A key criterion of successful cancer surgery is the ability to remove all vestiges of the tumor and thereby greatly reduce the chances that the cancer will recur. That’s difficult, because surgeons can’t actually see in real time the difference between diseased and healthy tissue. But a team at the Beth Israel Deaconess Medical Center (Boston, MA) has developed technology that it calls fluorescence-assisted resection and exploration (FLARE) to change that.
Consisting of a near-infrared (NIR) imager, a video monitor, and a computer, FLARE uses various NIR fluorophores that target cancer cells selectively when introduced into patients. Excited by appropriate LEDs, the contrast agents reveal the presence of cancer cells with high precision. To make the cells visible to surgeons, the imaging system converts the NIR light into bright colors laid over standard images of the surgical field on a video monitor. A foot switch lets physicians control multiple viewing angles and different magnification levels.
A pig’s hind leg is shown following injection with NIR contrast agents and imaging with NIR light. The imaging procedure highlights lymph flow. (Courtesy of Beth Israel Deaconess Medical Center)
The team is currently using the fluorophore indocyanine green, which is already FDA approved for other purposes. Targeted fluorophores for malignant cells, nerves, and tissues are under development. The team has developed an integrated LED/driver combination, mounted in thermally conductive silicone, which can be combined with a standard 25-mm-diameter filter to produce high-power filtered excitation light. For white light the researchers use Lumileds (San Jose, CA) 3 mm cool-white LEDs, while for 670 and 760 nm excitation they rely on Epitex (Kyoto, Japan) 5 mm LEDs. The color-video and two NIR cameras are mechanically aligned using a shock-resistant optical frame to provide precise matching of imagery.
The technique benefits cancer treatment in several ways. “By introducing exogenous NIR fluorescent contrast agents into the surgical field, the surgeon can perform lymph-node mapping, resect tumors, and avoid critical structures such as vessels and nerves, all under image guidance,” says team leader John Frangioni. The method also has potential for earlier diagnosis of solid tumors. “We believe that seeing is curing,” Frangioni adds. “If we can see cancer at an earlier stage than we now can, we will have a greater likelihood of curing it.”
Frangioni’s team originally applied FLARE to visualize the organs and body fluids of mice and the lymph nodes of pigs in real time. At the national meeting of the American Chemical Society (Philadelphia, PA; August 2008), he reported that the team has started a human clinical trial of the system’s use in mapping the lymph nodes of patients with breast cancer. At press time, a second clinical trial was due to start. This trial involves sentinel lymph-node mapping in thoracic cancer and will be carried out at Brigham and Women’s Hospital (Boston, MA). Sometime in 2009 the group will use FLARE in a study of perfusion in reconstructive plastic surgery. Beth Israel Deaconess has nonexclusively licensed the technology to GE Healthcare (Chalfont St. Giles, England) for conversion to clinical practice. –Peter Gwynne and Barbara Goode