Excluding cancers of the skin, breast cancer remains the most common cancer affecting the female population, and the second most deadly (behind lung cancer). In 2008 alone, over 182,000 women will have been newly diagnosed and nearly 41,000 will have died of this disease according to the American Cancer Society. While early detection through X-ray mammographic screening is starting to impact mortality rates, mammography still suffers from reduced sensitivity in younger women and women with dense breasts and from a significant false positive rate. In recent years tomographic optical breast imaging (TOBI) has made promising advances in providing tissue functional information to complement the structural images offered by established medical imaging modalities. In particular, our group has developed a combined optical/x-ray tomosynthesis device and obtained promising initial results from a limited clinical trial, where total hemoglobin contrast was observed to discriminate between malignant and benign lesions and normal tissue. Additionally, we observed that mammographic compression induces temporal changes in breast tissue optical properties and discovered that these variations may be used to calculate tissue oxygen consumption and blood flow, as well as carrying intrinsic information about the biomechanical properties of various tissue regions. Encouraged by these initial results we propose, in response to PAR-07-214, to develop a clinical system that integrates high temporal resolution TOBI with any commercial mammography or tomosynthesis device with the ability to acquire simultaneous x-ray and time-resolved optical images by employing x-ray translucent materials for the optical patient interface. The development of such a system will allow the performance of Phase I clinical trials in which the diagnostic performance of optical static, dynamic and metabolic markers can be evaluated to gather the necessary statistical information to plan a Phase II effectiveness trial. Leveraging long standing relationships, this proposal brings together the team of Dr. Boas, leading optical technology and algorithm development, TechEn Inc., a custom engineering company with substantial experience building turn-key optical imaging systems, and the clinical group of Dr. Kopans, a pioneer in the development of digital breast tomosynthesis. TechEn, in close collaboration with Dr. Boas'group will construct a commercial grade prototype of the dynamic optical imaging system and in collaboration with Dr. Kopans the system will be clinically tested on women presenting for breast cancer screening as well as for follow-up diagnosis with the goal of fine tuning clinical operating procedure and refining the instrumentation, as well as gathering initial data on the diagnostic value of optical tissue parameters, and their ability to enhance the sensitivity and specificity of x-ray tomosynthesis.

Public Health Relevance

development of optical cancer markers may improve sensitivity of x- ray mammography, leading to fewer missed early stage cancers;at the same time, improvements in specificity may decrease the number of un-necessary biopsies, thus reducing both patient anxiety and health care costs. PUBLIC HEALTH RELEVANCE: Development of optical cancer markers may improve sensitivity of x-ray mammography, leading to fewer missed early stage cancers;at the same time, improvements in specificity may decrease the number of un-necessary biopsies, thus reducing both patient anxiety and health care costs.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Nordstrom, Robert J
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Massachusetts General Hospital
United States
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