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

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.

[1]  S. Caruthers,et al.  19F magnetic resonance imaging for stem/progenitor cell tracking with multiple unique perfluorocarbon nanobeacons , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[2]  Zahi A Fayad,et al.  Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography , 2007, Nature Medicine.

[3]  Aaron M Mohs,et al.  Gadolinium(III)-based blood-pool contrast agents for magnetic resonance imaging: status and clinical potential , 2007, Expert opinion on drug delivery.

[4]  Jonathan R Lindner,et al.  Molecular imaging with targeted contrast ultrasound. , 2007, Current opinion in biotechnology.

[5]  Andreas Saleh,et al.  Imaging Inflammation in Acute Brain Ischemia , 2007, Stroke.

[6]  U. Flögel,et al.  In vivo 2D mapping of impaired murine cardiac energetics in NO‐induced heart failure , 2007, Magnetic resonance in medicine.

[7]  Ahmed Tawakol,et al.  In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. , 2006, Journal of the American College of Cardiology.

[8]  R. Bowtell,et al.  Sensitivity to local dipole fields in the CRAZED experiment: an approach to bright spot MRI. , 2006, Journal of magnetic resonance.

[9]  N. Frangogiannis.  Targeting the inflammatory response in healing myocardial infarcts. , 2006, Current medicinal chemistry.

[10]  J. Riess.  Perfluorocarbon-based Oxygen Delivery , 2006, Artificial cells, blood substitutes, and immobilization biotechnology.

[11]  Jeff W M Bulte,et al.  Hot spot MRI emerges from the background , 2005, Nature Biotechnology.

[12]  Eric T Ahrens,et al.  In vivo imaging platform for tracking immunotherapeutic cells , 2005, Nature Biotechnology.

[13]  Vikram D Kodibagkar,et al.  19F: a versatile reporter for non-invasive physiology and pharmacology using magnetic resonance. , 2005, Current medicinal chemistry.

[14]  U. Flögel,et al.  Direct comparison of magnetic resonance imaging and conductance microcatheter in the evaluation of left ventricular function in mice , 2005, Basic Research in Cardiology.

[15]  J. Thrall,et al.  Clinical molecular imaging. , 2004, Journal of the American College of Radiology : JACR.

[16]  Martin Bendszus,et al.  in Vivo Monitoring of Macrophage Infiltration in Experimental Ischemic Brain Lesions by Magnetic Resonance Imaging , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[17]  M. Brandl,et al.  5-Fluorouracil in vesicular phospholipid gels for anticancer treatment: entrapment and release properties. , 2003, International journal of pharmaceutics.

[18]  Michael Schroeter,et al.  Non-invasive induction of focal cerebral ischemia in mice by photothrombosis of cortical microvessels: characterization of inflammatory responses , 2002, Journal of Neuroscience Methods.

[19]  M. Krafft,et al.  Fluorocarbons and fluorinated amphiphiles in drug delivery and biomedical research. , 2001, Advanced drug delivery reviews.

[20]  D. Spahn,et al.  Blood substitutes Artificial oxygen carriers: perfluorocarbon emulsions , 1999, Critical care.

[21]  B. Dardzinski,et al.  Rapid tissue oxygen tension mapping using 19F inversion‐recovery echo‐planar imaging of P erfluoro‐15 ‐crown‐5‐ether , 1994, Magnetic resonance in medicine.

[22]  R R Price,et al.  In vivo fluorine‐19 MR imaging: Relaxation enhancement with Gd‐DTPA , 1994, Journal of magnetic resonance imaging : JMRI.

[23]  D. Smith,et al.  Phagocytosis of a fluorescently labeled perflubron emulsion by a human monocyte cell line. , 1994, Artificial cells, blood substitutes, and immobilization biotechnology.

[24]  J. Duyn,et al.  Fast proton spectroscopic imaging of human brain using multiple spin‐echoes , 1993, Magnetic resonance in medicine.

[25]  G. Sze,et al.  Developing spinal column: gadolinium-enhanced MR imaging. , 1991, Radiology.

[26]  R. Weissleder,et al.  Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging. , 1990, Radiology.

[27]  C. Higgins,et al.  Perfluoroctylbromide: a reticuloendothelial-specific and tumor-imaging agent for computed tomography. , 1982, Radiology.

[28]  Paul A. Bottomley,et al.  19F magnetic resonance imaging , 1977 .

[29]  K. Adachi,et al.  A new method of preparation of a self-perforated micro plastic grid and its application. , 1965, Journal of electron microscopy.