The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in breast cancer sentinel lymph node mapping

Abstract

Background: 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.

Methods: 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 (99m)Tc-sulfur colloid lymphoscintigraphy. In addition, 12.5 microg of indocyanine green (ICG) diluted in human serum albumin (HSA) was used as an NIR fluorescent lymphatic tracer.

Results: 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 (99m)Tc- lymphoscintigraphy and nine SLNs were identified by NIR fluorescence, although results differed in two patients. No adverse events were encountered.

Conclusions: We describe the successful clinical translation of a new NIR fluorescence imaging system for image-guided oncologic surgery.

Figure 1

The FLARE™ Near-Infrared Fluorescence Imaging System: A. Detailed schematic of imaging head. B. Optical light paths and filtration for the FLARE™ imaging system having a color video camera, and two independent and simultaneous NIR cameras (700 nm emission and 800 nm emission). D1 = 680 nm dichroic mirror. D2 = 770 nm dichroic mirror.

Figure 2

Deployment in the Operating Room and Range of Motion: A. Portable imaging system and satellite monitor stand deployed in the operating room. Footswitch not shown. B. Six degrees-of-freedom range of motion (gray arrows) and brake release buttons of the imaging head.

Figure 3

Simultaneous, NIR Fluorescent Pan-Lymph Node Mapping and Sentinel Lymph Node Mapping in Swine: All lymph nodes of the mesentery (bracket) fluoresce at 700 nm (pseudo-colored red) after a single intravenous injection of 1 mg/kg methylene blue. An SLN (arrow) fluorescing at 800 nm (pseudo-colored green) is identified after intra-parenchymal injection of 10 µM ICG:HSA into the colon wall, and appears yellow. The lymphatic channel (LC) feeding the SLN appears green. All camera exposure times were 67 msec. Data are representative of n = 5 pigs.

Figure 4

NIR Fluorescent Sentinel Lymph Node Mapping in Women with Breast Cancer: Shown are color video images (left), 800 nm NIR fluorescence images (middle) and a pseudo-colored (lime green) merge of the two (right) after injection (Inj.) of 10 µM ICG:HSA. A. The four SLNs (arrows) identified and resected for Patient #1. 800 nm camera exposure time was 200 msec. B. The single SLN identified and resected for Patient #2. Shown are flow through a lymphatic channel (LC) and position of the SLN (arrow; top row), identification of the SLN (arrow; middle row), and a zoomed image of the SLN (arrow) during resection (bottom row). Note multiple non-SLNs nearby. 800 nm camera exposure time was 200 msec.

Figure 4

NIR Fluorescent Sentinel Lymph Node Mapping in Women with Breast Cancer: Shown are color video images (left), 800 nm NIR fluorescence images (middle) and a pseudo-colored (lime green) merge of the two (right) after injection (Inj.) of 10 µM ICG:HSA. A. The four SLNs (arrows) identified and resected for Patient #1. 800 nm camera exposure time was 200 msec. B. The single SLN identified and resected for Patient #2. Shown are flow through a lymphatic channel (LC) and position of the SLN (arrow; top row), identification of the SLN (arrow; middle row), and a zoomed image of the SLN (arrow) during resection (bottom row). Note multiple non-SLNs nearby. 800 nm camera exposure time was 200 msec.