Assessing nuclear morphology in thick tissues using fLCI

描述(申请人提供)：这项研究的目标是发展一种新的光学技术，傅立叶域低相干干涉测量(FLCI)，目的是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获得了关于散射光的亚表面结构的信息，并且具有用体外样品探测核形态的敏感性。在此，我们建议进一步发展FLCI技术，以应用于原位探测上皮细胞的核形态。这项拟议的研究的成功完成将带来一种新的方法来检测与癌前组织状态相关的核形态变化。FLCI设置的简单性表明，它可以很容易地通过光纤探头实现，适合在内窥镜手术中应用。事实上，FLCI不需要组织切片或外源性造影剂，这意味着该技术可以提供一种评估活体人类上皮组织健康的方法。FLCI技术的基础是检测散射光的波长相关性以确定结构特征，同时使用低相干干涉测量来获得深度分辨率。正是这种光散射和干涉计量学的结合，使得FLCI非常适合于探测完整的上皮组织中的核形态。光散射技术检测亚波长结构变化的能力使fLCI能够检测到使用常规成像方法无法可视化的核形态变化。深度分辨测量的能力允许选择性地检查位于表面下约100米处的上皮基底层的细胞核特征，这是对组织健康最有诊断意义的。这项研究的长期目标是创造一种基于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建立FLCI可以测量完整组织样本中的核形态来证明使用FLCI实现这一目的的可行性。为了实现上述目标，我们采取了以下具体目标：(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：我们将改进对FLCI数据的分析和处理，以提高测量光散射结构的精度。(3)动物研究：我们将对动物上皮组织进行实验，以展示FLCI检测完整样本中的核形态和检测癌前病变的能力。

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.