Perivascular spaces in healthy young subjects
Giuseppe Barisano1,2,3, Farshid Sepehrband1, Nasim Sheikh-Bahaei3, Meng Law1,3,4, and Arthur W. Toga1

1Laboratory of Neuroimaging, University of Southern California, Los Angeles, CA, United States, 2Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, United States, 3Department of Radiology, Keck Hospital of University of Southern California, Los Angeles, CA, United States, 4Department of Radiology, Alfred Health, Melbourne, Australia


Enlargement of perivascular spaces has been associated with a number of diseases. However, morphological features of perivascular spaces in healthy subjects and their clinical role are still not completely understood. We analyzed on MRI perivascular spaces in a large sample of healthy young subjects. Our results showed a high inter-subjects variability of perivascular spaces. Twins presented similar amount of perivascular spaces. Perivascular spaces in basal ganglia were significantly correlated with subjects’ height, brain volume, and brainstem volume. These findings are relevant for all future studies investigating the role of perivascular spaces.


Perivascular spaces (PVS), also known as Virchow-Robin spaces, are tubular fluid-filled structures that surround small blood vessels penetrating the brain parenchyma. In the past, PVS were regarded as having no clinical consequence, but recently they have gained increasing attention from the scientific community thanks to the discovery of the glymphatic system1. Moreover, the improved spatial resolution offered by high- and ultra-high-field MRI is leading to accurate mapping of PVS2. Enlargement of PVS has been associated not only with aging, but also with a number of pathophysiological conditions3. However, physiological imaging characteristics of PVS in healthy subjects are still not clear.


In this study, we analyzed PVS in a large sample of normal subjects from the Human Connectome Project4. Demographic data and volume of many brain regions extracted with Freesurfer were collected as well. PVS were independently rated by two readers on axial T2-weighted images at 3T MRI using a validated 4-point visual rating scale3. In basal ganglia (PVSBG) and centrum semi-ovale (PVSCS): 0=no PVS, 1=1-10 PVS, 2=11–20 PVS, 3=21–40 PVS, and 4=>40 PVS; in the midbrain (PVSMB): 0=no PVS, 1=PVS visible. The total PVS score (PVStot) for each subject was calculated as the sum of the single scores.


One hundred healthy subjects (53 females, 47 males; mean age 28.3, range 22-36) were randomly selected from the HCP database. Nine pairs of monozygotic twins were also included in the analysis. The mean number of enlarged PVSCS and PVSBG were 34.7 (range 11-78) and 9.2 (range 3-20), respectively. Each twin showed a similar amount and distribution of PVS compared with the sibling, both in basal ganglia and centrum semiovale. The highest grade of PVSCS was found in 35% of cases; 58% of subjects had enlarged PVS in the midbrain. PVSCS and PVSBG were significantly correlated (p<0.001). Moreover, PVSBG was significantly correlated with subjects’ height (p=0.01), brain volume (p=0.005), and brainstem volume (p=0.005).

Discussion & Conclusion

Identifying the physiological factors affecting PVS in normal subjects is fundamental in order to better understand the significance of PVS in pathological states and, ultimately, PVS function. This study demonstrates that a high inter-subjects variability of enlarged PVS is detectable in a healthy young population. This level of variability was maintained between the pairs of twins, but the number of PVS in a twin was comparable to that of the sibling. This finding suggests a potential genetic contribution to the number and distribution of PVS. Additionally, more than 1/3 of subjects presented with what is considered as abnormal level of PVS, highlighting the need for the development of a new rating scale. We also found that some morphological factors may affect PVS in normal subjects, particularly in basal ganglia, suggesting the importance of statistical adjustment for brain size when studying PVS. These results are relevant for all future studies investigating the role of PVS in pathological conditions and across different groups.


No acknowledgement found.


1. Iliff JJ, Wang M, Liao Y, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med. 2012;4(147):1-11. doi:10.1126/scitranslmed.3003748

2. Barisano G, Sepehrband F, Ma S, et al. Clinical 7T MRI: are we there yet? A review about magnetic resonance imaging at ultra-high field. Br J Radiol. October 2018. doi:10.1259/bjr.20180492

3. Potter GM, Chappell FM, Morris Z, Wardlaw JM. Cerebral perivascular spaces visible on magnetic resonance imaging: development of a qualitative rating scale and its observer reliability. Cerebrovasc Dis. 2015;39(3-4):224-231. doi:10.1159/000375153

4. Van Essen DC, Ugurbil K, Auerbach E, et al. The Human Connectome Project: A data acquisition perspective. Neuroimage. 2012;62(4):2222-2231. doi:10.1016/j.neuroimage.2012.02.018


T2-weighted images showing high inter-subjects variability of perivascular spaces, both in centrum semiovale (A and C) and in basal ganglia (B and D). Cases A and B have a low number of perivascular spaces, whereas cases C and D present a high number of perivascular spaces.

Scatterplots depicting the statistically significant relationship between PVS in basal ganglia and subjects' height (A), brain volume (B), and brainstem volume (C)

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)