The long-term goal of this study is to improve colonoscopic performance via a novel optical technology. While colonoscopy is the "gold standard" for colorectal cancer (CRC) screening, the concern over missed lesions (~25% of adenomas and ~4-5% of carcinomas) results in overly frequent and hence unproductive colonoscopies. This squanders the finite endoscopic capacity thereby depriving many subjects from undergoing this potentially life-saving procedure. Our team has recently developed a novel optics technology which allows probing of the sub-epithelial microvasculature with unprecedented accuracy. Using this approach, we have reported, for the first time, that early colon carcinogenesis is accompanied by the early increase in mucosal blood supply (EIBS) that is present not only in a precancerous lesion itself (e.g. adenomatous polyp) but also in endoscopically and histologically normal mucosa surrounding the lesion. EIBS appeared to be an early marker of the "field carcinogenesis". This was confirmed in both animal models and in vivo human studies. EIBS was the most pronounced in the colonic segment (~1/3 of colon) that harbored neoplasia and the magnitude mirrored the proximity to the lesion. Based on these observations, we hypothesize that real-time EIBS assessment will improve colonoscopic neoplasia detection. We propose to determine threshold levels of microvascular blood content for discrimination of colonic segments that harbor neoplasia. We will optimize algorithms to adjust for confounding effects of factors such as age, gender, smoking, colonic region, etc. Finally, we will rigorously assess EIBS guidance benefit by performing a parallel (EIBS-aided vs. conventional) colonoscopy study. Miss rates for conventional and EIBS- aided colonoscopy will be compared. We believe that the clinical application will allow the endoscopist to rapidly determine whether a colonic segment harbors neoplasia. We believe that EIBS-guided colonoscopy will reduce adenoma miss rate leading to better clinical outcomes, fewer wasted follow up colonoscopies and hence more capacity for primary population screening.

Public Health Relevance

The proposed work aims to decrease the neoplasia miss rate of colonoscopy. The methodology takes advantage of a novel biological effect: increased microvascular mucosal blood supply that is expressed in a colonic segment harboring neoplasia. This increased blood supply can be detected via a colonoscopically-compatible fiber-optic probe during colonoscopy to identify colonic segments that are most likely to harbor adenomas and, thus, guide colonoscopy. The major public health benefits are expected to be the improved detection of precancerous colonic lesions during colonoscopy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA109861-07
Application #
8234894
Study Section
Special Emphasis Panel (ZRG1-DIG-F (90))
Program Officer
Ossandon, Miguel
Project Start
2004-07-01
Project End
2014-02-28
Budget Start
2012-05-16
Budget End
2013-02-28
Support Year
7
Fiscal Year
2012
Total Cost
$228,259
Indirect Cost
$27,568
Name
Northwestern University at Chicago
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
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Tiwari, Ashish K; Crawford, Susan E; Radosevich, Andrew et al. (2011) Neo-angiogenesis and the premalignant micro-circulatory augmentation of early colon carcinogenesis. Cancer Lett 306:205-13
Roy, Hemant K; Hensing, Thomas; Backman, Vadim (2011) Nanocytology for field carcinogenesis detection: novel paradigm for lung cancer risk stratification. Future Oncol 7:1-3
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
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
Roy, Hemant K; Gomes, Andrew; Turzhitsky, Vladimir et al. (2008) Spectroscopic microvascular blood detection from the endoscopically normal colonic mucosa: biomarker for neoplasia risk. Gastroenterology 135:1069-78
Turzhitsky, Vladimir M; Gomes, Andrew J; Kim, Young L et al. (2008) Measuring mucosal blood supply in vivo with a polarization-gating probe. Appl Opt 47:6046-57
Roy, Hemant K; Wali, Ramesh K; Kim, Young et al. (2007) Inducible nitric oxide synthase (iNOS) mediates the early increase of blood supply (EIBS) in colon carcinogenesis. FEBS Lett 581:3857-62
Siegel, Michael P; Kim, Young L; Roy, Hemant K et al. (2006) Assessment of blood supply in superficial tissue by polarization-gated elastic light-scattering spectroscopy. Appl Opt 45:335-42