Fluorine MR Imaging of Inflammation in Atherosclerotic Plaque in Vivo

Ruud B van Heeswijk; Maxime Pellegrin; Ulrich Flögel; Christine Gonzales; Jean-François Aubert; Lucia Mazzolai; Juerg Schwitter; Matthias Stuber

doi:10.1148/radiol.14141371

Fluorine MR Imaging of Inflammation in Atherosclerotic Plaque in Vivo

Radiology. 2015 May;275(2):421-9. doi: 10.1148/radiol.14141371. Epub 2014 Dec 12.

Authors

Ruud B van Heeswijk¹, Maxime Pellegrin, Ulrich Flögel, Christine Gonzales, Jean-François Aubert, Lucia Mazzolai, Juerg Schwitter, Matthias Stuber

Affiliation

¹ From the Department of Radiology (R.B.v.H., M.S.), Angiology Service (M.P., J.F.A., L.M.), Cardiology Service (C.G., J.S.), and Cardiac Magnetic Resonance Center (C.G., J.S.), University (UNIL) and University Hospital of Lausanne (CHUV), Rue de Bugnon 46, Lausanne 1011, Switzerland; CardioVascular Magnetic Resonance Research Center (CVMR), Center for Biomedical Imaging (CIBM), Lausanne, Switzerland (R.B.v.H., M.S.); and Department of Cardiovascular Physiology, Heinrich Heine University, Düsseldorf, Germany (U.F.).

PMID: 25496216
DOI: 10.1148/radiol.14141371

Abstract

Purpose: To preliminarily test the hypothesis that fluorine 19 ((19)F) magnetic resonance (MR) imaging enables the noninvasive in vivo identification of plaque inflammation in a mouse model of atherosclerosis, with histologic findings as the reference standard.

Materials and methods: The animal studies were approved by the local animal ethics committee. Perfluorocarbon (PFC) emulsions were injected intravenously in a mouse model of atherosclerosis (n = 13), after which (19)F and anatomic MR imaging were performed at the level of the thoracic aorta and its branches at 9.4 T. Four of these animals were imaged repeatedly (at 2-14 days) to determine the optimal detection time. Repeated-measures analysis of variance with a Tukey test was applied to determine if there was a significant change in (19)F signal-to-noise ratio (SNR) of the plaques and liver between the time points. Six animals were injected with a PFC emulsion that also contained a fluorophore. As a control against false-positive results, wild-type mice (n = 3) were injected with a PFC emulsion, and atherosclerotic mice were injected with a saline solution (n = 2). The animals were sacrificed after the last MR imaging examination, after which high-spatial-resolution ex vivo MR imaging and bright-field and immunofluorescent histologic examination were performed.

Results: (19)F MR signal was detected in vivo in plaques in the aortic arch and its branches. The SNR was found to significantly increase up to day 6 (P < .001), and the SNR of all mice at this time point was 13.4 ± 3.3. The presence of PFC and plaque in the excised vessels was then confirmed both through ex vivo (19)F MR imaging and histologic examination, while no signal was detected in the control animals. Immunofluorescent histologic findings confirmed the presence of PFC in plaque macrophages.

Conclusion: (19)F MR imaging allows the noninvasive in vivo detection of inflammation in atherosclerotic plaques in a mouse model of atherosclerosis and opens up new avenues for both the early detection of vulnerable atherosclerosis and the elucidation of inflammation mechanisms in atherosclerosis.

Publication types

Evaluation Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Disease Models, Animal
Fluorine*
Inflammation / complications
Inflammation / diagnosis*
Magnetic Resonance Imaging / methods*
Male
Mice
Mice, Inbred C57BL
Plaque, Atherosclerotic / complications
Plaque, Atherosclerotic / diagnosis*

Substances

Fluorine