Contrast ultrasonography: Cancer characterization (Proceedings)
Grey-scale ultrasound has proven to be modestly sensitive for neoplastic nodules in the liver. In cases where there are many nodules, especially larger or coalescing nodules, ultrasound is more likely to detect the nodules. When the nodules are isoechoic, few in number, very small or located in difficult to image portions of the liver, the nodules may go undetected. Even when the nodules are seen, the confidence regarding whether they are benign "old dog" changes or malignancy may be quite low. This presentation will review the current state-of-the-art in ultrasound imaging for the detection and characterization of liver nodules.
Ultrasound contrast agents are basically bubbles of encapsulated gas. The capsule constituents of commercial contrast agents vary with the manufacturer, but most commonly is an inert lipoprotein in 2nd generation agents. The shell of Definity® is composed of a mixture of 3 lipids having molecular weights ranging from 670 to 5750. Only one contrast agent, Optison®, with a shell composed of human albumin, may be immune-active. Due to reported allergic reactions, Optison® is considered contraindicated for use in dogs and cats.The luminal gas also varies between manufacturers. In first generation contrast agents such as Levovist®, air was the gas used. But air is not a powerful sound generator and been replaced in 2nd generation agents with inert gases. Examples of these inert gases in the newer 2nd generation agents include octofluoropropane (Definity®) and sulfur hexafluoride (SonoVue®).
These encapsulated bubbles need to be small enough to pass through the lungs without significant attrition and, therefore, reach the liver in sufficient numbers to provide enhancement. Bubbles made by agitation of saline are too large (>50 µm) to pass through the lungs, are very short-lived and are not as reflective as commercial contrast agents. Unlike the chemical contrast agents of CT and MR, ultrasound contrast agents have a fairly wide distribution of sizes, depending on type and manufacturer. Definity® has a spectrum of size ranging from 1.1 to 3.3 µm with 98% less than 10 µm. At this size, large numbers of reach the abdominal structures after 1st pass through the lung.
Imaging these bubbles is a technological challenge. Many ultrasound innovations have been developed as a corollary of contrast imaging. Tissue harmonic ultrasound technology was developed incidental to contrast ultrasound research. The goal of contrast ultrasound technology is to elicit a large sound signal, larger than from the tissues, from these bubbles. Until recently this was accomplished through harmonic technology. Bubbles are much more powerful emitters of harmonic signal (=nonlinear response) than any biological tissue. Each bubble, depending on type and size, has a characteristic resonant frequency. At this resonant frequency the bubbles emit a disproportional large amount of harmonic signal. The trick is to insonify the bubbles with the correct magnitude (mechanical index) of resonant frequency sound and then filter all the returning signal to isolate the bubble portion.
Harmonic ultrasound has been the most common method that takes advantage of the nonlinear response of bubble contrast agents to their respective resonant frequency. Harmonic frequency are multiples of the transmitted sound frequency (4 MHz transmitted has a harmonic frequency of 8 MHz). Various technologies exists to eliminate the fundamental transmitted signal and isolate the harmonic bubble signal. Many of these methods suffer from a low signal-to-noise ratio, or are difficult to optimize on the particular machine system. The harmonic signal is always much weaker the transmitted fundamental.
A newer technology involves the isolation of the bubble signal from the nonlinear fundamental component. This involves utilization of phase and amplitude changes unique to the nonlinear bubble response. The advantage to this technique is the comparative high signal-to-noise ratio of the fundamental signal (compared to a harmonic component) and ability to image at higher frequencies.