Polarization Spectroscopy and Imaging of Pre-Cancer

描述(由申请人提供)： 癌症是美国第二大死因。大多数癌症是由上皮细胞引起的。早期诊断浸润性癌前病变可以显著降低癌的发病率和死亡率。因此，迫切需要高灵敏度和高成本效益的筛查和诊断技术来识别可治愈的癌前病变。上皮性癌前病变具有多种结构和形态特征，包括核大小增大、核浆比增大、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-间质的相互作用，间质层发生了显著的变化。目前临床诊断的一个主要局限性是，只有在侵入性活检后才能评估与早期癌变相关的形态和分子变化。光学技术可以非侵入性和实时地评估上皮组织的形态和生化变化。这项提议的目的是开发一种基于偏振反射光谱和成像的新技术，以实现对与癌变相关的上皮和潜在结缔组织的形态和结构变化的非侵入性实时检测和监测。这项建议的目的是：(1)建立上皮组织和间质偏振反射光谱的理论模型；(2)检验在人类癌症进展不同阶段的组织模型中的理论预测；(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)设计、建造和测试一种新型的用于体内偏振反射光谱的光纤内窥镜；(5)评估内窥镜在口腔黏膜临床研究中的应用。(6)研制一种基于偏振照明和探测原理的成像仪，并对其进行临床试验。这里提出的廉价光学传感器可以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.