Advancing optical imaging of electrical activation and repolarisation of the heart using genetically altered models

Project completed 2014.

Supervisors:
Professor Steve Watson, Institute of Cardiovascular Sciences
Dr Larissa Fabritz, Institute of Cardiovascular Sciences
Dr Brenda Finney, Institute of Cardiovascular Sciences
Dr Hamid Dehghani, School of Computer Sciene
Professor Zoe Pikramenou, School of Chemistry

The main aim of this project is to develop a high speed optical mapping system to study cardiac electrophysiology. This includes development of hardware and software. Optical mapping is a fluorescence technique where a sample is loaded with a voltage sensitive dye which alters intensity according to the potential of the cell membrane. These changes in voltage give rise to action potential signals. The importance of changes in membrane voltage is indicative of multiple events occurring in numerous ion channels. These events also occur at high speed and the fluorescence intensity changes are very small hence the need for high speed imaging and quantum efficiencies. Analysis of these images includes the development of isochronal mapping to determine patterns of activation, and also the measurement of conduction velocities. The general outcome of this system is to aid in the studies of common arrhythmias afflicting the general population such as atrial fibrillation.

The development of this imaging system requires many novel methods to face several challenges to ever increase spatial and temporal resolution. The design mainly focuses on use of a second generation CMOS camera coupled with novel algorithms to generate isochronal maps and action potential duration measurements with little user input required during analysis to eliminate as much bias as possible. These algorithms are written on the MATLAB platform and can perform a multitude of automated steps to negate the effects of noise, low signal quality, and baseline drift correction from photo bleaching. Thus far this system has yielded promising results and much potential for use in preclinical experimentation.

Link to ethesis: http://etheses.bham.ac.uk/6744/