TY - JOUR AU - Xu, He N. AU - Kadlececk, Stephen AU - Shaghaghi, Hoora AU - Zhao, Huaqing AU - Profka, Harilla AU - Pourfathi, Mehrdad AU - Rizi, Rahim AU - Li, Lin Z. PY - 2016 TI - Differentiating inflamed and normal lungs by the apparent reaction rate constants of lactate dehydrogenase probed by hyperpolarized 13 C labeled pyruvate JF - Quantitative Imaging in Medicine and Surgery; Vol 6, No 1 (February 28, 2016): Quantitative Imaging in Medicine and Surgery (Clinical and Technical Advances on Lung Imaging) Y2 - 2016 KW - N2 - Background: Clinically translatable hyperpolarized (HP) 13 C-NMR can probe in vivo enzymatic reactions, e.g., lactate dehydrogenase (LDH)-catalyzed reaction by injecting HP 13 C-pyruvate into the subject, which is converted to 13 C labeled lactate by the enzyme. Parameters such as 13 C-lactate signals and lactate-to-pyruvate signal ratio are commonly used for analyzing the HP 13 C-NMR data. However, the biochemical/biological meaning of these parameters remains either unclear or dependent on experimental settings. It is preferable to quantify the reaction rate constants with a clearer physical meaning. Here we report the extraction of the kinetic parameters of the LDH reaction from HP 13 C-NMR data and investigate if they can be potential predictors of lung inflammation. Methods: Male Sprague-Dawley rats (12 controls, 14 treated) were used. One dose of bleomycin (2.5 U/kg) was administered intratracheally to the treatment group. The lungs were removed, perfused, and observed by the HP-NMR technique, where a HyperSense dynamic nuclear polarization system was used to generate the HP 13 C-pyruvate for injecting into the lungs. A 20 mm 1 H/ 13 C dual-tuned coil in a 9.4-T Varian vertical bore NMR spectrometer was employed to acquire the 13 C spectral data every 1 s over a time period of 300 s using a non-selective, 15-degree radiofrequency pulse. The apparent rate constants of the LDH reaction and their ratio were quantified by applying ratiometric fitting analysis to the time series data of 13C labeled pyruvate and lactate. Results: The apparent forward rate constant k p =(3.67±3.31)×10 −4 s −1 , reverse rate constant k l =(4.95±2.90)×10 −2 s −1 , rate constant ratio k p /k l =(7.53±5.75)×10 −3 for the control lungs; k p =(11.71±4.35)×10 −4 s −1 , k l =(9.89±3.89)×10 −2 s −1 , and k p /k l =(12.39±4.18)×10 −3 for the inflamed lungs at the 7 th day post treatment. Wilcoxon rank-sum test showed that the medians of these kinetic parameters of the 7-day cohort were significantly larger than those of the control cohort (P k p and k p /k l positively correlated with lactate labeling signals. No correlation was found between k l and lactate labeling signals. Conclusions: The results indicate bleomycin-induced lung inflammation significantly increased both the forward and reverse reaction rate constants of LDH and their ratio at day-7 after bleomycin treatment. UR - https://qims.amegroups.org/article/view/9292