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Biomedical Optics & Medical Imaging

Near-infrared fluorescence could improve cancer surgery

A low-cost, safe, and easy-to-use imaging system lets a surgeon see surgical anatomy and invisible fluorescence: this both simultaneously and in real time.
17 August 2006, SPIE Newsroom. DOI: 10.1117/2.1200607.0331

In 2006, approximately 1.4 million new cases of cancer will be reported in the United States.1 For people under 85 years of age, cancer is the leading cause of death, taking over half a million lives a year. Near-infrared (NIR)-fluorescence imaging could improve human-cancer surgery by providing sensitive, specific, and real-time visualization of normal and disease processes during surgery.

When cancer is detected during its early stages, surgical resection of tumors remains the primary treatment. Complete removal of the tumor prior to metastasis—the spreading of cancer cells throughout the body—is the best way to ensure a full recovery and to minimize the risk of recurrence. Moreover, the presence of cancer cells in regional lymph nodes indicates metastasis and necessitates more aggressive, systemic treatment, such as chemotherapy. In many cancer surgeries, oncologists remove several lymph nodes in the region of the tumor to detect metastasis through the lymphatic system. Identifying the first lymph node to receive lymphatic drainage—that is, the sentinel lymph node—minimizes the number of biopsies required to determine the stage of the cancer.

Furthermore, tumor margins are poorly defined and difficult to visualize. The five-year recurrence of certain cancers—including colorectal and breast—remains quite high, possibly due to partial removal of the primary tumor or the presence of small metastases that are invisible to the surgeon. A visual aid that maps the sentinel lymph node and assists the surgeon during tumor resection could improve the odds of completely removing diseased tissue.

We have developed a low-cost, safe, and easy-to-use NIR-fluorescence imaging system that permits a surgeon to simultaneously see surgical anatomy and invisible NIR fluorescence in real-time and with high spatial resolution. To translate this technology to the clinic, members of the Frangioni laboratory and GE Global Research Center have received a Bioengineering Research Partnership funded by the U.S. National Institutes of Health.

Why NIR?

Introducing an NIR-fluorescent optical-contrast agent into the body provides an aid to visualization. There are several advantages to using NIR rather than visible fluorophores. First, tissue contains intrinsically fluorescent components that glow when excited by blue or green light. This autofluorescence can interfere with the fluorescence of an imaging dye. Shifting the excitation wavelength to the NIR minimizes the amount of background autofluorescence relative to that from the dye.3 Second, the attenuation coefficient of tissue is significantly lower in the NIR than in the visible, so fluorescence can be observed from deeper objects.

During the first year of this grant, we successfully completed the design and construction of an NIR-fluorescence imaging system for open surgery. In realizing this system, we overcame several engineering challenges. For example, we developed a system—with no moving parts—that simultaneously monitors two different NIR fluorophores and provides color video of the surgical anatomy. Our newest design uses two dichroic mirrors in series. These direct three types of light—color (400–670nm), NIR emission 1 (683–717nm), and NIR emission 2 (>800nm)—to three different cameras.

In order to make surgical imaging a reality, we also needed a low-profile, high-power light source that was not laser-based. It must be fully contained in a sterile drape, generate fluence rates of 12.5–25mW/cm2 to excite two different fluorophores, and supply white light to illuminate the surgical field. We achieved these specifications with more than 800 LEDs in a low-profile unit comprised of square modules. Each module is roughly 25mm on a side and houses 20 LEDs, and the whole system is driven by custom-designed, scalable electronics. Given the extremely high heat load generated by these LEDs, we also designed a cooling system that permits remote monitoring and control of the light-source temperature. The entire unit is mounted in an aluminum housing and contained within a sterilizable NIR-transmissive shield and drape.

Using these engineering advances, we continue to develop novel techniques for real-time surgical guidance. The chemists on our team continue to improve targeted NIR fluorophores for image-guided cancer resection. Figure 1 highlights how a NIR dye dramatically enhances visualization of the lymphatic system during identification of the sentinel lymph node.

Figure 1. This color video (left) shows a porcine foot. Within seconds of injecting the foot with a near-infrared fluorescent tracer for the lymphatic system, the tracer migrates up the lymphatic chain, which first diverges (shown) then converges to the sentinel lymph node.2 Simultaneous acquisition of color video and NIR fluorescence permits pseudocoloring (lime green) of the otherwise-invisible NIR fluorescence and overlay onto the color-video image (right).

The end point of our study will be an intraoperative NIR-fluorescence imaging system for human clinical trials. Immediate cancer-surgery applications include image-guided mapping of the sentinel lymph node, image-guided cancer resection with real-time assessment of surgical margins, and intraoperative detection of occult metastases in the surgical field. This imaging system will also ensure that critical structures such as nerves and blood vessels are visualized and avoided. Taken together, our work describes an academic-industrial partnership engineered for successful translation of a general-purpose, optical-imaging technology to the clinic.

Siavash Yazdanfar
GE Global Research
Niskayuna, NY
John Frangioni
Beth Israel Deaconess Medical Center
Boston, MA