Neuropathology of Vascular Brain Health: Insights From Ex Vivo Magnetic Resonance Imaging–Histopathology Studies in Cerebral Small Vessel Disease

Abstract

Sporadic cerebral small vessel disease (SVD) is a major contributor to vascular cognitive impairment and dementia in the aging human brain. On neuropathology, sporadic SVD is characterized by abnormalities to the small vessels of the brain predominantly in the form of cerebral amyloid angiopathy and arteriolosclerosis. These pathologies frequently coexist with Alzheimer disease changes, such as plaques and tangles, in a single brain. Conversely, during life, magnetic resonance imaging (MRI) only captures the larger manifestations of SVD in the form of parenchymal brain abnormalities. There appears to be a major knowledge gap regarding the underlying neuropathology of individual MRI-detectable SVD abnormalities. Ex vivo MRI in postmortem human brain tissue is a powerful tool to bridge this gap. This review summarizes current insights into the histopathologic correlations of MRI manifestations of SVD, their underlying cause, presumed pathophysiology, and associated secondary tissue injury. Moreover, we discuss the advantages and limitations of ex vivo MRI-guided histopathologic investigations and make recommendations for future studies.

Dementia with Lewy bodies: Impact of co‐pathologies and implications for clinical trial design

“…Nevertheless, the same review showed increased MRI‐assessed white matter hyperintensity (WMH) burden in individuals with DLB compared to cognitively unremarkable participants, which was consistently supported by neuropathological data. An ongoing challenge is that although WMH is considered a marker of cerebrovascular disease, other etiologies, including AD‐associated pathology and axonal loss, may associate with WMH 63–65 …”

Underlying microangiopathy and functional outcome of simultaneous multiple intracerebral hemorrhage

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“…Enlarged perivascular spaces (EPVS) in the centrum semiovale (CSO) and exclusively cortical cerebral microbleeds (CMBs) are consistently associated with CAA. In contrast, EPVS in the basal ganglia (BG) and deep CMBs presumably account for hypertensive angiopathy ( Greenberg et al, 2009 ; Charidimou et al, 2013 , 2017 ; van Veluw et al, 2022 ). Previous studies noted that there was a higher burden of total CMBs among SMICH patients; ( Stemer et al, 2010 ; Chen et al, 2016 ) however, the number of CMBs stratified by different locations (deep vs. lobar) had not been evaluated, and the phenotypes of other cerebral small vessel disease (SVD) MRI markers remained unclear.…”

Should individual timeline and serial CT/MRI panels of all patients be presented in acute brain insult cohorts? A pilot study of 45 patients with decompressive craniectomy after aneurysmal subarachnoid hemorrhage

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