Selective infarct zone imaging with intravenous acoustically activated droplets.

Abstract

BACKGROUND:Microbubbles (MB) can be compressed to nanometer-sized droplets and reactivated with diagnostic ultrasound; these reactivated MB possess unique imaging characteristics. OBJECTIVE:We hypothesized that droplets formed from compressing Definity MB may be used for infarct-enhancement imaging. METHODS:Fourteen rats underwent ligation of their left anterior descending (LAD) artery, and five pigs underwent 90 minute balloon occlusions of their mid LAD. At 48 hours in rats, transthoracic ultrasound was performed at two and four minutes following 200 μL intravenous injections (IVI) of Definity droplets (DD), at which point the MI was increased from 0.5 to 1.5 to assess for a transient contrast enhancement zone (TEZ) within akinetic segments. In pigs, 1.0 mL injections of DD were administered and low frame rate (triggered end systolic or 10 Hz) imaging 2-4 minutes post iVI to selectively activate and image the infarct zone (IZ). Infarct size was defined by delayed enhancement magnetic resonance imaging (DE-MRI) and post-mortem staining (TTC). RESULTS:Increasing MI to 1.5 (at two or four minutes after IVI) resulted in a TEZ in rats, which correlated with infarct size (r = 0.94, p<0.001). A TEZ was not seen at 2-4 minutes in any rat (n = 8) following Definity MB injections. Fluorescent staining confirmed DD presence within the infarct zone 10 minutes after intravenous injection. In pigs, selective enhancement within the IZ was achieved by using a low frame rate single pulse harmonic mode; IZ size matched the location seen with DE-MRI and correlated with TTC defect size (r = 0.90, p<0.05). CONCLUSION:DD formulated from commercially available MB can be acoustically activated for selective infarct enhancement imaging.