Abstract

This study was aimed at developing a new approach for in vivo detection of inflammation by 19 F magnetic resonance imaging (MRI) using biochemically inert emulsified perfluorocarbons (PFCs). PFCs have been clinically used as blood substitutes and are known to be phagocytized by the reticuloendothelial system. Local inflammation was provoked in two murine models of acute cardiac and cerebral ischemia, respectively, followed by intravenous injection of PFCs. A typical example of anatomically matching 1 H and 19 F images obtained at 9.4 Tesla 4 days after myocardial infarction is shown below. The 1 H image (left) clearly shows the presence of ventricular dilatation and wall thinning within the infarcted area (I), and in the corresponding 19 F image (middle) a signal pattern matched in shape of the free left ventricular wall. Merging of these images (right) confirms the localization of PFCs within the anterior, lateral, and posterior wall. In all animals (n=8) studied, 19 F signal was also detected in the adjacent chest tissue, where thoracotomy for infarction was performed (T). No background signal from other tissue was observed. Repetitive MRI revealed in both injury models a time-dependent infiltration of injected PFCs into infarcted areas, and histology demonstrated a colocalization of PFCs with cells of the monocyte-macrophage system. Using rhodamine-labelled PFCs, circulating monocytes/macrophages were identified to be the main cell fraction taking up injected PFCs. In conclusion, PFCs can serve as positive contrast agent for detection of inflammatory processes by MRI, permitting high spatial resolution and an excellent degree of specificity due to lack of any 19 F background.

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