Abstract Body: Introduction: Disruption of the blood-brain barrier (BBB) is thought occur during the ischemic injury that leads to the formation and progression of vascular white matter hyperintensities (WMH). In this study, we estimated BBB disruption using dynamic contrast-enhanced MRI (DCE-MRI) in human subjects at risk for cardiovascular disease. The volume transfer constant, K^trans, an indicator of BBB permeability and flow, was estimated in four regions of interest (ROI) surrounding ischemic white matter hyperintensities (WMH) to estimate where the BBB disruption was highest and ongoing ischemic injury was more likely to occur. The ROI consisted of WMH lesions, penumbra (4 voxels beyond the WMH), surrounding normal-appearing white matter (NAWM), and grey matter (GM). Hypothesis: Since previous studies have suggested that the penumbra of WMH may be a site of active pathology, our hypothesis was that K^transwould be larger there.
Methods: We included 112 volunteers from the GeneSTAR study, an ongoing family-based study of people at risk for cardiovascular disease, age = 63.1 ± 9.6 years, 60.71% females. Anatomical and functional images, including DCE-MRI, were obtained using a 3T MRI. K^trans was calculated by applying the Patlak model (Nordic ICE ^(TM)). Whole brain segmentation masks, retrieved from the anatomical images, including WMH, the penumbra, NAWM and GM were applied on the K^trans maps. Mean K^trans was thereafter calculated for each ROI by first excluding the values below 2SD of the mean K^trans in NAWM.
Result: K^trans (mean±SD) for each ROI is shown in Table 1. Notice that the penumbra had the highest average K^trans(2.63 ± 0.26) while K^trans was 2.42 ± 0.23, in WMH, 1.20 ± 0.23, in NAWM, and 1.97 ± 0.21 in NAWM (Table 1). The Wilcoxon signed-rank test shows a statistically significant difference between the K^trans values in the WMH lesions and the penumbra (p = 0.002).
Conclusion: Quantitative 3T DCE-MRI analysis revealed that the penumbra surrounding the leading edge of the WMH had the highest estimate of K^trans which may reveal a higher BBB permeability. This pattern suggests the penumbra, on the edge of the WMH, had the highest ongoing ischemic activity and may be an area of interest for targeted intervention to prevent WMH expansion.