Ischemic Memory Imaging With Myocardial Contrast ECG Detects Myocardial Ischemia in Animal Models

Ischemic memory imaging with myocardial contrast echocardiography (MCE) was effective with phosphatidylserine microbubbles (MB-PS) at detecting recent but resolved myocardial ischemia, according to recent data published in JACC: Cardiovascular Imaging.

Ischemic memory imaging techniques that can detect and spatially assess resolved myocardial ischemia are currently being developed for timely evaluation of patients with chest pain. Researchers of this study hypothesized that MB-PS could identify the spatial extent of recent, but resolved, myocardial ischemia without infarction.

“MCE is an attractive approach for this application since ultrasound is increasingly used in the emergency department for rapid assessment of patients with a variety of conditions, and requires only a short duration to perform,” they wrote.

Researchers performed MCE molecular imaging with MB-PS 1.5, 3.0, and 6.0 hours after brief 10-minute myocardial ischemia in mice. The data were compared to selectin-targeted microbubbles (MB-PSGL-1).

In a separate cohort of mice, researchers performed MCE molecular imaging with Sonazoid, a commercially-produced PS-containing agent at 1.5 and 3.0 hours after ischemia reperfusion. The procedure was also performed in dogs undergoing 135 minutes of ischemia and 60 minutes of reflow, and in closed-chest and non-ischemic dogs. They assessed the mechanism for MB-PS attachment by intravital microscopy of post-ischemic muscle and by flow cytometry analysis of cell-MB interactions.

In the mice that underwent ischemia-reperfusion without infarction, signal enhancement in the risk-area for MB-PS and MB-PSGL-1 was similar at reflow times at 1.5 hours (23.3 ± 7.3 vs 30.7 ± 4.1 IU), 3 hours (42.2 ± 6.2 vs 33.9 ± 7.4 IU), and 6 hours (24.1 ± 4.3 vs 25.5 ± 4.7 IU). The signal in the risk-area was significantly higher than remote region at all of the reflow times for MB-PS and MB-PSGL-1 (P<.05).

Sonazoid also yielded strong risk-area enhancement at 1.5 hours (34.7 ± 5.0 IU) and 3.0 hours (52.5 ± 4.5 IU), which was approximately 3-fold greater compared with the control region. The Sonazoid signal in dogs was more than 5-fold higher compared with closed-chest control myocardium (42.2 ± 8.1 vs 7.9 ± 3.3 IU; P<.001).

The mechanistic studies revealed that MB-PS attached directly to venular endothelium and adherent leukocytes, which was dependent on C1q and C3 serum components.

“In summary, we have demonstrated that MCE ischemic memory imaging even in non-infarcted tissue is possible using the complement-mediated interaction between PS-containing microbubbles,” the authors concluded. “The degree of signal enhancement is robust and similar to that produced by selectin-targeted agent.”

“These preclinical experiments form the basis for the potential investigation for diagnostic imaging of inflammation and injury, including myocardial ischemia, using agents that are feasible for human use.”

Reference

Mott B, Packwood W, Xie A, et al. Echocardiographic ischemic memory imaging through complement-mediated vascular adhesion of phosphatidylserine-containing microbubbles. JACC Cardiovasc Imaging. 2016. doi:10.1016/j.jcmg.2015.11.031.