Optical Detection of Neural Activity With Phase Sensitive Interferometry

使用相敏干涉测量法光学检测神经活动

• 批准号: 7753212
• 负责人: Boris Hyle Park
• 金额: $ 24.6万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7753212
• 关键词: Action Potentials; Address; Animals; Area; Award; Behavior; Biological Neural Networks; Biomedical Engineering; California; Cell Count; Cells; Chemicals; Collaborations; Complement; Contrast Media; Detection; Development; Dyes; Educational process of instructing; Electrodes; Electrophysiology (science); Eye; Faculty; Fiber; Foundations; Funding; Future; Goals; Hand; Histocompatibility Testing; Image; In Vitro; Individual; Interferometry; Lateral; Lead; Light; Limulus; Limulus polyphemus; Magnetic Resonance Imaging; Mentors; Methods; Nerve; Neurons; Neurosciences; Neurosciences Research; Optic Nerve; Optical Coherence Tomography; Optical Methods; Optics; Phase; Physics; Physiological; Positioning Attribute; Process; Rattus; Research; Research Personnel; Research Project Grants; Research Proposals; Research Training; Resolution; Retina; Structure; Supervision; Swelling; Techniques; Technology; The Sun; Thick; Time; Training; Universities; Visual system structure; Work; Xiphosura; base; bioimaging; clinical application; compound eye; experience; in vitro activity; in vivo; minimally invasive; myelination; nanoscale; novel; optical imaging; receptor; relating to nervous system; sciatic nerve

This ROO transition application on the development of optical methods for imaging transient structural changes associated with neural activity integrates rigorous physics, biomedical, and neuroscience research to further the research goals of the original K99/R00 proposal. The mentored (K99) phase has allowed Dr. B. Hyle Park a successful transition to an independent research positioii in the Bioengineering department at the University of California, Riverside. The parameters of the position provide for start-up funding, space, and support that are comparable or exceed that of other recently hired faculty. Furthermore^ it also provides for at least 75% protected research time with a generous amount of teaching relief. The independent (ROO) phase will further Dr. Park's development as an independent researcher and facilitate successful application for an independent research grant (ROl). Having completed his graduate research in physics with a strong focus on biomedical imaging, particularly in the development and clinical application of polarization-sensitive optical coherence tomo^phy, Dr. Park has complemented this grounding in biomedical optics with coursework in and hands-on laboratoiy experience with current neuroscience techniques. His research proposal addresses the need for non-contact detection of neural structure and activity. Current techniques for detection of action potential propagation involve direct contact with electrodes or introduction of chemical markers, such as Ca^^ dyes. The focus of this K99/R00 is optical detection of transient structural changes that accompany spike propagation in neurons using a phasesensitive interferometric technique known as spectral-domain optical coherence tomography (SD-OCT). An important first step in optically detecting activity in nerves is the ability to identify them in SD-OCT images. During the mentored (K99) phase, it was shown that unmyelinated limulus lateral compound optic nerve and myelinated rat sciatic nerve can be idientifled fiom surrounding other tissue types in structural images, providing valuable groundwork for future in vivo application of optical detection of neural activity as it allows for differentiation of myelinated and non-myelinated neurons versus other tissue types within acquired images. These results also demonstrate that quantitative analysis of optical images of nerve structure is capable of non-destructive assessment of the degree of nerve myelination. A correlation between electrically recorded action potential propagation with optical detection of associated axonal thickness changes was established, and such detection is possible for single impulses without requiring averaging of results from repeated trials. The independent phase ofthis propos^ aims to further develop this optical technique such that it can be applied to detailed studies of the interaction between individual cells in and behavior of functional neural networks. Successful completion of the proposed research will enable optical detection of the structure and activity of nerves and neuronal ensembles in vilro, and lay the groundwork for in vivo application as well as providing the preliminary results necessary fbr a successful ROI application. This work not only has potential ^plication as a complement to electrophysiology, but would be of use where optical detection could be siibstituted where introduction of a large number of electrodes can be problematic and in clinically important regions, such as the retina, that are largely inaccessible with current techniques.

这种 ROO 转变应用在光学方法的开发上，用于对与相关的瞬态结构变化进行成像 神经活动整合了严格的物理学、生物医学和神经科学研究，以进一步实现最初的研究目标 K99/R00 提案。指导 (K99) 阶段使 B. Hyle Park 博士成功过渡到独立研究 加州大学河滨分校生物工程系博士。该位置的参数规定 启动资金、空间和支持可与其他最近聘用的教师相媲美或超过。此外^还提供 至少 75% 的受保护研究时间以及大量的教学减免。独立（ROO）阶段将进一步推动博士的发展。 Park 作为独立研究员的发展并促进了独立研究补助金 (ROl) 的成功申请。 完成了物理学研究生研究，重点关注生物医学成像，特别是在开发和 Park 博士补充了偏振敏感光学相干断层扫描的临床应用 生物医学光学，包括当前神经科学技术的课程作业和实验室实践经验。他的研究 该提案解决了对神经结构和活动进行非接触式检测的需求。当前检测动作的技术 电势传播涉及与电极的直接接触或引入化学标记物，例如Ca^^染料。重点是 该 K99/R00 使用相敏器件光学检测伴随神经元尖峰传播的瞬态结构变化 干涉测量技术称为谱域光学相干断层扫描 (SD-OCT)。重要的第一步 光学检测神经活动是指能够在 SD-OCT 图像中识别神经活动。在指导（K99）阶段， 表明无髓鲎外侧复合视神经和有髓大鼠坐骨神经可从周围识别 结构图像中的其他组织类型，为未来神经光学检测的体内应用提供了宝贵的基础 活性，因为它允许在获取的图像中区分有髓神经元和非有髓神经元与其他组织类型。 这些结果还表明，神经结构光学图像的定量分析能够进行非破坏性的分析。 评估神经髓鞘形成的程度。电记录的动作电位传播与 建立了相关轴突厚度变化的光学检测，并且这种检测对于单脉冲是可能的，无需 需要对重复试验的结果进行平均。该提案^的独立阶段旨在进一步开发这种光学 技术，使其可应用于单个细胞之间的相互作用和功能性行为的详细研究 神经网络。成功完成拟议的研究将使光学检测神经的结构和活动成为可能 和体外神经元集成，为体内应用奠定基础并提供初步结果 成功的投资回报率申请所必需的。这项工作不仅具有作为电生理学补充的潜力，而且 在可以采用光学检测且引入大量电极可能出现问题的情况下将很有用 在临床上重要的区域，例如视网膜，目前的技术基本上无法到达。