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Magnetic resonance microimaging of intraaxonal water diffusion in live excised lamprey spinal cord
Masaya Takahashi1, David B Hackney, Guixin Zhang
1Departments of Radiology and Neurology, University of Pennsylvania Medical Center, 1 Silverstein, 3400 Spruce Street, Philadelphia, PA 19104 USA. mtakahas@caregroup.harvard.edu
Abstract:
Anisotropy of water diffusion in axon tracts, as determined by diffusion-weighted MRI, has been assumed to reflect the restriction of water diffusion across axon membranes. Reduction in this anisotropy has been interpreted as degeneration of axons. These interpretations are based primarily on a priori reasoning that has had little empirical validation. We used the experimental advantages of the sea lamprey spinal cord, which contains several very large axons, to determine whether intraaxonal diffusion is isotropic and whether anisotropy is attributable to restriction of water mobility by axon surface membranes. Through the application of magnetic resonance microimaging, we were able to measure the purely intraaxonal diffusion characteristics of the giant reticulospinal axons (20-40 microm in diameter). The intraaxonal apparent diffusion coefficients of water parallel (longitudinal ADC, l-ADC) and perpendicular (transverse ADC, t-ADC) to the long axis were 0.98 +/- 0.06 (10(-3) mm2 sec) and 0.97 +/- 0.11 (10(-3) mm2 sec), respectively. In white matter regions that included multiple axons, l-ADCs were almost identical regardless of axon density in the sampled axon tract. By comparison, t-ADCs were reduced and varied inversely with the number of axons (and thus axolemmas) in a fixed cross-sectional area. Thus, diffusion was found to be isotropic when measured entirely within a single axon and anisotropic when measured in regions that included multiple axons. These findings support the hypothesis that the cell membrane is the primary source of diffusion anisotropy in fiber tracts of the central nervous system.
Insights
Diffusion MRI anisotropy in axon tracts is primarily caused by cell membranes, not axon degeneration. Water diffusion within a single axon is isotropic, but multiple axons create anisotropy.
Area of Science:
- Neuroscience
- Biophysics
- Medical Imaging
Background:
- Diffusion-weighted MRI (DW-MRI) measures water diffusion in the brain.
- Anisotropy in axon tracts is often interpreted as axon degeneration.
- This interpretation lacks robust empirical validation.
Purpose of the Study:
- To investigate whether intra-axonal water diffusion is isotropic.
- To determine if axon surface membranes restrict water mobility, causing diffusion anisotropy.
- To empirically validate the interpretation of DW-MRI anisotropy in axon tracts.
Main Methods:
- Utilized sea lamprey spinal cords with large axons for experimental advantages.
- Employed magnetic resonance microimaging to measure intra-axonal diffusion.
- Quantified apparent diffusion coefficients (ADCs) parallel (l-ADC) and perpendicular (t-ADC) to axon long axis.
Main Results:
- Intra-axonal diffusion within single giant axons was found to be isotropic (l-ADC ≈ t-ADC).
- In white matter regions with multiple axons, transverse ADCs (t-ADCs) were reduced.
- t-ADCs varied inversely with axon density, indicating membrane restriction.
Conclusions:
- Water diffusion is isotropic within individual axons.
- The cell membrane (axolemma) is the primary determinant of diffusion anisotropy in central nervous system fiber tracts.
- This finding challenges previous interpretations of DW-MRI anisotropy as solely indicative of axon degeneration.