Jackson, LH; (2017) Cardiac Imaging for Regenerative Therapy and Tissue Engineering. Doctoral thesis , UCL (University College London).

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Abstract

Cardiovascular disease remains the number 1 cause of death worldwide. Over the past 20 years, therapies for treating cardiac disease have come of age and coronary heart disease in particular has seen a revolution in new treatments such as statins, stents and beta blockers. These therapies have slowed death rates and have shown potential to minimise ischemia induced atrophy following myocardial infarction. Crucially however, they are unable to recover lost heart function due to cardiomyocyte death, resulting in poor prognosis for patients. Myocardial regeneration therapy is a new strategy towards treating cardiac disease that engrafts regenerative cells and biomaterials to the myocardium to stimulate repair of tissue and restore contractile function. Cardiac regeneration therapy has made a rapid translation from preclinical research to clinical trials with the first trial in humans published in 2001. Clinical trials in the years since however have produced underwhelming results and there is a general consensus that further preclinical optimisation with powerful non-invasive imaging data will be key to the future success of regenerative medicine in humans. Magnetic resonance imaging is unparalleled in providing non-invasive multiparametric imaging of both global and regional cardiac structure and function. MRI provides high spatiotemporal resolution and multiple contrast mechanisms revealing information about molecular changes in the myocardium. These imaging abilities make MRI a versatile and powerful tool in the preclinical optimisation of cardiac regeneration therapies. Over the chapters presented in this thesis I have established a set of MR imaging techniques that enable valuable in vivo characterisation of cardiac function and structure in for use in studies of regenerative therapy. It is hoped that the methods developed over the course of this thesis aid in the uptake of imaging applications in studies of regenerative medicine and that the wide range of imaging tools demonstrated help to bring regenerative medicine closer to practical clinical therapy.

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