Although new cancer treatment methods developed in the past decade have shown promise in minimally or noninvasive eradication of tumors, surgery remains the primary treatment paradigm for most solid tumors. Surgeons previously relied on pre-operative images for tumor resection, but recent efforts to provide image guidance in the operating room have significantly improved tumor localization. Optical imaging techniques, in particular, have found a niche in the operating room because of their relatively low cost, use of non-ionizing radiation, fast data acquisition, and real-time image guidance. However, microscopic optical technologies have small field of view, which confines their use to sampling small tissue volumes. Current intraoperative planar imaging systems display 2D images on computer monitors, requiring the surgeon to alternate between the surgical site and the monitor. The large size of these systems challenges their use in small surgical suites and hampers portability. Tomographic approaches are capable of 3D display, but the complex instrumentation and intensive image analysis precludes real-time feedback and may require steep learning curve for operators. Another related overarching problem is the prevalence of positive surgical margins because of the lack of a reliable imaging agent for intraoperative surgical margin assessment, leading to costly repeat visits. Therefore, there is a compelling need to develop an accurate, affordable, user-friendly, portable, and versatile intraoperative imaging system with real-time imaging capability. The technology platform should also be able of providing real-time assessment of surgical margins. To accomplish these goals, we will develop an intra-operative near-infrared (NIR) fluorescence/reflectance 3D imaging goggle system that can accurately image tumor boundaries, small positive nodules, and provide image guidance in real-time. Intraoperative surgical margin assessment will be aided by a tumor-selective optical imaging agent optimized for the goggle system. At the development stage, the goggle system will use information from the molecular probe to optimize the detection scheme. Specifically, we will develop and optimize a hands-free 3D head-mounted fluorescence imaging and display system, and a near infrared imaging agent for in vivo staining of tumor margins. We will then use the goggle system for molecular imaging of small animal models of breast cancer, as well as canine breast cancer patients. Pharmacology and safety data generated from these studies will be used for investigational new drug (IND) and device exemption (IDE) application to the FDA.

Public Health Relevance

We will develop a simple wearable imaging system to guide surgeons in visualizing tumors in the operating room. Detection of tumor boundaries will be accomplished with a near-infrared fluorescent molecular probe. The synergistic coupling of tumor-selective fluorescent molecular probe with real-time fluorescence imaging using the goggle system will prevent the need for revisits to remove additional tumors missed during the first procedure, thereby saving costs and undue stress to patients.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BMIT-J (01))
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Farahani, Keyvan
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Washington University
Schools of Medicine
Saint Louis
United States
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Miller, Jessica P; Egbulefu, Christopher; Prior, Julie L et al. (2016) Gradient-Based Algorithm for Determining Tumor Volumes in Small Animals Using Planar Fluorescence Imaging Platform. Tomography 2:17-25
Som, Avik; Raliya, Ramesh; Tian, Limei et al. (2016) Monodispersed calcium carbonate nanoparticles modulate local pH and inhibit tumor growth in vivo. Nanoscale 8:12639-47
Sun, Jessica; Miller, Jessica P; Hathi, Deep et al. (2016) Enhancing in vivo tumor boundary delineation with structured illumination fluorescence molecular imaging and spatial gradient mapping. J Biomed Opt 21:80502
Som, Avik; Bloch, Sharon; Ippolito, Joseph E et al. (2016) Acidic extracellular pH of tumors induces octamer-binding transcription factor 4 expression in murine fibroblasts in vitro and in vivo. Sci Rep 6:27803
Gao, Shengkui; Mondal, Suman B; Zhu, Nan et al. (2015) Image overlay solution based on threshold detection for a compact near infrared fluorescence goggle system. J Biomed Opt 20:016018
Kotagiri, Nalinikanth; Sudlow, Gail P; Akers, Walter J et al. (2015) Breaking the depth dependency of phototherapy with Cerenkov radiation and low-radiance-responsive nanophotosensitizers. Nat Nanotechnol 10:370-9
Mondal, Suman B; Gao, Shengkui; Zhu, Nan et al. (2015) Binocular Goggle Augmented Imaging and Navigation System provides real-time fluorescence image guidance for tumor resection and sentinel lymph node mapping. Sci Rep 5:12117
Zhu, Nan; Huang, Chih-Yu; Mondal, Suman et al. (2015) Compact wearable dual-mode imaging system for real-time fluorescence image-guided surgery. J Biomed Opt 20:096010
Gilson, Rebecca C; Tang, Rui; Som, Avik et al. (2015) Protonation and Trapping of a Small pH-Sensitive Near-Infrared Fluorescent Molecule in the Acidic Tumor Environment Delineate Diverse Tumors in Vivo. Mol Pharm 12:4237-46
Tang, Rui; Xue, Jianpeng; Xu, Baogang et al. (2015) Tunable ultrasmall visible-to-extended near-infrared emitting silver sulfide quantum dots for integrin-targeted cancer imaging. ACS Nano 9:220-30

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