The objective of this project is to develop a system to optically record fluorescence signals from heart tissues in vivo. Fluorescent dyes have been used to record biological processes from the heart for more than a decade. Specifically, staining the heart with voltage-sensitive dyes -which emit fluorescence that varies with the membrane potential-and using high-speed cameras has allowed investigators to track propagation of the electrical impulse in normal and abnormal conditions, and to elucidate the mechanisms of heart rhythm disorders. The technique has been expanded to map other biological processes, such as intracellular calcium, mitochondrial depolarization, and others. However, the technique has been limited to the explanted heart, or ex vivo heart tissues or cells. Evaluation and treatment of heart rhythm disorders requires the clinician to assess propagation of the cardiac electrical impulse in vivo. Available clinical systems are limited to collecting extracellular electrical field signals from electrodes inserted in the heart, which provide extremely low spatial resolution. Cardiofocus(R) has developed a prototype endoscopic catheter designed to enable in vivo light delivery and collection for visualization of heart tissues. The system contains all the necessary components to excite and collect fluorescence signals. We propose to develop the catheter to record in vivo optical fluorescence signals, and to validate it to map propagation of the electrical impulse and other biological processes in the heart.
Aim #1 is to maximize fluorescent dye loading in heart tissues in vivo and evaluate potential dye toxicity. Different routes of dye delivery (intra-arterial, intra-venous, or pericardial), loading protocols, and systemic effects will be evaluated in vivo swine models.
Aim#2 is to optimize the optical components of the catheter system and maximize light transmission for dye excitation and fluorescence collection. Building up on our current clinical prototype, we will optimize light sources, fiber optics, and balloon construction to maximize fluorescence recordings.
Aim #3 is to delineate, in pigs, the role of pulmonary vein activations in cholinergic atrial fibrillation in vivo as a first validation of the technique.
Current techniques for evaluating heart rhythm disorders rely on multi-electrode catheters to record electrical signals from different cardiac sites, and have poor spatial resolution to map electrical propagation patterns. Fluorescent dyes have allowed to record simultaneous recordings from thousands of sites in ex vivo cardiac preparations. We propose to adapt a cardiac endoscopic catheter for recording cardiac fluorescent signals in vivo and hope that such a catheter will allow detailed understanding of cardiac rhythm disorders, particularly atrial fibrillation, the most common one, and may assist in new therapy developments.
