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.     

Automated separation of gray and white matter from MR images of the human brain

A simple automatic procedure for segmentation of gray and white matter in high resolution 1.5T T1-weighted MR human brain images was developed and validated. The algorithm is based on histogram shape analysis of MR images that were corrected for scanner nonuniformity. Calibration and validation was done on a set of 80 MR images of human brains. The automatic method's values for the gray and white matter volumes were compared with the values from thresholds set twice by the best three of six raters. The automatic procedure was shown to perform as good as the best rater, where the average result of the best three raters was taken as reference. The method was also compared with two other histogram-based threshold methods, which yielded comparable results. The conclusion of the study thus is that automated threshold based methods can separate gray and white matter from MR brain images as reliably as human raters using a thresholding procedure.     

Use of normative distribution of gray to white matter ratio in orthogonal planes in human brain studies and computer-assisted neuroradiology

Purpose  

Although the brain has been extensively studied, relationships of gray (GM) to white (WM) matters in individual sections as typically acquired and read radiologically have not yet been examined. A novel GM/WM-based approach with a compact whole brain representation is introduced and applied to study the brain and perform neuroimage processing.     

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...     

Fusion of white and gray matter geometry: A framework for investigating brain development

Current neuroimaging investigation of the white matter typically focuses on measurements derived from diffusion tensor imaging, such as fractional anisotropy (FA). In contrast, imaging studies of the gray matter oftentimes focus on morphological features such as cortical thickness, folding and surface curvature. As a result, it is not clear how to combine findings from these two types of approaches in order to obtain a consistent picture of morphological changes in both gray and white matter.In this paper, we propose a joint investigation of gray and white matter morphology by combining geometrical information from white and the gray matter. To achieve this, we first introduce a novel method for computing multi-scale white matter tract geometry. Its formulation is based on the differential geometry of curve sets and is easily incorporated into a continuous scale-space framework.We then incorporate this method into a novel framework for “fusing” white and gray matter geometrical information. Given a set of fiber tracts originating in a particular cortical region, the key idea is to compute two scalar fields that represent geometrical characteristics of the white matter and of the surface of the cortical region. A quantitative marker is created by combining the distributions of these scalar values using Mutual Information. This marker can be then used in the study of normal and pathological brain structure and development. We apply this framework to a study on autism spectrum disorder in children. Our preliminary results support the view that autism may be characterized by early brain overgrowth, followed by reduced or arrested growth (Courchesne, 2004).     

Fusion of white and gray matter geometry: A framework for investigating brain development

Current neuroimaging investigation of the white matter typically focuses on measurements derived from diffusion tensor imaging, such as fractional anisotropy (FA). In contrast, imaging studies of the gray matter oftentimes focus on morphological features such as cortical thickness, folding and surface curvature. As a result, it is not clear how to combine findings from these two types of approaches in order to obtain a consistent picture of morphological changes in both gray and white matter.In this paper, we propose a joint investigation of gray and white matter morphology by combining geometrical information from white and the gray matter. To achieve this, we first introduce a novel method for computing multi-scale white matter tract geometry. Its formulation is based on the differential geometry of curve sets and is easily incorporated into a continuous scale-space framework.We then incorporate this method into a novel framework for “fusing” white and gray matter geometrical information. Given a set of fiber tracts originating in a particular cortical region, the key idea is to compute two scalar fields that represent geometrical characteristics of the white matter and of the surface of the cortical region. A quantitative marker is created by combining the distributions of these scalar values using Mutual Information. This marker can be then used in the study of normal and pathological brain structure and development. We apply this framework to a study on autism spectrum disorder in children. Our preliminary results support the view that autism may be characterized by early brain overgrowth, followed by reduced or arrested growth (Courchesne, 2004).     

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.     

Fractional anisotropy of cerebral white matter and thickness of cortical gray matter across the lifespan

We examined age trajectories of fractional anisotropy (FA) of cerebral white matter (WM) and thickness of cortical gray matter (GM) in 1031 healthy human subjects (aged 11-90 years). Whole-brain FA and GM thickness values followed quadratic trajectories with age but the relationship between them was linear, indicating that a putative biological mechanism may explain the non-linearity of their age trajectories. Inclusion of the FA values into the quadratic model of the whole-brain and regional GM thickness changes with age made the effect of the age(2) term no longer significant for the whole-brain GM thickness and greatly reduced its significance for regional GM thickness measurements. The phylogenetic order of cerebral myelination helped to further explain the intersubject variability in GM thickness. FA values for the early maturing WM were significantly better (p=10(-6)) at explaining variability in GM thickness in maturing (aged 11-20) subjects than FA values for the late maturing WM. The opposite trend was observed for aging subjects (aged 40-90) where FA values for the late maturing WM were better (p=10(-16)) at explaining the variability in GM thickness. We concluded that the non-linearity of the age trajectory for GM thickness, measured from T1-weighted MRI, was partially explained by the heterogeneity and the heterochronicity of the age-related changes in the microintegrity of cerebral WM. We consider these findings as the evidence that the measurements of age-related changes in GM thickness and FA are driven, in part, by a common biological mechanism, presumed to be related to changes in cerebral myelination.     

磁共振扩散张量成像在显示正常人脑白质纤维中的应用

目的应用DTI技术显示正常人脑白质纤维,探讨其与解剖学描述的一致性。方法20名健康志愿者行颅脑MRI与颅脑单次激发回波平面扩散张量成像扫描(b值=0,500s/mm2),在SiemensLeonardo工作站应用纤维束跟踪软件(SiemensStandar12dirs)进行后处理重建出白质纤维束。结果对主要白质纤维如皮质脊髓束、皮质核束、胼胝体、扣带、上纵束、下纵束、上枕额束、下枕额束、钩束进行模拟显示,不同纤维需要选择适合的感兴趣区、各向异性阈值、角度阈值、步长和体素内采样数目等参数,显示结果与解剖学描述具有较好的一致性。结论利用扩散张量成像技术可模拟显示正常人脑白质纤维,与解剖学描述具有较好的一致性,是在活体中研究人脑白质纤维的一种较可靠的方法。     

The molecular basis for gray and white matter contrast in phase imaging

Direct magnetic resonance phase images acquired at high field have been shown to yield superior gray and white matter contrast up to 10-fold higher compared to conventional magnitude images. However, the underlying contrast mechanism is not yet understood. This study demonstrates that the water resonance frequency is directly shifted by water-macromolecule exchange processes (0.040 ppm/mM for bovine serum albumin) and might be a major source of contribution to in vivo phase image contrast. Therefore, magnetic resonance phase imaging based on the proposed contrast mechanism could potentially be applied for in vivo studies of pathologies on a macromolecular level.     

Automatic identification of gray and white matter components in polarized light imaging

Polarized light imaging (PLI) enables the visualization of fiber tracts with high spatial resolution in microtome sections of postmortem brains. Vectors of the fiber orientation defined by inclination and direction angles can directly be derived from the optical signals employed by PLI analysis. The polarization state of light propagating through a rotating polarimeter is varied in such a way that the detected signal of each spatial unit describes a sinusoidal signal. Noise, light scatter and filter inhomogeneities, however, interfere with the original sinusoidal PLI signals, which in turn have direct impact on the accuracy of subsequent fiber tracking. Recently we showed that the primary sinusoidal signals can effectively be restored after noise and artifact rejection utilizing independent component analysis (ICA). In particular, regions with weak intensities are greatly enhanced after ICA based artifact rejection and signal restoration.Here, we propose a user independent way of identifying the components of interest after decomposition; i.e., components that are related to gray and white matter. Depending on the size of the postmortem brain and the section thickness, the number of independent component maps can easily be in the range of a few ten thousand components for one brain. Therefore, we developed an automatic and, more importantly, user independent way of extracting the signal of interest. The automatic identification of gray and white matter components is based on the evaluation of the statistical properties of the so-called feature vectors of each individual component map, which, in the ideal case, shows a sinusoidal waveform. Our method enables large-scale analysis (i.e., the analysis of thousands of whole brain sections) of nerve fiber orientations in the human brain using polarized light imaging.     

Cross-relaxation imaging reveals detailed anatomy of white matter fiber tracts in the human brain

Cross-relaxation imaging is a new quantitative MRI modality, which allows mapping of fundamental parameters determining the magnetization transfer (MT) effect in tissues, cross-relaxation rate constant (k) and bound pool fraction (f). This study introduces a new time-efficient technique for cross-relaxation imaging, which obtains three-dimensional (3D) whole-brain k and f maps with scan time of <30 min and isotropic spatial resolution of 1.4 mm. The technical principle of the method is based on four-point fit of a matrix model of pulsed MT to imaging data obtained with variable offset frequency saturation while using a complimentary R1 (=1 / T1) map. Anatomical correlations of in vivo cross-relaxation parametric maps were evaluated in three healthy subjects. The f maps revealed correspondence of areas with highly elevated f = 12-15% to major fiber tracts such as corpus callosum, anterior commissure, optic radiations, and major brain fasciculi. The rest of white matter (WM) demonstrated lower f = 9-11%, resulting in clear visual contrast of fiber tracts. Even lower f = 6.5-8.5% were found in gray matter (GM) with the highest f = 8.5% in the anterior thalamus. Distribution of k was relatively uniform in WM and produced sharp contrast between GM and WM (k = 1.6 and 3.3 s(-1), respectively). The most marked feature of k maps was their ability to visualize the corticospinal tract, which had elevated k = 3.4-3.8 s(-1) but appeared invisible on f maps. The observed patterns on f maps can be explained by variations in the density of myelinated fibers, while the trends of k may reflect regional differences in axonal organization. Cross-relaxation imaging can be used in various clinical studies focused on brain development and white matter diseases.     

抑郁症灰白质表面积性别差异研究

目的探讨重性抑郁症(major depressive disorder,MDD)患者灰白质表面面积改变的性别差异,并分析其与不同性别患者临床特征间的关系。材料与方法前瞻性收集61例MDD患者和匹配的61例健康对照(两组均为男性25例、女性36例)行3D T1WI高分辨率磁共振扫描,用freeSurfer软件进行图像预处理,获得全脑各区域的灰、白质表面面积图像,采用双因素方差分析计算并提取四组间灰、白质表面面积的性别差异脑区,行post-hoc检验进行各组间两两比较,将男女性MDD性别差异脑区与临床资料进行相关分析。结果性别差异主结果显示双侧额上回、颞中回及左侧额中回喙部、枕外侧回灰、白质表面面积均存在差异,且双侧颞上回、左侧中央前回、岛叶、右侧额叶三角部、眶额内侧回、梭状回、顶下小叶白质表面面积及左侧缘上回、右侧额中回喙部、中央前回、颞下回、梭状回、前缘扣带回、枕外侧回、顶下小叶灰质表面面积存在差异(P<0.01,Bonforroni校正)。进一步post-hoc两两比较发现以上脑区女性MDD组灰、白质表面面积均小于男性MDD组(P<0.01,Bonforroni校正)。相关分析显示男性MDD组右侧额中回喙部(r=-0.398,P=0.049)及梭状回(r=-0.440,P=0.028)灰质表面面积与汉密尔顿抑郁量表评分呈负相关,左侧颞中回灰质表面面积与男性MDD病程呈负相关(r=-0.419,P=0.037)。结论MDD患者灰、白质表面面积均存在性别差异,但是差异脑区并不完全重叠,这些差异脑区可能与男女性MDD患者临床表现和发病率的差异有关。     

Global and local gray matter loss in mild cognitive impairment and Alzheimer's disease

PURPOSE: Mild cognitive impairment (MCI) is thought to be the prodromal phase to Alzheimer's disease (AD). We analyzed patterns of gray matter (GM) loss to examine what characterizes MCI and what determines the difference with AD. MATERIALS AND METHODS: Thirty-three subjects with AD, 14 normal elderly controls (NCLR), and 22 amnestic MCI subjects were included and underwent brain MR imaging. Global GM volume was assessed using segmentation and local GM volume was assessed using voxel-based morphometry (VBM); VBM was optimized for template mismatch and statistical mass. RESULTS: AD subjects had significantly (12.3%) lower mean global GM volume when compared to controls (517 +/- 58 vs. 590 +/- 52 ml; P < 0.001). Global GM volume in the MCI group (552 +/- 52) was intermediate between these two: 6.2% lower than AD and 6.5% higher than the controls but not significantly different from either group. VBM showed that subjects with MCI had significant local reductions in gray matter in the medial temporal lobe (MTL), the insula, and thalamus compared to NCLR subjects. By contrast, when compared to subjects with AD, MCI subjects had more GM in the parietal association areas and the anterior and the posterior cingulate. CONCLUSION: GM loss in the MTL characterizes MCI, while GM loss in the parietal and cingulate cortices might be a feature of AD.     

基于体素的形态学方法评价急性脊髓损伤患者脑灰白质体积改变

目的 采用基于体素的形态学（VBM）分析方法探讨急性脊髓损伤（SCI）患者脑灰白质体积改变。方法 对16例急性SCI患者（受伤时间< 30天,SCI组）和20名年龄、性别匹配的正常志愿者（对照组）行脑3D T1W序列扫描,采用VBM分析方法比较2组脑灰白质体积,获得脑灰质体积差异有统计学意义的脑区;测量或计算脑组织体积（BTV）、全脑体积（TIV）、脑灰质体积（GMV）、脑白质体积（WMV）、脑脊液体积（CSFV）和脑灰质分数（GMF）、脑白质分数（WMF）和脑组织分数（BTF）。结果 与对照组相比,SCI组双侧下额叶、岛叶、内侧前额叶及前扣带皮质、小脑后叶灰质体积减小,内囊水平皮质脊髓束体积减小。SCI组与对照组间GMV、WMV、CSFV、BTV、TIV及GMF、WMF、BTF差异均无统计学意义（P均> 0.05）。结论急性SCI导致远隔部位情绪处理相关脑区灰质及皮质脊髓束萎缩,有助于探讨急性SCI对大脑结构产生影响的作用机制。     

Changes in brain gray matter due to repetitive painful stimulation

Using functional imaging, we recently investigated how repeated painful stimulation over several days is processed, perceived and modulated in the healthy human brain. Considering that activation-dependent brain plasticity in humans on a structural level has already been demonstrated in adults, we were interested in whether repeated painful stimulation may lead to structural changes of the brain. 14 healthy subjects were stimulated daily with a 20 min pain paradigm for 8 consecutive days, using structural MRI performed on days 1, 8, 22 and again after 1 year. Using voxel based morphometry, we are able to show that repeated painful stimulation resulted in a substantial increase of gray matter in pain transmitting areas, including mid-cingulate and somatosensory cortex. These changes are stimulation dependent, i.e. they recede after the regular nociceptive input is stopped. This data raises some interesting questions regarding structural plasticity of the brain concerning the experience of both acute and chronic pain.     

Automated fiber tracking of human brain white matter using diffusion tensor imaging

Reconstruction of white matter tracts based on diffusion tensor imaging (DTI) is currently widely used in clinical research. This reconstruction allows us to identify coordinates of specific white matter tracts and to investigate their anatomy. Fiber reconstruction, however, relies on manual identification of anatomical landmarks of a tract of interest, which is based on subjective judgment and thus a potential source of experimental variability. Here, an automated tract reconstruction approach is introduced. A set of reference regions of interest (rROIs) known to select a tract of interest was marked in our DTI brain atlas. The atlas was then linearly transformed to each subject, and the rROI set was transferred to the subject for tract reconstruction. Agreement between the automated and manual approaches was measured for 11 tracts in 10 healthy volunteers and found to be excellent (kappa>0.8) and remained high up to 4-5 mm of the linear transformation errors. As a first example, the automated approach was applied to brain tumor patients and strategies to cope with severe anatomical abnormalities are discussed.     

Joint source based morphometry identifies linked gray and white matter group differences

We present a multivariate approach called joint source based morphometry (jSBM), to identify linked gray and white matter regions which differ between groups. In jSBM, joint independent component analysis (jICA) is used to decompose preprocessed gray and white matter images into joint sources and statistical analysis is used to determine the significant joint sources showing group differences and their relationship to other variables of interest (e.g. age or sex). The identified joint sources are groupings of linked gray and white matter regions with common covariation among subjects. In this study, we first provide a simulation to validate the jSBM approach. To illustrate our method on real data, jSBM is then applied to structural magnetic resonance imaging (sMRI) data obtained from 120 chronic schizophrenia patients and 120 healthy controls to identify group differences. JSBM identified four joint sources as significantly associated with schizophrenia. Linked gray-white matter regions identified in each of the joint sources included: 1) temporal--corpus callosum, 2) occipital/frontal--inferior fronto-occipital fasciculus, 3) frontal/parietal/occipital/temporal--superior longitudinal fasciculus and 4) parietal/frontal--thalamus. Age effects on all four joint sources were significant, but sex effects were significant only for the third joint source. Our findings demonstrate that jSBM can exploit the natural linkage between gray and white matter by incorporating them into a unified framework. This approach is applicable to a wide variety of problems to study linked gray and white matter group differences.