Abstract Body: Introduction: Blood-brain barrier (BBB) dysfunction is increasingly recognized as a key factor in the pathogenesis of cerebral small vessel disease (cSVD). Typical brain Magnetic Resonance Imaging (MRI) findings of cSVD include white matter hyperintensities (WMH). Based on their anatomical locations, WMH can be classified as Periventricular WMH (PVWMH), which are immediately adjacent to the ventricles, or deep WMH (DWMH), which are subcortical. This study aimed to investigate the relationship between BBB permeability as measured by Dynamic Susceptibility Contrast (DSC) MRI, and changes in total WMH, PVWMH, and DWMH volume over 10-13 years in asymptomatic individuals enriched for vascular risk factors. Hypothesis: Higher K2 measurements, which reflect leakage of contrast due to increased BBB permeability, derived from second MRI will corelate with increases in WMH, DWMH, and PVWMH volume that occurred over the previous decade.
Methods: We included 100 volunteers from GeneSTAR, an ongoing family-based study of families enriched for vascular risk factors and cardiovascular disease, age = 63.3 ± 9.5 years, 60% females, 63% Hypertension, 22% African Americans. Two MRI’s were obtained 10-13 years apart using 3T scanners. At each visit total WMH, PVWMH and DWMH volumes were determined using automated software with consistent co-registration (Figure 1). K2 was measured for each individual by averaging the highest 100 voxels (hotspots) within the regions of interest in each individual lesion using a gadolinium-based DSC-MRI at the second visit (Figure 2). Linear regression models used to analyze the relationship between K2 and volume changes in total WMH, PVWMH, and DWMH, adjusting for age, systolic blood pressure, race, sex, and education.
Results: Positive correlations between K2 at time point two and changes in volume were statistically significant for total WMH (R-squared = 0.497, p = 0.006), PVWMH (R-squared = 0.461, p = 0.0085), but did not reach significance for DWMH (R-squared = 0.394, p = 0.08) (Figure 3).
Conclusion: The robust correlation between K2 and overall WMH volume change underscores the potential of K2 as a biomarker for monitoring ongoing disease activity for subclinical cerebrovascular changes in at-risk populations.