Improving colonoscopic miss rate by real time microvascular blood analysis

项目摘要/说明 此小型企业技术转让应用程序的目标是验证和 一种改进的结肠镜检查息肉检测方法商业化：光谱 来自内窥镜下正常粘膜的微血管血液评估。遗漏的病变 结肠镜检查是一个主要问题(保守估计约占腺瘤的25% 和~4%-5%的癌症)，造成毁灭性的临床和法医学后果。 虽然正在开发各种辅助方法，但这些方法要么缺乏敏感性，要么缺乏 临床医学的实用性。我们的突破性技术四维弹性 光散射指纹技术(4D-ELF)在上皮下层组织中实现了前所未有的准确性 微血管分析。使用这一方法，我们第一次报告说， 组织学正常粘膜早期血供增加(EIBS) 有患结肠癌风险的实验动物。因此，EIBS似乎是一个较早的 “野外致癌”的标记物。这在人类结肠镜检查研究中得到了证实 同时使用组织活检和光纤4D-ELF探头(约400名患者)。重要的是 微血管血含量的增加仅在结肠段可检测到。 (约1/3的结肠)，包藏病变和大小反映了接近 息肉。基于这个初步数据，我们假设EIBS的实时评估 将提高结肠镜检查中发现肿瘤的准确性。在第一阶段， 我们建议确定微血管含血量的阈值(截止)水平 (总血红蛋白和脱氧血红蛋白)用于区分含有肿瘤的结肠节段 考虑各种潜在的EIBS影响因素(年龄、性别等)。具有里程碑意义的 过渡到第二阶段的项目将开发出高度精确的 预测规则。第二阶段将包括一项随机研究，以评估REAL的影响 1600例患者腺瘤发现率的时间信息。腺瘤检测 将比较使用和不使用EIBS时的费率。我们的保守估计是EIBS 指导将使息肉漏检率至少提高50%。我们认为EIBS-Guidance 将允许内窥镜医生快速确定结肠段是否含有 肿瘤。如果EIBS为阴性，则可以进行快速目视检查。此外，它还 将有助于相对常见的情况，如无法到达盲肠或粘膜 被残留的大便遮住。另一方面，如果读数显示息肉不是 很容易看到，然后绘制EIBS震级图可以提供精确的 本地化。鉴于这种技术成熟的方法在临床上的前景，我们 设想这一点可以很容易地由美国生物光学公司通过直接 制造/分销基于探头的系统。或者，EIBS检测可以 通过与内窥镜的配对直接结合到结肠镜中 公司。

Project Summary/Description The goal of this small business technology transfer application is to validate and commercialize an improved means of polyp detection during colonoscopy: spectroscopic microvascular blood assessment from the endoscopically normal mucosa. Missed lesions on colonoscopy are a major problem (conservatively estimated to be ~25% of adenomas and ~4-5% of carcinomas) with devastating clinical and medico-legal consequences. While various adjuvant approaches are being developed, these lack either sensitivity or practicality for clinical medicine. Our breakthrough technology four dimensional elastic light-scattering fingerprinting (4D-ELF) allows unprecedented accuracy in sub-epithelial microvasculature analysis. Using this approach, we have reported, for the first time, that there is an early increase in blood supply (EIBS) in the histologically normal mucosa in experimental animals at risk for colon neoplasia. Thus, EIBS appeared to be an early marker of the "field carcinogenesis". This was confirmed in human colonoscopic studies using both tissue biopsies and a fiberoptic 4D-ELF probe (~400 patients). Importantly, the increased microvascular blood content was only detectable in the colonic segment (~1/3 of colon) that harbored the lesion and the magnitude mirrored the proximity to the polyp. Based on this preliminary data we hypothesize that real-time EIBS assessment will improve accuracy of neoplasia detection during colonoscopy. In phase 1 of the STTR, we propose to determine threshold (cut-off) levels of microvascular blood content (total and deoxyhemoglobin) for discrimination of colonic segments that harbor neoplasia factoring various potential EIBS modifying factors (age, gender, etc). The milestone for transition into phase 2 of the project will be the development of a highly accurate prediction rule. Phase 2 will consist of a randomized study to assess the impact of real time EIBS information on adenoma detection rate in 1600 patients. Adenoma detection rate with and without EIBS will be compared. Our conservative estimate is that EIBS guidance will improve polyp miss rate by at least a 50%. We believe that EIBS-guidance will allow the endoscopist to rapidly determine whether a colonic segment harbors neoplasia. If EIBS is negative, then rapid visual inspection is possible. Furthermore, it would aid in the relatively common scenarios such as inability to reach cecum or mucosal obscuration by residual stool. If, on the other hand, readings suggest a polyp that is not readily visualizable, then mapping the EIBS magnitude could provide precise localization. Given the clinical promise of this technologically-mature approach, we envision that this can be readily commercialized by American BioOptics through direct manufacturing/distribution of a probe-based system. Alternatively, EIBS detection could be incorporated directly into the colonoscope via parternship with an endoscope company.