Selective in vivo visualization of immune-cell infiltration in a mouse model of autoimmune myocarditis by fluorine-19 cardiac magnetic resonance.
BACKGROUND
The goal of this study was to characterize the performance of fluorine-19 ((19)F) 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 (19)F-CMR. (19)F-labeled cells should, therefore, generate an exclusive signal at the inflamed regions within the myocardium.


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 (19)F-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 (19)F-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 (19)F signal (rs=0.96; P<0.001), the (19)F signal-to-noise ratio (rs=0.92; P<0.001), and the (19)F signal integral (rs=0.96; P<0.001) at day 21 correlated with the histological myocarditis severity score.


CONCLUSIONS
In vivo (19)F-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.
Department of Radiology, University Hospital (CHUV), Lausanne, Switzerland. ruud.mri@gmail.com
Ruud B
RB
van Heeswijk
Jonathan
J
De Blois
Gabriela
G
Kania
Christine
C
Gonzales
Przemyslaw
P
Blyszczuk
Matthias
M
Stuber
Urs
U
Eriksson
Juerg
J
Schwitter
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005461:Fluorine / Q000008:administration & dosage / Q000493:pharmacokinetics; D005466:Fluorocarbons / Q000008:administration & dosage / Q000493:pharmacokinetics; D006098:Granulocytes / Q000276:immunology; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009205:Myocarditis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D059629:Signal-To-Noise Ratio
D005466:Fluorocarbons; D005461:Fluorine