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Brain Advance Access originally published online on April 29, 2009
Brain 2009 132(5):1210-1220; doi:10.1093/brain/awp042
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© The Author (2009). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

In vivo measurement of axon diameter distribution in the corpus callosum of rat brain

Daniel Barazany1, Peter J. Basser2 and Yaniv Assaf1

1 Department of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel 2 Section of Tissue Biophysics and Biomimetics, The National Institute of Child Health and Human Development, The National Institutes of Health, Bethesda, MD, USA

Correspondence to: Yaniv Assaf, Department of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel E-mail: asafyan{at}zahav.net.il

Here, we present the first in vivo non-invasive measurement of the axon diameter distribution in the rat corpus callosum. Previously, this measurement was only possible using invasive histological methods. The axon diameter, along with other physical properties, such as the intra-axonal resistance, membrane resistance and capacitance etc. helps determine many important functional properties of nerves, such as their conduction velocity. In this work, we provide a novel magnetic resonance imaging method called AxCaliber, which can resolve the distinct signatures of trapped water molecules diffusing within axons as well as water molecules diffusing freely within the extra-axonal space. Using a series of diffusion weighted magnetic resonance imaging brain scans, we can reliably infer both the distribution of axon diameters and the volume fraction of these axons within each white matter voxel. We were able to verify the known microstructural variation along the corpus callosum of the rat from the anterior (genu) to posterior (splenium) regions. AxCaliber yields a narrow distribution centered ~1 µm in the genu and splenium and much broader distributions centered ~3 µm in the body of the corpus callosum. The axon diameter distribution found by AxCaliber is generally broader than those usually obtained by histology. One factor contributing to this difference is the significant tissue shrinkage that results from histological preparation. To that end, AxCaliber might provide a better estimate of the in vivo morphology of white matter. Being a magnetic resonance imaging based methodology, AxCaliber has the potential to be used in human scanners for morphological studies of white matter in normal and abnormal development, and white matter related diseases.

Key Words: MRI; brain; corpus callosum; axon diameter distribution; diffusion

Abbreviations: ADC, apparent diffusion coefficient; ADD, axon diameter distribution; CHARMED, Composite Hindered and Restricted Model of Diffusion; DTI, diffusion tensor imaging; DWI, diffusion weighted imaging; EPI, echo planar imaging; FA, fractional anisotropy

Received August 18, 2008. Revised January 29, 2009. Accepted February 2, 2009.


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