Estimating axon radius using diffusion-relaxation MRI: calibrating a surface-based relaxation model with histology.

Area of Science:

• Neuroimaging
• Biomarkers
• Tissue Microstructure

Background:

• Axon radius is a key biomarker for brain diseases and influences action potential speed.
• Current Diffusion MRI (dMRI) methods struggle to detect small human brain axon radii (<1 micrometer).
• Advanced MRI techniques sensitive to small axon radii are essential.

Purpose of the Study:

• To investigate if surface-based axonal relaxation links intra-axonal T2 and T1 times with axon radius.
• To develop and validate a novel MRI method for estimating axon radius in the human brain.

Main Methods:

• Acquired unique in vivo human diffusion-T1-T2 relaxation MRI data (3T scanner, b=6,000 s/mm2).
• Collected additional diffusion-T2 data for model evaluation.
• Estimated intra-axonal relaxation times using a diffusion-relaxation model on spherical mean signals.
• Calibrated the model using postmortem histology from the corpus callosum.

Main Results:

• The surface-based relaxation model successfully explained the relationship between relaxation times and histological axon radius.
• A novel calibration approach was developed to predict axon radius.
• Predicted axon radii closely matched histological measurements in the corpus callosum.

Conclusions:

• The proposed MRI method effectively estimates axon radius by leveraging surface-based relaxation processes.
• This technique offers a promising non-invasive approach for assessing brain microstructure and potential disease biomarkers.
• The findings support the development of advanced MRI methods for sensitive axon radius measurement.