Elastic light scattering for the detection of the field effect in colorectal carcinogenesis.

摘要

Colorectal cancer (CRC) remains the second leading cause of cancer deaths in the United States. Given that CRC is preventable and curable if diagnosed early, widespread screenings have been proposed to reduce CRC fatalities. For instance, colonoscopy has been shown to dramatically reduce CRC mortality through both detection of CRC at an early, curable stage and actual cancer prevention. Because screening the entire high-risk population (∼60 million Americans over age 50) with colonoscopy is impractical, there is a strong need for novel initial-screening techniques that are highly sensitive and accurate. We expanded the use of biomedical optics to address this problem. First, we developed four-dimensional elastic light scattering "fingerprinting" (4D-ELF), an "optical biopsy" technique. We used 4D-ELF to measure the spectral, angular, azimuthal, and polarization dependence of light backscattered by living biological tissues, thus providing the most comprehensive description of the light scattering to obtain unique quantitative information about the microarchitecture of living cells and tissues. In the studies with animal models of CRC, we observed for the first time that marked 4D-ELF alterations preceded previously recognized histologic and molecular markers of CRC. Second, by use of 4D-ELF we observed for the first time an increased microvascular blood supply at premalignant stages of CRC. This novel finding of the early increased blood supply may be exploited for CRC chemoprevention, and may potentially provide novel and important insights into the biology of the initial stages of CRC. Finally, we developed a novel optical technique, low-coherent backscattering (LOBS) spectroscopy, for depth-resolved, speckle-free, spectroscopic assessments of tissue optical properties. Specifically, we demonstrated that the combination of: (1) low spatial coherence, broadband illumination, and (2) low temporal coherence, spectrally-resolved detection significantly facilitates coherent backscattering (CBS) observation in biological tissue and other random media with long transport mean free path lengths, which had previously been beyond the reach of conventional CBS investigations. We further demonstrated that the depth-resolved LCBS spectroscopy has the potential for identifying the location of the origin of precancerous transformations in the colon. The unprecedented sensitivity of the optical alterations supports the potential of LCBS for CRC screening and risk-stratification.