Ischemia/Reperfusion Injury Enhances Accumulation of Perfluoropropane Droplets

Perfluoropropane droplets (PD) are nanometer-sized particles that can be formulated from commercially available contrast agents. The preferential retention of PDs in diseased microvascular beds can be detected by ultrasound imaging techniques after acoustic activation and offers an opportunity for the detection of such processes as scar formation or inflammation. We hypothesized that in the presence of ischemia/reperfusion (I/R) injury, retention of intravenously injected PDs would be enhanced.

Using an established intravital microscopy model of rat cremaster microcirculation, we determined the retention and subsequent acoustic activation behavior of PDs in exteriorized rat cremaster tissue. DiI-labeled droplets (200 µL) were administered intravenously. Acoustic activation was achieved with a clinical ultrasound system at two ultrasound frequencies (1.5 and 7 MHz).

Fluorescent microbubbles could be detected in the microvasculature after intravenous injection of PDs and subsequent acoustic activation. Increased retention of PDs was observed in the I/R group compared with control group with both ultrasound frequencies (p < 0.05). Using higher-resolution microscopy, we found evidence that some droplets extravasate to the outside of the endothelial border or are potentially engulfed by leukocytes.

Our data indicate that targeted imaging of the developing scar zones might be possible with ultrasound activation of intravenously injected PDs, and a method of targeting therapies to these same regions could be developed.