Depth-resolved imaging of myocardial excitation

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DESCRIPTION (provided by applicant): Understanding the mechanisms that underlie abnormalities of electrical conduction in the heart is the key to the development of effective antiarrhythmic therapies. During the last decade, significant progress has been made in imaging electrical excitation waves in the heart using voltage-sensitive fluorescent dyes. However, until recently imaging that uses voltage-sensitive dyes was limited primarily to the epicardial surface. Therefore the design of tools for visualization of electrical activity inside the myocardial wall is likely to have a major impact on the field. The ultimate goal of the proposed studies is to develop a new optical imaging technology for detecting sources of arrhythmia hidden inside the myocardial wall. The new technology will combine methods of diffusive optical tomography with specific knowledge of electrical processes in the heart and their characteristics. The first major step towards our main objective will be to create a family of realistic tissue-specific and dye-specific computer models for reconstructing optical images from 3D distributions of the transmembrane potential in myocardial tissue (forward problem). Using this methodology, termed below virtual optical imaging (VOI), we will create a web-accessible library containing the optical signatures of major types of activation patterns. The solution of the forward problem will provide key elements for solving the inverse problem - reconstructing 3D distributions of the transmembrane potential from optical signals. The specific aims of the project are: 1) To develop a realistic model of light transport in myocardial tissue based on direct measurements of light absorption and scattering. 2) To couple the light transport model to a model of electrical wave propagation. The combination will predict voltage-dependent optical signals during normal propagation and 3-dimensional reentrant activity. 3) To develop and validate experimental techniques and deconvolution algorithms for imaging intramural sources of excitation including ectopic foci producing radial spread of excitation, and scroll wave filaments - the organizing centers of 3D reentrant activity in myocardial tissue. Successful completion of the project should significantly improve ones ability to interpret optical recordings and will ultimately enable depth-resolving detectors for imaging the intramural sources underlying the most lethal arrhythmias.