Quantitative magnetization transfer imaging in postmortem multiple sclerosis brain

Klaus Schmierer1, Daniel J Tozer, Francesco Scaravilli

  • 1Department of Brain Repair and Rehabilitation, Institute of Neurology, University College London, London, United Kingdom. k.schmierer@ion.ucl.ac.uk

Abstract

Insights

Quantitative magnetization transfer MRI measures, specifically the fraction of macromolecular protons (fB), correlate with myelin content and axonal density in multiple sclerosis brains, suggesting potential for patient monitoring.

Area of Science:

  • Neuroimaging
  • Biomarkers
  • Multiple Sclerosis Research

Background:

  • Multiple Sclerosis (MS) is a demyelinating disease affecting white matter (WM).
  • Accurate in vivo assessment of myelin, axonal integrity, and gliosis in MS lesions is crucial for disease monitoring and therapeutic evaluation.

Purpose of the Study:

  • To investigate the relationship between quantitative magnetization transfer (qMT) MRI parameters, specifically the fraction of macromolecular protons (fB) and T2 relaxation of the macromolecular pool (T2B), with myelin content, axonal density, and gliosis in postmortem multiple sclerosis (MS) brains.

Main Methods:

  • qMT MRI was performed on unfixed postmortem brain slices from 20 MS subjects.
  • Myelin content, axonal count, and gliosis severity were quantified histologically.
  • Statistical analyses included t-tests and multiple regression to assess correlations.

Main Results:

  • qMT indices (fB and T2B) from postmortem MS brains aligned with reported in vivo values.
  • A strong inverse correlation was found between myelin content and fB (r = -0.80, P < 0.001), and between axonal count and fB (r = -0.79, P < 0.001).
  • fB significantly differed between normal-appearing white matter, remyelinated lesions, and demyelinated lesions, while T2B showed no association with histological measures.

Conclusions:

  • The fraction of macromolecular protons (fB) in MS white matter is significantly influenced by myelin content.
  • fB derived from qMT MRI shows promise as a potential imaging biomarker for monitoring disease progression and treatment response in patients with multiple sclerosis.