Introductions

To investigate how dilated perivascular space (dPVS) affects water drainage in surrounding tissue and whether there is any distance-related pattern of water distribution around dPVS. Further, we hypothesized that interstitial water clearance processes reflected by dPVS are different in healthy ageing and subjects with severe cerebral small vessel disease (CSVD).

Method

28 healthy adult subjects, 20 healthy elderly subjects, and 15 elderly subjects with severe cerebral small vessel disease (lacunar infarction 6 month prior to the scan) were included in our study. DPVS were segmented using a deep-learning based algorithm[1] based on T2 image. Automatically segmented mask were then flipped to the contralateral hemisphere, and overlapping of flipped mask and original dPVS mask were removed from flipped mask, resulting a control mask. Control mask represented normal white matter area where dPVS are highly prevalent. For each voxel, a distance to the nearest dPVS (D_p) and a distance to the nearest control mask (D_c) were calculated. NODDI model was used to obtain the volume fraction of isotropic diffusing water content (Viso, reflecting water with free movement such as water in dilated PVS) and volume fraction of water movement within axon (Vic, reflecting the integrity of myelinated structure) within each voxel. Then we plotted the pattern of NODDI parameter changes with D_p and D_c. [Fig 1.]

Results

In all 3 groups, the V_ic around dPVS didn’t differ from that of the control points (Pair-wise t-test P values >0.05 at all distance ranges). However, V_iso from 0~2mm around dPVS is significantly higher than that of control points in all groups. And V_iso from 2~4mm from dPVS is significantly lower than that of control points in healthy adult group and healthy elderly group. In the LA group we didn’t observed such decrease of V_iso around dPVS.[Fig 2] ANOVA analysis results suggests that there are significant differences in V_iso within 2mm from the dPVS between the 3 groups (P<0.001). Further post-hoc analysis using LSD correction revealed that the differences were significant between each pair of the 3 groups. [Fig 3] The LA group had the highest V_iso in within dPVS, while the healthy adult group had the lowest. Pearson correlation test between V in dPVS and the V across the entire normal white matter showed significant positive correlation in the Healthy Elderly group and the Healthy Adult group (P<0.001), but not in the LA group (P=0.888). [Fig 4]

Discussion

The discovery of increased V_iso at 0~2mm around dPVSs is most likely to be driven by the water signal inside the dPVSs, especially considering our image have a spatial resolution of 2m. V_iso in healthy adults and healthy elderly subjects are decreased in areas from 2~4mm around dPVS when compared to normal white matter areas with highly prevalent PVS dilation. This decrease is also visible in subjects with extensive CSVD, but the effect is weaker. One possible explanation is these dPVSs or “MR-visible” PVSs in healthy subjects could accelerate draining of interstitial fluid around it. Though there are currently no direct evidence to prove the dPVSs could accelerate fluid drainage, some studies observed diurnal fluctuation of diffusion signal caused by changes in the perivascular pathway, which suggest the possibility of PVS dilating or closing to adjust fluid drainage. the Viso changes in the dPVS of healthy subjects are highly correlated with the global white matter Viso, which could be interpreted as a mechanism of maintaining fluid balance. While in the CSVD subject the Viso in dPVS and global white matter are no longer correlated in our study, supporting the hypothesis of dysfunctional PVS in CSVD subjects.

Conclusion

DPVS showed different distance-related pattern in healthy subjects and subjects with severe CSVD, suggesting dPVS played different roles in healthy and CSVD.

References

1. Lian C, Zhang J, Liu M et al. Multi-channel multi-scale fully convolutional network for 3D perivascular spaces segmentation in 7T MR images. MED IMAGE ANAL. 2018;46:106-117