In Vivo Heteronuclear Magnetic Resonance Spectroscopy

Lizarbe, Blanca; Cherix, Antoine; Gruetter, Rolf

doi:10.1007/978-1-4939-7531-0_11

Cited by 9 publications

(7 citation statements)

References 35 publications

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“…Moreover, the 13 C MRS-detected increased fatty-acid metabolism is consistent with the larger astrocytic areas and mitochondrial density found in the ARC nucleus of HFD mice. 138 Interestingly, the same study reported a noticeable shift from glutamatergic to GABAergic neurotransmission on HFD animals, 125 consistent with the development of the defective control of energy homeostasis reported in HFDs. 11 Similar effects on GABAergic metabolism have been described under ketogenic diets, 137,139 where the described increase in GABAergic neurotransmission is believed to originate from the metabolism of ketone bodies to AcCoA and the concomitant decrease in the cerebral pool of oxaloacetate (OAA).…”

Section: Magnetic Resonance Imaging and Spectroscopy Of Cerebral Altesupporting

confidence: 63%

“…124 Furthermore, when combined with the infusion of 13 C-labelled compounds, MRS can be used to evaluate metabolic fluxes. 125 Remarkably, in vivo and ex vivo MRS are sensitive enough to detect changes in very small structures (<9µL), such as the mouse hypothalamus. 126,127 Using 1 H MRS techniques in vivo, 22 authors investigated longitudinal changes of the hypothalamic neurochemical profile in mice fed HFD.…”

Section: Magnetic Resonance Imaging and Spectroscopy Of Cerebral Altementioning

confidence: 99%

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Magnetic resonance assessment of the cerebral alterations associated with obesity development

Lizarbe

Campillo

Guadilla

et al. 2020

J Cereb Blood Flow Metab

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Obesity is a current threat to health care systems, affecting approximately 13% of the world’s adult population, and over 18% children and adolescents. The rise of obesity is fuelled by inadequate life style habits, as consumption of diets rich in fats and sugars which promote, additionally, the development of associated comorbidities. Obesity results from a neuroendocrine imbalance in the cerebral mechanisms controlling food intake and energy expenditure, including the hypothalamus and the reward and motivational centres. Specifically, high-fat diets are known to trigger an early inflammatory response in the hypothalamus that precedes weight gain, is time-dependent, and eventually extends to the remaining appetite regulating regions in the brain. Multiple magnetic resonance imaging (MRI) and spectroscopy (MRS) methods are currently available to characterize different features of cerebral obesity, including diffusion weighted, T2 and volumetric imaging and 1H and 13C spectroscopic evaluations. In particular, consistent evidences have revealed increased water diffusivity and T2 values, decreased grey matter volumes, and altered metabolic profiles and fluxes, in the brain of animal models and in obese humans. This review provides an integrative interpretation of the physio-pathological processes associated with obesity development in the brain, and the MRI and MRS methods implemented to characterize them.

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Section: Magnetic Resonance Imaging and Spectroscopy Of Cerebral Altesupporting

confidence: 63%

Section: Magnetic Resonance Imaging and Spectroscopy Of Cerebral Altementioning

confidence: 99%

Magnetic resonance assessment of the cerebral alterations associated with obesity development

Lizarbe

Campillo

Guadilla

et al. 2020

J Cereb Blood Flow Metab

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“…Large improvements in sensitivity in animal and human studies have been achieved by detecting 13 C labeling indirectly via the J scalar coupling to bound 1 H nuclei , enhancing spatial resolution to several cm 3 at 4 Tesla as well as allowing MRSI acquisition . A detailed evaluation of the sensitivity and resolution advantages of different inverse and direct 13 C acquisition has recently been published .…”

Section: Future Prospects For 13c Mrs Studies In Humansmentioning

confidence: 99%

“…The ability to hyperpolarize 13 C labeled substrates such as pyruvate to levels 10,000x or more than the natural polarization, has generated great excitement in the MR field. While the applications in brain have been mostly focused on animal models, recent hyperpolarized data have been acquired in human brain 15. A primary limitation for studying the brain, outside of brain cancer, is due to the blood brain barrier, consisting of the capillary endothelia, which restricts the rate of [1‐ 13 C] pyruvate entry into the brain relative to other organs and makes it rate limiting .…”

Section: Future Prospects For 13c Mrs Studies In Humansmentioning

confidence: 99%

In vivo ¹³C and ¹H‐[¹³C] MRS studies of neuroenergetics and neurotransmitter cycling, applications to neurological and psychiatric disease and brain cancer

et al. 2019

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In the last 25 years 13 C MRS has been established as the only noninvasive method for measuring glutamate neurotransmission and cell specific neuroenergetics. Although technically and experimentally challenging 13 C MRS has already provided important new information on the relationship between neuroenergetics and neuronal function, the high energy cost of brain function in the resting state and the role of altered neuroenergetics and neurotransmitter cycling in disease. In this paper we review the metabolic and neurotransmitter pathways that can be measured by 13 C MRS and key findings on the linkage between neuroenergetics, neurotransmitter cycling, and brain function. Applications of 13 C MRS to neurological and psychiatric disease as well as brain cancer are reviewed. Recent technological developments that may help to overcome spatial resolution and brain coverage limitations of 13 C MRS are discussed. | INTRODUCTIONBrain cells are highly specialized metabolically and functionally. Prior to the advent of 13 C MRS there was no method of studying cell specific brain metabolism in vivo. As described in this review 13 C MRS in combination with selectively 13 C labeled substrates has allowed the study of how metabolism supports function in the three major brain cell types, glutamatergic neurons, GABAergic neurons, and glia. Glutamatergic neurons Abbreviations: ANLS, astrocyte neuronal lactate shuttle; ATP, adenosine tri phosphate; AV, arterio-venous; CMRglc (ox), cerebral metabolic rate of oxidative glucose consumption; CMRglc (ox)-N, cerebral metabolic rate of neuronal oxidative glucose consumption; CMRglc, cerebral metabolic rate of glucose consumption; DMI, deuterium metabolic imaging; EEG, electroencephalogram;GABA, gamma amino butyric acid; GBM, glioblastoma; HSQC, heteronuclear single quantum coherence; MDD, major depressive disorder; MRS, magnetic resonance spectroscopy; MRSI, magnetic resonance spectroscopic imaging; NMDA, N methyl D aspartate; nOe, nuclear Overhauser effect; PET, positron emission tomography; SAR, specific absorption rate; T1DM, type 1 diabetes mellitus; TCA, tricarboxylic acid cycle; Vcycle, Velocity (flux) of the glutamate/GABA/glutamine cycle.; VTCA, velocity of the tricarboxylic acid cycle release the major excitatory neurotransmitter glutamate and GABAergic neurons release the major inhibitory neurotransmitter gamma amino butyric acid (GABA). Information transfer in the brain is largely coded by the pattern and timing of glutamate and GABA neurotransmitter release in vesicles with glutamate release leading to depolarization at the postsynaptic terminal and GABA release leading to hyperpolarization 1 . As described in this review, studies primarily using 13 C MRS have shown that the energy required to support neuronal signaling is the dominant energy cost of the brain even under resting awake conditions. The large majority of glutamate and a significant fraction of GABA is taken up by a class of cells called glia. Glia are not directly involved in brain communication but are critical f...

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“…Non-invasive indirect carbon-13 Magnetic Resonance Spectroscopy ( 1 H-[ 13 C]-MRS) was performed as previously described 59,94 . The experimental set-up was comparable to that of 1 H-MRS, with two main differences: (1) animals underwent femoral vein cannulation for the infusion of uniformly labeled 13 C-glucose ([U- 13 C 6 ]Glc) for a scan of ~230min duration; and (2) the coil included a 13 C channel.…”

Section: Methodsmentioning

confidence: 99%

Deletion ofCrtc1leads to hippocampal neuroenergetic impairments associated with depressive-like behavior

Cherix

Poitry‐Yamate

Lanz

et al. 2020

Preprint

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Mood disorders (MD) are a major burden on society as their biology remains poorly understood, challenging both diagnosis and therapy. Among many observed biological dysfunctions, homeostatic dysregulation, such as metabolic syndrome (MeS), shows considerable comorbidity with MD. Recently, CREB-regulated transcription coactivator 1 (CRTC1), a regulator of brain metabolism, was proposed as a promising factor to understand this relationship. Searching for imaging biomarkers and associating them with pathophysiological mechanisms using preclinical models, can provide significant insight into these complex psychiatric diseases and help the development of personalized healthcare. Here, we used neuroimaging technologies to show that deletion of Crtc1 in mice leads to an imaging fingerprint of hippocampal metabolic impairment related to depressive-like behavior. By identifying the underlying molecular/physiological origin, we could assign an energy-boosting mood-stabilizing treatment, ebselen, which rescued behavior and neuroimaging markers. Finally, our results point towards the GABAergic system as a potential therapeutic target for behavioral dysfunctions related to metabolic disorders. This study provides new insights on Crtc1's and MeS's relationship to MD and establishes depression-related markers with clinical potential.

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In Vivo Heteronuclear Magnetic Resonance Spectroscopy

Cited by 9 publications

References 35 publications

Magnetic resonance assessment of the cerebral alterations associated with obesity development

Magnetic resonance assessment of the cerebral alterations associated with obesity development

In vivo ¹³C and ¹H‐[¹³C] MRS studies of neuroenergetics and neurotransmitter cycling, applications to neurological and psychiatric disease and brain cancer

Deletion ofCrtc1leads to hippocampal neuroenergetic impairments associated with depressive-like behavior

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In Vivo Heteronuclear Magnetic Resonance Spectroscopy

Cited by 9 publications

References 35 publications

Magnetic resonance assessment of the cerebral alterations associated with obesity development

Magnetic resonance assessment of the cerebral alterations associated with obesity development

In vivo 13C and 1H‐[13C] MRS studies of neuroenergetics and neurotransmitter cycling, applications to neurological and psychiatric disease and brain cancer

Deletion ofCrtc1leads to hippocampal neuroenergetic impairments associated with depressive-like behavior

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In vivo ¹³C and ¹H‐[¹³C] MRS studies of neuroenergetics and neurotransmitter cycling, applications to neurological and psychiatric disease and brain cancer