Multimodal Postmortem MRI and Histopathological Analysis Reveal Complex Signal Origins of White Matter Hyperintensity in Alzheimer's Disease

Motivation: White matter hyperintensities (WMHs) is common in patients with Alzheimer's Disease and dementia, but the pathological basis of their MRI signature remains unclear. Goal(s): To establish direct correlations between MRI and histopathology to understand the pathological origins of WMH's MRI signatures using postmortem specimens. Approach: We implemented a systematic pipeline combining postmortem multimodal MRI matched, histology, and antemortem MRI data from the same subject. Results: Postmortem MRI revealed increased diffusivity and prolonged relaxivity in WMHs. Histopathological validation revealed demyelination, white matter vacuolation, and abnormal glial activities. Impact: Direct comparisons between multimodal MRI and histopathological findings revealed the complex pathological underpinnings of WMHs in Alzheimer's Disease. These insights advance our understanding of MRI signal changes with WMHs development and progression in vivo.