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

Maaike Van Den Boomen,Carlijn V C Bouten,Hans C Van Assen,Patricia Y W Dankers,Katrien Vandoorne,Hanne B Kause

doi:10.1038/s41598-019-55864-7

Abstract

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, T1-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.

Highlights

Regenerative therapies based on injectable biomaterials, hold an unparalleled potential for treating myocardial ischemia
We showed that a local catheter injection of this UPy-hydrogel into porcine hearts after myocardial infarction (MI) allowed local release of hepatocyte growth factor (HGF) and insulin growth factor 1 (IGF1) reducing the size of the infarct scar[14]
The UPyGF-hydrogel loaded with IGF1 and vascular endothelial growth factor (VEGF) was intramyocardially injected at two locations at the border of the ischemic area 2 min before reperfusion (Fig. 1b)

Summary

Introduction

Regenerative therapies based on injectable biomaterials, hold an unparalleled potential for treating myocardial ischemia. We report the development and longitudinal application of multiparametric cardiac magnetic resonance imaging (MRI) to evaluate a hydrogel-based cardiac regenerative therapy. The multiparametric approach contained dynamic contrast enhanced MRI that measured improved vessel features by assessing fractional blood volume and permeability*surface area product, T1-mapping that displayed reduced fibrosis, and tagging MRI that showed improved regional myocardial strain in hydrogel treated infarcts. We showed that a local catheter injection of this UPy-hydrogel into porcine hearts after MI allowed local release of hepatocyte growth factor (HGF) and IGF1 reducing the size of the infarct scar[14]. Albumin-based dynamic contrast enhanced (DCE) MRI allows noninvasive assessment of vascular density and permeability, which are both vessel features that could indicate angiogenesis[19,20]. Tagging MRI to measure strain, indicates local (re)muscularization[23]

Methods

Results

Conclusion