Triple-marker cardiac MRI detects sequential tissue changes of healing myocardium after a hydrogel-based therapy

Regenerative therapies based on injectable biomaterials, hold an unparalleled potential for treating myocardial ischemia. Yet, noninvasive evaluation of their efficacy has been lagging behind. Here, we report the development and longitudinal application of multiparametric cardiac magnetic resonance imaging (MRI) to evaluate a hydrogel-based cardiac regenerative therapy. A pH-switchable hydrogel was loaded with slow releasing insulin growth factor 1 and vascular endothelial growth factor, followed by intramyocardial injection in a mouse model of ischemia reperfusion injury. Longitudinal cardiac MRI assessed three hallmarks of cardiac regeneration: angiogenesis, resolution of fibrosis and (re)muscularization after infarction. The multiparametric approach contained dynamic contrast enhanced MRI that measured improved vessel features by assessing fractional blood volume and permeability*surface area product, T(1)-mapping that displayed reduced fibrosis, and tagging MRI that showed improved regional myocardial strain in hydrogel treated infarcts. Finally, standard volumetric MRI demonstrated improved left ventricular functioning in hydrogel treated mice followed over time. Histology confirmed MR-based vessel features and fibrotic measurements. Our novel triple-marker strategy enabled detection of ameliorated regeneration in hydrogel treated hearts highlighting the translational potential of these longitudinal MRI approaches.