Increase In CSF Volume Research Articles

Progression in WMH volume is accompanied by higher gray matter loss: One‐year follow‐up MRI study in TATA Longitudinal Study on Aging Cohort of India

AbstractBackgroundSmall vessel disease pathologies such as white matter hyperintensity (WMH) and loss in neuroanatomical volumes with aging have been investigated across various cross‐ sectional and longitudinal‐aging studies in different parts of world. However, it is yet not extensively investigated whether the changes in WMH kinetics over the period impacts the neuroanatomical health? Here, we have measured changes in WMH and neuroanatomic‐volumes, in an ongoing longitudinal study on aging in India called TATA longitudinal study on aging (TLSA), at the baseline and one‐year‐follow‐up visit. The TLSA‐study is a prospective, community‐based, cohort study that comprises of cognitively healthy, educated, and multilingual individuals of both genders aged ≥45 years. The subjects are recruited from urban‐Bangalore, a large metropolitan city in southern India.MethodMRI measurements were conducted on 3T whole‐body‐scanner. MRI study performed close to the first clinical and cognitive‐examination is termed as baseline visit (V0), while MRI close to one‐year follow‐up is termed as V1. T2w‐FLAIR, 3D‐MPRAGE and DWI MRI were performed at both V0‐ and V1‐visits. WMH was quantified using T2w‐FLAIR and MPRAGE‐T1w images. Anatomical volumes were determined using Freesurfer. The volumes were normalized to the total‐intracranial‐volume. Changes in WMH and anatomic volume were calculated as (Volume at V1 – Volume at V0).ResultChanges in WMH and neuroanatomic volumes were evaluated for 128‐subjects who had MRI at both the visits, V0 and V1. Quantification of change in WMH (Delta‐WMH) in the TLSA‐subjects revealed that 65% of the subjects showed progression in WMH‐volume while another 35% did not show WMH‐progression. This indicated that there is a subset of cohorts that showed progression in WMH volume (+0.5‐7.9 ml) while another subset of subjects had no change in WMH over the period. Segmentation of neuroanatomical‐volume showed that the subset of the cohort that showed WNH‐progression over the one‐year period had significantly larger reduction in gray‐matter and increase in CSF volume at V1 compared to another subset that did not had changes in WMH.ConclusionProgression in WMH may be associated with increased vascular insult to the brain resulting in substantial gray‐matter loss and ventricular increase. Increase in WMH volume may fasten the neuroanatomic deteriorations with aging.

Cerebrospinal fluid is a significant fluid source for anoxic cerebral oedema.

Cerebral oedema develops after anoxic brain injury. In two models of asphyxial and asystolic cardiac arrest without resuscitation, we found that oedema develops shortly after anoxia secondary to terminal depolarizations and the abnormal entry of CSF. Oedema severity correlated with the availability of CSF with the age-dependent increase in CSF volume worsening the severity of oedema. Oedema was identified primarily in brain regions bordering CSF compartments in mice and humans. The degree of ex vivo tissue swelling was predicted by an osmotic model suggesting that anoxic brain tissue possesses a high intrinsic osmotic potential. This osmotic process was temperature-dependent, proposing an additional mechanism for the beneficial effect of therapeutic hypothermia. These observations show that CSF is a primary source of oedema fluid in anoxic brain. This novel insight offers a mechanistic basis for the future development of alternative strategies to prevent cerebral oedema formation after cardiac arrest.

Поражение подкорковых структур головного мозга при различных фенотипах рассеянного склероза и их прогностическая значимость

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease that affects the central nervous system, mainly in young people, and leads to inevitable disability. The purpose of the study is to determine the degree of involvement of subcortical structures in the pathological process in multiple sclerosis and to assess their prognostic significance. 80 patients with relapsing-remitting (n=48) and secondary progressive (n=32) phenotypes of MS were examined; the control group consisted of 20 healthy people of the corresponding age and gender. Clinical assessment was carried out on the following scales: EDSS, MSSS, MMSE, FAB, MoCA, SDMT, Beck’s test and HADS. All patients underwent MRI of the brain and MR-morphometry using the Freesurfer 6.0 software. In patients with multiple sclerosis, the neurodegenerative process is represented by a decrease in the volumes of the caudate nucleus and putamen, an increase in the volume of the third and lateral ventricles, an increase in CSF volume, and the presence of «black holes». The volume of the third and lateral ventricles, as well as the volume of CSF (general neurodegeneration), depends on the duration of the disease. The degree of disability (EDSS) is influenced by the volumes of the caudate nucleus, globus pallidus, nucleus accumbens, and brainstem. In turn, cognitive decline is influenced by the volume of the thalamus, basal nuclei, brainstem, the volume of the lateral ventricles, and a decrease in the volume of the white matter and cerebellar cortex. Thus, dynamic assessment and monitoring of the volume of subcortical structures of the brain using MR-morphometry can act as a prognostic factor in the transition of the relapsing-relapsing phenotype of multiple sclerosis to the secondary progressive phenotype. English version of this article on pp. 404-411 is available at URL: https://panor.ru/articles/subcortical-brain-lesions-in-different-phenotypes-of-multiple-sclerosis-and-their-prognostic-significance/63941.html

Spiral MRSI and tissue segmentation of normal-appearing white matter and white matter lesions in relapsing remitting multiple sclerosis patients☆

PurposeTo evaluate the performance of novel spiral MRSI and tissue segmentation pipeline of the brain, to investigate neurometabolic changes in normal-appearing white matter (NAWM) and white matter lesions (WML) of stable relapsing remitting multiple sclerosis (RRMS) compared to healthy controls (HCs). MethodsSpiral 3D MRSI using LASER-GOIA-W [16,4] was undertaken on 16 RRMS patients and 9 HCs, to acquire MRSI data from a large volume of interest (VOI) 320 cm3 and analyzed using LCModel. MRSI data and voxel tissue segmentation were compared between the two cohorts using t-tests. Support vector machine (SVM) was used to classify tissue types and assessed by accuracy, sensitivity and specificity. ResultsCompared to HCs, RRMS demonstrated a statistically significant reduction in all mean brain tissues and increase in CSF volume. Within VOI, WM decreased (−10%) and CSF increased (41%) in RRMS compared to HCs (p < 0.001). MRSI revealed that total creatine (tCr) ratios of N-acetylaspartate and glutamate+glutamine in WML were significantly lower than NAWM-MS (−9%, −8%) and HCs (−14%, −10%), respectively. Myo-inositol/tCr in WML was significantly higher than NAWM-MS (14%) and HCs (10%). SVM of MRSI yielded accuracy, sensitivity and specificity of 86%, 95%, and 70%, respectively for HCs vs WML, which were higher than HC vs NAWM and WML vs NAWM models. ConclusionThis study demonstrates the benefit of MRSI in evaluating MS neurometabolic changes in NAWM. SVM of MRSI data in the MS brain may be suited for clinical monitoring and progression of MS patients. Longitudinal MRSI studies are warranted.

Voxel-wise deviations from healthy aging for the detection of region-specific atrophy.

The identification of pathological atrophy in MRI scans requires specialized training, which is scarce outside dedicated centers. We sought to investigate the clinical usefulness of computer-generated representations of local grey matter (GM) loss or increased volume of cerebral fluids (CSF) as normalized deviations (z-scores) from healthy aging to either aid human visual readings or directly detect pathological atrophy.Two experienced neuroradiologists rated atrophy in 30 patients with Alzheimer's disease (AD), 30 patients with frontotemporal dementia (FTD), 30 with dementia due to Lewy-body disease (LBD) and 30 healthy controls (HC) on a three-point scale in 10 anatomical regions as reference gold standard. Seven raters, varying in their experience with MRI diagnostics rated all cases on the same scale once with and once without computer-generated volume deviation maps that were overlaid on anatomical slices. In addition, we investigated the predictive value of the computer generated deviation maps on their own for the detection of atrophy as identified by the gold standard raters.Inter and intra-rater agreements of the two gold standard raters were substantial (Cohen's kappa κ > 0.62). The intra-rater agreement of the other raters ranged from fair (κ = 0.37) to substantial (κ = 0.72) and improved on average by 0.13 (0.57 < κ < 0.87) when volume deviation maps were displayed. The seven other raters showed good agreement with the gold standard in regions including the hippocampus but agreement was substantially lower in e.g. the parietal cortex and did not improve with the display of atrophy scores. Rating speed increased over the course of the study and irrespective of the presentation of voxel-wise deviations.Automatically detected large deviations of local volume were consistently associated with gold standard atrophy reading as shown by an area under the receiver operator characteristic of up to 0.95 for the hippocampus region. When applying these test characteristics to prevalences typically found in a memory clinic, we observed a positive or negative predictive value close to or above 0.9 in the hippocampus for almost all of the expected cases. The volume deviation maps derived from CSF volume increase were generally better in detecting atrophy.Our study demonstrates an agreement of visual ratings among non-experts not further increased by displaying, region-specific deviations of volume. The high predictive value of computer generated local deviations independent from human interaction and the consistent advantages of CSF-over GM-based estimations should be considered in the development of diagnostic tools and indicate clinical utility well beyond aiding visual assessments.

Assessing the Relationship between Neurocognitive Performance and Brain Volume in Chronic Moderate-Severe Traumatic Brain Injury.

Characterize the scale and pattern of long-term atrophy in gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) in chronic moderate-severe traumatic brain injury (TBI) and its relationship to neurocognitive outcomes. The TBI group consisted of 17 males with primary diagnosis of moderate-severe closed head injury. Participants had not received any systematic, post-acute rehabilitation and were recruited on average 8.36 years post-injury. The control group consisted of 15 males matched on age and education. Neurocognitive battery included widely used tests of verbal memory, visual memory, executive functioning, and attention/organization. GM, WM, and CSF volumes were calculated from segmented T1-weighted anatomical MR images. Voxel-based morphometry was employed to identify brain regions with differences in GM and WM between TBI and control groups. Chronic TBI results in significant neurocognitive impairments, and significant loss of GM and WM volume, and significant increase in CSF volume. Brain atrophy is not widespread, but it is rather distributed in a fronto-thalamic network. The extent of volume loss is predictive of performance on the neurocognitive tests. Significant brain atrophy and associated neurocognitive impairments during the chronic stages of TBI support the notion that TBI results in a chronic condition with lifelong implications.

Acceleration of White Matter Hyperintensity Burden Preceding Onset of Mild Cognitive Impairment (S24.006)

Objective: Determine the timing of white matter hyperintensity (WMH) burden acceleration in relation to mild cognitive impairment (MCI) onset. Background Cerebral white matter change, observed as hyperintensities on T2 MRI, are very common in cognitively intact elderly. Those with greater baseline and rates of WMH accumulation are at increased risk of MCI, a likely precursor of progressive dementia. The timing of acceleration of WMH increase relative to clinical transition to MCI has not been established. Design/Methods: 189 cognitively intact older volunteers from the Oregon Brain Aging Study underwent yearly evaluations, including brain MRI, and cognitive testing. MCI was defined as being the first of two consecutive Clinical Dementia Rating scores of 0.5 or higher. The time before MCI, when the change in WMH burden accelerates, was assessed using a mixed-effects model with a change point for subjects who developed MCI during follow up. Results: During a follow up duration of up to 22.2 years, 135 subjects developed MCI. Acceleration in %WMH volume increase occurred 10.6 years before MCI onset. On average, the annual rate of change in %WMH increased an additional 3.3% after the change point. Acceleration in %ventricular CSF volume increase and total brain volume decrease occurred 3.7 and 5.0 years before the onset of MCI, respectively. Out of 63 volunteers who converted to MCI and had autopsy, only 28.5% had Alzheimer9s disease (AD) as the sole etiology of their dementia, while almost just as many had both AD and significant ischemic cerebrovascular disease present. Conclusions: Acceleration in WMH burden, a common indicator of cerebrovascular disease in the elderly, is a pathological change that emerges early in the pre-symptomatic phase leading to MCI. Monitoring longitudinal WMH change may thus be useful in determining those at risk for cognitive impairment and for planning strategies for introducing disease specific modifying therapies prior to dementia onset. Supported by: NIH (P30 AG08017, M01 RR000334, R01 AG024059), Department of Veterans Affairs, Storms Family Fund at the Oregon Community Foundation, T&J Meyer Foundation. Disclosure: Dr. Silbert has nothing to disclose. Dr. Dodge has nothing to disclose. Dr. Perkins has nothing to disclose. Dr. Lahna has nothing to disclose. Dr. Kaye has received personal compensation for activities with Eli Lilly & Company as a participant on a data safety and monitoring board. Dr. Kaye has received research support from Elan Corporation, Danone Medical, Bristol-Myers Squibb Company, Satoris, and Intel.

Distinct Brain Volume Changes Correlating with Clinical Stage, Disease Progression Rate, Mutation Size, and Age at Onset Prediction as Early Biomarkers of Brain Atrophy in Huntington's Disease

Searching brain and peripheral biomarkers is a requisite to cure Huntington's disease (HD). To search for markers indicating the rate of brain neurodegenerative changes in the various disease stages, we quantified changes in brain atrophy in subjects with HD. We analyzed the cross-sectional and longitudinal rate of brain atrophy, quantitatively measured by fully-automated multiparametric magnetic resonance imaging, as fractional gray matter (GM, determining brain cortex volume), white matter (WM, measuring the volume of axonal fibers), and corresponding cerebral spinal fluid (CSF, a measure of global brain atrophy), in 94 gene-positive subjects with presymptomatic to advanced HD, and age-matched healthy controls. Each of the three brain compartments we studied (WM, GM, and CSF) had a diverse role and their time courses differed in the development of HD. GM volume decreased early in life. Its decrease was associated with decreased serum brain-derived-neurotrophic-factor and started even many years before onset symptoms, then decreased slowly in a nonlinear manner during the various symptomatic HD stages. WM volume loss also began in the presymptomatic stage of HD a few years before manifest symptoms appear, rapidly decreasing near to the zone-of-onset. Finally, the CSF volume increase began many years before age at onset. Its volume measured in presymptomatic subjects contributed to improve the CAG-based model of age at onset prediction. The progressive CSF increase depended on CAG mutation size and continued linearly until the last stages of HD, perhaps representing the best marker of progression rate and severity in HD (R(2)= 0.25, P < 0.0001).

Deformation-based brain morphometry to track the course of alcoholism: Differences between intra-subject and inter-subject analysis

Substantial changes in brain morphology mark the course of alcoholism from development through dependence, recovery, and relapse. These changes can be characterized with deformation-based morphometry, which quantifies shape differences between anatomical structures, either in different subjects (cross-sectional) or in the same subject over time (longitudinal). Here we present analyses of data from a longitudinal magnetic resonance imaging (MRI) study on the effects of alcoholism on brain structure. Images were acquired from alcoholic women ( n = 7, mean age 47.8 ± 8.3 years) and age-matched control women ( n = 16, mean age 51.2 ± 7.5 years). From each subject, we acquired two structural MR brain images, separated by approximately 2 years (mean 21.6 ± 7 months). We performed two types of morphometry using log-Jacobian maps of inter-subject and intra-subject nonrigid coordinate transformations, justified by the invariance of relevant statistics (mean, standard deviation, z-score, and t-test) under changes of the spatial and temporal reference coordinate system. With all images from one time point, a cross-sectional inter-subject morphometry determined group differences between alcoholics and normal controls. We compared these results with longitudinal intra-subject morphometry based on two images per subject acquired at different times (approximately 2 years apart). Inter- and intra-subject analysis produced partially conflicting results. Whereas the intra-subject analysis indicated faster ventricular volume increases in the alcoholics (+ 11% per year) than in the controls (+ 2% per year), the inter-subject analysis showed, on average, smaller absolute ventricle volumes in the alcoholics than in the controls (− 33% relative volume). These differences were confirmed by manual planimetry and were statistically significant whether tested based on difference or change, integrated over the volume of the ventricles. Other changes and group differences were consistent between the two analyses, e.g., reduction of white matter (including corpus callosum) and increase in CSF volume, and these are in agreement with established effects of alcoholism on brain structure. We conclude that intra-subject morphometry of longitudinal data is preferable to inter-subject morphometry for detecting dynamic changes due to a disease, especially when only small samples are available. Our analysis demonstrates that the distinction between group differences observed at a point in time vs. over time is not merely academic but can substantially reduce the validity of the outcomes of actual morphometric studies. This discrepancy in results underscores the importance of distinguishing between volume differences and volume changes in morphometric analyses.

Mapping the brain in autism. A voxel-based MRI study of volumetric differences and intercorrelations in autism

Autism is a disorder of neurodevelopment resulting in pervasive abnormalities in social interaction and communication, repetitive behaviours and restricted interests. There is evidence for functional abnormalities and metabolic dysconnectivity in 'social brain' circuitry in this condition, but its structural basis has proved difficult to establish reliably. Explanations for this include replication difficulties inherent in 'region of interest' approaches usually adopted, and variable inclusion criteria for subjects across the autism spectrum. Moreover, despite a consensus that autism probably affects widely distributed brain regions, the issue of anatomical connectivity has received little attention. Therefore, we planned a fully automated voxel-based whole brain volumetric analysis in children with autism and normal IQ. We predicted that brain structural changes would be similar to those previously shown in adults with autism spectrum disorder and that a correlation analysis would suggest structural dysconnectivity. We included 17 stringently diagnosed children with autism and 17 age-matched controls. All children had IQ >80. Using Brain Activation and Morphological Mapping (BAMM) software, we measured global brain and tissue class volumes and mapped regional grey and white matter differences across the whole brain. With the expectation that volumes of interconnected regions correlate positively, we carried out a preliminary exploration of 'connectivity' in autism by comparing the nature of inter-regional grey matter volume correlations with control. Children with autism had a significant reduction in total grey matter volume and significant increase in CSF volume. They had significant localized grey matter reductions within fronto-striatal and parietal networks similar to findings in our previous study, and additional decreases in ventral and superior temporal grey matter. White matter was reduced in the cerebellum, left internal capsule and fornices. Correlation analysis revealed significantly more numerous and more positive grey matter volumetric correlations in controls compared with children with autism. Thus, using similar diagnostic criteria and image analysis methods in otherwise healthy populations with an autistic spectrum disorder from different countries, cultures and age groups, we report a number of consistent findings. Taken together, our data suggest abnormalities in the anatomy and connectivity of limbic-striatal 'social' brain systems which may contribute to the brain metabolic differences and behavioural phenotype in autism.

Changes in premorbid brain volume predict Alzheimer's disease pathology.

To assess whether changes in antemortem MRI brain volume measurements are valid predictors of subsequent Alzheimer disease (AD) pathology. Thirty-nine subjects, 15 nondemented and 24 with cognitive impairment, were followed until death. Regional postmortem measures of senile plaque (SP) and neurofibrillary tangle (NFT) severity were examined in relationship to cross-sectional and longitudinal volumetric measurements obtained from antemortem MRI. Total brain volume change over time was related to the accumulation of cortical NFT. The rate of ventricular CSF volume increase was related to both cortical NFT and SP. The last hippocampal volume prior to death was related to hippocampal NFT burden; the rate of hippocampal volume atrophy was not related to hippocampal NFT pathology. These significant relationships continue to exist when all nondemented subjects are excluded from analysis. In subjects with cognitive impairment, the best predictor of cortical NFT and SP is the rate of ventricular volume increase. Excluding subjects with long duration between MRI and death did not appreciably alter results. MRI volumes measured over time are valid biomarkers of pathologic progression of AD across a range of antemortem clinical states. The rate of ventricular volume enlargement can be used to monitor disease progression or response to treatment in future clinical trials that are targeted at NFT and SP pathology.

Increased differentiation of intracranial white matter lesions by multispectral 3D-tissue segmentation: preliminary results

MRI is a very sensitive imaging modality, however with relatively low specificity. The aim of this work was to determine the potential of image post-processing using 3D-tissue segmentation technique for identification and quantitative characterization of intracranial lesions primarily in the white matter. Forty subjects participated in this study: 28 patients with brain multiple sclerosis (MS), 6 patients with subcortical ischemic vascular dementia (SIVD), and 6 patients with lacunar white matter infarcts (LI). In routine MR imaging these pathologies may be almost indistinguishable. The 3D-tissue segmentation technique used in this study was based on three input MR images (T1, T2-weighted, and proton density). A modified k-Nearest-Neighbor (k-NN) algorithm optimized for maximum computation speed and high quality segmentation was utilized. In MS lesions, two very distinct subsets were classified using this procedure. Based on the results of segmentation one subset probably represent gliosis, and the other edema and demyelination. In SIVD, the segmented images demonstrated homogeneity, which differentiates SIVD from the heterogeneity observed in MS. This homogeneity was in agreement with the general histological findings. The LI changes pathophysiologically from subacute to chronic. The segmented images closely correlated with these changes, showing a central area of necrosis with cyst formation surrounded by an area that appears like reactive gliosis. In the chronic state, the cyst intensity was similar to that of CSF, while in the subacute stage, the peripheral rim was more prominent. Regional brain lesion load were also obtained on one MS patient to demonstrate the potential use of this technique for lesion load measurements. The majority of lesions were identified in the parietal and occipital lobes. The follow-up study showed qualitatively and quantitatively that the calculated MS load increase was associated with brain atrophy represented by an increase in CSF volume as well as decrease in “normal” brain tissue volumes. Importantly, these results were consistent with the patient’s clinical evolution of the disease after a six-month period. In conclusion, these results show there is a potential application for a 3D tissue segmentation technique to characterize white matter lesions with similar intensities on T2-weighted MR images. The proposed methodology warrants further clinical investigation and evaluation in a large patient population.