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Influence of injection site, microvascular pressureand ultrasound variables on microbubble-mediated delivery of microspheres to muscle

Ji Song, PhD^*, John C. Chappell, BS^*, Ming Qi, BS^*, Eric J. VanGieson, PhD^*, Sanjiv Kaul, MD, FACC and Richard J. Price, PhD^*,*

^* Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA
Cardiovascular Division, University of Virginia, Charlottesville, Virginia, USA

View larger version (144K): [in a new window]   Figure 1 Discrete extravasation points created by the application of 1 MHz ultrasound to microbubbles flowing through skeletal muscle capillaries. Several extravasation points are highlighted with arrows in B. The specimen is from treatment group C. The bars indicate 1 mm.

View larger version (60K): [in a new window]   Figure 2 Polymer microspheres that have been delivered to muscle through extravasation points created by microbubble insonation. Groups A–F and a control group (G), in which ultrasound was applied to polymer microspheres (PMs) and a 5% albumin solution, are represented. The PMs are limited to the intravascular space in control specimens. The treatment groups are described in Table 1. The bar indicates 200 µm.

View larger version (24K): [in a new window]   Figure 3 Bar graphs illustrating the effect of the pulsing interval (PI) on extravasation point creation and fluorescent polymer microsphere delivery to muscle. (A) Mean gray-scale level above baseline and the number of extravasation points per unit surface area after a 40-s arterial injection, as a function of PI. No significant differences were observed at p < 0.05. (B) Data in part A normalized to the number of applied ultrasound pulses. *p < 0.05 versus 1-s PI. **p < 0.05 versus 5-s PI.

View larger version (16K): [in a new window]   Figure 4 Bar graph illustrating the effect of arterial versus venous microbubble injection on extravasation point creation and fluorescent polymer microsphere delivery to the muscle. No significant differences were observed between the groups.

View larger version (19K): [in a new window]   Figure 5 Bar graphs illustrating the effect of arterial injection time on extravasation point creation and fluorescent polymer microsphere delivery to the muscle. (A) Mean gray-scale level above baseline and the number of extravasation points per unit surface area for 10- and 40-s arterial injection durations. (B) Data in part A normalized to the total number of applied ultrasound pulses. *p < 0.05 versus 40-s injection group.

View larger version (18K): [in a new window]   Figure 6 Representative pressure tracings for transverse arterioles before, during and after 10-s (A) and 40-s (B) arterial injections of microbubbles and PMs. Microvascular pressure increased during injection for both groups, but then fell below baseline immediately after injection. (C) Bar graph showing the mean pressure increase above baseline during injection in feed arterioles. *p < 0.05 versus 40-s injection group. **p < 0.05 versus baseline.