Quantitative measurement of cancer metabolism using stimulated echo hyperpolarized carbon-13 MRS

• Published in: Magnetic resonance in medicine Vol. 71; no. 1; pp. 1 - 11
• Main Authors: Swisher, Christine Leon, Larson, Peder E. Z., Kruttwig, Klaus, Kerr, Adam B., Hu, Simon, Bok, Robert A., Goga, Andrei, Pauly, John M., Nelson, Sarah J., Kurhanewicz, John, Vigneron, Daniel B.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.01.2014; Wiley Subscription Services, Inc
• Subjects: Alanine - chemistry; Algorithms; Animal models; Animals; Biomarkers, Tumor - metabolism; cancer; Carbon Isotopes - pharmacokinetics; Computer Simulation; hyperpolarized Carbon-13 MRS; kinetics; Lactic Acid - metabolism; Liver Neoplasms - metabolism; Magnetic Resonance Spectroscopy - methods; metabolism; Mice; Mice, Transgenic; Models, Biological; Pyruvic Acid - metabolism; Reproducibility of Results; Sensitivity and Specificity; STEAM; stimulated echo; STEAM; stimulated echo; cancer; metabolism; hyperpolarized Carbon-13 MRS; kinetics
• ISSN: 0740-3194; 1522-2594
• DOI: 10.1002/mrm.24634

Purpose Magnetic resonance spectroscopy of hyperpolarized substrates allows for the observation of label exchange catalyzed by enzymes providing a powerful tool to investigate tissue metabolism and potentially kinetics in vivo. However, the accuracy of current methods to calculate kinetic parameters has been limited by T1 relaxation effects, extracellular signal contributions, and reduced precision at lower signal‐to‐noise ratio. Theory and Methods To address these challenges, we investigated a new modeling technique using metabolic activity decomposition‐stimulated echo acquisition mode. The metabolic activity decomposition‐stimulated echo acquisition mode technique separates exchanging from nonexchanging metabolites providing twice the information as conventional techniques. Results This allowed for accurate measurements of rates of conversion and of multiple T1 values simultaneously using a single acquisition. Conclusion The additional measurement of T1 values for the reaction metabolites provides further biological information about the cellular environment of the metabolites. The new technique was investigated through simulations and in vivo studies of transgenic mouse models of cancer demonstrating improved assessments of kinetic rate constants and new T1 relaxation value measurements for hyperpolarized 13C‐pyruvate, 13C‐lactate, and 13C‐alanine. Magn Reson Med 71:1–11, 2014. © 2013 Wiley Periodicals, Inc.