Histological correlation of diffusional kurtosis and white matter modeling metrics in cuprizone-induced corpus callosum demyelination

• Published in: NMR in biomedicine Vol. 27; no. 8; pp. 948 - 957
• Main Authors: Falangola, Maria F., Guilfoyle, David N., Tabesh, Ali, Hui, Edward S., Nie, Xingju, Jensen, Jens H., Gerum, Scott V., Hu, Caixia, LaFrancois, John, Collins, Heather R., Helpern, Joseph A.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-08-2014; Wiley Subscription Services, Inc
• Subjects: Animals; corpus callosum; Corpus Callosum - pathology; Cuprizone; Demyelinating Diseases - chemically induced; Demyelinating Diseases - pathology; demyelination; Diffusion; Diffusion Tensor Imaging; DKI; Male; Mice, Inbred C57BL; mouse; MRI; Statistics, Nonparametric; White Matter - pathology; mouse; cuprizone; diffusion; DKI; MRI; demyelination; corpus callosum
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.3140

The cuprizone mouse model is well established for studying the processes of both demyelination and remyelination in the corpus callosum, and it has been utilized together with diffusion tensor imaging (DTI) to investigate myelin and axonal pathology. Although some underlying morphological mechanisms contributing to the changes in diffusion tensor (DT) metrics have been identified, the understanding of specific associations between histology and diffusion measures remains limited. Diffusional kurtosis imaging (DKI) is an extension of DTI that provides metrics of diffusional non‐Gaussianity, for which an associated white matter modeling (WMM) method has been developed. The main goal of the present study was to quantitatively assess the relationships between diffusion measures and histological measures in the mouse model of cuprizone‐induced corpus callosum demyelination. The diffusional kurtosis (DK) and WMM metrics were found to provide additional information that enhances the sensitivity to detect the morphological heterogeneity in the chronic phase of the disease process in the rostral segment of the corpus callosum. Specifically, in the rostral segment, axonal water fraction (d = 2.6; p < 0.0001), radial kurtosis (d = 2.0; p = 0.001) and mean kurtosis (d = 1.5; p = 0.005) showed the most sensitivity between groups with respect to yielding statistically significant p values and high Cohen's d values. These results demonstrate the ability of DK and WMM metrics to detect white mater changes and inflammatory processes associated with cuprizone‐induced demyelination. They also validate, in part, the application of these new WMM metrics for studying neurological diseases, as well as helping to elucidate their biophysical meaning. Copyright © 2014 John Wiley & Sons, Ltd.
This work investigates diffusional kurtosis and white matter modeling metrics in cuprizone‐induced corpus callosum demyelination. We have found that DK and WMM metrics provide complementary information enhancing the sensitivity to the morphological heterogeneity of the process seen in the rostral segment of the corpus callosum, and can be used as markers for the degree of chronic demyelination in this model.