This project will develop manganese-enhanced MRI (Magnetic Resonance Imaging; MEMRI) as a high-resolution imaging method to monitor heart repair. MEMRI detects functional heart muscle by tracking manganese uptake through calcium channels, offering a safer and more precise alternative to current techniques.
Using in vivo models, we will test whether new heart tissue formed by regenerative therapies is functional. This approach could provide a powerful biomarker for evaluating cardiac repair in future clinical trials.
Challenges
Clinical translationOrganisations
- University College London
- University of Edinburgh
- King's College London
In depth
Effective translation of the therapeutics developed in REACT will require in vivo monitoring of safety and efficacy. MRI, CT and ultrasound have been used to follow cardiac function in clinical and preclinical trials of cell therapies but have not been used to evaluate changes in myocardial viability. Radionuclide imaging methods can quantify myocardial metabolism, but are low resolution, require exposure to ionising radiation, and reflect the viability of all cell types within the heart, not just the cardiomyocytes.
We will develop manganese-enhanced MRI (MEMRI) as a high resolution and translational imaging method for evaluating the extent and functionality of newly formed myocytes in our in vivo heart models. Manganese uptake occurs through voltage-gated calcium channels and thus reflects myocyte contractility.
We first want to compare the MEMRI to histological techniques when we serial quantify myocardial function. We will also stimulate myocyte proliferation in an in vivo model of chronic myocardial infarction and follow functional regeneration using MEMRI. This means that MEMRI could be a bespoke imaging biomarker to endogenous myocardial regeneration which could be used as a surrogate endpoint in clinical trials.