T₁ nuclear magnetic relaxation dispersion of hyperpolarized sodium and cesium hydrogencarbonate‐¹³C

Abstract

In vivo pH mapping in tissue using hyperpolarized hydrogencarbonate- C has been proposed as a method to study tumor growth and treatment and other pathological conditions related to pH changes. The finite spin-lattice relaxation times (T ) of hyperpolarized media are a significant limiting factor for in vivo imaging. Relaxation times can be measured at standard magnetic fields (1.5 T, 3.0 T etc.), but no such data are available at low fields, where T values can be significantly shorter. This information is required to determine the potential loss of polarization as the agent is dispensed and transported from the polarizer to the MRI scanner. The purpose of this study is to measure T dispersion from low to clinical magnetic fields (0.4 mT to 3.0 T) of different hyperpolarized hydrogencarbonate formulations previously proposed in the literature for in vivo pH measurements. C-enriched cesium and sodium hydrogencarbonate preparations were hyperpolarized using dynamic nuclear polarization, and the T values of different samples were measured at different magnetic field strengths using a fast field-cycling relaxometer and a 3.0 T clinical MRI system. The effects of deuterium oxide as a dissolution medium for sodium hydrogencarbonate were also analyzed. This study finds that the cesium formulation has slightly shorter T values compared with the sodium preparation. However, the higher solubility of cesium hydrogencarbonate- C means it can be polarized at greater concentration, using less trityl radical than sodium hydrogencarbonate- C. This study also establishes that the preparation and handling of sodium hydrogencarbonate formulations in relation to cesium hydrogencarbonate is more difficult, due to the higher viscosity and lower achievable concentrations, and that deuterium oxide significantly increases the T of sodium hydrogencarbonate solutions. Finally, this work also investigates the influence of pH on the spin-lattice relaxation of cesium hydrogencarbonate- C measured over a pH range of 7 to 9 at 0.47 T.

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Longitudinal Measurements of Intra- and Extracellular pH Gradient in a Rat Model of Glioma

“…The resulting hyperpolarized solution had a 13 C bicarbonate concentration of 150 mmol/L and a pH of 7.4 at 37°C. The in vitro spin lattice relaxation time and polarization values of the 13 C nucleus were 26.2 ± 1.4 s and ∼7.5% measured at 3 T ( 24 ).…”

Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance

“…pH i can also be quantified from HP 13 CO 2 produced from [1- 13 C]pyruvate in organs with high pyruvate dehydrogenase flux, most notably the heart [98,99]. Although the short T 1 of [ 13 C]bicarbonate/ 13 CO 2 (~10 s in vivo [91,92,93,97,100]) poses a significant challenge for obtaining sufficient spatial resolution, recent advances in hyperpolarization approaches, including HP precursor decarboxylation [93,94,101], as well as advanced HP imaging sequences [96,102,103], can provide significant gains in available HP signal and its effective utilization. Nevertheless, HP image resolution (2–10 mm) is currently coarser than other modalities and MR approaches.…”