Apparent rate constant mapping using hyperpolarized [1-13C]pyruvate

• Published in: NMR in biomedicine Vol. 27; no. 10; pp. 1256 - 1265
• Main Authors: Khegai, O., Schulte, R. F., Janich, M. A., Menzel, M. I., Farrell, E., Otto, A. M., Ardenkjaer-Larsen, J. H., Glaser, S. J., Haase, A., Schwaiger, M., Wiesinger, F.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.10.2014; Wiley Subscription Services, Inc
• Subjects: [1-13C]pyruvate; Algorithms; Animals; Carbon-13 Magnetic Resonance Spectroscopy - methods; dynamic metabolic imaging; Female; Humans; hyperpolarized 13C; kinetic modeling; Kinetics; L-Lactate Dehydrogenase - metabolism; Least-Squares Analysis; Mammary Neoplasms, Experimental - chemistry; MCF-7 Cells - chemistry; metabolic exchange rate; Models, Chemical; MRSI; Pyruvates - analysis; Rats, Inbred F344; Signal-To-Noise Ratio; Spheroids, Cellular; Suspensions; Time Factors; hyperpolarized 13C; dynamic metabolic imaging; [1-13C]pyruvate; MRSI; kinetic modeling; metabolic exchange rate
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.3174

Hyperpolarization of [1‐13C]pyruvate in solution allows real‐time measurement of uptake and metabolism using MR spectroscopic methods. After injection and perfusion, pyruvate is taken up by the cells and enzymatically metabolized into downstream metabolites such as lactate, alanine, and bicarbonate. In this work, we present comprehensive methods for the quantification and interpretation of hyperpolarized 13C metabolite signals. First, a time‐domain spectral fitting method is described for the decomposition of FID signals into their metabolic constituents. For this purpose, the required chemical shift frequencies are automatically estimated using a matching pursuit algorithm. Second, a time‐discretized formulation of the two‐site exchange kinetic model is used to quantify metabolite signal dynamics by two characteristic rate constants in the form of (i) an apparent build‐up rate (quantifying the build‐up of downstream metabolites from the pyruvate substrate) and (ii) an effective decay rate (summarizing signal depletion due to repetitive excitation, T1‐relaxation and backward conversion). The presented spectral and kinetic quantification were experimentally verified in vitro and in vivo using hyperpolarized [1‐13C]pyruvate. Using temporally resolved IDEAL spiral CSI, spatially resolved apparent rate constant maps are also extracted. In comparison to single metabolite images, apparent build‐up rate constant maps provide improved contrast by emphasizing metabolically active tissues (e.g. tumors) and suppression of high perfusion regions with low conversion (e.g. blood vessels). Apparent build‐up rate constant mapping provides a novel quantitative image contrast for the characterization of metabolic activity. Its possible implementation as a quantitative standard will be subject to further studies. Copyright © 2014 John Wiley & Sons, Ltd. A quantification algorithm for time‐resolved hyperpolarized 13C MRSI allows us to characterize metabolite signal dynamics by two apparent rate constants. Combined with temporally resolved IDEAL spiral CSI, apparent build‐up rate constant maps were obtained, which provided a novel quantitative image contrast for the characterization of metabolic activity.