Dual frequency intravascular ultrasound for super-resolution imaging of vasa vasorum and thin fibrous cap of vulnerable atherosclerotic plaques

PROJECT SUMMARY The underlying mechanism for up to 75% of acute coronary syndromes (ACS) of myocardial infarction is considered to be due to vulnerable atherosclerotic plaques (AP) rupture. The increased density of coronary vasa vasorum (VV) around AP has known to be associated with plaque instability and plaque rupture, especially when the fibrous cap is thin. This strongly suggests that imaging both VV and thin fibrous cap can be a new strategy for accurate classification, timely intervention, and effective management of the rupture- prone AP to prevent ACS. Although Intravascular optical coherence tomography (IV-OCT) has shown promise for vulnerable AP evaluation at high resolution, it has limited imaging depth. Conventional Intravascular ultrasound (IVUS) has the advantage of improved imaging depth, however, despite successful clinical investigations in the past decades, a critical technical limitation with spatial resolution remains unsolved. To overcome the technical challenge and address the unmet clinical need, the goal of this project is to develop and validate a new super-resolution intravascular ultrasound (SR-IVUS) technology enabling effective imaging of VV to assess plaque vulnerability with unprecedented high resolution and deep penetration depth. Specifically, we will develop an innovative, first-of-its-kind 1.75D array at 20 MHz, which will provide a high-resolution 3D mapping of the VV network at depth. The major benefit of the 1.75D array is its ability to reject out-of-plane clutter artifacts which are currently challenging in SR realization with a 1D array. We will also combine a 60 MHz single element broadband transducer for accurately identifying the thin fibrous cap with the 1.75D array to make a dual mode probe. This enables comprehensive imaging capabilities for combined, co-registered 3D VV network imaging with morphology and location of the fibrous cap. Our specific aims are: SA 1: Develop a dual mode SR-IVUS catheter and system. SA 1a: Develop 60 MHz single element transducer and 20 MHz 1.75D array transducer. SA 1b: Integrate 60 MHz single element transducer and 20 MHz 1.75D array transducer with a configurable high-frequency imaging system. SA 2: Implement the algorithm of SR-IVUS imaging for vasa vasorum and the fibrous cap thickness measurement. SA 3: Evaluate the developed prototype SR-IVUS system for imaging the VV and fibrous cap using rabbit AP model. If successfully developed and validated, the new SR-IVUS device equipped with high resolution comparable to IV-OCT and at large imaging depth will push forward clinical validation of IVUS and widespread adoption in clinics with high impact. In particular, during the percutaneous coronary intervention, the vulnerability of the target culprit plaques and nearby unspecified plaques but have high potential of future rupture can be more accurately characterized for timely, effective intervention, providing a paradigm shift in the contemporary management of the vulnerable plaques, a major reduction in morbidity and mortality associated with AP rupture, and a lasting clinical impact.