Selective In Vivo Visualization of Immune-Cell Infiltration in a Mouse Model of Autoimmune Myocarditis by Fluorine-19 Cardiac Magnetic Resonance

Abstract

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. 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 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 ( r s =0.96; P <0.001), the 19 F signal-to-noise ratio ( r s =0.92; P <0.001), and the 19 F signal integral ( r s =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.

Fluorine MR Imaging of Inflammation in Atherosclerotic Plaque in Vivo

“…Immunofluorescent histologic results further demonstrated PFC absorption by cell types other than macrophages, which is in line with the findings of other studies (16,31). However, since the FITC is covalently linked only to the phospholipids in the emulsion and not to the perfluoro-15-crown-5 ether, it should be noted that we cannot be certain that these two components of the FITC PFC are still 100% associated with one another, especially at the later imaging time points.…”

Carvedilol improves biventricular fibrosis and function in experimental pulmonary hypertension

“…Lungs were stained with HE to assess for monocrotalineinduced injury, blinded to group allocation, using an established histological score from 0 (no injury) to 1 [14]. Myocarditis severity was scored as described previously to assess for monocrotaline-induced myocarditis treated by carvedilol using a semiquantitative scale: 0, no inflammatory infiltrates; 1, small foci of inflammatory cells between myocytes; 2, larger foci of >100 inflammatory cells; 3, >10 % of a crosssection involved; 4, >30 % of a cross-section involved [15].…”

In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence

“…Overall, the vast majority of studies that perform cell tracking with 19 F MRI have employed spin echo sequences. [16][17][18][19][37][38][39][40] Using the 3D bSSFP sequence, we injected and detected 1.5×10 6 Cell Sense-labeled hMSC in vivo on day 0 using a spatial resolution of 2 mm 3 (2 µL). If we assume that on day 0 all of the injected cells are present and evenly distributed, then we detected 30,000 cells per voxel.…”