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Short T1 Fraction as a Marker of Myelin Content: Evidence from Postmortem MRI and Histology
Chenyang Li1,2, Dominique Leitner3, Zifei Liang1,2
1Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University Grossman School of Medicine, New York, New York, USA.
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.
Insights
The short-T1 fraction shows strong correlation with myelin content in brain white matter. This finding supports its potential as a clinically translatable biomarker for assessing myelin integrity.
Area of Science:
- Neuroimaging
- Biomarker Discovery
- White Matter Integrity
Background:
- Myelin damage is a hallmark of neurological disorders.
- Accurate assessment of myelin integrity is crucial for diagnosis and treatment.
- Current imaging techniques have limitations in quantifying myelin.
Purpose of the Study:
- To evaluate the short-T1 fraction as a potential biomarker for white matter myelin integrity.
- To validate the short-T1 fraction against histological myelin staining.
- To assess the clinical translatability of the short-T1 fraction.
Main Methods:
- Acquired multi-inversion-time MRI data from postmortem brain specimens and ex vivo tissue blocks.
- Generated short-T1 fraction maps using inverse Laplace transform.
- Correlated short-T1 fraction maps with T2-based myelin water imaging and myelin-stained histology.
- Acquired in vivo short-T1 fraction data from volunteers with white matter hyperintensities (WMHs).
Main Results:
- Postmortem MRI revealed reduced short-T1 fractions in WMHs.
- Short-T1 fraction strongly correlated with myelin content in histological sections.
- T1-T2 correlation analysis indicated association with the myelin water component.
- In vivo data showed consistent reductions in short-T1 fractions within WMHs.
Conclusions:
- The short-T1 fraction is closely associated with myelin content in white matter.
- This metric shows promise as a clinically translatable biomarker for myelin integrity.
- Further research can explore its application in various neurological conditions.
