广泛性焦虑障碍和强迫障碍的基于体素的大脑灰质体积研究

目的:应用磁共振成像(MRI)技术探讨广泛性焦虑障碍(GAD)和强迫障碍(OCD)患者大脑灰质体积的特征性表现。方法:选取符合精神障碍诊断与统计手册第四修订版(DSM-IV-TR)或疾病和有关健康问题的国际统计分类第十次修订本(ICD-10)诊断标准的28例GAD、25例OCD及39例健康对照。全部研究对象完成高分辨率结构磁共振成像扫描,使用汉密顿焦虑量表(HAMA)和耶鲁布朗强迫量表(Y-BOCS)评估患者的焦虑或强迫症状严重程度。在全脑范围内采用基于体素的形态学分析方法,分别比较各组研究对象之间灰质体积的差异,并探讨GAD和OCD患者全脑灰质体积与HAMA和Y-BOCS总分的相关性。结果:与健康对照相比,GAD左侧前扣带回脑区灰质体积增加(P=0.016,小体积校正),OCD患者双侧眶额皮层等脑区灰质体积下降(P0.001,未校正);GAD患者较OCD患者在双侧眶额皮层等多个脑区灰质体积增加(P0.001,未校正)。GAD患者的HAMA总分与右侧颞叶的灰质体积增加相关,而OCD患者的HAMA总分则与眶额皮层等脑区的灰质体积变化相关(P0.001,未校正)。讨论:GAD和OCD患者并未共享相同的灰质体积异常脑区,两种疾病可能具有完全不同的大脑结构特征,并且其焦虑症状具有不同的神经机制。     

强迫症患者大脑灰质体积变化——基于体素的形态学分析

目的探讨强迫症(OCD)患者大脑灰质体积的变化,并分析其在发病过程中可能存在的相关机制。方法选择31例年龄17～47岁重度强迫症患者和31例正常对照被试者,获取脑结构磁共振T1图像,使用基于体素的形态学测量(VBM)方法,比较强迫症组和对照组大脑灰质体积的差异,并将患者灰质体积差异区与其临床评分进行相关分析。结果与对照组相比,OCD患者在左侧壳核、岛叶、运动前区、顶上小叶以及右侧角回处体积显著减小。左侧壳核和岛叶的体积与患者贝克焦虑量表(BAI)评分成显著负相关。结论左侧壳核、岛叶、运动前区、顶上小叶以及右侧角回的灰质体积变化影响了该脑区功能,从而导致了OCD患者的部分症状。其中左侧壳核以及岛叶的损伤与患者焦虑情绪的异常密切相关。     

正常人和精神分裂症患者脑灰质体积分析的性别效应

目的:通过比较男性和女性正常人、男性和女性精神分裂症患者之间的脑灰质体积差异,探讨脑结构分析中的性别效应。方法:采集60例正常人(30例男性)和96例精神分裂症患者(48例男性)的高分辨率三维脑结构磁共振图像,运用基于体素的形态测量法(VBM)进行分析,获得每一个体的脑灰质体积图像。采用两样本t检验分别比较男性和女性正常人,男性和女性精神分裂症患者之间的脑灰质体积差异。结果:与女性正常人相比,男性正常人左侧的颞中回和额中回、右侧的边缘叶和颞中回的灰质体积较大(P<0.001),而左侧尾状核和右侧海马的灰质体积较小(P<0.001)。与女性精神分裂症患者相比,男性患者双侧的颞下回和海马、左侧的颞上回和颞中回的灰质体积较大(P<0.001),而未发现灰质体积较小的脑区。结论:性别效应是影响正常人或精神分裂症患者脑结构分析的重要因素。     

基于VBM-DARTEL的局灶性皮质发育不良脑灰质体积异常检测方法

目的:局灶性皮质发育不良(Focal Cortical Dysplasia,FCD)是导致药物难治性癫痫的重要病因之一。如何应用磁共振影像探究FCD全脑解剖结构的异常变化部位和定位,对临床诊断和治疗具有重要意义。方法:本文建立一种基于VBM-DARTEL的FCD脑灰质异常检测方法。该方法包括对磁共振结构像进行图像分割、DARTEL模板制作、图像标准化等,最后使用双样本独立t检验统计分析患者组和对照组全脑灰质体积的差异,从而得到FCD脑灰质的病变特征。结果:与正常对照组相比,FCD患者组双侧大脑半球存在广泛脑区的灰质体积异常;FCD患者的脑灰质存在萎缩,并伴有灰质体积异常增大的脑区,且多集中在额叶和颞叶等区域。结论:基于DARTEL的VBM方法可以有效地检测FCD患者脑灰质体积的异常变化,且能准确定位FCD病灶。     

多发性硬化和视神经脊髓炎的脑灰质结构分析

目的 利用基于体素的形态学测量(VBM)和基于皮层的脑形态学测量(SBM)方法对多发性硬化(MS)和视神经脊髓炎(NMO)患者脑灰质体积及皮层厚度进行比较分析,探讨这两种疾病的脑灰质结构变化的差异。方法 对21例MS患者,16例NMO患者以及19例健康对照者行磁共振常规序列扫描,基于Matlab2014a平台的统计参数工具SPM12以及SPM12下的小工具CAT12,对VBM和SBM方法处理的数据进行分析。结果 MS组与正常对照(NC)组相比,经高斯随机场(GRF)校正后,MS组在左侧枕上回、左侧楔叶、左侧距状皮质、左侧楔前叶、左侧中央后回、左侧中央旁小叶、右侧楔叶、左侧额中回、左侧额上回和左侧额内侧回灰质体积显著性减少(P<0.05);经族系错误(FWE)法校正后,MS组在左侧中央旁小叶、左侧额上回和左侧楔前叶皮层厚度显著性减少(P<0.05)。NMO组与NC组相比,经GRF校正后,NMO组在左侧中央后回、左侧中央前回、左侧顶下小叶、右侧中央前回和右侧额中回灰质体积显著性增加(P<0.05);NMO组在左侧枕中回、左侧枕上回、左侧颞下回、右侧枕中回、左侧额上回眶部、...     

阴性症状为主的精神分裂症男性患者认知功能及灰质密度改变

目的:运用基于体素的脑形态测量学方法(VBM),探讨以阴性症状为主的精神分裂症男性患者大脑结构形态学的改变,及其与精神病理学症状的关系。方法:15例阴性症状为主的成年男性精神分裂症患者和15例正常对照参与实验,所有研究对象均接受威斯康星卡片分类测验(WCST)与磁共振检查,获取磁共振T1加权像和高分辨率3D图像后进行VBM分析,比较患者组和正常对照组局部脑区灰质密度的差异性。结果:在威斯康星测验中,阴性症状为主的精神分裂症患者完成测查的总应答数、错误应答数和持续性错误数显著高于正常对照组,正确应答数和完成分类数与正常对照组没有显著差异。VBM分析显示患者右侧额上回,左侧额中回,左额内侧回,右侧楔叶,左侧颞中回的灰质密度较正常对照组低,未发现患者组灰质密度有明显增高的脑区。结论:以阴性症状为主的精神分裂症患者存在显著的额叶执行功能低下;双侧额叶灰质密度的下降可能是其执行功能损害的病理生理基础。     

空气细颗粒物PM2.5对人体各系统危害的研究

随着人类工业化进程的加快,空气污染逐渐加重。其中,细颗粒物（PM）污染对人体健康的危害最大。国内外大量研究表明,作为雾霾重要组成部分的PM2.5可诱发或加重各个系统的疾病。笔者就PM2.5对人体呼吸系统、循环系统、中枢神经系统、机体代谢及免疫、泌尿生殖系统、血液系统、消化系统、皮肤及其他系统危害的研究进展进行综述。     

空气细颗粒物(PM_(2.5))及其致病性的研究现状

在日常病理诊断工作中,在肺、淋巴结、脾脏及一些器官切片的尘细胞及间质内经常能够看到一些黑色颗粒状物质--尘粒,有人称之为"碳粉"颗粒,一般认为其对人体没有致病性.目前的研究认为肺等器官内的"碳粉"尘粒实际上是被尘细胞吞噬的悬浮在大气中固体和液体的颗粒物(ambient air particulate matter,PM).全世界每年有270万人死于空气污染,PM为其主要污染物,大量研究也表明PM对心血管、呼吸等系统疾病的发病率和死亡率都是一个独立的危险因素,其致病性可累及多个系统,并为一些病因不明的疾病提供新的假说,已逐渐引起人们的高度重视[1～3].     

联合应用VBM方法和DTI技术对精神分裂症小脑结构的研究

目的分别应用磁共振扩散张量成像技术(DTI)和基于体素的形态分析法(VBM)对精神分裂症患者小脑中脚和上脚白质纤维情况与小脑的灰白质密度进行初步探究。方法应用GESigna3.0TMRI扫描仪,分别对按照精神分裂症诊断标准确诊的14例患者及14名健康对照者行DTI和三维快速扰相梯度翻转恢复(3D-SPGR)序列扫描,检测双侧小脑中脚和上脚感兴趣区的各向异性分数值(FA)及小脑灰白质密度,应用成组t检验对病例组和正常对照组的以上数据进行比较。结果精神分裂症病例组左侧小脑上脚的FA值较正常对照组显著降低(<0.05),小脑局部脑区的灰质密度与正常组相比发生了显著改变,差异区域主要位于小脑前叶(<0.05),小脑的白质密度与正常组相比未发现显著改变脑区。结论 DTI技术和VBM方法的联合应用对精神分裂症患者的研究有着重要的应用价值。     

基于体素的和基于形变的形态学测量在轻度认知障碍识别上的比较研究

目的 比较基于体素的形态学测量(voxel-based morphometry,VBM)和基于形变的形态学测量(deformation-based morphometry,DBM)在检测轻度认知功能障碍(mild cognitive impairment,MCI)灰质异常及相应分类识别性能上的差异,为结构态分析方法的选择提供依据.方法 利用VBM和DBM对27例MCI患者及30例健康对照的磁共振结构像进行分析,分别统计比较获得相应的组间结构异常脑区,并将异常脑区作为分类特征构建相应的MCI诊断识别模型,最终通过评价异常脑区的空间分布特征及分类识别准确率来评估两种方法的差异.结果 VBM和DBM均发现MCI患者在海马、海马旁回、杏仁核、岛叶等脑区发生结构改变,但VBM方法还在额中回、颞中回等脑区发现异常.VBM确定的结构异常得到了86.0％的最佳准确度,而DBM方法的准确度为77.2％,虽然在性能表现上稍差,但发现的特征与VBM的最优特征具有一致性.结论 VBM方法可以发现更多的MCI结构异常,而DBM方法则能发现具有较强敏感性的结构异常,因而提示在磁共振结构像研究中应将两者结合应用.     

Association of white matter hyperintensities and gray matter volume with cognition in older individuals without cognitive impairment

Both presence of white matter hyperintensities (WMH) and smaller total gray matter volume on brain magnetic resonance imaging (MRI) are common findings in old age, and contribute to impaired cognition. We tested whether total WMH volume and gray matter volume had independent associations with cognition in community-dwelling individuals without dementia or mild cognitive impairment (MCI). We used data from participants of the Rush Memory and Aging Project. Brain MRI was available in 209 subjects without dementia or MCI (mean age 80; education = 15 years; 74 % women). WMH and gray matter were automatically segmented, and the total WMH and gray matter volumes were measured. Both MRI-derived measures were normalized by the intracranial volume. Cognitive data included composite measures of five different cognitive domains, based on 19 individual tests. Linear regression analyses, adjusted for age, sex, and education, were used to examine the relationship of logarithmically-transformed total WMH volume and of total gray matter volume to cognition. Larger total WMH volumes were associated with lower levels of perceptual speed (p < 0.001), but not with episodic memory, semantic memory, working memory, or visuospatial abilities (all p > 0.10). Smaller total gray matter volumes were associated with lower levels of perceptual speed (p = 0.013) and episodic memory (p = 0.001), but not with the other three cognitive domains (all p > 0.14). Larger total WMH volume was correlated with smaller total gray matter volume (p < 0.001). In a model with both MRI-derived measures included, the relation of WMH to perceptual speed remained significant (p < 0.001), while gray matter volumes were no longer related (p = 0.14). This study of older community-dwelling individuals without overt cognitive impairment suggests that the association of larger total WMH volume with lower perceptual speed is independent of total gray matter volume. These results help elucidate the pathological processes leading to lower cognitive function in aging.     

Sex dimorphism in gray/white matter volume and diffusion tensor during normal aging

The purpose of this study is to elucidate sex differences in global and regional gray/white matter volume, mean diffusivity (MD), and fractional anisotropy (FA) during normal aging using voxel‐based analysis. We studied 245 healthy right‐handed subjects with a wide range of ages (115 women, 22–70 years; 130 men, 21–71 years). Regarding global effects, inclusion of a quadratic age term improved the fit to data for white matter fraction and MD, but not for global gray matter volume/fraction or FA. Regarding regional effects, we found anterior‐dominant volume loss, FA decrease predominantly in the anterior white matter, and MD increase predominantly in perisylvian regions and periventricular white matter against age for both sexes. Compared with women, we found a steeper FA decline for men in the right inferior fronto‐temporal areas, extending to the anterior cingulate cortex, and an accelerated MD increase for men in the bilateral frontal, temporal, and parietal areas. There was no area in which interaction of sex with age was significant for regional volume, or in which a steeper FA decline or accelerated MD increase for women was significant. Our results provide strong evidence of sex dimorphism in global and focal diffusion characteristics during normal aging. Copyright © 2010 John Wiley & Sons, Ltd.     

结节病肉芽肿细胞内空气细颗粒物元素组成及来源分析

目的 分析结节病肉芽肿细胞(吞噬细胞、类上皮细胞、多核巨细胞)内空气细颗粒物(PM2.5)的元素组成及来源,探讨结节病与PM2.5的相关性.方法 收集50例结节病病变组织、10例非结节病成人尸检肺组织、18例PM2.5支气管灌注染毒大鼠肺组织(有肉芽肿病灶)石蜡包埋标本,采集大气中PM2.5,分别行HE染色、沃森-斯塔理(Warthin-Starry,WS)银染色,应用共聚焦显微镜拉曼光谱和透射电镜-能谱对上述部分病例标本肉芽肿细胞和尘细胞内的PM2.5及大气PM2.5的成分进行分析,用X线荧光分析技术对所采集大气PM2.5的主要元素成分进行分析.结果 结节病病变组织、非结节病成人尸检肺组织、PM2.5支气管灌注染毒大鼠肺组织及大气中PM2.5共4组标本中PM2.5的拉曼光谱和元素组成非常相似,均以碳质成分为主要特征.结论 为结节病肉芽肿细胞中的PM2.5来源于大气PM2.5提供了进一步的依据,从而不能完全除外结节病患者可能是对PM2.5易感的个体的可能性.

Abstract：

Objective To explore the source of the fine particulate matter (PM2.5) in the sarcoidosis granulomatous cell and the relationship between the sarcoidosis and the PM2.5 in the atmosphere.Methods Paraffin-embedded tissues of 50 cases of human sarcoidosis biopsy samples, 10 cases of nonsarcoidosis autopsy lung samples, 18 cases of lung tissues (with granulomatous lesions) of rats exposed to PM2.5 by bronchial infusion, and the free PM2.5 sample in the atmosphere were collected. The characteristics of tissues above mentioned were observed under the light microscopy, which stained by HE staining and Warthin-Starry silver staining. The characteristics of the PM2.5 in the four groups were analyzed using confocal Raman microscopy. The component of the PM2.5 in the sarcoidosis granuloma was analyzed using transmission electron microscope-energy dispersive X-ray detector (TEM-EDX), and the component of the PM2.5 in the atmosphere was analyzed with X-ray fluorescence separately. Results The PM2.5 in the four groups have the similar Raman spectrum, they share the feature of carbonaceous composition, the element component of PM2.5 in the human sarcoidosis was the same as PM2.5 in the atmosphere. Conclusion The study provided the further evidence that the PM2.5 in the sarcoidosis lesion was from PM2.5 in the atmosphere,and it should be not excepted that sarcoidosis may be a sensitive individual reaction to the PM2.5 inhaled from the atmosphere.     

Ultrafine but not fine particulate matter causes airway inflammation and allergic airway sensitization to co-administered antigen in mice

BACKGROUND: Airborne particulate matter (PM) is an important factor associated with the enhanced prevalence of respiratory allergy. The PM adjuvant activity on allergic sensitization is a possible mechanism of action involved, and the induction of airway inflammation is suggested to be of importance in PM-induced adjuvant activity. OBJECTIVE: Because differently sized PM have different toxic potentials, we studied the role of particle size in the induction of airway inflammation and allergic sensitization. This was done using fine (0.250 and 0.260 micro m) and ultrafine (0.029 and 0.014 micro m) titanium dioxide (TiO(2)) and carbon black particles (CBP) with known differences in airway toxicity. METHODS: Mice were intranasally exposed to ovalbumin (OVA) alone or in combination with one of the different particles. The induction of airway inflammation and the immune adjuvant activity were studied in the lungs and lung-draining peribronchial lymph nodes (PBLN) at day 8. OVA-specific antibodies were measured at day 21, and the development of allergic airway inflammation was studied after OVA challenges (day 28). RESULTS: When administered at the same total particle mass (200 micro g), exposure to ultrafine TiO(2) and CBP-induced airway inflammation, and had immune adjuvant activity. The latter was shown by increasing both the PBLN cell numbers and the production of OVA-specific T-helper type 2 (Th2) cytokines (IL-4, IL-5, IL-10 and IL-13). Whereas OVA-specific IgE and IgG1 levels in serum were only increased in animals exposed to the ultrafine TiO(2), allergic airway inflammation could be detected in both ultrafine TiO(2)-and CBP-treated groups after challenges with OVA. CONCLUSION: Our data show that only the ultrafine particles, with a small diameter and a large total surface area/mass, cause airway inflammation and have immune adjuvant activity in the current model supporting the hypothesis that particle toxicity is site-dependent and related to adjuvant activity.     

Detection of differentiated changes in gray matter in children with progressive hydrocephalus and chronic compensated hydrocephalus using voxel-based morphometry and machine learning

Currently, no neuroimaging study has reported the detection of specific imaging biomarkers that distinguish the progressive hydrocephalus (PH) and chronic compensated hydrocephalus (CH). Our main focus is to evaluate the different structural changes in classifying the two types of hydrocephalus children. Twenty-two children with hydrocephalus (12 PHs and 10 CHs) and 30 age-matched healthy controls were enrolled and the T1-weighted imaging was collected in the study. A customized voxel-based morphometry (VBM) approach and support vector machine (SVM) were combined to investigate the structural changes and group classification. Comparing with the controls and CH, PH groups invariably showed a significant decrease of GM volume in the bilateral hippocampus/parahippocampus, insula, and motor-related areas. SVM applied to the GM volumes of bilateral hippocampus/parahippocampus, insula, and motor-related areas correctly identified hydrocephalus children from normal controls with a statistically significant accuracy of 88.46% (p ≤ .001). In addition, SVM applied to GM volumes of the same regions correctly identified PH from CH with a statistically significant accuracy of 77.27% (p ≤ .009). Using VBM analysis, we characterized and visualized the GM changes in children with hydrocephalus. Machine learning results further confirmed that a significant decrease of the bilateral hippocampus/parahippocampus, insula, and motor-related GM volume can serve as a specific neuroimaging index to distinguish the children with PH from the children with CH and controls at individual. The findings could help to aid the identification of individuals with PH in clinical practice.     

Longitudinal absolute metabolite quantification of white and gray matter regions in healthy controls using proton MR spectroscopic imaging

The purpose of this study was to evaluate quality parameters, metabolite concentrations and concentration ratios, and to investigate the reproducibility of quantitative proton magnetic resonance spectroscopic imaging (¹H‐MRSI) of selected white and gray matter regions of healthy adults. 2D‐quantitative short‐T_E ¹H‐MRSI spectra were obtained at 1.5T from the healthy human brain. Subjects (n = 12) were scanned twice with an interval of six months. Absolute metabolite concentrations were obtained based on coil loading, taking into account differences in sensitivity of the phased‐array head coil. Spectral quality parameters, absolute metabolite concentrations, concentration ratios, and their reproducibility were determined and compared between time‐points using a repeated measures general linear model. The quality of the spectra of selected brain areas was good, as determined by a mean spectral linewidth between 4.8 and 7.3 Hz (depending on the region). No significant differences between the two time‐points were observed for spectral quality, concentrations, or concentration ratios. The mean intrasubject coefficient of variation (CoV) varied between 4.0 and 8.5% for total N‐acetylaspartate, 7.2 and 10.8% for total creatine, 5.9 and 9.8% for myo‐inositol, and 8.0 and 13.3% for choline, and remained below 20% for glutamate. CoV was generally lower when concentration ratios were considered. The study shows that longitudinal quantitative short‐T_E ¹H‐MRSI generates reproducible absolute metabolite concentrations in healthy human white and gray matter. This may serve as a background for longitudinal clinical studies in adult patients. Copyright © 2014 John Wiley & Sons, Ltd.     

The role of gray and white matter segmentation in quantitative proton MR spectroscopic imaging

Since the brain's gray matter (GM) and white matter (WM) metabolite concentrations differ, their partial volumes can vary the voxel's ¹H MR spectroscopy (¹H‐MRS) signal, reducing sensitivity to changes. While single‐voxel ¹H‐MRS cannot differentiate between WM and GM signals, partial volume correction is feasible by MR spectroscopic imaging (MRSI) using segmentation of the MRI acquired for VOI placement. To determine the magnitude of this effect on metabolic quantification, we segmented a 1‐mm³ resolution MRI into GM, WM and CSF masks that were co‐registered with the MRSI grid to yield their partial volumes in approximately every 1 cm³ spectroscopic voxel. Each voxel then provided one equation with two unknowns: its i‐ metabolite's GM and WM concentrations C_i^GM, C_i^WM. With the voxels' GM and WM volumes as independent coefficients, the over‐determined system of equations was solved for the global averaged C_i^GM and C_i^WM. Trading off local concentration differences offers three advantages: (i) higher sensitivity due to combined data from many voxels; (ii) improved specificity to WM versus GM changes; and (iii) reduced susceptibility to partial volume effects. These improvements made no additional demands on the protocol, measurement time or hardware. Applying this approach to 18 volunteered 3D MRSI sets of 480 voxels each yielded N‐acetylaspartate, creatine, choline and myo‐inositol C_i^GM concentrations of 8.5 ± 0.7, 6.9 ± 0.6, 1.2 ± 0.2, 5.3 ± 0.6mM, respectively, and C_i^WM concentrations of 7.7 ± 0.6, 4.9 ± 0.5, 1.4 ± 0.1 and 4.4 ± 0.6mM, respectively. We showed that unaccounted voxel WM or GM partial volume can vary absolute quantification by 5–10% (more for ratios), which can often double the sample size required to establish statistical significance. Copyright © 2012 John Wiley & Sons, Ltd.