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

美国癌症协会估计，今年将报告48,330例新的口腔和咽部癌症病例。早期确诊，5年生存率为83%。然而，当诊断为中晚期时，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进行小手术来移除局部肿瘤，但后期治疗可能需要手术切除部分面部和颈部，因此大大降低了患者的生活质量。不幸的是，良性口腔病变有时很难与异型增生或早期浸润性癌症区分开来，即使对医疗保健专业人员来说也是如此。因此，尽管口腔很容易进行直接检查，但只有31%的患者在早期得到诊断。因此，迫切需要新的临床技术来对口腔癌和异型增生进行可靠的早期诊断。目前已有几种口腔癌筛查工具问世，包括脱落细胞学、活体染色、唾液试验和光学问诊；然而，没有一种工具被证明能够与临床相关的敏感性和特异性。我们假设，口腔癌和异型增生的几个生物标志物可以通过内源性荧光寿命成像(FLIM)准确地定量，从而使敏感度和特异度足以用于早期检测。这项生物工程研究拨款的重点是开发和验证一种成本效益高的广域多光谱薄膜内窥镜，用于口腔癌和异型增生的非侵入性原位检测。为此，我们制定了三个具体目标。目的1：设计并制作一种高性价比的口腔上皮组织活体成像多光谱胶片内窥镜。目的2：开发基于FLIM的口腔上皮癌和异型增生的快速、自动早期检测算法。目的3：在一项先导性临床研究中，前瞻性地量化所建议的薄膜内窥镜工具对口腔上皮癌和异型增生的无创早期检测的能力。这些目标的成功实现将带来一种新的、准确和经济的临床工具，用于非侵入性原位早期检测癌症和异型增生。这种工具可能有助于显著提高每年确诊的33,000多名中晚期口腔癌患者的预期寿命和生活质量。除了早期诊断，该工具还可以在口腔癌患者的临床管理中的每一个步骤上提供帮助，包括治疗指导和疾病复发的监测。最后，这种临床工具在口腔上皮癌中的成功证明将预示着其他上皮性癌症的未来成功，这些癌症占所有癌症的80%以上。

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.