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Updated: May 17, 2026

In vivo Imaging of Optic Nerve Fiber Integrity by Contrast-Enhanced MRI in Mice
Published on: July 22, 2014
White-matter diffusion fMRI of mouse optic nerve
William M Spees1, Tsen-Hsuan Lin, Sheng-Kwei Song
1Biomedical MR Laboratory, Department of Radiology, Washington University School of Medicine, St Louis, MO 63110, USA. spees@wustl.edu
Abstract:
Non-invasive assessment of white-matter functionality in the nervous system would be a valuable basic neuroscience and clinical diagnostic tool. Using standard MRI techniques, a visual-stimulus-induced 27% decrease in the apparent diffusion coefficient of water perpendicular to the axonal fibers (ADC(perpendicular)) is demonstrated for C57BL/6 mouse optic nerve in vivo. No change in ADC(||) (diffusion parallel to the optic nerve fibers) was observed during visual stimulation. The stimulus-induced changes are completely reversible. A possible vascular contribution was sought by carrying out the ADC(perpendicular) measurements in hypercapnic mice with and without visual stimulus. Similar effects were seen in room-air-breathing and hypercapnic animals. The in vivo stimulus-induced ADC(perpendicular) decreases are roughly similar to literature reports for ex vivo rat optic nerve preparations under conditions of osmotic swelling. The experimental results strongly suggest that osmotic after-effects of nerve impulses through the axonal fibers are responsible for the observed ADC decrease.
Insights
This study shows that visual stimulation causes a reversible decrease in water diffusion perpendicular to nerve fibers in mouse optic nerves using MRI. This finding suggests osmotic changes related to nerve impulses are responsible for altered white matter function.
Area of Science:
- Neuroscience
- Medical Imaging
- Biophysics
Background:
- Non-invasive assessment of white matter functionality is crucial for basic neuroscience and clinical diagnostics.
- Standard MRI techniques offer potential for evaluating nervous system function in vivo.
- Understanding water diffusion changes in white matter can reveal underlying physiological processes.
Purpose of the Study:
- To investigate the effects of visual stimulation on water diffusion in the mouse optic nerve in vivo.
- To determine if observed diffusion changes are related to axonal activity or vascular factors.
- To elucidate the biophysical mechanisms underlying stimulus-induced alterations in white matter diffusion.
Main Methods:
- Utilized standard magnetic resonance imaging (MRI) techniques to measure the apparent diffusion coefficient (ADC) of water.
- Performed in vivo measurements on C57BL/6 mouse optic nerves.
- Assessed diffusion parallel (ADC(||)) and perpendicular (ADC(perpendicular)) to axonal fibers during visual stimulation, including hypercapnic conditions to rule out vascular contributions.
Main Results:
- Demonstrated a significant 27% decrease in ADC(perpendicular) during visual stimulation, indicating altered water diffusion perpendicular to nerve fibers.
- Observed no significant change in ADC(||) (parallel to fibers) during visual stimulation.
- Confirmed that the stimulus-induced ADC(perpendicular) decrease is completely reversible and occurs similarly in normocapnic and hypercapnic conditions, suggesting a non-vascular origin.
Conclusions:
- The results strongly suggest that osmotic after-effects of nerve impulses, leading to axonal swelling, are the primary cause of the observed decrease in ADC(perpendicular).
- This study provides evidence for a novel non-invasive method to assess white matter functionality based on stimulus-induced diffusion changes.
- The findings have implications for understanding nerve impulse dynamics and developing new diagnostic tools for neurological disorders.

