TUMOR DIAGNOSTICS BY LIGHT SCATTERING

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 现在正在开发不切除组织的组织诊断的光学技术，在患者护理和医疗成本方面都提供了比组织活检等标准技术显著的优势。例如，光学技术速度更快，不需要镇静剂，并且消除了与组织切除相关的并发症，如感染。这项建议的目的是开发和测试偏振弹性散射谱。弹性散射谱(ESS)测量进入组织、在组织内散射并重新发射的光的波长依赖性。在偏振ESS中，传输的光是偏振的，检测到的光通过偏振器测量。检测到的光可以提供有关形态属性和血红蛋白浓度的信息。例如，已经证明了对细胞复制速度的敏感性，对模型系统的测量表明，可以确定散射体的大小和浓度。为了充分发挥这项技术的潜力，需要了解光与组织的基本相互作用。这项建议的第一个具体目标是确定细胞的特定结构特征如何影响光散射。下一个目标将是检查致癌和非致瘤上皮细胞之间的光散射差异。上皮细胞特别有趣，因为大多数癌症起源于上皮细胞。以前的工作表明，细胞在三维培养中诱导的环境可以导致致癌细胞和非致瘤细胞的光散射不同。在研究散射特性的同时，将为活体使用开发和实施改进的测量技术。最后，将进行临床试验，以确定偏振弹性散射光谱在检测/诊断鳞状上皮、反应性/修复组织、低度不典型增生、高度不典型增生和浸润性癌中的作用。宫颈癌的筛查和诊断是光学癌症检测技术进入的理想舞台。组织很容易拿到，低精度的巴氏涂片试验已经证明了筛查方法的实用性。ESS有可能快速采样组织并精确定位特定病理的位置。ESS可能会取代巴氏涂片，作为一种频率较低的测试或作为辅助检查。如果极化ESS可以用来确定ASCUS(不确定意义的非典型鳞状细胞)巴氏涂片结果的意义，它可能会导致显著的成本节约。ASCUS是巴氏涂片检测到的最常见的异常，每年的随访费用估计为45亿美元。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Optical techniques for tissue diagnosis without the removal of tissue are now being developed which offer significant advantages over standard techniques, such as tissue biopsy, both in terms of patient care and medical costs. For example, optical techniques are faster, sedatives are not needed, and complications associated with tissue removal such as infection are eliminated. The aim of this proposal is to develop and test polarized elastic scattering spectroscopy. Elastic scattering spectroscopy (ESS) measures the wavelength dependence of light that has entered the tissue, been scattered within the tissue and re-emitted. In polarized ESS the delivered light is polarized and the detected light is measured through polarizers. The detected light can provide information about both the morphological properties and the hemoglobin concentration. For example, a sensitivity to the rate at which cells are replicating has been demonstrated and measurements of model systems have shown that scatterer size and concentration can be determined. In order for this technique to reach its full potential an understanding of the fundamental interactions of light with tissue is needed. The first specific aim of this proposal is to determine how specific structural features of cells contribute to light scattering. The next aim will be to examine light scattering differences between tumorigenic and non-tumorigenic epithelial cells. Epithelial cells are particularly interesting, because most cancers originate from epithelial cells. Previous work demonstrated that the environment induced by cells in 3-D culture can cause a difference in light scattering from tumorigenic and non-tumorigenic cells. In parallel with the study of scattering properties improved measurement techniques will be developed and implemented for in vivo use. Finally, clinical trials will be performed to determine the utility of polarized elastic scattering spectroscopy to detect/diagnose squamous epithelium, reactive/repairing tissue, low grade dysplasia, high grade dysplasia and invasive carcinoma. Screening and diagnosis of cervical cancer is an ideal arena for the entry of optical techniques for cancer detection. The tissue is easily accessible and the low-accuracy Pap smear test has already demonstrated the utility of screening methods. ESS has the potentially to rapidly sample tissue and pinpoint locations of specific pathologies. Potentially ESS could replace Pap smears as a less frequent test or serve as an adjunct. If polarized ESS could be used to determine the significance of an ASCUS (atypical squamous cells of uncertain significance) Pap smear result, it could result in significant cost savings. ASCUS is the most common anomaly detected by Pap smears and annual follow up is estimated to cost $4.5 billion per year.