Dynamic hyperpolarized carbon‐13 MR metabolic imaging of nonhuman primate brain

Abstract

Purpose To investigate hyperpolarized 13C metabolic imaging methods in the primate brain that can be translated into future clinical trials for patients with brain cancer. Methods 13C coils and pulse sequences designed for use in humans were tested in phantoms. Dynamic 13C data were obtained from a healthy cynomolgus monkey brain using the optimized 13C coils and pulse sequences. The metabolite kinetics were estimated from two-dimensional localized 13C dynamic imaging data from the nonhuman primate brain. Results Pyruvate and lactate signal were observed in both the brain and the surrounding tissues with the maximum signal-to-noise ratio of 218 and 29 for pyruvate and lactate, respectively. Apparent rate constants for the conversion of pyruvate to lactate and the ratio of lactate to pyruvate showed a difference between brain and surrounding tissues. Conclusion The feasibility of using hyperpolarized [1-13C]-pyruvate for assessing in vivo metabolism in a healthy nonhuman primate brain was demonstrated using a hyperpolarized 13C imaging experimental setup designed for studying patients with brain tumors. The kinetics of the metabolite conversion suggests that this approach may be useful in future studies of human neuropathology.

Optimal Glass-Forming Solvent Brings Sublimation Dynamic Nuclear Polarization to 129Xe Hyperpolarization Biomedical Imaging Standards

“…[40][41] This would allow producing batches of 300 -1600 mL HP xenon gas, depending on the solvent used for the sample preparation. Note that, although residual vapor of ethanol or other alcohol widely and routinely used in clinical environment should not be a major issue, the purity of the extracted gas would have to be checked prior to move to human applications.…”

The use of hyperpolarized carbon-13 magnetic resonance for molecular imaging

“…Spatial selectivity can be incorporated by adding slice selection over a region of interest. This method is useful for organ-specific applications [125,126] as well as tumor xenografts [108,109]. Other methods with 3D localization have been subsequently introduced including a Point RESolved Spectroscopy (PRESS) pulse sequence with a slice-selective 90° RF excitation pulse followed by two refocusing pulse pairs along the other axes [118].…”

Alternating Acquisition Technique for Quantification of in vitro Hyperpolarized [1-13C] Pyruvate Metabolism

“…[1][2][3][4][5][6][7][8][9][10][11][12][13] C] pyruvate) and the product (i.e. [1][2][3][4][5][6][7][8][9][10][11][12][13] C] lactate) from other sites. Here, the effect of excitation flip angles and T 1 relaxation is not considered.…”

“…After dissolution into aqueous state, 2.0 mL of the hyperpolarized substrate was injected into the test tube filled with 4.0 mL of LDH (15 U) and 60 uL of NADH (500 mM) solution over 9s. The amount of LDH used for the in vitro experiments was determined from separate experiments (data not shown) conducted to recreate typical hyperpolarized [1][2][3][4][5][6][7][8][9][10][11][12][13] C] spectra obtained in normal in vivo cases. The test tube was placed inside the plastic holder structure made as part of the custom-built 13 C-tuned solenoid coil prior to the injection.…”

“…Furthermore, recent advent of dissolution-based dynamic nuclear polarization (DNP) method (10) has allowed spectroscopic acquisition, metabolism quantification and even in vivo imaging of metabolites labeled with 13 C. Direct spectroscopic examination of metabolic pathways of 13 C molecules for both normal and diseased tissues utilizing this new technical breakthrough has shown great clinical potential in the last decade (11)(12)(13). Hyperpolarized 13 C MRS studies were primarily focused on utilizing lactate dehydrogenase (LDH)-catalyzed 13 C label exchange between injected hyperpolarized [1][2][3][4][5][6][7][8][9][10][11][12][13] C] pyruvate and [1][2][3][4][5][6][7][8][9][10][11][12][13] C] lactate and also [1][2][3][4][5][6][7][8][9][10][11][12][13] C] alanine via alanine aminotransferase …”