Advanced Quantitative Microstructure Imaging in Autism: A Review of Methodology, Group Differences, and Associations With Developmental Outcomes.

Emerging evidence highlights widespread alterations in white matter microstructure in autism. Advances in magnetic resonance imaging (MRI) have enabled more precise examinations of these microstructural changes, leading to increased use of quantitative MRI techniques in autism research. This review summarizes the current landscape of these techniques, focusing on methodology, group differences, developmental associations, and regional variations. Following PRISMA guidelines, 34 studies published between 2006 and 2024 that employed advanced MRI techniques were reviewed. These included diffusion MRI signal representations (diffusion kurtosis imaging [DKI] and constrained spherical deconvolution [CSD]) and biophysical models (neurite orientation dispersion and density imaging [NODDI] and white matter tract integrity [WMTI]), as well as relaxometry and magnetization transfer imaging (MTI). CSD and NODDI were the most frequently used, while MTI was the least utilized, with notable variations in acquisition parameters and processing methods across the techniques. Findings suggest relatively consistent lower values of fixel-based analysis measures (CSD) and neurite density index (NODDI) across major white matter regions, while findings from DKI, WMTI, and relaxometry varied. Measures from these techniques were associated with various developmental outcomes, including cognitive, emotional, and social behaviors. Limitations and implications are also discussed.