1、Multi-detectorspiralCTstudyoftherelationshipsbetweenpulmonaryground-glassnodulesandbloodvesselsEurRadiol(2013)23:32713277Abstract Objective:Toinvestigatetherelationshipsbetweenpulmo-naryground-glassnodules(GGN)andbloodvesselsandtheirdiagnosticvaluesindifferentiatingGGNs.Conclusion:DifferentGGNshaved
2、ifferentrelationshipswithvessels.UnderstandingandrecognisingcharacteristicGGN-vesselrelationshipsmayhelpidentifywhichGGNsaremorelikelytobemalignant.KeyPoints Multi-detectorCToffersnewinformationaboutground-glassnodules.Differenttypesofground-glassnoduleshavedifferentrelationshipswithvessels.Thismayh
3、elpidentifywhichground-glassnodulesarelikelytobemalignant.IntroductionWiththeextensiveacceptanceoflow-dosemulti-detectorspiralCTinlungcancerscreening,thenumberofdetectedGGNsorfocalground-glassopacities(fGGOs)hasdramaticallyincreased.GGNscanresultfromneoplasms,suchaspulmonaryadenocarcinoma,orbenigndi
4、seases,suchasfocalfibrosis,inflammationoralveolarhaemorrhage.Inaddition,pre-invasiveabnormalities,includingatypicaladenomatoushyperplasia(AAH)andadenocarcinomainsitu(AIS).IthasbeenreportedthattheproportionofmalignancyinGGNsishigherthaninsolidpulmonarynodules(SPNs)andthemajorityofmalignantGGNsareaden
5、ocarcinoma.Duetoimagingresemblance,however,itisextremelychallengingtodifferentiatemalignantGGNsfromtheaforementionedbenigncounterparts.AccuratedifferentialdiagnosisofGGNswillassistphysicianstomaketreatmentdecisionsandimprovetreatmentoutcomesandprognosis.Severalinvestigatorshavesuggestedthatanalysiso
6、frelationshipsbetweenSPNsandsurroundingvesselscanhelppredictthelikelihoodofmalignancyinsuchnodules.TherelationshipbetweenGGNsandbloodvesselsremainsunknown.WhetherthisrelationshipcanbeutilisedtofacilitatethediagnosisofmalignantGGNsisaworthyofinvestigation.MaterialsandmethodsPatients Theimagingdataofp
7、atientswithpulmonaryGGNsreceivingthin-sectionmulti-detectorCTexaminationatourhospitalinJanuary2011throughNovember2012wereretrospectivelyreviewed.Alllesionsweresolitaryandmostofthem(104/108)surgicallyresectedwithin2weeksafterCTscanning.InclusioncriteriaTheGGNsizewaslessthan3cminthelargestdimension.gr
8、ound-glassopacity(GGO)comprisedmorethan50%oftheareaofthelesiononCT.-Anareaofover50%GGOwassetasthecutoffvaluetoexcludesolid/semi-solidlesions.-AlthoughsolidnodulesfrequentlyhadGGOcomponentsaroundtheirmargin,probablyrepresentingsurroundingoedemaormerelypooraerationofthesurroundinglungtissuesduetocompr
9、essionorretractionbynodules,thesenoduleshadalreadybeenwellinvestigatedusingCTandthereforewerenotthestudyobjectsUltimately,108patientswereenrolledintothisstudy,including38malesand70femaleswithmeanageof58.1812.89years(range,22to79years).43patientswereasymptomatic,28hadrespiratorysymptoms,and37hadlungc
10、ancerriskfactors,suchassmokingandfamilyhistory.Accordingtopathologicalfindings,GGNsweredividedintothreegroups:(1)Benigndiseasegroup(10cases),includingfournodulesdiagnosedwithacombinationofclinicalsymptomsandimagingpresentations(nodulesdisappearedorgraduallyreducedinsizeonmultiplefollow-upCTimaging)a
11、ndsixnodulesconfirmedbypathologicalexamination(1caseofsclerosinghaemangiomaand5casesofchronicinflammation).(2)Preinvasivediseasegroup(24cases),including7AAHsand17AISs.(3)theinvasiveadenocarcinomagroup(74cases),confirmedpathologically,therewere39non-mucinousminimallyinvasiveadenocarcinomas(MIA)and35i
12、nvasiveadenocarcinomas(IAC;specifically,13lepidicpredominantadenocarcinomas;19acinus-predominantadenocarcinomas;2papillary-predominantadenocarcinomasand1solidpredominantwithmucin粘蛋白production).CTimaginganalysis protocolparameters:0.625-mmsectionwidthwitha0.625-mmreconstructioninterval,pitchof0.984,1
13、20kVand250mA.Allimageswerereviewedwithahigh-resolution,2,0481,560pixel,standardlungwindow(ww,1,500HU;wl,-500HU)andmediastinalwindow(ww,350HU;wl,50HU)GGNscanbefurthersubdividedintomixedground-glassnodules(mGGNs)andpureground-glassnodules(pGGNs).ThepercentageoftheGGOcomponentwascalculatedasfollows:(DG
14、GO-D)/DGGO100,whereDGGOisthelargestdiameteroftheentirelesionandDisthelargestdiameterofthesolidcomponentwithinthelesion.BloodvesselanalysiswasperformedintermsofvascularmorphologyandvascularrelationshipswithGGNlesions.thediameterofpulmonaryvesselsgraduallydecreasesfromthehilumtowardtheperiphery.Ifthed
15、iameterofthevascularsegmentwithinlesionswaslargerthantheproximalsegmentorlesionvesselswereapparentlywiderthanothervesselsatthesamebranchlevel,thevesselwasdeemedasabnormalvascularbroadening.Thevesselswereconsideredtobedistortedorrigidiftravelingastrayfromtheexpectednormalcourse.Multiplesupplyingvesse
16、ls,withdifferentoriginatingsources,convergingtowardalesion,wereprobablyindicativeofanincreasedbloodcirculationwithin.Tofurtherclarifyaffiliationsofsupplyingvessels,wetracedvascularcoursesslice-wisebackwardtomajorvesselsinthehilum.TherelationshipsbetweentheGGNsandsupplyingbloodvesselswereanalysedinax
17、ialimages,MPRimagesCPRimages.theGGN-vesselrelationshipswerecategorizedintofourtypesaccordingtoimagingfeatures:typeI(pass-by),vesselspassedbyGGNswithoutdetectablesupplyingbranchestolesions.typeItypeII(pass-through),vesselspassedthroughthelesionswithoutobviousmorphologicalchangesintravelingpathorsize.
18、typeIII(distorted/dilated),vesselswithinlesionsweretortuousorrigidwithoutanincreaseinamounttypeIV(complicated),morecomplicatedvasculatureotherthandescribedintheaforementionedtypeswithinGGNs,forinstance,coexistenceofirregularvasculardilationandvascularconvergencefrommultiplesupplyingvessels.Pathologi
19、calanalysis ThepathologicaldiagnosisandcategorisationofAAH,AIS,MIAandIACweremadebasedonthenewpulmonaryadenocarcinomaclassification,2011edition.GGNswereresectedbyvideo-assistedthoracoscopyorthoracotomysurgery.Allhistologicalpreparationsandanalyseswereperformedbytwoseniorpathologists.Inthecaseofdisagr
20、eements,aconsensuswasreachedaftermutualdiscussionand/orconsultationwithathirdpathologist.StatisticalanalysisSPSS16.0forWindows,SPSS,Chicago,IllIndependentttestwasusedtocomparedifferentpathologicalgroups(benigndiseases,preinvasivediseasesandinvasiveadenocarcinoma)ofGGN.Correlationsbetweenpathological
21、findingsofGGNsandGGN-vesselrelationshipswereexaminedusingSpearmansranktest.GGN-vesselrelationshipsbetweenMIAandIACdiseaseswerecomparedusingPearsonschi-squaredtest.Whentherewasanexpectedvalue1orapretestprobabilityclosetothetestlevel,Fishersexacttestwasusedinstead.Statisticalresultswereconsideredsigni
22、ficantwhenthePvaluewaslessthan0.05.ResultsSize variation of GGN lesions TheaverageGGNsizeinthebenigngroup,preinvasivegroupandadenocarcinomasgroupwas8.12.5mm,9.35.6mmand14.86.0mm,respectively.Nosignificantdifferencesexistedbetweenthepreinvasivegroupandthebenigngroup(t=0.64,p=0.53).However,thereweresi
23、gnificantdifferencesbetweenbenignandpreinvasivegroupsandtheinvasiveadenocarcinomagroup(t=6.31,p=0.00;t=3.98,p=0.00).Correlations between GGN-vessel relationships and pathological findings Of108GGNs,typeI,II,IIIandIVGGNvessellrelationshipswereobservedin9,58,21and20cases,respectively.thetypeIIGGN-vess
24、elrelationshipwasthedominantrelationshipineachpathologicalgroup,seenin9benign(90.0%),16preinvasive(66.7%)and33invasive(44.6%)GGNparedwiththelowincidenceoftypeIIIandIVrelationshipsinbenignandpreinvasivegroupsthecombinedincidenceoftypeIII(25.7%)andIV(25.7%)relationshipsintheinvasiveadenocarcinomagroup
25、reached51.3%.MIA couldpresentfourtypes,withtypeIIasthemajortype(48.7%).ThecombinationoftypeIIandIVcomprised about80%oftheMIAsubgroup;forIAC,typeIIandIII hadthesameproportionof40%,hencethecombinationof 80%.StatisticalstudiesshowednodifferenceintypeIIbuta significantdifferencewasfoundintypeIIIandIVbet
26、ween MIAandIAClesions(p=0.02).Thevessel(s)travelingthroughGGNcouldbeartery(ies)(categoryA),vein(s)(categoryB),orartery(ies)andvein(s)(categoryC).TherewerenosignificantdifferencesandcorrelationsbetweenvascularcategoriesandGGNgroups(p=0.50and0.96,respectively).Afurtherexaminationofthecorrelationbetwee
27、nvascularcategoriesandGGNswithtypeIIIandIVrelationshipsdidnotgenerateanysignificantresults(p=0.70).Discussion Solitarypulmonarynodules(SPNs)arecommonfindingsinCTexaminationsandcanbedividedintotwogroupsbasedondensityvariation:solidnodulesandGGNs.In2011,theInternationalAssociationfortheStudyofLungCanc
28、er,theAmericanThoracicSocietyandtheEuropeanRespiratorySocietyproposedanewclassificationforlungadenocarcinomas.Inthenewclassificationsystem,thetermbronchioloalveolarcarcinoma(BAC)isnolongerused.TheformerBACconceptapplicabletomultiplecategoriesinthenewclassificationsystem,suchasAIS,MIAandthemucinoussu
29、btypeofadenocarcinoma.BothAISandAAHlesionsareclassifiedaspreinvasiveadenocarcinomaunderthenewclassificationsystem EarlystagelungcancersoftenpresentasGGNsinCTimages;thus,itisimportanttobefamiliarwiththecharacteristicsofGGNswithmalignantpotential,astimelysurgicalresectionwillimprovepatientsurvivalandq
30、ualityoflife,andforpatientswithbenignGGNs,unnecessarysurgicalprocedurescanbeavoided.Clinicaldatahaveshownthatnodulesizeisanindependentpredictivefactorofmalignancy,withsizeincreasingthelikelihoodofmalignancyincreasing,consistentwithourresultsthatthemeansizesofGGNsinbenign,preinvasiveandadenocarcinoma
31、groupswere8.1mm,9.3mmand14.7mm.Clinicalexperiencehasdemonstratedthatsomecommonimagingfeaturesofmalignantnodules,suchaspleuralindentation,spiculationandlobulation,areseldomseeninveryearlystagemalignantGGNs.Thisdemandsfurtherinvestigationofthisparticularabnormalimagingfindingtominimisemisdiagnosis.Int
32、hemanagementofGGNsinourpatients,clinicalguidelinesfromtheFleischnerSocietyandNationalComprehensiveCancerNetwork(NCCN)werereferenced.Eachindividualcasewasdiscussedbyamultidisciplinaryteam,includingdiagnosticradiologists,thoracicsurgeonsandpathologists,togenerateconsequentmanagementstrategies.Allpatie
33、ntsreceivedadequatefollow-upobservationwith/withoutsupportiveorantiinflammatorytreatment,whichexplainedthefactthatfourGGNsdisappearedpriortothenextscheduledCTexamination.Exceptforthesefourcaseswithoutbiopsy,nodularlesionsintheremaining104patientsweresurgicallyremovedbecauseofthecontinuousincreaseins
34、izeand/ormassonfollow-upimagingstudies.ConsideringthedramaticallyincreasingincidenceoflungcancerinChina,patientsandphysiciansareveryalerttoitandthetreatmentmightbemoreaggressivethaninWesterncountries.Tumourbiologystudieshaverevealedthatvasculatureremodellingorneoangiogenesisisoneoftheinitiatingevent
35、soccurringintheearlystageoftumourdevelopment.Therefore,analysisofGGNsandrelatedbloodsupplyingvesselscouldprovideinformationonGGNdifferentiation.SmallbloodvesselsandtherelationshipsbetweenvesselsandlesionscanbereadilyrevealedandevaluatedinCTimagesacquiredwithmodernmulti-detectorscanners,especiallywhe
36、nimagingdataarepost-processedusingadvancedcomputertechniques,includingMPRandCPR.ManystudieshavedemonstratedthatrelationshipsbetweenSPNsandvessels,especiallythevascularconvergencesign(VCS),arevaluableforestimationofthemalignancypotentialofSPNs SomestudiesindicatedthatdiseaseprogressionfromAAH,AIS,MIA
37、toIACisacomplicated,polygene-involveddynamicprocess.MIAorIACmaygraduallydevelopfromAAHandAIS.InterstitialfibrehyperplasiawithinlesionsisthemaincontributingfactortotypeIIIandIVvascularmorphologicalchanges.theformationmechanismofVCS,leadingtotheconclusionthatthecourseofadjacentvesselsissubjecttolesion
38、s,especiallywhendiseasesinfiltratethebronchiovascularbundleandinterlobularsepta Asaresult,involvedvesselsmightappeardistorted,rigidorconcentratedtowardsthelesion.Thus,itisreasonabletopostulate假设thatthevascularconvergencesigncommonlyseeninSPNs.Actually,thetypeIVGGN-vesselrelationshipresemblesVCStosom
39、edegree.Theinvasiveadenocarcinomagroupiscomposedoftwosubgroups,MIAandIAC.SubgroupanalysisshowedMIAandIAChaddifferentpatternsofGGN-vesselrelationships.TypeIIIvascularmorphologicalchangeswereobservedmoreoftenintheIACthanMIAsubgroup,indicatingthatwithincreasingmalignancy,fibrehyperplasiastimulatedbymal
40、ignanttissuesmaybecomemoresevere,andsubsequentlyimpactsonvasculaturebecomeaggravated.Furthermore，tumourmetabolismisfasterthaninnormaltissues;therefore,thebloodsupplydemandedbytumoursismuchhigherthaninnormaltissues.Thesemechanismsindirectlyleadtovesselproliferationandirregularluminaldilation.Somestud
41、ieshaveshownthatendogenousand/orextrinsictumorangiogenesisandneovascularisationcouldbethedrivingfactorsofvascularabnormalitiesobservedinmalignantearlystage.AsaCTimagingsign,VCSdescribesarelationshipbetweenSPNsandvessels,oneormultiplevesselsconcentratingtowardsandpassingthroughlesionsorbeingtruncated
42、attheedgeoflesions.Involvedvesselsmayappeartortuous,rigidorirregularlywideningandlinktopulmonaryarteriesorpulmonaryveins.Inthisstudy,theGGN-vesselrelationshipswerecategorizedintofourtypes.StatisticalanalysisindicatedthatwhentherelationshipwastypeIIIorIV,especiallytypeIV,itwashighlylikelythatGGNswere
43、malignantinvasiveadenocarcinoma,withMIAmorethanIAC.Incontrast,themajorityofbenignandpreinvasivecaseswasseenintypeIortypeIIGGN-vesselrelationships.Amajordrawbackofthisstudyisthelimitednumberofcases,especiallyinthebenigngroup,whichmaycompromisethediagnosticpower.Hence,aprospectiveclinicaltrialwithmore
44、GGNcasesiswarrantedtofurtherevaluateandvalidatethediagnosticvalueoffindingsinthisstudy.Additionally,thisstudycouldbestrengthenediftheanalysiswereconductedwithacombinationofvesseltypesandotherGGNfeatures,suchassizeandmass.Massmeasurementscanreflectlesiongrowthearlierwithlessvariabilitythandiametermea
45、surements.Inconclusion,thisstudydemonstratesthatdifferentGGNsmighthavedifferentrelationshipswithvesselsduetovariationindevelopmentalbiologyandbehaviour.UnderstandingandrecognizingGGN-vesselrelationshipsinCTimagingandthestrongcorrelationbetweeninvasiveadenocarcinomaandtypeIIIandIVrelationshipsmayhelpidentifywhichGGNsaremorelikelytobemalignant.
