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PositronEmission Tomography forRadiation Treatment
J. Daniel Bourland, PhD
Department of RadiationOncologyBioanatomic ImagingandTreatment ProgramWake ForestUniversity Schoolof Medicine
Winston-Salem,North Carolina, [email protected]
Images© of citedauthorsor corporations
Outline: Part1
• Physicsof PET andPET-CT
• OncologyImagingwith FDG PET
• PETandRadiationTreatmentPlanning
• Summary
Work supportedin partby research grantsfrom North CarolinaBaptist Hospital, VarianMedical Systems,andGEHealthcare
Positron Annihilation
ββββ+
ββββ-nucleus
β+ range
511 keV γ
511 keV γ180o
• Coincidencedetection of two0.511 MeV photons
• Annihilation radiation frompositron-electron pair
• Photondirectionsat180oatannihilationpoint -different fromdecay point� rangeof positron
• Positronemitters with biologicalcompatibility
• Low Z (typically), protonrich,short half-lives
• “Local” productionwith acyclotron
Physics of PETandPET-CT• CE-Imaging: The Physicsand Technology of Radionuclide
Imaging – IIIWednesday,7:30:00AM - 9:25:00AM, Room:L100J– 7:30 AM WE-SAMS-L100J-1BasicPhysicsof PET and PET/CT - F.
Fahey*– 8:25 AM WE-SAMS-L100J-2PET/CT Performance Evaluation
Techniquesand Quality Assurance- B. Kemp*
• PET-CT Workshop• Wednesday,4:00:00 PM - 5:30:00PM, Room:L100E
WE-E-L100E-1 PET CT Workshop - PET/CT ScannerOffering From Different M anufacturers - J. Anderson*, O.Mawlawi*, M. Georgiou*
PET Radionuclidesbiologically compatible,short half-life
Radionuclide Half-Life “ run” speed
Fluorine18 (18F) 110min fast
Carbon 11 (11C) 20 min
Nitrogen13 (13N) 10 min
Oxygen15 (15O) 122sec
Rubidium82 (82Ru) 75 sec very fast(cardiac) Non-corrected
PETCs-attenuatedcorrected
CT-attenuatedcorrected
Phantomwith‘normal’ uptakeexcept left lungthathasair andonespherical‘hottumor’
CT image
Courtesyof K Mah, Univ Toronto,Sunnybrook
With
Without
1. Intensities under-estimatedat depth2. Intensities over-estimated on surface3. Intensities over-estimated for low
density objects (lung)
With and WithoutAttenuation Correction
1.3.
2.
FromRohren, Turkington,Coleman: Radiology2004;231:305-332
FDG PETImaging
PET Imaging in Oncology• Diagnosis– lesscommon
• Staging- yes• TargetDefinition
– Radiationtreatment
– Other“ targeted” therapy
• Re-staging– yes
• TreatmentEvaluation
PET Imaging• Activity distribution is imaged
– Physiology, function, biology
• Complementary to(~anatomic)CT and MR
• Increasedsensitivitycomparedto CT alone
• Most indicationsapprovedforreimbursementareoncology
2-[18F]-fluoro-2-deoxy-D-glucose(FDG)
• 18Fluorine-FDG is mostcommontracer• Malignant tissuesmayhaveincreasedglycolysisandincreasedFDG uptake• FDG-PETimagesare mapsof glucosemetabolism – non-specificimaging
• Diff icultieswith smalltumors(< 3 – 10 mm diameter)• Use increasing– 200 PET-CT scanners in 2 years*• PET-CT hybrid scanners:registration solved
Courtesyof K Mah, Univ Toronto,Sunnybrook*FromBradley, Thorstad, Mutic, et al.,IJROBP 59(1):78-86,2004.
Example: Non-SmallCell LungCancerDiagnosis Staging Re-Staging
FromRohren, Turkington, Coleman: Radiology2004;231:305-332
Example: Head& Neck CancerDiagnosis Staging Re-Staging
FromRohren, Turkington, Coleman:Radiology 2004; 231:305-332
PET and Radiation TreatmentPlanning
• Main contribution – Staging: TargetLocalization– Very important:stagedeterminestreatmentapproach
– Binary results:presence/absenceof disease,metastasis
• Dramaticdifferencespossible– Treatmentmode:reamo, chemo,beamo(EGShaw)
• none,one,all three?10-30% NSCLCpatientsstagechanges
– Radiationtreatment fields: ie, inclusion of nodes• Estimation – bettercoverageof targetwith PET in 30 – 60%of
patients receiving definitive radiationtreatment*
*FromBradley, Thorstad, Mutic, et al., IJROBP59(1):78-86,2004.
ColonCancer:PossibleTreatmentFieldsNodeNegative NodePositive
Adaptedfrom Rohren, Turkington, Coleman:Radiology 2004; 231:305-332
No TreatmentSimpleField Field IncludesNodalRegion
FDG PETand Staging, Localization
Changein stagebeforeandafter PET-CT
FromKoshy, Paulino, Howell et al., Head& Neck,27:6494-502,2005.
Impacton sizeof PTV: CT vs PET/CT
0
200
400
600
800
1000
1200
0 200 400 600 800 1000 1200
PTVCT (cm 3)
PT
VC
T/F
DG
(cm
3 )
Observer 1
Observer 2
Observer 3
• Relativechangesrangedfrom 0.40to 1.86
• In 5 of 23 cases,newFDG nodesdetectedthatincreasedPTV
MahMah, Caldwell,, Caldwell,UngUng et al. IJROBP52,2002et al. IJROBP52,2002Courtesyof K Mah, Univ Toronto,Sunnybrook
FDG PETandRadiationTreatmentChangein PTV andprescribeddose
FromKoshy, Paulino, Howell et al., Head& Neck,27:6494-502,2005.
PETmaydecreasetargetvolumesvs CT
CT: Purple PET/CT: Green
Courtesyof K Mah, Univ Toronto,Sunnybrook
Changesin targetoutlinetranslateto reducedtreatmentfield size
PTV basedon PET/CT
PTV basedon CT only
GTV: CT v PET-CTUseof PET-CT mayreduceGTV/CTV
GTV-CT GTV-PET-CT
FromSchwartz, Ford,Rajendran, et al., Head& Neck27(6): 478-487, 2005.
Ex: FDG-PETincreasedthe targetvolume
Pre-PET: RLL lesion with rightparatracheal node
Post-PET: RLL lesionwith rightparatracheal; subcarinal; andhilarlymphadenopathy (some< 1 cmon CT)
GTV increased to encompassthesenodalregions.
Courtesyof K Mah, Univ Toronto,Sunnybrook
Impactof PET-CT on RT VolumeDelineationUsingCombinedPET-CT Scanner: WashU Group
• Prospective study : 26 NSCLC patients– 8/26(31%)PETchangedstaging– Of 24 still plannedradically
• In 3, PET/CTreducedvolumecomparedto CT alonedueto atelectasis• In 10,PET/CT increasedvolumeasunsuspected nodaldisease was
detected• In 1, newseparatetumorfocuswas foundin samelung
– Overall PET/CT resultedin alterationsin radiationplanninginover 50%of patients by comparisonto CT alone.
Bradley,J et al. IJROBP59,2004
Process: PETin Radiation Treatment
• Cancer diagnosis� biopsy,imaging
• Treatmentposition, immobilization
• PETimaging in treatmentposition
• Expert imagereview
• Imagetransfer– DICOM, other?
• Imageregistration (if needed)
• Targetlocalization anddefinition
• Treatmentplanning
PET-CTSimulator
• Adjacentcontrol, scanner,inject-wait, lab, and toilet
• 1/8 in Pb; control, scanner– adjacentwaiting, scannerbkg
• 1/2 in Pb; inject-wait, toilet• Isotopeprep near on-site• CT, PET-CT operationis
quality – future additionalQA testing
• SharedVirtual Simulation• Lasermarkingsystem• AutomatedPACSarchive,
selective pushto TPS• Normalaccesssecurity
MR
PET-CT
MR Control
VirtualSim
PET
-CT
Control
MRAnnex
Inject-Wait
Office
Office
Wait
MREquip
Wait
Target Definition
• Qualitative:Expert clinical review– Visual, inclusionof clinical historyanddata
– Abovebackground
• Quantitative:Voxel intensityvalues– 40-50%of peak intensity (abovebackground?)
– StandardizedUptakeValue(SUV) of ROI• ie, SUV > 2.5 indicatespositivefor cancer
– Regiondeterminedby PET,extentby CT
RadiationTreatmentPlanning with PETTargetDefinition
Dependingon image windowandlevel setting, targetvolumecanchangeby 50%.Also:a) SUV not apartof DICOM datab) SUV util ity unclear
Samepatientimage:different window andlevel!
TheDigital ContourA Threshold Process
Peak
ThresholdValue
Bkg
TargetWidth
TheDigital ContourA Threshold Process
Peak
ThresholdValue
Bkg
TargetWidth
StandardizedUptakeValue (SUV)
• Semi-quantitativemeasureof glucosemetabolism• Essentially:Averagevoxel valuewithin anROI
– normalizedby activity andbody weight
• Relative to anindividualpatient– Malignancyv benign– Tumorgrade– Treatmentresponse– Prognosis (?) – biological models
In part from Rohren, Turkington, Coleman:Radiology 2004; 231:305-332
SUV Limitations
• Semi-quantitativemeasureof glucosemetabolism• Definition of theROI (CT? self-referencing),and its
location overtime (ie, scanto scan)• Tumorheterogeneity: necrosis, variablegrade• Tumorvolumechangeswith time• Smalltumorsdifficult to image (size� resolution)• Glucoseload?
Consensus?Quantificationof FDG uptake?
In partfrom Greven: SemRadOnc14:2, 2004.
PET-BasedTargeting – H/N
K Greven, PI
• 7 methodsThre shold vs Method H&N
0
2
4
6
8
10
40% 45% 50% BG 1 BG 2 BG 3 BG 4
Thresh old Method
Th
resh
old
SU
V
Patient 1
Patient 2
Patient 3
Lesion Volume vs Method H&N
0
5
10
15
20
25
30
35
40% 45% 50% BG 1 BG 2 BG 3 BG 4
Thresh old Method
Vo
lum
e(c
c)
Patient 1
Patient 2
Patient 3
airway + signal
Unpublished:Lawrence, Greven, Bourland,et al. 2007
Target Definition: “a mess” (R Jeraj)
Nestle et al 2005, J Nucl Med 46 (8), 1342.
TargetDefinition: “a mess”
Nestle et al 2005, J Nucl Med 46 (8), 1342.
DeviceQAGeometricPhantoms
GTV-CT andGTV-PETOtherIssue:Inter-observerVariation
PET CT
FromCaldwell, Mah, Ung, et al., IJROBP51(4):923-931, 2001
Acknowledgements
• Work supportedin part by researchgrantsfromNorth CarolinaBaptistHospital,Varian MedicalSystems,andGE Healthcare
• KathyMah, Universityof Toronto,Sunnybrook• SasaMutic, Washington University in St. Louis• AssenKirov, MemorialSloanKettering,NY, NY
Summary: Part1
• Physicsof PET andPET-CT
• PETin oncology:Staging� TreatmentPath
• PETandRadiationTreatmentPlanning– Localization of regions to betreated
– Targeting,contourdelineation, with limits
RobertJeraj, PhD
PET in TreatmentAssessment