EFFECT OF MICROSPHERE SIZE DISTRIBUTION ON THE ULTRASONOGRAPHIC CONTRAST EFFICACY OF AIR-FILLED ALBUMIN MICROSPHERES IN THE LEFT-VENTRICLE OF DOG HEARTS

RATIONALE AND OBJECTIVES. The in vitro ultrasonographic contrast effic acy of air-filled albumin microspheres has been found to depend on the size distribution of microspheres, The objective of the current study was to empirically describe the relationship between the size distrib ution of injected air-filled albumin microspheres and the in vivo cont rast efficacy after lung capillary filtration in a dog model, METHODS. Twenty different air-filled microspheres with large and well-defined differences in size distribution were prepared from nine different bat ches of Albunex(R) (Molecular Biosystems Inc.) and subsequently charac terized by Coulter counting, The in vivo ultrasonographic contrast enh ancement of these preparations was investigated with a VingMed CFM750 in closed chest model in six mongrel dogs, The observed contrast effic acy, measured as gray-level enhancement in the left ventricle (LV), wa s correlated to the microsphere size distribution, using both univaria te and multivariate approaches. RESULTS. The results demonstrated a si gnificant contribution to LV contrast efficacy from microspheres large r than approximately 7 mu m, and a lack of contribution from microsphe res smaller than approximately 7 mu m. Linear relationships were found between LV contrast efficacy, and both the number concentration of mi crospheres between 8 to 12 mu m and the total microsphere volume conce ntration. No significant covariance between in vivo contrast efficacy and the number concentration between 1 to 38 mu m or 4 to 10 mu m was observed, The multivariate model showed a significant contribution to the in vivo gray-level enhancement from microspheres in the size range 7 to 15 mu m, with optimal efficacy per microsphere at approximately 13 mu m. CONCLUSIONS. Large microspheres (> 7 mu m), which had been ex pected to be trapped in the lung capillary bed, contribute most of the observed ultrasound contrast in the LV of the heart.