Hyperpolarized 13C-Magnetic Resonance Spectroscopy

Abstract

Myocardial metabolic abnormalities have been demonstrated widely in diverse cardiac diseases. Metabolic impairment may be secondary to the underlying pathophysiological mechanism; however, in most conditions, it could be considered a direct cause, or at least a cofactor, in the functional abnormalities of the heart. Article see p 895 A more complete understanding of the myocardial metabolic changes associated with cardiac diseases may lead to pharmacological studies and potentially new metabolic-targeted drugs. In heart failure, agents that act through the optimization of cardiac metabolism may be particularly attractive as they could potentially work without exerting negative hemodynamic effects; this would allow for their addition to current therapies.1 It has been demonstrated that shifting the metabolic substrate of the heart from fatty acids to carbohydrate oxidation can improve pump function and delay the progression of heart failure.2 That said, in spite of the initial enthusiasm over drugs that showed promising metabolic effects in vitro, few clinical benefits have been unequivocally demonstrated. A robust imaging technique, which would allow the direct assessment of metabolism in vivo, is essential to understanding the metabolic changes and the effectiveness of pharmacological drugs. Unfortunately, nuclear medicine techniques, such as positron emission tomography and single photon emission computed tomography, are unable to detect the metabolized tracers and distinguish between different downstream metabolites.3 Magnetic resonance spectroscopy (MRS) with hyperpolarized 13C-enriched substrates is a promising imaging technique for the evaluation of cardiac metabolism in vivo. Because the natural amount of 13C in biological tissue is low, a sufficient signal:noise ratio for 13C-MRS is obtained by increasing the polarization level (hyperpolarization) of these compounds. Currently, dynamic nuclear polarization is the most widely used hyperpolarization technique for 13C-enriched molecules and this enables an increased signal:noise ratio of ≈10 000-fold.4 13C-MRS allows for a …