September 1, 2006 (Vol. 26, No. 15)

Company’s High-resolution, In situ Imaging Method Provides Real-time, Noninvasive Tool

VisualSonics ( markets and develops high-resolution, micro-ultrasound imaging systems to life science researchers worldwide.

The company launched its Vevo™ micro-ultrasound platform in 2003. By 2005, VisualSonics had sold over 200 systems, experienced a 145% compounded annual growth rate, reached $24 million in annualized sales, and obtained ISO 9001:2000 registration. All this good news comes from making ultrasound for mice, says Tom Little, president and CEO of VisualSonics, based in Toronto.

VisualSonics’ Vevo 770 high-resolution, micro-ultrasound imaging system offers preclinical researchers a new way to view and quantify minute physiological structures and functions in vivo and in real time with near microscopic resolution. Researchers are using the Vevo 770 to quantify angiogenesis, tumor growth, cardiovascular disease, and plaque formation in small animal models. “We specifically tailored ultrasound for the preclinical research market,” Little says.

In general, ultrasound is the most widely installed clinical-imaging modality, and most people are familiar with its ability to image pregnancies. These clinical ultrasound units operate at less than 15 megahertz and have a resolution of 300 microns, which is perfect for viewing a human pregnancy, according to Little.

At the University of Toronto, biophysicist Stuart Foster, Ph.D., wanted to improve ultrasound to view smaller structures, such as arteries and blood flowing through them. He tinkered with the physics of ultrasound and boosted the frequency to 85 megahertz, thereby increasing resolution to 30 microns. To commercialize his micro-ultrasound prototype, Dr. Foster founded VisualSonics in 1999, and he serves as its chairman and CSO.

Imaging Preclinical Phenotypes

Vevo’s imaging capabilities complement the explosion of genomics data coming from the Human Genome Project. As scientists struggle to understand phenotypes or how genes affect diseases and responses to treatments, micro-ultrasound imaging provides a noninvasive tool for viewing complex biological mechanisms in real-time.

Matthew Springer, M.D., a cardiology researcher at the University of California, San Francisco, injects stem cells into areas of infarct in attempts to rejuvenate heart muscle in mice. Micro-ultrasound eliminates the need for invasive surgery to implant the stem cells. “Dr. Springer uses the Vevo to guide the needle into the wall of the beating heart to inject the stem cells,” says Little.

One research team observes the real-time formation of plaque in the coronary arteries of mice with micro-ultrasound. Before adopting the Vevo, expensive and time-consuming MRI and histology were used. A number of biotech and pharma companies developing drugs for heart disease “have Vevo written into their atherosclerotic protocols to image plaque in blood vessels,” adds Little.

Another requirement that Vevo fulfills is the “need to see the expression of genes in small animal models,” explains Little. Imaging living animals is particularly important for cardiovascular, cancer, developmental biology, and stem cell research. With the Vevo technology, researchers can view the valves, chambers, walls, and plaque formation in an adult mouse heart, as well as in an embryonic mouse heart. Although mice are the most common animal models for preclincal studies, Vevo also works well with zebrafish, chick embryos, and rats.

Besides tapping into imaging on the smaller scale, micro-ultrasound also allows pharma and biotech researchers to conduct longitudinal studies on the same animals over long periods. This greatly reduces the number of animals that must be sacrificed for histological or pathological examination. Observing physiological changes in the same animal in vivo in response to drug treatments or other interventions also provides more realistic physiological data.

3-D Images

In addition, researchers who study cancer can now grow and monitor tumor cells orthotopically, because the Vevo technology provides 3-D images of tumor growth or regression in situ. Although calipers give fair 2-D estimates of the size of surface tumors, “they can be dramatically wrong if the tumor penetrates into the animal,” notes Little.

VisualSonics recently announced an exclusive arrangement to have MicroMarker Molecular Imaging kits manufactured by Bracco Group. This will allow the Vevo’s functionality to include anatomical, functional, and now molecular imaging.

Jonathan Lindner, M.D., developed the Vevo technology, which consists of microbubbles with attached ligands that target certain molecules. Dr. Lindner, who is now at the Oregon Health and Sciences University, was named VisualSonics’ chief molecular advisor in February. He will guide the creation of kits and protocols to use contrast agents to target myocardial perfusion, tumor perfusion, inflammation, and angiogenesis.

Micro-ultrasonic imaging with the Vevo replaces traditional methods says Little. Currently, VisualSonics micro-ultrasound technology has no direct competition globally. “We have indirect competition,” says Little, in that scientists continue to use calipers and histology or more costly MRI.

“Where as an MRI unit can cost up to $2.5 million and takes minutes to hours to generate images, the Vevo costs $175,000 and provides images nearly instantaneously. The market opportunity for VisualSonics is over $2.9 billion,” says Little.

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