1、Multi-detectorspiralCTstudyoftherelationshipsbetweenpulmonaryground-glassnodulesandbloodvesselsEurRadiol(2022)23:32713277第一页,共四十页。AbstractObjective:Toinvestigatetherelationshipsbetweenpulmo-naryground-glassnodules(GGN)andbloodvesselsandtheirdiagnosticvaluesindifferentiatingGGNs.Conclusion:DifferentG
2、GNshavedifferentrelationshipswithvessels.UnderstandingandrecognisingcharacteristicGGN-vesselrelationshipsmayhelpidentifywhichGGNsaremorelikelytobemalignant.第二页,共四十页。KeyPointsMulti-detectorCToffersnewinformationaboutground-glassnodules.Differenttypesofground-glassnoduleshavedifferentrelationshipswith
3、vessels.Thismayhelpidentifywhichground-glassnodulesarelikelytobemalignant.第三页,共四十页。IntroductionWiththeextensiveacceptanceoflow-dosemulti-detectorspiralCTinlungcancerscreening,thenumberofdetectedGGNsorfocalground-glassopacities(fGGOs)hasdramaticallyincreased.GGNscanresultfromneoplasms,suchaspulmonary
4、adenocarcinoma,orbenigndiseases,suchasfocalfibrosis,inflammationoralveolarhaemorrhage.第四页,共四十页。Inaddition,pre-invasiveabnormalities,includingatypicaladenomatoushyperplasia(AAH)andadenocarcinomainsitu(AIS).IthasbeenreportedthattheproportionofmalignancyinGGNsishigherthaninsolidpulmonarynodules(SPNs)an
5、dthemajorityofmalignantGGNsareadenocarcinoma.Duetoimagingresemblance,however,itisextremelychallengingtodifferentiatemalignantGGNsfromtheaforementionedbenigncounterparts.第五页,共四十页。AccuratedifferentialdiagnosisofGGNswillassistphysicianstomaketreatmentdecisionsandimprovetreatmentoutcomesandprognosis.Sev
6、eralinvestigatorshavesuggestedthatanalysisofrelationshipsbetweenSPNsandsurroundingvesselscanhelppredictthelikelihoodofmalignancyinsuchnodules.TherelationshipbetweenGGNsandbloodvesselsremainsunknown.WhetherthisrelationshipcanbeutilisedtofacilitatethediagnosisofmalignantGGNsisaworthyofinvestigation.第六
7、页,共四十页。MaterialsandmethodsPatientsTheimagingdataofpatientswithpulmonaryGGNsreceivingthin-sectionmulti-detectorCTexaminationatourhospitalinJanuary2022throughNovember2022wereretrospectivelyreviewed.Alllesionsweresolitaryandmostofthem(104/108)surgicallyresectedwithin2weeksafterCTscanning.第七页,共四十页。Inclu
8、sioncriteriaTheGGNsizewaslessthan3cminthelargestdimension.ground-glassopacity(GGO)comprisedmorethan50%oftheareaofthelesiononCT.-Anareaofover50%GGOwassetasthecutoffvaluetoexcludesolid/semi-solidlesions.-AlthoughsolidnodulesfrequentlyhadGGOcomponentsaroundtheirmargin,probablyrepresentingsurroundingoed
9、emaormerelypooraerationofthesurroundinglungtissuesduetocompressionorretractionbynodules,thesenoduleshadalreadybeenwellinvestigatedusingCTandthereforewerenotthestudyobjects第八页,共四十页。Ultimately,108patientswereenrolledintothisstudy,including38malesand70femaleswithmeanageof58.1812.89years(range,22to79yea
10、rs).43patientswereasymptomatic,28hadrespiratorysymptoms,and37hadlungcancerriskfactors,suchassmokingandfamilyhistory.第九页,共四十页。Accordingtopathologicalfindings,GGNsweredividedintothreegroups:(1)Benigndiseasegroup(10cases),includingfournodulesdiagnosedwithacombinationofclinicalsymptomsandimagingpresenta
11、tions(nodulesdisappearedorgraduallyreducedinsizeonmultiplefollow-upCTimaging)andsixnodulesconfirmedbypathologicalexamination(1caseofsclerosinghaemangiomaand5casesofchronicinflammation).(2)Preinvasivediseasegroup(24cases),including7AAHsand17AISs.第十页,共四十页。(3)theinvasiveadenocarcinomagroup(74cases),con
12、firmedpathologically,therewere39non-mucinousminimallyinvasiveadenocarcinomas(MIA)and35invasiveadenocarcinomas(IAC;specifically,13lepidicpredominantadenocarcinomas;19acinus-predominantadenocarcinomas;2papillary-predominantadenocarcinomasand1solidpredominantwithmucin粘蛋白production).第十一页,共四十页。CTimaginga
13、nalysisprotocolparameters:0.625-mmsectionwidthwitha0.625-mmreconstructioninterval,pitchof0.984,120kVand250mA.Allimageswerereviewedwithahigh-resolution,2,0481,560pixel,standardlungwindow(ww,1,500HU;wl,-500HU)andmediastinalwindow(ww,350HU;wl,50HU)GGNscanbefurthersubdividedintomixedground-glassnodules(
14、mGGNs)andpureground-glassnodules(pGGNs).ThepercentageoftheGGOcomponentwascalculatedasfollows:(DGGO-D)/DGGO100,whereDGGOisthelargestdiameteroftheentirelesionandDisthelargestdiameterofthesolidcomponentwithinthelesion.第十二页,共四十页。Bloodvesselanalysiswasperformedintermsofvascularmorphologyandvascularrelati
15、onshipswithGGNlesions.thediameterofpulmonaryvesselsgraduallydecreasesfromthehilumtowardtheperiphery.Ifthediameterofthevascularsegmentwithinlesionswaslargerthantheproximalsegmentorlesionvesselswereapparentlywiderthanothervesselsatthesamebranchlevel,thevesselwasdeemedasabnormalvascularbroadening.Theve
16、sselswereconsideredtobedistortedorrigidiftravelingastrayfromtheexpectednormalcourse.第十三页,共四十页。Multiplesupplyingvessels,withdifferentoriginatingsources,convergingtowardalesion,wereprobablyindicativeofanincreasedbloodcirculationwithin.Tofurtherclarifyaffiliationsofsupplyingvessels,wetracedvascularcour
17、sesslice-wisebackwardtomajorvesselsinthehilum.TherelationshipsbetweentheGGNsandsupplyingbloodvesselswereanalysedinaxialimages,MPRimagesCPRimages.第十四页,共四十页。theGGN-vesselrelationshipswerecategorizedintofourtypesaccordingtoimagingfeatures:typeI(pass-by),vesselspassedbyGGNswithoutdetectablesupplyingbran
18、chestolesions.typeI第十五页,共四十页。typeII(pass-through),vesselspassedthroughthelesionswithoutobviousmorphologicalchangesintravelingpathorsize.第十六页,共四十页。typeIII(distorted/dilated),vesselswithinlesionsweretortuousorrigidwithoutanincreaseinamount第十七页,共四十页。typeIV(complicated),morecomplicatedvasculatureotherth
19、andescribedintheaforementionedtypeswithinGGNs,forinstance,coexistenceofirregularvasculardilationandvascularconvergencefrommultiplesupplyingvessels.第十八页,共四十页。PathologicalanalysisThepathologicaldiagnosisandcategorisationofAAH,AIS,MIAandIACweremadebasedonthenewpulmonaryadenocarcinomaclassification,2022
20、edition.GGNswereresectedbyvideo-assistedthoracoscopyorthoracotomysurgery.Allhistologicalpreparationsandanalyseswereperformedbytwoseniorpathologists.Inthecaseofdisagreements,aconsensuswasreachedaftermutualdiscussionand/orconsultationwithathirdpathologist.第十九页,共四十页。StatisticalanalysisSPSS16.0forWindow
21、s,SPSS,Chicago,IllIndependentttestwasusedtocomparedifferentpathologicalgroups(benigndiseases,preinvasivediseasesandinvasiveadenocarcinoma)ofGGN.CorrelationsbetweenpathologicalfindingsofGGNsandGGN-vesselrelationshipswereexaminedusingSpearmansranktest.GGN-vesselrelationshipsbetweenMIAandIACdiseaseswer
22、ecomparedusingPearsonschi-squaredtest.Whentherewasanexpectedvalue1orapretestprobabilityclosetothetestlevel,Fishersexacttestwasusedinstead.StatisticalresultswereconsideredsignificantwhenthePvaluewaslessthan0.05.第二十页,共四十页。ResultsSize variation of GGN lesionsTheaverageGGNsizeinthebenigngroup,preinvasiv
23、egroupandadenocarcinomasgroupwas8.12.5mm,9.35.6mmand14.86.0mm,respectively.Nosignificantdifferencesexistedbetweenthepreinvasivegroupandthebenigngroup(t=0.64,p=0.53).However,thereweresignificantdifferencesbetweenbenignandpreinvasivegroupsandtheinvasiveadenocarcinomagroup(t=6.31,p=0.00;t=3.98,p=0.00).
24、第二十一页,共四十页。Correlations between GGN-vessel relationships and pathological findingsOf108GGNs,typeI,II,IIIandIVGGNvessellrelationshipswereobservedin9,58,21and20cases,respectively.thetypeIIGGN-vesselrelationshipwasthedominantrelationshipineachpathologicalgroup,seenin9benign(90.0%),16preinvasive(66.7%)a
25、nd33invasive(44.6%)GGNcases.第二十二页,共四十页。comparedwiththelowincidenceoftypeIIIandIVrelationshipsinbenignandpreinvasivegroupsthecombinedincidenceoftypeIII(25.7%)andIV(25.7%)relationshipsintheinvasiveadenocarcinomagroupreached51.3%.第二十三页,共四十页。MIA couldpresentfourtypes,withtypeIIasthemajortype(48.7%).Thec
26、ombinationoftypeIIandIVcomprised about80%oftheMIAsubgroup;forIAC,typeIIandIII hadthesameproportionof40%,hencethecombinationof 80%.StatisticalstudiesshowednodifferenceintypeIIbuta significantdifferencewasfoundintypeIIIandIVbetween MIAandIAClesions(p=0.02).第二十四页,共四十页。Thevessel(s)travelingthroughGGNcou
27、ldbeartery(ies)(categoryA),vein(s)(categoryB),orartery(ies)andvein(s)(categoryC).TherewerenosignificantdifferencesandcorrelationsbetweenvascularcategoriesandGGNgroups(p=0.50and0.96,respectively).第二十五页,共四十页。AfurtherexaminationofthecorrelationbetweenvascularcategoriesandGGNswithtypeIIIandIVrelationshi
28、psdidnotgenerateanysignificantresults(p=0.70).第二十六页,共四十页。DiscussionSolitarypulmonarynodules(SPNs)arecommonfindingsinCTexaminationsandcanbedividedintotwogroupsbasedondensityvariation:solidnodulesandGGNs.In2022,theInternationalAssociationfortheStudyofLungCancer,theAmericanThoracicSocietyandtheEuropean
29、RespiratorySocietyproposedanewclassificationforlungadenocarcinomas.Inthenewclassificationsystem,thetermbronchioloalveolarcarcinoma(BAC)isnolongerused.TheformerBACconceptapplicabletomultiplecategoriesinthenewclassificationsystem,suchasAIS,MIAandthemucinoussubtypeofadenocarcinoma.BothAISandAAHlesionsa
30、reclassifiedaspreinvasiveadenocarcinomaunderthenewclassificationsystem第二十七页,共四十页。EarlystagelungcancersoftenpresentasGGNsinCTimages;thus,itisimportanttobefamiliarwiththecharacteristicsofGGNswithmalignantpotential,astimelysurgicalresectionwillimprovepatientsurvivalandqualityoflife,andforpatientswithbe
31、nignGGNs,unnecessarysurgicalprocedurescanbeavoided.第二十八页,共四十页。Clinicaldatahaveshownthatnodulesizeisanindependentpredictivefactorofmalignancy,withsizeincreasingthelikelihoodofmalignancyincreasing,consistentwithourresultsthatthemeansizesofGGNsinbenign,preinvasiveandadenocarcinomagroupswere8.1mm,9.3mma
32、nd14.7mm.Clinicalexperiencehasdemonstratedthatsomecommonimagingfeaturesofmalignantnodules,suchaspleuralindentation,spiculationandlobulation,areseldomseeninveryearlystagemalignantGGNs.第二十九页,共四十页。Thisdemandsfurtherinvestigationofthisparticularabnormalimagingfindingtominimisemisdiagnosis.Inthemanagemen
33、tofGGNsinourpatients,clinicalguidelinesfromtheFleischnerSocietyandNationalComprehensiveCancerNetwork(NCCN)werereferenced.Eachindividualcasewasdiscussedbyamultidisciplinaryteam,includingdiagnosticradiologists,thoracicsurgeonsandpathologists,togenerateconsequentmanagementstrategies.Allpatientsreceived
34、adequatefollow-upobservationwith/withoutsupportiveorantiinflammatorytreatment,whichexplainedthefactthatfourGGNsdisappearedpriortothenextscheduledCTexamination.第三十页,共四十页。Exceptforthesefourcaseswithoutbiopsy,nodularlesionsintheremaining104patientsweresurgicallyremovedbecauseofthecontinuousincreaseinsi
35、zeand/ormassonfollow-upimagingstudies.ConsideringthedramaticallyincreasingincidenceoflungcancerinChina,patientsandphysiciansareveryalerttoitandthetreatmentmightbemoreaggressivethaninWesterncountries.第三十一页,共四十页。Tumourbiologystudieshaverevealedthatvasculatureremodellingorneoangiogenesisisoneoftheiniti
36、atingeventsoccurringintheearlystageoftumourdevelopment.Therefore,analysisofGGNsandrelatedbloodsupplyingvesselscouldprovideinformationonGGNdifferentiation.SmallbloodvesselsandtherelationshipsbetweenvesselsandlesionscanbereadilyrevealedandevaluatedinCTimagesacquiredwithmodernmulti-detectorscanners,esp
37、eciallywhenimagingdataarepost-processedusingadvancedcomputertechniques,includingMPRandCPR.ManystudieshavedemonstratedthatrelationshipsbetweenSPNsandvessels,especiallythevascularconvergencesign(VCS),arevaluableforestimationofthemalignancypotentialofSPNs第三十二页,共四十页。Somestudiesindicatedthatdiseaseprogre
38、ssionfromAAH,AIS,MIAtoIACisacomplicated,polygene-involveddynamicprocess.MIAorIACmaygraduallydevelopfromAAHandAIS.InterstitialfibrehyperplasiawithinlesionsisthemaincontributingfactortotypeIIIandIVvascularmorphologicalchanges.theformationmechanismofVCS,leadingtotheconclusionthatthecourseofadjacentvess
39、elsissubjecttolesions,especiallywhendiseasesinfiltratethebronchiovascularbundleandinterlobularsepta第三十三页,共四十页。Asaresult,involvedvesselsmightappeardistorted,rigidorconcentratedtowardsthelesion.Thus,itisreasonabletopostulate假设thatthevascularconvergencesigncommonlyseeninSPNs.Actually,thetypeIVGGN-vesse
40、lrelationshipresemblesVCStosomedegree.Theinvasiveadenocarcinomagroupiscomposedoftwosubgroups,MIAandIAC.SubgroupanalysisshowedMIAandIAChaddifferentpatternsofGGN-vesselrelationships.第三十四页,共四十页。TypeIIIvascularmorphologicalchangeswereobservedmoreoftenintheIACthanMIAsubgroup,indicatingthatwithincreasingm
41、alignancy,fibrehyperplasiastimulatedbymalignanttissuesmaybecomemoresevere,andsubsequentlyimpactsonvasculaturebecomeaggravated.Furthermore,tumourmetabolismisfasterthaninnormaltissues;therefore,thebloodsupplydemandedbytumoursismuchhigherthaninnormaltissues.Thesemechanismsindirectlyleadtovesselprolifer
42、ationandirregularluminaldilation.第三十五页,共四十页。Somestudieshaveshownthatendogenousand/orextrinsictumorangiogenesisandneovascularisationcouldbethedrivingfactorsofvascularabnormalitiesobservedinmalignantearlystage.AsaCTimagingsign,VCSdescribesarelationshipbetweenSPNsandvessels,oneormultiplevesselsconcentr
43、atingtowardsandpassingthroughlesionsorbeingtruncatedattheedgeoflesions.第三十六页,共四十页。Involvedvesselsmayappeartortuous,rigidorirregularlywideningandlinktopulmonaryarteriesorpulmonaryveins.Inthisstudy,theGGN-vesselrelationshipswerecategorizedintofourtypes.Statisticalanalysisindicatedthatwhentherelationsh
44、ipwastypeIIIorIV,especiallytypeIV,itwashighlylikelythatGGNsweremalignantinvasiveadenocarcinoma,withMIAmorethanIAC.Incontrast,themajorityofbenignandpreinvasivecaseswasseenintypeIortypeIIGGN-vesselrelationships.第三十七页,共四十页。Amajordrawbackofthisstudyisthelimitednumberofcases,especiallyinthebenigngroup,wh
45、ichmaycompromisethediagnosticpower.Hence,aprospectiveclinicaltrialwithmoreGGNcasesiswarrantedtofurtherevaluateandvalidatethediagnosticvalueoffindingsinthisstudy.Additionally,thisstudycouldbestrengthenediftheanalysiswereconductedwithacombinationofvesseltypesandotherGGNfeatures,suchassizeandmass.Massm
46、easurementscanreflectlesiongrowthearlierwithlessvariabilitythandiametermeasurements.第三十八页,共四十页。Inconclusion,thisstudydemonstratesthatdifferentGGNsmighthavedifferentrelationshipswithvesselsduetovariationindevelopmentalbiologyandbehaviour.UnderstandingandrecognizingGGN-vesselrelationshipsinCTimagingandthestrongcorrelationbetweeninvasiveadenocarcinomaandtypeIIIandIVrelationshipsmayhelpidentifywhichGGNsaremorelikelytobemalignant.第三十九页,共四十页。内容总结Multi-detectorspiralCTstudyoftherelationshipsbetweenpulmonaryground-glassnodulesandbloodvessels。Discussion第四十页,共四十页。