Improving colonoscopic miss rate by real time microvascular blood analysis

描述(申请人提供)：这一小型企业技术转让应用程序的目标是验证和商业化一种改进的结肠镜检查期间息肉检测方法：来自内窥镜正常黏膜的光谱微血管血液评估。结肠镜检查遗漏的病变是一个主要问题(保守估计约占腺瘤的25%，癌的约4%-5%)，具有毁灭性的临床和法医学后果。虽然正在开发各种辅助方法，但这些方法对临床医学来说要么缺乏敏感性，要么缺乏实用性。我们的突破性技术四维弹性光散射指纹(4D-ELF)使上皮下微血管分析具有前所未有的准确性。使用这种方法，我们第一次报道，在有结肠肿瘤风险的实验动物中，组织学上正常的粘膜早期血液供应(EIBS)增加。因此，Eibs似乎是“现场致癌”的早期标志。在使用组织活检和光纤4D-ELF探头(约400名患者)的人类结肠镜研究中证实了这一点。重要的是，微血管血含量的增加仅在病变所在的结肠段(约1/3的结肠)可检测到，其大小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的第一阶段，我们建议确定微血管血含量(总和脱氧血红蛋白)的阈值(截止)水平，以区分含有肿瘤的结肠段，并考虑各种潜在的EIBS修饰因素(年龄、性别等)。过渡到项目第二阶段的里程碑将是开发一种高度准确的预测规则。第二阶段将包括一项随机研究，以评估实时EIBS信息对1600名患者腺瘤发现率的影响。比较使用EIBS和不使用EIBS时腺瘤的发现率。我们的保守估计是，EIBS指导将使息肉漏检率至少提高50%。我们相信，EIBS引导将允许内窥镜医生快速确定结肠段是否存在肿瘤。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，如无法到达盲肠或粘膜被残留的大便遮挡。另一方面，如果读数显示息肉不容易被观察到，那么绘制EIBS震级图可以提供准确的定位。鉴于这一技术成熟的方法在临床上的前景，我们预计，美国生物光学公司可以通过直接制造/分销基于探测器的系统，将其很容易地商业化。或者，EIBS检测可以通过与内窥镜公司的合作直接结合到结肠镜中。大多数结直肠癌是美国人癌症死亡的第二大原因，它是由息肉引起的。结肠镜检查可以识别和移除这些息肉，从而实际上预防结肠癌。然而，至少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漏检率，又可以帮助加快手术速度。这可能对美国的结肠癌预防工作具有重要意义。

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.