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MRI-scale histology validates spatial sensitivity of in-vivo MRI-based axon radius estimation
Laurin Mordhorst1,2, Luke J Edwards3,4, Maria Morozova4,5
1Department of Neuroradiology, University of Luebeck, Luebeck, Germany.
Imaging Neuroscience (Cambridge, Mass.)
|June 25, 2026
Summary
Magnetic resonance imaging (MRI) can estimate axon radius, a potential biomarker for neurological disorders. This study validates MRI estimates against large-scale human brain histology, paving the way for clinical applications.
Area of Science:
- Neuroimaging
- Histology
- Biomarker Development
Background:
- Axon radius is a promising biomarker for neurological disorders.
- Current in-vivo MRI estimation is limited on clinical scanners and lacks validation.
- Existing histology methods offer only sparse sampling and qualitative assessment.
Purpose of the Study:
- To validate in-vivo MRI-based axon radius estimation against large-scale human brain histology.
- To assess the feasibility of translating MRI axon radius estimation to clinical scanners.
- To identify challenges and potential solutions for improving MRI sensitivity.
Main Methods:
- Utilized large-scale human corpus callosum histology, sampling 46 million axons across 35 regions.
- Performed MRI scans on an advanced research scanner to estimate axon radius.
- Conducted simulations to evaluate the feasibility of clinical scanner translation and SNR requirements.
Main Results:
- Demonstrated a significant spatial correlation between MRI radius estimates and histological data.
- Provided quantitative proof that MRI radius estimates reflect underlying white matter microstructure.
- Simulations suggest clinical translation is feasible with high-gradient systems but requires SNR gains.
Conclusions:
- MRI-based axon radius estimation is a valid approach for assessing white matter microstructure.
- Clinical translation requires overcoming SNR limitations and potential modeling bottlenecks.
- Further advancements in MRI technology and modeling are necessary for widespread clinical adoption.
