Dataset Information

Multiband spectral-spatial RF excitation for hyperpolarized [2-¹³ C]dihydroxyacetone ¹³ C-MR metabolism studies.

ABSTRACT:

Purpose

To develop a specialized multislice, single-acquisition approach to detect the metabolites of hyperpolarized (HP) [2-¹³ C]dihydroxyacetone (DHAc) to probe gluconeogenesis in vivo, which have a broad 144 ppm spectral range (∼4.6 kHz at 3T). A novel multiband radio-frequency (RF) excitation pulse was designed for independent flip angle control over five to six spectral-spatial (SPSP) excitation bands, each corrected for chemical shift misregistration effects.

Methods

Specialized multiband SPSP RF pulses were designed, tested, and applied to investigate HP [2-¹³ C]DHAc metabolism in kidney and liver of fasted rats with dynamic ¹³ C-MR spectroscopy and an optimal flip angle scheme. For comparison, experiments were also performed with narrow-band slice-selective RF pulses and a sequential change of the frequency offset to cover the five frequency bands of interest.

Results

The SPSP pulses provided a controllable spectral profile free of baseline distortion with improved signal to noise of the metabolite peaks, allowing for quantification of the metabolic products. We observed organ-specific differences in DHAc metabolism. There was two to five times more [2-¹³ C]phosphoenolpyruvate and about 19 times more [2-¹³ C]glycerol 3-phosphate in the liver than in the kidney.

Conclusion

A multiband SPSP RF pulse covering a spectral range over 144 ppm enabled in vivo characterization of HP [2-¹³ C]DHAc metabolism in rat liver and kidney. Magn Reson Med 77:1419-1428, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

SUBMITTER: Marco-Rius I

PROVIDER: S-EPMC5040611 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Publications

Multiband spectral-spatial RF excitation for hyperpolarized [2-<sup>13</sup> C]dihydroxyacetone <sup>13</sup> C-MR metabolism studies.

Marco-Rius Irene I Cao Peng P von Morze Cornelius C Merritt Matthew M Moreno Karlos X KX Chang Gene-Yuan GY Ohliger Michael A MA Pearce David D Kurhanewicz John J Larson Peder E Z PE Vigneron Daniel B DB

Magnetic resonance in medicine 20160328 4

<h4>Purpose</h4>To develop a specialized multislice, single-acquisition approach to detect the metabolites of hyperpolarized (HP) [2-<sup>13</sup> C]dihydroxyacetone (DHAc) to probe gluconeogenesis in vivo, which have a broad 144 ppm spectral range (∼4.6 kHz at 3T). A novel multiband radio-frequency (RF) excitation pulse was designed for independent flip angle control over five to six spectral-spatial (SPSP) excitation bands, each corrected for chemical shift misregistration effects.<h4>Methods< ...[more]

PMID: 27017966

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Project description:IntroductionThe normal heart has remarkable metabolic flexibility that permits rapid switching between mitochondrial glucose oxidation and fatty acid (FA) oxidation to generate ATP. Loss of metabolic flexibility has been implicated in the genesis of contractile dysfunction seen in cardiomyopathy. Metabolic flexibility has been imaged in experimental models, using hyperpolarized (HP) [2-13C]pyruvate MRI, which enables interrogation of metabolites that reflect tricarboxylic acid (TCA) cycle flux in cardiac myocytes. This study aimed to develop methods, demonstrate feasibility for [2-13C]pyruvate MRI in the human heart for the first time, and assess cardiac metabolic flexibility.MethodsGood Manufacturing Practice [2-13C]pyruvic acid was polarized in a 5T polarizer for 2.5-3 hours. Following dissolution, QC parameters of HP pyruvate met all safety and sterility criteria for pharmacy release, prior to administration to study subjects. Three healthy subjects each received two HP injections and MR scans, first under fasting conditions, followed by oral glucose load. A 5cm axial slab-selective spectroscopy approach was prescribed over the left ventricle and acquired at 3s intervals on a 3T clinical MRI scanner.ResultsThe study protocol which included HP substrate injection, MR scanning and oral glucose load, was performed safely without adverse events. Key downstream metabolites of [2-13C]pyruvate metabolism in cardiac myocytes include the glycolytic derivative [2-13C]lactate, TCA-associated metabolite [5-13C]glutamate, and [1-13C]acetylcarnitine, catalyzed by carnitine acetyltransferase (CAT). After glucose load, 13C-labeling of lactate, glutamate, and acetylcarnitine from 13C-pyruvate increased by 39.3%, 29.5%, and 114%, respectively in the three subjects, that could result from increases in lactate dehydrogenase (LDH), pyruvate dehydrogenase (PDH), and CAT enzyme activity as well as TCA cycle flux (glucose oxidation).ConclusionsHP [2-13C]pyruvate imaging is safe and permits non-invasive assessment of TCA cycle intermediates and the acetyl buffer, acetylcarnitine, which is not possible using HP [1-13C]pyruvate. Cardiac metabolite measurement in the fasting/fed states provides information on cardiac metabolic flexibility and the acetylcarnitine pool.

Dataset Information

Multiband spectral-spatial RF excitation for hyperpolarized [2-¹³ C]dihydroxyacetone ¹³ C-MR metabolism studies.

Purpose

Methods

Results

Conclusion

Publications

Multiband spectral-spatial RF excitation for hyperpolarized [2-<sup>13</sup> C]dihydroxyacetone <sup>13</sup> C-MR metabolism studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Multiband spectral-spatial RF excitation for hyperpolarized [2-13 C]dihydroxyacetone 13 C-MR metabolism studies.

Purpose

Methods

Results

Conclusion

Publications

Multiband spectral-spatial RF excitation for hyperpolarized [2-<sup>13</sup> C]dihydroxyacetone <sup>13</sup> C-MR metabolism studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Multiband spectral-spatial RF excitation for hyperpolarized [2-¹³ C]dihydroxyacetone ¹³ C-MR metabolism studies.