fmri在功能性慢性內(nèi)臟痛研究中的進(jìn)展課件

fMRI在功能性慢性內(nèi)臟痛研究中的應(yīng)用和進(jìn)展

TheapplicationandprogressoffMRIinthestudyoffunctionalchronicvisceralpain

江蘇省xxx重點(diǎn)實(shí)驗(yàn)室

JiangsuProvincekeyLabofxxx14級(jí)研究生：xxx

導(dǎo)師：xxx教授

綜述報(bào)告結(jié)語(yǔ)與展望fMRI在CRD實(shí)驗(yàn)動(dòng)物中的應(yīng)用fMRI在臨床IBS病人中的應(yīng)用及進(jìn)展目錄fMRI與功能性慢性內(nèi)臟痛背景簡(jiǎn)介

一、二、三、四、一、fMRI與功能性慢性內(nèi)臟痛背景簡(jiǎn)介

計(jì)算機(jī)體層成像(CT)20世紀(jì)50~60年代70~80年代80~90年代19世紀(jì)末20世紀(jì)初

X線放射診斷學(xué)正電子發(fā)射成像(PET)單光子發(fā)射體層成像(SPECT)磁共振功能成像〔FMRI〕超聲成像(USG)核素γ閃爍成像(γ-scintigraphy)計(jì)算機(jī)體層成像(CT)磁共振成像(MRI)數(shù)字血管減影(DSA)1.1醫(yī)學(xué)影像學(xué)開(kāi)展簡(jiǎn)史

1.2fMRI歷史194619731992199119771990取得了臨床MRI掃描器的專(zhuān)利；Mansfield使用回波成像(EPI)序列更快的得到圖像FelixBloch和EdwardPurcell分別發(fā)現(xiàn)了核磁共振(NuclearMagneticResonance)現(xiàn)象Lauterbur提出NMR可以用來(lái)成像Ogawa通過(guò)T2加權(quán)像觀察到BOLD效應(yīng)

Belliveau首次通過(guò)對(duì)比機(jī)制觀察到功能圖像

Ogawa&Kwong發(fā)表了通過(guò)BOLD信號(hào)成像的結(jié)果1.3fMRI簡(jiǎn)介功能性磁共振成像〔functionalMagneticResonanceImaging，fMRI〕：是利用磁振造影來(lái)測(cè)量神經(jīng)元活動(dòng)所引發(fā)之血液動(dòng)力的改變。目前主要是運(yùn)用在研究人及動(dòng)物的腦或脊髓。capillary含氧血紅蛋白去氧血紅蛋白BloodOxygenLevelDepend1.4功能性慢性內(nèi)臟痛簡(jiǎn)介功能性慢性內(nèi)臟痛〔Functionalchronicvisceralpain〕：是一種以腹痛或腹部不適,伴或不伴排便習(xí)慣改變?yōu)樘卣鞯奈改c功能性疾病,病癥至少持續(xù)3個(gè)月,但結(jié)腸組織未見(jiàn)明顯病理學(xué)變化。功能性慢性內(nèi)臟痛IBSCRD與內(nèi)臟傷害性感受處理息息相關(guān)的三個(gè)環(huán)路：

Emerana.Mayeretal.,Gastroenterology(2006)C穩(wěn)態(tài)傳入網(wǎng)絡(luò)包括：臂旁核、丘腦、島葉、dACC等。穩(wěn)態(tài)傳入網(wǎng)絡(luò)〔homeostatic-afferentnetwork〕Figure1.Ascendingprojectionsofhomeostaticafferents.(B)Spino-thalamo-corticalsystem.(C)Corticalmodulationofhomeostaticafferentinputtothecentralnervoussystem.1.4.2情緒-覺(jué)醒網(wǎng)絡(luò)〔emotional–arousalnetwork〕

和皮層處理網(wǎng)絡(luò)〔cortical–modulatorynetwork〕Fig.2.Cortical-affectivecircuiteffectiveconnectivitymodel.J.S.Labusetal.Pain(2021)情緒-覺(jué)醒環(huán)路:

杏仁核、藍(lán)斑復(fù)合體、嘴側(cè)/膝下/膝上扣帶回等；皮層處理環(huán)路:前額葉皮質(zhì)、眶顳額葉皮質(zhì)等。

Fig.3.Sexdifferencesinactivationofthehomeostaticafferent,emotional–arousal,andcortical–modulatorynetworksinresponsetonoxiousvisceralstimulation.

MaleFemaleZ.Wangetal.,Pain(2021)1.4.3內(nèi)臟刺激腦部環(huán)路聯(lián)系二、fMRI在臨床IBS病人中的應(yīng)用IBS患者與正常人之間腦局部一致性(ReHo)的差異Figure4.

ReHodifferencesbetweenIBSpatientsandcontrols.J.KEetal.,NeurogastroenterolMotil(2021)中央后回、丘腦、小腦蚓、頂葉aMCC、pACC、sACC、vm/dl/vlPFCIBS組在給予撫慰劑后接受直腸刺激的腦區(qū)激活Figure.5.Rectaldistension-inducedneuralactivationinthecingulatecortex(A)andthesomatosensorycortex(S1/S2,B).JuliaSchmidetal.,Neurogastroenterology(2021)MCC、島葉、丘腦、杏仁核PCCS1、小腦S2S1、S2IBS組和對(duì)照組接受直腸刺激后的腦區(qū)激活Figure6.

Majorsitesofactivationdifferencesbetweenirritablebowelsyndrome(IBS)andhealthycontrolsubjects.C.L.Kwanetal.,Neurology(2005)對(duì)照組和IBS組接受直腸刺激誘導(dǎo)的腦區(qū)激活Figure7.(A–D)BrainactivationincontrolsandIBSpatientsduringsubliminalandliminalrectaldistensions.(E)Seedregionsdefinedintheanteriorinsula(left)andaMCC(right)basedonrectaldistension-inducedactivationinthe

controlgroup.(F)Seedregionsdefinedsimilarlyinthebilateralanteriorinsula(left)andpACC(right)intheIBSpatientgroup.X.LIU，NeurogastroenterolMotil(2021)PCC、PAGaMCC、insula、dmPFC、caudate,andPAG感覺(jué)運(yùn)動(dòng)皮質(zhì)、vmPFC運(yùn)動(dòng)皮質(zhì)

SMAthalamus,SMA,下頂葉組內(nèi)、組間激活功能區(qū)的比較Figure8.(A)Comparisonofbrainactivationbetweensubliminalandliminalstimulationconditionsinthecontrolgroup.(B)ThesameintheIBSpatientgroup.(C)GroupcomparisonofbrainactivationbetweencontrolsandIBSpatientsduringsubliminalstimulation.(D)Thesameduringliminalstimulation.對(duì)照組和IBS組島葉和扣帶回種子區(qū)的功能聯(lián)系Figure9.(AandB)FunctionalconnectivityoftheinsulaseedsinthecontrolandIBSgroupsduringliminalstimulation.(CandD)ThesameintheaMCC(incontrols)andpACC(inIBSpatients)seedsduringliminalstimulation.(EandF)GroupcomparisonsofinsularandcingulatefunctionalconnectivitybetweencontrolsandIBSpatients.(IBSVS.controls:dmPFC,vmPFC,dlPFC,andPCC)dlPFCIBS組和對(duì)照組在情緒認(rèn)知過(guò)程中的性別差異Fig.10.

Sexdifferences(IBS+HC)forME-MF(ME-MF=matchingemotion–matchingform).J.S.Labusetal.Pain(2021)Fig.11.DiseaseandsexdifferencesforME-MF.IBS女性病人腦區(qū)注意力相關(guān)網(wǎng)絡(luò)的fMRIC.S.HUbbardetal.,NeurogastroenterolMotil(2021)Figure12。

StatisticalTmapsfortheregionofinterestanalysesforthealtering,orienting，andexecutivecontrolconditionsoftheAttentionNetworkTest(ANT).健康成年人接受直腸擴(kuò)張刺激的纖維束聯(lián)系Fig.13.Connectionsbetweenthemainareasactivatedduringvisceralperception.X.Moissetetal.,EuropeanJournalofPain(2021)目前關(guān)于IBS的fMRI研究主要集中在靜息態(tài)、不同條件直腸刺激下的腦區(qū)變化，便秘型和腹瀉型差異、性別差異，撫慰劑效應(yīng)、痛覺(jué)期待因素、注意力因素、不同的干預(yù)治療措施對(duì)IBS腦區(qū)變化的影響。近年來(lái)，關(guān)于IBS在情緒、認(rèn)知、情感處理中的進(jìn)展得到了關(guān)注，為探討情感體驗(yàn)成分在疼痛的作用中提供了更多的依據(jù)和思考。三、fMRI在實(shí)驗(yàn)動(dòng)物中的應(yīng)用雄性S-D大鼠在接受不同壓力下CRD刺激后的腦區(qū)激活J.Lazovicetal.,NeurogastroenterolMotil(2005)Figure14.AxialfMRIimagesoftheratbrainatthepressuresof40mmHg(A)60mmHg(B)and80mmHg(C),ofthesameanimal.amygdalaHypothalamus（PVN）NTStrigeminalnucleusFigure15.AxialfMRIimagesoftheratbrainduringtherectalballoonstimulationatthepressureof60mmHg(A)and80mmHg(B),ofthesameanimal.SCPAGthalamusCblHiIL、PL雄性F344大鼠腦內(nèi)杏仁核植入皮質(zhì)酮對(duì)內(nèi)臟刺激的fMRI變化Figure16.SpecificnucleiactivatedinratswithCORT(AandC)micropelletsbutnotactivatedinratswithCHOL(BandD)〔A、B：40mmHgor；C、D：60mmHg〕.Figure17.Specificnucleiactivatedby60mmHgCRDbutnotat40mmHgCRDinratswitheitherCORT(CandD)orCHOL(AandB)(A、C:60mmHg;B、D:40mmHg).AnthonyC.Johnsonetal.,PlosOne(2021)Wistar大鼠接受CRD的SPECT局部腦血流〔regionalcerebralbloodflow，rCBF〕顯像Fig.18.Comparisonofchangesinregionalcerebralbloodflow-relatedtissueradioactivityinresponseto60-mmHgcolorectaldistensioninfemaleandmalerats.Z.Wangetal.,Pain(2021)目前關(guān)于fMRI在CRD模型所致慢性內(nèi)臟痛的實(shí)驗(yàn)尚未開(kāi)展。接受急性結(jié)直腸內(nèi)臟刺激的動(dòng)物在fMRI中的研究也較少，重復(fù)刺激和單次刺激的差異與否，不同的給藥途徑，不同藥物的干預(yù)等都存在較大的科研價(jià)值。當(dāng)然fMRI活體動(dòng)物成像麻醉對(duì)實(shí)驗(yàn)存在一定的影響，但活體成像后動(dòng)物可以繼續(xù)進(jìn)行分子生物學(xué)等實(shí)驗(yàn)，在一定程度上降低了實(shí)驗(yàn)相關(guān)性數(shù)據(jù)的個(gè)體差異和組間、組內(nèi)差異，由此關(guān)于CRD模型在fMRI中的根底研究亟待開(kāi)展。四、結(jié)語(yǔ)與展望從認(rèn)知神經(jīng)科學(xué)的角度，研究人腦對(duì)復(fù)雜任務(wù)的解決固然重要，但復(fù)雜任務(wù)刺激不利于臨床應(yīng)用；多數(shù)研究都集中在孤立腦區(qū)的激活與否，沒(méi)有考慮腦區(qū)之間的相互關(guān)系，即忽略了區(qū)域之間時(shí)間上的關(guān)聯(lián)性；通過(guò)激活腦區(qū)的功能相關(guān)性，可以為神經(jīng)生物學(xué)、分子生物學(xué)、藥理學(xué)和行為學(xué)治療等提供更有指導(dǎo)意義的思路；研究說(shuō)明臨床上關(guān)于IBS的中樞認(rèn)知處理過(guò)程在疾病的發(fā)生開(kāi)展中具有重要作用，但受倫理學(xué)、治療干預(yù)尤其是腦區(qū)等的限制，其開(kāi)展受到一定的阻礙；由于模型構(gòu)建、小動(dòng)物磁共振實(shí)驗(yàn)裝置等的限制，目前關(guān)于fMRI在功能性慢性內(nèi)臟痛實(shí)驗(yàn)動(dòng)物上的研究甚少，生命早期CRD作為IBS病人的經(jīng)典模型之一，開(kāi)展此慢性內(nèi)臟痛動(dòng)物實(shí)驗(yàn)，實(shí)現(xiàn)與臨床科研之間的生物轉(zhuǎn)化亟待解決。參考文獻(xiàn)1.Lazovic,J,Wrzos,H.F,Yang,Q.X,etal.Regionalactivationintheratbrainduringvisceralstimulationdetectedbyc-fosexpressionandfMRI[J].Neurogastroenterology&Motility,2005,17(4):548–556.2.Annalisa,DalLago,AlbertoE,Minetti,Pietro,Biondetti,etal.Magneticresonanceimagingoftherectumduringdistension.[J].DiseasesoftheColon&Rectum,2005,48(6):1220-1227.3.KwanCL,DiamantNE,PopeG,,etal.Abnormalforebrainactivityinfunctionalboweldisorderpatientswithchronicpain.[J].Neurology,2005,65(8):1268-1277.4.LawalA,KernM,SidhuH,etal.Novelevidenceforhypersensitivityofvisceralsensoryneuralcircuitryinirritablebowelsyndromepatients.[J].Gastroenterology,2006,130(1):26–33.5.JohnsonAC,BrentM,JelenaL,etal.BrainActivationinResponsetoVisceralStimulationinRatswithAmygdalaImplantsofCorticosterone:AnfMRIStudy[J].PlosOne,2021,5(1)::e8573.6.LarssonMBO,KirstenT,CraigAD,etal.BrainResponsestoVisceralStimuliReflectVisceralSensitivityThresholdsinPatientsWithIrritableBowelSyndrome[J].Gastroenterology,2021,142(3):463-472.7.KeszthelyiD,TroostFJ,MascleeAA.Irritablebowelsyndrome:methods,mechanisms,andpathophysiology.Methodstoassessvisceralhypersensitivityinirritablebowelsyndrome.[J].AmericanJournalofPhysiologyGastrointestinal&LiverPhysiology,2021,303(2):G141-54.8.ElsenbruchS,KotsisV,BensonS,etal.Neuralmechanismsmediatingtheeffectsofexpectationinvisceralplaceboanalgesia:AnfMRIstudyinhealthyplaceborespondersandnonresponders[J].Pain,2021,153(2):382-90.9.Jui-YangH,KilpatrickLA,JenniferL,etal.PatientswithChronicVisceralPainShowSex-RelatedAlterationsinIntrinsicOscillationsoftheRestingBrain[J].JournalofNeuroscience,2021,33(29):11994-12002.10.LabusJS,ArpanaG,KristenC,etal.Sexdifferencesinemotion-relatedcognitiveprocessesinirritablebowelsyndromeandhealthycontrolsubjects.[J].Pain,2021,154(10):2088–2099.11.ZhuX,ZhuX,ChenW,etal.TheApplicationofFunctionalMagneticResonanceImaginginanInfantRatModelofIrritableBowelSyndrome[J].GastroenterologyResearch&Practice,2021,2021(5):637-645.12.TownerRA,SmithN,SaundersD,etal.ContrastEnhancedMagneticResonanceImagingasaDiagnosticTooltoAssessBladderPermeabilityandAssociatedColonCrossTalk:PreclinicalStudiesinaRatModel[J].JournalofUrology,2021,193(4):1394-1400.13.X.Liu,A.Silverman,M.Kern,etal.Excessivecouplingofthesaliencenetworkwithintrinsicneurocognitivebrainnetworksduringrectaldistensioninadolescentswithirritablebowelsyndrome:apreliminaryreport[J].Neurogastroenterology&Motility,2021.14.MakinTR,FilippiniN,DuffEP,etal.Network-levelreorganisationoffunctionalconnectivityfollowingarmamputation[J].Neuroimage,2021,28:217–225.15.IcenhourA,LanghorstJ,BensonS,etal.N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