Abstract 353: Diagnostic Utility of Contrast Ultrasound for Identifying Abnormal Adventitial Neovascularization During Atherosclerosis Progression
Background: The density of vasa vasorum (VV) within atherosclerotic plaque correlates with histologic features of plaque vulnerability. Contrast enhanced ultrasound (CEUS) is a promising tool to visualize VV. We evaluated the diagnostic utility of CEUS for identifying abnormal adventitial neovascularization during atherosclerosis progression.
Methods: New Zealand rabbits (n=20) were fed a high-fat diet for 3 weeks. After 1 week on the diet, bilateral femoral artery balloon injury was used to cause accelerated atherosclerosis. Non-linear femoral CEUS (10 MHz, MI 0.3) was performed at 0, 2, 4, and 6 weeks post-injury. Peak videointensity (VI) in adventitial regions of interest was normalized to luminal VI. At each study time point, 5 rabbits were euthanized, yielding 10 arterial lesions that were sectioned for immunohistology. Adventitial VV was quantified by counting the number of microvessels and their total cross-sectional area (VVCSA).
Results: Plaque size (% lumen area) progressed over time: 0 weeks 41%, 6 weeks 98% (p<0.001), as did VVCSA (p<0.001). Peak VI also progressed with time (p<0.01) showing a strong linear correlation with VVCSA (Spearman’s Rho 0.84, p<0.001). We defined abnormal neovascularization as VVCSA associated with severe stenosis, as identified by ROC curves: a 5-fold VVCSA median increase from baseline was chosen, with 100% sensitivity and 94% specificity to detect 70% stenosis. Based on ROC curves, a 3-fold median peak VI increase from baseline had the best diagnostic accuracy for detecting abnormal neovascularization and was used to define a positive CEUS. A positive CEUS predicted abnormal neovascularization with a sensitivity of 100%, specificity of 88%, and positive and negative likelihood ratios of 8.5 and 0, respectively (p<0.001). Whereas the pre-test probability of histologic abnormal neovascularization was 58%, the post-test probability was 92% after a positive CEUS, and 0% after a negative CEUS.
Conclusions: CEUS peak VI strongly correlates with histologically quantified VV, and identifies the presence of abnormal plaque neovascularization: a positive CEUS significantly increases the probability of histologically confirmed abnormal neovascularization, while a negative CEUS essentially rules it out.