This is a proposal to establish a Bioengineering Research Partnership (BRP) to develop a novel biophotonics methodology for population-wide colorectal cancer (CRC) screening. While colonoscopy has remarkable efficacy at both diagnosis and malignancy prevention, CRC remains the second leading cause of cancer deaths largely because the vast majority (>80%) of Americans do not undergo colonoscopy. Unfortunately, screening the entire eligible population (>87 million Americans over age 50) through colonoscopy is practically impossible because of cost, patient non-compliance, complications and lack of sufficient endoscopic capacity. Instead of performing colonoscopy on the entire population, targeting the group at risk for developing neoplasia would allow focusing of this finite endoscopic resource on subjects who will actually benefit from this test. However, no existing pre-colonoscopic screening test has adequate sensitivity and predictive value. The proposed program is based on two novel, complementary biophotonics techniques, elastic light scattering fingerprinting (ELF) and low-coherence enhanced backscattering (LEBS) spectroscopy developed by our multidisciplinary team comprised of biomedical and electrical engineers, physicists, gastroenterologists, cancer biologists, and biostatisticians. A key capability of ELF and LEBS is that they sense changes in histologically normal tissue at a distance from a precancerous lesion. These spectral markers represent the only currently known, highly accurate and practical means of detecting the "field effect" of colon cancer. This opens a possibility to identifying patients who may harbor neoplasia by assessment of histologically and colonoscopically normal-appearing rectal mucosa only. Based on our preliminary data, we hypothesize that ELF/LEBS will be able to identify subjects who do and do not harbor neoplasia anywhere in the colon based on the optical alterations in the rectal mucosa that will be assessed without the need for colonoscopy and bowel preparation. The lack of bowel preparation and the unprecedented sensitivity may make the proposed technique an ideal tool for pre-colonoscopy CRC screening. We propose to develop instrumentations that clinicians will find user friendly and perform a definitive multicenter validation study using 4000 patients. Once completed, this approach will provide a quantum leap towards the first population-wide CRC screening.

Public Health Relevance

Although colonoscopy is efficient at colon cancer prevention, it is practically impossible to use colonoscopy for population screening and the development of an initial, pre-colonoscopy screening test is urgently needed. We propose to develop a non-invasive test for population colon cancer screening that is based on a new biophotonics technology. The test will require the optical examination of rectal tissue without colonoscopy and bowel preparation and will identify the presence of precancerous lesions throughout the entire colon. In the future, this test can be implemented during an annual exam by a primary care physician to determine the need for colonoscopy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-SBIB-V (50))
Program Officer
Nordstrom, Robert J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Northwestern University at Chicago
Biomedical Engineering
Schools of Engineering
United States
Zip Code
Stypula-Cyrus, Yolanda; Mutyal, Nikhil N; Dela Cruz, Mart et al. (2014) End-binding protein 1 (EB1) up-regulation is an early event in colorectal carcinogenesis. FEBS Lett 588:829-35
Damania, Dhwanil; Subramanian, Hariharan; Backman, Vadim et al. (2014) Network signatures of nuclear and cytoplasmic density alterations in a model of pre and postmetastatic colorectal cancer. J Biomed Opt 19:16016
Radosevich, Andrew J; Mutyal, Nikhil N; Rogers, Jeremy D et al. (2014) Buccal spectral markers for lung cancer risk stratification. PLoS One 9:e110157
Yi, Ji; Radosevich, Andrew J; Stypula-Cyrus, Yolanda et al. (2014) Spatially resolved optical and ultrastructural properties of colorectal and pancreatic field carcinogenesis observed by inverse spectroscopic optical coherence tomography. J Biomed Opt 19:36013
Cherkezyan, Lusik; Stypula-Cyrus, Yolanda; Subramanian, Hariharan et al. (2014) Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study. BMC Cancer 14:189
Black, Kvar C L; Sileika, Tadas S; Yi, Ji et al. (2014) Bacterial killing by light-triggered release of silver from biomimetic metal nanorods. Small 10:169-78
Cherkezyan, Lusik; Subramanian, Hariharan; Backman, Vadim (2014) What structural length scales can be detected by the spectral variance of a microscope image? Opt Lett 39:4290-3
Patel, Mihir; Gomes, Andrew; Ruderman, Sarah et al. (2014) Polarization gating spectroscopy of normal-appearing duodenal mucosa to detect pancreatic cancer. Gastrointest Endosc 80:786-93.e1-2
Mutyal, Nikhil N; Radosevich, Andrew; Tiwari, Ashish K et al. (2013) Biological mechanisms underlying structural changes induced by colorectal field carcinogenesis measured with low-coherence enhanced backscattering (LEBS) spectroscopy. PLoS One 8:e57206
Chandler, John E; Subramanian, Hariharan; Maneval, Charles D et al. (2013) High-speed spectral nanocytology for early cancer screening. J Biomed Opt 18:117002

Showing the most recent 10 out of 43 publications