Using [1‐<sup>13</sup>C]lactic acid for hyperpolarized <sup>13</sup>C MR cardiac studies

Chen, Albert P.; Lau, Justin Y. C.; Alvares, Rohan D. A.; Cunningham, Charles H.

doi:10.1002/mrm.25354

Cited by 25 publications

(27 citation statements)

References 38 publications

(74 reference statements)

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“…Rapid demagnetization of the label by means of molecule-specific T 1 relaxation (e.g., with a decay constant of 45 s for aqueous [1][2][3][4][5][6][7][8][9][10][11][12][13] C]lactate at 3T) mostly precludes reliable detection of additional intermediates or products. Due to this rapid demagnetization, HP 13 C studies with metabolically active probes are generally limited to very rapid biochemical pathways.…”

Section: Background On Methods For Probing Pathways Of Glucose Recyclmentioning

confidence: 99%

Detection of localized changes in the metabolism of hyperpolarized gluconeogenic precursors¹³C-lactate and¹³C-pyruvate in kidney and liver

et al. 2016

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Purpose The purpose of this study was to characterize tissue-specific alterations in metabolism of hyperpolarized (HP) gluconeogenic precursors 13C-lactate and 13C-pyruvate by rat liver and kidneys under conditions of fasting or insulin-deprived diabetes. Methods Seven normal rats were studied by MR spectroscopic imaging of both HP 13C-lactate and 13C-pyruvate in both normal fed and 24 h fasting states, and seven additional rats were scanned after induction of diabetes by streptozotocin (STZ) with insulin withdrawal. Phosphoenolpyruvate carboxykinase (PEPCK) expression levels were also measured in liver and kidney tissues of the STZ-treated rats. Results Multiple sets of significant signal modulations were detected, with graded intensity in general between fasting and diabetic states. An approximate two-fold reduction in the ratio of 13C-bicarbonate to total 13C signal was observed in both organs in fasting. The ratio of HP lactate-to-alanine was markedly altered, ranging from a liver-specific 54% increase in fasting, to increases of 69% and 92% in liver and kidney, respectively, in diabetes. Diabetes resulted in a 40% increase in renal lactate signal. STZ resulted in 5.86-fold and 2.73-fold increases in PEPCK expression in liver and kidney, respectively. Conclusion MRI of HP 13C gluconeogenic precursors may advance diabetes research by clarifying organ-specific roles in abnormal diabetic metabolism.

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Section: Background On Methods For Probing Pathways Of Glucose Recyclmentioning

confidence: 99%

Detection of localized changes in the metabolism of hyperpolarized gluconeogenic precursors¹³C-lactate and¹³C-pyruvate in kidney and liver

et al. 2016

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“…Combined approaches using both [1- 13 C] and [2- 13 C] pyruvate [190, 191] or dual-enriched [1,2- 13 C 2 ] pyruvate allow for simultaneous investigation of pyruvate dehydrogenase flux, TCA cycle flux, and pH [192]. Other 13 C-labeled substrates applied to cardiac functional or metabolic imaging include [U- 13 C] α-ketobutyrate [193], [1- 13 C] lactic acid [194, 195], [1- 13 C] acetate [196–199], 13 C urea [200], and [1- 13 C] butyrate [201, 202]. Recently, co-polarization of 13 C urea and [1- 13 C] pyruvate was demonstrated to simultaneously assess myocardial perfusion and metabolism [80].…”

Section: Applications Of Hyperpolarized 13c Mri To Pre-clinical Anmentioning

confidence: 99%

Magnetic resonance imaging with hyperpolarized agents: methods and applications

et al. 2017

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In the past decade, hyperpolarized (HP) contrast agents have been under active development for MRI applications to address the twin challenges of functional and quantitative imaging. Both HP helium (3He) and xenon (129Xe) gases have reached the stage where they are under study in clinical research. HP 129Xe, in particular, is poised for larger scale clinical research to investigate asthma, chronic obstructive pulmonary disease, and fibrotic lung diseases. With advances in polarizer technology and unique capabilities for imaging of 129Xe gas exchange into lung tissue and blood, HP 129Xe MRI is attracting new attention. In parallel, HP 13C and 15N MRI methods have steadily advanced in a wide range of pre-clinical research applications for imaging metabolism in various cancers and cardiac disease. The HP [1-13C] pyruvate MRI technique, in particular, has undergone phase I trials in prostate cancer and is poised for investigational new drug trials at multiple institutions in cancer and cardiac applications. This review treats the methodology behind both HP gases and HP 13C and 15N liquid state agents. Gas and liquid phase HP agents share similar technologies for achieving non-equilibrium polarization outside the field of the MRI scanner, strategies for image data acquisition, and translational challenges in moving from pre-clinical to clinical research. To cover the wide array of methods and applications, this review is organized by numerical section into 1) a brief introduction, 2) the physical and biological properties of the most common polarized agents with a brief summary of applications and methods of polarization, 3) methods for image acquisition and reconstruction specific to improving data acquisition efficiency for HP MRI, 4) the main physical properties that enable unique measures of physiology or metabolic pathways, followed by a more detailed review of the literature describing the use of HP agents to study 5) metabolic pathways in cancer and cardiac disease and 6) lung function in both pre-clinical and clinical research studies, 7) some future directions and challenges, and 8) an overall summary.

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“…As the physiological plasma concentrations of lactate can be higher than those of pyruvate [1–10 m m versus 3–6 m m , respectively], the use of lactate may represent a viable and potentially safer alternative to pyruvate, as higher concentrations of lactate can be used to achieve an increase in SNR. Recently, it was shown that neat [1‐ 13 C]lactic acid without the addition of any solvent or glassing agent can be used for the preparation of hyperpolarized [1‐ 13 C]lactate in solution .…”

Section: Spectroscopy Of Cardiac Metabolismmentioning

confidence: 99%

MRS: a noninvasive window into cardiac metabolism

et al. 2015

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A well-functioning heart requires a constant supply of a balanced mixture of nutrients to be used for the production of adequate amounts of adenosine triphosphate, which is the main energy source for most cellular functions. Defects in cardiac energy metabolism are linked to several myocardial disorders. MRS can be used to study in vivo changes in cardiac metabolism noninvasively. MR techniques allow repeated measurements, so that disease progression and the response to treatment or to a lifestyle intervention can be monitored. It has also been shown that MRS can predict clinical heart failure and death. This article focuses on in vivo MRS to assess cardiac metabolism in humans and experimental animals, as experimental animals are often used to investigate the mechanisms underlying the development of metabolic diseases. Various MR techniques, such as cardiac (31) P-MRS, (1) H-MRS, hyperpolarized (13) C-MRS and Dixon MRI, are described. A short overview of current and emerging applications is given. Cardiac MRS is a promising technique for the investigation of the relationship between cardiac metabolism and cardiac disease. However, further optimization of scan time and signal-to-noise ratio is required before broad clinical application. In this respect, the ongoing development of advanced shimming algorithms, radiofrequency pulses, pulse sequences, (multichannel) detection coils, the use of hyperpolarized nuclei and scanning at higher magnetic field strengths offer future perspective for clinical applications of MRS.

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Using [1‐¹³C]lactic acid for hyperpolarized ¹³C MR cardiac studies

Cited by 25 publications

References 38 publications

Detection of localized changes in the metabolism of hyperpolarized gluconeogenic precursors¹³C-lactate and¹³C-pyruvate in kidney and liver

Detection of localized changes in the metabolism of hyperpolarized gluconeogenic precursors¹³C-lactate and¹³C-pyruvate in kidney and liver

Magnetic resonance imaging with hyperpolarized agents: methods and applications

MRS: a noninvasive window into cardiac metabolism

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Using [1‐13C]lactic acid for hyperpolarized 13C MR cardiac studies

Cited by 25 publications

References 38 publications

Detection of localized changes in the metabolism of hyperpolarized gluconeogenic precursors13C-lactate and13C-pyruvate in kidney and liver

Detection of localized changes in the metabolism of hyperpolarized gluconeogenic precursors13C-lactate and13C-pyruvate in kidney and liver

Magnetic resonance imaging with hyperpolarized agents: methods and applications

MRS: a noninvasive window into cardiac metabolism

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Using [1‐¹³C]lactic acid for hyperpolarized ¹³C MR cardiac studies

Detection of localized changes in the metabolism of hyperpolarized gluconeogenic precursors¹³C-lactate and¹³C-pyruvate in kidney and liver

Detection of localized changes in the metabolism of hyperpolarized gluconeogenic precursors¹³C-lactate and¹³C-pyruvate in kidney and liver