Abstract 14722: Dual-Targeted Microbubbles Improve the Detection of Previously Ischemic Myocardium by Echocardiography
Introduction: Echocardiography using targeted microbubbles (MB) has been shown to detect previously-ischemic regions of myocardium by molecularly targeting cell adhesion molecules that are displayed on the activated endothelial surface after ischemia/reperfusion injury. We hypothesized that the accuracy and sensitivity of detection could be improved by constant infusion and dual-targeting, respectively.
Methods: Ischemia/reperfusion injury was induced in 8 male C57BL/6 mice with 15-min LAD occlusions. After 2h of reperfusion, hearts of the closed-chest mice were imaged in long-axis with a Sequoia 15L8 transducer at 14 MHz. Each mouse received 3 of 4 MB preparations in random order: Sialyl Lewis X MB (MBX), anti-VCAM MB (MBV), Sialyl Lewis X + anti-VCAM MB (MBD), and isotype control MB (MBI). MB concentrations were approximately 200x10^6/mL, and 100 μL were infused at a constant rate of 25 μL/min via tail vein catheter. After imaging, mouse hearts were excised and stained with TTC/Phthalo blue dye to assess area at risk, and compared to regional time intensity curve (RTIC) retrieved from video data (Panel A).
Results: Example RTIC for MBD shows enhanced MB signals during and after MB infusion in the anterior apical region of the heart (Panel A). In Panel B, normalized intensities are significantly higher for MBD, MBX, and MBV, compared to MBI (p<0.05). Furthermore, normalized intensity for MBD is higher than both MBX and MBV (p<0.05). Receiver operating curve analysis using blue dye as the gold standard showed accurate detection of both ischemic and non-ischemic regions using MBD (AUC = 0.90), MBX (AUC = 0.89), and MBV (AUC = 0.97).
Conclusions: Molecular imaging of endothelial cell adhesion molecules in closed-chest mice is possible using constant infusion of MB. Dual-targeted MB yield greater MB signals than single-targeted MB when delivered using constant infusion, improving both the sensitivity and accuracy of this technique to measure risk regions in intact mice.
Author Disclosures: D. Lin: None. Y. Tian: None. A.L. Klibanov: None. J.A. Hossack: None. B.A. French: None.
- © 2014 by American Heart Association, Inc.