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Updated: Jul 13, 2026
Probing the Brain in Autism Using fMRI and Diffusion Tensor Imaging
Published on: September 12, 2011
White Matter Perivascular Space Burden in Children With Autism Spectrum Disorder and Typically Developing Controls:
Chiara Girardi1, Denis Peruzzo2, Francesca Castellotti1
1Neuroradiology Unit, Scientific Institute IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy.
Insights
Perivascular spaces (PVS) volume and count in white matter did not differ between children with autism spectrum disorder (ASD) and typically developing (TD) controls. PVS burden is not an early-childhood biomarker for ASD.
Area of Science:
- Neuroimaging
- Developmental Neuroscience
- Biomarker Discovery
Background:
- Perivascular spaces (PVS) are crucial for brain waste clearance in typically developing (TD) children.
- The role and burden of PVS in children with autism spectrum disorder (ASD) remain largely uncharacterized.
Purpose of the Study:
- To quantitatively assess differences in white matter (WM) PVS burden between children with ASD and TD controls.
- To investigate the potential of WM PVS as a biomarker for early childhood ASD using automatic segmentation techniques.
Main Methods:
- Utilized a Human Connectome Project pipeline for enhanced perivascular contrast (EPC) imaging.
- Applied a Weakly Supervised Perivascular Spaces Segmentation algorithm to quantify WM PVS volume (WM-PVSv) and count (WM-PVSc) in 98 children with ASD and 38 TD children (ages 2-8).
- Employed statistical analyses including Welch's t-test, chi-square, ANCOVA, and mixed-effects models, adjusting for age, sex, and other relevant brain volumes.
Main Results:
- No significant differences in WM-PVSv or WM-PVSc were found between the ASD and TD groups after adjusting for covariates (p > 0.12).
- White matter volume was significantly associated with both WM-PVSv and WM-PVSc.
- Frontal WM showed the highest normalized PVS count, while deep WM exhibited the highest PVS volume fraction in both groups.
Conclusions:
- WM PVS measures correlate with individual white matter volume rather than diagnostic group.
- Current findings do not support WM-PVS burden as a reliable biomarker for early childhood ASD.
- Further research may explore PVS in different developmental stages or in relation to other ASD-related neurobiological factors.
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.
