Characteristics and clinical value of an intravenous echo-enhancement agent in evaluation of high-grade internal carotid stenosis.

: Although ultrasound is a highly useful tool for clinical diagnosis, it has certain limitations in accurately quantifying internal carotid stenosis or diagnosing internal carotid occlusion. However, these limitations can be overcome by increasing the echogenicity of flowing arterial blood by use of echo-enhancement agents. Two phase III studies assessed the usefulness of the IV transpulmonary echo enhancer Levovist (SH U 508A) in improving characterization and quantification of severe internal carotid stenosis on ultrasound scans. In addition, Levovist-induced enhancement characteristics of the Doppler frequency spectrum have been analyzed. To be included in the study reviewed here, patients had to have a high-grade (> or = 70%) stenosis or occlusion of an internal carotid artery (ICA), as judged by conventional angiography or by standard cervical Doppler ultrasound. Patients were excluded from consideration if they were pregnant or nursing, had a history of galactosemia, or had received an ionic contrast medium within 24 hours before or after the intended administration of Levovist. Written informed consent was obtained from all patients before entry into the study. Of 32 patients (14 women, 18 men, median age 64 yr) who were included in this study, high-grade stenosis was verified in 30 ICA vessels and occlusion was verified in two vessels. After admission into the study, the carotid bifurcation was insonated in all patients using a 7.5-MHz linear array transducer for color Doppler-assisted duplex imaging and a 4-MHz pulsed-wave Doppler for velocity spectrum measurements before and after injection of the echo enhancement agent Levovist. Levovist-induced increases in carotid blood echogenicity began 11 +/- 2 seconds (mean +/- SD) after the start of injection, peaked at 21 +/- 2 dB, and had a half-life of 75 seconds. A fast Fourier transform of the original Doppler velocity spectrum demonstrated Levovist-induced enhancement throughout the entire velocity spectrum, with an increase in ICA blood flow velocity paralleling an increase in reflected ultrasound energy. Quantitative vascular measurements (cross-sectional luminal area reduction and plaque length) obtained before and during echo enhancement were highly correlated (r > 0.90). However, visualization of the entire length of the intrastenotic residual flow lumen, was significantly improved by Levovist enhancement (52% versus 83%; p = 0.01). Levovist considerably increased interpretable data by improving image quality in patients with high-grade carotid stenosis. Furthermore, the significant improvement in visualization of the residual flow lumen suggests that echo-enhancement agents may be most useful in improving the ultrasonography-based diagnosis of internal carotid occlusion.