Contrast ultrasonography for 2-D opacification of heart cavities, peripheral vessels, kidney and muscle

Abstract

Contrast ultrasonography of peripheral vessels and peripheral organs has been only sparsely used to evaluate peripheral tissue blood flow. The purpose of the study was to characterize intraluminal opacification of renal and femoral arteries and veins, of skeletal muscle and renal parenchyma after intraarterial (IA) injection of BY963, a newly developed ultrasound contrast agent being evaluated in Phase II and III trials, and to compare it with opacification of heart cavities after intravenous injection (IV) in dogs. A further purpose was to quantitate possible opacification losses during the first transcapillary passage of BY963 through pulmonary and peripheral microcirculation. BY963 was administered at the dose of 5 mL/animal/vascular territory (0.2 mL/kg). The peak intensity (intensity units = IU) and the area-under-the-curve (AUC, IU × heart cycles) were estimated from regions-of-interest placed in the right ventricle (RV), left ventricle (LV), main renal artery and vein, kidney, femoral artery and vein and adductor muscle. Following single IV injection, the average peak intensity and AUC values were 33 ± 3 (mean ± SE) and 674 ± 109 for the RV, and 27 ± 2 and 870 ± 74 for the LV ( p < 0.05), respectively. Following single IA injection in the descending aorta, the average peak intensities and AUC values were 30 ± 2 and 613 ± 139 in the renal artery and 26 ± 4 ( p < 0.05) and 639 ± 151 in the renal vein (nonsignificant), respectively. For the femoral vessels, the average peak intensities and AUC values were 30 ± 3 and 469 ± 63 in the femoral artery, and 21 ± 2 ( p < 0.05) and 517 ± 44 in the femoral vein (nonsignificant), respectively. The values for the output-to-input intensity ratios for peak intensity and AUC were 0.82 ± 0.06 and 1.36 ± 0.12 for the LV/RV ratio, 0.73 ± 0.08 and 1.02 ± 0.05 for the renal vein/renal artery ratio, and 0.71 ± 0.09 and 1.16 ± 0.13 for the femoral vein/femoral artery ratio, respectively (nonsignificant). In conclusion, these results demonstrate the high opacification potency of BY963 in the LV, renal and femoral veins, being of the same order of magnitude as that in the RV, renal and femoral arteries, respectively. Finally, the loss of opacification properties of BY963 during the first transcapillary (pulmonary or peripheral-capillary) passage is minimal.