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Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized ¹³C magnetic resonance.

ABSTRACT: The mammalian brain relies primarily on glucose as a fuel to meet its high metabolic demand. Among the various techniques used to study cerebral metabolism, ¹³C magnetic resonance spectroscopy (MRS) allows following the fate of ¹³C-enriched substrates through metabolic pathways. We herein demonstrate that it is possible to measure cerebral glucose metabolism in vivo with sub-second time resolution using hyperpolarized ¹³C MRS. In particular, the dynamic ¹³C-labeling of pyruvate and lactate formed from ¹³C-glucose was observed in real time. An ad-hoc synthesis to produce [2,3,4,6,6-²H₅, 3,4-¹³C₂]-D-glucose was developed to improve the ¹³C signal-to-noise ratio as compared to experiments performed following [U-²H₇, U-¹³C]-D-glucose injections. The main advantage of only labeling C3 and C4 positions is the absence of ¹³C-¹³C coupling in all downstream metabolic products after glucose is split into 3-carbon intermediates by aldolase. This unique method allows direct detection of glycolysis in vivo in the healthy brain in a noninvasive manner.

SUBMITTER: Mishkovsky M

PROVIDER: S-EPMC5601924 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundOptimal treatment selection for localized renal tumors is challenging because of their variable biologic behavior and limitations in the preoperative assessment of tumor aggressiveness. The authors investigated the emerging hyperpolarized (HP) 13 C magnetic resonance imaging (MRI) technique to noninvasively assess tumor lactate production, which is strongly associated with tumor aggressiveness.MethodsEleven patients with renal tumors underwent HP 13 C pyruvate MRI before surgical resection. Tumor 13 C pyruvate and 13 C lactate images were acquired dynamically. Five patients underwent 2 scans on the same day to assess the intrapatient reproducibility of HP 13 C pyruvate MRI. Tumor metabolic data were compared with histopathology findings.ResultsEight patients had tumors with a sufficient metabolite signal-to-noise ratio for analysis; an insufficient tumor signal-to-noise ratio was noted in 2 patients, likely caused by poor tumor perfusion and, in 1 patient, because of technical errors. Of the 8 patients, 3 had high-grade clear cell renal cell carcinoma (ccRCC), 3 had low-grade ccRCC, and 2 had chromophobe RCC. There was a trend toward a higher lactate-to-pyruvate ratio in high-grade ccRCCs compared with low-grade ccRCCs. Both chromophobe RCCs had relatively high lactate-to-pyruvate ratios. Good reproducibility was noted across the 5 patients who underwent 2 HP 13 C pyruvate MRI scans on the same day.ConclusionsThe current results demonstrate the feasibility of HP 13 C pyruvate MRI for investigating the metabolic phenotype of localized renal tumors. The initial data indicate good reproducibility of metabolite measurements. In addition, the metabolic data indicate a trend toward differentiating low-grade and high-grade ccRCCs, the most common subtype of renal cancer.Lay summaryRenal tumors are frequently discovered incidentally because of the increased use of medical imaging, but it is challenging to identify which aggressive tumors should be treated. A new metabolic imaging technique was applied to noninvasively predict renal tumor aggressiveness. The imaging results were compared with tumor samples taken during surgery and showed a trend toward differentiating between low-grade and high-grade clear cell renal cell carcinomas, which are the most common type of renal cancers.

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Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized ¹³C magnetic resonance.

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Dataset Information

Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized 13C magnetic resonance.

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OmicsDI is part of the ELIXIR infrastructure

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Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized ¹³C magnetic resonance.