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Longitudinal 19F magnetic resonance imaging of brain oxygenation in a mouse model of vascular cognitive impairment using a cryogenic radiofrequency coil

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Abstract

Introduction

We explored the use of a perfluoro-15-crown-5 ether nanoemulsion (PFC) for measuring tissue oxygenation using a mouse model of vascular cognitive impairment.

Methods

Seventeen C57BL/6 mice underwent stereotactic injection of PFC coupled to a fluorophore into the striatum and corpus callosum. Combined 1H/19F magnetic resonance imaging (MRI) to localize the PFC and R1 mapping to assess pO2 were performed. The effect of gas challenges on measured R1 was investigated. All mice then underwent bilateral implantation of microcoils around the common carotid arteries to induce global cerebral hypoperfusion. 19F-MRI and R1 mapping were performed 1 day, 1 week, and 4 weeks after microcoil implantation. In vivo R1 values were converted to pO2 through in vitro calibration. Tissue reaction to the PFC was assessed through ex vivo immunohistochemistry of microglial infiltration.

Results

R1 increased with increasing oxygen concentrations both in vitro and in vivo and the strength of the 19F signal remained largely stable over 4 weeks. In the two mice that received all four scans, tissue pO2 decreased after microcoil implantation and recovered 4 weeks later. We observed infiltration of the PFC deposits by microglia.

Discussion

Despite remaining technical challenges, intracerebrally injected PFC is suitable for monitoring brain oxygenation in vivo.

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Acknowledgements

The authors thank Dr. med. Esmeralda Heiden and Christa Josties for their valuable assistance in establishing the histology protocol used in this study. This work was supported by the Stiftung Charité (BIH_PRO_317), the DFG Cluster of Excellence NeuroCure (Exc 257), SFB 1116, DFG grants FL 303/6-1/TE 1209/1-1, and the Federal Ministry of Education and Research (BMBF; 01EO0801, Center for Stroke Research Berlin). Funders played no role in the design, analysis, or reporting of this study.

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Authors and Affiliations

  1. Department of Experimental Neurology and Center for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

    Ahmed A. Khalil, Susanne Mueller, Marco Foddis, Larissa Mosch, Janet Lips, Ingo Przesdzing, Ulrich Dirnagl & Philipp Boehm-Sturm

  2. Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

    Ahmed A. Khalil

  3. Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany

    Ahmed A. Khalil

  4. Charité, Universitätsmedizin Berlin, NeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Berlin, Germany

    Susanne Mueller, Ulrich Dirnagl & Philipp Boehm-Sturm

  5. Experimental Cardiovascular Imaging, Molecular Cardiology, Heinrich-Heine-University of Düsseldorf, Düsseldorf, Germany

    Sebastian Temme & Ulrich Flögel

  6. Berlin Institute of Health (BIH), Berlin, Germany

    Ulrich Dirnagl

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  1. Ahmed A. Khalil
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Contributions

Study conception and design: AAK, ST, UF, UD, PB-S. Acquisition of data: AAK, SM, MF, LM, JL, IP, PB-S. Analysis and interpretation of data: AAK, IP, PB-S. Drafting of manuscript: AAK, PB-S. Critical revision: AAK, SM, MF, LM, JL, IP, ST, UF, UD, PB-S

Corresponding author

Correspondence to Ahmed A. Khalil.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Khalil, A.A., Mueller, S., Foddis, M. et al. Longitudinal 19F magnetic resonance imaging of brain oxygenation in a mouse model of vascular cognitive impairment using a cryogenic radiofrequency coil. Magn Reson Mater Phy 32, 105–114 (2019). https://doi.org/10.1007/s10334-018-0712-x

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