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Basic Science and Pathogenesis.

Chenyang Li1, Dominique Leitner1, Huize Pang1

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This study links white matter hyperintensities (WMH) MRI signals to specific brain pathologies in Alzheimer's disease. High-resolution MRI and histology reveal WMH signal origins, improving in vivo interpretation.

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Area of Science:

  • Neuroimaging
  • Neuropathology
  • Alzheimer's Disease and Related Dementias (AD/ADRD)

Background:

  • White matter hyperintensities (WMHs) are key MRI biomarkers in AD/ADRD.
  • Histopathology links WMHs to demyelination and neuroinflammation.
  • Direct correlation between in vivo MRI and histopathology is challenging.

Purpose of the Study:

  • To bridge clinical MRI findings of WMHs with histopathological data.
  • To utilize multiparametric and multiscale MRI in dementia brains.
  • To quantitatively correlate in vivo MRI signals with specific histopathological features.

Main Methods:

  • Inclusion of two post-mortem AD brains.
  • Sequential 3T MRI acquisitions (whole-hemisphere and high-resolution ex vivo).
  • Sectioning of brain tissue blocks for imaging and histology.

Main Results:

  • Postmortem WMH contrast comparable to in vivo imaging.
  • WMHs showed increased mean diffusivity (MD) and prolonged T1, T2, T2* relaxation times.
  • Histopathology confirmed spatial overlap and revealed vacuolation, demyelination, astrogliosis, and neuroinflammation.

Conclusions:

  • Joint analysis of postmortem MRI and histopathology reveals complex WMH signal origins.
  • Elevated diffusivity and prolonged relaxation times correlate with histological findings.
  • Provides insights into the in vivo signal composition of WMHs.