Glucose metabolism in brown adipose tissue determined by deuterium metabolic imaging in rats

Riis-Vestergaard, Mette Ji; Laustsen, Christoffer; Mariager, Christian Østergaard; Schulte, Rolf F.; Pedersen, Steen B.; Richelsen, Bjørn

doi:10.1038/s41366-020-0533-7

Cited by 30 publications

(35 citation statements)

References 42 publications

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“…Both of these processes would limit the total amount of HDO eliminated from [ 2 H 7 ]glucose given by intravenous injection. A significant consideration for this method is the physiological effect of administering what is equivalent to a glucose tolerance test to the subject 24 . Insulin sensitivity might play a large role in the interpretation of metabolic images produced by this method.…”

Section: Discussionmentioning

confidence: 99%

Deuterated water imaging of the rat brain following metabolism of [²H₇]glucose

Mahar

Zeng

Giacalone

et al. 2021

Magnetic Resonance in Med

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Purpose: To determine whether deuterated water (HDO) generated from the metabolism of [ 2 H 7 ]glucose is a sensitive biomarker of cerebral glycolysis and oxidative flux. Methods: A bolus of [ 2 H 7 ]glucose was injected through the tail vein at 1.95 g/kg into Sprague-Dawley rats. A 2 H surface coil was placed on top of the head to record 2 H spectra of the brain every 1.3 minutes to measure glucose uptake and metabolism to HDO, lactate, and glutamate/glutamine. A two-point Dixon method based on a gradient-echo sequence was used to reconstruct deuterated glucose and water (HDO) images selectively. Results: The background HDO signal could be detected and imaged before glucose injection. The 2 H NMR spectra showed arrival of [ 2 H 7 ]glucose and its metabolism in a time-dependent manner. A ratio of the HDO to glutamate/glutamine resonances demonstrates a pseudo-steady state following injection, in which cerebral metabolism dominates wash-in of HDO generated by peripheral metabolism. Brain spectroscopy reveals that HDO generation is linear with lactate and glutamate/glutamine appearance in the appropriate pseudo-steady state window. Selective imaging of HDO and glucose is easily accomplished using a gradient-echo method. Conclusion: Metabolic imaging of HDO, as a marker of glucose, lactate, and glutamate/glutamine metabolism, has been shown here for the first time. Cerebral glucose metabolism can be assessed efficiently using a standard gradient-echo sequence that provides superior in-plane resolution compared with CSI-based techniques. K E Y W O R D S [ 2 H 7 ]glucose, brain, DMRI, HDO, metabolism 1 | INTRODUCTION Glucose is the principal source of energy in the brain, and its dynamic uptake and use remain a key topic after decades of research. Metabolic imaging using MR-based methods has traditionally been limited to 1 H-based spectroscopic detection of metabolites through CSI or single-voxel spectroscopy. 1,2 Although these methods have been of immense How to cite this article: Mahar R, Zeng H, Giacalone A, Ragavan M, Mareci TH, Merritt ME. Deuterated water imaging of the rat brain following metabolism of [ 2 H 7 ]glucose.

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Section: Discussionmentioning

confidence: 99%

Deuterated water imaging of the rat brain following metabolism of [²H₇]glucose

Mahar

Zeng

Giacalone

et al. 2021

Magnetic Resonance in Med

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“…Research in MR molecular imaging has yielded two promising isotopic approaches for imaging glucose metabolism: "hyperpolarized (HP) 13 C MRI" [1][2][3] and "deuterium metabolic imaging" (DMI). [4][5][6][7][8][9] Although there are multiple possible avenues for 13 C hyperpolarization, HP- 13 C MRI most frequently relies on prepolarization of 13 C-labeled substrates by dynamic nuclear polarization followed by rapid dissolution to produce massive (although short-lived) signal enhancements of four to five orders of magnitude beyond the Boltzmann polarization at clinically feasible MRI field strengths, 1 enabling targeted metabolic investigations by spectroscopic imaging. 2 The short lifetime of 13 C magnetization demands tight study logistics and rapid, carefully calibrated MRI scans.…”

Section: Introductionmentioning

confidence: 99%

“…Considering the high current interest in both of these approaches for MR metabolic imaging, the purpose of this study is to provide a direct comparison between results of HP-13 C MRI and DMI for imaging cerebral glucose metabolism in individual rats at 4.7 T. Detailed comparisons are presented based on data acquired using both modalities under substantially equivalent experimental conditions, with data sets collected consecutively during the same scanning session for each rat. Although an early DMI study included limited human results at 4 T, 4 all prior results in small animals have been obtained at ultrahigh field strengths of 9.4 T, 5,9 11.7 T, 4 and 16.4 T. [6][7][8] While 4.7 T is not a recognized clinical field strength, this work demonstrates the basic potential of preclinical DMI studies much closer to the widely accepted clinical high field strength of 3 T.…”

Section: Introductionmentioning

confidence: 99%

Comparison of hyperpolarized ¹³C and non‐hyperpolarized deuterium MRI approaches for imaging cerebral glucose metabolism at 4.7 T

Morze

Engelbach

Blazey

et al. 2020

Magnetic Resonance in Med

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The purpose of this study was to directly compare two isotopic metabolic imaging approaches, hyperpolarized (HP) 13 C MRI and deuterium metabolic imaging (DMI), for imaging specific closely related segments of cerebral glucose metabolism at 4.7 T. Methods: Comparative HP-13 C and DMI neuroimaging experiments were conducted consecutively in normal rats during the same scanning session. Localized conversions of [1-13 C]pyruvate and [6,6-2 H 2 ]glucose to their respective downstream metabolic products were measured by spectroscopic imaging, using an identical 2D-CSI sequence with parameters optimized for the respective experiments. To facilitate direct comparison, a pair of substantially equivalent 2.5-cm double-tuned X/ 1 H RF surface coils was developed. For improved results, multidimensional low-rank reconstruction was applied to denoise the raw DMI data. Results: Localized conversion of HP [1-13 C]pyruvate to [1-13 C]lactate, and [6,6-2 H 2 ]glucose to [3,3-2 H 2 ]lactate and Glx-d (glutamate and glutamine), was detected in rat brain by spectroscopic imaging at 4.7 T. The SNR and spatial resolution of HP-13 C MRI was superior to DMI but limited to a short time window, whereas the lengthy DMI acquisition yielded maps of not only lactate, but also Glx production, albeit with relatively poor spectral discrimination between metabolites at this field strength. Across the individual rats, there was an apparent inverse correlation between cerebral production of HP [1-13 C]lactate and Glx-d, along with a trend toward increased [3,3-2 H 2 ]lactate. Conclusion: The HP-13 C MRI and DMI methods are both feasible at 4.7 T and have significant potential for metabolic imaging of specific segments of glucose metabolism. K E Y W O R D S brain, dynamic nuclear polarization, imaging, stable isotopes 1796 | von MoRZE Et al. How to cite this article: von Morze C, Engelbach JA, Blazey T, et al. Comparison of hyperpolarized 13 C and non-hyperpolarized deuterium MRI approaches for imaging cerebral glucose metabolism at 4.7 T.

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“…While in the brain, good field homogeneity and the lack of a lipid signal are a prerequisite for robust quantification of glutamate/glutamine and lactate, in lipid-rich BAT, the presence of a relatively large lipid signal at about 1.3 ppm from natural abundant 2 H lipids (which is typically much larger than the lactate signal originating from injected 2 H-labeled glucose) is expected to make quantification of 2 H-labeled lactate at 1.33 ppm a challenge. Surprisingly, no lipid peak contaminations were reported in the DMI BAT study by Riis-Vestergaard et al (146), despite the high fat content typically present in the BAT of rats. Aside from the lipid contamination, which can be a major confounding factor in the interpretation of DMI spectra of fat tissues, it is important to note that 2 H SNR scales as the square of the magnetic field strength; thus, high magnetic field strengths will be paramount for human translation of this technique.…”

Section: Multi-modal Imaging (Pet-mri) [Widely Used Technique]mentioning

confidence: 79%

Magnetic Resonance Imaging Techniques for Brown Adipose Tissue Detection

Junker

Branca

et al. 2020

Front. Endocrinol.

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Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) methods can non-invasively assess brown adipose tissue (BAT) structure and function. Recently, MRI and MRS have been proposed as a means to differentiate BAT from white adipose tissue (WAT) and to extract morphological and functional information on BAT inaccessible by other means. Specifically, proton MR (1 H) techniques, such as proton density fat fraction mapping, diffusion imaging, and intermolecular multiple quantum coherence imaging, have been employed to access BAT microstructure; MR thermometry, relaxometry, and MRI and MRS with 31 P, 2 H, 13 C, and 129 Xe have shown to provide complementary information on BAT function. The purpose of the present review is to provide a comprehensive overview of MR imaging and spectroscopy techniques used to detect BAT in rodents and in humans. The present work discusses common challenges of current methods and provides an outlook on possible future directions of using MRI and MRS in BAT studies.

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Glucose metabolism in brown adipose tissue determined by deuterium metabolic imaging in rats

Cited by 30 publications

References 42 publications

Deuterated water imaging of the rat brain following metabolism of [²H₇]glucose

Deuterated water imaging of the rat brain following metabolism of [²H₇]glucose

Comparison of hyperpolarized ¹³C and non‐hyperpolarized deuterium MRI approaches for imaging cerebral glucose metabolism at 4.7 T

Magnetic Resonance Imaging Techniques for Brown Adipose Tissue Detection

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Glucose metabolism in brown adipose tissue determined by deuterium metabolic imaging in rats

Cited by 30 publications

References 42 publications

Deuterated water imaging of the rat brain following metabolism of [2H7]glucose

Deuterated water imaging of the rat brain following metabolism of [2H7]glucose

Comparison of hyperpolarized 13C and non‐hyperpolarized deuterium MRI approaches for imaging cerebral glucose metabolism at 4.7 T

Magnetic Resonance Imaging Techniques for Brown Adipose Tissue Detection

Contact Info

Product

Resources

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Deuterated water imaging of the rat brain following metabolism of [²H₇]glucose

Deuterated water imaging of the rat brain following metabolism of [²H₇]glucose

Comparison of hyperpolarized ¹³C and non‐hyperpolarized deuterium MRI approaches for imaging cerebral glucose metabolism at 4.7 T