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Although previous studies using diffusion tensor imaging (DTI) found smaller values of fractional anisotropy (FA) in the white matter, predominantly in the frontal lobe, of patients with MDD, studies using diffusion kurtosis imaging (DKI) are scarce. Here, we used DKI whole\u2010brain analysis with tract\u2010based spatial statistics (TBSS) to investigate the brain microstructural abnormalities in MDD. Twenty\u2010six patients with MDD and 42 age\u2010 and sex\u2010matched control subjects were enrolled. To investigate the microstructural pathology underlying the observations in DKI, a compartment model analysis was conducted focusing on the corpus callosum. In TBSS, the patients with MDD showed significantly smaller values of FA in the genu and frontal portion of the body of the corpus callosum. The patients also had smaller values of mean kurtosis (MK) and radial kurtosis (RK), but MK and RK abnormalities were distributed more widely compared with FA, predominantly in the frontal lobe but also in the parietal, occipital, and temporal lobes. Within the callosum, the regions with smaller MK and RK were located more posteriorly than the region with smaller FA. Model analysis suggested significantly smaller values of intra\u2010neurite signal fraction in the body of the callosum and greater fiber dispersion in the genu, which were compatible with the existing literature of white matter pathology in MDD. Our results show that DKI is capable of demonstrating microstructural alterations in the brains of patients with MDD that cannot be fully depicted by conventional DTI. Though the issues of model validation and parameter estimation still remain, it is suggested that diffusion MRI combined with a biophysical model is a promising approach for investigation of the pathophysiology of MDD.<\/jats:p>","DOI":"10.1002\/nbm.3938","type":"journal-article","created":{"date-parts":[[2018,5,30]],"date-time":"2018-05-30T09:32:14Z","timestamp":1527672734000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Diffusional kurtosis imaging and white matter microstructure modeling in a clinical study of major depressive disorder"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9151-6739","authenticated-orcid":false,"given":"Kouhei","family":"Kamiya","sequence":"first","affiliation":[{"name":"Department of Radiology The University of Tokyo  Tokyo Japan"},{"name":"Department of Radiology Juntendo University School of Medicine  Tokyo 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