Scanning techniques further ultrasound contrast's cause

Agent-specific imaging techniques help reduce artifacts and realize potential of microbubble agents for macro- and microvasculature assessment

Gas-filled microbubbles have generated considerable interest as a means of improving ultrasound's ability to gather vascular information. Dedicated scanning techniques, which have boosted the sensitivity and specificity of microbubble-assisted imaging, are now helping to clarify the agents' full potential, according to experts in the field.

Microbubbles work as blood-pool agents, staying within the vascular space during their trip through the cardiopulmonary circulation. Addition of contrast can generally rescue a standard color Doppler examination and improve visualization of small blood vessels. More advanced approaches, such as real-time scanning with a low mechanical index using phase inversion or frequency filtering techniques, can enhance the contrast between moving microbubbles and stationary tissue, according to Prof. Carlos Bartolozzi, chair of diagnostic and interventional radiology at the University of Pisa in Italy. Quantification of the signal remains problematic, however, because of the physical nature of the contrast media.

"The bubbles may be of different sizes, or they may concentrate in certain vascular territories. There can be problems with sticking or bubble destruction," Bartolozzi said during a special session on contrast-enhanced ultrasound at ECR 2006.

PROBLEMATIC MICROBUBBLES

Another difficulty associated with microbubble agents is the generation of artifacts from the huge increase in signal intensity, said Dr. Jean-Michel Correas, a radiologist at Necker Hospital in Paris. Methods do exist to reduce these unwanted effects. Blooming artifacts can be limited by slowing the infusion of contrast, while systolic artifacts may resolve themselves within a few minutes. But the best remedy may be to switch to newer sequences that take advantage of the bubbles' resonant properties.

"These new techniques to image microbubbles are proving to be more reliable, and they provide fewer artifacts," Correas said.

Ultrasound contrast is most useful in the macrovasculature when examinations involve deep vessels, complex anatomy, low flow rates, and calcified plaques, according to Correas. In the aorta, for example, unenhanced color Doppler is generally sufficient to detect and follow aneurysms. Microbubble agents may be required to assess mural thromboses or pinpoint aortic leaks. Contrast may also be called for if unenhanced Doppler analysis of the renal arteries is normal but clinical signs suggest otherwise. Addition of microbubbles may demonstrate the flow acceleration and turbulence indicative of stenosis.

Contrast can help improve visualization in the venous system as well; for example, when evaluating renal vein thrombosis. Diagnosis of this disease can be critical, but it is sometimes difficult to see the entire course of the vein on unenhanced examinations.

"If you use a contrast agent, you will be able to improve detection of the vessel," Correas said. "However, you must be careful, because blooming can obscure partial vein thromboses. This is why we are going to use techniques different from the standard color Doppler examination, which is probably not the most suitable or most appropriate technique to visualize microbubbles."

TWO INNOVATIONS

At the same Congress session, Dr. Thomas Albrecht, senior radiologist at Charite-University Medicine in Berlin, reiterated the importance of using contrast-specific imaging techniques when working with microbubble agents. He highlighted two innovations that have improved the sensitivity of contrast-enhanced ultrasound in the microvasculature: contrast pulse sequencing and microflow imaging.

Contrast pulse sequencing involves a combination of phase inversion and amplitude modulation. The resulting nonlinear fundamental response from the bubble and the nonlinear harmonic response are then summed to improve sensitivity. Microflow imaging sums multiple consecutive frames to form a single image. This should be especially helpful when imaging small vessels containing very few bubbles. Such techniques can bring imaging resolution down to the precapillary level, demonstrating vessels with diameters of just 20 to 40 microns, Albrecht said. At this level of resolution, ultrasound could be used to monitor the effect of anti-angiogenic and/or cytotoxic cancer drugs on tumor vasculature.

"Changes in vascularity may well precede changes in tumor size, so when the vessels shut down, we should see this before we see any tumor shrinkage," he said. "That may allow us to return responders to alternative therapies at a much earlier stage than we do at present."

Contrast-enhanced ultrasound is now used routinely for the detection and characterization of focal liver lesions, thanks to the characteristic patterns generated from dynamic imaging, Albrecht said. Published studies have found that these lesions can be diagnosed accurately postcontrast with a sensitivity of 70% to 90%. Based on these, the correct distinction between benign and malignant lesions is being made in 90% of cases.

Application of microbubble contrast in other abdominal organs is tied more closely to individual cases. Contrast may assist in the detection of splenic lesions, though it is unlikely to aid characterization. Adding contrast similarly fails to help in differentiation of renal tumors, but the agents can help sort pseudotumors from real tumors and clarify the outcome of radiofrequency ablation.

Further studies are required to work out the best role for contrast-enhanced ultrasound in superficial organs, Albrecht said. Information on tumor hypervascularity can increase the sensitivity of prostate cancer detection on ultrasound from 40% to 65%. The improvement is good but not sufficient to eliminate the need for biopsies.

Dynamic imaging information can also help differentiate benign breast lesions from cancerous tumors. Malignant lesions typically show prolonged enhancement compared with the rapid wash-out of fibroadenomas. This phenomenon may be due to microbubbles pooling in vascular lakes, sticking to irregular endothelium, or leaving the intravascular space through an irregular endothelial lining.

"This is exactly the opposite of what you see on contrast-enhanced MRI, where malignant tumors are the ones that wash out," Albrecht said.