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. 2025 Mar;67(3):599-611.
doi: 10.1007/s00234-025-03546-9. Epub 2025 Jan 24.

Perivascular and parenchymal brain fluid diffusivity in patients with a recent small subcortical infarct

Salvatore Rudilosso  1   2 , Emma Muñoz-Moreno  3 , Carlos Laredo  3 , Angels Calvet  3 , Alejandro Rodríguez-Vázquez  4 , Andres Girona  4 , Maria Dels Angels Calderon  5 , Federico Zarco  6 , Francisco Gil-López  7 , Adrià Arboix  7 , Maria Valdes Hernandez  8 , Roberto Duarte Coello  8 , Xabier Urra  4   5 , Joanna M Wardlaw  8 , Ángel Chamorro  4   3   5
Affiliations

Perivascular and parenchymal brain fluid diffusivity in patients with a recent small subcortical infarct

Salvatore Rudilosso et al. Neuroradiology. 2025 Mar.

Abstract

Purpose: Fluid exchanges between perivascular spaces (PVS) and interstitium may contribute to the pathophysiology of small vessel disease (SVD). We aimed to analyze water diffusivity measures and their relationship with PVS and other SVD imaging markers.

Methods: We enrolled 50 consecutive patients with a recent small subcortical infarct. We collected clinical variables, including vascular risk factors and sleep quality scales. All patients underwent a 3-Tesla MRI with standard structural sequences and multishell-diffusion images to obtain extracellular free water content (FW) and water diffusivity along the perivascular space (ALPS) index. We obtained volumetric measurements of white matter hyperintensities (WMH) and PVS, and the number of lacunes and microbleeds. To analyze the association between PVS, ALPS index, FW, and SVD imaging features, we utilized linear regression models including age, sex, history of hypertension and diabetes, Pittsburgh Sleep Quality Index, WMH, and brain volume.

Results: All patients (mean age 70 years, 36% women) had usable data. FW and PVS were strongly associated in all models (0.008 < Beta < 0.054; P < 0.045). Higher FW was related to the other SVD features in univariable models and remained significant for WMH (1.175 < Beta < 1.262; P < 0.001) and brain volume (Beta < 0.0001; P < 0.002) in multivariable models. ALPS index was not associated with FW, PVS, or any other SVD markers.

Conclusions: The increased extracellular water in SVD suggests that impaired brain fluid exchanges, PVS dilation, and other SVD features are linked. Further investigation is needed to determine the specificity of the ALPS index to PVS diffusion.

Keywords: Small vessel disease; Diffusivity; Glymphatic; Lacunar stroke; Perivascular spaces.

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Conflict of interest statement

Declarations. Ethics approval: The study was approved by the Ethical Committee for Research on Medicines of the Hospital Clínic (HCB/2022/0589). All procedures performed in this study were in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent: Written informed consent was obtained from all individual participants included in the study. Competing interests: On behalf of all authors, the corresponding author states that there is no conflict of interest.

References

    1. Wardlaw JM et al (2019) Small vessel disease: mechanisms and clinical implications. Lancet Neurol 18(7):684–696 - DOI - PubMed
    1. Tian Y et al (2022) The underlying role of the glymphatic system and meningeal lymphatic vessels in cerebral small vessel disease. Biomolecules 12(6):748 - DOI - PubMed - PMC
    1. Wardlaw JM et al (2020) Perivascular spaces in the brain: anatomy, physiology and pathology. Nat Rev Neurol 16(3):137–153
    1. Taoka T et al (2017) Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in alzheimer’s disease cases. Jpn J Radiol 35(4):172–178 - DOI - PubMed
    1. Taoka T et al (2024) Diffusion tensor image analysis along the perivascular space (DTI-ALPS): revisiting the meaning and significance of the method. Magn Reson Med Sci 23(3):268–290 - DOI - PubMed - PMC

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