轻度阿尔茨海默病患者脑功能网络度中心度改变的初步研究

目的:利用度中心度(degree centrality,DC)的方法探讨轻度阿尔茨海默病(Alzheimer's disease,AD)患者及遗忘型轻度认知功能障碍(amnestic mild cognitive impairment,aMCI)患者在静息态下脑功能网络连接属性的改变。方法:收集12例轻度AD患者、12例aMCI患者和15名健康老年志愿者(normal control,NC组)参加试验。所有受试者均行简易精神状态检查量表(mini-mental state examination,MMSE)及其他系列量表测试,评估其认知水平,并采集静息态功能MRI数据,经预处理和后处理计算出全脑DC值图,采用双样本t检验进行组间比较,分别检测轻度AD组与NC组、aMCI组与NC组间DC分布图间的统计学差异。结果:与NC组相比,轻度AD患者DC值减低的脑区主要分布在左侧眶部额下回、左侧额中回、左侧额下回、左侧后扣带回及右侧后扣带回;aMCI患者则分布于右侧楔前叶、左侧楔叶、右侧楔叶、右侧枕上回、右侧枕中回、左侧颞上回及右侧角回脑区DC值较NC组减低,而右侧前扣带回、左侧海马、左侧胼胝体压部的DC值较NC组升高。结论:基于静息态功能MRI数据的DC分析观察到轻度AD患者及aMCI患者在一些脑区发生了功能连接改变,DC作为一种新的基于体素水平描述脑网络属性的方法,可能对理解AD病理机制及观察其脑网络属性的改变提供了一个新视角。     

基于MRI影像组学和机器学习诊断抑郁症研究进展

抑郁症为常见神经心理疾病,目前尚无客观诊断标准。MRI可提供脑结构、白质纤维束完整性及静息态和任务态下脑功能等多方面信息;MRI影像组学和机器学习(ML)有助于建立个体化诊断抑郁症模型。本文对基于MRI影像组学及ML诊断抑郁症研究进展进行综述。     

多模态MRI在阿尔茨海默病早期诊断中的研究进展

阿尔茨海默病(Alzheimer's disease,AD)是发生于中老年人中最常见的中枢神经系统退行性疾病,以进行性认知障碍和行为非认知功能能力的减低为主要症状。近年来,随着磁共振成像(magnetic resonance imaging,MRI)多种序列的逐渐成熟,多模态MRI诊断在AD早期诊断中占有越来越重要的角色;作者就磁共振成像中结构性磁共振(structural magnetic resonance imaging,s MRI)、磁共振波谱成像(magnetic resonance spectroscopy,MRS)、磁共振弥散张量成像(diffusion tensor imaging,DTI)和磁共振扩散峰度成像(diffusion kurtosis imaging,DKI)、磁敏感加权成像(susceptibility weighted imaging,SWI)和定量磁敏感成像(quantitative susceptibility mapping,QSM)及静息态功能磁共振(functional MRI,f MRI)在AD早期诊断中的应用进行综述。     

超急性期轻度脑外伤患者静息态功能性磁共振成像研究

目的利用静息态功能磁共振成像(resting-state functional magnetic resonance imaging,rs-f MRI)低频振幅(amplitude of low-frequency fluctuation,ALFF)探讨超急性期(24 h)轻度脑外伤(mild traumatic brain injury,m TBI)患者脑功能的异常变化。材料与方法选取符合纳入标准的52例m TBI患者(m TBI组)及与之相匹配的21名健康者(对照组)行rs-f MRI扫描,并应用静息态脑功能数据辅助处理(data processing assistant for resting state f MRI,DPARSF)软件进行预处理,对2组的ALFF进行对比分析。结果与健康对照组相比,ALFF显著减低的区域有小脑后叶、右枕叶中回及中央后回;ALFF显著增高的区域有双侧额叶、内侧前额叶、双侧尾状核及岛叶。结论在常规磁共振成像无异常发现的情况下,ALFF技术可以更好地发现m TBI患者超急性期静息态脑功能的异常。     

慢性疼痛的静息态功能磁共振成像研究进展

慢性疼痛属于临床病症,其范围广泛涉及多个系统,病程通常在3个月以上。慢性疼痛患者的脑结构和功能均发生改变,学习和记忆能力受到影响。目前,慢性疼痛引发脑功能改变的机制尚未完全阐明。近年来,功能磁共振成像(functional MRI,f MRI)被广泛运用于慢性疼痛脑功能改变的神经病理机制研究。本文主要综述静息态f MRI在慢性疼痛脑功能改变的最新研究进展。     

左旋甲状腺素对甲状腺功能减退症患者脑默认网络静息态功能连接的影响

目的研究甲状腺功能减退症(简称甲减)患者在左旋甲状腺激素(L-T4)替代治疗前后,默认网络脑区静息态脑功能连接的改变。方法运用静息态功能磁共振(rsf MRI)技术检测14例初诊成人原发性甲减患者在左旋甲状腺素替代治疗前后及15例健康对照的静息态脑功能连接强度。结果利用基于种子的分析方法显示,健康对照组前后两次扫描双侧丘脑与后扣带回/楔前叶的功能连接强度差异无统计学意义;甲减组治疗后扫描时,双侧丘脑的丘脑枕区域与后扣带回/楔前叶之间的功能连接强度较治疗前出现显著性下降(左侧:P=0.007,右侧:P=0.001)。结论甲减患者双侧丘脑与后扣带回/楔前叶之间静息态脑功能连接强度在左旋甲状腺素替代治疗后较治疗前显著降低。     

静息态功能MRI脑网络用于研究帕金森病伴冻结步态进展

冻结步态（FOG）是帕金森病（PD）致残性步态障碍。静息态功能MRI（rs-fMRI）可反映静息态下脑功能连接（FC）,有助于揭示FOG病理生理机制。本文就rs-fMRI脑网络用于研究PD伴FOG进展进行综述。     

双相情感障碍的静息态功能MRI研究进展

磁共振成像(MRI)技术在评估脑解剖结构及功能变化方面得到日益广泛的应用,并逐渐成为临床研究双相障碍(BD)的重要工具。作者就静息态功能磁共振成像的常用分析方法及其在BD研究中的应用进展进行文献综述,以期为BD的病理机制研究提供影像学依据。     

现代脑功能磁共振诠释传统针刺机制

功能磁共振成像(functional MRI,fMRI)近年在针灸脑效应、针灸治病脑机制研究的应用逐渐增多,取得了新的进展。研究在健康受试者及患者的治疗前后进行,采用任务态、静息态、脑结构等多模态成像方法,观察针刺后的脑形态、功能激活及网络的变化,初步发现了人体经穴针刺的脑效应特征,特别是针灸疗效相关的脑功能及网络变化规律,丰富了针灸脑科学的内涵。     

急性轻型创伤性脑损伤的静息态脑功能磁共振成像研究

目的探讨轻型创伤性脑损伤(m TBI)患者急性期脑功能改变磁共振成像特征。方法利用静息态功能磁共振成像(RS-f MRI)低频震荡幅度(ALFF)数据分析方法。12例m TBI患者和10例健康对照者纳入研究,RS-f MRI数据采用GE公司MR750 3.0 T成像系统获得。使用矩阵实验室(MATLAB)R2007a软件包搭建数据分析环境,应用统计参数图(SPM5)软件包、静息态功能磁共振数据处理工具包(REST)V1.8、高级版静息态f MRI数据处理助手软件包(DPARSFA)V2.0及MRI图像查看与分析软件包(MRIcron)等软件进行数据的预处理、统计分析和结果显示。结果 1 m TBI组较健康对照组比较,ALFF值降低脑区主要包括:小脑后叶、小脑扁桃体、下半月小叶、右侧颞上回、右侧颞中回、顶叶及中央后回等;2m TBI组与健康对照组比较,ALFF值升高脑区主要包括:边缘叶、扣带回、楔前叶、左侧颞上回、左侧颞中回、右侧额上回、右侧额中回及右侧额下回等;3 m TBI患者存在明显的临床表现及认知功能变化,如肢体平衡及协调能力、记忆、语言、情绪反应等。结论 m TBI组多个脑功能区存在明显异常,这可能与其典型的临床表现及认知功能改变有关,静息态功能磁共振成像下脑区的改变可能会为m TBI患者诊断提供一定价值。     

阿尔茨海默症功能脑网络研究进展

近年来功能磁共振成像作为一种新兴的技术,被广泛应用于功能脑网络的研究中,一些功能脑网络被定义,如感觉运动网络、语言网络、默认模式网络、背侧注意网络、额顶叶控制网络、突显网络、中央执行网络等。阿尔茨海默症作为一种严重的神经退行性疾病,一直是脑科学中的研究热点,功能脑网络的研究为揭示其发病机制及早期诊断提供了可靠的依据。本文对功能脑网络用于阿尔茨海默症的研究进展进行综述。     

静息态fMRI观察轻、中度阿尔茨海默病患者脑区功能连接异常

目的 探讨轻、中度阿尔茨海默病（AD）患者全脑功能连接改变及差异。方法 对轻、中度AD患者（轻、中度AD组,各25例）及25名健康体检者（对照组,25名）行静息态fMRI。计算全脑116个脑区的功能连接,以单因素方差分析3组功能连接的差异,采用双样本t检验比较2组间功能连接对的差异。结果 与轻度AD组比较,中度AD组小脑内部及后扣带回与颞叶海马等的功能连接减低,双侧海马间、后扣带回与内侧眶部额上回等脑区功能连接增加。与对照组比较,轻度AD组双侧海马间、小脑蚓部间功能连接增加,后扣带回与颞部海马、眶部额中回及背外侧额上回等脑区功能连接减低;中度AD组表现为小脑内部以及后扣带回与颞部海马、眶部额中回等脑区功能连接减低,后扣带回与内侧眶部额上回以及双侧海马等脑区功能连接增加（P均< 0.05）。结论 中度与轻度AD患者脑功能连接异常存在差异,包括小脑内、双侧海马间连接异常,后扣带回连接减低以及微弱代偿。     

MRI研究轻度认知障碍大脑连接改变及其机制进展

阿尔茨海默病(AD)是进行性发展的神经退行性疾病;轻度认知障碍(MCI)是正常衰老与痴呆之间的过渡状态,为预防性治疗AD的关键阶段。弥散张量成像(DTI)和血氧水平依赖功能MRI(BOLD-fMRI)常用于评估大脑结构及功能连接及解释其相关机制。本文就MRI研究MCI大脑连接改变及其机制进展进行综述。     

Toward the Validation of Functional Neuroimaging as a Potential Biomarker for Alzheimer’s Disease: Implications for Drug Development

Despite investments carried out in the research since Alzheimers disease (AD) was firstly defined as an isolated clinical entity, there is still a lack of appropriate cure and effective therapies to halt or slow the disease progression. While fundamental research has provided a better characterization of AD, much remains to be done for the development of new biological treatment strategies. It is now being debated whether functional neuroimaging (FNI) could help improve diagnostic accuracy and become a possible biomarker of AD. The primary purpose of this review was to determine whether data already published in the literature meet formal technology assessment standards for using regional cerebral blood flow (rCBF) or glucose metabolism (rCMRGlu) as a biomarker for AD. The secondary purpose was to identify any remaining gaps that might need to be systematically addressed before drug developers and regulators accept FNI as a biomarker for AD. The present paper reviews the literature regarding metabolic positron emission tomography (PET) and perfusion single photon emission computed tomography (SPECT) studies in AD. There is evidence that treatment with acetylcholinesterase inhibitors (AChEI) leads to changes in brain physiology within the brain regions critical to AD pathology, i.e. the temporal, parietal and frontal association cortex. However, a thorough analysis combining functional and neuropsychological data has not yet been attempted, and much research is needed to validate the role of FNI as a surrogate endpoint for AD clinical trials.     

Changes in hippocampal connectivity in the early stages of Alzheimer's disease: evidence from resting state fMRI

A selective distribution of Alzheimer's disease (AD) pathological lesions in specific cortical layers isolates the hippocampus from the rest of the brain. However, functional connectivity between the hippocampus and other brain regions remains unclear in AD. Here, we employ a resting state functional MRI (fMRI) to examine changes in hippocampal connectivity comparing 13 patients with mild AD versus 13 healthy age-matched controls. Hippocampal connectivity was investigated by examination of the correlation between low frequency fMRI signal fluctuations in the hippocampus and those in all other brain regions. We found that functional connectivity between the right hippocampus and a set of regions was disrupted in AD; these regions are: medial prefrontal cortex (MPFC), ventral anterior cingulate cortex (vACC), right inferotemporal cortex, right cuneus extending into precuneus, left cuneus, right superior and middle temporal gyrus and posterior cingulate cortex (PCC). We also found increased functional connectivity between the left hippocampus and the right lateral prefrontal cortex in AD. In addition, rightward asymmetry of hippocampal connectivity observed in elderly controls was diminished in AD patients. The disrupted hippocampal connectivity to the MPFC, vACC and PCC provides further support for decreased activity in "default mode network" previously shown in AD. The decreased connectivity between the hippocampus and the visual cortices might indicate reduced integrity of hippocampus-related cortical networks in AD. Moreover, these findings suggest that resting-state fMRI might be an appropriate approach for studying pathophysiological changes in early AD.     

Discriminative analysis of early Alzheimer's disease using multi-modal imaging and multi-level characterization with multi-classifier (M3)

Increasing attention has recently been directed to the applications of pattern recognition and brain imaging techniques in the effective and accurate diagnosis of Alzheimer's disease (AD). However, most of the existing research focuses on the use of single-modal (e.g., structural or functional MRI) or single-level (e.g., brain local or connectivity metrics) biomarkers for the diagnosis of AD. In this study, we propose a methodological framework, called multi-modal imaging and multi-level characteristics with multi-classifier (M3), to discriminate patients with AD from healthy controls. This approach involved data analysis from two imaging modalities: structural MRI, which was used to measure regional gray matter volume, and resting-state functional MRI, which was used to measure three different levels of functional characteristics, including the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo) and regional functional connectivity strength (RFCS). For each metric, we computed the values of ninety regions of interest derived from a prior atlas, which were then further trained using a multi-classifier based on four maximum uncertainty linear discriminant analysis base classifiers. The performance of this method was evaluated using leave-one-out cross-validation. Applying the M3 approach to the dataset containing 16 AD patients and 22 healthy controls led to a classification accuracy of 89.47% with a sensitivity of 87.50% and a specificity of 90.91%. Further analysis revealed that the most discriminative features for classification are predominantly involved in several default-mode (medial frontal gyrus, posterior cingulate gyrus, hippocampus and parahippocampal gyrus), occipital (fusiform gyrus, inferior and middle occipital gyrus) and subcortical (amygdale and pallidum of lenticular nucleus) regions. Thus, the M3 method shows promising classification performance by incorporating information from different imaging modalities and different functional properties, and it has the potential to improve the clinical diagnosis and treatment evaluation of AD.     

Magnetic resonance approaches to brain aging and Alzheimer disease-associated neuropathology

The noninvasive, nonradioactive, quantitative nature of magnetic resonance techniques has propelled them to the forefront of neuroscience and neuropsychiatric research. In particular, recent advances have confirmed their enormous potential in patients with Alzheimer disease (AD). Structural and functional magnetic resonance (MR) imaging have demonstrated significant correlation with clinical outcomes and underlying pathology and are used increasingly in the AD clinic. This review will highlight the role of high-resolution structural MR imaging and functional magnetic resonance imaging in the identification of atrophic and hemodynamic changes in AD and their potential as diagnostic biomarkers and surrogates of therapeutic response. Advanced MR techniques based on diffusion, perfusion, and neurochemical abnormalities in the aging brain will be presented briefly. These newer techniques continue to expand our understanding of neuropathology in the aging brain and are likely to play an important clinical role in the future.     

脑涨落图检测阿尔茨海默病病人脑神经递质变化特点

目的:利用脑涨落图仪探索阿尔茨海默病(AD)病人脑神经递质变化特点。方法:采集经过《临床痴呆评定量表》(CDR)评定的20例AD病人的脑电功率信号,与集中体检的正常老人18例脑电功率进行比较,分析AD病人脑神经递质变化的特点。结果:与正常组相比,痴呆组脑内GABA和Glu两种递质显著降低(P<0.05),5-HT显著升高(P<0.05)。相关分析表明:5-HT、ACh、NE等的功率与临床痴呆评分呈明显负相关,Glu的相对功率与CDR评分呈显著性正相关,NE则呈负相关。结论:AD病人脑内的GABA和Glu的功能相对较弱,5-HT的功能增强,Ach则未见明显变化。AD病人的整体脑功能下降,但脑内的各种功能状态能够保持大体平衡。5-HT、ACh、NE等的功能高低与痴呆病情的严重程度成反比。     

Activation in the premotor cortex during mental calculation in patients with Alzheimer's disease: relevance of reduction in posterior cingulate metabolism

In vivo brain imaging of people with Alzheimer's disease (AD) has suggested the presence of functional disintegration in the posterior-anterior brain network from the posterior cingulate cortex (PCC) to the prefrontal cortex. To investigate the relationship between the baseline posteromedial metabolism and prefrontal neural activity during cognitomnemonic tasks in AD patients, we measured both glucose metabolism at baseline and cerebral blood flow (CBF) during the execution of mental calculation tasks (serial number subtraction) in 10 early-stage AD patients and six healthy subjects. The present study employed positron emission tomography with (18)F-fluorodeoxyglucose and H(2)(15)O. Group comparison using the region-of-interest (ROI) method and voxel-based statistical parametric mapping (SPM99) showed significant reduction in glucose metabolism in the PCC of the AD group. The PCC metabolism in the AD group was negatively correlated with scores on the Mini-Mental State Examination and with correct responses to the arithmetic task. During the arithmetic task, regional CBF increased significantly in the left parietal and bilateral prefrontal cortices in the normal group, whereas the bilateral premotor cortices were significantly activated in the AD group. Regression analysis showed a significant inverse correlation between the premotor activation and the baseline PCC metabolism in the AD group. These results suggest that the premotor cortex plays a compensatory role in executing mental calculations in AD patients with reduced posteromedial functions, which might reflect the dynamic aspect of the pathophysiology of early AD.     

Altered spontaneous activity in Alzheimer's disease and mild cognitive impairment revealed by Regional Homogeneity

Alzheimer's disease (AD), the most prevalent cause of dementia in the elderly, is characterized by progressive cognitive and intellectual deficits. Most patients with mild cognitive impairment (MCI) are thought to be in a very early stage of AD. Resting-state functional magnetic resonance imaging reflects spontaneous brain activities and/or the endogenous/background neurophysiological process of the human brain. Regional Homogeneity (ReHo) can provide a fast method for mapping regional activity across the whole brain. Little has been previously published about where or how spontaneous activity differs between MCI and AD, although many previous fMRI studies have shown that the activity pattern is altered in MCI/AD. In the present study, we first used the ReHo method to explore differences in regional spontaneous activities throughout the whole brain between normal controls (NC) and people with MCI and with AD. A one-way ANOVA was performed to determine the regions in which the ReHo differs between the three groups, and then a post hoc analysis was performed to evaluate differences in the pattern among the three groups. Finally a correlation analysis was done between the ReHo index of these regions and clinical variables in order to evaluate the relationship between ReHo and cognitive measures in the AD and MCI groups. An exploratory classification analysis also demonstrated that ReHo measures were able to correctly separate subjects in 71.4% of the cases. Altered brain spontaneous activations were found in the medial prefrontal cortex, the bilateral posterior cingulate gyrus/precuneus and the left inferior parietal lobule (IPL) in both MCI and AD. In MCI, the ReHo index in the left IPL was higher than that of the NC, which could indicate the presence of a compensatory mechanism in MCI. More obviously, the correlation analysis indicated that the lower the memory and other cognitive abilities, the lower the ReHo in patients with MCI and AD. Combining our findings with the results in earlier studies, we propose that the spontaneous activity pattern in the resting state could potentially be used as a clinical marker for MCI/AD.