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The impact of realistic axonal shape on axon diameter estimation using diffusion MRI
Hong-Hsi Lee1, Sune N Jespersen2, Els Fieremans1
1Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, USA; Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, New York, NY, USA.
Neuroimage
|August 18, 2020
Summary
Axonal shape variations confound diffusion MRI measurements of inner diameter. Our theory and simulations show beading and undulations lead to overestimation, but directional averaging can improve accuracy.
Area of Science:
- Neuroimaging
- Biophysics
- Computational Neuroscience
Background:
- Diffusion MRI is crucial for studying axonal microstructure, often modeling axons as ideal cylinders.
- Real axons exhibit complex shapes, including caliber variations (beading) and directional changes (undulations), which complicate diffusion MRI signal interpretation.
- Existing models may not fully capture how these anatomical complexities affect diffusion MRI metrics.
Purpose of the Study:
- To develop a theoretical framework for intra-axonal diffusion MRI signals that accounts for realistic axonal shapes.
- To investigate how axonal beading and undulations confound estimates of inner axonal diameter.
- To establish relationships between diffusion MRI metrics and axonal morphology.
Main Methods:
- Developed a coarse-graining theory for intra-axonal diffusion MRI signals based on 3D diffusion.
- Derived analytical relationships between diffusion MRI metrics (e.g., radial diffusivity D⊥(t), kurtosis K⊥(t)) and axonal shape.
- Validated the theory using Monte Carlo simulations on synthetic and electron microscopy-derived realistic axon models.
Main Results:
- Axon diameter estimates are significantly overestimated (approx. twofold in narrow pulse limit) due to beading and undulations.
- Axonal caliber variations alter narrow-pulse kurtosis, while undulations primarily cause overestimation in wide-pulse limits at low b-values.
- Directional averaging of high-b signals can mitigate the effects of undulations, yielding more accurate diameter estimations.
Conclusions:
- Realistic axonal morphology, not just ideal cylinders, must be considered for accurate diffusion MRI-based diameter estimation.
- The developed theory provides a quantitative link between axonal shape complexity and diffusion MRI metrics.
- Advanced signal processing, like directional averaging, can improve the reliability of microstructural measurements in white matter.
