多層螺旋CT肺結(jié)節(jié)和血管的關(guān)系

Multi-detectorspiralCTstudyoftherelationships

betweenpulmonaryground-glassnodulesandbloodvessels

EurRadiol(2013)23:3271–3277AbstractObjective:Toinvestigatetherelationshipsbetweenpulmo-naryground-glassnodules(GGN)andbloodvesselsandtheirdiagnosticvaluesindifferentiatingGGNs.Conclusion:DifferentGGNshavedifferentrelationshipswithvessels.UnderstandingandrecognisingcharacteristicGGN-vesselrelationshipsmayhelpidentifywhichGGNsaremorelikelytobemalignant.KeyPointsMulti-detectorCToffersnewinformationaboutground-glassnodules.Differenttypesofground-glassnoduleshavedifferentrelationshipswithvessels.Thismayhelpidentifywhichground-glassnodulesarelikelytobemalignant.Introduction

Withtheextensiveacceptanceoflow-dosemulti-detectorspiralCTinlungcancerscreening,thenumberofdetectedGGNsorfocalground-glassopacities(fGGOs)hasdramaticallyincreased.GGNscanresultfromneoplasms,suchaspulmonaryadenocarcinoma,orbenigndiseases,suchasfocalfibrosis,inflammationoralveolarhaemorrhage.Inaddition,pre-invasiveabnormalities,includingatypicaladenomatoushyperplasia(AAH)andadenocarcinomainsitu(AIS).IthasbeenreportedthattheproportionofmalignancyinGGNsishigherthaninsolidpulmonarynodules(SPNs)andthemajorityofmalignantGGNsareadenocarcinoma.Duetoimagingresemblance,however,itisextremelychallengingtodifferentiatemalignantGGNsfromtheaforementionedbenigncounterparts.

AccuratedifferentialdiagnosisofGGNswillassistphysicianstomaketreatmentdecisionsandimprovetreatmentoutcomesandprognosis.SeveralinvestigatorshavesuggestedthatanalysisofrelationshipsbetweenSPNsandsurroundingvesselscanhelppredictthelikelihoodofmalignancyinsuchnodules.TherelationshipbetweenGGNsandbloodvesselsremainsunknown.WhetherthisrelationshipcanbeutilisedtofacilitatethediagnosisofmalignantGGNsisaworthyofinvestigation.MaterialsandmethodsPatientsTheimagingdataofpatientswithpulmonaryGGNsreceivingthin-sectionmulti-detectorCTexaminationatourhospitalinJanuary2011throughNovember2012wereretrospectivelyreviewed.Alllesionsweresolitaryandmostofthem(104/108)surgicallyresectedwithin2weeksafterCTscanning.InclusioncriteriaTheGGNsizewaslessthan3cminthelargestdimension.ground-glassopacity(GGO)comprisedmorethan50%oftheareaofthelesiononCT.----Anareaofover50%GGOwassetasthecutoffvaluetoexcludesolid/semi-solidlesions.---AlthoughsolidnodulesfrequentlyhadGGOcomponentsaroundtheirmargin,probablyrepresentingsurroundingoedemaormerelypooraerationofthesurroundinglungtissuesduetocompressionorretractionbynodules,thesenoduleshadalreadybeenwellinvestigatedusingCTandthereforewerenotthestudyobjectsUltimately,108patientswereenrolledintothisstudy,including38malesand70femaleswithmeanageof58.18±12.89years(range,22to79years).43patientswereasymptomatic,28hadrespiratorysymptoms,and37hadlungcancerriskfactors,suchassmokingandfamilyhistory.Accordingtopathologicalfindings,GGNsweredividedintothreegroups:Benigndiseasegroup(10cases),includingfournodulesdiagnosedwithacombinationofclinicalsymptomsandimagingpresentations(nodulesdisappearedorgraduallyreducedinsizeonmultiplefollow-upCTimaging)andsixnodulesconfirmedbypathologicalexamination(1caseofsclerosinghaemangiomaand5casesofchronicinflammation).(2)Preinvasivediseasegroup(24cases),including7AAHsand17AISs.

(3)theinvasiveadenocarcinomagroup(74cases),confirmedpathologically,therewere39non-mucinousminimallyinvasiveadenocarcinomas(MIA)and35invasiveadenocarcinomas(IAC;specifically,13lepidicpredominantadenocarcinomas;19acinus-predominantadenocarcinomas;2papillary-predominantadenocarcinomasand1solidpredominantwithmucin粘蛋白

production).CTimaginganalysisprotocolparameters:0.625-mmsectionwidthwitha0.625-mmreconstructioninterval,pitchof0.984,120kVand250mA.Allimageswerereviewedwithahigh-resolution,2,048×1,560pixel,standardlungwindow(ww,1,500HU;wl,-500HU)andmediastinalwindow(ww,350HU;wl,50HU)GGNscanbefurthersubdividedintomixedground-glassnodules(mGGNs)andpureground-glassnodules(pGGNs).ThepercentageoftheGGOcomponentwascalculatedasfollows:([DGGO-D])/DGGO×100,whereDGGOisthelargestdiameteroftheentirelesionandDisthelargestdiameterofthesolidcomponentwithinthelesion.BloodvesselanalysiswasperformedintermsofvascularmorphologyandvascularrelationshipswithGGNlesions.thediameterofpulmonaryvesselsgraduallydecreasesfromthehilumtowardtheperiphery.Ifthediameterofthevascularsegmentwithinlesionswaslargerthantheproximalsegmentorlesionvesselswereapparentlywiderthanothervesselsatthesamebranchlevel,thevesselwasdeemedasabnormalvascularbroadening.Thevesselswereconsideredtobedistortedorrigidiftravelingastrayfromtheexpectednormalcourse.Multiplesupplyingvessels,withdifferentoriginatingsources,convergingtowardalesion,wereprobablyindicativeofanincreasedbloodcirculationwithin.Tofurtherclarifyaffiliationsofsupplyingvessels,wetracedvascularcoursesslice-wisebackwardtomajorvesselsinthehilum.TherelationshipsbetweentheGGNsandsupplyingbloodvesselswereanalysedinaxialimages,MPRimagesCPRimages.

theGGN-vesselrelationshipswerecategorizedintofourtypesaccordingtoimagingfeatures:typeI(pass-by),vesselspassedbyGGNswithoutdetectablesupplyingbranchestolesions.typeI

typeII(pass-through),vesselspassedthroughthelesionswithoutobviousmorphologicalchangesintravelingpathorsize.typeIII(distorted/dilated),vesselswithinlesionsweretortuousorrigidwithoutanincreaseinamounttypeIV(complicated),morecomplicatedvasculatureotherthandescribedintheaforementionedtypeswithinGGNs,forinstance,coexistenceofirregularvasculardilationandvascularconvergencefrommultiplesupplyingvessels.Pathologicalanalysis

ThepathologicaldiagnosisandcategorisationofAAH,AIS,MIAandIACweremadebasedonthenewpulmonaryadenocarcinomaclassification,2011edition.GGNswereresectedbyvideo-assistedthoracoscopyorthoracotomysurgery.Allhistologicalpreparationsandanalyseswereperformedbytwoseniorpathologists.Inthecaseofdisagreements,aconsensuswasreachedaftermutualdiscussionand/orconsultationwithathirdpathologist.StatisticalanalysisSPSS16.0forWindows,SPSS,Chicago,IllIndependentttestwasusedtocomparedifferentpathologicalgroups(benigndiseases,preinvasivediseasesandinvasiveadenocarcinoma)ofGGN.CorrelationsbetweenpathologicalfindingsofGGNsandGGN-vesselrelationshipswereexaminedusingSpearman’sranktest.GGN-vesselrelationshipsbetweenMIAandIACdiseaseswerecomparedusingPearson’schi-squaredtest.Whentherewasanexpectedvalue<1orapretestprobabilityclosetothetestlevel,Fisher’sexacttestwasusedinstead.StatisticalresultswereconsideredsignificantwhenthePvaluewaslessthan0.05.

Results

SizevariationofGGNlesionsTheaverageGGNsizeinthebenigngroup,preinvasivegroupandadenocarcinomasgroupwas8.1±2.5mm,9.3±5.6mmand14.8±6.0mm,respectively.Nosignificantdifferencesexistedbetweenthepreinvasivegroupandthebenigngroup(t=?0.64,p=0.53).However,thereweresignificantdifferencesbetweenbenignandpreinvasivegroupsandtheinvasiveadenocarcinomagroup(t=?6.31,p=0.00;t=?3.98,p=0.00).CorrelationsbetweenGGN-vesselrelationshipsandpathologicalfindingsOf108GGNs,typeI,II,IIIandIVGGNvessellrelationshipswereobservedin9,58,21and20cases,respectively.thetypeIIGGN-vesselrelationshipwasthedominantrelationshipineachpathologicalgroup,seenin9benign(90.0%),16preinvasive(66.7%)and33invasive(44.6%)GGNcases.

comparedwiththelowincidenceoftypeIIIandIVrelationshipsinbenignandpreinvasivegroupsthecombinedincidenceoftypeIII(25.7%)andIV(25.7%)relationshipsintheinvasiveadenocarcinomagroupreached51.3%.MIA

couldpresentfourtypes,withtypeIIasthemajortype

(48.7%).ThecombinationoftypeIIandIVcomprised

about80%oftheMIAsubgroup;forIAC,typeIIandIII

hadthesameproportionof40%,hencethecombinationof

80%.StatisticalstudiesshowednodifferenceintypeIIbuta

significantdifferencewasfoundintypeIIIandIVbetween

MIAandIAClesions(p=0.02).Thevessel(s)travelingthroughGGNcouldbeartery(ies)(categoryA),vein(s)(categoryB),orartery(ies)andvein(s)(categoryC).TherewerenosignificantdifferencesandcorrelationsbetweenvascularcategoriesandGGNgroups(p=0.50and0.96,respectively).AfurtherexaminationofthecorrelationbetweenvascularcategoriesandGGNswithtypeIIIandIVrelationshipsdidnotgenerateanysignificantresults(p=0.70).DiscussionSolitarypulmonarynodules(SPNs)arecommonfindingsinCTexaminationsandcanbedividedintotwogroupsbasedondensityvariation:solidnodulesandGGNs.In2011,theInternationalAssociationfortheStudyofLungCancer,the

AmericanThoracicSocietyandtheEuropeanRespiratorySocietyproposedanewclassificationforlungadenocarcinomas.Inthenewclassificationsystem,thetermbronchioloalveolarcarcinoma(BAC)isnolongerused.TheformerBACconceptapplicabletomultiplecategoriesinthenewclassificationsystem,suchasAIS,MIAandthemucinoussubtypeofadenocarcinoma.BothAISandAAHlesionsareclassifiedaspreinvasiveadenocarcinomaunderthenewclassificationsystem

EarlystagelungcancersoftenpresentasGGNsinCTimages;thus,itisimportanttobefamiliarwiththecharacteristicsofGGNswithmalignantpotential,astimelysurgicalresectionwillimprovepatientsurvivalandqualityoflife,andforpatientswithbenignGGNs,unnecessarysurgicalprocedurescanbeavoided.Clinicaldatahaveshownthatnodulesizeisanindependentpredictivefactorofmalignancy,withsizeincreasingthelikelihoodofmalignancyincreasing,consistentwithourresultsthatthemeansizesofGGNsinbenign,preinvasiveandadenocarcinomagroupswere8.1mm,9.3mmand14.7mm.Clinicalexperiencehasdemonstratedthatsomecommonimagingfeaturesofmalignantnodules,suchaspleuralindentation,spiculationandlobulation,areseldomseeninveryearlystagemalignantGGNs.Thisdemandsfurtherinvestigationofthisparticularabnormalimagingfindingtominimisemisdiagnosis.InthemanagementofGGNsinourpatients,clinicalguidelinesfromtheFleischnerSocietyandNationalComprehensiveCancerNetwork(NCCN)werereferenced.Eachindividualcasewasdiscussedbyamultidisciplinaryteam,includingdiagnosticradiologists,thoracicsurgeonsandpathologists,togenerateconsequentmanagementstrategies.Allpatientsreceivedadequatefollow-upobservationwith/withoutsupportiveorantiinflammatorytreatment,whichexplainedthefactthatfourGGNsdisappearedpriortothenextscheduledCTexamination.Exceptforthesefourcaseswithoutbiopsy,nodularlesionsintheremaining104patientsweresurgicallyremovedbecauseofthecontinuousincreaseinsizeand/ormassonfollow-upimagingstudies.ConsideringthedramaticallyincreasingincidenceoflungcancerinChina,patientsandphysiciansareveryalerttoitandthetreatmentmightbemoreaggressivethaninWesterncountries.Tumourbiologystudieshaverevealedthatvasculatureremodellingorneoangiogenesisisoneoftheinitiatingeventsoccurringintheearlystageoftumourdevelopment.Therefore,analysisofGGNsandrelatedbloodsupplyingvesselscouldprovideinformationonGGNdifferentiation.SmallbloodvesselsandtherelationshipsbetweenvesselsandlesionscanbereadilyrevealedandevaluatedinCTimagesacquiredwithmodernmulti-detectorscanners,especiallywhenimagingdataarepost-processedusingadvancedcomputertechniques,includingMPRandCPR.ManystudieshavedemonstratedthatrelationshipsbetweenSPNsandvessels,especiallythevascularconvergencesign(VCS),arevaluableforestimationofthemalignancypotentialofSPNsSomestudiesindicatedthatdiseaseprogressionfromAAH,AIS,MIAtoIACisacomplicated,polygene-involveddynamicprocess.MIAorIACmaygraduallydevelopfromAAHandAIS.InterstitialfibrehyperplasiawithinlesionsisthemaincontributingfactortotypeIIIandIVvascularmorphologicalchanges.theformationmechanismofVCS,leadingtotheconclusionthatthecourseofadjacentvesselsissubjecttolesions,especiallywhendiseasesinfiltratethebronchiovascularbundleandinterlobularseptaAsaresult,involvedvesselsmightappeardistorted,rigidorconcentratedtowardsthelesion.Thus,itisreasonabletopostulate假設(shè)

thatthevascularconvergencesigncommonlyseeninSPNs.Actually,thetypeIVGGN-vesselrelationshipresemblesVCStosomedegree.Theinvasiveadenocarcinomagroupiscomposedoftwosubgroups,MIAandIAC.SubgroupanalysisshowedMIAandIAChaddifferentpatternsofGGN-vesselrelationships.TypeIIIvascularmorphologicalchangeswereobservedmoreoftenintheIACthanMIAsubgroup,indicatingthatwithincreasingmalignancy,fibrehyperplasiastimulatedbymalignanttissuesmaybecomemoresevere,andsubsequentlyimpactsonvasculaturebecomeaggravated.Furthermore，tumourmetabolismisfasterthaninnormaltissues;therefore,thebloodsupplydemandedbytumoursismuchhigherthaninnormaltissues.Thesemechanismsindirectlyleadtovesselproliferationandirregularluminaldilation.Somestudieshaveshownthatendogenousand/orextrinsictumorangiogenesisandneovascularisationcouldbethedrivingfactorsofvascularabnormalitiesobservedinmalignantearlystage.AsaCTimagingsign,VCSdescribesarelationshipbetweenSPNsandvessels,oneormultiplevesselsconcentratingtowardsandpassingthroughlesionsorbeingtruncatedattheedgeoflesions.Involvedvesselsmayappeartortuous,rigidorirregularlywideningandlinktopulmonaryarteriesorpulmonaryveins.Inthisstudy,theGGN-vesselrelationshipswerecategorizedintofourtypes.StatisticalanalysisindicatedthatwhentherelationshipwastypeIIIorIV,especiallytypeIV,itwashighlylikelythatGGNsweremalignantinvasiveadenocarcinoma,withMIAmorethanIAC.Incontrast,themajorityofbenignandpreinvasivecaseswasseenintypeIortypeIIGGN-vesselrelationships.Amajordrawbackofthisstudyisthelimitednumberofcases,especiallyinthebenigngroup,whichmaycompromisethediagnosticpower.Hence,aprospectiveclinicaltrialwithmoreGGNcasesiswarrantedtofurtherevaluateandvalidatethediagnosticvalueoffindingsinthisstudy.Additionally,thisstudycouldbestrengthenediftheanalysiswereconductedwithacombinationofvesseltypesandotherGGNfeatures,suchassizeandmass.Massmeasurementscanreflectlesiongrowthearlierwithlessvariabilitythandiametermeasurements.Inconclusion,thisstudydemonstratesthatdifferentGGNsmighthavedifferentrelationshipswithvesselsduetovariationindevelopmentalbiologyandbehaviour.UnderstandingandrecognizingGGN-vesselrelationshipsinCTimagingandthestrongcorrelationbetweeninvasiveadenocarcinomaandtypeIIIandIVrelationshipsmayhelpidentifywhichGGNsaremorelikelytobemalignant.附錄資料：不需要的可以自行刪除兒童孤獨(dú)癥早期篩查名稱問題自閉癥、孤獨(dú)癥、kanner綜合征嬰兒精神分裂廣泛性發(fā)育障礙：孤獨(dú)癥、阿斯伯格綜合征、雷特綜合征、退化性精神病、不能分類的廣泛性發(fā)育障礙孤獨(dú)癥譜系障礙（ASD）：包括孤獨(dú)癥、阿斯伯格綜合征、未分類的廣泛性發(fā)育障礙。孤獨(dú)癥的主要表現(xiàn)1、交流障礙2、語言障礙3、狹隘興趣和重復(fù)刻板行為孤獨(dú)癥的語言障礙

不會說話或說話遲，是就診首位原因半數(shù)以上患兒終身無語？（15%）語言倒退自言自語、聽不懂或無意義的語言電視廣告語言語言刻板、重復(fù)、鸚鵡式語言你我（人稱代詞）不分自我中心的話題語言倒退與孤獨(dú)癥09年的一項(xiàng)研究表明語言技能喪失是孤獨(dú)癥兒童特有的現(xiàn)象15%的孤獨(dú)癥譜系障礙兒童顯示出語言喪失孤獨(dú)癥的交流障礙不（少）看不點(diǎn)頭不（少）指不搖頭不（少）應(yīng)不尋求安慰不（少）說該怕不怕不參照不該怕卻怕不炫耀該笑（哭）不笑（哭）孤獨(dú)癥的交流障礙缺乏目光對視，“目中無人”獨(dú)自嬉玩，不合作通常不怕陌生人不喜歡擁抱或避免與他人接觸無恰當(dāng)?shù)纳眢w語言，例如點(diǎn)頭搖頭極少微笑、難相處與父母的依戀情感障礙或延緩不恰當(dāng)、奇怪的或延遲的交流或情感反應(yīng)孤獨(dú)癥的刻板行為種類繁多，各個(gè)兒童不同時(shí)期表現(xiàn)不一重復(fù)動作（看手、轉(zhuǎn)圈、搖晃等）重復(fù)行為（開關(guān)、撕紙、看電視廣告、天氣預(yù)報(bào)、同一首歌、天線寶寶）重復(fù)刻板語言強(qiáng)迫行為（睡眠、路線、排便、座位）強(qiáng)迫思維（重復(fù)問題、難以擺脫的痛苦）對某些物件或事情（科學(xué)事實(shí)）不尋常興趣孤獨(dú)癥兒童的智力半數(shù)以上正?；虺?yōu)秀機(jī)械記憶力音樂、繪畫和藝術(shù)能力科學(xué)領(lǐng)域的興趣和能力，少數(shù)在某一或幾方面有特殊能力智障學(xué)者現(xiàn)象智力正常范圍兒童智力結(jié)構(gòu)顯著異常，通常PIQ>VIQ孤獨(dú)癥兒童的感覺異常聽知覺敏感，喜愛某些聲音，對另一些聲音特別恐懼觸覺異常，表現(xiàn)在對物件的好惡痛覺異常，多不怕痛視覺異常：對特別圖像的喜好或厭惡、喜歡斜視、倒視本體覺異常：喜歡坐車、怕坐電梯、喜旋轉(zhuǎn)。運(yùn)動一般十分靈活孤獨(dú)癥的其他表現(xiàn)多數(shù)兒童多動明顯，來回跑動不知疲倦少數(shù)兒童有癲癇不聽話、違拗、攻擊、自傷、沖動、固執(zhí)、激動等行為多見，可能與父母教育方式有關(guān)日常生活自理能力差孤獨(dú)癥的診斷沒有特異性實(shí)驗(yàn)室診斷手段CT,MRI,SPECT,PET,腦電圖，染色體等檢查有助于鑒別診斷根據(jù)典型臨床表現(xiàn)孤獨(dú)癥診斷不難診斷可根據(jù)DSM-Ⅳ或ICD-10為標(biāo)準(zhǔn)CHAT,CARS,ABC是國內(nèi)常用篩查量表ADI-R,ADOS是診斷“金標(biāo)準(zhǔn)”，新的篩查量表如SRS考慮了譜系障礙的問題孤獨(dú)癥篩查的重要性孤獨(dú)癥流行病學(xué)研究：發(fā)病率的變遷1/110孤獨(dú)癥的病因?qū)W研究：尚未明了，遺傳主導(dǎo)、環(huán)境改變表型孤獨(dú)癥的診斷現(xiàn)況：自由診，年齡偏大孤獨(dú)癥的治療研究：尚無藥物，但可治早期合理系統(tǒng)化干預(yù)訓(xùn)練，絕大部分兒童會有不同程度改善，一部分孩子可能獲得基本痊愈或基本具備自主生活、學(xué)習(xí)和工作能力（痊愈率為3%~25%）早期篩查的必要性大多數(shù)孤獨(dú)癥兒童的父母開始肯定的擔(dān)心與尋求幫助是在2歲時(shí)90%的兒童在24月以內(nèi)表現(xiàn)異常，50-60%在12月以內(nèi)表現(xiàn)異常；出現(xiàn)癥狀到引起父母