1 2 qiba profile. fdg-pet/ct as an imaging biomarker ... · 121 fdg-pet/ct imaging can be used for...

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QIBAProfile.FDG-PET/CTasanImagingBiomarker3

MeasuringResponsetoCancerTherapy4

Version1.135

TechnicallyConfirmedVersion6

November18,20167

Copyright©2016:RSNA 89

Notetousers–whenreferencingthisQIBAProfiledocument,pleaseusethefollowingformat:

FDG-PET/CTTechnicalCommittee.FDG-PET/CTasanImagingBiomarkerMeasuringResponsetoCancerTherapy,QuantitativeImagingBiomarkersAlliance,Version1.13,TechnicallyConfirmedVersion.QIBA,November18,2016.Availablefrom:RSNA.ORG/QIBA.

Copyright©2016:RSNA Page:2

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TableofContents121.ExecutiveSummary.......................................................................................................................................313

SummaryforClinicalTrialUse......................................................................................................................414

2.ClinicalContextandClaims...........................................................................................................................515

ApplicationsandEndpointsforClinicalTrials...............................................................................................516

Claim:MeasureChangeinSUV.....................................................................................................................617

3.ProfileDetails................................................................................................................................................718

3.1.SubjectHandling....................................................................................................................................819

3.2.ImageDataAcquisition........................................................................................................................1520

3.3.ImagingDataReconstructionandPost-Processing..............................................................................2121

3.4.ImageAnalysis(UPICTSection9).........................................................................................................2422

3.5.ImageInterpretationandReporting(UPICTSection10)......................................................................2423

3.6.QualityControl.....................................................................................................................................2524

4.Conformance...............................................................................................................................................3525

4.1.ImageAcquisitionSite..........................................................................................................................3526

4.2.PET/CTAcquisitionDevice....................................................................................................................3627

4.3.ReconstructionSoftware......................................................................................................................4228

4.4.ImageAnalysisWorkstation.................................................................................................................4429

4.5.SoftwareVersionTracking...................................................................................................................4730

References.......................................................................................................................................................4831

Appendices......................................................................................................................................................5132

AppendixA:AcknowledgementsandAttributions.....................................................................................5133

AppendixB:BackgroundInformationforClaim.........................................................................................5434

AppendixC:ConventionsandDefinitions...................................................................................................5735

AppendixD:Model-specificInstructionsandParameters..........................................................................6236

AppendixE:DataFieldstobeRecordedintheCommonDataFormatMechanism...................................6637

AppendixF:TestingPET/CTDisplayandAnalysisSystemswiththeFDG-PET/CTDRO..............................6738

AppendixG:Vendor-neutralPseudo-codesforSUVCalculation................................................................7139

AppendixH:ConsensusFormulaforComputingLean-Body-MassNormalizationforSUVs.......................7340

AppendixI:QIBAFDGPET/CTImagingSiteandScannerChecklists...........................................................7641


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1.ExecutiveSummary43

ThisQIBAProfiledocumentsspecificationsandrequirementstoprovidecomparabilityandconsistencyfor44quantitative FDG-PET across scanners in oncology. It can be applied to both clinical trial use as well as45individualpatientmanagement.Thisdocumentorganizesacquisition,reconstructionandpost-processing,46analysisandinterpretationasstepsinapipelinethattransformsdatatoinformationtoknowledge.47

The document, developed through the efforts of the QIBA FDG-PET Biomarker Committee, has shared48contentwith the FDG-PETUPICTprotocol, aswell as additionalmaterial focusedon thedevicesused to49acquireandanalyzetheFDG-PETdata.50

Part 4: Conformance Specifications

QIBA Profile for FDG-PET imaging

Part 2: Claim: The specific statement on measurement ability

Part 3: QIBA Acquisition Protocol: Based on UPICT protocol

Part 1: Executive Summary

51Figure1:IllustrationoftheProfilecomponents52

TheProfilePart3islargelyderivedfromtheFDG-PETUPICTprotocolforFDG-PETimaginginclinicaltrials.53In theUPICTprotocol, there isacarefullydevelopedhierarchywith tiered levelsofprotocolcompliance.54This reflects the recognition that there are valid reasons toperform trials usingdifferent levels of rigor,55even for the same disease/intervention combination. For example, a high level of imagemeasurement56precision may be needed in small, early-phase trials whereas a less rigorous level of precision may be57acceptableinlarge,late-phasetrialsofthesamedruginthesamediseasesetting.58

ThethreelevelsofcomplianceforUPICTprotocolsaredefinedas:59

ACCEPTABLE:failingtomeetthisspecificationwillresultindatathatislikelyunacceptablefortheintended60useofthisprotocol.61

TARGET:meeting this specification is considered tobeachievablewith reasonableeffort andequipment62andisexpectedtoprovidebetterresultsthanmeetingtheACCEPTABLEspecification.63

IDEAL: meeting this specification may require unusual effort or equipment, but is expected to provide64betterresultsthanmeetingtheTARGET.65

ACCEPTABLEvaluesarealwaysprovidedforeachparameterinaUPICTProtocol.Whenthereisnoreason66toexpectbetter results (e.g. in termsofhigher imagequality,greaterconsistency, lower radiationdose,67etc.),TARGETandIDEALvaluesarenotprovided.68

ThisProfiledrawsontheACCEPTABLEcomponentsoftheUPICTProtocol.LaterrevisionsofthisProfileare69


expected to draw on the Target and then Ideal categories of the UPICT Protocol. The Target and Ideal70categories are intended to account for advances in the field and the evolving state-of-the-art of FDG-71PET/CTimaging.TheseconceptsareillustratedinFigure2below.72

UPICT Protocol for FDG-PET imaging

• Acceptable...

• Target...

• Ideal...

• Acceptable...

• Target...

• Ideal...

• Acceptable...

• Target...

• Ideal...

Protocol sections

Protocol - Profile relationship

Part 4: Conformance Specifications

QIBA Profile for FDG-PET imaging

Part 2: Claim: The specific statement on measurement ability

Part 3: QIBA Acquisition Protocol: Based on UPICT protocol

Part 1: Executive Summary

73

Figure2.RelationshipbetweentheUPICTProtocolandtheProfile.74

SummaryforClinicalTrialUse75

TheQIBAFDG-PET/CTProfiledefinesthebehavioralperformance levelsandqualitycontrolspecifications76for whole-body FDG-PET/CT scans used in single- and multi-center clinical trials of oncologic therapies.77While the emphasis is on clinical trials, this process is also intended to apply for clinical practice. The78specificclaimsforaccuracyaredetailedbelowintheClaims.79

The specifications thatmust bemet to achieve conformancewith this Profile correspond to acceptable80levels specified in the FDG-PETUPICTProtocol. Theaimof theQIBAProfile specifications is tominimize81intra-andinter-subject,intra-andinter-platform,andinter-institutionalvariabilityofquantitativescandata82duetofactorsotherthantheinterventionunderinvestigation.FDG-PET/CTstudiesperformedaccordingto83thetechnicalspecificationsofthisQIBAProfileinclinicaltrialscanprovidequalitativeand/orquantitative84data for single time-point assessments (e.g., diagnosis, staging, eligibility assessment, investigation of85predictive and/or prognostic biomarker(s)) and/or for multi-time-point comparative assessments (e.g.,86responseassessment,investigationofpredictiveand/orprognosticbiomarkersoftreatmentefficacy).87

A motivation for the development of this Profile is that while a typical PET/CT scanner measurement88system (including all supporting devices) may be stable over days or weeks, this stability cannot be89expected over the time that it takes to complete a clinical trial. In addition, there are well known90differencesbetweenscannersandortheoperationofthesametypeofscanneratdifferentimagingsites.91

Theintendedaudiencesofthisdocumentinclude:92

• Technicalstaffofsoftwareanddevicemanufacturerswhocreateproductsforthispurpose.93• Biopharmaceutical companies, oncologists, and clinical trial scientists designing trials with imaging94

endpoints.95• Clinicalresearchprofessionals.96


• Radiologists, nuclear medicine physicians, technologists, physicists and administrators at healthcare97institutionsconsideringspecificationsforprocuringnewPET/CTequipment.98

• Radiologists, nuclear medicine physicians, technologists, and physicists designing PET/CT acquisition99protocols.100

• Radiologists, nuclear medicine physicians, and other physicians making quantitative measurements101fromPET/CTimages.102

• Regulators, nuclear medicine physicians, oncologists, and others making decisions based on103quantitativeimagemeasurements.104

Note that specifications stated as 'requirements' in this document areonly requirements to achieve the105claim,not'requirementsonstandardofcare.'Specifically,meetingthegoalsofthisProfileissecondaryto106properlycaringforthepatient.107

Asummaryofthespecificationsrequiredtoachievetheclaim,andformattedasachecklist,areprovidedin108Appendix I. The corresponding specifications are indicated as bold text in the tables of normative109statementsbelowasdescribedinAppendixC.ThischecklistmaybeusedtoascertainaPETimagingsite’s110qualificationforquantitativeimagingaccordingtotheQIBAFDGPET/CTprofile.111

2.ClinicalContextandClaims112

FDGisaglucoseanalogue.Therationaleforitsuseinoncologyisbasedonthetypicallyincreasedrateof113glycolysis intumorscomparedtonormaltissue.FDGistransported intotumorcellsviaglucosetransport114proteins,usuallyup-regulatedintumorcells.OnceinternalizedFDGisphosphorylatedtoFDG-6-phosphate;115it does not progress any further along the glycolytic pathway and becomes substantially metabolically116trapped.FDGuptakeisnotspecificfortumorcellsandtherearesomenormaltissuesandotherprocesses117with increased glucose turnover, e.g. infection and inflammation, that show elevated uptake or118accumulationofFDG.119

ApplicationsandEndpointsforClinicalTrials120

FDG-PET/CTimagingcanbeusedforawiderangeofclinicalindicationsandresearchquestions.Theseare121addressed more completely in the FDG-PET/CT UPICT Protocol (UPICT section 1.1). This QIBA Profile122specificallyaddressestherequirementsformeasurementoftumorFDGuptakewithPET/CTasanimaging123biomarkerforevaluatingtherapeuticresponse.124

Biomarkersusefulinclinicalresearchforpatientstratificationorevaluationoftherapeuticresponsewould125beusefulsubsequentlyinclinicalpracticefortheanalogouspurposesofinitialchoiceoftherapyandthen126individualizationoftherapeuticregimenbasedontheextentanddegreeofresponseasquantifiedbyFDG-127PET/CT.128

ThetechnicalspecificationsdescribedintheProfileareappropriateforquantificationoftumorFDGuptake129andmeasuring longitudinal changes within subjects. However,many of the Profile details are generally130applicabletoquantitativeFDG-PET/CTimaginginotherapplications.131

FDG-PETscansaresensitiveandspecificfordetectionofmostmalignanttumors[Fletcher2008].Coverage132foroncologyimagingproceduresintheUSbytheCentersforMedicareandMedicaidServicesareexplicitly133listedintheNationalCoverageDetermination(NCD)forPositronEmissionTomography(PET)Scans(220.6).134FDG-PET scans reliably reflect glucose metabolic activity of cancers and this metabolic activity can be135


measuredwithhighreproducibilityovertime.Longitudinalchangesintumor18F-FDGaccumulationduring136therapy often can predict clinical outcomes earlier than changes in standard anatomic measurements137[Weber2009].Therefore, tumormetabolic responseorprogressionasdeterminedby tumorFDGuptake138can serveasapharmacodynamicendpoint inwell-controlledPhase I andPhase IIA studiesaswell asan139efficacyendpointinPhaseIIandIIIstudies.Intumor/drugsettingswheretheprecedingphaseIItrialshave140showna statistically significant relationshipbetween FDG-PET response and an independentmeasureof141outcome, changes in tumor FDGactivitymay serve as theprimary efficacy endpoint for regulatory drug142approvalinregistrationtrials.143

Claim:MeasureChangeinSUV144

ConformancetothisProfilebyallrelevantstaffandequipmentsupportsthefollowingclaims:145

Claim 1: Tumor glycolytic activity as reflected by themaximum standardized uptake value (SUVmax) is146measurablefromFDG-PET/CTwithawithin-subjectcoefficientofvariationof10-12%.147

Claim2:AmeasuredincreaseinSUVmaxof39%ormore,oradecreaseof-28%ormore,indicatesthata148truechangehasoccurredwith95%confidence.149

Thefollowingimportantconsiderationsarenoted:150

1.ThisClaimappliesonlytotumorsthatareconsideredevaluablewithPET.Inpracticethismeanstumors151of aminimumsizeof 2 cmandabaseline SUVmaxof 4 g/ml (e.g. [Wahl 2009, de Langen2012]).More152detailsonwhattumorsareevaluablearedescribedinsection3.6.5.3.153

2.DetailsoftheclaimwerederivedfromareviewoftheliteratureandaresummarizedinAppendixB.154

3.Thepublishedasymmetriclimitsofrepeatabilityarebasedonobservationsthatthetest-retestSUVmax155differencesdonotfollowaNormaldistribution,butthatthedifferences(d)ofthelogarithmsofthetest-156retestSUVmaxvaluesdofollowaNormaldistributionwithastandarddeviationofSD(d)[Velasquez2009,157Weberetal.2015].The95%repeatabilitycoefficient (RC) in the log-Normaldistribution (i.e.±1.96SD(d))158aresymmetricabout themean.Thissuggests thatwhenthese limitsareconvertedback toSUVunitsby159exponentiation using RC = 100(exp(±1.96SD(d)) -1), the SUV RC limits are necessarily asymmetric. In160addition,notethatifthestandarddeviationisnotlargecomparedwiththelevelofthemeasurement,then161itcanbeshownthat100(exp(SD(d)/sqrt(2))-1) isapproximatelyequal to thewithin-subjectcoefficientof162variation,expressedasapercent[BlandandAltman1996,Velasquez2009].IfweassumeawCVof12%for163SUVmax,thentherepeatabilitycoefficientsare(-28%,+39%),consistentwiththefindingsbyVelasquezet164al.foradvancedgastrointestinalmalignancies,andthoseofWeberetalfornon-smallcelllungcancer.Asa165possiblymoreintuitivemotivationthatasymmetriclimitscanbeexpected,wesupposetwomeasurements166SUVmax1=7.0andSUVmax2=9.75,then167(SUVmax2-SUVmax1)/SUVmax1=+39%168(SUVmax1-SUVmax2)/SUVmax2=-28%169In other words, there is net change in SUVmax of 2.75 in either direction representing a physiological170differencebetweentwodiseasestates:Asanincreaseitis+39%,orasadecreaseitis-28%171

4.ThisClaimisapplicableforsingle-centerstudiesusingthesamescanner.Formulti-centerstudies,ifFDG-172PET/CTimagingisperformedusingthesamescannerandprotocolforeachpatientateachtimepoint(as173describedintheProfile),thenitisanticipatedthatthisClaimwillbemet.174

5.ThisClaimisbasedonSUVmaxduetotheevidenceprovidedinthescientificliterature.However,theuse175ofSUVmetricsderived from larger regions-of-interest (e.g.SUVpeak)are tobeencouraged,as theymay176


provideimprovedrepeatability.Inaddition,theuseofautomatedand/orcentralizedanalysismethodswill177further improve SUV repeatability. Note thatwhile relative limits appear to be appropriate for SUVmax178measures, itmay be that absolute limitsmay bemore appropriate for SUVs based onmean values for179volumetricROIs[NahmiasandWahl2008].180

6.WhiletheClaimhasbeeninformedbyanextensivereviewoftheliterature, it iscurrentlyaconsensus181Claimthathasnotyetbeensubstantiatedbystudiesthatstrictlyconformtothespecificationsgivenhere.182In addition, we note that this Claim should be re-assessed for technology changes, such as PSF (point183spread function)based reconstructionorTOF (timeof flight) imaging thatwerenotutilized inpublished184test-retest studies. A standard utilized by a sufficient number of studies does not exist to date. The185expectationisthatfromfuturestudiesand/orfieldtesting,datawillbecollectedandchangesmadetothis186ClaimortheProfilespecificationsaccordingly.187

188

3.ProfileDetails189

Thefollowingfigureprovidesagraphicaldepictionthatdescribesthemarkeratatechnicallevel.190

191Figure3:TheassaymethodforcomputingandinterpretingglycolyticmetabolicactivityusingPET/CTmay192beviewedasapipelineusingeitheroneortwoormorescansequences.ThemeasureSUVxreferstooneof193severalpossibleSUVmeasures,suchasSUVmax,SUVmeanorSUVpeak,withnormalizationbybodyweight194orleanbodymass.195

PatientsmaybeselectedorreferredforFDG-PET/CTimagingthoughavarietyofmechanisms.Inaddition,196patientsareoftenrequiredtoundergoscreeningaccordingtopre-scanrequirementssuchasfastinglevels197and/orserumglucoselevelsasdescribedbelow.198

TheimagingstepscorrespondingtoFigure1are:199

1) Patientsorsubjectsarepreparedforscanning(e.g.6hrfasting).FDGisadministered.Patientwaits200quietlyforbio-distributionanduptakeofFDG(typically60min)201


2) ScandatafromthePETandCTexamsisacquired.202

3) DatacorrectiontermsareestimatedandPET(andCT)imagesarereconstructed.203

4) Quantitativemeasurementsareperformed.204

5) Imagesarereviewedforqualitativeinterpretation.205

Notethatsteps4and5mayoccurineitherorderoratthesametime.Moredetailsontherequirements206aregivenbelow.207

Imagesmaybeobtainedatmultiple timepointsoverdaysorweeks,notablyataminimumof two time208points before and after therapeutic intervention for a response assessment as is considered by this209document.ThechangeinFDGuptakeistypicallyassessedasapercentageaccordingtotheformula:210

[(post-treatmentmetabolicactivity–pre-treatmentmetabolicactivity)/pre-treatmentmetabolicactivity]211x100%.Responsecriteriaarethenappliedtocategorizetheresponseassessment.Theseresponsecriteria212arebeyondthescopeofthisdocument,butarediscussedinthePERCISTproposal[Wahl2009].213

ThefollowingsectionsdescribethemajorcomponentsillustratedinFigure3:214

Section Title Performedby

3.1 SubjectHandling

Personnel,(includingTechnologistsandSchedulers)atanImageAcquisitionFacility

3.2 ImageDataAcquisition

Technologist,atanImageAcquisitionFacilityusinganAcquisitionDevice

3.3 ImageDataReconstruction

Technologist,atanImageAcquisitionFacilityusingReconstructionSoftware

3.4 ImageAnalysis ImagingPhysicianorImageAnalystusingoneormoreAnalysisSoftwaretools

3.5 ImageInterpretation

ImagingPhysicianbeforeorafterinformationobtainedbyImageAnalysisusingapre-definedResponseAssessmentCriteria

Imagedata acquisition, reconstruction andpost-processing are considered to address the collection and215structuringofnewdatafromthesubject.Imageanalysisisprimarilyconsideredtobeacomputationalstep216that transforms the data into information, extracting important values. Interpretation is primarily217consideredtobejudgmentthattransformstheinformationintoknowledge.218

3.1.SubjectHandling219

ThisProfilewillreferprimarilyto'subjects',keepinginmindthattherecommendationsapplytopatientsin220general,andthatsubjectsareoftenpatientstoo.221

3.1.1SubjectSelection,Timing,andBloodGlucoseLevels222

The study protocol should include specific directions as to themanagement of subjects with abnormal223fasting blood glucosemeasurementswhether known to be diabetic or not.While it is known that high224levels of circulating blood glucose reduce FDG uptake, there is a paucity of scientific data to suggest a225specific cutoff for abnormally highblood glucosemeasurements or if these subjects should be excluded226fromclinicaltrialsthatuseFDG-PET/CTscandata.Itisimportanttodefinehowsuchsubjectsandthedata227from their imaging studieswill bemanaged to ensure comparability of imaging datawithin and among228


clinicaltrials.Specifically,considerationshouldbegiventotheexclusionofsubjectswithabnormalfasting229bloodglucosewhenquantitativeFDG-PET/CT isbeingusedas thestudy’sprimaryendpoint.Refer tothe230FDG-PET/CTUPICTProtocolforDiabeticSchedulingandManagementdiscussion(UPICTSection4.2.2).Itis231alsorecommendedthatthestudyspecifieswhatlevelofwithinsubjectvariabilityinserumglucoselevelsis232acceptableacrosstimepointsandhowsubjectsthatfalloutsidethatrangewillbeinterpreted.233

3.1.1.1TimingofImagingTestRelativetoInterventionActivity(UPICTSection1.2)234

The study protocol should specifically define an acceptable time interval that should separate the235performanceoftheFDG-PET/CTscanfromboth(1)theindexinterventionand(2)otherinterventions(e.g.236chemotherapy, radiotherapy or prior treatment). This initial scan (or time point) is referred to as the237“baseline”scan(ortimepoint).Thetimeintervalbetweenthebaselinescanandtheinitiationoftreatment238should be specified as well as the time intervals between subsequent FDG-PET studies and cycles of239treatment. Additionally, the study protocol should specifically define an acceptable timing variance for240performance of FDG-PET/CT around each time point at which imaging is specified (i.e., the acceptable241windowoftimeduringwhichtheimagingmaybeobtained“onschedule”).Thetimingintervalandwindow242are dependent upon 1) the utility for the FDG-PET/CT imaging within the clinical trial, 2) the clinical243question that is being investigated and 3) the specific intervention under investigation. Suggested244parameters for timingof FDG-PET/CTwithinoncologic trials aremore completely addressed in theFDG-245PET/CTUPICTProtocolsection1.2.246

3.1.1.2.TimingRelativetoConfoundingActivities(UPICTSection3.2)247

Activities, tests and interventions thatmight increase the chance for falsepositive and/or falsenegative248FDG-PET/CT studies shouldbe avoidedprior to scanning. Theallowable interval between thepotentially249confoundingeventandtheFDG-PET/CTexamwillbedependentonthenatureoftheconfoundingvariable.250For example, inflammation may cause focally increased FDG-PET activity (e.g. from a percutaneous or251excisional biopsy of a suspiciousmass) ormight lead to the appearance of a non-malignantmass (e.g.,252hematoma)ontheCTportionofthestudy.Apercutaneousablationprocedureofaknownmalignantfocus253maycausefocallyincreasedFDG-PETactivityand/oranimmediatepost-ablationincreaseintheapparent254volumeoftheablatedtargetlesion.ThetimeofonsetandthedurationoftheincreasedFDG-PETactivity255and/orthechangeinlesionvolumemightbedifferentforthesetwoconfoundingfactors.256

If iodinated contrast is to be used for the CT portion of the PET/CT study, conflictwith other tests and257treatmentsshouldbeavoidedcongruentwithcommunitystandardsofcare(e.g.,thyroidscan).258

3.1.1.3.TimingRelativetoAncillaryTesting(UPICTSection3.3)259

AvoidschedulingteststhatmightconfoundthequalitativeorquantitativeresultsoftheFDG-PET/CTstudy260within the timeperiodprior to the scan. Forexample, a glucose tolerance test shouldnotbe scheduled261during the 24 hours prior to the performance of FDG-PET/CT. Similarly, other tests that might involve262increasingplasmaglucose, insulin,orcorticosteroid levels shouldalsobeavoided.Exercisecardiacstress263testing should be avoided during the twenty-four (24) hours prior to the performance of FDG-PET/CT.264Similarly,otherteststhatmightinvolvevigorousexerciseandtherebyincreasemusclemetabolicfunction265shouldalsobeavoided.266

3.1.2SubjectPreparation(UPICTSection4)267

Management of the subject can be considered in terms of three distinct time intervals (1) prior to the268imaging session (prior to arrival and upon arrival), (2) during the imaging session and (3) post imaging269


session completion. The pre-imaging session issues are contained in this sectionwhile the intra-imaging270issuesarecontainedinsection3.2.1onimagedataacquisition.271

3.1.2.1.PriortoArrival(UPICTSection4.1)272

Themain purpose of subject preparation is to reduce tracer uptake in normal tissue (kidneys, bladder,273skeletal muscle, myocardium, brown fat) while maintaining and optimizing tracer uptake in the target274structures(tumortissue).Formoredetail,refertotheFDGPETUPICTProtocol(Section4.1)thataddresses275(1)Dietary,(2)FluidIntake,and(3)OtheractivitiesthatmayaffecttissueFDGuptake.276

(1) Dietary277

a. Diabeticmanagement–RefertoFDG-PET/CTUPICTProtocolsections1.7.2and4.2.2278

b. Fastingstatus -Subjectsshouldnoteatany food (eitheroralorparenteral) forat leastsix279hourspriortotheanticipatedtimeofFDGadministration.280

(2) FluidIntake:Adequatehydration(beforeandafterFDGadministration)isimportantbothtoensure281asufficiently lowFDGconcentrationinurine(fewerartifacts)andtoreduceradiationexposureto282the bladder. Adequate hydration is especially important when contrast CT imaging will be used.283Whicheverhydrationstrategyisused(howmuchandwhentoadminister),theprotocolshouldbe284uniformamongsitesduringatrial.SpecifichydrationrecommendationsarepresentedintheFDG-285PET/CTUPICTProtocol(referenceSection4.2.1).Thefluidadministeredshouldnotcontainglucose286orcaffeine.287

(3) OtherActivities:TominimizeFDGuptakeinmuscle,thesubjectshouldavoidstrenuousorextreme288exercisebeforethePETexamforatleast6hours(preferablyforatimeperiodof24hours).289

The conformance issues around these parameters are dependent upon adequate communication and290oversight of the Scheduler or Technologist at the Image Acquisition Facility with the subject.291Communicationwiththesubjectandconfirmationofconformanceshouldbedocumented.292

3.1.2.2.UponArrival(UPICTSection4.2)293

Uponarrival1)confirmationofsubjectcompliancewithpre-procedureinstructionsand2)theoccurrence294of potentially confounding events (see listing in Section 4.2.1 of FDG-PET/CT UPICT Protocol) should be295documentedontheappropriatecasereportforms.296

There should be documentation of subject-specific risk factors including, but not limited to, previous297contrastreactions(ifiodinatedcontrastistobeused).298

3.1.2.3PreparationforExam(UPICTSection4.2.3)299

InordertoavoidheterogeneousphysiologicaldistributionoftheFDG,itiscriticalthatsubjectpreparation300afterarrivalandpriortoimagingisstandardizedamongallsitesandsubjectsthroughouttheconductofthe301clinicaltrial.302

• Thewaitingandpreparationroomsshouldberelaxingandwarm(>75°For22°C)duringtheentire303uptakeperiod (and for as long as reasonablypracticableprior to injection, at least 15minutes is304suggestedasacceptable).Blanketsshouldbeprovidedifnecessary.305

• The subject should remain recumbent or may be comfortably seated; activity and conversation306shouldbekepttoanabsoluteminimum.Forexample,thesubjectshouldbeaskedtorefrainfrom307speaking,chewing,orreadingduringtheuptakeperiod.Forbrainimagingthesubjectshouldbeina308


roomthatisdimlylitandquietforFDGadministrationandsubsequentuptakeperiod.309

• After FDG injection, the subject may use the toilet, preferably not for the initial 30 minutes310immediately after injectionof FDG, primarily to avoidmuscular uptakeduring thebiodistribution311phaseofFDG-uptake.Thesubjectshouldvoidimmediately(within5–10minutes)priortotheFDG-312PET/CTimageacquisitionphaseoftheexamination.313

• Bladdercatheterizationisnotroutinelynecessary;butifdeemednecessary(e.g.,fortheevaluation314ofasubjectwithapelvictumorsuchascervicalorprostatecancer),thecathetershouldbeplaced315prior to injection of FDG. If bladder catheterization is performed, additional strategies to avoid316trappinghighactivitypocketsofactivitywithinthebladdershouldbeconsideredsuchasretrograde317fillingofthebladdertodilutetheresidualactivity.318

• Following the administration of FDG, the subject should drink 500 ml of water (or receive by319intravenousadministration250-500mlofnon-glucosecontainingfluid).Fluidintakemayneedto320bemodifiedforthosesubjectsonfluidrestriction.321

• Forspecificareasofanatomicinterest(e.g.,tumorslocatedinthelowerabdomen,pelvisorkidney)322intravenousdiureticagentsmaybeused(e.g.,20–40mgoffurosemidegiven15minutesafterthe323administrationofFDG).Ifbladdercatheterizationisperformed,IVdiureticsshouldbeadministered324asdescribedheresoastoensurethattheconcentrationofactivityintherenalcollectingsystems325andbladderisrelativelydilute.326

• Sedationisnotroutinelyrequired,butisnotcontraindicatedprovidedthatthesedativeuseddoes327not interferewith the uptake of FDG. Sedationmay have utility in specific clinical circumstances328suchasinsubjectswithbrain,headandnecktumorsorbreastcancer,claustrophobicsubjects,or329children.Thesedativeeffectshouldlastforthedurationofimageacquisition;detailedspecifications330aredependentuponthemedicationusedandtherouteofadministration.331

• Theamountoffluidintakeanduseofallmedications(e.g.,diuretic,sedative)mustbedocumented332ontheappropriatecasereportform.333

• Subjects undergoing a CT scan should empty their pockets and remove any clothing containing334metalandanymetallicjewelryfromthebodypartstobescanned,changingintoahospitalgownif335necessary.336

Parameter Entity/Actor Specification

HeightandWeight ImagingTechnologist

TheTechnologistshallmeasureanddocumentsubjectheightandweightandenterthisinformationintothescannerduringthePET/CTacquisition.

SubjectbodyweightshallbemeasuredatthetimeofeachPET/CTscanwithstandardizedmeasurementdevicesandwiththesubjectinanexaminationgownorlightclothing.SubjectheightshallbemeasuredanddocumentedatthetimeofbaselineFDG-PETscanwithstandardizedmeasurementdevice.Measurementofsubjectheightisnotrequiredateachsubsequenttimepointunlessothersubject-centricfactors(e.g.growthinpediatricpopulationorshrinkageinelderlypopulation)arerelevantincombinationwithaprolonged



intervalbetweenimagingtimepointssuchthatachangeinheightmightbesignificant.

Ifsubjectcannotbemovedfromthebed,thedateandsourceofinformationshouldbedocumented.

TheTechnologistshallmeasuresubjectheightandweightandenterthisinformationintoacommondataformatmechanismusedforrecordingallneededinformation(AppendixE).

• DiabeticMonitoringandManagement(UPICTSection4.2.2)337

The subject’s blood glucose level should bemeasured [using CLIA-approved, CLIA cleared, or equivalent338(outside US) glucosemeasurement device or laboratory] within the preceding 2 hours (ideally within 1339hour,especiallyinsubjectswithdiabetes)ofFDGadministrationanddocumented.340


Bloodglucoselevelmeasurement

ImagingTechnologistorLabTechnologist

Within2hoursprecedingFDGadministration,shallmeasureanddocumenttimeofsubjectbloodglucosecollection.GlucosemeasurementshouldbeperformedusingaCLIAapproved,CLIAcleared,orequivalent(outsideUS)glucosemeasurementdevice.Ifthemeasurementisalwaysperformedatinjectiontimeorotherwiseaccordingtoaprotocolrelativetoinjectiontime,thismaybedocumentedintheprotocol.

Deviationsfromthisprocessshallbedocumented.

Bloodglucoseleveldocumentation

ImagingTechnologistorLabTechnologist

Shallentertheresultsofthebloodglucoseassayandthetimeofblooddrawonacasereportformorsimilarsubjectinformationsheet.

Shallentertheresultsofthebloodglucoseassayintoacommonformatmechanismusedforrecordingallneededinformation(AppendixE).

BloodglucoselevelThreshold

ImagingTechnologist

ShallenforcetheglucosethresholdsforimagingasdefinedintheProtocol;ifnot,thenreasonfornon-conformanceshallbeprovidedanddocumentedoncasereportformorsimilarsubjectinformationsheet.

Shalldocumentanyinformationonnon-conformancewiththeprotocolintoacommonformatmechanismusedforrecordingallneededinformation(AppendixE).


3.1.3.Imaging-relatedSubstancePreparationandAdministration(UPICTSection5)341

3.1.3.1.RadiotracerPreparationandAdministration342

3.1.3.1.1RadiotracerDescriptionandPurpose343

FDGshouldbeofhighqualityandpurity. Forexample, theFDGradiopharmaceuticalmustbeproduced344underCurrentGoodManufacturingPracticeasspecifiedbytheFDA,EU,EuropeanPharmacopeaorother345appropriate national regulatory agency. U.S. regulations such as 21CFR212 or USP<823>346Radiopharmaceuticals for Positron Emission Tomography must be followed in the U.S. or for trials347submitted toUSRegulatory. For example, in theUS, for clinical practice, FDGproduction underNDAor348ANDAorunderINDforresearchpurposesismandatory.349

3.1.3.1.2RadiotracerActivityCalculationand/orSchedule(UPICTSection5.2)350

The18F-FDGactivityadministered rangesbetweenabout185–740MBq (5–20mCi).Theadministered351activitytypicallydependsuponthelocalimagingprotocol.Thelocalprotocolmayrequirefixedactivity,or352theactivitymayvaryasafunctionofvariousparameters includingbutnot limitedtosubjectsizeorage,353scanner model, scanning mode, or percentage of scan bed (slice) overlap. To date there are no data354providing evidence of superiority of parameter-dependent administered activity protocols. The exact355activityandthetimeatwhichactivity iscalibratedshouldberecorded.Residualactivityremaining inthe356tubing, syringe or automated administration system or any activity spilled during injection should be357recorded.TheobjectiveistorecordthenetamountofFDGradiotracerinjectedintothesubjecttoprovide358accuratefactorsforthecalculationoftheSUV.Theuseofautomatedactivitymeasurementandinjection359devicesisallowedifaccuracyisverified.360


AdministeredFDGRadiotracerActivity

ImagingTechnologist

TheTechnologistshall

1. Assaythepre-injectionFDGactivity(i.e.radioactivity)andtimeofmeasurement,

2. InjecttheFDGasprescribedintheprotocol,withintherangedefinedintheprotocol.

3. RecordthetimethatFDGwasinjectedintothesubject,

4. Assaytheresidualactivityinthesyringe(andreadilyavailabletubingandcomponents)afterinjectionandrecordthetimeofmeasurement.

ThesevaluesshallbeenteredintothescannerduringthePET/CTacquisition.

Forscannersthatdonotprovideforentryofresidualactivityinformation,thenetinjectedradioactivityshouldbemanuallycalculatedbydecaycorrectingallmeasurementstothetimeofinjectionandthensubtractingtheresidualradioactivityfromthepre-injectionradioactivity.ThenetinjectedradioactivityisthenenteredintothescannerduringthePET/CTacquisition.

Alldatadescribedhereinonactivityadministrationshallbe



documented.

Alldatashouldbeenteredintothecommondataformatmechanism(AppendixE).

3.1.3.1.3RadiotracerAdministrationRoute(UPICTSection5.4)361

FDG shouldbeadministered intravenously througha largebore (24 gaugeor larger) indwelling catheter362placedanatomicallyremote(e.g.,contralateralextremitytositeofdiseaseifatallpossible)toanysite(s)of363suspectedpathology, preferably in an antecubital vein. Intravenousports shouldnot beused, unless no364other venous access is available. If a port is used, an additional flush volume should be used. As365reproducible and correct administration of FDG is required for quantification purposes, extravasation or366paravenous administration should be avoided. If an infiltration or extraneous leakage is suspected, the367event and expected quantity should be recorded and the infiltration site should be imaged. The368approximateamountofinfiltrationshouldbeestimatedfromtheimageswherepossible.Iftheinfiltration369isgreaterthan5%oftheadministeredactivityandthequantitativeresultfromtheFDG-PET/CTstudyisa370primaryorsecondaryendpoint,thedatapointmightbecensoredfromrevieworthesubjectmightnotbe371included in the study. The anatomical location of the injection site should be documented on the372appropriatecasereportformorintheCommonDataFormatMechanism(AppendixE).373

Presuming that the IV access is properly functioning, the same route of administrationmaybeused for374iodinatedcontrastasisusedforFDG.375


FDGAdministration

TechnologistTechnologistshalladministerFDGintravenouslythroughalargebore(24gaugeorlarger)indwellingcatheterplacedanatomicallyremotetoanysitesofsuspectedpathology,preferablyinanantecubitalvein.Intravenousportsshouldnotbeused,unlessnoothervenousaccessisavailable.

Inthecaseofmanualadministration,athree-wayvalvesystemshouldbeattachedtotheintravenouscannulasoastoallowatleasta10ccnormal(0.9%NaCl)salineflushfollowingFDGinjection.Forautomatedinjectiondevicesalternateflushingmechanismsareallowed.

Suspectedinfiltrationorextraneousleakage

Technologistand/orPhysicianorPhysicist

Technologistshalldocumentanysuspectedinfiltration,leakage,orexternalcontaminationandconsiderscanningtheinjectionsiteand/orcontaminatedmaterials.

RecordtheeventandexpectedamountofFDGintothecommondataformatmechanism(AppendixE).

3.1.3.2CTContrastMaterialPreparationandAdministration376

TheuseofCTcontrastmaterialduringFDG-PET/CTimagingiscomplexandanalyzedindetailintheUPICT377


FDG-PETProtocol(Section3.2).Insummary,thepresenceofIVand/ororalcontrastmaterialimprovesthe378detectionoflesionswithCTandmayimprovetheanatomiclocalization,interpretation,andanalysisofthe379FDG-PET/CTexam.However,thepresenceofcontrastmaterialmayaffecttheattenuationcorrectionofthe380PETscanwithconsequentbiasinmeasuredSUVs.381


CTContrastAgent

Technologist TechnologistshallrecordthetypeandamountofCTContrastAgent.

1.Wasoralcontrastused:Type[Positive,Negative],amount(volumeincc).

2.WasIVcontrastuse:Amount(volumeincc),timeofinjection.

RecordtheeventandexpectedamountofCTContrastAgentintothecommondataformatmechanism(AppendixE).

3.2.ImageDataAcquisition382

ThissectionsummarizestheimagingprotocolsandproceduresthatshallbeperformedforanFDG-PET/CT383exam.DetaileddescriptionsareincludedinthereferencedFDG-PET/CTUPICTprotocolsections.384

Themotivationforcontrollingtheimageacquisitionastightlyasdescribedhereisthatoverthecourseofa385trial,hardwareandsoftwareupdateswilloccur.TheintentoftheProfileistoensurethattheinstrument386givesthesameresultsoverthedurationofthetrial.387

For consistency, clinical trial subjects should be imaged on the same device over the entire course of a388study.Iftheimagingrequirementsarequalitativei.e.forrelativequantitation,forexamplethepresenceor389absenceofalesionoralesionSUVrelativetoareferenceregion,thenareplacementscannermaybeused390ifitisproperlyqualified.Itisimperative,however,thatthetrialsponsorbenotifiedofscannersubstitution391ifitoccurs.392

Forclinicaltrialswithquantitativeimagingrequirements,asubjectshouldhaveallscansperformedononly393one scanner unless quantitative equivalence with a replacement scanner can be clearly demonstrated.394However, it shouldbenotedthat therearecurrentlynoacceptedcriteria fordemonstratingquantitative395equivalencebetweenscanners.ItisanticipatedthatfutureversionofthisProfilewillprovidesuchcriteria.396

The follow up scans should be performed with identical acquisition parameters as the first (baseline),397inclusiveofalltheparametersrequiredforboththeCTandPETacquisitions.398

TheFDG-PET/CTUPICTProtocol(Section7.1.1)describesscanningstrategiesthatcanbeusedinaclinical399trial. For strategy 1, there is no intent to obtain a diagnostic CT scan at the FDG-PET imaging session,400howevera low-doseCTscan isneeded forattenuationcorrection.For strategy2,adiagnosticCTscan is401obtained. There are further considerations that must be followed for each of the two strategies. The402workflow chosen for a given protocol should be described in the protocol and should be tailored403commensurate to the level of expectation of the obtained data (e.g. qualitative or quantitative SUV404analysis).405

Strategy1: For FDG-PET/CT inwhich theCT is used for attenuation correctionand localizationonly (not406intendedasaclinicallydiagnosticCT):407

• CTScout(i.e.topogramorscanogrametc.),followedby408

• CTforanatomiclocalizationandattenuationcorrection,followedby409


• PETEmissionscanacquisition410

Strategy 2: For FDG-PET/CT in which a clinically diagnostic CECT is also required, ONE of the following411optionsshouldbeused.Strategy2aispreferablesinceitavoidsany,allbeitpossiblyminimal,impactofIV412contrastenhancementonattenuationcorrectionandthereforeSUVdetermination.413

Strategy2a414

• FollowStrategy1(above)415

• AcquireanadditionalIVcontrast-enhanceddiagnosticCTscan416

Strategy2b417

• PerformanIVcontrast-enhanceddiagnosticCTscan418

• FollowStrategy1(above)419

420


ScanningStrategy(Workflow)

TechnologistTechnologistshallfollowProfilecompliantworkflowstrategy,whichwillbecompatiblewithAcquisitionDevicecapability.Thesameworkflowusedatbaselineshallbeusedatallsubsequenttimepoints.

421

Forbothstrategies,thereareseveralcommonissuesspecifictotheCTexamthatmayhaveanimpacton422quantitativeFDG-PEToutput,whichneedattentionandprotocolspecification.These include (1)contrast423material administration, (2) respiratorymotionmanagement instructions and (3) CT scanning technique424(kVp,mAsandpitch).Belowisasummaryoftheacceptablelevelofbehavior/procedureforeachofthese425threeissues.426

Ataminimum,all these issues shouldbeaddressed in theclinical trialprotocol, ideallywithconsistency427across all sites and all subjects (both inter-subject, and intra- and inter-facility) with the target of428consistencyacrossalltimepointsforeachgivensubject.Theactualdetailsof imagingforeachsubjectat429each time point should always be recorded. Any particular clinical trial should NOT allow some sites to430implementonestrategyandothersitestoimplementthealternative.431

CTExamVariablesandSpecifications:432

ContrastAgents - Thepresenceof a positive contrast agent (IVor oral), by affecting theCT attenuation433map,mayaffectSUVquantitation[Mawlawi2006].Ifthisweretheonlyconsideration,thenidealwouldbe434toprohibitCTcontrastadministration.However, insomeclinicalsituations(dependentupontumortype,435tumorbehavioror levelofanatomic interest), thebenefitofCTcontrastagentsmayoutweigh thesmall436errors induced in SUV measurement that may include increased SUV variability. Each protocol should437specifythedesiredapproachforthegivenstudy.Most importantly, foreachsubject, thesameapproach438shouldbefollowedforallimagingtimepoints.439

IncaseswhereCTcontrastagentsareused,therearetwomainstrategies:440

Strategy1:NoIV;dilutepositiveoralcontrastallowed441

Strategy2:Usenegativeordilutepositiveoralcontrastforthenon-attenuationCTscan.Ensurethat442


thediagnosticCTacquisition(whichmaybeperformedwithIVcontrast)isperformedconsistently443foragivensubjectacrossalltimepoints.444


CTContrastagent

Technologist CTcontrastagentsshallbegivencommensuratewiththeworkflowstrategyasselectedfromabove.

3.2.1ImagingProcedure445

ThePET/CTexamconsistsoftwocomponents,thePETemissionscanandtheCTtransmissionscan(which446mayhavemultiplecomponents).Fromthesedatasets,thenon-attenuation-correctedPETimagesmaybe447reconstructed for quality control purposes and attenuation-corrected PET images are reconstructed for448qualitative interpretation and quantitative analysis. Instrument specifications relevant to the Acquisition449DeviceareincludedinSection4Conformance–AcquisitionDevice.450

3.2.1.1TimingofImageDataAcquisition451

FDGuptake intobothtumorsandotherbodytissues isadynamicprocessthatmay increaseatdifferent452rates and peak at various time points dependent upon multiple variables. Therefore, it is extremely453importantthat(1)ingeneral,thetimeintervalbetweenFDGadministrationandthestartofemissionscan454acquisitionisconsistentand(2)whenrepeatingascanonthesamesubject,itisessentialtousethesame455intervalbetweeninjectionandacquisitioninscansperformedacrossdifferenttimepoints.456

Whilethe“target”traceruptaketimeis60minutes,the“acceptable”windowisfrom55to75minutesto457ensure that imaging does not begin prematurely so as to allow adequate tumor uptake of FDG and to458accountforthepracticalityofworkflowthatcanresultindelaysinimaginglaterthan60minutesafterFDG459injection.Theexacttimeof injectionmustberecorded;thetimeof injection initiationshouldbeusedas460the time to be recorded as the radiotracer injection time. The injection and flush should be completed461within one minute with the rate of injection appropriate to the quality of the vein accessed for FDG462administrationsoastoavoidcompromisingtheintegrityoftheinjectionvein463

When performing a follow-up scan on the same subject, especially in the context of therapy response464assessment,itisessentialtoapplythesametimeintervalwithtargetwindowof±10minutesprovidedthat465thescanmustnotbeginpriorto55minutesaftertheinjectionofFDG.Whilethereismajorityviewofthe466committee thata tighter (narrower) timewindow,e.g.+/-5minutes, isbetter, thecurrentperformance467specification iswritten tobalancepractical and ideal. If a limitedanatomy scan is obtainedat follow-up468afterawholebodyscanwasperformedatbaseline,oneshouldconsideradjustingthetimingofthefollow469up scan to be congruentwith the timing for the same anatomic region as achieved during the baseline470study.471

If, for scientific reasons, an alternate time (between activity administration and scan acquisition) is472specified in a specific protocol, then the rationale for this deviation should be stated; inter-time point473consistencymuststillbefollowed.474


TracerInjectionTime

Technologist ThetimeofFDGinjectionshallbeenteredintoPET/CTscannerconsoleduringtheacquisition.

TracerUptake Technologist TheTechnologistshallensurethatthetraceruptaketimeforthe



Time:

baselinescanis60minutes,withanacceptablerangeof55to75minutes.

Whenrepeatingascanonthesamesubject,especiallyinthecontextoftherapyresponseassessment,theTechnologistshallapplythesametimeinterval±10minutesprovidedthatthescanmustnotbeginpriorto55minutesaftertheinjectionofFDG.

Thefollowingsectionsdescribetheimagingprocedure.475

3.2.1.2SubjectPositioning(UPICTSection7.2.1)476

Consistentpositioningavoidsunnecessary variance inattenuation, changes in gravity-induced shapeand477fluiddistribution,orchangesinanatomicalshapeduetoposture,contortion,etc.DuringPET-CT,subjects478shouldbepositionedinthecenterofthefieldofview(FOV),preferablywiththesubjects’armspositioned479overheadforwhole-bodyimaging(tominimizebeamhardeningandFOVtruncationartifacts).Inthecase480ofdedicatedbrainorhead/neckscans,thearmsshouldbepositioneddownalongthebody.Ifthesubjectis481physicallyunabletomaintainarmsaboveheadfortheentirewhole-bodyexaminationthenthearmscan482be positioned along the side before the start of the scan, unless the protocol specifically excludes such483subjects. Armpositioning in a particular subject should be consistent between the PET emission and CT484transmissionscansateachtimepointandshouldbeasconsistentaspossibleacrossalltimepoints.485

Respiratory motion causes SUV errors by two mechanisms: motion blurring and errors in attenuation486correctiondue tomismatchesbetweenCT-basedattenuationmapandemissiondata [Liu2009].Various487strategiescouldbeusedtominimize,documentandcompensateforrespiratorymotion.Shallowbreathing488shallbeperformedduringCTACacquisition(seeUPICTProtocolsection7.1.1).Thesubjectshould(a)be489monitoredand if breathingpattern is not consistentwith shallowbreathingexpectation, coached in the490breathingprotocoland(b) remainmotionless throughoutthescan. AlternateCTstrategies forachieving491PET/CTmatchmaybeconsideredifitcanbeverifiedthatPETACartifactsinthevicinityofthediaphragm492areroutinelyminimal.Itisofutmostimportancethatthepatientnotbeinend-inspirationphaseduringCT493forPET/CT.494

TheTechnologistshalldocumentfactorsthatadverselyinfluencesubjectpositioningorlimittheabilityto495complywithinstructions(e.g.breath-hold,shallowbreathing,remainingmotionless,etc.).496

497


SubjectPositioning

Technologist TheTechnologistshallpositionthesubjectaccordingtotheUPICTspecificationsand/orspecificprotocolspecificationsconsistentlyforallscans.

498


PositioningNon-conformance

TechnologistTheTechnologistshalldocumentissuesregardingsubjectnon-conformancewithpositioning.

TheTechnologistshalldocumentissuesregardingsubjectnon-


conformancewithbreathingandpositioningusingthecommondataformatmechanism(AppendixE).

499


Respiratorymotionminimization

Technologist IfthepatientisobservedtotakeadeepbreathduringtheCTscanitshouldbedocumentedandarepeatCTstudyshouldbeconsidered.


PET/CTScanner

ThePET/CTscannershallprovidemethodstominimizethePETimageerrorsintroducedbyrespiratorymotion.

500


Breathingandmotionnon-conformance

Technologist

TheTechnologistshalldocumentissuesregardingsubjectnon-conformancewithbreathingandmotion.

TheTechnologistshalldocumentissuesregardingsubjectnon-conformancewithbreathingandmotionusingthecommondataformatmechanism(AppendixE).

501

3.2.1.3ScanningCoverageandDirection(UPICTSection7.1.1)502

FormostOncology indications, anatomic coverage should include from the skull base (external auditory503meatus)tothemid-thigh.Ifotherrangesareused,whichmaybeappropriateforspecificclinicaltrials,then504theclinical trialprotocolshouldprovidespecific instructionswith justification.Multiple factorsaffect the505decision regarding the scan direction. For example, scanning caudocranial minimizes effects from506increasing bladder activity during the scan, important for image quality in the pelvis. For some tumors507locatedinthehead,neck,orupperthoraxitmaybemoreimportanttostartattheheadtominimizehead508andarmmotionbetweenPETandCT.Scanningdirectionshouldbespecifiedintheclinicaltrialprotocol.It509is critical that for a given subject, scanning direction on baseline scans be duplicated at follow-up time510points.511


ScanningDirection

Technologist TheTechnologistshallscanthesubjectcaudocranialforwholebodyexaminationunlessotherwisespecifiedbytheprotocol.Eachpatientshouldbescannedconsistently(inthesamedirection)overalltimepoints.

ThescanningdirectionshallbeenteredintothePET/CTconsoleduringtheacquisitionandwillberecordedbythescannerintotheappropriateDICOMfield.



AnatomicCoverage

Technologist TheTechnologistshallperformthescansuchthattheanatomiccoverageisacquiredaccordingtotheprotocolspecificationsandthesameforalltimepoints.

512

3.2.1.4ScannerAcquisitionModeParameters513

WedefineacquisitionmodeparametersasthosethatarespecifiedbytheTechnologistatthestartofthe514actualPET/CTscan.These include theacquisition timeperbedposition, thebedoverlap, theacquisition515mode(2Dor3D),withorwithoutcardiacand/orrespiratorygatingandCTtechnique.Theseparametersdo516not include aspects of the acquisition that occur earlier (e.g. injected amount of 18F-FDG or uptake517duration,CTcontrastagentinjection)orlater(e.g.reconstructionparameters)intheoverallscanprocess.518

PETAcquisition519

520


PETacquisitionmode StudySponsor

ThekeyPETacquisitionmodeparameters(e.g.,timeperbedposition,acquisitionmode,withorwithoutgating)shallbespecifiedinamannerthatisexpectedtoproduceacceptablylowimagenoiseregardlessofthescannermakeandmodel.

Thekeyacquisitionmodeparametersshallbespecifiedaccordingtopre-determinedharmonizationparameters.

PETacquisitionmode Technologist

ThekeyPETacquisitionmodeparameters(e.g.,timeperbedposition,acquisitionmode,withorwithoutgating)shallbesetasspecifiedbystudyprotocolandusedconsistentlyforallpatientscans.

521

CTAcquisition522

FortheCTacquisitioncomponentofthePET/CTscan,thisProfileonlyaddressestheaspectsrelatedtothe523quantitativeaccuracyofthePETimage.InotherwordsaspectsofCTdiagnosticaccuracyarenotaddressed524in this Profile. In principle any CT technique (parameters include kVp, mAs, pitch, and collimation) will525sufficeforaccuratecorrectionsforattenuationandscatter.However,ithasbeenshownthatforestimating526PETtraceruptakeinbone,lowerkVpCTacquisitionscanbemorebiased.ThushigherkVpCTacquisitions527arerecommended ingeneral. Inaddition if there isthepotential forartifacts intheCT imageduetothe528choiceofacquisitionparameters(e.g.truncationoftheCTfieldofview),thentheseparametersshouldbe529selected appropriately to minimize propagation of artifacts into the PET image through CT-based530attenuation and scatter correction. Finally, extremely low x-ray flux can lead to a bias in CT images.531ProtocolsshouldallowhighenoughmAstoavoidthisartifact.532

533




CTacquisitionmode StudySponsor

ThekeyCTacquisitionmodeparameters(kVp,mAs,pitch,andcollimation)shallbespecifiedinamannerthatisexpectedtoproducecomparableresultsregardlessofthescannermakeandmodelandwithappropriateradiationdosesconsistentfortheroleoftheCTscan:diagnosticCTscan,anatomicallocalization,oraccuratecorrectionsforattenuationandscatter.

CTdosereductiontechniquesmaybeusedifdemonstratedtoretainquantitativeaccuracy.

CTacquisitionmode Technologist

ThekeyCTacquisitionmodeparameters(kVp,mAs,pitch,andcollimation)shallbesetasspecifiedbystudyprotocolandusedconsistentlyforallsubjectscans.

534

535

536


537

RegardingCTradiationexposure, the lowestradiationdosenecessarytoachievethediagnosticobjective538shouldbeused.Foragivenprotocol,thepurposeofperformingtheCTscan(withtheintentofattenuation539correctiononlyorattenuationcorrectionandanatomiclocalizationversusoneintendedfordiagnosticCT540purposeswithcontrastandbreath-hold)shouldbedetermined.TheCTtechnique(tubecurrent,rotation541speed,pitch, collimation, kVp, and slice thickness)used should result inas lowas reasonablyachievable542exposureneededtoachievethenecessaryPET imagequality.Thetechniqueusedforan imagingsession543shouldberepeatedforthatsubjectforallsubsequenttimepointsassumingitwasproperlyperformedon544thefirststudy.545

3.3.ImagingDataReconstructionandPost-Processing546

3.3.1ImagingDataReconstruction(UPICTSection7.3)547

Reconstructed image data is the PET image exactly as produced by the reconstruction process on the548PET/CT scanner, i.e. a PET image volume with no processing other than that occurring during image549reconstruction. This is always a stackofDICOMslices/files constituting a PET image volume that canbe550analyzed on one or more of the following: PET scanner console, PET image display workstation, PACS551system,etc.SeeSection4Conformance–ImageReconstructionSoftwareforspecifications.552

The PET reconstruction parameters include the choice of reconstruction algorithm, number of iterations553andsubsets(foriterativealgorithms),thetypeandamountofsmoothing,thefieldofviewandvoxelsize.554The quantitative accuracy of the PET image should be independent of the choice of CT reconstruction555parameters,althoughthishasnotbeenuniformlyvalidated.Inaddition,ifthereisthepotentialforartifacts556in theCT imagedue to thechoiceofprocessingparameters (e.g. compensation for truncationof theCT557fieldofview),thentheseparametersshouldbeselectedappropriatelytominimizepropagationofartifacts558intothePETimagethroughCT-basedattenuationandscattercorrection.559


560


PETimagereconstruction StudySponsor

ThekeyPETreconstructionparameters(algorithm,iterations,smoothing,fieldofview,voxelsize)shallbespecified.Theimagevoxelsizeshouldbe<5mm(stronglyprefer3–4mm),with<3mmvoxelsforheadandneckimaging.

ThekeyPETimagereconstructionparametersshallbespecifiedaccordingtopre-determinedharmonizationparameters.

PETimagereconstruction Technologist

ThekeyPETreconstructionparameters(algorithm,iterations,smoothing,fieldofview,voxelsize)shallbefollowedandsetasspecified.

Correctionfactors Technologist

Allquantitativecorrectionsshallbeappliedduringtheimagereconstructionprocess.Theseincludeattenuation,scatter,randoms,dead-time,andefficiencynormalizations.

Calibrationfactors Scanner

AllnecessarycalibrationfactorsneededtooutputPETimagesinunitsofBq/mlshallbeautomaticallyappliedduringtheimagereconstructionprocess.

561

562

As part of the image reconstruction and analysis, correction factors for known deviations from the563acquisitionprotocolcanpotentiallybeapplied.Thesecorrectionscaninclude,forexample,compensation564formistakes indataentry[Kinahan2010],variations inFDGuptakeperiod[Beaulieu2003],anderrors in565scannercalibrationfactors[Lockhart2011].Correctionsforknowndataentryerrorsanderrorsinscanner566calibrationfactorsshouldbecorrectedpriortothegenerationofthereconstructedimages,orimmediately567afterwards.Correctionsthataremoread-hocinnature,e.g.correctionsforvariationsinFDGuptakeperiod568orplasmaglucoselevelsorpartialvolumecorrection,shouldonlybeappliedaspartoftheimageanalysis569step.Thatis,notusedtomodifythereconstructedPETimage.570

3.3.2ImageDataPost-processing(UPICTSection8)571

Processedimagedataareimagesthathavebeentransformedinsomemanner,includingbutnotlimitedto:572smoothing, image zoom, rotation/translation, resampling, interpolation, slice averaging,MIP, etc. This is573typically a stack of DICOM slices/files constituting a PET image volume. If image registration or574interpolation is required, thenwhere applicable, perform theROI analysis on theoriginal PET image set575usingappropriatelymodifiedROIs.TheintentistopreservethenumericalaccuracyofthetruePETimage576values.577

Standard whole-body FDG-PET oncology studies typically include all necessary data corrections and578processingwithinthereconstructionprocessanddonotrequireadditionalprocessingotherthan(e.g.)data579


de-identification.Moreadvancedstudiessuchasthoseincludingdynamicimagingmayrequireadditional580processingasspecifiedintheindividualprotocol.581

Briefly described here are concepts presented in UPICT Section 8.2.3 regarding difference between582‘visualized data’ and ‘data used for quantification’. At the acceptable level, for visual583inspection/interpretationofPET/CTdatausingthedisplayworkstation,bi-linearortri-linear interpolation584andzoomingmaybeusedtodisplaytheimagesinadifferentmatrixsizethantheoriginaldata.Inaddition,585so-calledmaximum intensity projections (MIP)may be generated as theymay facilitate localization and586detectionoflesions.Additionalprocessing,suchaszooming,re-binning,reorientationandfilteringmaybe587applieduponuserrequestonly.Usershouldbeabletomanipulatecolorscalesettings(window/leveland588colortable).Itshouldalwaysbepossibletoreverttothedefaultorientation,zoomandbinsize(preferably589a‘reverttodefault’buttonisavailable).590

591

3.3.3ImagingDataStorageandTransfer592

DiscussionsofarchivingPETdataoftenmention'rawdata'.Thisisanambiguoustermasitcanreferto:593scannerrawdata(i.e.,sinogramsorlist-mode)orimagerawdata.Toavoidconfusion,thetermrawdata594shouldnotbeusedwithoutmakingitclearwhichformisunderdiscussion.595ImagerawdataistheimagedataexactlyasproducedbythereconstructionprocessonthePETorPET/CT596scanner,i.e.,astackofDICOMslices/filesconstitutingaPETimagevolumewithnoprocessingotherthan597thatoccurringduringimagereconstruction.ThisisalwaysastackofDICOMslices/filesconstitutingaPET598imagevolumethatcanbeanalyzedononeormoreofthefollowing:PETscannerconsole,PETimage599displayworkstation,PACSsystem,etc.600Post-processedimagedataareimagesthathavebeentransformedafterreconstructioninsomemanner,601includingbutnotlimitedto:smoothing,imagezoom,rotation/translation,resampling,interpolation,slice602averaging,MIP,etc.Suchimagesmaybeonlyproducedfortemporaryanalysisanddisplay,ortheymaybe603savedasDICOMslices/files,andcanstillbeanalyzedononeormoreofthefollowing:PETscannerconsole,604PETimagedisplayworkstation,PACSsystem,etc.605Forarchivingatthelocalsiteorimagingcorelab(ifrelevant),themostimportantdataaretheoriginal606images,i.e.,theimagerawdata.Intheunlikelyeventthatthescannerrawdata(whichshouldbearchived607bythelocalsite)isrequiredforlaterreprocessing;thisshouldbemadeclearintheprotocol.608609

610


Dataarchiving Technologist TheoriginallyreconstructedPETimages(imagerawdata),withandwithoutattenuationcorrection,andCTimagesshallalwaysbearchivedatthelocalsite.

IfprocessedPETimagesarerequired,theyshallbearchivedasseparatesecondarydatasets.

Ifscannerrawdataneedtobearchivedforfuturereprocessing,thisshouldbedefinedprospectivelyintheProtocol.

611


3.4.ImageAnalysis(UPICTSection9)612

The Image Analyst, through interaction with the Workstation Analysis tools, shall be able to perform613specifiedmeasurements. ImageAnalysis has qualitative and quantitative tasks. Both require consistency614andimagesofsufficientquality.Quantitativeimagingrequiresadditionalsystemcharacteristicsdescribed615furtherinthisProfile.616

3.4.1InputData617

TheoutputimagesofReconstruction,butnotPostprocessing,areconsideredtheinputforImageAnalysis.618IftheImageAnalystaltersinputdata(e.g.zoom),theoriginalinputdatawillbemaintainedasaseparate619file,bothtobestored.(SeeSection3.2)620

3.4.2MethodstoBeUsed621

Eachtissue/organtobe investigatedquantitatively(eithertumor lesionornormaltissue) ischaracterized622bydefiningaregion-of-interest(ROI)andcalculatingaparametersuchasthemaximumSUVwithintheROI.623Theimageanalystwillusetools(asdefinedinSection4.4Conformance–ImageAnalysisWorkstation)to624defineROIsandmeasureSUVs.625

3.4.3RequiredCharacteristicsofResultingData(UPICTSection9.3)626

ThespecifictrialprotocolshallprospectivelydefinetheSUVparameterthatisrequiredforeachlesion,or627normal tissue, which will be used for the imaging endpoint. Some studies may also compare different628metrics and will require recording multiple parameters. SUV measures (and the analysis tools used to629obtainthem,includingsoftwareversion)shallbespecifiedforeachprotocolandshallbeusedconsistently630acrossallsubjectsandacrossallsequentiallesionmeasurements.631

SUV’sareintendedasameasureofrelativeuptakeandinthatsense,canberegardedasdimensionless632(unitless);however,usingstrictinterpretationoftheunitsforthecommoncalculationofbodyweight633normalization,thisyieldsunitsofg/ml.Undertheassumptionthatonaverage1mloftissueweighs1gm634(e.g.,water),adimensionlessSUVwouldbeobtained.Displaysystemmanufacturestypically,butnot635always,indicateunitsofg/mlifimagesarescaledtoSUVswithabodyweightnormalization.Thisis636presumablytodifferentiatebetweenbodyweight(orlean-body-mass)andbody-surface-area637normalizations,whichwouldshowdifferentunits(andvalues).Basedonthelackofconsensusandthat638manydisplaysystemsalreadyuseunits,therecommendationbelowistouseunitsofg/ml.639640Itshouldbeclearwhichvaluesbelongtowhichlesion.ThiscanbedonebycapturingDICOMcoordinates641alongwiththeSUVorsecondaryscreencapturesoftheROIforidentification.Itshouldbereportedwhich642SUVmeasureisused,i.e.statisticandtypeofnormalization.643

Ifareferencetissue(e.g.liver)SUVismeasured,then,thatSUVshouldbereportedalongwithlesionSUV644data.645

Theanalysissoftwareshouldgenerateareport.646

3.5.ImageInterpretationandReporting(UPICTSection10)647

NoQIBAProfilespecificationcanbeprovidedforimageinterpretationatthistime.ImageInterpretationis648consideredtobebeyondthescopeofthisdocument.RefertoFDG-PET/CTUPICTProtocol(Section10).In649addition, further interpretationof thequantitative results (e.g.PERCIST [Wahl2009])and/ornormalizing650


SUV to reference tissue values (e.g. liver or blood pool) can also be specified as part of a specific trial651protocol.652

Typicallythetrialprotocolwillstatehowquantitativeresponseismeasured.Forexample,responsecanbe653basedonthehottest lesion,butsometimesthechangeof thesumofSUVs isused. Inotherwords,how654quantitativeresponseismeasureshouldbespecifiedaprioribythetrial itself.Thisalsoappliestotarget655lesionselection.656

657


ImageReporting

ImagingFacility ImagingreportsshallbepopulatedfromDICOMheaderinformationusingstructuredreporting.

658

3.6.QualityControl659

ThefollowingsectiondealswithmultipleaspectsofqualitycontrolinFDG-PET/CTstudies.(SeeFDG-PET/CT660UPICT Protocol Section 12 for additional information). This includes selecting and qualifying a PET/CT661imaging facility, imagingpersonnelandPET/CT scannersandancillaryequipment. Inaddition, theuseof662phantomimaging(priortostudyinitiationandongoing)isdiscussedaswellasidentifyingsubjectswhose663data may need to be censored due to lack of data integrity. Finally, post-image-acquisition quality664assessmentisdetailed.665

3.6.1ImagingFacility666

It is essential to implement quality processes that ensure reliable performance of the scanner and667consistentimageacquisitionmethodology.Theseprocessesmustbeinplacepriortosubjectimagingand668be followed for the duration of the trial. A facility “imaging capability assessment” is a prerequisite to669facility selection for participation in any clinical trial involving the use of FDG-PET/CT as an imaging670biomarker.Thisimagingcapabilityassessmentwillinclude:671

• Identificationofappropriateimagingequipmentintendedforuseinthetrial672

• Documented performance of required quality control procedures of the scanner and ancillary673equipment(e.g.dosecalibrator,glucosemeter,etc.)674

• Radiotracerqualitycontrolprocedures675

• Experienceofkeypersonnel(technologists,radiologists,physicistsand/orotherimagingexperts)676

• Procedurestoensureimagingprotocolconformanceduringthetrial677

3.6.1.1 SiteAccreditation/QualificationMaintenance678

Whilst imaging facility accreditation is generally considered to be adequate for routine clinical practice679purposes (e.g., ACR, IAC, and TJC), facility qualification (e.g., SNM-CTN,ACRIN, and imaging core labs) is680requiredforclinicalresearch/clinicaltrialparticipation.Inordertobeconsideredtobecompliantwiththis681Profile, an imaging scanner/facilitymust provide documentation of current qualified status. Appropriate682forms,checklistsorotherprocessdocumentsshouldbemaintainedandpresenteduponrequesttoverify683


that ongoing quality control procedures are being performed in a timelymanner as dictated by specific684clinical study requirements. If exceptions to any of the performance standards stated below occur and685cannotberemediatedonsite,thesiteshouldpromptlycommunicatetheissuetotheappropriateinternal686overseerforadviceastohowtheirregularityshouldbemanaged.Inadditiontodocumentingthelevelof687performance required for this Profile (and the level of performance achieved), the frequency of facility688accreditation/qualificationalsoneedstobedescribed.689

ItisimportanttonotethatthatimagingfacilityAccreditationand/orQualification,asdefinedinthisProfile,690areconsiderednecessary,butarenotsufficient forconformancewith thisProfile.Forconformancewith691theProfile,andthustosupporttheclaimsoftheProfile,allnormativerequirementsmustbemet.692


Accreditation/Qualification

ImagingSite&ImageAcquisitionDevice

ShallmaintainanddocumentAccreditedstatusforclinicalpractice(ACR,IAC,TJC,etc.)orQualifiedstatusforclinicaltrials(e.g.ACRIN,SNM-CTN,CALGB,CROs,etc.).

3.6.2ImagingFacilityPersonnel693

Foreachof thepersonnelcategoriesdescribedbelow,thereshouldbetraining,credentialing,continuing694education and peer review standards defined. Guidelines for training/credentialing for each resource695categoryaresummarizedbelow(UPICTProtocolSection2.1).696


PersonnelRoster

ImagingFacilityCoordinator

Eachsiteshall,atthetimeoftrialactivationandpriortosubjectaccrual,havethesupportofcertifiedtechnologists,physicists,andphysicians(asdefinedbelow),experiencedintheuseofFDG-PET/CTintheconductofoncologicalclinicaltrials.

Technologist ImagingFacilityCoordinator

TechnologistcertificationshallbeequivalenttotherecommendationspublishedbytherepresentativesfromtheSocietyofNuclearMedicineTechnologistsSection(SNMTS)andtheAmericanSocietyofRadiologicTechnologists(ASRT)andshouldalsomeetalllocal,regional,andnationalregulatoryrequirementsfortheadministrationofionizingradiationtopatients.

MedicalPhysicist

ImagingFacilityCoordinator

MedicalphysicistsshallbecertifiedinMedicalNuclearPhysicsorRadiologicalPhysicsbytheAmericanBoardofRadiology(ABR);inNuclearMedicinePhysicsbytheAmericanBoardofScienceinNuclearMedicine(ABSNM);inNuclearMedicinePhysicsbytheCanadianCollegeofPhysicistsinMedicine;orequivalentcertificationinothercountries;orhave3yearsofPETexperience.Regardlessofcertification,thephysicistshouldhavespecificexperienceinPETanditsquantitativeuse.



Physician ImagingFacilityCoordinator

PhysiciansoverseeingandinterpretingPET/CTscansshallbequalifiedbytheABR(Diagnosticand/orNuclearRadiology)orAmericanBoardofNuclearMedicine(ABNM)orequivalentwithintheUnitedStatesoranequivalententityappropriateforthegeographiclocationinwhichtheimagingstudy(ies)willbeperformedand/orinterpreted.

697

3.6.3FDG-PET/CTAcquisitionScanner698

FDG-PET/CTstudiesasdescribedinthisProfilerequireadedicatedPET/CTscanner.PET/CTscannersshould699be identifiedbasedonmanufacturer, nameandmodel.Hardware specifications shouldbedocumented.700Scannersoftwarenameandversionshouldbedocumentedatthetimeoftrialinitiationandatthetimeof701anyandallupdatesorupgrades.702

The PET/CT scanner must undergo routine quality assurance and quality control processes (including703preventivemaintenanceschedules)appropriateforclinicalPET/CTapplications,asdefinedbyprofessional704and/or regulatory agencies. In order to assure adequate quantitative accuracy and precision of PET/CT705imagingresults,additionalqualityassurancemeasuresarerequired,asdiscussedbelow.706


PhysicalInspection

Technologist Shall,onadailybasis,checkgantrycoversintunnelandsubjecthandlingsystem.

QA/QCChecks Technologist AllQA/QCproceduresrecommendedbythemanufacturershallbeperformedatthefrequencyrecommendedbythemanufactureranddocumented.AtableofQA/QCproceduresforasubsetofspecificPET/CTscannersfromeachvendorisincludedinAppendixG.2.

DailyQAproceduresshallbeperformedpriortoanysubjectscan.

3.6.3.1AncillaryEquipment707

3.6.3.1.1DoseCalibrator708

ThefollowingguidelinesarecollectedfromANSIstandardN42.13,2004andIAEATechnicalReportSeries709TRS-454.AllrequirementsassumemeasurementsonunitdosesofFDGandthatcalibrationsourcesarein710the'syringe'geometry(i.e.,nobulkdoses).711

The Constancy test ensures reproducibility of an activity measurement over a long period of time by712measuringalong-livedsourceofknownactivity.713

The Accuracy test ensures that the activity values determined by the dose calibrator are correct and714traceabletonationalorinternationalstandardswithinreporteduncertainties.715

TheLinearitytestconfirmsthat,foranindividualradionuclide,thesamecalibrationsettingcanbeapplied716toobtainthecorrectactivityreadoutovertherangeofuseforthatdosecalibrator.717


718


Constancy Technologist Shallbeevaluateddaily(orafteranydosecalibratorevent)usingaNIST-traceable(orequivalent)simulatedF-18,Cs-137,orCo-57dosecalibratorstandardandconfirmedthatnetmeasuredactivityontheF-18settingdiffersbynogreaterthan±2.5%fromdaytoday.

Accuracy

Technologist Shallbeevaluatedmonthly(orafteranydosecalibratorevent)withaNIST-traceable(orequivalent)Cs-137,Co-57,orsimulatedF-18dosecalibratorstandard.Shallconfirmthatnetmeasuredactivitiesdiffernogreaterthan±2.5%fromexpectedvalue.

ThescannercalibrationshallbetestedusingaNIST-traceable(orequivalent)simulatedF-18sourceobject,e.g.auniformcylinder,largeenoughtoavoidpartialvolumeeffectsorotherresolutionlosses.

Shallbeevaluatedmonthly(orafteranydosecalibratorevent)withaNIST-traceable(orequivalent)simulatedF-18dosecalibratorstandard.Shallconfirmthatnetmeasuredactivitiesdiffernogreaterthan±2.5%fromexpectedvalue.

Linearity TechnologistorRadiationsafetyofficerorQualifiedMedicalPhysicist

Shallbeevaluatedatleastannually(orafteranydosecalibratorevent)andshouldbewithin±2.5%ofthetruevalueoveranoperatingrangeof37-1110MBq(1to30mCi).

PETRadiationDose

DoseCalibrator ShallrecordtheradiationdosefromtheadministeredactivityandaccompanyinginformationinaDICOMRadiopharmaceuticalAdministrationRadiationDoseStructuredReport.

719

3.6.3.1.2Scalesandstadiometers720

Scalesandstadiometersshouldbeinspectedandcalibratedatinstallationandannually.721

722


Scalesandstadiometers

Approvedpersonnel

Shallbeevaluatedannuallyorafteranyrepairbyqualifiedpersonnel.

Shallbeconfirmedthaterrorislessthan+/-2.5%fromexpectedvaluesusingNIST-traceableorequivalentstandards.


3.6.3.1.3Bloodglucoselevelmeasurementdevice723

GlucosemeasurementsshouldbemadeusingaCLIA-approved,CLIA-cleared,orequivalent(outsidetheUS)724glucosemeasurementtechnique.725


Bloodglucoselevelmeasurementdevice

Approvedpersonnel

ShallhaveQA/QCtestingandcalibrationperformedusingaCLIA-approved,CLIA-cleared,orequivalent(outsideUS)procedure.

726

3.6.3.1.4Clocksandtimingdevices727

PET/CT scanner computer and all clocks in an imaging facility used to record activity/injection728measurementsshouldbesynchronizedtostandardtimereferencewithin+/-1minute.These includeany729clocksor timekeeping systems thatareconnectedwitha subject’sFDG-PET/CTstudy, inparticular those730associatedwiththedosecalibrator,theinjectionroom,thescanner,andtheacquisitioncomputer(s).The731synchronizationofall clocks (todate, timeofdayand to timezone) shouldbemonitoredperiodicallyas732partofongoingQAprogram.Inparticular,clocksshouldbeinspectedimmediatelyafterpoweroutagesor733civilchangesforDaylightSavings(NA)orSummerTime(Eur). Correctsynchronizationcouldbeachieved734usingtheConsistentTimeIntegrationProfileasdefinedintheIHEITInfrastructureTechnicalFramework.735TheConsistentTimeProfilerequirestheuseoftheNetworkTimeProtocol(NTP)(www.NTP.org).736


Scannerandsiteclocks

Approvedpersonnel

PET/CTscannercomputerandallclocksinanImagingfacilityusedtorecordactivity/injectionmeasurementsshallbesynchronizedtostandardtimereferencewithin+/-1minute.

SynchronizationofallclocksusedintheconductoftheFDG-PET/CTstudyshallbecheckedweeklyandafterpoweroutagesorcivilchangesforDaylightSavings(NA)orSummerTime(Eur)

Scannerandsiteclocks

SpecificDevice ProvidetimesynchronizationaspertheIHEConsistentTimeIntegrationProfile.

Dosecalibratorclock

DoseCalibrator Electronicrecordofoutputfromadosecalibratorshallbesynchronizedwithothertimekeepingdevices.

737

3.6.4PhantomImaging738

Toqualify thePET/CT scanner for clinical practiceor for a clinical trial, a phantom imagingprocedure is739required.Inadditiontocertaingenerallyavailable,commonlyusedphantoms,purpose-specificphantoms740maybeprovidedtosimulatecertaintypesofcancersoranatomiclocationsandthereforemightvaryfrom741trial to trial based on the need to evaluate particular diagnostic, staging and/or treatment response742performanceand/oranatomiclocation.Optionsthatmightbeconsideredonaper-protocolbasisinclude,743butarenotlimitedto:744


1. eachsiteusesasinglephantomforthedurationofthetrialbutnotnecessarilythesamemodelof745phantomusedatothersites746

2. allsitesusephantomsofthesamemodelforthedurationofthetrial747

3. allsitesusephantomsbuilttoprecisespecificationsforthedurationofthetrial748

4. allsitesshareasinglephantomforthedurationofthetrial.749

The phantom scans and performance evaluation should be performed prior to the start of a trial and750repeated during the course of the trial as specified by the individual protocol. Any changes to scanner751equipment, either hardware or software, should be immediately reported to the trial sponsor and/or752imagingCROandmay result in theneed for re-qualificationprior to imaging additional trial subjects. In753particular,itisstronglyrecommendedthatsubjectsinalongitudinalstudybescannedonthesamePET/CT754systemwiththesamesoftwareversionwheneverpossible.755

Imagenoiselevelsaremeasuredusingananthropomorphicphantom(e.g.NEMA,ACR,SNM,EANM)witha756uniform area to assess image ‘noise’ bymeans of the coefficient of variation (COV), also known as the757relativestandarddeviation(%RSD),whichisexpressedasapercentageandisdefinedasCOV=(SD/Mean)758x100,forthevoxelvalueswithinaspecifiedvolumeofinterest(VOI).Thephantomshouldbefilledsuch759that theactivityconcentration in theuniformarea isapproximately3.7–7.4kBq/ml (0.1 to0.2uCi/ml),760similar totheexpectedaveragenormaltissueconcentrationat thetimeof imaging inanaverageweight761(70-80kg)subjectincombinationwiththeintendedFDGdosage.Thephantomshouldbescannedusingthe762minimaltimeperbedspecifiedinthetrialprotocolorusingtheroutinelyappliedtimeperbedinthelocal763clinicalsetting.Moreover, imagereconstructionmethodsandsettingsshouldequalthosespecifiedinthe764trialprotocolorequalthoseroutinelyappliedinthelocalclinicalsetting.Aregionofinterest(ROI)should765bepositionedentirelywithinthephantom’suniformareaandasmuchaspossiblecentrallylocatedwithin766thephantom.TheROIshouldbeacubicalorrectangularvolume,withthelengthofeachsideascloseas767possibleto,butnolessthan,3cm.Aspheremeasuringnolessthan3cm.indiametermayalsobeusedas768theROIonsystemsthathavethecapabilitytoaccommodatethisstrategy.TheCOVofthevoxelvaluesthus769determinedshouldberecordedandshouldbebelow15%.IftheCOVofthevoxelvaluesthusdeterminedis770above15%,theacquisitiontimeshouldbeincreasedaccordingly.771

The normative list below is based on theNEMA ImageQuality, ACR, and uniform cylinder phantoms as772appropriate.773


Phantomtests:Frequency

ImagingSite Shallperformanddocumentresultsofthefollowingtestsnolessthanquarterly.

Phantomtests:crosscalibrationwithdosecalibrator

ImagingSite Shallperformquarterlyandafterscannerupgrades,maintenanceorrepairs,newsetupsandmodificationstothedosecalibrator.

Phantomtests:SUVmeasurements

ImagingSite UsingACRoruniformcylinderphantomorequivalentshallobtainanSUVforalargecentralROIof1.0withanacceptablerangeof0.9to1.1.

UsingACRoruniformcylinderphantomorequivalentshallobtainanSUVforalargecentralROIof1.0withanacceptablerangeof



0.95to1.05.

Phantomtests:axialuniformitymeasurements

ImagingSite Usinguniformcylinderphantomorequivalentshallobtainaslice-to-slicevariabilityoflessthan10%forthesliceswithinthecentral80%oftheaxialFOV

Usinguniformcylinderphantomorequivalentshallobtainaslice-to-slicevariabilityoflessthan5%forthesliceswithinthecentral80%oftheaxialFOV

Phantomtests:resolutionmeasurements

ImagingSite Shallperformandsuccessfullyobtainphantomimagingresultsforcoldandhotobjectimagingasdescribed.Forcoldobjectimaging,thetestphantomwillbetheACRPETphantomortheDeluxeJasczakphantom(orequivalent)withsixsetsofacrylicrodsarrangedinapie-shapedpatternwiththefollowingdiameters:4.8,6.4,7.9,9.5,11.1,and12.7mm.The9.5,11.1,and12.7mmdiameterrodsmustbevisible;ifnecessaryupto1cmsliceaveragingcanbeused.Forhotobjectresolution,thefillable12mmdiameter‘hot’cylinderfortheACRphantommustbevisible;forCTNphantom,allhotobjectsgreaterthan10mmmustbevisibleandforNEMAphantom,13mmspheremustbevisible.AlsoseeSection3.6.4.2."

Harmonizedimagereconstructionprotocolsareavailable.(i.e.,knownrecoverycoefficientsversussizeforagiventestobjectsuchasthemodifiedNEMANU-2ImageQualityphantom

Phantomtests:noisemeasurements

ImagingSite ThephantomshallbefilledwithanFDGconcentrationofactivityconcentrationintheuniformareais(approximately0.1to0.2µC/ml)andscannedusingtheintendedacquisitionprotocol.Usingarectangularorsphericalregionascloseaspossibleto,butnosmallerthan,3cmtoaside,theCOVofthevoxelvalueswithintheregionshouldbebelow15%,forthesliceswithinthecentral80%oftheaxialFOV.

774

3.6.4.1UniformityandCalibration775

Verificationofscannernormalizationwithauniformphantomisaminimumrequirementforallscanners776used inclinical trials includingthosethatonlyhavequalitativeendpoints.FortrialswithquantitativePET777measurements, this assessment should also include a comparison against a dose calibrator to ensure778quantitativeaccuracy;thatis,acomparisonoftheabsoluteactivitymeasuredversusthemeasuredamount779injected should be performed. This comparison is particularly important after software or hardware780upgrades.Ifthetrialrequiresabsolutequantificationinbaselineimagesorabsolutechangesinlongitudinal781studies,itshouldbeconsideredtoincludeanimagequalityand/orcontrastrecoveryQCassessmentaspart782


of the routineQC procedures and/or scanner validation process, see Appendix E of theUPICT Protocol.783Clinical trials using only relative changes in longitudinal studies may not require contrast recovery784assessmentsprovidedthere isappropriateconsiderationfortheminimumsizeoftarget lesionsbasedon785thepartialvolumeeffect.786

Anessential requirement forextractingquantitativedata from images is that therebeknowncalibration787accuracy and precision and/or cross calibration of the PET/CT system against the (locally) used dose788calibrator (within 10%). The QC procedures should utilize the same acquisition/reconstruction protocol,789softwareandsettingsthatareusedforthesubjectscans.790


UniformityQC TechnologistorPhysicist

Atleastquarterlyandfollowingsoftwareupgrades,shallassesstransverseandaxialuniformityacrossthecentral80%ofimageplanesbyimagingauniformcylinderphantom.

1. Thestandarddeviationofalargecentral2DROIshallbecomparedwithsimilarpreviousscanstocheckformeasurabledifferences.

2. Themeanvaluesofalargecentral2DROIfortheseimageslicesshallbecomparedwithsimilarpreviousscanstocheckformeasurabledifferences.

CrossCalibration Technologistorphysicist

Atleastquarterlyandfollowingsoftwareupgradesorchangestothedosecalibrator,shallperformcheckstomonitorandidentifydiscrepanciesbetweenthePETscanneranddosecalibrator.

791

3.6.4.2Resolution(UPICTSection12.1.1.11)792

Theassessmentofadequateresolutionshouldincludebothaqualitativeevaluation(usingclinicalimages)793and quantitative assessment (using phantom-defined criteria). The phantom-defined requirements are794morecompletelydescribedinUPICTprotocolSection12.1.1.11.795


Resolution NuclearMedicinePhysician

Shallperform,onatleastanannualbasis,anddocumentaqualitativeresolutionQCtestbyusingtheroutineimageprocessingprotocolsanddemonstratingresolutionofnormalgrossanatomicfeatureswithinclinicalimagesofthebrain,heartandabdomen.

Resolution MedicalPhysicist Shallperform(onatleastanannualbasis)anddocumentperformanceofaquantitativeassessment(usingaphantomwithdifferingsizedefinedtargetssuchastheACRorNEMAIQphantomsprocessedwithroutineimagereconstructionprotocols)forlesionresolution.


3.6.4.3Noise(UPICTSection12.1.1.12)796


Noise MedicalPhysicist Shallperformqualitativeorquantitativeassessmentofimagenoiseinphantomimagestobeofconsistentandacceptablequality.

797

3.6.4.4Phantomimagingdataanalysis798

ForPETimageanalysis,therearemanycombinationsofhardwareandsoftwarethatareused.Thesoftware799alonecomprisesmultiplelayersincludingtheoperatingsystem,severalbasemodulesforinputanddisplay,800and the components that draw/calculate ROIs and calculate SUVs. It has been demonstrated that even801changes intheunderlyingoperatingsystemcanproducechanges inthequantitativeoutputproducedby802the display and analysis system [Gronenschild 2012]. Surprisingly little effort (outside manufacturer's803internal processes) has been applied to testing or validating the quantitative accuracy of SUV804measurementsproducedbydisplayandanalysismethods.805

Toprovideamethod for testingandvalidatingquantitativeaccuracyofSUVmeasurementsproducedby806the display and analysis methods, the QIBA FDG-PET/CT Biomarker Committee has developed an FDG-807PET/CTdigitalreferenceobject(DRO),whichisasynthetictestobjectcomprisedofstackedDICOMimages808representinganFDG-PETimagevolumeandanalignedCTimagevolume.ThePETandCTimagesarebased809on theNEMA/MITANU-2 ImageQualityphantom.TheDROhaspre-determined testobjects toevaluate810ROIfunctionalityandpre-determinedDICOMheaderinformationtotestSUVcalculations.SincetheDROis811created synthetically, any image display software is expected to reproduce the known values exactly,812except for the insignificant machine precision errors. Further details are given in Appendix F.813Recommendedversionsofvendor-neutralpseudo-codesforSUVcalculationaregiveninAppendixG.All814softwareusedforimageanalysisshouldbeverifiedbytheproceduresin4.4.3.815


ImageAnalysisSoftware

Imagingsite. All software used for image analysis shall be verified by theproceduresin4.4.3.

3.6.5QualityControlofFDG-PET/CTstudies816

3.6.5.1 DataIntegrity817

The integrity of DICOM image headers should be reviewed and confirmed for DICOM standard818conformance,regulatoryconformance(includingprivacyprotection,suchasmayberequiredbysuchrules819astheHIPAAPrivacyRuleifapplicable),protocolconformance,sufficiencyfortheintendedanalysis(e.g.,to820computeSUV)andconsistencywithsourcedatasuchasCRFs. Insomecases, internalreferencessuchas821thelivercanbeusedforqualitycontroltoconfirmacceptablerangesofSUVs.822

3.6.5.2 DeterminationofImageQuality823

CT images should be reviewed by the Image Analyst for assessment of image quality and for potential824artifacts suchasbeamhardening,metalobjects,andmotion.PET images shouldbecompared to theCT825imagesforproperimageregistrationandpotentialattenuationcorrectionartifacts.Bothuncorrectedand826attenuationcorrectedimagesmayneedtobeassessedtoidentifyanyartifactscausedbycontrastagents,827


metalimplantsand/orsubjectmotion.Forexample,movementormis-registrationcanleadtopoorquality828quantitative data and invalid numbers. Some imagesmay be too poor in quality to quantify. Statistical829quality of images is important to report, but not a full substitute for quality. Liver noise assessment as830definedperPERCIST[Wahl2009]isconsideredareasonablestart.831

3.6.5.3 DeterminationofEvaluableTumorLesions832

Thedefinitionofspecific tumorsthatareevaluableshouldbeaddressedprospectively intheclinical trial833protocol. Protocol-specific guidelines should document whether or not minimum size criteria and/or834minimumbaselineSUVcriteriafortargetlesionqualificationsareused,andifso,howsuchcriteriawillbe835used.836

Thecriteriabelowrepresentthebestknownpracticesbasedonpublisheddata,andcanprovideaguideline837fordeterminingevaluability.838

SelectionofTargetLesions(UPICTSection10.2.1.1)839

The lesion tobemeasured shouldbe freeof artifacts, forexample, fromnearby intenseFDGcontaining840structures(likethebladder)orduetomotionorattenuationcorrectionartifacts.841

MinimumBaselineSUV(UPICTSection10.2.1.1.1)842

FromtheSNMGlobalHarmonizationSummit (2010)and in themeta-analysisbydeLangenetal (2012),843therewasconsensusthattoreliablymeasureachangeintheFDGuptakeofalesion,ahighbaselineFDG844uptakeisnecessary.Forillustration,a30%decreaseinlesionuptakemaybemorereliablymeasured,and845potentiallymoremeaningful, if the initial lesionuptakehadanSUVof5g/mlasopposedtoanSUVof2846g/ml.847

UPICT Acceptable level: Aminimum FDG-avidity is required and should be specified in the clinical trial848protocol. Thiscanbedeterminedbyeitherasubject-specific thresholdasproposedwithPERCIST [Wahl8492009]orasageneralcutoff.Forageneralcutoff,aSUVmaxof4issuggestedforalltargetlesions,although850insomesettingsalowerminimumSUVmaxmaybeacceptable,suchasinthelungorbreast.Alternative851methodshavebeenproposed[LodgeandWahl2013].852

ThemeasurementformeanliverSUVismadeusinga3-cmdiametersphericalROIplacedintherightlobe853of the liver at the level ofmain portal vein and equidistant between the porta hepatis and lateral liver854margin.CareshouldbetakentoavoidplacingtheROIclosetotheedgeoftheliver[Subramaniam2012].855FurtherdetailsaregiveninUPICTSection10.2.1.1.1.Iftheliverisnotinthefieldofvieworisabnormaltoa856degreethatnormallivercannotbeassessed,thenthealternatecomparatoristouseaminimumthreshold857levelof2.0xmeanSUVofbloodpool ina3DROIdefinedasa1cmdiametercylinder inthedescending858thoracicaortaextendingover2cm,trackingthelongaxisoftheaorticlumen,avoidingthewalloftheaorta859orareasofplaqueorcalcification.IfthedescendingaortaisnotevaluableaVOIofthesamevolumeshould860bemeasuredfromelsewhereinthethoracicaorta.861

MinimumLesionSize862

TheSNMGlobalHarmonizationSummitsuggeststhattumorsshouldtypicallybeover2cmindiameterfor863target lesion inclusionatbaseline.Lesionssmallerthan2cm(orotherwisenoteasilymeasurable)witha864highenoughFDGuptake,maystillbeevaluable.865

Evaluation of lesion size (e.g., longest diameter) may be difficult. This may be due to intrinsic lesion866characteristics (e.g., infiltrative or CT lesion isodensity to surrounding tissue) or due to the anatomic867locationoftumor(e.g.,bonemarrowsite).LesionssubjecttopartialvolumeeffectofSUVmeasurement,868


notably due to anatomic location and attenuation correction errors (e.g., peri-diaghragmatic lesions at869eitherlungbaseorhepaticdome)potentiallyshouldbeexcluded.870

3.6.5.4 DeterminationofsubjectsunsuitableforFDG-PET/CTanalysis871

ReferenceSection3.1.1"SubjectSelection,Timing,andBloodGlucoseLevels"872

3.6.6QualityControlofInterpretation873

Topromotequantifiableperformancestandardsforthequalitycontrolofinterpretationthereisaneedfor874intra-readervariabilitystudies.Ina2-Readerparadigm,theninter-readervariabilityisneededaswell.Itis875currently unclearwhat statistics to evaluate and how these performancemetrics should be used in the876analysis.877

4.Conformance878

RelationofthisProfiletoExpectationsforQIBAProfileCompliance879

Definitions(fromAppendixC):880

Qualified: The imaging site is formally approved by an appropriate body (i.e. ACRIN, CQIE, SNMMI-CTN,881EANM-EARL,NCRI,animaginglaboratoryorCRO)foraspecificclinicalresearchstudy.882

Accredited:Approvalbyanindependentbodyorgroupforbroadclinicalusage(requiresongoingQA/QC)883e.g.ACR,IAC,TJC.884

Compliant: The imaging site and equipment meet all the requirements described herein, which are885necessarytomeettheQIBAProfileclaim.886

Therequirementsincludedhereareintendedtoestablishabaselinelevelofcapabilities.Providinghigher887levels of performance or advanced capabilities is both allowed and encouraged. Furthermore the QIBA888Profile is not intended to limit equipment suppliers in any way with respect to how they meet these889requirements.InstitutionsmeetingthestatedcriteriaareconsideredtobeQIBACompliant.890

4.1.ImageAcquisitionSite891

Typicallyclinicalsitesareselectedduetotheircompetence inoncologyandaccess toasufficiently large892subjectpopulationunderconsideration.Forimagingitisimportanttohaveavailabilityof:893

• Appropriateimagingequipmentandqualitycontrolprocesses,894

• Appropriateancillaryequipmentandaccesstoradiotracerandcontrastmaterial,895

• ExperiencedTechnologists(CTandPETtrained)forthesubjecthandlingandimagingprocedure,896

• Appropriately trained Radiologists/Nuclear Medicine Physicians for image analysis and diagnostic897interpretation,898

• Appropriatelytrainedimageanalysts,withoversightbyaRadiologistorNuclearMedicinePhysician,899

• MedicalPhysicssupporttoensureappropriatescannerandequipmentcalibration,900

• ProcessesthatassureimagingQIBAProfile-compliantimagegenerationinappropriatetimewindow901

AQA/QCprogramforPET/CTscannersandancillarydevicesmustbeinplacetoachievethegoalsofthe902clinicaltrial.Theminimumrequirementsarespecifiedabove.Thisprogramshallinclude(a)elementsto903


verifythatimagingfacilitiesareperformingimagingstudiescorrectlyand(b)elementstoverifythat904facility'sPET/CTscannersareperformingwithinspecifiedcalibrationvalues.Thesemayinvolve905additionalPETandCTphantomtestingthataddressissuesrelatingtobothradiationdoseandimage906quality(whichmayincludeissuesrelatingtowatercalibration,uniformity,noise,spatialresolution–in907theaxialplane-,reconstructedslicethicknessz-axisresolution,contrastscale,andothers)and908constancy.Thereisagreementthatsomeperformancetesting(e.g.,constancyphantom)addsvalue;909however,acceptableperformancelevels,frequencyofperformance,triggersforactionandmitigation910strategiesneedfurtherdefinitionbeforethesecanberequired.Thisphantomtestingmaybedonein911additiontotheQAprogramdefinedbythedevicemanufacturerasitevaluatesperformancethatis912specifictothegoalsoftheclinicaltrial.913

914


PET/CTScanner

AcquisitionFacility

ThisProfileshallonlyaddressfullringPET/CTscanners.

CTScannerCalibration

Technologist Shallperformdailywaterequivalentphantomanalysis;ensurethatoutputisacceptableandmanuallyenteronform/electronicdatabase.

PETScannerCalibration

Technologist Shallperformdaily/weekly/monthlyscannerQAasrecommendedbymanufacturer;ensurethatoutputvaluesareacceptableandmanuallyenteronform/electronicdatabase

PETScannerCalibrationConstancyCheck

Technologist Shallperformconstancyphantom(e.g.,Ge-68cylinder)scan(preferablyNISTtraceableorequivalenttogatherinformationregardinguniformityaswell)atleastweeklyandaftereachcalibration.

Dosecalibrator

ImagingsiteorManufacturer

CalibratedtoF-18usingNISTtraceablesourceorequivalenteitherbysiteorcalibratormanufacturer.

915

4.2.PET/CTAcquisitionDevice916

DistinctfromtheperformancespecificationsandfrequencyoftestingdescribedinSection4.1whichapply917to quality control of the Acquisition Device at the imaging facility, this Section defines performance918specificationsof theAcquisitionDevicetobemetupon leavingthemanufacturing facility. Inorder tobe919compliantwiththisProfile,theAcquisitionDeviceshouldbeheldtothesamestandardwhetheramobile920utility or a fixed installation; a mobile scanner may require additional calibration to achieve this921performance.922

ThePET/CTscannershoulduseDICOMattributestofollowversionnumbersofsoftwarefor:1Acquisition,9232Reconstruction,3Post-processing,4DisplayandROIanalysis,5DynamicAnalysis.NotethatthisProfile924does not specify dynamic imaging performance requirements. Performance requirements regarding925softwareversionidentification,documentationandtrackingacrosstimearedescribedinSection4.5.926

ThePET scanacquisition start time shouldbeused for thedecay reference timeand the integralmodel927should be used for decay correction. The scanner should perform all decay corrections (i.e. not the928


operator).ImagedataaretobegiveninunitsBq/ml.“Derived”images(distinctfrom“Original”)shouldbe929flaggedfollowingtheDICOMstandardandshouldretainthescanacquisitiondateandtimefields.930

All needed information for fully corrected administered activity (e.g. residual activity, injection time,931calibrationtime)isrequired.Notethatuseofthetermadministeredactivitybelowreferstofullycorrected932netradioactivity.933

Baseline level (i.e. equivalent to the UPICT protocol level of 'Acceptable') compliance requires that the934DICOMimagesetfromthesubject’sPET/CTscanandnecessarymetadata(thatisnotcurrentlycapturedby935all PET scanner acquisition processes) is captured in trial documentation, e.g. case report forms. The936metadata isrequiredtoperformthequantitativeanalysisandperformqualitycontrolonSUVcovariates.937Thisincludesforexample,post-injectionresidualactivityandsubjectheight.Thisdatashouldbecaptured938inthe'CommonDataFormatMechanism'asdescribedinAppendixE.939

The DICOM format used by the PET/CT scanner should meet the Conformance Statement written by940manufacturerofthePET/CTsystem.PETdatashallbeencodedintheDICOMPETorEnhancedPETImage941StorageSOPClass,andinactivity-concentrationunits(Bq/ml)withadditionalparametersinpublicDICOM942fieldstocalculateSUVs(e.g.height,weight,scalefactors).CTdatashouldbeencodedinCTorEnhancedCT943ImageStorageSOPClass.DICOMdatashallbetransferredusingtheDICOMPart8networkprotocoloras944offlineDICOMPart10filesformediastorageincludingCDsandDVDs.Theyshallbetransferredwithoutany945formoflossycompression.946

Themeta-information is the information that is separate,or inaddition to, the imagevalues (inunitsof947Bq/ml) that is deemed necessary for quantitatively accurate representation of PET SUVs. The meta-948informationmayalsoincludeotherinformationbeyondthatneedforcalculationofSUVs,i.e.thetypeand949or sequencing of therapy, the blood glucose levels, the scanner SUV stability history, etc. The actual950mechanism of capturing the information is not specified in this Profile. The intent here is to list what951informationshouldbecapturedrather than themechanism itself.Themechanismcan range frompaper952notes,toscannedformsorelectronicdatarecords,todirectentryfromthemeasurementequipmentinto953pre-specifiedDICOMfields(i.e.fromthePET/CTscannerorauxiliarymeasurementdevicessuchasthedose954calibrator).Ideallyallofthespecifiedmeta-datawillbecapturedbydirectelectronicentrytoDICOMfields,955aftersuitablemodificationoftheDICOMformatforPETimaging.956

Insomefacilityworkflows,theAcquisitionDevicemayalsoprovideworkstation/analysistoolfunctionality.957Forexample,thedisplayofanSUVstatistic(consideredinSection4.4.1)ordisplayofTracerUptakeTime958(consideredinSection4.4),mayalsoapplytotheAcquisitionDevice,ifusedinthismanner.959

Theconceptendorsedhereisthattheneededmeta-dataisidentified.ThroughrevisionsofthisProfile,the960DICOMstandard,and technology themeta-data is inserted into theanalysis stream (Figure3) inamore961directmannerandtechnologyandacceptedstandardsevolve.962

963


CTcalibrationtracking

AcquisitionDevice

DailywaterequivalentphantomvaluesshallbetrackedintheDICOMheader.

PETcalibrationfactor

AcquisitionDevice

ThecurrentSUVcalibrationfactorshallbeincludedintheDICOMheader.

PETQAstatus Acquisition Date/timeandstatusofsystem-wideQAchecksshouldbe



Device capturedseparately.

Dosecalibratorcalibration

AcquisitionDevice

CalibrationfactorforanF-18NIST-traceable(orequivalent)sourcewithidentifyinginformationshallbetrackedintheDICOMheaderwithDate/Time.

PETScannercalibration

AcquisitionDevice

Shallbeabletobecalibratedaccordingtothefollowingspecifications:UsingauniformcylindercontainingF-18inwater(ideallythesameusedfordosecalibratorcross-calibration)

Slice-to-slicevariabilityshallbenomorethan±5%(notincludingendslices,asperACRPETCoreLab).

In-planeuniformityforabovephantomshallbelessthan5%.

Immediatelyaftercalibration,usingthesamefilledphantomandscannedsufficientlylongtominimizestatisticalnoise,andanACR-typeROIanalysis

TheaveragemeasuredSUVshallbeintherangeof0.98to1.02.(NotethisisnottheperformanceexpectedduringclinicalimagingoperationasdiscussedinpreambletothisSection).Thistechniqueremovesthevariabilityduetoradionclidemeasurement.

Weight AcquisitionDevice

Shallbeabletorecordpatientweightinlbsorkgassuppliedfromthemodalityworklistoroperatorentryintoscannerinterface.ShallbestoredinPatientWeightfield(0010,1030)intheDICOMimageheader,asperDICOMstandard.

Patientweightshallbespecifiablewith4significantdigits.

Patientweightshallbetransferrabledirectlyfrommeasurementdeviceintoscannerbyelectronic,HIS/RIS,orothermeans,bypassingalloperatorentry,butstillpermittingoperatorcorrection.

Height AcquisitionDevice

Shallbeabletorecordpatientheightinfeet/inchesorcm/massuppliedfromthemodalityworklistoroperatorentryintoscannerinterface.ShallbestoredinPatientSizefield(0010,1020)intheDICOMimageheader,asperDICOMstandard.

Patientheightshallbespecifiablewith3significantdigits.

Patientheightshallbetransferrabledirectlyfrommeasurementdeviceintoscannerbyelectronic,HIS/RIS,orothermeans,bypassingalloperatorentry,butstillpermittingoperatorcorrection.



Bloodglucoselevel AcquisitionDevice

ShallbeabletoRecordpatientbloodglucoselevel,inunitsofmg/dl,ormMol/l,timeofmeasurement,assuppliedbyoperatorentryintothescannerinterface.ShallberecordedintheDICOMimageheaderintheAcquisitionContextSequenceusingDICOMPS3.16TID3471PETCovariatesAcquisitionContext.

PatientbloodglucoselevelshallbetransferrabledirectlyfrommeasurementdeviceintothescannerusingtheModalityWorklistNM/PETProtocolContextTID15101,bypassingalloperatorentry,butdisplayingittotheoperatorandstillpermittingoperatorcorrection.

AdministeredRadionuclide

AcquisitionDevice

Shallbeabletoentertheradionuclidetype(i.e.F-18)byoperatorentryintothescannerinterfaceandthroughpredefinedprotocolShallberecordedinRadionuclideCodeSequence(0054,0300)intheDICOMimageheader[e.g.(C-111A1,SRT,“18Fluorine”)].

Shallbeabletoaccepttheradionuclidetype(i.e.F-18)directlyfromthemeasurementdevice(dosecalibrator)ormanagementsystem,usingtheSup159RadiopharmaceuticalAdministrationRadiationDoseReportbypassingalloperatorentry,butstillpermittingoperatorcorrection.

Shallbeabletoaccepttheradionuclidetype(i.e.F-18)fromtheDICOMModalityWorklisteitherfromtheNM/PETProtocolContext,ifpresent,orbyderivingiffromtheRequestedProcedureCodeviaalocallyconfigurabletableofvalues.

AdministeredRadiotracer

AcquisitionDevice

Shallbeabletorecordtheradiotracer(i.e.FDG),assuppliedbyoperatorentryintothescannerinterface.ShallberecordedinRadionuclideCodeSequencefield(0054,0300)intheDICOMimageheader,e.g.(C-B1031,SRT,“FluorodeoxyglucoseF18”).

AdministeredRadiotracerradioactivity

AcquisitionDevice

Shallbeabletoentertheadministeredradioactivity,inbothMBqandmCi,assuppliedbyoperatorentryintothescannerinterface.ShallberecordedinRadionuclideTotalDosefield(0018,1074)intheDICOMimageheaderinBq.

Shallbeabletorecordwithseparateentryfieldsonscannerinterface:

(1) thepre-injectionFDGradioactivity

(2) timeofmeasurementofpre-injectionFDGradioactivity

(3) theresidualactivityafterinjection

(4) timeofmeasurementtheresidualradioactivityafterinjection

Shallautomaticallycalculatetheadministeredradioactivityand



storeintheRadionuclideTotalDosefield(0018,1074)intheDICOMimageheader.

Alternatively,shallbeabletoreceivethisinformationasperDICOMSupplement159.

PatientAdministeredRadiotracerradioactivityinformationshallbetransferreddirectlyfrommeasurementdeviceintoscannerbyelectronic,HIS/RIS,orothermeans,bypassingalloperatorentry,butstillpermittingoperatorcorrection.

AdministeredRadiotracerTime

AcquisitionDevice

Shallbeabletorecordthetimeofthestartofactivityinjectionassuppliedbyoperatorentryintothescannerinterface.ShallberecordedinRadiopharmaceuticalStartDateTimefield(0018,1078)(preferred)orRadiopharmaceuticalStartTimefield(0018,1072).

Shallbeabletorecordthetimeofthestartofactivityinjectionassuppliedbyoperatorentryintothescannerinterface.ShallberecordedinRadiopharmaceuticalStartDateTimefield(0018,1078).I.e.,notRadiopharmaceuticalStartTimefield(0018,1072).

Shallbeabletorecordthetimeofthestopofactivityinjectionassuppliedbyoperatorentryintothescannerinterface.ShallberecordedinRadiopharmaceuticalStopDateTimefield(0018,1079).

DecayCorrectionMethodology

AcquisitionDevice

EncodedvoxelvalueswithRescaleSlopefield(0028,1053)appliedshallbedecaycorrectedbythescannersoftware(nottheoperator)toasinglereferencetime(regardlessofbedposition),whichisthestarttimeofthefirstacquisition,whichshallbeencodedintheSeriesTimefield(0008,0031)fororiginalimages.

CorrectedImagefield(0028,0051)shallincludethevalue“DECY”andDecayCorrectionfield(0054,1102)shallbe“START”,whichmeansthattheimagesaredecaycorrectedtotheearliestAcquisitionTime(0008,0032).

ScanningWorkflow AcquisitionDevice

ShallbeabletosupportProfileProtocol(Section3)PETandCTorder(s)ofacquisition.

Shallbeabletopre-defineandsave(byimagingsite)aProfileacquisitionProtocolforpatientacquisition.

Shallbeabletointerpretpreviously-reconstructedpatientimagestoregenerateacquisitionprotocol.

Shallbeconfigurabletostore(orreceive)acquisitionparametersaspre-definedprotocols(inaproprietaryorstandardformat),toallowre-useofsuchstoredprotocolstomeetmulti-center



specificationsandtoachieverepeatableperformanceacrosstimepointsforthesamesubject.

CTAcquisitionParameters

AcquisitionDevice

Shallrecordallkeyacquisitionparameters(technique)intheCTimageheader,usingstandardDICOMfields.

CTbasedattenuationcorrection

AcquisitionDevice

ShallrecordinformationinPETDICOMimageheaderwhichCTimageswereusedforcorrections(attenuation,scatter,etc.).

PET-CTAlignment AcquisitionDevice

ShallbeabletoalignPETandCTimageswithin±2mminanydirection.

ShallbeabletoalignPETandCTimageswithin±2mminanydirectionwithaloadupto150kgovertheco-scanlength.

ActivityConcentrationintheReconstructedImages

AcquisitionDevice

Shallbeabletostoreandrecord(rescaled)imagedatainunitsofBq/mlanduseavalueofBQMLforUnitsfield(0054,1001).

TracerUptakeTime

AcquisitionDevice

ShallbederivablefromthedifferencebetweentheRadiopharmaceuticalDateTimefield(0018,1078)(preferred)orRadiopharmaceuticalStartTimefield(0018,1072)andtheSeriesTimefield(0008,0031)orearliestAcquisitionTimefield(0008,0032)intheseries(i.e.,thestartofacquisitionatthefirstbedposition),whichshouldbereportedasseriestimefield(0008,0031).

PETVoxelsize AcquisitionDevice

SeeSection4.3(PETVoxelsize)undertheReconstructionSoftwarespecificationrequirements.

CTVoxelsize AcquisitionDevice

ShallbenogreaterthanthereconstructedPETvoxelsize.

Voxelsshallbesquare,althougharenotrequiredtobeisotropicintheZ(head-foot)axis.

NotrequiredtobethesameasthereconstructedPETvoxelsize.

SubjectPositioning AcquisitionDevice

ShallbeabletorecordthesubjectpositioninthePatientOrientationCodeSequencefield(0054,0410)(whetherproneorsupine)andPatientGantryRelationshipCodefieldSequence(0054,0414)(whetherheadorfeetfirst).

ScanningDirection AcquisitionDevice

Shallbeabletorecordthescanningdirection(craniocaudalv.caudocranial)intoanappropriateDICOMfield.



DocumentationofExamSpecification

AcquisitionDevice

Shallbeabletodefinetheextentofanatomiccoveragebasedondistancefromdefinedlandmarksite(e.g.vertex,EAM).(boththelandmarklocation(anatomically)andthedistancescannedfromlandmark)wouldrequireDICOMtags).

Shallbeabletobereportableforfuturescanningsessions.

TheAcquisitionDeviceshallrecordthez-axisFOVwhichrepresentstheactualdistanceofscananatomiccoverage(cms).

DifferentialAcquisitionTime

AcquisitionDevice

Shallbeabletoacquireandrecordnonuniformscantimesdependentuponareasofclinicalconcern.RecordingcanbedonethroughtheuseofActualFrameDuration(0018,1242)andFrameReferenceTime(0054,1300).

DICOMConformance

AcquisitionDevice

AllimagedataandscanparametersshallbetransferableusingappropriateDICOMfieldsaccordingtotheDICOMconformancestatementforthePET/CTscanner.

DICOMDatatransferandstorageformat

PET/CTScannerorDisplayWorkstation

PETimagesshallbeencodedintheDICOMPETorEnhancedPETImageStorageSOPClass,usingactivity-concentrationunits(Bq/ml)withadditionalparametersstoredinpublicDICOMfieldstoenablecalculationofSUVs.

PETimagesshallbetransferredandstoredwithoutanyformoflossycompression.

964


DICOMEditing AcquisitionDevice

ShallbeabletoeditallfieldsrelevantforSUVcalculationandbloodglucosebeforeimagedistributionfromscanner.

Shallprovideappropriatewarningsifoverridingofthecurrentvaluesisinitiated.

965

4.3.ReconstructionSoftware966

ReconstructionSoftwareshallpropagatetheinformationcollectedatthepriorSubjectHandlingand967ImagingAcquisitionstagesandextenditwiththoseitemsnotedintheReconstructionsection.968


Metadata ReconstructionSoftware

ShallbeabletoaccuratelypropagatetheinformationcollectedatthepriorstagesandextenditwiththoseitemsnotedintheReconstructionsection.

Datacanbereconstructedincludingallcorrectionsneededforquantificationaswellaswithoutscatterand969attenuationcorrection.Analyticaloriterativereconstructionmethodsshouldbeapplied.Ifthesystemis970


capableofprovidingresolutionrecoveryand/ortimeofflight,thenthedecisionto‘turnon’or‘turnoff’971this/thesecapabilitiesshouldbemadeprospectively,asdictatedbythespecificprotocol,andshouldbe972consistentforagivensubjectacrossmultipletimepoints.973

StandardizationofreconstructionsettingsisnecessarytoobtaincomparableresolutionandSUVrecoveries974acrossthesamesubjectandinter-subjectacrosssites.975


DataCorrections

ReconstructionSoftware

PETemissiondatamustbeabletobecorrectedforgeometricalresponseanddetectorefficiency,systemdeadtime,randomcoincidences,scatterandattenuation.

ReconstructionMethodology


Shallbeabletoprovideimageswithoutresolutionrecovery.

Shallbeabletoindicate,forbothTOFandResolutionrecovery,ifeitherarebeingusedforpurposesofimagereconstruction.

ReconstructionMethodology/Output


Shallbeabletoperformreconstructionswithandwithoutattenuationcorrection.

DataReconstruction2D/3DCompatibility


Shallbeabletoperformreconstructionofdataacquiredin3Dmodeusingfully3Dimagereconstructionalgorithms.

Shallbeabletoperformreconstructionofdataacquiredin2Dmodeusing2Dimagereconstructionalgorithms.

Quantitativecalibration

Reconstructionsoftware

Shallapplyappropriatequantitativecalibrationfactorssuchthatallimageshaveunitsofactivityconcentration,e.g.kBq/mL.

Multi-beddata Reconstructionsoftware

Shallcombinedatafrommultipleover-lappingbedpositions(includingappropriatedecaycorrections)soastoproduceasinglethreedimensionalimagevolume.

Voxelsize Reconstructionsoftware

Shallallowtheusertodefinetheimagevoxelsizebyadjustingthematrixdimensionsand/ordiameterofthereconstructionfield-of-view.

ShallbeabletoreconstructPETvoxelswithasize4mmorlessinallthreedimensions(asrecordedinVoxelSpacingfield(0028,0030)andcomputedfromthereconstructionintervalbetweenImagePosition(Patient)(0020,0032)valuesofsuccessiveslices).

Pixelsshallbesquare,althoughvoxelsarenotrequiredtobeisotropicinthez(head-foot)axis.

ShallbeabletoreconstructPETvoxelswithasizeof3mmorlessinallthreedimensions(asrecordedinVoxelSpacingfield(0028,0030)



andcomputedfromthereconstructionintervalbetweenImagePosition(Patient)(0020,0032)valuesofsuccessiveslices).

Voxelsshallbeisotropic.

Reconstructionparameters


Shallallowtheusertocontrolimagenoiseandspatialresolutionbyadjustingreconstructionparameters,e.g.numberofiterations,post-reconstructionfilters.

ShallbeabletorecordreconstructionparametersusedinimageDICOMheaderusingtheEnhancedPETIOD,developedbyDICOMworkinggroup.

Reconstructionprotocols


Shallallowasetofreconstructionparameterstobesavedandautomaticallyapplied(withoutmanualintervention)tofuturestudiesasneeded.

976

4.4.ImageAnalysisWorkstation977

Theimageanalysisworkstationshallhavetheabilitytoreceiveandpropagatethedataoutput(imagingand978metadata)collectedfromtheprioractivities(SubjectHandling,ImageAcquisition,ReconstructionandPost-979Processing).Withtheinputdata,theanalysisworkstation(andsoftwareanalysistools)willbeabletomake980useofcertainattributevaluestoperformcertainmeasurementsandcomputationalanalysis.Theanalysis981workstationandsoftwaremaybecoupledtothePET/CTscannersystemorprovidedbya3rd-partyvendor.982


Metadata ImageAnalysisWorkstation

ShallbeabletoaccuratelypropagatetheinformationcollectedatthepriorstagesandextenditwiththoseitemsnotedintheImageAnalysisWorkstationsection.

ShallbeabletodisplayallinformationthataffectsSUVseitherdirectlyincalculation(e.g.patientweight,injectedactivity)orindirectly(uptaketime,plasmaglucoseconcentration).

TracerUptakeTime:Display

ImageAnalysisWorkstation

Shallbecapabletodisplayorincludelinktodisplaythenumberofminutesbetweeninjectionandinitiationofimaging(asperderivationguidelinesdescribedinSection4.2).

983

InputforImageAnalysisisconsideredoutputofReconstructionandPostprocessingsoftwareactivity.Ifthe984ImageAnalystaltersinputdata(e.g.zoom)thisisconsideredpartofImageAnalysisactivity.Ifthisoccurs,985theoriginalinputdatawillbemaintainedasaseparatefile,bothtobestored,includingdescriptionof986manipulationinanaudittrailfileorinadedicatedDICOMtagsection(Section3.2).987

988


Referencetime ImageAnalysis ShalluseeithertheAcquisitionTimefield(0008,0032)or



fordecaycorrection

Workstation RadiopharmaceuticalStartTime(0018,1072),ifnecessary.Ifaseries(derivedornot)isbasedonAcquisitionTimedecaycorrection,theearliestAcquisitionTime(0008,0032)shallbeusedasthereferencetimefordecaycorrection.

989

4.4.1RegionofInterest(ROI)definition990

Thescanner-display-analysissystemshallprovideatoolfortheusertodefineboth2Dand3Dregionsof991interest(ROIs).WhiletheROIcanbedrawnonprocessedimages,theSUVcalculationshouldbeperformed992fromunprocessed(raw)imagedata(SeeSection3.3.2).TheseROIswillthenbeusedcalculateSUVvalues993asdescribedinthenextsection.994

Thespecificationsbelowarefordefinedregionsforthecalculationof(1)averagevaluewithinanROI(i.e.995SUVmean) (2)maximumvaluewithin anROI (i.e. SUVmax) (3) average valuewithin a fixed-sizeROI (i.e.996SUVpeak) (4) average value within a fixed-size ROI (i.e., SUVpeak), but with the location automatically997selectedtomaximizethemeanvalue.ForSUVpeakmeasures, theuseofpartialvoxelvaluestosecurea9981.2cmdiametersphere(or1ccvolume)ROIisappropriateanddesirable.999

1000


VoxelInclusionPolicy

AnalysisTool Shalldescribevoxelinclusionmethodologyandweightingpolicyincludingplacementcriteriaandtotalvolume.

Useamethodequivalenttoweightingforpartialvoxels;fullyincludedvoxelsuseweightof1.0.Weightingshouldbeproportionatetovolumesofvoxelsthatarepartlyincluded.

ROISpecifications AnalysisTool ShalldescribecapabilitiesandlimitsofROIspecificationandplacement.

DimensionsandcenterlocationofROI(box,ellipse,orellipsoid)shallbespecifiableto±1mm.

ForSUVpeakmeasures,thelocationwithinatargetsearchregionthatyieldsthehighestmeanvalueofa1ccregionshallbefoundautomaticallyandreproducibly.

ROIDefinitionTools

AnalysisTool ShallprovideatoolanduserstrategytoallowtheplacementofanROItodeterminetheaveragevaluewithintheROI.

ShallprovideatoolanduserstrategytoallowtheplacementofanROItodeterminethevalueandlocationofthevoxelwiththemaximumvaluewithinanROI.

Shallprovideatoolanduserstrategytoallowtheplacementofa1cmdiameterROI(either2Dor3D)todeterminetheaveragevaluewithintheROI.



Shallprovideatoolanduserstrategytoallowautomaticplacementofa1cmdiameterROI(either2Dor3D)suchthattheaveragevaluewithintheROIismaximized.

Edge/VolumeDetection

AnalysisTool ShallprovidethresholdmethodsfordefininganROIbasedonimagevalues.

Shallclearlyspecifywhichthresholdmethodisusedandrelevantparametersvalues.

ThreeROIdefinitionmethodsshallbeprovided:Fixedvalue,%ofmaximumvoxel,oredgedetection/segmentationmethods.

ROIsaving/retrieve Analysis/Archival Shallhavethecapabilitytolabel,save,recallandeditROIs.

Shallhavethecapabilitytotracktumorinformationacrosslongitudinalscans.Inadditiontolesion(andnormalreferenceregion)identification,thismayincludecrosstimepointmappingoflesionstrackedonthebasisofconsistentanatomicand/orfunctionalactivity.Otherlesioncharacteristics,suchaslesionname(withconsistentanatomiclabeling),lesionlocation,ROI/VOIsize,correspondinganatomic(CT)imageorslicenumber,SUVmetric(s)andassessmentoftumorheterogeneitymayalsobetrackedandcapturedusingstandardDICOMobjects.

ROIDisplayStatistics

AnalysisTool Shall have the capability to output to the screen display theselectedstatisticsoftheROI.Theseinclude,butarenotlimitedto: Area, volume, mean, maximum, minimum, standarddeviation. Units can be selectable as activity concentration[Bq/ml]orSUV[g/ml](SeeSection3.4.3).

Shall have the capability to display results with at least twodecimalplaces.

ShalloutputROIOutputStatisticstoStructuredDataReportingDICOMfiles.

Shallcalculateresultsdirectlyfromtheoriginallyreconstructedvoxels(notfrominterpolatedand/orzoomedimages).

Theworkstationandrepositoryshallbeabletocreate,storeandretrievemarkups(i.e.ROIs)usedforSUV1001measurements inaccordancewithastandarddefinitionforROIsthatprovidesaknownbalancebetween1002precisionandaccuracy.1003

4.4.2CalculationofStandardizedUptakeValue(SUV)1004

TheROIdefinitionandanalysissoftwareisresponsibleforSUVcalculation,e.g.withdecaycorrectiontothe1005appropriate reference time. Moreover, the manufacturer should implement both versions of SUV1006normalizations (body weight or lean body mass). Recommended vendor-neutral pseudo-codes for SUV1007


calculationaregiveninAppendixG.1008

1009


SUVCalculation AnalysisTool ShallhavethecapabilitytocorrectlycalculateSUVsaccordingtothevendor-neutralpseudo-codesforSUVcalculationgiveninAppendixG.

VolumeofDistributionSurrogate

AnalysisTool ShallhavethecapabilitytocalculateSUVsusingasasurrogatefortheVolumeofDistribution:bodyweight,leanbodymass,andbodysurfacearea(BSA).

LeanbodymassshallbecalculatedaccordingtotheformulaofJames[James1976,Hallynck1981]:

Males:LBM=1.10(w)–128(w^2/h^2)

Females:LBM=1.07(w)–148(w^2/h^2)

BodysurfaceareashallbecalculatedaccordingtotheDuBoisformula:BSA(m^2)=(0.007184)((w)^(0.425))((h)^(0.725))

[Vu2002]

Wherew=weightinkgandh=heightincm.

1010

4.4.3ImageAnalysisWorkstationPerformanceSpecifications1011

Thedigitalreferenceobject(DRO),whichisasyntheticPET(andCT)image,shallbeusedinorderto1012evaluateconformancetothelevelofperformanceofanalysisstation/displaystation.Usersshouldusethe1013DRO(aspertheDROuser'sguideinAppendixF)toverifycorrectimplementationofROIplacement,SUV1014calculations,andPETandCTimagealignment.1015


PerformanceEvaluation

AnalysisWorkstation

ShallusetheDROtoverifyadequateperformanceasdescribedinAppendixF.

AnalysisAccuracy AnalysisWorkstation

ForeachofthespecifiedROIsintheDRO(AppendixF)thecorrectSUVvaluesshallbereplicatedbytheAnalysisWorkstation.

AlignmentAccuracy

AnalysisWorkstation

ThePETandCTDROobjectshallappearperfectlyalignedinthetransverse,coronal,andsagittalviews.

DICOMConformance

AnalysisWorkstation

ShallbeabletoreadandapplyallmandatoryDICOMPETIODattributes,aswellasanyadditionaloptionalDICOMattributesspecifiedinthisprofile(includingthoseprivateattributesdefinedinAnnexGforSUVcalculation).

4.5.SoftwareVersionTracking1016


Ideally,thePET/CTscannershouldbeabletobuildalistontheconsoleofthedatesofallsoftwareversions1017(software changes that might impact quantitative accuracy would typically be inclusive of hardware1018change). Furthermore, the scanner software version should be identified and tracked across time, with1019updates and changes in scanner software noted during the course of the trial. At aminimum, Software1020Versions should be manually recorded during the qualification along with the phantom imaging1021performancedataandtherecordshouldbeupdatedforeverysoftware-upgradeoverthedurationofthe1022trial.This includestheflaggingofthe impactonquantificationfornow; inthefuture,recordallsoftware1023versionnumbersinDICOMheader.1024

1025


SoftwareVersiontracking

AcquisitionDevice

Shallrecordthesoftwareversion(s)usedforacquisitionandreconstructioninappropriateDICOMfield(s).

Softwareversionback-testingcompatibility

Workstation Shallprovidemechanismtoprovideanalysisoftheimagedatausingupdatedaswellasprior(platform-specific)versionsofanalysissoftware.

1026

References1027

International Atomic Energy Agency (IAEA), Technical Report Series No. 454: Quality Assurance for1028RadioactivityMeasurementinNuclearMedicine,IAEA,Vienna(2006).1029

Medicare National Coverage DeterminationsManual Chapter 1, Part 4 (Sections 200 – 310.1) Coverage1030Determinations(Rev.142,02-03-12).1031

http://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads//ncd103c1_part4.pdf1032Referenced19April2012.1033

QIBAUPICTProtocol:http://qibawiki.rsna.org/index.php?title=UPICT.1034

AdamsMC,TurkingtonTG,WilsonJM,WongTZ.Asystematic reviewof the factorsaffectingaccuracyof1035SUVmeasurements.AJRAmJRoentgenol195(2):310-320,2010.PMID:20651185.1036

BeaulieuS,KinahanP,TsengJ,DunnwaldLK,SchubertEK,PhamP,LewellenB,MankoffDA.SUVvarieswith1037time after injection in (18)F-FDG PET of breast cancer: characterization and method to adjust for time1038differences.JNuclMed44(7):1044-1050,2003.PMID:12843218.1039

Bland,JMandDGAltman.“MeasurementErrorProportionalTotheMean.”BMJ313,no.7049(1996):106.1040

BoellaardR.StandardsforPETimageacquisitionandquantitativedataanalysis.JNuclMed50Suppl1:11S-104120S,2009.PMID:19380405.1042

BoellaardR,O’DohertyMJ,WeberWA,MottaghyFM,LonsdaleMN,StroobantsSG,OyenWJ,KotzerkeJ,1043HoekstraOS,PruimJ,MarsdenPK,TatschK,HoekstraCJ,VisserEP,ArendsB,VerzijlbergenFJ,ZijlstraJM,1044ComansEF,LammertsmaAA,PaansAM,WillemsenAT,BeyerT,BockischA,Schaefer-ProkopC,DelbekeD,1045BaumRP,ChitiA, KrauseBJ. FDGPET andPET/CT: EANMprocedure guidelines for tumourPET imaging:1046version1.0.EurJNuclMedMolImaging37(1):181-200,2010.PMID:19915839.1047

BoellaardR.Needforstandardizationof18F-FDGPET/CTfortreatmentresponseassessments.JNuclMed1048


52Suppl2:93S-100S,2011.PMID:22144561.1049

BucklerAJ,BresolinL,DunnickNR,SullivanDC,AertsHJ,BendriemB,BendtsenC,BoellaardR,BooneJM,1050ColePE,ConklinJJ,DorfmanGS,DouglasPS,EidsaunetW,ElsingerC,FrankRA,GatsonisC,GigerML,Gupta1051SN,GustafsonD,HoekstraOS,JacksonEF,KaramL,KelloffGJ,KinahanPE,McLennanG,MillerCG,Mozley1052PD, Muller KE, Patt R, Raunig D, Rosen M, Rupani H, Schwartz LH, Siegel BA, Sorensen AG, Wahl RL,1053Waterton JC, Wolf W, Zahlmann G, Zimmerman B. Quantitative imaging test approval and biomarker1054qualification:interrelatedbutdistinctactivities.Radiology259(3):875-884,2011.PMID:21325035.1055

Buckler AJ, Bresolin L, Dunnick NR, Sullivan DC. A collaborative enterprise for multi-stakeholder1056participation in the advancement of quantitative imaging. Radiology 258(3):906-914, 2011. PMID:105721339352.1058

Burger IA,HuserDM,BurgerC, vonSchulthessGK,BuckA.Repeatabilityof FDGquantification in tumor1059imaging:averagedSUVsaresuperiortoSUVmax.NuclMedBiol39(5):666-670,2012.PMID:22381783.1060

de Langen AJ, Vincent A, Velasquez LM, van Tinteren H, Boellaard R, Shankar LK, Boers M, Smit EF,1061Stroobants S, Weber WA, Hoekstra OS. Repeatability of 18F-FDG uptake measurements in tumors: a1062metaanalysis.JNuclMed53(5):701-708,2012.PMID:22496583.1063

DelbekeD,ColemanRE,GuiberteauMJ,BrownML,RoyalHD,SiegelBA,TownsendDW,BerlandLL,Parker1064JA, Hubner K, StabinMG, Zubal G, KachelriessM, Cronin V, Holbrook S. Procedure guideline for tumor1065imagingwith18F-FDGPET/CT1.0.JNuclMed47(5):885-895,2006.PMID:16644760.1066

DootRK,ScheuermannJS,ChristianPE,KarpJS,KinahanPE.Instrumentationfactorsaffectingvarianceand1067biasofquantifyingtraceruptakewithPET/CT.MedPhys37(11):6035-6046,2010.PMID:21158315.1068

DootRK,KurlandBF,KinahanPE,MankoffDA.DesignconsiderationsforusingPETasaresponsemeasure1069insinglesiteandmulticenterclinicaltrials.AcadRadiol19(2):184-190,2012.PMID:22104290.1070

FaheyFH,KinahanPE,DootRK,KocakM,ThurstonH,PoussaintTY.VariabilityinPETquantitationwithina1071multicenterconsortium.MedPhys37(7):3660-3666,2010.PMID:20831073.1072

Fletcher JW,DjulbegovicB,SoaresHP,SiegelBA, LoweVJ, LymanGH,ColemanRE,WahlR,Paschold JC,1073AvrilN,EinhornLH,SuhWW,SamsonD,DelbekeD,GormanM,ShieldsAF.Recommendationsontheuse1074of18F-FDGPETinoncology.JNuclMed49(3):480-508,2008.PMID:18287273.1075

FringsV,deLangenAJ,SmitEF,vanVeldenFH,HoekstraOS,vanTinterenH,BoellaardR.Repeatabilityof1076metabolicallyactivevolumemeasurementswith18F-FDGand18F-FLTPETinnon-smallcell lungcancer.J1077NuclMed51(12):1870-1877,2010.PMID:21078791.1078

Gronenschild EH, Habets P, Jacobs HI, Mengelers R, Rozendaal N, van Os J, Marcelis M. The effects of1079FreeSurferversion,workstationtype,andMacintoshoperatingsystemversiononanatomicalvolumeand1080corticalthicknessmeasurements.PLoSOne7(6):e38234,2012.PMID:22675527.1081

HallettWA,Maguire RP,McCarthy TJ, SchmidtME, Young H. Considerations for generic oncology FDG-1082PET/CTprotocolpreparationindrugdevelopment.IDrugs10(11):791-796,2007.PMID:17968761.1083

HattM, Cheze-Le Rest C, Aboagye EO, Kenny LM, Rosso L, Turkheimer FE, Albarghach NM,Metges JP,1084PradierO,VisvikisD. Reproducibility of 18F-FDGand3’-deoxy-3’-18F-fluorothymidinePET tumor volume1085measurements.JNuclMed51(9):1368-1376,2010.PMID:20720054.1086

JaceneHA,LeboulleuxS,BabaS,ChatzifotiadisD,GoudarziB,TeytelbaumO,HortonKM,KamelI,Macura1087KJ,TsaiHL,Kowalski J,WahlRL.Assessmentof interobserver reproducibility inquantitative18F-FDGPET1088


andCTmeasurementsoftumorresponsetotherapy.JNuclMed50(11):1760-1769,2009.PMID:19837757.1089

Jackson T, ChungMK,MercierG,OzonoffA, SubramaniamRM. FDGPET/CT interobserver agreement in1090headandneckcancer:FDGandCTmeasurementsoftheprimarytumorsite.NuclMedCommun33(3):305-1091312,2012.PMID:22227560.1092

KamibayashiT,TsuchidaT,DemuraY,TsujikawaT,OkazawaH,KudohT,KimuraH.Reproducibilityofsemi-1093quantitativeparameters inFDG-PETusingtwodifferentPETscanners: influenceofattenuationcorrection1094methodandexaminationinterval.MolImagingBiol10(3):162-166,2008.PMID:18408977.1095

Kinahan PE, Doot RK, Wanner-Roybal M, Bidaut LM, Armato SG, Meyer CR, McLennan G. PET/CT1096Assessment of Response to Therapy: Tumor ChangeMeasurement, Truth Data, and Error. Transl Oncol10972(4):223-230,2009.PMID:19956382.1098

KinahanPE,FletcherJW.Positronemissiontomography-computedtomographystandardizeduptakevalues1099inclinicalpracticeandassessingresponsetotherapy.SeminUltrasoundCTMR31(6):496-505,2010.PMID:110021147377.1101

KrakNC,BoellaardR,HoekstraOS,Twisk JW,HoekstraCJ,LammertsmaAA.EffectsofROIdefinitionand1102reconstructionmethodonquantitativeoutcomeandapplicabilityinaresponsemonitoringtrial.EurJNucl1103MedMolImaging32(3):294-301,2005.PMID:15791438.1104

KumarV,NathK,BermanCG,KimJ,TanvetyanonT,ChiapporiAA,GatenbyRA,GilliesRJ,EikmanEA.1105VarianceofSUVsforFDG-PET/CTisgreaterinclinicalpracticethanunderidealstudysettings.ClinNucl1106Med.2013Mar;38(3):175-82.doi:10.1097/RLU.0b013e318279ffdf.PMID23354032[PubMed-inprocess].1107

Liu C, Pierce LA,AlessioAM, KinahanPE. The impact of respiratorymotionon tumorquantification and1108delineationinstaticPET/CTimaging.PhysMedBiol54(24):7345-7362,2009.PMID:19926910.1109

LockhartCM,MacDonaldLR,AlessioAM,McDougaldWA,DootRK,KinahanPE.Quantifyingandreducing1110theeffectofcalibrationerroronvariabilityofPET/CTstandardizeduptakevaluemeasurements.JNuclMed111152(2):218-224,2011.PMID:21233174.1112

LodgeM,Wahl,R.CharacterizingtherepeatabilityofoncologyPETstandardizeduptakevalues.JNuclMed111354(2):335,2013.1114

MawlawiO,ErasmusJJ,MundenRF,PanT,KnightAE,MacapinlacHA,PodoloffDA,ChasenM.Quantifying1115theeffectofIVcontrastmediaonintegratedPET/CT:clinicalevaluation.AJRAmJRoentgenol186(2):308-1116319,2006.PMID:16423932.1117

Minn H, Zasadny KR, Quint LE,Wahl RL. Lung cancer: reproducibility of quantitativemeasurements for1118evaluating 2-[F-18]-fluoro-2-deoxy-D-glucose uptake at PET. Radiology 196(1):167-173, 1995. PMID:11197784562.1120

NahmiasC,WahlLM.Reproducibilityofstandardizeduptakevaluemeasurementsdeterminedby18F-FDG1121PETinmalignanttumors.JNuclMed49(11):1804-1808,2008.PMID:18927325.1122

NakamotoY,ZasadnyKR,MinnH,WahlRL.Reproducibilityofcommonsemi-quantitativeparameters for1123evaluating lung cancer glucose metabolism with positron emission tomography using 2-deoxy-2-1124[18F]fluoro-D-glucose.MolImagingBiol4(2):171-178,2002.PMID:14537140.1125

NestleU,KrempS,Schaefer-SchulerA,Sebastian-WelschC,HellwigD,RubeC,KirschCM.Comparisonof1126different methods for delineation of 18F-FDG PET-positive tissue for target volume definition in1127radiotherapy of patients with non-Small cell lung cancer. J Nucl Med 46(8):1342-1348, 2005. PMID:1128


16085592.1129

Subramaniam R, et al. FDG PET/CT Liver SULmean: Inter-reader agreement and impact of placement of1130volumeofinterest.Radiology2012(inpress).1131

VuTT.Standardizationofbodysurfaceareacalculations.JournalofOncologyPharmacyPractice8(2-3):49-113254,2002.1133

VelasquezLM,BoellaardR,KolliaG,HayesW,HoekstraOS,LammertsmaAA,GalbraithSM.Repeatabilityof113418F-FDGPETinamulticenterphaseIstudyofpatientswithadvancedgastrointestinalmalignancies.JNucl1135Med50(10):1646-1654,2009.PMID:19759105.1136

Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: Evolving Considerations for PET1137responsecriteriainsolidtumors.JNuclMed50Suppl1:122S-150S,2009.PMID:19403881.1138

Weber WA, Ziegler SI, Thodtmann R, Hanauske AR, Schwaiger M. Reproducibility of metabolic1139measurementsinmalignanttumorsusingFDGPET.JNuclMed40(11):1771-1777,1999.PMID:10565769.1140

WeberWA.Assessingtumorresponsetotherapy.JNuclMed50Suppl1:1S-10S,2009.PMID:19380403.1141

Weber,WA,CAGatsonis,PDMozley,LGHanna,AFShields,DRAberle,RGovindan,DATorigian,JSKarp,JQ1142Yu,RMSubramaniam,RAHalvorsen,BASiegel,6678ResearchteamACRIN,andResearchteamMK-0646-1143008.“Repeatabilityof18f-FdgPET/CTinAdvancedNon-SmallCellLungCancer:ProspectiveAssessmentin21144MulticenterTrials.”JNuclMed56,no.8(2015):1137–43.1145

YoungH,BaumR,CremeriusU,HerholzK,HoekstraO,LammertsmaAA,PruimJ,PriceP.Measurementof1146clinicalandsubclinicaltumourresponseusing[18F]-fluorodeoxyglucoseandpositronemissiontomography:1147reviewand1999EORTCrecommendations.EuropeanOrganizationforResearchandTreatmentofCancer1148(EORTC)PETStudyGroup.EurJCancer35(13):1773-1782,1999.PMID:10673991.1149

1150

Appendices1151

AppendixA:AcknowledgementsandAttributions1152

This document is proffered by the Radiological Society of North America (RSNA) Quantitative Imaging1153Biomarker Alliance (QIBA) FDG-PET/CT Biomarker Committee. The FDG-PET/CT Biomarker Committee is1154composed of physicians, scientists, engineers and statisticians representing the imaging device1155manufacturers, image analysis software developers, image analysis facilities and laboratories,1156biopharmaceutical companies, academic institutions, government research organizations, professional1157societies, and regulatory agencies, among others. Amore detailed description of the QIBA FDG-PET/CT1158groupanditsworkcanbefoundatthefollowingweblink: http://qibawiki.rsna.org/index.php?title=FDG-1159PET_tech_ctte1160

ThefollowingweremembersoftheQIBAFDG-PET/CTBiomarkerCommitteeduringthewritingofthis1161Profile(inalphabeticalorder):1162

1163

QIBAFDG-PETBiomarkerCommittee(inalphabeticalorder)

PaulE.Kinahan,PhD(Co-Chair) UniversityofWashington


LingX.Shao,PhD(Co-Chair) PhilipsHealthcareRichardL.Wahl,MD,FACR(Co-Chair) JohnsHopkinsUniversityKeithAllberg RadQual,LLCRamseyD.Badawi,PhD UniversityofCalifornia,DavisStellaM.Batalles,MD InstitutoCardiovasculardeRosarioRichardBaumgartner,PhD MerckResearchLaboratoriesBernardBendriem,PhD SiemensMedicalSolutionsUSARonaldBoellaard,PhD VUMedicalCenter,Amsterdam,NLJohnBuatti,MD UniversityofIowaChrisBuckle,MD UniversityofChicagoAndrewJ.Buckler,MS ElucidBioimagingInc.JaniceCampbell,PhD Wm.BeaumontHospitalPaulL.Carson,PhD UniversityofMichiganHealthSystemMichaelE.Casey,PhD SiemensSungChang,PhD AmgenSandraChica,MD NovartisPaulE.Christian UniversityofUtah/SNMMIQIBARepresentativeDavidA.Clunie,MBBS PixelMedDanielCoiro DelfinImagemPatriciaE.Cole,MD,PhD EliLillyandCompanyPeterDavidCorr,MD UAEUniversityBarbaraCroft,PhD DukeUniversityShivaK.Das,PhD DukeUniversitySimonDeBruin,MSEE SegamiCorporationToddDeckard,MSEE VitalImages,Inc.JonDeVries,MBA MergeHealthcareRobertK.Doot,PhD UniversityofPennsylvaniaGaryS.Dorfman,MD WeillCornellMedicalCollegeVinayA.Duddalwar,MD,FRCR USC/NorrisComprehensiveCancerCenterRichardM.Eaton,JD MedicalImaging&TechnologyAlliance(MITA)EdwardA.Eikman,MD MoffittCancerCenterBrianElston WashingtonUniversityRichardA.Frank,MD,PhD,FFPM GEHealthcareKirkFrey,MD,PhD UniversityofMichiganDanielGagnon,PhD ToshibaSusanGalbraith,PhD AstrazenecaConstantineGatsonis,PhD BrownUniversityIgorD.Grachev,MD,PhD GEHealthcareMichaelGraham,PhD,MD UniversityofIowaDonaldP.Harrington,MA,MD StateUniversityofNewYorkMarkusT.Harz,PhD FraunhoferMEVIS,InstforMedicalImageComputingHowardHigley,PhD CCSAssociates,Inc.OttoHoekstra,MD VUMedicalCenter,Amsterdam,NLJohnM.Hoffman,MD UniversityofUtahBlaineC.Horvath,RT BioClinica,Inc.


WilliamHowe,MD,PhD SiemensMedicalSolutionsUSAYuyingC.Hwang,PhD AmgenToddJohnson,MS VitalImages,Inc.LisaR.Karam,PhD NISTGaryJ.Kelloff,MD CancerImagingProgram,NCIRobertKoeppe,PhD UniversityofMichiganSteveKohlmyer GEHealthcareFeng-Ming(Spring)Kong,MD,PhD UniversityofMichiganMartinA.Lodge,PhD JohnsHopkinsUniversityLawrence(Larry)R.MacDonald,PhD UniversityofWashingtonMarianneMaffoni TeraRecon,Inc.PiotrManiawski PhilipsHealthcarePaulMarsden,MD King'sCollegeLondonTimothyJ.McCarthy,PhD PfizerAlexander(Sandy)McEwan,MB SNMMIColinG.Miller,PhD BioClinica,Inc.MatthewP.Miller,PhD GEHealthcareMichaelA.Miller,PhD IndianaUniversityNeruMunshi,PhD PAREXELInternationalDennisNelson,PhD MIMvistaCorp.SarahJ.Nelson,PhD UniversityofCalifornia,SanFranciscoChuckNortmann PhilipsHealthcareMiguelH.Pampaloni,MD UniversityofCaliforniaSanFranciscoAnshumanPanda,PhD MayoClinicSeong-HoonPark,MD WonkwangUniversitySchoolofMedicineSoniaH.Pearson-White,PhD TheBiomarkersConsortium,FNIHEricS.Perlman,MD PerlmanAdvisoryGroupLarryAlanPierce,PhD UniversityofWashingtonLucyPike,PhD King'sCollegeLondonWolfS.Richter PharmtraceChristinaL.Sammet,PhD NorthwesternUniversitySteffenSammet,MD,PhD UniversityofChicagoSubhendraN.Sarkar,PhD,RT BethIsraelDeaconessHospitalAnnetteSchmid,PhD PAREXELInternationalLalithaShankar,MD,PhD NIHBarryA.Siegel,MD WashingtonUniversityinSt.LouisDebiSimone GEHealthcareAnandK.Singh,MD Harvard-MassachusettsGeneralHospitalAnneM.Smith,PhD SiemensMedicalSolutionsUSA,Inc.JuergenSoldner SiemensMedicalSolutionsUSA,Inc.RathanSubramaniam,MD,PhD JohnsHopkinsUniversityDanielC.Sullivan,MD DukeUniversityJohnJ.Sunderland,PhD UniversityofIowaFukHayTang,PhD HongKongPolytechnicUniversityUkihideTateishi,MD,PhD YokohamaCityUniversityGraduateSchoolofMedicine


ValerieTreyer,PhD Consultant,NeuroscientistTimothyG.Turkington,PhD DukeUniversityRonaldVanHeertum,MD BioClinica,Inc.MattVanderhoek,PhD HenryFordHospitalRonaldVanHeertum,MD BioClinica,Inc.EtienneVonLavante,D.Phil MiradaMedicalWenliWang,PhD ToshibaWolfgangWeber,MD MemorialSloan-KetteringCancerCenterRalphWickenhoefer,MD CentralHospitalGermanArmedForcesScottD.Wollenweber,PhD GEHealthcareJohnG.Wolodzko,PhD BioClinica,Inc.RoxanneYaghoubi AcademyofRadiologyResearchJeffreyT.Yap,PhD Harvard-DanaFarberCancerInstituteBrendaYe,MD FDATerryS.Yoo,PhD CDERKwon-HaYoon,MD,PhD WonkwangUniversityHelenYoung,PhD AstraZenecaT.C.Zhao,PhD TeraRecon,Inc.BrianE.Zimmerman,PhD NIST1164

TheFDG-PET/CTBiomarkerCommitteeisdeeplygratefulforthesupportandtechnicalassistanceprovided1165bythestaffoftheRadiologicalSocietyofNorthAmerica.1166

1167

AppendixB:BackgroundInformationforClaim1168

A number of publications report test-retest repeatability for tumor SUV measurements with FDG PET1169[1,2,3,4,5,6,7,8,9]. Table 1 lists these publications and summarizes some of their results. Comparing1170repeatability measurements from the various reports is complicated by the different methodologies1171employedineachstudyandalsothedifferentmetricsusedtocharacterizerepeatability.1172

Table 1. Selected repeatability parameters extracted from literature publications. Where multiple SUV1173types were reported, preference was given to SUVmax as this SUV definition was more comparable1174between studies. The columnmarked ‘Inferred wCV’ is an estimate of the within-subject coefficient of1175variationbaseduponthereportedparametersandmaynotappearintheoriginalmanuscripts.Detailsof1176howtheseInferredwCVvalueswerederivedaredescribedinthetextandinTable2.1177


11781179

Theregion-of-interest(ROI)orvolume-of-interest(VOI)methodologyvariedbetweenpublications.Minnet1180al [1] report SUVmean derived from a fixed size 1.2 × 1.2 cm region-of-interest.Weber et al [2] report1181SUVmean derived from a volume-of-interest defined by a 50% isocontour. The remaining papers report1182SUVmax,althoughdataformultipleROIdefinitionsweresometimesreported.BecauseSUVmaxwasmore1183commonlyreportedamongsttheserepeatabilitypapersandwasmorecomparablebetweenstudies,table11841focusedprimarilyonSUVmax.1185

Nahmias and Wahl [5] report SUVmax but, unlike the other publications, they present their results in1186absoluteSUVunits,asopposedtorelativeunits.Directcomparisonwiththeotherreportswastherefore1187not possible. Kamibayashi et al [6] compared the repeatability of SUVs measured on different scanner1188systems,whereas theother reports involve test-retest studieson the same scanner. For this reason the1189Kamibayashi data were also not directly comparable with the other papers. The remaining publications1190[3,4,7,8,10]areamenabletomoredirectcomparisonastheyallreporttherepeatabilityofSUVmax,with1191testandreteststudiesbothperformedonthesamescannersystem.1192

Afurthercomplicationwhencomparingreportsisthedifferentmetricsusedtocharacterizerepeatability.1193Intable1wetranslatethereportedrepeatabilitymeasurementstoawithin-subjectcoefficientofvariation1194(wCOV)toallowamoredirectcomparison.Basedonthedatainthelast5rowsoftable1[3,4,7,8,10], it1195canbeseenthatthewithinsubjectcoefficientofvariationforSUVmaxwasintherange10.0–12.0%.1196

Table 2 summarizes the relationships that were involved in converting the published repeatability1197parameterstowithin-subjectcoefficientofvariation.1198

1199

Table2.Relationshipsusedtocomparerepeatabilitymetricsfoundintheliterature.1200


12011202

Oneassumptionthatwasmadeduringtheseconversionswasthatthepercentagedifference(D)between1203test-retestSUVmeasurementswasnormallydistributedwithzeromean.Whilethisassumptionmaynotbe1204strictlyapplicableoverawide rangeofSUVs, it isanassumption that is implicitlybeingmadewhenever120595%limitsofrepeatabilityareemployed[7,8].Applyingthissameassumptiontothestudiesthatreportthe1206mean absolute percentage difference (D_MAD) allows their results to be simply related to the other1207publicationsthatreportthestandarddeviationbyD_MAD=sqrt(2/pi)D_SD,asshownbelow.1208

D_MAD = 1σ 2π

x − µ e−x−µ( )22σ 2 dx

−∞

∞

∫

= 2σ 2π

x − µ( )e−x−µ2

2σ 2 dx0

∞

∫

let r = x − µ( )2

2σ 2 , and dr = x − µ( )σ 2 dx, and limits are unchanged

x=0

x=∞

∫ →r=0

r=∞

∫then,

D_MAD = 2πσ e−r dr

0

∞

∫ = 2πσ e−r

∞

0= 2

πσ 1− 0[ ]= 2

πσ ! 0.80σ

1209References1210

1 MinnH,ZasadnyKR,QuintLE,WahlRL.Lungcancer:reproducibilityofquantitativemeasurementsfor1211evaluating2-[F-18]-fluoro-2-deoxy-D-glucoseuptakeatPET.Radiology,196,1(1995),167-173.1212

2 Weber WA, Ziegler SI, Thodtmann R, Hanauske A-R, Schwaiger M. Reproducibility of metabolic1213measurementsinmalignanttumorsusingFDGPET.JNuclMed,40,11(1999),1771-1777.1214

3 NakamotoY,ZasadnyKR,MinnH,WahlRL.Reproducibilityofcommonsemi-quantitativeparameters1215for evaluating lung cancer glucosemetabolismwith positron emission tomography using 2-deoxy-2-1216[18F]fluoro-D-glucose.MolImagingBiol,4(2002),171-178.1217


4 KrakNC,BoellaardR,HoekstraOS,TwiskJWR,HoekstraCJ,LammertsmaAA.EffectsofROIdefinition1218and reconstructionmethodonquantitativeoutcomeand applicability in a responsemonitoring trial.1219EurJNuclMedMolImaging,32,3(2005),294-301.1220

5 NahmiasC,WahlLM.Reproducibilityofstandardizeduptakevaluemeasurementsdeterminedby18F-1221FDGPETinmalignanttumors.JNuclMed,49,11(2008),1804-1808.1222

6 KamibayashiT,TsuchidaT,DemuraY,etal.Reproducibilityofsemi-quantitativeparametersinFDG-PET1223usingtwodifferentPETscanners:influenceofattenuationcorrectionmethodandexaminationinterval.1224MolImagingBiol,10(2008),162-166.1225

7 VelasquezLM,BoellaardR,KolliaG,etal.Repeatabilityof18F-FDGPETinamulticenterphase1study1226ofpatientswithadvancedgastrointestinalmalignancies.JNuclMed,50,10(2009),1646-1654.1227

8 HattM,Cheze-LeRestC,AboagyeEO,KennyLM,RossoL,TurkheimerFE,AlbarghachNM,MetgesJP,1228Pradier O, Visvikis D. Reproducibility of 18F-FDG and 3'-deoxy-3'-18F-fluorothymidine PET tumor1229volumemeasurements.JNuclMed.,51(2010),1368-1376.1230

9 KumarV,NathK,BermanCG,KimJ,TanvetyanonT,ChiapporiAA,GatenbyRA,GilliesRJ,EikmanEA.1231VarianceofSUVsforFDG-PET/CTisgreaterinclinicalpracticethanunderidealstudysettings.ClinNucl1232Med.2013Mar;38(3):175-82.PMID233540321233

10 Weber,WA,CAGatsonis,PDMozley,LGHanna,AFShields,DRAberle,RGovindan,DATorigian,JSKarp,1234JQYu,RMSubramaniam,RAHalvorsen,BASiegel,6678ResearchteamACRIN,andResearchteamMK-12350646-008. “Repeatability of 18f-Fdg PET/CT in Advanced Non-Small Cell Lung Cancer: Prospective1236Assessmentin2MulticenterTrials.”JNuclMed56,no.8(2015):1137–43.1237

11.Bland,JMandDGAltman.“MeasurementErrorProportionaltotheMean.”BMJ313,no.7049(1996):1238106.1239

1240

AppendixC:ConventionsandDefinitions1241

ConventionUsedtoRepresentProfilerequirements1242

Requirements foradhering to thisProfilearepresented in tables/boxesas shown in theexamplebelow.1243Shaded boxes are intended future requirements, and are not at this time required for adhering to the1244Profile.Boldtextisusedforrequirementsthatareformattedaschecklists,whichareprovidedinAppendix1245I.Theformatusedisthefollowing:1246


Normativetext:Clearboxesarecurrentrequirements

Shadedboxesareintendedforfuturerequirements

Boldtextindicatesrequirementsincludedinchecklists(AppendixI)

1247

Itemswithintablesarenormative(i.e.arerequiredinordertobecompliantwiththeQIBAprotocol).The1248intentofthenormativetextistobeprescriptiveanddetailedtofacilitateimplementation.Ingeneralthe1249


intentistospecifythefinalstateoroutput,andnothowthatistobeachieved.1250

Allothertextoutsideofthesetablesisconsideredinformativeonly.1251

Acondensedtablefromsection3.2.1.2‘SubjectPositioning’isreproducedbelowasanillustrativeexample.1252

1253



Technologist IfthepatientisobservedtotakeadeepbreathduringtheCTscanitshouldbedocumentedandarepeatCTstudyshouldbeconsidered.


PET/CTScanner

ThePET/CTscannershallprovidemethodstominimizethePETimageerrorsintroducedbyrespiratorymotion.

Breathingandmotionnon-conformance

Technologist

TheTechnologistshalldocumentissuesregardingsubjectnon-conformancewithbreathingandmotion.

TheTechnologistshalldocumentissuesregardingsubjectnon-conformancewithbreathingandmotionusingthecommondataformatmechanism(AppendixE).

1254

1255

Definitions1256

18F-FDGorFDG:2-deoxy-2-(18F)fluoro-D-glucose,aglucoseanalog,withthepositron-emittingradioactive1257isotopefluorine-18substitutedforthenormalhydroxylgroupatthe2'positionintheglucosemolecule.1258FDGisthemostcommonlyused(>90%)radiotracerinPETimaging.1259

Accreditation: Approval by an independent body or group for broad clinical usage (requires ongoing1260QA/QC)e.g.ACR,IAC,TJC(listedbelow).1261

AC:AttenuationCorrection.Attenuationisaaneffectthatoccurswhenphotonsemittedbytheradiotracer1262insidethebodyareabsorbedby interveningtissue.Theresult is thatstructuresdeep inthebodyare1263reconstructedashaving falsely low (or evennegative) traceruptake. ContemporaryPET/CT scanners1264estimate attenuation using integrated x-ray CT equipment. While attenuation-corrected images are1265generallyfaithfulrepresentationsofradiotracerdistribution,thecorrectionprocessisitselfsusceptible1266tosignificantartifacts.1267

Conformance:Meetingthe listofrequirementsdescribed inthisdocument,whicharenecessarytomeet1268themeasurementclaimsforthisQIBAProfile.1269

CRF:CaseReportForm(CRF)isapaperorelectronicquestionnairespecificallyusedinclinicaltrialresearch.1270TheCRF isusedbythesponsorof theclinical trial (ordesignatedCROetc.) tocollectdata fromeach1271participatingsite.Alldataoneachpatientparticipatinginaclinicaltrialareheldand/ordocumentedin1272theCRF,includingadverseevents.1273

CT: X-ray computed tomography (CT) is a medical imaging technique that utilizes X-rays to produce1274tomographicimagesoftherelativex-rayabsorption,whichiscloselylinkedtotissuedensity.1275


DICOM:DigitalImagingandCommunicationsinMedicine(DICOM)isasetofstandardsformedicalimages1276andrelatedinformation.Itdefinesformatsformedicalimagesthatcanbeexchangedinamannerthat1277preservesthedataandqualitynecessaryforclinicaluse.1278

Dose:Canrefertoeitherradiationdoseorasajargontermfor'totalradioactivity'.Forexample,10mCIof127918F-FDGisoftenreferredtoasa10mCidose.1280

FDG:See18F-FDG.1281

LBM:LeanBodyMassiscalculatedbysubtractingbodyfatweightfromtotalbodyweight.TheLeanbody1282mass(LBM)hasbeendescribedasanindexsuperiortototalbodyweightforprescribingproperlevels1283ofmedicationsandforassessingmetabolicdisorders.1284

mCi:millicuries.Anon-SIunitof radioactivity,definedas1mCi=3.7×10^7decaysper second.Clinical1285FDG-PETstudiesinject(typically)5to15mCiof18F-FDG.1286

MBq:megabequerel.AnSI-derivedunitofradioactivitydefinedas1.0×10^6decayspersecond.1287

Metabolic Response / Metabolic Disease. A classification based on the visible level of FDG uptake1288associated with malignant solid tumors. There are several specific classifications depending on the1289criteriaused:1290

• CMR: CompleteMetabolic Response.A complete resolutionof FDG-PETuptakewithin the tumor1291volumesothatitisindistinguishablefromthesurroundingnormaltissue.1292

• PMR: Partial Metabolic Response. A reduction in FDG uptake. The thresholds used for this1293determination depend on the criteria used. Two such criteria are the EORTC [Young, 1999] and1294PERCIST[Wahl,2009]proposals.1295

• PMD:ProgressiveMetabolicDisease.AnincreaseinFDGuptakerelativetoapredefinedthreshold.1296

• SMD:StableMetabolicDisease.NochangeinFDGuptakerelativetopredefinedthresholds.1297

PERCIST:PETResponseCriteria forSolidTumors [Wahl,2009].A frameworkproposed forusingFDG-PET1298imagingasacancertherapyresponsecriteriaforsolidtumors.Proposedasamoreaccuratealternative1299toRECISTforseveraltypesofsolidtumors.1300

PET:Positronemission tomography (PET) isa tomographic imaging technique thatproducesan imageof1301theinvivodistributionofaradiotracer,typicallyFDG.1302

PET/CT:Positronemissiontomography/computedtomography(PET/CT)isamedicalimagingsystemthat1303combines inasinglegantrysystembothPositronEmissionTomography(PET)andanx-rayComputed1304Tomography (CT) scanners, so that images acquired from both devices can be taken nearly-1305simultaneously.1306

Profile: A QIBA Profile is a document that describes a specific performance Claim and how it can be1307achieved.AProfileconsistsofoneormoreClaimsandassociatedDetails.1308

• Claims:tellauserwhatcanbeaccomplishedbyfollowingtheProfile.1309

• Details:tellavendorwhatmustbeimplementedintheirproduct;andtellauserwhatprocedures1310arenecessary.1311

QA: Quality Assurance. Proactive definition of the process or procedures for task performance. The1312maintenanceofadesired levelofquality inaserviceorproduct,esp.bymeansofattentiontoevery1313stageoftheprocessofdeliveryorproduction.1314


QC: Quality Control. Specific tests performed to ensure target requirements of QA program are met.1315Typicallybytestingasampleoftheoutputagainstthespecification.1316

Qualification: Approved by an independent body or group for either general participation in clinical1317research (ACRIN-CQIE , SNM-CTNothers)or fora specific clinical trial (requiresongoingQA/QC).This1318includesCROs,ACRIN,SNM-CTN,CALGBandothercorelaboratories.1319

RECIST:ResponseEvaluationCriteria inSolidTumors (RECIST).A setofpublished rules thatdefinewhen1320cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progression") during1321treatments.Basedonanatomicalsizechangesofsolidtumors.Commonlyusedbutalsocontroversial.1322

ROI:Regionofinterest.Aregioninanimagethatisspecifiedinsomemanner,typicallywithuser-controlled1323graphicalelementsthatcanbeeither2Dareasor3Dvolumes.Theseelementsinclude,butnotlimited1324to, ellipses, ellipsoids, rectangles, rectangular volumes, circles, cylinders, polygons, and free-form1325shapes. An ROI can also be defined by a segmentation algorithm that operates on the image.1326Segmentation algorithms include, but are not limited to, fixed-value thresholding, fixed-percentage1327thresholding,gradientedgedetection,andBayesianmethods.WiththedefinitionofanROI,metricsare1328then calculated for the portion of the imagewithin the ROI. Thesemetrics can include, but are not1329limitedto,mean,maximum,standarddeviation,andvolumeorarea.NotethatthetermROIcanrefer1330toa2Dareaonasingleimagesliceora3Dvolume.Insomecases,thetermROIisusedtoreferto2D1331areaandthetermvolumeofinterest(VOI)isusedtorefertoa3Dvolume.InthisProfilethetermROIis1332usedtorefertoboth2Dareasand3Dvolumesasneeded.1333

SUV: Standardized uptake value. A measure of relative radiotracer uptake within the body. Typically1334definedforatimepointtasSUV(t)=r(t)/(d’/V),wherer(t)isthemeasuredradioactivityconcentration1335withintheROI(typicallyinunitsofkBq/ml),d’isthedecay-correctedinjectedradioactivity(or'dose'),1336andVisasurrogateforthedistributionvolume.Typically,patientweightor leanbodymassareused1337forV.1338

Notes:1339

1. TheSUVcanchangeovertime,someasuringr(t) ataconsistenttimepointisrecommended.1340

2. Eitherbodyweightor leanbodymassareusedforasurrogateforthedistributionvolume,sothe1341SUVunitsareg/ml(Section3.4.3)1342

3. Forauniformdistributionofradiotracer,theSUVeverywherewouldbeexactly1g/ml.1343

4. ThemeasuredSUVstatisticistypicallyoneofthefollowing:1344

i. SUVmean:TheaverageSUVwithintheROI.1345

ii. SUVmax:ThemaximumSUVwithintheROI.1346

iii. SUVpeak:TheaverageSUVwithina fixed-sizedROI, typicallya1cmdiametersphere.The1347sphereslocationisadjustedsuchthattheaverageSUVismaximized.1348

iv. TLG:Totallesionglycolysis.ThesummedSUVwithintheROI.1349

TOF:TimeofFlight(TOF)isaPETimagingtechniqueutilizingdifferentialannihilationphotontraveltimes1350tomoreaccuratelylocalizetheinvivodistributionofaradiotracer.1351

UPICT:UniformProtocolsForImaginginClinicalTrials(UPICT).ARSNA-QIBAinitiativethatseekstoprovide1352alibraryofannotatedprotocolsthatsupportclinicaltrialswithininstitutions,cooperativegroups,and1353trials consortia. TheUPICTprotocols arebasedon consensus standards thatmeet aminimumsetof1354


criteriatoensureimagingdataquality.1355

VOI:Volumeofinterest.SeedefinitionforROI.1356

1357

Organizations1358

AAPM:TheAmericanAssociationofPhysicistsinMedicineisamembersocietyconcernedwiththetopics1359of medical physics, radiation oncology, imaging physics. The AAPM is a scientific, educational, and1360professionalorganizationofover8,000medicalphysicists.1361

ACR:The36,000membersof|includeradiologists,radiationoncologists,medicalphysicists,interventional1362radiologists,nuclearmedicinephysiciansandalliedhealthprofessionals.1363

ACRIN:TheAmericanCollegeofRadiologyImagingNetwork(ACRIN)isaprogramoftheAmericanCollege1364of Radiology and a National Cancer Institute cooperative group. Focused on cancer-related research in1365clinicaltrials.1366

CLIA: Clinical Laboratory Improvement Amendments: Accreditation system for establishing quality1367standardsforlaboratorytesting.1368

CQIE:TheCentersofQuantitativeImagingExcellence(CQIE)programwasdevelopedbyACRINinresponse1369toasolicitationforproposalsissuedinDecember2009bySAIC-FrederickonbehalfoftheNationalCancer1370Institute (NCI). Theprimaryobjectiveof theCQIEProgram is toestablisha resourceof ‘trial ready’ sites1371within theNCICancerCentersProgram thatare capableof conductingclinical trials inwhich there isan1372integralmolecularand/orfunctionaladvancedimagingendpoint.1373

CRO:ContractResearchOrganizationAcommercialornot-for-profitorganizationdesignatedtoperforma1374centralizedandstandardizedcollection,analysis,and/orreviewofthedatageneratedduringaclinicaltrial.1375Additionalactivitieswhichmaybeperformedbyan imagingcore lab includetrainingandqualificationof1376imaging centers for the specific imaging required in a clinical trial, development of imaging acquisition1377manuals, development of independent imaging review charters, centralized collection and archiving of1378imagesreceivedfromstudysites,performingpre-specifiedqualitycontrolchecks/testsonincomingimages1379and development and implementation of quality assurance processes and procedures to ensure that1380imagessubmittedareinaccordwithimagingtimepointsspecifiedinthestudyprotocolandconsistentwith1381thequalityrequiredtoallowtheprotocol-specifiedanalysis/assessments1382

CTN: The Clinical Trials Network (CTN) was formed by SNMMI in 2008 to facilitate the effective use of1383molecularimagingbiomarkersinclinicaltrials.1384

EANM: The European Association of Nuclear Medicine (EANM) constitutes the European umbrella1385organizationofnuclearmedicineinEurope1386

EARL:EANMResearchLtd(EARL)wasformedbyEANMin2006topromotemulticentrenuclearmedicine1387andresearch.1388

ECOG-ACRIN:ANationalCancerInstitutecooperativegroupformedfromthe2012mergeroftheEastern1389CooperativeOncologyGroup(ECOG)andtheAmericanCollegeofRadiologyImagingNetwork(ACRIN).1390

EORTC:TheEuropeanOrganizationforResearchandTreatmentofCancerorEORTCisaninternationalnon-1391profit organization that develops, coordinates, and stimulates cancer laboratory and clinical research in1392Europe.1393

EMA:EuropeanMedicinesAgency is a EuropeanUnionagency for theevaluationofmedicinalproducts.1394


RoughlyparalleltotheU.S.FoodandDrugAdministration(FDA),butwithoutFDA-stylecentralization.1395

FDA:FoodandDrugAdministration is responsible forprotectingandpromotingpublichealth in theU.S.1396throughtheregulationandsupervisionoffoodsafety,tobaccoproducts,dietarysupplements,prescription1397and over-the-counter pharmaceutical medications, vaccines, biopharmaceuticals, blood transfusions,1398medicaldevices,electromagneticradiationemittingdevices,andveterinaryproducts.1399

IAC:TheIntersocietalAccreditationCommission(IAC)providesaccreditationprogramsforVascularTesting,1400Echocardiography,Nuclear/PET,MRI,CT/Dental,CarotidStentingandVeinCenter.1401

MITA: The Medical Imaging & Technology Alliance is a division NEMA that develops and promotes1402standardsformedicalimagingandradiationtherapyequipment.Thesestandardsarevoluntaryguidelines1403thatestablishcommonlyacceptedmethodsofdesign,production,testingandcommunicationforimaging1404andcancertreatmentproducts.1405

NCRI: National Cancer Research Institute. The National Cancer Research Institute (NCRI) is a UK-wide1406partnership between the government, charity and industry which promotes co-operation in cancer1407research among the 22 member organizations for the benefit of patients, the public and the scientific1408community.1409

NEMA:NationalElectricalManufacturersAssociationisaforumforthedevelopmentoftechnicalstandards1410byelectricalequipmentmanufacturers.1411

NIST: National Institute of Standards and Technology is ameasurement standards laboratorywhich is a1412non-regulatoryagencyoftheUnitedStatesDepartmentofCommerce.1413

QIBA:QuantitativeImagingBiomarkersAlliance.TheQuantitativeImagingBiomarkersAlliance(QIBA)was1414organizedbyRSNAin2007touniteresearchers,healthcareprofessionalsandindustrystakeholdersinthe1415advancementofquantitativeimagingandtheuseofbiomarkersinclinicaltrialsandpractice.1416

RSNA:RadiologicalSocietyofNorthAmerica(RSNA).Aprofessionalmedicalimagingsocietywithmorethan141747,000members, includingradiologists, radiationoncologists,medicalphysicistsandalliedscientists.The1418RSNAhoststheworld’slargestannualmedicalmeeting.1419

SNMMI: Society of Nuclear Medicine and Molecular Imaging (formerly called the Society of Nuclear1420Medicine (SNM)). A nonprofit scientific and professional organization that promotes the science,1421technologyandpracticalapplicationofnuclearmedicineandmolecularimaging.SNMMIrepresents18,0001422nuclear and molecular imaging professionals worldwide. Members include physicians, technologists,1423physicists,pharmacists,scientists,laboratoryprofessionalsandmore1424

TJC: The Joint Commission (TJC) accredits and certifies health care organizations and programs in the1425UnitedStates.1426

USP:United States Pharmacopeial Convention establisheswritten and physical (reference) standards for1427medicines,foodingredients,dietarysupplementproductsandingredientsintheU.S.1428

1429

AppendixD:Model-specificInstructionsandParameters1430

Thepresenceofspecificproductmodels/versionsinthefollowingtablesshouldnotbetakentoimplythat1431thoseproductsare fully compliantwith theQIBAProfile.ConformancewithaProfile involvesmeetinga1432varietyofrequirementsofwhichoperatingbytheseparametersisjustone.Todetermineifaproduct(and1433aspecificmodel/versionofthatproduct)iscompliant,pleaserefertotheQIBAConformanceDocumentfor1434


thatproduct.1435

D.1.ImageAcquisitionParameters1436

The following technique tables list acquisitionparameter values for specificmodels/versions that canbe1437expectedtoproducedatameetingtherequirementsofSection3.6.4('PhantomImaging').1438

Thesetechniquetablesmayhavebeenpreparedbythesubmitterofthisimagingprotocoldocument,the1439clinical trial organizer, the vendor of the equipment, and/or some other source. (Consequently, a given1440model/versionmayappearinmorethanonetable.)Thesourceislistedatthetopofeachtable.1441

Sitesusingmodels listedhereareencouragedtoconsiderusingtheseparametersforbothsimplicityand1442consistency.Sitesusingmodelsnotlistedheremaybeabletodevisetheirownacquisitionparametersthat1443resultindatameetingtherequirementsofSection3.6.4andconformtotheconsiderationsinSection4.In1444somecases,parametersetsmaybeavailableasanelectronicfilefordirectimplementationontheimaging1445platform.1446

D.2.QualityAssuranceProcedures1447

Examples of recommend quality assurance procedures are shown for specific GE, Philips, and Siemens1448PET/CTscannersinthetablesbelow.1449


Dev

ice

Freq

uenc

yPe

rfor

man

ce R

equi

rem

ent

Ope

rato

rD

aily

Sta

ffD

aily

Sta

ffD

aily

No

artif

acts

. Wat

er 0

± 4

CT

Sta

ff

Noi

se a

nd A

rtifa

cts.

O

n bo

dy p

hant

omD

aily

No

artif

acts

. Tef

lon

pin

= 89

0± 5

0 C

T W

ater

0±

4 C

TS

taff

Mon

thly

No

artif

acts

. Lar

ge A

cryl

ic p

in d

iam

eter

is

50 ±

1 m

m. A

ll 7

reso

lutio

n ho

les

visi

ble.

Fi

ve o

f the

six

low

con

trast

acu

lon

pins

de

tect

able

. Wat

er 0

±4, N

ylon

100

± 1

5,

Pol

yeth

ylen

e 75

± 1

5, T

eflo

n 10

16 ±

50,

A

cryl

ic +

140

± 15

, Lex

an +

116

± 15

Sta

ff

Adv

ance

d te

st a

s ne

eded

Wid

th a

t 50%

Max

of t

he Im

puls

e R

espo

nse

prof

ile s

houl

d be

1.4

5 m

m ±

0.

10 m

m.

Phy

sici

st/s

ervi

ce

Adv

ance

d te

st a

s ne

eded

Ave

rage

of a

lum

inim

um s

trips

with

in

tole

renc

e of

val

ues

stat

ed in

man

ual.

Phy

sici

st/s

ervi

ceS

yste

m In

itial

izat

ion

Dai

lyC

ompl

etio

n of

pro

gram

Phy

sici

st/s

ervi

ceB

asel

ine

colle

ctio

n (a

nalo

g of

fset

s of

all

phot

omul

tiplie

r cha

nnel

s)D

aily

Valu

es w

ithin

rang

e. S

ucce

ss m

essa

geS

taff

PM

T ga

in c

alib

ratio

nD

aily

All

PM

Ts c

alib

rate

d w

ithin

targ

et g

ain.

No

Faile

d m

essa

ge.

Sta

ff

Ene

rgy

test

and

ana

lysi

sD

aily

Ene

rgy

cent

roid

s ap

prox

imat

ely

100.

FW

HM

< F

WH

M th

resh

old.

Sta

ff

Tim

ing

test

Dai

lyA

gree

men

t with

sys

tem

tim

ing

agai

nst t

he

calib

ratio

n se

tting

sS

taff

Em

issi

on s

inog

ram

col

lect

ion

and

anal

ysis

Dai

lyS

taff

Aut

omat

ed S

yste

m In

itial

izat

ion

Dai

ly, p

resc

hedu

led

to s

horte

n da

ily Q

CC

ompl

etio

n of

pro

gram

Sta

ffA

utom

ated

Bas

elin

e co

llect

ion

Dai

ly, p

resc

hedu

led

to s

horte

n da

ily Q

CVa

lues

with

in ra

nge.

Sta

ffU

nifo

rmity

che

ckM

onth

lyvi

sual

ly in

spec

t for

non

uni

form

ities

Sta

ff

SU

V c

alib

ratio

nE

very

6 m

onth

s, a

fter r

ecal

ibra

tion,

whe

n S

UV

val

idat

ion

show

s di

scre

panc

yN

o w

arni

ng m

essa

ge fo

r cal

gen

prog

ram

Sta

ffS

UV

val

idat

ion

Eve

ry 2

mon

ths,

whe

n P

M is

per

form

edR

OI a

vera

ge s

houl

d be

1.0

(0.9

- 1.

1).

Sta

ff, s

ervi

ce

Impu

lse

Res

pons

e

Slic

e th

ickn

ess

CT

PE

T

QA

proc

edur

es a

nd s

ched

ules

for P

hilip

s G

emin

i TF,

V3.

3 an

d V3

.4Q

A Pr

oced

ure

Dai

ly P

ET

CT

Aut

oQC

Tube

Cal

ibra

tion

Air

Cal

ibra

tion

Noi

se. O

n he

ad p

hant

om

Con

trast

sca

le a

nd a

rtifa

cts

1450


Dev

ice

Freq

uenc

yPe

rfor

man

ce R

equi

rem

ent

Ope

rato

rC

ompu

ters

Dai

ly o

r as

need

edN

/ALo

cal S

taff

Dai

ly o

r afte

r 2 h

ours

of i

nact

ivity

N/A

Loca

l Sta

ffD

aily

Loca

l Sta

ffD

aily

Loca

l Sta

ff

Con

trast

Sca

leA

cqui

re s

cans

dai

lyTh

e di

ffere

nce

in C

T nu

mbe

rs b

etw

een

the

Ple

xigl

as re

solu

tion

bloc

k an

d w

ater

= 1

20,

varia

tion

10%

Loca

l Sta

ff

Hig

h C

ontra

st S

patia

l Res

olut

ion

Acq

uire

sca

ns d

aily

The

stan

dard

dev

iatio

n fo

r an

RO

I in

the

1.6m

m b

ar p

atte

rn s

houl

d eq

ual 3

7 ±

4 fo

r th

e st

anda

rd a

lgor

ithm

Loca

l Sta

ff

Low

Con

trast

Det

ecta

bilit

yA

cqui

re s

cans

dai

lyLo

cal S

taff

Noi

se a

nd U

nifo

rmity

Acq

uire

sca

ns d

aily

CT

num

ber f

or w

ater

of 0

± 3

HU

for t

he

cent

er R

OI.

The

unifo

rmity

diff

eren

ce

betw

een

the

Cen

ter R

OI a

nd th

e av

erag

e of

the

edge

RO

Is s

houl

d be

0 ±

3 fo

r Sm

all

Bod

y (0

± 1

0 m

axim

um d

evia

tion

if La

rge

Bod

y is

use

d). N

oise

in th

e ce

nter

of t

he

imag

e to

app

roxi

mat

ely

equa

l 4.3

± 0

.5.

Loca

l Sta

ff

Slic

e Th

ickn

ess

Acq

uire

sca

ns d

aily

Slic

e th

ickn

ess

shou

ld n

ot v

ary

by m

ore

than

± 1

mm

from

the

expe

cted

val

ueLo

cal S

taff

Lase

r Lig

ht A

ccur

acy

Acq

uire

sca

ns d

aily

Loca

l Sta

ffA

fter t

ube

repl

acem

ent o

r as

PM

Ser

vice

Coi

ncid

ence

Dai

lyLo

cal S

taff

PE

T co

inci

denc

e m

ean

Dai

lyLo

cal S

taff

PE

T co

inci

denc

e va

rianc

eD

aily

Loca

l Sta

ffS

ingl

esD

aily

Loca

l Sta

ffP

ET

sing

les

mea

nD

aily

Loca

l Sta

ffP

ET

sing

les

varia

nce

Dai

lyLo

cal S

taff

Dea

dtim

eD

aily

Loca

l Sta

ffP

ET

mea

n de

adtim

eD

aily

Loca

l Sta

ffTi

min

gD

aily

Loca

l Sta

ffP

ET

timin

g m

ean

Dai

lyLo

cal S

taff

Ene

rgy

Dai

lyLo

cal S

taff

PE

T en

ergy

shi

ftD

aily

Loca

l Sta

ff

Wee

kly

Con

trast

val

ue fo

r a 3

mm

obj

ect i

s le

ss

than

5 H

U. T

ypic

al v

aria

tion

is ±

0.5

HU

.Lo

cal S

taff

Wee

kly

Loca

l Sta

ffQ

uarte

rly (i

f app

ropr

iate

for t

he s

yste

m)

Loca

l Sta

ffQ

uarte

rly (i

f app

ropr

iate

for t

he s

yste

m)

Loca

l Sta

ffQ

uarte

rlyLo

cal S

taff

Qua

rterly

Loca

l Sta

ffE

very

18

mon

ths

Ser

vice

QA

proc

edur

es a

nd s

ched

ules

for G

E D

isco

very

ST,

STE

, Rx

and

Dis

cove

ry 6

00/7

00 s

erie

s PE

T/C

T sy

stem

s

CT

PE

T

Est

ablis

h ne

w D

QA

base

line

Ge-

68 s

ourc

e pi

n re

plac

emen

t

Full

syst

em c

alib

ratio

n

Gen

erat

or c

alib

ratio

ns

Cle

an d

atab

ase

PE

T 2D

nor

mal

izat

ion

PE

T 2D

wel

l cou

nter

cor

rect

ion

PE

T 3D

nor

mal

izat

ion

and

wel

l cou

nter

cor

rect

ion

CT

QA

phan

tom

PE

T D

aily

Qua

lity

Ass

uran

ce

(DQ

A)

QA

Proc

edur

e

PE

T si

ngle

s up

date

gai

n

Air

calib

ratio

ns (f

ast c

als)

CT

tube

war

m u

pS

yste

m re

boot

1451


Dev

ice

Freq

uenc

yPe

rfor

man

ce R

equi

rem

ent

Ope

rato

rD

aily

at

Sta

rtu

pN

/AS

taff

Da

ilyN

/AS

taff

Fo

ur

tim

es d

aily

N/A

Sta

ffD

aily

N/A

Sta

ffW

ee

kly

N/A

Sta

ffC

T

Ch

ecku

p/C

alib

ratio

nD

aily

, a

fte

r 6

0 m

inu

tes o

f fu

ll lo

ad

, w

ith

in 1

ho

ur

of

pa

tie

nt

sca

nS

taff

Wa

ter

HU

Da

ilyR

esu

lts s

tate

d a

s "

in t

ole

ran

ce

" W

ate

r H

U =

0 +

/- 4

Sta

ffP

ixe

l n

ois

eD

aily

Re

su

lts s

tate

d a

s "

in t

ole

ran

ce

"S

taff

Tu

be

vo

lta

ge

sD

aily

Re

su

lts s

tate

d a

s "

in t

ole

ran

ce

"S

taff

Da

ily n

orm

aliz

atio

nD

aily

Da

ily v

s.

sta

nd

ard

ch

i-sq

ua

re <

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1452


AppendixE:DataFieldstobeRecordedintheCommonDataFormat1453

Mechanism1454

Thelistbelowcomprisesmeta-information(i.e.inadditiontoimagevaluesofkBq/ml)thatisnecessaryfor1455quantitativelyaccurate(i.e.knownandminimaluncertainties)ofPETSUVs.Theintenthereistolistwhat1456information should be captured rather than the mechanism itself. The format and corresponding1457mechanismofdatacapture/presentationiscurrentlyunspecified,butrangesfrompapernotes,toscanned1458forms or electronic data records, to direct entry from the measurement equipment (i.e., the PET/CT1459scanner or auxiliary measurement devices such as the dose calibrator) into pre-specified DICOM fields.1460Ideally all of the specified meta-data will be captured by direct electronic entry to DICOM fields, after1461suitablemodificationoftheDICOMformatforPETimaging.1462

Theconceptendorsedhereisthattheneededmeta-dataisidentified.ThroughrevisionsofthisProfile,the1463DICOMstandard,and technology themeta-data is inserted into theanalysis stream (Figure3) inamore1464directmannerandtechnologyandacceptedstandardsevolve.1465

• The needed information, where feasible, is listed in order from least frequently changing to most1466frequentlychanging.1467

• In all cases notewhethermeasurements aremadedirectly or estimated. If the latter case, note the1468sourceof information and thedate and time (e.g. if subject cannot bemoved frombed tomeasure1469weightorheight).1470

Datafieldstoberecorded:1471

1. Sitespecific1472a. Siteinformation(includenameand/orotheridentifiers)1473b. Scannermakeandmodel1474c. HardwareVersionnumbers1475d. SoftwareVersionnumbers1476e. Confirmationthatscannerusedwaspreviouslyqualified(ornot)1477

2. Protocolspecific1478a. PET1479

i. Durationperbed1480ii. Bedoverlap1481iii. Acquisitionmode(2Dor3D)1482iv. Reconstructionmethod1483

b. CTtechnique14843. ScannerspecificQA/QC1485

a. Mostrecentcalibrationfactors(scanner)1486b. Scannerdailycheckvalues1487c. mostrecentclockcheck1488d. mostrecentscannerQA/QC1489

4. Subjectexamspecific1490a. Height1491b. Weight1492c. Fastingtimeassessment1493d. Bloodglucoseconcentrationandtimeofsampling1494e. Pre-andpost-injectionassayedactivitiesandtimesofassay1495


f. Injectiontime1496g. Siteofinjection(andassessmentofinfiltration)1497h. Netinjectedactivity(calculatedincludingdecaycorrection)1498i. Uptaketime1499

AppendixF:TestingPET/CTDisplayandAnalysisSystemswiththeFDG-PET/CT1500

DigitalReferenceObject1501

ThePET/CTDigitalReferenceObject(DRO)isasyntheticallygeneratedsetofDICOMimagefilesofknown1502voxel values for positron emission tomography (PET) and x-ray computed tomography (CT). The PET/CT1503DROisintendedtotestthecomputationofstandardizeduptakevalues(SUVs)byPET/CTdisplaystations.It1504isalsointendedtotestregionofinterest(ROI)calculationsandalignmentbetweenthePETandCTimages.1505This ismotivatedbyvendor-specificvariations inPETDICOMformatsusedforSUVs.Thedevelopmentof1506thePET/CTDROissupportedbytheQuantitativeImagingBiomarkerAlliance(QIBA).1507

TheprimarygoalsandobjectivesofthePET/CTDigitalReferenceObjectaretosupporttheQIBAFDG-PET1508'TechnicalValidation'effortsforProfiledevelopment.Thiswillbedoneby(1)evaluationandvalidationof1509SUV calculations in PET images, (2) evaluation and validation of ROI calculations and (3) providing a1510common reference standard that can be adopted and modified by PET/CT scanner and display station1511manufacturers.1512

ThePETandCT componentsof the Imagesof theDROareeachasetofDICOMformatfiles,onefileper image slice. Each set of files are typicallygrouped as a stack to form an image volume.Representative sections through the CT and PETimagevolumesareshownbelow.The synthetic test object is based on, but is notidentical to, the NEMANU-2 PET test phantom [JNuclMed,vol.43no.101398-1409,2002].ThePETobjecthasadded'testvoxels'togetherwith2Dand3D 'testpatterns'. Ineachobject, the thicknessoftheexteriorshellis3mm,thethicknessofthehotspherewallsis1mm,andthethicknessofthelung insertwallis2mm.1513

1514

The CT DRO showing Hounsfield The PET DRO with the SUVbw


Unitsforeachstructure. valuesofeachstructure.

Image fusion of the CT and PETDROsshowingperfectalignment

Coronal view of the PET DROshowing the 2D test pattern inslice40 (left) aswell as the3Dcubictestpattern(right)

1515

StructureoftheCTandPETDROs.1516

TheCTObject1517

The CT object is 512 × 512 × 110 voxels, and is stored in 110DICOM files named 000001.dcm through1518000110.dcm,numericallyorderedsothat000001.dcmcorrespondstoslice1intheimagevolume.1519

The CT object has a reconstruction diameter of 500millimeters and an axial extent of 220millimeters,1520resultinginavoxelsizeof500/512×500/512×2(0.9765625×0.9765625×2.0)millimeters3.1521

The interior of the phantom body and the interiors of the hot spheres have voxels with values of 01522HounsfieldUnits (HU), simulatingwater in thebodyand the interiorof thehotspheres.Theshellof the1523body,lunginsertwall,andhotspherewallshavevoxelssetto120HU,simulatingpolymethylmethacrylate.1524Thevoxels interiortothelunginsertaresetto-650HU,simulatinglungattenuationmaterial.Thevoxels1525exteriorofthephantombodyaresetto-1000HU,simulatingair.Thesevaluesareindicatedintheabove1526figure.NOTE:Partialvolumeeffectswillalterthevoxelvaluesnearthebordersofdifferentregions.1527

1528

ThePETObject1529

The PET object consists of a 256 × 256 × 110 voxel image volume stored in 110 DICOM files named1530000001.dcmthrough000110.dcm,similartotheCTobjectdescribedabove.1531

ThePETobjecthas a reconstructiondiameterof 500millimeters andanaxial extentof 220millimeters,1532resultinginavoxelsizeof500/256×500/256×2(1.953125×1.953125×2.0)millimeters3.1533

ThevoxelsinteriortothephantombodyaresettoanSUVvalueof1.00.Thevoxelsinteriortothesixhot1534spheresaresettoanSUVbwvalueof4.00.Thevoxelscorrespondingtothepolymethylmethacrylateshell1535andtheexteriorof thephantombodyand interior to the lung insertareset toanSUVbwvalueof0.00.1536NOTE:Partialvolumeeffectswillalterthevoxelvaluesnearthebordersofdifferentregions.1537

Therearetwotestvoxelsinslice40oftheDRO.Thetestvoxelfurthestfromthelargesthotsphereinslice153840issettoanSUVbwvalueof4.11.Thetestvoxelclosesttothelargesthotsphereinslice40issettoan1539SUVbwvalueof-0.11.NOTE:Thereisnopolymethylmethacrylateshellsurroundingthetestvoxels inthe1540PETobject, andnopartial volumeeffects surrounding the test voxels. An SUV less than zero is possible1541whenusingPETimagereconstructionmethodssuchasanalyticfilteredbackprojection.1542


TherearetwotestpatternsinthePETDRO,asquare(2D)checkerboardpatterninslice40,andacubic(3D)1543checkerboard pattern centered in slice 40. The 3D cubic test pattern appears closest to the largest hot1544sphereinanaxialviewofslice40.1545

EachtestpatternconsistsofacheckerboardofvoxelswithalternatingSUVbwvaluesof0.10and0.90Both1546the2Dsquareand3Dcubictestpatternshaveedgemeasurementsof40mm.TheSUVbwvaluesofeach1547regionofthePETDROareshownintheabovefigure.1548

Usersof theDROareasked todownload thepackage, import thePETandCTobjects into their viewing1549software,performregionofinterest(ROI)analyses,andsubmittheresultsbacktothiswebsite.1550

1551

Procedure1552

UsersoftheDigitalReferenceObjectarerequestedto:1553

1.DownloadtheDRO(orimportfromCD)andtheuserreportform.1554

2.VerifytheDROfilesarepresent.1555

3.ImporttheDROintotheviewingsoftware.1556

4.PerformROIanalysisoftheDRO.1557

5.Submitthecompletedreportandstoreacopylocally.1558

1559


ReportForm-Page11560

1561


ReportForm-Page21562

1563

15641565

AppendixG:Vendor-neutralPseudo-codesforSUVCalculation1566

G.1Genericversion1567

This appendix contains the consensus opinion on the generic form of SUV calculation from PET DICOM1568images.Agenericpseudo-codeisusedwith"//"signifyingthebeginningofacommentfieldtotheendof1569theline.ThisversionassumesthePETIODisbeingusedandnottheEnhancedPETIOD:unitsareBQML,no1570privatedataelementsrequired,seriestimeisOK.UpdatedasofSeptember28,2012.Themostuptodate1571version is maintained on the QIBA FDG-PET Wiki page1572(http://qibawiki.rsna.org/index.php?title=Standardized_Uptake_Value_SUV).Notethatthisisbasedonour1573mostcompleteunderstandingatthistime,butrequirescarefulvalidationifimplemented.Inparticular,itis1574stronglyrecommendednottouseSeriesDateandSeriesTimefordecaycorrection.1575//SUVcannotbecalculatedifanyofthespecifiedDICOMattributesaremissingoremptyorzero1576ifCorrectedImage(0x0028,0x0051)containsATTNandDECAYandDecayCorrection(0x0054,0x1102)isSTART{1577

ifUnits(0x0054,0x1001)areBQML{1578halflife=RadionuclideHalfLife(0x0018,0x1075)inRadiopharmaceuticalInformationSequence(0x0054,0x0016)//seconds1579


ifSeriesDate(0x0008,0x0021)andTime(0x0008,0x0031)arenotafterAcquisitionDate(0x0008,0x0022)andTime(0x0008,0x0032){1580 scanDateandTime=SeriesDateandTime1581

startTime=RadiopharmaceuticalStartTime(0x0018,0x1072)inRadiopharmaceuticalInformationSequence(0x0054,0x0016)1582//startDateisnotexplicit…assumesameasSeriesDate;butconsiderspanningmidnight1583decayTime=scanTime–startTime //seconds1584//RadionuclideTotalDoseisNOTcorrectedforresidualdoseinsyringe,whichisignoredhere…1585injectedDose=RadionuclideTotalDose(0x0018,0x1074)inRadiopharmaceuticalInformationSequence(0x0054,0x0016)//Bq1586decayedDose=injectedDose*pow(2,-decayTime/halflife)1587weight=Patient'sWeight(0x0010,0x1030) //inkg1588SUVbwScaleFactor=(weight*1000/decayedDose)1589//RescaleInterceptisrequiredtobe0forPET,butuseitjustincase1590//Rescaleslopemayvaryperslice(GE),andcannotbeassumedtobeconstantfortheentirevolume1591SUVbw=(storedpixelvalueinPixelData(0x7FE0,0x0010)+RescaleIntercept(0x0028,0x1052))*RescaleSlope(0x0028,0x1053)1592

*SUVbwScaleFactor //g/ml1593}1594

}1595}1596

1597

G.2Robustversion1598

ThisappendixcontainstheconsensusopiniononthemostrobustformofSUVcalculationfromPETDICOM1599images.UpdatedasofSeptember28,2012.ThemostuptodateversionismaintainedontheQIBAFDG-1600PETWikipage (http://qibawiki.rsna.org/index.php?title=Standardized_Uptake_Value_SUV).Note that this1601isbasedonourmostcompleteunderstandingatthistime,butrequirescarefulvalidationifimplemented.1602Inparticular,itisstronglyrecommendednottouseSeriesDateandSeriesTimefordecaycorrection.1603

1604//SUVcannotbecalculatedifanyofthespecifiedDICOMattributesaremissingoremptyorzero1605ifCorrectedImage(0x0028,0x0051)containsATTNandDECAYandDecayCorrection(0x0054,0x1102)isSTART{1606

ifUnits(0x0054,0x1001)areBQML{1607halflife=RadionuclideHalfLife(0x0018,0x1075)inRadiopharmaceuticalInformationSequence(0x0054,0x0016)//seconds1608ifSeriesDate(0x0008,0x0021)andTime(0x0008,0x0031)arenotafterAcquisitionDate(0x0008,0x0022)andTime(0x0008,0x0032){1609

scanDateandTime=SeriesDateandTime1610 }1611 else{ //maybepost-processedseriesinwhichSeriesDateandTimearedateofseriescreationunrelatedtoacquisition1612 ifGEprivatescanDateandTime(0x0009,0x100d,“GEMS_PETD_01”)present{1613

scanDateandTime=GEprivatescanDateandTime(0x0009,0x100d,“GEMS_PETD_01”)1614}1615else{1616

//elsemaybeSiemensserieswithalteredSeriesDateandTime1617//eithercheckearliestofallimagesinseries(forallbedpositions)(wrongforcaseofPETsyngo3.xmulti-injection)1618scanDateandTime=earliestAcquisitionDate(0x0008,0x0022)andTime(0x0008,0x0032)inallimagesofseries1619

or1620//backcomputefromcenter(averagecountrate)oftimewindowforbedposition(frame)inseries(reliableinall1621

cases)1622


//AcquisitionDate(0x0008,0x0022)andTime(0x0008,0x0032)arethestartofthebedposition(frame)1623//FrameReferenceTime(0x0054,0x1300)istheoffset(ms)fromthescanDateandTimewewanttotheaverage1624

countratetime1625if(FrameReferenceTime(0x0054,0x1300)>0&&ActualFrameDuration(0018,1242)>0){1626

frameduration=ActualFrameDuration(0018,1242)/1000 //DICOMisinms;wantseconds1627decayconstant=ln(2)/halflife1628decayduringframe=decayconstant*frameduration1629averagecountratetimewithinframe=1/decayconstant*ln(decayduringframe/(1–exp(-decayduring1630

frame)))1631scanDateandTime=AcquisitionDate(0x0008,0x0022)andTime(0x0008,0x0032)1632

- FrameReferenceTime(0x0054,0x1300)/1000+averagecountratetimewithinframe1633

}1634}1635

}1636startTime=RadiopharmaceuticalStartTime(0x0018,0x1072)inRadiopharmaceuticalInformationSequence(0x0054,0x0016)1637//startDateisnotexplicit…assumesameasSeriesDate;butconsiderspanningmidnight1638decayTime=scanTime–startTime //seconds1639//RadionuclideTotalDoseisNOTcorrectedforresidualdoseinsyringe,whichisignoredhere…1640injectedDose=RadionuclideTotalDose(0x0018,0x1074)inRadiopharmaceuticalInformationSequence(0x0054,0x0016)//Bq1641decayedDose=injectedDose*pow(2,-decayTime/halflife)1642weight=Patient'sWeight(0x0010,0x1030) //inkg1643SUVbwScaleFactor=(weight*1000/decayedDose)1644

}1645elseifUnits(0x0054,0x1001)areCNTS{1646 SUVbwScaleFactor=Philipsprivatescalefactor(0x7053,0x1000,“PhilipsPETPrivateGroup”)1647 //if(0x7053,0x1000)notpresent,but(0x7053,0x1009)ispresent,then(0x7053,0x1009)*RescaleSlope1648

//scalespixelstoBq/ml,andproceedasifUnitsareBQML1649}1650elseifUnits(0x0054,0x1001)areGML{1651 SUVbwScaleFactor=1.0 //assumesthatGMLindicatesSUVbwinsteadofSUVlbm1652}1653

}1654//RescaleInterceptisrequiredtobe0forPET,butuseitjustincase1655//Rescaleslopemayvaryperslice(GE),andcannotbeassumedtobeconstantfortheentirevolume1656SUVbw=(storedpixelvalueinPixelData(0x7FE0,0x0010)+RescaleIntercept(0x0028,0x1052))*RescaleSlope(0x0028,0x1053)*SUVbwScaleFactor//g/ml1657

1658

AppendixH:ConsensusFormulaforComputingLean-Body-MassNormalization1659

forSUVs1660

ItisimportantthatthePETcommunityisconsistentinitscomputationofSUVLBM,particularlyinlightofthe1661recent article byWahl et al. (1) that proposes using SUVLBM as part of the PERCIST criteria to monitor1662treatmentresponse.1663

TwodifferentformulasforestimatingmaleLeanBodyMass-normalizedSUV(SUVLBM)arecurrentlybeing1664


usedinthePETcommunity.ThetwovariationsoftheformulaforestimatingLBMformalesareasfollows:1665

LBM(male)=(1.10xWeight)-128x(Weight/Height)2 [1]1666

LBM(male)=(1.10xWeight)-120x(Weight/Height)2 [2]1667

Wheretheunitsforweightarekg,andtheunitsforheightarecm.Onlyoneformulaisbeingusedforthe1668calculationoffemaleLBM(2,3):1669

LBM(female)=(1.07xWeight)-148x(Weight/Height)2 [3]1670

Bothversionsforestimatingmaleleanbodymass(equation1fromHallyncketal.(2)andequation2from1671MorganandBray(3))arebasedontheoriginalworkofJames(4),whichinturnwerederivedfromafitof1672(weight/height2)topercentagebodyfatasmeasuredbyskinfoldmeasurements.Equation1istheversion1673widelyusedbythepharmacologycommunityandcanbeconsideredthe'correct'version(5-7).1674

Thesecondversionoftheequation[2]canbetracedbacktoanarticlebyMorganandBray(3), inwhich1675theformulapresentedbyHallyncketal.(2)islikelymisquoted,sincethearticle(2)isreferencedelsewhere1676inMorganandBray(3)withoutdiscussionofthedifferenceinformulaswhere120wassubstitutedfor1281677as a coefficient. The first incorporation of this formula for computing LBM into SUV calculations was1678describedinSugawaraetal(8),whichcitestheMorganandBraypaper(3).Itisthisversionoftheformula1679formales,with120asthecoefficient,thathasbeensometimesquotedinthePETliterature.Sugawaraetal1680(8)usedonlydataforfemalepatients,whichcitestheformulaforestimatingfemaleLBMbyMorganand1681Bray(3),whichinturnmatchestheHallyncketal.(2)paper.1682

Althoughtheimpactofthisdifferenceincoefficientisrelativelyminorforpatientswithanormalbodymass1683index(BMI(kg/m2)=(weight/height2),itdoesvaryasafunctionofthepatient’sweight/heightratio.For1684example,forapatientofheight180cmandweight75kg(BMI:23)thevalueofSUVLBMascomputedbythe1685twoformulawoulddifferbylessthan1.5%forregionswithanSUVLBMof~1.However,foramalepatient1686ofthesameheightbutweighing150kg(BMI:46),thedifferenceinSUVLBMforthesameregionswouldbe1687~7%.1688

Incomparingequations[1]and[2],itisrecommendedthatequation[1]beusedinpreferencetoequation1689[2]. However, although the James (2) is themost commonly used data source for equations estimating1690LBM, it is well known that it is incorrect for extreme BMI values (5-7). Janmahasatian et. al (5) have1691proposedalternativeequationsforLBM:1692

LBM(male)(kg)= (9270xWeight)/(6680/(216xBMI)) [4]1693

LBM(female)(kg)= (9270xWeight)/(8780/(244xBMI)) [5]1694

TheserevisedformulasforLBMhaveachievedsomeacceptanceinthepharmacologycommunity(6,7),and1695futureversionsofthisProfilemayrecommendequations[4]and[5]insteadofequations[1]and[3].There1696are also continuing efforts to comeupwithmore accuratemethods for estimating LBM, through direct1697measurementonaper-patientbasisusingCT(9).However,thedifferentmethodsprovidingestimatesof1698LBMtypicallyhaveunknownlevelsofbiasandvariance.Thusconsistencyandstandardizationarelikelyto1699yieldlargerimprovementsinstudypowerforclinicaltrials,whencomparedtopotentialimprovementsin1700accuracyofLBMestimation.1701

References1702

1.Wahl,R.,Heather,J.,Kasamon,Y.,Lodge,M.(2009)FromRECISTtoPERCIST:EvolvingConsiderationsfor1703PETResponseCriteriainSolidTumours.JNM50(5);122S-150S.1704


2.HallynckTH,SoepHH,ThomisJA,BoelaertJ,DaneelsR,DettliL.(1981)Shouldclearancebenormalized1705tobodysurfaceorleanbodymass.BrJclinPharmac11:523-526.1706

3.Morgan,D.,BrayK.(1994)LeanBodyMassasapredictorofdrugdosage:ImplicationsforDrugTherapy.1707ClinicalPharmacokinetics26(4);292-307.1708

4.James,W.(1976)ResearchonObesity.London.HerMajesty’sStationaryOffice.1709

5.JanmahasatianS,DuffullSB,AshS,WardLC,ByrneNM,GreenB.Quantificationofleanbodyweight.Clin1710Pharmacokinet44(10):1051-1065,2005.PMID:16176118.1711

6.HanPY,DuffullSB,KirkpatrickCM,GreenB.Dosing inobesity:asimplesolutiontoabigproblem.Clin1712PharmacolTher82(5):505-508,2007.PMID:17952107.1713

7.HanleyMJ,AbernethyDR,GreenblattDJ.Effectofobesityonthepharmacokineticsofdrugsinhumans.1714ClinPharmacokinet49(2):71-87,2010.PMID:20067334.1715

8.Sugawara,Y.,Zasadny,K.,Neuhoff,A.,Wahl,R.(1999)ReevaluationoftheSUVforFDG:Variationswith1716bodyweightandmethodsforcorrection.Radiology213;521-525.1717

9. Chan T. Computerizedmethod for automatic evaluation of lean bodymass from PET/CT: comparison1718withpredictiveequations.JNuclMed53(1):130-137,2012.PMID:22128325.1719

1720

AppendixI:QIBAFDGPET/CTImagingSiteandScannerChecklists1721

1722

QIBAFDGPET/CTImagingSite1723

ThefollowingchecklistmaybeusedtoascertainaPETimagingsite’squalificationforquantitativeimaging1724according to theQIBA FDGPET/CT profile. Answersmay be provided either as “current practice” or as1725“feasible”,dependingonthecontext,but itshouldbemadeclearbothwhichwasexpectedandhowthe1726siteanswered.1727

1728

SiteandPersonnelQualifications

1. Thesiteisaccredited(ACR,IAC,TJC,etc.)orhasQualifiedstatusforclinicaltrials(ECOG-ACRIN,SNMMI-CTN,EARL,CROs,etc.)

__yes__no

2. Thesitehasthesupportoftechnologists,physicists,andphysiciansexperiencedintheuseofFDG-PET/CT,andmeetingthequalificationsdescribedbelow.

__yes__no

3. Technologists:PETstudiesareperformedbytechnologistswhosecertificationisequivalenttotherecommendationspublishedbytherepresentativesfromtheSocietyofNuclearMedicineTechnologistsSection(SNMTS)ortheAmericanSocietyofRadiologicTechnologists(ASRT)andshouldalsomeetalllocal,regional,andnationalregulatoryrequirementsfortheadministrationofionizingradiationtopatients.

__yes__no


4. Physicists:ThemedicalphysicistiscertifiedinMedicalNuclearPhysicsorRadiologicalPhysicsbytheAmericanBoardofRadiology(ABR);inNuclearMedicinePhysicsbytheAmericanBoardofScienceinNuclearMedicine(ABSNM);inNuclearMedicinePhysicsbytheCanadianCollegeofPhysicistsinMedicine;orequivalentcertificationinothercountries;orhave3yearsofPETexperience.Regardlessofcertification,thephysicistshouldhavespecificexperienceinPETanditsquantitativeuse.

__yes__no

5. PhysiciansoverseeingandinterpretingPET/CTscansarequalifiedbytheABR(Diagnosticand/orNuclearRadiology)orAmericanBoardofNuclearMedicine(ABNM)orequivalentwithintheUnitedStatesoranequivalententityappropriateforthegeographiclocationinwhichtheimagingstudy(ies)willbeperformedand/orinterpreted.

__yes__no

ImagingProcedures

6. PatientheightandweightareenteredintoscannerduringPET/CTacquisition. __yes__no

7. Bloodglucoseismeasuredforeachpatientwithin2hoursprecedingFDGadministration.Measuredvalueandmeasurementtimearedocumented.

__yes__no

8. Ifandwhenglucosethresholdisexceeded,thereasonshallbedocumented. __yes__no

9. Foreachpatient,thepre-injectionFDGactivityismeasuredandinjectedandresidualactivityismeasured.Initialandresidualmeasurementtimesandinjectiontimeareenteredintotheconsole.

__yes__no

10. FDGisadministeredthrougha24-gaugeorlargerindwellingcatheterplacedanatomicallyremotetoanysitesofsuspectedpathology,preferablyinanantecubitalvein.Intravenousportsshouldnotbeused,unlessnoothervenousaccessisavailable.

Inthecaseofmanualadministration,athree-wayvalvesystemshouldbeattachedtotheintravenouscannulasoastoallowatleasta10ccnormal(0.9%NaCl)salineflushfollowingFDGinjection.Forautomatedinjectiondevicesalternateflushingmechanismsareallowed.

__yes__no

11. Forfollow-upscans,patientsareimagedwiththesameworkflow(i.e.patienthandling,imagingacquisition,imageprocessing,andimageanalysis)asforbaselinescans.

__yes__no

12. TheFDGuptaketime(frominjectiontoscan)is60minutes,withanacceptablerangeof55-75minutes.Whenrepeatingascanonthesamesubject,uptaketimeforthe2ndscaniswithin10minutesofthatforthefirstscan.

__yes__no

13. IfthepatientisobservedtotakeadeepbreathduringtheCTscanitisdocumentedandarepeatCTstudyisconsidered.

__yes__no

14. Whenapatientisrescanned,thesamescandirectionisused. __yes__no

15. ReconstructedPETimages,withandwithoutattenuationcorrection,andCTimagesarearchivedattheimagingsite.

__yes__no

QA/QC


16. ThesiteperformsallPET/CTscannerQA/QCproceduresrecommendedbythemanufacturerandattherecommendedfrequency(e.g.,daily,weekly,quarterly)andassuresthattheoutputvaluesareacceptable.

__yes__no

17. DailyQAproceduresareperformedpriortoanysubjectscan. __yes__no

18. Awaterorwater-equivalentphantomisscannedandevaluateddailyandacceptableoutputisensured.

__yes__no

19. DosecalibratorconstancyisevaluateddailyontheF-18setting.Day-to-daydifferencesnogreaterthan2.5%areallowed.Cs-137,Co-57,orsimulatedF-18maybeused.

__yes__no

20. Thedosecalibratoraccuracyisevaluatedmonthlywithmeasuredvaluesdifferingnomorethan2.5%fromtheactualsourcevalue.Cs-137,Co-57,orsimulatedF-18maybeused.

__yes__no

21. Dosecalibratorlinearityisassessedatleastannuallyoverarangeof37-1110MBq,withdeviationofnomorethan2.5%overtheentirerange.

__yes__no

22. Scalesforpatientweightmeasurementareevaluatedannuallyorafteranyrepairbyqualifiedpersonnel,witherrornomorethan2.5%fromexpectedvaluesusingaNIST-traceableorequivalentstandard.

__yes__no

23. TheglucosemeasuringdeviceismeasuredandtestedaccordingtoaCLIA-approved,CLIA-cleared,orequivalent(ifoutsidetheUnitedState)procedure.

__yes__no

24. ThePET/CTscannercomputerandallclocksintheimagingfacilityusedtorecordactivity/injectionmeasurementsaresynchronizedtostandardtimereferencewithin+/-1minute.

SynchronizationofallclocksusedintheconductoftheFDG-PET/CTstudyischeckedweeklyandafterpoweroutagesorcivilchangesforDaylightSavings(NorthAmerica)orSummerTime(Europe).

__yes__no

25. QuantitativeCalibrationAccuracy:PETscannerquantitativeaccuracyrelativetothedosecalibratorisverifiedquarterlyandafterscannerupgrades,maintenanceorrepairs,newsetupsandmodificationstothedosecalibratorviaauniformphantomscanofactivitymeasuredinthedosecalibrator,achievingalargecentralROImeanSUVvalueof1.0(acceptablerange0.9-1.1).

__yes__no

26. AxialUniformity:Usingauniformcylinderphantomorequivalentshallobtainaslice-to-slicevariabilityoflessthan10%forthesliceswithinthecentral80%oftheaxialFOV.

__yes__no

27. PETResolution:Coldrods(asintheJaszczakorACRPETphantoms)ofdiameter9.5mmorsmallermustbevisible.Ahotcylinder(asintheACRPETphantom)of12mmorsmallermustbevisibleORthe13mmsphereoftheNEMAimagequalityphantommustbevisible.

__yes__no

28. PETnoise:Inauniformphantomof0.1to0.2µCi/mlF-18concentrationthecoefficientofvariationofvoxelvalueswithinarectangularorcircularregionofatleast3cm(sideordiameter)mustbenogreaterthan15%forallsliceswithinthecentral80%oftheaxialFOV.

__yes__no

SpecificPersonnelResponsibilities


29. Atechnologistorphysicistassessesuniformity(within-planeandacrossslices)andcompareswithpreviousresults.Quarterlyandfollowingsoftwareupgrades.

__yes__no

30. AtechnologistorphysicistshallperformtheQuantitativeCalibrationAccuracytest.Quarterlyandfollowingsoftwareupgradesorchangestothedosecalibrator

__yes__no

31. Aphysicistshallperformanddocumentperformanceofaquantitativeassessment(usingaphantomwithdifferingsizedefinedtargetssuchastheACRorNEMAIQphantomsprocessedwithroutineimagereconstructionprotocols)forlesionresolution.Annually.

__yes__no

32. AphysicistShallperformaquantitativeassessmentofimagenoiseinphantomimagestobeofconsistentandacceptablequality.Annually.

__yes__no

1729

1730

QIBAFDGPET/CTScannerChecklist1731

Thefollowingquestionnaire/checklistmaybeusedtoascertainaPETscanner’squalificationfor1732quantitativeimagingaccordingtotheQIBAFDGPET/CTProfile.1733

1734 Parameter Specification Pass?

1. Calibrationfactors

AllnecessarycalibrationfactorsneededtooutputPETimagesinunitsofBq/mlshallbeautomaticallyappliedduringtheimagereconstructionprocess.

2. PETScannercalibration

Shallbeabletobecalibratedaccordingtothefollowingspecifications:UsingauniformcylindercontainingF-18inwatersolution(ideallyusingthesamesolutionusedfordosecalibratorcross-calibration)

Slice-to-slicevariabilityshallbenomorethan±5%(notincludingendslices,asperACRPETCoreLab).

3. Weight Shallbeabletorecordpatientweightinlborkgassuppliedfromthemodalityworklistoroperatorentryintoscannerinterface.ShallbestoredinPatientWeightfield(0010,1030)intheDICOMimageheader,asperDICOMstandard.

4. Height Shallbeabletorecordpatientheightinfeet/inchesorcm/massuppliedfromthemodalityworklistoroperatorentryintoscannerinterface.ShallbestoredinPatientSizefield(0010,1020)intheDICOMimageheader,asperDICOMstandard.

5. AdministeredRadionuclide

Shallbeabletoentertheradionuclidetype(i.e.F-18)byoperatorentryintothescannerinterfaceandthroughpredefinedprotocol.ShallberecordedinRadionuclideCodeSequence(0054,0300)intheDICOMimageheader[e.g.(C-111A1,SRT,“18Fluorine”)].

6. AdministeredRadiotracer

Shallbeabletorecordtheradiotracer(i.e.FDG),assuppliedbyoperatorentryintothescannerinterface.ShallberecordedinRadionuclideCodeSequencefield(0054,0300)intheDICOMimageheader,e.g.(C-B1031,SRT,“FluorodeoxyglucoseF18”).

7. AdministeredRadiotracerradioactivity

Shallbeabletoentertheadministeredradioactivity,inbothMBqandmCi,assuppliedbyoperatorentryintothescannerinterface.ShallberecordedinRadionuclideTotalDosefield(0018,1074)intheDICOMimageheaderinBq.

8. Administered Shallbeabletorecordthetimeofthestartofactivityinjectionassuppliedby


RadiotracerTime

operatorentryintothescannerinterface.ShallberecordedinRadiopharmaceuticalStartDateTimefield(0018,1078)(preferred)orRadiopharmaceuticalStartTimefield(0018,1072).

9. DecayCorrectionMethodology

EncodedvoxelvalueswithRescaleSlopefield(0028,1053)appliedshallbedecay-correctedbythescannersoftware(nottheoperator)toasinglereferencetime(regardlessofbedposition),whichisthestarttimeofthefirstacquisition,whichshallbeencodedintheSeriesTimefield(0008,0031)fororiginalimages.

CorrectedImagefield(0028,0051)shallincludethevalue“DECY”andDecayCorrectionfield(0054,1102)shallbe“START”,whichmeansthattheimagesaredecay-correctedtotheearliestAcquisitionTime(0008,0032).

10. ScanningWorkflow

ShallbeabletosupportProfileProtocol(Section3)PETandCTorder(s)ofacquisition.

Shallbeabletopre-defineandsave(byimagingsite)aProfileacquisitionProtocolforpatientacquisition.

11. CTAcquisitionParameters

Shallrecordallkeyacquisitionparameters(technique)intheCTimageheader,usingstandardDICOMfields.

12. PET-CTAlignment

ShallbeabletoalignPETandCTimageswithin±2mminanydirection.

13. ActivityConcentrationintheReconstructedImages

Shallbeabletostoreandrecord(rescaled)imagedatainunitsofBq/mlanduseavalueofBQMLforUnitsfield(0054,1001).

14. TracerUptakeTime

ShallbederivablefromthedifferencebetweentheRadiopharmaceuticalDateTimefield(0018,1078)(preferred)orRadiopharmaceuticalStartTimefield(0018,1072)andtheSeriesTimefield(0008,0031)orearliestAcquisitionTimefield(0008,0032)intheseries(i.e.,thestartofacquisitionatthefirstbedposition),whichshouldbereportedasSeriesTimefield(0008,0031).

15. PETVoxelsize

SeeSection4.3(PETVoxelsize)undertheReconstructionSoftwarespecificationrequirements.

16. CTVoxelsize ShallbenogreaterthanthereconstructedPETvoxelsize.

Voxelsshallbesquareintransaxialdimensions,althougharenotrequiredtobeisotropicintheZ(head-foot)axis.

NotrequiredtobethesameasthereconstructedPETvoxelsize.

17. SubjectPositioning

ShallbeabletorecordthesubjectpositioninthePatientOrientationCodeSequencefield(0054,0410)(whetherproneorsupine)andPatientGantryRelationshipCodefieldSequence(0054,0414)(whetherheadorfeetfirst).

18. DICOMConformance

AllimagedataandscanparametersshallbetransferableusingappropriateDICOMfieldsaccordingtotheDICOMconformancestatementforthePET/CTscanner.

19. DICOMDatatransferandstorageformat

PETimagesshallbeencodedintheDICOMPETorEnhancedPETImageStorageSOPClass,usingactivity-concentrationunits(Bq/ml)withadditionalparametersstoredinpublicDICOMfieldstoenablecalculationofSUVs.

PETimagesshallbetransferredandstoredwithoutanyformoflossy


compression.

20. Metadata ShallbeabletoaccuratelypropagatetheinformationcollectedatthepriorstagesandextenditwiththoseitemsnotedintheReconstructionsection.

21. DataCorrections

PETemissiondatamustbeabletobecorrectedforgeometricalresponseanddetectorefficiency,systemdead-time,randomcoincidences,scatterandattenuation.

22. ReconstructionMethodology

Shallbeabletoprovideimageswithoutresolutionrecovery.

23. ReconstructionMethodology/Output

Shallbeabletoperformreconstructionswithandwithoutattenuationcorrection.

24. DataReconstruction2D/3DCompatibility

Shallbeabletoperformreconstructionofdataacquiredin3Dmodeusingfully3Dimagereconstructionalgorithms.

Shallbeabletoperformreconstructionofdataacquiredin2Dmodeusing2Dimagereconstructionalgorithms.

25. Quantitativecalibration

Shallapplyappropriatequantitativecalibrationfactorssuchthatallimageshaveunitsofactivityconcentration,e.g.kBq/mL.

26. Multi-beddata

Shallcombinedatafrommultipleover-lappingbedpositions(includingappropriatedecaycorrections)soastoproduceasinglethree-dimensionalimagevolume.

27. Voxelsize Shallallowtheusertodefinetheimagevoxelsizebyadjustingthematrixdimensionsand/ordiameterofthereconstructionfield-of-view.

ShallbeabletoreconstructPETvoxelswithasize4mmorlessinallthreedimensions(asrecordedinVoxelSpacingfield(0028,0030)andcomputedfromthereconstructionintervalbetweenImagePosition(Patient)(0020,0032)valuesofsuccessiveslices).

Voxelsshallbesquareintransaxialdimensions,althoughvoxelsarenotrequiredtobeisotropicinthez(head-foot)axis.

28. Reconstructionparameters

Shallallowtheusertocontrolimagenoiseandspatialresolutionbyadjustingreconstructionparameters,e.g.numberofiterations,post-reconstructionfilters.

29. Reconstructionprotocols

Shallallowasetofreconstructionparameterstobesavedandautomaticallyapplied(withoutmanualintervention)tofuturestudiesasneeded.

1735

1 2 qiba profile. fdg-pet/ct as an imaging biomarker ... · 121 fdg-pet/ct imaging can be used for...

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