Developing ex vivo mri models to characterise the individual tissue characteristics driving normal propagation and arrhythmias in the equine heart

Background

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

Our interdisciplinary team aims to use novel imaging techniques to elucidate the relationships between structure and function in the equine athletic heart, in health and disease.  This PhD will deliver fibre pattern and structural data to underpin our work, with specific relevance to 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.  We have preliminary data using diffusion tensor MRI (DT-MRI), demonstrating the feasibility of this technique in large tissues such as the equine heart and showing the fibre arrangement that underpins the mechanical function in the equine ventricles and atrium.  This imaging technique offers the opportunity to perform ‘virtual histology’, identifying areas of myofibre disarray, such as that produced by tissue fibrosis.  This MRI data will be combined with source data from other modalities such as ultrasound and electranatomic mapping to begin our plans to generate three-dimensional anatomically accurate computational models, so called ‘digital twins’.  These can be population-based to investigate cardiac disease from a general perspective and/or may be tailored to specific patients and potentially used to guide individualised treatment plans.¹⁷

Aims

The specific aims of this PhD project centre around static ex vivo MRI imaging to:

• Create an equine atrial and ventricular, anatomic and fibre tract, three-dimensional atlas
• Combine structural data from the MRI with structural and functional data from electroanatomic mapping and or echocardiography (carried out by the team prior to euthanasia) to start the process of creating a three-dimensional equine heart model that can be used as the template for developing individualized cardiac digital twins

Broader aims of this work are to:

• Determine the relationship between normal electrical propagation (as assessed by in vivo electroanatomic mapping) and myofiber tracts (as assessed by ex vivo MRI) in the equine atrium
• Determine 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

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