Polarization Spectroscopy and Imaging of Pre-Cancer

描述（由申请人提供）： 癌症是美国第二大死亡原因。大多数癌症是上皮起源的。早期诊断浸润前上皮瘤变可显著降低癌的发病率和死亡率。因此，迫切需要高灵敏度和成本效益的筛查和诊断技术，以确定可治愈的癌前病变。上皮癌前病变的特征在于多种结构和形态学特征，包括核大小增加、核/胞质比增加、染色质增多和多形性。此外，越来越多的证据表明，在癌变的最早阶段，由于上皮-基质相互作用，基质层发生了显著变化。目前临床诊断的一个主要局限是，与早期癌变相关的形态学和分子变化只能在侵入性活检后进行评估。光学技术可以非侵入性地实时评估上皮组织中的形态学和生物化学变化。该提案的目的是开发一种基于偏振反射光谱和成像的新技术，以实现对上皮和与癌变相关的底层结缔组织中的形态和结构变化的非侵入性实时检测和监测。本研究的目的是：（1）建立上皮组织和间质偏振反射光谱的理论模型，（2）在不同癌症发展阶段的人体上皮组织模型中检验理论预测，（3）利用理论模型确定偏振反射光谱对上皮细胞核形态和间质形态的敏感性，（4）建立上皮细胞核和间质形态的偏振反射光谱模型。（4）设计、构建和测试一种新型的偏振反射光谱光纤内窥镜，（5）评价该内窥镜在口腔粘膜临床研究中的应用。(6)开发基于偏振照明和检测原理的成像仪器，并在临床试验中测试该装置。这里提出的廉价光学传感器可以通过减少不必要的活检数量，实现诊断和治疗的结合，并减少对临床专业知识的需求，从而立即使医疗保健受益。

DESCRIPTION (provided by applicant): Cancer is the second leading cause of death in the US. The majority of cancers are of epithelial origin. Early diagnosis of pre-invasive epithelial neoplasia can dramatically reduce the incidence and mortality of carcinoma. Thus, there is a desperate need for highly sensitive and cost-effective screening and diagnostic techniques to identify curable precancerous lesions. Epithelial pre-cancers are characterized by a variety of architectural and morphological features including increased nuclear size, increased nuclear/cytoplasmic ratio, hyperchromasia and pleomorphism. In addition, there is increasing evidence of significant changes occurring in the stromal layer at the earliest stages of carcinogenesis as a result of epithelial-stromal interactions. A major limitation of current clinical diagnosis is that morphological and molecular changes associated with early carcinogenesis can be assessed only after invasive biopsy. Optical techniques can assess morphologic and biochemical alterations in epithelial tissue, non-invasively and in real-time. The goat of this proposal is to develop a new technology based on polarized reflectance spectroscopy and imaging to enable non-invasive real-time detection and monitoring of morphological and architectural changes in epithelium and underlying connective tissue associated with carcinogenesis. The aims of this proposal are to: (1) develop theoretical models for polarized reflectance spectroscopy of epithelial tissue and stroma; (2) to test the theoretical predictions in tissue models of human epithelium at different stages of cancer progression; (3) to use the theoretical models to determine the sensitivity of polarized reflectance spectroscopy to morphology of epithelial nuclei and morphology of stroma; (4) to design, construct and test a new fiber optic endoscope for polarized reflectance spectroscopy in vivo; (5) to evaluate the endoscope in clinical studies of oral cavity mucosa. (6) to develop an imaging instrument based on the principles of polarized illumination and detection and to test this device in clinical trials. The inexpensive optical sensors proposed here can immediately benefit health care by reducing the number of unnecessary biopsies, enabling combined diagnosis and therapy, and reducing the need for clinical expertise.