Independent contributions of cortical gray matter atrophy and ventricle enlargement for predicting neuropsychological impairment in multiple sclerosis

The primary goal of this study was to investigate associations between regional gray matter (GM) atrophy and neuropsychological function in multiple sclerosis (MS), while accounting for the influence of central brain atrophy (i.e. third ventricle enlargement). Using a cross-sectional design, we studied 59 MS patients with brain MRI and neuropsychological testing. Regional gray matter fractions (rGMFs) were calculated from MRI images for 11 homologous brain areas using the semiautomatic brain region extraction (SABRE) technique. Neuropsychological testing followed consensus panel guidelines and included tests emphasizing episodic memory, working memory and processing speed. The analytic approach was stepwise linear regression, with forward selection and p<0.05 threshold for significance. Consistent with previous research, there were significant correlations between third ventricle width and neuropsychological tests. Stepwise linear regression analyses controlling for third ventricle width retained rGMFs obtained from specific regions within the prefrontal cortex. Left frontal atrophy was associated with tests emphasizing auditory/verbal memory. Right frontal atrophy was associated with impairment in visual episodic and working memory. For the first time, we show an independent relationship between cortical atrophy and cognitive impairment after accounting for the effects of central atrophy.     

Segmentation of brain magnetic resonance images for measurement of gray matter atrophy in multiple sclerosis patients

Multiple sclerosis (MS) affects both white matter and gray matter (GM). Measurement of GM volumes is a particularly useful method to estimate the total extent of GM tissue damage because it can be done with conventional magnetic resonance images (MRI). Many algorithms exist for segmentation of GM, but none were specifically designed to handle issues associated with MS, such as atrophy and the effects that MS lesions may have on the classification of GM. A new GM segmentation algorithm has been developed specifically for calculation of GM volumes in MS patients. The new algorithm uses a combination of intensity, anatomical, and morphological probability maps. Several validation tests were performed to evaluate the algorithm in terms of accuracy, reproducibility, and sensitivity to MS lesions. The accuracy tests resulted in error rates of 1.2% and 3.1% for comparisons to BrainWeb and manual tracings, respectively. Similarity indices indicated excellent agreement with the BrainWeb segmentation (0.858–0.975, for various levels of noise and rf inhomogeneity). The scan-rescan reproducibility test resulted in a mean coefficient of variation of 1.1% for GM fraction. Tests of the effects of varying the size of MS lesions revealed a moderate and consistent dependence of GM volumes on T2 lesion volume, which suggests that GM volumes should be corrected for T2 lesion volumes using a simple scale factor in order to eliminate this technical artifact. The new segmentation algorithm can be used for improved measurement of GM volumes in MS patients, and is particularly applicable to retrospective datasets.     

脑灰质异位症的MRI诊断（附18例分析）

目的：提出脑灰质异位症的ＭＲＩ诊断分型,提高对本病的认识。材料和方法：分析１８例脑灰质异位症的临床的ＭＲＩ表现类型。结果：灰质异位症依据形态与位置,主张将其分为四型,本组中Ⅰ型３例,Ⅱ型６例、Ⅲ型５例,Ⅳ型４例。结论：灰质异位症的ＭＲＩ表现具有特征性,将其分型能够提高对本病的认识,有利于作出正确的诊断;。     

Application of an automated voxel-based morphometry technique to assess regional gray and white matter brain atrophy in a canine model of aging

In recent years, voxel-based morphometry (VBM) has emerged as a technique to examine regional brain changes associated with normal and pathological aging. Despite its popularity in studies of human aging, application of VBM to animal models of brain aging is rare. In the present study, VBM techniques were developed to validate earlier region of interest (ROI) measures of brain aging in the dog and to provide a more comprehensive analysis of local changes in a canine model of brain aging. Consistent with previous findings, frontal lobe atrophy increased with age, most notably in aged male dogs. Age-related gray matter reductions were also observed in parietal and temporal lobes, thalamus, cerebellum, and brainstem. Temporal lobe atrophy was particularly prominent in old females. A number of age-related changes in white matter not previously explored in the dog were also identified with VBM. Specifically, aged males exhibited greater decreases in the internal capsula and cranial nerve bundles compared to decreased volumes in the alveus of the hippocampus in old female dogs. Together, the present results indicate that application of VBM techniques in a canine model of aging yields more comprehensive information regarding topographical patterns of brain aging in male and female dogs than previously reported using traditional manual ROI methods.     

Evidence for a direct association between cortical atrophy and cognitive impairment in relapsing-remitting MS

Cognitive deficits affecting memory, attention and speed of information processing are common in multiple sclerosis (MS). The mechanisms of cognitive impairment remain unclear. Here, we examined the association between neuropsychological test performance and brain atrophy in a group of mildly disabled patients with relapsing-remitting MS. We applied voxel-based morphometry (SPM2) to investigate the distribution of brain atrophy in relation to cognitive performance. Patients had lower scores than control subjects on tests of memory and executive function, including the PASAT, Digit Span Backward and a test of short-term verbal memory (Memo). Among patients, but not healthy controls, performance on the PASAT, a comprehensive measure of cognitive function and reference task for the cognitive evaluation of MS-patients, correlated with global grey matter volume as well as with grey matter volume in regions associated with working memory and executive function, including bilateral prefrontal cortex, precentral gyrus and superior parietal cortex as well as right cerebellum. Compared to healthy subjects, patients showed a volume reduction in left temporal and prefrontal cortex, recently identified as areas predominantly affected by diffuse brain atrophy in MS. A comparison of low performers in the patient group with their matched control subjects showed more extensive and bilateral temporal and frontal volume reductions as well as bilateral parietal volume loss, compatible with the progression of atrophy found in more advanced MS-patients. These findings indicate that MS-related deficits in cognition are closely associated with cortical atrophy.     

Global average gray and white matter N-acetylaspartate concentration in the human brain

Since the amino acid derivative N-acetylaspartate (NAA) is almost exclusive to neuronal cells in the adult mammalian brain and its concentration has shown local (or global) abnormalities in most focal (or diffuse) neurological diseases, it is considered a specific neuronal marker. Yet despite its biological and clinical prominence, the relative NAA concentration in the gray and white matter (GM, WM) remains controversial, with each reported to be higher than, equal to, or less than the other. To help resolve the controversy and importantly, access the NAA in both compartments in their entirety, we introduce a new approach to distinguish and quantify the whole-brain average GM and WM NAA concentration by integrating MR-image segmentation, localized and non-localized quantitative (1)H-MRS. We demonstrate and validate the method in ten healthy volunteers (5 women) 27+/-6 years old (mean+/-standard-deviation) at 1.5T. The results show that the healthy adult human brain comprises significantly less WM, 39+/-3%, than GM 60+/-4% by volume (p<0.01). Furthermore, the average NAA concentration in the WM, 9.5+/-1.0 mM, is significantly lower than in GM, 14.3+/-1.1 mM (p<0.01).     

应用基于体素的形态测量学分析工作记忆老化的脑灰质萎缩基础

目的利用基于体素的形态测量学(VBM)方法探讨老年人工作记忆能力衰退与脑灰质萎缩间的关系。方法在30名老年人(老年组)和38名青壮年人(对照组)中分别进行keep-track任务和2-back任务两种工作记忆任务检测。对所有受试者进行高分辨力MR扫描,并使用统计参数图(SPM)8软件进行VBM分析,比较老年组与对照组的脑灰质体积差异,并在老年组内利用多元回归分析寻找与工作记忆任务能力下降相关的责任萎缩脑区。结果与对照组相比,老年组工作记忆能力显著衰退,且出现广泛的脑灰质萎缩。老年组中,与keep-track任务能力相关的萎缩脑区主要位于双侧前额叶中下部、运动前区、顶叶后下部和小脑;与2-back任务相关的萎缩脑区主要位于左侧的前额叶下部、运动前区和颞叶。左腹侧运动前区(BA6)皮层的灰质体积与两个任务的行为学数据均存在显著相关性。结论老年人工作记忆能力下降与工作记忆神经网络的灰质萎缩有关。     

The vasocontractive action of norepinephrine and serotonin in deep arterioles of rat cerebral gray matter

To examine the direct effects of norepinephrine (NE) and serotonin (5-HT) on the contractility of arterioles in the gray matter of the rat cerebrum, we micro-perfused arterioles in vitro and observed the changes in luminal diameter under the stop-flow condition with constant intraluminal pressure. While the average diameter of the lumen of arterioles was 39.9 +/- 9.7 microm (n=7) in Hepes-buffered saline, the average in 10(-7) M NE in the extraluminal solution changed into smaller in saline by 21.1 +/- 5.4% (n=7). The contractile effect of NE shows a dose-dependent curve between the 10(-7) and 10(-5) M. The contractile response to 10(-6) M NE was significantly reduced by yohinbin, an alpha2 blocker. 10(-6) M NE applied to the lumen also caused contraction of arterioles by 12.4 +/- 5.3% in diameter (n=5). 5-HT at 10(-7) M in the extraluminal solution caused contraction of arterioles by 10.9 +/- 4.4% in diameter (n=7). 5-HT in the extraluminal solution caused contraction of arterioles in a dose dependent manner between 10(-10) and 10(-6) M. The contractile effect of 5-HT at 10(-6) M was strongly reduced by 10(-6) M ketanserin, a 5-HT2 receptor antagonist. 5-HT applied to the lumen had no effect at all (n=6), however NE applied to the lumen caused contraction. These results strongly suggest that 5-HT plays a significant role in arteriolar contractility only from the cerebrospinal fluid (CSF) side, while NE is an important regulator of arteriolar contractility from both the CSF and blood circulation sides.     

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...     

复发缓解型多发性硬化患者脑深部灰质核团铁沉积特征及与脑静脉血氧含量的相关性

目的 采用磁敏感加权成像（SWI）探讨复发缓解型多发性硬化（RRMS）患者脑深部灰质核团铁沉积的特点及其与脑静脉血氧含量的关系。方法 收集42例RRMS患者（RRMS组）及52名健康志愿者（对照组）,行常规MRI及SWI。应用SPIN软件生成并处理滤过后相位图,测量双侧大脑内静脉（ICV）、大脑中深静脉（DMCV）、双侧基底静脉（BV）、丘纹上静脉（STV）及双侧尾状核头（HCN）、苍白球（GP）、壳核（PUT）、丘脑（THA）、黑质（SN）及红核（RN）的相位值。结果 除双侧THA及右侧RN相位值外,RRMS患者双侧HCN、GP、PUT、SN及左侧RN相位值均较对照组减低（P均<0.05）。RRMS组BV、DMCV与左侧PUT（r=0.41、0.44, P均<0.05）、右侧PUT相位值呈正相关（r=0.38、0.43,P均<0.05）,ICV与左侧PUT相位值呈正相关（r=0.37,P=0.01）。结论 RRMS患者脑深部灰质核团的铁沉积明显增高,且与脑内静脉血氧含量降低具有相关性。     

The correlation between brain gray matter volume and empathizing and systemizing quotients in healthy children

The abilities to empathize and to systemize, two fundamental dimensions of cognitive style, are characterized by apparent individual differences. These abilities are typically measured using an empathizing quotient (EQ) and a systemizing quotient (SQ) questionnaire, respectively. The purpose of this study was to reveal any correlations between EQ and SQ scores and regional gray matter volumes in healthy children by applying voxel-based morphometry to magnetic resonance images. We collected MRIs of brain structure and administered children's versions of the EQ and SQ questionnaires (EQ-C and SQ-C, respectively) to 261 healthy children aged 5-15 years. Structural MRI data were segmented, normalized, and smoothed using an optimized voxel-based morphometric analysis. Next, we analyzed the correlation between regional gray matter volume and EQ-C and SQ-C scores adjusting for age, sex, and intracranial volume. The EQ-C scores showed significant positive correlations with the regional gray matter volumes of the left fronto-opercular and superior temporal cortices, including the precentral gyrus, the inferior frontal gyrus, the superior temporal gyrus, and the insula, which are functionally related to empathic processing. Additionally, SQ-C scores showed a significant negative correlation with the regional gray matter volume of the left posterior parietal cortex, which is functionally involved in selective attention processing. Our findings suggest that individual differences in cognitive style pertaining to empathizing or systemizing abilities could be explained by differences in the volume of brain structures that are functionally relevant to empathizing and systemizing.     

脊髓小脑共济失调3型患者脑白质及灰质微结构改变

目的 观察脊髓小脑共济失调3型(SCA3)患者脑白质及灰质微结构改变。方法 前瞻性招募37例SCA3患者(症状组)、15例SCA3患者直系亲属(症状前组)及35名健康志愿者(对照组),采集全脑3D T1WI及弥散峰度成像(DKI);对白质及灰质结构进行组间两两比较，针对存在差异脑区提取相关指标，分析脑白质及灰质结构改变与共济失调等级量表(SARA)的相关性。结果 症状前组纤维束受损主要见于双侧小脑上、中、下脚及大脑脚等处，其平均弥散峰度(MK)、径向弥散峰度(Kr)、轴向弥散峰度(Ka)及部分各向异性(FA)均低于对照组(P均<0.02);症状组受损纤维束广泛存在于双侧小脑上、中、下脚、大脑脚、内囊后肢、胼胝体、丘脑后辐射(包括视辐射)及上放射冠，其MK、Kr、Ka及FA均低于症状前组及对照组(P均<0.02)。相比对照组，症状组双侧小脑半球(前叶、后叶)、脑桥、延髓、双侧壳核及豆状核灰质体积(GMV)显著减少、双侧丘脑GMV显著增加(P均<0.02);相比症状前组，症状组脑桥GMV显著减低(P<0.02)。症状前组与对照组全脑GMV差异均无统计学意义(P均&g...     

Correlation among body height, intelligence, and brain gray matter volume in healthy children

A significant positive correlation between height and intelligence has been demonstrated in children. Additionally, intelligence has been associated with the volume of gray matter in the brains of children. Based on these correlations, we analyzed the correlation among height, full-scale intelligence quotient (IQ) and gray matter volume applying voxel-based morphometry using data from the brain magnetic resonance images of 160 healthy children aged 5-18 years of age. As a result, body height was significantly positively correlated with brain gray matter volume. Additionally, the regional gray matter volume of several regions such as the bilateral prefrontal cortices, temporoparietal region, and cerebellum was significantly positively correlated with body height and that the gray matter volume of several of these regions was also significantly positively correlated with full-scale intelligence quotient (IQ) scores after adjusting for age, sex, and socioeconomic status. Our results demonstrate that gray and white matter volume may mediate the correlation between body height and intelligence in healthy children. Additionally, the correlations among gray and white matter volume, height, and intelligence may be at least partially explained by the effect of insulin-like growth factor-1 and growth hormones. Given the importance of the effect of environmental factors, especially nutrition, on height, IQ, and gray matter volume, the present results stress the importance of nutrition during childhood for the healthy maturation of body and brain.     

宫内感染与脑白质损伤

脑室周围白质软化(periventricular leukomalacia,PVL)是大脑白质的一种损伤,也是新生儿脑损害的一种重要表现,并且可能是脑瘫的神经病理学基础[1].PVL的预后不良,可导致脑性瘫痪、癫痫、智力低下、听力、视力及语言障碍等,造成患儿终生残疾,因此已成为新的临床、公共卫生和社会问题.近年来,随着产科和围产保健技术的迅速发展、胎儿心率监护和胎儿超声的应用、高危新生儿病房的设立,人们曾乐观地预测PVL的发病数量将明显减少.     

In vivo detection of gray and white matter differences in GABA concentration in the human brain

A novel selective multiple quantum filtering-based chemical shift imaging method was developed for acquiring GABA images in the human brain at 3 T. This method allows a concomitant acquisition of an interleaved total creatine image with the same spatial resolution. Using T(1)-based image segmentation and a nonlinear least square regression analysis of GABA-to-total creatine concentration ratios in frontal and parietal lobes of healthy adult volunteers as a function of the tissue gray matter fraction, the mean GABA concentration in gray and white matter was determined to be 1.30+/-0.36 micromol/g and 0.16+/-0.16 micromol/g (mean+/-SD, n=13), respectively. It is expected that this method will become a useful tool for studying GABAergic function in the human brain in vivo.     

Unsupervised identification of white matter tracts in a mouse brain using a directional correlation-based region growing (DCRG) algorithm

The inner product of the major eigenvectors of adjacent pixels, known as the directional correlation (DC), has been used previously as a quantitative index to investigate directional similarity in white matter (WM) tracts. A high degree of directional similarity (i.e., high DC) among pixels within individual WM tracts was observed. Based on this observation, a region growing algorithm was employed to propagate an area from a seed point as a function of the DC threshold (DCt) to manually identify WM tracts in two-dimensional (2D) slices from diffusion tensor imaging (DTI). In the present study, an improved unsupervised DC based region growing (DCRG) method was implemented to reduce the operator-dependent variance and to improve the ease of use of the technique. By employing improved method, a multi-slice DTI data set of an in vivo mouse brain was used to identify the external capsule, visual pathway, and corpus callosum. The resultant WM tracts are computer rendered in three-dimensional (3D) images with anatomical images as structural references. In addition, three sets of ex vivo mouse brain data were used to examine the effects of different slice thickness and the signal-to-noise ratio (SNR) to the outcome of DCRG.