Noninvasive Immunometabolic Cardiac Inflammation Imaging Using Hyperpolarized Magnetic Resonance. Issue 8 (13th April 2018)

• Record Type: Journal Article
• Authors: Lewis, Andrew J.M.; Miller, Jack J.; Lau, Angus Z.; Curtis, Mary K.; Rider, Oliver J.; Choudhury, Robin P.; Neubauer, Stefan; Cunningham, Charles H.; Carr, Carolyn A.; Tyler, Damian J.
• Is Part Of: Circulation research. Volume 122:Issue 8(2018)
• Publication Date: 2018-04-13
• Subjects: animals -- cell line -- magnetic resonance imaging -- monocytes -- myocardial infarction; Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.117.312535
• Languages: English
• ISSNs: 0009-7330

Abstract

Abstract : Rationale: : Current cardiovascular clinical imaging techniques offer only limited assessment of innate immune cell-driven inflammation, which is a potential therapeutic target in myocardial infarction (MI) and other diseases. Hyperpolarized magnetic resonance (MR) is an emerging imaging technology that generates contrast agents with 10- to 20 000-fold improvements in MR signal, enabling cardiac metabolite mapping. Objective: : To determine whether hyperpolarized MR using [1- 13 C]pyruvate can assess the local cardiac inflammatory response after MI. Methods and Results: : We performed hyperpolarized [1- 13 C]pyruvate MR studies in small and large animal models of MI and in macrophage-like cell lines and measured the resulting [1- 13 C]lactate signals. MI caused intense [1- 13 C]lactate signal in healing myocardial segments at both day 3 and 7 after rodent MI, which was normalized at both time points after monocyte/macrophage depletion. A near-identical [1- 13 C]lactate signature was also seen at day 7 after experimental MI in pigs. Hyperpolarized [1- 13 C]pyruvate MR spectroscopy in macrophage-like cell suspensions demonstrated that macrophage activation and polarization with lipopolysaccharide almost doubled hyperpolarized lactate label flux rates in vitro; blockade of glycolysis with 2-deoxyglucose in activated cells normalized lactate label flux rates and markedly inhibited the production of key proinflammatory cytokines. Systemic administration of 2-deoxyglucose after rodent MI normalized the hyperpolarized [1- 13 C]lactate signal in healing myocardial segments at day 3 and also caused dose-dependent improvement in IL (interleukin)-1β expression in infarct tissue without impairing the production of key reparative cytokines. Cine MRI demonstrated improvements in systolic function in 2-DG (2-deoxyglucose)–treated rats at 3 months. Conclusions: : Hyperpolarized MR using [1- 13 C]pyruvate provides a novel method for the assessment of innate immune cell-driven inflammation in the heart after MI, with broad potential applicability across other cardiovascular disease states and suitability for early clinical translation. Abstract : Supplemental Digital Content is available in the text.