MR-compatible Devices for the Diagnosis and Treatment of Cardiomyopathies

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Cardiac magnetic resonance (CMR) is a non-invasive imaging technique with exquisite soft-tissue detail for the assessment of heart structure and function and provides an excellent screening tool but cannot always obviate more invasive procedures, such as endomyocardial biopsy (EMB). Interventional CMR (iCMR) is a minimally invasive technique without radiation, which has been hampered by the lack of non-ferrous devices that can be easily visualized, enabling the navigation of tasks, such as EMB, safely. Currently, one in nine deaths in the US is attributed to heart failure (HF), with health care costs exceeding $30 billion in 2013. Of the ~5.1 million Americans with HF, the definitive treatment is heart transplantation (HTx), where rejection is assessed with endomyocardial biopsy (EMB) – a procedure performed under X-ray guidance to obtain random samples of the right ventricular septum. However, many patients, especially children with cardiomyopathy and after HTx and HF caused by non-ischemic cardiomyopathies (NICM), do not have global changes to the myocardium, but rather, patchy disease, which is often restricted to limited portions of the left ventricle. Thus, EMB may yield a definitive diagnosis in <20% of the cases. As complications of EMB include ventricular puncture, pericardial tamponade, stroke, and death, the risk-benefit ratio of EMB limits its use. However, accurate diagnosis of cardiomyopathies or early recognition of heart rejection can lead to definitive treatment or measures to avoid heart rejection, respectively, with enormous individual patient impact. Therefore, we propose to develop an MRI-compatible suite of interventional devices to allow direct targeting of diseased myocardium (based on CMR) for EMB and treatment of cardiomyopathies, for both right- and left-sided catheterization. To this end, we will develop an active pigtail catheter with a guidewire for iCMR cardiac catheterization to be used in combination with an active MR-steerable sheath/bioptome device or transmyocardial injection catheter. These devices will enable direct targeting of the disease to increase diagnostic yield and decrease complications. Currently, there are no commercially available active MR-visible EMB, pigtail, or injection catheters. Significant advances to our realization of a clinically relevant MR-EMB device include the creation of a sharp-jaw EMB mechanism that is safe from heating, but provides a specific MR signature when the device is open vs. closed, and injection devices that can determine myocardial apposition so that therapeutics reach the intended target of the myocardium. Furthermore, as pediatric HTx patients receive up to six EMBs in the first year, the iCMR suite of devices will significantly reduce ionizing radiation in a particularly vulnerable population. Our research proposal will develop these devices in a canine model of spontaneous NICM that is similar in size to children's hearts to ensure these are compatible with pediatric interventions. Our extensive expertise in MRI interventional devices and CMR will be used to achieve this objective. Thus, our goal will be to develop these MR-guided devices to expand the reach of iCMR to children and adults.