Breast conserving therapy (BCT), lumpectomy and radiation therapy, is a standard of care for early breast cancer. Current practice for assessing surgical margins includes post-operative H&E histology of the surgical specimen as well as intraoperative frozen-section analysis (FSA). However FSA has limitations in sensitivity, destructive effects of freezing on tissue, and increases surgical procedure times. Up to 40% of patients require a second surgery because of positive or close surgical margins. Repeat surgeries can delay adjuvant therapy, increase patient morbidity and increase health care costs. Our hypothesis is that the rate of second surgeries from positive or close margins can be significantly reduced using real-time nonlinear microscopy (multiphoton microscopy) for intraoperative assessment of lumpectomy specimens. We have preliminary data using nonlinear microscopy on freshly excised breast surgical specimens that achieves 95.4% sensitivity and 93.3% specificity for detecting invasive cancer and DCIS versus benign breast tissue, compared with H&E histology in blinded reading by 3 pathologists. This program is a multidisciplinary collaboration between investigators at the Massachusetts Institute of Technology and Departments of Pathology, Radiology and Surgery at Beth Israel Deaconess Medical Center, Harvard Medical School.
Aim 1. This aim will: (1) Develop clinical nonlinear microscopy technology for use in the pathology laboratory. (2) Validate real time nonlinear microscopy margin assessment using simulated lumpectomies from mastectomy specimens. (3) Confirm the exogenous stain used for nonlinear microscopy does not interfere with immunohistochemical assays.
Aim 2. Investigate nonlinear microscopy for intraoperative assessment of surgical specimens and assess impact on the rate of second surgeries. The primary endpoint is the rate of repeat surgeries in a study group with intraoperative margin assessment and standard post- operative histological surgical margin assessment, versus a control group receiving the clinical standard of post-operative histology without intraoperative imaging.
Aim 3. Develop advanced nonlinear microscopy and image processing technology and investigate other cancer pathologies. We will develop advanced methods, such as 3D imaging, multiple contrast channels using selected endogenous or exogenous fluorophores and molecular probes, in addition to image processing and display methods to enhance diagnostic performance or provide quantitative metrics. Pathology imaging will be performed on head and neck, lung and thyroid cancer specimens which may benefit from future intraoperative assessment. If successful, this project could provide an intraoperative pathology imaging technique that could not only significantly reduce the rate of second surgeries in breast cancer lumpectomies, but also have wide spread applications in surgical oncology.

Public Health Relevance

Breast conserving therapy (BCT), lumpectomy and radiation therapy, is a standard of care for early breast cancer, however up to 40% of patients require second surgeries because of cancer on the surgical margin. This program investigates nonlinear microscopy (multiphoton microscopy) as a method for real time imaging of surgical specimens, which could provide intraoperative information and reduce the rate of second surgeries.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA178636-02
Application #
8721902
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Zhang, Yantian
Project Start
2013-09-01
Project End
2018-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
$328,480
Indirect Cost
$67,628
Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02142
Cahill, Lucas C; Giacomelli, Michael G; Yoshitake, Tadayuki et al. (2018) Rapid virtual hematoxylin and eosin histology of breast tissue specimens using a compact fluorescence nonlinear microscope. Lab Invest 98:150-160
Liang, Kaicheng; Wang, Zhao; Ahsen, Osman O et al. (2018) Cycloid scanning for wide field optical coherence tomography endomicroscopy and angiography in vivo. Optica 5:36-43
Yoshitake, Tadayuki; Giacomelli, Michael G; Quintana, Liza M et al. (2018) Rapid histopathological imaging of skin and breast cancer surgical specimens using immersion microscopy with ultraviolet surface excitation. Sci Rep 8:4476
Lee, Hsiang-Chieh; Ahsen, Osman O; Liu, Jonathan J et al. (2017) Assessment of the radiofrequency ablation dynamics of esophageal tissue with optical coherence tomography. J Biomed Opt 22:76001
Liang, Kaicheng; Ahsen, Osman O; Wang, Zhao et al. (2017) Endoscopic forward-viewing optical coherence tomography and angiography with MHz swept source. Opt Lett 42:3193-3196
Ahsen, Osman O; Lee, Hsiang-Chieh; Liang, Kaicheng et al. (2017) Ultrahigh-speed endoscopic optical coherence tomography and angiography enables delineation of lateral margins of endoscopic mucosal resection: a case report. Therap Adv Gastroenterol 10:931-936
Lee, Hsiang-Chieh; Ahsen, Osman O; Liang, Kaicheng et al. (2017) Endoscopic optical coherence tomography angiography microvascular features associated with dysplasia in Barrett's esophagus (with video). Gastrointest Endosc 86:476-484.e3
Wan, Sunhua; Lee, Hsiang-Chieh; Huang, Xiaolei et al. (2017) Integrated local binary pattern texture features for classification of breast tissue imaged by optical coherence microscopy. Med Image Anal 38:104-116
Liang, Kaicheng; Ahsen, Osman O; Lee, Hsiang-Chieh et al. (2016) Volumetric Mapping of Barrett's Esophagus and Dysplasia With en face Optical Coherence Tomography Tethered Capsule. Am J Gastroenterol 111:1664-1666
Giacomelli, Michael G; Husvogt, Lennart; Vardeh, Hilde et al. (2016) Virtual Hematoxylin and Eosin Transillumination Microscopy Using Epi-Fluorescence Imaging. PLoS One 11:e0159337

Showing the most recent 10 out of 20 publications