MRI is a key modality in clinical care, with well over 150 million scans performed annually for diagnosis and treatment monitoring. Its major strengths are multi-contrast and the lack of ionizing radiation. However, its Achilles-heel is cost: typically millions of euros to purchase, site, and maintain, and also requires highly skilled technicians. As a result, MRI is available only in larger hospitals in the developed world, and unlike other imaging modalities plays little role in population screening. In the developing world, MRI systems are far too expensive and complex to purchase and maintain, and over 70% of the world’s population has zero access to MRI, which could be critical in treating diseases such as hydrocephalus, stroke, head trauma and viral infections. The aims of PASMAR are to develop new low-field MRI systems which will enable a role in medical screening in the developed world, as well as providing an affordable, sustainable and accessible platform for the developing world. The major thrust of PASMAR is methodological, designing new types of low-cost low-field systems for specific clinical applications, and optimizing all aspects of system performance to overcome the challenge of much lower MRI signal. I aim to develop, in consultation with clinical colleagues locally and via ongoing collaborations with engineers and clinicians in Africa, specialized systems which can be used for adult/pediatric brain, orthopedics and lung/spine scanning, as well as new types of inexpensive handheld ultra-lightweight surface scanners. These take advantage of the enormous flexibility of designing permanent magnet arrays with completely new geometries, targeted for specific organs. I will focus on portability to maximize patient reach and minimize siting requirements, accessibility via dramatically reduced system costs, and sustainability via modular and open source design to allow local maintenance and repair.

The incidence of cardiac arrhythmias in Europe is increasing because of aging and unexpected side effects of drugs, such as chemotherapeutics. To understand mechanisms underlying these conditions requires reliable preferably human models. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are presently good candidates since they share the genome of the individual from whom they are derived and can thus recapitulate genetic, ethnic and gender contributions to the cardiac disease phenotypes. However, their immature state and high inter- and intra-line variability is limiting their value as preclinical models. In the proposed project, I will address these issues through an interdisciplinary approach combining a unique 3D culture maturation system developed in my host lab with my expertise in electrophysiology. I will characterize gene expression and electrical properties of single cardiomyocytes simultaneously with view to directly correlating genes with function and identify molecular markers associated with the functionally mature cardiac phenotype. Two genetic cardiac diseases (one caused by an imprinted gene, the other by a postnatally expressed splice variant) for which the host already has hiPSC lines, will be used as proof of concept that hiPSC-CM maturation in this system is sufficient (i) to reveal disease phenotypes not evident in conventional culture and (ii) to identify molecular markers suitable for selecting mature hiPSC-CMs for drug testing. Overall, this project will provide the first functionally-relevant gene signature of (mature) hiPSC-CMs, and thus be an important advance in modelling all cardiomyocyte autonomous cardiac diseases more precisely for (personalized) drug screening. The outcome will be available to academic and private researchers to enhance rates of drug discovery and safety, and promote hiPSC-CMs as validated adult cardiac models to replace, at least in part, the use of animal models.