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Quantification of normal-appearing white matter tract integrity in multiple sclerosis: a diffusion kurtosis imaging study

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Abstract

Our aim was to characterize the nature and extent of pathological changes in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS) using novel diffusion kurtosis imaging-derived white matter tract integrity (WMTI) metrics and to investigate the association between these WMTI metrics and clinical parameters. Thirty-two patients with relapsing–remitting MS and 19 age- and gender-matched healthy controls underwent MRI and neurological examination. Maps of mean diffusivity, fractional anisotropy and WMTI metrics (intra-axonal diffusivity, axonal water fraction, tortuosity and axial and radial extra-axonal diffusivity) were created. Tract-based spatial statistics analysis was performed to assess for differences in the NAWM between patients and controls. A region of interest analysis of the corpus callosum was also performed to assess for group differences and to evaluate correlations between WMTI metrics and measures of disease severity. Mean diffusivity and radial extra-axonal diffusivity were significantly increased while fractional anisotropy, axonal water fraction, intra-axonal diffusivity and tortuosity were decreased in MS patients compared with controls (p values ranging from <0.001 to <0.05). Axonal water fraction in the corpus callosum was significantly associated with the expanded disability status scale score (ρ = −0.39, p = 0.035). With the exception of the axial extra-axonal diffusivity, all metrics were correlated with the symbol digits modality test score (p values ranging from 0.001 to <0.05). WMTI metrics are thus sensitive to changes in the NAWM of MS patients and might provide a more pathologically specific, clinically meaningful and practical complement to standard diffusion tensor imaging-derived metrics.

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Acknowledgments

This study was supported in part by National Multiple Sclerosis Society (NMSS RG 5120A3/1), the Noto Foundation to Inglese M, and by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award number R01NS088040 to Fieremans E.

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Correspondence to Matilde Inglese.

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Conflict of interest

Ivan de Kouchkovsky has nothing to disclose. Dr. Lazar Fleysher has nothing to disclose. Dr. Els Fieremans has received research grants from NIH, ADDF and Avid Radiopharmaceuticals. Dr. Robert I. Grossman has nothing to disclose. Dr. Matilde Inglese has received research grants from NIH, NMSS, Novartis Pharmaceuticals Corp., Teva Neuroscience.

Ethical standards

This study was approved by the Institutional Board of Research Associates at the NYU School of Medicine and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from all subjects prior to their inclusion in this study.

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de Kouchkovsky, I., Fieremans, E., Fleysher, L. et al. Quantification of normal-appearing white matter tract integrity in multiple sclerosis: a diffusion kurtosis imaging study. J Neurol 263, 1146–1155 (2016). https://doi.org/10.1007/s00415-016-8118-z

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  • DOI: https://doi.org/10.1007/s00415-016-8118-z

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