Quantification of in vivo metabolic kinetics of hyperpolarized pyruvate in rat kidneys using dynamic 13 C MRSI

作者：Tao Xu, Dirk Mayer, Meng Gu, Yi‐Fen Yen, Sonal Josan, James Tropp, Adolf Pfefferbaum, Ralph E. Hurd, Daniel M. Spielman · 发表于：NMR in Biomedicine · 年份：2011 · DOI：10.1002/nbm.1719 · 被引用次数：51 · 研究领域：Advanced NMR Techniques and Applications、Advanced MRI Techniques and Applications、Solid-state spectroscopy and crystallography

With signal-to-noise ratio enhancements on the order of 10,000-fold, hyperpolarized MRSI of metabolically active substrates allows the study of both the injected substrate and downstream metabolic products in vivo. Although hyperpolarized [1-(13)C]pyruvate, in particular, has been used to demonstrate metabolic activities in various animal models, robust quantification and metabolic modeling remain important areas of investigation. Enzyme saturation effects are routinely seen with commonly used doses of hyperpolarized [1-(13)C]pyruvate; however, most metrics proposed to date, including metabolite ratios, time-to-peak of metabolic products and single exchange rate constants, fail to capture these saturation effects. In addition, the widely used small-flip-angle excitation approach does not correctly model the inflow of fresh downstream metabolites generated proximal to the target slice, which is often a significant factor in vivo. In this work, we developed an efficient quantification framework employing a spiral-based dynamic spectroscopic imaging approach. The approach overcomes the aforementioned limitations and demonstrates that the in vivo (13)C labeling of lactate and alanine after a bolus injection of [1-(13)C]pyruvate is well approximated by saturatable kinetics, which can be mathematically modeled using a Michaelis-Menten-like formulation, with the resulting estimated apparent maximal reaction velocity V(max) and apparent Michaelis constant K(M) being unbiased with res...