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Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
A time-dependent diffusion MRI signature of axon caliber variations and beading
Hong-Hsi Lee1, Antonios Papaioannou2, Sung-Lyoung Kim2
1Center for Biomedical Imaging and Center for Advanced Imaging Innovation and Research (CAI2R), Department of Radiology, New York University School of Medicine, New York, NY, 10016, USA. Honghsi.Lee@nyulangone.org.
Abstract:
MRI provides a unique non-invasive window into the brain, yet is limited to millimeter resolution, orders of magnitude coarser than cell dimensions. Here, we show that diffusion MRI is sensitive to the micrometer-scale variations in axon caliber or pathological beading, by identifying a signature power-law diffusion time-dependence of the along-fiber diffusion coefficient. We observe this signature in human brain white matter and identify its origins by Monte Carlo simulations in realistic substrates from 3-dimensional electron microscopy of mouse corpus callosum. Simulations reveal that the time-dependence originates from axon caliber variation, rather than from mitochondria or axonal undulations. We report a decreased amplitude of time-dependence in multiple sclerosis lesions, illustrating the potential sensitivity of our method to axonal beading in a plethora of neurodegenerative disorders. This specificity to microstructure offers an exciting possibility of bridging across scales to image cellular-level pathology with a clinically feasible MRI technique.
Insights
Diffusion MRI reveals micrometer-scale brain microstructure by detecting axon caliber variations. This technique shows promise for imaging cellular pathology in neurodegenerative disorders using Magnetic Resonance Imaging (MRI).
Area of Science:
- Neuroimaging
- Biophysics
- Cellular Neuroscience
Background:
- Magnetic Resonance Imaging (MRI) offers non-invasive brain visualization but lacks cellular resolution.
- Current MRI techniques are limited to millimeter-scale resolution, significantly coarser than cellular dimensions.
Purpose of the Study:
- To demonstrate diffusion MRI's sensitivity to micrometer-scale axonal variations.
- To identify the origins of diffusion MRI signal time-dependence.
- To explore the potential of this technique for detecting microstructural changes in neurological disorders.
Main Methods:
- Diffusion MRI was used to measure the along-fiber diffusion coefficient over varying diffusion times.
- Monte Carlo simulations were performed using 3D electron microscopy data of mouse corpus callosum.
- The time-dependence signature was analyzed in human white matter and multiple sclerosis lesions.
Main Results:
- A signature power-law diffusion time-dependence of the along-fiber diffusion coefficient was identified.
- Simulations confirmed that this time-dependence originates from axon caliber variations, not other subcellular structures.
- A decreased amplitude of this time-dependence was observed in multiple sclerosis lesions.
Conclusions:
- Diffusion MRI can detect micrometer-scale axon caliber variations, bridging the gap between MRI resolution and cellular structures.
- The findings suggest this technique is sensitive to axonal beading and microstructural pathology in neurodegenerative diseases.
- This MRI method holds potential for early diagnosis and monitoring of neurological conditions affecting white matter microstructure.
