Clinical translation of hyperpolarized magnetic resonance for cardiovascular and metabolic diseases

• Main Author: Lewis, Andrew
• Other Authors: Neubauer, Stefan ; Rider, Oliver ; Tyler, Damian
• Published: University of Oxford 2017
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.729304

Cardiovascular diseases continue to pose an unacceptable societal burden, mandating the development of new and improved methods for their diagnosis, monitoring and treatment. Current cardiovascular magnetic resonance imaging techniques provide exquisite structural and functional information, but their ability to assess the molecular processes underlying cardiac function in health and disease is limited by inherent insensitivity. Hyperpolarized magnetic resonance is a new technology which overcomes this limitation, creating molecular contrast agents with an improvement in magnetic resonance signal of up to five orders of magnitude. One key molecule, hyperpolarized [1-¹³C]pyruvate, shows particular promise for the assessment of cardiac energy metabolism and other fundamental biological processes with clinical relevance. This thesis describes a programme of translational research in hyperpolarized magnetic resonance conducted with the aims of identifying priority disease states for translational hyperpolarized MR studies, and of enabling first human cardiovascular studies using the technique. We identify important and new potential roles for hyperpolarized magnetic resonance in both the diagnosis, and potentially treatment, of heart disease associated with metabolic diseases and also in ischaemic heart disease. Hyperpolarized [1-¹³C]pyruvate also has high potential for rapid clinical translation from the laboratory to patients with cardiovascular disease, though the production and administration of clinical-grade hyperpolarized molecules poses significant challenges. We present strategies to overcome these challenges, and describe the first human cardiovascular experience with hyperpolarized magnetic resonance.