Anatomy and white matter connections of the inferior frontal gyrus

The inferior frontal gyrus (IFG) is involved in the evaluation of linguistic, interoceptive, and emotional information. A detailed understanding of its subcortical white matter anatomy could improve postoperative morbidity related to surgery in and around this gyrus. Through GQI‐based fiber tracking validated by gross anatomical dissection as ground truth, we characterized the fiber tracts of the IFG based on relationships to other well‐known neuroanatomic structures. Diffusion imaging from the Human Connectome Project for 10 healthy adult controls was used for fiber tracking analysis. We evaluated the IFG as a whole based on its connectivity with other regions. All tracts were mapped in both hemispheres, and a lateralization index was calculated based on resultant tract volumes. Ten cadaveric dissections were then performed using a modified Klingler technique to demonstrate the location of major tracts. We identified four major connections of the IFG: a white matter bundle corresponding the frontal aslant tract connecting to the superior frontal gyrus; the superior longitudinal fasciculus connecting to the inferior parietal lobule, lateral occipital area, posterior temporal areas, and the temporal pole; the inferior fronto‐occipital fasciculus connecting to the cuneus and lingual gyrus; and the uncinate fasciculus connecting to the temporal pole. A callosal fiber bundle connecting the inferior frontal gyri bilaterally was also identified. The IFG is an important region implicated in a variety of tasks including language processing, speech production, motor control, interoceptive awareness, and semantic processing. Postsurgical outcomes related to this region may be better understood in the context of the fiber‐bundle anatomy highlighted in this study. Clin. Anat. 32:546–556, 2019. © 2019 Wiley Periodicals, Inc.     

融合白质fMRI的dMRI纤维追踪重建研究

基于弥散磁共振成像(dMRI)的纤维束重建,是分析大脑白质结构的主要工具.现有的纤维追踪成像算法受dMRI分辨率及成像机理约束,在构建大脑白质灰质边界区域的纤维时成像性能和准确性大大下降.为克服该缺陷,提出一种结合功能磁共振成像(fMRI)的新型dMRI纤维追踪成像算法.该算法引入表征白质中fMRI信号各向异性的空间相...     

Enriched Environment and White Matter in Aging Brain

Normal aging is commonly associated with decreased cognitive functions, which could be conspicuously alleviated by enriched environment (EE) with physical, social, and sensory stimuli, suggesting that aging brain still has intriguing plasticity. Multiple researches have been carried out to explore the structural and the molecular changes in aging brain, which would be considered for evidences that EE regulated brain plasticity. Because there is no significant neuron loss in aging cerebral cortex and the white matter is crucial for cognitive functions, this review focused on the age‐related white matter changes and the effects of EE on aged white matter. Data from our stereology laboratory revealed that age‐related spatial memory declines had more to do with white matter alterations, which were due to marked demyelination and loss of oligodendrocytes in the white matter. We also demonstrated that EE recovered spatial memory impairment and increased white matter volume by promoting marked remyelination in aged brain. This review approached the issue that EE might contribute to normal aging and be beneficial for those suffering from demyelinated diseases. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

基于Log-Euclidean矩阵的脑白质扩散张量场的正则化处理

在临床诊断时为了较快获得数据,扩散张量图像的质量常常不能得到保证,其正则化处理特别重要。为此,本研究提出一种基于Log-Euclidean矩阵的新算法对张量图像进行评估预处理,首先对张量特征值进行自然指数运算以实现张量场到Log-Euclidean矢量场的转换,再通过有限差分法计算矢量场梯度函数最小值,从而实现矢量场的去噪平滑,之后对矢量场取自然对数运算映射回张量空间。在1名志愿者脑扩散张量图像上进行白质纤维束跟踪测试,结果表明该方法有效避免了白质纤维束跟踪中杂从的出现,提高了跟踪平滑性。     

Stereological Investigation of Age‐Related Changes of the Capillaries in White Matter

We, for the first time, investigated the age‐related changes of the capillaries in white matter using immunohistochemistry and stereological techniques. Ten young female (7 months) and 10 aged female (27 months) rats were used. The total length, total volume, and total surface area of the capillaries in white matter of aged rats were all significantly lower than those of young rats. The age‐related changes of the capillaries in white matter may have important implications for age‐related white matter atrophy and age‐related cognitive impairments. Anat Rec 293:1400–1407, 2010. © 2010 Wiley‐Liss, Inc.     

Demyelination Induces the Decline of the Myelinated Fiber Length in Aged Rat White Matter

To determine the exact reason for the age‐related decline of the myelinated fiber length in white matter, we performed this study. In middle‐aged rats, there was age‐related loss of the unmyelinated fibers with large diameters. The demyelination of the myelinated fibers with small diameters in middle‐aged rat white matter might make the age‐related decrease of the unmyelinated fibers with small diameters in the white matter unnoticeable. However, in old‐aged female rats, the unmyelinated fibers with large and small diameters significantly degenerated together and that the unmyelinated fibers formed from the demyelination of the myelinated fibers could not replenish the age‐related loss of the unmyelinated fibers in the white matter. In conclusion, this study suggested that demyelination of myelinated fibers with small diameters in aged white matter might be the key mechanism of the significant decline of the myelinated fiber length in aged white matter. Anat Rec, 292:528–535, 2009. © 2009 Wiley‐Liss, Inc.     

Age‐Related Changes of the Oligodendrocytes in Rat Subcortical White Matter

The age‐related changes, of the oligodendrocytes in rat subcortical white matter, were investigated in this study. The oligodendrocytes in subcortical white matter were labeled with anti‐2′,3′‐cyclic nucleotide 3′‐phosphodiesterase antibody (anti‐CNPase antibody, a specific marker of oligodendrocytes). The total number of CNPase⁺ cells was estimated with an unbiased stereological technique, the optical fractionator. In this study, we found that the total number of CNPase⁺ cells in the young male rats and aged male rats was 14.4 ± 1.2 × 10⁶ and 9.0 ± 1.0 × 10⁶, respectively. The total number of the CNPase⁺ cells in the subcortical white matter of aged rats was significantly decreased by 37.5% when compared to young male rats. This study demonstrated that there was an aged‐related decrease of the oligodendrocytes in subcortical white matter. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.     

Stereological Methods for Estimating the Myelin Sheaths of the Myelinated Fibers in White Matter

In the present study, efficient and unbiased stereological techniques to investigate the myelin sheaths of the myelinated fibers in rat white matter were established. In the present design, four tissue blocks were obtained from the entire white matter of rat brain in a uniform, random fashion. Isotropic, uniform random (IUR) sections were ensured by the use of the isector technique. One section with the thickness of 60 nm was cut from the center of each epon block. Eight to 10 fields of vision were randomly photographed under a transmission electron microscope. The total length of the myelinated fibers and the total volume of the myelin sheaths in the white matter were the products of the length density, volume density, and the volume of the white matter obtained with the Cavalieri principle. The mean areas of the myelinated fibers profiles and myelin sheaths were estimated with the point counting technique. The inner and outer perimeters of the myelin sheaths were estimated by the use of a line grid, and the thickness of the myelin sheaths was estimated by direct orthogonal measurements in uniform, random locations. The described methods will provide very useful tools for future quantitative studies of changes in the myelin sheaths of white matter in various experimental conditions and in various neurodegenerative diseases. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.     

High Mean Platelet Volume Is Associated with Cerebral White Matter Hyperintensities in Non-Stroke Individuals

PurposeThe mean platelet volume (MPV) is regarded as a marker for thrombosis, atherosclerosis, and inflammation in various vascular diseases. However, it still remains unclear whether plasma MPV is associated with cerebral white matter hyperintensities (WMH) and cerebral microvascular pathology in the elderly population.Materials and MethodsWe examined whether MPV level is associated with the presence of cerebral WMH on brain magnetic resonance imaging from 870 non-stroke outpatient subjects. The subjects were divided into three groups according to the consecutive level of MPV (low T1, middle T2, and high T3 MPV tertile groups). To determine the association of MPV levels with the WMH, logistic regression and receiver operating characteristic curve analyses were conducted.ResultsSubjects with higher MPV level were older and more likely to have hypertension, diabetes mellitus, and low renal function. Cerebral WMH were more prevalent in subjects with higher MPV level. After adjusting for confounding factors, moderate to severe cerebral WMH were significantly associated with high MPV tertile level. This association remained significant after adjusting for other cerebral vascular pathologies. T2 [odds ratio (OR): 1.49, 95% confidence interval (CI): 1.03–2.15] and T3 MPV tertile groups (OR: 1.51, 95%CI: 1.04–2.20) had more cerebral WMH lesions compared to T1 MPV tertile group. In addition, the subjects with higher Fazekas scores showed higher MPV level (p=0.020).ConclusionWe found that high MPV level is independently associated with cerebral WMH. This result suggests that platelet activation plays a role in the development of cerebral WMH.     

Molecular Changes in White Matter Adjacent to an Active Demyelinating Lesion in Early Multiple Sclerosis

A stereotactic biopsy of a 17-year-old woman revealed an active inflammatory demyelinating lesion compatible with pattern III multiple sclerosis (MS) according to Lucchinetti et al . The biopsy included a white matter region distant from the active inflammatory demyelinating lesion with abnormal MRI signal, lacking histopathological signs of demyelination and/or oligodendrocyte apoptosis. Expression analysis of this area revealed a strong up-regulation of neuronal nitric oxide synthase (nNOS). Furthermore, detection of nitrotyrosine provided evidence for reactive nitrogen species (RNS)-mediated damage to oligodendrocytes. Concomitantly, genes involved in neuroprotection against oxidative stress such as heme oxygenase 1 were up-regulated. Even though a single case report, this study shows earliest molecular changes in white matter surrounding an actively demyelinating lesion during the first manifestation of MS, pointing toward a more widespread pathological process. Therapeutic targeting of the identified mechanisms of tissue injury might be crucial to prevent further lesion formation or secondary tissue damage.     

White Matter Hypoperfusion and Damage in Dementia: Post‐Mortem Assessment

Neuroimaging has revealed a range of white matter abnormalities that are common in dementia, some that predict cognitive decline. The abnormalities may result from structural diseases of the cerebral vasculature, such as arteriolosclerosis and amyloid angiopathy, but can also be caused by nonstructural vascular abnormalities (eg, of vascular contractility or permeability), neurovascular instability or extracranial cardiac or vascular disease. Conventional histopathological assessment of the white matter has tended to conflate morphological vascular abnormalities with changes that reflect altered interstitial fluid dynamics or white matter ischemic damage, even though the latter may be of extracranial or nonstructural etiology. However, histopathology is being supplemented by biochemical approaches, including the measurement of proteins involved in the molecular responses to brain ischemia, myelin proteins differentially susceptible to ischemic damage, vessel‐associated proteins that allow rapid measurement of microvessel density, markers of blood–brain barrier dysfunction and axonal injury, and mediators of white matter damage. By combining neuroimaging with histopathology and biochemical analysis, we can provide reproducible, quantitative data on the severity of white matter damage, and information on its etiology and pathogenesis. Together these have the potential to inform and improve treatment, particularly in forms of dementia to which white matter hypoperfusion makes a significant contribution.     

Frontal white matter association with sleep quality and the role of stress

An important measure of brain health is the integrity of white matter connectivity structures that link brain regions. Studies have found an association between poorer sleep quality and decreased white matter integrity. Stress is among the strongest predictors of sleep quality. This study aimed to evaluate the association between sleep quality and white matter and to test if the relationship persisted after accounting for stress. White matter microstructures were measured by diffusion tensor imaging in a population of Old Order Amish/Mennonite (N = 240). Sleep quality was determined by the Pittsburgh Sleep Quality Index. Current stress levels were measured by the perceived stress scale. Exposure to lifetime stress was measured by the lifetime stressor inventory. Microstructures of four white matter tracts: left and right anterior limbs of internal capsule, left anterior corona radiata, and genu of corpus callosum were significantly correlated with sleep quality (all p ≤ 0.001). The current stress level was a significant predictor of sleep quality (p ≤ 0.001) while lifetime stress was not. PSQI remained significantly associated with white matter integrity in these frontal tracts (all p < 0.01) after accounting for current stress and lifetime stress, while current and lifetime stress were not significant predictors of white matter in any of the four models. Sleep quality did not have any substantial mediation role between stress and white matter integrity. Sleep quality was significantly associated with several frontal white matter tracts that connect brain structures important for sleep regulation regardless of current or past stress levels.     

Cerebral Amyloid Angiopathy,Subcortical White Matter Disease and Dementia: Literature Review and Study in OPTIMA

Cerebral amyloid angiopathy (CAA) is of increasing clinical and research interest as the ability to detect it and its consequences by neuroimaging in living subjects has advanced. There is also increasing interest in understanding its possible role in the development of intracerebral hemorrhage, Alzheimer's disease (AD) and vascular dementia. In this article, the literature on this subject is reviewed and novel findings relating CAA to subcortical white matter damage in 224 subjects in the Oxford project to Investigate Memory and Ageing (OPTIMA) are reported. The relationship between CAA and subcortical tissue damage in the OPTIMA subjects was found to be critically dependent on ApoE genotype, there being a positive relationship between measures of CAA and subcortical small vessel disease in ApoEε4 carriers and a significant negative relationship in ApoEε2 carriers. These findings draw attention, as have many other studies, to the importance of ApoE genotype as a major risk factor not only for dementia but also for damage to blood vessels in the aging brain.     

首发重症抑郁症的弥散张量成像研究:基于纤维束示踪的空间统计学分析结果

目的:应用基于纤维束示踪的空间统计分析(Tract-Based Spatial Statistics,TBSS)方法,探讨重症抑郁症病患者全脑白质纤维的完整性是否受到损害。方法:对20(8男,12女)例重症抑郁症病患者组和20(8男,12女)例与抑郁症组按性别、年龄、教育程度匹配的正常人进行全脑弥散张量成像扫描。应用TBSS方法来比较两组的各向异性分数。结果:抑郁症组的左侧内囊前肢、右侧海马旁回、左侧后扣带回的各向异性分数显著低于正常组(P<0.05,t>3,校正),患者组内囊前肢的各向异性分数和抑郁症严重程度呈现负相关。结论:白质病变在抑郁症发病早期即已存在,这些病变区域主要涉及前额叶和边缘系统等与认知和情感调节关系较密切的神经环路的纤维束,这些改变可能导致皮层和皮层下连接受损,从而有利于深入了解抑郁症疾病的发病机理。     

Age‐Associated White Matter Lesions: The MRC Cognitive Function and Ageing Study

Cerebral white matter lesions (WML) are common in the aging brain and are associated with dementia and depression. They are associated with vascular risk factors and small vessel disease, suggesting an ischemic origin, but recent pathology studies suggest a more complex pathogenesis. Studies using samples from the population‐representative Medical Research Council Cognitive Function and Ageing Study neuropathology cohort used post‐mortem magnetic resonance imaging to identify WML for further study. Expression of hypoxia‐related molecules and other injury and protective cellular pathways in candidate immunohistochemical and gene expression microarray studies support a role for hypoxia/ischemia. However, these approaches also suggest that immune activation, blood–brain barrier dysfunction, altered cell metabolic pathways and glial cell injury contribute to pathogenesis. These abnormalities are not confined to WML, but are also found in apparently normal white matter in brains with lesions, suggesting a field effect of white matter abnormality within which lesions arise. WML are an active pathology with a complex pathogenesis that may potentially offer a number of primary and secondary intervention targets.     

精神分裂症患者及其健康同胞脑白质密度研究

目的:观察精神分裂症患者及其健康同胞脑白质密度的特点.方法:用基于像素的形态学测量法比较三组的白质密度.结果:在左侧前额叶和胼胝体膝部,患者及同胞的白质密度值显著小于正常对照组,患者和同胞之间的差异未达到统计学意义水平.结论:左侧前额叶和胼胝体膝部白质密度值降低可能与精神分裂症的患病风险有关.     

Diffusion Tensor Imaging of White Matter Tracts in the Dog Brain

Diffusion weighted imaging sequences are now widely available on Magnetic Resonance Imaging (MRI) scanners. Diffusion Tensor Imaging (DTI) of the brain is able to show white matter tracts and is now commonly used in human medicine to study brain anatomy, tumors, structural pathways,… The purpose of this study was to show the interest of DTI to reveal the white matter fibers in the dogs' brain. DTI MR Images for this study were obtained with a 3 T system of 4 dogs euthanized for other reasons than neurological disorders. Combined fractional anisotropic (FA) and directional maps were obtained in the first 2 hours after death. The heads were amputated immediately after scanning and stored in 10% formalin until preparation for dissection. An experienced anatomist tracked white matter tracts with clinical relevance using the scanner software. The selected tracts were REFVIDume rendered and correlated with gross dissection. Using DTI we were able to track relevant neurological connections, such as the corticospinal tract, the optic and the cerebellar tract. The three dimensional anatomy is better presented using modern visualization techniques. DTI seems to be a valuable tool in order to present clinically relevant white matter tracts to neurological clinicians and researchers. Anat Rec, 296:340–349, 2013. © 2013 Wiley Periodicals, Inc.     

HFE H63D,C282Y and AGTR1 A1166C Polymorphisms and Brain White Matter Lesions in the Aging Brain

Abstract: Incidental white matter lesions (WML) are a common neuroradiological finding in elderly people and have been linked to dementia and depression. Various mechanisms including hypoxia and increased production of reactive oxygen species (ROS) are implicated in the etiology of WML. The hemochromatosis (HFE) gene p.H63D and p.C282Y polymorphisms have been linked to dysregulation of iron metabolism and increased levels of ROS, whereas Angiotensin II receptor 1 (AGTR1) c.1166A → C polymorphism is known as a vascular risk factor. These genetic polymorphisms were characterized in brains donated to the UK MRC Cognitive Function and Ageing Study (CFAS) to assess their potential role in the risk for development of age-related WML. The study cohort comprised 258 brain donated to CFAS. WML severity was assessed in the postmortem brain donations using magnetic resonance imaging (MRI) scans and scored using the Scheltens’ scale. Polymerase chain reaction (PCR) amplification of extracted DNA followed by restriction enzyme digestion was used to genotype the samples. Genotypes were validated using direct sequencing in a smaller sample. The results show that HFE p.H63D polymorphism is not associated with WML severity in the whole cohort. However, there is a significant association of the D allele with severity of WML in noncarriers of the APOE ε4 allele. No association is demonstrated between the HFE p.C282Y nor the AGTR1 c.1166A → C polymorphisms and WML severity. The HFE gene appears to be a genetic risk factor for severe aging WML independently of the APOE ε4 genotype. This would support the role of iron-related oxidative stress, in addition to previously studied factors, e.g., hypoxia as potential risk factors for developing prominent aging WML.