The etiology and evolution of magnetic resonance imaging-visible perivascular spaces: Systematic review and meta-analysis

Serhat V Okar; Fengling Hu; Russell T Shinohara; Erin S Beck; Daniel S Reich; Benjamin V Ineichen

doi:10.3389/fnins.2023.1038011

The etiology and evolution of magnetic resonance imaging-visible perivascular spaces: Systematic review and meta-analysis

Front Neurosci. 2023 Mar 30:17:1038011. doi: 10.3389/fnins.2023.1038011. eCollection 2023.

Authors

Serhat V Okar¹, Fengling Hu², Russell T Shinohara², Erin S Beck^{1

3}, Daniel S Reich¹, Benjamin V Ineichen^{1

4

5}

Affiliations

¹ Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
² Department of Biostatistics, Epidemiology, and Informatics, Penn Statistics in Imaging and Visualization Center, University of Pennsylvania, Philadelphia, PA, United States.
³ Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
⁴ Department of Neuroradiology, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁵ Center for Reproducible Science, University of Zurich, Zurich, Switzerland.

Abstract

Objectives: Perivascular spaces have been involved in neuroinflammatory and neurodegenerative diseases. Upon a certain size, these spaces can become visible on magnetic resonance imaging (MRI), referred to as enlarged perivascular spaces (EPVS) or MRI-visible perivascular spaces (MVPVS). However, the lack of systematic evidence on etiology and temporal dynamics of MVPVS hampers their diagnostic utility as MRI biomarker. Thus, the goal of this systematic review was to summarize potential etiologies and evolution of MVPVS.

Methods: In a comprehensive literature search, out of 1,488 unique publications, 140 records assessing etiopathogenesis and dynamics of MVPVS were eligible for a qualitative summary. 6 records were included in a meta-analysis to assess the association between MVPVS and brain atrophy.

Results: Four overarching and partly overlapping etiologies of MVPVS have been proposed: (1) Impairment of interstitial fluid circulation, (2) Spiral elongation of arteries, (3) Brain atrophy and/or perivascular myelin loss, and (4) Immune cell accumulation in the perivascular space. The meta-analysis in patients with neuroinflammatory diseases did not support an association between MVPVS and brain volume measures [R: -0.15 (95%-CI -0.40-0.11)]. Based on few and mostly small studies in tumefactive MVPVS and in vascular and neuroinflammatory diseases, temporal evolution of MVPVS is slow.

Conclusion: Collectively, this study provides high-grade evidence for MVPVS etiopathogenesis and temporal dynamics. Although several potential etiologies for MVPVS emergence have been proposed, they are only partially supported by data. Advanced MRI methods should be employed to further dissect etiopathogenesis and evolution of MVPVS. This can benefit their implementation as an imaging biomarker.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=346564, identifier CRD42022346564.

Keywords: Virchow-Robin spaces; biomarker; enlarged perivascular spaces; etiology; etiopathogenesis; magnetic resonance imaging; meta-analysis; systematic review.

Publication types

Systematic Review

Grants and funding

BI was supported by the UZH FAN Alumni and the Swiss National Science Foundation (SNSF, 407940_206504 and P400PM_183884). EB was supported by a Career Transition Award from the National Multiple Sclerosis Society. RS was partially funded by R01NS112274. This study was partially supported by the Intramural Research Program of NINDS and NIH.