Endogenous fluorescence lifetime endoscopy for early detection of oral cancer and dysplasia

美国癌症协会估计，今年将有48330例新的口腔和咽部癌症病例报告。如果在早期诊断，5年生存率为83%。然而，当诊断为中期或晚期时，5年生存率分别降至62%和38%。此外，虽然早期治疗可能只需要小手术切除局部肿瘤，但后期治疗可能需要手术切除部分面部和颈部，从而大大降低患者的生活质量。不幸的是，即使是医疗保健专业人员，有时也很难将良性口腔病变与不典型增生或早期侵袭性癌症区分开来。因此，尽管口腔很容易直接检查，但只有31%的患者在早期阶段被诊断出来。因此，迫切需要新的临床技术来可靠地早期诊断口腔癌和不典型增生。一些口腔癌的筛查工具已经商业化，包括剥脱细胞学、生命染色、唾液试验和光学询问；然而，它们都没有被证明具有临床相关的敏感性和特异性。我们假设口腔癌和不典型增生的几种生物标志物可以通过内源性荧光寿命成像（FLIM）准确量化，从而使灵敏度和特异性水平足以用于早期检测。这项生物工程研究资助的重点是开发和验证一种具有成本效益的宽视场多光谱FLIM内窥镜，用于口腔癌和不典型增生的无创原位检测。为此目的，我们制定了三个具体目标。目的1：设计并制造一种具有成本效益的多光谱FLIM内窥镜，用于口腔上皮组织的体内成像。目的2：开发基于快速和自动化FLIM的口腔上皮癌和非典型增生早期检测算法。目的3：在一项试点临床研究中，量化拟议的FLIM内窥镜工具在无创早期检测口腔上皮癌和不典型增生方面的能力。这些目标的成功完成将导致一种新的、准确的和具有成本效益的临床工具，用于非侵入性原位癌症和不典型增生的早期检测。这种工具可能有助于显著改善每年被诊断为中晚期的33,000多名口腔癌患者的预期寿命和生活质量。除了早期诊断，该工具还可以协助口腔癌患者临床管理的每一步，包括治疗指导和疾病复发监测。最后，该临床工具在口腔上皮性癌症中的成功将预示着未来在其他上皮性癌症（占所有癌症的80%以上）中的成功。

The American Cancer Society estimates that 48,330 new cases of cancer in the oral cavity and pharynx will be reported this year. When diagnosed at early stages, the 5-year survival rate is 83%. However, when diagnosed at intermediate or advance stages, the 5-year survival rate drops to 62% and 38%, respectively. In addition, while early stage treatment may only require minor surgery to remove the localized tumor, later stage treatment could require surgical removal of parts of the face and neck, hence drastically reducing the patient’s quality of life. Unfortunately, benign oral lesions are sometimes difficult to distinguish from dysplasia or early invasive cancer even for healthcare professionals. As a result, only 31% of patients are diagnosed at early stages despite the fact that the oral cavity is easily accessible for direct examination. Hence, there is a critical need for new clinical technologies for reliable early diagnosis of oral cancer and dysplasia. Several screening tools for oral cancer have been commercially available, including exfoliative cytology, vital staining, salivary test, and optical interrogation; however, none of them have been demonstrated to be capable of clinically relevant sensitivity and specificity. We hypothesize that several biomarkers for oral cancer and dysplasia can be accurately quantified by endogenous fluorescence lifetime imaging (FLIM) thus enabling levels of sensitivity and specificity adequate for early detection. This bioengineering research grant focuses on developing and validating a cost-effective wide-field multispectral FLIM endoscope for noninvasive in situ detection of oral cancer and dysplasia. To that end we have developed three specific aims. Aim 1: To design and build a cost-effective multispectral FLIM endoscope for in vivo imaging of epithelial tissue in the oral cavity. Aim 2: To develop algorithms for fast and automated FLIM based early detection of oral epithelial cancer and dysplasia. Aim 3: To quantify prospectively in a pilot clinical study the capability of the proposed FLIM endoscopic tools for noninvasively early detection of oral epithelial cancer and dysplasia. The successful completion of these aims will result in a novel, accurate and cost-effective clinical tool for noninvasive in situ early detection of cancer and dysplasia. Such a tool could potentially help to improve significantly both the life expectancy and the quality of life for the more than 33,000 oral cancer patients being diagnosed each year at intermediate and advance stages. Beyond early diagnosis, this tool could also assist at every step involved on the clinical management of oral cancer patients, including treatment guidance and monitoring of disease recurrence. Finally, the demonstrated success of this clinical tool in oral epithelial cancer will herald future success with other cancers of epithelial origin, which accounts for more than 80% of all cancers.