Use of contrast in ultrasound
In 1968, Drs Pravin M. Shah and Raymond Gramiak at the University of Rochester, New York, were conducting a study with the ultimate goal to investigate whether heart stroke volume could be estimated from the extent and duration of cusp separation of the aortic valve, as measured with M-mode ultrasound. Simultaneously, as the reference, they also measured cardiac output with the indicator dilution technique. Here, a bolus of a dye (indocyanine green) is injected and blood is sampled downstream to determine the rate at which the indicator has been transported from the injection site. In Dr Shah’s own account of the experiments, he explains that the routine at his university then was to place a catheter in the left atrium with the trans-septal technique, i.e. inserting the catheter in a vein and penetrating into the left atrium via the right atrium. During the injections of the dye, somewhat to their surprise, they observed a striking echo enhancement across the aorta. The enhancement also appeared when saline and dextrose in water was flushed through the catheter. Dr Gramiak reminded himself of a comment from Dr Claude Joyner, that a temporary echo-enhancement could be observed during saline injections, and they speculated that miniature bubbles produced by gaseous cavitation upon rapid injection of the fluid gave rise to the enhancement, and raised the idea that this could be used as a contrast agent. An in vitro study by Frederick Kremkau provided strong evidence that gas bubbles were actually responsible for the echo enhancement. It is interesting to note how discoveries are made independently around the world, when the time is ripe. At the same time in Lund, Drs Inge Edler and Kjell Lindström performed studies to measure blood flow in the heart. At this point no ultrasound Doppler signals had been recorded from the inside of the heart, and they used a calf heart in an in vitro model to verify that signals could be obtained when water and blood was led through the model.