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WIREs Nanomed Nanobiotechnol
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Visualization of inflammation using 19F‐magnetic resonance imaging and perfluorocarbons

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Abstract Inflammation plays a central pathophysiological role in a large number of diseases. While conventional magnetic resonance imaging (MRI) can depict gross tissue alterations due to proton changes, specific visualization of inflammation is an unmet task in clinical medicine. 19F/1H MRI is a novel technology that allows tracking of stem and immune cells in experimental disease models after labelling with perfluorocarbon (PFC) emulsions. 19F markers such as PFC compounds provide a unique signal in vivo due to the negligible 19F background signal of the body. Concomitant acquisition of 1H images places the labelled cells into their anatomical context. This novel imaging technique has been applied to monitor immune cell responses in myocardial infarction, pneumonia, bacterial abscess formation, peripheral nerve injury, and rejection of donor organs after transplantation. Upon systemic application PFC nanoparticles are preferentially phagozytosed by circulating monocytes/macrophages and, thus, the fluorine signal in inflamed organs mainly reflects macrophage infiltration. Moreover, attenuation of the inflammatory response after immunosuppressive or antibiotic treatments could be depicted based on 19F/1H‐MRI. Compared to other organ systems 19F‐MRI of neuroinflammation is still challenging, mainly because of lack in sensitivity. In focal cerebral ischemia early application of PFCs revealed ongoing thrombotic vessel occlusion rather than cell migration indicating that timing of contrast agent application is critical. Current restrictions of 19F/1H‐MRI in sensitivity may be overcome by improved imaging hardware, imaging sequences and reconstruction techniques, as well as improved label development and cell labelling procedures in the future. WIREs Nanomed Nanobiotechnol 2012, 4:438–447. doi: 10.1002/wnan.1168 This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

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Visualisation of abscess formation with 19F magnetic resonance imaging (19F‐MRI) in a murine thigh infection model with Staphylococcus aureus. A bacterial suspension was inoculated into the left thigh muscle in mice. Two days later a perfluorocarbon (PFC) emulsion was injected intravenously and 19F/1H‐MRI performed on day 3 after infection (24 h after injection of the PFC emulsion). (a) The T2 map reveals an area with long T2 times (hyperintense) indicating infected muscle tissue in the lower part of the figure. The T2 map is presented in the pseudo color ‘hot’. (b) The corresponding 19F‐MRI shows signal accumulation (19F signal: pseudo color blue) at the outer rim of the abscess area reflecting recruitment of granulocytes and macrophages.27 (Reprinted with permission from Ref 27. Copyright 2011 University of Würzburg)

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Multicolor 19F magnetic resonance imaging(19F MRI) of occlusive thrombus formation in cerebral photothrombosis (PT). PT lesion in the brain of a mouse which received two chemically shifted perfluorocarbon (PFC) compounds sequentially. PFCA with a multi‐resonant perfluorooctlybromid was administered immediately after the end of illumination to induce PT while single‐resonant PFCB with a peak at 90 ppm was injected with 2 h delay (a, b). Representative coronal slides of the mouse brain 3 and 8 days after induction of the PT infarction are shown (c). Administration of the first emulsion (PFCA, blue) directly after induction of PT led to a fluorine signal throughout the cortical infarction (C2) while the second 19F marker (PFCB, red) that was applied 2 h later accumulated only at the outer margins sparing the center of the infarcted zone (C3). Combined overlay of the 1H turbo spin echo (TSE) data with data from both PFC compounds allowed visualization of the distinct marker distribution in a single 3D in vivo measurement (C4). The fluorine signals are due to intravascular trapping of the PFC emulsions during thrombus formation which begins in the center of the lesion as revealed by histological analysis (not shown).37 An additional 19F signal of both compounds can be observed at the site of the skin incision at the skull on the left side. (Reprinted with permission from Ref 37. Copyright 2011 University of Würzburg)

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in vivo 19F magnetic resonance imaging(19F‐MRI) of neuroinflammation after lysolecithin‐induced demyelination of the left sciatic nerve.31 The rat is lying in a supine position. (a–c) show coronal (a), sagittal (b), and axial (c) 1H MR slices through the hind quarters of a rat 5 days after nerve injury providing anatomical orientation. (d–f) represent superimposed 19F/1H images: Note the distinct fluorine signal representing macrophage infiltration into areas of nerve injury on the left side and the absence of signal in the contralateral intact sciatic nerve.

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