Imaging the Perivascular Space as a Potential Biomarker of Neurovascular and Neurodegenerative Diseases

Abstract

Although the brain lacks conventional lymphatic vessels found in peripheral tissue, evidence suggests that the space surrounding the vasculature serves a similar role in the clearance of fluid and metabolic waste from the brain. With aging, neurodegeneration, and cerebrovascular disease, these microscopic perivascular spaces can become enlarged, allowing for visualization and quantification on structural MRI. The purpose of this review is to: (i) describe some of the recent pre-clinical findings from basic science that shed light on the potential neurophysiological mechanisms driving glymphatic and perivascular waste clearance, (ii) review some of the pathobiological etiologies that may lead to MRI-visible enlarged perivascular spaces (ePVS), (iii) describe the possible clinical implications of ePVS, (iv) evaluate existing qualitative and quantitative techniques used for measuring ePVS burden, and (v) propose future avenues of research that may improve our understanding of this potential clinical neuroimaging biomarker for fluid and metabolic waste clearance dysfunction in neurodegenerative and neurovascular diseases.

Keywords: Alzheimer’s disease; Cerebrovascular disease; Dementia; Interstitial fluid drainage; Perivascular metabolic clearance; Perivascular space; Virchow–Robin space.

Fig. 1

Schematic representation of the brain’s perivascular Virchow–Robin space and surrounding tissues. The cortical perivascular space is bounded by the adventitia of the vessel and the astrocyte end-feet, and is filled with CSF from the subarachnoid space. Metabolic waste, such as Aβ is thought to accumulate around the blood vessel, possibly resulting in perivascular blockage and enlargement of the space, as shown on the right vessel

Fig. 2

Radiologist confirmed BG-ePVS on T1, PD, T2, and FLAIR (left to right). Top row shows typical ePVS (red arrowhead) in compliance with the <3 mm STRIVE size criteria, with most appearing as linear or slit-like in appearance (Wardlaw et al. 2013). Bottom row shows extremely large ePVS (red arrows) exceeding the STRIVE size criteria, with a more rounded spherical shape. These ePVS examples demonstrate the difficulty in implementing hard rules based on size and shape criteria, and also how they are difficult to visualize and delineate on FLAIR, particularly in the basal ganglia where they are commonly found (Color figure online)

Fig. 3

Pathology slides with venous collagenosis. Slide A (left) shows a large caliber periventricular vein with collagenous thickening of the wall. Slide B (right) collagenosis of the smaller venules. The venous walls are stained green using Masson trichrome staining. Courtesy of Dr. Juan Bilbao