The FLARE™ Intraoperative Near-Infrared Fluorescence Imaging System: A First-in-Human Clinical Trial in Breast Cancer Sentinel Lymph Node Mapping
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Invisible NIR fluorescent light can provide high sensitivity, high-resolution, and real-time image-guidance during oncologic surgery, but imaging systems that are presently available do not display this invisible light in the context of surgical anatomy. The FLARE™ imaging system overcomes this major obstacle.
Color video was acquired simultaneously, and in real-time, along with two independent channels of NIR fluorescence. Grayscale NIR fluorescence images were converted to visible “pseudo-colors” and overlaid onto the color video image. Yorkshire pigs weighing 35 kg (n = 5) were used for final preclinical validation of the imaging system. A six-patient pilot study was conducted in women undergoing sentinel lymph node (SLN) mapping for breast cancer. Subjects received 99mTc-sulfur colloid lymphoscintigraphy. In addition, 12.5 μg of indocyanine green (ICG) diluted in human serum albumin (HSA) was used as an NIR fluorescent lymphatic tracer.
The FLARE™ system permitted facile positioning in the operating room. NIR light did not change the look of the surgical field. Simultaneous pan-lymphatic and SLN mapping was demonstrated in swine using clinically available NIR fluorophores and the dual NIR capabilities of the system. In the pilot clinical trial, a total of nine SLNs were identified by 99mTc- lymphoscintigraphy and nine SLNs were identified by NIR fluorescence, although results differed in two patients. No adverse events were encountered.
We describe the successful clinical translation of a new NIR fluorescence imaging system for image-guided oncologic surgery.
We thank Barbara L. Clough and Mireille Rosenberg for clinical trial preparation, Judith Hirshfield-Bartek for assistance with patient medical histories, Eiichi Tanaka, M.D. for preliminary swine studies, and Sunil Gupta and Razvan Ciocan for technical assistance with the imaging system. This study was supported by the following grants from the National Institutes of Health (National Cancer Institute) to JVF: Bioengineering Research Partnership grant #R01-CA-115296 and Quick Trials for Imaging grant #R21-CA-130297. We thank the following individuals and companies for their contributions to this project: Gordon Row (Yankee Modern Engineering), Kelly Stockwell and Paul Millman (Chroma Technology), David Comeau and Robert Waitt (Albright Technologies), Gary Avery, Phil Dillon, and Ed Schultz (Qioptiq Imaging Solutions), Jeffrey Thumm (Duke River Engineering), Michael Paszak and Victor Laronga (Microvideo Instruments), Colin Johnson (LAE Technologies), Robert Eastlund (Graftek Imaging), John Fortini (Lauzon Manufacturing), Steve Huchro (Solid State Cooling), Clay Sakewitz and Will Richards (Design and Assembly Concepts), Ken Thomas and Fernando Irizarry (Sure Design), Paul Bistline and Phil Bonnette (Medical Technique, Inc.), Mathew Silverstein (L-com), and Jim Cuthbertson (Nashua Circuits).
This study was supported by the following grants from the National Institutes of Health (National Cancer Institute) to JVF: Bioengineering Research Partnership grant #R01-CA-115296 and Quick Trials for Imaging grant #R21-CA-130297. All intellectual property associated with the FLARETM imaging system is owned by the Beth Israel Deaconess Medical Center, which has licensed it nonexclusively to GE Healthcare. As inventor of the technology, Dr. Frangioni may someday receive royalties if a product is commercialized. No other authors have any financial interest in this study.
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