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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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.
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.
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.
Despite remaining technical challenges, intracerebrally injected PFC is suitable for monitoring brain oxygenation in vivo.
KeywordsOxygenation Vascular cognitive impairment 19F-MRI Perfluoro-15-crown-5-ether
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.
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
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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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