Characterization and Reduction of Noise in PET Data Using Mvw-Pca

IT 09 003
Examensarbete 30 hp
Mars 2009
Characterization and Reduction
of Noise in PET Data Using
MVW-PCA
Per-Edvin Svensson
Institutionen fr informationsteknologi
Department of Information Technology

Teknisk- naturvetenskaplig fakultet
UTH-enheten

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ngstrmlaboratoriet
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Abstract
Characterization and Reduction of Noise
in PET Data Using MVW-PCA
Per-Edvin Svensson
Masked Volume-Wise Principal Component Analysis (MVW-PCA) is used in Positron
Emission Tomography (PET) to distinguish structures with different kinetic behaviours
of an administered tracer. In the article where MVW-PCA was introduced, a noise
pre-normalization was suggested due to temporal and spatial variations of the noise
between slices. However, the noise pre-normalization proposed in that article was
only applicable on datasets reconstructed using the analytical method Filtered
Back-Projection (FBP). This study aimed at developing a new noise pre-normalization
that is applicable on datasets regardless of whether the dataset was reconstructed
with FBP or an iterative reconstruction algorithm, such as Ordered Subset
Expectation Maximization (OSEM).
A phantom study was performed to investigate the differences of expectation values
and standard deviations of datasets reconstructed with FBP and OSEM. A novel noise
pre-normalization method named "higher-order principal component noise
pre-normalization" (HOPC noise pre-normalization) was suggested and evaluated
against other pre-normalization methods on both synthetic and clinical datasets.
Results showed that MVW-PCA of data reconstructed with FBP was much more
dependent on an appropriate pre-normalization than analysis of data reconstructed
with OSEM. HOPC noise pre-normalization showed an overall good performance
with both FBP and OSEM reconstructions, whereas the other pre-normalization
methods only performed well with one of the two methods.
The HOPC noise pre-normalization has potential for improving the results from
MVW-PCA on dynamic PET datasets independent of used reconstruction algorithm.
Tryckt av: Reprocentralen ITC
IT 09 003
Examinator: Anders Jansson
mnesgranskare: Ewert Bengtsson
Handledare: Pasha Razifar
5
Preface
This master thesis is the result of a study performed in Uppsala, Sweden, at
GE Healthcare in co-operation with Centre for Image Analysis (CBA). The
author is currently nishing his studies as a master student in Engineering
physics and Electrical engineering at The Institute of Technology at Linkping
University. During the early phases of the project the author cooperated with
two students who simultaneously performed their master thesis work at GE
Healthcare within the same area [1, 2]. Therefore there are some similarities
between the reports. This concerns the background chapter, 2, and parts of
the synthetic study presented in sections 3.2.5 and 4.2.2. Apart from the work
presented in this master thesis, work has been made on an application used to
view and analyse dynamic Positron Emission Tomography (PET) data.
The results of the studies have resulted in four manuscripts, listed below,
that either have been or are to be submitted for publication in scientic journals.
P Razifar, H H Muhammed, F Engbrant, P-E Svensson, J Olsson, E Bengts-
son, B Lngstrm, and M Bergstrm, Performance of principal compo-
nent analysis and independent component analysis with respect to signal
extraction from noisy positron emission tomography data a study on
computer simulated images. Accepted for publication (2009)
P-E Svensson, J Olsson, F Engbrant, E Bengtsson, B Lngstrm and
P. Razifar, Characterization and reduction of noise in dynamic positron
emission tomography data using masked volume-wise principal component
analysis. Manuscript (2009)
J Olsson, R Oweinus, P-E Svensson, F Engbrant, B Lngstrm, E Bengts-
son, and P Razifar, Automated Method for Generation of Input Function
in Positron Emission Tomography Studies Using Masked Volume-Wise
Principal Component Images. Manuscript (2009)
F Engbrant, P-E Svensson, J Olsson, B Lngstrm, E Bengtsson, and
P Razifar, Application of Masked Volume-Wise Principal Component
Analysis on In Vivo Animal Positron Emission Tomography Studies Using
Flourine. Manuscript (2009)
I would also like to thank a few people for helping me with this master thesis:
My supervisor, Pasha Razifar for his great commitment and support through-
out the whole project.
My friends and colleagues, Johan Olsson and Fredrik Engbrant with whom
I have had a lot of interesting and fruitful discussions.
My father, Per-ke Svensson for proofreading and giving valuable feed-
back on the report.
Contents
Acronyms and abbreviations 9
1 Introduction 11
1.1 Setting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.2 Aim . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.3 Structure of the thesis . . . . . . . . . . . . . . . . . . . . . . . . 12
2 Background 13
2.1 Tomographical imaging modalities . . . . . . . . . . . . . . . . . 13
2.1.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
2.1.2 Anatomical information . . . . . . . . . . . . . . . . . . . 13
2.1.3 Physiological information . . . . . . . . . . . . . . . . . . 14
2.1.4 Integrated imaging modalities . . . . . . . . . . . . . . . . 16
2.1.5 Dierences and applications . . . . . . . . . . . . . . . . . 16
2.2 Positron emission tomography . . . . . . . . . . . . . . . . . . . . 17
2.2.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.2.2 Types of PET studies . . . . . . . . . . . . . . . . . . . . 18
2.2.3 Acquisition . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2.2.4 Noise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.2.5 Corrections . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.2.6 Reconstruction . . . . . . . . . . . . . . . . . . . . . . . . 20
2.3 Principal component analysis . . . . . . . . . . . . . . . . . . . . 20
2.3.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2.3.2 Algorithm . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2.3.3 Pre-normalizations . . . . . . . . . . . . . . . . . . . . . . 21
3 Materials and methods 23
3.1 Characterization of noise . . . . . . . . . . . . . . . . . . . . . . . 23
3.1.1 Motive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
3.1.2 The acquisition . . . . . . . . . . . . . . . . . . . . . . . . 23
3.1.3 Selection of samples . . . . . . . . . . . . . . . . . . . . . 24
3.1.4 Expectation value . . . . . . . . . . . . . . . . . . . . . . 24
3.1.5 Standard deviation . . . . . . . . . . . . . . . . . . . . . . 24
3.1.6 Correlation between slices . . . . . . . . . . . . . . . . . . 25
3.1.7 Correlation between frames . . . . . . . . . . . . . . . . . 25
3.1.8 Correlation between samples within the same slice . . . . 26
8 Characterization and Reduction of Noise in PET Data Using MVW-PCA
3.1.9 Correlation between samples within the same slice from
one realization . . . . . . . . . . . . . . . . . . . . . . . . 26
3.2 Reduction of noise . . . . . . . . . . . . . . . . . . . . . . . . . . 28
3.2.1 Masked volume-wise PCA . . . . . . . . . . . . . . . . . . 28
3.2.2 Reconstruction from selected principal components . . . . 29
3.2.3 Background noise pre-normalization . . . . . . . . . . . . 30
3.2.4 Higher-order principal component pre-normalization . . . 30
3.2.5 Synthetic images . . . . . . . . . . . . . . . . . . . . . . . 31
3.2.6 Clinical study . . . . . . . . . . . . . . . . . . . . . . . . . 37
4 Results 39
4.1 Characterization of noise . . . . . . . . . . . . . . . . . . . . . . . 39
4.1.1 Frames . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
4.1.2 Slices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
4.1.3 Correlation between samples within the same slice . . . . 41
4.1.4 Correlation between samples within the same slice from
one realization . . . . . . . . . . . . . . . . . . . . . . . . 42
4.2 Reduction of noise . . . . . . . . . . . . . . . . . . . . . . . . . . 44
4.2.1 Higher-order principal component pre-normalization . . . 44
4.2.2 Synthetic images . . . . . . . . . . . . . . . . . . . . . . . 45
4.2.3 Clinical study . . . . . . . . . . . . . . . . . . . . . . . . . 49
5 Closing remarks 53
5.1 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
5.1.1 Interpretation of PC images . . . . . . . . . . . . . . . . . 53
5.1.2 Noise characteristics . . . . . . . . . . . . . . . . . . . . . 54
5.1.3 Reduction of noise in PET data using MVW-PCA . . . . 55
5.2 Future work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
5.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Bibliography 56
List of Figures 60
List of Tables 62
Contents 9
Acronyms and abbreviations
ACF Auto-Correlation Function
BN Background Noise
CT Computed Tomography
FBP Filtered Back-Projection
FDG Fluorodeoxyglucose
fMRI Functional Magnetic Resonance Imaging
FORE FOurier REbinning
FOV Field of View
FWHM Full Width at Half Maximum
LOR Line of Response
HOPC Higher-Order Principal Component
MRI Magnetic Resonance Imaging
MSE Mean Squared Error
MVW Masked Volume-Wise
OSEM Ordered Subset Expectation Maximization
PCA Principal Component Analysis
PC Principal Component
PET Positron Emission Tomography
PIB Pittsburgh Compound-B
ROI Region of Interest
ROM Removal of Mean
SV Standardized Variables
SPECT Single Photon Emission Computed Tomography
TAC TimeActivity Curve
VOI Volume of Interest
WSS Weak-Sense Stationary
Chapter 1
Introduction
1.1 Setting
Positron Emission Tomography (PET) is a non-invasive imaging modality used
to visualize the functionality in tissues and organs in vivo in medical and research
applications [3]. PET is based on measuring the concentration of a molecule
labelled with a radionuclide, known as a tracer, designed to follow a specic
physiological or biochemical path. The scanner detects photons that are a result
from positron-electron annihilation events, creating an image or a set of images
showing the tracer concentration in the scanned object.
PET data is acquired either as a static image volume from the whole scan
or as a dynamic sequence of image volumes from dierent times of the scan.
Whole body acquisition is mostly performed as static PET studies often used
to detect tumours, whereas studies of the brain are performed as dynamic PET
studies and used to detect neurological disorders such as Parkinsons disease,
Alzheimers disease, phobia and schizophrenia by studying the kinetic behaviour
of the tracer.
However, PET data suers from noise and the dierent areas and tissues
can be hard to discern. There are several methods for analysing PET data
such as kinetic modelling, summation and multivariate image analysis methods.
It has been shown that Masked Volume-Wise Principal Component Analysis
(MVW-PCA) can be used as a multivariate method that without modelling
assumptions can separate tissues and organs with dierent kinetic behaviours
of the PET tracer in dierent components [4]. In this approach, a new pre-
normalization was suggested prior to application of PCA since noise variance
varies, both temporally and spatially within a dataset. However the proposed
pre-normalization approach is only applicable on datasets reconstructed using
analytical methods such as Filtered Back-Projection (FBP).
1.2 Aim
The aim of this project was to characterize noise in PET data reconstructed with
FBP and Ordered Subset Expectation Maximization (OSEM), and to reduce the
noise using MVW-PCA.
1.3 Structure of the thesis
This thesis is divided into ve chapters where the rst is the introduction. The
second chapter is a technical background to dierent tomographical imaging
modalities with focus on PET. This chapter also contains an introduction to
the multivariate analysis method PCA and a new application to dynamic PET
data called MVW-PCA. The materials and methods used in this project are
described in chapter 3. The results are presented in chapter 4 and discussed in
chapter 5.
Chapter 2
Background
2.1 Tomographical imaging modalities
2.1.1 Overview
In the context of medical imaging, an imaging modality is any of the various
types of equipment used to acquire images of the body. Tomography is a tech-
nique based on generating two-dimensional slices through a section of a three di-
mensional volume. Tomogram generating imaging modalities include Computed
Tomography (CT), Magnetic Resonance Imaging (MRI), Positron Emission
Tomography (PET), Single Photon Emission Computed Tomography (SPECT),
combinations and variations of these [3]. Each imaging modality has its own
advantages, and is therefore used in dierent research areas and for diagnosing
dierent disorders. These imaging modalities are used to obtain either anatom-
ical information, physiological information or both by integrating two imaging
modalities.
2.1.2 Anatomical information
Computed tomography
Computed Tomography (CT) uses x-rays to visualize thin slices through the
human body [5]. An x-ray tube and a detector are placed in the CT cameras
gantry on opposite sides of the patient. The patient is gradually passed through
the gantry as the system is rotated creating images from dierent angles yielding
a three-dimensional x-ray image of the patient. The images have low structural
noise and high contrast between bone and soft tissue, see gure 2.1(a) [3].
Magnetic resonance imaging
Magnetic Resonance Imaging (MRI) is based on the relaxation properties of ex-
cited hydrogen nuclei (single protons) and generates images with high structural
denition in soft tissue, see gure 2.1(b). The patient is placed in a station-
ary magnetic eld, causing a small fraction of the spinning protons to line up
in parallel or anti-parallel direction compared to the eld, this puts them in
specic energy states. Radio frequency pulses are sent into the body, mak-
ing the protons rotate in phase with the pulses and putting them in a state
of higher energy. When the stimulation is turned o, the protons emit their
excitation energy as a radio signal. This signal can generate a cross sectional
image, where dierent proton densities are represented by brighter or darker
areas in the image. Dierent relaxation times generate images with dierent
contrast. In brain imaging T1-weighted images (using the shorter spin-lattice
relaxation time) are used to dierentiate between white and grey matter of the
brain. T2-weighted images (using longer spin-spin relaxation time) are used
for investigation of diseased parts of the brain [3]. Applications in research
include Diusion MRI, which measures the diusion of water molecules in bio-
logical tissues; Multinuclear Imaging, which uses relaxation properties of other
molecules than hydrogen; and in eld research, where portable instruments use
the magnetic eld of the earth.
(a) (b)
Figure 2.1: Anatomical images. (a) is a coronal CT image of a torso
1
whereas
(b) is a sagittal MRI image of a head
2
.
2.1.3 Physiological information
Functional magnetic resonance imaging
Functional Magnetic Resonance Imaging (fMRI) is based on MRI and measures
the haemodynamic response, the change in blood ow, related to neural activity
in the brain. Haemoglobin has dierent magnetic properties depending on if
its oxygenated or deoxygenated, making the signal dependent of the level of
oxygenation. This allows mapping of the functionality of dierent parts of
the brain, see gure 2.2(a). The patient needs to lie still during the scan,
1
Image courtesy of Dr Jens Srensen, Uppsala University Hospital, Sweden
2
Department of Mathematics, Uppsala University, http://www.math.uu.se
Background 15
which usually takes between 15 minutes and 2 hours. Movement in excess of 3
millimetres will give unusable data. Images are usually taken every 14 seconds
[6].
Single photon emission computed tomography
Single Photon Emission Computed Tomography (SPECT) is based on counting
single photons that are emitted by gamma emitting radiopharmaceuticals. The
tracer is administrated intravenously, and the patient is positioned into a gamma
camera. Projection data is acquired covering 360 degrees around the patient.
The distribution of radiolabel molecules is measured and gives functional or
biochemical information, see gure 2.2(b) [3].
Positron emission tomography
Positron Emission Tomography (PET) is based on detection of positron-electron
annihilations events. A PET scan is prepared by administrating a radionuclide
to the patient. In more than 95% of the studies this is done intravenously by
injection, but the radionuclide can also be administrated orally by taking a pill
or by inhalation of gas. When the radionuclide decays, a positron is emitted.
The positron travels a few millimetres until it has lost its energy by collisions
and scatterings with the surrounding matter. When enough energy is lost the
positron annihilates with an electron and generates two co-linear photons, each
with 511keV energy, in anti-parallel directions. These photons are detected
approximately at the same time. Interaction between the photon and the crystal
in the detectors generates light ashes that are converted to electronic pulses
that are in turn recorded by the cameras electronics. PET generates images
with biological and functional information about the kinetic behaviour of the
radiotracer [3], see gure 2.2(c). Since PET is the imaging modality used in this
thesis, more details about PET will be discussed in section 2.2.
(a) (b) (c)
Figure 2.2: Functional images. (a) is an fMRI image of a brain
3
, (b) a coronal
SPECT image of a torso
4
and (c) a coronal PET image of a torso
5
.
3
Stanford Medicine, http://stanmed.stanford.edu
4
Image courtesy of Dr Pasha Razifar, GE Healthcare, Sweden
5
Image courtesy of Dr Jens Srensen, Uppsala University Hospital, Sweden
2.1.4 Integrated imaging modalities
PET/CT
PET/CT is a combination of PET and CT [7, 8]. The CT data replace the
transmission data from a regular PET scan, which is used for corrections in the
acquired data and helps with localization of the structures [3].
PET/MRI
Compared to PET/CT systems, PET/MRI not only oers improved contrast
in soft-tissue and reduced levels of ionizing radiation, but also MRI-specic infor-
mation such as functional, spectroscopic and diusion tensor imaging. PET/MRI
has been successfully implemented for pre-clinical studies but combining PET
and MRI for clinical use has proven to be a very challenging task. Technical
advances in this area are expected in the near future [9].
SPECT/CT
SPECT/CT is a device containing a CT system and a gamma camera on a single
gantry [10]. The SPECT procedure is performed, and then complemented with
a CT transmission scan. The transmission data is used for corrections in the
reconstruction of the projections [3]. Finally the data from the two imaging
modalities are also merged into a composite image.
2.1.5 Dierences and applications
CT scans are faster and more cost ecient than MRI and PET scans. CT images
contain less structural information and detail than MRI but they have relatively
low noise magnitude. The CT images have a high contrast between areas in the
body with dierent densities, like bone and soft tissues, but nearly no contrast
within the soft tissues. It can therefore be hard to distinguish pathological from
healthy structures and dierent soft tissues from each other in the CT-images,
and the high radiation dose limits the possibility of repeated scans [3]. CT is
relatively unsuitable for diagnosing disorders in the brain. However it is widely
used in oncology and for diagnosing heart diseases.
MRI provides greater contrast between soft tissues than CT, and is therefore
useful in neurological, musculoskeletal, cardiovascular, and oncological imaging.
MRI provides little information about the functionality of the brain. Medical
or bio stimulation implants such as pacemakers are considered a risk-increasing
factor, towards MRI scanning because of the magnetic and radio frequency
elds. However when using MRI or fMRI, the patient is not exposed to radiation
[3].
PET has a high level of statistical noise that limits its eciency [3]. The
information about the radio-chemicals used for particular functions is capable of
giving important support to research and diagnosis. It is often used in oncology
and drug development, and can also provide diagnosis in several neurological
disorders such as schizophrenia, Alzheimers disease, Parkinsons disease and
phobia [1114].
PET/CT has the advantages from both PET and CT. PET have high
sensitivity when it comes to functional and biochemical information, whereas
Background 17
CT gives high quality structural images [7, 8]. The combination has proved to
increase the diagnostic value compared to each imaging modality used separately
[15]. PET/CT has an important role in whole body imaging in oncology. It is
faster and more accurate than PET or CT alone for the depiction of malignancy.
SPECT projections suer from highly smoothed images and poor camera
resolution. On the other hand it provides 3D information that can complement
other studies. Therefore, it can provide information about localised function
in internal organs, such as functional cardiac or brain imaging. Research areas
include paediatrics [16].
SPECT/CT hybrid studies give accurate localization of tumours, measure-
ment of invasion into surrounding tissues, and characterization of their func-
tional status [10]. Two of SPECTs weaknesses are the long scanning time
needed and the poor resolution in the resulting images.
2.2 Positron emission tomography
2.2.1 Overview
PET is a non-invasive tomographic technique used to obtain anatomical and
physiological information in vivo in healthy and pathological organs and tissues.
PET has proven to be a useful tool in diagnosing cancer and cardiac diseases
and has an increasingly important role in providing earlier diagnosis in several
neurological disorders such as Alzheimers disease, Parkinsons disease, phobia,
epilepsy and cancer [1113]
Modern PET cameras mainly consist of a translating bed surrounded by
a set of detector rings. The detector rings contains crystal detectors (over
18.000 detectors) capable of creating a large number of trans-axial images with
a resolution depending on the scanner and image reconstruction algorithm.
(a) (b)
Figure 2.3: PET Camera GE/Advance Nxi
6
, where (a) shows the gantry and
translating bed, whereas (b) shows the detector ring.
6
General Electric, http://www.ge.com
2.2.2 Types of PET studies
PET images used for investigations of the body are usually acquired as a set
of stationary images across the body called static imaging. PET studies of the
brain are often performed dynamically, meaning that the acquired data is a set
of images from the same volume but from dierent time sequences. This makes
it possible to analyse the kinetic behaviour of the used tracer in dierent parts
of the brain. These multivariate image sets can be used to obtain physiological,
biochemical and functional information of the brain using analysis methods
such as kinetic modelling, compartment modelling, summation or multivariate
analysis [1721].
2.2.3 Acquisition
A complete PET study consists of three dierent scans; blank scan, transmission
scan and emission scan.
The blank scan is performed every day to normalize the detectors of the
camera, which are highly sensitive and therefore have dierent eciency. The
blank scan is performed with no patient in the camera. Instead of a tracer a
radioactive rod source rotating around the cameras gantry yield the detectable
photons [3].
The transmission scan is performed using the same source as in the blank
scan but with the object in the Field of View (FOV). The data from the trans-
mission scan and the blank scan is used for a so-called attenuation correction
to compensate for the scanned objects geometry, and the fact that the photons
from the decay site have to travel through dierent amounts of tissue when go-
ing in dierent directions. In an integrated system such as a PET/CT camera
the CT data can replace the transmission scan [3].
The emission scan is based on detection of positron-electron annihilation
events. When performing a PET emission scan a molecule, labelled with a
short-lived positron emitting radionuclide such as
11
C or
18
F, called a tracer is
administered to the patient prior to or during the scan. There is a wide range
of dierent tracers used in PET. A radionuclide is created using a cyclotron
or generator and is incorporated into a compound designed to follow a specic
physiological path. The radionuclide used when creating PET tracers is short
lived. Hence reducing the amount of radiation exposed to the patient, see table
2.1. This also makes it possible to perform several scans on the same patient
using the same or dierent kinds of tracer (multi-tracer study) [3].
Nuclide
+
energy [MeV]
+
range [mm] Half life [min]
11
C 0.96 1.1 20.3
15
O 1.70 2.5 2.04
18
F 0.64 0.6 110
68
Ga 1.90 2.9 67.7
Table 2.1: Commonly used isotopes in clinical PET studies.
When the substance decays it emits a positron and a neutrino. After travel-
ling a short distance, typically a few millimetres, the positron annihilates with
Background 19
an electron in the surrounding tissue. This annihilation event yields two co-
linear, anti-parallel, photons with 511 keV energy each. If detectors detect the
photons on opposite sides of the cameras FOV within a timing window of about
1012 ns (a photon travels 3 m in 10 ns) the event is registered as a true
coincidence. When a 511 keV photon hits one of the crystals a light ash is
emitted and registered by a photo detector. The light ash is converted to an
electrical pulse that is registered by the cameras electronics. After a detec-
tor has detected a photon it is paralysed for a short period of time. During
this so-called dead-time the detector cannot detect any photons. Apart from
dead-time there are a number of dierent factors that eect the precision of
the scan result, two major factors are random coincidences and scattered co-
incidences. Random coincidences are detections originating from two dierent
annihilations, but whose generated photons hit opposite detectors within the
time-window. Scattered coincidences are detections in which one or both of the
photons have been scattered in the tissue before hitting the detector, result-
ing in a Line of Response (LOR) (the line through the detectors detecting the
coincidence) that does not correspond to the position of the annihilation [3].
2.2.4 Noise
In traditional PET scanners, the main sources of noise are in decreasing order of
magnitude: emission, transmission and blank scan [22]. With newer attenuation
correction modes, e.g. CT, the noise from emission is clearly dominating. The
detector system only aects the magnitude of the noise whereas the recording
system, various corrections, the image reconstruction method and its parameters
also aect the distribution and correlation of the noise [3].
Radioactive decay, measured by PET detectors, obey the Poisson distribu-
tion. With an expected number of counts during a given time interval this
distribution will have the standard deviation

. The deviation from for each
sample from this distribution is dened as noise.
Apart from the statistical noise in the signal there are many factors that
aect the noise both during the acquisition and the reconstruction. Some fac-
tors that aect noise during the acquisition are the choice of acquisition mode,
scan duration, amount of administered tracer, geometry of tracer distribution,
detector eciencies, attenuation, dead-time, random coincidences and scattered
photons pairs that falsely have been registered as true coincidences. When re-
constructing the PET data the applied correction methods as well as the choice
of reconstruction algorithm have a heavy impact on the statistical properties of
the noise [3].
2.2.5 Corrections
Acquisition data from PET scans contain several errors that need to be compen-
sated for prior to the reconstruction procedure. These compensations include
corrections for dierences in detector eciencies, random coincidences, scattered
coincidences, dead-time and attenuation correction, where attenuation correc-
tion is the main factor to aect the measured counts in PET acquisition. Since
a scanned object usually is not symmetric, the photons need to travel through
dierent amounts of tissue. By using the results from the blank scan and the
transmission scan these dierences in attenuation can be compensated for [3].
2.2.6 Reconstruction
The two most commonly used methods for reconstructing tomographic data are
Filtered Back-Projection (FBP) and Ordered Subset Expectation Maximization
(OSEM). FBP is an analytical and computationally ecient inversion algorithm
for the two-dimensional radon transform that is both fast and easy to implement.
OSEM on the other hand is an optimized iterative expectation maximization
algorithm, which iteratively maximizes a target function in order to reconstruct
the tomographic data. In practice FBP produces relatively high noise variance in
regions with low signal compared to OSEM. OSEM on the other hand produces
noise that is more dependent on the signal, with high noise levels in high signal
regions and low noise levels in low signal regions.
2.3 Principal component analysis
2.3.1 Overview
Principal Component Analysis (PCA), also known as Hotelling or Karhunen-
Love (KL) transform, was discovered by Karl Pearson in 1901 [23]. It is a
method that explaines the variance-covariance structure through linear combi-
nations of the original variables. Each linear combination, known as Principal
Component (PC), is picked in such a way that it maximizes the variance, which
is the same as minimizing the Mean Squared Error (MSE). This is done under
the constraint that the norm of its weight vector equals one and that the new
PC is uncorrelated to all previous PCs. Even though there may be many vari-
ables, a large part of the systems total variability can often be accounted for by
a small number of PCs. The PCs can then replace the variables without any
signicant loss of information. PCAs general objectives are data reduction and
interpretation [24].
2.3.2 Algorithm
Each observation x
1
, x
2
, . . . , x
p
is stored as a row vector in the input matrix
X =
_
_
x
11
x
12
. . . x
1n
x
21
x
22
. . .
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
x
p1
x
p2
. . . x
pn
_
_
= [x
1
, x
2
, . . . , x
p
]
T
. (2.1)
The unbiased estimate of the covariance matrix associated with X is
S
X
=
_
_
s
11
s
12
. . . s
1p
s
21
s
22
. . .
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
s
p1
s
p2
. . . s
pp
_
_
(2.2)
where
s
ik
=
1
n 1
n
j=1
(x
ij
x
i
)(x
kj
x
k
). (2.3)
Background 21
If S
X
has the eigenvalue-eigenvector pairs (
1
, e
1
), (
2
, e
2
), . . . , (
p
, e
p
) where
1

2
. . .
p
0 and the eigenvectors are stored in the matrix E =
[e
1
, e
2
, . . . , e
p
]
T
the principal components are dened as
Y = EX = [y
1
, y
2
, . . . , y
p
]
T
(2.4)
where the variance is given by
V ar(y
i
) = e
T
i
S
X
e
i
=
i
, i = 1, 2, . . . , p (2.5)
and covariance by
Cov(y
i
, y
k
) = e
T
i
S
X
e
k
= 0, i = k. (2.6)
2.3.3 Pre-normalizations
Depending on the application it is often preferred to normalize data prior to
PCA. The most commonly used pre-normalizations prior to PCA are the
Removal of Mean (ROM) and Standardized Variables (SV) pre-normalization.
When pre-normalizing a dataset X the variables are mapped to a new set of
pre-normalized variables Z.
Removal of mean
If observations are known to have a non-zero expectation value it should be
subtracted from the observation to avoid PC
1
to always point in that direction.
In many datasets the expectation value is unknown but can be estimated by the
arithmetic mean. Removal of the arithmetic mean is the default option in most
implementations of PCA. The pre-normalized variable with removed mean is
dened as
z
ik
= x
ik
x
i
(2.7)
where x
ik
is the kth input variable in observation i.
Standardized variables
Observations may have dierent variations in the measurements and PCs from
non-normalized data are in general not invariant to this. A common approach
to handle this is to standardize the variables, giving each variable zero expec-
tation value and unit variance. This is done by removing the arithmetic mean
from the observations and then scale them with their standard deviation. The
standardized variable to x
ik
is dened as
z
ik
=
x
ik
x
i
s
i
(2.8)
where s
i
is the estimated standard deviation of the observation i. When using
pre-normalization to standardized variables PCA will choose eigenvectors based
on correlation instead of covariance [24].
Chapter 3
Materials and methods
3.1 Characterization of noise
3.1.1 Motive
A phantom study was performed in order to characterize the noise in PET data
reconstructed with FBP and OSEM.
3.1.2 The acquisition
The study was performed on an eXplore VISTA Dual-Ring small animal PET
scanner (GE Healthcare) seen in gure 3.1. The unit contains 2 rings of 18
phoswich detector modules capable of performing 3D data acquisition with an
axial Field of View (FOV) of 48 mm and an eective trans-axial FOV of 67 mm.
The spatial resolution is 0.81.0 mm for reconstructions made with OSEM and
1.51.8 mm for reconstructions made with FBP [25].
Figure 3.1: eXplore VISTA small animal PET scanner
1
In the experiments a phantom with two cylindrical inserts was used. Both
inserts was 15 mm in diameter. The insert in the upper part of the gantry was
lled with 223 kBq/cm
3
of
18
F and the insert in the left part of the gantry with
73 kBq/cm
3
of
18
F. The duration of the emission scan was 90 minutes.
1
General Electric, http://www.ge.com
Acquired data was reconstructed from list mode to a dynamic dataset by
rst applying the FOurier REbinning (FORE) algorithm to produce 61 two
dimensional sinograms with a spatial resolution of 175 for 128 angles spanning
the axial FOV for 18 frames. Corrections were made to compensate for the
decay of
18
F. Two datasets were then reconstructed from the sinograms using
OSEM and FBP in 2D mode. The dimensions of the reconstructed data were
175 175 61 18.
3.1.3 Selection of samples
Three circular Region of Interests (ROIs) of equal size were selected. One for
each insert and one for a region where there were no radioactive substance
present. Each ROI had a diameter of 11 mm which gave N
ROI
= 633 sample
points per ROI. The 4 mm reduction in diameter compared to the inserts was
chosen to avoid most of the spillover eects since the spatial resolution measured
with Full Width at Half Maximum (FWHM) is less than 2 mm for the eXplore
VISTA scanner [25], see gure 3.2.
Figure 3.2: An FBP reconstruction of slice 31 in the rst frame, showing a cross
section of the two inserts. The outline of the three ROIs is drawn in white.
3.1.4 Expectation value
The expectation value was estimated for each ROI in all slices and frames for
both FBP and OSEM using the arithmetic mean
x =
1
N
ROI
N
ROI
i=1
x
i
. (3.1)
3.1.5 Standard deviation
The sample standard deviation was calculated for each ROI in all slices and
frames for both FBP and OSEM using the square root of the unbiased sample
Materials and methods 25
variance
s =
_
1
N
ROI
1
N
ROI
i=1
(x
i
x)
2
. (3.2)
3.1.6 Correlation between slices
Before estimating the correlation between slices all samples within each ROI
were divided into 9 groups where every third sample in u and v direction was
put in the same group. This was done in order to reduce correlation between
samples within the same group since this would alter the correlation estimate.
The distance between the samples was set to three since a shorter distance would
result in considerably more correlation between the samples within each group
and a longer distance would lead to too few samples in each group. It shall also
be mentioned that even though the data was divided into groups the arithmetic
mean of all samples within a ROI was used to estimate the expectation value
for all samples within that ROI.
For each group the correlation matrix of the correlations between the m
slices is
R
Slices
=
_
_
1 r
12
. . . r
1m
r
21
1 . . .
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
r
m1
r
m2
. . . 1
_
_
, r
ik
=
s
ik
s
ii
s
kk
(3.3)
where the covariances are calculated with the sample covariance
s
ik
=
1
p N
Group
1
p
n=1
N
Group
j=1
(x
ijn
x
i
)(x
kjn
x
k
). (3.4)
N
Group
is the number of samples within the current group and p is the number
of frames. x
ijn
is the j:th sample in the current group and ROI in slice i (or k
for the corresponding variable x
kjn
) at frame n. x
in
(or x
kn
) is the mean of all
samples in all groups in the current ROI in slice i (or k) and frame n.
The mean of the 9 correlation matrices was calculated, and the two diagonals
closest to the main diagonal was plotted for each ROI and dataset.
3.1.7 Correlation between frames
The estimation of the correlation between frames was done in much the same
way as for slices. The samples in each ROI were divided into 9 groups, the
sample correlation matrix of the correlations between the p frames is
R
Frames
=
_
_
1 r
12
. . . r
1p
r
21
1 . . .
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
r
p1
r
p2
. . . 1
_
_
, r
ik
=
s
ik
s
ii
s
kk
(3.5)
where the covariances are calculated with the sample covariance
s
ik
=
1
m N
Group
1
m
w=1
N
Group
j=1
(x
ijw
x
i
)(x
kjw
x
k
). (3.6)
N
Group
is the number of samples within the current group and m is the number
of slices. x
ijw
is the j:th sample in the current group and ROI in frame i (or k
for the corresponding variable x
kjw
) at slice w. x
iw
(or x
kw
) is the mean of all
samples in all groups in the current ROI in frame i (or k) and slice w.
The mean of the 9 correlation matrices was calculated and the diagonal
closest to the main diagonal was plotted for each ROI and dataset.
3.1.8 Correlation between samples within the same slice
A PET slice can be seen as a stochastic process with properties that can be
estimated if enough independent realizations are available. One way of acquiring
independent realizations of a slice or a whole scan is to perform gated scans
[26]. In this study only one scan was available and the dierent slices in each
observation had to be used. Since 2D reconstruction was used the dierences
in the statistical properties of the dierent slices were small enough to treat
the slices as separate realizations of the same stochastic process of a slice. The
calculations are similar to those for the correlation between slices and frames but
there is one sample correlation matrix with the lags (k
1
, k
2
) for each choice of
coordinates (u, v), i.e. the correlation matrix is four dimensional with elements
given by
r
u,v,u+k
1
,v+k
2
=
s
u,v,u+k
1
,v+k
2
s
u,v,u,v
s
u+k
1
,v+k
2
,u+k
1
,v+k
2
(3.7)
with covariances estimated from the sample covariance
s
u,v,u+k
1
,v+k
2
=
1
p m1
p
n=1
m
w=1
(x
u,v,w,n
x
u,v
)(x
u+k
1
,v+k
2
,w,n
x
u+k
1
,v+k
2
).
(3.8)
x
u,v,w,n
is the sample at coordinate (u, v, w, n) and x
u,v
is the mean of the
samples at coordinate (u, v) over all frames and slices.
The correlation at dierent coordinates (u, v) within a slice for FBP and
OSEM reconstructed data was investigated, both inside the three ROIs and
outside the inserts. The dierences in extent, orientation and isotropy of the
correlation in datasets reconstructed with FBP and OSEM where studied.
from one realization
Auto-Correlation Function (ACF) is a property of a stochastic process that
describe its correlation between dierent points in time, or space depending of
the unity of the dimensions in the stochastic process. So far the dierent slices
have been treated as dierent realizations of a stochastic process of a slice when
estimating the ACF between points within a slice. If the stochastic process is
Weak-Sense Stationary (WSS) the ACF can also be estimated from a single
realization. WSS is a weaker form of stationarity that requires mean and ACF
to be independent of time, or coordinate within the slice in this case. If X[u, v]
is the stochastic process of a slice these two criterion are written as
E{X[u, v]} = m (3.9)
and
E{X[u + k
1
, v + k
2
]X[u, v]} = E{X[k
1
, k
2
]
2
}. (3.10)
If a region A in a slice is WSS the samples within that region can be used to
estimate the ACF, that is the same for every point within this region. To do
this a smaller region B inside region A is used. An estimate used to estimate the
auto-correlation coecient (normalized auto-correlation) for coordinate (u, v) is
dened as
r
k
1
,k
2
=
(u,v)A
(x[u, v] x
k
1
,k
2
)
_
b[u k
1
, v k
2
]
b
_

(u,v)A
(x[u, v] x
k
1
,k
2
)
2
(u,v)A
_
b[u k
1
, v k
2
]
b
_
2
(3.11)
where b is the template region within B with the arithmetic mean

b, x is the
realization of the slice and x
k
1
,k
2
the mean of x in a region of size B placed
on the coordinate (u, v). Even though only a single realization x is used, the
estimate will approach the autocorrelation function as the size of A and B is
increased.
The estimate has at least two applications. If used on WSS signals it es-
timates the ACF and if used on non-WSS signals it identies similarities and
periodicities within the signal (how well B is correlated with A).
This estimate was used in dierent parts of a trans-axial slice and the results
were compared to the ACF estimates in section 3.1.8.
To compare this estimate to the sample correlation the region A was set to
21 21 pixels, and it was then placed on the centre of each ROI in the centre
slice in the middle frame in the dataset. This estimated the ACF for the 5
neighbouring samples in each direction for each ROI (B was set to an 11 11
pixel region).
3.2 Reduction of noise
3.2.1 Masked volume-wise PCA
PCA can be performed on a set of images of any dimension, for example images
of an object from dierent points in time. PCA will then separate the images
into PC-images where early PC-images describe most of the variance within
the input set of images. This approach has been used on dynamic PET data
resulting in images with high contrast between structures with dierent kinetic
behaviours of a tracer. PCA can be performed with either slices or volumes as
observations, and either on the whole dataset or on selected parts [4].
Since it is common that only a limited part of a dataset contains informa-
tion that is actually of interest, the dataset can be masked to only include data
within this Volume of Interest (VOI). This procedure reduces memory usage,
computation time and also has the advantage that the directions of the eigen-
vectors only are dependent of data inside the VOI and not inuenced by noise
or other disturbing signals in the background.
Masked Volume-Wise PCA (MVW-PCA) is performed in a number of steps:
A mask representing the scanned object is created from either transmission im-
ages from PET, or CT if a PET/CT study is performed. The mask is used to
extract the VOI from the background and can also be used to perform back-
ground noise pre-normalization, described in section 3.2.3. PCA is performed
on the data within the VOI. PCs created with MVW-PCA is referred to as
MVW-PCs[4]. To view the MVW-PCs they are placed back into the mask, see
gure 3.3.

Frame 1
Frame 2
Frame p
PET data
Mask Masked
data volumes
MVW-PCs Unmasked
MVW-PCs
Pre-normalize and mask PCA Unmask
Figure 3.3: Illustration of the MVW-PCA procedure.
In this report a slightly dierent approach is used when creating the unmasked
MVW-PCs. Instead of projecting the masked pre-normalized data onto the
eigenvectors retrieved from the PCA, the pre-normalized non-masked PET data
is projected onto the eigenvectors. This gives an identical result inside the mask
as seen in gure 3.4, the memory usage and speed is the same, but the removed
background will still be visible instead of the sharp mask border and the padded
zeroes seen in gure 3.4(a). Another advantage of using this method is that no
information in the PET dataset is lost during the MVW-PCA and the whole
original dataset can therefore be reconstructed using the method described in
section 3.2.2.
(a)

50
40
30
20
10
0
10
20
30
40
50
(a)
(b)

50
40
30
20
10
0
10
20
30
40
50
(b)
Figure 3.4: A slice from MVW-PC
1
showing the dierences between masked
data (a) and non-masked data (b) projected onto the rst eigenvector. The
study was performed on the brain of a patient with alzheimers disease injected
with the tracer
11
C-Pittsburgh Compound-B.
3.2.2 Reconstruction from selected principal components
Since the signl in PET datasets is temporally correlated whereas the noise is
not, MVW-PCA can be used to reduce the dimensionality of datasets. In the
space spanned by the MVW-PCs the signal is mostly described by lower-order
MVW-PCs whereas noise is described by higher-order MVW-PCs. It is therefore
usefull to be able to separate data spanned by the low-order MVW-PCs from
data spanned by the higher-order MVW-PCs in the original frame-space.
Since PCA and MVW-PCA with non-masked data merely perform a change
of basis of the pre-normalized data, no quantitative information is lost during
the MVW-PCA and the full original dataset or parts of it can be reconstructed
from the MVW-PCs.
As described in the section 2.3.2 PCs are created from the equation
Y = EZ,
where Z is the pre-normalized data. To retrieve the pre-normalized data from
all MVW-PCs one can simply use the inverse of E.
Z = E
1
Y
In order to calculate a selected number of MVW-PCs from the pre-normalized
data, rows that correspond to unwanted MVW-PCs are removed from E, creat-
ing

E and

Y. In the same way columns that correspond to unwanted MVW-PCs
are removed from E
1
in order to calculate the modied pre-normalized data

Z
from the selected number of MVW-PCs in

Y. Something to notice is that E is
an orthogonal eigenvector matrix that have the property E
T
= E
1
which saves
computation time. MVW-PCs may now eciently be removed from Z without
any unnecessary calculations using
Z =

E
-1
Y =

E
-1
EZ =

E
T
EZ = AZ,
where A =

E
T
E. The modied input matrix

X is then retrieved from

Z by
doing the inverse normalization. A ow chart of the procedure is shown in gure
3.5.
X Z Y
X

Z

Y
Pre-normalization MVW-PCA
Un-normalization Change of basis
Removal of
MVW-PCs
Figure 3.5: Removal of MVW-PCs from X
3.2.3 Background noise pre-normalization
When performing 2D reconstructions of PET data, each slice tends to have
varying levels of noise. Since PCA cannot separate variance due to signal from
variance due to noise, it is desirable to have each slice scaled with the standard
deviation of the noise to get unit noise variance in every observation. In PET
data reconstructed with FBP the background contains a large amount of noise.
Background noise pre-normalization use a mask to separate the background
from the VOI in order to estimate the standard deviation of the background in
each slice. The pre-normalization is performed using the equation
z
ik
=
x
ik
x
i
s
w
(3.12)
where s
w
is the estimated standard deviation for the samples within the back-
ground of slice w where the sample x
ik
is located. Background noise pre-
normalization is only used on PET data reconstructed with FBP since the noise
in data reconstructed with OSEM is too signal dependent, which results in noise
magnitudes close to zero outside the VOI [4].
3.2.4 Higher-order principal component pre-normalization
Higher-Order Principal Component (HOPC) pre-normalization is a novel method
presented for the rst time in this report. Much like Background Noise (BN)
pre-normalization it retrieves an estimate of each slices standard deviation,
which is then used for pre-normalizing the slices. Since the reconstruction of
early MVW-PCs is a good approximation of the expectation value in a dataset,
it can be removed and the standard deviation of the reconstruction of the rest
of the MVW-PCs should approximately be that of the noise.
The pre-normalization can be divided into three steps. The rst is to do
MVW-PCA on the whole FOV (can also be performed on the VOI if speed
is of high importance) without any pre-normalization and set the rst MVW-
PC to zero. The second step is to reconstruct the MVW-PCs and estimate
the standard deviation in each slice in the reconstruction. The third step is
to perform the prenormalization described in equation 3.12 but with the new
estimated noise standard deviation s
w
.
X Z
X
s
w
Removal of
lower-order PCs
Estimation of
std
(x
ik
x
i
)/s
w
Figure 3.6: Late Principal Component Pre-normalization
The advantage with HOPC pre-normalization compared to background noise
pre-normalization is that it is not dependent on the presence of noise in the
background and that the background noise is proportional to the amount of
noise in the rest of the slice.
In order to decide the number of early MVW-PCs to use in the reconstruction
of late MVW-PCs the standard deviation of the estimated noise was compared
to the standard deviation of the background in datasets reconstructed with
FBP. To retrieve a quantitative measure of how well the two curves t, one of
the curves was multiplied with a scalar value that minimizes the MSE. This
was done since PCA picks the same eigenvectors no matter the scale of the
input data. The MSE for the two curves was then calculated. The comparisons
were made on two clinical datasets reconstructed with FBP, where the rst was
a dataset retrieved from a full body scan with the tracer Fluorodeoxyglucose
(FDG) described in section 3.2.6, and the second was a brain study with the
tracer Pittsburgh Compound-B (PIB).
3.2.5 Synthetic images
Motive
To get an understanding of how PCA acts on actual dynamic PET data, syn-
thetic images were produced. This was chosen as a starting point to the project
since realizations of noise and signal are known prior to the analysis and can
be used to validate the results. Another advantage of using synthetic images
is the possibility to modify and study one parameter at a time to get a better
understanding of how the analysis method react to dierent input.
Signal
In this study MATLAB (The Mathworks Inc., Natick, Massachusetts) was used
to create various datasets of dynamic synthetic images. The synthetic images
had one slice per observation with a size of 128 128 pixels that included four
geometric structures. The spatial size and the kinetic behaviour of the structures
was chosen to resemble the cerebellum (CBL), occipital cortex (Occip), frontal
cortex (FrntCx) and white matter (WhitM) in PET studies with the tracer
11
C
labelled PIB as seen in gure 3.7.
CBL
WhitM
FrntCx
Occip
(a) Spatial structures
10 20 30 40 50
0
0.5
1
1.5
2
2.5
3
3.5
Time [min]
C
o
n
c
e
n
t
r
a
t
i
o
n

o
f

a
c
t
i
v
i
t
y

[
B
q
/
c
m
3
]

Noise
CBL
FrntCx
WhitM
Occip
(b) Temporal expectation
values
10 20 30 40 50
0
0.5
1
1.5
2
2.5
3
3.5
Time [min]
C
o
n
c
e
n
t
r
a
t
i
o
n

o
f

a
c
t
i
v
i
t
y

[
B
q
/
c
m
3
]

Noise
CBL
FrntCx
WhitM
Occip
(c) Temporal standard devi-
ations
Figure 3.7: Spatial and temporal behaviour of the signal structures. The spatial
background mask used in background noise pre-normalization is shown in a black
colour.
The temporal behaviour of the four TimeActivity Curves (TACs) was cal-
culated with the kinetic function
k(t) = e
t
(1 e
t
), (3.13)
using the parameters found in table 3.1. Spatially all regions had a constant
value. The signal was then convoluted with a point-spread function to create a
spillover eect similar to that of images retrieved from a PET scanner. The time
interval between the dierent frames was set to an interval used in 24-frame (60
min) PET studies with the tracer PIB and the values in the time vector t was
set to the centre of each interval, see table 3.2.
Structure Function
CBL (mean) k
1
(t) 4.0 0.04 0.8
FrntCx (mean) k
2
(t) 3.0 0.01 1.0
WhitM (mean) k
3
(t) 1.5 0.007 0.7
Occip (mean) k
4
(t) 3.5 0.02 1.0
Noise (std.) k
n
(t) 0.7 0.03 1.5
Table 3.1: Parameters for the temporal functions.
Noise
Raw PET data is usually considered to be Poisson distributed, but after recon-
struction the noise is often approximated as normal distributed. The standard
deviation, k
n
, of the noise was calculated with equation 3.13 with parameters
from table 3.1. The standard deviation of the added noise was spatially con-
stant, which is a simplication of the noise typically seen in data reconstructed
with FBP. Both spatially correlated and uncorrelated noise was studied. To
correlate the noise, it was convoluted with a low pass lter followed by a mul-
tiplication with a scalar for each frame to compensate for the loss of standard
Frame Length [min] Time, t [min]
1 0.5 0.25
2 0.5 0.75
3 0.5 1.25
4 0.5 1.75
5 1 2.5
6 1 3.5
7 1 4.5
8 1 5.5
9 1 6.5
10 1 7.5
11 1 8.5
12 1 9.5
13 1 10.5
14 3 12.5
15 3 15.5
16 5 18.5
17 5 22.5
18 5 27.5
19 5 32.5
20 5 37.5
21 5 42.5
22 5 47.5
23 5 52.5
24 5 57.5
Table 3.2: Time protocol for a 24-frame scan (60 min) with the tracer PIB.
deviation. The same realization of the noise was used for both uncorrelated and
correlated noise.
The synthetic datasets, x(t), were dened with the model
x(t) =
_
4
i=1
k
i
(t) v
i
_

v
+ c
t
(k
n
(t) n)
e
, (3.14)
where v
i
is a vector dening the spatial structure i, seen in gure 3.7(a). k
i
(t)
and k
n
(t) also shown in gure 3.7 are the functions dened by equation 3.13
with parameters from table 3.1. n is a noise vector for the entire slice that
has zero mean and unit variance.
v
and
n
are point spread functions (low
pass lters) and c
t
a constant used to compensate for the reduction in standard
deviation caused by the convolution.
Generated datasets
Three synthetic datasets were generated using the kinetic functions and struc-
tures described in section 3.2.5 and 3.2.5. The rst set consisted of nothing
more than the signal, which is the four regions convoluted with a point-spread
function that gave the edges a blurry appearance, see gure 3.8. The second
and third dataset had the same signal components as the rst dataset, but with
added Gaussian noise. The second dataset has uncorrelated noise that can be
seen in gure 3.9, and the third dataset had correlated noise that is shown in
gure 3.10.

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1
1.5
2
2.5
3
Figure 3.8: Montage of dataset without any noise. The sequence should be seen
along rows starting from the upper left corner and ending in the lower right.
Pre-normalization
All datasets described in 3.2.5 were pre-normalized with the ROM pre-normalization,
pre-normalized to SV, BN pre-normalized with the background mask seen in g-
ure 3.7(a) and Higher-Order Principal Component (HOPC) pre-normalized.
Estimates
Since the signal in the synthetic datasets was known in advance, it was used to
retrieve accurate estimates of the noise.
The standard deviation of the noise in the pre-normalized noisy datasets was
calculated by subtracting the non-noisy dataset that had been pre-normalized
with the same coecients as the two noisy datasets.
In order to get a quantitative evaluation of the performance of the dierent
pre-normalizations, reconstructions of early PCs was used and compared to
the correct signal. To measure the error in the reconstructions the MSE was
calculated with
MSE =
1
N p
(u,v,n)S
(x[u, v, n] x[u, v, n])
2
, (3.15)
where N is the number of samples in an observation, p is the number of obser-
vations, (u, v, n) are the coordinates within a synthetic dataset S, x[u, v, n] is
the signal dataset and x[u, v, n] is the reconstructed dataset.

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]
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
Figure 3.9: Montage of dataset with uncorrelated noise. The sequence should
be seen along rows starting from the upper left corner and ending in the lower
right.

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3
3.5
4
4.5
5
Figure 3.10: Montage of dataset with correlated noise. The sequence should
be seen along rows starting from the upper left corner and ending in the lower
right.
The MSE was calculated on datasets reconstructed with; the rst PC, the
rst two PCs, the rst three PCs and the rst four PCs. This was done
on both the dataset with uncorrelated and correlated noise, and for all pre-
normalizations.
3.2.6 Clinical study
In order to compare HOPC pre-normalization to other pre-normalization meth-
ods prior to MVW-PCA on clinical data, two VOIs were placed on regions with
dierent kinetic behaviour. Dimension reduction was then used to reconstruct
datasets from various numbers of early MVW-PCs. Two dierent estimates
were used on the pre-normalized datasets in order to measure the performance
of the pre-normalizations. In this way it was possible to compare the amount
of signal accounted for by the MVW-PCs and also to compare the reduction of
noise within each VOI.
Dataset and VOIs
A clinical dynamic PET dataset from a full body scan performed with the
tracer FDG was used. The dataset had 14 frames and both FBP and OSEM
reconstructions were available. The time protocol described in table 3.3 was
used during the acquisition.
Frame Length [min] Time, t [min]
1 1 0.5
2 1 1.5
3 1 2.5
4 1 3.5
5 1 4.5
6 3 6.5
7 3 9.5
8 3 12.5
9 3 15.5
10 3 18.5
11 5 22.5
12 5 27.5
13 5 32.5
14 10 40
Table 3.3: Time protocol for a 14-frame full body scan (45 min) with the tracer
FDG.
Two VOIs were selected from the data reconstructed with OSEM. The rst
VOI was placed on a tumour on the liver and the second VOI on the stomach.
Dimension reduction
Both datasets reconstructed with FBP and OSEM were pre-normalized with
the ROM, SV, BN and HOPC pre-normalization, creating eight new datasets.
MVW-PCA was performed on all of these datasets and reconstructions were
made with MVW-PC
1
, with MVW-PC
1
and MVW-PC
2
, with MVW-PC
1
,
MVW-PC
2
and MVW-PC
3
, and so on until all but the last MVW-PC (MVW-PC
14
)
was used in a reconstruction. In this way 104 datasets (2 4 13 = 104) were
created.
Estimates
The most common way to measure the signal within a VOI or ROI is to calculate
the arithmetic mean of the samples. Therefore it is important to compare the
arithmetic mean in regions within the original dataset to the mean in the same
regions in the dimension-reduced datasets. This is important since the dierence
in quantitative measurements should not deviate too much. In order to get a
scalar estimate that could be used to compare the dierences in arithmetic mean
for all frames, the MSE of the mean was calculated with
MSE
mean
=
1
p
p
n=1
( x[n] x[n])
2
(3.16)
where p is the number of frames, x[n] is the arithmetic mean within the VOI
of the original data and x[n] is the mean within the VOI of the reconstructed
data.
Usually, when drawing a VOI within a structure, the volume is not com-
pletely homogeneous. There are variations in scale between the TACs but they
all share a similar kinetic behaviour. Since TACs that only diers in scale can
be described by one PC, MVW-PCA was performed on the VOI in order to
nd one MVW-PC than optimally represents the TACs in a mean square sense.
This optimal component was reconstructed and referred to as x[u, v, w, n]. To
measure the deviation from x[u, v, w, n] the MSE was used. The MSE between
x[u, v, w, n] and the reconstructed signal is
MSE
x
=
1
p N
VOI
p
n=1
VOI
( x[u, v, w, n] x[u, v, w, n])
2
. (3.17)
In other words, MSE
x
is the mean of the squared dierence between the N
VOI
estimated optimal TACs and the corresponding reconstructed TACs. p is the
number of frames.
Chapter 4
Results
4.1 Characterization of noise
4.1.1 Frames
To visualize the dierence in arithmetic mean and sample standard deviation
for the ROIs in dierent frames, the arithmetic mean of the measurements in
all slices were calculated. The result is shown in gure 4.1.
20 40 60 80
0
10
20
30
40
(d)
20 40 60 80
0
10
20
30
(e)
20 40 60 80
0
5
10
15
(f)
20 40 60 80
0
100
200
(a)
20 40 60 80
0
20
40
(b)
20 40 60 80
0
5
10
(c)
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3
]
Time [min]
Figure 4.1: Arithmetic mean (a)(c) and sample standard deviation (d)(f) for
FBP (dashed lines) and OSEM (solid lines) over time in the three ROIs: High
activity ROI (a) and (d), low activity ROI (b) and (e), and no activity ROI (c)
and (f).
OSEM had a slightly higher expectation value in the high and low activity
ROIs compared to FBP, whereas the expectation value in the no activity ROI is
a lot lower for OSEM compared to FBP. OSEM also showed a heavy decrease
in standard deviation in the low and no activity ROIs compared to FBP. Apart
from the dierences between FBP and OSEM one can see that the arithmetic
mean is constant, whereas the standard deviation shows a positive trend over
time.
Correlation between dierent frames should be close to zero and the es-
timated correlation coecient for the closest neighbouring frames, shown in
gure 4.2, conrms this.
20 40 60 80
0
0.5
1
(a)
20 40 60 80
0
0.5
1
(b)
20 40 60 80
0
0.5
1
(c)
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t
Frame
Figure 4.2: Correlation coecient for FBP (dashed lines) and OSEM (solid
lines) for the closest neighbouring frames in the three ROIs: High activity ROI
(a), low activity ROI (b), and no activity ROI (c).
4.1.2 Slices
To visualize the dierence in arithmetic mean and sample standard deviation
for the ROIs in dierent slices, the arithmetic mean of the measurements in all
frames were calculated. The result is shown in gure 4.3.
20 10 0 10 20
0
50
100
150
(d)
20 10 0 10 20
0
20
40
60
(e)
20 10 0 10 20
0
10
20
30
40
(f)
20 10 0 10 20
0
100
200
300
(a)
20 10 0 10 20
0
20
40
60
(b)
20 10 0 10 20
0
10
20
30
(c)
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m
3
Axial offset [mm]
Figure 4.3: Arithmetic mean (a)(c) and sample standard deviation (d)(f) for
FBP (dashed lines) and OSEM (solid lines) for dierent axial osets in the
three ROIs: High activity ROI (a) and (d), low activity ROI (b) and (e), and
no activity ROI (c) and (f).
The same dierences in expectation value and standard deviation between
OSEM and FBP seen in gure 4.1 where visible in 4.3. Other general obser-
vations were that the outer slices close to the opening of the gantry had lower
expectation value than the ones near the centre and that the standard deviation
Results 41
had a characteristic shape with high values near the edges and two peeks at slice
25 and 37. The estimated expectation value in the no activity ROI also had
this shape. One can also see that odd slices tend to have a slightly higher stan-
dard deviation compared to the even neighbouring slices, resulting in a jagged
appearance.
An inspection of the slice correlation matrix diagonals indicated that there
were correlations to the closest neighbouring slice. The estimated correlation
coecient to the closest and second closest neighbouring slice is shown in gure
4.4.
20 10 0 10 20
0
0.5
1
(d)
20 10 0 10 20
0
0.5
1
(e)
20 10 0 10 20
0
0.5
1
(f)
20 10 0 10 20
0
0.5
1
(a)
20 10 0 10 20
0
0.5
1
(b)
20 10 0 10 20
0
0.5
1
(c)
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Slice
Figure 4.4: Correlation coecient for the closest (a)(c), and the second closest
(d)(f) neighbouring slices for FBP (dashed lines) and OSEM (solid lines) in
the three ROIs: High activity ROI (a), low activity ROI (b), and no activity
ROI (c).
The only visible dierence in correlation between slices when comparing FBP
and OSEM is in the no activity region where FBP has a lower correlation co-
ecient compared to OSEM. In general, the correlation coecient between
neighbouring slices is approximately 0.4 near the centre of the gantry, com-
pared to 0.2 closer to the edges. One can also distinguish a pattern in the
correlation with an almost at peak between the 26th and 36th slice pair. The
correlation to the second nearest neighbouring slice is close to zero.
The sample correlation at the centre coordinate within the three regions is shown
in gure 4.5. The rst column shows sum images with a marked dot and small
rectangle. The dot indicates the centre coordinate, and the rectangle shows an
11 11 pixel region of neighbouring samples to which the correlation has been
calculated. The second column shows the correlation in FBP data, and the
third column show the correlation in OSEM data.
The correlation in data reconstructed with FBP and OSEM has very dierent
properties. In regions where both FBP and OSEM has isotropic correlation, as
can be seen in the upper row, the width of the correlation in FBP is smaller than
the width of the correlation in OSEM. But, this is not true for all coordinates
since the amount of correlation is highly dependent on the orientation of the
correlation. In this dataset the correlation in the FBP data was oriented towards
the strongest region of activity while the correlation in OSEM was orthogonally
oriented towards the closest region of activity. Overall, the correlation in OSEM
has a larger extent in the non-orientation direction and is more isotropic in
regions with activity compared to the correlation in FBP.
Coordinate & Region FBP OSEM
50 100 150
20
40
60
80
100
120
140
160

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0.01
0.015
0.02
0.025
0.03
5 0 5
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5

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160

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0.03
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5 0 5
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5 0 5
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1
0.5
0
0.5
1
Figure 4.5: Sample correlation coecient for data reconstructed with FBP and
OSEM for the centre coordinate within each ROI.
from one realization
The result of the ACF estimate for WSS regions is shown in gure 4.6. In the
rst column two rectangles are drawn on the slice used when calculating the
ACF estimate. The largest rectangle corresponds to the region A where the
signal should be WSS and the smallest region has the size of the 11 11 pixel
region B for which the correlation is calculated. Since the region A is assumed
to be WSS the whole region will have the same estimated ACF, with a size equal
to that of B. The correlation for FBP and OSEM data is shown in column two
and three.
There are similarities between this estimated correlation and the sample
correlation, for example in the high intensity region (rst row) the correlation in
the FBP data has a small extent compared to that of OSEM, and the correlation
in the FBP data has the same orientation as the sample correlation. In this slice
Results 43
realization the orientation of the correlation in OSEM was diered from the
sample correlation. For example within the high intensity region the correlation
was not as isotropic as the sample correlation and the orientation in the low
and no activity regions is not as easy to distinguish as it is with the sample
correlation. Another observation is that this estimate much more often yields
negative correlation compared to the sample correlation.
Regions FBP OSEM
50 100 150
20
40
60
80
100
120
140
160

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0.015
0.02
0.025
0.03
0.035
5 0 5
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1
0.5
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0.5
1
Figure 4.6: Correlation coecient for each ROI in data reconstructed with FBP
and OSEM, estimated with the ACF estimate for WSS regions.
4.2 Reduction of noise
4.2.1 Higher-order principal component pre-normalization
The scaled standard deviation of data with one to three low-order MVW-PCs
removed and the estimated standard deviation of the background noise is shown
in gure 4.7.
2 4 6 8 10 12 14
1000
2000
3000
4000
5000
6000
7000
8000
(a)
5 10 15 20
500
1000
1500
2000
2500
3000
3500
4000
4500
(b)
S
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a
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]
Frame
Figure 4.7: Scaled plots of the standard deviation used by the HOPC pre-
normalization, from a full body study using the tracer FDG (a) and a brain
study using the tracer PIB (b). HOPC
1
(), HOPC
2
() and HOPC
3
() are
compared to the background noise (). The HOPC index corresponds to the
number of low-order MVW-PCs that where removed in the pre-normalization
step.
To measure the deviation from the standard deviation of the reconstructions
compared to the background noise, the MSE was calculated for reconstructions
with up to 13 low-order MVW-PCs removed. The result is shown in 4.8.
1 2 3 4 5 6 7 8 9 10 11 12 13
10
5
10
6
10
7
10
8
(a)
1 2 3 4 5 6 7 8 9 10 11 12 13
10
5
10
6
10
7
(b)
M
S
E
[
(
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m
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)
2
]
Low-order MVW-PCs removed
Figure 4.8: MSE of the scaled standard deviation, used by HOPC pre-
normalization, with respect to the standard deviation of the background noise.
(a) shows the result from the full body study and (b) shows the result from the
brain study.
Figure 4.8 shows that reconstruction without the rst or the two rst MVW-
PCs, in the HOPC pre-normalization, results in scaling coecients that are
close to the BN pre-normalization in a mean square sense.
Results 45
4.2.2 Synthetic images
PCs and eigenvectors
PCA was performed on the dataset without any added noise. The data was nor-
malized with the default removal of mean pre-normalization. The PCs, eigen-
vectors as well as the corresponding eigenvalues are shown in gure 4.9.
PC
1
PC
2
PC
3
PC
4
PC
5
e
1
e
2
e
3
e
4
e
5
10 20 30 40 50
1
0.5
0
0.5
1
Time [min]
10 20 30 40 50
1
0.5
0
0.5
1
Time [min]
10 20 30 40 50
1
0.5
0
0.5
1
Time [min]
10 20 30 40 50
1
0.5
0
0.5
1
Time [min]
10 20 30 40 50
1
0.5
0
0.5
1
Time [min]
1
6.1
2
1.2 10
1
3
2.1 10
3
4
7.9 10
5
5
0
Figure 4.9: The rst ve PCs, corresponding eigenvectors and eigenvalues for
synthetic data without noise. Samples with red colour are positive while samples
in blue colour are negative.
PCA on the dataset without any added noise gave four principal components
according to the fth eigenvalue that is zero, indicating that the eigenvector has
zero length. According to the rst eigenvector, PC
1
is similar to a mean image
but has a slight emphasis on early pre-normalized frames. One can also see that
all PCs contain both positive and negative samples.
The PCA on pre-normalized datasets with added uncorrelated and correlated
Gaussian noise is shown in gure 4.10 and 4.11. The used pre-normalizations
were Removal of Mean (ROM), SV, BN and HOPC pre-normalization with
MVW-PC
1
removed.
Removal of Mean (ROM) pre-normalization gave one PC with low noise while
the other three methods gave two PCs with very similar appearance. This can
also be seen in the corresponding eigenvectors since late eigenvectors tend to
have a Dirac, indicating that the PC describes the noise in that frame very well.
The BN and HOPC pre-normalization resulted in early eigenvectors with very
similar appearance. No signicant dierences were seen between the datasets
with correlated and uncorrelated noise.
HOPC
BN
SV
ROM
PC
1
PC
2
PC
3
PC
4
HOPC
BN
SV
ROM
e
1
e
2
e
3
e
4
10 20 30 40 50
1
0.5
0
0.5
1
Time [min]
10 20 30 40 50
1
0.5
0
0.5
1
Time [min]
10 20 30 40 50
1
0.5
0
0.5
1
Time [min]
10 20 30 40 50
1
0.5
0
0.5
1
Time [min]
10 20 30 40 50
1
0.5
0
0.5
1
Time [min]
10 20 30 40 50
1
0.5
0
0.5
1
Time [min]
10 20 30 40 50
1
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1
Time [min]
10 20 30 40 50
1
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1
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10 20 30 40 50
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10 20 30 40 50
1
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1
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Time [min]
10 20 30 40 50
1
0.5
0
0.5
1
Time [min]
Figure 4.10: PCs and eigen vectors for synthetic data without correlation that
were normalized with ROM, SV, BN and HOPC pre-normalization.
Results 47
HOPC
BN
SV
ROM
PC
1
PC
2
PC
3
PC
4
HOPC
BN
SV
ROM
e
1
e
2
e
3
e
4
10 20 30 40 50
1
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1
Time [min]
10 20 30 40 50
1
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0
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1
Time [min]
10 20 30 40 50
1
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Time [min]
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Time [min]
10 20 30 40 50
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Time [min]
10 20 30 40 50
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Time [min]
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Time [min]
10 20 30 40 50
1
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1
Time [min]
10 20 30 40 50
1
0.5
0
0.5
1
Time [min]
Figure 4.11: PCs and eigenvectors for synthetic data with correlation that were
normalized with ROM, SV, BN and HOPC pre-normalization.
Noise variance in pre-normalized datasets
The expectation value in each point, dened by the signal dataset, was used in
order to calculate the standard deviation in every slice, seen in gure 4.12.
10 20 30 40 50
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Time [min]
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o
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o
f

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[
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/
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3
]

RoM
SV
BN
HOPC
(a)
10 20 30 40 50
0
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[
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RoM
SV
BN
HOPC
(b)
Figure 4.12: Standard deviation in pre-normalized data with uncorrelated noise
(a) and correlated noise (b).
The noise standard deviation in the BN pre-normalized dataset is close to con-
stant, while the standard deviation of the noise in the datasets pre-normalized
with the other three pre-normalizations show a negative trend.
Mean squared error of reconstructions
The calculated MSE for datasets with uncorrelated and correlated noise are
shown in gure 4.13.
1 2 3 4
0
0.01
0.02
0.03
0.04
0.05
0.06
0.07
M
S
E

[
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q
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/
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m
6
]
Number of early PCs used in reconstruction

ROM
SV
BN
HOPC
(a)
1 2 3 4
0
0.01
0.02
0.03
0.04
0.05
0.06
0.07
M
S
E

[
B
q
2
/
c
m
6
]
Number of early PCs used in reconstruction

ROM
SV
BN
HOPC
(b)
Figure 4.13: MSE of reconstructions with early PCs for datasets with uncorre-
lated noise (a) and correlated noise(b).
The best reconstruction is obtained by pre-normalizing with BN and recon-
structing the dataset with MVW-PC
1
and MVW-PC
2
. The next best result is
obtained by using HOPC or SV pre-normalization.
Results 49
4.2.3 Clinical study
Dimension reduction
Figure 4.14 shows the arithmetic mean in the original data and reconstructions
with low-order MVW-PCs measured in the tumour-VOI and the stomach-VOI.
This shows the dierences between the tumour and stomach TAC, and also that
the regions require a dierent amount of MVW-PCs in order to be reconstructed
with an adequately small error. The number of MVW-PCs depends on both
region and pre-normalization method.
0 20 40
0
5
10
15
x 10
4
(e)
0 20 40
0
5
10
15
x 10
4
(f)
0 20 40
0
5
10
15
x 10
4
(g)
0 20 40
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15
x 10
4
(h)
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4
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8
10
x 10
4
(a)
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2
4
6
8
10
x 10
4
(b)
0 20 40
2
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6
8
10
x 10
4
(c)
Original
ROM
SV
BG
HOPC
1
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Time [min]
Figure 4.14: Arithmetic mean within the tumour-VOI (a)(c) and the stomach-
VOI (d)(g), measured for dierent reconstructions. (a) and (b) is reconstruc-
tion with only the rst MVW-PC, (c) and (d) is with the rst two, (e) and (f)
is with the rst three and (g) is with the rst four MVW-PCs.
Measurements
The MSE of the arithmetic mean in the reconstructed datasets is shown in gure
4.15. It should be observed that the vertical axes have a logarithmic scale. The
error decreases for every added MVW-PC in the reconstruction. MVW-PCA
with BN and HOPC pre-normalizations describe the arithmetic mean for the
tumour better than MVW-PCA with the ROM and SV pre-normalizations in
early MVW-PCs. The dierences between the pre-normalizations are signicant
in the FBP data, not because BN and HOPC performs better on FBP data
than on OSEM data, but because ROM and SV performs worse with FBP than
on the OSEM data. This dierence can be seen in gure 4.15 (a)(b) with
reconstruction [3, 4, 5, 6] and in (c)(d) with reconstruction [4, 5, 6].
To get an understanding of what a certain MSE corresponds to in deviation
from the correct mean, the MSE, in gure 4.15 (b) and (d) can be compared to
the mean curves in gure 4.14. For example the sudden reduction in MSE for
both the BN and HOPC pre-normalizations when reconstructing the stomach
with the rst three and the rst four MVW-PCs (reconstruction 3 and 4) in
gure 4.15 (d) is visible in gure 4.14 (f) and (g).
ROM
SV
Background
HOPC
1
HOPC
2
1 2 3 4 5 6 7 8 9 10 11 12 13
10
5
10
6
10
7
10
8
10
9
(c)
1 2 3 4 5 6 7 8 9 10 11 12 13
10
2
10
4
10
6
10
8
10
10
(d)
1 2 3 4 5 6 7 8 9 10 11 12 13
10
5
10
6
10
7
10
8
10
9
(a)
1 2 3 4 5 6 7 8 9 10 11 12 13
10
2
10
4
10
6
10
8
10
10
(b)
M
S
E
m
e
a
n
[
(
B
q
/
c
m
3
)
2
]
Reconstruction
Figure 4.15: MSE of the arithmetic mean in dierent reconstructions for dier-
ent pre-normalizations.
The MSE of the data compared to on the optimal reconstruction of the VOI
(described in section 3.2.6) is shown in gure 4.16. These bar graphs show that
the optimal reconstruction of the tumour is retrieved from reconstructing the
rst three MVW-PCs in the HOPC pre-normalized dataset, for both FBP and
OSEM. The optimal reconstruction of the stomach with FBP data is retrieved
from reconstructing the rst ve MVW-PCs with BN pre-normalization, and the
optimal reconstruction with OSEM data is retrieved from the rst six MVW-
PCs with SV pre-normalization.
The ROM and SV pre-normalizations did not perform well on FBP recon-
structed data, and BN pre-normalization did not perform well on OSEM recon-
structed data. HOPC pre-normalization performed fairly well on both the FBP
and OSEM reconstructed dataset.
Results 51
ROM
SV
Background
HOPC
1
HOPC
2
1 2 3 4 5 6 7 8 9 10 11 12 13
10
7
10
8
10
9
(c)
1 2 3 4 5 6 7 8 9 10 11 12 13
10
8
10
9
10
10
(d)
1 2 3 4 5 6 7 8 9 10 11 12 13
10
7
10
8
10
9
(a)
1 2 3 4 5 6 7 8 9 10 11 12 13
10
8
10
9
10
10
(b)
M
S
E
x
[
(
B
q
/
c
m
3
)
2
]
Reconstruction
Figure 4.16: Mean squared error in dierent reconstructions for dierent pre-
normalizations, compared to the optimal signal x[u, v, w, n].
Qualitative examples
Slices from the three lowest-order MVW-PCs from datasets reconstructed with
FBP and OSEM is illustrated in 4.17. HOPC pre-normalization was used when
performing the MVW-PCA.
(d)

50
0
50
(e)

10
5
0
5
10
(f)

20
10
0
10
20
(a)

20
10
0
10
20
(b)

5
0
5
(c)

10
0
10
Figure 4.17: Slices from the three rt MVW-PCs from datasets reconstructed
with FBP in (a)-(c) and OSEM in (d)-(f). Most of the adrenal tumour and the
general tracer behaviour is described by MVW-PC
1
in (a) and (d). MVW-PC
2
in (b) and (e) describes the early tracer accumulation in the kidneys, while the
tracer concentration in the stomach can be separated with MVW-PC
3
shown
in (c) and (f).
An example of a slice from a frame in a dimension-reduced dataset is shown
in gure 4.18. This dataset was reconstructed with OSEM and pre-normalized
with the HOPC pre-normalization. It was then dimension-reduced to the ve
lowest-order MVW-PCs. The dimension reduced dataset have a more homoge-
neous appearance and the ickering of pixels, when viewing several frames in a
sequence, have been reduced.
(a)

(b)

C
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x 10
4
Figure 4.18: One of the slices in the original (a) and dimension reduced (b)
datasets showing the tumour.
Chapter 5
Closing remarks
5.1 Discussion
5.1.1 Interpretation of PC images
Since samples in PET data are positive and related to the decay, one might
expect to see high values in regions with high tracer concentration. This is
however not valid for PC images since they are merely linear combinations of
pre-normalized frames, that have zero mean and both positive and negative val-
ues. On top of this, there usually are both positive and negative weights in the
linear combinations. PC
1
will point in one of the two opposite directions that
minimize the mean square error between the original data and its projection
onto PC
1
. PC
2
can then be arbitrarily chosen in one of two directions that
minimize the mean square error of the remaining parts of the signal, each direc-
tion representing opposite deviations from the kinetic behaviour described by
PC
1
. An illustration is shown in gure 5.1.
f
1
f
2
(e
1
,
1
)
(e
2
,
2
)
Figure 5.1: Illustration of a dataset where frame 1 and 2 are correlated. PC
1
points in one of the two opposite directions with maximum variance and PC
2
points in one of the two directions orthogonal to PC
1
.
To visualize the PCs a colour map without emphasis of the sign is used in this
report. Positive values go from red to yellow, negative from blue to cyan whereas
values close to zero are dark. An example is shown in gure 5.2.

100
80
60
40
20
0
20
40
60
80
100
(a) PC2

100
80
60
40
20
0
20
40
60
80
100
(b) PC2 with opposite sign
Figure 5.2: Example of the colour map used for PCs. The backbone and the
two urinary tracts of a mouse are visible with opposite signs in PC
2
5.1.2 Noise characteristics
The rst aim of this project was to characterize the noise in PET data recon-
structed with FBP and OSEM.
In the phantom study it was shown that OSEM had a higher expectation
value in high activity regions and lower expectation value in regions where there
is no activity, compared to FBP. In high activity regions the standard deviation
of OSEM and FBP data is close to identical whereas OSEM has a standard
deviation close to zero in regions without any activity.
It was also shown that, when using this camera, the slices closest to the
opening of the gantry had a signicantly reduced mean and increased standard
deviation in the measurements. One of the reasons the standard deviation was
higher at the outer slices compared to the centre of the gantry is that the camera
uses 3D acquisition, which results in less LORs passing through the points in the
outer slices. An explanation to why the slices near one of the edges had reduced
mean values is that the phantom was not completely symmetrically inserted,
resulting in dierent amount of out of eld detections at the two edges. The
constant arithmetic mean but slight increase in variance over time is due to the
decay correction.
It was shown that the noise in each frame is uncorrelated, which is the rea-
son why noise ends up in late components when using PCA. Since the signal is
highly correlated the eigenvectors will more likely point in the direction of the
correlation. It was also shown that there exists correlation between slices. This
correlation is due to the fact that the eXplore Vista scanner use 3D acquisition
with FORE before the 2D FBP and OSEM reconstructions. However, the corre-
lation between slices is small and mostly aects the closest neighbouring slices.
The slice correlation also depends on the slice position and is largest closest to
the centre of the gantry and smaller at the ends.
Spatial correlation in trans-axial slices is very dependent on whether FBP
or OSEM reconstruction has been used. In regions where both FBP and OSEM
has isotropic correlation the extent of the correlation is much larger for OSEM
than for FBP. For FBP the orientation of the correlation is oriented towards the
region of strongest activity whereas the orientation of the correlation for OSEM
is orthogonally oriented towards the closest region of activity. This means that
there are major dierences between the extent, orientation and isotropy in FBP
Closing remarks 55
and OSEM reconstructed data.
The ACF estimate described in section 3.1.9 did show strong similarities
with the sample correlation but the result was noisy and the estimate for a
given coordinate varied heavily between slices. This was not mainly due to that
less samples was used in the estimate, but because the selected region A was
not completely WSS. Even though the mean should be the same in the whole
ROI the ACF should not. However, the advantage of this estimate over the
sample correlation, described in 3.1.8, is that it can be used when only one slice
realization is available, and even though it is noisy it can give a hint of the
amount of correlation that is present in a homogeneous region.
5.1.3 Reduction of noise in PET data using MVW-PCA
The study of synthetic images was a good starting point in understanding how
PCA with dierent pre-normalizations treat dierent input data. Since the sig-
nal without any added noise consisted of four structures with linear independent
TACs, four PCs were required in order to describe the whole signal as seen in
gure 4.9 (notice that
5
is zero, meaning that PC
5
spans zero variance). A
good pre-normalization method should help PCA to separate signal from noise
as much as possible in early PCs.
Since PCA does not take the spatial position of pixels into account, spatial
correlation of the noise between neighbouring pixels will have no eect what
so ever on the orientation of the eigenvectors if enough frames are used. The
synthetic study with uncorrelated and correlated noise conrmed this.
Comparison of the dierent pre-normalization methods on the synthetic data
showed that when noise was added to the signal the default method of removing
the arithmetic mean could only separate one component and the deviations from
PC
1
was spread amongst the remaining components. Standardizing the vari-
ables prior to PCA helped to separate the structures into earlier PCs. Although
not distinguishable in the actual images seen in gure 4.10 and 4.11, BN pre-
normalization separated the signal from noise best in the rst two components
according to gure 4.13. Both HOPC and BN separated most of the signal into
two components with a relatively low amount of noise. In gure 4.12 it was also
shown that, just like the BN pre-normalization, the HOPC pre-normalization
scales the data so that the noise variance is close to one. It should be pointed
out that the noise used in the synthetic study resembles that of FBP; hence the
great performance of BN did not come as a surprise.
Dimension reduction on clinical data proved to be an ecient way of remov-
ing noise, while keeping the dynamic property of the data. This is an important
feature since noise reduced TACs can be extracted, which is not possible when
looking at a summation image or a single PC, which is common today. Dimen-
sion reduction can be performed as long as the measured structure is mostly
described by the reconstructed PCs. For example it is important that the pa-
tient is still during the scan since movements tend to end up in late PCs and
will then be removed.
Both the MSE
mean
graphs in gure 4.15 and the MSE
x
graphs in gure
4.16 clearly shows that the ROM and the SV pre-normalizations should be
avoided when analysing FBP reconstructed data. BN did not perform well on
OSEM data, which was expected since it is dependent on noise in the back-
ground and will not function at all if the background values are zero. No pre-
normalization was superior to all the other on all datasets, but since the HOPC
pre-normalization performed well on all of the datasets, unlike the other pre-
normalization methods, it showed great potential. If the best possible quality is
needed the appropriate pre-normalization has to be decided from case to case,
depending on the dataset and structure of interest.
5.2 Future work
Some of the ideas that came up during the study were considered to be too time
consuming to be included in the scope of this master theses. Here is a list of
ideas that can be used in case of further studies within this area:
Investigate if there is an appropriate pre-normalization that can be used
when creating the MVW-PCs used by the HOPC pre-normalization.
Develop a rule of decision to decide the number of high order MVW-PCs
to use in the HOPC pre-normalization.
Develop a rule of decision to decide the number of low order MVW-PCs to
use when reducing noise through dimension reduction with MVW-PCA.
Investigate the possibility of using variance estimates for each sample, in
order to pre-normalize a dataset sample-wise instead of slice-wise, as is
done in the BN and HOPC pre-normalization.
Investigate the orientation of the correlation for dierent reconstruction
algorithms.
During the study it was clear that single precision oating-point data reduced
the numerical precision of the result substantially. But, due to the low perfor-
mance of the used computer, double precision could not be used for the large
datasets. This should be taken into account when reconstructing large datasets
in the future.
5.3 Conclusion
MVW-PCA analysis of Filtered Back-Projection (FBP) reconstructed data is
more dependant on an appropriate pre-normalization than analysis of Ordered
Subset Expectation Maximization (OSEM) reconstructed data. Higher-Order
Principal Component (HOPC) pre-normalization can be used on datasets re-
constructed with both methods and shows promising results.
Dimension reduction with MVW-PCA in combination with HOPC pre-normalization
was a good method of reducing noise in Positron Emission Tomography (PET)
datasets.
Correlation in FBP reconstructed PET data is oriented towards the region
of strongest activity whereas correlation in OSEM reconstructed PET data is
orthogonally oriented towards the closest region of activity.
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List of Figures
2.1 Anatomical images created with CT and MRI. . . . . . . . . . . 14
2.2 Functional images created with fMRI, SPECT and PET. . . . . . 15
2.3 PET Camera GE/Advance Nxi . . . . . . . . . . . . . . . . . . . 17
3.1 eXplore VISTA small animal PET scanner . . . . . . . . . . . . . 23
3.2 Cross section of the phantom. . . . . . . . . . . . . . . . . . . . . 24
3.3 Illustration of the MVW-PCA procedure. . . . . . . . . . . . . . 28
3.4 Masked and non-masked MVW-PC
1
. . . . . . . . . . . . . . . . 29
3.5 Removal of MVW-PCs from X . . . . . . . . . . . . . . . . . . . 30
3.6 Late Principal Component Pre-normalization . . . . . . . . . . . 31
3.7 Spatial and temporal behaviour of the signal structures. . . . . . 32
3.8 Montage of the dataset without any noise. . . . . . . . . . . . . . 34
3.9 Montage of the dataset with uncorrelated noise. . . . . . . . . . . 35
3.10 Montage of the dataset with correlated noise. . . . . . . . . . . . 35
4.1 Arithmetic mean and standard deviation for frames. . . . . . . . 39
4.2 Correlation coecient for neighbouring frames. . . . . . . . . . . 40
4.3 Arithmetic mean and standard deviation for slices. . . . . . . . . 40
4.4 Correlation coecient for neighbouring slices. . . . . . . . . . . . 41
4.5 Correlation for FBP and OSEM in three ROIs . . . . . . . . . . 42
4.6 Correlation for FBP and OSEM in three ROIs, using WSS estimate 43
4.7 Standard deviation used by HOPC pre-normalization . . . . . . . 44
4.8 MSE of scaled standard standard deviation . . . . . . . . . . . . 44
4.9 The rst ve PCs in non-noisy synthetic data . . . . . . . . . . . 45
4.10 PCs and eigen vectors for synthetic data without correlation . . . 46
4.11 PCs and eigenvectors for synthetic data with correlation . . . . . 47
4.12 Standard deviation in synthetic pre-normalized data . . . . . . . 48
4.13 MSE of reconstructions with early PCs . . . . . . . . . . . . . . . 48
4.14 Arithmetic mean within the tumour and the stomach . . . . . . . 49
4.15 MSE of the arithmetic mean in reconstructed data . . . . . . . . 50
4.16 MSE of the reconstructed data . . . . . . . . . . . . . . . . . . . 51
4.17 Qualitative examples of MVW-PCs from FBP and OSEM . . . . 52
4.18 Tumour in the original and dimension reduced dataset . . . . . . 52
5.1 Illustration of a correlated dataset. . . . . . . . . . . . . . . . . . 53
5.2 Example of the colour map used for Principal Components (PCs) 54
List of Tables
2.1 Commonly used isotopes in clinical PET studies. . . . . . . . . . 18
3.1 Parameters for the temporal functions. . . . . . . . . . . . . . . . 32
3.2 Time protocol for a 24-frame scan (60 min) with the tracer PIB. 33
3.3 Time protocol for a 14-frame full body scan (45 min) with the
tracer FDG. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

Characterization and Reduction of Noise in PET Data Using Mvw-Pca

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