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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA115296-09
Application #
8504728
Study Section
Special Emphasis Panel (ZRG1-SBIB-V (50))
Program Officer
Baker, Houston
Project Start
2005-09-29
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
9
Fiscal Year
2013
Total Cost
$1,362,767
Indirect Cost
$442,247
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Wada, Hideyuki; Hyun, Hoon; Kang, Homan et al. (2016) Intraoperative Near-Infrared Fluorescence Imaging of Thymus in Preclinical Models. Ann Thorac Surg :
Boogerd, Leonora S F; Handgraaf, Henricus J M; Lam, Hwai-Ding et al. (2016) Laparoscopic detection and resection of occult liver tumors of multiple cancer types using real-time near-infrared fluorescence guidance. Surg Endosc :
Hyun, Hoon; Henary, Maged; Gao, Tielong et al. (2016) 700-nm Zwitterionic Near-Infrared Fluorophores for Dual-Channel Image-Guided Surgery. Mol Imaging Biol 18:52-61
Boonstra, Martin C; van Driel, Pieter B A A; van Willigen, Danny M et al. (2015) uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery. Oncotarget 6:14260-73
Wada, Hideyuki; Hyun, Hoon; Vargas, Christina et al. (2015) Sentinel Lymph Node Mapping of Liver. Ann Surg Oncol 22 Suppl 3:S1147-55
Bordo, Mark W; Oketokoun, Rafiou; Cross, Conor J et al. (2015) High-Throughput Sorting and Placement of One-Bead-One-Compound (OBOC) Libraries from Bulk to Single Wells in Organic Solvent. ACS Comb Sci 17:303-9
Hyun, Hoon; Park, Min Ho; Owens, Eric A et al. (2015) Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging. Nat Med 21:192-7
Vargas, Christina R; Nguyen, John T; Ashitate, Yoshitomo et al. (2015) Near-infrared imaging for the assessment of anastomotic patency, thrombosis, and reperfusion in microsurgery: a pilot study in a porcine model. Microsurgery 35:309-14
Gibbs, Summer L; Genega, Elizabeth; Salemi, Jeffery et al. (2015) Near-infrared fluorescent digital pathology for the automation of disease diagnosis and biomarker assessment. Mol Imaging 14:
Wada, Hideyuki; Hyun, Hoon; Vargas, Christina et al. (2015) Pancreas-targeted NIR fluorophores for dual-channel image-guided abdominal surgery. Theranostics 5:1-11

Showing the most recent 10 out of 124 publications