Association between morphologic features of intracranial distal arteries and brain atrophy indexes in cerebral small vessel disease: a voxel-based morphometry study

BACKGROUND: Brain atrophy represents a final common pathway for pathological processes in patients with cerebral small vessel disease (CSVD) and is now recognized as a strong independent predictor of clinical status and progression. The mechanism underlying brain atrophy in patients with CSVD is not yet fully comprehended. This study aims to investigate the association of morphologic features of intracranial distal arteries (A2, M2, P2 and more distal) with different brain structures [gray matter volume (GMV), white matter volume (WMV), and cerebrospinal fluid volume (CSFV)]. Furthermore, we also examined whether a correlation existed between these cerebrovascular characteristics and GMV in different brain regions. METHOD: A total of 39 participants were eventually enrolled. The morphologic features of intracranial distal arteries based on TOF-MRA were extracted and quantified using the intracranial artery feature extraction technique (iCafe). The brain 3D-T1 images were segmented into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) using the “Segment” tool in CAT12 for the voxel-based morphometry (VBM) analysis. Univariable and multivariable linear regression models were used to investigate the relationship between these cerebrovascular features and different brain structures. Partial correlation analysis with a one-tailed method was used to evaluate the relationship between these cerebrovascular features and GMV in different brain regions. RESULTS: Our findings indicate that both distal artery length and density were positively correlated with GM fraction in CSVD patients, regardless of whether univariable or multivariable linear regression analyses were performed. In addition, distal artery length (β = −0.428, p = 0.007) and density (β = −0.337, p = 0.036) were also found to be negative associated with CSF fraction, although this relationship disappeared after adjusting for potential confounders. Additional adjustment for the effect of WMHs volume did not change these results. In subgroup anasysis, we found that participants in the highest distal artery length tertile had significantly higher GM fraction and lower CSF fraction level than participants in the lowest distal artery length tertile. In partial correlation analysis, we also found that these cerebrovascular characteristics associated with regional GMV, especially subcortical nuclear. CONCLUSION: The morphologic features of intracranial distal arteries, including artery length, density and average tortuosity, measured from 3D-TOF MRA, are associated with generalized or focal atrophy indexes of CSVD.