Development of new NIR probes to study human cardiac excitation

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DESCRIPTION (provided by applicant): This project is a collaboration between SUNY Upstate Medical University and Kaunas Medical University, Lithuania. The goal of the collaboration is to extend to human tissues novel optical imaging techniques for visualization of electrical activity in the heart and to explore its potential for clinical applications. This project is an extension of a partnership grant in Bioengineering Research (NIH Grant No. 5R01HL07163501) involving the research groups of Dr. A. Pertsov (PI) at SUNY Upstate Medical University, Dr. D. Boas at the Massachusetts General Hospital NMR Center, Dr. L. Loew at the University of Connecticut Health Center (Co-PI), and the group of Dr. D. Weitz at Harvard University (Co-PI). The new technology will utilize diffusive optical tomography and novel near infrared (NIR) voltage-sensitive dyes. The specific aims of the project are: (i) To measure optical properties of human cardiac tissues, such as absorption and scattering, necessary for solving the forward problem (key element of the reconstruction). To study characteristics (membrane binding and voltage sensitivity) of novel styryl NIR voltage-sensitive dyes with optimized lipophilic tails in human cardiac myocytes/tissues. To optimize excitation/emission filters and dye loading protocols for human studies; (ii) To assess any acute toxicity and phototoxicity of voltage-sensitive dyes in isolated human cardiac myocytes and in cardiac tissue; (iii) To conduct pilot optical mapping studies of excitation wave propagation in isolated human cardiac tissue and explanted heart. The proposed study will benefit US cardiac research by providing unique knowledge about the performance of NIR voltage-sensitive dyes in human cardiac tissues. By having a collaboration with the US, the first optical mapping system in Lithuania will be built. Lithuanian collaborators will be trained in state-of-the-art optical mapping techniques, thus advancing Lithuanian cardiac research. In conclusion, a successful collaboration will result in the development of a novel cardiac imaging technology, the first step towards its clinical application. It will also provide a solid basis for further mutually beneficial international cooperation. PUBLIC HEALTH RELEVANCE: The treatment of dangerous cardiac arrhythmias relies on accurate electrophysiological identification (mapping) of pathological regions of myocardium that are subsequently removed using radio- frequency ablation. This international collaboration is intended to explore a new mapping technology utilizing near-infrared fluorescent voltage-sensitive molecular probes, which bind to cell membranes and change fluorescence according to membrane potential. The new technology should have a significant advantage over conventional mapping utilizing electrical recordings by increasing the resolution and speeding up the identification of ablation targets.