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Objective <p>The glymphatic system is vital for metabolic waste clearance, and its impairment has been implicated in various neurological disorders. We investigated the relationship between structural perivascular space (PVS) burden and the DTI-ALPS index (A non-invasive proxy reflecting perivascular diffusion characteristics) in healthy young adults, to evaluate their utility as complementary markers of subclinical perivascular alterations.</p> Methods <p>Twenty-four healthy volunteers (mean age: 32.3 ± 6.2 years) underwent 3T MRI including 64-direction diffusion tensor imaging. The DTI-ALPS index was calculated via an automated ROI method with visual quality control. Participants with Pittsburgh Sleep Quality Index (PSQI) &gt; 5 were excluded. PVS burden (count and score) was assessed in the basal ganglia and centrum semiovale according to STRIVE criteria. Inter-rater agreement between two blinded neuroradiologists was assessed using Cohen’s weighted kappa (κw). Group differences based on enlarged PVS (EPVS &gt; 3&#xa0;mm) were analyzed using Mann-Whitney U tests with effect size calculations.</p> Results <p>Strong negative correlations were found between the DTI-ALPS index and total PVS score (ρ = −0.869) and total PVS count (ρ = −0.888) (<i>p</i> &lt; 0.001). Participants with EPVS (<i>n</i> = 11) exhibited significantly lower DTI-ALPS indices (<i>p</i> &lt; 0.001; rank-biserial correlation = 0.972). Regression analysis revealed PVS load independently explained 76.3% of DTI-ALPS variance (R² = 0.763) after controlling for age. Post-hoc power analysis confirmed adequate statistical power for all primary analyses (1 − β &gt; 0.99) despite the modest sample size, owing to the large observed effect sizes.</p> Conclusion <p>In healthy young adults, increased PVS burden and the presence of EPVS are strongly associated with reduced DTI-ALPS index values. This robust structure–diffusion coupling may hypothetically reflect subclinical alterations in glymphatic clearance capacity, though causal functional interpretation requires direct validation. PVS analysis may serve as a complementary, non-invasive radiological marker for monitoring perivascular integrity at its subclinical stages.</p>

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Are perivascular spaces truly incidental? Evidence of structural–diffusion coupling in healthy young adults

  • 期刊论文

  • 发表日期：

    2026年8月3日

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  • Abdulkadir Ermiş,
  • Tehran Aliyeva,
  • Ali Behram Salar,
  • Melih Akan,
  • Uğur Çekmez,
  • Sena Ekinci Ermiş,
  • Gülhan Ertan Akan,
  • Erkingül Birday

摘要

Objective

The glymphatic system is vital for metabolic waste clearance, and its impairment has been implicated in various neurological disorders. We investigated the relationship between structural perivascular space (PVS) burden and the DTI-ALPS index (A non-invasive proxy reflecting perivascular diffusion characteristics) in healthy young adults, to evaluate their utility as complementary markers of subclinical perivascular alterations.

Methods

Twenty-four healthy volunteers (mean age: 32.3 ± 6.2 years) underwent 3T MRI including 64-direction diffusion tensor imaging. The DTI-ALPS index was calculated via an automated ROI method with visual quality control. Participants with Pittsburgh Sleep Quality Index (PSQI) > 5 were excluded. PVS burden (count and score) was assessed in the basal ganglia and centrum semiovale according to STRIVE criteria. Inter-rater agreement between two blinded neuroradiologists was assessed using Cohen’s weighted kappa (κw). Group differences based on enlarged PVS (EPVS > 3 mm) were analyzed using Mann-Whitney U tests with effect size calculations.

Results

Strong negative correlations were found between the DTI-ALPS index and total PVS score (ρ = −0.869) and total PVS count (ρ = −0.888) (p < 0.001). Participants with EPVS (n = 11) exhibited significantly lower DTI-ALPS indices (p < 0.001; rank-biserial correlation = 0.972). Regression analysis revealed PVS load independently explained 76.3% of DTI-ALPS variance (R² = 0.763) after controlling for age. Post-hoc power analysis confirmed adequate statistical power for all primary analyses (1 − β > 0.99) despite the modest sample size, owing to the large observed effect sizes.

Conclusion

In healthy young adults, increased PVS burden and the presence of EPVS are strongly associated with reduced DTI-ALPS index values. This robust structure–diffusion coupling may hypothetically reflect subclinical alterations in glymphatic clearance capacity, though causal functional interpretation requires direct validation. PVS analysis may serve as a complementary, non-invasive radiological marker for monitoring perivascular integrity at its subclinical stages.