Towards Quantification of Inflammation in Atherosclerotic Plaque in the Clinic – Characterization and Optimization of Fluorine-19 MRI in Mice at 3 T

• Published in: Scientific reports 2019-11, Vol.9 (1), p.17488-12, Article 17488
• Main Authors: Darçot, Emeline, Colotti, Roberto, Pellegrin, Maxime, Wilson, Anne, Siegert, Stefanie, Bouzourene, Karima, Yerly, Jérôme, Mazzolai, Lucia, Stuber, Matthias, van Heeswijk, Ruud B.
• Format: Article
• Language: English
• Subjects: 13/1; 13/31; 13/51; 59; 59/57; 64/60; 692/308/575; 692/53/2421; 692/699/75/593/2100; 692/700/1421/1628; Animals; Aortic arch; Apolipoproteins; Arteriosclerosis; Atherosclerosis; Dendritic cells; Dendritic Cells - metabolism; Disease Models, Animal; Feasibility Studies; Flow Cytometry; Fluorine; Fluorine-19 Magnetic Resonance Imaging - instrumentation; Humanities and Social Sciences; Humans; Immunohistochemistry; Inflammation; Leukocytes (neutrophilic); Macrophages; Macrophages - metabolism; Magnetic resonance imaging; Male; Mice; Mice, Knockout, ApoE; multidisciplinary; Neutrophils - metabolism; NMR; Nuclear magnetic resonance; Perfluorocarbons; Plaque, Atherosclerotic - diagnostic imaging; Plaque, Atherosclerotic - genetics; Plaque, Atherosclerotic - immunology; Plaques; Rodents; Science; Science (multidisciplinary); Signal-To-Noise Ratio; Translation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-53905-9

Fluorine-19 ( 19 F) magnetic resonance imaging (MRI) of injected perfluorocarbons (PFCs) can be used for the quantification and monitoring of inflammation in diseases such as atherosclerosis. To advance the translation of this technique to the clinical setting, we aimed to 1) demonstrate the feasibility of quantitative 19 F MRI in small inflammation foci on a clinical scanner, and 2) to characterize the PFC-incorporating leukocyte populations and plaques. To this end, thirteen atherosclerotic apolipoprotein-E-knockout mice received 2 × 200 µL PFC, and were scanned on a 3 T clinical MR system. 19 F MR signal was detected in the aortic arch and its branches in all mice, with a signal-to-noise ratio of 11.1 (interquartile range IQR = 9.5–13.1) and a PFC concentration of 1.15 mM (IQR = 0.79–1.28). Imaging flow cytometry was used on another ten animals and indicated that PFC-labeled leukocytes in the aortic arch and it branches were mainly dendritic cells, macrophages and neutrophils (ratio 9:1:1). Finally, immunohistochemistry analysis confirmed the presence of those cells in the plaques. We thus successfully used 19 F MRI for the noninvasive quantification of PFC in atherosclerotic plaque in mice on a clinical scanner, demonstrating the feasibility of detecting very small inflammation foci at 3 T, and advancing the translation of 19 F MRI to the human setting.