The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in breast cancer sentinel lymph node mapping.
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.
Troyan
Susan L
SL
Breast Care Center, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Kianzad
Vida
V
Gibbs-Strauss
Summer L
SL
Gioux
Sylvain
S
Matsui
Aya
A
Oketokoun
Rafiou
R
Ngo
Long
L
Khamene
Ali
A
Azar
Fred
F
Frangioni
John V
JV
D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000601:surgery; D004396:Coloring Agents; D005260:Female; D005453:Fluorescence; D005470:Fluorometry / Q000379:methods*; D006801:Humans; D007208:Indocyanine Green; D007432:Intraoperative Period; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D010865:Pilot Projects; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D021701:Sentinel Lymph Node Biopsy; D025321:Surgery, Computer-Assisted; D034421:Sus scrofa; D013671:Technetium Tc 99m Sulfur Colloid
D004396:Coloring Agents; D019275:Radiopharmaceuticals; D013671:Technetium Tc 99m Sulfur Colloid; D007208:Indocyanine Green