The grant application responds to Program Announcement Number PA-14-147 (Ruth L. Kirschstein National Research Service Award for Individual Predoctoral Fellows) by proposing a study on utilizing optical scattering signatures for intraoperative breast tumor margin diagnosis using a newly invented, wide field, non-contact scatter imaging technique called structured light scatteroscopy imaging (SLSI). Breast conserving surgery (BCS) is a routine treatment for localized breast cancer, but there is a well-known issue of determining the boundaries of the tumor during its excision. The proposed system will rapidly produce wide field optical scatter images of the entire resected margin, which then will be run through previously trained classifier algorithms to yield maps of suspected breast tumor pathologies, to guide future resection procedures. An optimized, spectrally resolved SLSI system will be developed to meet imaging constraints of the operating room and the excision procedure. The finalized system will then be calibrated and validated on tissue simulating phantoms with known scattering parameters through a comparison of experimental measurements and Monte Carlo simulations of the phantoms. With the fully developed SLSI system, an ongoing collaboration with the National Institute of Standards and Technology and Dartmouth will amass measurements of freshly excised lumpectomy specimens, which will be co-registered to histopathological diagnoses. This data set will then be analyzed to determine diagnostically discriminate scatter parameters and image features. This library of scatter parameters and image features with accompanying breast pathology diagnoses will then be used to develop, train, and validate an optimal classification algorithm, which could then be used in real time during future BCS procedures to classify measurements of the tumor margin into maps of breast tumor margin with diagnostic probabilities. The efficacy of these algorithms will be evaluated by imaging freshly resected specimens of unknown diagnosis and performing receiver operator characteristic analysis on the classified probability maps. To realize the potential to reduce the rate of re-excision procedures, the complete system will then be implemented into a planned prospective clinical trial, which will be separately organized and managed through a separately funded Academic Industry Partnership. The Dartmouth team, involving engineering, surgery, pathology and feature classification expertise has completed multiple studies utilizing spectroscopic scatter imaging to classify breast tissue pathologies over the past 5 years, and the proposed system overcomes the shortcomings of the previously investigated systems and simultaneously leverages their benefits. The candidate will be trained in all pertinent aspects of this work to succeed in a surgical/pathology imaging systems research career, focused on novel tools to characterize breast cancer in situ.

Public Health Relevance

This project aims to develop, optimize, and translate a new optical imaging technique to help guide surgeons delineate the boundary of a breast tumor during an excision procedure. This new imaging technique has the potential to greatly reduce the rate of re-excision procedures to remove tumor left behind during the first excision, thereby decreasing patient morbidity and healthcare costs.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31CA196308-02
Application #
9268401
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Perkins, Susan N
Project Start
2016-05-01
Project End
2019-04-30
Budget Start
2017-05-01
Budget End
2018-04-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Dartmouth College
Department
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
McClatchy 3rd, David M; Zuurbier, Rebecca A; Wells, Wendy A et al. (2018) Micro-computed tomography enables rapid surgical margin assessment during breast conserving surgery (BCS): correlation of whole BCS micro-CT readings to final histopathology. Breast Cancer Res Treat 172:587-595
McClatchy, David M; Rizzo, Elizabeth J; Meganck, Jeff et al. (2017) Calibration and analysis of a multimodal micro-CT and structured light imaging system for the evaluation of excised breast tissue. Phys Med Biol 62:8983-9000