Assessing nuclear morphology in thick tissues using fLCI

使用 fLCI 评估厚组织中的核形态

基本信息

批准号：
7230090
负责人：
Adam Wax
金额：
$ 11.5万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-04-14 至 2008-12-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The objective of this research is to develop a new optical technique, Fourier-domain Low Coherence Interferometry (fLCI), for the purpose of probing the nuclear morphology of epithelial cells within intact tissues. Our preliminary experiments show that fLCI obtains information about sub-surface structures which scatter light as well as possessing the sensitivity to probe nuclear morphology with in vitro samples. Here we propose to further develop the fLCI technique for application to probing the nuclear morphology of epithelial cells in situ. Successful completion of the proposed research will lead to a new method for detecting the nuclear morphology changes associated with pre-cancerous tissue states. The simplicity of the fLCI setup suggests that it easily could be implemented with an optical fiber probe, suitable for application during endoscopic procedures. The fact that fLCI does not require tissue sectioning or exogenous contrast agents implies that the technique could provide a means for assessing the health of human epithelial tissues in vivo. The basis of the fLCI technique is to detect the wavelength dependence of scattered light to determine structural features while simultaneously using low-coherence interferometry to obtain depth resolution. It is this combination of light scattering and interferometry which makes fLCI well suited to the task of probing nuclear morphology within intact epithelial tissues. The ability of light scattering techniques to detect sub-wavelength structural changes enables fLCI to detect nuclear morphology variations which cannot be visualized using ordinary imaging methods. The capability for depth-resolved measurements allows for selective examination of cell nuclei features in the basal layer of the epithelium, lying approximately 100 m beneath the surface, which are most diagnostic of tissue health. The long-range goal of this research is to create an fLCI-based biomedical diagnostic device for the purpose of detecting early cancer in humans. The research plan proposed here will demonstrate the feasibility of using fLCI for this purpose by establishing that fLCI can measure nuclear morphology within intact tissue samples. In order to accomplish the stated objectives we adopt the following specific aims: (1 ) Instrument Development: We will refine our optical system to optimize the fLCI measurements for probing thick tissues. (2) Theoretical modeling: We will improve our analysis and processing of fLCI data to better the accuracy achieved in measuring light scattering structures. (3) Animal Studies: We will execute experiments with animal epithelial tissues which will demonstrate the ability of fLCI to detect nuclear morphology within intact samples and for detecting pre-cancerous changes.

描述（由申请人提供）：本研究的目的是开发一种新的光学技术，即傅里叶域低相干干涉测量法（fLCI），用于探测完整组织内上皮细胞的核形态。我们的初步实验表明，fLCI 可以获得有关散射光的次表面结构的信息，并且具有用体外样品探测核形态的灵敏度。在这里，我们建议进一步开发 fLCI 技术，用于原位探测上皮细胞的核形态。成功完成拟议的研究将产生一种检测与癌前组织状态相关的核形态变化的新方法。 fLCI 设置的简单性表明它可以轻松地使用光纤探头实现，适合内窥镜手术期间的应用。 fLCI 不需要组织切片或外源造影剂这一事实意味着该技术可以提供一种评估体内人体上皮组织健康状况的方法。 fLCI 技术的基础是检测散射光的波长依赖性以确定结构特征，同时使用低相干干涉测量来获得深度分辨率。正是光散射和干涉测量的结合使得 fLCI 非常适合探测完整上皮组织内的核形态。光散射技术检测亚波长结构变化的能力使 fLCI 能够检测使用普通成像方法无法可视化的核形态变化。深度分辨测量功能允许选择性检查上皮基底层（位于表面下方约 100 m）的细胞核特征，这对组织健康最具诊断意义。这项研究的长期目标是创建一种基于 fLCI 的生物医学诊断设备，用于检测人类早期癌症。这里提出的研究计划将通过确定 fLCI 可以测量完整组织样本内的核形态来证明使用 fLCI 实现此目的的可行性。为了实现既定目标，我们采取以下具体目标： (1) 仪器开发：我们将改进我们的光学系统，以优化探测厚组织的 fLCI 测量。（2）理论建模：我们将改进fLCI数据的分析和处理，以提高光散射结构测量的精度。 (3) 动物研究：我们将用动物上皮组织进行实验，这将证明 fLCI 检测完整样本中的核形态和检测癌前变化的能力。