Towards Colonscopy-free Colon Cancer Screening by Enhanced Light Backscattering

描述（由申请人提供）：本申请致力于开发一种用于结直肠癌（CRC）筛查的新型非侵入性深度分辨光学成像技术，即低相干增强后向散射光谱（EBS）。尽管结肠镜检查在减少CRC方面非常有效，但由于各种原因，包括费用，患者不情愿和资源可用性，通过结肠镜检查筛查整个高危人群（> 6000万50岁以上的美国人）是不可能的。因此，针对最高风险的患者对于设计有效且具有成本效益的CRC筛查策略至关重要。许多风险分层技术利用了结肠癌发生的“场效应”，即在一个区域导致肿瘤的遗传/表观遗传改变应该在整个结肠粘膜中都可以检测到。因此，在最容易接近的结肠粘膜（即直肠）中检测早期事件可能导致准确的长期风险评估。然而，迄今为止，技术限制阻碍了这一方法。我们的数据表明，深度分辨的EBS有能力检测的微观/纳米结构的后果的分子变化的“场效应”，以前所未有的准确性。这项工作建立在我们的发展，第一次尽我们所知，EBS光谱高度敏感的传感深度分辨组织微结构的变化。我们的动物和试点人类研究表明，EBS标志物的性能上级所有传统的CRC标志物。基于我们的初步数据，我们假设直肠粘膜的EBS检查可以准确预测结肠肿瘤，因此需要结肠镜检查。为了开发用于CRC筛查的EBS，我们建议开发内窥镜兼容的EBS探针并发现新的EBS标记物。这些以前的和新的EBS标志物将被用来制定预测规则的存在和不存在的肿瘤在500例患者接受结肠镜检查。这将在一项前瞻性临床研究中得到验证。将来，这些光谱标记物可以在常规直肠检查期间用EBS光纤探针进行测定，而无需肠道准备，从而提供了确定最佳CRC筛查方案的实用且准确的方法，例如需要结肠镜检查。

DESCRIPTION (provided by applicant): This application addresses development of a novel non-invasive depth-resolved optical imaging technique, low-coherence enhanced backscattering spectroscopy (EBS), for colorectal cancer (CRC) screening. CRC remains the second leading cause of cancer death in the U.S. Although colonoscopy is remarkably effective in reducing CRC, screening the entire at-risk population (>60 million Americans over age 50) through colonoscopy is impossible for a variety of reasons including expense, patient reluctance and resource availability. Thus, targeting patients at the highest risk is crucial for designing efficacious and cost-effective CRC screening strategies. Many risk-stratification techniques exploit the "field effect" of colon carcinogenesis, the notion that the genetic/epigenetic alterations that lead to a tumor in one area should be detectable throughout the colon mucosa. Thus, detecting early events in the most readily accessible colonic mucosa (i.e. rectum) could lead to accurate long term risk assessment. However, technological limitations have, to date, stymied this approach. Our data demonstrate that depth-resolved EBS has the ability to detect the micro/nanoscale architectural consequences of the molecular changes in the "field effect" with unprecedented accuracy. This work builds upon our development, for the first time to the best of our knowledge, of EBS spectroscopy for highly sensitive sensing of depth-resolved changes in tissue microarchitecture. Our animal and pilot human studies indicate that EBS markers have performance superior to all conventional markers of CRC. Based on our preliminary data, we hypothesize that EBS interrogation of the rectal mucosa should allow accurate prediction of colonic neoplasia and hence need for colonoscopy. In order to develop EBS for CRC screening, we propose to develop an endoscopically compatible EBS probe and discover new EBS markers. These previous and novel EBS markers will be used to formulate prediction rules for both the presence and absence of neoplasia in 500 patients undergoing colonoscopy. This will then be validated in a prospective clinical study. In the future these spectral markers may be assayed with an EBS fiber-optic probe during a routine rectal examination without the need for bowel preparation, thus providing a practical and accurate means of determining the optimal CRC screening regimen, such as the need for colonoscopy.