Optimization of the size distribution and myocardial contrast effect of perfluorocarbon-filled albumin microbubbles by lyophilization under continuous negative pressure

This study was undertaken to evaluate the effect of lyophilization under co ntinuous negative pressure on perfluoropropane-filled albumin microbubble s ize distribution and myocardial contrast effect. Three different microbubbl e preparations were studied: (1) 1% albumin solution without a sugar (Optis on), (2) 1% albumin and 5% dextrose (PESDA), and (3) 1% albumin and 5% fruc tose (PESFA). The 2 preparations containing sugar were also subjected to ly ophilization under continuous negative pressure. Microbubble size distribut ion was measured with a Coulter Multisizer II (Beckman Coulter, Inc, Fuller ton, Calif). The microbubbles were injected intravenously into a rat during intravital microscopy of the mesenteric microcirculation. Finally, the dif ferent albumin microbubbles were injected intravenously into 10 dogs, and m yocardial contrast effect was assessed by videodensitometry. Results of the Coulter counter studies showed lyophilized PESFA to have a smaller size di stribution with 99.9% +/- 0.1% of microbubbles <10 mu m in diameter and 88. 5% +/- 1.4% <4 mu m in diameter (P < .05 compared with Optison or PESDA). O n intravital microscopy, PESFA microbubbles behaved as intravascular tracer s without microvascular plugging or coalescence. Finally, myocardial peak g ray scale and area under the curve were significantly higher for PESFA than for PESDA or Optison, respectively. In conclusion, lyophilization of perfl uoropropane-filled albumin microbubbles results in smaller microbubbles wit h a more uniform size distribution and brighter myocardial contrast. In add ition, the substitution of fructose for dextrose improves size distribution and contrast effect. These findings have important implications regarding the use of novel imaging technologies that take advantage of microbubble de struction to image myocardial perfusion.