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. 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. 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%). The absence of histopathological confirmation limit the interpretation of our findings. 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.

中文翻译：

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神经突方向分散和密度成像揭示了自闭症成人的白质微结构改变

表明自闭症行为异常与白质 (WM) 微结构改变之间关联的证据正在增加。扩散张量成像 (DTI) 广泛用于推断组织微观结构。然而，由于缺乏特异性，报道的自闭症 DTI 测量差异的潜在病理学仍然知之甚少。在这里，我们应用神经突定向分散和密度成像 (NODDI) 来量化和定义与成人自闭症相关的 WM 微观结构变化的更具体原因。比较了 NODDI（神经突密度指数 [NDI]、取向分散指数和各向同性体积分数 [ISOVF]）和 DTI（分数各向异性 [FA]、平均扩散率 [MD]、轴向扩散率和径向扩散率 [RD]）测量值自闭症（N = 26；19 名男性和 7 名女性；32.93 ± 9. 24 岁）和年龄和性别匹配的典型发育（TD；N = 25；17 名男性和 8 名女性；34.43 ± 9.02 岁）组使用基于区域的空间统计和感兴趣区域分析。还进行了使用留一法交叉验证 (LDA-LOOCV) 的线性判别分析，以评估自闭症和 TD 扩散测量的判别能力。与 TD 组相比，自闭症组的 NDI 显着降低和 ISOVF 升高，分别表明神经突密度降低和细胞外游离水增加，主要在连合和长程联合束中，但具有明显的优势侧。与之前的报道一致，与 TD 组相比，自闭症组的 FA 较低，MD 和 RD 较高。尤其，LDA-LOOCV 表明，与 FA、MD 和 RD 相比，NDI 和 ISOVF 具有相对更高的准确度（82%）和特异性（NDI，84%；ISOVF，88%）（准确度，67-73%；特异性，68 –80%）。缺乏组织病理学证实限制了对我们研究结果的解释。我们的研究结果表明，NODDI 测量可能可用作成像生物标志物来诊断成人自闭症并评估其行为特征。此外，NODDI 允许解释先前关于自闭症患者 WM 扩散张量指标变化的发现。我们的研究结果表明，NODDI 测量可能可用作成像生物标志物来诊断成人自闭症并评估其行为特征。此外，NODDI 允许解释先前关于自闭症患者 WM 扩散张量指标变化的发现。我们的研究结果表明，NODDI 测量可能可用作成像生物标志物来诊断成人自闭症并评估其行为特征。此外，NODDI 允许解释先前关于自闭症患者 WM 扩散张量指标变化的发现。