13C imaging—a new diagnostic platform

Månsson, Sven; Johansson, Edvin; Magnusson, Peter; Chai, Chun-Ming; Hansson, Georg; Petersson, Johan; Ståhlberg, Freddy; Golman, Klaes

doi:10.1007/s00330-005-2806-x

Cited by 173 publications

(153 citation statements)

References 48 publications

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“…It is possible that a different metabolic pattern can be found when using high levels of 13 C-pyruvate to visualize metabolism under non-steady-state conditions with a short time window. The ratio between CO 2 and HCO 3 Ϫ in tissue is directly related to the pH, and a low concentration of HCO 3 Ϫ therefore also may be explained by a low pH in the examined area.…”

Section: Resultsmentioning

confidence: 98%

Real-time metabolic imaging

Golman¹,

Zandt²,

Thaning³

2006

Proc. Natl. Acad. Sci. U.S.A.

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629

847

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The endogenous substance pyruvate is of major importance to maintain energy homeostasis in the cells and provides a window to several important metabolic processes essential to cell survival. Cell viability is therefore reflected in the metabolism of pyruvate. NMR spectroscopy has until now been the only noninvasive method to gain insight into the fate of pyruvate in the body, but the low NMR sensitivity even at high field strength has only allowed information about steady-state conditions. The medically relevant information about the distribution, localization, and metabolic rate of the substance during the first minute after the injection has not been obtainable. Use of a hyperpolarization technique has enabled 10 -15% polarization of 13 C1 in up to a 0.3 M pyruvate solution. i.v. injection of the solution into rats and pigs allows imaging of the distribution of pyruvate and mapping of its major metabolites lactate and alanine within a time frame of Ϸ10 s. Real-time molecular imaging with MRI has become a reality.13 C ͉ dynamic nuclear polarization ͉ hyperpolarized ͉ MRI ͉ spectroscopy T he technique for increase in signal-to-noise ratio of Ͼ10,000 times in liquid-state NMR and the use of this technique for molecular imaging with endogenous substances generated through the process of dynamic nuclear polarization (DNP) has been reported (1, 2). In both these studies, 13 C-enriched urea was used as an example of an endogenous substance that could be polarized to a high degree (37% for 13 C and 8% for 15 N) and used for high-resolution imaging of the cardiovascular system in rats.It was suggested that the signal enhancement could be used not only for visualizing the cardiovascular system but also for improved perfusion measurements and that it may allow realtime metabolic mapping of other endogenous substances such as alanine, glutamine, and acetate. Such studies should be possible if the relaxation time of the 13 C-labeled site in the hyperpolarized molecule is long enough and the metabolic products retain sufficient fraction of the nonequilibrium polarization. The possibilities for doing perfusion studies using 13 C labeled hyperpolarized substances have recently been reviewed by Månsson et al. (3), but the application of visualizing metabolic processes by using hyperpolarized substances have not yet been described.To reveal information about the metabolic status of the tissue, magnetic resonance (MR) spectroscopy has been used, employing nuclei like 1 H, 13 C, 31 P, and 19 F (4, 5). The main application areas have been brain, muscle, and prostate tissue. Information on fluxes through metabolic pathways is less straightforward to obtain though. Traditionally, 13 C NMR spectroscopy in combination with 13 C-labeled (enriched) substrates has been used to visualize the label applied, its metabolic intermediates, and͞or its end products during steady-state conditions. In certain cases the metabolic rates can be indirectly estimated by using mathematical modeling (6), for example, in determining the flux through the...

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Section: Resultsmentioning

confidence: 98%

Real-time metabolic imaging

Golman¹,

Zandt²,

Thaning³

2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

629

847

View full text Add to dashboard Cite

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“…These all center around the concept of 13 C hyperpolarization, which has been pioneered by the group headed by Golman. [203][204][205][206][207][208][209] Using these techniques, signal-to-noise ratio enhancements of more than 10,000:1 have been achieved in vitro. Historically, many metabolic pathways have been probed using either 14 C or (more recently) 11 C as radiolabels.…”

Section: Summary and Future Directionsmentioning

confidence: 99%

Recent Advances in Magnetic Resonance Neurospectroscopy

Rosen

Lenkinski

2007

Neurotherapeutics

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Summary:Over the past two decades, proton magnetic resonance spectroscopy (proton MRS) of the brain has made the transition from research tool to a clinically useful modality. In this review, we first describe the localization methods currently used in MRS studies of the brain and discuss the technical and practical factors that determine the applicability of the methods to particular clinical studies. We also describe each of the resonances detected by localized solvent-suppressed proton MRS of the brain and discuss the metabolic and biochemical information that can be derived from an analysis of their concentrations. We discuss spectral quantitation and summarize the reproducibility of both single-voxel and multivoxel methods at 1.5 and 3-4 T. We have selected three clinical neurologic applications in which there has been a consensus as to the diagnostic value of MRS and summarize the information relevant to clinical applications. Finally, we speculate about some of the potential technical developments, either in progress or in the future, that may lead to improvements in the performance of proton MRS.

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“…Non-proton MRI, although it is not part of routine clinical exams, allows for instance useful investigation of the human heart when tuned to the frequencies of 31 P or 23 Na, which are both naturally abundant isotopes with non-zero spin. The low abundance of 13 C (1%) prevented carbon-based MRI until ex-vivo pre-polarization of its nuclei in selected bio-compatible molecules was used to provide dramatic signal enhancement [34,35].…”

Section: Lung Mri With Polarized Noble Gasesmentioning

confidence: 99%

Magnetic Resonance Imaging: From Spin Physics to Medical Diagnosis

Nacher

2009

The Spin

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Abstract. Two rather similar historical evolutions are evoked, each one originating in fundamental spin studies by physicists, and ending as magnetic resonance imaging (MRI), a set of invaluable tools for clinical diagnosis in the hands of medical doctors. The first one starts with the early work on nuclear magnetic resonance, the founding stone of the usual proton-based MRI, of which the basic principles are described. The second one starts with the optical pumping developments made to study the effects of spin polarization in various fundamental problems. Its unexpected outcome is a unique imaging modality, also based on MRI, for the study of lung physiology and pathologies.

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13C imaging—a new diagnostic platform

Cited by 173 publications

References 48 publications

Real-time metabolic imaging

Real-time metabolic imaging

Recent Advances in Magnetic Resonance Neurospectroscopy

Magnetic Resonance Imaging: From Spin Physics to Medical Diagnosis

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