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J. Czernin, M. Dahlbom, O. Ratib, C. Schiepers Atlas of PET/CT Imaging in Oncology Springer-Verlag Berlin Heidelberg GmbH J. Czernin, M. Dahlbom O. Ratib, C. Schiepers Atlas of PET/CT Imaging in Oncology With a Foreword by Michael E. Phelps With 647 Figures and 13Tab1es Springer Authors ISBN 978-3-642-62141-3 ISBN 978-3-642-18517-5 (eBook) DOI 1IO0..1I(0)()0771</j97788-3-3-6-6~24-21-81581571-57-5 J. Czernin,MD M.Dahlbom,MD LibraryofCongressControl umber:2004102323 C.Schiepers,MD.PhD This work is subjcct to copyright. AII rights are reserved, DepartmentofMolecularandMedicalPharmacology whetherthewholeorpartofthematerialisconcerned,specifi callytherightsoftranslation,reprinting.reuscof illustrations. DavidGeffenSchoolofMedicineatUCLA recitation, broadcasting,reproductionon microfilmor inany 10833 LeConteAvenue,AR-I44 CHS otherway,andstorageindatabanks.Duplicationofthispubli LosAngeles,CA90095-6942 cationorpartsthereofispermittedonlyunderthcprovisionsof USA theGermanCopyrightLawofSeptember9.1965.inilscurrent version,andpermissionforusemUSI alwaysbcobtained from O.Ratib.MD.PhD.FAHA Springer-Verlag.Violationsareliableforprosecutionunderthe GermanCopyrightLaw. DepartmentofRadiologicalSciences DavidGeffenSchoolofMedicineat UCLA 100MedicalPlaza,Suite 100 ©Springer-VerlagBerlinHeidelberg2004 Room 1-403 Originallypublishedby Springer-Verlag BerlinHeidclbergNewYorkin2004 LosAngeles,CA90095 Softcover reprintofthchardcovcr Istedition 2004 USA Theuseofgeneraldescriptivenarncs,registerednamcs,trude marks, etc. in this publication does not imply. even in the absenceofaspecificstatcmcnt,tha;suchnamesarccxcmptfrom Contributors therelevantprotective lawsandregulationsandthereforefree forgeneraluse. T.Beyer ProducIliability:Thepublisherscannotguaranteetheaccuracy M.Seltzer ofany infonnationaboutdosageand applicationcontained in D.Townsend this book. Ineveryindividualcase the uscr mustchecksuch C.Yap informationbyconsultingthcrelevantliterature. Editor:UteHeilmann,Heidelbcrg Deskeditor:WiJmaMcHugh.Heidelberg Productioneditor:BemdWieland,Heidelbcrg Coverdesign:F.Steinen,eStudioCalarnar,Spain Dataconversion:AM-productionsGmbll,Wiesloch 21/3111-5 4 32 1 SPI 11414264 Printedonacid-frecpaper Preface Michael E. Phelps The positron emission tomography (PET) andalsoestablishedascientificbasisforthemolecu scannerwasdevelopedtoprovidea molecularimag larimagingproceduresemployedinPET. ingtechnologyforexamining the biologyof normal In about 2 millionclinical PET studies there cellular functionand its transformationto disease in has notbeenone reported complication.This results the living subject.This is achieved by selectingtar primarilyfrom the factthat PETemployees a radio getsofnormaltissueanddisease(proteins,RNAand tracer technique in which the probe concentrations DNA)ofbiochemicalprocessesof interestandlabel aretypicallyintherangeoffemtomolespergramtis ing a molecularprobeselectivefor the target witha sue so there are little to no significant mass effects positron emitting radionuclide (e.g., F-18, C-II , N exertedonbiochemicalorbiologicalprocess. 13,0-15,1-124,Cu-64,Ga-68). Twoexamplesrele While the scientific foundation of PET was vant to cancer illustratethis.The first is 2-deoxy-2 being built there were also dramatic events taking IF-18]fluorodeoxy-D-glucose (FDG)thattargetsthe placeinbiologyinwhichdisciplineswereshiftingto glucose transporter protein and the enzyme hexoki "molecular"- molecularbiology,moleculargenetics, nase that phosphorylatesglucose as the first step in molecularpharmacology,bio-and nanotechnologies, the glycolytic pathway. FDG is a competitive sub genomics,proteomicsandsystemsbiologythatwere stratewithglucoseandprovidesthe meansto image all accompaniedand enabled by revolutionarytech the rate of glycolosis throughoutthe body.The sec nologydevelopmentsthatmadethenewsciencepos ond probe is 3'-IF-18] fluoro-3'-deoxythymidine sible.These efforts beganto change the way people (FLT) that targets the pyrimidine transporter and thought about and performed science and began thymidinekinasethat phosporylates thymidine. FLT building a new knowledge and technology base of isa competitivesubstratewiththymidineto provide moleculardiagnostics and molecular therapeutics to the means to image DNA replication and thus cell establishtheprinciplesandpracticesofanewmolec proliferation. Both glycolosis and DNA replication ularmedicine. arehighlyamplifiedinneoplasticdegeneration. This new molecular world placed more SincePETisaquantitativeimagingtechnique emphasis on imagingproving an in vivo link in the thatcanmeasurethetissueconcentrationoftheimag discoverypathwaytobringthenewknowledgeofthe ingprobeovertime,itprovidesthemeanstotranslate molecular basis of disease to the care of patients. biochemistry,biology and pharmacology laboratory From this came a growing discipline of molecular assaysintotheexaminationsinlivingsubjects.While imaging,withPETina leadershiproleinthe invivo x-raycomputedtomography(CT) movedquickly to applications.Many other imagingtechnologieshave clinical applications after its invention, the first 15 gatheredaroundthisthemetoprovidemolecularand yearsofPETwerefocusedonresearch.Thisinvolved structure information, including optical imaging, translating and validating a wide array of in vitro magnetic resonance imaging (MRI), single photon molecularassaysintoinvivoonesandusingthemto computed tomography(SPECT),CT and ultrasound buildabiologicalbridgebetweeninvitroandinvivo imaging. Molecular imaging is now becoming a biologicalsciences.Inaddition,PETwasusedtodis robustfieldofitsown. cover many aspects of normal biological functions As partof thischange manyin vivo imaging andthoseofdiseaseinlivinganimalsandtheultimate technologiesanddisciplineswerealso beingmerged laboratoryto study human disease, the patient.This atthe instrument(e.g.,PET/CT)or probelevel(PET built a scientific foundation for PETbased on well andopticalreportergenesinthesamegeneconstruct) established principles of biochemistry and biology togaintheadvantageofboth.Thegoalistocombine Preface V molecularassaysfrom different technologies,as well PET/CTalso provides advantages inthe drug as combining biological and anatomical information. discovery processinevaluatingpharmacokineticsand Further, molecular diagnostics and molecular thera pharmacodynamicswith PET withCT betterdefining peutics were merging together with common disease the anatomical structures inwhich drugs actions take targets and building molecular probes (therapeutic place, both at the disease target and throughout the and imaging) together to assist each other in the dis organ systems of the body.These discovery-oriented covery processand inthecare of patients. studies will also define and evolve into new practice PET/CT in cancer, the subject of this Atlas, approaches in the way molecular diagnostics and illustrates many featuresof the evolutionary and rev therapeuticsareemployed togethertoimprovepatient olutionary changes occurring. PET using FOG to selection through a more biologically informative image glycolosis reached a point incancerwhere the pictureofthepatient,direct determination therapeutic literature showed that it was from 9 to 43% more doses and therapeutic outcomes. accurate than anatomical imaging for diagnosing, This Atlas provides a thoughtful and well staging, restaging and assessing therapeutic respons illustrated educationalapproach fordefining the prin es in a large numberof differentcancers and that the ciplesandgood practices ofPET/CT. The additionof inclusion of PET in the clinical evaluation changed the CD-ROM allows teachers and studentsto manip treatment in 15 to 50% of patients,depending on the ulateand navigate throughimagesaswellasblending clinical question. There are,however,specific cases anatomical and biological information or concealing where each technique isbetter than theother. Inaddi information to provide flexibility inindividualteach tion, PET/CT presents a picture of human anatomy ing methods.The Atlassystematically provides clini upon which biological information within structures cal presentations of the cancers of the various organ of the body is added. This combined information systems from diagnosis to staging, recurrent disease allowsbetterdelineationofdisease within orbetween and therapeutic response to help design the best structures, as well as guiding surgical and radiation patient management. It provides a comprehensive planning and biopsyby using both structureand biol educationaltoolforradiologistsandnuclearmedicine ogy identification and characterization. Therefore, it specialists who want to learn about molecular became clear that PET/CT is better than PET or CT PET/CTimaging. alone. VI Atlas of PETleT Imaging in Oncology Table of Contents Part 1: Clinical and Technical Principles Chapter 3: Anatomical Masses vs. Viable Tumor . 99 Introduction . . . . . . . . . . . 1 Cases: Principles of PET/CTImaging . 3 3.1 EccentricTumorViability . 100 3.2 TumorViability 102 Afuture for PETtCT. . . . . . . 12 3.3 LiverCyst. . . . 104 PETtCTImageAcquisition Protocols 3.4 TumorViability . 106 and Imaging OataWorkflow . . 21 3.5 TumorNecrosis. 108 Acquisition Schemes 3.6 PartiallyNecroticNasopharyngeal for Combined 18F-FOG-PET/CT . . . .. 30 CarcinomaMetastasis . . . . . . 110 3.7 PartiallyNecroticLungMetastasis From FOG-PETto FOG-PETtCT Imaging 46 ofGlioblastomaMultiforme . . . . 112 Normal Pattern and Common Pitfalls of FOG-PET Image Interpretation . . . . 54 Chapter 4: Cancers of Headand Neck 117 Cases: 4.1 SquamousCellCarcinoma Part 2: Atlas oftheTongue . . . . . . . . . . . . . . 118 4.2. ThyroidCancer . . . . . . . . . . . . 120 Chapter 1: PET/CTImageArtifacts 63 4.3 NeuroendocrineTumor. . . . . . . . 122 Cases: 4.4 TonsillarSquamousCellCarcinoma . 124 1.1 CardiacPacemaker 66 4.5 SalivaryDuctCarcinoma. . 126 1.2 HipProsthesis . . . 68 4.6 SquamousCellCarcinoma. . . . . . 128 1.3 DentalArtifact . . . 70 1.4 PermanentCentralIntravenous Chapter 5: Solitary Pulmonary Nodules 133 LineArtifact. . . . . . . . . 72 Cases: 1.5 Respiratory MotionArtifact. . . 74 5.1 SolitaryPulmonaryNodule . 134 5.2 SolitaryPulmonaryNodule. 136 Chapter 2: Physiological Variants 79 5.3 Hamartoma....... .. 138 Cases: 5.4 Coccidiomycosis . . . . . . 140 2.1 BrownFat . . . . . . . . . . 80 5.5 SolitaryPulmonaryNodule . 142 2.2 Vocal CordActivity. . . . . . 82 2.3 Rebound ThymicHyperplasia 84 2.4 BloodPoolActivity . . . . . . 86 2.5 ThyroidUptake. . . . . . . . . 88 2.6 Post-SurgicallyAlteredAnatomy. 90 2.7 Post-Surgical Variant. 92 2.8 PancreaticMass . . . . . . . . . 94 Table of Contents VII Chapter6: Lung Cancer 147 Chapter9: Cancers of the Skin 229 Cases: Cases: 6.1 Lung Cancer . . . . 148 9.1 Melanoma 230 6.2 Lung Cancer . . . . 150 9.2 Melanoma 232 6.3 Mucin-Producing Adenocarcinoma 9.3 Restaging Melanoma. 234 of the Lung . . . . . . . . . . . 152 9.4 Metastatic Melanoma 236 6.4 Lung Cancer and Granuloma. . 154 9.5 Ocular Melanoma .. 238 6.5 Malignant and Benign Diseases 156 6.6 Carcinoid...... ..... 158 Chapter10: Breast Cancer. 243 6.7 Status post Pneumonectomy . 160 Cases: 6.8 PleuralCarcinomatosis. 162 10.1 Extensive Metastatic Disease 244 6.9 Mesothelioma ...... ... 164 10.2 Lung and Bone Metastases 246 10.3 Metastatic Breast Cancer. . . 248 Chapter7: 10.4 Internal Mammary LymphNodes. 250 Cancers of the Gastrointestinal Tract . 169 10.5 Breast Implants. . . . . . . . . 252 Cases: 10.6 Inflammatory Breast Cancer . . 254 7.1 Cholangiocarcinoma.. 170 10.7 Benign and Malignant Masses. 256 7.2 Esophageal Cancer. . . 172 10.8 Two PrimaryCancers. . . . . . 258 7.3 Esophageal Carcinoma. 174 7.4 Rectal Cancer. . . . . . 176 Chapter 11:Gynecological Cancers . 263 7.5 Gallbladder and Pancreatic Cancer 178 Cases 7.6 ResidualTumor Viability . . . . . 180 11.1 FallopianTubeCarcinoma . . . . 264 7.7 Gastro-Esophageal Cancer 11.2 Widespread Metastatic Ovarian Cancer 266 with Unexpected Distant Disease 182 11.3 Metastatic Ovarian Cancer . 268 7.8 Metastatic Rectal Carcinoma . . . 184 11.4 Cervical Cancer. 270 7.9 Colon and Hepatocellular Cancer 186 11.5 Ovarian Cancer. 272 7.10 Pancreatid Cancer . . . . . 188 11.6 Uterine Cancer . 274 7.11 Gastric Cancer . . . . . . . 190 7.12 Carcinoma of theAppendix 192 Chapter 12: 7.13 Small Liver Metastasis Cancers of the Genito-Urinary System 279 from Colon Cancer . . . . 194 Cases: 7.14 Recurrent and Metastatic 12.1 Prostate Cancer . . . 282 Colon Cancer. . . . . . 196 12.2 Renal Cell Carcinoma 284 7.15 Rectal Carcinoma. . . . 198 12.3 Renal Cell Carcinoma 286 7.16 Sigmoid Colon Cancer . 200 12.4 Bladder Cancer . . . . 288 12.5 Testicular Cancer. . . 290 Chapter 8: Lymphoma 205 12.6 Transitional Cell Cancer 292 Cases: 8.1 Lymphoma . ... 206 Chapter 13: Benign Diseases 297 8.2 Chronic Myelogenous Leukemia . 208 Cases: 8.3 Hodgkins's Lymphoma . . . . . . 210 13.1 Osteopoikilosis . . . . . 298 8.4 Treatment Response . . . . . . . 212 13.2 Inflammation, Infection . 300 8.5 Localization of Malignant LymphNode 214 13.3 Foreign Body Reaction . 302 8.6 Lymphoma. .... . . .. 216 13.4 Uterine Fibroid 304 8.7 Non-Hodgkin's Lymphoma . 218 13.5 Fistula 306 8.8 Lymphoma Staging . . 220 13.6 Sarcoidosis . . . . 308 8.9 Contrast PET/CT 13.7 TubularAdenoma 310 of Hodgkins's Disease 222 13.8 Fibrous Displasia . 312 8.10 Hodgkin's Lymphoma 224 13.9 Pneumonia. . . . 314 VIII Atlas of PETtCT Imaging in Oncology Introduction J. Czernin, M. Dahlbom, O. Ratib, C. Schiepers, C. Yap Positron Emission Tomography. introduced consists of a brief didactic portion and an extensive almost three decades ago by Phelps and Hoffman,' selection of interesting and challenging case exam hasonlyrecentlybeenacceptedasthemostimportant ples. and innovative tool forcancer imaging.The diagnos The didactic portion of the book includes a tic and prognostic accuracy of PET imaging with F reviewofthetechnicalprinciplesofPETandPETICT 18 deoxyglucose (FDG) ranges from 80-90% for imaging by M. Dahlbom and C.Schiepers who also many cancers?and issuperior toanatomical imaging. discuss differences in PET and CT technology However, PET imaging is limited in its ability to between different commercially available systems. assignmolecularabnormalitiestospecificanatomical D. Townsend,' who introduced the PETICT structures. This limitation has been recently over technology provides in chapter 3 the outlook for the come by the introduction of "in-line", "hybrid" futureofdual modality imaging. PETICT systems- that have dramatically increased Different opinions have been voiced regard the visibility of molecular imaging within the radiol ing the optimal imaging protocols. One school of ogy and oncology community. PETICT has intro thought believes that CT should only be used for duced radiologists to the concept and importance of attenuation correction and lesion localization while molecular imaging and helps to conceptualize the others demand that the most elaborate contrast and inherent limitations of size criteria for defining high-resolution studies should be performed. In any anatomicalabnormalitiesas malignantorbenign.The event, many of these debates have not resulted in a molecular informationprovided byPETenablesradi consensus and it appears likely that the specific ologists for the first time to clearly characterize expertise ofthe users will at least initially determine anatomicalabnormalitiesascancerous or not. On the the implementationofspecific imaging protocols.O. other hand, molecular imaging benefits from the Ratib and T. Beyer will also discuss this and other anatomical framework provided by CT. Hyper-meta issues related to image interpretation and navigation. boliclesionscannowbeassignedto specificanatom J.Czerninsummarizes the clinical experience ical structures. and research studies examining the impact and use Sales figures for PETICT have surpassed fulness ofPETICT.A large number of abstracts thus those of"stand alone" PET systems and itis predict far addressed the additional value of PETICT over ed that more than 90%ofPET will be PETICT inthe PET alone for staging and restaging of cancer. near future. Recently a prospective study was published in the The introduction ofthis technology results in New EnglandJournalofMedicine>thatcomparedthe new training requirements for radiologists and diagnostic accuracy of integrated PET andCT to that nuclear medicine specialists.Radiologists need to be ofPET and CT alone in patients with non-small cell familiar withthe concept ofmolecular imaging while lung cancer.These and otherstudies are reviewed by competence in cross-sectional anatomy is required indetailbyJ.Czernin. from nuclear medicine. A review of the normal FDG distribution in the human body, the pitfalls and normal variants by TheAtlas of PETICT Imaging serves anedu M.Seltzer and C.Schiepers ispresented inchapter7 cational purpose and isdesigned to teach radiologists and completesthe didactic section. and nuclear medicine specialists about important aspects of molecular imaging and nuclear medicine The Atlas section illustrates the benefits but specialists aboutthe benefits ofanatomic imaging.It alsopitfallsofcombinedPETICTimaging.Examples Introduction 1 J. Czernin et al., Atlas of PET/CT Imaging in Oncology © Springer-Verlag Berlin Heidelberg 2004 of artifacts and physiological variants (brown fat, References blood pool, thyroid uptake, muscle activity) are pre sented. The role of PET/CT for imaging cancers of I. Phelps ME, Hoffman EJ,Mullani NA, Ter-Pogossian the head and neck,solitary pulmonary nodules,lung MM. Application of annihilation coincidence detection to transaxial reconstruction tomography. J Nucl Med. cancer, cancers of the gastrointestinal tract, lym 1975;16(3):210-224. phoma,cancersofthe skin,breastcancer,gynecolog 2. CzeminJ,Phelps ME.Positronemission tomography icalcancers,andcancersof thegenito-urinarysystem scanning: current and future applications. Annu Rev Med. is illustrated. Examples of benign diseases include 2002;53:89-112. inflammation,granuloma and benign tumors. 3. BeyerT,Townsend DW,BrunT,Kinahan PE,Charron M, Roddy R,Jerin J,Young J, Byars L, Nutt R. A combined Each case includes a brief history,a specific PET/CT scanner for clinical oncology. J Nucl Med. teaching point that emphasizes image findings, and 2000;41(8):1369-1379. provides relevant clinical follow-up information and 4. Townsend DW, Cherry SR.Combining anatomy and a brieflistof relevant publications. function: the path to true image fusion. Eur Radiol. 2001;11(10):1968-1974. 5. LardinoisD,WederW,HanyTF,Kamel EM,Korom S, A special and unique feature of the Atlas, Seifert B, von Schulthess GK, Steinert He. Staging of non assembledand designed byO.Ratib,isan interactive small-celllungcancerwith integrated positron-emissiontomog CD-ROM that provides the original PET and CT raphy and computed tomography. N Engl J Med. images of each case in selected planes enabling the 2003;348(25):2500-2507. users to manually adjust the blending intensity of 6. Israel0,KeidarZ,Bar-Shalom R,GaitiniD,Beck D, AmitA.Hybrid PET/CT imaging with FDG in management of eachmodalityinafusedimage. Inaddition,userscan patientswithgynecologicmalignancies.JNuclMed.2003;44(5 display the clinical history, imaging techniques and Suppl):I29P. diagnostic findings of each case as well as the corre 7. AntochG,Stattaus J,NematAT,Mamitz S,Beyer T, sponding specific teaching point. An "option" button Kuehl H,Bockisch A,Debatin JF,Freudenberg LS.Non-small allowsturningonandoffgraphicannotationsandleg celllungcancer:dual-modalityPET/CTinpreoperativestaging. Radiology.2003;229(2):526-533. ends for each image. The CD is designed to be an 8. CohadeC,OsmanM,LealJ,WahlRL.Directcompar effective teaching tool through a user-friendly and ison of 18F-FDG PET and PET/CT in patients withcolorectal intuitivegraphic interface for navigatingthrough 100 carcinoma.J Nucl Med.2003;44(11):1797-1803. selected clinical cases covering many frequently 9. FreudenbergLS,AntochG,Schutt P,BeyerT,Jentzen encountered cancers. W,MullerSP,GorgesR,NowrousianMR,BockischA,Debatin JF.FDG-PET/CT inre-stagingof patientswithlymphoma. Eur The CD-ROM is also designed to become a JNucl Med MolImaging.2003;inpress. convenient diagnosticcompanionforretrieving refer 10. Hany TF, Steinert HC, Goerres GW, Buck A, von ence imagesoftypical clinical casesthat maybeused SchulthessGK.PETdiagnosticaccuracy:improvement with in ascomparativestudiesfordiagnostic interpretationof line PET-CT system: initial results. Radiology. similarcases inclinical routine. 2002;225(2):575-581. II. FukuiMB,BlodgettTM,MeltzerCe.PET/CTimaging in recurrent head and neck cancer. Semin Ultrasound CT MR. The convincingconceptof merging molecular 2003;24(3):157-163. with anatomical imaging has driven the clinical acceptance ofPET/CT. Initial data are emerging that strongly suggest that PET/CT imaging results in a higher diagnostic accuracy than PET imaging alone. 4.6-11 The introduction ofPET/CT demands a fresh lookat the training requirements for specialists inthe field of molecular-anatomical imaging. It is hoped that the Atlas of PET/CT imaging results in a better understanding of the capabilities of PET/CT, and in tum, to improved care and management of cancer patients. 2 Atlas of PETteT Imaging inOncology

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