Abstract 2902: Myocardial Ischemic Memory Imaging Using Fundamental High Frequency Ultrasound
Background: Using microbubbles (MB) targeted to P-selectin, we have previously shown that echocardiography can identify recent myocardial ischemia in rats undergoing transient coronary occlusion. This approach used clinical harmonic systems with low transmit frequencies, yielding high sensitivity for MBs but suboptimal spatial resolution for rodent imaging. Ultrasound (US) imaging systems tailored for rodents necessarily operate at high frequencies, beyond MB resonance, potentially decreasing sensitivity for MB detection. Because myocardial molecular imaging in rodents would be a useful research tool, we tested the hypothesis that high frequency, fundamental imaging can be employed for this application.
Methods: A nitrogen/perfluorobutane gas-containing microbubble (mean size 2.2 ± 1.2μm) was conjugated to the P-selectin ligand, sialyl LewisX (MBsLex) or control Lewis C (MBCTL). Five anesthetized open chest rats had 15 min left anterior descending coronary ligation. Ten min after reflow, non-targeted MBs (MicroMarker™, VisualSonics Inc.) were injected (inj) to confirm reperfusion. Fifteen min after reflow, each rat received 1 intravenous inj of 5 x 107 MBCTL or MBsLex in alternating sequence. Six min after inj, US imaging at 25MHz (Vevo 770, VisualSonics Inc.) commenced, followed by a high power pulse to destroy MBs, and repeat imaging after MB replenishment. Post-destruction images were subtracted from the 6 min images to derive the signal from MB adhesion in regions of interest drawn over the risk area.
Results: Non-targeted MB inj confirmed homogeneous myocardial contrast enhancement. Videointensity in the risk area was higher after inj of MBsLex (20±6) than after inj of MBCTL (12±6, p<0.003). In 1 rat without prior ischemia, videointensity in the LAD bed was the same for MBsLex and MBCTL. Infarct size by triphenyl tetrazolium chloride staining was <5% of left ventricular myocardium.
Conclusions: Detection and spatial localization of recent myocardial ischemia using P-selectin-targeted MBs is possible at the high US frequencies required for rodent cardiac imaging, without an absolute requirement for harmonics. This opens significant opportunities for high spatial resolution ultrasound molecular imaging in small animal models.