CELLULAR AND NUCLEAR SIZING IN NORMAL AND ABNORMAL SOFT

涉及皮肤和底层软组织的疾病比比皆是。这些组织涉及广泛的先天性、炎症性、感染性、创伤性和肿瘤过程。除了体格检查，这些病变的诊断大多是侵入性的、耗时的和昂贵的，通常需要手术切除或活检，然后进行病理检查。一种无创、高效、低成本的评估皮肤和软组织细胞变化的技术在许多疾病的治疗中将是非常有价值的。众所周知，正常核的特征直径在4到7微米之间，而发育不良的核通常增大，最大可达20微米。因此，在大多数人类组织中，增大的细胞核是癌症、异型增生和细胞再生的主要细胞指标。目前用于确定组织中细胞核大小的方法，如图像分析和流式细胞术，需要分散在液体介质或组织切片中的细胞样本，而不能用于活体细胞分析。R03的应用旨在开发一种新的光学方法，使我们能够直接从组织中的多次散射光或光子迁移测量中提取体内核尺寸分布。我们对核大小的想法是使用基于模型的计算算法来重建组织散射光谱中包含的核大小分布。我们对原子核尺寸分布的测量可以实时提供。我们的方法还将允许我们恢复其他散射体的大小分布，例如血细胞。有了这一能力，我们将能够检测到由于这些其他子结构的大小变化而导致的异常。因此，这项应用的具体目标是：(1)继续开发用于提取核大小分布的正则化逆算法，(2)使用组织模型、培养细胞和人体皮肤等效实验来评估和优化计算机算法和基于CD的连续波光学光谱系统的集成功能，以及(3)基于在人体受试者试验期间获得的初步数据来评估我们的集成光学系统。

Diseases involving the skin and underlying soft tissues are legions. These tissues are involved by a wide range of congenital, inflammatory, infectious, traumatic, and neoplastic processes. Aside from physical examination, the diagnosis of most of these lesions is invasive, time- consuming, and costly, often requiring surgical excision or biopsy followed by pathological investigations. A non-invasive, efficient, low cost technique of evaluating skin and soft tissue cellular changes would be extremely valuable in the management of numerous conditions. It is known that normal nuclei have a characteristic diameter between 4 and 7mum, while dysplastic nuclei generally enlarge and can be as large as 20 mum. Thus, enlarged nuclei are primary cellular indicators of cancer, dysplasia and cell regeneration in most human tissues. Current methods such as image analysis and flow cytometry used to size nuclei in tissue require dispersed cellular samples in liquid media or tissue sections which cannot be used for in vivo analysis of cells. This R03 application is aimed to develop a novel optical method that will allow us to extract in vivo nuclear size distribution directly from multiply scattered light or photon migration measurement in tissue. Our idea for nuclear sizing is to use model-based computational algorithms to reconstruct the nuclear size distribution that is contained in the tissue scattering spectral. Our measurement of nuclear size distribution can be provided in real-time. Our approach will also allow us to recover the size distributions of other scatterers such as blood cells. With this capability, we will be able to detect abnormalities due to the size changes of these other substructures. Thus, the specific aims of this application are: (1) to continue the development of regularized inverse algorithms for the extraction of nuclear size distribution, (2) to evaluate and optimize the integrated functioning of the computer algorithms and a CD-based continuous-wave optical spectral system using tissue phantom, cultured cell and the human skin equivalent experiments, and (3) to evaluate our integrated optical system based on preliminary data obtained during a human subjects trial.