Development of in vivo NMR techniques for studying the impact of Ocean acidification and warming on the neurophysiology of Antartic fishes
Final Report Abstract
Ocean acidification and warming as a consequence of climate change affect marine organisms. Thus, for example, neurological changes have been observed in polar cod, which were induced by ocean acidification and warming. As a potential cause, a connection between the neurological impairments and changes in intracellular pH (pHi) has been postulated as it was described for animal models in preclinical research. Therefore, the non-invasive determination of the intracellular pH (pHi) with high spatial and temporal resolution is of great interest. A promising tool for noninvasive pH measurements is the CEST contrast (Chemical Exchange Saturation Transfer) in Magnetic Resonance Imaging (MRI), which enables the indirect detection of endogenous or exogenous molecules with exchangeable protons using changes in the NMR signal of the water pool. The CEST effect mainly depends on the metabolite concentration and the exchange rate between this metabolite and water, which in turn is influenced by physical and physiological parameters. These properties enable CEST to be used for the in vivo determination of changes in metabolite concentration and pH. The current project was aimed at the development and adaption of the measurement method for CEST MRI and its application for determining changes in pHi with a high temporal and spatial resolution in the brain of marine fish. CEST from glutamate to water (GluCEST) was experimentally investigated in a broad temperature and pH range. The applicability of GluCEST to determine relative changes in pH even at low temperatures depends on glutamate concentration and the parameters used in the experiments. Localized 1H NMR spectroscopy in combination with quantification algorithms incorporating a priori knowledge is an established method for the quantification of metabolite concentrations. In most cases, these algorithms use model functions based on chemical shifts at 37°C. Therefore, the temperature dependency of the chemical shifts for important metabolites has been examined to avoid systematic quantification errors caused by the use of incorrect prior knowledge for spectra recorded at temperatures different from 37°C. The exchange rates show an exponential behavior as a function of temperature, thus offering a completely new picture of metabolites whose exchange regime offers the possibility to determine a CEST effect at temperatures near the freezing point of water. In this context, the taurine based TauCEST effect was investigated in a broad pH and temperature range. Investigations showed that the specificity of TauCEST offers the possibility to use this method as a suitable tool to detect pHi changes in the brain of polar cod at 1 °C. The first in vivo application of the TauCEST effect in the brain of polar cod showed an increase of about 1.5-3% under different CO2 concentrations. Localized 1H NMR spectroscopy, which was successfully adapted for the in vivo application in the brain of marine fish at 9.4 T, indicated no significant changes in concentration for those metabolites that mainly contribute to the CEST effect. Thus, the in vivo application of TauCEST proves to be an adequate method for determining non-invasively relative changes in pHi with high spatial and temporal resolution in the brain of polar cod during exposure to elevated CO2 concentrations.
Publications
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Investigating GluCEST and its specificity for pH mapping at low temperatures. NMR Biomed 2015; 28(11):1507-1517
Wermter FC, Bock C, Dreher W
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Investigating GluCEST for pH mapping at low temperatures: A feasibility study. ESMRMB 2015 32nd Annual Scientific Meeting, Edinburgh, 1-3 October 2015
Wermter FC, Bock C, Dreher W
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The specificity of GluCEST imaging at low temperatures. ESMRMB 2015 32nd Annual Scientific Meeting, Edinburgh, 1-3 October 2015
Wermter FC, Bock C, Dreher W
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MRI and MRS on preserved samples as a tool in fish ecology. Magn Reson Imaging 2017; 38:39-46
Bock C, Wermter FC, Mintenbeck K
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pH-Bildgebung am Gehirn von polaren Fischen: eine TauCEST Anwendung. DS ISMRM 2017 20te Jahrestagung, Göttingen, 16-17 November 2017
Wermter FC, Maus B, Bock C, Dreher W
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Temperature dependence of 1H NMR chemical shifts and its influence on estimated metabolite concentrations. Magn Reson Mater Phy 2017; 30(6):579-590
Wermter FC, Mitschke N, Bock C, Dreher W
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CO2 induced pHi changes in the brain of polar fish: a TauCEST application. Joint Annual Meeting ISMRM-ESMRMB, Paris, France, 16-21 June 2018
Wermter FC, Maus B, Pörtner HO, Dreher W, Bock C
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CO2 induced pHi changes in the brain of polar fish: a TauCEST application. NMR Biomed 2018; 31(8); e3955
Wermter FC, Maus B, Pörtner HO, Dreher W, Bock C
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Direct signal detection of exchangeable protons of metabolites with high SNR using ultrashort-TE, short-TR 1H MRSI without water presaturation. Joint Annual Meeting ISMRM-ESMRMB, Paris, France, 16-21 June 2018
Dreher W, Wermter FC
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In vivo 31P-MRS of muscle bioenergetics in marine invertebrates: Future ocean limits scallops’ performance. Magn Reson Imaging 2019; 61:239-246
Bock C, Wermter FC, Schalkhausser B, Blicher ME, Pörtner HO, Lannig G, Sejr MK
