Our hypothesis is that near-infrared (NIR) fluorescence has the potential to revolutionize image-guided surgery. At the beginning of our first award period, there were neither optimized imaging systems nor optimized contrast agents to test this hypothesis. Nevertheless, in only 31/2 years, our Bioengineering Research Partnership (BRP), comprised of the Frangioni Laboratory at the Beth Israel Deaconess Medical Center (BIDMC), GE Healthcare, and Siemens Corporate Research, has designed, constructed, and disseminated the FLARE (Fluorescence-Assisted Resection and Exploration) intraoperative NIR fluorescence imaging system. By exploiting several innovations in hardware and software, FLARE is capable of visualizing two independent channels of NIR fluorescence in real-time, with high sensitivity and resolution, and simultaneously with surgical anatomy. In addition to validating the technology in over 200 rodent and 100 large animal surgeries, we have exceeded the original Specific Aims by translating FLARE to the clinic where it is now being used in three separate, NIH-funded clinical trials in breast cancer SLN mapping, lung cancer SLN mapping, and perforator vessel mapping. We have also leveraged our resources to add the Patonay/Strekowski Laboratory at Georgia State University (GSU), recognized leaders in NIR fluorophore chemistry, to our BRP and with them have developed ultra-low background heptamethine indocyanines for potential clinical translation. Despite these advances, there remain four fundamental areas in the field that require ongoing investigation: 1) the development of minimally-invasive (e.g., laparoscopy/endoscopy) NIR fluorescence technology for the approximately 50% of human surgeries that are no longer performed using "open" incisions, 2) the addition of spatially-modulated light capabilities to quantify tissue optical properties, especially tissue oxygenation, in the absence of exogenous NIR fluorophores, 3) the addition of fluorescence lifetime imaging (FLIM) capability to FLARE to improve separation of exogenous NIR fluorophores from tissue autofluorescence, and 4) the first-in-human testing of novel NIR fluorophores that will lay the foundation for future disease-specific contrast agents. We focus the Specific Aims of this competing renewal application on these four key areas, and have updated our BRP to include Qioptiq LINOS, Inc., experts in optical engineering, Yankee Modern Engineering, experts in medical device mechanical engineering, Albright Technologies, Inc., experts in micro-fabrication and silicone heat dissipation technology, the Electronics Design Facility of Boston University, experts in laser control electronics and digital light processing (DLP), and Seres Laboratories, one of the few cGMP chemistry contractors with experience in producing heptamethine indocyanines. GSU will continue to assist with cGMP scale-up. Finally, we propose to intensify clinical translation activities during the second award period, including first-in-human trials of the engineering and chemistry innovations that arise from this BRP.
Near-infrared light is invisible to the human eye, but penetrates relatively deeply into living tissue. It is therefore ideal for image-guided surgery, because it provides surgeons with high- sensitivity, high-resolution detection of diseases, such as cancer, without changing the look of the surgical field. We propose a Bioengineering Research Partnership (BRP) that brings together leaders in their respective fields to create the next-generation of imaging systems and contrast agents that are necessary to make this technology widely available to patients.
|Tummers, Quirijn R J G; Verbeek, Floris P R; Prevoo, Hendrica A J M et al. (2015) First experience on laparoscopic near-infrared fluorescence imaging of hepatic uveal melanoma metastases using indocyanine green. Surg Innov 22:20-5|
|Park, Min Ho; Hyun, Hoon; Ashitate, Yoshitomo et al. (2014) Prototype nerve-specific near-infrared fluorophores. Theranostics 4:823-33|
|Ashitate, Yoshitomo; Hyun, Hoon; Kim, Soon Hee et al. (2014) Simultaneous mapping of pan and sentinel lymph nodes for real-time image-guided surgery. Theranostics 4:693-700|
|van Driel, P B A A; van der Vorst, J R; Verbeek, F P R et al. (2014) Intraoperative fluorescence delineation of head and neck cancer with a fluorescent anti-epidermal growth factor receptor nanobody. Int J Cancer 134:2663-73|
|Tummers, Q R J G; Verbeek, F P R; Schaafsma, B E et al. (2014) Real-time intraoperative detection of breast cancer using near-infrared fluorescence imaging and Methylene Blue. Eur J Surg Oncol 40:850-8|
|Schaafsma, B E; Verbeek, F P R; Elzevier, H W et al. (2014) Optimization of sentinel lymph node mapping in bladder cancer using near-infrared fluorescence imaging. J Surg Oncol 110:845-50|
|Hyun, Hoon; Owens, Eric A; Narayana, Lakshminarayana et al. (2014) Central C-C Bonding Increases Optical and Chemical Stability of NIR Fluorophores. RSC Adv 4:58762-58768|
|Verbeek, Floris P R; van der Vorst, Joost R; Tummers, Quirijn R J G et al. (2014) Near-infrared fluorescence imaging of both colorectal cancer and ureters using a low-dose integrin targeted probe. Ann Surg Oncol 21 Suppl 4:S528-37|
|Verbeek, Floris P R; Troyan, Susan L; Mieog, J Sven D et al. (2014) Near-infrared fluorescence sentinel lymph node mapping in breast cancer: a multicenter experience. Breast Cancer Res Treat 143:333-42|
|Hyun, Hoon; Wada, Hideyuki; Bao, Kai et al. (2014) Phosphonated near-infrared fluorophores for biomedical imaging of bone. Angew Chem Int Ed Engl 53:10668-72|
Showing the most recent 10 out of 95 publications