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Background Evidences suggesting the association between behavioral anomalies in autism and white matter (WM) microstructural alterations are increasing. Diffusion tensor imaging (DTI) is widely used to infer tissue microstructure. However, due to its lack of specificity, the underlying pathology of reported differences in DTI measures in autism remains poorly understood. Herein, we applied neurite orientation dispersion and density imaging (NODDI) to quantify and define more specific causes of WM microstructural changes associated with autism in adults. Methods NODDI (neurite density index [NDI], orientation dispersion index, and isotropic volume fraction [ISOVF]) and DTI (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity, and radial diffusivity [RD]) measures were compared between autism (N = 26; 19 males and 7 females; 32.93 ± 9.24 years old) and age- and sex-matched typically developing (TD; N = 25; 17 males and 8 females; 34.43 ± 9.02 years old) groups using tract-based spatial statistics and region-of-interest analyses. Linear discriminant analysis using leave-one-out cross-validation (LDA-LOOCV) was also performed to assess the discriminative power of diffusion measures in autism and TD. Results Significantly lower NDI and higher ISOVF, suggestive of decreased neurite density and increased extracellular free-water, respectively, were demonstrated in the autism group compared with the TD group, mainly in commissural and long-range association tracts, but with distinct predominant sides. Consistent with previous reports, the autism group showed lower FA and higher MD and RD when compared with TD group. Notably, LDA-LOOCV suggests that NDI and ISOVF have relatively higher accuracy (82%) and specificity (NDI, 84%; ISOVF, 88%) compared with that of FA, MD, and RD (accuracy, 67–73%; specificity, 68–80%). Limitations The absence of histopathological confirmation limit the interpretation of our findings. Conclusions Our results suggest that NODDI measures might be useful as imaging biomarkers to diagnose autism in adults and assess its behavioral characteristics. Furthermore, NODDI allows interpretation of previous findings on changes in WM diffusion tensor metrics in individuals with autism.

Background and Purpose ―Microstructural damage in the brain induced by chronic ischemia is suggested to play a pivotal role in the neurocognitive dysfunction of adults with Moyamoya disease (MMD). We investigated specific changes in the brain microstructure and their correlations with neurocognitive dysfunction in patients with MMD using a multishell diffusion magnetic resonance imaging technique called neurite orientation dispersion and density imaging. Methods— We evaluated 26 patients with MMD (16–63 years old, 20 females) and 20 age- and sex-matched normal volunteers using neurite orientation dispersion and density imaging and neuropsychological batteries. Neurite orientation dispersion and density imaging calculates 2 parameters: the intracellular volume fraction (Vic), which reflects the axon density in the white matter and dendrite density in the cortex, and the orientation dispersion index (OD), which reflects the network complexity. The microstructural damage and its correlation with neurocognitive performance were evaluated by performing a whole-brain analysis using SPM12 and correlation analysis with regional values. Results— Patients with MMD had significantly lower Vic in the white matter and a lower OD mainly in the cortex than those of the controls ( P <0.001, family-wise error corrected). Of all neuropsychological scores, Processing Speed Index (PS) exhibited the strongest correlation with Vic in the white matter ( P <0.001, family-wise error corrected). The Vic and OD values for regions with group differences, including both temporoparietal and frontal areas, correlated with neurocognitive performance (absolute r=0.37–0.64; P <0.01). Conclusions— Chronic ischemia in MMD may decrease the axon density in the white matter and dendrite density in the cortex (Vic) and simplify network complexity (OD), leading to neurocognitive dysfunction. Processing Speed Index may be the most sensitive index used to evaluate the ischemic burden, and the posterior part of the brain may play an important role in neurocognitive function. Clinical Trial Registration— URL: http://www.umin.ac.jp/ctr/ . Unique identifier: UMIN000023082.

Neurocognitive and psychiatric disorders have significant consequences for quality of life in patients with Parkinson's disease (PD). In the current study, we evaluated microstructural white matter (WM) alterations associated with neurocognitive and psychiatric disorders in PD using neurite orientation dispersion and density imaging (NODDI) and linked independent component analysis (LICA). The indices of NODDI were compared between 20 and 19 patients with PD with and without neurocognitive and psychiatric disorders, respectively, and 25 healthy controls using tract‐based spatial statistics and tract‐of‐interest analyses. LICA was applied to model inter‐subject variability across measures. A widespread reduction in axonal density (indexed by intracellular volume fraction [ICVF]) was demonstrated in PD patients with and without neurocognitive and psychiatric disorders, as compared with healthy controls. Compared with patients without neurocognitive and psychiatric disorders, patients with neurocognitive and psychiatric disorders exhibited more extensive (posterior predominant) decreases in axonal density. Using LICA, ICVF demonstrated the highest contribution (59% weight) to the main effects of diagnosis that reflected widespread decreases in axonal density. These findings suggest that axonal loss is a major factor underlying WM pathology related to neurocognitive and psychiatric disorders in PD, whereas patients with neurocognitive and psychiatric disorders had broader axonal pathology, as compared with those without. LICA suggested that the ICVF can be used as a useful biomarker of microstructural changes in the WM related to neurocognitive and psychiatric disorders in PD.