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Multimodalneuroimagingbasedclassificationofautismspectrumdisorderusinganatomical,neurochemical,andwhitemattercorrelatesNeuroimagingtechniques,suchasfMRI,structuralMRI,diffusiontensorimaging(DTI),andprotonmagneticresonancespectroscopy(1H-MRS)haveuncoveredevidenceforwidespreadfunctionalandanatomical（解剖学的）brainabnormalitiesinautismspectrumdisorder(ASD)suggestingittobeasystem-wideneuralsystemsdisorder.Nevertheless,mostpreviousstudieshavefocusedonexaminingoneindexofneuropathology（神经病理学的一个指标）throughasingleneuroimagingmodality（神经影像学形态）,andseldomusingmultiplemodalitiestoexaminethesamecohortofindividuals（几乎没有用多种方式检测同一批人）.Thecurrentstudyaimstobringtogethermultiplebrainimagingmodalities(structuralMRI,DTI,and1H-MRS)toinvestigatetheneuralarchitectureinthesamesetofindividuals(19high-functioningadultswithASDand18typicallydeveloping(TD)peers).（把多个大脑成像模式放到一起来研究同一组人（19个高功能ASD和18个正常人）的神经体系结构）Morphometryanalysisrevealedincreasedcorticalthickness（皮层增厚）inASDparticipants,relativetotypicalcontrols,acrosstheleftcingulate左扣带,leftparsopercularisoftheinferiorfrontalgyrus额下回,leftinferiortemporalcortex颞叶皮层,andrightprecuneus楔前叶,andreducedcorticalthicknessinrightcuneusandrightprecentralgyrus.ASDadultsalsohadreducedfractionalanisotropy(FA)andincreasedradialdiffusivity(RD)fortwoclustersontheforcepsminorofthecorpuscallosum,revealedbyDTIanalyses.1H-MRSresultsshowedareductionintheN-acetylaspartate/Creatineratioindorsalanteriorcingulatecortex(dACC背侧前扣带皮层)inASDparticipants.Adecisiontreeclassificationanalysisacrossthethreemodalitiesresultedinclassificationaccuracyof91.9%withFA,RD,andcorticalthicknessaskeypredictors.ExaminingthesamecohortofadultswithASDandtheirTDpeers,thisstudyfoundalterationsincorticalthickness皮质厚度的改变,whitematter(WM)connectivity,andneurochemicalconcentrationinASD.Thesefindingsunderscorethepotentialformultimodalimagingtobetterinformontheneuralcharacteristicsmostrelevanttothedisorder.2.Method&materials2.1.ParticipantsNineteenhigh-functioningadultswithASD(15males/4females;meanage:27.1years)and18typicallydeveloping(TD)peers(14males/4females;meanage:24.6years)participatedinthismultimodalneuroimagingstudy(seeTable1forde-mographicinformation).ThegroupswerematchedonageandIQ.Full-scaleIQ(FSIQ),verbalIQ(VIQ),andperformanceIQ(PIQ)wereassessedusingtheWechslerAbbreviatedScaleofIntelligence(WASI)(Wechsler,1999),handednessusingtheEdinburghHandednessInventory(Oldfield,1971),andASDsymptomsusingtheRitvoAutismAspergerDiagnosticScale-Revised(RAADS-R)(Ritvoetal.,2011).Age,FSIQ,VIQ,andPIQwerenotsignificantlydifferentbetweengroups.TheASDgroupscoredsignificantlyhigherontheRAADS-RcomparedtotheirTDpeers(seeTable1).ParticipantswithASDhadreceivedadiagnosisofanASDbasedonAutismDiagnosticInterview-Revised(ADI-R)(Rutter,LeCouteur,&Lord,2003)symptomsandAutismDiagnosticObservationSchedule(ADOS)(Lordetal.,2000).TDparticipantswerescreenedthroughaself-reporthistoryquestionnairetoruleoutneurologicaldisorders,suchasASD,ADHD,orTourette'sDisorder,thatcouldpotentiallyconfoundtheresults.SeveralASDparticipantsreportedtakingmedications,includingstimulantmedication(n¼6),antidepressants(n¼8),anxietymedication(n¼1),andantipsychoticmedication(n¼1).EightASDparticipantsreportednomedications,andnoTDpartic-ipantsreportedtakingmedication.Finally,allparticipantswerereportedtobenon-smokers.ThestudywasapprovedbytheInstitutionalReviewBoardofouruniversity,andallpar-ticipantsprovidedinformedconsentfortheirparticipationinthestudy.StructuralMRI,DTI,andMRspectroscopydatawereacquiredfromallparticipants.SeeSupplementaryFig.1foraflow-chartoverviewoftheproceduresinvolvedinmultimodalneuroimagingmethod.Table1—Participantdemographicinformation.2.3.1H-MRSimagingImagingwasperformedona3Thead-onlyscanner(SiemensAllegra,Erlangen,Germany)withacircularlypolarizedtransmit/receiveheadcoil.Aseriesofsagittal,coronal,andaxialT1-weightedanatomicalscanswereacquiredfor1H-MRSvoxelplacement(gradient-recalledechosequence;TR¼250msec,TE¼3.48msec,flipangle¼70,512Â512matrixsize,5mmslicethickness,and1.5mmgap).Sliceswerealignedtoanatomicalmidlinetocontrolforheadtilt.The1H-MRSvoxelfordorsalanteriorcingulatecortex(dACC)(20Â27Â10mm)waspositionedaroundthecenteroftheACC,identifiedcentrallyintheGMabovetheanteriorcorpuscallosum.The1H-MRSvoxelforposteriorcingulatecortex(PCC)(20Â27Â20mm)waspositionedabovethespleniumofthecorpuscallosumwiththelongaxisparalleltotheparieto-occipitalsulcus.Thesevoxelswereplacedonthebasisofthesagittalandcoronalimages,suchthattheamountofGMinthevoxelasviewedontheT1-weightedimagesismaximized.Followingmanualshimming,tooptimizefieldhomogeneityacrossthevoxel,water-suppressedspectrawerecollectedwiththepoint-resolvedspectroscopysequence(PRESS;TR/TE¼2000/80msec,1200Hzspectralbandwidth,1024points,128averages,4min24secscanningtime).MRSdatawereprocessedinjMRUI(version5.0)(Naressietal.,2001).TheresidualwaterpeakwasremovedusingtheHankel-Lanczossingularvaluesdecompositionfilter(Pijnappel,VandenBoogaart,DeBeer,&VanOrmondt,1992).SpectrawerequantifiedinthetimedomainbytheAMARESalgorithm阿玛算法(advancedmethodforaccurate,robu