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. 2025 Nov;62(5):1496-1506.
doi: 10.1002/jmri.70023. Epub 2025 Jun 29.

Perivascular Space Burden in Children With Autism Spectrum Disorder Correlates With Neurodevelopmental Severity

Giulia Frigerio  1 , Gloria Rizzato  1 , Denis Peruzzo  2 , Tommaso Ciceri  2   3 , Elisa Mani  4 , Fabiola Lanteri  4 , Valentina Mariani  4 , Massimo Molteni  4 , Nivedita Agarwal  1
Affiliations

Perivascular Space Burden in Children With Autism Spectrum Disorder Correlates With Neurodevelopmental Severity

Giulia Frigerio et al. J Magn Reson Imaging. 2025 Nov.

Abstract

Background: Cerebral perivascular spaces (PVS) are involved in cerebrospinal fluid (CSF) circulation and clearance of metabolic waste in adult humans. A high number of PVS has been reported in autism spectrum disorder (ASD) but its relationship with CSF and disease severity is unclear.

Purpose: To quantify PVS in children with ASD through MRI.

Study type: Retrospective.

Population: Sixty six children with ASD (mean age: 4.7 ± 1.5 years; males/females: 59/7).

Field strength/sequence: 3T, 3D T1-weighted GRE and 3D T2-weighted turbo spin echo sequences.

Assessment: PVS were segmented using a weakly supervised PVS algorithm. PVS count, white matter-perivascular spaces (WM-PVStot) and normalized volume (WM-PVSvoln) were analyzed in the entire white matter. Six regions: frontal, parietal, limbic, occipital, temporal, and deep WM (WM-PVSsr). WM, GM, CSF, and extra-axial CSF (eaCSF) volumes were also calculated. Autism Diagnostic Observation Schedule, Wechsler Intelligence Scale, and Griffiths Mental Developmental scales were used to assess clinical severity and developmental quotient (DQ).

Statistical tests: Kendall correlation analysis (continuous variables) and Friedman (categorical variables) tests were used to compare medians of PVS variables across different WM regions. Post hoc pairwise comparisons with Wilcoxon tests were used to evaluate distributions of PVS in WM regions. Generalized linear models were employed to assess DQ, clinical severity, age, and eaCSF volume in relation to PVS variables. A p-value < 0.05 indicated statistical significance.

Results: Severe DQ (β = 0.0089), mild form of autism (β = -0.0174), and larger eaCSF (β = 0.0082) volume was significantly associated with greater WM-PVStot count. WM-PVSvoln was predominantly affected by normalized eaCSF volume (eaCSFvoln) (β = 0.0242; adjusted for WM volumes). The percentage of WM-PVSsr was higher in the frontal areas (32%) and was lowest in the temporal regions (11%).

Data conclusion: PVS count and volume in ASD are associated with eaCSFvoln. PVS count is related to clinical severity and DQ. PVS count was higher in frontal regions and lower in temporal regions.

Evidence level: 4.

Technical efficacy: Stage 3.

Keywords: CSF drainage; autism spectrum disorder; deep learning; neurodevelopment; pediatric; perivascular spaces.

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Figures

FIGURE 1
FIGURE 1
Overview of the adopted workflow. Workflow used for analyzing 3D‐T1w and 3D‐T2w DICOM files. Initially, the images underwent preprocessing via the HCP preprocessing pipeline. Then, WM parcellation was utilized to generate a mask of WM regions of interest. Additionally, pre‐processed T1w and T2w images were used to generate Enhanced Perivascular space Contrast (EPC) images, which served as input for the WPSS algorithm for PVS segmentation.
FIGURE 2
FIGURE 2
T1w image and WM regions of interest. T1w image (left); WM parcellation masks were merged to create six WM regions of interest (right). These include deep WM, frontal, limbic, occipital, parietal, and temporal lobes.
FIGURE 3
FIGURE 3
PVS count distribution in WM regions. The percentage of PVS is significantly higher in the frontal region and lower in the temporal region. X: Outliers; ***: Significant difference with p < 0.0001 (Bonferroni corrected). WM: white matter, PVS: perivascular spaces.
FIGURE 4
FIGURE 4
PVS VF in WM regions. The percentage of PVS VF is higher in the deep WM region (showing no statistically significant difference with respect to the parietal region) and lower in the temporal region. p‐values are Bonferroni corrected. X: Outliers; ***: Significant difference with p < 0.0001. WM: white matter, PVS: perivascular spaces, VF: volume fraction.
See this image and copyright information in PMC

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