In order to optimize the risk-benefit and cost-effectiveness of colonoscopy for colorectal cancer (CRC) screening, risk-stratification is of paramount importance. Exploitation of the """"""""field effect"""""""" in which readily accessible colonic mucosa (i.e. rectum) should reflect the neoplastic risk throughout the colon, is an attractive proposition. However, current markers such as distal/rectal adenomas and aberrant crypt foci (ACF) lack the sensitivity and predictive value for clinical utility. We have recently developed four-dimensional elastic light scattering """"""""fingerprinting"""""""" (4D-ELF), a biomedical optics technology that allows us to gather heretofore unattainable quantitative information about nano/micro-architecture of living epithelia in situ. Using 4D-ELF, we discovered several spectral signatures in histologically normal mucosa that preceded all conventional biomarkers of CRC and served as one of the earliest markers of the """"""""field effect"""""""" in experimental models of colon carcinogenesis. Indeed, rectal spectral markers had unprecedented sensitivity, specificity, positive and negative predictive values for neoplastic risk. Pilot studies confirmed the relevance of these spectral markers to humans. The proposed project will test the hypothesis that rectal spectral markers can predict the occurrence of concurrent and future colonic neoplasia. In this application, we propose to construct an endoscopically compatible 4D-ELF probe in order to assess performance characteristic of prediction rules of rectal spectral markers (established and novel) for neoplasia detected on colonoscopy in average risk patients. We will also ascertain the ability of spectral markers to predict future neoplasia by evaluating rectal ACF number and adenoma occurrence in surveillance endoscopies of patients undergoing CRC resection. Finally, we will perform initial studies to understand the biological basis of spectral markers. In the future, spectral markers may be assayed with a 4D-ELF probe during a routine rectal examination (without the need for bowel preparation or colonoscopy) thus providing a practical and accurate means of determining the optimal CRC screening regimen, such as the need for colonoscopy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA112315-03
Application #
7230941
Study Section
Clinical and Integrative Gastrointestinal Pathobiology Study Section (CIGP)
Program Officer
Wagner, Paul D
Project Start
2005-08-01
Project End
2010-05-31
Budget Start
2007-06-07
Budget End
2008-05-31
Support Year
3
Fiscal Year
2007
Total Cost
$170,197
Indirect Cost
Name
Northwestern University at Chicago
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
Roy, Hemant K; Gomes, Andrew J; Ruderman, Sarah et al. (2010) Optical measurement of rectal microvasculature as an adjunct to flexible sigmoidosocopy: gender-specific implications. Cancer Prev Res (Phila) 3:844-51
Turzhitsky, Vladimir; Rogers, Jeremy D; Mutyal, Nikhil N et al. (2010) Characterization of light transport in scattering media at sub-diffusion length scales with Low-coherence Enhanced Backscattering. IEEE J Sel Top Quantum Electron 16:619-626
Roy, Hemant K; Turzhitsky, Vladimir; Kim, Young et al. (2009) Association between rectal optical signatures and colonic neoplasia: potential applications for screening. Cancer Res 69:4476-83
Backman, Vadim; Subramanian, Hariharan; Pradhan, Prabhakar et al. (2009) Detecting alterations in cell ultrastructure with optical imaging. Conf Proc IEEE Eng Med Biol Soc 2009:6325-6
Capoglu, Ilker R; Rogers, Jeremy D; Taflove, Allen et al. (2009) Accuracy of the Born approximation in calculating the scattering coefficient of biological continuous random media. Opt Lett 34:2679-81
Subramanian, Hariharan; Roy, Hemant K; Pradhan, Prabhakar et al. (2009) Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy. Cancer Res 69:5357-63
Gomes, Andrew J; Roy, Hemant K; Turzhitsky, Vladimir et al. (2009) Rectal mucosal microvascular blood supply increase is associated with colonic neoplasia. Clin Cancer Res 15:3110-7
Subramanian, Hariharan; Pradhan, Prabhakar; Liu, Yang et al. (2009) Partial-wave microscopic spectroscopy detects subwavelength refractive index fluctuations: an application to cancer diagnosis. Opt Lett 34:518-20
Turzhitsky, Vladimir; Liu, Yang; Hasabou, Nahla et al. (2008) Investigating population risk factors of pancreatic cancer by evaluation of optical markers in the duodenal mucosa. Dis Markers 25:313-21
Subramanian, Hariharan; Pradhan, Prabhakar; Liu, Yang et al. (2008) Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells. Proc Natl Acad Sci U S A 105:20118-23

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