Towards Colonscopy-free Colon Cancer Screening by Enhanced Light Backscattering

通过增强光后向散射实现免结肠镜检查结肠癌筛查

• 批准号: 7496723
• 负责人: Vadim Backman
• 金额: $ 27.5万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-17 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7496723
• 关键词: Aberrant crypt foci; Address; Age; American; Animals; Apoptosis; Architecture; Area; Azoxymethane; Benefits and Risks; Biological; Biological Assay; Biological Markers; Biomedical Engineering; Cancer Etiology; Cancer Patient; Cessation of life; Clinical; Clinical Medicine; Clinical Research; Colon; Colon Carcinoma; Colonic Adenoma; Colonic Neoplasms; Colonoscopy; Colorectal Cancer; Compatible; Complication; Costs and Benefits; Data; Depth; Detection; Development; Diagnosis; Distal; Double-Blind Method; Early Diagnosis; Ensure; Epigenetic Process; Epithelium; Event; Fiber Optics; Fingerprint; Flexible fiberoptic sigmoidoscopy; Future; Gastroenterologist; Genetic; Genus Cola; Goals; Grant; Healthcare; Histologic; Hospitals; Imaging Techniques; In Situ; Individual; Intestines; Invasive; Knowledge; Laboratories; Lead; Lesion; Light; Malignant Neoplasms; Molecular; Mucous Membrane; Neoplasms; Numbers; Optics; Patient Noncompliance; Patient Recruitments; Patients; Performance; Phase; Plague; Population; Populations at Risk; Predictive Value; Preparation; Primary Care Physician; Procedures; Proliferation Marker; Prospective Studies; Publishing; Purpose; Range; Rate; Rectum; Research; Research Infrastructure; Research Personnel; Resolution; Resources; Risk; Risk Assessment; Screening procedure; Spectrum Analysis; Staging; Stratification; Submucosa; Techniques; Technology; Testing; Time; Tissues; Translational Research; Treatment Protocols; United States National Institutes of Health; Universities; Validation; Work; adenoma; base; cancer prevention; colon carcinogenesis; colorectal cancer prevention; colorectal cancer screening; cost; design; fascinate; human data; human study; in vivo; innovation; instrument; interest; light scattering; miniaturize; multidisciplinary; nano; nanoscale; neoplastic; novel; optical imaging; prevent; programs; prospective; prototype; rectal; tumor

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.

描述（由申请人提供）：本申请旨在开发一种新型的非侵入性深度分辨率光学成像技术，低相干增强后向散射光谱（EBS），用于结直肠癌（CRC）筛查。在美国，结直肠癌仍然是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，但由于各种原因，包括费用、患者不愿意和资源可用性，通过结肠镜检查筛查整个高危人群（约6000万50岁以上的美国人）是不可能的。因此，针对风险最高的患者是设计有效且具有成本效益的CRC筛查策略的关键。许多风险分层技术利用了结肠癌发生的“场效应”，即导致一个区域肿瘤的遗传/表观遗传改变应该在整个结肠粘膜中都能检测到。因此，在最容易到达的结肠粘膜（即直肠）发现早期事件可能导致准确的长期风险评估。然而，迄今为止，技术上的限制阻碍了这种方法。我们的数据表明，深度分辨率EBS能够以前所未有的精度检测“场效应”中分子变化的微/纳米尺度结构后果。这项工作建立在我们开发的基础上，这是我们所知的第一次，用于组织微结构中深度分辨变化的高灵敏度传感的EBS光谱。我们的动物和初步人体研究表明，EBS标记物的性能优于所有常规的结直肠癌标记物。根据我们的初步数据，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。为了开发用于结直肠癌筛查的EBS，我们建议开发一种内窥镜兼容的EBS探针并发现新的EBS标记物。这些以前的和新的EBS标记物将用于制定500例结肠镜检查患者肿瘤存在和不存在的预测规则。这将在一项前瞻性临床研究中得到验证。在未来，这些光谱标记物可以在常规直肠检查中使用EBS光纤探针进行检测，而无需进行肠道准备，从而为确定最佳的CRC筛查方案（例如是否需要结肠镜检查）提供实用而准确的方法。