, H. von Tengg-Kobligk 1. Department of Nuclear Medicine, University of Heidelberg, Heidelberg 69117, Germany 4

Transcription

1 106 Experimentl Oncology 31, , 2009 (June) Exp Oncol , 2, IMAGE FUSION using ct, mri nd pet FOR TREATMENT PLANNING, NAVIGATION AND FOLLOW UP IN PERCUTANEOUS rf F.L. Giesel 1, 2, 3, A. Mehndirtt 2, 4, J. Locklin 1, M.J. McAuliffe 5, S. White 6, P.L. Choyke 7, M.V. Knopp 8, B.J. Wood 1, 9, U. Herkorn 3 1, 2, 8, H. von Tengg-Koligk 1 Deprtment of Rdiology, Clinicl Center, Ntionl Institutes of Helth, Bethesd 20892, MD, USA 2 Germn Cncer Reserch Center (dkfz), Deprtment of Rdiology, Heidelerg 69120, Germny 3 Deprtment of Nucler Medicine, University of Heidelerg, Heidelerg 69117, Germny 4 School of Medicl Science nd Technology, Indin Institute of Technology, Khrgpur , Indi 5 Ntionl Institutes of Helth, Center for Informtion Technology, Bethesd 20892, MD, USA 6 New Jersey School of Medicine, Newrk, NJ, USA 7 Ntionl Institutes of Helth, Moleculr Imging Progrm, Ntionl Cncer Institute, Bethesd 20892, MD, USA 8 The Ohio Stte University, Deprtment of Rdiology, Columus 43210, OH, USA 9 Ntionl Institutes of Helth, Surgery Brnch, Ntionl Cncer Institute, Bethesd 20892, MD, USA Aim: To evlute the fesiility of fusion of morphologic nd functionl imging modlities to fcilitte tretment plnning, proe plcement, proe re-positioning, nd erly detection of residul disese following rdiofrequency ltion (RFA) of cncer. Methods: Multi-modlity dtsets were seprtely cquired tht included functionl (FDG-PET nd DCE-MRI) nd stndrd morphologic studies (CT nd MRI). Different comintions of imging modlities were registered nd fused prior to, during, nd following percutneous imge-guided tumor ltion with rdiofrequency. Different lgorithms nd visuliztion tools were evluted for oth intr-modlity nd inter-modlity imge registrtion using the softwre MIPAV (Medicl Imge Processing, Anlysis nd Visuliztion). Semi-utomted nd utomted registrtion lgorithms were used on stndrd PC worksttion: 1) lndmrk-sed lest-squres rigid registrtion, 2) lndmrk-sed thin-plte spline elstic registrtion, nd 3) utomtic voxel-similrity, ffine registrtion. Results: Intr- nd inter-modlity imge fusion were successfully performed prior to, during nd fter RFA procedures. Fusion of morphologic nd functionl imges provided useful view of the sptil reltionship of lesion structure nd functionl significnce. Fused xil imges nd segmented three-dimensionl surfce models were used for tretment plnning nd post-rfa evlution, to ssess potentil for optimizing needle plcement during procedures. Conclusion: Fusion of morphologic nd functionl imges is fesile efore, during nd fter rdiofrequency ltion of tumors in dominl orgns. For routine use, the semi-utomted registrtion lgorithms my e most prcticl. Imge fusion my fcilitte interventionl procedures like RFA nd should e further evluted. Key Words: imge fusion, rdiofrequency ltion, registrtion, registrtion lgorithms, tretment plnning. The vlue of imge processing nd fusion hs een investigted for dignostic nd prognostic purposes; still it hs een less studied tool for interventionl rdiologicl procedures. Registrtion nd fusion of rdiologicl imges is y no mens new post processing technique [1 5]. There re numerous technicl pproches descried to colesce imging dt from different modlities [6 8] nd use them to provide etter helth cre for the ptient. Registrtion is defined s ligning the two imging dt sets sptilly to ech other. While fusion is defined s overlying them nd visulizing them s one imge. Algorithms for registrtion of ntomicl nd functionl dt sets hve een mostly studied in fixed or rigid orgns such s the spine or rin [2, 4, 7, 9, 10]. But registrtion is somewht more difficult in region with physiologic movements like the neck [11] or in moving orgns such s lungs [12, 13]. Mjor ch llenges due to Received: Jnury 19, *Correspondence: Fx: E-mil: f.giesel@dkfz.de Arevitions used: CT computed tomogrphy; DCE dynmic contrst enhnced; DICOM digitl imging nd communictions in medicine; FDG-PET [F-18] 2-deoxy-2-fluoro-D-glucose positron emission tomogrphy; Gd-DTPA gdolinium diethylenetrimine-pent-cetic cid; MRI mgnetic resonnce imging; PACS picture rchiving nd communiction system; RFA rdiofrequency ltion. physiologic motion nd the non-rigid nture of orgns hve limited the prcticl implementtion of imge fusion for dominl interventionl procedures for dignostic nd prognostic resons. Recent studies hve shown tht fusion of dominl imges from different modlities cn improve dignosis nd monitoring of disese progression [14 16]. New hyrid-imging systems comining positron emission tomogrphy (PET) or single photon emission computed tomogrphy (SPECT) with computed tomogrphy (CT) offer one-stop exmintion promoting the dignostic nd prognostic potentils for extr-crnil pplictions of imge fusion in cncer [17 21]. Imge fusion hs proven useful for evlution of ptients with cncer suppor ting dignosis, stging, tretment plnning, monitoring the response to therpy including disese progression [22]. Minimlly invsive imge-guided therpy like rdiofrequency therml ltion is eing routinely used, especilly in the liver, lung, one nd kidney [23 26] nd improves survivl for certin ptients [27]. Optiml outcomes of percutneous rdiofrequency ltion (RFA) re highly dependent upon ccurte trgeting of the neoplstic tissue nd monitoring of the resulting therml lesion. Success of tretment is intimtely linked to the volumetric sptil reltionship of neoplstic tissue to the therml lesion mrgins. An ccurte sptil understnding of this reltionship tht is redily cces-

2 Experimentl Oncology 31, , 2009 (June) 107 sile my provide feedck du ring pre-tretment plnning, procedurl nvigtion, erly detection of re-growth improving prognosis. Idel imge guidnce for RFA llows ccurte proe plcement for sphere-pcking with sufficient overlp to void gps of su-lethl heting, nd to tret smll mrgin of norml tissue eyond the neoplstic tissue orders. This is chllenging tsk nd is prone to humn error. The procedure is to e followed y repeted scnning nd look for disese progression. Imge fusion ws studied with n imge processing softwre used efore, during, nd fter RFA interventions. Fusion of morphologic nd functionl imge dt might improve sptil pprecition nd visuliztion of tumor nd its reltion to therml lesion mrgins. MATERIAL AND METHODS All reported ptients were enrolled under investigtionl protocols tht were pproved y the Investigtionl Review Bords (IRB) of the NIH. Written informed consent ws otined from ll ptients prior to the procedures. For this report ptients nd imges were selected if they could demonstrte the fesiility nd vlue of the presented fusion technique. Imging modlities. Morphologic imging ws performed with nd without contrst enhncement using CTi nd Light Speed CT (GE Medicl Systems, Milwukee, WI) nd 1.5 Tesl mgnetic resonnce imging (MRI) (GE Medicl Systems, Milwukee, WI). Functionl imging included fluoro-18 leled deoxyglucose (FDG)-PET (GE Medicl Systems, Milwukee, WI) nd Dynmic Contrst enchnced (DCE)-MRI using the ove mentioned scnner. Prior to RFA (pre-tretment phse) ech ptient underwent contrst-enhnced CT. Some ptients lso hd PET nd contrst enhnced MRI or DCE-MRI scns. After the initil RFA tretment ws completed, ml olus of iodinted contrst medium ws dministered intrvenously nd CT of the trget orgn ws performed (procedurl phse). After two month ptients were followed up with CT nd in some cses dditionly with PET or DCE-MRI (Post-tretment phse). Dt flow nd imge post processing. Source dt ws rchived on the hospitl picture rchive nd communiction system (PACS, Kodk, Rochester, NY) in the stndrd imging DICOM (Digitl imging nd communictions in medicine) formt (Fig. 1). Relevnt dt sets were retrieved from the PACS onto personl computer (PC) worksttion (1.4 GHz processor, 512 MB RAM, MS Windows 2000 Professionl). Imge fusion of morphologic nd functionl dt ws performed prior, during nd fter RFA etween the sme (intr-modlity) nd different modlities (inter-modlity) (Fig. 2). Intr- nd inter-modlity registrtion ws crried out using oth semi-utomted lndmrk-sed methods lest squres [28], thin-plte-splines [29] nd utomtic voxel-similrity method, n optimized utomted registrtion (OAR) [30, 31], ville in the ppliction MIPAV (Medicl Imge Processing nd Visuli ztion, Ntionl Institutes of Helth, Bethesd, MD) using the ove descried worksttion. Registrtion lgorithms used included: 1) lest-squres rigid registrtion, 2) thin-plte spline elstic registrtion, nd 3) utomted voxel-similrity mesure ffine registrtion using either correltion rtio or mutul informtion cost functions. Intr-modlity registrtion of pre- nd post-tretment CT dtsets ws ccomplished using n utomtic ffine (12 degrees of freedom) registrtion lgorithm. This intrmodlity imge fusion process used correltion-rtio voxel-simulrity cost function to guide the registrtion of the imges. To enhnce the visuliztion of two fused im ges, MIPAV provides mny tools tht llow the user to independently personlize the contrst, rightness nd lookup tles for ech dtset. Adjustment nd lending the mount ech imge contriutes to the finl comined disply cn e performed in rel-time. Fig. 1. Workflow for ptients scheduled for RFA. Initil imging includes morphologic nd/or functionl imging. DICOM imges re sent directly or vi PACS to PC worksttion for imge registrtion nd fusion. The results re pushed to lptop tht is tken into the procedure suite where ptient informtion cn e retrieved. During RFA, imge fusion cn e performed on the lptop, which my receive dt from PACS or CT scnner. Follow-up morphologic nd functionl imging dt is lter fused with pre-procedure imging dt on worksttion Fig. 2. Imge fusion comines the visuliztion chrcteristics of mlignnt lesions seen with morphologic (CT, MRI) nd functionl (PET, DCE-MRI) imging efore, during, nd fter RFA. After RFA the reltion nd chrcteristics of tumor nd therml lesion cn e ssessed in fused dt set. Vrious comintions re possile, including intr-modlity (e. g. pre-ct vs post-ct) or inter-modlity (e. g. pre-ct vs pre-pet) Different thresholds nd color lookup-tles were evluted for visuliztion regrding the imging modlity nd comintion of dt sets. Imge fusion, volume nd surfce rendering including multi-plnr visuliztion were performed on the sme worksttion using the ove mentioned MIPAV softwre. A lptop PC (1.4 GHz processor, 512 MB RAM, Windows 2000 Professionl) ws used for intr-procedurl fusions nd for intr-procedurl disply (see Fig. 1). RESULTS Fusion results vried in ccurcy depending upon orgn shift, respirtory vritions, lesion or orgn shrinkge, nd positionl chnges. The semi-mnul lndmrk methods (lest squres, thin-plte splines) required longer setup times due to selection of lndmrks

3 108 Experimentl Oncology 31, , 2009 (June) (~10 20 min without cropping). This ws less prcticl for intr-procedurl nvigtion, nd required trined user. However, pplying the utomted voxel-similrity ffine registrtion lgorithm to cropped volumes produced resonle processing times, fcilitting fusion during tretments (3 5 min with cropping). Cropping the imge hd two mjor dvntges: first, cropping significntly reduced processing time nd second, cropping loclized the registrtion of the imges, reducing non-liner distortion rtifcts, thus improving the ffine registrtion process. The voxel-similrity registrtion technique ws the fstest nd thus potentilly most useful method for registrtion during tretments (Fig. 3). However, the lndmrk methods hve uilt-in internl control, nd were etter in selected cses for specific ptients (Fig. 4, 5). The lndmrk-sed elstic method (thin plte spline) ws more ccurte for registrtion of orgn shift in some cses (Fig. 6). However, elstic methods lter the ctul imging dt, nd thus hve potentil for error. Pre-tretment phse. The CT scns provided primrily morphologic informtion on orgn ntomy, tumor environment, djcent lrge vsculture, nd vsculr supply (see Fig. 3; 4, ). Functionl imging y PET nd DCE-MRI scns llowed functionl lesion ssessment of the metolic (see Fig. 4, ) or phrmcokinetic microvsculr sttus of the lesion (see Fig. 5, ). RFA needle trjectories were plnned sed on conventionl mentl registrtion, nd retrospectively vlidted with fused imges (see Fig. 6, ; Fig. 7). In ddition, fused 3D-imges with PET or DCE-MRI confirmed or fcilitted neoplstic trgets. Volume rendering of lesions helped to understnd the sptil reltion of the tumor nd surrounding structures, which ws not ovious from the conventionl two-dimensionl view (see Fig. 4, d). Similr fused comintions loclized suspicious residul tumor tht would need repeted RFA (see Fig. 5, 6, c). DCE-MRI showed suspicious residul untreted tumor (see Fig. 5, ), which ws confirmed with pre tretment PET fused to pre tretment CT (Fig. 5, ). Procedurl phse. Fused imges especilly helped to guide RFA in ptients were CT lone could not define recurrent tumor (see Fig. 6, c nd d) The procedurl imges were registered to the pre-tretment imges. Fused imges of pre-tretment-ct nd intr-procedurl c d Fig. 3. CT scn nd elstic fusion imges of kidney tumor nd post-rfa therml lesion. Contrst enhnced xil CT slices show left kidney lesion efore RFA (, rrow) nd therml lesion two months fter RFA (, rrow). Due to chnge in kidney shpe post ltion, elstic registrtion method is used to fuse pre- nd post-rfa imges (c nd d), which defines tretment mrgins (drk lue)

4 Experimentl Oncology 31, , 2009 (June) 109 c d Fig. 4. Ptient with metsttic pncretic crcinom isolted to the liver. Pre-RFA contrst enhnced xil CT slice () shows detiled morphology with 4 possile trgets (rrows) for tretment. PET () shows norml FDG uptke in 2 nterior liver lesions. Intermodlity PET/CT fusion (c) loclizes ctive lesions (crosshirs). Volume rendering (d) visulizes metolic ctivity with 3 dimensionl detils Fig. 5. Ptient with residul tumor following RFA for multiple liver metstses. Dynmic contrst enhnced MRI () compred to fused PET/CT () confirms tumor nd correltes vsculr phrmcokinetics with metolic ctivity

5 110 Experimentl Oncology 31, , 2009 (June) c d Fig. 6. CT, MRI, nd PET imges of ptient with colorectl crcinom with liver metstses. Axil CT () nd MRI () slices post-rfa showing only morphology (rrows) ppering negtive for recurrence. Retrospective off-line fusion of CT nd PET dt sets (c) vlidtes pthologyproven residul tumor long the posterior order of the liver. Repet tretment trgeted with sptil knowledge of PET ctivity (d) post-rfa CT rpidly defined dequte tretment mrgins well using OAR technique (see Fig. 7). If questionle res re identified with possile residul tumor, then repeted RFA cn e considered efore the ptient is removed from the room, lthough fusion ws not used prospectively in our study to lter ny tretment pln. Post-tretment phse. Conventionl ssessment is sed on visul comprison to determine whether the pre-tretment lesions nd post-tretment res re well mtched (see Fig. 3, nd ). However, registered nd fused imges my provide etter visuliztion of sutle diffe rences (see Fig. 3, c nd d ; 7, 8, 9). Follow-up imging cn e fused to pre-rfa imging to compre tumor to tretment mrgin, however this method ecomes less useful the longer the follow-up, given tht post-rfa lesions will shrink with time (see Fig. 9). Technicl Results. Free network flow of DICOM im ges ws chieved etween PACS, imging scnners nd PC worksttions. MIPAV provided oth volume rendering s well s multi-plnr disply of fused imges for lesion visuliztion with CT, MRI nd PET dtsets. Rigid (see Fig. 4; 9, c) nd elstic (see Fig. 3, Fig. 9, d f) registrtion methods were successfully pplied intr-opertively ut cn e chllenged due to orgn shrinkge t follow up. Choosing ccurte nd homologous lndmrks, in ech of the volume dtsets ws rther time consuming, even more for inter modlity registrtion e.g. PET-CT. The OAR method ws fster nd pprecited during the procedurl phse. Cropping the imge hd two mjor dvntges; first, cropping significntly reduced processing time. Second, cropping loclized the registrtion, reducing non-liner distortion rtifcts, thus improving the ffine registrtion process y nrrowing the processing to the volume of interest. DISCUSSION Previous studies hve shown tht imge fusion is powerful methodology to enhnce dignostic nd follow up imging in cncer ptients [30, 32 34]. Different registrtion lgorithms hve een used successfully for non-interventionl pplictions in the pst [29, 35], nd were successfully pplied in this study

6 Experimentl Oncology 31, , 2009 (June) 111 c d Fig. 7. Right kidney tumor in ptient with von Hipple-Lindu syndrome. Pre-RFA fused with post-rfa contrst enhnced xil CT slices (from superior to inferior, c) using optimized utomted registrtion (OAR) method with correltion rtio voxel-similrity cost function. Imges c were cropped nd colo rized with MIPAV tools to speed the registrtion process nd enhnce visuliztion. The pre-tretment CT ppers in gry nd the post-tretment CT is in color, i. e. the yellow tretment mrgin (thin rrows) overlys the originl gryscle tumor (thick rrows). Notice the thin mrgin (doule tiled rrow) in () which could potentilly hve een site of recurrence; however, 6 month, 1 yer, nd 18 months (d) post tretment scns showed no recurrence. Although there ws thin mrgin, fusion correctly depicted n dequte therml lesion to RFA for liver nd kidney tumors. Registrtion nd fusion my e useful during interventionl procedures nd my ssist efore, during, nd fter RFA [21]. Often morphologic nd functionl imging studies provide seprte nd complimentry informtion. Registrtion of pre- nd post-rfa imges my provide nother window into the often-sutle sptil reltionships etween tumor nd post-rfa therml lesion. Conventionl interprettion uses mentl re gistrtion [9]; however computer proces sing my provide more ojective nd exct view [36]. Imge fusion hs mtured predomintely for rigid structures (rin nd one), nd mny technicl detils hve lredy een refined, however, severl mjor prolems remin while performing imge fusion fter RFA. The prolem of respirtory motion is inherent to the imging itself. Imge fusion is esily performed on the rin [2] ecuse the skull is rigid structure tht prohiits significnt movements. Unlike the rin, the dominl cvity is not sttionry, nd orgns cn significntly lter their shpe nd loction. These chnges cn e due to rething, the position of the ptient on the tle, orgn shift, chnge in orgn shpe, hydrtion sttus, stomch contents, nd the RFA procedure itself etc. Not surprisingly, this cused mis-registrtion nd hmpered the fusion process in the kidney nd liver in some cses. Orgn shift nd shrinkge were encountered, s therml lesions tend to shrink fter RFA. This is prolemtic for retrospective fusion of post-rfa imges to

7 112 Experimentl Oncology 31, , 2009 (June) c Fig. 8. Ptient with lesion t liver dome. Contrst enhnced xil CT slice shows low ttenution lesion djcent to high ttenution lesion (rrow) in dome of liver (). Rigid registrtion of PET/CT pre-rfa shows norml FDG uptke over low ttenution lesion djcent to high ttenution lesion (). Post-RFA CT fused with pre-rfa PET (c) verifies RFA tretment zone with mrgins covering the re of norml FDG uptke (rrow) c d e f Fig. 9. Post processed cropped nd colorized CT efore RFA, fter RFA, nd fused imge using rigid nd elstic registrtion methods. Top row ( c) is rigid registrtion wheres the ottom row (d f) is elstic registrtion. The first column (, d) is pre-rfa CT. The second column (, e) is 2 months post RFA CT scn. Rigid registrtion (c) mtches hnd picked ntomy from one imge to the other without ltering either source imge. This my result in mismtch (rrow) since the orgn hs shifted in the time intervl etween imging. Elstic registrtion (f) lso uses lndmrks for point-to-point registrtion, ut llows deformtion of ntomy to etter mtch the re of interest (rrow) pre-rfa imges to ssess for dequcy of tretment mrgin (see Fig. 9). If weeks to months re llowed to pss efore post-rfa imging, then registrtion my show the now-shrunken therml lesion to e smller thn the tumor, giving the flse impression of indequte tretment. This occurred repetedly when we compred 2-month post-rfa imges to pre-rfa imges in kidney tumor ptients, who did not suffer susequent recurrence yers lter (see Fig. 7). The size of the sfety mrgin my influence the utility of this technique [37]. In the liver, 5 10 mm mrgin of norml tissue urned my e esier to mentlly co-register thn ptient with fmilil renl cell crcinom, where only severl mm mrgin is desirle, to preserve norml kidney function given the predisposition for synchronous nd metchronous tumor development over lifetime. For the ltter, this technique my e more useful. If tumor only presents during rteril phse imging, co-registrtion my enle using the sptil informtion of tht rief rteril phse for locliztion during procedure. Imge registrtion lets the physicin use off-line prior imging in the procedure room. Any imging dtset cn e registered to CT spce, which cn then e used to guide rootic needle plcements for point nd click tumor destruction [38].

8 Experimentl Oncology 31, , 2009 (June) 113 This is powerful tool tht my gin importnce in the future s tumor-specific nd cell-specific contrst gents re developed. Fusion my lso enle iopsy of metoliclly ctive regions of tumor, which could fcilitte more ccurte iopsy nd improved informtion on the temporl nd sptil evolution of tumor genomic or proteomic profile. This in turn could help tilor ptient-specific drug regimens. Region cropping proved to e rpid nd simple method of scling down the lrge imging dtsets into computtionlly workle size. While future optimiztions re plnned nd processing speeds re improving, the registrtion process took 3 5 min, which mkes this technique cliniclly relevnt for intr-procedurl monitoring nd nvigtion. Monitoring nd nvigtion during RFA currently suffers from imging limittions. Ultrsound gs shdows the urn, CT contrst increses risk of renl toxicity, CT fluoroscopy hs potentilly high rdition doses to the user, nd MR thermometry is not widely ville, is costly, nd requires RF switch ox or lternting imging Rf-signls with tretment currents. Electromgnetic trcking during RFA my register pre-procedurl imging to the ptient for use during needle mnipultion nd is eing further investigted s n lternte method llowing use of pre-procedurl imging during interventions [39]. Verstile fusion softwre with multiple ville methods of rigid nd elstic registrtion my improve chnces for optiml fusion for given ptient [40, 41], s ech method hs own inherent strengths nd weknesses. However, fusion cn fcilitte interventions in select scenrios. Further vlidtion is indicted efore these techniques cn e routinely utilized or pplied to nvigtion systems or tretment plnning softwre. Current methods of monitoring tretment during RFA re indequte nd my represent the lrgest technicl limittion of RFA tody. Erly detection of the tumor ctivity could potentilly improve outcomes y llowing for erly repet intervention efore regrowth results in geometriclly-unfvorle configurtion. In ddition, method 1 (lest squres) genertes rigid trnsformtion, which involves 6 degrees of freedom (3 rottions nd 3 trnsltions). Method 2 (thin plte splines) is non-liner nd cn provide richer registrtion thn method 1 since this method cn ddress non-liner registrtion prolems (e. g., rething rtifcts, orgn shift, nd orgn deformtion). However, the ccurcy of these two lndmrk registrtion methods is sensitive to user trining nd expertise in choosing lndmrks. In ddition, it cn e time consuming nd difficult to find enough lndmrks to produce nd cceptle registrtion. However, the ffine voxel-similrity utomtic method is invrint to the user nd often provides n cceptle result. This method hs up to 12 degrees of freedom (3 rottions, 3 trnsltions, 3 scle nd 3 skew). While this my yield useful results, this method does not ddress rething rtifcts very well. Voxel similrity methods use sttistics sed on comprisons of voxel intensities etween two dtsets. Correltion rtio nd cross-correltion mesures re typiclly used to register intr-modlity dtsets. Normlized mutul informtion is typiclly used for inter-modlity registrtion. Correltion rtio nd normlized mutul informtion cost functions were used in this study for method 3 for intr nd inter modlity registrtion, respectively. To fully visulize two fused imges, it is importnt to e le to djust the coloriztion or lookup tles, rightness, nd contrst of ech imge independently. In ddition, it is lso importnt to e le to djust the mount of lending etween the two fused imges. Hving the ility to modify these imge ttriutes gretly improves the visuliztion of lesions, vessels, nd necrotic tissue. Such visuliztion is vitl to the ccurte ssessment of RFA sfety mrgins (see Fig. 3 nd Fig. 7). The most sujectively effective color schemes were sved, which llowed the further utomtion of routine post-processing steps. In ddition, surfcerendering techniques llowed for locli ztion nd the visul quntifiction of oth pre-tretment lesion nd post-tretment ltion volumes. Imge processing nd multimodlity fusion re mture dignostic tools tht should e further evluted for potentil utility during interventionl rdiology procedures. ACKNOWLEDGMENTS This work ws supported in prt y the Intrmurl Reserch Progrm of the NIH. The uthors thnk Stephen Bchrch, MD, Ingmr Bitter, PhD nd Grce Ko, MD for their support. REFERENCES 1. Krmer EL, Noz ME, Snger JJ, et l. CT-SPECT fusion to correlte rdioleled monoclonl ntiody uptke with dominl CT findings. Rdiology 1989; 172: Pietrzyk U, Herholz K, Fink G, et l. An interctive technique for three-dimensionl imge registrtion: vlidtion for PET, SPECT, MRI nd CT rin studies. J Nucl Med 1994; 35: Whl RL, Quint LE, Cieslk RD, et l. Antometolic tumor imging: fusion of FDG PET with CT or MRI to loclize foci of incresed ctivity. J Nucl Med 1993; 34: Mountz JM, Zhng B, Liu HG, Inmpudi C. A reference method for correltion of ntomic nd functionl rin imges: vlidtion nd clinicl ppliction. Semin Nucl Med 1994; 24: Correi JA. Registrtion of nucler medicine imges. J Nucl Med 1990; 31: Mintz JB, Viergever MA. A survey of medicl imge registrtion. Med Imge Anl 1998; 2: Viergever MA, Mintz JB, Stokking R. Integrtion of functionl nd ntomicl rin imges. Biophys Chem 1997; 68: Ci J, Chu JC, Recine D, et l. CT nd PET lung imge registrtion nd fusion in rdiotherpy tretment plnning using the chmfer-mtching method. Int J Rdit Oncol Biol Phys 1999; 43: Ferrri de Oliveir L, Azevedo Mrques PM. Coregistrtion of rin single-positron emission computed tomogrphy nd mgnetic resonnce imges using ntomicl fetures. J Digit Imging 2000; 13: Soottk SB, Bredow J, Beuthien-Bumnn B, et l. Comprison of functionl rin PET imges nd introper-

9 114 Experimentl Oncology 31, , 2009 (June) tive rin-mpping dt using imge-guided surgery. Comput Aided Surg 2002; 7: Schoder H, Yeung HW, Gonen M, et l. Hed nd neck cncer: clinicl usefulness nd ccurcy of PET/CT imge fusion. Rdiology 2004; 231: Ktyl S, Krmer EL, Noz ME, et l. Fusion of immunoscintigrphy single photon emission computed tomogrphy (SPECT) with CT of the chest in ptients with non-smll cell lung cncer. Cncer Res 1995; 55: 5759s 63s. 13. D Amico TA, Wong TZ, Hrpole DH, et l. Impct of computed tomogrphy-positron emission tomogrphy fusion in stging ptients with thorcic mlignncies. Ann Thorc Surg 2002; 74: Forster GJ, Lumnn C, Nickel O, et l. SPET/CT imge co-registrtion in the domen with simple nd costeffective tool. Eur J Nucl Med Mol Imging 2003; 30: Goerres GW, Burger C, Schwitter MR, et l. PET/CT of the domen: optimizing the ptient rething pttern. Eur Rdiol 2003; 13: Antoch G, Knj J, Buer S, et l. Comprison of PET, CT, nd dul-modlity PET/CT imging for monitoring of imtini (STI571) therpy in ptients with gstrointestinl stroml tumors. J Nucl Med 2004; 45: Keidr Z, Isrel O, Krusz Y. SPECT/CT in tumor imging: technicl spects nd clinicl pplictions. Semin Nucl Med 2003; 33: Isrel O, Mor M, Gitini D, et l. Comined functionl nd structurl evlution of cncer ptients with hyrid cmer-sed PET/CT system using (18)F-FDG. J Nucl Med 2002; 43: Seemnn MD. PET/CT: fundmentl principles. Eur J Med Res 2004; 9: Townsend DW, Crney JP, Yp JT, Hll NC. PET/CT tody nd tomorrow. J Nucl Med 2004; 45: 4S 14S. 21. Yp JT, Crney JP, Hll NC, Townsend DW. Imgeguided cncer therpy using PET/CT. Cncer J 2004; 10: Isrel O, Keidr Z, Iosilevsky G, et l. The fusion of ntomic nd physiologic imging in the mngement of ptients with cncer. Semin Nucl Med 2001; 31: Wood BJ, Rmkrnsingh JR, Fojo T, et l. Percutneous tumor ltion with rdiofrequency. Cncer 2002; 94: Gervis DA, McGovern FJ, Arellno RS, et l. Renl cell crcinom: clinicl experience nd technicl success with rdiofrequency ltion of 42 tumors. Rdiology 2003; 226: Thnos L, Mylon S, Pomoni M, et l. Primry lung cncer: tretment with rdio-frequency therml ltion. Eur Rdiol 2004; 14: Goetz MP, Cllstrom MR, Chroneu JW, et l. Percutneous imge-guided rdiofrequency ltion of pinful metstses involving one: multicenter study. J Clin Oncol 2004; 22: Jio LR, Hnsen PD, Hvlik R, et l. Clinicl shortterm results of rdiofrequency ltion in primry nd second ry liver tumors. Am J Surg 1999; 177: Arun KS, Hung TS, Blostein SD. Lest-squre fitting of two 3d point sets. IEEE Trns Pttern Anl Mchine Intell 1987; 9: Rohr K, Stiehl HS, Sprengel R, et l. Lndmrk-sed elstic registrtion using pproximting thin-plte splines. IEEE Trns Med Imging 2001; 20: Fulher P, Nelson A, Meht L, O Donnell J. The Fusion of ntomic nd physiologic tomogrphic imges to enhnce ccurte interprettion. Clin Positron Imging 2000; 3: Jenkinson M, Smith S. A glol optimiztion method for roust ffine registrtion of rin imges. Medicl Imge Anlysis 2001; 5: Mutic S, Plt JR, Butker EK, et l. Qulity ssurnce for computed-tomogrphy simultors nd the computed-tomogrphy-simultion process: report of the AAPM Rdition Therpy Committee Tsk Group No 66. Med Phys 2003; 30: Scott AM, Mcpinlc H, Zhng JJ, et l. Clinicl pplictions of fusion imging in oncology. Nucl Med Biol 1994; 21: Turkington TG, Jszczk RJ, Pelizzri CA, et l. Accurcy of registrtion of PET, SPECT nd MR imges of rin phntom. J Nucl Med 1993; 34: Meyer CR, Boes JL, Kim B, et l. Demonstrtion of ccurcy nd clinicl verstility of mutul informtion for utomtic multimodlity imge fusion using ffine nd thinplte spline wrped geometric deformtions. Med Imge Anl 1997; 1: Vnnier MW, Gyou DE. Automted registrtion of multimodlity imges. Rdiology 1988; 169: Berer E, Siperstein A. Locl recurrence fter lproscopic rdiofrequency ltion of liver tumors: n nlysis of 1032 tumors. Ann Surg Oncol 2008; 15: Wood BJ, Bnovc F, Friedmn M, et l. CT-integrted progrmmle root for imge-guided procedures: comprison of free-hnd nd root-ssisted techniques. J Vsc Interven Rdiol 2003; 14: Wood B J, Zhng H, Durrni A, et l. Nvigtion with electromgnetic trcking for interventionl rdiology procedures: fesiility study. J Vsc Interv Rdiol 2005; 16: Archip N, Ttli S, Morrison P, et l. Non-rigid registrtion of pre-procedurl MR imges with intr-procedurl unenhnced CT imges for improved trgeting of tumors during liver rdiofrequency ltions. Med Imge Comput Comput Assist Interv Int Conf Med Imge Comput Comput Assist Interv 2007; 10: Fujiok C, Horiguchi J, Ishifuro M, et l. A fesiility study: evlution of rdiofrequency ltion therpy to heptocellulr crcinom using imge registrtion of preopertive nd postopertive CT. Acd Rdiol 2006; 13: Copyright Experimentl Oncology, 2009