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例口腔和咽部癌症新病例。在早期诊断时，5年生存率为83%。然而，当在中期或晚期诊断时，5年生存率分别下降到62%和38%。此外，虽然早期治疗可能只需要小手术来切除局部肿瘤，但后期治疗可能需要手术切除面部和颈部的部分，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发育不良或早期浸润性癌症区分开来，即使是医疗保健专业人员。因此，尽管口腔很容易直接检查，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，用于可靠的口腔癌和发育不良的早期诊断。口腔癌的几种筛查工具已上市，包括脱落细胞学、活体染色、唾液检测和光学询问;然而，它们中没有一种被证明能够具有临床相关的灵敏度和特异性。我们假设，口腔癌和异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）准确定量，从而使灵敏度和特异性水平足以早期检测。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：设计和构建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FLIM的口腔上皮癌和异型增生的快速自动早期检测算法。目标3：在一项试点临床研究中，前瞻性地量化拟议FLIM内窥镜工具用于口腔上皮癌和异型增生非侵入性早期检测的能力。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，用于癌症和异型增生的非侵入性原位早期检测。这样的工具可能有助于显着提高预期寿命和生活质量的33,000多名口腔癌患者被诊断为中期和晚期每年。除了早期诊断外，该工具还可以帮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的监测。最后，这种临床工具在口腔上皮癌中的成功将预示着未来在其他上皮来源的癌症中的成功，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.