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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL071762-03
Application #
6914972
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Program Officer
Lathrop, David A
Project Start
2003-07-15
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
3
Fiscal Year
2005
Total Cost
$266,000
Indirect Cost
Name
Upstate Medical University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210
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Mitrea, Bogdan G; Caldwell, Bryan J; Pertsov, Arkady M (2011) Imaging electrical excitation inside the myocardial wall. Biomed Opt Express 2:620-33
Caldwell, Bryan J; Wellner, Marcel; Mitrea, Bogdan G et al. (2010) Probing field-induced tissue polarization using transillumination fluorescent imaging. Biophys J 99:2058-66
Mitrea, Bogdan G; Wellner, Marcel; Pertsov, Arkady M (2009) Monitoring intramyocardial reentry using alternating transillumination. Conf Proc IEEE Eng Med Biol Soc 2009:4194-7
Zemlin, Christian W; Mitrea, Bogdan G; Pertsov, Arkady M (2009) Spontaneous onset of atrial fibrillation. Physica D 238:969-975
Danko, Charles G; Pertsov, Arkady M (2009) Identification of gene co-regulatory modules and associated cis-elements involved in degenerative heart disease. BMC Med Genomics 2:31
Walton, Richard D; Mitrea, Bogdan G; Pertsov, Arkady M et al. (2009) A novel near-infrared voltage-sensitive dye reveals the action potential wavefront orientation at increased depths of cardiac tissue. Conf Proc IEEE Eng Med Biol Soc 2009:4523-6
Matiukas, Arvydas; Pertsov, Arkady M; Kothari, P et al. (2009) Optical mapping of electrical heterogeneities in the heart during global ischemia. Conf Proc IEEE Eng Med Biol Soc 2009:6321-4
Zemlin, Christian W; Bernus, Olivier; Matiukas, Arvydas et al. (2008) Extracting intramural wavefront orientation from optical upstroke shapes in whole hearts. Biophys J 95:942-50

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