In vivo ¹³carbon metabolic imaging at 3T with hyperpolarized ¹³C‐1‐pyruvate

Abstract

We present for the first time dynamic spectra and spectroscopic images acquired in normal rats at 3T following the injection of 13 C-1-pyruvate that was hyperpolarized by the dynamic nuclear polarization (DNP) method. Spectroscopic sampling was optimized for signal-to-noise ratio (SNR) and for spectral resolution of 13 C-1-pyruvate and its metabolic products 13 C-1-alanine, 13 C-1-lactate, and 13 C-bicarbonate. Dynamic spectra in rats were collected with a temporal resolution of 3 s from a 90-mm axial slab using a dual 1 H-13 C quadrature birdcage coil to observe the combined effects of metabolism, flow, and T 1 relaxation. In separate experiments, spectroscopic imaging data were obtained during a 17-s acquisition of a 20-mm axial slice centered on the rat kidney region to provide information on the spatial distribution of the metabolites. Conversion of pyruvate to lactate, alanine, and bicarbonate occurred within a minute of injection. Alanine was observed primarily in skeletal muscle and liver, while pyruvate, lactate, and bicarbonate concentrations were relatively high in the vasculature and kidneys. In contrast to earlier work at 1. Historically, magnetic resonance (MR) has been a technique associated with low sensitivity, limited by small differences in energy-state populations dictated by the Boltzmann distribution. Increases in magnetic field strength provide modest improvements in the population distribution and thus the sensitivity, but the polarization at thermal equilibrium is fundamentally limited by the low nuclear gyromagnetic ratios. Applications of MRI have thus been focused on imaging the 1 H nucleus occurring in very high concentrations in fat and water in vivo. Clinical 1 H spectroscopy has been possible for metabolites in relatively high concentrations, while spectroscopy of nuclei with lower gyromagnetic ratios, and thus less favorable population distributions, has been difficult at best.Methods to produce substantially altered population distributions or "hyperpolarization" by dynamic nuclear polarization (DNP) and other techniques have been known for a long time (1-6), but have not been applicable to in vivo studies due to the necessity of polarization at very low temperatures (1.2 K) and high fields. The recent development of techniques to achieve high polarization in the solid state and retain a high degree of polarization through fast dissolution procedures (7-9) has provided a mechanism to produce enhancements of MR signals by up to five orders of magnitude compared to thermal equilibrium at typical MR field strengths, thus providing the possibility of directly imaging metabolites of low concentration in vivo. In addition, the potential now exists for directly observing low concentrations of 13 C-labeled compounds in vivo and following their metabolism over short periods of time. Prior studies performed at 1.5T (10,11) have demonstrated the use of hyperpolarized 13 C-labeled pyruvate to directly monitor metabolism in vivo, and to observe the conversion of pyruvate to lactate and alanin...

Compressed sensing for resolution enhancement of hyperpolarized 13C flyback 3D-MRSI

“…All animal studies were carried out under a protocol approved by the Institutional Animal Care and Use Committee. A more detailed description of the polarization and animal care procedures can be found in [4][5].…”

“…With the development of techniques to maintain hyperpolarization of carbon-13 in liquid state [1], it has become possible to use 13 C substrates (tracers) for medical imaging [2]. More recent studies have used the metabolically active substrate [l- 13 C]pyruvate to examine its conversion to [l- 13 C]lactate, [l- 13 C]alanine, and 13 C-bicarbonate [3][4][5]. Spectroscopic examination of these metabolic pathways in the presence and absence of disease has enormous diagnostic potential.…”

Feasibility of using hyperpolarized [1-13C]lactate as a substrate for in vivo metabolic 13C MRSI studies

“…The RF coil used in these experiments was a dual-tuned 1 H-13 C coil with a quadrature 13 C channel and linear 1 H channel constructed based on an earlier design (7) and used in prior hyperpolarized 13 C pyruvate studies (3)(4)(5). The inner coil diameter was 8 cm and the length of the coil was 9 cm to accommodate rats of varying size.…”

“…This development has enabled in vivo 13 C MR studies at high signal to noise ratio (SNR) following injection of pre-polarized 13 C substrates (2). It has been shown by using [l-13 C]pyruvate as the substrate for hyperpolarized 13 C MRS/MRSI experiment, real time cellular metabolism can be studied in normal and diseased tissues in vivo (3)(4)(5). These studies have shown the ability to detect the metabolic conversion of the hyperpolarized [l-13 C]pyruvate into [l-13 C]lactate, [l-13 C]alanine and 13 C-bicarbonate after in vivo injection in animal models.…”

“…These studies have shown the ability to detect the metabolic conversion of the hyperpolarized [l-13 C]pyruvate into [l-13 C]lactate, [l-13 C]alanine and 13 C-bicarbonate after in vivo injection in animal models. In these studies using pre-polarized 13 C pyruvate as the substrate, the concentration of pyruvate in the injected solution was much higher than the endogenous concentration (3)(4)(5). Thus one of the processes that can be probed in these conditions is the cellular conversion of the 13 C pyruvate bolus to 13 C lactate (6).…”