The American Cancer Society estimates that a total of 192,370 new invasive breast cancers and 62,280 new cases of in situ breast cancer are diagnosed annually. Women with operable breast cancer undergo Breast Conserving Surgery (BCS), also called lumpectomy or partial mastectomy. On average between 50 to 75% of patients with breast cancer undergo BCS followed by radiation therapy. Approximately 20-70% of women undergoing BCS have to return for a repeat surgery due to incomplete removal of the cancer at the first BCS. There is a significant unmet need for a rapid and practical tool for intra-operative assessment of breast tumor margins. The broad goal of this BRP is to bring multiple investigators from Duke University and the University of Wisconsin, Madison together to develop and validate a miniature optical spectral imaging strategy for intra- operative imaging of tumor margins in patients undergoing BCS. Achieving this goal requires significant innovation in optical physics and engineering, and will leverage advances in thin film detectors, waveguides, and on-board electronics.
The specific aims of the proposed work are: (1) to design, construct and refine a miniature spectral imaging device and software for quantitative optical spectral imaging, (2) to verify the spectral imaging technology performance metrics through rigorous bench testing, (3) to develop and optimize an automated device-tissue interface platform and to minimize sources of systematic and random errors at the device-tissue interface, and (4) to test the miniature spectral imaging device for the detection of margin positivity in approximately 150 patients undergoing BCS. The proposed clinical studies will serve as an important basis for larger scale successor clinical studies. It is theorized that the miniature optical spectral imaging system developed and tested in this BRP grant will result in a practical clinical tool for rapid intra- operative assessment of breast tumor margins, i.e., it will help guide the surgeon to either complete the surgery, if margins are negative, or re-excise additional tissue, if margins are positive at the time of first surgery, thus avoiding an un-necessary re-excision. The implications are significant in that tens of thousands of unnecessary surgeries could be prevented each year. The technology proposed in this research could also be extended to the assessment of tumor margins in patients with other types of cancers, including the brain, prostate and head and neck. This novel technology also has the potential to serve as a low cost solution for global cancer diagnostics.

Public Health Relevance

Our long-term scientific aim is to develop and apply a novel optical strategy for intra-operative assessment of breast tumor margins. The technology we propose to develop will be pragmatically designed and refined for use in an intra-operative setting. A tool for intra-operative margin assessment is significantly relevant to public in that it will contribute to a decrease in re-excision surgeries in patients with breast cancer.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Special Emphasis Panel (ZRG1-SBIB-V (55))
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Krosnick, Steven
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Duke University
Biomedical Engineering
Schools of Engineering
United States
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Nichols, Brandon S; Llopis, Antonio; Palmer, Gregory M et al. (2017) Miniature spectral imaging device for wide-field quantitative functional imaging of the morphological landscape of breast tumor margins. J Biomed Opt 22:26007
Hu, Fangyao; Martin, Hannah; Martinez, Amy et al. (2017) Distinct Angiogenic Changes during Carcinogenesis Defined by Novel Label-Free Dark-Field Imaging in a Hamster Cheek Pouch Model. Cancer Res 77:7109-7119
Hu, Fangyao; Morhard, Robert; Murphy, Helen A et al. (2016) Dark field optical imaging reveals vascular changes in an inducible hamster cheek pouch model during carcinogenesis. Biomed Opt Express 7:3247-3261
Kennedy, Stephanie; Caldwell, Matthew; Bydlon, Torre et al. (2016) Correlation of breast tissue histology and optical signatures to improve margin assessment techniques. J Biomed Opt 21:66014
Fu, Henry L; Mueller, Jenna L; Whitley, Melodi J et al. (2016) Structured Illumination Microscopy and a Quantitative Image Analysis for the Detection of Positive Margins in a Pre-Clinical Genetically Engineered Mouse Model of Sarcoma. PLoS One 11:e0147006
Mueller, Jenna L; Gallagher, Jennifer E; Chitalia, Rhea et al. (2016) Rapid staining and imaging of subnuclear features to differentiate between malignant and benign breast tissues at a point-of-care setting. J Cancer Res Clin Oncol 142:1475-86
Nichols, Brandon S; Schindler, Christine E; Brown, Jonathon Q et al. (2015) A Quantitative Diffuse Reflectance Imaging (QDRI) System for Comprehensive Surveillance of the Morphological Landscape in Breast Tumor Margins. PLoS One 10:e0127525
Mueller, Jenna L; Fu, Henry L; Mito, Jeffrey K et al. (2015) A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins. Int J Cancer 137:2403-12
Dhar, Sulochana; Miller, David M; Jokerst, Nan M (2014) High responsivity, low dark current, heterogeneously integrated thin film Si photodetectors on rigid and flexible substrates. Opt Express 22:5052-9
Fu, Henry L; Mueller, Jenna L; Javid, Melodi P et al. (2013) Optimization of a widefield structured illumination microscope for non-destructive assessment and quantification of nuclear features in tumor margins of a primary mouse model of sarcoma. PLoS One 8:e68868

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