Hyperpolarized sensors for probing metabolism in microfluidic organ-on-chip platforms

Hyperpolarized (HP) magnetic resonance imaging has emerged as a promising method for probing the biological characteristics of living tissue. A sensor molecule (e.g. pyruvate, fumarate, acetate) is hyperpolarized and injected into a patient, and the resulting metabolic flux can be used to assess cell viability, tumour response to therapy, and perform pH mapping, to name a few examples. Two significant barriers stand in the way of the widespread implementation of HP imaging: (1) the current hyperpolarization method, dissolution dynamic nuclear polarization (dDNP) is cumbersome, expensive, and requires expertise to operate the equipment, and; (2) preclinical method development relies heavily on the use of animal models which inhibits rapid screening of experiments. To overcome these limitations, in this project I will: (1) implement parahydrogen-induced polarization as the hyperpolarization method, which is significantly cheaper, easier to use, and can produce the hyperpolarized metabolites at a higher rate than dDNP, and; (2) perform the hyperpolarized imaging in organ-on-a-chip devices, which closely mimic in vivo conditions but allow for experiments to be performed at a greater rate, and can use human tissue as opposed to animal tissue to more closely mimic real conditions. The specific focus in this project will be to investigate whether HP metabolic imaging can provide insight into the progression of muscular dystrophy in human muscle tissue.