Probing cardiac metabolism by hyperpolarized 13C MR using an exclusively endogenous substrate mixture and photo-induced nonpersistent radicals

Jessica A M Bastiaansen*, Hikari A I Yoshihara, Andrea Capozzi, Juerg Schwitter, Rolf Gruetter, Matthew E Merritt, Arnaud Comment

*Corresponding author for this work

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Abstract

To probe the cardiac metabolism of carbohydrates and short chain fatty acids simultaneously in vivo following the injection of a hyperpolarized 13 C-labeled substrate mixture prepared using photo-induced nonpersistent radicals. Droplets of mixed [1-13 C]pyruvic and [1-13 C]butyric acids were frozen into glassy beads in liquid nitrogen. Ethanol addition was investigated as a means to increase the polarization level. The beads were irradiated with ultraviolet light and the radical concentration was measured by ESR spectroscopy. Following dynamic nuclear polarization in a 7T polarizer, the beads were dissolved, and the radical-free hyperpolarized solution was rapidly transferred into an injection pump located inside a 9.4T scanner. The hyperpolarized solution was injected in healthy rats to measure cardiac metabolism in vivo. Ultraviolet irradiation created nonpersistent radicals in a mixture containing 13 C-labeled pyruvic and butyric acids, and enabled the hyperpolarization of both substrates by dynamic nuclear polarization. Ethanol addition increased the radical concentration from 16 to 26 mM. Liquid-state 13 C polarization was 3% inside the pump at the time of injection, and increased to 5% by addition of ethanol to the substrate mixture prior to ultraviolet irradiation. In the rat heart, the in vivo 13 C signals from lactate, alanine, bicarbonate, and acetylcarnitine were detected following the metabolism of the injected substrate mixture. Copolarization of two different 13 C-labeled substrates and the detection of their myocardial metabolism in vivo was achieved without using persistent radicals. The absence of radicals in the solution containing the hyperpolarized 13 C-substrates may simplify the translation to clinical use, as no radical filtration is required prior to injection.
Original languageEnglish
JournalMagnetic Resonance in Medicine
Volume79
Issue number5
Pages (from-to)2451-2459
Number of pages9
ISSN0740-3194
DOIs
Publication statusPublished - 2018

Keywords

  • Carbon-13
  • Energy metabolism
  • Hyperpolarization
  • Metabolic imaging
  • Oxidative metabolism

Cite this

Bastiaansen, Jessica A M ; Yoshihara, Hikari A I ; Capozzi, Andrea ; Schwitter, Juerg ; Gruetter, Rolf ; Merritt, Matthew E ; Comment, Arnaud. / Probing cardiac metabolism by hyperpolarized 13C MR using an exclusively endogenous substrate mixture and photo-induced nonpersistent radicals. In: Magnetic Resonance in Medicine. 2018 ; Vol. 79, No. 5. pp. 2451-2459.
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abstract = "To probe the cardiac metabolism of carbohydrates and short chain fatty acids simultaneously in vivo following the injection of a hyperpolarized 13 C-labeled substrate mixture prepared using photo-induced nonpersistent radicals. Droplets of mixed [1-13 C]pyruvic and [1-13 C]butyric acids were frozen into glassy beads in liquid nitrogen. Ethanol addition was investigated as a means to increase the polarization level. The beads were irradiated with ultraviolet light and the radical concentration was measured by ESR spectroscopy. Following dynamic nuclear polarization in a 7T polarizer, the beads were dissolved, and the radical-free hyperpolarized solution was rapidly transferred into an injection pump located inside a 9.4T scanner. The hyperpolarized solution was injected in healthy rats to measure cardiac metabolism in vivo. Ultraviolet irradiation created nonpersistent radicals in a mixture containing 13 C-labeled pyruvic and butyric acids, and enabled the hyperpolarization of both substrates by dynamic nuclear polarization. Ethanol addition increased the radical concentration from 16 to 26 mM. Liquid-state 13 C polarization was 3{\%} inside the pump at the time of injection, and increased to 5{\%} by addition of ethanol to the substrate mixture prior to ultraviolet irradiation. In the rat heart, the in vivo 13 C signals from lactate, alanine, bicarbonate, and acetylcarnitine were detected following the metabolism of the injected substrate mixture. Copolarization of two different 13 C-labeled substrates and the detection of their myocardial metabolism in vivo was achieved without using persistent radicals. The absence of radicals in the solution containing the hyperpolarized 13 C-substrates may simplify the translation to clinical use, as no radical filtration is required prior to injection.",
keywords = "Carbon-13, Energy metabolism, Hyperpolarization, Metabolic imaging, Oxidative metabolism",
author = "Bastiaansen, {Jessica A M} and Yoshihara, {Hikari A I} and Andrea Capozzi and Juerg Schwitter and Rolf Gruetter and Merritt, {Matthew E} and Arnaud Comment",
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pages = "2451--2459",
journal = "Magnetic Resonance in Medicine",
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Probing cardiac metabolism by hyperpolarized 13C MR using an exclusively endogenous substrate mixture and photo-induced nonpersistent radicals. / Bastiaansen, Jessica A M; Yoshihara, Hikari A I; Capozzi, Andrea; Schwitter, Juerg; Gruetter, Rolf; Merritt, Matthew E; Comment, Arnaud.

In: Magnetic Resonance in Medicine, Vol. 79, No. 5, 2018, p. 2451-2459.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Probing cardiac metabolism by hyperpolarized 13C MR using an exclusively endogenous substrate mixture and photo-induced nonpersistent radicals

AU - Bastiaansen, Jessica A M

AU - Yoshihara, Hikari A I

AU - Capozzi, Andrea

AU - Schwitter, Juerg

AU - Gruetter, Rolf

AU - Merritt, Matthew E

AU - Comment, Arnaud

PY - 2018

Y1 - 2018

N2 - To probe the cardiac metabolism of carbohydrates and short chain fatty acids simultaneously in vivo following the injection of a hyperpolarized 13 C-labeled substrate mixture prepared using photo-induced nonpersistent radicals. Droplets of mixed [1-13 C]pyruvic and [1-13 C]butyric acids were frozen into glassy beads in liquid nitrogen. Ethanol addition was investigated as a means to increase the polarization level. The beads were irradiated with ultraviolet light and the radical concentration was measured by ESR spectroscopy. Following dynamic nuclear polarization in a 7T polarizer, the beads were dissolved, and the radical-free hyperpolarized solution was rapidly transferred into an injection pump located inside a 9.4T scanner. The hyperpolarized solution was injected in healthy rats to measure cardiac metabolism in vivo. Ultraviolet irradiation created nonpersistent radicals in a mixture containing 13 C-labeled pyruvic and butyric acids, and enabled the hyperpolarization of both substrates by dynamic nuclear polarization. Ethanol addition increased the radical concentration from 16 to 26 mM. Liquid-state 13 C polarization was 3% inside the pump at the time of injection, and increased to 5% by addition of ethanol to the substrate mixture prior to ultraviolet irradiation. In the rat heart, the in vivo 13 C signals from lactate, alanine, bicarbonate, and acetylcarnitine were detected following the metabolism of the injected substrate mixture. Copolarization of two different 13 C-labeled substrates and the detection of their myocardial metabolism in vivo was achieved without using persistent radicals. The absence of radicals in the solution containing the hyperpolarized 13 C-substrates may simplify the translation to clinical use, as no radical filtration is required prior to injection.

AB - To probe the cardiac metabolism of carbohydrates and short chain fatty acids simultaneously in vivo following the injection of a hyperpolarized 13 C-labeled substrate mixture prepared using photo-induced nonpersistent radicals. Droplets of mixed [1-13 C]pyruvic and [1-13 C]butyric acids were frozen into glassy beads in liquid nitrogen. Ethanol addition was investigated as a means to increase the polarization level. The beads were irradiated with ultraviolet light and the radical concentration was measured by ESR spectroscopy. Following dynamic nuclear polarization in a 7T polarizer, the beads were dissolved, and the radical-free hyperpolarized solution was rapidly transferred into an injection pump located inside a 9.4T scanner. The hyperpolarized solution was injected in healthy rats to measure cardiac metabolism in vivo. Ultraviolet irradiation created nonpersistent radicals in a mixture containing 13 C-labeled pyruvic and butyric acids, and enabled the hyperpolarization of both substrates by dynamic nuclear polarization. Ethanol addition increased the radical concentration from 16 to 26 mM. Liquid-state 13 C polarization was 3% inside the pump at the time of injection, and increased to 5% by addition of ethanol to the substrate mixture prior to ultraviolet irradiation. In the rat heart, the in vivo 13 C signals from lactate, alanine, bicarbonate, and acetylcarnitine were detected following the metabolism of the injected substrate mixture. Copolarization of two different 13 C-labeled substrates and the detection of their myocardial metabolism in vivo was achieved without using persistent radicals. The absence of radicals in the solution containing the hyperpolarized 13 C-substrates may simplify the translation to clinical use, as no radical filtration is required prior to injection.

KW - Carbon-13

KW - Energy metabolism

KW - Hyperpolarization

KW - Metabolic imaging

KW - Oxidative metabolism

U2 - 10.1002/mrm.27122

DO - 10.1002/mrm.27122

M3 - Journal article

VL - 79

SP - 2451

EP - 2459

JO - Magnetic Resonance in Medicine

JF - Magnetic Resonance in Medicine

SN - 0740-3194

IS - 5

ER -