Ultrasound Targeted Molecular Imaging in Large Arteries to Predict AAA Risk

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Abdominal aortic aneurysm (AAA) causes over 10,000 deaths annually in the US. The majority of AAA are silent and asymptomatic until rupture. If detected early, surgical interventions have been proven effective with in-hospital mortalities < 4% compared to mortality higher than 40% in already ruptured AAAs. Ultrasound- based maximum diameter measurements of AAA is currently the primary determinant of its rupture risk with 5.5 cm often used as the decision criteria. However, it has been reported that up to 23% of AAAs ruptured at a diameter less than 5 cm and up to 60% of AAAs with a diameter greater than 5 cm never experienced rupture Thus, more reliable predictors of rupture risk are urgently needed. In particular, a molecular imaging positive finding may assist with risk stratification in cases where anatomic-based findings are ambiguous (e.g. aortic diameter in range 4.5 - 6.5 cm). Molecular imaging is a promising approach for early detection of AAA risk that contrasts with anatomical imaging in which only relatively late AAA progression is detectable. The correlation between risk of AAA rupture and biomarkers has been demonstrated. MRI, optical, and PET methods have all demonstrated pre-clinical success in detection of markers for AAA rupture but none of these modalities simultaneously meets the need for rapid, low-cost, radiation-free, molecular marker detection necessary to achieve widespread clinical adoption. Ultrasound-based molecular imaging is an ideal modality because it meets the above needs and existing instrumentation, already in use for making diameter measurements during existing AAA screening protocols, requires only very minor adaptation. Unfortunately, existing ultrasound- based molecular imaging is unable to measure molecular marker concentration in large blood vessel environments, and thus AAA risk assessment using ultrasound has not yet been attempted. The present investigators have recently invented a new ultrasound-based molecular imaging strategy that overcomes the limitations of previous techniques in large blood vessel environments. This method, referred to as “modulated Acoustic Radiation Force” (mARF)-based imaging, is the first ultrasound technology to demonstrate quantitative measurements of molecular marker con-centration (in units of sites/μm2) in large blood vessels. Earlier and more accurate prediction of future AAA rupture risk will improve mortality rates and reduce healthcare costs associated with AAA.