Molecular Imaging of Inflammation and Extracellular Matrix Remodelling After Myocardial Infarction

Abstract

Myocardial infarction (MI) and associated morbidity and mortality is one of the major health care problems in western societies. Magnetic resonance imaging (MRI) has great potential for quantification of key biological processes post MI, such as inflammatory cell recruitment and extracellular matrix (elastin and collagen deposition) remodelling with the use of novel target specific contrast agents. During the acute phase following MI, the degree and duration of the inflammatory response critically affects myocardial remodelling and cardiac function. 19F perfluorocarbons (PFCs) uptaken by inflammatory cells allow direct detection and quantification of the temporal and spatial evolution of the inflammatory response in the injured myocardium. During the maturation phase, the synthesis of elastin and collagen, important ECM proteins, is upregulated. De novo elastin synthesis can be imaged by MRI using an elastin-specific contrast agent (Gd-ESMA). In this study, we explored the merits of multinuclear 1H/19F MRI for the simultaneous assessment and quantification of cardiac inflammation and elastin deposition in a murine model of MI in wild-type and knockout animals. 19F containing particles, uptaken by macrophages, were used to investigate inflammatory cell recruitment into injured myocardium and Gd-ESMA was used to evaluate changes in elastin content in the ECM post-MI.

Date of Award	1 Nov 2017
Original language	English
Awarding Institution	King's College London
Supervisor	Rene Botnar (Supervisor) & Ajay Shah (Supervisor)