Data from around the world released at the 2005 RSNA meeting suggest that contrast-enhanced ultrasound use in molecular imaging will expand. Applications include the evaluation of tumor angiogenesis and lymph node metastases at nearly cellular levels as well as guidance, delivery, and assessment of gene therapy.
While animal studies have dominated microbubble contrast agent research, trials on humans have started to surface. Researchers have developed sophisticated applications of microbubble agents and learned to take advantage of ultrasound's noninvasive, real-time imaging edge, said Flemming Forsberg, Ph.D., a professor of radiology at Thomas Jefferson University.
Forsberg and colleagues assessed 15 patients suspected with prostate cancer with contrast-enhanced transrectal ultrasound. They used an ultrasound biomicroscopy system and special software to evaluate tumors' microvessel density and compared findings against biopsy. They found a statistically significant difference between malignant and benign microvessel densities. Density values from individual ultrasound modes-including gray-scale phase inversion harmonic imaging and color and power Doppler-fluctuated considerably. Diagnosis using all three modes, however, provided a statistically significant correlation.
Another Jefferson group compared contrast ultrasound with blue dye scintigraphy and gold standard surgical dissection for detection of malignant sentinel lymph nodes from melanoma. Dr. Barry Goldberg and colleagues assessed 28 swine melanomas. Although blue dye-guided surgical dissection identified more malignant nodes, investigators found contrast-enhanced lymphosonography topped lymphoscintigraphy in this animal model. Lymphosonography identifies draining lymphatic channels and can guide biopsy or surgical resection of suspicious nodes in real-time. It can also spare patients and physicians from unnecessary exposure to radioactive agents.
U.K.-based researchers evaluated the use of microbubble contrast agents for gene therapy. Drs. Stefania Xenariou, Hai-Dong Liang, Martin Blomley, and colleagues at the Brompton and Hammersmith Hospital Campuses of Imperial College in London used the agent Optison to boost the transfection of nonviral agents such as naked plasmid DNA and polyethylenimine complexes to treat cystic fibrosis in mice. They found Optison was an efficient delivery system.
Another group of investigators evaluated an ultrasound contrast agent's ability to induce gene transfer in vitro. Drs. Yun-Chao Chen, Hai-Dong Liang, and colleagues at the Imperial College and at the Huazhong University of Science and Technology in Wuhan City, China, found that a microbubble contrast agent could significantly increase transfer rates in three different cell lines.
Investigators used an encoding green-fluorescent protein to assess gene delivery, cell viability, and transfection efficiency in the cell lines. Cells exposed to low power ultrasound plus Optison had double the gene transfer rate than those without contrast.
