Improving colonoscopic miss rate by real time microvascular blood analysis

描述（由申请人提供）：该小型企业技术转让申请的目标是验证结肠镜检查期间息肉检测的改进方法并将其商业化：从内窥镜检查正常粘膜进行光谱微血管血液评估。结肠镜检查中遗漏病变是一个主要问题（保守估计约为腺瘤的25%和约癌的4-5%），具有破坏性的临床和医学法律后果。虽然正在开发各种辅助方法，但这些方法缺乏临床医学的敏感性或实用性。我们的突破性技术四维弹性光散射指纹（4D-ELF）允许在上皮下微血管分析前所未有的准确性。使用这种方法，我们已经报道，第一次，有一个早期增加的血液供应（EIBS）在组织学正常的粘膜在实验动物的结肠肿瘤的风险。因此，EIBS似乎是“现场致癌”的早期标志物。这在使用组织活检和光纤4D-ELF探头的人类结肠镜研究中得到证实（约400例患者）。重要的是，增加的微血管血液含量仅在存在病变的结肠段（约1/3的结肠）中可检测到，并且幅度反映了息肉的接近程度。基于这些初步数据，我们假设实时EIBS评估将提高结肠镜检查中肿瘤检测的准确性。在STTR的第1阶段，我们建议确定微血管血液含量（总血红蛋白和脱氧血红蛋白）的阈值（截止）水平，用于区分包含各种潜在EIBS修饰因素（年龄，性别等）的肿瘤的结肠段。过渡到项目第二阶段的里程碑将是开发高度准确的预测规则。第2阶段将包括一项随机研究，以评估真实的时间EIBS信息对1600例患者腺瘤检出率的影响。将比较有和没有EIBS的腺瘤检出率。我们的保守估计是，EIBS指导将使息肉漏诊率至少提高50%。我们相信EIBS引导将允许内镜医师快速确定结肠段是否有瘤形成。如果EIBS为阴性，则可以进行快速目视检查。此外，它将有助于相对常见的情况，如无法到达盲肠或残留粪便造成的粘膜模糊。另一方面，如果读数表明息肉不容易可视化，则绘制EIBS幅度可以提供精确的定位。考虑到这种技术成熟的方法的临床前景，我们设想这可以很容易地由美国生物光学公司通过直接制造/分销基于探针的系统进行商业化。或者，EIBS检测可以通过与内窥镜公司的合作直接纳入结肠镜。大多数结直肠癌，美国人癌症死亡的第二大原因，来自息肉。结肠镜检查可以识别并去除这些息肉，从而实际上预防结肠癌。然而，至少有四分之一的息肉在结肠镜检查中被遗漏，导致癌症死亡和需要进行更频繁的结肠镜检查。在我们的应用中，我们建议测试一种新的生物医学光学技术，该技术既可以大大降低息肉错过率，又有助于加快手术速度。这对美国的结肠癌预防工作可能具有重要意义。

DESCRIPTION (provided by applicant): 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. Most colorectal cancers, the second leading cause of cancer deaths among Americans, arise from polyps. Colonoscopy can identify and remove these polyps thus actually preventing colon cancer. However, at least a quarter of all polyps are missed on colonoscopy leading to cancer deaths and the need to perform more frequent colonoscopies. In our application, we propose to test a novel biomedical optics technology that could both greatly decrease polyp miss rate and also help speed-up the procedures. This could have major importance for colon cancer prevention efforts in the United States.