MRI evaluation of injectable hyaluronic acid-based hydrogel therapy to limit ventricular remodeling after myocardial infarction.
Injectable biomaterials are an attractive therapy to attenuate left ventricular (LV) remodeling after myocardial infarction (MI). Although studies have shown that injectable hydrogels improve cardiac structure and function in vivo, temporal changes in infarct material properties after treatment have not been assessed. Emerging imaging and modeling techniques now allow for serial, non-invasive estimation of infarct material properties. Specifically, cine magnetic resonance imaging (MRI) assesses global LV structure and function, late-gadolinium enhancement (LGE) MRI enables visualization of infarcted tissue to quantify infarct expansion, and spatial modulation of magnetization (SPAMM) tagging provides passive wall motion assessment as a measure of tissue strain, which can all be used to evaluate infarct properties when combined with finite element (FE) models. In this work, we investigated the temporal effects of degradable hyaluronic acid (HA) hydrogels on global LV remodeling, infarct thinning and expansion, and infarct stiffness in a porcine infarct model for 12 weeks post-MI using MRI and FE modeling. Hydrogel treatment led to decreased LV volumes, improved ejection fraction, and increased wall thickness when compared to controls. FE model simulations demonstrated that hydrogel therapy increased infarct stiffness for 12 weeks post-MI. Thus, evaluation of myocardial tissue properties through MRI and FE modeling provides insight into the influence of injectable hydrogel therapies on myocardial structure and function post-MI.
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Shauna M
SM
Dorsey
Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jeremy R
JR
McGarvey
Department of Mechanical Engineering, University of Kentucky, Lexington, KY 40506, USA.
Hua
H
Wang
Department of Mechanical Engineering, University of Kentucky, Lexington, KY 40506, USA.
Amir
A
Nikou
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Leron
L
Arama
Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kevin J
KJ
Koomalsingh
Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA.
Norihiro
N
Kondo
Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA.
Joseph H
JH
Gorman
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
James J
JJ
Pilla
Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA.
Robert C
RC
Gorman
Department of Mechanical Engineering, University of Kentucky, Lexington, KY 40506, USA; Department of Surgery, University of Kentucky, Lexington, KY 40506, USA.
Jonathan F
JF
Wenk
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: burdick2@seas.upenn.edu.
Jason A
JA
Burdick
D000818:Animals; D020342:Finite Element Analysis; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage / Q000627:therapeutic use*; D007267:Injections; D008279:Magnetic Resonance Imaging; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D013552:Swine; D020257:Ventricular Remodeling / Q000187:drug effects*
D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid
Finite element analysis; Hyaluronic acid; Hydrogel; Left ventricular remodeling; Magnetic resonance imaging; Mechanical properties