without submersion in water, the presence of water somewhat suppressed this trend (Fig. 4.3). This water induced
suppression was strongest for the FC14 and FC30 kernels which lack beam
hardening correction.
As expected, submersion in water increased image noise, as reflected by the
standard deviation of opacity values. This increase exceeded a factor of 10
for the "sharp" kernel (FC30), and a factor of 7 for the "soft" kernels. Noise
also increased with increasing diameter of the radiopaque sheath and hence
the attenuation amounting to a factor of 1.3 between an absent layer and
the layer of 24mm thickness.
53
CT opacity of "trabecular" rod (Hounsfield Units)
400
CT opacity of "trabecular" rod (Hounsfield Units)
CT opacity of "trabecular" rod versus

thickness of surrounding "cortical" layer (in water)
Kernel
750
FC 04
FC 14
FC 30
500
250
-250
zero
2.5mm
6.5mm
11.5mm
24mm
Thickness of "cortical" layer
Figure 4.3 CT values measured in the enclosed Perspex rod (immersed in water). Average 2 plotted for each region of interest.
The only cases in which the ROIs mean opacity matches the known value for
Perspex is in the absence of contrast fluid while submerged in water, and in
air when a beam hardening correcting kernel (FC04) is used.
4.4
Discussion
Significant overestimation of the phantoms CT opacity was observed whenever it was enclosed by a radiopaque contrast fluid sheath. The overestimation was observed for kernels with and without beam hardening correction, and with and without submersion in water. Beam hardening most likely
lies at the root of this problem, but surprisingly has the opposite effect as
the "cupping" described by [Brooks and Chiro, 1976], leading to an increase
rather than decrease in observed CT numbers. The observed overestimation
is not due to partial volume effects since the ROI was chosen in a uniform
54
region of the phantom, separated from its edges by much more than the
scanners point spread radius [Dore and Goussard, 1997].
Femoral cortical bone may reach a thickness exceeding 6.0mm for males, decreasing to 2.5mm for elderly females [Bousson et al., 2000] and has opacity
and geometry comparable to the contrast fluid used in this study. The trabecular bone of older patients often has opacities similar to or lower than the
Perspex rod used in this study [Ciarelli et al., 1991]. We therefore expect to
find comparable behaviour in clinical CT scans.
, where x is the CT number in HU and is the apparent ash density in g/cm3 .

Inserting the reference value of 122 HU we obtain an estimated ash density
of 0.112 g/cm3 . When instead using 160 HU the value one could encounter
with a sheath of 3mm of cortical bone - we obtain 0.127 g/cm3 an overestimation of 13.6%.
We assess the resulting error in estimated elastic properties by using the power
relationship described by Keller [Keller, 1994],
E = 10.5 2.29
, where is apparent ash density in g/cm3 and E is the Youngs modulus
in GPa. Inserting the values computed above, we obtain Youngs moduli of
69.5 MPa and 93.1 MPa respectively an overestimation of 33.9%. Due to
55
= 0.0004x + 0.063
CT
The observed CT opacity bias, however, will cause errors in the derived density of trabecular bone. The magnitude of this error can be assessed by using
the well-established linear relationship between HU and trabecular bone ash
density reported by [Mosekilde et al., 1989], namely
CHAPTER 4
Perspex has a known CT number of 122 HU 5 HU [Brown et al., 2008]. We

measured mean CT numbers of 156 HU and 181 HU using the standard FC30
bone kernel to image the rod surrounded by a 2.5mm and 6.5mm sheath
respectively while submerged in water. These values increased to 199 HU
and 233 HU when the targets were not submerged. When the bone kernel
was substituted for the beam hardening correcting FC04 kernel we measured
values of 146 HU and 162 HU when submerged but lowering to 125 and
146 HU in air. While the per-voxel noise of the sharp bone kernel had a
wide distribution, the standard error of the mean was small and this did not
invalidate it as an estimator of mean tissue density.
the higher exponent relating cortical ash density to Youngs modulus we expect even larger errors if comparable overestimation occurs in cortical bone
regions [Schaffler and Burr, 1988].
Such inaccuracies might render derived FEM models inaccurate, and prove
disastrous where absolute values of stress and strain are computed. In these
cases we suggest using dual energy QCT and/or including a calibration phantom in the same instantaneous field of view as the target. Relative differences
between FEM configurations might be less affected. As patient specific FEM
modelling becomes ever more popular this issue requires careful model validation.
Acknowledgements
This research is supported by the Dutch Technology Foundation STW, which
is the applied science division of NWO, and the Technology Programme of the
Ministry of Economic Affairs (project number LKG 7943).
56
5
Voxel classification of
periprosthetic tissues of the hip
CHAPTER 5
57
CLASSIFICATION
Adapted from:
IEEE International Symposium on Biomedical Imaging:
From Nano to Macro, pp 13411344, April 2010.
doi: 10.1109/ISBI.2010.5490245
VOXEL
Daniel F. Malan, Charl P. Botha,

Rob G.H.H. Nelissen, Edward R. Valstar
Abstract
We present an automated algorithm which classifies periprosthetic tissues in
CT scans of patients with loosened hip prostheses. To our knowledge this
is the first application of CT voxel classification to periprosthetic tissues of
the hip. We use several image features including multi-scale image intensity, multi-scale image gradient and distance metrics. Seven classifier types
were trained using five manually segmented clinical CT datasets, and their
classification performance compared to manual segmentations using a leaveone-out scheme. Using this technique we are able to correctly segment the
majority of each of the six tissue categories, in spite of low bone densities,
metal-induced CT imaging artefacts and inter-patient and inter-scan variation. Our automated classifier forms a pragmatic first step towards eventual
automatic tissue segmentation.
Keywords automatic, classification, segmentation, computed tomography, periprosthetic, osteolysis
5.1
Introduction
The most significant complication that threatens the long-term survival of a

total hip arthroplasty (THA) is periprosthetic osteolysis [Bauer and Schils,
1999, Walde et al., 2005] which involves resorption of bone and replacement
by soft fibrotic tissue. Once osteolysis develops it usually progresses, eventually leading to mechanical instability and prosthesis loosening.
Minimally invasive refixation of loosened prostheses is possible [de Poorter
et al., 2008a] but requires the location and extent of fibrotic lesions to be
known pre-operatively. Recent studies have shown that CT is more sensitive and accurate than traditional radiographs in detecting and measuring
such lesions [Walde et al., 2005, Garcia-Cimbrelo et al., 2007]. However, the
steady increase in resolution offered by modern CT scanners make traditional
manual segmentation extremely time-consuming, thereby limiting users utilization of the available data.
CT of suffers from metal-induced artefacts [Lemmens et al., 2009] which drastically complicate automatic segmentation near prostheses. To make things
worse patients suffering from prosthetic loosening often have very poor bone
quality yielding low CT image contrast with intensity values overlapping those
of other tissues. Statistical Shape Models are useful for segmenting objects
from low quality image data, but fare badly when modelling pathological tis58
sues (such as fibrotic lesions) with no generalizable geometry [Heimann and

Meinzer, 2009] and/or consisting of several small isolated regions.
CHAPTER 5
Several papers have been published describing automatic statistical pixel- or

voxel segmentation of clinical data. By combining several complementary image features, voxel classifiers deliver reasonable classification performance in
spite of metal-induced CT imaging artefacts, and without resorting to explicit
geometrical modelling or human intervention. Radiographs [Loog and van
Ginneken, 2006], MRI [Folkesson et al., 2007] and CT [van Rikxoort et al.,
2009] have been subjected to pixel/voxel classification. Standard approaches
generally make use of multi-scale image intensity as well as higher order spatial derivatives to describe local image variations and texture. Image intensity variation between scans can complicate X-ray and MRI feature selection,
but CT scanners are largely immune to this due to their well defined and calibrated output measured in Hounsfield Units (HU). The geometric position
of the image pixels or voxels can be omitted [Loog and van Ginneken, 2006]
or incorporated [van Rikxoort et al., 2009] into the classifiers feature space,
although care must be taken so that the chosen features remain invariant to
inter-scan orientation and scaling offsets.
VOXEL
59
CLASSIFICATION
The aim of this study was to develop an automated voxel classifier that can
serve as the first step in a segmentation pipeline, eventually leading to patientspecific mechanical modelling. We are interested in the 3D distribution of
bone, cement and fibrotic tissue around the prosthesis, which defines the hips
mechanical stability. In this paper we present statistical voxel classifiers that
classify periprosthetic tissues into six possible tissue categories, namely cement, fibrotic lesion, trabecular bone, cortical bone, intramedullary canal and
exterior. To our knowledge this is the first time that such a 3D statistical voxel
classifier has been applied to periprosthetic CT image data. The classifiers are
trained on manually segmented CT scans of five patients with clinically loose
prostheses, and evaluated in a (per patient) leave-one-out scheme. Image
features are chosen so that they can be computed fully automatically. Once
trained, tissue classification can be performed automatically, delivering an approximate tissue distribution as output. This initial classification forms a good
foundation for further post-processing and eventual automatic segmentation.
5.2
5.2.1
Method
Image parameters
We obtained data from five different patients diagnosed with loose femoral
prostheses causing pain and immobility. Each patient was scanned in a Toshiba
Aquilion CT scanner using its FC30 bone kernel", yielding the highest possible resolution, at the cost of increased noise. All scans were performed with
a peak tube voltage of 135kV. Since we obtained the clinical data retrospectively there was some inter-scan variation, most notably tube current (150mA
to 400mA) and in-slice voxel spacing (0.44mm to 0.59mm). All scans had a
slice thickness of 1mm. The scanner was set to include a single hip in its
reconstruction field of view.
In addition to normal between-patient anatomical differences we also note
that different prosthesis designs and sizes were used. All prostheses were
of cobalt-chrome, thereby presenting a worst case scenario, since titanium
implants yield fewer artefacts.
5.2.2
Choosing image features
As pre-processing step we selected the upper part of each femur as a region of

interest (ROI). Thanks to the artificial joint we have good separation between
bony structures of the femur and pelvis. ROI extraction can therefore be
performed automatically, although this falls outside the scope of this article.
We decided on using eleven image features at every voxel location. Following an approach similar to previous authors [Loog and van Ginneken,
2006, Folkesson et al., 2007, van Rikxoort et al., 2009] we used CT grayscale
values at multiple scales as our first four features. These features describe
the native in-slice voxel resolution (0.5mm x 0.5mm x 1mm) along with
Gaussian-smoothed versions having spherical standard deviations of 1mm,
2mm and 5mm. Features five to eight consist of the image gradient magnitude computed from at the same scales as the grayscale features.
The rationale behind using a Gaussian multi-scale approach is twofold. Firstly,
by combining neighbouring pixel values, we tend to average out individual voxel noise (at the cost of resolution). Secondly, by adding information of neighbouring voxels we include neighbourhood information to every
voxel (for example we can discern between an isolated bright voxel and a
bright voxel in a bright neighbourhood, without doing explicit neighbourhood searches). Similarly to [van Ginneken et al., 2006] and in constrast to
[Folkesson et al., 2007] we decided against using second-order and higher
60
derivatives as feature descriptors, arguing that these are excessively sensitive

to image noise and contribute little additional information to our model.
The last three features (numbers nine to eleven) are distance metrics, chosen
to be automatically computable and insensitive to rotational and translational
offsets. In each of these three cases we compute the signed distance in millimeters, so as to be independent of the scan resolution and anisotropies.
Firstly, we compute the distance from the metal prosthesis. Metal has such a
high contrast in CT that it can easily be found by performing a simple threshold at e.g. 5000 HU. This feature gives us useful information as to the centredness of any given voxel, which is useful since periprosthetic tissues are
approximately radially distributed.
Training the voxel classifiers
To provide training and validation labels to the image voxels, an experienced

user manually segmented each femur using the interactive MITK software
tool [Maleike et al., 2009]. The segmented masks were then used to select
61
CLASSIFICATION
5.2.3
VOXEL
Lastly we compute the the signed distance from the convex hull formed by the
femur. We note that this adds information because femoral tissues have said
radial distribution, with cortical bone being closest to the outer hull of the femur. We compute this feature by first thresholding the volume of interest (at
600 HU). The threshold of 600 HU was chosen so that only cortical bone, cement and the metal prosthesis fall above the threshold. We then subtract a per
slice 7x7x1 voxel dilated mask of the metal prosthesis, thereby retaining only
cortical bone and cement, along with possibly isolated metal-induced imaging
artefacts. Next, we perform a cascaded 3x1x1 + 1x3x1 morphological opening to remove remaining metal-induced noise voxels. The result is a thresholded mask containing many islands and holes, caused by the CT shadow
of the prosthesis, trabecular bone, fibrous tissue, intramedullary canal and
zones of low bone density. Computing the slice-by-slice convex hull of this
mask gives us a reasonable approximation to the convex hull of the femurs
cortical shell.
CHAPTER 5
The second distance metric is computed along the scan (Z) axis from the centre of the prosthesis head. This can automatically be computed by the mean
voxel location of the prosthesis head, which is easily recognizable from the
previously mentioned threshold due to its increased diameter at one extremity. Due to the geometrical constraint of a patient lying on the CT gantry the
prosthesiss long axis is always aligned with the scan direction, giving this
distance a consistent interpretation.
Figure 5.1 Projection of the six tissue categories represented in feature space
the relevant voxels for the eleven image feaures. The statistical classifiers
were constructed and trained on these features using PRTOOLS [Duin et al.,
2007], a pattern recognition toolbox for MATLAB.
Our classification task involves separating six distinct tissue types as collections of points in an eleven-dimensional space. Figure 5.1 shows a 2D projection along the computed axes of greatest separation of the 11 dimensional
training voxel feature space. We see poor separation between classes indicating a very challenging classification problem. Selecting an appropriate
classifier for this task is not a straightforward choice. Authors of recently
published medical voxel classifiers have opted for a colourful mix of k-nearestneighbour (kNN) [van Ginneken et al., 2006, Folkesson et al., 2007], linearand quadratic discriminant (LDC & QDC) [van Rikxoort et al., 2009], decision trees [Akselrod-Ballin et al., 2009] and neural networks, to name a few.
In this paper we chose to compare several available classifiers namely LDC,
62
QDC, Parzen, kNN, back-propagation neural network as well as a combined

voting" classifier composed of simple LDC and kNN classifiers.
The five different patient CTs were use to test the classifiers in a rotating leaveone-out scheme, where each time the classifiers were trained on four of the
CT datasets and tested on the remaining set. At each step in the leave-one-out
scheme we transform all features such that the training features have a zero
mean and unit variance. Depending on the classifier we use a suitable sized
random subset of training voxels. We use a subset of all available training
voxels to keep the training time in check a kNN classifier, for example, needs
to store all training data internally. For each classifier we use an equal number
of training samples per tissue class, along with equal priors.
5.3
Results & Discussion
63
CLASSIFICATION
Figure 5.3 illustrates that automatic voxel segmentation correctly identifies

the general distribution of the separate tissues, even before any additional
post-processing. Looking at Table 5.1, we see that the most problems occur
when classifying cement and fibrotic tissue. Both of these exist close to the
metal prosthesis where they are strongly affected by metal artefacts. Voting
between each voxel and its neighbours soft (continuous) classification can
improve filtering of misclassifications by incorporating more geometrical coherence.
VOXEL
Our small dataset of five patients is a limitation in assessing the true potential of these methods. The limitation lies not in the number of data points
available during training, but rather in their ability to represent the variation in human femora and scan parameters. However, it can be expected that
segmentation performance will increase as larger and therefore more general
training sets become available.
CHAPTER 5
The different classifiers performance is shown in Fig. 5.2. We see that the
very fast LDC and QDC classifiers are generally less capable than the more
complex alternatives. We were surprised at the relatively poor results obtained with the 3-layer back propagation neural network. The combined
classifier delivered good classification results, although we found the Parzen
classifier to have the most stable response across all tissue classes and test
cases.
Figure 5.2 Median classification error for different tissues and classifiers
Manual
seg.
Canal
Cement
Cortical
Exterior
Fibrous
Trabecular
Canal
Automatic classification
Cem Cort Ext
Fibr
Trab
98.5
1.8
1.5
0.2
1.6
0.0
0.4
67.3
6.0
2.0
15.9
1.6
0.0
2.7
7.0
12.8
12.7
72.0
0.3
6.3
78.2
1.7
6.4
3.8
0.0
0.4
1.1
78.4
2.0
12.8
0.8
21.5
6.1
4.9
61.4
9.7
Table 5.1 Confusion matrix for the Parzen classifier over all test femora (see
also Fig. 5.2)
64
CHAPTER 5
VOXEL
CLASSIFICATION
(a)
(b)
(c)
Figure 5.3 a) Sagittal CT slice next to b) its tissue classification using manual
segmentation and c) our automatic Parzen classifier
65
5.4
Conclusion & Future work
The voxel classifier presented in this paper offers an automatic tool for performing an initial segmentation of 3D CT scans of loosened hip prostheses.
We achieve a correct classification rate ranging between 66% and 70% for
fibrotic lesions, bone and cement, the tissues we are most interested in. The
result obtained represents a useful first step towards automated segmentation, and a significant improvement above simple threshold-based segmentation. Future work will include post-processing the initial classification result
by incorporating neighbourhood voting and the the classification certainty
associated with each voxel. We see this solution as the first step in a fully
automatic tissue segmentation pipeline.
66
6
The addition of Graph Cuts to
voxel classification for automated
segmentation of pathological
periprosthetic hip anatomy
CHAPTER 6
SEGMENTING
Daniel F. Malan, Charl P. Botha, Edward R. Valstar
WITH
GRAPH
CUTS
Adapted from:
International Journal of Computer Assisted Radiology and Surgery,
Volume 8, Issue 1, pp 6374, January 2013.
doi: 10.1007/s11548-012-0671-z
67
Abstract
Purpose:
Automated patient-specific image-based segmentation of tissues surrounding
aseptically loose hip prostheses is desired. For this we present an automated
segmentation pipeline that labels periprosthetic tissues in computed tomography (CT). The intended application of this pipeline is in pre-operative planning.
Methods:
Individual voxels were classified based on a set of automatically extracted image features. Minimum cost graph cuts were computed on the classification
results. The graph cut step enabled us to enforce geometrical containment
constraints, such as cortical bone sheathing the femurs interior. The solutions novelty lies in the combination of voxel classification with multi-label
graph cuts and in the way label costs were defined to enforce containment
constraints.
Results:
The segmentation pipeline was tested on a set of twelve manually segmented
clinical CT volumes. The distribution of healthy tissue and bone cement was
automatically determined with sensitivities greater than 82% and pathological fibrous interface tissue with a sensitivity exceeding 73%. Specificity exceeded 96% for all tissues.
Conclusions:
The addition of a graph cut step improved segmentation compared to voxel
classification alone. The pipeline described in this paper represents a practical
approach to segmenting multi-tissue regions from CT.
6.1
Introduction
Periprosthetic osteolysis leading to aseptic loosening is one of the foremost

problems limiting the survival of hip prostheses [Agarwal, 2004]. Loosening
caused by osteolysis is characterized by extensive resorption of bone and its
replacement by soft fibrous interface tissue that offers little mechanical stability. Surgical treatment becomes necessary when prosthesis loosening ensues.
During open revision surgery, the old prosthesis and its cement mantle, along
68
with surrounding fibrous interface tissue, are removed, after which a new
prosthesis is placed.
Revision surgery is very demanding on the patient, therefore experimental
techniques substitute open surgery with minimally invasive cement injection
to fixate the loosened prosthesis [de Poorter et al., 2008a, Raaijmaakers and
Mulier, 2010]. At the time of writing these procedures are annually only performed on a handful of patients, with a much larger potential target group
if proven successful. During minimally invasive refixation the surgeon is limited to working under fluoroscopic guidance and can only apply cement to
two or three injection sites. Proper pre-operative planning is therefore essential. Femoral strength and stability may be simulated using finite element
(FEM) modelling [Cody et al., 1999, Schileo et al., 2007] but requires threedimensional (3D) tissue segmentation for creation of patient-specific models.
CHAPTER 6
SEGMENTING
WITH
69
CUTS
Plain radiographs such as in Fig. 6.1(a) are the default imaging modality
for diagnosing osteolysis [Garcia-Cimbrelo et al., 2007]. While sufficient for
diagnosis, radiographs do not capture the 3D distribution of periprosthetic
tissues, where computed tomography (CT) remains the imaging modality of
GRAPH
Figure 6.1 a) Coronal X-ray radiograph of femur with osteolysis (arrows), b)

coronal CT slice of the same hip, c) manual segmentation showing periprosthetic
tissues. The boundary of the region of interest (ROI) is indicated by the dotted
line.
choice [Walde et al., 2005, Cahir et al., 2007]. Unfortunately, CT suffers from
image degradation in the vicinity of metal prostheses [Watzke and Kalender,
2004, Liu et al., 2009]. Image degradation makes the 3D classification of
periprosthetic tissues a difficult task especially for low-contrast tissues other
than cortical bone. Patients suffering from osteolysis generally have very low
bone quality, which exacerbates segmentation problems. In some cases cortical bone, normally thick and easy to discern, is reduced to a thin shell of its
former extent and may show regions of very low image intensity.
Manual segmentation of this kind of volume is difficult and too labour intensive for routine use. As an alternative, automatic or semiautomatic techniques
have been developed. To segment skeletal structures, [Zoroofi et al., 2003]
use histogram-based thresholding and binary morphological steps. [Kang
et al., 2003] use an automatic region-growing technique augmented by manual correction. [Yokota et al., 2009] segment the boundary of diseased hip
bones with a hybrid statistical shape model. Statistical models based on principal component analysis require well-defined natural shape and tissue distributions [Shlens, 2009] and are therefore, similar to atlas-based methods
[Sharma and Aggarwal, 2010], ill-suited to sporadic lesions and surgically
modified joints fitted with prostheses.
We set out to develop an automatic 3D CT segmentation pipeline that can segment all mechanically distinct tissues in hip CT volumes, including periprosthetic osteolytic lesions. The envisioned application was to assist with preoperative planning and the creation of patient-specific finite element models
to analyse prosthesis stability.
The main contributions of this work are the following:
We extend the prototype voxel classification scheme of [Malan et al.,
2010] while simultaneously reducing the feature set to an optimized
subset. Using this reduced feature set, we implement a k-centres + knearest neighbours voxel classifier.
We use s/t graph cuts [Boykov et al., 2001] to obtain a hard multilabel tissue segmentation from the probabilistic tissue map computed by
the aforementioned voxel classifier. To our knowledge this is the first
medical image segmentation application of multilabel graph cuts to the
output of a probabilistic voxel classifier.
Following the example of [Delong and Boykov, 2009], we incorporate
geometric containment constraints as part of the graph-cut segmenta70
tion. The novelty of our approach lies in our definition of the data
cost term which enables us to define per-node costs. This enables us to
use a publically available multilabel graph-cut software library [Veksler,
2010] for solving either the unconstrained or constrained case.
6.2
6.2.1

Imaging
We retrieved twelve anonymized clinical CT data sets from twelve patients

suffering aseptically loose femoral prostheses. All scans were made with
Toshiba Aquilion (Toshiba Medical Systems, Japan) scanners using the FC30
bone kernel. We retroactively obtained clinical data and therefore had to
accept inter-scan variation, most notably the tube current (150 mA to 400
mA), peak voltage (120 kV or 135 kV) and in-plane voxel spacing (0.44 mm
to 0.59 mm).
6.2.2
Manual segmentation
71
CUTS
We used the manually segmented CT image volumes to train voxel classifiers and secondly to serve as ground truth for evaluating the performance
of our automatic tissue segmentation. A rotating per-patient leave-one-out
GRAPH
Performance metrics
WITH
6.2.3
SEGMENTING
First, a region of interest (ROI) was delimited. The metal prosthesis was
removed by thresholding at 5000 Hounsfield Units (HU). The ROI was then
segmented into separate regions of cement, cortical bone, trabecular bone,
fibrous interface tissue, intramedullary canal, and exterior muscle tissue. Fig.
6.1(c) and Fig. 6.2(b) show examples of segmentations thus obtained. It
proved difficult to manually distinguish some regions in the low image quality
CT volumes. We left these regions unclassified to prevent false positives in the
classifier training sets. An example of a difficult to segment region is shown
in the upper part of Fig. 6.2(a). The manual segmentations correctness was
verified by an experienced orthopaedic surgeon (RN). Inter-observer tissue
segmentation was evaluated by having a second independent human operator
re-segment four randomly selected femurs.
CHAPTER 6
An experienced operator (DM) manually segmented each CT volume using

the Medical Imaging Interaction Toolkit (MITK) version 0.12.2 [Maleike et al.,
2009]. Segmentation was performed using free-hand drawing on intermittent
slices with intermediate contours completed by interpolation.
Figure 6.2 Cross-section through the proximal femur. a) Original CT, b) manually designated tissue regions. Black areas were left unassigned, c) classifier
probability map for trabecular bone. Each tissue class has such a map. d) Maximum posterior probability, e) segmentation by multi-label graph cut without
containment, f) segmentation by multilabel graph cut with containment.
scheme was used. Voxel classifier performance was evaluated by counting

the percentage of correctly classified voxels per tissue class, shown as a confusion matrix in Table 6.6. Similar to [van der Lijn et al., 2008] we evaluated
the final segmented volumes by their Dice similarity coefficients compared
to ground truth. The Dice coefficient is a value between 0 and 1, where 1.0
represents perfect agreement and 0.0 represents completely disjoint segmentations. The coefficient is defined as 2 (|A B|) / (|A| + |B|), where |A| denotes
the volume of region A and A B is the intersection of regions A and B [Zou
et al., 2004].
6.2.4
Computation of image features
To serve as input for voxel classification, thirteen candidate image feature

volumes, listed in Table 6.1, were computed from every original CT volume.
72
1
2
3
4
5
6
7
8
9
10
11
12
13
CT volume at original resolution (0.5 mm x 0.5 mm x 0.5 mm)

Metal artifact reduced (MAR) CT volume.
CT smoothed with = 0.5 mm isotropic Gaussian filter
Image Gradient magnitude of feature nr. 3
Distance (in mm) to the threshold-segmented prosthesis surface
Signed distance from prosthesis head, along prosthesis long axis
Signed distance from convex hull of the femurs cortical bone
Angle cosine to prosthesis neck in plane perpendicular to long axis
Signed radial gradient of MAR smoothed by = 0.5 mm
Table 6.1 The thirteen candidate image features.
73
CUTS
The next feature was the signed distance from the femurs outer surface. The
geometry of the femur is initially unknown to us. By thresholding the ROI
between 800 HU and 3000 HU and excluding all voxels within 3.5 mm of
GRAPH
The tenth feature consisted of the signed distance from the prosthesis heads
centroid, measured parallel to the femurs long axis. The prosthesiss long
axis was automatically computed as the first principal spatial component of
the prosthesis distal half. This direction closely corresponds to the alignment
of the femurs long axis.
WITH
The next feature consisted of the shortest Euclidian distance to the prosthesis surface. The prosthesis was automatically detected as the largest object
exceeding a threshold of 5000 HU. This value was appropriate for all cobaltchromium and steel prostheses.
SEGMENTING
Similar to previous studies [Loog and van Ginneken, 2006, Folkesson et al.,
2007, van Rikxoort et al., 2009] we used multiscale image and image gradient values as features. Isotropic Gaussian low-pass (blurring) with standard
deviations of 0.5 mm, 1 mm and 2 mm, along with their image gradient magnitudes, were computed from the original CT volume.
CHAPTER 6
We used the method of [Kalender et al., 1987], implemented in MATLAB

R2009b (Mathworks Inc., MA, USA), to compute the metal artefact reduced
(MAR) volume. All other image features were computed using proprietary
software developed in the DeVIDE Runtime Environment [Botha and Post,
2008].
metal components, we capture the majority of voxels representing cortical

bone. Recall that CT image slices are always approximately perpendicular to
the femurs long axis. While a human femur is not convex in three dimensions,
it is approximately convex in any cross-section perpendicular to its long axis.
For every image slice we therefore approximated the femurs outline by the
two-dimensional convex hull of the thresholded voxels.
The twelfth candidate feature was the cosine of the angle of each voxel relative to that of the femur head. This planar angle cosine was measured around
the central axis of the prosthesis stem.
The last candidate feature was the image gradient of the smoothed MAR image, using a 0.5 mm Gaussian kernel, computed in the radial direction perpendicular to the prosthesis long axis.
6.2.5
Classifier construction and feature selection
We constructed statistical classifiers using PRSD Studio (PR Sys Design, Delft,
The Netherlands) [PRS, 2012], a toolbox that offers implementations of various classification algorithms. Our training data consisted of all twelve manually segmented CT volumes, where individual image voxels were regarded as
separate objects. All classifiers were trained and evaluated using a rotating
per-patient leave-one-out scheme.
We defined six tissue classes: cortical bone, trabecular bone, bone cement,
fibrotic tissue, intramedullary canal, and tissue exterior to the femur. Equal
per-class priors were used to prevent infrequent but important tissues like
fibrotic zones being suppressed during optimization. Features were scaled to
have unit variance. Both forward and backward selection processes were then
used to determine an optimal subset of the thirteen candidate image features.
Each classifier computed a soft probabilistic classification, i.e. probabilities
of belonging to the six tissue classes instead of hard unambiguous labels.
Parametric classifiers that construct internal probability density functions directly output soft classifications. Others like the kNN classifier output featurespace distances that were subsequently converted to unit-sum probabilities by
using the normalized inverse of their class separation distances.
Classification performance was compared between the following classification algorithms available in PRSD Studio: linear, quadratic, Gaussian mixture model, kNN with k equal to 1, 3 and 10, a Parzen classifier, neural net,
naive Bayes and a decision tree. A k-centres algorithm was used as kNN preprocessing step. Each classifier was trained and tested identically.
74
6.2.6
Segmentation by maximum posterior probability
The most straightforward approach for converting the soft classifier output
to a hard segmentation was by independently assigning, for every voxel,
the class with highest posterior probability. An example of the classification
results obtained with this scheme is shown in Fig. 6.2(d).
6.2.7
Segmentation by graph cuts
Maximum posterior probability classification is prone to noise and irregular

segmentation geometry as seen in Fig. 6.2(d). To counter this we instead used
multilabel graph cuts to transform the soft classifier output into a multilabel
segmentation. For this we used and adapted the publically available gco-v3.0
multilabel graph-cut library [Veksler, 2010].
11 8
6
6
1
CUTS
75
GRAPH
A cut is minimal if its associated energy is smaller or equal to the energy of any
other cut of the same graph. This energy typically consists of two parts: a data
cost and a smoothness cost [Boykov and Kolmogorov, 2004]. The data cost
of each node is computed from the mismatch between its observed properties
and those of its assigned label. Following the example of [Boykov et al., 2001]
we defined each voxels data costs as the negative logarithm of its per-class
WITH
Figure 6.3 a) An example 2D graph cut. a 3 4 bitmap image. b) Graph with

two highlighted nodes to show data costs for being assigned either white or
black. Edge weights were chosen inversely proportional to image gradient. c)
A cut of the graph with resultant data cost for every node and the smoothness
cost for every severed edge.
SEGMENTING
CHAPTER 6
An image may be expressed as a graph by representing individual image pixels

or voxels as graph nodes and representing their neighbourhood relationships
with edges. Graph-cut algorithms, also known as minimum cut/maximum
flow algorithms, offer a computationally efficient way of minimizing certain
energy functions defined on a graph [Greig et al., 1989, Ahuja et al., 1993].
Fig. 6.3 shows how a 2D image may be segmented by a graph cut.
membership probability. The smoothness cost of each severed edge may be

defined inversely proportional to local image gradient.
0
1
CC
B
A
Figure 6.4 Left: a 2D image with three regions. Right: each pixel p is represented by a node pair x pA and x pB . Right: Edges are shown for a single nodes
edge pair. Smoothness costs are represented by undirected in-plane edges. The
A contains B relationship is enforced by an infinity-weight directed edge from
plane B to A. B sheathed in at least 1 pixel width of A is enforced by directed
edges to its 4-connected neighbourhood.
[Delong and Boykov, 2009] show how a directed binary graph with two nodes
for every image pixel may be constructed to enforce geometric containment,
attraction or exclusion. A 2D example of a containment enforcing graph is
shown in Fig. 6.4. Every image pixel is represented by two graph nodesthese
node pairs define two separate planes. Within each plane, every node is
connected to its neighbours using 4-connected undirected (or bidirectional)
edges. Directed edges link node pairs between the planes to enforce containment and attraction relationships.
x pA value
0
0
1
1
x pB value
0
1
0
1
Label of p defined by (x pA,x pB )

C
n/a
A
B
Data cost Dp
log(Pr(C))
K
log(Pr(A))
log(Pr(B))
Table 6.2 The pairwise data costs of the nodes in 6.4 as defined by [Delong
and Boykov, 2009].
The graph for a 3D voxel grid is analogous to the 2D model, the difference
being the replacement of the 4-connected pixel-node planes A and B with two
8-connected voxel-node grids. A binary cut on this graph assigns every node
76
Variable
x pA
x pA
x pB
x pB
Value
0
1
0
1
Data cost Dp
log(Pr(C)) + max A
log(Pr(A)) + max A
max A
log(Pr(A)) log(Pr(B)) + max A
Table 6.3 Our data costs depend only on each nodes own binary label.
a value of one or zero. The label of every pixel is defined by the assignment
of binary values to its corresponding node pair, as in Table 6.2.
The difference of our approach compared to that of Delong and Boykov is that
we assigned data costs to individual nodes in the graphdependent only on
the binary values which the nodes may individually assume, not on pairwise
labelling. The advantage of this is that it allows computation of the minimum
graph cut using standard graph-cut libraries such as gco-v3.0 [Veksler, 2010].
Segmentation by single multilabel graph cut on classifier output
CUTS
77
GRAPH
We started with smoothness costs similar to the Potts model of [Boykov et al.,
2001, Boykov and Kolmogorov, 2004], but with larger values assigned to tissues that are expected to be non-adjacent, such as between exterior muscle
tissue and either the intramedullary canal or fibrous interface tissue. These
costs, shown in Table 6.4, satisfy the definition of a metric as required for
convergence of the -expansion algorithm [Kolmogorov and Zabih, 2004],
that is, V (, ) V (, ) + V (, ) and V (, ) = 0 for all labels , , . The
costs of Table 6.4 were additionally scaled with a spatially varying term that
WITH
6.2.8
SEGMENTING
We defined max A = max ( log(A)), computed across all voxels. This constant
term prevents any individual data costs from being negativea requirement
of the gco-v3.0 library. The additional global data cost is therefore maxA times
the number of nodes, a known constant. Since the same labelling minimizes
all equivalent energy functions that differ by a constant, the solution is an
equivalent labelling.
CHAPTER 6
Starting with Table 6.2 we replaced the costs of pairwise node assignments
by the summed costs of each pairs two separate components, leading to Table 6.3. This new definition yields the same pairwise costs, up to a constant. For example: the data cost of assigning (0,0) to x pA and x pB becomes
[ log (Pr(C)) + max A] + [max A] = log (Pr(C)) + 2 max A.
depended on the image intensity gradient at each voxels location. This factor
was defined as Sd = exp(c Gd ), having a value of 1.0 in areas with zero gradient and exponentially decaying with increasing gradient. The subscript d
refers to the orthogonal direction, that is, x, y or z. Gd is the CT image
gradient magnitude in the given direction, expressed in HU/mm, and exp
refers to the exponential function. The parameter c is a scaling parameter
that we set to 0.008 to provide the desired falloff rate.
Outside
Canal
Fibrous
Trabecular
Cortical
Cement
Outside
0
-
Canal
2
0
-
Fibrous
2
1
0
-
Trabecular
2
2
1
0
-
Cortical
1
1
1
1
0
-
Cement
2
1
1
1
1
0
Table 6.4 Symmetric smoothness cost matrix used for the standard multi-label
-expansion graph cut algorithm.
6.2.9
Segmentation by stepwise multilabel graph cut with geometrical

containment
The gco-v3.0 library used for solving the unconstrained multilabel problem
does not support directed graphs or labels defined on pairs of nodes. Since
graph directionality is essential to the containment relationships in Fig. 6.4
and 5, we modified the code to enable edge directionality. The first modification consisted of allowing asymmetric neighbourhood relationships; that
is, node p being a neighbour of node q does not imply that node q must be
a neighbour of p. The second modification was for allowing the asymmetric smoothness costs of Table 6.5 that were subsequently scaled to also be
inversely proportional to image gradient as described in the previous section.
Value 0
Value 1
Value 0
0
0
Value 1
1
0
Table 6.5 Smoothness cost matrix used for the containment-enforcing twolayer binary-valued graph of 6.4.
Looking at Fig. 6.4 and Table 6.2 we see that the asymmetry of Table 6.5
78
ensures that the infinity cost of a containment-rule violation is correctly

enforced. Assigning (0,1) to the (x pA, x pB ) node pair is illegal and does not
correspond to any tissue label.
This transgression is prohibited by the smoothness cost of 1 multiplied by
the graphs infinity-weight edge, resulting in infinite cost. Conversely, the
(1,0) assignment corresponding to the label A is allowed. Multiplying the
zero smoothness cost and infinite edge weight yields zero cost. Spatially
neighbouring voxels are connected by bidirectional edges equivalent to the
undirected edges of Fig. 6.4. Here, label discontinuities are penalized as before, since exactly one of the bidirectional edges will cross a (0,1) transition.
SEGMENTING
WITH
GRAPH
Including multiple containment relationships in a single graph cut complicates graph construction and data cost terms. We instead opted for the data
cost structure of Table 6.3 that only allows three tissue zones at a time. We
desired two containment constraintsthe femur having an uninterrupted cortical shell and trabecular bone being enclosed in cortical bone. Each of these
constraints required a separate graph-cut step. The remaining tissues were
separated using a standard -expansion multilabel graph cut as described by
[Boykov et al., 2001].
CHAPTER 6
We used containment relationships to force the region defined by the union

of intramedullary canal, cement, fibrous interface tissue and trabecular bone
to be enclosed in a layer of cortical bone with a thickness of at least one voxel.
This was motivated by the fact that the whole femur is enclosed in cortical
bone, even though this layer can be very thin and difficult to discern in the
proximal femur. Likewise, we created a penalty term to discourage trabecular bone from not being enclosed in a layer of cortical bone of at least a
single-voxel thickness. An example of this is shown in Fig. 6.2(e) where an
unconstrained graph-cut solution allows holes in the encompassing cortical
bone. In Fig. 6.2(f) we see that the containment constraint enforces a continuous cortical sheath.
CUTS
79
Figure 6.5 A coronal slice showing the three-step segmentation process. Steps
1 and 2 enforce geometrical containment relationships.
The resulting three-step segmentation process is shown in Fig. 6.5.

1. The ROI is segmented into three classes: exterior, cortical, and interior
using a containment relationship that forces the interior to be enclosed
in a cortical shell of at least single-voxel thickness.
2. The interior and cortical regions are re-segmented into trabecular,
cortical and rest. A containment relationship similar to step 1 specifies
trabecular bone to be enclosed in cortical bone. The final cortical region
consists of the union of the cortical regions from steps 2 and 3.
3. Finally, the rest tissue from step 2 is segmented into cement, fibrous
and canal using a three-label -expansion graph cut without containment restriction.
6.3
6.3.1
Results
Feature and classifier selection
Using both forward and backward feature selection on disjoint training and
test sets, we identified an optimal subset of nine features. Removing any
80
of these or adding any of the remaining features increased the classification

error. Referring to Table 6.1, these nine features, ranked from most to least
important, were numbers 10, 11, 2, 4, 9, 13, 7, 1, 5. It is important to note
that these features were not necessarily the best individual discriminators,
but instead provided the best combined classification power when used as a
set.
Tissue
Fibrotic
Trabecular
Voxels correctly classied (%)
100
80
60
40
20
0
1
10
11
Number of CT training volumes
81
CUTS
In Table 6.6 we see that the classifier using the maximum probability criterion
managed to correctly classify the large majority of labelled voxels. The most
difficult tissues were fibrous interface tissue (66.7%) and trabecular bone
GRAPH
Tissue segmentation
WITH
6.3.2
SEGMENTING
Using these nine features, we evaluated different classifier algorithms. We

found the best overall classification performance using a kNN classifier with
k = 3, after pre-processing the input data with a k-centres algorithm with
k = 2000. We evaluated the classifiers learning curve as it was trained on
successively larger patient sets. Testing was performed in a per-patient leaveone-out manner. The results for the difficult-to-classify fibrous and trabecular
tissues are plotted in Fig. 6.6.
We see that classification performance tended to stabilize once a training set
size of at least five CT volumes was reached. Further increasing the number of
training sets did not significantly improve median classification performance
but did reduce the occurrence of negative outliers.
CHAPTER 6
Figure 6.6 Voxel classifier sensitivities for the two most difficult-to-classify
tissues versus number of CT training volumes.
(81.1%)both being low in CT image contrast and located close to the prosthesis in the zone most affected by metal artefacts. Graph-cut post-processing
improved classification performance relative to maximum posterior classificationmost notably for the fibrotic and trabecular tissue classes. Sensitivity
and specificity of the final constrained graph-cut segmentation are shown in
6.7.
Label
Method
Automatically segmented
Exterior Canal Fibr.
Trab.
Cort.
Cem.
2.18
2.09
0.52
0.59
4.45
5.14
2.71
3.86
86.79
86.40
5.19
4.41
0.47
0.70
0.96
0.55
3.83
3.43
1.20
0.22
5.79
3.27
84.74
86.64
Manual seg.
Exterior
Canal
Fibrotic
Trabecular
Cortical
Cement
MPP
CGC
MPP
CGC
MPP
CGC
MPP
CGC
MPP
CGC
MPP
CGC
85.71
89.47
0.00
0.00
2.04
0.11
5.72
2.76
0.96
4.08
0.42
0.03
0.00
0.00
97.46
98.50
0.51
0.22
0.00
0.00
0.96
0.71
1.24
1.29
2.18
1.53
0.31
0.00
66.67
73.04
8.18
8.28
3.90
3.43
5.80
5.33
8.65
4.76
0.00
0.00
11.70
3.49
81.08
82.90
2.92
3.90
1.17
0.42
Table 6.6 Confusion matrix showing median classification performance of our

kNN2k classifier when labelling each voxel with its maximum posterior probability (MPP, upper rows) and constrained graph cuts (CGC, lower rows). Bold
values on the main diagonal represent the sensitivities, i.e. the percentages of
each tissue type that was classified correctly.
In the example slice of Fig. 6.2 we see that the geometrically unconstrained
graph-cut procedure considerably smoothed the segmentation result, with
many of the isolated noisy misclassifications removed. The same general tissue distribution was maintained, including a gap in the outer shell of cortical
bone. With the constrained graph-cut approach we note that the gap in the
outer cortical shell has been closed, and the region of trabecular bone is fully
enclosed and shielded from fibrous tissue by a layer of cortical bone as was
required by our containment rule. We note from Fig. 6.7 that there is still
an obvious difference between our automated segmentation methods and a
82
second human segmenter but are encouraged by the overlapping Dice coefficients ranges.
Label
Exterior
Canal
Fibrotic
Trabecular
Cortical
Cement
Sensitivity (%)
89.47
95.50
73.04
82.90
86.40
86.64
Specificity (%)
98.60
99.56
96.29
97.49
96.78
98.37
Table 6.7 Sensitivity and specificity of the constrained graph-cut solution, computed from 6.6.
Method
max(p)
Graph Cut
Graph Cut + Containment
Inter-observer
1.0
0.6
CHAPTER 6
Dice coecient
0.8
0.4
0.2
Outside /
Exterior
Canal
Fibrotic
Trabecular
Cortical
Cement
Tissue
CUTS
83
GRAPH
Across all tissues we find that the graph-cut segmentations, both with and
without geometric constraints, have significantly higher Dice coefficients than
using maximum probability classification. This was confirmed using a Wilcoxon
signed rank test (p < 0.001 in both cases). Compared to the graph-cut
method without containment, however, geometric containment shows no statistically significant improvement in Dice coefficient (p = 0.466). Geometric containment had its greatest value in qualitative segmentation improvementfor example, the closing of holes in the cortical shell, as seen in Fig..
WITH
Figure 6.7 Comparison of manually segmented ground truth with maximum

posterior probability, graph cut and constrained graph cut. Inter-observer variability, computed with a second human segmenter, is also shown.
SEGMENTING
0.0
6.2. The lack of statistically significant improvement in Dice coefficient therefore tells only part of the tale.
6.3.3
Computational cost
For a typical CT volume of interest consisting of 200200300 voxels, the

total running time of our segmentation pipeline was approximately 15 min.
This time was recorded on a 3.0 GHz Intel Core-i7 desktop computer running
Microsoft Windows7 64-bit with 12 GB of working memory. Computation of
the nine image features took approximately 10 min. Subsequent soft classification by the trained voxel classifier took 3 min. The post-processing of
the classification output by the graph-cut algorithm took approximately 40 s
regardless of whether containment relationships were specified or not. Since
our algorithms currently rely on single-threaded operation, we envisage a
substantial possible speed increase should we modify our code to harness
processor cores simultaneously.
The most memory intensive operation was the graph-cut step where, in addition to MATLABs base footprint of 200 MB, a peak amount of 600 MB without
containment or 1,100 MB with containment was required.
We note that the execution time and memory requirements of feature generation, voxel classification and the graph-cut algorithm all show linear dependence on the number of classified voxels. This is in accordance with the
findings of [Delong and Boykov, 2009], and we experimentally affirmed it.
Discussion
We constructed and optimized a voxel classifier that uses a diverse set of automatically computable image features. The retention of several derived distance metrics in the optimal feature subset showed that image features other
than intensities and gradients are beneficial. This was emphasized by observing that the original CT volume ranked as only the eighth most important
feature.
The most straightforward way to convert statistical classifier output to a final
labelling is by assigning, for each voxel, the label with maximum posterior
probability. This classification method leads to noisy results with an excessive
number of label transitions. We know that biological tissues tend to form
contiguous regions. The maximum posterior probability classification does
not incorporate this prior knowledge.
We showed that the -expansion graph-cut algorithm of [Boykov et al., 2001]
can be applied to obtain an improved segmentation result. The required data
84
cost terms are easily computed from the voxel classifiers output probabilities, and the obtained results exhibit the contiguousness we expect. The
resulting segmentations are a qualitative and quantitative improvement over
standalone voxel classification.
Additional containment relationships, implemented as modifications to the
method of [Delong and Boykov, 2009], have their biggest effect on the segmentation of fibrotic tissue and trabecular bone. This desired result is as
expected, since we specifically enforce the containment of these two tissues
in a shell of cortical bone. The containment relationships simultaneously enable us to close unwanted holes in the segmentation of thin shell regions of
cortical bone.
CHAPTER 6
In Fig. 6.7, just as in Tables 6.6 and 6.7, we note that we had the least success
with the softer, irregularly shaped, low-contrast fibrous tissue and trabecular
bone. There is a notable outlier in each of the Canal, Trabecular and Cortical tissue classes, but given the small sample size and large inter-scan variation this not completely unexpected. Indeed the canal outlier occurred for
a data set where almost no intra-medullary canal was included in the defined
ROI, thereby leading to a negligibly small volume and low Dice coefficient between successive segmentations. The outliers for trabecular and cortical bone
both occurred for the same data set, which had an unusually small femur diameter. This highlights the importance of having a sufficiently large training
set to cover the expected inter-patient variationan assumption which failed
for this single data set.
SEGMENTING
Limitations to this study include the small number of CT volumes used for
training and evaluation. Fig. 6.6 suggests, however, that the twelve CT data
sets used in this study were sufficiently representative for the goals of this
paper.
GRAPH
85
CUTS
Since all automatic segmentation algorithms can occasionally fail, it will be

good to allow manual segmentation corrections in future work. This could
be approached similar to the method of [Egger et al., 2011]. As in previous
literature we used the Dice similarity coefficient to evaluate segmentation
accuracy. In future work it will be important to examine the relationship
WITH
In Fig. 6.7 we saw that human inter-observer variability has a similar order of magnitude, albeit smaller, than differences between automated and
human segmentation. Since we can only evaluate classifier performance relative to the manually segmented ground truth which is itself subject to error
and simplification, subtle improvements due to geometrical containment may
be obscured in our measurements.
between volumetric segmentation accuracy and derived modelling accuracy,

such as when using finite elements.
A further limitation of this study is that all CT image volumes were obtained
from the same make of scanner and from the same hospital. By pooling the
available data sets we obtained a collection of image volumes containing real
clinical data with heterogeneous scan parameters. We foresee the presented
algorithm to work similarly well on data from other centres but did not have
the opportunity to verify this claim.
Despite CTs proven diagnostic superiority over standard radiographs [Cahir
et al., 2007, Schwarz et al., 2003], it is still not routinely performed on patients suffering osteolysis and therefore limited our access to clinical data.
Traditional open revision surgery is performed under visual guidance and
therefore does not require accurate 3D-image-based tissue segmentation. However, we foresee this situation changing. Minimally invasive refixation is already performed as an alternative to refixation in frail patients [de Poorter
et al., 2008a, Raaijmaakers and Mulier, 2010], and here, the surgeon is much
more dependent on image-based pre-operative planning.
Finite element modelling is a powerful tool for computing mechanical stability of the femur [Cody et al., 1999, Schileo et al., 2007] but requires 3D
tissue distribution models. These advances may lead to validation and wider
application of minimally invasive cement injection. This will, in turn, fuel the
demand for automated segmentation techniques such as the one described in
this paper.
6.4
Conclusion
We presented a complete pipeline for segmenting periprosthetic tissues in

clinical CT volumes of patients with hip prostheses. Due to low tissue contrast and the presence of beam hardening artefacts, these image volumes are
extremely difficult to segmenteven manually by a trained human operator.
We applied our algorithm to tissues that pertain to aseptically loose hip prostheses, namely cortical bone, trabecular bone, fibrous interface tissue, bone
cement, intramedullary canal, and tissue exterior to the femur. Voxel classification offers a way of combining the strengths of several complementary
image features, including metal artefact reduced image data that involve data
loss if used on its own [Malan et al., 2012b]. We showed how tissue classifiers
results may be improved by coupling them with a graph-cut post-processing
step. We further showed how an adaptation to the algorithm of [Delong and
Boykov, 2009] can be used to incorporate geometrical assumptions into the
86
graph-cut segmentation process. Using this, we enforced the requirement

that the femur be enclosed in a layer of cortical bone and trabecular bone to
be sheathed in cortical bone. Compared to before, these restrictions helped
to close segmentation holes caused by low contrast and partial volume effects
in the input CT data.
To our knowledge, in the field of medical image segmentation, this is the
first use of graph cuts on voxel classifier output since the pioneering work of
[van der Lijn et al., 2008]. In contrast to their study we extend our solution to
a multilabel, as opposed to binary, problem. Not only are the graph-cut solutions qualitatively better than voxel classification on its own, but we show that
they quantitatively better represent the manually segmented ground truth in
terms of their Dice coefficients, our measure for geometric similarity.
The pipeline described in this paper represents a practical approach to segmenting multitissue regions from CT. The demonstrated approach to containment relationships improves the solution wherever such a priori knowledge
is available. We demonstrated our solution using clinical CT images of tissues surrounding metal hip prostheses suffering from low contrast and beam
hardening artefacts.
Acknowledgments
SEGMENTING
WITH
GRAPH
This research is supported by the Dutch Technology Foundation STW, which

is the applied science division of NWO, and the Technology Programme of
the Ministry of Economic Affairs (project number LKG 7943). The authors
sincerely thank Professor Rob Nelissen for verifying the correctness of the
manually segmented ground truth and Noeska Smit for the re-segmentation
of several of the data sets for evaluating inter-observer variability. We furthermore thank David Tax and Marco Loog from the pattern recognition group at
Delft University of Technology for their helpful input.
CHAPTER 6
Our proposed solution succeeds for this specific application and may in future
also be applied to other anatomical regions and imaging environments that
are subject to similar constraints.
CUTS
87
7
Sparse particle-based
multi-material volume meshing
for conformal 3D meshes
CHAPTER 7
SPARSE
Daniel F. Malan, Christian Kehl,

Elmar Eisemann, Edward R. Valstar
MESHING
89
Abstract
We present a conformal volume mesher that creates tetrahedral meshes from
a multi-material image volume. The raison dtre for our mesher is the importance yet difficulty of creating suitable volume meshes in applications such
as three dimensional biomechanical finite-element analysis. The input to our
method is a segmented multi-material image volume defined on a regular
grid such as those generated by Computed Tomography or Magnetic Resonance Imaging. The first step converts the volume to a set of dense topologypreserving surface meshes. During intermediate steps seed particles are defined and optimized so that they will ultimately serve as vertices of the output
mesh. The final density of these optimized seed particles can be controlled
by the user. The optimized seed particles are inserted as vertices into the
dense surface meshes and all other mesh vertices are iteratively removed,
until only the seed particles vertices remain. Our output mesh uses fewer
elements and/or obtains lower geometric approximation errors than comparable Delaunay-triangulation-based methods, as those methods need to rely
on additional and restrictive sampling criteria
7.1
Introduction
Finite element simulation is useful in many medical contexts, including orthopaedics [Bessho et al., 2009, Reggiani et al., 2007, Schileo et al., 2007,
Taddei et al., 2006], oncology [Samani et al., 2001], cardiology [Sankaran
et al., 2012] and neurology [Joldes et al., 2010]. Often, the meshes underlying these simulations are derived from segmented image volumes. In many
cases, multi-material data is involved, which can describe distinct material
regions, e.g., a metal hip prosthesis surrounded by cement embedded in the
femur, the latter of which consists of both dense cortical and porous trabecular bone [Andreykiv et al., 2012]. For such cases, multiple sub-meshes need
to be derived. These sub-meshes are often connected and interact with each
other via shared boundaries. For a faithful simulation of interaction across
boundaries, the derived sub-meshes should be conformal to each other, i.e.,
mesh vertices and edges on shared interface boundaries must coincide.
In addition to mesh conformity, geometric mesh quality plays an important
role in finite element simulations. The number of mesh elements, the geometric accuracy of the mesh, as well as the aspect ratios of individual mesh
elements influence performance and accuracy of simulations that build upon
them [Babuska and Aziz, 1976, Burkhart et al., 2013].
90
Figure 7.1 Mesh conformity means that all vertices and all edges on the shared
boundary are identically defined: three of the conforming pairs of triangles are
highlighted.
91
MESHING
Our solution endeavours to provide a volumetric mesh with low geometric approximation error while offering direct user control over the number of mesh
elements. Further, the definition of the resulting meshes surface vertices by
a unique set of optimized particles ensures that shared boundaries are kept
conformal.
SPARSE
Fig. 7.1 shows the meaning of mesh conformity using two partial spheres that
touch in a shared plane. This figure emulates Fig.7 in [Meyer et al., 2008],
with the notable difference that it shows output of CVMesh after using a segmented voxel grid with two distinct foreground labels, while Fig.7 in [Meyer
et al., 2008] used synthetically constructed regular isosurfaces as input.
CHAPTER 7
In this paper, we propose the Conformal Volume Mesher (CVMesh) a novel

meshing algorithm that constructs tetrahedral meshes from multi-material
image volumes. It starts by transforming a multi-material segmented image
volume into a set of dense initial meshes. Seed particles are then distributed
and their positions optimized on the isosurfaces corresponding to these dense
meshes using the method of [Meyer et al., 2007, Meyer et al., 2008]. Once
optimized, the particles are integrated as vertices into the dense mesh. Afterwards, all original mesh vertices are iteratively removed, keeping only the
newly-added vertices. Using this method, a set of water-tight closed surface
meshes is maintained for each material in every intermediate step.
7.2
Related Work
The problem of generating a volumetric tetrahedral mesh can be reduced to

the problem of generating a closed triangle surface mesh, since the latter may
be reliably converted into the former by adding interior nodes only. This step
does not modify the surface triangles in any way [George et al., 1991].
Several established approaches exist to generate triangular surface meshes
from a single material (i.e. binary) image volume. Marching Cubes (MC)
[Lorensen and Cline, 1987] is one of the most well-known and widely-used
algorithms, as it can quickly generate topologically correct, closed surfaces.
Care must however be taken in choosing a reliable MC implementation to
avoid the possibility of topological artefacts [Etiene et al., 2012]. The main
limitation of MC is its uniformly high triangle density that directly corresponds to the input image voxel resolution. When applied to a high resolution voxel grid such as those generated by Computed Tomography (CT) or
Magnetic Resonance Imaging (MRI), the resulting surface meshes must typically be decimated to obtain a tractable number of elements [Garland and
Heckbert, 1997, Knapp, 2002].
A multi-material extension of MC exists [Wu and Sullivan, 2003], but as
holds for the original MC algorithm, it produces high triangle counts. These
dense multi-material meshes are conformal, but standard decimation techniques cannot be directly applied as these operate on each sub-mesh individually and do not guarantee conformity across multi-material interfaces.
Native multi-material meshing algorithms based on adaptive decimation exist [Wang, 2007, Kahnt et al., 2011, Young et al., 2008] and form the basis
of commercial meshing software such as Simpleware +FE, Visage Amira and
Materialise Mimics [Sim, 2013, Ami, 2013, Mat, 2013].
As an alternative to decimating dense precursor meshes, other meshing algorithms rely on direct Delaunay triangulation for multi-material mesh generation [Boltcheva et al., 2009, Kahnt et al., 2011]. These algorithms first compute the desired vertex distribution and then reconstruct the triangulated surface from the vertices. For non-degenerate vertex distributions the Delaunay
triangulation is unique, ensuring conformity of vertices and edges on multimaterial interfaces. To ensure topologically-correct surfaces, an "-sampling
requirement needs to be satisfied. This requirement states that the maximum
Euclidean distance between mesh vertices, expressed as a fraction " of the
local feature size (LFS), should not exceed a certain value [Boissonnat and
Oudot, 2005]. The value of " = 0.06 has theoretically been proven to be
sufficient for 3D applications [Amenta and Bern, 1998], while experiments
92
suggest that " = 0.5 may be a more realistic loose upper bound for practical
applications [Meyer et al., 2007].
[Meyer et al., 2007] used a particle optimization algorithm to distribute mesh
vertices and have developed their algorithm to enable meshing of multiple
materials [Meyer et al., 2008]. The advantage that particle based methods
have over direct mesh refinement is that it abstracts the shape that need to
be meshed as an implicit surface, which allows for scale invariance. Particles
are optimized independent of the underlying image grid in accordance to an
energy function. The final particle distribution corresponds to the vertices of
the output mesh, which are Delaunay-triangulated to generate the algorithms
output. One advantage of their approach is the slowly varying vertex spacing
that is obtained, which results in good triangle aspect ratios. Their particle
distribution depends on the meshed objects level-set representation and is
largely independent of the underlying image resolution.
Our algorithm follows the general approach of [Meyer et al., 2008], but introduces a modification in the way that the triangle mesh is generated from
the optimized particle cloud. This modification allows us to obtain sparser
meshes for a given minimum feature size. Not being forced to increase the
minimum feature size as a strict function of particle spacing allows lower geometrical errors, lower mesh element counts, or sometimes both.
Our algorithm starts with a multi-material segmented image volume defined
93
MESHING
Algorithm
SPARSE
7.3
CHAPTER 7
Meyer et al.s algorithm has been integrated into the BioMesh3D [Callahan
et al., 2007] package, which is distributed as part of the open-source SciRun
software package [Bitter et al., 2007]. While it offers user control over geometric smoothing and triangle count, the "-sampling requirement remains
mandatory just as for all Delaunay triangulation schemes. This requirement
leads to a trade-off between the minimum triangle density and the minimum
allowable amount of geometric smoothing. We found that surface details are
quickly smoothed away and simultaneously the triangle count can remain
high, even when using the maximum allowable value of " = 0.5. Our findings
in this regard are supported by the literature [Fayolle and Pasko, 2012]. The
approach we propose is not restricted by the strict "-sampling requirement
inherent to Delaunay triangulation schemes, which enables our algorithm to
better conserve sharp features. This is possible as violating the "-sampling
requirement allows a more liberal redistribution of vertices with the goal of
reducing surface approximation errors.
Figure 7.2 Transformation of a dense input mesh to a topologically identical

sparse output mesh by the sequence of a) augmentation, b) decimation and c)
edge flipping.
in a regular voxel grid, i.e. each and every voxel has been assigned one and
only one categorical label. The number of possible labels has to be at least
two a binary segmentation consisting of foreground and background but
otherwise may be any integer.
Using the same approach of [Meyer et al., 2008], each material label is converted to a grayscale volume whose zero level-set isosurface corresponds to
the materials boundary. Each materials level-set surface is then smoothed to
remove unwanted noise or spurious details.
The smoothed level-set isosurfaces are used to compute each materials medial axis [Hesselink and Roerdink, 2008]. These medial axes, together with
user-definable parameters " and are used to construct a sizing field for each
material label we refer the reader to [Meyer et al., 2007] for details on its
definition. In our algorithm the value of " does not need to satisfy the Delaunay "-sampling requirement [Amenta and Bern, 1998] that would otherwise
have been applicable, and may therefore be chosen to exceed a value of 0.5.
The smoothed level-set isosurfaces serve additional purposes - firstly they are
each converted to a dense watertight surface mesh via MC. These meshes
have topological and geometrical precision, but also a very high number of
triangles that make them unsuitable for direct finite element simulation. The
final surface meshes that our algorithm will construct will be a refinement
of these meshes, but with a different, sparser, distribution of vertices. The
distribution of this final set of vertices is determined by the output of an iterative particle optimization process, where each particle represents a mesh
vertex. These particles originate from a collection of seed particles that are
initially uniformly and densely distributed on the smoothed level-set isosurfaces. Where material labels share a boundary, these seed particles are shared
94
by assigning them to both surfaces simultaneously. Hereby, no vertex duplication or discrepancies occur, which is important to achieve conformity. The
particle positions are optimized in an iterative process where they are treated
as particles in a mechanical system that have repulsive and attractive forces
relative to each other. Particles do not occupy discrete grid positions; each is
free to move on the level-set isosurface boundary to which is was assigned.
As optimization progresses particles are removed where their density exceeds
the requirements set by the sizing field, resulting in a particle count that is
typically much lower than the initial number of seed particles.
Once the particle distribution has been optimized, we use these to define the
output mesh in a three-step approach to derive watertight meshes that are
then converted to tetrahedral meshes.
First, all particle-vertices are iteratively inserted as vertices into the dense
MC-generated isosurface meshes, i.e. every particle is inserted as a vertex into
every material boundary mesh on which it is located. In the second phase only
the newly-added vertices are kept, while all others are iteratively removed.
This process is illustrated in Fig. 7.2. For conformity, not only vertices, but
also edges need to coincide. Edge conformity is enforced by a final series of
edge flips in the constructed meshes.
SPARSE
MESHING
95
CHAPTER 7
The topology of the output mesh is not deduced from the vertex distribution
but is determined by the dense MC-generated mesh. An important feature of
our algorithm is that each vertex insertion or deletion step maintains watertightness and topological correctness of all the meshes that are involved. This
fact is crucial, as it allows us to define the final meshs vertices by a vertex-set
that does not respect the "-sampling requirement. No explicit constraint is
placed on the edges that are created each time a vertex is inserted or when a
vertex is removed. This freedom allows our algorithm to choose local triangulations that maintain healthy aspect ratios for the newly created triangles,
while minimizing the geometric Hausdorff distance to the original dense MC
surface mesh.
Algorithm 7.3.1: CVMESH(LabelVolume I, r, ", )

for each mat er ial i I
i level-set isosurface of i
i smoothed i
do Ti dense triangle surface mesh of i
mi medial axis of i
si sizing field as a function of mi , " and
s Pseed Uniformly distribute seed particles on

for all ,
s
Popt Optimize distribution of Pseed using ,
for each mat
er ial i I
for each par t icle p Popt
if p belongs to i
do Ti0
do
then insert p into mesh Ti as vertex
for each augmented
boundary mesh Ti0
for each ver t ex v Ti0
if v
/P
do Ti00
do
then remove vertex from Ti0
Flip edges to ensure edge conformity between meshes
7.4
Implementation
CVMesh is implemented as a collection of modules that run in the open-source

DeVIDE Runtime Environment [Botha and Post, 2008]. Individual components use a combination of Python and C++, with extensive use of the Visualization Toolkit (VTK) [Schroeder et al., 1996], Teem [Tee, 2013] and Vispack
[Ross T. Whitaker, 2013] libraries. The final conversion step from a mesh to
a tetrahedral volume is performed using Tetgen [Si, 2006].
The initial input surfaces for each material label are smoothed using the Tightening algorithm of [Williams and Rossignac, 2007]. Dense isosurface meshes
are computed using VTKs Marching Cubes algorithm. Computation of the
3D medial axis is a computationally hard problem [Coeurjolly et al., 2008]
and can take up an inordinate amount of time to compute. For this we used
the Integer Medial Axis (IMA) algorithm of [Hesselink and Roerdink, 2008]
that computes a discrete approximation of the medial axis in linear runtime,
greatly speeding up the algorithm compared to the brute force sampling approach used by BioMesh3D. To prevent possible artefacts in the output IMA,
arising from its discrete nature, we explicitly bound the feature size from be96
low by a specified minimum radius of curvature (in practice 0.8 times the
voxel size).
The particle positions are optimized using an adapted version of the particlesystem-mm module [Par, 2014] also used in BioMesh3D. They are then iteratively inserted as vertices into the dense mesh after which all other vertices
are iteratively removed. Every vertex that is removed creates a hole, which is
immediately closed using a local triangulation scheme, analogous to that of
Knapp [Knapp, 2002].
We attempt to avoid the creation of an advancing border separating dense
and sparse mesh regions, as such a transition zone that combines short and
long edge lengths easily leads to triangles with unfavourable aspect ratios.
To that end, vertices are added and removed by placing them in a processing
queue with random ordering. At each insertion or deletion we first check
for the creation of an undesirable crease or self-intersection, and where this
occurs we move the problematic vertex to the back of the processing queue.
This process continues until all vertices have been processed.
7.5
Bunny (binary image volume)
97
MESHING
The first example we present is a 173 x 173 x 181 isotropic voxel volume
image obtained by manual segmentation of the Stanford bunny CT dataset
[Levoy, 2008]. It is a genus 0 object with two materials (foreground and
background). This binary example illustrates differences between our algorithm and that of [Meyer et al., 2007], as implemented in BioMesh3D. In
Table 7.1, we show numerical results for Figs. 7.4 and 7.6 that illustrate the
advantage of being able to raise " above 0.5. For " = 1.0 we achieve a lower
element count as well as a lower geometrical error. The former is due to the
sparser vertex sampling, while the latter is achieved by not having to use the
unique Delaunay triangulation instead having been chosen more freely to
minimize geometrical error.
SPARSE
7.5.1
Results
CHAPTER 7
Conformal edge connectivity across material transitions is enforced by a series of edge flip passes. Each pass ensures that a given pair of meshes have
conforming edges on their shared boundary. For each of these passes, one of
the material labels is chosen as master, and the other as slave. All co-located
vertices on the slave mesh are forced to have an identical edge connectivity as
the master mesh. Going through all mesh interactions systematically, at most
(m2 m)/2 edge flip passes are needed, where m is the number of materials.
(a)
(b)
Figure 7.3 The Marching Cubes surface of a) the original segmented volume
and b) the smoothed level-set isosurface.
98
In Fig. 7.3a we see the Marching-Cubes isosurface of the Stanford Bunny obtained directly from the CT image volume. Stair-stepping artefacts, a result
of the binary segmentation on the isotropic voxel grid, are clearly visible. In
Fig. 7.3b, the isosurface is shown after smoothing by limiting the isosurfaces
radius of curvature to r = 0.8 using the tightening algorithm [Williams and
Rossignac, 2007].
In Fig. 7.4a, we see the dense Delaunay-meshed surface that results from
the particle distribution using " = 0.5 applied to the curvature-limited isosurface of Fig. 7.3b. Areas of high curvature require a very high number of
particles, yielding a mesh with a very high element count. Starting with the
original isosurface of Fig. 7.3b and, instead using CVMeshs iterative vertex
insertion technique, we are able to safely increase " without smoothing the
model. In Fig. 7.4b we show the result using " = 1.0, leading to fewer unnecessary vertices on fine features. The overall distribution becomes sparser
and more uniform, while simultaneously even lowering the geometric error
as measured by the Hausdorff distance.
Tooth dataset (multiple materials)
The multi-material 103 x 94 x 161 isotropic human CT Tooth dataset was

cropped from the dataset used in the IEEE Transfer Function Bake-Off [Pfister
et al., 2001] and is also freely distributed with BioMesh3D [Bio, 2015]. The
dataset consists of four materials: air, dentine, enamel, and root. The results
for this dataset are summarized in Table 7.2.
In Fig. 7.7a, we see a sparse vertex distribution (2002, 2686 and 384 particles for the enamel, dentine and root respectively) superimposed on the highresolution isosurfaces meshes of the three material labels. For this example,
99
MESHING
7.5.2
SPARSE
CVMesh can dramatically reduce the number of mesh elements without causing invalid mesh topology. In Fig. 7.6a, the identical vertex distribution
that leads to an inconsistent mesh using BioMesh3D is used to achieve a
topologically-correct output.
CHAPTER 7
In BioMesh3D, adhering to the "-sampling of 0.5, we have to increase the

radius of curvature in order to reduce the element count, but this leads to a
severe detail loss. At the same time, the tightening operation cannot lower
the curvature in thin regions such as the bunnys ears, maintaining a locally
dense vertex distribution. In Fig. 7.5a the radius was increased to r = 15
while " remained unchanged at 0.5. Increasing " leads to fewer elements, but
also disrespects the "-sampling requirement, potentially leading to incorrect
topology. Fig. 7.5b shows such topological errors at the bunnys ears.
(a)
(b)
Figure 7.4 a) Particle distribution for " = 0.5. This value of " is considered
a loose upper bound for safe Delaunay meshing [Meyer et al., 2007]. b) Using
CVMesh we can safely use a particle distribution of " = 1.0.
100
(a)
CHAPTER 7
SPARSE
MESHING
(b)
Figure 7.5 Reducing vertex count by a) increasing the radius of curvature leads
to severe detail loss, while b) only increasing " preserves more detail, but when
Delaunay triangulation is used leads to degenerate mesh reconstruction in thin
regions.
101
(a)
(b)
Figure 7.6 a) Topologically correct surface mesh generated using CVMeshs

iterative refinement, using the same vertex distribution of Fig. 7.5b. b) Cut view
of the tetrahedra-filled mesh.
102
CHAPTER 7
(b)
103
MESHING
Figure 7.7 For the Tooth dataset we see a) If the "-sampling requirement
is not met, Delaunay triangulation creates an invalid triangulation, especially
visible in the interior. b) CVMesh creates a topologically correct multi-material
mesh with identical vertices as in a.
SPARSE
(a)
# Surface mesh vertices

# Surface triangles
# Tetrahedra
Hausdorff distance
Mean Hausdorff dist.
Triangle quality: mean
Triangle quality: stddev.
Tetrahedron quality: mean
Tetrahedron quality: stddev.
r = 0.8
" = 0.5
(Delaunay)
25,109
50,258
202,219
0.896
0.104
0.79
0.21
0.64
0.19
r = 0.8
" = 1.0
(CVMesh)
15,361
30,718
177,552
0.874
0.0938
0.7
0.26
0.66
0.22
r = 0.8
" = 5.0
(CVMesh)
558
1,170
43,596
3.75
0.496
0.78
0.22
0.73
0.18
Table 7.1 Mesh metrics for the Bunny dataset.
traditional decimation techniques cannot be used, as per-material decimation breaks conformity on multi-material interfaces. Fig. 7.7b illustrates the
topologically-incorrect surface mesh obtained via BioMesh3D in combination
with the sparse vertex distribution. Especially, the tooths inner root structure
is affected and incorrectly split into two sub-volumes. This is not unexpected,
as the used sampling of " = 3.0 is almost guaranteed to be unsuitable for a
Delaunay surface reconstruction. In Fig. 7.7c, we see that CVMesh preserves
the correct topology and better approximates the models thin extremities.
7.5.3
Femur dataset (multiple materials, anisotropic scan)
The Femur dataset was obtained for manually segmenting a clinical CT volume comprising 250 x 250 x 500 anisotropic image voxels. The dataset The
voxel spacing was 0.4mm 0.5mm 0.8mm. As such it was the highest resolution dataset we examined and also had the highest number of materials
six. In addition to the background these six materials (prosthesis, cement,
intramedullary canal, trabecular bone, cortical bone and fibrous tissue) were
segmented and featured extensive contact areas. Results for this mesh are
shown in Fig. 7.8 and Table 7.2.
7.6
Discussion
In summary, CVMesh uses the original mesh to track topology, which enables
more aggressive particle-based sampling strategies than in reconstruction by
104
Figure 7.8 The output obtained for the femur data-set, cut along a plane to
show the interior tetrahedra and six distinct material regions.
Femur dataset
r = 0.8
" = 4.0
(CVMesh)
7
5,965,683
0.5 0.4 0.8mm
21,393
45,694
182,493
3.81
0.085
0.71
0.65
CHAPTER 7
SPARSE
MESHING
# Materials
# Segmented image voxels
Voxel spacing
# Surface mesh vertices
# Surface triangles
# Tetrahedra
Hausdorff distance
Mean Hausdorff dist.
Triangle quality: mean
Tetrahedron quality: mean
Tooth dataset
r = 0.8
" = 3.0
(CVMesh)
4
410,826
1 1 1
3,981
10,124
65,442
1.83
0.117
0.83
0.72
Table 7.2 Mesh metrics for the Tooth and Femur datasets.
105
Bunny
Tooth
Femur
# Segmented voxels
Smoothing (tightening)
Medial Axis
Sizing Field
Particle optimization
Vertex insertion
Vertex decimation
Edge flipping
758,706
41 sec
18 sec
105 sec
840 sec
4.8 sec
87.7 sec
2.2 sec
410,826
77 sec
13 sec
35 sec
2220 sec
31 sec
184 sec
9.7 sec
5,965,683
7 min
72 min
21 min
483 min
16 min
38 min
3 min
Total time (CVMesh)
18 min
43 min
640 min
Table 7.3 Unoptimized execution times for the Bunny, Tooth and Femur
datasets.
Delaunay triangulation. The upshot of the additional freedom in vertex placement is the ability to achieve better geometric approximations with fewer
mesh elements.
Specifically, we demonstrate that CVMesh can be used successfully with high
values of " that violate the "-sampling requirement described by [Amenta
and Bern, 1998] and [Meyer et al., 2007]. The upshot of this freedom is that
coarser meshes can be used to achieve a given level of geometric accuracy.
CVMesh maintains mesh topology at the end of each vertex addition or vertex removal. Removing a vertex temporarily causes a hole which needs to be
closed so that topology is maintained. The mesh patch that is removed along
with a vertex consisting of all triangles connected to the vertex must be
manifold and the resulting hole must also be closeable using another manifold patch, without intersection of any mesh triangles. These assumptions
automatically holds when the "-sampling requirement is respected and generally also holds beyond this limit as shown in the examples of this paper, e.g.
at least up to " = 5.0. As we cannot rely on a theoretical proof of this observation, our re-meshing steps are algorithmically checked for intersections at
every mesh modification step.
In its current form, the transformation of a mesh from a the dense MC isosurface to the final particle-defined mesh, as described in Algorithm 7.3.1, is an
iterative process that is performed for each material sequentially. This process allows for reordering of vertex operations and closes the holes created by
vertex removal so as to minimize geometrical error. The lack of synchroniza106
CHAPTER 7
SPARSE
tion between the processing of the meshes belonging to different materials

mean that adjacent edges are initially not identically defined even though the
vertices are. These edge mismatches are solved in the algorithms final edge
flipping step but the algorithm may in future be improved by processing all
material meshes in parallel instead of sequentially.
Our algorithm has an inherent limitation in that extremely sparse sampling
of a thin curved volume can lead to unavoidable self-intersections as shown
in Fig. 7.9. To avoid, or at least detect this we heuristically check for selfintersections during iterative mesh decimation. For the meshing examples in
this paper we did not encounter this issue.
In its current implementation CVMesh is still slow for large datasets, as shown
in Table 7.3 that shows the runtimes of our experiments on an Intel i7 950
desktop PC running at 3.07 GHz. The algorithm has not been particularly optimized, and especially the vertex insertion, vertex removal and edge flipping
steps have been implemented as unoptimized single-threaded Python code.
In CVMesh the theoretically challenging task of medial axis computation represents a small fraction of the total algorithm time due to our selection of the
efficient IMA algorithm. The majority of CVMeshs run-time is spent on optimizing particle positions, which is an obvious target for future optimization
such as massive parallelization on a GPU [Kim et al., 2012].
The minimum number of vertices that is needed to represent any single, connected, genus-0 object is four, in which case the resultant mesh region will
be a single tetrahedron. This limitation is relevant whenever a materials segmented label field contains one or more tiny, disconnected, islands that may
be insufficiently sampled. To solve this we pre-filter the segmented image to
remove small islands, or disallowing particles that insufficiently sample small
isolated isosurface islands can prevent this situation from occurring.
MESHING
Figure 7.9 Cross-section illustration of self-intersection that may be caused by

an extremely sparse, degenerate, vertex distribution.
The degenerate vertex distribution show in Fig. 7.9 invariably leads to an

unacceptable result. As opposed to this inherently degenerate case, tran107
sient self-intersections at intermediate mesh refinement steps may be allowed.

However we did not allow this in our implementation, as it is difficult to foresee whether self-intersection during an intermediate step will eventually be
resolved by additional decimation. Our algorithm therefore permutes the
order of vertex processing whenever an operation would have led to selfintersection. If this process fails, the meshing algorithm terminates with the
warning that a degenerate vertex distribution was detected a solution to
which would be to specify a smaller value to " or a larger radius of curvature.
This situation was not observed in our experiments.
7.7
Conclusion
We presented a viable approach to multi-material conformal tetrahedral meshing that does not use Delaunay triangulation.
The final density of these optimized seed particles can be controlled by the
user, and need not adhere to the Delaunay "-sampling constraint for the algorithm to succeed. This freedom enables the output mesh to have fewer elements and/or lower geometric approximation errors than comparable Delaunaytriangulation-based methods.
The output of our algorithm is intended to be suitable for finite-element analysis, which is important for applications such as biomechanical simulations.
In the examples shown in this paper we were able to generate tetrahedral
meshes with a tractable number of mesh elements, while these elements were
also well behaved in terms of their aspect ratios and geometric error as measured by their Hausdorff distances relative to the input label field.
Acknowledgements
We would like to thank Charp P. Botha for his contributions to the supervision
of this project, as well as Peter Schaafsma who contributed a vital idea to our
solution.
108
8
A fluoroscopy-based planning and
guidance software tool for
minimally invasive hip refixation
by cement injection
GUIDANCE
109
FLUOROSCOPY-BASED
Adapted from:
International Journal of Computer Assisted Radiology and Surgery,
First Online, August 2015.
doi: 10.1007/s11548-015-1252-8
CHAPTER 8
Daniel F. Malan, Stfan J. van der Walt,

Renata G. Raidou, Bas van den Berg, Berend C. Stoel,
Charl P. Botha, Rob G.H.H. Nelissen, Edward R. Valstar
Abstract
Purpose
In orthopaedics, minimally invasive injection of bone cement is an established
technique. We present HipRFX, a software tool for planning and guiding a
cement injection procedure for stabilizing a loosening hip prosthesis. HipRFX
works by analysing a pre-operative CT and intraoperative C-arm fluoroscopic
images.
Methods
HipRFX simulates the intraoperative fluoroscopic views that a surgeon would
see on a display panel. Structures are rendered by modelling their X-ray attenuation. These are then compared to actual fluoroscopic images which allows
cement volumes to be estimated. Five human cadaver legs were used to validate the software in conjunction with real percutaneous cement injection into
artificially created peri-prosthetic lesions.
Results
Based on intraoperatively obtained fluoroscopic images, our software was
able to estimate the cement volume that reached the pre-operatively planned
targets. The actual median target lesion volume was 3.58 ml (range 3.17 to
4.64 ml). The median error in computed cement filling, as a percentage of
target volume, was 5.3% (range 2.2%-14.8%). Cement filling was between
17.6% and 55.4% (median 51.8%).
Conclusions
As a proof-of-concept, HipRFX was capable of simulating intraoperative fluoroscopic C-arm images. Furthermore, it provided estimates of the fraction of
injected cement deposited at its intended target location, as opposed to cement that leaked away. This level of knowledge is usually unavailable to the
surgeon viewing a fluoroscopic image, and may aid in evaluating the success
of a percutaneous cement injection intervention.
Keywords:
Fluoroscopy, DRR, pre-operative planning, hip arthroplasty, percutaneous, Xray, simulation
110
Introduction
The long-term survival of hip prostheses are primarily limited by the occurrence of aseptic loosening [Agarwal, 2004]. This pathological process involves extensive resorption of bone adjacent to the prosthesis and its replacement by fibrous tissue that offers little mechanical stability. Minimally invasive cement injection, already an established technique in the orthopaedic
field of vertebroplasty [Phillips, 2003], has in recent years been used experimentally to treat hip prosthesis loosening [de Poorter et al., 2008a, Raaijmaakers and Mulier, 2010].
Injected cement stabilizes a loosened prosthesis by re-establishing rigid mechanical contact between bone and the existing peri-prosthetic cement mantle
[Andreykiv et al., 2012]. Knowing the amount of cement that reaches its intended target may therefore be important in judging the success of a cement
injection procedure.
111
GUIDANCE
Cement injection is typically performed over the course of fewer than ten minutes due to polymethylmethacrylate (PMMA) bone cement hardening within
FLUOROSCOPY-BASED
Once needles have been placed, cement is injected. During cement injection,
the amount of deposited cement can directly be monitored by the position of
the syringes plunger which is marked in millilitres, as shown in Fig.8.1a. The
spatial distribution of the injected cement can be estimated by looking at 2D
X-ray fluoroscope projections as shown in Fig. 8.1b, where it appears as darkened image areas. The distribution of injected cement may also be monitored
using three dimensional (3D) intraoperative CT as shown in Fig. 8.1c. Currently, relying on 2D fluoroscopy for monitoring the flow of injected cement
during minimally invasive prosthesis stabilization is the clinical standard [de
Poorter et al., 2008a, Raaijmaakers and Mulier, 2010].
CHAPTER 8
Cement is injected through hollow needles that access the target lesions.
Needle insertion may be guided by two dimensional (2D) X-ray fluoroscopic
supervision. Using intraoperative Computed Tomography (CT), more accurate guidance of needles out-of-plane displacement and rotation may be performed [Puri et al., 2006] but this presupposes the availability of CT hardware in the treatment room. More recently, systems have become available
that use a combination of pre-operative CT and intraoperative fluoroscopy.
One such example is XperGuide (Philips, Best, The Netherlands) [Leschka
et al., 2012, Ruijters et al., 2008], where the accurate alignment of the patient, fluoroscopy images and the CT image volume depends on specialized
hardware.
(a)
(b)
(c)
Figure 8.1 Percutaneous cement injection can be monitored by looking at a) the

syringes plunger, b) fluoroscopic projections, or c) intraoperative cross-sectional
CT slices.
this time span. Of the three intraoperative monitoring methods shown in Fig.
8.1, only CT provides true 3D information. CT cannot be continuously active
throughout the procedure due to its higher radiation, as well as the need for
the surgeon to have access to the patient. This makes 3 D flow monitoring
with CT scan difficult. Lastly, in practice, CT hardware is seldomly available
in the treatment room. The patient needs to be slid into and out of the the CT
tunnel, and medical staff need to stand clear while the X-ray source is active
to reduce radiation exposure. 3D CT can be performed intermittently at best
[de Poorter, 2010].
We present a proof-of-concept software tool that enables the volume of injected cement to be quantitatively estimated, using a single pre-operative CT
image volume, a pre-operatively defined cement target, and one or more intraoperatively acquired 2D fluoroscopic images. This estimate may be performed for each image as it is read from the fluoroscope. The software is
designed to augment specific aspects of a minimally invasive cement injection procedure including planning, execution and analysis.
In this paper we describe our proof-of-concept planning software and then
proceed to analyse its use in a pre-clinical cadaver experiment that was performed at our institution. In this experiment, percutaneous cement injection
was planned in HipRFX and subsequently performed as for real human patients by an experienced orthopaedic surgeon.
112
8.1
8.1.1

Workflow
FLUOROSCOPY-BASED
GUIDANCE
113
CHAPTER 8
The workflow in which our software is to be used is illustrated in Fig. 8.2.

Our proof-of-concept software performs steps 34 and 9. Steps 2 and 8 are
currently performed with human intervention, using external software.
Firstly, our software allows a surgeon to plan a cement injection procedure
using a pre-operatively acquired CT as template. Secondly, our software can
compute Digitally Reconstructed Radiographs (DRRs) from a pre-operative
CT [Galvin et al., 1995]. DRRs are simulated 2D X-ray radiographs, computed
from CT. DRRs can be used in guidance, or in estimating cement quantities.
Thirdly, our software allows for a rough quantitative estimate of the resulting
3D cement distribution to be made. This is done by comparing the observed
intraoperative fluoroscopic images to DRRs that are generated from the preoperative CT volume.
When using HipRFX, the first step is to load a pre-operative CT volume of the
affected hip. The user then specifies a 3D target mask" that delineates the
sub-volume(s) that should be filled with bone cement, i.e. osteolytic lesion(s).
In our experiments we used the stand-alone MITK software [Maleike et al.,
2009] to perform these segmentations, but any medical volume segmentation
tool may be used for this purpose. The segmented cement mask is then read
by HipRFX as a binary image volume input file.
Once cement injection targets have been defined, the user has the possibility
of adding and positioning virtual cement injection needles that access the
designated target(s). If desired, additional segmented anatomical structures
may be concurrently loaded and displayed.
From the moment that a CT volume is loaded, our software is able to interactively simulate fluoroscopic images based on a virtual C-arm that may
be freely rotated. The goal of this simulation is to subsequently compare it
with the actual intra-operative fluoroscopic images. Images may be simulated with or without designated needles and injected cement. By comparing
actual intraoperative fluoroscopic images to these simulated imagesboth
in the complete absence, as well as in the complete presence of the intended
cement fillingwe generate 2D difference images between observed and simulated outcomes. These difference images are transformed to a 2D cement
filling" images that may be back-projected into the 3D volume to create a volumetric cement filling map. For each position in the cement filling image,
the filling values sensitivity to noise may be computed. For example: regions
Figure 8.2 The envisaged workflow of planning and executing a minimally

invasive hip refixation using HipRFX. Steps 8 and 9 could conceptually be performed continually, in real time, during the execution of step 7.
that are occluded by a dense metal prosthesis show few image differences
between a high and low degree of cement filling. Here, even a small amount
of image noise may have an effect on the computed cement filling value. This
is further described in Section 8.1.3.2.
8.1.2
Software User Interface
HipRFX is implemented as a module in the DeVIDE Runtime Environment

[Botha and Post, 2008] and makes extensive use of the Visualization ToolKit
(VTK), NumPy and SciPy [van der Walt et al., 2011].
114
The functionality contained in HipRFX is split across four separate panels, as

explained in Fig. 8.3. Each panel has its own distinct purpose. We now describe the functionality and underlying methods of each panel separately. In
its current proof-of-concept form, the image registration and intensity matching is performed by an external tool we built with scikit-image [van der Walt
et al., 2014].
Planning panel
115
GUIDANCE
The first view the user is presented with is the planning panel, shown in Fig.
8.4. As soon as a CT volume is loaded, it is rendered in a slice view and as a
3D volume. The panel contains two viewports showing 3D renderings of the
hips bony structures from anterior-posterior (A) and medio-lateral (B) perspectives. To facilitate the positioning of the needles, the isovalues used for
3D rendering may be adjusted to provide the right amount of context. The
central viewport contains a slice-based viewer that can manipulated interactively (C). The user may load 3D segmented structures of interest. Examples
include osteolytic lesions, or arteries and nerves that need to be avoided dur-
FLUOROSCOPY-BASED
8.1.2.1
CHAPTER 8
Figure 8.3 Overview of HipRFXs main activities, split among its four panels.
Components are grouped as functional units.
Figure 8.4 The planning panel provides 3D context renderings (A, B), an interactive slice-view, and control buttons (D). Cement injection needles (shown
here in blue and red) can be added to reach desired cement injection targets.
ing surgery. Any number of cement injection needles can be virtually inserted
into the CT volume and manipulated. The right-hand panel (D) contains
controls to adjust the viewports display parameters, to perform distance and
angle measurements, and to add, manipulate and remove needles.
8.1.2.2
DRR panel
The Digitally Reconstructed Radiograph (DRR) panel shown in Fig. 8.5 allows a simulated fluoroscope to be interactively viewed and manipulated.
The majority of the panel is taken up by the interactively rendered fluoroscopic image (A). Each image frame is created by a ray casting algorithm that
directly simulates the propagation of X-rays through the patient as shown in
Fig. 8.8 [Bifulco et al., 2002]. The user may manually adjust the brightness
and contrast to match the operating room fluoroscopes settings (B), either to
predetermined values obtained from calibration, or visually.
An interactive 3D representation of the patient and the fluoroscopic C-arm is
provided (C). The orientation of the C-arm and accompanying fluoroscopic
116
view may be interactively manipulated to match the operating rooms setup.
The image may be inverted to either emulate fluoroscopy or X-ray radiographs

the simulated X-ray attenuation algorithm is identical between these modes.
This is an aesthetic choice to be made by the modality that the surgeon is
most familiar with.
Needles or segmented cement targets that have been loaded in the Planning
View (Fig. 8.4) are realistically overlayed in the DRR image. In this way the
operator sees a simulation that corresponds to the fluoroscopic view he/she
would see intraoperatively.
CHAPTER 8
117
GUIDANCE
Snapshots may be saved to the Guidance Panel along with the accompanying
C-arm orientation as shown in Fig. 8.6. These snapshots of expected fluoroscopic views may then be used as a roadmap to guide the surgeon along
planned steps during the procedure.
FLUOROSCOPY-BASED
Figure 8.5 The DRR panel interactively simulates the fluoroscopic view a surgeon would see (A), including the effect of adding needles or bone cement. Snapshots may be saved at the press of a button, for later reference.
8.1.2.3
Step-by-step Guidance panel
In the DRR Panel shown in Fig. 8.5, the operator is allowed to store a number
of DRR snapshots for later reference. Snapshots are displayed in a grid view,
and clicking on any snapshot recalls the corresponding C-arm orientation that
was used. These snapshots can act as an intraoperative road-map since at any
time the operator may visually compare them to the live fluoroscopy image.
Changes in fluoroscopic images may be subtle between steps, e.g. between
partial and complete cement filling. The software can highlight the difference between any pair of snapshotsthis creates a copy of the image with
differences overlayed in blinking red (see Fig. 8.6).
Figure 8.6 The guidance panel records simulated fluoroscopic snapshots. Differences between frames may be computed and displayed as overlays (shown in
red in the centre snapshot). An example of an X-ray-mode DRR is shown in the
centre-right. In the centre of the bottom row the fluoroscope C-arms position is
shown that corresponds to the selected snapshot.
8.1.2.4
Cement filling feedback panel
Differences between real intraoperative fluoroscopic images and DRRs may

be analysed to yield estimates of cement filling. Along with filling estimates,
118
sensitivity to image noise, i.e. certainty" may be computed. The purpose

of the cement filling feedback panel is to visualize these computed values.
Using a bivariate colormap similar to those of [Moreland, 2009], we represent
certainty with luminance and filling with huesee Fig. 8.7.
Algorithm
119
GUIDANCE
We are able to estimate the volume of injected cement by comparing an observed fluoroscopic image to simulated fluoroscopic images. First we generate
a set of two DRRs. The first DRR simulates the fluoroscopic view in the absence of percutaneously injected cement. The second DRR simulates the fluoroscopic view when the target is completely filled with cement, as illustrated
in Fig. 8.11. During the cement-injection procedure, real observed fluoroscopic images represent scenarios that lie in between these two extremes. By
numerically computing the image intensity differences between the observed
FLUOROSCOPY-BASED
8.1.3
CHAPTER 8
Figure 8.7 The cement filling feedback panel. A slice through the CT volume
is shown on the left, with a 3D rendering of the whole cement target on the
right. Yellow indicates target areas that are filled with cement, whereas blue
areas indicate a lack thereof. Luminance increases with certainty.
fluoroscopic image and the two DRRs, our software numerically estimates the
amount of cement that was injected.
8.1.3.1
Computing the amount of cement
The DRR image formation process is illustrated in Fig. 8.8. Every element in
the CT volume has at least one X-ray path that passes through it to the DRR
image plane. The DRR formation is a discrete approximation of the physical
X-ray imaging process, and is explained in Appendix A.
Figure 8.8 DRRs are formed by simulating the propagation of X-rays through
a CT image volume
We can estimate the total volume of cement in the 3D CT by estimating the

distance that each ray travelled through cement on its path from X-ray source
to the image. The distance that each ray travelled through cement can be
expressed as the distance that it travelled through the target, multiplied by
the fraction of this distance that was filled with cement. We call this fraction
the fill fraction", F = sc /s t as shown in Fig. 8.9.
In Appendix A we explain the linear relationship between the length of an
X-ray path through a uniform substance and the cumulative absorption coefficient r a y by which the ray is attenuated. We can therefore rewrite the
fill fraction as F = c / t , where c is the cumulative attenuation coefficient
contributed by the cement-filled portion of the target. t is the cumulative
absorption coefficient that the target would have contributed if it was completely filled with cement. From the superposition principlealso explained
120
in Appendix Awe can express c as the difference between the cumulative

attenuation coefficients of the entire ray and of the ray portion that passes
through no cement, i.e. c = r a y none . Combining all of the above, we
can rewrite the fill fraction as
F=
par t ial none

f ul l none
(8.1)
where the subscript partial refers to the actual partially filled observed volume, as may be observed intraoperatively. The subscript none refers to the
case where cement is completely absent, and full refers to the case where
complete cement filling of the target is achieved.
FLUOROSCOPY-BASED
From Appendix A we know how to relate attenuation coefficients r a y to fluoroscopy image intensity I, allowing us to rewrite Eq. 8.1 in terms of image
intensities:
CHAPTER 8
Figure 8.9 The filling fraction F = sc /s t is the distance that each ray passes
through cement, expressed as a fraction of the target areas thickness along that
ray.
GUIDANCE

log I par t ial + log (I none )

F=
log I f ul l + log (I none )
121
which becomes

log I par t ial /I none
.
F=
log I f ul l /I none
(8.2)
I none and I f il l ed refer to the fluoroscopy images seen when either no cement is
injected and when the target volume is completely cement-filled. In an intraoperative setting one never has access to I f illed while I none could be recorded at
the start of the procedure. We chose to simulate both I none and I f illed by using
our DRR algorithm on the pre-operative CT volume. Note that I par t ial corresponds to the observed intraoperative fluoroscopy image that is available continuously during the cement injection procedure. An example of I none ,I f illed
and I par t ial is shown in Figure 8.11. This triad of images allows us to compute
F for all pixels in the 2D fluoroscopy image where these values are defined,
as shown in Fig. 8.13. The value of F for an arbitrary pixel in the image is
denoted by F x, y .
To obtain a quantitative cement volume estimate, we need to weigh each
pixels F x, y with the thickness s t of the cement target at the point through
which the associated ray passed. We call these the projection weights"
illustrated in Fig. 8.10. The projection weights correspond directly to s t in
Fig. 8.9, albeit appropriately scaled to yield a millilitre-valued output.
The projection weights W are directly proportional to the attenuation coefficients that a completely cement-filled target would contribute to the rays
terminating on each pixel. This is illustrated in Fig. 8.10 and can be mathematically expressed by referencing Eq. 8.7 in Appendix A. Here I cement is
the image that would result from X-rays passing only through the completely
filled cement target and nothing else, as shown in Fig. 8.12. Mathematically:
1
W s t t = log I cement .
k
As F = sc /s t , it follows that W F sc . Looking at Fig. 8.9 we note that
summing sc for every ray through the CT volume provides an approximation
to the amount of cement contained in the partially filled target.
We can now compute an absolute quantitative estimate of the volume of the
filled portion of the cement target. This is done by calculating the weighted
122
Figure 8.10 The projection weights scale linearly with the thickness of the
cement through which rays pass to reach the image plane.
sum of the fill fractions over all image pixels, and multiplying the result with
the volume of the complete cement target, in millilitres:
P
Vf il l ed =
x, y
Wx, y F x, y
P
x, y
Wx, y

Vt ar g et
(8.3)
FLUOROSCOPY-BASED
GUIDANCE
123
CHAPTER 8
A necessary prerequisite for computing Eqs. 8.2 and 8.3 is that all relevant
DRR and fluoroscopy images are registered, i.e. that their field of view are the
same, that they have the same brightness and contrast, and that their subject
is in the same position. In our proof-of-concept system and in our experimental set-up, calibration was approximated visually. In a practical clinical
system such pre-operative registration should instead be automatically and
robustly implemented, and orientation recorded via angle encoders attached
to the imaging hardware. To correct for mismatches in our experiments, we
applied suitable rigid similarity transformation that corrects for scale, rotation and translation in each fluoroscopic image. These parameters were estimated from four manually selected point correspondences in each image pair.
Brightness and contrast were corrected by linearly adjusting the intensity of
the fluoroscopic image to match that of the DRR in a least squares sense.
Additional caveats apply. The cement fill fraction F in Eq. 8.2 is only defined
in image regions onto which the cement target project, and only where the
(a)
(b)
(c)
Figure 8.11 a) Pre-operative DRR showing no injected cement. b) Postoperative DRR showing complete cement filling of the intended cement target.
c) Intraoperative fluoroscopic image showing partial cement filling.
(a)
(b)
Figure 8.12 a) The cement-only image I cement . b) The subset of the image
over which F can be computed using Eq. 8.2.
image brightness is not fully saturated. This is illustrated in Fig. 8.12. All
other areas in the image are marked as non-computable. Non-computable
areas include those where the thick metal prosthesis completely absorbs the
X-ray beam, as this would result in a zero-valued denominator I none in Eq. 8.2.
In non-computable areas falling inside the domain of I cement , F is interpolated
using thin plate spline radial basis functions, as shown in Fig. 8.13. In our
experiments we manually delineated suitable regions within the domain of
124
(a)
(b)
(c)
Figure 8.13 a) The cement filling image F from Eq. 8.2. b) F , after its interpolation to the area spanned by I cement . c) The certainty image C computed using
Eq. 8.4.
(a)
(b)
(c)
125
GUIDANCE
Once F has been computed over the whole 2D projected cement filling domain, it may be back-projected along the ray path to 3D and visualized in in
the cement filling feedback panel as shown in Fig. 8.7.
FLUOROSCOPY-BASED
I cement to serve as input to the interpolation algorithm, thereby excluding areas

where needles were present or where cement leaked into the incision created
during preparation of the test femurs. This is shown in Fig. 8.14.
CHAPTER 8
Figure 8.14 A mask were used to designate a valid subset of the computed
cement filling projection in our experimental data. a) Manually selected regions
are superimposed in white, and exclude confounding objects such as metal needles. b) Input to the interpolation algorithm. Non-computable regions are shown
with a diagonally hatched pattern. c) The interpolated output.
8.1.3.2
Sensitivity of the output to image noise
Fluoroscopy images contain some degree of image noise that may distort the
derived cement filling values. In areas occluded by radio-dense materials such
as the prosthesis, little or no information about cement filling can be deduced.
The uncertainty inherent in the resulting cement filling computation can be
explicitly analysed. This uncertainty is essentially equal the degree that the
result is affected by noise in the input image. Where dense metal objects
like the prosthesis occlude the image, the useful signal is attenuated while
image noise remains constant. This results in a very low signal to noise ratio,
resulting in unreliable cement filling estimates. For each pixel, the sensitivity
of the filling fraction F to noise can be approximated as its derivative with
respect to the observed fluoroscopic image intensity:
S =
I o bser ved
log (I obser ved /I none )

=
I o bser ved log I f ull /I none
1
.
=
I o bser ved log I f ull /I none
S is only defined for the regions where F is directly computable.

The reciprocal of the sensitivity function defines what we call the
certainty image C:

C = I o bser ved log I f ul l /I none .
(8.4)
All non-computable pixels in C are set to zero. An example of the certainty

image is shown in Fig. 8.13.
As was the case for F , we may re-project C along the projection rays and
visualize it in three dimensions on the cement filling feedback panel. F and
C are then combined in a single bi-variate colour mapping shown in Fig. 8.7.
The sensitivity of the overall cement volume estimate Vf illed may be computed
by applying the weights W to each individual pixels filling value sensitivity S
in the same way as it was done in Eq. 8.3:
P
S f il l ed =
x, y
Wx, y S x, y
P
x, y
126
Wx, y

Vt ar g et .
(8.5)
8.1.4
Validation Experiment on cadaver specimens
Substituting real fluoroscopic images with simulated DRRs allowed for perfect
image registration, as all the required images could be generated using the
exact same projection parameters. However, to test our software in a physically representative workflow using realistic clinical hardware, we enacted
minimally invasive hip refixation procedures on five ex-articulated cadaver
legs. The workflow we followed mirrors that shown in Fig. 8.2. An experienced orthopaedic surgeon was asked to perform the minimally invasive
cement injectiona procedure with which he was familiar.
8.1.4.1
Preparation of cadaver specimens
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Five ex-articulated cadaver legs were obtained. Each leg included the whole
femoral region, from the superior to the inferior epiphysis. In order to simulate peri-prosthetic lesions that could be filled with cement, we used a similar
approach as that of [Kraaij et al., 2012]. Two experienced orthopaedic surgeons placed cemented polished Exeter stems (Stryker, Limerick, Ireland) in
each femur. Exeter stems of sizes 3 and 4 (both with an offset of 44 mm)
were used, with the most appropriate size chosen for each leg.
Since we used cadaveric legs which were exarticulated in the hip joint, they
provided free access to the femoral head and neck. The soft tissues of each
legs were kept intactthis was important so as to provide a realistic target
for percutaneous cement injection.
After each prosthesis was placed and the cement hardened, the prosthesis
was again removed. The straight-edged and smoothly polished wedge-shaped
Exeter prosthesis surface enables such removal without damaging the cement
mantle [Malan et al., 2012b]. After removing the prosthesis, a single cut
through the skin and muscle tissue onto the bone surface was made with a
dissecting knife, perpendicularly to the femur shaft. The femur itself was
then sawed through with a bone saw. The leg was then tilted open along
the cut line to allow access to the femur shaft where it was bisected. Lesions
were created using an abrasive drill bit in an identical way as was previously
performed by [Malan et al., 2012b]. The muscle tissue on the opposite side
of the incision was kept intact, preventing the two semi-bisected halves of the
leg to separate completely. After lesions were created, the prostheses were
re-inserted. The snug fit between prosthesis and cement mantle ensured that
the original alignment of the two partially bisected leg halves was restored in
each case. The soft tissue around the incision perimeter was sewn closed so
that the soft tissue could recover some degree of conformity as well.
8.1.4.2
Pre-operative planning
After preparation, each femur was CT scanned with its prosthesis in place.
This CT image corresponded to the diagnostic pre-operative CT scan that a patient would routinely have performed if he/she was eligible for minimally invasive hip prosthesis refixation [de Poorter et al., 2008a, Egawa et al., 2009].
The peri-prosthetic lesions of each leg were manually segmented in 3D from
the CT volume using the Medical Imaging Interaction Toolkit (MITK 0.12.2),
an interactive medical image segmentation software tool [Maleike et al., 2009].
These segmented lesions defined the cement injection targets that we wished
to fill in the subsequent minimally invasive cement injection step.
Following the workflow described in Fig. 8.2, we used HipRFX to read the CT
image volume and the manually delineated segmentations, and then to virtually place vertebroplasty needles to reach these lesions. We manually chose
applicable angles for orienting the C-arm fluoroscope, after which we saved
DRR snapshots of the expected view, both before and after cement injection.
8.1.4.3
Cement injection
An experienced orthopaedic surgeon who has previously performed percutaneous cement injection in more than thirty patients, performed the procedure on each of the prepared cadaver legs. Standard clinical grade needles (Biomet VerteShark Access, 11Gx15cm), vertebroplasty cement (Biomet
Bone Cement V) and mixing sets (Optivac Procedure Set) were usedall supplied by Biomet Europe BV (Dordrecht, The Netherlands). Intraoperative fluoroscopy was performed using a standard clinical C-arm fluoroscope (Philips
BV Pulsera , Best, The Netherlands).
As opposed to a traditional percutaneous procedure where no pre-operative
guidance was available, an assistant held a 10.1 inch tablet-computer (Asus
TF700T, Taipei, Taiwan) in view of the surgeon on which the precomputed
DRR snapshots were displayed. A photo of one of our experiments is shown
in Fig. 8.15.
For each cadaver, the C-arm was moved to the appropriate position as indicated by the planning snapshot. Vertebroplasty needles were subsequently
inserted as per pre-operative plan. As opposed to patients, the bones of the
cadavers were not affected by osteolysis and necessitated insertion of the needles by first drilling into the bone using a thin drill bit. Even with pre-drilling,
inserting the needles into the bone required a surgical hammer to supply sufficient force. In four of the five legs both planned needles could be inserted,
128
Figure 8.15 An assistant shows a simulated fluoroscopic image to the surgeon.

Intraoperative fluoroscopic images are visible in the background. The cadaver
leg is situated on the table, underneath the C-arm fluoroscope. The faces of the
surgeon and assistant were anonymized for publication.
Acquisition of ground truth data
Fluoroscopic images obtained during our cadaver experiment were captured

and saved to file. HipRFX was then set to simulate an equivalent projection
129
GUIDANCE
8.1.4.4
FLUOROSCOPY-BASED
Polymethylmethacrylate (PMMA) bone cement was then mixed and injected

under fluoroscopic C-arm guidance. The cement flow was fluoroscopically
monitored in real-time, as is usually done in this kind of procedure [de Poorter
et al., 2008a, Raaijmaakers and Mulier, 2010]. Cement injection was continued until the peri-prosthetic space appeared filled or until the cement started
leaking into the surrounding tissue.
CHAPTER 8
while needle breakage limited use to inserting a single needle in the remaining leg.
viewpoint as used with the intraoperative C-arm fluoroscopy. Matching was

performed manually, interactively and according to visual similarity, as the Carm fluoroscope we used did not record the exact projection anglesneither
visually nor in accompanying metadata. Our only guidelines to ensure consistency were the apparent agreement between the virtual C-arm positions
and those used for the experiment, subjective agreement between the planning DRRs and those observed during the procedure, and the knowledge that
HipRFXs theoretical focal length and field of view matched those of the Carm..
Two simulated DRRs were created for each real fluoroscopic image: one representing the pre-operative state, and a second representing ideal cement filling of the target lesions that were segmented by hand in the pre-operative
CT volume. We used the procedure described in section 8.1.2.4 to estimate
cement filling.
After the cement had hardened, the cadaver legs were all returned to storage.
A post-operative CT scan of each treated cadaver leg was performed. This step
is not part of the workflow depicted in Fig. 8.2 but allowed for accurate and
independent post-operative cement volume measurements to be performed,
using manual delineation in the MITK software [Maleike et al., 2009, Malan
et al., 2012a].
8.2
Results
Fig. 8.16 shows a side-by-side comparison between a fluoroscopy image obtained during the cadaver experiment and a corresponding HipRFX-generated
DRR. Both of these images were generated using the actual experimental attained cement distribution the fluoroscopic image created at the end of the
cement injection, and the DRR generated using the post-operative CT volume.
When the fluoroscopic image was made the cement had not yet hardened.
Some changes to the cement distribution are visible between the images, especially where cement leaked outside the femoral shaft. The physical incision
that resulted from our experimental preparation method can be seen as the
radiolucent band into which the cement leaked.
We observed that much of the leaked cement did so into the incisions created by our experimental method. This is clearly visible in Fig. 8.16. We
compared all computed values with ground truth values measured in postoperative CT. With a median of 81% (range 55%-84%), the cement leakage
in our experiment was higher than observed in real patients [Malan et al.,
2014]. The filling percentage (median 52%, range 18%-55%) was compa130
(a)
(b)
Figure 8.16 a) Real fluoroscopy image during cadaver experiment vs. b)

HipRFX-generated DRR from post-operative CT with overlayed virtual needles.
A region of cement leakage is indicated by white arrows. The incision created
during preparation is visible as a light-coloured line extending into the zone of
cement leakage.
131
GUIDANCE
For each real fluoroscopic image, HipRFX was used to estimate the amount of
cement that was injected into the target region. Two of the five legs were each
imaged from two different angles. The median estimation error, expressed as
FLUOROSCOPY-BASED
Table 8.1 Cement filling estimates for the five femora using HipRFX. Ground
truth values were obtained by directly measuring them from independent postoperative CT volumes. .
CHAPTER 8
rable to that observed in real patients. The properties of the experimentally

created cadaver leg lesions and the subsequent injected cement volumes are
shown in Table 8.1.
Target
Injected
Cement
Filling
Cement vol.
volume
cement
filling of
estimate
estimation
(ground
(incl.
target
using HipRFX
error as
truth)
leaked) (ground truth)
% of target
3.58 ml 11.64 ml
51.8%
46.2% | 50.3% 5.6% | 1.6%
3.20 ml 8.90 ml
52.0%
46.8%
5.2%
3.17 ml 3.75 ml
33.4%
31.2%
2.3%
4.64 ml 4.69 ml
17.6%
32.5% | 21.8% 14.9% | 4.2%
4.09 ml 5.03 ml
55.4%
65.3%
9.8%
a percentage of the cement target volumes, was 5.2% (range 1.6%-14.9%).

These results are also summarized in Table 8.1.
To examine the role that experimental inaccuracies and assumptions had on
our results, we further differentiated the absolute per-pixel errors made in
the 2D filling images" like those in Fig. 8.13. We compared results when
using either a) our real experimentally obtained fluoroscopic images that include unaccounted-for cement leakage, image noise and possible geometricand-image-intensity registration errors, b) simulated fluoroscopic images that
include unaccounted-for cement leakage but with perfect registration, and c)
simulated fluoroscopic images with no cement leakage. For each of these scenarios we furthermore distinguished between the estimation error made in
the computable" and the non-computable" interpolated regions that were
described and illustrated in Fig 8.14. Results are shown in Fig. 8.17.
Figure 8.17 Experimentally obtained cement filling estimation errors using

HipRFX. a) errors when analysing real fluoroscopic data compared to b) the
equivalent errors when substituting real fluoroscopic images with simulated fluoroscopic images. In c) cement leakage was omitted from the simulated images.
Mean absolute per-pixel errors as well as the final integrated cement volume
estimate errors are shown.
The simulated fluoroscopic images for (b) were DRRs that used the complete
post-operative 3D cement distribution, segmented in the post-operative CTs.
The simulated fluoroscopic images for (c) were identical to (b) except that it
excluded all leaked cement. As our cement filling algorithm does not model
132
cement leakage this modification meets the assumption inherent in our cement estimation algorithm, which is that all injected cement projecting onto
the image of the cement target must also be located within the cement target.
After the performing the experiment, we discussed our proof-of-concept software with the orthopaedic surgeon who participated. He valued the preoperative planning capabilities that the software offers without necessitating
additional or new clinical hardware. He stated that HipRFX represented a
promising development in image-based guidance, and also represents a step
towards reducing the need for intraoperative CT imaging.
8.3
Discussion
133
GUIDANCE
Our pre-operative software tool is built around the assumption that C-arm
fluoroscopy is the dominant intraoperative technology for monitoring percutaneous cement injection, and will most likely remain so for the foreseeable
future. Additionally, we assume that at least a single pre-operative CT image
volume will be available before commencement of surgical planning. These
two assumptions are compatible with existing radiological protocol for mini-
FLUOROSCOPY-BASED
By visually judging the agreement between a simulated desired outcome and

real intraoperative images, a surgeon could be aided in judging whether sufficient cement penetration has been achieved. An obvious deviation between
simulated and observed fluoroscopic images may alert him to unwanted outcomes, such as cement leakage. In addition, we experimentally showed that
HipRFX can compute numerical estimates of the injected cement volume.
CHAPTER 8
Minimally invasive hip refixation by cement injection is a novel and experimental technique for refixing loosened orthopaedic implants. To our knowledge there currently exists no task-specific tool for planning or performing
this procedure. Our experimental HipRFX system has been purpose-designed
for this task and uses existing fluoroscopic hardware to provide intraoperative guidance and to analyse the distribution of injected cement. HipRFX can
simulate fluoroscopic images and computes cement volume estimates and a
combined filling-and-uncertainty distribution. Should it be used used intraoperatively, our system could provide a surgeon with valuable extra information
that currently is either absent, or can only be obtained after the fact. HipRFX
focuses on simulating and analysing the fluoroscopic images a surgeon would
see including the realistic fluoroscopic appearance of injected bone cement.
This allows us to progress beyond needle guidance and to also simulate and
assess the cement filling.
mally invasive cement injections [de Poorter et al., 2008a, Raaijmaakers and
Mulier, 2010].
The Philips XperGuide [Fichtinger et al., 2005, Leschka et al., 2012] system
shows some similarities with our approach to intraoperative guidance as it
also bases its guidance on a prior CT volume, and also combines this with live
single-plane C-arm fluoroscopy. However, XperGuide is focused on guiding
needle biopsies only and achieves this by overlaying glyphs onto radiological images. Unlike XperGuide our system is, in principle, compatible with all
existing CT imagers and fluoroscopes. This was demonstrated in our cadaver
experiment where we used a commercial C-arm fluoroscope that precluded
any any direct calibration between our software and the imaging hardware.
Here we showed that HipRFX is capable of estimating the volume of cement
to have reached pre-operatively defined target lesions. While we used postoperative CT as ground truth to compare our results to, post-operative CT
does not form any part of our workflow as shown in Fig. 8.2.
Where they project to the same pixel positions, our algorithm cannot distinguish leaked cement from cement inside the target region. A large amount of
leaked cement may therefore negatively affect the accuracy of the cement filling estimation, whereby the algorithm interprets leaked cement to be located
in the target lesion. This view is supported by Fig. 8.17 that shows much
reduced estimation errors when we analysed DRRs where leaked cement was
digitally removed.
An independent analysis of real patient data showed that cement leakage is
prevalent in clinical practice [Malan et al., 2014]. Given this reality of cement leakage, HipRFX plays the important role of specifically estimating the
injected cement fraction that reaches a target lesion. This fraction is presumed
to be the one that directly contributes to the stability of a hip prosthesis [Andreykiv et al., 2012]. Cement leakage was exacerbated in our experiments by
the cadaver legs having been sawed through, thereby providing an easy escape route for injected cement. Even in this challenging scenario the median
cement volume estimate error was 5.2% (range 1.6%-14.9%). We are encouraged by this result, especially considering the limitations of our experimental
set-up.
Residual image registration mismatches limited the accuracy with which our
algorithm could deduce cement filling. From Fig. 8.17 we made the paradoxical observation that, for the fluoroscopy images, the estimation error was
higher in computable than in interpolated regions. We explain this by random image noise being present in fluoroscopic images that cause per-pixel
134
fluctuations in filling estimation. By contrast, the interpolated regions are

smooth and show a lower per-pixel absolute error. This explanation is supported by the observation that the errors in the computable regions decreased
when we substituted the fluoroscopic images with DRRs, while the interpolated regions error decreased by less. We observed that per-pixel estimation
errors tended to cancel out when they were summed, resulting in a reduced
estimation error for the total cement volume.
A limitation of HipRFX in its current form is its inability to directly record
the position and projection parameters of the relevant fluoroscope. In fact, in
our experiments these parameters were not numerically recorded at all. The
simulated C-arm was visually and manually aligned to match the DRRs with
the recorded fluoroscopic image. The inevitable discrepancies that resulted
from such qualitative alignment required us to perform image registration, as
schematically illustrated in Fig. 8.2. Iterative techniques that match radiographs with CT-derived DRRs [Guziec et al., 1998, Russakoff et al., 2005]
may in future improve registration accuracy. Calibrated systems using accurate angle encoders such the Philips XperGuide may in future be constructed
for our application and make the system easier to use and more robust.
GUIDANCE
135
FLUOROSCOPY-BASED
Our system may in future be used to compute optimal C-arm orientations for
performing an intervention. This can be done by maximizing the image difference between DRRs of the expected pre-operative and post-operative situation. Large image differences indicate that the changes caused by the planned
procedure are clearly visible this then represents an informative viewing
angle. Differences may enable discernment between correct and incorrect
needle placement, or between sufficient and insufficient cement filling. The
parameter space that needs to be traversed in this case consists only of the Carms elevation and azimuth i.e. a two dimensional optimization problem.
When a C-arm fluoroscope needs to be positioned accurately to within 5 degrees, all possible orientations may be examined in fewer than 800 iterations.
Given the speed with which DRRs and difference images can be computed,
this brute force approach would be feasible for optimizing the view for each
CHAPTER 8
In clinical practice, needle placement is mainly performed under the supervision of single-plane fluoroscopy [Raaijmaakers and Mulier, 2010, de Poorter
et al., 2008a]. Intraoperative CT may also be used for more accurate 3D
guidance. Similar to Philips XperGuide our software has the potential to be
developed to guide a surgeon during needle placement. One possibility would
be to simulate a correctly placed needle and overlay it in live fluoroscopy. We
leave the exploration of this topic to future work.
desired step in the cement injection procedure, while being guaranteed to

find the global optimum.
Another direction for future work would be to combine the estimates obtained
from several distinctly oriented fluoroscopy images. A stereo fluoroscopy system [Baka et al., 2011] may be used for this purpose, or several single plane
fluoroscopic images may be taken successively from different angles. The
area occluded by a large metal prosthesis would be different for each image
and the combined estimate may be considerably more accurate than either
estimate on its own.
We are encouraged by the feedback received from the orthopaedic surgeon
who used HipRFX in planning and executing the cadaver experiment. We
foresee that, in future, the techniques described in this paper could provide
surgeons with sufficient insight and feedback on percutaneous cement injection procedures to avoid the use of explicit 3D imaging tools in the operating
room. We believe that the ability to glean quantitative estimates of the cement
volume that is deposited in a desired target region, without having to resort
to 3D imaging modalities, is novel. This approach may be applied to any
application where radiopaque cement in injected, including vertebroplasty.
Acknowledgements
We wish to sincerely thank Fred van Immerseel, Dr Marc Nieuwenhuijse and
Dr Huub van der Heide who assisted us in preparing the cadaver specimens.
Also Noeska Smit, who operated the C-arm fluoroscope during the cadaver
experiments.
136
Appendix A: DRR generation by ray casting

Assuming a bundle of mono-energetic X-ray photons with mean energy E and
no scattering, the X-ray flux X that reaches a detector after passing along path
s is:
X = X 0 e
D
0
(s,E)ds
(8.6)
where X 0 is the sources emitted X-ray flux, D is the length of the path that the
X-ray photons travel to reach the detector, and (s, E) is the X-ray absorption
coefficients of the matter that the X-rays
pass through [Kalender, 2005] . It is important to note that the superposition principle holds for X-ray absorption coefficients; if an X-ray bundle successively passes through two material regions with X-ray absorption
a coeffi 0 1 (s)ds
cients
(s)
and
(s)
respectively,
then
Eq.
8.6
yields
X
=
(X
e
)
a
0
b
ba
b
a 2 (s)ds
( 0 (s)ds+ a 2 (s)ds)
e
= X0e
, showing that the equivalent total absorption coefficient is the sum of the two individual absorption coefficients. Consequently the equivalent X-ray absorption coefficient for an entire ray, r a y =
D
(s, E)ds , varies linearly with the distance the ray passes through a uni0
form substance. If we know the values of r a y for two X-ray paths passing
through different thicknesses of cement, we would be able to relate these
thicknesses to one another.
FLUOROSCOPY-BASED
The required X-ray absorption that needs to be plugged into Eq. 8.6 can be
directly read from a CT volume. The constituent volume elements (voxels")
in a CT volume are quantified in Hounsfield Units (HU). The Hounsfield Unit
is dimensionless and is defined by the physical X-ray absorption coefficient of
the material that was imaged, as well as that of water and air:
CHAPTER 8
Because X-rays are photons, it comes as little surprise that Eq. 8.6 is identical to the light absorption term used in direct volume visualization, a well
established 3D image rendering technique that simulates light propagation
through physical objects [Preim and Botha, 2013a]. This allows for the X-ray
imaging process to be approximated with efficient GPU-optimized ray tracing
algorithms that have become an essential part of modern medical visualization software [Preim and Botha, 2013b].
GUIDANCE
1000 ( wat er )
1000
1000
CT =
wat er ai r
wat er
137
This relationship between CT number and X-ray absorption coefficient is linear, allowing Eq. 8.6 to simulate X-ray absorption when the absorption coefwat er
ficient is set to = 1000
(C T + 1000) for every point along the rays path.
To understand how one may estimate cement volumes from numerically comparing fluoroscopy images it is also necessary to understand the relationship
between X-ray flux and fluoroscope image brightness. The transmissivity of a
developed X-ray film is defined as T = I/I0 at every point, where I can be interpreted as the intensity of light emanating from a position on the observed
image when it is back-lit by a light-source with intensity I0 . The blackening
of of the X-ray film or digital detectors output image as it is exposed to X-rays
is called its optical density, and is defined as the base-ten logarithm of the
reciprocal of its transmissivity, i.e. D = log10 (I0 /I).
Figure 8.18 Optical films characteristic curve also known as the H&D curve
Over a certain working range, an X-ray detectors optical density has a linear
relationship to the logarithm of received photon flux. This is illustrated in the
detectors characteristic H&D curve as illustrated in Fig. 8.18. The slope of
this linear relationship is called the detectors Gamma ( ).
Medical fluoroscopic images are displayed as the negative image of traditional X-ray radiographs, with the background being white and radiopaque
structures such as bone being dark. This is the also the default display mode
we used in generating DRRs, in which case the characteristic curve is the vertically mirrored version of the H&D curve in Fig. 8.18, i.e. with a linear region
that has a slope of negative , or
138
I0
I
I0
ln
I
log10
= log10 X + c
= k ln X + p
= k ln(X 0 e
D
0
(s,E)ds
)+p
(s, E)ds) + p
= k (ln X 0
0
D
= k
(s, E)ds + (p k ln X 0 )
0
= k r a y + q
, where c, k,p and q are placeholders for constant values and r a y represents
the integral of the X-ray absorption coefficients along the whole path which
the X-ray beam passed from the source to the detector. In a digital fluoroscopy
image, the image brightness and contrast may be adjusted arbitrarily. To be
accurace, our cement-filling algorithm requires that the image intensities are
scaled so that I0 has a value of 1.0 and q is zero. This can be achieved by automatically computing the appropriate image brightness and contrast. Under
the aforementioned conditions this implies that:
ln I = k r a y
(8.7)
CHAPTER 8
where the image I is interpreted as having an intensity range of [0, 1].
FLUOROSCOPY-BASED
GUIDANCE
139
9
General Discussion
CHAPTER 9
DISCUSSION
The research in this thesis represents part of a project to develop a new set of
tools to support minimally invasive treatment for aseptically loose hip prostheses. In Chapter 1, Fig. 1.1 illustrated how the elements of this project
relate to one another. These elements are intended to work together as an
integrated whole, and we undertook our research as members of a multidisciplinary research group. Together, we aimed to contribute to an integrated
solution that improves the planning and execution of minimally invasive stabilization of aseptically loosening hip prostheses. Each of the following topics
plays a role: Image processing (this thesis), pre-operative planning and intraoperative guidance (this thesis), mechanical finite element simulations, and
surgical instrument design.
9.1
The effect of fibrous interface tissue before cement injection
Fibrous interface tissue should ideally be removed before an aseptically loose

prosthesis is stabilised, as osteolysis is progressive and self-propagating [Park
et al., 2004]. Computer simulations have shown that interface tissue removal
increases the mechanical stability of a hip prosthesis [Andreykiv et al., 2012].
Currently, there are no minimally invasive instruments with which to manually remove fibrous interface tissue before bone cement is injected. To examine the effect that removal of interface tissue had in actual patients, we
analysed the post-operative CTs of patients that were treated at our institution between 2006 to 2011 (Chapter 3). These patients all eventually received percutaneous cement injections to stabilise their aseptically loose hip
prostheses, yet their treatment differed in one important aspect: One patient group was pre-operatively treated using gene-directed enzyme pro-drug
therapy (GDEPT) to eliminate fibrous interface tissue, while the other group
received no pre-operative treatment. Our measurements indicated that preoperative treatment increased the volume and efficacy of percutaneous cement injection into the periprosthetic targets. From our results we deduced
that prior removal of periprosthetic fibrous interface tissue may enable better
cement flow and cement penetration. This may in turn lead to better prosthesis stabilisation. The implication of this result is that new instruments by
which fibrous interface tissue can be removed would benefit the patient. The
development of such instruments fall outside the scope of this thesis, but is being further pursued by researchers at our institution [Kraaij et al., 2012, den
Dunnen et al., 2013].
142
9.2
Image capture and image processing
Surgeons who perform hip surgery often judge traditional two dimensional
(2D) X-ray radiographs to be sufficient for diagnosis and planning their procedures. X-rays are relatively cheap, fast, and deliver only a low radiation
dose. For the diagnosis of arthritic damage to a hip, a high-resolution 2D
X-ray image shows the associated narrowed joint space and uneven femoral
surface. A suitable prosthesis size may be selected by overlaying templates
directly on the printed X-ray plate. Hip arthroplasty is performed during open
surgery that gives the surgeon direct visual and tactile access to the affected
hip, providing him/her with the direct intra-operative insight that is required
to perform the procedure. When instead working percutaneously through a
minor incision, the surgeon cannot directly see the tips of his/her instruments.
The surgeon therefore becomes dependent on medical imaging or guidance
to provide the necessary intra-operative insight. Because the patients body is
a complex 3D object, 2D X-ray images may not be sufficient to meet the needs
of minimally invasive surgery.
Three dimensional (3D) medical imaging technology, also known as crosssectional imaging, has dramatically improved over the last two decades. Modern Computed Tomography (CT) and Magnetic Resonance (MR) imaging devices are now widely available and produce image volumes of the human
body that can resolve details of 0.5mm or finer in any spatial direction.
DISCUSSION
143
CHAPTER 9
At the time we performed our research, CT was seen as the modality of choice
for quantifying periprosthetic osteolysis [Egawa et al., 2009], and may still
be seen as such. We therefore based our image processing and planning software on CT. Medical CT scanners are designed to image the human body. As
metal differs dramatically from biological tissues, CT image-reconstruction
algorithms ecounter problems when a hip containing a hip prostheses is imaging. Metal-induced imaging artefacts ensue. To improve image quality, metal
artefact reduction (MAR) algorithms have been developed that suppress the
severe beam hardening" seen in CT [Cahir and Toms, 2009]. Artefact reduction by projection interpolation is one of the oldest MAR methods [Glover
and Pelc, 1981] and has continued to garner interest in recent years [Oehler
et al., 2008, Veldkamp et al., 2010]. Alternative iterative and algebraic approaches to CT MAR have been developed [Bal and Spies, 2006, Lemmens
et al., 2009, Boas and Fleischmann, 2011, Gondim Teixeira et al., 2014], yet
to our knowledge projection interpolation remains the only method to have
been clinically implemented by a major CT manufacturer [Watzke and Kalender, 2004]. The limited uptake of MAR can possibly be explained by the
observation that metal artefacts are, in practice, not as destructive as one is

led to believe. The severity of star streak" artefacts shown in publications on
the topic [Boas and Fleischmann, 2011, Lemmens et al., 2009, Kalender et al.,
1987] depend on the contrast window chosen; some information that appears
lost may be recovered if the complete intensity range of the data is considered. There is also the issue that MAR may in itself degrade image detail,
especially directly adjacent to a metal prosthesis. In our research we found
that MAR by linear sinogram interpolation reduced our ability to delineate
peri-prosthetic lesions created in cadaver specimens [Malan et al., 2012b].
While MAR used in isolation has its drawbacks, we showed in Chapters 5 and
6 that MAR is useful when used to augment instead of replace standard CT
images.
Metal-induced image artefacts not only occur in CT, but also in MRI and ultrasound [Sofka, 2007]; each by a different underlying mechanism. In our
experience orthopaedic surgeons are well aware of the difficulties associated
with imaging close to metal implants, yet less so of available mitigation strategies. This is especially true for MRI which research shows to be safe [Kumar
et al., 2006] and useful [Cahir and Toms, 2009, Lee et al., 2007, Potter and
Foo, 2006] for peri-prosthetic imaging of the hip. For this reason we believe
that MRI may in future become an increasingly valuable tool for assessing
osteolysis.
A 3D image volume provides a wealth of data that can be used for preoperative planning and simulation. Common orthopaedic procedures for
which CT-based pre-operative planning systems have been developed include
hip arthroscopy [Audenaert et al., 2012], shoulder arthroplasty [Botha and
Post, 2001], hip arthroplasty [Dick et al., 2009] and knee arthroplasty [Ellis,
2005]. Before being useful for modelling aseptic loosening, some crucial postprocessing steps need to be taken on a medical image volume.
9.3
Transforming medical images to 3D models of the hip
3D image volumes may be used for powerful and beautiful medical visualizations [Preim and Botha, 2013b]. However beautiful these visualizations
can be, it is bio-mechanical simulations that are often the desired tool for
performing quantitative analyses. Such analyses usually require that intensity images with clearly defined tissue boundaries are segmented to form a
multi-material 3D model.
The golden standard for 3D image segmentation is manual delineation by a
trained human [Seim et al., 2008, Lim et al., 2006]. It is difficult to interact
144
with a 3D volume via a computers 2D display and therefore segmentation

is often performed in a slice-by-slice manner. With the steady increase in
resolution of modern MRIs and CTs, manual segmentation may already be
prohibitively time consuming for routine clinical practice. Manual, or even
semi-automated image segmentation is a tedious and labour-intensive task
that benefits greatly from automation [Heimann et al., 2009]. In this thesis
we preferred automated over semi-automatic methods whenever we could.
145
DISCUSSION
In our approach to tissue classification we used several complementary image volumes simultaneouslyincluding unprocessed, spatially filtered, and
metal-artefact-reduced image volumes. Graph cuts is a powerful segmentation technology that has, up to now, not been widely applied in medical
imaging outside of selected settings [van der Lijn et al., 2008, Merickel et al.,
2007]. The addition of Graph Cuts to our classifier enabled us to enforce geometrical constraints that would not have been achievable by treating each
image voxel individually, and it improved our classification results notably.
CHAPTER 9
The research community has already invested much effort into designing and
improving automated tissue classification algorithms. Advances in automatic
segmentation include examples as diverse as for the liver [Heimann et al.,
2009], brain [van der Lijn et al., 2008], heart [van Assen et al., 2006], lungs
[van Rikxoort et al., 2009] and retinal lesions [Snchez et al., 2011]. In
this thesis we investigated whether one can automatically segment the periprosthetic tissues and structures of a hip that is affected by osteolysis [Malan
et al., 2010, Malan et al., 2012a]. We wanted to discern tissues relevant to
the creation of a finite element model of the aseptically loosening hip prosthesis [Andreykiv et al., 2012]. These include cortical bone, trabecular bone,
fibrous interface tissue, bone cement, and the metal prosthesis. Our problem
was especially challenging for two reasons: Firstly, the presence of a metal
prosthesis degrades the CT image quality. Secondly, peri-prosthetic osteolysis
does not have a well-defined normally distributed variation around an average shape [Scheerlinck et al., 2008, Howie et al., 2007]. The powerful class
of statistical shape models" and active appearance models" that rely on the
assumption of Gaussian shape distributions [Heimann and Meinzer, 2009]
were therefore largely eliminated from our solution space. To make matters
even more challenging, this thesis addressed a medical procedure which is
itself still considered experimental. As such there exist few publications on
this topic and there were no publicly available data-sets or competing algorithms with which to compare ourssomething that is of great value in image
segmentation research [Heimann et al., 2009, Martin et al., 2001].
Before mechanical simulation of a bone can be performed, even a segmented

3D tissue map must be converted into an appropriate simulation model [Taddei et al., 2006, Andreykiv et al., 2012]. The Finite Element Method (FEM)
[Cody et al., 1999] is a well-established and validated method of modelling
stresses, strains and deformations in continuum models and is used in countless applications including the automotive world, civil engineering, and modelling the human body. In its standard form the FEM requires the simulated
model to be represented as a mesh of connected elementstypically tetrahedra [Bryan et al., 2010]. The number of mesh elements need to be kept low
enough for the model to be tractable, while in a multi-material model nodes
and edges must conform on all material interfaces.
In simulations of man-made structures, the input to the meshing algorithm
are often models created in computer aided design (CAD) software. These
models are analytically defined and their surfaces are threfore noise-free and
easy to discretize cleanly using a limited number of elements. In contrast,
the segmented tissue map obtained from a 3D medical image volume is discretized as a dense grid of rectangular voxels that can be seen as a noisy
approximation of the underlying structures. Converting this dense grid to a
volumetric mesh can create an intractable number of mesh elements. Singlematerial meshing methods exist that can create well-behaved meshes with a
limited element-count [Labelle and Shewchuk, 2007]. Doing the same for
multi-material volumes is more challenging, and the lack of widely available
solutions have provided an opportunity for some companies to build commercial software to perform this task [Pettersen and Hgetveit, 2011]. In
Chapter 7 we built upon prior work [Meyer et al., 2008] and extended their
particle-based algorithm for multi-material meshing. Particle based methods
have an advantage over direct mesh refinement in that it abstracts the shape
that need to be meshed as an implicit surface, which allows for scale invariance. We presented a proof-of-concept software mesher that, compared to the
Delaunay-based algorithm on which it builds, allows sparser multi-material
meshes to be created without having to sacrifice geometric surface accuracy
by excessive smoothing.
CT has its shortcomings in the presence of a large metal prosthesis, yet has
one distinct advantage over e.g. MRI and ultrasound: it quantifies the human body in Hounsfield units. The Hounsfield Unit is an objective and reproducible measure that directly corresponds to the physical rate at which X-rays
are absorbed by the bodys tissues. This in turn allows mechanical material
properties to be derived from a CT image. Mechanical properties may then be
146
assigned to patient-specific models of, for example, the femur [Bessho et al.,
2009]. We caution that dense bone and metallic prostheses have a measurable
effect on image intensity values and may disrupt algorithms that rely strongly
on absolute image intensity values for tissue classification. We briefly looked
into this topic in Chapter 4.
9.4
Planning and guiding a minimally invasive procedure
Software by which the execution of orthopaedic operations can be planned

are already in clinical use. Examples include software for needle biopsies
[Braak et al., 2010] and for planning hip arthroscopy [Audenaert et al., 2012].
3D planning software commonly use CT or MRI image volumes as input, and
can manipulate and visualize data either on standard desktop computers or
dedicated hardware stations. Planning may be performed prior to an operation and outside of the operating room. Ideally, such software should also
help the surgeon to operate according to the predetermined plan that is constrained by the operating room environment. Limitations may include the
amount of time allowed for treating the patient and the need to maintain
sterility, i.e. that computer interfaces may not be physically touched.
The stabilizing effect of injected cement on a loosened hip prosthesis depends
on how much contact is re-established between the bone and cement surrounding the prosthesis [Andreykiv et al., 2012]. In our specific application
of minimally invasive cement injection, knowing the amount of cement that
reached its intended target may therefore be important in judging the success
of the procedure.
147
DISCUSSION
We believed thatif at all possibleit is preferable to design a guidance system that does not require novel imaging equipment to be present in the operating room. Re-use of existing technology may ease adoption of a new planning system and will reduce costs. An X-ray C-arm fluoroscope is commonly
CHAPTER 9
A well-established intra-operative guidance approach that is often used in orthopaedics is to attach reflective optical markers to the patients body and
the surgeons instruments, and then to track the movement of these with a
stereoscopic camera system [Bthis et al., 2004]. This is a useful approach
in positioning rigid instruments. In our application we are, however, also interested in the progressive distribution of radiopaque cement fluid before it
hardenssomething that optical markers cannot help us with. The amount
of deposited cement can traditionally only be quantified by the displacement
of the cement syringes plunger, on which calibrated millilitre marks are indicated along the side.
available in the operating room due to its compact size, multiple uses and
relatively low cost, whereas CT and MRI are not. In Chapter 8 we therefore
presented HipRFX, a proof-of-concept guidance system that requires only an
intra-operative X-ray fluoroscope to be present during a cement-injection operation, assuming that a CT image was obtained beforehand. We are not the
first to use this approachThe Philips XperGuide guidance system for needle
biopsies [Braak et al., 2010] also makes use of pre-operatively acquired CT
for planning and intra-operative X-ray fluoroscopy for guidance. Our system
does, however, deliver some innovations that we have not yet come across
elsewhere. These include the ability to quantitatively estimate injected cement volumes based on fluoroscopy images only.
In pre-clinical tests our software was able to generate reasonable estimates of

the percutaneously injected cement volume that reached the intended target
information that would otherwise not be quantitatively known from a single
post-operative fluoroscopic image. Our system can furthermore record a stepby-step series of simulated fluoroscopy images. These simulated fluoroscopy
snapshots may guide a surgeon during the execution of a minimally invasive cement injection procedure by alerting him/her of deviations from the
plan, or indicating when the intended goal has been achieved. The promising
results we obtained in Chapter 8 were despite the sub-optimal conditions under which we performed our experiments, namely that the hardware we used
was uncalibrated and required several estimation steps that may be avoided
in future.
Our guidance software may be further developed along several lines. One
idea is to improve cement estimates by integrating the information obtained
from multiple 2D fluoroscopic views that were taken simultaneously or in
quick succession from different angles. Another idea is to use our software to
automatically compute the optimal C-arm view angles to use for an intended
intervention. The need for needle placement guidance may also in future
be addressed by our system, as is done in the Philips XperGuide [Racadio
et al., 2007, Leschka et al., 2012]. The planning and guidance approach
we showcased with HipRFX may eventually also have applications beyond
the procedure for which is was developed. One such possible application
could be vertebroplasty [Phillips, 2003], which also relies on the injection of
radiopaque bone cement.
148
9.5
Perspectives on the Future
DISCUSSION
149
CHAPTER 9
At the time of writing, percutaneous hip prosthesis refixation is still considered novel and even experimental, yet it has already helped several patients
at our institution who would otherwisebecause of their frail healthnot
have qualified for surgery. There are currently no purpose-made tools for this
novel minimally invasive orthopaedic procedure. While we addressed several
aspects of imaging a patients hip and pre-operative planning, a multi-faceted
approach that goes wider than the content of this thesis is needed to advance
this procedure towards greater maturity.
Despite CTs established role pre-operative imaging of peri-prosthetic loosening [Cahir et al., 2007], several recent studies have shown that Magnetic
Resonance Imaging (MR) has great potential in imaging the peri-prosthetic
region of the hip, even in the presence of large metallic prostheses [Cahir and
Toms, 2009, Sofka, 2007, Walde et al., 2005]. The additional advantage that
MRI delivers no ionising radiation will be especially advantageous when one
considers younger patients. We believe that the tissue classification algorithm
described in Chapters 5 and 6 of this thesis will allow adaptation to MRI. Our
algorithm teaches itself to classify tissues from heterogenous data, and does
not depend on any inherent quality of CT.
Throughout this thesis we used the example of a loose femoral stem to illustrate and test our work. While a loosening prosthesis stem is indeed often the
reason for a failing hip prosthesis, the acetabular cup component also fails
[Howie et al., 2007] at rates reported to be even higher than for the femoral
stem [Keener et al., 2003, Swe, 2013, Dut, 2013]. We hypothesize that the
methods we developed are also adaptable to the acetabular cup, as well as to
other joints where aseptic loosening can occur such as the knee.
The algorithms and software we developed can all be described as proofof-concept. None of the software has been developed to industrial-level robustness, and can therefore not yet be clinically validated. The scope of our
research left some resolvable yet important bottlenecks unaddressed. One
of these is the infrastructure for enabling effortless data-flow between the
different components described in the thesis. This infrastructure includes file
format conversions, network communication with picture archiving and communication (PACS) systems to obtain CT image data, reading images from
intra-operative C-arm fluoroscopic devices, and communicating models to finite element modelling software. Image registration and intensity matching
between intra-operative fluoroscopic images and simulated fluoroscopic images was demonstrated, but not fully automated nor integrated in our soft-
ware platform. Steps as these are not necessarily interesting in a research

context, yet are extremely important from an operational standpoint and may
require substantial effort to implement properly.
The ability to simulate the biomechanics of the affected hip may need to be
improved in order to compute optimal cement placement [Andreykiv et al.,
2012]. The development and validation of new surgical instruments is desired
so that peri-prosthetic fibrous interface tissue may removed prior to cement
injection [Malan et al., 2014]. Research on the aforementioned topics was
conducted at our institute concurrently with the work in this thesis, but much
work remains.
Patient-specific bio-mechanical modelling may currently still be a niche technique due its combined requirements for advanced 3D imaging, software than
can transform such images into 3D models, as well as suitable simulation
software. Success stories include unique pathologies that preclude the use of
standardised prostheses, such as creating prostheses for missing parts of a patients skull [Esses et al., 2011, Metzger et al., 2008]. When fast and reliable
automatic image volume segmentation techniques become available, routine
clinical applications to patient-specific modelling may follow. A recent example where patient-specific simulations made the transition to a mainstream orthopaedic application is that of femoro-acetabular impingement [Audenaert
et al., 2012]. We foresee that routine patient-specific 3D modelling will eventually become the norm for a full gamut of orthopaedic applications, as capabilities of 3D modelling tools improve and their cost lowers.
Given the ever growing number of patients that receive hip prostheses and
prostheses of other major joints, we expect that ever more patients will be
affected by the clinical problem of prosthesis loosening caused by aseptic
periprosthetic osteolysis. We believe that the analysis and treatment of aseptic
prosthesis loosening will therefore require continued attention and we look
forward to developments in this field.
150
9.6
Conclusion
In this thesis we examined how computer software can be used to assist a

minimally invasive cement injection procedure that is intended to stabilize
an aseptically loose hip prosthesis. We chose to base our methods on the
output of widely available medical imaging hardware such as Computed Tomography (CT) and X-ray fluoroscopy. We believe that solutions using widely
available imaging hardware has a better chance of being widely applicable
and adoptable into existing clinical practice.
Taken as a whole, this thesis addresses several aspects that constitute a medical imaging workflow to support percutaneous hip prosthesis refixation by
cement injection. Throughout our research we focused on CT as the source
of 3D medical images. Through the analysis of clinical data from our institution, we conclude that prior removal of periprosthetic fibrous interface tissue
may enable better cement flow and penetration.
One of our goals was to enable the generation of finite element mesh of the
hip that include the complexities of aseptic loosening. This has to be done
without resorting to a solution that generates a superfluous number of mesh
elements. To this end, we presented an automated pipeline for segmenting
periprosthetic tissues in clinical CT volumes of patients with hip prostheses.
We subsequently improved on a viable approach to multi-material conformal
tetrahedral meshing.
151
DISCUSSION
The algorithms and software that we developed can all be described as proofof-concept. Throughout this thesis we have used the example of a loose
femoral stem to illustrate and test our work, and we believe that the methods
we developed may also be applicable to the femoral cup, as well as other joints
where aseptic loosening occurs. We have proposed some paths along which
our initial steps may be taken further, and we look forward to see where these
paths will lead.
CHAPTER 9
We also worked towards a pre-operative planning and intra-operative guidance tool. For this we developed HipRFX, a proof-of-concept software module.
In pre-clinical tests HipRFX was able to simulate intra-operative fluoroscopic
C-arm images, providing the surgeon with a step-by-step series of snapshots
with which to compare the operation as it is performed. We were furthermore
able to generate estimates of the percutaneously injected cement volume that
actually reached the intended targets.
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168
Summary
In this thesis we examined how computer software can be used to analyse
medical images of an aseptically loosening hip prosthesis and subsequently
to plan and guide a minimally invasive cement injection procedure to stabilize
the prosthesis. The research in this thesis was undertaken as a member of a
research group where, since 2005, a novel treatment method to this end was
developed and tested on a small group of selected patients.
We specifically endeavoured to develop automated or semi-automated algorithms that could enable patient-specific planning and treatment within the
time constraints of clinical practice. It was also our goal to make use of existing medical imaging hardware, such as Computed Tomography (CT) and
C-arm fluoroscopy, so that solutions arising from this research could eventually be adopted into existing practice.
The first topic we addressed was the detection and measurement of periprosthetic bone lesions from CT image volumes. In Chapter 2 experimentally examined whether we could accurately measure the volumes of periprosthetic
bone lesions in the presence of image artefacts caused by the presence of a
metal hip prosthesis. The answer to this question was important as many
of our subsequent experiments and algorithms depended on the visibility of
these lesions in three dimensional (3D) CT image volumes. In the presence of
a large metallic prosthesis, severe "beam hardening" image artefacts degrade
image quality. We found that we were able to delineate these periprosthetic
lesions, although metal artefact reduction (MAR) by linear sinogram interpolation reduced our ability to delineate lesions. This is counter-intuitive as
the goal of MAR is to improve image quality. While MAR used in isolation
has its drawbacks, we showed in Chapters 5 and 6 that MAR is useful when
it is combined with unprocessed CT images to improve tissue classification
results.
In Chapter 3 we examined post-operative CTs of patients that were treated
at our institution in the period spanning 2006 to 2011. These patients all
169
eventually received percutaneous cement injection to refixate their aseptically

loose hip prosthesis, but their treatment differed in one important aspect: one
patient group was pre-operatively treated using gene-directed enzyme prodrug therapy (GDEPT) to kill fibrous interface tissue, while the other group
received no pre-operative treatment. We measured the volumes of each patients periprosthetic osteolytic lesions, as well as the volume of cement that
was injected during the procedure. Our results showed that patients who underwent pre-operative GDEPT to kill fibrous tissue exhibited larger injected
cement volumes than those who did not. From this we deduced that prior
removal of periprosthetic fibrous interface tissue enabled better cement flow
and cement penetration that might in turn lead to better prosthesis refixation. We propose that new instruments by which fibrous interface tissue may
be removed would aid the success of the procedure.
In our experiments in Chapter 4 we briefly examined whether radio-dense
materials such as those encountered in the hip can significantly alter the CT
image intensity values observed in adjacent structures. We found that this is
indeed the case, and cautioned that this effect may disrupt algorithms that
rely strongly on absolute image intensity values for tissue classification or for
deriving numerical material properties such as elasticity. We concluded the
chapter by providing some estimates of errors that may be introduced into
derived finite element models if such inaccuracies are allowed to propagate
to the computational stage.
In Chapter 5 we developed a tissue classification algorithm that may automatically label periprosthetic bone, cement and fibrous interface tissue. The
ability to label these tissues is important for mechanically simulating an invivo hip prosthesis. We first explored the use of statistical classifiers that treat
3D image cubes (voxels) as individual entities. Every voxel was represented
by a set of numerical values corresponding to image features. Our algorithm
combines several complementary image processing outputs, including MAR,
to arrive at its output.
In Chapter 6 we added 3D constrained graph cuts to the voxel classification technique developed in the previous chapter. Graph Cuts enabled us
to enforce geometrical knowledge in our tissue classification that could not
be achieved by treating each image voxel individually. We proceeded to test
our classification pipeline on a set of twelve clinical CT volumes. We were
able to classify the periprosthetic tissues we were interested in with sensitivities exceeding 73% and specificities exceeding 96%. While this result was
not as good as a human performing the task manually, our algorithm could
170
perform its task on a standard personal computer in half an houreven in its

unoptimised state. This is comparable to the amount of time that would be
required by a trained human expert.
In Chapter 7 we improved an existing particle-based multi-material meshing
algorithm. This allowed sparser multi-material meshes to be created without
having to sacrifice geometric surface accuracy by excessive smoothing. As
an example, we showed how our adjusted algorithm was able to generate a
tetrahedral multi-material mesh from the six million segmented image voxels
of a femur dataset, the output of which consisted of 200,000 tetrahedra that
retained the shape of all segmented tissue regions with an average surface
error of less than 0.1 mm and never exceeding 3.9 mm at any point.
In Chapter 8 we turned our attention to how one can use the information
and models gained from algorithms such as those in the preceding chapters
to help a surgeon plan and execute a minimally invasive cement injection operation. For this we developed HipRFX, a proof-of-concept software module.
In pre-clinical tests HipRFX was able to simulate intra-operative fluoroscopic
C-arm images, providing the surgeon with a step-by-step series of snapshots
with which to compare the operation as it is performed. We were furthermore
able to generate estimates of the percutaneously injected cement volume that
actually reached the intended targets. The feedback we received from the
orthopaedic surgeon who used HipRFX during this emulated procedure was
positive, citing useful per-operative information that complemented his workflow without taking up unnecessary time or space in the operating room, nor
required new operating room hardware.
We conclude this thesis in Chapter 9 with a general discussion and future
directions for continuing the work we presented.
171
Samenvatting
In dit proefschrift onderzochten wij hoe computer software gebruikt kan worden om medische beelden van een aseptisch loslatende heupprothese te analyseren, een minimaal invasieve cementinjectie procedure te plannen, en uiteindelijk te begeleiden. We hebben in het bijzonder getracht geautomatiseerde
of semi-geautomatiseerde algoritmen te ontwikkelen die patint-specifieke
planning en behandeling mogelijk kunnen maken binnen de beperkingen
van de klinische praktijk. Het was eveneens ons doel om gebruik te maken
van bestaande medische beeldvormingshardware, zoals Computed Tomography (CT) en C-arm fluoroscopie. Het onderzoek in dit proefschrift werd
uitgevoerd in een onderzoeksgroep waar vanaf 2005 een nieuwe behandelmethode voor dit doel is ontwikkeld. Deze behandelmethode is inmiddels
ook al toegepast op een kleine groep geselecteerde patinten.
Het eerste onderwerp waar wij ons op richtten was de detectie en meting van
periprothetisch botlaesies in CT beeldvolumes. In hoofdstuk 2 onderzochten
wij of periprothetische botletsels nauwkeurig gemeten konden worden in de
aanwezigheid van beeldartefacten die door een metale heupprothese veroorzaakt werden. Het antwoord op deze vraag was van belang omdat veel van onze
verdere experimenten en algoritmes afhankelijk zijn van de zichtbaarheid van
deze laesies in de driedimensionale (3D) CT-beelden. In de aanwezigheid
van een grote metalen prothese veroorzaken "beam hardening" beeldartefacten ernstige degradatie van beeldkwaliteit. We waren niettemin in staat
om deze periprosthetische laesies af te bakenen, hoewel metalen artefactreductie (MAR) door lineaire sinogram-interpolatie ons hinderde in het afbakenen van de laesies. Dit is interessant, aangezien MAR juist als doel heeft
beeldkwaliteit te verbeteren. Terwijl MAR in isolatie nadelen heeft, toonden
we in de hoofdstukken 5 en 6 dat MAR handig is wanneer het met onbewerkte
CT-beelden gecombineerd wordt en zodoende weefsel classificatie resultaten
kunnen verbeteren.
In het hoofdstuk 3 onderzochten we post-operatieve CTs van patinten die
173
bij onze instelling behandeld werden gedurende de jaren 2006 tot en met
2011. Deze patinten kregen uiteindelijk allemaal percutane cementinjecties
om hun aseptisch loszittende heupprothesen te refixeren. Hun behandeling
verschilde echter wat betreft een belangrijk aspect: n patintengroep werd
preoperatief behandeld met gen-gestuurde enzym prodrug therapie (GDEPT)
om het vezelachtige interface weefsel te doden, terwijl de andere groep geen
pre-operatieve behandeling kreeg. We maten de volumen van periprosthetische osteolytische laesies bij elke patint, alsmede de hoeveelheid cement dat
gedurende de procedure werd genjecteerd. Wij maten bij patinten die preoperatieve GDEPT ondergingen meer genjecteerd cement dan bij degenen die
de behandeling niet ondergingen. Hieruit leiden wij af dat voorafgaande verwijdering van periprosthetische interface weefsel betere doorstroming van cement en cementpenetratie mogelijk maken, dat op zijn beurt weer kan leiden
tot een betere prothese-refixatie. We suggereren dat nieuwe instrumenten
waarmee interface-weefsel verwijderd kan worden het succes van de procedure zou kunnen verhogen.
In het hoofdstuk 4 onderzochten we door een experiment in hoeverre radioopaque materialen zoals heupbotten het CT intensiteitswaarden in nabijgelegen structuren kunnen verstoren. We ontdekten dat dit inderdaad het geval
is, en waarschuwden dat dit effect algoritmes kunnen verstoren wanneer zij
sterk afhankelijk zijn van absolute beeldintensiteit-waarden. Voorbeelden van
gevoelige algoritmes zijn die die voor indeling van weefsels of voor het afleiden van numerieke materiaaleigenschappen zoals elasticiteit gebruikt worden. We sloten het hoofdstuk af met door een voorbeeld van numerieke
fouten te laten zien die in eindige elementmodellen op kunnen treden als
dergelijke onjuistheden niet uitgeschakeld worden.
In het hoofdstuk 5 ontwikkelden we een algoritme voor classificatie van weefselsoorten dat automatisch periprothetisch bot, cement en vezelig interfaceweefsel kan onderscheiden. De mogelijkheid om deze weefsels te onderscheiden is belangrijk voor mechanische simulatie van een in-vivo heupprothese.
Allereerst onderzochten wij het gebruik van statistische classificatie algoritmes
die 3D-beeldelementen (voxels) als individuele entiteiten behandelen. Iedere
voxel werd vertegenwoordigd door een reeks numerieke waarden die
overeenkomen met beeldeigenschappen. Ons algoritme combineert verschillende complementair bewerkte beelden, waaronder MAR, om tot een antwoord te komen.
In het hoofdstuk 6 voegden wij het gebruik van constrained graph cuts" toe
tot ons eerder-ontwikkelde voxel classificatie-techniek die in het vorige hoofd174
stuk ontwikkeld werd. Graph Cuts stelde ons in staat om geometrische kennis
in onze weefselclassificatie te gebruiken die niet mogelijk zou zijn geweest
wanneer elk voxel als individu behandeld werd. Vervolgens testten wij onze
classificatie-pijplijn op een set van twaalf klinische CT volumes. We waren in
staat om de relevante periprosthetische weefsels met gevoeligheden van meer
dan 73% en specificiteiten van meer dan 96% te classificeren. Hoewel dit
resultaat niet zo goed was als een volledig handmatige mensgestuurde classificatie, kan ons algoritme haar taak op een standaard computer uitvoeren
in een half uur zelfs in zijn niet-geoptimaliseerde toestand. Dit is vergelijkbaar met de hoeveelheid tijd die een opgeleide menselijke expert nodig zou
hebben.
In het hoofdstuk 7verbeterden we een bestaand partikel-gebaseerde multimateriaal meshing algoritme. Dit stelt ons in staat minder-dichte multimateriaal driehoekjesmodellen en tetrader-modellen te creren zonder veel
geometrische nauwkeurigheid prijs te geven of gladheid van het driehoekjesmodel af te dwingen. Als voorbeeld toonden we aan hoe het aangepast algoritme een tetradrische multi-materiaal netwerk van de zes miljoen beeldvoxels van een gesegmenteerde femur dataset genereert, waarvan wij uiteindelijk 200,000 tetraders overhouden die de vorm van de afzonderlijke weefselgebieden met een gemiddelde fout van minder dan 0,1 mm benaderde.
In het hoofdstuk 8 richtten wij onze aandacht op hoe informatie en modellen, zoals die in de voorgaande hoofdstukken beschreven, aan een chirurg
kunnen worden doorgegeven op zodanige wijze dat dit nuttig is bij het plannen en uitvoeren van een minimaal invasieve cementinjectie-operatie. Hiervoor ontwikkelden we HipRFX, een proof-of-concept softwaremodule. In een
preklinische test was HipRFX in staat intra-operatieve fluoroscopische C-arm
afbeeldingen te simuleren die de chirurg een stap-voor-stap serie van snapshots gaf. Die waren te gebruiken als referentie tijdens het uitvoeren van
zijn gesimuleerde operatie. We waren bovendien in staat om schattingen te
maken van de percutane genjecteerde cement volumes die daadwerkelijk de
beoogde doelen bereikten. De feedback die we van de orthopedisch chirurg
ontvingen was positief, vooral met betrekking tot de manier waarop de additionele intraoperatieve informatie zijn workflow aanvulde, zonder onnodig
veel tijd of ruimte in de operatiekamer op te nemen of om nieuwe apparatuur
in de operatiekamer aan te schaffen.
We sloten dit proefschrift af met een algemene discussie in hoofdstuk 9 waar
wij toekomstige richtingen voor de voortzetting van het onderzoek uit dit
proefschrift bespreken.
175
Curriculum Vitae
Danil Franois Malan was born on 22 October 1979 in Tygerberg, South
Africa. In 1997 he matriculated at Stellenbosch High School, placing 5th
in the Western Cape Province. He spent 1998 as a Rotary International exchange student. In 2001 and 2002 obtained the degrees B.Sc. (mathematical
sciences) and Hons. B.Sc. (applied mathematics), both cum laude, at the
University of Stellenbosch. He completed his M.Sc. (engineering sciences)
cum laude in 2005 with the thesis titled 3D Tracking Between Satellites using
Monocular Computer Vision".
From 2005 Francois did scientific programming at Integrated Seismic Systems
International (ISSI) on the outskirts of Stellenbosch. Here he contributed
to software for modelling stresses and seismicity in mining environments.
In 2007 he joined Sunspace to work on mission control software for South
Africas small Earth observation satellite called SumbandilaSat.
In 2008 Francois relocated to The Netherlands to pursue a PhD in medical
image processing and visualization at Leiden University. His work included
collaboration with the medical visualization group at Delft University of Technology where he also successfully supervised three M.Sc. students. His own
PhD research was funded by the Dutch organization for scientific research,
NWO. During this period Francois also served for one year as a board member for the PhD candidates Network of the Netherlands (PNN). As product
manager at Clinical Graphics from 2012-2013, he worked on visualization of
femoro-acetabular hip impingement.
Francois now again pursues his earlier engineering interests in the field of
space applications. Since returning to South Africa in 2014 he is product
manager for space-borne imaging systems at Space Advisory Company, as well
as a systems engineer contributing to the Square Kilometer Array project.
In his spare time Francois enjoys sport and the outdoorsincluding running,
snowboarding and squash. He is also a keen photographer.
177
Acknowledgements
The PhD process is notorious for being long and emotionally difficult. When I
started this journey I knew the stereotypes, saw friends become those stereotypes, and regularly laughed at PhD Comics". In the end my own long experience was a difficult one, but along the way I also had the best experiences
of my life. With many of the people that were part of this journey I expect to
remain close friends for the rest of our lives.
The work that culminated in this thesis was performed in the Medical Delta,
a collaboration betwee the Department of Orthopaedics at Leiden University
Medical Center and the Departments of 3ME and Intelligent Systems at Delft
University of Technology.
Specifically I want to thank Charl Botha who was my co-supervisor and mentor. By initially spreading news of this PhD position to South Africa he started
it all. Charl inducted me into The Netherlands and showed the way to becoming well integrated and (almost) Dutch. As a friend he is a constant source of
enthusiasm, inspiration and new experiences.
I also thank my two main supervisors: Edward Valstar who made the whole
project possible and patiently steered its direction, and Rob Nelissen for the
warm and down-to-earth sincerity with which he headed our department.
Peter Krekel, who helped me find a house in Delft even before I met him,
shared journeys and music festivals, and eventually became my colleague at
the company he himself founded - weve had a long and meaningful journey.
Peter Schaafsma, for his lively philosophy. Wynand, whom I met in South
Africa as a fellow student, who became a fellow PhD candidate in Delft, a
house-mate, a colleague at Clinical Graphics, and eventually again a fellow
South African resident in the beautiful Cape.
179
Noeska, Thomas, Changgong, Peter Kok, Renata and Gerwin - my excellent

office-mates in Delft over the years. Elmar for his academic support. Ruud
for the coffee, and Bart for his enthusiasm about photography and nature.
Ricardo and Luisa for their humour and friendship. Bas and Christian whom
I had the privilege of supervising. Nienke, Nora, Vikas, Bouke, and my colleagues at the LUMC. Sander, Frans and the guys from our CdE cycling group.
Tom, Anna and Malou at PNN who were also dependable friends.
Fred at the LUMCs Anatomy department. Koos, Paul, Raoul and Berend at
Medical Physics. To the majority of my other colleagues at the LUMC in Leiden, at the TU Delft, at PNN and at Clinical Graphics and Yes!Delft whose
names I omit here I greatly enjoyed interacting with you!
Familie Rohof, who I knew for many years before coming to their country, and
who were my family in Oosterhout. Annemarie and Andr who welcomed me
in Delfts inner city in the early years. Anne-Marie for her loyal friendship and
support. Tjaart, with whom I shared so many experiences. Andriy and Marta,
my first and best Ukrainian friends, who became my family and gave me their
home in difficult times. Lauren, for being a wonderful friend and partner to
Stfan. Stfan who was and still is there for me as best friend, travel partner,
and who even co-authored the last chapter of this thesis - your support and
contributions are invaluable to me.
My mother who supported my choices throughout. Thys and Lynda, for their
wisdom and guidance. Theo, Marga, Eveline and Reiner who were a familiy
to me. Lastly and most importantly Linda, who believed in me more than
anyone else and became part of who I am.
180

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Cover Page

The handle http://hdl.handle.net/1887/36019 holds various files of this Leiden University

Pinning down loosened prostheses:

Danil Franois Malan

About the cover:

Pinning down loosened prostheses:

Danil Franois Malan

Prof.dr. R.G.H.H Nelissen

Dr. C.P. Botha

This work was carried out in the ASCI graduate

2 Measuring femoral lesions despite CT metal artefacts

3 Percutaneous bone cement refixation of aseptically loose hip

5 Voxel classification of periprosthetic tissues of the hip

6 The addition of Graph Cuts to voxel classification for automated

7.5.3 Femur dataset (multiple materials, anisotropic scan) 104

Introduction and motivation

Aseptic prosthesis loosening: the clinical problem

Existing options for treating aseptic hip prosthesis loosening

and osteoblasts. Osteolysis may act as a normal biological process of the

A new integrated planning and treatment approach

Figure 1.1 A schematic illustration of an integrated approach to minimally

Structure of this thesis

In Chapter 7 we address the issue of creating 3D finite element meshes from

Measuring femoral lesions despite

Daniel F. Malan, Charl P. Botha, Gert Kraaij,

In comparison, non-PI algorithms are computationally expensive and remain

Although there still exists no general solution for removing metal-induced

decrease the manual segmentation performance of such lesions? Does MAR

Materials and Methods

Figure 2.2 Flow chart of the experiments performed in this study.

Image registration, distance metrics, and contrast metrics were computed

For each segmentation boundary we computed the median image gradient

To answer whether the presence of metal degrades segmentation performance,

The second question is whether PI MAR improves segmentation performance

Measured Volume Difference (ml)

We found no significant correlation between the lesion size or DXA T-score

Figure 2.6 Hausdorff distances compared to resin ground-truthed results

Average Hausdorff Distance (mm)

Michelson Contrast across

Figure 2.8 Dice coefficients compared to resin ground-truthed results show

Edge Gradient Magnitude ( HU / mm )

Figure 2.11 A CT slice showing fibrous-tissue lesions (arrows). A: with resin

OF INTERFACE TISSUE REMOVAL

Daniel F. Malan, Edward R. Valstar, Rob G.H.H. Nelissen

Percutaneous bone cement

Materials and Methods

Our candidate population consisted of twenty two patients at our hospital

OF INTERFACE TISSUE REMOVAL

Revision surgery has higher perioperative mortality and morbidity rates in

and we consequently had to exclude patients for whom no post-operative

In a previously published cadaveric study examining periprosthetic femoral

OF INTERFACE TISSUE REMOVAL

Figure 3.2 Cement flow was monitored using intra-operative fluoroscopy

OF INTERFACE TISSUE REMOVAL

Figure 3.3 Cement flow was monitored using intra-operative fluoroscopy

The cement-only groups radiolucent lesion volumes ranged from 13.8 ml to

OF INTERFACE TISSUE REMOVAL

OF INTERFACE TISSUE REMOVAL

Refixation of aseptic loosened hip stems by percutaneous cement injection

D.F. Malan, B.C. Stoel, J. Geleijns, E.R. Valstar

Materials and Methods

ular bone. CT opacities measured in these enclosed regions might therefore

Observed opacity in the ROI increased strongly as the surrounding thickness

Thickness of "cortical" layer