Because of the lack of any ¹⁹F background in the body, detected signals from injected ¹⁹F-containing compounds are highly specific. An exact anatomical localization of fluorinated substances within the organism can easily obtained by acquisition of morphological matching ¹H and ¹⁹F MR images and subsequent merging of the anatomical corresponding images (see below).

However, in our present investigations we used perfluoro-15-crown-5 ether, a PFC in which all 20 fluorine nuclei are chemically and magnetically equivalent (see chemical structure at the left) and thus exhibits superior properties for ¹⁹F MRI detection. This substance is a liquid which is completely insoluble in water and, therefore, must be emulsified for application into the circulation. The particle size of the emulsion was chosen to ensure an optimal uptake by cells of the organism's immune defense.

The upper row illustrates the principle of the combined ¹H/¹⁹F MRI approach: The end-diastolic ¹H image (left) clearly shows the presence of ventricular dilatation and wall thinning within the infarcted area, and in the corresponding ¹⁹F image (middle), a signal pattern matched the shape of the free left ventricular wall. Merging of these images (right) confirms the localization of PFCs within the anterior, lateral, and posterior walls. Furthermore, ¹⁹F signal also was detected in the adjacent chest tissue, where thoracotomy for the surgical intervention was performed. Note that otherwise no background ¹⁹F signal from other tissue is present.

MRI data were confirmed by histology using PFCs additionally labelled with rhodamine. Immunohistochemisty further revealed the fluorescence to be associated with macrophages in the infarcted tissue (Flögel et al, 2008).

Although strong PFC signals were found in ex vivo ¹⁹F images of blood components (→ see here), in vivo signals from PFCs in the circulation were not detectable at all (e.g. no signal within ventricular chambers; see figure above). Even when ¹⁹F images were acquired immediately after injection, no ¹⁹F signal from the streaming blood could be observed because the pulse sequence used for ¹⁹F MRI (RARE, Rapid Acquisition with Relaxation Enhancement) results in a signal void of flowing blood particles. Therefore, detected signals can be attributed unequivocally to accumulated PFCs in the tissue without contamination from ¹⁹F signals of circulating PFCs.

¹⁹F signal also was transiently observed supracranially at the location of skin incision (bottom left). Characteristic ¹H and ¹⁹F images acquired from an individual mouse 7, 9, 12, and 19 days after focal cerebral ischemia was induced definitely show movement of the PFCs with the rim of the shrinking infarct over time (bottom).

In summary, the results show that intravenously applied PFCs accumulate after phagocytosis in inflammatory areas, where they can be detected by ¹H/¹⁹F MRI. PFCs, therefore, can serve as a “positive” contrast agent for the detection of inflammation by MRI, 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.