Design of an ultrasound contrast agent for myocardial perfusion.

Abstract

Myocardial contrast echography (MCE) has been a major research objective in cardiovascular ultrasound for almost two decades. The design of a contrast agent fulfilling the needs of MCE requires taking into consideration a number of points: a basic decision has to be made whether a deposit agent or a free-flowing agent would be more appropriate and whether an agent active at low/medium mechanical index (MI) is preferable to an agent active only at high MI; only a small percentage of the cardiac output enters the coronary microcirculation, which means that highly sensitive bubble detection methods, such as harmonic imaging or pulse inversion, are needed; the low velocity of blood in the microcirculation that leads to extensive bubble destruction during imaging means that intermittent imaging and/or an agent active at low MI is (are) required; the duration of the contrast effect must be sufficient to allow a complete examination and is affected by the rate of contrast administration; the performance of the contrast agent should not be equipment-dependent. The ultimate goal in MCE is to be able to quantify blood flow in the various segments to determine if adequate oxygenation is achieved. Ultrasound-mediated bubble destruction followed by the measurement of bubble replenishment kinetics opens new perspectives for quantification. SonoVue is a free-flowing ultrasound contrast agent made of sulphur hexafluoride microbubbles stabilized by a highly elastic phospholipid monolayer. SonoVue is able to produce myocardial opacification at a wide range of acoustic pressures and in particular at MIs as low as 0.1. Its performance is not equipment-dependent. Good results for myocardial opacification have been observed in all animal species tested (dogs, minipigs, rabbits), using continuous as well as intermittent imaging. Trials are in progress to demonstrate the clinical utility of SonoVue for rest and stress perfusion studies, in particular for the diagnosis of CAD, the detection of myocardial infarction, the assessment of the success of interventions and myocardial viability, and the detection of hibernating myocardium.