Objective. Attenuation of radio frequency (RF) signals limits the use of contrast echocardiography. The harmonic-to-fundamental ratio (HFR) of the RF signals compensates for attenuation. We tested whether HFR analysis measures the left ventricular nonperfused area under simulated experimental attenuation. Methods. Radio frequency image data from short axis systolic projections were obtained from 11 open-chest dogs with left anterior descending or left circumflex coronary artery occlusion followed by left atrial bolus injection of a perflutren microbubble contrast agent. Clinical attenuation was simulated by calibrated silicone pads interposed between the epicardial surface and the transducer to induce mild (7-dB) and severe (14-dB) reduction of the backscattered RF signals. Harmonic-to-fundamental ratio values were calculated for each image pixel for 0-, 7-, and 14-dB attenuation conditions and reproducibly showed a "perfused area" and a "nonperfused area." A reference nonperfused area was obtained by manual delineation in high-quality contrast scans. Results. Correlations of the HFRdetected and manually outlined perfusion defect areas were R = 0.92 for 0 dB, R = 0.94 for 7 dB, and R = 0.90 for 14 dB; the mean difference was less than 0.36 cm 2 (negligible) in all 3 attenuation settings. Conclusions. Attenuation compensation by our HFR method allows precise measurement of myocardial perfusion defect areas in contrast scans with simulated high level of attenuation. Key words: contrast echocardiography; harmonic ultrasound; myocardial perfusion; radio frequency signal; ultrasound attenuation. ontrast microbubbles are intravascular blood tracers that enhance myocardial circulation and provide a means for assessing the extent of perfusion defects in patients with myocardial ischemia during myocardial contrast echocardiographic scans. A specific scanning regimen, which induces destruction of microbubbles within the thickness of an ultrasonographic cross-sectional plane and measures their rate of replenishment, fosters the assessment of an ischemic area and allows quantitation of regional perfusion flow.1 Whether an experimental closed-chest setting or a clinical setting is evaluated, and whether a perfusion defect area is related to a completely or partially obstructed coronary artery, a common limitation exists: attenuation of the transmitted and received ultrasonic signals. This is a fundamental limitation of ultrasonography that contributes to heterogeneity in echogenicity and artifacts
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