Imaging Regional Metabolic Changes in the Ischemic Rat Heart In Vivo Using Hyperpolarized [1-C]Pyruvate

Overview

Journal Tomography

Publisher MDPI

Specialty Radiology

Date 2018 Jul 26

PMID 30042976

Authors

Mette Hauge Lauritzen

Peter Magnusson

Christoffer Laustsen

Sadia Asghar Butt

Jan Henrik Ardenkjaer-Larsen

Lise Vejby Sogaard

Olaf B Paulson

Per Akeson

Affiliations

Soon will be listed here.

Abstract

We evaluated the use of hyperpolarized C magnetic resonance imaging (MRI) in an open-chest rat model of myocardial infarction to image regional changes in myocardial metabolism. In total, 10 rats were examined before and after 30 minutes of occlusion of the left anterior descending coronary artery using hyperpolarized [1-C]pyruvate. Cardiac metabolic images of [1-C]pyruvate and its metabolites [1-C]lactate, [1-C]alanine, and [C]bicarbonate were obtained before and after ischemia. Significant reduction in the [1-C]alanine and [1-C]lactate signals were observed in the ischemic region post ischemia. The severity of the ischemic insult was verified by increased blood levels of troponin I and by using late contrast-enhanced MRI that showed enhanced signal in the ischemic region. This study shows that hyperpolarized MRI can be used to image regional metabolic changes in the in vivo rat heart in an open-chest model of ischemia reperfusion. Hyperpolarized MRI enables new possibilities for evaluating changes in cardiac metabolism noninvasively and in real time, which potentially could be used for research to evaluate new treatments and metabolic interventions for myocardial ischemia and to apply knowledge to future application of the technique in humans.

References

Ball D, Cruickshank R, Carr C, Stuckey D, Lee P, Clarke K . Metabolic imaging of acute and chronic infarction in the perfused rat heart using hyperpolarised [1-13C]pyruvate. NMR Biomed. 2013; 26(11):1441-50. DOI: 10.1002/nbm.2972. View

Ye J, Yang L, Sethi R, Copps J, Ramjiawan B, Summers R . A new technique of coronary artery ligation: experimental myocardial infarction in rats in vivo with reduced mortality. Mol Cell Biochem. 1997; 176(1-2):227-33. View

Lauritzen M, Laustsen C, Butt S, Magnusson P, Sogaard L, Ardenkjaer-Larsen J . Enhancing the [13C]bicarbonate signal in cardiac hyperpolarized [1-13C]pyruvate MRS studies by infusion of glucose, insulin and potassium. NMR Biomed. 2013; 26(11):1496-500. DOI: 10.1002/nbm.2982. View

Schroeder M, Swietach P, Atherton H, Gallagher F, Lee P, Radda G . Measuring intracellular pH in the heart using hyperpolarized carbon dioxide and bicarbonate: a 13C and 31P magnetic resonance spectroscopy study. Cardiovasc Res. 2009; 86(1):82-91. PMC: 2836261. DOI: 10.1093/cvr/cvp396. View

Schroeder M, Clarke K, Neubauer S, Tyler D . Hyperpolarized magnetic resonance: a novel technique for the in vivo assessment of cardiovascular disease. Circulation. 2011; 124(14):1580-94. PMC: 3189851. DOI: 10.1161/CIRCULATIONAHA.111.024919. View

JOHNS T, Olson B . Experimental myocardial infarction. I. A method of coronary occlusion in small animals. Ann Surg. 1954; 140(5):675-82. PMC: 1609650. DOI: 10.1097/00000658-195411000-00006. View

Neely J, Morgan H . Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. Annu Rev Physiol. 2009; 36:413-59. DOI: 10.1146/annurev.ph.36.030174.002213. View

Schroeder M, Atherton H, Ball D, Cole M, Heather L, Griffin J . Real-time assessment of Krebs cycle metabolism using hyperpolarized 13C magnetic resonance spectroscopy. FASEB J. 2009; 23(8):2529-38. PMC: 2717776. DOI: 10.1096/fj.09-129171. View

Tiwari R, Jain A, Khan Z, Kohli V, Bharmal R, Kartikeyan S . Cardiac troponins I and T: molecular markers for early diagnosis, prognosis, and accurate triaging of patients with acute myocardial infarction. Mol Diagn Ther. 2012; 16(6):371-81. DOI: 10.1007/s40291-012-0011-6. View

10.

Chen A, Hurd R, Schroeder M, Lau A, Gu Y, Lam W . Simultaneous investigation of cardiac pyruvate dehydrogenase flux, Krebs cycle metabolism and pH, using hyperpolarized [1,2-(13)C2]pyruvate in vivo. NMR Biomed. 2011; 25(2):305-11. PMC: 4618301. DOI: 10.1002/nbm.1749. View

11.

Golman K, Petersson J, Magnusson P, Johansson E, Akeson P, Chai C . Cardiac metabolism measured noninvasively by hyperpolarized 13C MRI. Magn Reson Med. 2008; 59(5):1005-13. DOI: 10.1002/mrm.21460. View

12.

Oh-Ici D, Wespi P, Busch J, Wissmann L, Krajewski M, Weiss K . Hyperpolarized Metabolic MR Imaging of Acute Myocardial Changes and Recovery after Ischemia-Reperfusion in a Small-Animal Model. Radiology. 2015; 278(3):742-51. DOI: 10.1148/radiol.2015151332. View

13.

Cunningham C, Lau J, Chen A, Geraghty B, Perks W, Roifman I . Hyperpolarized 13C Metabolic MRI of the Human Heart: Initial Experience. Circ Res. 2016; 119(11):1177-1182. PMC: 5102279. DOI: 10.1161/CIRCRESAHA.116.309769. View

14.

Atherton H, Schroeder M, Dodd M, Heather L, Carter E, Cochlin L . Validation of the in vivo assessment of pyruvate dehydrogenase activity using hyperpolarised 13C MRS. NMR Biomed. 2010; 24(2):201-208. PMC: 4604661. DOI: 10.1002/nbm.1573. View

15.

Patel M, Korotchkina L . Regulation of the pyruvate dehydrogenase complex. Biochem Soc Trans. 2006; 34(Pt 2):217-22. DOI: 10.1042/BST20060217. View

16.

Minoves M, Garcia A, Magrina J, Pavia J, Herranz R, Setoain J . Evaluation of myocardial perfusion defects by means of "bull's eye" images. Clin Cardiol. 1993; 16(1):16-22. DOI: 10.1002/clc.4960160104. View

17.

Dodd M, Ball D, Schroeder M, Le Page L, Atherton H, Heather L . In vivo alterations in cardiac metabolism and function in the spontaneously hypertensive rat heart. Cardiovasc Res. 2012; 95(1):69-76. PMC: 4617603. DOI: 10.1093/cvr/cvs164. View

18.

WROBLEWSKI F, Ruegsegger P, LADUE J . Serum lactic dehydrogenase activity in acute transmural myocardial infarction. Science. 1956; 123(3208):1122-3. DOI: 10.1126/science.123.3208.1122. View

19.

Moreno K, Sabelhaus S, Merritt M, Sherry A, Malloy C . Competition of pyruvate with physiological substrates for oxidation by the heart: implications for studies with hyperpolarized [1-13C]pyruvate. Am J Physiol Heart Circ Physiol. 2010; 298(5):H1556-64. PMC: 2867437. DOI: 10.1152/ajpheart.00656.2009. View

20.

Opie L . Metabolism of free fatty acids, glucose and catecholamines in acute myocardial infarction. Relation to myocardial ischemia and infarct size. Am J Cardiol. 1975; 36(7):938-53. DOI: 10.1016/0002-9149(75)90086-7. View