TY - JOUR
T1 - Selective in vivo visualization of immune-cell infiltration in a mouse model of autoimmune myocarditis by fluorine-19 cardiac magnetic resonance
AU - Van Heeswijk, Ruud B.
AU - De Blois, Jonathan
AU - Kania, Gabriela
AU - Gonzales, Christine
AU - Blyszczuk, Przemyslaw
AU - Stuber, Matthias
AU - Eriksson, Urs
AU - Schwitter, Juerg
PY - 2013/3
Y1 - 2013/3
N2 - Background-The goal of this study was to characterize the performance of fluorine-19 (19F) cardiac magnetic resonance (CMR) for the specific detection of inflammatory cells in a mouse model of myocarditis. Intravenously administered perfluorocarbons are taken up by infiltrating inflammatory cells and can be detected by 19F-CMR. 19F-labeled cells should, therefore, generate an exclusive signal at the inflamed regions within the myocardium. Methods and Results-Experimental autoimmune myocarditis was induced in BALB/c mice. After intravenous injection of 2×200 μL of a perfluorocarbon on day 19 and 20 (n=9) after immunization, in vivo 19F-CMR was performed at the peak of myocardial inflammation (day 21). In 5 additional animals, perfluorocarbon combined with FITC (fluorescein isothiocyanate) was administered for postmortem immunofluorescence and flow-cytometry analyses. Control experiments were performed in 9 animals. In vivo 19F-CMR detected myocardial inflammation in all experimental autoimmune myocarditis-positive animals. Its resolution was sufficient to identify even small inflammatory foci, that is, at the surface of the right ventricle. Postmortem immunohistochemistry and flow cytometry confirmed the presence of perfluorocarbon in macrophages, dendritic cells, and granulocytes, but not in lymphocytes. The myocardial volume of elevated 19F signal (rs=0.96; P<0.001), the 19F signal-to-noise ratio (rs=0.92; P<0.001), and the 19F signal integral (r s=0.96; P<0.001) at day 21 correlated with the histological myocarditis severity score.Conclusions-In vivo 19F-CMR was successfully used to visualize the inflammation specifically and robustly in experimental autoimmune myocarditis, and thus allowed for an unprecedented insight into the involvement of inflammatory cells in the disease process.
AB - Background-The goal of this study was to characterize the performance of fluorine-19 (19F) cardiac magnetic resonance (CMR) for the specific detection of inflammatory cells in a mouse model of myocarditis. Intravenously administered perfluorocarbons are taken up by infiltrating inflammatory cells and can be detected by 19F-CMR. 19F-labeled cells should, therefore, generate an exclusive signal at the inflamed regions within the myocardium. Methods and Results-Experimental autoimmune myocarditis was induced in BALB/c mice. After intravenous injection of 2×200 μL of a perfluorocarbon on day 19 and 20 (n=9) after immunization, in vivo 19F-CMR was performed at the peak of myocardial inflammation (day 21). In 5 additional animals, perfluorocarbon combined with FITC (fluorescein isothiocyanate) was administered for postmortem immunofluorescence and flow-cytometry analyses. Control experiments were performed in 9 animals. In vivo 19F-CMR detected myocardial inflammation in all experimental autoimmune myocarditis-positive animals. Its resolution was sufficient to identify even small inflammatory foci, that is, at the surface of the right ventricle. Postmortem immunohistochemistry and flow cytometry confirmed the presence of perfluorocarbon in macrophages, dendritic cells, and granulocytes, but not in lymphocytes. The myocardial volume of elevated 19F signal (rs=0.96; P<0.001), the 19F signal-to-noise ratio (rs=0.92; P<0.001), and the 19F signal integral (r s=0.96; P<0.001) at day 21 correlated with the histological myocarditis severity score.Conclusions-In vivo 19F-CMR was successfully used to visualize the inflammation specifically and robustly in experimental autoimmune myocarditis, and thus allowed for an unprecedented insight into the involvement of inflammatory cells in the disease process.
KW - MRI
KW - Mouse
KW - Myocarditis
KW - Perfluorocarbon
UR - http://www.scopus.com/inward/record.url?scp=84877295796&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877295796&partnerID=8YFLogxK
U2 - 10.1161/CIRCIMAGING.112.000125
DO - 10.1161/CIRCIMAGING.112.000125
M3 - Article
C2 - 23343515
AN - SCOPUS:84877295796
SN - 1941-9651
VL - 6
SP - 277
EP - 284
JO - Circulation: Cardiovascular Imaging
JF - Circulation: Cardiovascular Imaging
IS - 2
ER -