Raman, Mekala R.

AbstractIntroductionCerebrovascular lesions on MRI are common in Alzheimer's disease (AD) dementia, but less is known about their frequency and impact on dementia with Lewy bodies (DLB).MethodsWhite‐matter hyperintensities (WMHs) and infarcts on MRI were assessed in consecutive DLB (n = 81) and AD dementia (n = 240) patients and compared to age‐matched and sex‐matched cognitively normal subjects (CN) from a population‐based cohort.ResultsDLB had higher WMH volume compared to CN, and WMH volume was higher in the occipital and posterior periventricular regions in DLB compared to AD. Higher WMH volume was associated with history of cardiovascular disease and diabetes but not with clinical disease severity in DLB. Frequency of infarcts in DLB was not different from CN and AD dementia.DiscussionIn DLB, WMH volume is higher than AD and CN and appears to be primarily associated with history of vascular disease.

ABSTRACTBACKGROUND AND PURPOSEPathologic diagnosis is the gold standard in evaluating imaging measures developed as biomarkers for pathologically defined disorders. A brain MRI atlas representing autopsy‐sampled tissue can be used to directly compare imaging and pathology findings. Our objective was to develop a brain MRI atlas representing the cortical regions that are routinely sampled at autopsy for the diagnosis of Alzheimer's disease (AD).METHODSSubjects (n = 22; ages at death = 70‐95) with a range of pathologies and antemortem 3T MRI were included. Histology slides from 8 cortical regions sampled from the left hemisphere at autopsy guided the localization of the atlas regions of interest (ROIs) on each subject's antemortem 3D T1‐weighted MRI. These ROIs were then registered to a common template and combined to form one ROI representing the volume of tissue that was sampled by the pathologists. A subset of the subjects (n = 4; ages at death = 79‐95) had amyloid PET imaging. Density of β‐amyloid immunostain was quantified from the autopsy‐sampled regions in the 4 subjects using a custom‐designed ImageScope algorithm. Median uptake values were calculated in each ROI on the amyloid‐PET images.RESULTSWe found an association between β‐amyloid plaque density in 8 ROIs of the 4 subjects (total ROI n = 32) and median PiB SUVR (r2 = .64; P < .0001).CONCLUSIONSIn an atlas developed for imaging and pathologic correlation studies, we demonstrated that antemortem amyloid burden measured in the atlas ROIs on amyloid PET is strongly correlated with β‐amyloid density measured on histology. This atlas can be used in imaging and pathologic correlation studies.

PurposeRelaxation time constants are useful as markers of tissue properties. Imaging ex vivo tissue is done for research purposes; however, T1 relaxation time constants are altered by tissue fixation in a time‐dependent manner. This study investigates regional changes in T1 relaxation time constants in ex vivo brain tissue over 6 months of fixation.MethodsFive ex vivo human brain hemispheres in 10% formalin were scanned over 6 months. Mean T1 relaxation time constants were measured in regions of interest (ROIs) representing gray matter (GM) and white matter (WM) regions and analyzed as a function of fixation time.ResultsCortical GM ROIs had longer T1 relaxation time constants than WM ROIs; the thalamus had T1 relaxation time constants similar to those of WM ROIs. T1 relaxation time constants showed rapid shortening within the first 6 weeks after fixation followed by a slower rate of decline.ConclusionBoth GM and WM T1 relaxation time constants of fixed brain tissue show rapid decline within the first 6 weeks after autopsy and slow by 6 months. This information is useful for optimizing MR imaging acquisition parameters according to fixation time for ex vivo brain imaging studies. Magn Reson Med 77:774–778, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

ABSTRACTBACKGROUNDDisability progression in multiple sclerosis (MS) remains incompletely understood. Unlike lesional measures, central nervous system atrophy has a strong correlation with disability. Theiler's murine encephalomyelitis virus infection in SJL/J mice is an established model of progressive MS. We utilized in vivo MRI to quantify brain and spinal cord atrophy in this model and analyzed the temporal relationship between atrophy and disability.METHODSInfected and control mice were followed for 12 months. Disability was assessed periodically using rotarod assay. Volumetric MRI datasets were acquired at 7 Tesla. Ventricular volume and C4‐5 spinal cord cross‐sectional area measurements were performed using Analyze 10.RESULTSAt 3 months, brain atrophy reached statistical significance (P = .005). In contrast, disability did not differ until 4 months post‐infection (P = .0005). Cord atrophy reached significance by 9 months (P = 0.009). By 12 months, brain atrophy resulted in 111.8% increased ventricular volume (P = .00003), while spinal cord cross‐sectional area was 25.6% reduced (P = .001) among cases.CONCLUSIONSOur results suggest that significant brain atrophy precedes and predicts the development of disability, while spinal cord atrophy occurs late and correlates with severe disability. The observed temporal relationship establishes a framework for mechanisms of disability progression and enables further investigations of their underlying substrate.