Interdependence of structure and function: using MRI to determinine the individual tissue characteristics driving atrial fibrillation in the equine heart

Background

Many clinically normal large breed athletic horses develop atrial fibrillation (AF), which leads to clinically significant health, performance, and safety (for horse riding) problems.  The reason why some large breed horses develop AF and others don’t is poorly understood but believed to be due to undetermined individual atrial tissue and/or electrical characteristics, whereby longstanding atrial enlargement and/or dysfunction causes remodelling of atrial tissue microstructure.  The ensuing development of tissue fibrosis and myofibre dissaray is thought to cause conduction anisotropy, rendering the tissue more susceptible to fibrillation.

This PhD will work in our group investigating the relationship between microstructure and electrical function in the equine heart.  The candidate will engage in a programme of work developing and analysing MRI data from stored and contemporaneously collected equine hearts, imaged ex vivo.  Cardiac MRI is an emerging tool that can provide detailed information on cardiac structure, including microstructure.  Cardiac MRI is not currently feasible in live horses but ex vivo techniques have the potential to inform studies on basic cardiac microstructure and to provide insight into the tissue determinants of normal and abnormal electrophysiology.  Our group has acquired preliminary data using diffusion tensor MRI (DT-MRI), demonstrating the feasibility of this technique in large tissues such as the equine heart, showing the fibre arrangement that underpins the mechanical function in the equine ventricles.  Additionally, we have preliminary data using DT-MRI for evaluating tissue fibre orientation in the left atrium.  This imaging technique offers the opportunity to perform ‘virtual histology’, identifying areas of myofibre disarray, such as that produced by tissue fibrosis.

Aims

This PhD will be part of a larger programme of work, aiming to resolve the relationship between microstructure and electrical function, in health or disease, by:

• Using static ex vivo MRI evaluation to create an equine atrial and ventricular, anatomic and fibre tract, three-dimensional atlas
• Determining the relationship between the electrical propagation (as assessed by in vivo electroanatomic mapping) and myofiber tracts (as assessed by ex vivo MRI) in the equine atrium
• Determining the relationship between electrical dysfunction (as assessed by voltage mapping and conduction velocity in vivo), microstructural disarray (MRI ex vivo) and fibrosis (histology in vitro).

Training outcomes for the candidate

• Critical thinking, scientific methodology, statistical analytical methods, scientific writing and presentation skills
• MRI protocol development and image acquisition
• Strong grasp of programming skills in python, and ideally some experience with MRTrix or similar command-line data processing