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Femtosecond laser pulses to model and treat brain diseases.

机译：飞秒激光脉冲可模拟和治疗脑部疾病。

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摘要

Tightly focusing femtosecond laser pulses into bulk media, such as brain tissue, can generate high intensities within the focal volume. With sufficient laser energies, nonlinear absorption of femtosecond laser pulses by the media can take place. This thesis takes advantages of these nonlinear processes to image the cortical vasculature in live anesthetized rodent, and induce localized tissue disruption. We used two-photon excited fluorescence (2PEF) microscopy to image fluorescently labeled cortical vasculature in vivo. In this technique, two-photons are simultaneously absorbed to generate fluorescence that is localized within the focal volume, where intensity is greatest. Scanning the focus enables three-dimensional imaging since out-of-focus fluorescence is not generated. Higher-order nonlinear absorption processes that lead to plasma and cavitation bubble formation are used to induce localized tissue disruption. Together these nonlinear tools enable fine-detailed studies of the cortical vasculature and precise ablation of tissue.;To understand the potential role of small venule strokes in the development of cognitive disorders, we investigated the blood flow and vascular effects in individual vessels after inducing single venule occlusions using femtosecond laser ablation. To better understand the blood flow and metabolic responses during an epileptic seizure, we use a several optical techniques to investigate the neurovascular and neurometabolic activity during pre-ictal and ictal phases of focal seizures. Using 2PEF microscopy we reveal the presence of vasoconstriction in arterioles surrounding the focus prior to seizure onset. The deposition of energy within the focal volume can also used to make incisions in bulk brain to disrupt tissue. Using our laser scalpel, we produced sub-surface cortical incisions and characterized the cut width and depth as a function of different laser energies. We then employed this cutting technique to determine the efficacy of sub-surface cuts in stopping seizure propagation. We then showcased a technique to produce welds at the unexposed interface between two pieces of glass and characterized their size as a function of multiple experimental parameters. Joint strength of the fused glass was tested in addition to investigating the changes in optical properties induced by the weld. Lastly, future experiments and advantages of nonlinear optical techniques are discussed.
机译：将飞秒激光脉冲紧密聚焦到诸如大脑组织之类的体积较大的介质中，可以在焦距范围内产生高强度。利用足够的激光能量，飞秒激光脉冲会被介质非线性吸收。本论文利用这些非线性过程的优势对活麻醉的啮齿动物的皮质脉管系统进行成像，并诱导局部组织破坏。我们使用双光子激发荧光（2PEF）显微镜对体内荧光标记的皮质脉管系统进行成像。在这种技术中，两个光子同时被吸收以生成荧光，该荧光位于焦点体积内，强度最大。扫描焦点可以进行三维成像，因为不会产生离焦荧光。导致血浆和空化气泡形成的高阶非线性吸收过程用于诱导局部组织破坏。这些非线性工具共同实现了对皮层脉管系统和组织精确消融的详细研究。为了了解小静脉搏动在认知障碍发展中的潜在作用，我们在诱导单个血管后研究了单个血管的血流和血管效应使用飞秒激光消融术治疗小静脉阻塞。为了更好地了解癫痫发作期间的血流和代谢反应，我们使用了几种光学技术来研究局灶性发作的发作前和发作期的神经血管和神经代谢活动。使用2PEF显微镜，我们揭示了癫痫发作之前围绕焦点的小动脉中存在血管收缩。焦点体积内的能量沉积也可用于在大量大脑中切开切口以破坏组织。使用我们的激光手术刀，我们制作了皮下皮下切口，并根据不同的激光能量对切割的宽度和深度进行了表征。然后，我们采用这种切割技术来确定亚表面切割在阻止癫痫发作传播中的功效。然后，我们展示了一种在两块玻璃之间的未暴露界面处产生焊缝的技术，并根据多个实验参数来确定其大小。除了研究焊接引起的光学性能变化外，还测试了熔融玻璃的接合强度。最后，讨论了非线性光学技术的未来实验和优点。

著录项

  • 作者

    Nguyen, John.;

  • 作者单位

    Cornell University.;

  • 授予单位 Cornell University.;
  • 学科 Biology Neurobiology.;Physics Optics.;Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2011
  • 页码 252 p.
  • 总页数 252
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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