Novel stress T1-mapping applications for the assessment of cardiovascular disease

Cardiovascular disease (and particularly coronary artery disease and ischaemic heart disease) remains the leading cause of morbidity and mortality worldwide. There is increasing need for non-invasive imaging tests and biomarkers that could allow early therapeutic interventions and help risk-stratify and prognosticate to improve individual outcomes. Cardiovascular magnetic resonance (CMR) is a powerful non-invasive and radiation-free imaging tool that can comprehensively evaluate cardiac structure, function, and ischaemia, and allows advanced myocardial tissue characterisation. Stress T1-mapping is a promising contrast-free CMR application that assesses coronary vasodilatory reserve and has shown utility in the non-invasive assessment of cardiovascular disease during adenosine vasodilator stress. However, this field has not progressed beyond original proof-of-principle studies, is limited by method sensitivity and choice of pharmacological stress agent, and has not been validated against gold standard invasive coronary physiology. This Thesis addresses these issues by performing further clinical validation and method development work towards standardising the technique across a range of T1-mapping methods and stress agents.
I first built on the existing adenosine stress T1-mapping proof-of-principle groundwork by performing further clinical validation. This was done in a cohort of patients with end-stage renal disease (ESRD) referred for kidney transplantation, who are most likely to benefit from a non-invasive and contrast-free imaging assessment for cardiovascular disease. I demonstrated for the first time that stress T1-mapping has good diagnostic performance for the detection of obstructive coronary artery disease (CAD) in patients with ESRD, as validated against invasive coronary physiology in a systematic study.
I next explored the feasibility of stress T1-mapping using alternative pharmacological stress agents. I demonstrated that regadenoson (a ‘coronary-specific’, selective A2A receptor agonist vasodilator) is a viable alternative for stress T1-mapping applications by modelling regadenoson stress T1 dynamics over time in healthy volunteers. I also directly compared the performance and variability of commonly used T1-mapping methods (ShMOLLI and MOLLI variants) for stress and post-contrast T1-mapping. I showed that ShMOLLI stress T1-mapping has the strongest relationship with quantitative myocardial blood flow and has a greater effect size with less variability compared to the other T1-mapping methods tested. I then applied this in a cohort of patients with CAD and showed that regadenoson stress T1-mapping has similar clinical efficacy to adenosine for detecting obstructive CAD and differentiating between normal, remote, ischaemic, and infarcted myocardium.
Finally, I demonstrated the suitability of alternative pharmacological stress agents (dobutamine and dipyridamole) for future stress T1-mapping applications, which included successful translation of the technique to an external international centre. I showed that dobutamine and dipyridamole are both viable and potentially cost-effective stress agents to use for stress T1-mapping.
Overall, this Thesis reports on further development of the highly promising and novel stress T1-mapping technique for the assessment of cardiovascular disease without contrast agents, including clinical validation against invasive coronary physiology, clinical application in patients with CAD, and method comparison across a range of commonly used pharmacological stress agents and T1-mapping techniques.

Keywords: cardiovascular magnetic resonance
T1-mapping
cardiovascular disease
cardiology
Advisor: Ferreira, V
Piechnik, S
Neubauer, S