Towards Colonscopy-free Colon Cancer Screening by Enhanced Light Backscattering

描述(由申请人提供)：本申请旨在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，即低相干增强背向散射光谱(EBS)。结直肠癌仍然是美国癌症死亡的第二大原因。尽管结肠镜检查在减少结直肠癌方面非常有效，但由于费用、患者不情愿和资源可获得性等多种原因，通过结肠镜检查整个高危人群(50岁以上的6000万美国人)是不可能的。因此，针对风险最高的患者，对于设计有效和具有成本效益的结直肠癌筛查策略至关重要。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/表观遗传变化应该在整个结肠粘膜中都能检测到。因此，检测最容易接触到的结肠粘膜(即直肠)中的早期事件可以导致准确的长期风险评估。然而，到目前为止，技术限制阻碍了这一方法的实施。我们的数据表明，深度分辨的EBS具有以前所未有的精度探测分子变化的微纳尺度结构后果的能力。这项工作建立在我们首次开发的EBS光谱学的基础上，据我们所知，EBS光谱学用于高度敏感地检测组织微结构中深度分辨的变化。我们的动物和先导人类研究表明，EBS标记物的性能优于所有传统的CRC标记物。根据我们的初步数据，我们假设直肠粘膜的EBS询问应该可以准确地预测结肠肿瘤，因此需要结肠镜检查。为了开发用于结直肠癌筛查的EBS，我们建议开发一种与内窥镜兼容的EBS探针，并发现新的EBS标记。这些以前的和新的EBS标志物将被用来制定500名接受结肠镜检查的患者是否有肿瘤的预测规则。这将在一项前瞻性的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中使用EBS光纤探头进行检测，而不需要肠道准备，从而提供了一种实用而准确的方法来确定最佳的CRC筛查方案，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.