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Optical sensing of tissue microstructure and cell nanostructure.

机译：组织微观结构和细胞纳米结构的光学传感。

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摘要

Recently there has been a major thrust to understand biological processes at the micro/nanoscale. Elastic light scattering offers us a powerful and non-invasive means of visualizing the biological medium, as the light scattering signals exhibit characteristic structure dependent patterns and hence are extremely sensitive to micro/nano architectural alterations in tissue and cells. However, in most elastic light scattering experiments the photons undergo several scattering events before exiting the medium thus loosing their sensitivity to micro and nanostructures within the tissue. We have developed two novel optical techniques, low coherence enhanced backscattering (LEBS) and partial wave spectroscopy (PWS) that are sensitive to both tissue microstructure and cell nanostructures. LEBS enables probing the microarchitecture of biological tissue by tracking the photons that travel very short distances and hence undergo very few scattering events. Here we developed both numerical and analytical models to understand the fundamental mechanisms of LEBS in biological tissue. Single-cell PWS on the contrary provides a practical means of characterizing cell organization at the nanoscale. Coupled with the mesoscopic light transport theory, PWS quantifies the nanoscale refractive index fluctuations within cells in terms of intracellular disorder strength. We demonstrated the nanoscale sensitivity of PWS using rigorous finite difference time domain (FDTD) simulations and experiments with nanostructured models. We also showed the potential of PWS in experiments with cell lines and an animal model of colon carcinogenesis, which established an increase in the degree-of-disorder in cell nanoarchitecture parallels genetic events in the early stages of carcinogenesis in otherwise microscopically/histologically normal-appearing cells. We demonstrated that this increase in the disorder strength is not only observed in tumor cells but also in the microscopically normal-appearing cells outside of the tumor in the field of carcinogenesis. Our results from three types of cancer: colon, pancreas and lung showed organ-wide alteration in cell nanoarchitecture, which appears to be a general event in carcinogenesis. These results have important implications in that PWS can be used as a new methodology to identify patients harboring malignant or premalignant tumors by interrogating the easily accessible tissue sites distant from the location of the lesion.
机译：近来，人们有很大的努力去了解微观/纳米尺度的生物过程。弹性光散射为我们提供了一种可视化生物介质的有力且非侵入性的手段，因为光散射信号显示出特征性的结构依赖性模式，因此对组织和细胞中的微纳米结构变化极为敏感。但是，在大多数弹性光散射实验中，光子在离开介质之前会经历几次散射事件，因此失去了它们对组织内微结构和纳米结构的敏感性。我们已经开发了两种新颖的光学技术，即低相干增强反向散射（LEBS）和部分波谱（PWS），它们对组织的微结构和细胞的纳米结构均敏感。 LEBS能够通过追踪传播非常短距离并因此经历很少散射事件的光子来探测生物组织的微体系结构。在这里，我们开发了数值模型和分析模型，以了解LEBS在生物组织中的基本机制。相反，单细胞PWS提供了表征纳米级细胞组织的实用方法。结合介观光传输理论，PWS根据细胞内无序强度量化了细胞内的纳米级折射率波动。我们使用严格的时差有限域（FDTD）模拟和纳米结构模型实验证明了PWS的纳米级灵敏度。我们还显示了PWS在细胞系和结肠癌发生动物模型实验中的潜力，该模型建立了在癌发生早期阶段细胞遗传学机制平行于遗传事件的细胞纳米结构中无序程度的增加，而在微观/组织学正常的情况下，出现细胞。我们证明，不仅在肿瘤细胞中，而且在致癌作用领域中，在肿瘤外部的显微镜下正常出现的细胞中也观察到这种无序强度的增加。我们从三种类型的癌症（结肠癌，胰腺癌和肺癌）得出的结果表明，细胞纳米结构中的器官范围发生了改变，这似乎是致癌作用中的一般事件。这些结果具有重要意义，因为PWS可以用作一种新方法，通过询问远离病变部位的易于接近的组织部位来鉴定出患有恶性或恶性肿瘤的患者。

著录项

  • 作者

    Subramanian, Hariharan.;

  • 作者单位

    Northwestern University.;

  • 授予单位 Northwestern University.;
  • 学科 Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 197 p.
  • 总页数 197
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物医学工程;
  • 关键词

  • 入库时间 2022-08-17 11:38:25

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