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

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. (19) F/(1) H MRI is a novel technology that allows tracking of stem and immune cells in experimental disease models after labelling with perfluorocarbon (PFC) emulsions. (19) F markers such as PFC compounds provide a unique signal in vivo due to the negligible (19) F background signal of the body. Concomitant acquisition of (1) H 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 (19) F/(1) H-MRI. Compared to other organ systems (19) F-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 (19) F/(1) H-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.

Noninvasive Imaging of Early Venous Thrombosis by 19 F Magnetic Resonance Imaging With Targeted Perfluorocarbon Nanoemulsions

“…In line with the reported half-life of factor XIIIa, application of α2 AP -PFCs >60 minutes after thrombus induction no longer resulted in detectable 19 F magnetic resonance imaging signals. Corresponding results were obtained in ex vivo generated human clots.…”

“…Conclusions-Our results demonstrate that 1 H/ 19 F magnetic resonance imaging, together with α2 AP -PFCs, is a sensitive, noninvasive technique for the diagnosis of acute deep venous thrombi and pulmonary thromboemboli. Furthermore, ligand coupling by the sterol-based postinsertion technique represents a unique platform for the specific targeting of PFCs for in vivo 1 H MRI is difficult because small, nonocclusive thrombi have only a minor impact on blood flow and may not give rise to a clear signal in weighted images.…”

“…However, thrombus detection by conventional MRI Background-Noninvasive detection of deep venous thrombi and subsequent pulmonary thromboembolism is a serious medical challenge, since both incidences are difficult to identify by conventional ultrasound techniques. Methods and Results-Here, we report a novel technique for the sensitive and specific identification of developing thrombi using background-free 19 F magnetic resonance imaging, together with α2-antiplasmin peptide (α2 AP )-targeted perfluorocarbon nanoemulsions (PFCs) as contrast agent, which is cross-linked to fibrin by active factor XIII. Ligand functionality was ensured by mild coupling conditions using the sterol-based postinsertion technique.…”

“…Ligand functionality was ensured by mild coupling conditions using the sterol-based postinsertion technique. Developing thrombi with a diameter <0.8 mm could be visualized unequivocally in the murine inferior vena cava as hot spots in vivo by simultaneous acquisition of anatomic matching 1 H and 19 F magnetic resonance images at 9.4 T with both excellent signal-to-noise and contrast-to-noise ratios (71±22 and 17±5, respectively). Furthermore, α2…”

“…Until now, 19 F MRI has been used predominantly for immune cell tracking in a variety of clinically relevant inflammation models. [21][22][23][24][25][26][27][28][29] This approach is based on the rapid uptake of intravenously injected PFCs by circulating monocytes that subsequently migrate into the inflamed area, resulting in a local accumulation of 19 F-loaded immune cells. In the present study, we report a novel procedure for the generation of targeted PFCs that makes use of a sterol-based postinsertion technique (SPIT) to generate α2-antiplasminlabeled PFCs (α2 AP -PFCs).…”