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Miniaturized, Label Free Optical Systems for Imaging Brain Hemodynamics

机译：用于脑血流动力学成像的小型，无标签光学系统

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摘要

This dissertation focuses on instrumentation development for optical monitoring of hemodynamics in rodent brains, which would allow neurophysiologists, conducting pre-clinical research on brain diseases and disorders, to better understand disease onset and progression, and evaluate treatment options.;Three specific challenges in applying optical tools to brain imaging were addressed: (1) the limited robustness of optical imaging in the presence of misfocus, (2) the low sensitivity in imaging brain activity under anaesthesia in chronic, longitudinal studies, and (3) the limited penetration depth of optical microscopy in tissue.;Two methods were proposed to address misfocus-related imaging artefacts, which enable quantitative optical measurements of blood flow to take place across large fields of view and over long imaging time-frames. A system for blood flow monitoring with extended depth of field was developed, showing improved ability to accurately image flow speeds over large areas in the brain. In addition, a novel measure for misfocus was proposed, enabling robust autofocusing in the presence of measurement noise. A miniaturized, skull-mounted multi-modal optical imaging system was designed for imaging brain blood flow and oxygenation changes in freely-behaving animals. This device constituted the first demonstration of wide-field optical imaging of brain blood flow and oxygenation in a chronic setting, suitable for longitudinal studies of brain disease progression and investigating treatment efficacy. Lastly, a novel endoscopy method was proposed to measure flow speeds of scattering fluids through a single, multi-mode optical fiber. This endoscopy method could enable imaging blood flow speeds in deep brain structures using a minimally-invasive probe that is over 2x smaller than conventional micro-endoscopes used today.;Combined, the accomplishments described in this dissertation contributed to making optical measurements of brain hemodynamics applicable to a wider range of imaging assays, and to making optical imaging a more accessible tool for the study of brain vasculature.
机译：本论文的重点是用于光学监测啮齿动物大脑血流动力学的仪器开发，这将使神经生理学家对脑部疾病和病症进行临床前研究，以更好地了解疾病的发作和进展并评估治疗方案。解决了用于脑部成像的光学工具：（1）在存在聚焦错误的情况下，光学成像的鲁棒性有限；（2）在慢性，纵向研究中麻醉下对脑部活动成像的灵敏度低；（3）有限的穿透深度提出了两种方法来解决与散焦有关的成像伪像，这两种方法可以对大视野和长成像时间范围内的血流进行定量光学测量。开发了一种具有扩展景深的血流监测系统，该系统显示出提高的能力，可准确成像大脑大面积区域的血流速度。此外，提出了一种新的失焦措施，可以在存在测量噪声的情况下实现强大的自动聚焦。设计了一个微型的，头骨安装的多模式光学成像系统，用于对行为自由的动物的脑血流和氧合变化进行成像。该设备首次展示了在慢性环境中脑血流和氧合的广域光学成像技术，适用于脑疾病进展的纵向研究和研究治疗效果。最后，提出了一种新颖的内窥镜方法来测量通过单模光纤的散射流体的流速。这种内窥镜检查方法可以使用比目前使用的传统微型内窥镜小2倍的微创探头来成像深部大脑结构中的血流速度。结合本文所描述的成就，有助于光学测量脑血流动力学的适用性到更广泛的成像分析领域，并使光学成像成为研究脑血管的更便捷的工具。

著录项

  • 作者

    Sigal, Iliya.;

  • 作者单位

    University of Toronto (Canada).;

  • 授予单位 University of Toronto (Canada).;
  • 学科 Electrical engineering.;Biomedical engineering.;Medical imaging.
  • 学位 Ph.D.
  • 年度 2017
  • 页码 200 p.
  • 总页数 200
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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