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Metabolic changes assessed by MRS accurately reflect brain function during drug-induced epilepsy in mice in contrast to fMRI-based hemodynamic readouts


Seuwen, Aline; Schroeter, Aileen; Grandjean, Joanes; Rudin, Markus (2015). Metabolic changes assessed by MRS accurately reflect brain function during drug-induced epilepsy in mice in contrast to fMRI-based hemodynamic readouts. NeuroImage, 120:55-63.

Abstract

Functional proton magnetic resonance spectroscopy ((1)H-MRS) enables the non-invasive assessment of neural activity by measuring signals arising from endogenous metabolites in a time resolved manner. Proof-of-principle of this approach has been demonstrated in humans and rats; yet functional (1)H-MRS has not been applied in mice so far, although it would be of considerable interest given the many genetically engineered models of neurological disorders established in this species only. Mouse (1)H-MRS is challenging as the high demands on spatial resolution typically result in long data acquisition times not commensurable with functional studies. Here, we propose an approach based on spectroscopic imaging in combination with the acquisition of the free induction decay to maximize signal intensity. Highly resolved metabolite maps have been recorded from mouse brain with 12min temporal resolution. This enabled monitoring of metabolic changes following the administration of bicuculline, a GABA-A receptor antagonist. Changes in levels of metabolites involved in energy metabolism (lactate and phosphocreatine) and neurotransmitters (glutamate) were investigated in a region-dependent manner and shown to scale with the bicuculline dose. GABAergic inhibition induced spectral changes characteristic for increased neurotransmitter turnover and oxidative stress. In contrast to metabolic readouts, BOLD and CBV fMRI responses did not scale with the bicuculline dose indicative of the failure of neurovascular coupling. Nevertheless fMRI measurements supported the notion of increased oxidative stress revealed by functional MRS. Hence, the combined analysis of metabolic and hemodynamic changes in response to stimulation provides complementary insight into processes associated with neural activity.

Abstract

Functional proton magnetic resonance spectroscopy ((1)H-MRS) enables the non-invasive assessment of neural activity by measuring signals arising from endogenous metabolites in a time resolved manner. Proof-of-principle of this approach has been demonstrated in humans and rats; yet functional (1)H-MRS has not been applied in mice so far, although it would be of considerable interest given the many genetically engineered models of neurological disorders established in this species only. Mouse (1)H-MRS is challenging as the high demands on spatial resolution typically result in long data acquisition times not commensurable with functional studies. Here, we propose an approach based on spectroscopic imaging in combination with the acquisition of the free induction decay to maximize signal intensity. Highly resolved metabolite maps have been recorded from mouse brain with 12min temporal resolution. This enabled monitoring of metabolic changes following the administration of bicuculline, a GABA-A receptor antagonist. Changes in levels of metabolites involved in energy metabolism (lactate and phosphocreatine) and neurotransmitters (glutamate) were investigated in a region-dependent manner and shown to scale with the bicuculline dose. GABAergic inhibition induced spectral changes characteristic for increased neurotransmitter turnover and oxidative stress. In contrast to metabolic readouts, BOLD and CBV fMRI responses did not scale with the bicuculline dose indicative of the failure of neurovascular coupling. Nevertheless fMRI measurements supported the notion of increased oxidative stress revealed by functional MRS. Hence, the combined analysis of metabolic and hemodynamic changes in response to stimulation provides complementary insight into processes associated with neural activity.

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3 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology

04 Faculty of Medicine > Institute of Biomedical Engineering
Dewey Decimal Classification:170 Ethics
610 Medicine & health
Language:English
Date:15 October 2015
Deposited On:19 Nov 2015 14:31
Last Modified:05 Apr 2016 19:31
Publisher:Elsevier
ISSN:1053-8119
Publisher DOI:https://doi.org/10.1016/j.neuroimage.2015.07.004
PubMed ID:26166624

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