Noninvasive identification and assessment of functional brown adipose tissue in rodents using hyperpolarized 13C imaging

Lau, Angus Z.; Chen, A P; Gu, Yunyan; Ladouceur-Wodzak, Michelle; Nayak, Krishna S.; Cunningham, Charles H.

doi:10.1038/ijo.2013.58

Cited by 38 publications

(39 citation statements)

References 38 publications

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“…1B) can be readily interpreted by taking into account three equivalent and isotropic hyperfine couplings to the protons of the PA methyl group. A further isotropic hyperfine coupling to 13 C is observed when [1][2][3][4][5][6][7][8][9][10][11][12][13] C]PA is used (Fig. 1C).…”

Section: Resultsmentioning

confidence: 99%

“…To demonstrate the potential of the herein-presented method for generating imaging agents for in vivo MR, 80-mM hyperpolarized pyruvate solutions were prepared from UV-irradiated [1][2][3][4][5][6][7][8][9][10][11][12][13] C]PA samples using the hardware described in earlier publications (23,25). A 300-μL bolus was injected into a mouse femoral vein (n = 3) before acquiring real-time metabolic 13 C spectra and images.…”

Section: Resultsmentioning

confidence: 99%

“…To date, most preclinical developments have focused on samples of neat pyruvic acid (PA) to which suitable persistent radicals are added (6,(9)(10)(11)(12)(13)(14)(15)(16). In the dissolution step of the dissolution DNP method, the acid is transformed into its salt in physiological buffer.…”

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confidence: 99%

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Hyperpolarization without persistent radicals for in vivo real-time metabolic imaging

Eichhorn

Takado

Salameh

et al. 2013

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

107

171

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Hyperpolarized substrates prepared via dissolution dynamic nuclear polarization have been proposed as magnetic resonance imaging (MRI) agents for cancer or cardiac failure diagnosis and therapy monitoring through the detection of metabolic impairments in vivo. The use of potentially toxic persistent radicals to hyperpolarize substrates was hitherto required. We demonstrate that by shining UV light for an hour on a frozen pure endogenous substance, namely the glucose metabolic product pyruvic acid, it is possible to generate a concentration of photo-induced radicals that is large enough to highly enhance the 13 C polarization of the substance via dynamic nuclear polarization. These radicals recombine upon dissolution and a solution composed of purely endogenous products is obtained for performing in vivo metabolic hyperpolarized 13 C MRI with high spatial resolution. Our method opens the way to safe and straightforward preclinical and clinical applications of hyperpolarized MRI because the filtering procedure mandatory for clinical applications and the associated pharmacological tests necessary to prevent contamination are eliminated, concurrently allowing a decrease in the delay between preparation and injection of the imaging agents for improved in vivo sensitivity.is a very powerful imaging modality in terms of temporal and spatial resolution of anatomical structures. The modality is widespread, well established in clinical environments, and paramagnetic agents are used extensively for enhanced contrast or perfusion examination. MR is also a unique technique to obtain in vivo metabolic maps using the spectroscopic information that can be extracted from the time-domain acquisitions. In particular, it is possible to monitor the biochemical transformations of specific substrates that are delivered to subjects. Because it gives access to the kinetics of the conversion of substrates into metabolites, MR spectroscopy (MRS) of the carbon nuclei ( 13 C) is one of the most powerful techniques to investigate intermediary metabolism (1).The well-known weakness of MR as a spectroscopic technique is its relatively low sensitivity. It can be offset by so-called hyperpolarization methods, in particular the one based on dynamic nuclear polarization (DNP) (2), which is now commonly referred to as dissolution DNP and was first proposed about a decade ago (3). The hyperpolarized substrates obtained following dissolution DNP are biomolecules in aqueous solution with a largely out-ofequilibrium nuclear spin polarization corresponding to an enhancement of several orders of magnitude compared with the thermal equilibrium polarization attainable in MRI scanners. A basic requirement for DNP is the presence of unpaired electron spins in the sample to be hyperpolarized. These polarizing agents are usually incorporated in the form of persistent radicals. An inherent limit of any hyperpolarization method is that the intrinsic longitudinal nuclear spin relaxation will annihilate the polarization enhancement in the course of time to reach t...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Hyperpolarization without persistent radicals for in vivo real-time metabolic imaging

Eichhorn

Takado

Salameh

et al. 2013

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

107

171

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“…PDFF: proton density fat fraction, BMI: body mass index. could be detected by an increased conversion of pre-polarized (1 -13C) pyruvate into its downstream products 13C bicarbonate and (1 -13C) lactate [47]. Grimpo et al used 1H MRS to monitor the metabolic dynamics in murine BAT and detected a significant loss of free fatty acids from BAT after pharmacological stimulation [48].…”

Section: Brown Adipose Tissuementioning

confidence: 99%

Magnetic Resonance Imaging of Adipose Tissue in Metabolic Dysfunction

Franz

Syväri

Weidlich

et al. 2018

Fortschr Röntgenstr

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“…Hyperpolarized MR imaging uses in vitro nuclear spin polarization, providing orders of magnitude improvement in the signalto-noise ratio, as well as access to new substrates as contrast agents (87). For instance, breakdown of hyperpolarized 13 C-pyruvate into bicarbonate and lactate was recently demonstrated in norepinephrine-activated interscapular BAT in rats (88). Noble gases in particular have been used as hyperpolarized contrast agents owing to their inert nature and, consequently, lower potential for biologic effects.…”

Section: State Of the Art: Imaging Of Brown Adipose Tissuementioning

confidence: 99%

Imaging of Brown Adipose Tissue: State of the Art

Sampath

Bredella

et al. 2016

Radiology

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Noninvasive identification and assessment of functional brown adipose tissue in rodents using hyperpolarized 13C imaging

Abstract: The radiation-free nature and recent translation into the clinic of the hyperpolarized (13)C-imaging test may potentially facilitate trials of therapeutics targeting BAT activation in humans.

Cited by 38 publications

References 38 publications

Hyperpolarization without persistent radicals for in vivo real-time metabolic imaging

Hyperpolarization without persistent radicals for in vivo real-time metabolic imaging

Magnetic Resonance Imaging of Adipose Tissue in Metabolic Dysfunction

Imaging of Brown Adipose Tissue: State of the Art

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