Post-mortem 7 Tesla MRI detection of white matter hyperintensities: A multidisciplinary voxel-wise comparison of imaging and histological correlates

Abstract

Highlights Ultra high-field post mortem MRI is a valid tool for the study of white matter hyperintensities. Demyelination and parenchymal rarefaction are associated with FLAIR and T2 changes on 7 Tesla MRI. Age, length of fixation and pathological diagnosis are all significant predictors of white matter FLAIR voxel intensity.

Microvessel stenosis, enlarged perivascular spaces, and fibrinogen deposition are associated with ischemic periventricular white matter hyperintensities

“…All scans of postmortem tissue were performed at Western's Centre for Functional and Metabolic Mapping on a 7T Scanner (Siemens) following a previously described imaging protocol [ 33 ]. Briefly, frontal coronal sections were selected from each fixed brain and immersed in Galden HT‐270 perfluorinated fluid in a custom‐stacking device for imaging.…”

“…Determining vascular contributions to pvWMH on MRI imaging may be aided by the presence of periventricular infarcts (PVI) within the hyperintense tissue. Higher imaging resolution caused by advancements in MRI field strengths can detect small lesions of ischemic nature within pvWMH [ 33 ]. We have previously reported that the presence of these fluid filled cavities in brains with cerebrovascular disease are a significant contributor to the hyperintense signal in both the surrounding lesion and normal‐appearing white matter [ 33 ].…”

“…Higher imaging resolution caused by advancements in MRI field strengths can detect small lesions of ischemic nature within pvWMH [ 33 ]. We have previously reported that the presence of these fluid filled cavities in brains with cerebrovascular disease are a significant contributor to the hyperintense signal in both the surrounding lesion and normal‐appearing white matter [ 33 ]. Of the few studies that have considered PVI separately from pvWMH, associations with vascular stenosis and collagenosis have been reported [ 22 , 34 ], but whether there are resulting impairments to the BBB and glial cell activity is not well understood.…”

Expanding the horizon of research into the pathogenesis of the white matter diseases: Proceedings of the 2021 Annual Workshop of the Albert Research Institute for White Matter and Cognition

“…Traditionally, white matter changes are detected using magnetic resonance imaging (MRI) using T2 weighted fluid attenuated inversion recovery (FLAIR), appearing as white matter hyperintensities (WMH). The etiology and development of WMH are heterogeneous, but usually involve a loss of myelin and axon density, the primary end-stage pathological correlates of WMH [25]. Within both gray and white matter, glial cells present critical targets for therapeutic intervention and neuroprotection [26][27][28].…”

In vivo myelin imaging and tissue microstructure in white matter hyperintensities and perilesional white matter

“…One theory of WMH development suggests that early in disease pathology, venous collagenosis 10 and increased blood brain permeability 11 cause increased local interstitial fluid. This increased interstitial fluid then triggers a pathological cascade to glial (including oligodendroglial) and neuronal cells leading to demyelination and axonal damage 12,13 . Early interstitial fluid accumulation is potentially reversible, but usually the trend is for progression towards irreversible myelin loss and neuronal damage 8 .…”