Accuracy of finite element model-based multi-organ deformable image registration K. K. Brock, M.B, Sharpe, L. A Dawson, S.M, Kim, and D. A. Jaffray Citation: Medical Physics 82, 1647 (2005), dol 10.1118/1.1915012 View online: hittp://dx.dol.org/10.1118/1.1916012, View Table of Contents: hitp:/scitation. alp.org/content/aapmyjournalmedphys/32/69ver=pdfcov Published by the American Association of Physicists in Medicine Articles you may be interested in Position tracking of moving liver lesion based on real-time registration between 20 ultrasound and 3 preoperative images Med. Phys. 42, 336 (2018); 10.1118/1.4903945 Four-dimensional dose evaluation using deformable image registration in radiotherapy for liver cancer Med. Phys, 40, 011706 (2013), 10.1118/1.4769427 Accuracy and sensitivity of finite element model-based deformable registration of the prostate Med. 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Jattray Radiation Medicine Program, Princess Margaret Hospital, University Health Network {610 University Avenue, Toronto, Ontario, Canada MSG 29 (Received 31 August 2004; revised 21 March 2005; accepted for publication 24 March 2005; published 20 May 2005) [As more pretreatment imaging becomes integrated into the treatment planning process and full three-dimensional image-guidance becomes part of the treatment delivery the need for a deformable image registration technique becomes more apparent. A novel finite element model-based multi- organ deformable image registration method, MORFEUS, has been developed. The basis of this method is twofold: first, individual organ deformation can be accurately modeled by deforming the surface of the organ at one instance into the surface of the organ at another instance and assigning the material properties that allow the internal structures to be accurately deformed into the second- ary position and second, multi-organ deformable alignment can be achieved by explicitly defining the deformation of a subset of organs and assigning surface interfaces between organs. The feasi- bility and accuracy of the method was tested on MR thoracic and abdominal images of healthy Volunteers at inhale and exhale. For the thoracic cases, the lungs and external surface were explic- itly deformed and the breasts were implicitly deformed based on its relation tothe lung and external surface. For the abdominal cases, the liver, spleen, and external surface were explicitly deformed and the stomach and kidneys were implicitly deformed. The average accuracy (average absolute error) of the lung and liver deformation, determined by tracking visible bifurcations, was 0.19 (sd. 10.09), 0.28 (sd: 0.12) and 0.17(s.4.:0.07) cm, in the LR, AP. and IS directions, respectively. The average accuracy of implicitly deformed organs was 0.11 (sd: 0.11), 0.13 (sal: 0.12), and (0.08 (s.:0.09) cm, in the LR, AP, and IS directions, respectively. The average vector magnitude of the accuracy was 0.44 (s1.:0.20) em for the lung and liver deformation and 0.24 (s.d.:0.18) em for the implicitly deformed organs. The two main processes, explicit deformation of the selected organs and finite element analysis calculations, require less than 120 and 495 s, respectively. This platform can facilitate the integration of deformable image registration into online image guidance procedures, dose calculations, and tissue response monitoring as well as performing multi-modality image registration for purposes of treatment planning. © 2005 American Association of Physicists in Medicine. [DOK 10.1118/1.1915012} |. INTRODUCTION [As more pretreatment imaging (ie., PET MRS.“* 4D CT"? and MR'*") becomes integrated into the treatment planning process and full three-dimensional (3D) image- guidance (ie, kV and MV cone-beam,"* tomotherapy.”"* and conventional CT)7"~” becomes part of the treatment delivery the need for a deformable image registration technique becomes more apparent. In addition to beeing accurate and efficient, the image registration technique must include deformable alignment, allow various regions of interest to behave differently, and maintain the geometric integrity of regions of interest that are presented differently on different imaging modalities, Image intensity-hased deformable image registration has been shown to be very effective for single organ image registration." However, including multiple organs in the registration becomes challenging, as the interface between organs can be difficult to model using splines, fuid-flow, and optical flow. Boundary conditions are inherent in the biome- chanical modeling used in finite element analysis (FEA), Which allows multiple organs to be registered simulta. neously. 1647 Med. Phys. 32 (6), June 2005 (0094-2405/2005/32(6)1647/19/822.50 ‘An extensive amount of research has investigated the ben- efit of finite element modeling (FEM) in surgical simulation, especially for modeling brain deformation,’ however, only limited investigations into its potential in radiotherapy have been reported and has primarily focused on single or- gan deformable registration ‘A novel method has been developed to perform deform- able, multi-organ image registration using FEM. The basis of this method is twofold: first, individual organ deformation can be accurately modeled by deforming the surface of the Corgan at one instance into the surface of the organ at another instance and assigning the material properties that allow the internal structures to be accurately deformed into the second- ary position and second, multi-organ deformable alignment can be achieved by explicitly defining the deformation of a subset or limited number of organs and assigning surface interfaces between organs. Naturally occurring surrogates (or landmarks) for bound- ary registration across multiple imaging modalities are essen- tial for the proposed registration method. For some organs, such as the liver and lung, the boundary representation of the organ is consistent between different imaging modalities al- (© 2005 Am. Assoc. Phys. Med. 16474648 Brock et al: Accuracy of FEM-based multiorgan deformable image registration 1648 (Conese) a A —) TxPiannng ‘syste ( Fevosedatomaie (mage registaton system NN tion of FEMFEA into RTTP though the internal image intensity representation may vary Comparing the boundary representation and assigning rect material properties can allow explicit deformation of these organs. Other organs, such as the prostate, have incon- sistent boundary definition between imaging modalities, i the visible boundary of the prostate is inconsistent between MB, CT, and cone-beam CT. This subset of organs must be implicitly deformed by explicitly deforming neighboring ot- gans and assigning appropriate material properties and sur- face interfaces. In the case of the prostate, the bladder and rectal boundary representation is consistent between imaging ‘modalities and can serve as the explicitly deformed organs. In addition, as biological imaging advances the position of the biological target volume can also be inferred from the anatomical surrogates in a similar manner.” Conn Cee Corre Medical Physics, Vo. 32, No. 6, June 2005 ll, METHODS AND MATERIALS A FEM-based multi-organ deformable image registration platform, MORFEUS, was developed (o facilitate deformable registration of multi-modality images for tissue response tracking, image-guided radiotherapy, and improved dose cal- culations. This was achieved by integrating a FEM pre- processor (HYPERMESH version 6.0, Altair Engineering, Troy, Mb, FEA (ABaQus version 6.4, ABAQUS Inc, Pawtucket, RD, and radiation therapy treatment planning system (rIwwacte’ version 6.2b, Philips Radiation Oncology Sys- tems, Milpitas, CA), as shown in Fig. 1. The FEM pre- processor, HYPERMESH, is used {0 construct the FEM, assign ‘material properties, surface interfaces, and boundary condi- tions, and determine the boundary conditions using HYPER- MORPH, an application available in the software program. The FEA software package, ABAQUS, generates differential equations that describe the model constructed in the prepro- cessor and then solves these equations simultaneously. The treatment planning system (TPS) performs rigid body, bony registration of the multiple data sets, allows contouring of the selected regions of interest (ROIs), and provides a ‘method of exporting the ROIs. It is important to note that, although specific commercial products were used for this de- velopment and analysis, the general concept of FEM-based deformable image registration can be employed using any ‘commercial or research FEM, FEA, and TPS software, The process developed is illustrated in Fig. 2, and will be de- scribed in the following.4649 Brock et al: Accuracy of FEM-based multiorgan deformable image registration 1649 A. Data collection Five healthy female volunteers participated in research ethics board (REB) approved MR scanning study to image their thorax and abdominal regions at a normal inhalation and exhalation breath hold. The average age of the volun- teers was 33 years (range: 25-49). The volunteers (referred to as VI-V5) were scanned in the supine position, on a flat table without immobilization and with their arms over their head. A 3D inhalation and exhalation MR scan of the thorax, including the whole lungs and breasts, was acquired for each volunteer. The thoracic study was followed immediately by inhalation and exhalation scans of the abdominal region, it cluding liver, spleen, stomach, and kidneys. The volunteer's position was adjusted between the thorax and abdominal scans to optimize position in the scanner. An axial Fast-Spin Gradient Recovery (FSPGR) imaging sequence (TE/TR 1.6/325 ms, 1 NEX, FOV 3444 cm) was used forall scans combined with Array Spatial Sensitivity Encoding Tech- niques (ASSET™) to decrease imaging time and allow for complete coverage of organs of interest in one comfortable breath hold on a GE 1.5 T MR unit (Excite, 4 channel, GE Medical Systems, Milwaukee, WD). The sequence was cho- sen to optimize enhancement of vessel bifurcations in the liver and bronchial bifurcations in the lung. These structures, serve as anatomical landmarks to estimate the accuracy of the FEM-based deformable alignment. ‘The scanning time ranged from 22 to 36 s for a complete 256x256. vol- tume, where 1 is the number of slices necessary to cover the entire volume of interest. Slice thickness ranged from 4 to 5 mm with no gap, depending on patient breath hold comfort and 1 ranged from 50 to 58 for the abdomen scans and 54 to 59 for the thoracic scans. An ASSET calibration (Fast GRE calibration, TE/TR 1.4/3.6 ms, FOV 48, slice thickness 9 mm, 30 slices, 0:06 s imaging time) image was obtained at breath hold position prior to image acquisition. Following the imaging session, the images were trans- ferred into the treatment planning system, where the organs were segmented to generate anatomical ROIs, as shown in step | of Fig. 2. Segmentation of the ROIs produces a series, of discrete transverse “contours.” which are represented by a list of vertices and associated which each of the transverse images slices. The ROIs for the thorax data sets included right and left lungs, right and left breasts, spinal cord, and external surface, The ROIs for the abdominal scan included liver, spleen, stomach, right and left kidneys, and extemal surface. In addition all data sets had an “internal” ROL cre- ated which comprised the volume of the patient delineated by the extemal surface, but excluding a 0.5 cm isotropic ex- pansion of the spinal cord. The purpose of the internal ROL will become apparent in Sec. ILC. The ROls representing each organ Were converted from contours to a volumetric binary mask, and then exported from the TPS as a file. B. Conversion of ROIs to triangular surface mesh ‘The binary mask files were imported into a mathematical development environment used commonly for image analy sis (Interactive Data Language, IDL, Research Systems Inc.) Medical Physies, Vol. 32, No. 6, June 2005 Fo. 3. Smoothing process fr abdominal organs (a original mesh with no data reection and n0 smoothing, (b) reduced to 64% 64 daa, () results ‘fom (h) smoothed using a Laplacian smoothing with 10 iterations at a factor of 10, (a) roslt fom (6) smoothed in geomagic decimate (50 ‘To manage the size of the mesh generated, the data files were first reduced in siz from 256 x 256%. (N=slice number) to (64% 64%. The resampled binary files were then converted into a triangular surface mesh using an algorithm described by Klemp er ai” which is similar to the marching cubes algorithm.** Both algorithms search the data on a voxel-by- voxel basis, creating a triangle representation based on the intersection of the 3D contour surface with each voxel, dif- fering only in search algorithm implementation. The normal to the surface is also computed to define the “inside” and “outside” of the surface. The surface mesh, with an example triangular element, is shown in step 2 of Fig. 2. The mesh ‘was smoothed using a Laplacian smoothing described in Eq, (1), where Xi, isthe vertex é for iteration n, 2 is the smooth- ing factor, and af is the number of vertices that share a com- ‘mon edge with Xi,. Laplacian smoothing adjusts the vertices, in the mesh to smooth the shape, improving the appearance and shape, without significantly changing its topology. AS ) » Mia = Kiet FE Cy Ki ( ‘The mesh was smoothed with 10 iterations at a smoothing factor of 10 and further smoothed in Geomagic Decimator (Raindrop Geomagic, Raleigh, NC) using the “relax” (La- placian smoothing) function, for 50 iterations. An example of the process is illustrated in Fig. 3 In three cases (V3, V4, and V5), the inferior extent of the lung became extremely narrow and extended further into the abdominal cavity, Reduction to 64% 64 .V did not maintain this detail. For these three cases, the lung and breast data were only reduced to 128X128. A higher resolution was, used to ensure proper modeling of the inferior extent of the lung. To maintain a reasonable mesh size, the mesh was smoothed and the number of elements describing the surface was reduced, using the decimate function, in DECTMATOR™. ‘The decimate function reduces the number of elements de-1650 Brock ef, A p fe Fi. 4 Smoothing process fr lunes: (original mesh with no data educ- tion and no smoothing, (6) educed to 128% 128 data, (e) reduced to 128 128 smoothed (50 iteration) decimited to 75%, soothed (50 iterations) decimated to 75% and soothed (50 iterations) scribing the surface while maintaining as much of the origi- nal surface information as possible. Combining mesh deci- ration and Laplacian smoothing allows significant reduction in the number of elements while maintaining accurate mesh topology. The decimate (dec) and smoothing (using the relax, Laplacian smoothing function) schema utilized for the lung was R=50, dec=75, R=50, dec=75, R=50. For the breast, the decimate and smoothing schema was &=50 and dec =15, An example of the process is shown in Fig. 4 ©. Finite ment model construction ‘The triangular surface meshes representing the segmented organs for a given image set were imported into the FEM preprocessor. A 3D four-node tetrahedral FEM was created from all organ ROI triangular surface meshes. An example of a liver tetrahedral mesh is shown in step 3 of Fig. , with an inset showing an example of a tetrahedral element. The inte- rior FEM is created from the interior surface mesh, excluding all intemal organ FEMs. This completed the multi-organ sys- tem, Nodes on the surface of each organ FEM were defined to be common to both the organ FEM and the interior FEM resulting in a “tied” connection, The average median length of an element side was 0.49 cm and the average element volume was 0.03 cm ‘The spinal cord was allowed to move independently in these investigations and did not contribute tothe registration. The cord is a strong structure for use in aligning bony anatomy even under conditions of spinal column flexure. The spine was not needed in this alignment because both images were obtained at the same imaging session and therefore there was no difference in position of bony anatomy. It will be very useful to include the spine in multi-modality imaging or images obiained from the same modality but on different days when bony setup varies. ‘As indicated in step 4 of Fig. 2, material properties and surface interfaces were assigned to each organ. A linear elas- tic material model was used to describe the FEM. Material properties were assigned to each element in the multi-organ FEM with these properties varying between organs, but ho- rmogeneous in each organ. Material properties were taken Medical Physies, Vol. 32, No. 6, June 2005 curacy of FEM-based muiti-organ deformable image registration 1650 ‘Tass [Linear clastic material parameters for each ongan moved. Pos 0's rio, v hero of transverse contraction stain to lngitadial exten sion trainin the direction of stretching force, describes the compressibility ofthe mera. Young's modulus, £, the ratio of suess to stain on the loading plane along the loading direction, describes the stifnes ofthe mz terial, Poisson's aio ‘Young's modulus (E) (kPa) Tnieor ‘0.400 1 (abdomen) 60 (hora) Lone 0.480 50 Brcast 0450 9 Liver 0450 18 Spleen 0499 Stomach 0499 Kidney 0499 from the literature and then manually optimized by a justing the parameters on the first three volunteers (VI-V3) until the accuracy was 0.3 em or better for implicitly de- formed organs. These parameters were then validated by en- suring similar accuracy forthe remaining two volunteers (V4 and V5). Each subject was assigned the same organ-specific ‘material properties. The parameters for each organ are shown, in Table I. The Young’s Modulus for the stomach (500 kPa) is much larger than typical published values for soft tissue (1-100 kPa) This value was employed to accommodate the contents of the stomach as they were included in the FEM and no food or beverage intake instructions were given to the ‘volunteers prior to imaging. Finite element modeling has the ability to describe biome- chanical materials using simple and complex models. A sim- plistic model, the linear elastic material model, was used here as a starting point because parameters for complex mod- els are difficult to obtain for human tissues and significantly increase computational time. In the future, as more accurate ‘methods of obtaining material properties are further devel- oped, such as MR elastography, more complex models can be directly integrated into the MORFEUS system by changing the parameters in the model ***° D. Individual organ deformation When performing image alignment, one representation rust be selected as the “base model” that will be deformed into all other representations. The base model provides the relationship between all images. The ideal base model de- scribes the boundary representation of all regions of interest with geometric accuracy. The element structure of the base ‘model will also serve as the “storage” system for the patient for dose tracking, tumor classification, and tissue response Explicit organ deformation was performed on selected or- gzans in the model to achieve the multi-organ deformable alignment. Organ selection was based on the ability to ac rately contour and easily visualize on all images. For the abdominal data sets, the liver, spleen, and extemal were ex- plicitly deformed. For the thoracic data sets, the lungs and external were explicitly deformed. The exhale data set was the base model for the abdominal data sets, and deformable1651 Brock et registration was performed to align it to the secondary ‘model, the inhale data set. For the thoracic data sets, the inhale data set was the base model, and deformable registra- tion is performed to align it to the secondary model, the exhale data set. The exhale data set was used as the base ‘model for the abdominal scans to simulate the current treat- ment planning process for liver cancer at our institution, which performs treatment planning on the patient in the ex- hale breath hold position, which has been shown to be more reproducible." Research has shown a reduction in cardiac and lung doses when treating breast cancer patients at inspi- ration breath hold, therefore, the inhale data set was used as the base model for the thoracic scans.*"** The explicit organ deformation from one instance of g ‘ometry to another (i. from exhale to inhale) was performed using HYPERMORPH, a surface-based projection algorithm available in HYPERMESH, shown in step 5 of Fig. 2. For or- gans undergoing substantial motion, Le., a change in center of gravity (COG) of greater than 0.5 em, which can be de- scribed as rigid-body motion, a COG alignment was per- formed as an initial step. This was performed when deter- mining the deformable alignment of the liver and spleen. A COG registration was performed in the anterior-posterior, AP, and left-right, LR, directions only for the lung. No COG registration was performed for the extemal surface, as the back of the patient remained against the table during inhale and exhale breath holds For one case (V2 abdomen) substantial rotation was noted in the coronal plane. Initial results using only a COG regis- tration resulted in a poor surface alignment. A 7° in-plane rotation about the COG was applied in addition to the COG registration leading to a successful surface alignment. More patient data will be necessary to determine if this is a com- ‘mon problem, which may require a systematic solution, pos- sibly a more complex rigid body initial registration.°-*" The HYPERMORPH alignment procedure is outlined in Fig. 5. Both FEM surface mesh representations of the organ are imported into HvPERMEsH (Fig. 5(a)]. The FEM of the orga in the secondary model is converted to a surface and a COG registration is performed, if required, as defined above, Fig 5(b). The elements on the surface of the FEM of the organ in the base model are automatically grouped into a series of domains based on the curvature of the FEM. The relationship between the curvature of the FEM and the domains can be adjusted in the software—this results in more or less do- mains being created. The default parameters were used in this study and it will be the subject of further research to investigate the effect of these parameters. A “handle” is then automatically created which guides the nodes in each do- ‘main, coronal and sagittal view of FEM with handles, black dots, shown in Fig. 5(c). The domains, on the base model are mapped to the surface, from the secondary model. The handles drive the deformable alignment and an orthogonal node projection completes the alignment of the base-model FEM (o the surface of the secondary model, results shown in Fig. 5(d). It is important to emphasize that this is a node to surface alignment, not a node-to-node alignment between the corresponding FEM of the organs in the base and secondary Medical Physics, Vo. 32, No. 6, June 2005 \ccuracy of FEM-based multrorgan deformable image registration 1651 Fo, 5. uvrsgsonnn deformable registration: liver example: (a) inhale (pink) and exhale bie) iver, (b) aftr COG registration.) surface defined for inale liver (pink), () liver roe to deformable alignment, with handles (yellow), (¢) aller deformable liznment, and (@) exhale liver in inale position ‘model. The node to surface alignment eliminates the (time- consuming) need to identify corresponding points on two representations of a region of interest. Tis vector projection for each node, ie. the difference between each node position oon the base model and after the HYPERMORPH alignment, is then assigned as a boundary condition on the multi-organ base model. The HYPERMORPH process takes an average of 45-120 s on a Pentium 4 2.4 GHz processor, depending on the number of nodes and complexity of the FEM E. Finite element analysis, Once the HvPERMORPH alignment is performed on the se- lected organs and the results are applied as boundary condi- tions (constraints, displayed in step 6 of Fig. 2), finite ele- ment analysis (FEA) is performed to determine the displacements of all nodes not explicitly constrained with loads defined from the HYPERMORPH process, and the result- ing stress and strain on the elements. The FEA was performed as a static direct single step. The analysis was performed on a Quad Xeon MP 2.0 GHz Dell P6600 with 4 Gbytes of RAM. The average wall clock time for the FEA analysis was 332 s for the abdominal cases and4652 Brock et al: Accuracy of FEM-based multiorgan deformable image registration 1682 Tone I nerior-posterie, I feror~supero. Precision of bifurcation identifcation for the lung and liver (em). LR=leR-right AP Average LR ‘average 0s (Ons ‘Standard deviation 06 om Liver Lang aps RP ts 00 ool 006 Om 0m 00s 0.10 00s 0.6 495 s for the thoraci ases, The average total CPU time was 1064 s for the abdominal cases and 1623 s for the thorac The results of the FEA can be viewed as a set of displace- ment vectors, contoured color washes of the FEM of dis- placements (shown in step 7 of Fig. 2), stress, or strain, as an animation of the deformation results, or by applying the re- sults and comparing to the actual FEM of the secondary data set. Raw numerical data can also be exported for quantitative analysis. F. Accuracy and residual error calculation ‘The accuracy of the explicit organ deformation was deter- mined by calculating the difference between the actual dis- placement of the vessel and bronchial bifurcations identified oon both inhale and exhale data sets (ACT) to the displace- ‘ment predicted by the FEA (PRED). An average of 8.6 vessel bifurcations (range: 7-10) were selected in each liver and 10, bronchial bifurcations (range: 6-14) were selected in each lung. The bifurcations were selected to best encompass al of the organ volume, however the lung bifurcations were biased to the hilum area where bifurcations were larger and more easily seen on the MR image. The accuracy is reported as, both the average and standard deviation of the signed differ- ence (PRED-ACT), indicating any bias in the registration, and the average and standard deviation of the unsigned dif- ference ((PRED-ACT)), indicating the expected distance to agreement between the deformable registration and the dis- placement predicted by the bifurcations. The precision of selecting the same bifurcation location fon each MR scan was limited by the slice thickness, 4-5 mm, and the resolution of the image, an average in- plane pixel size of 0.14 by 0.14 cm, reduced slightly from the use of ASSET. For three liver scans and three lung scans, six randomly selected bifurcations were used to test repro- ducibility of bifurcation localization. Assessments were per- formed once a week, for four weeks. The reproducibility of bifurcation selection was determined by displaying the origi- nal identifying mark on the base image and having the cor- responding bifurcation on the secondary image dataset rese- lected in a random order. The accuracy of the deformable alignment of organs not explicitly deformed was determined by applying the results, of the FEA and then performing volumetric HYPERMORPHL deformable alignment between the predicted secondary posi- tion and the actual secondary position to determine the re- sidual error. The Volumetric HYPERMORPH process is an ex- Medical Physies, Vol. 32, No. 6, June 2005 pansion of the HYPERMORPH process described in Sec. IID and is performed on a volumetric tetrahedral mesh, Il, RESULTS A. Reproducibility of bifurcation selection ‘The precision of the bifurcation identification, determined by repeat bifurcation selection, was less than 0.1 em in each direction (Table Il). The maximum standard deviation for a bifurcation was 0.47, 0.20, and 0.25 em in the LR, AP, and IS direction, respectively B. Accuracy of individual organ deformable registration HYPERMORPH ongan deformation was successfully performed on the liver, spleen, lungs, and body organ meshes of all five volunteers. The average liver motion over all cases from exhale to inhale, based on FEM node displace- rents, and range of individual node displacements, was 0.09 cm (range: 1.42 t0 1.25 em), 0.75 em (range: 0.65 to 2.23 em), and ~1.20 em (range: ~3.15 to 0.78 cm), in the LR. AP. and IS direction, respectively. Positive displacement values indicate motion in the right, anterior, superior direction. The average lung motion from inhale to exhale, based on the FEM node displacements, was =O.lL cm (range: -2.11 to 1.81 cm), -0.78em_ (range: =2.11 to 089 em), and 0.59 em (range: ~1.11 to 5.30 em), in the LR, AP, and IS direction, respectively ‘The accuracy of the liver and lung deformable registration is summarized in Table IIL. The accuracy of the deformable registration ofthe liver, as measured by the average standard deviation ofthe difference (PRED-ACT) is les than 0.20 em in each direction, on the same order ofthe in-plane pixel size of the image, 0.14 cm. The average error is 0.10 cm or less in each direction, indicating no apparent systematic error in registration. The average absolute difference (|PRED-ACT)) is 0.12cm (sd. 0.07 cm), 0.17 cm (sd. 0.14em), and (0.14-em (s4. 0.10 cm), in the LR, AP, and IS direction, re- spectively. The accuracy of the deformable registration of the lung, as measured by the average standard deviation ofthe differ ence (PRED-ACT), is 0.26 em or less in each direction, also fon the same order of the in-plane pixel size of the image, (0.14 em. The average error is 0.17 em or less in the LR and IS direction, however, the average error is slightly larger, (0.24 and 0.40 em in the AP direction for the right and left lung, respectively, indicating a potential systematic AP erro.1653 anus HL Accuracy of deformable image registration for organs dirctly undergoing wvreasonr alignment, fr each volunteer andthe average over all ve, (PRED-ACT).(R=Righl, L=Lef, LR=let-righl, AP anterior-posteior,IS=inferie—superion (em). ‘verge (6) Ongan 1 ap 1s Liver 0051027) -0.10024) -0080.5) Vi Rhang 0111022) 0301015) 0.05(042), Lug 013/021) 0851018) -0.11018), Liver 1011210) -0.1710.27)-0.070.19) V2 Ring 032/018) 0281032) -0.030031) Lug 031/022) 0391033) -0.171028), Liver 004015) -0091017) 0.051021), V3 Klang 0.10(038) 0271008) 0.00(008), Lug 0271025) 0471019) 0.000019), Liver 1040.10) -0.100.21) 0.070014) Vi Klang 0071022), 024021) -0.180014) Lug 0127020) 0301039) -0.17016), Liver 04008) -0.040.10) 0.111017) VS Klang 0.08(0.2) 0101020) -0.030017), Lung 0s(ats) 0280.19) 0.10025), Liver 0.00014) -0.10(0.20) 0.030017) Average Lung 0.00.21) 024(049)-004022) Lung 0.170022) 0401026) -0071021) Overa 0.90.19) 0.181022) -0.03(0.20) ‘The average absolute difference (|PRED-ACT)) is 0.23 em (sd. 0.14em), 0.36 em (sd. 0.17 em), and 0.19 (sd. 0.14 cm), in the LR, AP, and IS direction, respectively ©. Accuracy of multl-organ deformable registration Multi-organ deformable registration was successfully per- formed for all five thoracic and abdominal cases. Figure 6 illustrates the initial differences between the exhale and in- hale position for thoracic and abdominal regions of one case, V4. Figure 6(a) illustrates the differences through a transpar- ency overlay of the abdominal region (left) and thoracic re- gion (right). Figure 6(b) shows the difference in organ posi- tion between inhale and exhale, for the abdominal region (left) and thoracic region (right). Organs to be registered are shown in multiple colors (exhale liver, spleen kidneys, and stomach for the abdominal region; inhale breast and lungs for the thoracic region) inhale abdominal organs are shown in blue and exhale thoracic organs are shown in orange. The results of the FEA are shown as a color wash on the organ meshes in Fig. 6(c). The average displacement and range over all volunteers, of the left and right kidneys, stomach, spleen, and right and left breasts are shown in Table LV. ‘The accuracy of the secondary-organ deformable registra- tion, shown in Table V, reflects the displacement ofall nodes representing the organ volume mesh between the predicted secondary position and actual secondary position. This error also includes the error in manual organ contouring, from Medical Physies, Vol. 32, No. 6, June 2005 Brock et al: Accuracy of FEM-based multiorgan deformable image registration 1653 which the organ mesh is created. The average error is less than 0.10 cm in each direction forall organs, standard devia tion of 0.21 cm or less in each direction, The average abso- lute difference (|PRED-ACT)) of implicitly deformed organs was O11 (sd: 0.11), 0.13 (sd: 0.12), and 0.08 {(sd.:0.09) om, in the LR, AP, and IS directions, respectively. Figure 7 illustrates the excellent agreement between the FEA predicted position (inhale for abdominal, exhale for thoracic) and the actual position. ‘The residual error for one case, ab- dominal V4, is highlighted in Fig. 8, which shows a color wash of the residual error as well as a plot of the vector residual error as a function on IS position, with correspon- dence to the color wash for the larger residual error regions for the stomach, Fig. 8(a) right kidney, Fig. 8(b), and left kidney, Fig. 8(c). The small clusters of residual error sup- ports the rationale that these discrepancies are largely due to local contouring errors, IV, DISCUSSION ‘A novel finite element model-based multiorgan image registration technique, MoRFEUS, has been described and its accuracy assessed. In addition to being fast and accurate, this biomechanical based method allows the registration of or- zzans based on their biomechanical properties and their posi- tion with respect to other organs, which are explicitly regis- tered. MoRFEUS has been developed through a combination of commercially available software programs; however, the fundamental aspects of the process (contour-based guided surface projection of a limited number of regions of interest to determine explicit deformation and the correct assignment of material properties and surface interfaces to determine im- plicit deformation) can be applied using other commercially available or in-house developed programs. Several param- eters associated with MORFEUS have been described in this ‘manuscript, with initial values reported. These parameters, which allow potentially great flexibility in the model, also require understanding and investigation. Research into the sensitivity and optimal values ofthese parameters is the sub- ject of current and future work Surface matching algorithms for deformable registration have been previously described for single organ deformable registration, most using an internal energy function, Ferrant ct al. describe a method for registering 3D intraoperative MR images of the brain using a deformable surface matching algorithm, based on iteratively image-derived forces and an energy minimization, which tracks the cortical surface and lateral ventricles* ‘The algorithm reduced surface-based landmark discrepancies from 1.0 cm to less than 0.1 em and subsurface landmarks from 0.6 to 0.3 em or less. Liang et al describe a method for single-organ image registration using FEM, organ boundary point correspondences, and a surface energy minimization. The algorithm was tested on simu- lated deformation of the rectum. The error in registration was, reduced from 0,9 cm (maximum) based on initial boundary point correspondence to 0.16 cm after optimization. Zhang tal. have reported on initial investigations using a deform-1654 Brock et al: Accuracy of FEM-based multiorgan defo able Jung model based on negative surface pressure, however quantitative results have not yet been reported.”* The accuracy of the direct organ deformable registration is dependent, to some extent, on the accuracy and consis- tency of the contouring and on material properties. Auto- contouring was performed on the lung and external surface, all other organs Were manually contoured in a clinically rea- sonable amount of time, Contouring was performed by @ physicist (KKB) and checked for accuracy and edited if re quired by a physician (LAD). Attention was paid in assessing the auto-contours of the Tung to ensure that the inclusion of bronchi was consistent between inhale and exhale images. ‘Taste IV, Ave (range) of organ motion (LR= rmable image registration 1654 Fi 2} FEM tanspareney overlay oe to registration, (0) comparison of FEM between exhale and inhale (ex hale abdominal organs in color, inkl blac inhale thorcie organs in clog, exhale in orange, () displace ‘ent contours of FEA rele (em) ini There is a small, yet potentially significant, systematic error in the AP direction of the lung accuracy, maximum of 0.47 cm for one volunteer, We are currently investigating this discrepancy, by creating a predicted, deformed MR image to compare to the actual MR image. Ongoing work will also assess deformable registration of the lung, using patient CT scans, where bronchial bifurcations should be easier to visu- alize, allowing more bifurcations to be localized for a more complete analysis of the accuracy of the deformable registra- tion of the lung The material properties for the liver and lung were deter- ‘mined after a patient population optimization, The optimal lt-tight, AP-anterioe—posterior sapere) LR Let kde 065) Right Kidney 0.15 (0.77 to 008) Stomach “017 1.19 1002) Speen 059 1.7610 1.00) Right breast -0.19 (-01 0 002) Left breast 0419 07 0 087) AP 1 0 003) 75 19-09) 0194 207 to 1.03) O71 C1a6 10178) 156.315 w~ 082 CLIT “1118 0.41 t 0.16) 084 136.0 =0118 0.40 t0 Medical Physics, Vo. 32, No. 6, June 20051655 anus V. Accuracy, average, and standard deviation, of secondary organs, ot diccly deformed wing woruksowen (PRED-ACT). (LR=lef-right eror posterior, IS=inferior-seperiog (cm) Average (standard deviation) Organ Le ap 1s Vi R Breast 004016) “o011007) LBreast-00310:15) -oo1i07) R Kidney -001(0.10) 0110.10) L Kidney -00310.24) 0021015) Stomach 0021014) —0.02¢ 9011013) V2 RBrast_ 8011010) 0.050015) -00410.10) L Brest -001(014) 0.04016) -00310.12) RKideey 0161023) 005027) -0011020) LKidney 0181023) 0270025) -0.121016) Stomach 0910.26) -0.15032) 011023) V3 RBrast_ 0191022) 0111016) LBrest 0040.13) =00710.10) R Kidney -001(0.10) 0031008) L Kidney 0.010:16) 0021010) Stomach 0.0910.19) 0111023) V4 R Breast -002(008) 0011008) LBresst—0.0010.12) 0071016) R Kidney 0010.14) 0710.11) L Kidney -0011009) 0.061009) Stomach 0040.10) 0020.2) VS RBrast_ 0021007) 0110.05) LBresst—-901(0.12) 0.101015) R Kidney 006(0:12) 0110.10) L Kidney -0071008) 0021008) Stomach 0040.17) 0071013) Average Breast 0.020014) 003009) L Breast 0.080.14) —-006(0.12 R Kidney 0.04018) 0010.2) L Kidney 0060.16) -00210:12) Stomach 004021) -0.040.17) Overall 0.000016) 0030.12) value of Poisson's ratio, v, across all five subjects, was 0.45 for the liver. Individual optimal values ranged from 0.36 to (0.49, however, the difference in the average bifurcation error computed with the population optimal value and the patient specific optimal value was less than 0,008 cm in all cases, indicating a relatively small fluctuation with changing ». An optimal » value was difficult to determine for the lung. ‘Trends varied between subjects as well as between LR, AP, and IS directions. The variation in the vector magnitude error of the FEA’s prediction of the bifurcation displacement was, 0.11 em or less between the range of 1=0.35 to 0.48, for all, subjects. The optimal value was determined from the error in the IS direction only for four of the five subjects, as one volunteer (V5) had an optimal » smaller than 0.35. The trends in the IS direction showed a distinct minimum for all four patients. The optimal value of v was 0.45 for the lung across all five subjects. This difference in optimal v between Medical Physies, Vol. 32, No. 6, June 2005 Brock et al: Accuracy of FEM-based multiorgan deformable image registration 1655 Fo, 7. Organ comparison with FEA reslts aplid. Predicted positon in blue (nhle abdominal organs, exhale thoracic organs) and actual postion ined. different directions of motion could explain the small sys- tematic error in the AP direction. Itis the goal of future work to investigate the potential benefit of anisotropic linear elas- tic material properties and hyperelastic material properties, using multi-step, incremental fixed boundary conditions. For organs explicitly deformed using the surface projec- tion method, Young’s modulus was irrelevant because a boundary constraint was applied to every node on the surface of the organ. A full optimization on all organ parameters was, not performed because of the coupled parameters, Young's, ‘modulus and Poisson’s ratio for each organ and dependence of the three separate organs in the thoracic case and five organs in the abdominal case. In the present study, the accuracy of secondary organ reg- istration is determined by comparing the predicted contour position with the actual contour position, since reliable inter- nal landmarks are not present. Efforts are ongoing to develop a method of generating a predicted image, from the FEA results, to compare to the actual image to allow for quantifi- cation of the error that is independent of the accuracy of the contours. ‘There are many potential applications for this registration ‘method. In the pretreatment setting, multi-modality images, can be registered to the planning CT using FEM-based de- formable image registration. Organs that can be easily visu1655 Brock ef, ‘super 7 Lisette I-07 je n88 08 <03 0m fan = 00 (emt re gos i Boa For 3 fa 7 ris cS superior Lina siPostiniem Fi, 8. Vector magnitude of the residual eror afer deformable registration ff the (a) stomach, (b) right kidney, and () left kidney. Frequency pot indiatng residual enor asa function of 1S postion (cm). Medical Physics, Vo. 32, No. 6, June 2005 \ccuracy of FEM-based multrorgan deformable image registration 1656 alized on each image data set can be contoured and used to ide the deformation of other regions of interest, which ‘may not be as easily visible on one imaging modality. This can be especially useful for registering MR to CT, where the tumor may have different image characteristics on each mo- dality and image deformation may compromise geometric accuracy. The proposed FEM-based deformable image reg tration will allow the tumor to be registered according to the ‘material properties and the deformation of the organ with which it resides. This will allow a direct comparison of the tumor region on MR to CT, whereas with image-intensity based registrations, the change in intensity of the tumor will drive the tumor on one imaging modality to match that on the other imaging modality, losing the ability to quantify the differences in the tumor across imaging modalities. In addi- tion to registering anatomical data, functional information can also be incorporated into the treatment planning process by registering functional images, such as MR spectroscopy. In addition to registering and comparing pretreatment im- ages from different modalities to compare tumor extent, posttreatment follow-up images can also be registered to determine tumor response and changes in normal tissue. As FEMLbased deformable image registration is biomechanical- based, it has the potential to model both normal tissue hy- pertrophy and tumor shrinkage for an accurate assessment of disease status and change in normal tissues. ‘Another application is the on-line treatment setting using, for example, cone-beam CT or MV CT. Registering the sur- rounding organs, visible on the CBCT or MVCT, to the plan- ning imaging data set which may include multiple imaging ‘modalities (¢g., PET, MRS), allows localization of a tumor or another functional volume of interest (e.g., hypoxic vol- lume) for atthe time of treatment, based on prior knowleda of the interaction between the tumor and surrounding organs. The combination of image-guidance registration and the abil- ity to track response of tissues to radiation has the potential to provide image-guidance and adaptive treatment to tumors, ‘which may respond quickly to radiation and therefore change during the course of treatment."® For each registration setting and anatomical location one ‘must determine the appropriate regions of interest to explic~ itly deform, For multiple scans during the same imaging ses- sion, such as variations in breath hold or monitoring of blad- der and rectal filing, setup error does not exist and therefore bony registration is not important. The majority of image registration includes setup error resulting from sublle changes in patient position, For these cases, bones should be included in the registration process, as discussed in Sec. ILC The accuracy of registration will increase as the number of organs explicitly deformed increases, however, this will also increase the amount of time required, For example, for a tumor located in the center of the liver, acceptable deform- able registration of the planning CT to the daily cone-beam CT may only require thatthe liver be accurately registered However, if the tumor is in the inferior region and there is, significant risk to the kidney and stomach, explicitly deform- ing the liver and spleen is necessary.1657 Brock et al: Accuracy of FEM-based multiorgan deformable image registration 1657 ion inear progression through deformati li ‘The results of the FEA can be illustrated as vector plots, indicating the motion and deformation of a selected ROL This is a natural assessment of a patient-specific intemal tar- get volume (ITV) margin, allowing for anisotropic margins, ‘Which will allow for sparing of normal tissue, These vectors can also be overlaid on the dose distribution to provide in- formation on the movement of sensitive structures into the high dose region Dose calculations and optimizations can also be improved by including respiration or other physiological motion by incorporating the motion and deformation info the dose calculation. *** Intermediate positions can be generated by linear interpolation of the FEA results. Figure 9 shows the progression of the thoracic organs over five steps from inhale to exhale position \V. CONCLUSIONS. In summary, a platform to perform multi-organ deform- able image registration using finite element modeling has Medical Physies, Vol. 32, No. 6, June 2005 Fo. 9. Linear progression from inital Peston to completion of deformable ‘egisttion fom inhale to exhale. Ex hale organs (ed) inhale organs hive), Inde external (light ray), exhale ex ‘eral (nt shown) been developed. Its feasibility and accuracy has been shown through deformable image registration of MR images at dif- {erent respiratory states for both the thorax and the abdomi- nal regions. Future research will expand this platform to per- form deformable registration in other anatomical sites, such as the pelvis and integrated into online image guidance pro- cedures, dose calculations that include deformation, and tu- ‘mor and normal tissue follow-up. 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