SBIR-STTR Award

Atrial fibrillation remains the most commonly occurring cardiac arrhythmia. It is associated with a lower quality of life and a higher rate of morbidity & mortality. Cryotherapy and radiofrequency catheter ablations for the purpose of eliminating atrial fibrillation have become a mainstream treatment option. They produce lesions that block the spread of electrical activity from the sites of abnormal activity, including the pulmonary veins. Today, there are limited means for real-time monitoring of tissue injury during cardiac ablation procedures. To address this need, we studied the fluorescence of endogenous NADH as a live marker of tissue injury during the ablation procedure and have confirmed the feasibility of this approach in blood perfused animal hearts. STTR Phase I support will provide us with the necessary funds to accelerate the project into its next phase. Studies will be conducted in small and large, fully-anesthetized open-chest animals. The goals of Aim1 are to compare the effectiveness of laser vs LED based illumination, sensitivity and spatial resolution of internal vs external cameras, and to test the shape and material for the inflatable balloons and to fit all the components within lumen of a 12Fr (4mm) diameter catheter. In Aim 2 several iterations of catheters designed by LuxCath will be brought to the GWU Institute of Surgical Endoscopy (WISE) surgical suite for testing. Images of NADH fluorescence will be acquired in real time to visualize gaps of viable tissue between ablation lesions at various clinically relevan sites, including the pulmonary veins. Electrical activity recordings will be linked to NADH images to correlate ablation gaps to the occurrence of post-ablation reentries. The immediate goal of Phase I is to develop a pre-clinical stand-alone visualization catheter that can be used during AF ablation procedures to evaluate the cardiac lesions around the ostia of the pulmonary veins. Ultimately, a new generation of stand- alone visualization catheters as well as ablation catheters incorporating visualization capabilities will be developed thus enabling real-time visualization of ablated tissue at the time of ablation or using the same device to perform the ablations. Such new imaging technologies will pave the way for easier, faster, safer, more cost-effective, and more reliable minimally invasive AF ablation procedures..

Public Health Relevance Statement:


Public Health Relevance:
Atrial fibrillation is a major heath concern and a primary cause of stroke and thromboembolism. Percutaneous cardiac catheter ablation is currently used to treat atrial fibrillation in order to eliminate a lifelong multidrug regimen but its main limitatio is high recurrence rate due to poor intra-procedural ablation monitoring. We propose develop and commercialize a new catheter-based imaging technology to directly see and monitor cardiac ablation lesions using endogenous tissue fluorescence to enable safer, faster, cheaper, and more reliable atrial fibrillation therapy.

Project Terms:
Ablation; Acute; Address; Animal Model; Animal Testing; Animals; Area; Arrhythmia; Atrial Fibrillation; base; Blood; Blood Vessels; Caliber; Cardiac; Cardiac ablation; Cardiac Myocytes; Catheters; cell injury; Cells; Chest; Clinical; clinically relevant; Coenzymes; Cold Therapy; Collagen; common treatment; compare effectiveness; Complex; cost effective; Data; design; Detection; Devices; Endocardium; Endoscopic Surgical Procedures; Environment; Family suidae; Fiber; flexibility; Fluorescence; Funding; Generations; Geometry; Goals; Heart; Heart Atrium; Heterogeneity; Histology; Image; Imagery; Imaging technology; injured; Injury; Institutes; Lasers; Lesion; Life; Light; Lighting; Link; Mainstreaming (Education); Measures; minimally invasive; Mitochondria; Monitor; Morbidity - disease rate; Mortality Vital Statistics; Muscle; Myocardial tissue; NADH; Operative Surgical Procedures; Oryctolagus cuniculus; Phase; Positioning Attribute; pre-clinical; Procedures; prototype; public health relevance; Pulmonary veins; Quality of life; radiofrequency; Radiofrequency Catheter Ablation; Radiofrequency Interstitial Ablation; Rattus; Recurrence; Regimen; Resolution; Rodent; Shapes; Site; Small Business Technology Transfer Research; Source; stroke; Surface; Techniques; Technology; Testing; Thermal Ablation Therapy; Thromboembolism; Time; Tissues; Ultraviolet Rays; UV sensitive; Validation; Width; Work

Atrial fibrillation (AF) remains the most commonly occurring cardiac arrhythmia. It is associated with a lower quality of life and a higher rate of morbidity & mortality primarily due to poor hemodynamics and often stroke. One of the main options to treat atrial fibrillation is to ablate abnormal sources of electrical activity using percutaneous radiofrequency (RF) catheters. RF lesions isolate the spread of abnormal electrical activity from various sites in the heart including the pulmonary veins. As a result, a cornerstone of therapy in AF ablation procedures is to electrically isolate the pulmonary veins (PVs) with RF lesions, essentially creating an electrical barrier between the arrhythmogenic foci inside the PVs and the rest of the heart. Often the cardiologist over- ablates or under-ablates leaving gaps which can still transmit the abnormal electrical activity to the rest of the heart. To date, there are limited means for real-time monitoring of tissue injury during RF ablation procedures and there are no means of directly visualizing ablated cardiac tissue to distinguish it from viable conducting tissue. Here we propose to create a new generation of imaging catheters to distinguish normal cardiac tissue from ablated cardiac tissue in real time. They operate based on spectral changes in tissue autofluorescence caused by thermal damage. Specifically, in Phase II we will expand the design of our current, 1st generation catheter, that relied on acquiring emission from a single spectral band, to include acquisition from multiple emission bands within an autofluorescence range of 380-600nm and to use post-acquisition analysis to reveal thermal damage to layers of endocardial collagen and underlying atrial muscle. The UV multispectral catheter will be then used to examine and visualize percutaneous RF ablation lesions in live large animals such as pigs. We also test on freshly excised donated human atrial tissue. The catheter will undergo extensive documentation, verification, and validation in order to be approved for use in a human study. Manufacturing process instructions will be developed and reviewed by the manufacturing partners who will construct, package, and sterilize the various catheter components. We will work with our clinical partners to develop a human study protocol, and will develop informed consent documentation, instructions for use, and other documentation necessary for ethics review and FDA approval. At the end of Phase II we aim to have a fully functional, statistically tested 12 Fr multispectral imaging catheter, approved and ready for first-in-man studies. Our ultimate long term goal is to develop a new generation of ablation catheters enabling real-time visualization of ablated cardiac tissue. This technology will pave the way for easier, faster, safer, more cost- effective, more reliable and minimally invasive AF ablation procedures by allowing cardiologists to see in real time if lesions are complete or if there are gaps that need to be filled in. in the case of a patient who has a recurrence post-ablation, the catheter will be used to quickly and efficiently identify where the gap is if one exists.

Public Health Relevance Statement:


Public Health Relevance:
Atrial fibrillation is a major health concern and a primary cause of stroke and thromboembolism. Percutaneous cardiac catheter ablation is currently used to treat atrial fibrillation in order to eliminate a lifelong multidrug regimen but its main limitaion is high recurrence rate due to poor intra-procedural ablation monitoring and the inability to visualize lesions directly. We propose to develop and commercialize a new generation of imaging catheters that enable direct real-time visualization of radiofrequency ablation lesions to achieve safer, faster, cheaper, and more reliable atrial fibrillation ablation therapy. .

Project Terms:
Ablation; Adhesives; Algorithms; Animals; Arrhythmia; Atrial Fibrillation; authority; Back; base; Blood; Cardiac; Cardiac ablation; Cartoons; Catheters; charge coupled device camera; Chest; Clinical; Collagen; cost effective; data acquisition; design; Documentation; Equilibrium; Ethics; Family suidae; Generations; Goals; Gray unit of radiation dose; Health; Heart; Heart Atrium; hemodynamics; Human; human study; Image; Image Analysis; Imagery; Individual; Industry; Informed Consent; Injury; Instruction; Left; Lesion; Libraries; Life; Light; Lighting; man; manufacturing process; Medical Device; meetings; Metals; minimally invasive; Monitor; Morbidity - disease rate; mortality; Muscle; Optics; Outcome; Pathology; Patients; Phase; Physicians; Principal Component Analysis; Procedures; Protocols documentation; prototype; public health relevance; Pulmonary veins; Qualifying; Quality of life; radiofrequency; Radiofrequency Catheter Ablation; Radiofrequency Interstitial Ablation; Recurrence; Regimen; Reporting; research study; Rest; Site; software development; Source; Speed; stroke; System; Technology; Testing; Thromboembolism; Time; Tissues; Ultraviolet Rays; UV sensitive; verification and validation; Work