BestPrac*ces:ClinicalandResearchIncidentalFindings

GregZaharchuk,MDPhDAssociateProfessorofRadiology

StanfordUniversityStanfordHealthcare

FactorsInfluencingIncidentalFindings

•  Bodypartscanned•  Ageofpa*ents•  Whethertheyhaveanypre-disposingcondi*ons– Hypertension,etc.

•  Typeofscanperformed(i.e.,amountofanatomyincluded)– OOenmostofthestudyisfMRIorothersequencesnottypicallyusedfordiagnosis

•  Operator’sexperience–  Technologists>Students,etc.

WhatisanIncidentalFinding?

•  “anincidentalfindingisafindingconcerninganindividualresearchpar*cipantthathaspoten*alhealthorreproduc*veimportanceandisdiscoveredinthecourseofconduc*ngresearchbutisbeyondtheaimsofthestudy.”

WolfSM,etal.ManagingIncidentalFindingsinHumanSubjectsResearch:AnalysisandRecommenda*ons.JournalofLaw,Medicine&Ethics.2008;36(2):219–248.

TwoMainModels

•  Researcherreferral•  Readeverything

ConsentForms:ResearcherReferral

•  Theinves*gatorsforthisprojectarenottrainedtoperformradiologicaldiagnosis,andthescansperformedinthisstudyarenotop*mizedtofindabnormali*es.Theinves*gatorsandStanfordarenotresponsibleforfailuretofindexis*ngabnormali*esinyourMRIscans.

•  However,onoccasiontheinves*gatormayno*ceafindingona

MRIscanthatseemsabnormal.Whenthisoccurs,aradiologistwillbeconsultedastowhetherthefindingmeritsfurtherinves*ga*on,inwhichcasetheprincipalinves*gatoroftheresearchstudybeingconductedwillcontactyouandyourprimarycarephysicianandinformyouofthefinding.

•  Thedecisionastowhethertoproceedwithfurtherexamina*onontreatmentliessolelywithyouandyourphysician.

Availableathjp://cafn.stanford.edu/index.php/Documents

Workflow:ResearcherReferral•  Someoneseessomething.

–  Donotalarmsubject(!)–  (Maybe)mechanismforimmediateradconsulta*on–  (Maybe)screeningbyamoreseniornon-MDonsite

•  Ifdeemedsignificantatthislevel,PImadeaware.•  Referredtoradiologistforareport(ofsomekind)

–  OOenlimited,becausenon-clinicalimagingprotocolisused•  ReportgiventoPI(maybe)withrecommenda*onsforfollow-up

•  Follow-upisresponsibilityofpa*ent–  Includinganyincurredexpenses

*ConsensusofworkflowsfromStanfordLucasCenter,StanfordCNI,UCSF,andMGH

Noac*onnecessary•  mostcommon

PossibleSequelae

B.Kimetal.,“IncidentalFindingsonPediatricMRImagesoftheBrain,”AJNRAmericanJournalofNeuroradiology2002;23:1674-1677.

Rou*nereferral•  Anatomicsequencesnot

adequatefordiagnosis•  Contrastneededbutnotgiven

Urgentreferral•  Follow-upinnextfewdays

Immediatereferral•  Intheory,cannotwaitfor

specialistread•  Leastcommon(fortunately)

IssueswithReferrals

Stressfulforpa-entMayleadtomoretests

FinancialcostsFalseposi-ves Poten-altreatablecauses

ALargeStudy•  Meta-analysis:16studies,19,559subjects•  Excludedwhitemajerlesions,silentinfarcts,andmicrobleeds,megacisternamagna,cavumseptumpellucidum,asymmetricventricles

•  Prevalenceof:– Non-neoplas*cfindings2.0%(95%CI1.1-3.1%)

•  Arachnoidcyst0.5%,Aneurysm0.35%,Chiari0.24%– Neoplas*cfindings0.7%(0.47-0.98%)

•  Meningioma0.29%,Pitadenoma0.15%,LGG0.05%•  Morecommononhigh-resolu*onstudies–  4.3%vs.1.7%

Morrisetal.Incidentalfindingsonbrainmagne*cresonanceimaging:systema*creviewandmeta-analysis,BMJ2009;339:b3016

ASmallStudy

•  ResearchMRIsesng– 23T,17T,13TPET/MRI– Circa1000humanscansperyear

•  Primarilyneurobrainscans(>70%)– AlotofEPI

•  Scansperformedprimarilybystudents&technologists(non-MD’sandnon-radiologists)

IncidentalFindings•  Reviewof2.5yearperiod(2013-2015)–  49/2500casesreferred,80%brain

– About2%oftotal

•  11casesrequiredcontac*ngsubject–  0.4%

•  2casesleadingtopossibleac*on–  0.1%

CasesNotRequiringFollow-up

•  Perivascularspaces,VRspaces(n=9)•  Nothing(n=4)•  Arachnoidcyst(n=2)•  Arachnoidgranula*on(n=2)•  Sinusdisease(n=2)•  Whitemajerhyperintensi*es(n=2)•  Pinealcys*clesion(n=2)•  Normalpituitary(n=2)

PerivascularSpacesa.k.a.Virchow-RobinSpaces

PerivascularSpacesa.k.a.Virchow-RobinSpaces

PerivascularSpacesa.k.a.Virchow-RobinSpaces

•  CSFsignalintensity•  Surroundingsmallvessels

•  Usuallybilateral•  Mostcommonloca*ons–  Basalganglia,espputamen

–  SupratentorialWM– Midbrain

ArachnoidCyst•  LocatedCSFcollec*ons•  CSFsignalintensity•  Canbelargeandhavemasseffect

•  Maythinadjacentskull•  Nounderlyingbrain*ssuechanges

•  Commonloca*ons–  Anteriortemporal*p(espL)–  Retrocerebellar–  Overfrontalconvexi*es

•  Almostneverintervenedupon

UrgentCase1

•  Smallsubacutesubduralhematoma– Observa*ononly,nointerven*onperformed

UrgentCase2

•  Pituitaryadenoma/Rathke’scleOcyst– Discussionwithneurosurgeonre:possiblesurgery

ResearcherReferralModel:Issues

•  Doesnotallowpar*cipantsto“optout”ofbeinginformedaboutevenminorfindings

•  Doesnotaddresspossiblesignificantfindingsthatarenotobviousenoughtobeiden*fiedbytheresearchteam– OOentechnologistorstudent

•  Alterna*ves

ReadEverythingModel

•  Allscansreadbyaneuroradiologist•  Example:NCANDAstudy– Studyofhealthyadolescentslookingatbrainchangesduetoalcoholconsump*on

– N=833•  Abnormali*esfoundin11.4%ofcases– 6%aOerremovingmegacisternamagna,etc.– 0.4%urgentreferrals(3/833)

Pfefferbaumetal.,CerebralCortex2015;1-21.

ReadEverythingModel

•  Moreabnormali*esdetected•  Mostnotrelevant•  Dilemmas:–  5graymajerheterotopiasfound– Allpresumablyasymptoma*c–  ?Shouldthisbereportedtochildren/parents?

•  Mostsevereabnormali*esprobablyfoundatsamerateasresearcherreferralmodel

•  Expensive(ifyouhavetopay)

Pfefferbaumetal.,CerebralCortex2015;1-21.

Conclusions•  Ifyouscan,youwillsee

abnormali*es•  Twomainmodels,lotsofdiscre*on

inbetween•  Beprepared

–  Informpa*entsviaconsentprocess–  Knowtheprocedureinyourlab–  Workonyourpokerface

•  Manywillbenormalvariantsorar*facts

•  Lowindexofsuspicionforreferralforresearchers

•  Youmaysavealife.•  Goodluck!

IwouldliketoacknowledgeAnneSawyer/GaryGlover(StanfordLucas),BobDougherty(StanfordCNI),Pra*kMukherjee(UCSF),andSteveStufflebeam/BruceRosen(MGH)forprovidingtheircenter’spolicies.

BartLane,MD,fordescribingtheproceduresforNCANDA.

Thistalkavailable@hjp://cafn.stanford.edu/index.php/LecturesQues*ons:gregz@stanford.edu