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Biomedical Optics & Medical Imaging

Pushing the limits of fluorescence image-guided surgery

A novel, low-cost, and miniature imaging system aids surgeons in identifying tumors for excision.
15 January 2013, SPIE Newsroom. DOI: 10.1117/2.1201212.004621

Currently, most surgeries are performed with the most basic set of tools that humans possess: their natural senses. During a procedure, this means a surgeon relies mainly on vision, looking at tissue color; and touch, probing tissue temperature and stiffness. As a result, surgical outcome often varies from surgeon to surgeon, with his or her experience being one of the most influential factors. Needless to say, it is the surgeons who are the first to feel frustrated about this situation: “If I could see cancer, I would be able to remove it completely from my patients. Can you help me do this?” The answer is not as straightforward as we would like, but there is definitely some good news and hope for improving the way surgeries are performed.

Near-infrared (near-IR) light, invisible to the human eye, can penetrate several millimeters into living tissues, and therefore can be used to ‘see’ what is inside the tissue using very simple and inexpensive camera systems. When combined with fluorescent agents that can potentially highlight cancer that needs to be removed, or critical structures that must be avoided (such as bile ducts, ureters, nerves, and vessels), the surgeon can identify these in real time during the procedure.1 Image-guided surgery is a novel field that focuses on developing tools for surgeons to see cancer and other diseases during surgery. Within this field, near-IR fluorescence imaging has garnered increasing levels of interest over the last decade with the development and translation to the clinic of novel devices and fluorescent agents for surgery. Ongoing and completed clinical trials suggest that fluorescence image guidance could have an impact on cancer surgery (sentinel lymph node mapping, liver and ovarian cancer imaging), and general surgery (ureters, bile duct, and vessel imaging).

Several fluorescence imaging systems have been developed and brought into use in human surgery using existing, clinically approved fluorescent contrast agents such as indocyanine green and methylene blue.1, 2 However, most of these systems are built for open surgical procedures, and their size precludes their use in small cavities. With surgery witnessing a shift toward minimally invasive procedures, new compact systems capable of near-IR fluorescence imaging are desperately needed. We have developed, optimized, and brought into clinical use a miniaturized fluorescence imaging system for oncologic surgery.3 It is the smallest, most versatile, clinically compatible near-IR imaging system developed to date, with a definitive advantage over previously developed systems when imaging inside small cavities and in cramped areas.

Figure 1. Multifiber ring design. The imaging system illumination is based on a small footprint, circular ring approach. A 1-to-19 multifiber bundle is used to transport near-infrared (near-IR) excitation light and white light from the coupler to the rings. Every single fiber is equally spaced at the bottom ring of the system. This approach allows for minimal footprint while ensuring homogeneous, safe illumination (as a Class 1 laser).

This system, termed FluoSTIC, relies on a compact ‘lipstick’ CCD camera (Jai, Denmark) inserted in a custom 19-fiber circular array (Fiber Tech Optica, Canada): see Figure 1. This fiber array is capable of homogeneously illuminating the surgical field with both white light and near-IR light by controlling the fibers' exit angle. Light from a 740nm laser diode and a white light source are combined and coupled to the fiber array. Emission fluorescent light is filtered through a high-efficiency interference filter (Chroma, VT). Specifically, this filtration scheme has been optimized to accommodate a broad range of fluorophores by privileging a wider emission band rather than optimal excitation efficiency, without any loss in performance.

Figure 2. (a) Schematic of all the components of the FluoSTIC fluorescence imaging system. The camera is inserted inside the illumination rings. The emission filter is placed at the bottom of the imaging lens. The body of the system is then placed over the whole assembly. (b) Pictures of the FluoSTIC imaging system. Left: Camera with filter inside the multifiber ring. Right: Housing protecting the device. A US quarter is shown between the two. GigE: Gigabit Ethernet. NA: Numerical aperture.

FluoSTIC measures 22mm in diameter, 200mm in length, and weighs less than 200g: see Figure 2. The system is capable of imaging a field of view of 30×40mm at 126mm working distance, with a fluence rate of 8mW/cm2 of near-IR excitation light and 1000lx of white light. While almost an order of magnitude smaller than other state-of-the-art fluorescence image-guided surgery systems, FluoSTIC maintains similar imaging quality and fluorescence performance: see Figure 3. Importantly, FluoSTIC has been designed in association with surgeons toward future clinical use. The system has been certified a Class 1 laser (the safest class possible) and approved for clinical use for human cancer surgery.

Figure 3. In vivo validation of FluoSTIC. Image-guided detection and excision of small tumor-positive nodules in mice. Left: White light image. Right: Near-IR fluorescence. Note the two positive nodules as pointed out by the white arrows.

With miniature and optimized devices such as FluoSTIC allowing more applications to be explored and new fluorescent molecules being developed for medical use,4 fluorescence image-guided surgery is poised to impact patient care. Our next challenges are the efficient integration of near-IR fluorescence imaging into more complex endoscopic devices5 and the validation of the technology by health care professionals.6 FluoSTIC contributes to both of these aspects, with a miniature format, low complexity, and low cost, which makes it an ideal candidate for clinical dissemination.

This work was supported in France by a Contrat de Projets État-Région grant.

Sylvain Gioux
Center for Molecular Imaging (CMI)
Beth Israel Deaconess Medical Center
Harvard Medical School
Jean-Guillaume Coutard, Jean-Marc Dinten
Electronics and Information Technology Laboratory (LETI)
Atomic Energy and Alternative Energies Commission (CEA)
Grenoble, France
Veronique Josserand, Jean-Luc Coll
Albert Bonniot Institute (IAB)
Université Joseph Fourier
Grenoble, France
Christian Righini
Head and Neck Surgery Department
University Hospital of Grenoble
Grenoble, France

Sylvain Gioux is the director of the Biomedical Optics and Engineering Laboratory at the CMI. His work focuses on the development of novel optical imaging and sensing technologies for clinical applications that can have a significant impact on health care. He is particularly interested in image-guided interventions. His contributions include the development and clinical translation of near-IR fluorescence and oxygenation imaging systems.

1. S. Gioux, H. S. Choi, J. V. Frangioni, Image-guided surgery using invisible near-infrared light: fundamentals of clinical translation, Mol. Imag. 9, p. 237-255, 2010.
2. S. L. Troyan, V. Kianzad, S. L. Gibbs-Strauss, S. Gioux, A. Matsui, R. Oketokoun, L. Ngo, A. Khamene, F. Azar, J. V. Frangioni, The FLARE™ intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in breast cancer sentinel lymph node mapping, Ann. Surg. Oncol. 16, p. 2943-2952, 2009.
3. S. Gioux, J. G. Coutard, M. Berger, H. Grateau, V. Josserand, M. Keramidas, C. Righini, J.-L. Coll, J.-M. Dinten, FluoSTIC: miniaturized fluorescence image-guided surgery system, J. Biomed. Opt. 17, p. 106014, 2012.
4. H. S. Choi, K. Nasr, S. Alyabyev, D. Feith, J. H. Lee, S. H. Kim, Y. Ashitate, H. Hyun, G. Patonay, L. Strekowski, M. Henary, J. V. Frangioni, Synthesis and in vivo fate of zwitterionic near-infrared fluorophores, Angew. Chem. Int'l Ed. 50(28), p. 6258-6263, 2011.
5. D. C. Gray, E. M. Kim, V. E. Cotero, A. Bajaj, V. P. Staudinger, C. A. Tan Hehir, S. Yazdanfar, Dual-mode laparoscopic fluorescence image-guided surgery using a single camera, Biomed. Opt. Express 3(8), p. 1880-1890, 2012.
6. http://www.theflarefoundation.org/ Homepage of the FLARE Foundation, a non-profit organization dedicated to making near-IR light-based technology available to as many patients as possible worldwide. Accessed 17 December 2012.