The long-range goal of this competing continuation proposal is to assess and improve the breast tumor screening, diagnostic and monitoring capabilities of diffuse optical tomography (DOT) with near infrared (NIR) light. Near-infrared diffuse optical tomography is based on the study of functional processes and provides several unique measurable parameters with potential to enhance breast cancer detection and characterization sensitivity and specificity. In particular, DOT provides functional information directly related to tumor patho- physiology (e.g. metabolic activity, angiogenesis, and blood flow/concentration). This information can be complementary to structural and functional information provided by traditional medical imaging. Furthermore unlike many diagnostic methods, DOT techniques utilize non-ionizing radiation, are non-invasive, and are often technologically simple and fast. Thus, as more information is acquired and analyzed, we expect diffuse optics to find a variety of niche applications in screening, diagnosis and cancer therapy monitoring. The proposed research builds on initial success and aims to continue to improve and explore DOT by implementing novel statistical analysis methods, by examining associations between histopathology and optical tumor signatures, by introducing a much-improved Generation II instrument into the clinic, and via pilot clinical studies exploring exogenous contrast agent imaging and neoadjuvant chemotherapy monitoring. The proposed research will derive patients from ongoing clinical trials and from the normal patient population at the Hospital of the University of Pennsylvania (HUP). The research includes the development of breast-DOT computer aided detection (CAD) analyses and software;in addition a range of patient-intensive (rather than exploratory) clinical trials are planned. Primary clinical studies (~100 patients, 50 normal subjects) will acquire data from normal and tumor bearing patients based on endogenous contrast. Pilot clinical studies will follow tumor progression during neoadjuvant chemotherapy (~25 patients, 25 normal subjects) and will measure fluorescence from an exogenous contrast agent, Indocyanine Green, as it washes into and out-of the tumor bearing breast (~50 patients, 25 normal subjects). Overall, the project will provide basic information needed for the design of more comprehensive, future DOT clinical trials.

Public Health Relevance

Approximately one in eight women in the United States will develop breast cancer, and of these about 30% will ultimately die of the disease. Despite considerable scientific progress, new technologies are still desirable to detect breast cancers earlier for treatment, to detect cancers missed by screening mammography, to improve cancer diagnosis and staging in selected situations, and to track tumor progression during cancer therapy and to assist in therapy planning. The long-range goal of this grant is to assess and improve the breast tumor screening, diagnostic and monitoring capabilities of diffuse optical tomography with near infrared light.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB002109-15
Application #
8272572
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Conroy, Richard
Project Start
1997-09-30
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2014-04-30
Support Year
15
Fiscal Year
2012
Total Cost
$444,568
Indirect Cost
$155,647
Name
University of Pennsylvania
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Busch, David R; Choe, Regine; Durduran, Turgut et al. (2014) Blood flow reduction in breast tissue due to mammographic compression. Acad Radiol 21:151-61
Choe, Regine; Putt, Mary E; Carlile, Peter M et al. (2014) Optically measured microvascular blood flow contrast of malignant breast tumors. PLoS One 9:e99683
Busch, David R; Choe, Regine; Durduran, Turgut et al. (2013) Towards non-invasive characterization of breast cancer and cancer metabolism with diffuse optics. PET Clin 8:
Ban, Han Y; Busch, David R; Pathak, Saurav et al. (2013) Diffuse optical tomography in the presence of a chest wall. J Biomed Opt 18:26016
Busch, David R; Guo, Wensheng; Choe, Regine et al. (2010) Computer aided automatic detection of malignant lesions in diffuse optical mammography. Med Phys 37:1840-9
Choe, Regine (2009) Diffuse optical tomography &spectroscopy in breast cancer characterization &therapy monitoring at UPENN. Conf Proc IEEE Eng Med Biol Soc 2009:6335-7
Choe, Regine; Konecky, Soren D; Corlu, Alper et al. (2009) Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography. J Biomed Opt 14:024020
Panasyuk, George Y; Wang, Zheng-Min; Schotland, John C et al. (2008) Fluorescent optical tomography with large data sets. Opt Lett 33:1744-6
Konecky, Soren D; Choe, Regine; Corlu, Alper et al. (2008) Comparison of diffuse optical tomography of human breast with whole-body and breast-only positron emission tomography. Med Phys 35:446-55
Konecky, Soren D; Panasyuk, George Y; Lee, Kijoon et al. (2008) Imaging complex structures with diffuse light. Opt Express 16:5048-60

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