ABDOMEN ULTRASOUND CONTRAST AGENTS

ULTRASOUND CONTRAST AGENTS IN THE ABDOMEN
Ultrasound contrast media have been well established for cardiac imaging since the 1980s and the first clinical use of such an agent was in 1968 and involved the injection of saline to identify echoes from the mitral valve. These early contrast agents were composed of relatively large (by todays standards) microbubbles of air in solution. They were unstable, shortlived and the bubbles were too large to pass through the capillary beds, hence their use exclusively for cardiac ultrasound.

Since those early years there have been a number of developments in the field of contrast ultrasound. Agents such as Albunex (Molecular Biosystems, San Diego, USA), consisting of albumin- coated microbubbles, were small enough to pass through the pulmonary capillaries and enter the left side of the heart; however they were too weak to withstand systolic pressure and could not therefore enter the blood pool in any appreciable quantity.

A more stable suspension was then produced,consisting of small microbubbles in the order of 2 - 5 µm which passed through the pulmonary capillary bed after intravenous injection, and acted as a true blood-pool agent. Called Levovist (Schering, Berlin, Germany), this is a galactosebased agent (99.9%) containing palmitic acid (0.1%) for stability, which traps air which is subsequently released when the bubbles burst. As the first stable blood-pool agent it could be used for examining the abdominal viscera and vasculature. By coincidence, microbubbles of this size can pass through the pulmonary capillaries and resonate at frequencies used in clinical diagnostic ultrasound (1 - 20 MHz). This resonance causes a much greater capacity for scattering the beam than that from a non-resonating particle and thus a stronger signal is produced of up to 25 dB on both grey-scale and Doppler. The Doppler signal from a contrast-enhanced blood vessel is therefore much easier to identify. In addition, vessels too small to be identified on normal grey-scale or nonenhanced Doppler scans can be identified when using a microbubble agent.

Despite the use of microbubble agents, blood flow in tiny vessels can still be difficult to detect; harmonic imaging techniques however aid detection further. When insonated with ultrasound of a certain frequency, microbubbles emit a secondary harmonic frequency twice that of the incident wave, in addition to the primary harmonic. As the second peak is a purer signal, this increases the sensitivity, enabling smaller vessels with slow flow to be successfully detected and distinguished from surrounding tissues. Many harmonic-based pulse methods are used with contrast agents and some of the more popular ones include pulse and phase inversion, for example pulse inversion is a dual pulse technique, 180º out of phase, resulting in summation of signal from non-linear scatterers (microbubbles) and cancellation of signal from linear scatterers (tissue).

Potential applications of these agents include situations in which ultrasound findings are equivocal or in which Doppler information is suboptimal. A contrast agent will enhance the Doppler ultrasound signal from the blood pool and increase diagnostic confidence. This may therefore obviate the need for other more invasive angiographic investigations. These agents therefore have the potential to extend the applications of Doppler ultrasound in the abdomen. With regard to the abdomen it can be useful in patients with chronic liver disease for the investigation of portal vein thrombosis. Increased sensitivity and specificity have been reported for examination of the portal vein, avoiding the need for contrast angiography. In patients with hepatic transplantation it is helpful in confirming hepatic artery patency in the early postoperative period: this can be difficult to confirm with conventional imaging alone.

Although it is felt intuitively that it may be of help in the diagnosis of renal artery stenosis, the evidence is as yet not convincing to support its routine use. The diagnosis and characterization of hepatic tumours are also improved with contrast agents as these agents, for example, Levovist and Sonovue, are preferentially taken up by the hepatosplenic parenchyma and so focal lesions appear as filling defects in much the same way as CT or MRI (Fig. 11.16). The exact site of accumulation within the liver is unknown but may be within the reticuloendothelial system or liver sinusoids. There is growing evidence to support the differentiation of lesions within the liver, not previously possible with conventional ultrasound,29,30 and certainly microbubble agents are helpful in the diagnosis of capillary haemangiomas, hepatomas and focal nodular hyperplasia. How are microbubble agents used currently? Generally an agent such as Sonovue, currently the most commonly used, which consists of a phospholipid membrane containing perfluorocarbon gas, is injected intravenously. Imaging, for example in the liver, can now be performed in both a hepatic arterial and portal venous phase similar to CT. Most imaging is performed with a harmonicbased technique pulse or phase inversion and utilizing a low mechanical index (< 0.15) to prolong longevity of the bubbles. Although there is no definitive evidence as yet to support its routine use, it is currently undergoing a number of trials comparing it with CT and MRI in the detection of focal liver disease, and early results are favourable.

Other simple substances, technically considered contrast agents, including water or saline, are used to outline the stomach (for example, to visualize the pancreas or to assess the nature of an epigastric mass) or the rectum. In the future, oral ultrasound contrast agents may be developed specifically to examine the stomach or colon and to reduce bowel gas.