Comparison of standard and optimized voxel-based morphometry for analysis of brain changes associated with temporal lobe epilepsy

We compared statistical parametric maps (SPMs) of group-wise regional gray matter differences between temporal lobe epilepsy (TLE) patients with unilateral hippocampal atrophy (HA) determined by manual volumetric analysis relative to a healthy control population using standard and optimized voxel-based morphometry (VBM). We also investigated the impact of customized neuroanatomical templates on SPMs. Standard and optimized VBM analyses of gray matter concentration (GMC) and gray matter volume (GMV) correctly identified HA, regardless of the template used for normalization. The distribution of hippocampal and extrahippocampal abnormalities differed according to the technique (standard v optimized; GMC v GMV), but was not dependent on template type (default v customized) within each technique. In particular, hippocampal GMC reduction was confined to subregions of hippocampus, whereas GMV reduction was observed in the hippocampal head, body, and tail. Unlike standard and optimized GMC reduction, symmetrical GMV reduction was observed in bilateral thalamus, lenticular nuclei, cerebellum, and ipsilateral entorhinal cortex, perirhinal cortex, and fusiform gyrus in both left and right HA patients. These results show that group-wise SPMs of GMC (i.e., regional distribution of gray matter) and GMV (i.e., volume per se) reduction can identify focal atrophy that has been quantified with manual region of interest techniques, although effects are attenuated in analyses of GMC. Unlike SPMs of GMC, analyses of GMV revealed similar extrahippocampal abnormalities as previous region-of-interest volumetric and histopathological studies of intractable TLE. We suggest that in studies of neurological disorders, optimized VBM analyses of GMV may reveal subtle neuroanatomical changes that are not identified in analyses of GMC.     

Voxel-based morphometry of unilateral temporal lobe epilepsy reveals abnormalities in cerebral white matter

Voxel-based morphometric (VBM) investigations of temporal lobe epilepsy have focused on the presence and distribution of gray matter abnormalities. VBM studies to date have identified the expected abnormalities in hippocampus and extrahippocampal temporal lobe, as well as more diffuse abnormalities in the thalamus, cerebellum, and extratemporal neocortical areas. To date, there has not been a comprehensive VBM investigation of cerebral white matter in nonlesional temporal lobe epilepsy. This study examined 25 lateralized temporal lobe epilepsy patients (13 left, 12 right) and 62 healthy controls in regard to both temporal and extratemporal lobe gray and white matter. Consistent with prior reports, gray matter abnormalities were evident in ipsilateral hippocampus and ipsilateral thalamus. Temporal and extratemporal white matter was affected ipsilateral to the side of seizure onset, in both left and right temporal lobe epilepsy groups. These findings indicate that chronic temporal lobe epilepsy is associated not only with abnormalities in gray matter, but also with concomitant abnormalities in cerebral white matter regions that may affect connectivity both within and between the cerebral hemispheres.     

颞叶癫痫儿童灰质异常脑区与神经心理学测验的关系及意义

[目的]评估儿童颞叶癫痫（ TLE）临床表现和神经心理学测验成绩与局部脑萎缩的相关性.[方法]症状性TLE患儿14例（海马萎缩所致中颞叶癫痫 9例,颞叶新皮质损伤所致TLE 5例）,健康对照儿童14名;中颞叶癫痫（ MTLE）成人及其对照各9例.所有入组对象进行脑MRI获取T1结构像,用像素为基础的形态测定法分析图像.所有儿童进行综合神经心理学测验.[结果]TLE患儿同侧海马和海马外周区灰质体积显著减小,灰质体积减小与神经心理学测验成绩显著相关（P〈0.05）.单侧海马萎缩的MTLE患儿中,癫痫发作区域同侧的海马灰质体积显著减小,同侧扣带和对侧额中回皮质萎缩,皮质萎缩程度及范围较同类成人患者小.[结论]与成人MTLE患者相似,儿童MTLE与海马和海马外周的细胞减少有关;儿童TLE灰质萎缩的程度和范围较成人患者小,仅限于额叶区;中颞叶和额叶区灰质体积的减小与神经心理学测验成绩显著相关;TLE患儿的认知或行为障碍是神经网络损伤的结果.     

Whole-brain voxel-based statistical analysis of gray matter and white matter in temporal lobe epilepsy

Volumetric MRI studies based on manual labeling of selected anatomical structures have provided in vivo evidence that brain abnormalities associated with temporal lobe epilepsy (TLE) extend beyond the hippocampus. Voxel-based morphometry (VBM) is a fully automated image analysis technique allowing identification of regional differences in gray matter (GM) and white matter (WM) between groups of subjects without a prior region of interest. The purpose of this study was to determine whole-brain GM and WM changes in TLE and to investigate the relationship between these abnormalities and clinical parameters. We studied 85 patients with pharmacologically intractable TLE and unilateral hippocampal atrophy and 47 age- and sex-matched healthy control subjects. The seizure focus was right sided in 40 patients and left sided in 45. Student's t test statistical maps of differences between patients' and controls' GM and WM concentrations were obtained using a general linear model. A further regression against duration of epilepsy, age of onset, presence of febrile convulsions, and secondary generalized seizures was performed with the TLE population. Voxel-based morphometry revealed that GM pathology in TLE extends beyond the hippocampus involving other limbic areas such as the cingulum and the thalamus, as well as extralimbic areas, particularly the frontal lobe. White matter reduction was found only ipsilateral to the seizure focus, including the temporopolar, entorhinal, and perirhinal areas. This pattern of structural changes is suggestive of disconnection involving preferentially frontolimbic pathways in patients with pharmacologically intractable TLE.     

Quantitative analysis of temporal lobe white matter T2 relaxation time in temporal lobe epilepsy

The objective of this study was to assess temporal lobe white matter (WM) quantitatively using T2 relaxometry in patients with pharmacologically intractable temporal lobe epilepsy (TLE). T2 relaxometry was performed using a dual-echo sequence with 23 contiguous oblique coronal slices in 56 consecutive TLE patients and in 30 healthy subjects. Averages of six slices were chosen to calculate T2 relaxation time in the temporal lobe WM (WM-T2) and the hippocampus (Hippo-T2). Twenty-seven patients had unilateral hippocampal atrophy (HA), and twenty-nine patients had normal hippocampal volumes (NV) on volumetric MRI. Mean WM-T2 was increased ipsilateral to the seizure focus in TLE patients with HA and those with NV (P < 0.001). Contralateral mean WM-T2 was increased in left and right TLE with HA (P < 0.001) and in right TLE with NV (P = 0.001). There was a positive correlation between WM-T2 and Hippo-T2. Individual analysis showed a prolongation of WM-T2 in about 70% of TLE patients with HA and NV. In half of the patients, WM-T2 increase was bilateral and symmetric. However, in 33% of patients with NV and bilateral symmetric increase in Hippo-T2, WM-T2 provided a correct lateralization of the seizure focus. Regardless of the pattern of T2 abnormalities, that is, bilateral symmetric or ipsilateral, the majority of patients with HA became seizure-free after surgery, while those with NV did not have a favorable outcome. In patients with NV, WM-T2 measurement may provide additional lateralizing information compared to Hippo-T2.     

Voxel-by-voxel comparison of automatically segmented cerebral gray matter--A rater-independent comparison of structural MRI in patients with epilepsy.

Quantitative evaluation of MRI in patients with epilepsy can give more information than qualitative assessment. Previously developed volume-of-interest-based methods identified subtle widespread structural changes in the neocortex beyond the visualized lesions in patients with malformations of cortical development (MCD) and hippocampal sclerosis (HS) and also in MRI-negative patients with juvenile myoclonic epilepsy (JME). This study evaluates a voxel-based automated analysis of structural MRI in epilepsy. After fully automated segmentation of cerebral gray matter from structural T1-weighted, high-resolution MRI scans, we applied the automated and objective technique of statistical parametric mapping (SPM) to the analysis of gray matter of 35 control subjects, 10 patients with partial seizures and MCD, 10 patients with left temporal lobe epilepsy (TLE) and HS, 10 patients with left TLE and normal MR quantitation of the hippocampus, and 20 patients with JME. At a corrected threshold of P < 0.05, significant abnormalities were found in 3/35 controls; in all 10 patients with MCD, 6 of whom had additional lesions beyond the margins of the visualized abnormalities; in 2/10 TLE patients with HS; in 2/10 MRI-negative TLE; and in 4/20 JME patients. Group comparisons between control subjects and HS patients identified the affected left temporal lobe with an increase in gray matter in the posterior temporal lobe, but did not identify hippocampal atrophy. The group of MRI-negative TLE patients showed no abnormalities compared with control subjects. Group comparison between control subjects and JME patients identified a mesial frontal increase in gray matter. The SPM-based voxel-by-voxel comparison of gray matter distribution identified MCD and abnormalities beyond the visualized lesion in individual MCD patients. The method did not reliably identify HS in individual patients or identify abnormalities in individual MRI-negative patients with TLE or JME in a proportion larger than the chance findings in the control group. Using group comparisons, structural abnormalities in the neocortical gray matter of patients with TLE and HS were lateralized to the affected temporal lobe. In patients with JME as a group, an increase in gray matter was localized to the mesial frontal area, corroborating earlier quantitative MRI findings.     

颞叶内侧癫痫全脑灰质基于体素的MRI形态分析

目的应用MRI基于体素的形态学测量方法（VBM）,分析颞叶内侧癫痫患者全脑灰质结构的改变。方法对23例颞叶内侧癫痫患者（其中右侧病变11例,左侧病变12例）,13例年龄性别与之匹配的健康志愿者行全脑扫描,应用磁化准备快速梯度回波成像序列获取三维结构图像。数据分析采用以SPM99软件包为基础的全自动VBM技术进行处理。结果与健康对照组比较,颞叶内侧癫痫患者显示了患侧和对侧海马,以及丘脑、扣带回等边缘系统结构灰质密度的减少。额叶及小脑皮层等结构也显示弥漫灰质密度的减少。结论VBM法操作简单,不但可检测颞叶内侧癫痫海马结构的异常,还可显示海马结构以外弥漫脑灰质结构的异常。     

MRI脑灰质形态学分析在双重病理所致颞叶癫痫的应用

目的应用基于体素形态学(VBM)及基于表面形态学(SBM)分析,探讨双重病理所致颞叶癫痫磁共振成像(MRI)脑灰质结构变化。方法收集病理确诊为海马硬化(HS)合并局灶性皮质发育不良(FCD)的双重病理颞叶癫痫患者36例(左侧癫痫组20例、右侧癫痫组16例)及健康对照组30例行MRI T_1WI 3D BRAVO序列扫描,使用SPM及Freesurfer软件分别进行灰质体积及皮层厚度、皮层表面积分析,并采用独立样本t检验获得有统计学差异脑区。结果左、右侧癫痫组与对照组比较,病侧大部分颞叶(含海马)灰质体积减小,左侧癫痫组同侧丘脑及杏仁核灰质体积减小,其差异均有显著统计学意义(FDR校正,P0.001,K≥20体素)。癫痫组均出现部分颞叶及颞叶以外脑区皮层增厚,但左、右侧癫痫组异常脑区存在不同;同时癫痫组病变侧颞叶脑区皮层表面积减小,上述差异均具有统计学意义(未校正,P0.01,顶点数≥100)。结论HS合并FCD致颞叶癫痫病变侧颞叶(含海马)灰质体积广泛缩小为主要形态学特征,皮层表面积减小对病变定侧也有一定作用,单纯通过皮层增厚观察双重病理中FCD存在一定局限性。     

基于体素的形态测量学观察两种亚型血管性认知障碍患者脑灰质萎缩的差异

目的 利用基于体素的形态测量学(VBM)方法观察由皮质下微血管病变导致的脑室周围白质脱髓鞘(PWMH)后轻度认知障碍的患者与关键部位单发梗死(SSI)后轻度认知障碍的患者灰质萎缩的差异。方法 根据神经心理学测试结果收集24例具有轻度认知障碍的脑梗死患者,根据MRI结果将其分为PWMH组(n=14)和SSI组(n=10);另选同期16名神经心理学测试结果正常、脑实质内未见明显梗死灶者作为对照组。对所有受检者行高分辨力结构MR扫描后进行VBM分析,比较组间灰质体积的差异。结果 与SSI组相比,PWMH组双侧额叶及颞叶灰质体积明显缩小,以双侧颞叶明显,左侧颞叶萎缩体素差为4086个,右侧颞叶为4154个,左侧额叶为1718个,右侧额叶为1141个。结论 PWMH患者与SSI患者具有不同的灰质萎缩特点。PWMH与神经退行性改变具有相似的灰质萎缩特点,提示该类型的血管性认知障碍可能合并或继发于神经退行性改变。     

轻度阿尔茨海默病脑血流灌注和脑灰质体积的改变

目的:探究轻度阿尔茨海默病(Alzheimer’s disease,AD)患者的脑血流(Cerebral blood flow,CBF)灌注和脑灰质体积的变化特点。方法:临床招募轻度AD患者和健康对照老年人进行包含3D-T1WI和3D伪连续动脉自旋标记(Three-dimensional pseudo-continuous arterial spin labeling,3D-pcASL)序列的磁共振扫描,运用统计参数图(Statistical parametric mapping,SPM)8软件对两组受试者全脑CBF图进行基于体素的全脑灌注差异的分析;采用基于体素的形态学测量方法(Voxel-based morphometry,VBM)比较两组受试者全脑灰质体积的差异;对灌注有差异的脑区的CBF与简易智力状态检查量表(Mini-mental state examination,MMSE)评分进行相关性分析。结果:共纳入轻度AD患者26例(年龄(73.0±6.8)岁,男16例),年龄、性别相匹配的健康对照者53例(年龄(73.7±8.2)岁,男23例)。与对照组相比,轻度AD组患者CBF灌注减低区主要位于双侧顶叶(以楔前叶、角回为主)、枕叶以及左侧颞叶和额叶;CBF灌注增高区主要位于右海马和海马旁回、右扣带回、基底节核团以及双侧额叶(以眶面和内侧面为主)(P<0.01,FDR校正,团块阈值>100像素)。轻度AD患者的脑灰质萎缩主要位于双侧颞叶内侧结构(海马、海马旁回、杏仁核),也累及双侧岛叶和基底节核团(P<0.01,FDR校正,团块阈值>100像素)。轻度AD组患者左颞顶叶脑回、双侧额上回的CBF值与MMSE评分呈现正相关;双侧内侧和旁扣带回、右前扣带回的CBF值与MMSE评分呈现负相关(P<0.05)。结论:轻度AD患者存在以顶叶为主的低灌注和以海马、基底节区、额叶为主的高灌注改变,而其灰质萎缩主要集中在双侧颞叶内侧结构。     

正常婴儿与隐源性婴儿痉挛症患儿大脑皮层灰质的MR形态学定量分析

目的通过对脑灰质结构进行定量分析,寻找隐源性婴儿痉挛可能的发病部位、探讨发病机制。方法对16例平均年龄6.4个月的隐源性婴儿痉挛患儿和年龄、性别匹配的16例正常婴儿进行脑部高分辨磁共振解剖成像,借助SPM脑成像处理软件对磁共振图像进行解剖分割,用基于体素的形态学对比方法定量检测患儿组和对照组全脑灰质的体积,比较两组间的差异。结果隐源性婴儿痉挛组在左额下回(47区)、右颞上回(22区)、左中央后回(1～2区)、右额中回(9/10区)、右中央前回(6区)、右扣带回(31区),左颞中回(21区)和颞上回(38区)等灰质体积明显减少,与正常婴儿组比较,差异有显著性(P<0.001)。结论隐源性婴儿痉挛患儿额叶和颞叶的灰质体积明显减少,以额叶和颞叶为主的皮层结构异常可能是本组患儿的发病原因。     

Patterns of cerebral atrophy in dementia with Lewy bodies using voxel-based morphometry

Previous cross-sectional MRI studies based on region-of-interest analyses have shown that increased cerebral atrophy is a feature of both Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Relative preservation of the hippocampus and temporal lobe structures in DLB compared to AD has been reported in region-of-interest-based studies. Recently, image processing techniques such as voxel-based morphometry (VBM) have been developed to provide an unbiased, visually informative, and comprehensive means of studying patterns of cerebral atrophy. We report the first study to use the voxel-based approach to assess patterns of cerebral atrophy in DLB compared to control subjects and AD. Regional gray matter volume loss was observed bilaterally in the temporal and frontal lobes and insular cortex of patients with DLB compared to control subjects. Comparison of dementia groups showed preservation of the medial temporal lobe, hippocampus, and amygdala in DLB relative to AD. Significant gray matter loss was also observed in the thalamus of AD patients compared to DLB.     

基于自动分割技术联合基于体素的形态学观察帕金森病脑灰质结构

目的 探讨基于自动分割技术联合基于体素的形态学(VBM)观察帕金森病(PD)患者全脑灰质异常区域及分布特征的应用价值。方法 基于自动分割技术,应用FIRST工具对29例PD患者(PD组)及30名健康人(对照组)的T1图像皮层下灰质结构精确分割,对比两组各灰质结构体积。并应用VBM方法对两组脑灰质图像进行比较。结果 两组右侧壳核皮层下灰质体积差异有统计学意义(t=10.201,P<0.05)。与对照组比较,PD组脑灰质体积(右侧初级运动皮层,双侧额叶、边缘叶、部分左侧小脑后叶、右侧小脑前叶、右侧小脑后叶、右侧颞叶、顶叶、壳核及左侧枕叶)广泛减少,部分左侧小脑后叶体积增加,两侧半球脑体积缺失不对称(右侧大于左侧)。结论 通过FIRST工具可精确分割并直接计算皮层下灰质结构体积,应用VBM技术可定量分析脑结构形态学异常;二者结合可较全面地表现PD脑灰质体积广泛减少的形态学特点。     

阿尔茨海默病及轻度认知障碍所致脑灰质体积及脑功能改变

目的 基于体素形态学分析(VBM)及静息态功能MRI(rs-fMRI)技术观察阿尔茨海默病(AD)及轻度认知障碍(MCI)患者全脑灰质体积及功能改变.方法 对AD(AD组)、MCI患者(MCI组)各30例及正常老年人30名(HC组)采集rs-fMRI和三维磁化强度预备梯度回波序列T1加权像,比较3组全脑灰质体积、脑区分...     

Voxel-based morphometry of the thalamus in patients with refractory medial temporal lobe epilepsy

Previous research has suggested that patients with refractory medial temporal lobe epilepsy (MTLE) show gray matter atrophy both within the temporal lobes as well as in the thalamus. However, these studies have not distinguished between different nuclei within the thalamus. We examined whether thalamic atrophy correlates with the nuclei's connections to other regions in the limbic system. T1-weighted MRI scans were obtained from 49 neurologically healthy control subjects and 43 patients diagnosed with chronic refractory MTLE that was unilateral in origin (as measured by ictal EEG and hippocampal atrophy observed on MRI). Measurements of gray matter concentration (GMC) were made using automated segmentation algorithms. GMC was analyzed both voxel-by-voxel (preserving spatial precision) as well as using predefined regions of interest. Voxel-based morphometry revealed intense GMC reduction in the anterior portion relative to posterior thalami. Furthermore, thalamic atrophy was greater ipsilateral to the MTLE origin than on the contralateral side. Here we demonstrate that the thalamic atrophy is most intense in the thalamic nuclei that have strong connections with the limbic hippocampus. This finding suggests that thalamic atrophy reflects this region's anatomical and functional association with the limbic system rather than a general vulnerability to damage.     

优化VBM算法和DARTEL算法分析阿尔茨海默病MRI

目的 探讨优化VBM算法和DARTEL算法在分析阿尔茨海默病（AD）患者MRI的差别。方法 利用两种算法对14例AD患者（AD组）和23名健康对照（NC组）的MRI进行分析,并对其全脑灰质进行基于体素的统计学比较。结果 两种算法均报告颞叶右侧、海马、海马沟、海马旁回、杏仁核、枕叶深部存在灰质萎缩,但DARTEL算法报告的簇明显多于优化VBM算法;另外,部分区域在设置P<0.005时优化VBM算法仍未见报告。结论 分析AD患者的MRI时,采用DARTEL算法比优化VBM算法更合理。     

帕金森病轻度认知功能障碍:基于体素的全脑灰质形态学研究

目的采用基于体素的形态学测量方法,分析帕金森病(PD)伴轻度认知功能损害(MCI)患者全脑灰质结构的变化。方法利用3.0T MR仪对22例伴MCI的PD患者(PD伴MCI组)、21例认知功能正常的PD患者(单纯PD组)及20名健康对照(NC组)进行T1W扫描。采用SPM8为基础的VBM8工具箱进行数据处理。结果与NC组比较,PD伴MCI组脑灰质萎缩见于双侧额叶、左侧颞叶、双侧枕叶、双侧小脑、左侧后扣带回及左侧海马区域;单纯PD组脑灰质萎缩集中出现于左侧额叶、颞叶。与单纯PD组相比,PD伴MCI组左侧颞中回和海马旁回出现灰质萎缩。结论伴有MCI的PD患者的脑灰质结构改变范围比不伴MCI者更广,提示PD患者认知功能改变存在脑形态结构水平的异常。     

Tractography of the parahippocampal gyrus and material specific memory impairment in unilateral temporal lobe epilepsy

INTRODUCTION: Temporal lobe epilepsy (TLE) is associated with disrupted memory function. The structural changes underlying this memory impairment have not been demonstrated previously with tractography. METHODS: We performed a tractography analysis of diffusion magnetic resonance imaging scans in 18 patients with unilateral TLE undergoing presurgical evaluation, and in 10 healthy controls. A seed region in the anterior parahippocampal gyrus was selected from which to trace the white matter connections of the medial temporal lobe. A correlation analysis was carried out between volume and mean fractional anisotropy (FA) of the connections, and pre-operative material specific memory performance. RESULTS: There was no significant difference between the left and right sided connections in controls. In the left TLE patients, the connected regions ipsilateral to the epileptogenic region were found to be significantly reduced in volume and mean FA compared with the contralateral region, and left-sided connections in control subjects. Significant correlations were found in left TLE patients between left and right FA, and verbal and non-verbal memory respectively. CONCLUSION: Tractography demonstrated the alteration of white matter pathways that may underlie impaired memory function in TLE. A detailed knowledge of the integrity of these connections may be useful in predicting memory decline in chronic temporal lobe epilepsy.     

基于体素的形态学分析偏头痛患者灰质异常:Meta分析

目的 采用激活似然估计（ALE）的Meta分析方法,探讨偏头痛患者基于体素的形态学（VBM）分析所得的脑灰质改变。方法 在中国知网、PubMed和Embase数据库中检索从2000年1月—2015年6月间基于VBM的偏头痛患者灰质变化的文献,然后通过GingerALE软件包对所检索结果进行Meta分析。结果 检索后共纳入包括246例偏头痛患者和245名健康对照者的10项研究。偏头痛患者双侧额下回（BA44区）、右侧中央前回（BA43、44区）、双侧额中回（BA6、9区）、双侧扣带回前部（BA32区）、左侧扣带回（BA24区）、右侧颞上回（BA22区）、左侧岛叶（BA13区）、右侧顶下小叶（BA40区）灰质与健康对照者比较均显著减少（P均<0.05）。结论 偏头痛患者脑灰质结构的改变为进一步研究与疼痛有关的脑神经网络的病理、生理机制提供了形态学依据。     

基于体素形态学测量技术对高原地区正常成人脑结构的研究

目的基于体素形态学测量(VBM)技术,分析久居高原地区(3000 m)正常成人脑结构体积的变化。材料与方法选取两组正常成人参与本次研究,其中包括高原组[男8例,女8例,平均年龄(21.81±2.07)岁]和与之年龄、受教育年限相匹配的平原组[男7例、女13例,平均年龄(21.85±1.90)岁],对每个被试行全脑扫描,获取3D-T1结构图像,利用VBM方法对全脑灰、白质图像进行统计学分析。结果与平原组比较,高原组正常成人左侧后扣带回、颞上回灰质体积增加;右侧岛叶灰质体积减低;白质体积增加区域为左侧丘脑、右侧额上回、左侧豆状核、左侧枕叶。结论利用VBM技术对MRI结构图像分析,能够客观显示高原地区相对平原地区正常成人脑部特定区域体积的变化,从而全面的评价高原长期低氧对脑结构的影响。