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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA171651-02
Application #
8605861
Study Section
Special Emphasis Panel (ZRG1-BMIT-J (01))
Program Officer
Farahani, Keyvan
Project Start
2013-01-16
Project End
2017-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
2
Fiscal Year
2014
Total Cost
$517,982
Indirect Cost
$120,492
Name
Washington University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Zhu, Nan; Mondal, Suman; Gao, Shengkui et al. (2014) Dual-mode optical imaging system for fluorescence image-guided surgery. Opt Lett 39:3830-2
Zhu, Nan; Mondal, Suman; Gao, Shengkui et al. (2014) Engineering light-emitting diode surgical light for near-infrared fluorescence image-guided surgical systems. J Biomed Opt 19:076018
Dreger, Tina; Watson, John T; Akers, Walter et al. (2014) Intravenous application of CD271-selected mesenchymal stem cells during fracture healing. J Orthop Trauma 28 Suppl 1:S15-9
Mondal, Suman B; Gao, Shengkui; Zhu, Nan et al. (2014) Real-time fluorescence image-guided oncologic surgery. Adv Cancer Res 124:171-211
Liu, Yang; Zhao, Yi-Ming; Akers, Walter et al. (2013) First in-human intraoperative imaging of HCC using the fluorescence goggle system and transarterial delivery of near-infrared fluorescent imaging agent: a pilot study. Transl Res 162:324-31
Shen, Duanwen; Bai, Mingfeng; Tang, Rui et al. (2013) Dual fluorescent molecular substrates selectively report the activation, sustainability and reversibility of cellular PKB/Akt activity. Sci Rep 3:1697
Sarder, Pinaki; Yazdanfar, Siavash; Akers, Walter J et al. (2013) All-near-infrared multiphoton microscopy interrogates intact tissues at deeper imaging depths than conventional single- and two-photon near-infrared excitation microscopes. J Biomed Opt 18:106012
Zhou, Mingzhou; Zhang, Xuan; Bai, Mingfeng et al. (2013) Click Reaction-Mediated Functionalization of Near-Infrared Pyrrolopyrrole Cyanine Dyes for Biological Imaging Applications. RSC Adv 3:6756-6758
Liu, Yang; Akers, Walter J; Bauer, Adam Q et al. (2013) Intraoperative detection of liver tumors aided by a fluorescence goggle system and multimodal imaging. Analyst 138:2254-7
Pu, Yang; Xue, Jianpeng; Wang, Wubao et al. (2013) Native fluorescence spectroscopy reveals spectral differences among prostate cancer cell lines with different risk levels. J Biomed Opt 18:87002

Showing the most recent 10 out of 12 publications