T2DM患者脑代谢及脑功能的fMRI系列研究

发布时间：2018-04-20 15:04

本文选题：2型糖尿病 + 波谱　；参考：《天津医科大学》2017年博士论文

【摘要】：研究目的:联合应用~1H-MRS、基于亚频段ALFF法及基于图论的脑功能网络分析方法,检测研究T2DM患者PCC区代谢物、亚频段下自发神经元活动及全脑功能网络拓扑结构的变化特点,旨在从神经影像学方面探寻T2DM伴认知障碍的早期生物标志物及其可能的发病机制。材料和方法:本研究共收集88个被试,根据MoCA评分将其分为T2DM认知正常组(T2DM组)31例,T2DM伴认知障碍组(T2DM-MCI组)22例,另35例为性别、年龄、受教育程度与T2DM组及T2DM-MCI组相匹配的健康对照者(HC组)。采集三组被试临床实验室指标及测试其认知功能。(1)采用单体素法采集双侧PCC区~1H-MRS波谱,读取NAA、Cr、Cho、mI曲线下面积,计算NAA/Cr、Cho/Cr、mI/Cr、NAA/Cho、NAA/mI比值,三组间行两两组间比较,并与临床实验室指标及认知功能评分做相关分析。(2)采集三组被试静息态fMRI数据,利用DPARSF软件预处理并分析Slow-5、Slow-4、Slow-2亚频段下,T2DM及T2DM-MCI组患者脑内ALFF值的改变。(3)采用BOLD-fMRI数据,利用Gretna软件以Power-264模板为模板构建大脑功能网络,计算脑功能网络的小世界属性、全局效率(Eg)、局部效率(Eloc)、节点全局效率(Eg),分析三组被试的脑功能网络小世界属性及Eg、Eloc及节点Eg的改变,并将这些指标与认知功能评分做相关性分析。结果:1.T2DM组与HC组相比,PCC区出现Cr、Cho减低,mI/Cr升高,NAA/mI减低,差异具有统计学意义(p0.05);T2DM-MCI组与HC组相比,PCC区出现NAA、Cr减低,mI升高,NAA/Cr、Cho/Cr、mI/Cr升高,NAA/mI减低,差异具有统计学意义(p0.05);T2DM-MCI与T2DM组相比,PCC区出现Cho/Cr升高,NAA/mI降低,差异具有统计学意义(p0.05)。相关分析发现,NAA含量与C肽呈正相关(r=0.948,p=0.042),NAA含量与AVLT评分趋向正相关(r=0.949,p=0.051),mI/Cr比值与MoCA评分呈负相关(r=-0.957,p=0.043)。2.T2DM及T2DM-MCI组在Slow-5及Slow-4频段检出异常的脑区均明显多于Slow-2频段;基底核团及岛叶在Slow-5频段检出;扣带回、楔前叶、SMA在Slow-5及Slow-4频段检出;额叶、颞叶、顶叶、小脑在三个频段均可检出,但是额叶ALFF减低在Slow-2段最明显。T2DM组较HC组相比ALFF减低的脑区为舌回、距状沟周围皮质及内侧前额叶;较T2DM组、HC组相比,T2DM-MCI组ALFF减低的脑区明显增多,而功能增强的脑区明显减少,减低的脑区涉及视觉系统、DMN网络、执行控制网络等。3.在0.05-0.4稀疏度下,T2DM与T2DM-MCI组脑功能网络仍具有小世界网络属性,但是其Lp增长、Eg减低,Cp及Eloc减低,差异无明显统计学意义(p0.05);T2DM组较HC组相比,节点Eg减低的脑区为:左侧内侧前额叶、顶下小叶、楔叶、PCC及右侧中央后回、颞下回、舌回、距状回;增高的脑区为左侧颞上回。T2DM-MCI组较HC组相比,节点Eg减低的脑区为:左侧额中回、额下回、颞下回、ACC、枕中回、角回及右侧中央后回;T2DM-MCI组与T2DM组相比节点Eg减低的脑区为右侧额中回、额下回、角回及左侧ACC、小脑,增高脑区为:左侧颞中回。相关分析显示,T2DM-MCI组双侧额中回、额下回、双侧颞中回、双侧顶下小叶、右侧岛叶、左侧颞上回Eg值与MoCA评分呈明显正相关性,(FDR校正,p0.05)。结论:1.采用~1H-MRS技术选定PCC脑区,探讨T2DM患者认知功能相关脑区微损伤引起的代谢物异常改变及其规律是可行和有效的;T2DM患者PCC区存在以NAA、Cr含量减低为标志的神经元破坏和能量代谢的减低;T2DM-MCI患者PCC区NAA/mI比值有望成为评估T2DM患者认知功能障碍的生物学指标。2.利用亚频段ALFF方法可以全面、细致地检出T2DM患者脑区自发神经元活动的异常,而且活动异常的脑区具有依频段分布的特点,即基底核团及岛叶在Slow-5频段检出;扣带回、楔前叶、SMA在Slow-5及Slow-4频段检出;额叶、颞叶、顶叶、小脑在三个频段均可检出,但是额叶ALFF减低在Slow-2段最明显。3.本研究发现,T2DM患者早期在枕叶及内侧前额叶即可出现损伤,而T2DM-MCI患者脑损伤进一步加重,损伤的脑区增多,主要累及视觉网络、DMN、执行控制网络等多个系统;说明T2DM患者出现认知功能障碍的机制可能是脑内多系统功能损伤的综合结果。4.T2DM与T2DM-MCI患者的脑功能网络仍保持小世界属性,但是功能整合及功能分化能力均呈减低的趋势,其中额中回及额下回效率的减低可能在T2DM患者由认知功能正常进展为认知功能障碍过程中发挥关键的作用。
[Abstract]:The purpose of this study is to detect the changes in the PCC region metabolites of T2DM patients, the spontaneous neuronal activity and the topological structure of the whole brain function network, based on the sub band ALFF method and the graph based brain functional network analysis method, aiming at exploring the early biomarkers of T2DM with cognitive impairment from the aspect of neuroimaging. Material and its possible pathogenesis. Materials and methods: a total of 88 subjects were collected in this study. According to the MoCA score, they were divided into 31 cases of T2DM cognitive normal group (group T2DM), 22 cases of T2DM with cognitive impairment group (group T2DM-MCI), and 35 cases of sex, age, and education degree with group T2DM and T2DM-MCI group (HC group). Three groups of subjects were collected. The clinical laboratory index and its cognitive function test. (1) using the single body element method to collect the ~1H-MRS spectrum of bilateral PCC region, read the area under the NAA, Cr, Cho, mI curve, calculate NAA/Cr, Cho/Cr, mI/Cr, NAA/Cho, NAA/mI ratio, and compare the 22 groups between the three groups, and do the correlation analysis with the clinical laboratory index and cognitive function score. (2) collect three groups of subjects Resting state fMRI data, using DPARSF software to preprocess and analyze the changes of ALFF value in the brain of group T2DM and T2DM-MCI under Slow-5, Slow-4, Slow-2 sub band. (3) using BOLD-fMRI data, using Gretna software to construct brain function network with Power-264 template as a template, calculate the small world property of brain functional network, global efficiency (Eg) and local effect. Rate (Eloc), node global efficiency (Eg), analyze the small world attributes of the brain function network in the three groups and the changes of Eg, Eloc and node Eg, and make the correlation analysis between these indexes and the cognitive function score. Results: the 1.T2DM group is compared with the HC group, and the PCC area appears Cr, Cho decreased, mI /Cr increases, and the difference has statistical significance. Compared with group HC, NAA, Cr decreased, mI increased, NAA/Cr, Cho/Cr, mI/Cr increased, NAA/mI decreased, and the difference was statistically significant (P0.05). T2DM-MCI compared with T2DM group, increased, decreased, and had statistical significance. There was a positive correlation with the AVLT score (r=0.949, p=0.051), and the mI/Cr ratio was negatively correlated with the MoCA score (r=-0.957, p=0.043).2.T2DM and T2DM-MCI groups detected in the Slow-5 and Slow-4 frequencies more than the Slow-2 bands; the basal nuclei and the insula were detected in the frequency segment; the cingulate gyrus and the anterior lobe of the wedge were detected in the frontal, frontal lobe, and the frontal lobe, The temporal lobe, the parietal lobe and the cerebellum could be detected in three frequency bands, but the ALFF in the frontal lobe was lower in the Slow-2 segment than in the HC group and the ALFF decreased in the brain area of the tongue, the peripheral cortex and the medial prefrontal cortex. Compared with the T2DM group and the HC group, the decrease of ALFF in the T2DM-MCI group was significantly increased, while the brain area of the function enhanced brain decreased obviously and reduced the brain. The area involved in the visual system, the DMN network, the executive control network and other.3. in the 0.05-0.4 sparsity, the T2DM and T2DM-MCI group brain functional networks still have small world network properties, but their Lp growth, Eg decrease, Cp and Eloc decrease, the difference is not significant (P0.05). Compared to the HC group, the brain area of the node is: the left medial prefrontal lobe, the top of the brain. Lower lobule, cuneate, PCC and right central posterior gyrus, inferior temporal gyrus, lingual gyrus, and partaliform gyrus; compared with the HC group in the left temporal upper temporal gyrus.T2DM-MCI group, the lower frontal gyrus, lower frontal gyrus, inferior temporal gyrus, ACC, occipital gyrus, angular gyrus, and right central posterior gyrus, and the brain area of the T2DM-MCI group and T2DM group in the right frontal area compared with the T2DM group were in the right frontal area. The posterior frontal gyrus, the angular gyrus and the left ACC, the cerebellum and the elevation of the brain were the middle temporal gyrus. The correlation analysis showed that the bilateral middle frontal gyrus, the lower frontal gyrus, bilateral temporal gyrus, bilateral apical lobule, right Island lobe, left temporal gyrus Eg value were positively correlated with the MoCA score, (FDR correction, P0.05). Conclusion: 1. the PCC brain area was selected by ~1H-MRS technique, and 1. the PCC brain area was selected by ~1H-MRS technique, and the discussion was discussed. Discussion of PCC brain region by ~1H-MRS technique, exploration The abnormal changes and rules of metabolites associated with cognitive function related brain region injury in T2DM patients are feasible and effective. In the PCC area of T2DM patients, the neuronal destruction and the reduction of energy metabolism marked by the decrease of NAA and Cr, and the PCC zone NAA/mI ratio in T2DM-MCI patients are expected to be a biological indicator for evaluating the cognitive dysfunction of T2DM patients. 2. using the subband ALFF method, the abnormal activity of spontaneous neuronal activity in the brain area of T2DM patients can be carefully detected, and the abnormal activity of the brain region is characterized by the frequency band distribution, that is, the basal nuclei and the insula are detected in the Slow-5 band; the cingulate gyrus, the anterior lobe of the wedge, and the SMA in the Slow-5 and Slow-4 frequency bands; the frontal, temporal, parietal, and cerebellum are in the three frequency. Duan Junke was detected by Duan Junke, but the most obvious.3. in the Slow-2 segment was found in the frontal lobe of the frontal lobe. It was found that the early occipital and medial prefrontal lobes could be damaged in the T2DM patients, while the brain damage was further aggravated and the brain area of the T2DM-MCI patients increased, which mainly involved the visual network, DMN, and the control network and so on. It showed that the T2DM patients had cognitive work. The mechanism of disability can be a comprehensive result of the impairment of multi system function in the brain..4.T2DM still maintains a small world property in the brain functional network of patients with T2DM-MCI, but the ability to function integration and function differentiation is decreased. The decrease of the middle and lower frontal gyrus may be the cognitive function of the cognitive function in T2DM patients. Play a key role in the process of obstacle.

【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R445.2;R587.2

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