Abnormal glymphatic system function in children with autism spectrum disorder: a diffusion kurtosis imaging study

The glymphatic system, responsible for clearing metabolic waste in the brain, may be impaired in neurodevelopmental and neurodegenerative disorders. This study aimed to assess glymphatic system function in children with autism spectrum disorder (ASD) and explore its relationship with the severity of core ASD features and developmental level. This study employed diffusion kurtosis imaging analysis along the perivascular space (DKI-ALPS) to assess glymphatic system function in children with ASD, dividing the ASD group into mild and severe subgroups to compare intergroup differences and differences with the typically developing (TD) group. Correlations between DKI-ALPS indices and clinical assessments, including the Childhood Autism Rating Scale (CARS) and Griffiths Developmental Scales (Chinese version, GDS-C), were also analyzed. The DKI-ALPS and diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) indices were calculated separately for the left and right hemispheres, with the average defined as their arithmetic mean. The DKI-ALPS index was further compared with the DTI-ALPS index, and its directional kurtosis components were analyzed to investigate underlying microstructural differences. DKI-ALPS indices were significantly lower in children with ASD than in TD children, with lower values in the severe subgroup than in the mild subgroup. The right and average DKI-ALPS indices were negatively correlated with CARS scores, while the right index was positively correlated with Hearing-Language and Eye-Hand Coordination scores. DKI-ALPS showed greater sensitivity than DTI-ALPS in detecting group differences and clinical associations. Directional analysis revealed significant alterations in y-axis projection and z-axis association kurtosis metrics.

This study provides preliminary evidence of glymphatic dysfunction in children with ASD, which is associated with the severity of core ASD features and developmental level. These findings offer novel imaging-based insights into ASD neurobiology.

• Glymphatic system dysfunction has been implicated in neurodegenerative disorders. Its role in autism spectrum disorder (ASD), particularly in children, remains underexplored. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) has limited sensitivity in detecting glymphatic changes.

• This study is the first to apply diffusion kurtosis imaging analysis along the perivascular space (DKI-ALPS) in children with ASD, revealing significant glymphatic impairment correlated with the severity of core ASD features and developmental levels. DKI-ALPS demonstrated higher sensitivity than DTI-ALPS.