本文選題：2型糖尿病 + 波譜��； 參考：《天津醫(yī)科大學(xué)》2017年博士論文

【摘要】：研究目的:聯(lián)合應(yīng)用~1H-MRS、基于亞頻段ALFF法及基于圖論的腦功能網(wǎng)絡(luò)分析方法,檢測(cè)研究T2DM患者PCC區(qū)代謝物、亞頻段下自發(fā)神經(jīng)元活動(dòng)及全腦功能網(wǎng)絡(luò)拓?fù)浣Y(jié)構(gòu)的變化特點(diǎn),旨在從神經(jīng)影像學(xué)方面探尋T2DM伴認(rèn)知障礙的早期生物標(biāo)志物及其可能的發(fā)病機(jī)制。材料和方法:本研究共收集88個(gè)被試,根據(jù)MoCA評(píng)分將其分為T(mén)2DM認(rèn)知正常組(T2DM組)31例,T2DM伴認(rèn)知障礙組(T2DM-MCI組)22例,另35例為性別、年齡、受教育程度與T2DM組及T2DM-MCI組相匹配的健康對(duì)照者(HC組)。采集三組被試臨床實(shí)驗(yàn)室指標(biāo)及測(cè)試其認(rèn)知功能。(1)采用單體素法采集雙側(cè)PCC區(qū)~1H-MRS波譜,讀取NAA、Cr、Cho、mI曲線下面積,計(jì)算NAA/Cr、Cho/Cr、mI/Cr、NAA/Cho、NAA/mI比值,三組間行兩兩組間比較,并與臨床實(shí)驗(yàn)室指標(biāo)及認(rèn)知功能評(píng)分做相關(guān)分析。(2)采集三組被試靜息態(tài)fMRI數(shù)據(jù),利用DPARSF軟件預(yù)處理并分析Slow-5、Slow-4、Slow-2亞頻段下,T2DM及T2DM-MCI組患者腦內(nèi)ALFF值的改變。(3)采用BOLD-fMRI數(shù)據(jù),利用Gretna軟件以Power-264模板為模板構(gòu)建大腦功能網(wǎng)絡(luò),計(jì)算腦功能網(wǎng)絡(luò)的小世界屬性、全局效率(Eg)、局部效率(Eloc)、節(jié)點(diǎn)全局效率(Eg),分析三組被試的腦功能網(wǎng)絡(luò)小世界屬性及Eg、Eloc及節(jié)點(diǎn)Eg的改變,并將這些指標(biāo)與認(rèn)知功能評(píng)分做相關(guān)性分析。結(jié)果:1.T2DM組與HC組相比,PCC區(qū)出現(xiàn)Cr、Cho減低,mI/Cr升高,NAA/mI減低,差異具有統(tǒng)計(jì)學(xué)意義(p0.05);T2DM-MCI組與HC組相比,PCC區(qū)出現(xiàn)NAA、Cr減低,mI升高,NAA/Cr、Cho/Cr、mI/Cr升高,NAA/mI減低,差異具有統(tǒng)計(jì)學(xué)意義(p0.05);T2DM-MCI與T2DM組相比,PCC區(qū)出現(xiàn)Cho/Cr升高,NAA/mI降低,差異具有統(tǒng)計(jì)學(xué)意義(p0.05)。相關(guān)分析發(fā)現(xiàn),NAA含量與C肽呈正相關(guān)(r=0.948,p=0.042),NAA含量與AVLT評(píng)分趨向正相關(guān)(r=0.949,p=0.051),mI/Cr比值與MoCA評(píng)分呈負(fù)相關(guān)(r=-0.957,p=0.043)。2.T2DM及T2DM-MCI組在Slow-5及Slow-4頻段檢出異常的腦區(qū)均明顯多于Slow-2頻段;基底核團(tuán)及島葉在Slow-5頻段檢出;扣帶回、楔前葉、SMA在Slow-5及Slow-4頻段檢出;額葉、顳葉、頂葉、小腦在三個(gè)頻段均可檢出,但是額葉ALFF減低在Slow-2段最明顯。T2DM組較HC組相比ALFF減低的腦區(qū)為舌回、距狀溝周?chē)べ|(zhì)及內(nèi)側(cè)前額葉;較T2DM組、HC組相比,T2DM-MCI組ALFF減低的腦區(qū)明顯增多,而功能增強(qiáng)的腦區(qū)明顯減少,減低的腦區(qū)涉及視覺(jué)系統(tǒng)、DMN網(wǎng)絡(luò)、執(zhí)行控制網(wǎng)絡(luò)等。3.在0.05-0.4稀疏度下,T2DM與T2DM-MCI組腦功能網(wǎng)絡(luò)仍具有小世界網(wǎng)絡(luò)屬性,但是其Lp增長(zhǎng)、Eg減低,Cp及Eloc減低,差異無(wú)明顯統(tǒng)計(jì)學(xué)意義(p0.05);T2DM組較HC組相比,節(jié)點(diǎn)Eg減低的腦區(qū)為:左側(cè)內(nèi)側(cè)前額葉、頂下小葉、楔葉、PCC及右側(cè)中央后回、顳下回、舌回、距狀回;增高的腦區(qū)為左側(cè)顳上回。T2DM-MCI組較HC組相比,節(jié)點(diǎn)Eg減低的腦區(qū)為:左側(cè)額中回、額下回、顳下回、ACC、枕中回、角回及右側(cè)中央后回;T2DM-MCI組與T2DM組相比節(jié)點(diǎn)Eg減低的腦區(qū)為右側(cè)額中回、額下回、角回及左側(cè)ACC、小腦,增高腦區(qū)為:左側(cè)顳中回。相關(guān)分析顯示,T2DM-MCI組雙側(cè)額中回、額下回、雙側(cè)顳中回、雙側(cè)頂下小葉、右側(cè)島葉、左側(cè)顳上回Eg值與MoCA評(píng)分呈明顯正相關(guān)性,(FDR校正,p0.05)。結(jié)論:1.采用~1H-MRS技術(shù)選定PCC腦區(qū),探討T2DM患者認(rèn)知功能相關(guān)腦區(qū)微損傷引起的代謝物異常改變及其規(guī)律是可行和有效的;T2DM患者PCC區(qū)存在以NAA、Cr含量減低為標(biāo)志的神經(jīng)元破壞和能量代謝的減低;T2DM-MCI患者PCC區(qū)NAA/mI比值有望成為評(píng)估T2DM患者認(rèn)知功能障礙的生物學(xué)指標(biāo)。2.利用亞頻段ALFF方法可以全面、細(xì)致地檢出T2DM患者腦區(qū)自發(fā)神經(jīng)元活動(dòng)的異常,而且活動(dòng)異常的腦區(qū)具有依頻段分布的特點(diǎn),即基底核團(tuán)及島葉在Slow-5頻段檢出;扣帶回、楔前葉、SMA在Slow-5及Slow-4頻段檢出;額葉、顳葉、頂葉、小腦在三個(gè)頻段均可檢出,但是額葉ALFF減低在Slow-2段最明顯。3.本研究發(fā)現(xiàn),T2DM患者早期在枕葉及內(nèi)側(cè)前額葉即可出現(xiàn)損傷,而T2DM-MCI患者腦損傷進(jìn)一步加重,損傷的腦區(qū)增多,主要累及視覺(jué)網(wǎng)絡(luò)、DMN、執(zhí)行控制網(wǎng)絡(luò)等多個(gè)系統(tǒng);說(shuō)明T2DM患者出現(xiàn)認(rèn)知功能障礙的機(jī)制可能是腦內(nèi)多系統(tǒng)功能損傷的綜合結(jié)果。4.T2DM與T2DM-MCI患者的腦功能網(wǎng)絡(luò)仍保持小世界屬性,但是功能整合及功能分化能力均呈減低的趨勢(shì),其中額中回及額下回效率的減低可能在T2DM患者由認(rèn)知功能正常進(jìn)展為認(rèn)知功能障礙過(guò)程中發(fā)揮關(guān)鍵的作用。
[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.

【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R445.2;R587.2

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