Ahmed A Khalil1,2,3, Susanne Mueller4,5, Marco Foddis4, Larissa Mosch4, Janet Lips4, Ingo Przesdzing4, Sebastian Temme6, Ulrich Flögel6, Ulrich Dirnagl4,5,7, Philipp Boehm-Sturm4,5. 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-abdelrahim.khalil@charite.de. 2. Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany. ahmed-abdelrahim.khalil@charite.de. 3. Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany. ahmed-abdelrahim.khalil@charite.de. 4. 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. 5. Charité, Universitätsmedizin Berlin, NeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Berlin, Germany. 6. Experimental Cardiovascular Imaging, Molecular Cardiology, Heinrich-Heine-University of Düsseldorf, Düsseldorf, Germany. 7. Berlin Institute of Health (BIH), Berlin, Germany.
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.
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.
Authors: Shweta Saini; Jennifer Poelmans; Hannelie Korf; James L Dooley; Sayuan Liang; Bella B Manshian; Rein Verbeke; Stefaan J Soenen; Greetje Vande Velde; Ine Lentacker; Katrien Lagrou; Adrian Liston; Conny Gysemans; Stefaan C De Smedt; Uwe Himmelreich Journal: iScience Date: 2019-09-18