Structured Illumination Microscopy and a Quantitative Image Analysis for the Detection of Positive Margins in a Pre-Clinical Genetically Engineered Mouse Model of Sarcoma.
Date
2016
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Attention Stats
Abstract
Intraoperative assessment of surgical margins is critical to ensuring residual tumor does not remain in a patient. Previously, we developed a fluorescence structured illumination microscope (SIM) system with a single-shot field of view (FOV) of 2.1 × 1.6 mm (3.4 mm2) and sub-cellular resolution (4.4 μm). The goal of this study was to test the utility of this technology for the detection of residual disease in a genetically engineered mouse model of sarcoma. Primary soft tissue sarcomas were generated in the hindlimb and after the tumor was surgically removed, the relevant margin was stained with acridine orange (AO), a vital stain that brightly stains cell nuclei and fibrous tissues. The tissues were imaged with the SIM system with the primary goal of visualizing fluorescent features from tumor nuclei. Given the heterogeneity of the background tissue (presence of adipose tissue and muscle), an algorithm known as maximally stable extremal regions (MSER) was optimized and applied to the images to specifically segment nuclear features. A logistic regression model was used to classify a tissue site as positive or negative by calculating area fraction and shape of the segmented features that were present and the resulting receiver operator curve (ROC) was generated by varying the probability threshold. Based on the ROC curves, the model was able to classify tumor and normal tissue with 77% sensitivity and 81% specificity (Youden's index). For an unbiased measure of the model performance, it was applied to a separate validation dataset that resulted in 73% sensitivity and 80% specificity. When this approach was applied to representative whole margins, for a tumor probability threshold of 50%, only 1.2% of all regions from the negative margin exceeded this threshold, while over 14.8% of all regions from the positive margin exceeded this threshold.
Type
Department
Description
Provenance
Subjects
Citation
Permalink
Published Version (Please cite this version)
Collections
Scholars@Duke
Melodi Javid Whitley
Melodi Javid Whitley, MD, PhD
Assistant Professor of Dermatology
Assistant Program Director for Trainee Research
Director of Transplant Dermatology
I am a physician scientist focused on the dermatologic care of solid organ transplant recipients. Clinically, I manage the the complex dermatologic side effects of immunosuppression with a focus on high-risk skin cancer. My research focuses on understanding the drivers of cutaneous malignancy in this population using translational approaches.
Diana Marcella Cardona
I am active in translational research involving gastrointestinal/hepatobiliary pathology [specifically transplant related pathology (GVHD and rejection) and carcinogenesis of the pancreas] and bone and soft tissue malignancies [imaging techniques for intraoperative margin assessment].
Nimmi Ramanujam
Nirmala (“Nimmi”) Ramanujam is the Robert W. Carr Professor of Biomedical Engineering and Professor of Cancer Pharmacology, Cancer Biology, and Global Health and founder of the Center for Global Women’s Health Technologies (GWHT) at Duke University. Her work addresses access gaps across the cancer care continuum both locally and globally. Her group develops low-cost imaging, artificial intelligence, and digital health platforms to decentralize the early detection of cervical cancer, and immune-based injectables and metabolic biomarkers for breast cancer treatment. Across both programs, she addresses access in different ways—expanding prevention where healthcare infrastructure is limited and improving access to treatment where therapies are available, yet lengthy and prohibitively expensive. She founded Calla Health to translate women’s health technologies into practice and co-developed The (In)visible Organ, a documentary that raises awareness and addresses stigma as barriers to care. She also leads experiential STEM initiatives that train students in systems-based, equity-centered technology development and she has authored a textbook, Biomedical Engineering and Global Health. She is a Fellow of the National Academy of Engineering and the National Academy of Inventors, a Fulbright Scholar, and recipient of a number of awards, notably of the Department of Defense Breast Cancer Innovator Award, the IEEE Biomedical Engineering Technical Field Award and the Anita B social impact award.
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.