1、fMRI在功能性慢性内脏痛研究中的应用和进展,The application and progress of fMRI in the study of functional chronic visceral pain,江苏省xxx重点实验室 Jiangsu Province key Lab of xxx,14级研究生：xxx 导师：xxx 教 授,综述报告,结语与展望,fMRI在CRD实验动物中的应用,fMRI在临床IBS病人中的应用及进展,目录,fMRI与功能性慢性内脏痛背景简介,一、,二、,三、,四、,一、fMRI与功能性慢性内脏痛背景简介,X 线 放射诊断学,正电子发射成像(PET)单光
2、子发射体层成像(SPECT)磁共振功能成像（FMRI）,超声成像(USG)核素 闪烁成像 (-scintigraphy),计算机体层成像(CT)磁共振成像(MRI)数字血管减影(DSA),1.1 医学影像学发展简史,1.2 fMRI历史,1.3 fMRI简介,功能性磁共振成像（functional Magnetic Resonance Imaging ，fMRI）：是利用磁振造影来测量神经元活动所引发之血液动力的改变。目前主要是运用在研究人及动物的脑或脊髓。,Blood Oxygen Level Depend,1.4 功能性慢性内脏痛简介,功能性慢性内脏痛（Functional chronic
3、 visceral pain）：是一种以腹痛或腹部不适, 伴或不伴排便习惯改变为特征的胃肠功能性疾病, 症状至少持续3个月, 但结肠组织未见明显病理学变化。,与内脏伤害性感受处理息息相关的三个环路：,Emeran a. Mayer et al., Gastroenterology(2006),C,稳态传入网络包括：臂旁核、丘脑、岛叶、dACC等。,1.4.1稳态传入网络（homeostatic- afferent network）,Figure 1. Ascending projections of homeostatic afferents. (B) Spino-thalamo-cortic
4、al system. (C) Cortical modulation of homeostatic afferent input to the central nervous system.,1.4.2 情绪-觉醒网络（emotionalarousal network）和皮层处理网络（corticalmodulatory network）,Fig. 2. Cortical-affective circuit effective connectivity model.,J.S. Labus et al. Pain(2013),情绪-觉醒环路: 杏仁核、蓝斑复合体、嘴侧/膝下/膝上扣带回等；,皮层
5、处理环路:前额叶皮质、眶颞额叶皮质等。,Fig. 3. Sex differences in activation of the homeostatic afferent, emotionalarousal, and corticalmodulatory networks in response to noxious visceral stimulation.,Male,Female,Z. Wang et al.,Pain(2009),1.4.3 内脏刺激脑部环路联系,二、fMRI在临床IBS病人中的应用,IBS患者与正常人之间脑局部一致性(ReHo)的差异,Figure 4. ReHo di
6、fferences between IBS patients and controls.,J. KE et al., Neurogastroenterol Motil (2015),中央后回、丘脑、小脑蚓、顶叶,aMCC、pACC、sACC、vm/dl/vlPFC,IBS组在给予安慰剂后接受直肠刺激的脑区激活,Figure .5. Rectal distension-induced neural activation in the cingulate cortex (A) and the somatosensory cortex (S1/S2, B).,Julia Schmid et al.,
7、Neurogastroenterology(2015),MCC、岛叶、丘脑、杏仁核,PCC,S1、小脑,S2,S1、S2,IBS组和对照组接受直肠刺激后的脑区激活,Figure 6. Major sites of activation differences between irritable bowel syndrome (IBS) and healthy control subjects.,C.L. Kwan et al., Neurology(2005),对照组和IBS组接受直肠刺激诱导的脑区激活,Figure 7. (AD) Brain activation in controls a
8、nd IBS patients during subliminal and liminal rectal distensions. (E) Seed regions defined in the anterior insula (left) and aMCC (right) based on rectal distension-induced activation in the control group.(F) Seed regions defined similarly in the bilateral anterior insula (left) and pACC (right) in
9、the IBS patient group.,X. L IU，Neurogastroenterol Motil (2015),PCC、PAG,aMCC、insula、dmPFC、caudate, and PAG,感觉运动皮质、 vmPFC,运动皮质,SMA,thalamus,SMA,下顶叶,组内、组间激活功能区的比较,Figure 8. (A) Comparis on of brain activation between subliminal and liminal stimulation conditions in the control group. (B) The same in th
10、e IBS patient group. (C) Group comparis on of brain activation between controls and IBS patients during subliminal stimulation. (D) The same during liminal stimulation.,对照组和IBS组岛叶和扣带回种子区的功能联系,Figure 9 .(A and B) Functional connectivity of the insula seeds in the control and IBS gr oups during limina
11、l stimulation. (C and D) The same in the aMCC (in controls ) and pACC (in IBS patients) seeds during liminal stimulation. (E and F) Group comparisons of insular and cingulate functional connectivity between controls and IBS patients. (IBS VS. controls: dmPFC, vmPFC, dl PFC, and PCC),dlPFC,IBS组和对照组在情
12、绪认知过程中的性别差异,Fig. 10. Sex differences (IBS + HC) for ME-MF (ME-MF = matching emotionmatching form) .,J.S. Labus et al. Pain(2013),Fig.11. Disease and sex differences for ME-MF.,IBS女性病人脑区注意力相关网络的fMRI,C. S. H Ubbard et al., Neurogastroenterol Motil (2015),Figure 12。 Statistical T maps for the region of
13、 interest analyses for the altering , orienting，and executive control conditions of the Attention Network Test (ANT) .,健康成年人接受直肠扩张刺激的纤维束联系,Fig.13. Connections between the main areas activated during visceral perception.,X. Moisset et al.,European Journal of Pain (2010),目前关于IBS的fMRI研究主要集中在静息态、不同条件直肠刺
14、激下的脑区变化，便秘型和腹泻型差异、性别差异，安慰剂效应、痛觉期待因素、注意力因素、不同的干预治疗措施对IBS脑区变化的影响。近年来，关于IBS在情绪、认知、情感处理中的进展得到了关注，为探讨情感体验成分在疼痛的作用中提供了更多的依据和思考。,三、fMRI在实验动物中的应用,雄性S-D大鼠在接受不同压力下CRD刺激后的脑区激活,J. Lazovic et al.,Neurogastroenterol Motil (2005),Figure 14. Axial fMRI images of the rat brain at the pressures of 40 mmHg (A) 60 mmHg
15、 (B) and 80 mmHg (C), of the same animal.,Figure 15 .Axial fMRI images of the rat brain during the rectal balloon stimulation at the pressure of 60 mmHg (A) and 80 mmHg (B), of the same animal.,SC,PAG,雄性F344大鼠脑内杏仁核植入皮质酮对内脏刺激的fMRI变化,Figure 16. Specific nuclei activated in rats with CORT (A and C) mic
16、ropellets but not activated in rats with CHOL (B and D) （A、B：40 mmHg or；C、D：60 mmHg ）.,Figure 17. Specific nuclei activated by 60 mmHg CRD but not at 40 mmHg CRD in rats with either CORT (C and D ) or CHOL (A and B)(A 、C:60 mmHg; B 、D: 40 mmHg).,Anthony C. Johnson et al., Plos One(2010),Wistar大鼠接受CR
17、D的SPECT局部脑血流（regional cerebral blood flow，rCBF）显像,Fig. 18. Comparison of changes in regional cerebral blood flow-related tissue radioactivity in response to 60-mmHg colorectal distension in female and male rats.,Z. Wang et al.,Pain(2009),目前关于fMRI在CRD模型所致慢性内脏痛的实验尚未开展。接受急性结直肠内脏刺激的动物在fMRI中的研究也较少，重复刺激和单
18、次刺激的差异与否，不同的给药途径，不同药物的干预等都存在较大的科研价值。当然fMRI活体动物成像麻醉对实验存在一定的影响，但活体成像后动物可以继续进行分子生物学等实验，在一定程度上降低了实验相关性数据的个体差异和组间、组内差异，由此关于CRD模型在fMRI中的基础研究亟待开展。,四、结语与展望,从认知神经科学的角度，研究人脑对复杂任务的解决固然重要，但复杂任务刺激不利于临床应用；多数研究都集中在孤立脑区的激活与否，没有考虑脑区之间的相互关系，即忽略了区域之间时间上的关联性；通过激活脑区的功能相关性，可以为神经生物学、分子生物学、药理学和行为学治疗等提供更有指导意义的思路；研究表明临床上关于IB
19、S的中枢认知处理过程在疾病的发生发展中具有重要作用，但受伦理学、治疗干预尤其是脑区等的限制，其发展受到一定的阻碍；由于模型构建、小动物磁共振实验装置等的限制，目前关于fMRI在功能性慢性内脏痛实验动物上的研究甚少，生命早期CRD作为IBS病人的经典模型之一，开展此慢性内脏痛动物实验，实现与临床科研之间的生物转化亟待解决。,参考文献,1.Lazovic, J, Wrzos, H. F, Yang, Q. X, et al. Regional activation in the rat brain during visceral stimulation detected by c-fos expr
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