Perivascular space burden in children with autism spectrum disorder correlates with neurodevelopmental severity

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.

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Identifiers

ORCID for Nivedita Agarwal: orcid.org/0000-0002-1387-9566

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