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Gray Matter Abnormalities in Schizophrenia Patients with Tardive Dyskinesia: A Magnetic Resonance Imaging Voxel-Based Morphometry Study  [PDF]
Cheng-Ta Li, Kun-Hsien Chou, Tung-Ping Su, Chu-Chung Huang, Mu-Hong Chen, Ya-Mei Bai, Ching-Po Lin
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0071034
Abstract: Objective The pathophysiological mechanism of TD remains unknown. All previous studies, using the region-of-interest method, focused on basal ganglion areas, were with inconsistent results. This whole-brain voxel-based morphometry (VBM) study investigate the grey matter abnormality of TD and its correlates with clinical ratings. Method High resolution T1-weighted brain volumetric MRI from 25 schizophrenia patients with TD (TD group), 25 age-, gender-, and handedness-matched schizophrenia patients without TD (non-TD group), and 25 matched healthy subjects (NC group) were analyzed using a VBM approach. Clinical ratings included the Positive and Negative Symptom Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), and the Simpson-Angus Scale (SAS). Results The TD group had significantly smaller total gray matter volumes than the NC group (p = 0.05). Compared to the non-TD group, the TD group had significantly higher PANSS negative (p<0.001), SAS (p<0.001), and AIMS (p<0.001) scores; and smaller bilateral inferior frontal gyrus, which correlated negatively with the PANSS negative scores (r = ?0.366, p<0.05); and smaller right superior frontal gyrus, which correlated negatively with AIMS scores (r = ?0.399, p<0.001), and PANSS general score (r = ?0.338, p<0.05). Limitations The cross-section design can’t separate the gray matter change to TD from the context of the illness of schizophrenia, although TD with more severe clinical psychopathology could be a phenotype. Conclusions The schizophrenia patients with TD had significantly reduced gray matter, mostly at the bilateral inferior frontal gyrus and the right superior frontal gyrus, which correlated with severity of clinical symptoms and involuntary movement, respectively.
Gray matter imaging in multiple sclerosis: what have we learned?
Hanneke E Hulst, Jeroen JG Geurts
BMC Neurology , 2011, DOI: 10.1186/1471-2377-11-153
Abstract: For many years, focal inflammatory demyelination in the white matter (WM) was considered the most important pathological 'hallmark' of multiple sclerosis (MS). However, demyelination in the cerebral cortex was already observed in early pathology studies by Sander (1898), Dinkler (1904), Schob (1907) and Dawson (1916) [1-4]. After these initial, largely casuistic, descriptions of demyelination in the gray matter (GM) of MS patients, the topic was largely disregarded. This was mostly due to difficulties involved with the visualization of cortical GM lesions in the post mortem setting, in which conventional histochemical staining procedures were applied, as well as to a predominant attention for the generally more conspicuous process of inflammatory WM demyelination.However, by the start of the 21st century, the focus within MS research slowly shifted back from WM to GM. In 2003, when new immunohistochemical staining techniques that improved the ex vivo detection of GM damage had become available, the presence and extent of GM demyelination was described in detail and pathophysiological processes causing GM damage, as well as its visualization with modern magnetic resonance imaging (MRI) techniques, became central issues in MS research (see Figure 1).This review will focus on what has been learned in the past decade of imaging GM pathology in MS. As will be shown, visualization of GM demyelination was difficult at first, but improved upon technical developments in the field. An important question that now remains is whether MRI visualization of GM pathology in MS is sufficient, or whether further improvement is still needed.After the first pivotal reports of GM damage in MS in the early 20th century, it was not until 1962 that Brownell and Hughes reported that 26% of the macroscopically visible lesions found in their post mortem material of 22 MS patients were (partly) located in or around the cortical and subcortical GM [5]. Extensive involvement of the cortex in MS p
Accuracy and Reliability of Automated Gray Matter Segmentation Pathways on Real and Simulated Structural Magnetic Resonance Images of the Human Brain  [PDF]
Lucas D. Eggert, Jens Sommer, Andreas Jansen, Tilo Kircher, Carsten Konrad
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0045081
Abstract: Automated gray matter segmentation of magnetic resonance imaging data is essential for morphometric analyses of the brain, particularly when large sample sizes are investigated. However, although detection of small structural brain differences may fundamentally depend on the method used, both accuracy and reliability of different automated segmentation algorithms have rarely been compared. Here, performance of the segmentation algorithms provided by SPM8, VBM8, FSL and FreeSurfer was quantified on simulated and real magnetic resonance imaging data. First, accuracy was assessed by comparing segmentations of twenty simulated and 18 real T1 images with corresponding ground truth images. Second, reliability was determined in ten T1 images from the same subject and in ten T1 images of different subjects scanned twice. Third, the impact of preprocessing steps on segmentation accuracy was investigated. VBM8 showed a very high accuracy and a very high reliability. FSL achieved the highest accuracy but demonstrated poor reliability and FreeSurfer showed the lowest accuracy, but high reliability. An universally valid recommendation on how to implement morphometric analyses is not warranted due to the vast number of scanning and analysis parameters. However, our analysis suggests that researchers can optimize their individual processing procedures with respect to final segmentation quality and exemplifies adequate performance criteria.
Detecting functional magnetic resonance imaging activation in white matter: Interhemispheric transfer across the corpus callosum
Erin L Mazerolle, Ryan CN D'Arcy, Steven D Beyea
BMC Neuroscience , 2008, DOI: 10.1186/1471-2202-9-84
Abstract: Both group and individual data were considered. At liberal statistical thresholds (p < 0.005, uncorrected), group level activation was detected in the isthmus of the corpus callosum. This region connects the superior parietal cortices, which have been implicated previously in interhemispheric transfer. At the individual level, five of the 24 subjects (21%) had activation clusters that were located primarily within the corpus callosum. Consistent with the group results, the clusters of all five subjects were located in posterior callosal regions. The signal time courses for these clusters were comparable to those observed for task related gray matter activation.The findings support the idea that, despite the inherent challenges, fMRI activation can be detected in the corpus callosum at the individual level. Future work is needed to determine whether the detection of this activation can be improved by utilizing higher spatial resolution, optimizing acquisition parameters, and analyzing the data with tissue specific models of the hemodynamic response. The ability to detect white matter fMRI activation expands the scope of basic and clinical brain mapping research, and provides a new approach for understanding brain connectivity.The vast majority of functional magnetic resonance imaging (fMRI) studies adhere to the assumption that activation is fundamentally restricted to gray matter regions (e.g., [1,2]). Two main factors support this assertion: 1) relative to gray matter, cerebral blood flow and volume are reduced in white matter (e.g., [3,4]); and 2) the neurophysiological source of fMRI has been linked to postsynaptic potentials (e.g., [5,6]), the majority of which take place in gray matter.However, Tettamanti and colleagues have argued that, despite the decreased perfusion relative to gray matter, there is no direct evidence against detecting white matter activation using fMRI [7]. Although it has been demonstrated that fMRI activation is more strongly linked to po
In vivo magnetic resonance imaging of the human limbic white matter  [PDF]
Susumu Mori
Frontiers in Aging Neuroscience , 2014, DOI: 10.3389/fnagi.2014.00321
Abstract: The limbic system mediates memory, behavior, and emotional output in the human brain, and is implicated in the pathology of Alzheimer’s disease and a wide spectrum of related neurological disorders. In vivo magnetic resonance imaging (MRI) of structural components comprising the limbic system and their interconnections via white matter pathways in the human brain has helped define current understanding of the limbic model based on the classical circuit proposed by Papez. MRI techniques, including diffusion MR imaging, provide a non-invasive method to characterize white matter tracts of the limbic system, and investigate pathological changes that affect these pathways in clinical settings. This review focuses on delineation of the anatomy of major limbic tracts in the human brain, namely, the cingulum, the fornix and fimbria, and the stria terminalis, based on in vivo MRI contrasts. The detailed morphology and intricate trajectories of these pathways that can be identified using relaxometry-based and diffusion-weighted MRI provide an important anatomical reference for evaluation of clinical disorders commonly associated with limbic pathology.
Late-life depression, heart failure and frontal white matter hyperintensity: a structural magnetic resonance imaging study
Almeida, J.R.C.;Alves, T.C.T.F.;Wajngarten, M.;Rays, J.;Castro, C.C.;Cordeiro, Q.;Telles, R.M.S.;Fraguas, R.J.;Busatto, G.F.;
Brazilian Journal of Medical and Biological Research , 2005, DOI: 10.1590/S0100-879X2005000300014
Abstract: the relevance of the relationship between cardiac disease and depressive symptoms is well established. white matter hyperintensity, a bright signal area in the brain on t2-weighted magnetic resonance imaging scans, has been separately associated with cardiovascular risk factors, cardiac disease and late-life depression. however, no study has directly investigated the association between heart failure, major depressive symptoms and the presence of hyperintensities. using a visual assessment scale, we have investigated the frequency and severity of white matter hyperintensities identified by magnetic resonance imaging in eight patients with late-life depression and heart failure, ten patients with heart failure without depression, and fourteen healthy elderly volunteers. since the frontal lobe has been the proposed site for the preferential location of white matter hyperintensities in patients with late-life depression, we focused our investigation specifically on this brain region. although there were no significant group differences in white matter hyperintensities in the frontal region, a significant direct correlation emerged between the severity of frontal periventricular white matter hyperintensity and scores on the hamilton scale for depression in the group with heart failure and depression (p = 0.016, controlled for the confounding influence of age). there were no significant findings in any other areas of the brain. this pattern of results adds support to a relationship between cardiovascular risk factors and depressive symptoms, and provides preliminary evidence that the presence of white matter hyperintensities specifically in frontal regions may contribute to the severity of depressive symptoms in cardiac disease.
Gray Matter Pathology in MS: Neuroimaging and Clinical Correlations  [PDF]
Justin Morris Honce
Multiple Sclerosis International , 2013, DOI: 10.1155/2013/627870
Abstract: It is abundantly clear that there is extensive gray matter pathology occurring in multiple sclerosis. While attention to gray matter pathology was initially limited to studies of autopsy specimens and biopsies, the development of new MRI techniques has allowed assessment of gray matter pathology in vivo. Current MRI techniques allow the direct visualization of gray matter demyelinating lesions, the quantification of diffuse damage to normal appearing gray matter, and the direct measurement of gray matter atrophy. Gray matter demyelination (both focal and diffuse) and gray matter atrophy are found in the very earliest stages of multiple sclerosis and are progressive over time. Accumulation of gray matter damage has substantial impact on the lives of multiple sclerosis patients; a growing body of the literature demonstrates correlations between gray matter pathology and various measures of both clinical disability and cognitive impairment. The effect of disease modifying therapies on the rate accumulation of gray matter pathology in MS has been investigated. This review focuses on the neuroimaging of gray matter pathology in MS, the effect of the accumulation of gray matter pathology on clinical and cognitive disability, and the effect of disease-modifying agents on various measures of gray matter damage. 1. Background Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS); focal areas of white matter demyelination have long been considered the key feature of MS [1]. Despite this belief that MS is primarily a white matter disease, early pathologic studies had reported focal areas of cortical demyelination in MS patients [2, 3]. In 1962, Brownell and Hughes [4] showed that, in MS, cortical demyelinating lesions represented up to 26% of the total number of cerebral plaques. Despite these early indications of the cortical pathology occurring in MS, in general very little attention was paid to cortical pathology. It is likely that this was due to both the difficulty in identifying cortical lesions at autopsy via conventional histochemical techniques and the marked conspicuity of inflammatory lesions in the white matter [5]. This focus on white matter demyelination rather than cortical pathology was initially compounded with the advent of MRI: conventional MRI techniques for imaging MS identify a majority of focal white matter lesions but are very insensitive for the detection of cortical MS lesions [6]. Despite initial focus on white matter demyelination, there has been increasing focus on the gray matter
Measurement of Cerebral White Matter Perfusion Using Pseudocontinuous Arterial Spin Labeling 3T Magnetic Resonance Imaging – an Experimental and Theoretical Investigation of Feasibility  [PDF]
Wen-Chau Wu, Shu-Chi Lin, Danny J. Wang, Kuan-Lin Chen, Ying-Ding Li
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0082679
Abstract: Purpose This study was aimed to experimentally and numerically investigate the feasibility of measuring cerebral white matter perfusion using pseudocontinuous arterial spin labeling (PCASL) 3T magnetic resonance imaging (MRI) at a relatively fine resolution to mitigate partial volume effect from gray matter. Materials and Methods The Institutional Research Ethics Committee approved this study. On a clinical 3T MR system, ten healthy volunteers (5 females, 5 males, age = 28±3 years) were scanned after providing written informed consent. PCASL imaging was performed with varied combinations of labeling duration (τ = 1000, 1500, 2000, and 2500 ms) and post-labeling delay (PLD = 1000, 1400, 1800, and 2200 ms), at a spatial resolution (1.56x1.56x5 mm3) finer than commonly used (3.5x3.5 mm2, 5-8 mm in thickness). Computer simulations were performed to calculate the achievable perfusion-weighted signal-to-noise ratio at varied τ, PLD, and transit delay. Results Based on experimental and numerical data, the optimal τ and PLD were found to be 2000 ms and 1500-1800 ms, respectively, yielding adequate SNR (~2) to support perfusion measurement in the majority (~60%) of white matter. The measurement variability was about 9% in a one-week interval. The measured white matter perfusion and perfusion ratio of gray matter to white matter were 15.8-27.5 ml/100ml/min and 1.8-4.0, respectively, depending on spatial resolution as well as the amount of deep white matter included. Conclusion PCASL 3T MRI is able to measure perfusion in the majority of cerebral white matter at an adequate signal-to-noise ratio by using appropriate tagging duration and post-labeling delay. Although pixel-wise comparison may not be possible, region-of-interest based flow quantification is feasible.
Evaluation of white matter in patients with multiple sclerosis through diffusion tensor magnetic resonance imaging
Andrade, Rachel E. Maia de;Gasparetto, Emerson L.;Cruz Jr., Luiz Celso Hygino;Ferreira, Fabiana Brito;Domingues, Roberto Cortês;Marchiori, Edson;Domingues, Romeu Cortês;
Arquivos de Neuro-Psiquiatria , 2007, DOI: 10.1590/S0004-282X2007000400002
Abstract: objective: to study the white matter of patients with multiple sclerosis (ms) with diffusion tensor magnetic resonance (mr) imaging (dti). method: forty patients with clinical-laboratorial diagnosis of relapsing-remitting ms and 40 age- and sex-matched controls, who underwent conventional and functional (dti) mr imaging, were included in the study. the dti sequences resulted in maps of fractional anisotropy (fa) and regions of interest were placed on the plaques, peri-plaque regions, normal-appearing white matter (nawm) around the plaques, contralateral normal white matter (cnwm) and normal white matter of the controls (wmc). the fa values were compared and the statistical treatment was performed with the mann-whitney u test. results: the mean fa in plaques was 0.268, in peri-plaque regions 0.365, in nawm 0.509, in cnwm 0.552 and in wmc 0.573. statistical significant differences in fa values were observed in plaques, peri-plaque regions and in nawm around the plaques when compared to the white matter in the control group. there was no significant difference between the fa values of the cnwm of patients with ms and normal white matter of controls. conclusion: patients with ms show difference in the fa values of the plaques, peri-plaques and nawm around the plaques when compared to the normal white matter of controls. as a result, dti may be considered more efficient than conventional mr imaging for the study of patients with ms.
HAM/TSP: association between white matter lesions on magnetic resonance imaging, clinical and cerebrospinal fluid findings
Puccioni-Sohler, Marzia;Gasparetto, Emerson;Cabral-Castro, Mauro Jorge;Slatter, Carla;Vidal, Cecilia M.;Cortes, Romeu Domingues;Rosen, Bruce R.;Mainero, Caterina;
Arquivos de Neuro-Psiquiatria , 2012, DOI: 10.1590/S0004-282X2012000400004
Abstract: objective: to investigate the association between clinical data, white matter lesions and inflammatory cerebrospinal fluid (csf) findings in htlv-1 associated myelopathy/tropical spastic paraparesis (ham/tsp). method: we studied brain and cervical spinal cord on magnetic resonance imaging (mri) and csf examinations of 28 brazilian ham/tsp patients. results: the majority of patients had severe neurological incapacity with edss median of 6.5 (3-8). the brain mri showed white matter lesions (75%) and atrophy (14%). the preferential brain location was periventricular. cervical demyelination lesions occurred in 11% of the cases, and cervical atrophy in 3.5%. one patient had enhancement lesions on t1 cervical spinal cord mri. cases with spinal cord lesions had signs of acute csf inflammation. the brain white matter lesions predominated in the patients with higher age. conclusion: our data suggest that an active inflammatory process is associated with the cervical spinal cord lesions in ham/tsp. the brain abnormalities are not related to the clinical picture of ham/tsp.
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