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Microstructural organization of axons in the human corpus callosum quantified by diffusion-weighted magnetic resonance spectroscopy of N-acetylaspartate and post-mortem histology. Brain Struct Funct 2014 Sep;219(5):1773-85



Pubmed ID




Scopus ID

2-s2.0-85027921911   69 Citations


Diffusion-weighted magnetic resonance spectroscopy of brain metabolites offers unique access to compartment-specific microstructural information on neural tissue. Here, we investigated in detail the diffusion characteristics of the neuronal/axonal markers N-acetylaspartateA +A N-acetyl aspartyl glutamate (tNAA) in a small region of the human corpus callosum at 7A T. The diffusion-weighted spectroscopy data were analyzed by fitting to a model in which information about cross-callosal tract orientation within the spectroscopy volume, obtained from diffusion tensor imaging data, was incorporated. We estimated the microscopic misalignment of axons (I? I? A =A 18.6A?A A?A 3.0A?) in excellent agreement with independent histological results (I? I? A =A 18.1A?A A?A 4.6A?) obtained from microscopic analysis of axonal orientations in the body of the corpus callosum from post-mortem human brain slices. We also robustly quantified the diffusion coefficient of tNAA (0.51A A?A 0.06A ??A 10(-3)A mm(2)/s) in axonal cytoplasm, unbiased by the tract curvature. This work supports the notion that microscopic axonal misalignment is a dominant microstructural property in white matter tracts and has a strong impact on the evaluation of tissue microstructure using diffusion information, and should therefore be taken into consideration in the evaluation of white matter microstructure. Additionally, this study enabled robust and unbiased assessment of the cytosolic diffusion coefficient of tNAA, a potential biomarker for axonopathy and neuronal degeneration.

Author List

Ronen I, Budde M, Ercan E, Annese J, Techawiboonwong A, Webb A


Matthew Budde PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aspartic Acid
Corpus Callosum
Diffusion Tensor Imaging
Glutamic Acid
Healthy Volunteers
Image Processing, Computer-Assisted
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Postmortem Changes