本文選題：精神分裂癥 + 磁共振成像��； 參考：《天津醫(yī)科大學(xué)》2017年博士論文

【摘要】：第一部分:精神分裂癥靜息態(tài)腦血流及血流連接的改變【目的】樣本量小和個(gè)體差異大是導(dǎo)致精神分裂癥靜息態(tài)腦血流(CBF)研究結(jié)果不一致的主要原因。精神分裂癥的CBF連接改變亦不是十分清楚。在本研究中,我們?cè)噲D闡明以下問(wèn)題:(1)精神分裂癥患者的CBF改變模式;(2)CBF改變與臨床指標(biāo)的關(guān)系;(3)精神分裂癥患者存在CBF改變的腦區(qū)是否也有CBF連接的改變。【方法】利用三維偽連續(xù)動(dòng)脈自旋標(biāo)記(3D-pcASL)成像技術(shù)測(cè)量100例精神分裂癥患者和94例正常對(duì)照的靜息態(tài)CBF,并使用標(biāo)準(zhǔn)化CBF減小個(gè)體變異。我們比較兩組受試者CBF的差異,并在患者中評(píng)估CBF改變和臨床指標(biāo)的相關(guān)性。并且,我們還比較了存在局部CBF改變腦區(qū)的CBF連接的組間差異�！窘Y(jié)果】和正常對(duì)照相比,精神分裂癥患者雙側(cè)顳下回、雙側(cè)丘腦、雙側(cè)殼核CBF增高,左側(cè)島葉、左側(cè)額中回、雙側(cè)前扣帶皮層、雙側(cè)枕中回CBF減低。校正灰質(zhì)體積以后,精神分裂癥患者CBF的改變?nèi)匀伙@著。在精神分裂癥患者中,CBF改變和臨床指標(biāo)存在顯著的相關(guān)性。更重要的是,我們發(fā)現(xiàn)精神分裂癥患者左側(cè)丘腦和右側(cè)額上回內(nèi)側(cè)部、左側(cè)島葉和左側(cè)中央前回的CBF連接減低。【結(jié)論】我們的發(fā)現(xiàn)提示精神分裂癥患者不僅存在局部CBF的異常,還存在CBF連接的改變,這些改變可能是精神分裂癥臨床癥狀的神經(jīng)機(jī)制。第二部分:基于擴(kuò)散峰度成像的精神分裂癥腦白質(zhì)損害研究【目的】擴(kuò)散峰度成像(DKI)技術(shù)是傳統(tǒng)擴(kuò)散張量成像(DTI)技術(shù)的延伸,該技術(shù)在探索神經(jīng)組織發(fā)育性或病理性改變時(shí)具有更高的敏感度和特異度。在本研究中,我們?cè)噲D評(píng)估DKI和DTI技術(shù)在探索精神分裂癥腦白質(zhì)異常中的能力及差異�！痉椒ā渴紫葘�(duì)94例精神分裂癥患者和91例正常對(duì)照行DKI和DTI圖像數(shù)據(jù)采集。評(píng)估腦白質(zhì)完整性的指標(biāo)包括:DKI數(shù)據(jù)解算得到部分各項(xiàng)異性(FA)、平均擴(kuò)散率(MD)、軸向擴(kuò)散率(AD)、徑向擴(kuò)散率(RD)、平均峰度值(MK)、軸向峰度值(AK)、徑向峰度值(RK);DTI數(shù)據(jù)解算得到FA、MD、AD、RD。利用基于纖維束的空間統(tǒng)計(jì)(TBSS)方法比較11個(gè)指標(biāo)的組間差異�！窘Y(jié)果】DKI指標(biāo)發(fā)現(xiàn)精神分裂癥白質(zhì)損害的敏感性(異常體素?cái)?shù)/全腦白質(zhì)骨架體素總數(shù))分別為:RD(37%)MK(34%)FA(24%)MD(21%)AK(20%)RK(3%);DTI指標(biāo)發(fā)現(xiàn)精神分裂癥白質(zhì)損害的敏感性分別為:RD(43%)FA(30%)MD(21%)。DKI擴(kuò)散指標(biāo)(RD、FA和MD)可以更敏感地探測(cè)到纖維排布一致的白質(zhì)區(qū)(胼胝體和內(nèi)囊前肢)異常,而DKI峰度指標(biāo)(MK和AK)可以更敏感地探測(cè)到纖維排布復(fù)雜的白質(zhì)區(qū)(皮層下白質(zhì)和放射冠)異常。并且,精神分裂癥MK的減低主要是由AK的減低引起,提示軸突受損,而FA的減低主要是由RD的增高引起,提示髓鞘損害�！窘Y(jié)論】這些發(fā)現(xiàn)提示DKI擴(kuò)散指標(biāo)及峰度指標(biāo)在探測(cè)精神分裂癥腦白質(zhì)損害時(shí)可以提供互補(bǔ)的信息,因而聯(lián)合應(yīng)用多指標(biāo)更易于揭示精神分裂癥的腦白質(zhì)病理?yè)p害機(jī)制。第三部分:家族型和散發(fā)型精神分裂癥靜息態(tài)腦功能網(wǎng)絡(luò)研究【目的】既往的研究發(fā)現(xiàn)家族型和散發(fā)型精神分裂癥患者的臨床癥狀和腦結(jié)構(gòu)有明顯差異,但是兩種亞型患者的腦功能差異卻不是十分清楚。在本研究中,我們?cè)噲D探究家族型和散發(fā)型精神分裂癥患者的靜息態(tài)腦功能網(wǎng)絡(luò)損害特征�！痉椒ā课覀儾杉�26例家族型精神分裂癥患者、26例散發(fā)型精神分裂癥患者和26例正常對(duì)照的靜息態(tài)功能磁功能成像(fMRI)數(shù)據(jù)。然后用圖論的方法構(gòu)建全腦功能網(wǎng)絡(luò),并比較三組被試腦功能網(wǎng)絡(luò)拓?fù)鋵傩?包括全局指標(biāo)、節(jié)點(diǎn)指標(biāo)和邊指標(biāo))的差異�！窘Y(jié)果】我們發(fā)現(xiàn)三組被試的腦功能網(wǎng)絡(luò)都滿足典型的小世界網(wǎng)絡(luò)拓?fù)鋵傩浴Ｔ谌炙?只有家族性精神分裂癥患者的聚類系數(shù)、小世界性、局部效率下降,提示該亞型患者的腦功能網(wǎng)絡(luò)向隨機(jī)化轉(zhuǎn)變。在局部水平,家族型和散發(fā)型精神分裂癥患者有不同特異性神經(jīng)環(huán)路的損害,包括全腦廣泛分布的節(jié)點(diǎn)中心性增高或減低及功能連接強(qiáng)度減低。并且,有些網(wǎng)絡(luò)指標(biāo)的改變與精神癥狀的嚴(yán)重程度有顯著的相關(guān)性�！窘Y(jié)論】這些發(fā)現(xiàn)提示家族型和散發(fā)型精神分裂癥患者的腦功能網(wǎng)絡(luò)拓?fù)浣Y(jié)構(gòu)損害存在不同的模式,而這可能是由于病因的不同所致。第四部分:精神分裂癥妄想癥狀的神經(jīng)機(jī)制研究【目的】妄想是精神分裂癥的主要陽(yáng)性癥狀之一,但妄想的神經(jīng)機(jī)制仍然不是十分清楚。在本研究中,我們?cè)噲D用多模態(tài)MRI技術(shù)探究精神分裂癥妄想癥狀的神經(jīng)機(jī)制�！痉椒ā课覀儾杉�19例妄想型精神分裂癥患者、30例無(wú)妄想型患者和30例正常對(duì)照的擴(kuò)散、結(jié)構(gòu)和灌注MRI數(shù)據(jù)。然后,用基于體素的分析方法比較部分各向異性(FA)、灰質(zhì)體積(GMV)和CBF的組間差異。【結(jié)果】和正常對(duì)照相比,無(wú)妄想型精神分裂癥患者存在廣泛白質(zhì)區(qū)FA和灰質(zhì)區(qū)GMV的減低;而妄想型精神分裂癥患者的FA和GMV相比于正常對(duì)照無(wú)顯著差異。相比于正常對(duì)照,兩種亞型精神分裂癥患者在前扣帶皮層和杏仁核表現(xiàn)出一致性的GMV減低,在額中回和島葉表現(xiàn)出一致性的CBF減低,在右側(cè)楔前葉表現(xiàn)出一致性的CBF增高。更重要的是,我們發(fā)現(xiàn)妄想型精神分裂癥患者前扣帶皮層的CBF相比于無(wú)妄想型患者進(jìn)一步減低�！窘Y(jié)論】這些發(fā)現(xiàn)提示妄想型精神分裂癥患者可能具有相對(duì)正常的腦結(jié)構(gòu)。此外,精神分裂癥患者前扣帶皮層血流灌注的過(guò)度減低可能與妄想癥狀的產(chǎn)生密切相關(guān)。第五部分:精神分裂癥言語(yǔ)性幻聽(tīng)的特異性腦血流改變【目的】既往研究發(fā)現(xiàn)言語(yǔ)性幻聽(tīng)(AVH)的產(chǎn)生與聽(tīng)覺(jué)/語(yǔ)言相關(guān)網(wǎng)絡(luò)的異常密切相關(guān)。但是,精神分裂癥言語(yǔ)性幻聽(tīng)的特異性CBF改變卻不是十分清楚。在本研究中,我們?cè)噲D在精神分裂癥患者中探究與言語(yǔ)性幻聽(tīng)癥狀相關(guān)的CBF改變�！痉椒ā课覀儾杉�35例言語(yǔ)性幻聽(tīng)型精神分裂癥患者、41例無(wú)幻聽(tīng)型患者和50例正常對(duì)照的ASL-MRI數(shù)據(jù)。然后使用基于體素的分析方法比較三組受試者CBF的差異�！窘Y(jié)果】和正常對(duì)照相比,兩種亞型精神分裂癥患者在雙側(cè)枕葉皮層、左外側(cè)前額葉皮層、左側(cè)島葉以及右側(cè)前扣帶皮層有一致性的CBF減低,在雙側(cè)外側(cè)顳葉皮層、雙側(cè)殼核、左側(cè)中扣帶皮層以及右側(cè)丘腦有一致性的CBF增高,這些一致性的CBF改變被定義為精神分裂癥共同的CBF改變。和無(wú)幻聽(tīng)型患者以及正常對(duì)照相比,言語(yǔ)性幻聽(tīng)型患者雙側(cè)枕葉皮層和左側(cè)頂葉皮層CBF減低,右側(cè)顳上回和右側(cè)尾狀核CBF增高,這些CBF的改變被定義為言語(yǔ)性幻聽(tīng)特異性CBF改變�！窘Y(jié)論】言語(yǔ)性幻聽(tīng)存在特異性CBF改變,即聽(tīng)覺(jué)區(qū)和紋狀體區(qū)CBF增高,視覺(jué)區(qū)和頂葉皮層CBF減低,該發(fā)現(xiàn)提示CBF的再分布與精神分裂癥言語(yǔ)性幻聽(tīng)癥狀密切相關(guān)。
[Abstract]:The first part: the changes in the resting state of the cerebral blood flow and blood flow connection in schizophrenia [Objective] the small sample size and the large individual difference are the main reasons for the disagreement of the resting state cerebral blood flow (CBF) results in schizophrenia. The CBF connection change of schizophrenia is not ten distinct. In this study, we try to clarify the following questions: ( 1) CBF changes in schizophrenic patients; (2) the relationship between CBF changes and clinical indicators; (3) whether there is a change in the CBF connection in the brain region of the schizophrenic patients as well as in the CBF changes. [Methods] the resting state CBF of 100 schizophrenics and 94 normal controls was measured by the three-dimensional pseudo-continuous arterial spin labeling (3D-pcASL) imaging technique. We compared the individual variation with standardized CBF. We compared the differences in CBF in the two subjects and assessed the correlation between the CBF changes and the clinical indicators in the patients. Furthermore, we also compared the differences in the group of CBF connections in the brain region of the local CBF. [results] the contrast to the normal contrast, the bilateral temporal gyrus, and the bilateral mound in schizophrenic patients Brain, bilateral putamen CBF increased, left insula, left middle frontal gyrus, bilateral anterior cingulate cortex, bilateral occipital gyrus, CBF decreased. After correction of gray matter volume, the changes of CBF in schizophrenic patients were still significant. In schizophrenia patients, there was a significant correlation between CBF changes and clinical indicators. More importantly, we found schizophrenia patients. CBF connections in the left thalamus and right medial frontal gyrus, left Island leaf and left precentral gyrus were reduced. [Conclusion] our findings suggest that schizophrenia patients not only have abnormalities in local CBF, but also the changes in CBF connections. These changes may be the neural mechanisms of the clinical symptoms of schizophrenia. The second part: Based on the proliferation peak Degree imaging of schizophrenia brain white matter damage study [Objective] diffusion kurtosis imaging (DKI) technology is the extension of traditional diffusion tensor imaging (DTI) technology. This technique has a higher sensitivity and specificity in exploring the developmental or pathological changes of nerve tissue. In this study, we try to evaluate the spirit of DKI and DTI in exploring the spirit. The ability and difference in the abnormal white matter of schizophrenia. [Methods] first of all, 94 patients with schizophrenia and 91 normal controls were collected for DKI and DTI images. The indicators for assessing the integrity of the white matter included: the DKI data were calculated to obtain partial heterosexual (FA), average diffusion rate (MD), axial diffusivity (AD), radial diffusivity (RD), and average peak Degree value (MK), axial kurtosis (AK) and radial kurtosis (RK); DTI data were calculated to obtain FA, MD, AD, and RD. using the spatial statistics (TBSS) method based on fiber bundles to compare the differences between the 11 indexes. [results] DKI indicators found that the sensitivity of white matter damage in schizophrenia (the number of abnormal voxels / total brain white matter cytoskeleton) was RD (37%) MK ( 34%) FA (24%) MD (21%) AK (20%) RK (3%); DTI index found that the sensitivity of RD (43%) FA (30%) MD (21%).DKI diffusion index (RD, FA and MD) can be more sensitive to detect the abnormal white matter area (corpus callosum and inner capsule forelimb) in fiber arrangement, and the index of kurtosis index can be more sensitive to detect the fiber row. The complex white matter area (subcortical white matter and radiant crown) is abnormal. And the decrease of MK in schizophrenia is mainly caused by the decrease of AK, indicating that the axon is damaged, and the decrease of FA is mainly caused by the increase of RD, suggesting the myelin damage. [Conclusion] these findings suggest that the DKI diffusion index and kurtosis index are in the detection of white matter loss in the brain of schizophrenia. The third part: the resting state brain functional network of familial and sporadic schizophrenics [Objective] to find out the clinical symptoms and brain of patients with familial and sporadic schizophrenia. There are significant differences in the structure, but the difference in brain function of the two subtypes is not very clear. In this study, we tried to explore the resting state brain function network damage characteristics of familial and sporadic schizophrenics. [Methods] We collected 26 familial schizophrenia patients and 26 schizophrenic patients. And 26 normal controls, resting functional magnetic functional imaging (fMRI) data. Then the whole brain functional network was constructed with graph theory, and the differences in the topological properties of the three groups were compared. [results] we found that the brain functional networks of the three groups were satisfied with the typical small world. Network topology properties. At the global level, only familial schizophrenia has a clustering coefficient, small cosmopolitan and local efficiency, suggesting that the brain function network of the subtype is changed to randomization. At the local level, the patients with familial and sporadic schizophrenia have different specific nerve loop damage, including the wide distribution of the whole brain. There is a significant correlation between the changes in some network indicators and the severity of mental symptoms. [conclusions] these findings suggest that there are different patterns of damage to the topological structure of the brain function network in patients with familial and sporadic schizophrenia, which may be due to The fourth part: the neurologic mechanism of paranoid symptoms of schizophrenia [Objective] delusion is one of the main positive symptoms of schizophrenia, but the nervous mechanism of delusion is still not very clear. In this study, we try to explore the neural mechanism of paranoid symptoms of schizophrenia with multimodal MRI technique. Methods: We collected 19 paranoid schizophrenic patients, 30 non paranoid patients and 30 normal controls with diffusion, structure and perfusion MRI data. Then, we compared partial anisotropy (FA), gray matter volume (GMV) and CBF between groups by voxel based analysis. There was a wide reduction in the white matter FA and the gray matter GMV in the patients with cleft disease, while the FA and GMV in paranoid schizophrenics had no significant differences compared to the normal controls. Compared to the normal controls, the two subtypes of schizophrenia showed a consistent GMV reduction in the anterior cingulate cortex and amygdala, and the middle frontal gyrus was consistent with the island leaf. CBF decreased and showed a consistent increase of CBF in the right anterior wedge. More importantly, we found that the CBF of the anterior cingulate cortex in paranoid schizophrenic patients was further lower than that of the undelusional patients. [Conclusion] these findings suggest that paranoid schizophrenics may have relatively normal brain structures. The excessive reduction of blood flow in the anterior cingulate cortex may be closely related to the occurrence of paranoid symptoms. Fifth part: specific cerebral blood flow changes in schizophrenic speech auditory hallucinations [Objective] previous studies have found that verbal auditory hallucinations (AVH) are associated with abnormal auditory / language related networks. The specific CBF changes in verbal auditory hallucinations were not very clear. In this study, we tried to explore CBF changes associated with verbal hallucinations in schizophrenic patients. [Methods] We collected 35 cases of auditory hallucinations, 41 cases without auditory hallucinations and 50 normal controls, and then ASL-MRI data. Using a voxel based analysis, the differences in CBF were compared between the three groups of subjects. [results] two subtypes of schizophrenic patients had a consistent CBF reduction in bilateral occipital cortex, left lateral prefrontal cortex, left insula, and right anterior cingulate cortex, in bilateral lateral temporal cortex, bilateral putamen, left middle buckle. The concordance of CBF increased in the cortex and the right thalamus, and these consistent CBF changes were defined as a common CBF change in schizophrenia. Compared with the non auditory and normal controls, the CBF decreased in the occipital and left parietal cortex of the speech auditory hallucinations, and the CBF in the right lateral temporal and right caudate nuclei increased, and these CBF The changes were defined as verbal hallucinations specific CBF changes. [Conclusion] there is a specific CBF change in speech auditory hallucinations, that is, the CBF of the auditory region and striatum is increased, and the visual area and the parietal cortex are reduced in CBF. This discovery suggests that the redistribution of CBF is closely related to the speech auditory hallucination of schizophrenia.

【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
【分類號(hào)】：R445.2;R749.3

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