Abstract

Purpose: To investigate the short-T1 fraction as a potential biomarker of white matter myelin integrity, using myelin histology as ground truth. Methods: Multi-inversion-time MRI data were acquired from four postmortem brain hemisphere specimens from donors with Alzheimer's disease on a clinical 3T scanner, and from five dissected tissue blocks containing white matter hyperintensities (WMHs) on a preclinical 3T system. Short-T1 fraction maps were generated using inverse Laplace transform to isolate short-T1 components and were compared with T2-based myelin water imaging metrics through joint T1-T2 correlation analysis. Short-T1 fraction maps from the tissue blocks were further compared with myelin-stained histology. In addition, in vivo short-T1 fraction data were acquired from two elderly volunteers with WMHs to demonstrate translational feasibility. Results: Postmortem MRI revealed reduced short-T1 fractions in WMHs. T1-T2 correlation analysis showed that the short-T1 fraction was closely associated with the short-T2 (myelin water) component. Strong correlations were observed between short-T1 fractions and optical densities from both Luxol Fast Blue- and myelin basic protein-stained histological sections, supporting the link between the short-T1 signal and myelin content. Consistent findings were also observed in vivo, where significant reductions in short-T1 fractions were detected within WMHs. Conclusion: The short-T1 fraction correlated with myelin content in postmortem brain white matter, supporting its potential as a clinically translatable biomarker of myelin integrity.