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. 2026 Jan 17.
doi: 10.1007/s00234-025-03899-1. Online ahead of print.

Disrupted age-related glymphatic patterns in children with deep gray matter hypoxic-ischemic encephalopathy: a diffusion tensor imaging analysis along the perivascular space study

Alex Mun-Ching Wong  1   2 , Tiing-Yee Siow  3   4 , Ming-Chou Chiang  4   5 , Jainn-Jim Lin  4   6 , Shin-Nan Lin  3   4 , Eddy Chien-Yuan Lin  7 , Cheng-Hong Toh  8   9
Affiliations

Disrupted age-related glymphatic patterns in children with deep gray matter hypoxic-ischemic encephalopathy: a diffusion tensor imaging analysis along the perivascular space study

Alex Mun-Ching Wong et al. Neuroradiology. .

Abstract

Purpose: Hypoxic-ischemic encephalopathy (HIE) remains a major cause of pediatric morbidity, with deep gray matter injury reflecting a severe pattern. The glymphatic system, a brain-wide perivascular network facilitating cerebrospinal and interstitial fluid exchange, may be vulnerable to disruption after HIE. We assessed glymphatic function in children with HIE-induced deep gray matter injury using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) and examined age-related patterns in glymphatic function.

Methods: DTI-ALPS analysis was retrospectively studied in 38 normative controls (mean ± SD, 26.94 ± 34.03 months) and 25 patients with HIE and deep gray matter injury (20.55 ± 32.49 months). Bilateral ALPS indices were calculated and correlated with age and pediatric cerebral performance category scale (PCPC) scores. Due to non-normal distributions, Spearman correlations and generalized linear models (Gamma distribution, log link) adjusted for age were used for group comparisons. Age-adjusted associations were evaluated using residual-based analyses.

Results: ALPS indices were significantly reduced in HIE patients compared to controls after age adjustment (Left: adjusted difference = 0.248, p < 0.001; Right: adjusted difference = 0.228, p < 0.001). In controls, ALPS indices positively correlated with age (Left: ρ = 0.730, p < 0.001; Right: ρ = 0.615, p < 0.001). After controlling for age using residual-based analyses, ALPS indices in patients negatively correlated with PCPC scores (Left: ρ = -0.468, p = 0.018; Right: ρ = -0.458, p = 0.021).

Conclusion: HIE disrupts normal age-related glymphatic patterns, and glymphatic dysfunction is associated with adverse functional outcomes.

Keywords: Age-related glymphatic patterns; Deep gray matter; Diffusion tensor imaging analysis along the perivascular space; Hypoxic-ischemic encephalopathy.

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Conflict of interest statement

Declarations. Ethical approval and consent to participate: Approval of our study was obtained from the institutional review board of Chang Gung Medical Foundation and informed consent from the participants was waived. All research procedures adhered to the tenets of the Declaration of Helsinki. Use of artificial intelligence: During the preparation of this manuscript, the authors utilized Claude Sonnet 3.7 and ChatGPT-4o to improve writing style and grammatical accuracy. The AI tools were not used to generate original scientific content, analyze data, or contribute to research findings. Following its use, the authors thoroughly reviewed, edited, and verified the content to ensure accuracy and integrity, and take full responsibility for its content. Competing interests: The authors declare no competing interests.

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