Voxel-based analyses of magnetization transfer imaging ofthe brain in hepatic encephalopathy
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AIM:To evaluate the spatial distribution of cerebral abnormalities in cirrhotic subjects with and without hepatic encephalopathy (HE) found with magnetization transfer imaging (MTI). METHODS:Nineteen cirrhotic patients graded from neurologically normal to HE grade 2 and 18 healthy control subjects underwent magnetic resonance imaging.They gave institutional-review-board-approved written consent.Magnetization transfer ratio (MTR) maps were generated from MTI.We tested for significant differences compared to the control group using statistical non-parametric mapping (SnPM) for a voxelbased evaluation. RESULTS:The MTR of grey and white matter was lower in subjects with more severe HE.Changes were found in patients with cirrhosis without neurological deficits in the basal ganglia and bilateral white matter.The loss in magnetization transfer increased in severity and spatial extent in patients with overt HE.Patients with HE grade 2 showed an MTR decrease in white and grey matter: the maximum loss of magnetization transfer effect was located in the basal ganglia [SnPM (pseudo-)t = 17.98,P = 0.0001]. CONCLUSION:The distribution of MTR changes in HE points to an early involvement of basal ganglia and white matter in HE.Keywords:
Magnetization transfer
Grey matter
Hepatic Encephalopathy
Statistical parametric mapping
Introduction: Multiple sclerosis (MS) is characterized by lesions in the white matter (WM) of the central nervous system. Magnetic resonance imaging is the most specific and sensitive method for diagnosis of multiple sclerosis. However, the ability of conventional MRI to show histopathologic heterogeneity of MS lesions is insufficient. Quantitative magnetization transfer imaging (qMTI) is a relatively new method to investigate pathologic processes of the brain tissue occurring in MS patients. Material and Methods: Voxel-based analyses allow regional comparisons between groups to be made for the whole brain in a single analysis. This is done by coregistering data from all individual subjects to a reference brain, generally referred to as the standard space, and then comparing them on a voxel-by-voxel basis. This study aimed to analyze whole-brain quantitative T1 maps, not to find global changes or changes in selected regions, but specifically to investigate the spatial distribution throughout the brain of T1 increases in MS WM with respect to control WM. In this study, 11 healthy controls, 10 relapsing-remitting (RR) MS patients and 13 CIS patients were studied using MT-MRI imaging. MT parameters, including magnetization transfer ratio (MTR), magnetization transfer rate between free protons and restricted macromolecular protons, Ksat and longitudinal relaxation times (with and without MT saturation pulse), T1sat and T1free values were evaluated. Results: The results showed that, at a group level, there is widespread involvement of WM throughout the brain in CIS MS and especially in RRMS, where a significant T1 increase was found in 15.58% of WM voxels (normals < RR). Discussion and Conclusion: This study demonstrates that WM in large parts of the brain is susceptible to disease processes in RR and CIS MS
Magnetization transfer
Grey matter
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AIM:To evaluate the spatial distribution of cerebral abnormalities in cirrhotic subjects with and without hepatic encephalopathy (HE) found with magnetization transfer imaging (MTI). METHODS:Nineteen cirrhotic patients graded from neurologically normal to HE grade 2 and 18 healthy control subjects underwent magnetic resonance imaging.They gave institutional-review-board-approved written consent.Magnetization transfer ratio (MTR) maps were generated from MTI.We tested for significant differences compared to the control group using statistical non-parametric mapping (SnPM) for a voxelbased evaluation. RESULTS:The MTR of grey and white matter was lower in subjects with more severe HE.Changes were found in patients with cirrhosis without neurological deficits in the basal ganglia and bilateral white matter.The loss in magnetization transfer increased in severity and spatial extent in patients with overt HE.Patients with HE grade 2 showed an MTR decrease in white and grey matter: the maximum loss of magnetization transfer effect was located in the basal ganglia [SnPM (pseudo-)t = 17.98,P = 0.0001]. CONCLUSION:The distribution of MTR changes in HE points to an early involvement of basal ganglia and white matter in HE.
Magnetization transfer
Grey matter
Hepatic Encephalopathy
Statistical parametric mapping
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Objective To investigate the changes of brain volumes in neuromyelitis optica (NMO)patients using voxel-based morphometry (VBM) method, and preliminarily explore the pattern of cerebral anatomical impairment. Methods Twenty-three clinically defined NMO patients and 15 gender and age matched healthy volunteers underwent 3-dimensional (3D) fast spoiled gradient echo (FSPGR) sequence scanning on 3.0 Tesla MR systen. Raw data was processed and analyzed using statistical parametric mapping (SPM) 5. Whole brain volumes included grey matter volume (GMV), white matter volume (WMV), total intracranial volume (TIV), grey matter fraction (GMF), white matter fraction (WMF),brain tissue fraction (BTF) and regional brain volumes between the two groups were compared by independent samples t-test and an Pearson were performed to compare the regional brain volumes and the ages. Results GMV of NMO group[(610. 2 ± 55.0) ml] was significantly decreased comparing to healthy control group[(657. 2 ± 36. 3) ml] (t = - 2. 915, P ＜ 0. 05). The age of NMO patients [(40 ± 9) years old] showed negative correlation with GMF [(42. 5 ± 2. 6) %] (r = - 0. 673, P ＜ 0. 05). Regional brain volume analysis showed decreased GMV in left insula and bilateral posterior cingutates in NMO patients,while decreased WMV was found in left frontal and left parietal white matter. Conclusion VBM could detect brain volume changes sensitively. Total grey matter volume in NMO patients was decreased comparing to HC group. Regional grey matter atrophy in NMO patients occurred in left insular and bilateral posterior cingutates, regional white matter atrophy occurred in left frontal and left parietal lobe.
Key words:
Neuromyelitis optica; Magnetic resonance imaging; Brain
Grey matter
Voxel-based morphometry
Statistical parametric mapping
Neuromyelitis Optica
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The classical view of MS as an inflammatory-demyelinating condition affecting the white matter (WM) of the central nervous system (CNS) has recently been challenged by the results of several magnetic resonance imaging (MRI) studies. These consistently show grey matter (GM) involvement, which correlates only moderately with the extent of WM pathology. Here we summarize how conventional and modern imaging-based techniques have quantified GM damage in MS, in terms of focal lesions, diffuse tissue abnormalities and irreversible tissue loss. Results from functional MRI studies, together with these new findings, are contributing to a significant change in our MS understanding. MS is now viewed as a global CNS condition, affecting both WM and GM, which has an early and important neurodegenerative component.
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We describe a semiautomated method to quantify uptake of 18F-labelled agents targeting β-amyloid plaques in cortical grey matter. We performed 90-min dynamic PET imaging of 39 Alzheimer's disease (AD) and 42 healthy control (HC) subjects following IV infusion of 18F-AV-45, 18F-AV-138, or 18F-AV144. PET images were registered to MRI and re-sliced to create a mean image by statistical parametric mapping (SPM). This was spatially normalized to Tailairach space. Images of 10 subjects were segmented to identify grey and white matter, cerebrospinal fluid and skull. Images from the first 10 min post-administration in the first 15 subjects were then analyzed. High flow areas were determined and compared to the previously segmented grey matter dataset. Volumes of interest (VOI) were created in orbitofrontal, temporal, parietal, occipital, posterior cingulate and precuneus cortical grey matter. Cerebellar grey matter and centrum semiovale white matter were used as reference regions. Time-activity curves (TACs) for the full dataset (15 HC, 15 AD) were then generated from the VOIs using a MATLAB code. Parametric images of amyloid retention were generated by averaging the images (approximately 50–70 min post- injection) from a subset of subjects and normalizing that to the cerebellum grey to get a standardized uptake value ratio (SUVR). Data across the subset of subjects was compared using the statistical methods of SPM. The VOI analysis showed increased uptake of 18F-tracers in cortical grey matter areas expected to contain β-amyloid plaques associated with Alzheimer's disease (AD) for all three tracers. The statistical analysis on the voxel specific parametric images showed significant uptake (p<0.05) in orbito-frontal and lateral temporal cortices as well as precuneus and posterior cingulate. Thus SPM statistical analysis supports the semiautomated VOIs quantification methods. These results are consistent with reported findings of amyloid pathology in AD in postmortem tissue. SPM analysis for the full set of data is underway and will be presented. Semiautomated approach provides a precise method for quantifying the uptake of 18F-labelled imaging agents for imaging β-amyloid plaque in multicenter trials.
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Objective: It is not established whether myalgic encephalomyelitis/chronic fatigue syndrome (CFS) is associated with structural brain changes. The aim of this study was to investigate this by conducting the largest voxel-based morphometry study to date in CFS. Methods: High-resolution structural 3 T cerebral MRI scanning was carried out in 26 patients with CFS and 26 age- and gender-matched healthy volunteers. Voxel-wise generalised linear modelling was applied to the processed MR data using permutation-based non-parametric testing, forming clusters at t>2.3 and testing clusters for significance at p<0.05, corrected for multiple comparisons across space. Results: Significant voxels (p<0.05, corrected for multiple comparisons) depicting reduced grey matter volume in the CFS group were noted in the occipital lobes (right and left occipital poles; left lateral occipital cortex, superior division; and left supracalcrine cortex), the right angular gyrus and the posterior division of the left parahippocampal gyrus. Significant voxels (p<0.05, corrected for multiple comparisons) depicting reduced white matter volume in the CFS group were also noted in the left occipital lobe. Conclusion: These data support the hypothesis that significant neuroanatomical changes occur in CFS, and are consistent with the complaint of impaired memory that is common in this illness; they also suggest that subtle abnormalities in visual processing, and discrepancies between intended actions and consequent movements, may occur in CFS.
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Voxel-based morphometry
Parahippocampal gyrus
Statistical parametric mapping
Occipital lobe
Gyrus
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Bipolar disorder (BP) traditionally has been considered as a recurrent illness with full recovery between episodes, and the absence of neuropathological abnormalities has usually been taken for granted. In recent times, the realization that, for many BP carries a poor prognosis, that cognitive deficits are often persistent and that structural brain abnormalities are detectable with modern imaging techniques has spurred the search for its neuropathological substrate. The shortcomings of post-mortem studies make the use of imaging techniques sensitive to neuropathological changes compelling. We report here the first study of BP patients using two such techniques in conjunction: magnetization transfer imaging (MTI) and voxel-based morphometry (VBM). Thirty-nine patients with BP (13 males and 26 females; 28 with BPI and 11 with BPII) and 35 healthy controls were investigated. Both high-resolution volumetric T1-weighted images and MT images were acquired from all subjects. Images were processed using a voxel-by-voxel analysis in statistical parametric mapping 2 (SPM2). The magnetization transfer ratio MTR, an index indicative of loss of macromolecular density, was reduced in the right subgenual anterior cingulate and adjacent white matter in bipolar patients compared with controls. VBM did not reveal significant volumetric differences between BP patients and controls in grey and white matter, but white matter density was significantly reduced bilaterally in prefrontal areas encompassing fronto-striatal connections. Our findings suggest that subtle abnormalities are present in the anterior cingulate and subgyral white matter in patients with BP in the absence of significant volumetric changes. These findings are in keeping with those of previously reported neuropathological studies and illustrate important similarities (involvement of the anterior cingulate) and differences (lack of widespread cortical abnormalities in BP) with our previous studies in schizophrenic patients using the same methodology.
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Statistical parametric mapping
Voxel-based morphometry
Grey matter
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Our aim was to explore a novel quantitative method [based upon an MRI-based image segmentation that allows actual calculation of grey matter, white matter and cerebrospinal fluid (CSF) volumes] for overcoming the difficulties associated with conventional techniques for measuring actual metabolic activity of the grey matter.We included four patients with normal brain MRI and fluorine-18 fluorodeoxyglucose (F-FDG)-PET scans (two women and two men; mean age 46±14 years) in this analysis. The time interval between the two scans was 0-180 days. We calculated the volumes of grey matter, white matter and CSF by using a novel segmentation technique applied to the MRI images. We measured the mean standardized uptake value (SUV) representing the whole metabolic activity of the brain from the F-FDG-PET images. We also calculated the white matter SUV from the upper transaxial slices (centrum semiovale) of the F-FDG-PET images. The whole brain volume was calculated by summing up the volumes of the white matter, grey matter and CSF. The global cerebral metabolic activity was calculated by multiplying the mean SUV with total brain volume. The whole brain white matter metabolic activity was calculated by multiplying the mean SUV for the white matter by the white matter volume. The global cerebral metabolic activity only reflects those of the grey matter and the white matter, whereas that of the CSF is zero. We subtracted the global white matter metabolic activity from that of the whole brain, resulting in the global grey matter metabolism alone. We then divided the grey matter global metabolic activity by grey matter volume to accurately calculate the SUV for the grey matter alone.The brain volumes ranged between 1546 and 1924 ml. The mean SUV for total brain was 4.8-7. Total metabolic burden of the brain ranged from 5565 to 9617. The mean SUV for white matter was 2.8-4.1. On the basis of these measurements we generated the grey matter SUV, which ranged from 8.1 to 11.3.The accurate metabolic activity of the grey matter can be calculated using the novel segmentation technique that we applied to MRI. By combining these quantitative data with those generated from F-FDG-PET images we were able to calculate the accurate metabolic activity of the grey matter. These types of measurements will be of great value in accurate analysis of the data from patients with neuropsychiatric disorders.
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The magnetization transfer ratio reflects the integrity of tissue structure, including myelination and axonal density. Mean magnetization transfer ratio fell in 18 untreated patients with multiple sclerosis both in normal appearing grey (-0.25 pu/year, p < 0.001) and white matter (-0.12 pu/year, p = 0.004). Conversely, mean magnetization transfer ratio was stable in 20 alemtuzumab-treated patients (grey matter: -0.01 pu/year, p = 0.87; white matter: -0.02 pu/year, p = 0.51). The gradient difference in grey matter was 0.25 pu/year (p < 0.001) after age-adjustment. These data suggest that in multiple sclerosis alemtuzumab protects against tissue damage in normal-appearing grey matter, perhaps by preventing new lesion formation.
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The present study combined optimized voxel-based morphometry and diffusion tensor imaging to detect age-related brain changes. We compared grey matter density maps (grey matter voxel-based morphometry) and white matter fractional anisotropy maps (diffusion tensor imaging-voxel-based morphometry) between two groups of 17 younger and 17 older women. Older women exhibited reduced white matter fractional anisotropy as well as decreased grey matter density most prominently in the frontal, limbic, parietal and temporal lobes. A discriminant analysis identified four frontal and limbic grey and white matter areas that separated the two groups most effectively. We conclude that grey matter voxel-based morphometry and diffusion tensor imaging voxel-based morphometry are well suited for the detection of age-related changes and their combination provides high accuracy when detecting the neural correlates of aging.
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