In the treatment of acute artery disease, percutaneous interventions using drug-eluting stents are the preferred method of treatment. Although effective for simple conditions (e.g., short lesions, single vessels), when treating tortuous or bifurcating vessels, drug-eluting stents can provide incomplete drug coverage, resulting in neointimal hyperplasia or acute thrombosis. The fixed dose and drug choice of the drug-eluting stent also limits the physician's ability to tailor treatment to the patient's individal need. Further, current methods rely on angiography for verification and quantification of successful angioplasty and stent deployment. Angiography provides no information regarding lumen diameter and plaque composition. In order to address these needs, SoundPipe is developing a flexible combined ultrasound imaging and therapy (CUIT) or theranostic catheter and control system for ultrasound and microbubble enhanced delivery of antiproliferative agents. This approach will use a "Detect, Displace, Deliver" (3D) therapy model to guide and effect therapy. Following balloon angioplasty, the lesion will be detected using intravascular ultrasound to verify catheter placement for drug delivery. Then, sirolimus (i.e. rapamycin)-bearing microbubbles will be infused through the catheter and localized to the vessel wall using ultrasound. Once the therapeutic microbubbles have been localized along the injured vessel wall, the combination of low frequency ultrasound and microbubbles will transiently permeabilize the cell membrane. This will cause delivery of the sirolimus from the microbubble shell, enabling localized therapy. This method may improve treatment of acute coronary events by enabling localized drug delivery independent of a mechanical delivery platform (e.g. balloon or stent), enabling on site control of drug dose, and enhancing drug uptake with the potential to reduce drug doses. This Phase I SBIR seeks to demonstrate that a CUIT catheter can provide 3D therapy for localized drug delivery and imaging feedback within a blood vessel. In order to prove this hypothesis, a Form, Fit, and Function prototype of a CUIT catheter and control system will be designed and developed to perform both low frequency microbubble-based therapy and high frequency imaging. Key technological innovations will be achieved in the integration of a therapeutic and high resolution IVUS system. With the proposed CUIT IVUS catheter system in place, system parameters will be optimized to maximize model drug delivery with the SoundPipe system in an ex vivo swine artery model. Plans for Phase II include user interface development for the IVUS drug delivery system and an in vivo swine model study of system efficacy. Public Health Relevance In the treatment of acute artery disease, percutaneous interventions using drug-eluting stents are the preferred method of treatment. Although effective for simple conditions (e.g., short lesions, single vessels), when treating tortuous or bifurcating vessels, drug-eluting stents can provide incomplete drug coverage, fixed drug dose, and fixed drug choice which limits the physician's ability to tailor treatment to the patient's individual ned. The long-term goal of this project is to provide interventional cardiologists with a more versatile and effective platform for treating lesions following PCI that incorporates detection and therapy in one platform, providing real time feedback throughout therapy and thus potentially improving patient outcomes.
