Optical tomography gains ground as research tool

Molecular imaging with near-infrared technology is already affecting medicine, albeit more in animal than clinical research.

VisEn Medical, a pioneer in this technology headquartered in Woburn, MA, launched its Fluorescence Molecular Tomography (FMT) in early September at the Society for Molecular Imaging meeting in Cologne, Germany. FMT is designed specifically for use on small animals.

The company began selling a precommercial version of the instrument and its line of optical probes in the first half of 2005. The lead time was enough for early adopters to come up with 18 presentations for the SMI meeting, addressing such topics as cancer drug testing, bone remodeling, and cardiovascular disease.

Optical tomography has proven potentially useful as a clinical diagnostic as well. Research conducted at the University of Connecticut, employing a handheld ultrasound transducer surrounded by near-infrared sensors, found that coregistered NIR and ultrasonic images can be used to zero in on early-stage breast tumors. The imaging combination can help physicians assess changes in tumor vasculature and let them better distinguish between malignant and benign lesions, potentially reducing the number of biopsies. It might be especially helpful in monitoring chemotherapy treatment and assessing changes of tumor vasculature during treatment.

The ability to measure tumor angiogenesis is especially helpful in highlighting early-stage cancers, as the vasculature in these lesions is not as heterogeneous or complex as that in larger tumors.

The researchers prospectively studied 81 breast lesions in 65 consecutive women. They used light absorption measurements to help calculate total hemoglobin concentration. They then performed ultrasound-guided biopsy on the lesions. Biopsy confirmed eight early-stage invasive tumors and 73 benign lesions. The sensitivity, specificity, positive predictive value, and negative predictive value of optical tomography were 100%, 96%, 73%, and 100%, respectively.

These results, published in the October issue of Radiology, are the latest in a decade of efforts to develop NIR optical tomography for breast cancer screening. Progress in optical imaging has come on the heels of biocompatible fluorescent markers, advances in imaging technology, and refinements in the mathematical models that make sense of the chaotic paths photons travel through the body.

Most of the successes have been scored in small animal research, where fluorescence molecular imaging enables visualization of the molecular distribution and action of drugs long before anatomic or functional effects are apparent. Fluorescence imaging promises to make animal research more efficient and cost-effective, because it will reduce the need to sacrifice animals in order to assess drug efficacy.

VisEn Medical describes its FMT system as the first to enable truly quantitative, deep tissue, 3D tomographic imaging of fluorescence in animals. The company also offers a line of optimized in vivo probes and technical support in the chemistry, biology, and pharmacology of imaging. These probes serve specific functions or illuminate specific disease states found in vivo. ProSense, for example, highlights protease activity in arthritis and oncology. AngioSense is a long-lasting vascular imaging agent used to illuminate angiogenesis in breast cancer.

Products are being shaped to address oncology, bone growth, cardiovascular disease, and inflammation. They are designed to be fundamentally translatable from animal imaging to the clinic. Ultimately, capabilities developed for animal research will be applied in clinical medicine, according to Kirtland G. Poss, president and CEO of VisEn Medical.

"The agents are built of clinically compatible components and have clinically relevant biologic profiles," he said.

Big pharma companies, such as Merck and Lilly, are using the companies' technologies to study disease processes and the action of experimental drugs in animals. With some modifications, whatever works in animals should work in humans, as animal studies provide the underlying basis for extending and documenting drug effects in human clinical trials. Taken one step further, molecular imaging techniques proven in human trials should be effective in diagnosing disease and monitoring therapy in patients.

"Our business is to develop agents that can be used preclinically and then clinically," Poss said. "We are partnering with device companies to address or attack disease areas where a much earlier and more specific understanding and visualization of disease adds to the diagnosis and treatment outcome."

Siemens Medical Solutions literally bought into this idea two years ago when it purchased an equity stake in VisEn. At the time, Siemens executives described the move as part of a broad effort to evaluate opportunities in healthcare.

VisEn was founded on those opportunities five years ago using technologies initially developed at the Center for Molecular Imaging Research at Massachusetts General Hospital. It has established five beta installations at pharmaceutical and academic sites. About 20 other pharmaceutical and academic customers have begun using the company's molecular imaging probes for small animal imaging studies.

Because optical tomography is physiologically rather than anatomically oriented, this technology might be paired with conventional means for plumbing the body. Efforts at Mass General have shown this potential in small animals. Vasilis Ntziachristos, Ph.D., and colleagues have combined MR with planar and fluorescence-mediated optical tomography to improve visualization of tumors in mice.

Brian W. Pogue, Ph.D., an associate professor of engineering at Dartmouth, has taken it a step further, integrating an NIR optical breast imaging system into a clinical MR scanner. Data are acquired by both systems during a single scan, and spectroscopic data on hemoglobin concentration are then superimposed on the MR T1-weighted images. This approach not only compensates for shortcomings in the spatial resolution of optical tomography, it improves MR breast imaging.

VisEn is exploring such possibilities, although Poss refused to provide any details.

"Deep tissue tomography and quantification of the optical signal lend themselves very well to multimodality applications," he said. "We are working on that type of thing all the time, internally and with partners."

Quantifying molecular activity is the key to unlocking the clinical potential of this technology, according to Poss. Through quantification, disease processes and patient response can be exactly defined.

"The ability to quantify the molecular basis of disease progression is what really will enable us to know what is happening," he said. "It will tell us what is really going on with the disease."