MINI REVIEW article
Front. Cell. Neurosci.
Sec. Cellular Neuropathology
This article is part of the Research TopicEvolution of Enlarged Perivascular Spaces in Neurologic Diseases: Unraveling the Progression and Clinical SignificanceView all 3 articles
"Mind the Gap" – Enlarged Perivascular Spaces as a Potential Magnetic Resonance Imaging Biomarker of Impaired Glymphatic Clearance in Brain Disorders
Provisionally accepted
- 1Department of Radiology and Biomedical Imaging, School of Medicine, Yale University, New Haven, United States
- 2Yale School of Medicine, New Haven, United States
- 3Icahn School of Medicine at Mount Sinai, New York, United States
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The abundant capillary network penetrating the brain parenchyma is surrounded by potential tubular fluid-filled regions referred to as perivascular spaces (PVS). PVS have a unique, complex history and are believed to act as a pathway for drainage of waste products from brain interstitial and cerebrospinal fluid as part of the glymphatic clearance system. The unique PVS "gap" spaces are eponymously linked to Virchow and Robin, who argued vigorously against each other in the 1800s over PVS's exact location and physiology. Currently, debates are ongoing regarding the predominant location of PVS as periarteriolar, perivenular, or both, and how they aid in clearing fluids from the brain parenchyma. In neurodevelopmental, neuropsychiatric, and neuropathological conditions, PVS can enlarge, referred to as enlarged perivascular spaces (ePVS, that are identifiable on Magnetic Resonance Imaging (MRI), with improved detection and resolution at higher magnetic field strengths. Quantification of ePVS enlargement on MRI using artificial intelligence (AI) imaging algorithms may serve as a potential non-invasive imaging biomarker for impaired glymphatic clearance and brain disorders. This mini review presents the historical background and pathophysiology of PVS and ePVS, and the current debates as to their exact location, potential as a neuroimaging biomarker, and how AI may aid in ePVS quantification.
Keywords: artificial intelligence, Autism Spectrum Disorder, enlarged perivascular spaces (ePVS), Glymphatic system, magnetic resonance imaging (MRI), Neurological Disease, Perivascular space (PVS)
Received: 06 Nov 2025; Accepted: 05 Feb 2026.
Copyright: © 2026 Kirsch, Herb, Verma and Balchandani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Claudia Francoise Eve Kirsch
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