Abstract

Carbon-13 (13C) can be hyperpolarized by Dynamic Nuclear Polarization (DNP) to increase the signal by 10,000 times. By hyperpolarizing 13C in the pyruvate molecule, radiation—induced lung injury (RILI) may be studied with Magnetic Resonance Imaging. In-vivo, pyruvate breaks down into lactate, alanine, bicarbonate and other metabolites in a time-dependent manner. The early stages of RILI lead to higher concentration of lactate in tissues. Therefore the ratio of pyruvate to lactate measured in rat lungs, following irradiation may provide an early indication of RILI. In the present study, dynamic MR spectroscopic techniques are developed to ensure proper quantification of these metabolites. [1-13C] labelled pyruvate (CIL, Cambridge, MA) was hyperpolarized by a commercially-available DNP system (Hypersense, Oxford Instruments). The DNP system utilizes low temperature (1.4 °K), high magnetic field strength (3.35 T) and irradiation with a microwave source (94.15 GHz) to polarize the pyruvate. Data were obtained following bolus injection of 3 ml of 0.8 mM [1-13C] pyruvic acid in the tail vein of healthy Sprague Dawley rats (400–450 g) following an animal care protocol approved by the Animal Use Subcommittee of the University Council on Animal Care at the University of Western Ontario. Pyruvate and lactate signals were identified based on their chemical shift from the obtained in-vivo dynamic spectra. The relative signal strength from these metabolites was quantified. This study demonstrated the capability of quantification of hyperpolarized [1-13C] labeled pyruvate and lactate from in-vivo dynamic spectra in rats which represents an important step toward studies of RILI.

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