Abstract 2480: Quantification of Plaque Neovascularization During Atherosclerosis Progression With Contrast Ultrasound: A Histologic Validation
Background: The density of vasa vasorum (VV) and abnormal neovascularization (neovasc) within atherosclerotic plaque correlates with histologic features of plaque vulnerability in post-mortem studies. A method to non-invasively detect VV in vivo would be clinically useful. Recently, contrast ultrasound (US) has shown potential for detecting VV and plaque neovasc. However, image parameters that accurately quantify plaque neovasc require further validation against a histologic standard. We tested the hypothesis that contrast US can quantify VV during atherosclerosis progression.
Methods: 5 New Zealand white rabbits received a high-fat diet for 3 weeks (wks). After 1 wk on the diet, bilateral femoral artery stenosis was induced by balloon injury. Non-linear US femoral imaging (10MHz) was performed at 2, 4, and 6 wks post injury during iv microbubble injection using destruction-replenishment to quantify blood velocity (β) and volume as peak videointensity (VI). VI was measured in plaque and adventitia and normalized to luminal VI. At 4 (n=3), and 6 (n=2) wks post injury, both femorals were sectioned (total 10 plaques) and stained for von-Willebrand factor (vWF). Intraplaque and adventitial VV were quantified by counting the number of stained microvessels. Plaque size (% lumen area) was measured from histology.
Results: Data were analyzed at 4 and 6 wks post injury, when plaque was detectable by US. Plaque progressed between 4 (48±26%) and 6 wks (98±3%, p<0.01), as did total number of VV (adventitial + plaque) (p< 0.01). Peak plaque VI was higher at 6 wks (0.9±0.2) vs 4 wks (0.6±0.1, p=0.06). The number of plaque neovessels linearly correlated to peak VI (r=0.83, p<0.003). Similar correlations existed for adventitial VV density vs. adventitial VI (r=0.80, p<0.006). β did not predict extent of VV.
Conclusions: We have validated an in vivo approach using contrast US that tracks pathologic neovasc in atherosclerotic plaque. This provides a unique research tool to gain new insight into plaque biology in real time. Because neovasc appears to predict plaque vulnerability, our data also suggest that this imaging technique could offer a powerful clinical approach to stratify cardiovascular risk and follow responses to therapy in patients with atherosclerotic disease.