Contrast-enhanced ultrasound finds niche

Contrast-enhanced ultrasound has an integral role to play in molecular imaging, according to studies presented Tuesday. Data from worldwide researchers suggest that applications for the evaluation of angiogenesis as well as for guidance, delivery, and assessment of gene therapy may signal new opportunities for ultrasound contrast agents.

Researchers have developed sophisticated applications of microbubble agents and learned to take advantage of ultrasound's noninvasive, real-time imaging advantage, said Flemming Forsberg, Ph.D., a professor of radiology at Thomas Jefferson University.

Forsberg and colleagues compared random sextant biopsy results for 15 patients suspected of prostate cancer with transrectal ultrasound imaging of microvessel density using the contrast agent Imagent. They used a special microscope and software to evaluate microvessel density and correlated histology against gray-scale phase inversion harmonic imaging (PIHI), color Doppler, and power Doppler results. They found that microvessel density was greater in malignant prostate tissue than in normal tissue.

Biopsy specimens confirmed that eight of the 15 patients had prostate cancer. The researchers found a statistically significant difference between malignant and benign microvessel densities (p = 0.0009). The correlation between microvessel density and individual ultrasound modes varied, sometimes negatively. However, the suspicion of cancer assessed with the three transrectal ultrasound modes correlated significantly with microvessel density (p<0.0007).

The small patient population sample was the greatest limitation in the study. The researchers observed a significant outcome deviation between the first 13 and the last two men enrolled for the study. They acknowledge the need for additional prospective studies in the future that include significantly larger population samples, Forsberg said.

Another study by Thomas Jefferson researchers compared contrast ultrasound with nuclear imaging and the gold standard blue dye with surgical dissection for the detection of malignant sentinel lymph nodes from melanoma.

Dr. Barry Goldberg and colleagues assessed 28 melanomas from 12 Sinclair swine because of their striking resemblance to human melanomas. Although blue dye-guided surgical dissection identified more malignant nodes, the investigators found that contrast-enhanced lymphosonography was better than lymphoscintigraphy for the detection of sentinel lymph nodes in this animal model.

In two other studies, investigators from China and the U.K. evaluated the feasibility of delivering gene therapy using microbubble contrast agents.

H. Liang, Ph.D., and colleagues at the Imperial College in London investigated whether Optison-enhanced ultrasound could increase nonviral lung transfection. They found this agent proved to be an efficient physical delivery system of gene therapy to the lungs.

The same researcher and another group of Sino-British investigators evaluated the ability of contrast ultrasound to induce cell gene transfer in vitro. They found that a microbubble contrast agent can significantly increase gene transfer rates in three different cell lines from mice.