Towards Quantification of Inflammation in Atherosclerotic Plaque in the Clinic \u2013 Characterization and Optimization of Fluorine-19 MRI in Mice at 3\u2009T

Emeline Darçot,Karima Bouzourene,Maxime Pellegrin,Matthias Stuber,Anne Wilson,Roberto Colotti,Lucia Mazzolai,Jérôme Yerly,Ruud B Van Heeswijk,Stefanie Siegert

doi:10.1038/s41598-019-53905-9

Towards Quantification of Inflammation in Atherosclerotic Plaque in the Clinic \u2013 Characterization and Optimization of Fluorine-19 MRI in Mice at 3\u2009T

Emeline Darçot, Karima Bouzourene + Show 8 more

Open Access

https://doi.org/10.1038/s41598-019-53905-9

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Abstract

Fluorine-19 (19F) 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 19F 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. 19F 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 19F 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 19F MRI to the human setting.

Highlights

Fluorine-19 (19F) magnetic resonance imaging (MRI) of perfluorocarbon (PFC) emulsions has been increasingly used for cell tracking and inflammation imaging due to its high specificity and the biological and chemical inertness of PFCs8–10
In images reconstructed with standard Fourier transform, the average SNR of the 19F signals identified as atherosclerotic plaques was 11.1and 47.9 ± 23.2 in the liver
Motion artifacts from the high PFC concentration in the reference tube were always present in the 3D 19F MR images, but due to the placement of the tube diagonally above the mouse, they never projected into the thorax

Summary

Introduction

Fluorine-19 (19F) magnetic resonance imaging (MRI) of perfluorocarbon (PFC) emulsions has been increasingly used for cell tracking and inflammation imaging due to its high specificity and the biological and chemical inertness of PFCs8–10. To compensate for the loss of sensitivity due to the translation from ultrahigh-magnetic-field animal scanners to lower-magnetic-field clinical scanners, both the MRI acquisition and reconstruction should be optimized This was already investigated in pigs and mice for myocardial infarction[19,20] without quantification of the 19F concentration at the inflammation site, and while it was quantitatively explored in a pair of mice for cancer[21] and ex vivo for cell tracking[22], it remains to be studied for small low-signal inflammation foci such as atherosclerotic plaques. After the ex vivo acquisitions, the immune cell populations identified by IFC were targeted to perform the immunohistochemistry analysis

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