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Published Online
on June 23, 2008

Circulation. 2008
Published online before print June 23, 2008, doi: 10.1161/CIRCULATIONAHA.107.737890
A more recent version of this article appeared on July 8, 2008
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Submitted on September 4, 2007
Accepted on April 28, 2008

In Vivo Monitoring of Inflammation After Cardiac and Cerebral Ischemia by Fluorine Magnetic Resonance Imaging

Ulrich Flögel PhD*, Zhaoping Ding MD, Hendrik Hardung PhG, Sebastian Jander MD, Gaby Reichmann PhD, Christoph Jacoby PhD, Rolf Schubert PhD, and Jürgen Schrader MD

From the Institut für Herz- und Kreislaufphysiologie (U.F., Z.D., C.J., J.S.) and Institut für Medizinische Mikrobiologie und Krankenhaushygiene (G.R.), Heinrich-Heine-Universität, Düsseldorf; Lehrstuhl für Pharmazeutische Technologie und Biopharmazie, Albert-Ludwigs-Universität Freiburg, Freiburg (H.H., R.S.); and Neurologische Klinik, Universitätsklinikum Düsseldorf, Düsseldorf (S.J.), Germany.

* To whom correspondence should be addressed. E-mail: floegel{at}uni-duesseldorf.de.

Background—In this study, we developed and validated a new approach for in vivo visualization of inflammatory processes by magnetic resonance imaging using biochemically inert nanoemulsions of perfluorocarbons (PFCs).

Methods and Results—Local inflammation was provoked in 2 separate murine models of acute cardiac and cerebral ischemia, followed by intravenous injection of PFCs. Simultaneous acquisition of morphologically matching proton (1H) and fluorine (19F) images enabled an exact anatomic localization of PFCs after application. Repetitive 1H/19F magnetic resonance imaging at 9.4 T revealed a time-dependent infiltration of injected PFCs into the border zone of infarcted areas in both injury models, and histology demonstrated a colocalization of PFCs with cells of the monocyte/macrophage system. We regularly found the accumulation of PFCs in lymph nodes. Using rhodamine-labeled PFCs, we identified circulating monocytes/macrophages as the main cell fraction taking up injected nanoparticles.

Conclusions—PFCs can serve as a "positive" contrast agent for the detection of inflammation by magnetic resonance imaging, permitting a spatial resolution close to the anatomic 1H image and an excellent degree of specificity resulting from the lack of any 19F background. Because PFCs are nontoxic, this approach may have a broad application in the imaging and diagnosis of numerous inflammatory disease states.


Key words: inflammation • ischemia • magnetic resonance imaging • monocytes • macrophages • perfluorocarbons


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Clinical Summaries
Circulation 2008 118: 105-106. [Full Text]