Medical Engineering Seminar

 In the U.S., the prevalence of overt coronary artery disease is about 7 million with up to 2 million procedures performed annually. Despite the advent of computed tomographic (CT) angiography, high resolution MRI, intravascular ultrasound (IVUS), near-infrared fluorescence (NIRF),²¹ and time-resolved laser-induced fluorescence spectroscopy, early identification of mechanically and metabolically unstable plaques remains an unmet clinical need to detect and prevent acute coronary syndromes and stroke. Fluid shear stress, in addition to its mechanical effects on vascular endothelial cells, imparts both metabolic and mechanical effects on vascular endothelial function. A complex flow profile develops at the arterial bifurcations (Figure). Oscillatory shear stress (OSS: bidirectional and axially misaligned flow) is considered to be atherogenic, promoting oxidative stress and inflammatory responses, whereas pulsatile shear stress (PSS: unidirectional and axially aligned flow) is deemed atheroprotective, down-regulating pro-inflammatory states. Encouraging results from our interdisciplinary team demonstrated that integration of intravascular shear stress (ISS) and endoluminal electrochemical impedance spectroscopy (EIS) distinguishes pre-atherogenic lesions associated with oxidative stress in fat-fed New Zealand White (NZW) rabbits. In this context, we hypothesize that oxLDL-rich lesions harbor distinct electrochemical properties in the vessel wall that can be measured by frequency-dependent electrochemical impedance to identify metabolically active atherosclerotic lesions. We will integrate a triad of intravascular sensing modalities, shear stress (ISS), ultrasound (IVUS), and electrochemical impedance (EIS), for early detection of metabolically unstable lesions.  This integrated sensing system would allow initial detection by disturbed shear, then visualization by IVUS, and then electrochemical characterization by EIS. Overall, by integrating electrochemical signals of active lipid-laden lesions with animal models of atherosclerosis, we will establish early detection of metabolically and mechanically unstable lesions for individualized intervention.