Ping Zeng1, Lijun Qian2, John Lof3, Elizabeth Stolze3, Soufiane El Kadi4, Thomas Bargar3, Jiri Sklenar5, Terry Matsunaga6, Feng Xie3, Thomas R Porter7. 1. Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China; Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, Nebraska. 2. Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China; Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, Nebraska. 3. Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, Nebraska. 4. Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, Nebraska; Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands. 5. Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon. 6. Department of Biomedical Engineering and Department of Medical Imaging, University of Arizona, Tucson, Arizona. 7. Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, Nebraska. Electronic address: trporter@unmc.edu.
Abstract
BACKGROUND: Perfluoropropane droplets formulated from commercial microbubbles exhibit different acoustic characteristics than their parent microbubbles, most likely from enhanced endothelial permeability. This enhanced permeability may permit delayed echo-enhancement imaging (DEEI) similar to delayed enhancement magnetic resonance imaging (DE-MRI). We hypothesized this would allow detection and quantification of myocardial scar. METHODS: In 15 pigs undergoing 90 minutes of left anterior descending ischemia by either balloon (n = 13) or thrombotic occlusion (n = 2), DE-MRI was performed at 2-24 days postocclusion. Delayed echo-enhancement imaging was performed at 2-4 minutes following an intravenous injection of 1 mL of 50% Definity (Lantheus Medical) compressed into 180 nm droplets; DEEI was attempted in all pigs with single-pulse harmonic imaging at 1.7 transmit/3.4 MHz receive. Myocardial defects observed with DEEI were quantified (percentage of infarct area) and compared with DE-MRI as well as postmortem staining. In six pigs, multipulse low-mechanical index (MI) fundamental nonlinear imaging (FNLI) with intermittent high-MI impulses was performed to determine whether droplet activation within the infarct zone was achievable with a longer pulse duration. RESULTS: The range of infarct size area by DE-MRI ranged from 0% to 46% of total left ventricular area. Single-pulse harmonic imaging detected a contrast defect that correlated closely with infarct area by DE-MRI (r = 0.81, P = .0001). The FNLI high-MI impulses resulted in droplet activation in both the infarct and normal zones. Harmonic subtraction of the FNLI images resulted in infarct zone enhancement that also correlated closely with infarct size (r = 0.83; P = .04). Droplets were observed on postmortem transmission electron microscopy within myocytes of the infarct and remote normal zone. CONCLUSION: Intravenously Definity nanodroplets can be utilized to detect and quantify infarct zone at the bedside using DEEI techniques.
BACKGROUND: Perfluoropropane droplets formulated from commercial microbubbles exhibit different acoustic characteristics than their parent microbubbles, most likely from enhanced endothelial permeability. This enhanced permeability may permit delayed echo-enhancement imaging (DEEI) similar to delayed enhancement magnetic resonance imaging (DE-MRI). We hypothesized this would allow detection and quantification of myocardial scar. METHODS: In 15 pigs undergoing 90 minutes of left anterior descending ischemia by either balloon (n = 13) or thrombotic occlusion (n = 2), DE-MRI was performed at 2-24 days postocclusion. Delayed echo-enhancement imaging was performed at 2-4 minutes following an intravenous injection of 1 mL of 50% Definity (Lantheus Medical) compressed into 180 nm droplets; DEEI was attempted in all pigs with single-pulse harmonic imaging at 1.7 transmit/3.4 MHz receive. Myocardial defects observed with DEEI were quantified (percentage of infarct area) and compared with DE-MRI as well as postmortem staining. In six pigs, multipulse low-mechanical index (MI) fundamental nonlinear imaging (FNLI) with intermittent high-MI impulses was performed to determine whether droplet activation within the infarct zone was achievable with a longer pulse duration. RESULTS: The range of infarct size area by DE-MRI ranged from 0% to 46% of total left ventricular area. Single-pulse harmonic imaging detected a contrast defect that correlated closely with infarct area by DE-MRI (r = 0.81, P = .0001). The FNLI high-MI impulses resulted in droplet activation in both the infarct and normal zones. Harmonic subtraction of the FNLI images resulted in infarct zone enhancement that also correlated closely with infarct size (r = 0.83; P = .04). Droplets were observed on postmortem transmission electron microscopy within myocytes of the infarct and remote normal zone. CONCLUSION: Intravenously Definity nanodroplets can be utilized to detect and quantify infarct zone at the bedside using DEEI techniques.
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