Published ahead of print on June 3, 2005, doi:10.1164/rccm.200503-379OC Am. J. Respir. Crit. Care Med., Volume 172, Number 4, August 2005, 494-500 A more recent version of this article appeared on August 15, 2005
Submitted on March 10, 2005 Molecular Magnetic Resonance Imaging of Pulmonary Emboli with a Fibrin-Specific Contrast AgentElmar Spuentrup1*,1 Department of Diagnostic Radiology, Aachen Technical University, Aachen, Germany, 2 EPIX Pharmaceuticals, Cambridge, MA, USA, 3 Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA * To whom correspondence should be addressed. E-mail: spuenti{at}rad.rwth-aachen.de.
Rationale and Objectives: The detection of pulmonary embolism is still challenging due to the often non-specific clinical findings. The aim of this study was to investigate the potential of molecular targeted MR-imaging of pulmonary emboli using low dose application of a fibrin-specific contrast agent (EP-2104R, EPIX Pharmaceuticals, Cambridge, MA, USA). Methods: Fresh clots from human blood were engineered ex-vivo and delivered in the lungs of eleven swine. Subsequently, a T1-weighted breath-hold 3D gradient-echo sequence was performed before as well as 5 minutes, 1 hour and 2 hours after systemic administration of 7.5(n=5) or 4(n=5) µmol/kg EP-2104R. One swine that did not receive any contrast agent served as a control. MR images were analyzed by two investigators and contrast-to-noise ratio (CNR) between the thrombus and the surrounding tissue (blood-pool and lung parenchyma) was assessed. Localization of thrombi was compared to 16-row multi-slice CT. Finally, the animals were sacrificed and thrombi were removed for assessment of Gadolinium concentration. Main Results: Prior to contrast media application thrombi were not visible on MR-images. One and 2 hours after contrast media injection pulmonary emboli were selectively visualized with high signal intensity foci, independent of the dosage used. A high Gadolinium concentration in thrombi was found after both dosages (83 ± 41 µM for 4 µmol/kg and 130 ± 57 µM for 7.5 µmol/kg) resulting in a similar high CNR on MR images (between 11 and 13). Conclusion: Systemic low dose application of EP-2104R allows for selective molecular MR-imaging of fresh pulmonary thrombembolism in a swine model. Key words: Magnetic Resonance Imaging Molecular Imaging Pulmonary Embolism Fibrin Contrast
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