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

Sci Rep. 2019 Dec 18;9(1):19366. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / pharmacology
  • Disease Models, Animal
  • Heart / diagnostic imaging*
  • Heart / drug effects
  • Humans
  • Hydrogels / pharmacology*
  • Hydrogen-Ion Concentration
  • Insulin-Like Growth Factor I / pharmacology
  • Mice
  • Myocardial Ischemia / diagnostic imaging*
  • Myocardial Ischemia / drug therapy
  • Myocardial Ischemia / pathology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / genetics
  • Regenerative Medicine
  • Vascular Endothelial Growth Factor A / pharmacology

Substances

  • Biocompatible Materials
  • Hydrogels
  • Vascular Endothelial Growth Factor A
  • insulin-like growth factor-1, mouse
  • Insulin-Like Growth Factor I