Contrast-enhanced dual-frequency super-harmonic Intravascular Ultrasound (IVUS) Imaging

Atherosclerotic cardiovascular disease is a leading cause of death worldwide, and one which often manifests without warning (Naghavi 2003). According to the 2014 update of Heart Disease and Stroke Statistics by the American Heart Association (Go et al. 2014), there are more than 2000 deaths every day in the USA on average, which is 1 death every 40 s. For up to 75% of acute coronary syndromes, the underlying pathological mechanism is hypothesized to be atherosclerotic plaque rupture (Naghavi 2003). Unfortunately, a high percentage of vulnerable plaques are also angiographically occult, and these are responsible for a high proportion of ensuing cardiac events resulting in either fatalities or requiring further interventional treatment (Glaser 2005; Goertz et al. 2007). For this reason, detection and characterization of plaques which are rupture prone is one of the most active areas of research in cardiology and biomedical imaging (Constantinides 1990). The vasa vasorum is a network of microvessels which supports larger vessels such as the aorta, and increased density of the vasa vasorum has been associated with a plaque advancing from a stable state to a rupture-prone state (Naghavi 2010; Moulton et al. 2003). Additionally, intraplaque hemorrhage occurring from thin-walled, immature microvessels has been present in plaques in many cases of sudden coronary death (Virmani 2005). Evidence suggests that vasa vasorum proliferation and associated angiogenesis and inflammation is associated with plaque instability and rupture (Virmani 2005; Kolodgie et al. 2003; Milei et al. 1998; Moreno and Fuster 2004). As our ability to predict the instability of atherosclerotic lesions remains a substantial challenge, there is an unmet need for new imaging methods to identify, detect, and differentiate these pathologies (Jaffer et al. 2006).