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Updated: Dec 23, 2025
Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis ALS
Published on: March 17, 2012
Multicomponent diffusion analysis reveals microstructural alterations in spinal cord of a mouse model of amyotrophic
Jin Gao1,2, Mingchen Jiang3, Richard L Magin4
1Department of Electrical and Computer Engineering, University of Illinois at Chicago, Chicago, IL, United States of America.
Abstract:
The microstructure changes associated with degeneration of spinal axons in amyotrophic lateral sclerosis (ALS) may be reflected in altered water diffusion properties, potentially detectable with diffusion-weighted (DW) MRI. Prior work revealed the classical mono-exponential model fails to precisely depict decay in DW signal at high b-values. In this study, we aim to investigate signal decay behaviors at ultra-high b-values for non-invasive assessment of spinal cord alterations in the transgenic SOD1G93A mouse model of ALS. A multiexponential diffusion analysis using regularized non-negative least squares (rNNLS) algorithm was applied to a series of thirty DW MR images with b-values ranging from 0 to 858,022 s/mm2 on ex vivo spinal cords of transgenic SOD1G93A and age-matched control mice. We compared the distributions of measured diffusion coefficient fractions between the groups. The measured diffusion weighted signals in log-scale showed non-linear decay behaviors with increased b-values. Faster signal decays were observed with diffusion gradients applied parallel to the long axis of the spinal cord compared to when oriented in the transverse direction. Multiexponential analysis at the lumbar level in the spinal cord identified ten subintervals. A significant decrease of diffusion coefficient fractions was found in the ranges of [1.63×10-8,3.70×10-6] mm2/s (P = 0.0002) and of [6.01×10-6,4.20×10-5] mm2/s (P = 0.0388) in SOD1G93A mice. Anisotropic diffusion signals persisted at ultra-high b-value DWIs of the mouse spinal cord and multiexponential diffusion analysis offers the potential to evaluate microstructural alterations of ALS-affected spinal cord non-invasively.
Insights
Diffusion-weighted MRI reveals microstructural changes in amyotrophic lateral sclerosis (ALS) spinal cords. Multiexponential analysis at ultra-high b-values detects significant diffusion alterations in SOD1G93A mice, offering potential for non-invasive assessment.
Area of Science:
- Neuroimaging
- Biophysics
- Medical Physics
Background:
- Spinal axon degeneration in amyotrophic lateral sclerosis (ALS) may alter water diffusion properties.
- Classical mono-exponential diffusion-weighted (DW) MRI models struggle to accurately represent DW signal decay at high b-values.
- Investigating ultra-high b-value signal decay is crucial for non-invasive spinal cord assessment in ALS.
Purpose of the Study:
- To explore signal decay behaviors at ultra-high b-values in the context of ALS.
- To assess spinal cord microstructural alterations in a transgenic SOD1G93A mouse model of ALS using advanced DW MRI techniques.
- To compare diffusion properties between ALS model mice and age-matched controls.
Main Methods:
- Ex vivo spinal cords from SOD1G93A and control mice underwent DW MRI with b-values up to 858,022 s/mm2.
- A multiexponential diffusion analysis employing the regularized non-negative least squares (rNNLS) algorithm was utilized.
- Diffusion coefficient fractions were quantified and compared between the groups across ten identified subintervals at the lumbar level.
Main Results:
- DW signal decay exhibited non-linear behavior with increasing b-values, showing faster decay parallel to the spinal cord's long axis.
- Multiexponential analysis revealed significant decreases in specific diffusion coefficient fractions in SOD1G93A mice within ranges of [1.63×10-8,3.70×10-6] mm2/s (P = 0.0002) and [6.01×10-6,4.20×10-5] mm2/s (P = 0.0388).
- Anisotropic diffusion signals were consistently observed even at ultra-high b-values.
Conclusions:
- Multiexponential diffusion analysis at ultra-high b-values can detect microstructural alterations in the ALS-affected spinal cord.
- This advanced DW MRI approach holds promise for the non-invasive evaluation of spinal cord pathology in ALS.
- Observed diffusion changes correlate with the neurodegenerative process in the SOD1G93A mouse model.
