Unveiling connections between venous disruption and cerebral small vessel disease using diffusion tensor image analysis along perivascular space (DTI-ALPS): A 7T MRI study

Background: Cerebral venous disruption is one of the characteristic findings in cerebral small vessel disease (CSVD), and its disruption may impede perivascular glymphatic drainage. And lower diffusivity along perivascular space (DTI-ALPS) index has been suggested to be with the presence and severity of CSVD. However, the relationships between venous disruption, DTI-ALPS index, and CSVD neuroimaging features remain unclear. Aims: To investigate the association between venous integrity and perivascular diffusion activity, and explore the mediating role of DTI-ALPS index between venous disruption and CSVD imaging features. Methods: In this cross-sectional study, 31 patients (mean age, 59.0 ± 9.9 years) were prospectively enrolled and underwent 7T MR imaging. DTI-ALPS index was measured to quantify the perivascular diffusivity. The visibility and continuity of deep medullary veins (DMVs) were evaluated based on a brain region-based visual score on high-resolution susceptibility weighted imaging. White matter hyperintensity (WMH) and perivascular space (PVS) were assessed using qualitative and quantitative methods. Linear regression and mediation analysis were performed to analyze the relationships among DMV scores, DTI-ALPS index, and CSVD features. Results: The DTI-ALPS index was significantly associated with the parietal DMV score [β = -0.573, p-corrected = 0.004]. Parietal DMV score was associated with WMH volume [β = 0.463, p-corrected = 0.013] and PVS volume in basal ganglia (β = 0.415, p-corrected = 0.028]. Mediation analyses showed that DTI-ALPS index manifested a full mediating effect on the association between parietal DMV score and WMH (indirect effect = 0.115, Pm=43.1%), as well as between parietal DMV score and PVS volume in basal ganglia (indirect effect = 0.161, Pm=42.8%). Conclusions: Cerebral venous disruption is associated with glymphatic activity, and with WMH and PVS volumes. Our results suggest cerebral venous integrity may play a critical role in preserving perivascular glymphatic activity; while disruption of small veins may impair the perivascular diffusivity, thereby contributing to the development of WMH and PVS enlargement.