title: N-acetyl-aspartate levels correlate with intra-axonal compartment parameters from diffusion MRI.
abstract: Diffusion MRI combined with biophysical modeling allows for the description of a white matter (WM) fiber bundle in terms of compartment specific white matter tract integrity (WMTI) metrics, which include intra-axonal diffusivity (Daxon), extra-axonal axial diffusivity (De||), extra-axonal radial diffusivity (De┴), axonal water fraction (AWF), and tortuosity (α) of extra-axonal space. Here we derive these parameters from diffusion kurtosis imaging to examine their relationship to concentrations of global WM N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho) and myo-Inositol (mI), as measured with proton MR spectroscopy ((1)H-MRS), in a cohort of 25 patients with mild traumatic brain injury (MTBI). We found statistically significant (p<0.05) positive correlations between NAA and Daxon, AWF, α, and fractional anisotropy; negative correlations between NAA and De,┴ and the overall radial diffusivity (D┴). These correlations were supported by similar findings in regional analysis of the genu and splenium of the corpus callosum. Furthermore, a positive correlation in global WM was noted between Daxon and Cr, as well as a positive correlation between De|| and Cho, and a positive trend between De|| and mI. The specific correlations between NAA, an endogenous probe of the neuronal intracellular space, and WMTI metrics related to the intra-axonal space, combined with the specific correlations of De|| with mI and Cho, both predominantly present extra-axonally, corroborate the overarching assumption of many advanced modeling approaches that diffusion imaging can disentangle between the intra- and extra-axonal compartments in WM fiber bundles. Our findings are also generally consistent with what is known about the pathophysiology of MTBI, which appears to involve both intra-axonal injury (as reflected by a positive trend between NAA and Daxon) as well as axonal shrinkage, demyelination, degeneration, and/or loss (as reflected by correlations between NAA and De┴, AWF, and α).
authors.affiliation: Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, USA; Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY, USA. Electronic address: ejg279@nyu.edu.
authors.forename: Elan J
authors.initials: EJ
authors.lastname: Grossman
authors.affiliation: Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, USA. Electronic address: Ivan.Kirov@nyumc.org.
authors.forename: Ivan I
authors.initials: II
authors.lastname: Kirov
authors.affiliation: Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, USA; Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY, USA. Electronic address: Oded.Gonen@nyumc.org.
authors.forename: Oded
authors.initials: O
authors.lastname: Gonen
authors.affiliation: Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, USA. Electronic address: Dmitry.Novikov@nyumc.org.
authors.forename: Dmitry S
authors.initials: DS
authors.lastname: Novikov
authors.affiliation: College of Arts and Sciences, New York University, New York, NY, USA. Electronic address: md2773@nyu.edu.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Davitz
authors.affiliation: Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, USA. Electronic address: Yvonne.Lui@nyumc.org.
authors.forename: Yvonne W
authors.initials: YW
authors.lastname: Lui
authors.affiliation: Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, USA. Electronic address: Robert.Grossman@nyumc.org.
authors.forename: Robert I
authors.initials: RI
authors.lastname: Grossman
authors.affiliation: Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, USA; Department of Neurology, Radiology, and Neuroscience, Mount Sinai School of Medicine, New York, NY, USA; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa, Genoa, Italy. Electronic address: matilde.inglese@mssm.edu.
authors.forename: Matilde
authors.initials: M
authors.lastname: Inglese
authors.affiliation: Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, USA. Electronic address: Els.Fieremans@nyumc.org.
authors.forename: Els
authors.initials: E
authors.lastname: Fieremans
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D007294:Inositol / Q000378:metabolism; D008297:Male; D008959:Models, Neurological; D066244:Proton Magnetic Resonance Spectroscopy; D066127:White Matter / Q000378:metabolism / Q000473:pathology
chemical_list: D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline
keywords: Diffusion MRI; Diffusion kurtosis imaging; Mild traumatic brain injury; NAA; Proton magnetic resonance spectroscopy; White matter tract integrity