White Matter Perivascular Space Burden in Children With Autism Spectrum Disorder and Typically Developing Controls: An Automated Quantitative MRI Study.

BACKGROUND: Perivascular spaces (PVS) are compartments involved in brain waste clearance. PVS are commonly observed in typically developing (TD) children; however, their burden in autism spectrum disorder (ASD) remains unclear. PURPOSE: To investigate whether quantitative white matter (WM) PVS burden differs between children with ASD and TD controls using automatic segmentation. STUDY TYPE: Observational. POPULATION: Ninety-eight children with ASD (age range: 2-8 years; mean age 4.8 ± 1.5 years; 78M/20F) and 38 TD children (age range: 2-8 years; mean age 5.5 ± 0.9 years; 23M/15F). FIELD STRENGTH/SEQUENCE: 3T; 3D T1-weighted ultrafast gradient-echo and 3D T2-weighted turbo spin-echo sequences. ASSESSMENT: Human Connectome Project pipeline was used to generate enhanced perivascular contrast (EPC) images. The Weakly Supervised Perivascular Spaces Segmentation algorithm was applied to EPC to segment PVS. PVS volume (WM-PVSv) and count (WM-PVSc) were quantified in total WM and six subregions (frontal, parietal, temporal, occipital, limbic, and deepWM). STATISTICAL TESTS: Welch's t-test, chi-square test, and ANCOVA for group differences; Spearman's rank correlation for age, structural brain volumes, and PVS metrics exploratory correlations; multivariable linear regression for global PVS metrics, and linear mixed-effects models for regional analyses, adjusted for age, sex, WM, and extra-axial cerebrospinal fluid volumes. RESULTS: In the adjusted models, no significant differences between ASD and TD were observed, as the diagnostic group was not independently associated with either WM-PVSv (ASD: 2.3 ± 1.2 cm3; TD: 2.0 ± 0.9 cm3; p = 0.228) or WM-PVSc (ASD: 832 ± 298; TD: 754 ± 260; p = 0.121), whereas WM volume was significantly associated with both metrics (β = 0.012 mm3 for WM-PVSv; β = 0.004 mm3 for WM-PVSc). In both ASD and TD, frontal WM exhibited the highest WM-PVScn (ASD: 37.0% ± 4.9%; TD: 28.9% ± 6.6%), whereas deep WM showed the highest WM-PVSvf (ASD: 0.010 ± 0.004; TD: 0.010 ± 0.003). DATA CONCLUSION: PVS measures appear to reflect inter-individual variability associated with WM volume. No evidence was found for WM-PVS burden as an early-childhood ASD biomarker. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.