Volumes Of Gray Matter Structures Research Articles

Cortex-to-caudate volume ratio as a predictor of cognitive decline in Alzheimer's disease and mild cognitive impairment

BackgroundBrain and cortical atrophy play crucial roles in supporting the clinical diagnosis of Alzheimer's disease (AD). This study hypothesized that the ratios of brain or cortical volume to subcortical gray matter structure volumes are potential imaging markers for cognitive alterations in AD dementia and amnestic mild cognitive impairment (aMCI). MethodsSeventy-seven subjects diagnosed with AD dementia or aMCI underwent baseline neuropsychological testing, 2-year follow-up cognitive assessments, and high-resolution T1-weighted MRI scans. Total brain/cortical volume and subcortical gray matter structure volumes were automatically segmented and measured. Univariate and multiple linear regression analyses were conducted to determine the associations between volumetric ratios and interval changes in cognitive scores. ResultsThe ratio of cortical volume to caudate volume showed the most significant association with changes in MoCA (B = 0.132, SE = 0.042, p = 0.002), MMSE (B = 0.140, SE = 0.040, p = 0.001), and CDR-SOB (B = −0.013, SE = 0.005, p = 0.007) scores over the 2-year follow-up period. These associations remained significant after adjusting for various covariates. Similar associations were observed for the ratios of cortical volume to putamen and globus pallidum volumes. ConclusionsThe cortex-to-caudate volume ratio is significantly associated with cognitive decline in AD dementia and aMCI. This ratio may serve as a useful biomarker for monitoring disease progression and predicting cognitive outcomes. Our findings highlight the importance of considering the relative atrophy of cortical and subcortical structures in understanding AD pathology.

Diffusion tensor imaging in mild cognitive impairment in community‐dwelling older adults in Taiwan

AbstractBackgroundMost structural magnetic resonance imaging studies of Alzheimer’s disease and mild cognitive impairment (MCI) have focused on volumes of gray matter structures in the medial temporal lobe. This study aims to investigate white matter microstructures using diffusion tensor imaging (DTI) in MCI and different types of MCI in a community‐based cohort of older adults in Taiwan.MethodThe DTIs of 372 older adults at baseline from a community‐based prospective cohort study, the Epidemiology of Mild Cognitive Impairment in Taiwan (EMCIT) were used. Among them, 74 were ascertained as MCIs including 53 amnestic MCIs and 21 non‐amnestic MCIs. Tract‐based spatial statistics (TBSS) were used to compare voxelwise fractional anisotrophy (FA) differences between MCI, amnestic (aMCI), non‐amnestic MCI (naMCI) and cognitively normal (CN) older adults.ResultMean age of participants was 70.7± 5.3 years. Older adults with MCI were older, have lower education and higher prevalence of diabetes and depression. The pattern of white matter integrity disruption tends to follow an anterior to posterior gradient with greater damage noted in posterior regions in MCI (Fig. 1). On further analysis, participants with aMCI showed disrupted integrity in multiple white matter tracts across the whole‐brain when compared with CNs (Fig. 2) whereas only few white matter regions with diffusion changes were found in aMCI as compared to CNs and with less significance.ConclusionThese findings indicate that the degeneration extensively exists in white matter tracts in MCI, especially naMCI. The results are consistent with the view that MCI is not a uniform disease entity and presents heterogeneity in the structural brain changes.

Beware of white matter hyperintensities causing systematic errors in FreeSurfer gray matter segmentations!

Volumetric estimates of subcortical and cortical structures, extracted from T1‐weighted MRIs, are widely used in many clinical and research applications. Here, we investigate the impact of the presence of white matter hyperintensities (WMHs) on FreeSurfer gray matter (GM) structure volumes and its possible bias on functional relationships. T1‐weighted images from 1,077 participants (4,321 timepoints) from the Alzheimer's Disease Neuroimaging Initiative were processed with FreeSurfer version 6.0.0. WMHs were segmented using a previously validated algorithm on either T2‐weighted or Fluid‐attenuated inversion recovery images. Mixed‐effects models were used to assess the relationships between overlapping WMHs and GM structure volumes and overall WMH burden, as well as to investigate whether such overlaps impact associations with age, diagnosis, and cognitive performance. Participants with higher WMH volumes had higher overlaps with GM volumes of bilateral caudate, cerebral cortex, putamen, thalamus, pallidum, and accumbens areas (p < .0001). When not corrected for WMHs, caudate volumes increased with age (p < .0001) and were not different between cognitively healthy individuals and age‐matched probable Alzheimer's disease patients. After correcting for WMHs, caudate volumes decreased with age (p < .0001), and Alzheimer's disease patients had lower caudate volumes than cognitively healthy individuals (p < .01). Uncorrected caudate volume was not associated with ADAS13 scores, whereas corrected lower caudate volumes were significantly associated with poorer cognitive performance (p < .0001). Presence of WMHs leads to systematic inaccuracies in GM segmentations, particularly for the caudate, which can also change clinical associations. While specifically measured for the Freesurfer toolkit, this problem likely affects other algorithms.

Evaluation of deep gray matter volume, cortical thickness and white matter integrity in patients with typical absence epilepsy: a study using voxelwise-based techniques.

The objective of this study was to evaluate the cortical thickness and the volume of deep gray matter structures, measured from 3D T1-weighted gradient echo imaging, and white matter integrity, by diffusion tensor imaging (DTI) in patients with typical absence epilepsy (AE). Patients (n=19) with typical childhood AE and juvenile AE, currently taking antiepileptic medication, were compared with control subjects (n=19), matched for gender and age. 3D T1 magnetization-prepared rapid gradient echo-weighted imaging and DTI along 30 noncolinear directions were performed using a 1.5-T MR scanner. FreeSurfer was used to perform cortical volumetric reconstruction and segmentation of deep gray matter structures. For tract-based spatial statistics analysis of DTI, a white matter skeleton was created, along with a permutation-based inference with 5000 permutations. A threshold of p<0.05 was used to identify abnormalities in fractional anisotropy (FA). The mean, radial, and axial diffusivities were also projected onto the mean FA skeleton. Patients with AE presented decreased FA and increased mean diffusivity and radial diffusivity values in the genu and the body of the corpus callosum and right anterior corona radiata, as well as decreased axial diffusivity in the left posterior thalamic radiation, inferior cerebellar peduncle, right cerebral peduncle, and right corticospinal tract. However, there were no significant differences in cortical thickness or deep gray matter structure volumes between patients with AE and controls. Abnormalities found in white matter integrity may help to better understand the pathophysiology of AE and optimize diagnosis and treatment strategies.

White Matter Microstructure and Subcortical Gray Matter Structure Volumes in Aspartylglucosaminuria; a 5-Year Follow-up Brain MRI Study of an Adolescent with Aspartylglucosaminuria and His Healthy Twin Brother.

Aspartylglucosaminuria is an inherited, lysosomal storage disease causing progressive decline in cognitive and motor functions. The aim of this study was to evaluate volumes of subcortical gray matter structures and white matter microstructure in aspartylglucosaminuria in adolescence in a longitudinal study for the first time. A boy with aspartylglucosaminuria and his healthy twin brother were imaged twice with a 3.0T MRI scanner at the ages of 10 and 15years. Subcortical gray matter structure volumes were measured using an atlas-based automatic method, and diffusion tensor imaging was used to evaluate the white matter microstructure of the corpus callosum and the thalamocortical pulvinar tracts. The subcortical gray matter structures were smaller at onset and diminished at follow-up in the affected twin, with the exception of the amygdala which was larger and remained the size. The largest difference in volume between the twins was found in the thalami. The total gray and white matter volumes decreased in the affected twin. In diffusion tensor imaging analysis, the fractional anisotropy was decreased at onset in the affected twin compared to the healthy brother in the evaluated tracts. The axial, radial and mean diffusivity values were increased in the affected twin. The difference between the twins increased slightly at follow-up. The findings suggest that volumetric measurements and diffusion tensor imaging based microstructural analysis may be useful modalities for monitoring disease progression and response to emerging treatment in aspartylglucosaminuria, but further studies with more subjects are necessary to confirm the results.

Head and Brain Size in Pediatric Multiple Sclerosis

Researchers at the Montreal Neurological Institute, the Hospital for Sick Children, Toronto, Canada; and Department of Neurology, Rennes, France conducted MRI measurements of whole brain and regional white matter, gray matter, and deep gray matter structure volumes in 38 patients (mean age 15.2+/-2.4 years) with pediatric-onset relapsing-remitting multiple sclerosis (MS).

Reduced head and brain size for age and disproportionately smaller thalami in child-onset MS

Whole brain and regional volume measurement methods were used to quantify white matter, gray matter, and deep gray matter structure volumes in a population of patients with pediatric-onset multiple sclerosis (MS). Subjects included 38 patients (mean age 15.2 ± 2.4 years) and 33 age- and sex-matched healthy control (HC) participants. MRI measures included intracranial volume, normalized brain volume, normalized white and gray matter volume, and volumes of the thalamus, globus pallidus, putamen, and caudate. Because these volumes vary across age and sex in children, we normalized the volume measurements for MS and control groups by computing z scores using normative values obtained from healthy children enrolled in the MRI Study of Normal Brain Development. The intracranial volume z score was significantly lower in the patients with MS (-0.45 ± 1.16; mean ± SD) compared with the HC participants (+0.25 ± 0.98; p = 0.01). Patients with MS also demonstrated significant decreases in normalized brain volume z scores (-1.09 ± 1.49 vs -0.05 ± 1.22; p = 0.002). After correction for global brain volume, thalamic volumes in the MS population remained lower than those of HCs (-0.68 ± 1.72 vs 0.15 ± 1.35; p = 0.02), indicating an even greater loss of thalamic tissue relative to more global brain measures. Moderate correlations were found between T2-weighted lesion load and normalized thalamic volumes (r = -0.44, p < 0.01) and normalized brain volume (r = -0.47, p < 0.01) and between disease duration and normalized thalamic volume (r = -0.58, p < 0.001) and normalized brain volume (r = -0.46, p < 0.01). When compared with age- and sex-matched control subjects, the onset of MS during childhood is associated with a smaller overall head size, brain volume, and an even smaller thalamic volume.

Differential effect of NMDA and AMPA receptor blockade on protein synthesis in the rat infarct borderzone

We investigated whether the known neuroprotective effects of two selective glutamate receptor antagonists, the NMDA antagonist MK-801 and the AMPA antagonist NBQX, are reflected in the regional cerebral protein synthesis rates (CPSR) in rats with middle cerebral artery occlusion (MCAO). Rats treated with either saline, MK-801 (5 mg/kg i.p.) or NBQX (30 mg/kg i.p. x 3) were subjected to permanent MCAO. Regional CPSR and volumes of gray matter structures displaying normal CPSR were measured in coronal cryosections of the brain by quantitative autoradiography following an i.v. bolus injection of 35S-labelled L-methionine 2 h after occlusion. MCAO completely inhibited protein synthesis in the lateral part of striatum and part of the adjacent frontoparietal cortex corresponding to the ischemic focus. Surrounding this, a metabolic penumbra with approximately 50% reductions in CPSR was present. Treatment with MK-801 significantly increased the volume of tissue with normal CPSR in the ischemic hemisphere compared to controls, whereas this was not seen with NBQX treatment. The results suggest that MK-801 and NBQX have different effects on peri-infarct protein synthesis after MCAO. Since both compounds reduce infarct size, it is questionable that acute inhibition of protein synthesis in focal ischemia is of significant importance to the final outcome of a stroke lesion.

A Semiautomated Method for Measuring Brain Infarct Volume

An accurate, reproducible method for determining the infarct volumes of gray matter structures is presented for use with presently available image analysis systems. Areas of stained sections with optical densities above that of a threshold value are automatically recognized and measured. This eliminates the potential error and bias inherent in manually delineating infarcted regions. Moreover, the volume of surviving normal gray matter is determined rather than that of the infarct. This approach minimizes the error that is introduced by edema, which distorts and enlarges the infarcted tissue and surrounding white matter.