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  Investigation of a Calcium-Responsive Contrast Agent in Cellular Model Systems: Feasibility for Use as a Smart Molecular Probe in Functional MRI

Angelovski, G., Gottschalk, S., Milošević, M., Engelmann, J., Hagberg, G., Kadjane, P., et al. (2014). Investigation of a Calcium-Responsive Contrast Agent in Cellular Model Systems: Feasibility for Use as a Smart Molecular Probe in Functional MRI. ACS Chemical Neuroscience, 5(5), 360-369. doi:10.1021/cn500049n.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-801F-C Version Permalink: http://hdl.handle.net/21.11116/0000-0001-2A21-B
Genre: Journal Article

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http://pubs.acs.org/doi/pdf/10.1021/cn500049n (Publisher version)
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 Creators:
Angelovski, G1, 2, Author              
Gottschalk, S2, 3, Author              
Milošević, M, Author
Engelmann, J2, 3, Author              
Hagberg, GE, Author
Kadjane, P2, 4, Author              
Andjus, P, Author
Logothetis, NK2, 4, Author              
Affiliations:
1Research Group MR Neuroimaging Agents, Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_2528691              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_1497794              
3Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497796              
4Department Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497798              

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 Abstract: Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca2+ may allow tracking neuronal activity independent of brain vasculature, thus avoiding the characteristic limitations of current fMRI techniques. Here we report an in vitro proof-of-principle study with a Ca2+-sensitive, Gd3+-based SCA in an attempt to validate its potential use as a functional in vivo marker. First, we quantified its relaxometric response in a complex 3D cell culture model. Subsequently, we examined potential changes in the functionality of primary glial cells following administration of this SCA. Monitoring intracellular Ca2+ showed that, despite a reduction in the Ca2+ level, transport of Ca2+ through the plasma membrane remained unaffected, while stimulation with ATP induced Ca2+-transients suggested normal cellular signaling in the presence of low millimolar SCA concentrations. SCAs merely lowered the intracellular Ca2+ level. Finally, we estimated the longitudinal relaxation times (T1) for an idealized in vivo fMRI experiment with SCA, for extracellular Ca2+ concentration level changes expected during intense neuronal activity which takes place upon repetitive stimulation. The values we obtained indicate changes in T1 of around 1ndash;6%, sufficient to be robustly detectable using modern MRI methods in high field scanners. Our results encourage further attempts to develop even more potent SCAs and appropriate fMRI protocols. This would result in novel methods that allow monitoring of essential physiological processes at the cellular and molecular level.

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 Dates: 2014-05
 Publication Status: Published in print
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 Identifiers: DOI: 10.1021/cn500049n
BibTex Citekey: AngelovskiGMEHKAL2014
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Title: ACS Chemical Neuroscience
Source Genre: Journal
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Pages: - Volume / Issue: 5 (5) Sequence Number: - Start / End Page: 360 - 369 Identifier: -