Novel Nano-pipette for imaging of deep cortical layers and deep brain structures

用于深层皮质层和深层大脑结构成像的新型纳米移液器

• 批准号: 7739664
• 负责人: Hamutal Slovin
• 金额: $ 13.61万
• 依托单位: BAR-ILAN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7739664
• 关键词: Accounting; Address; Agar; Air; Algorithms; Brain; Brain imaging; Cell Nucleus; Cerebral cortex; Characteristics; Code; Collection; Data; Development; Devices; Dyes; Electrodes; Fiber; Fluorescence; Functional Imaging; Future; Generations; Goals; Image; Imaging Techniques; Imaging technology; In Vitro; Laboratories; Light; Lighting; Maps; Mediating; Metals; Modeling; Monkeys; Nanotechnology; Neurons; Neurosciences; Optics; Outcome; Pattern; Population; Property; Rattus; Resolution; Semiconductors; Signal Transduction; Silicon Dioxide; Structure; Surface; System; Techniques; Technology; Testing; Time; Visual Cortex; Visual Perception; barrel cortex; base; cognitive function; in vivo; information processing; insight; lens; light scattering; millisecond; nano; neuromechanism; novel; novel strategies; optical imaging; photonics; public health relevance; sensor; voltage

DESCRIPTION (provided by applicant): Here we propose to develop a multi-functional nano-pipette (NP) for in vivo endoscopic imaging, combined with electrophysiological recording from deep cortical layers or deep brain structures. Using this NP, we plan to study neuronal mechanisms of information processing across cortical layers and from deep brain nuclei. Functional maps in the barrel cortex of rats and visual cortex of behaving monkeys are well established nowadays and can be demonstrated in 2D, using functional imaging techniques such as optical imaging of intrinsic signals (OI-IS), with high spatial resolution, or voltage-sensitive dye imaging (VSDI) with high spatio-temporal resolution. However, imaging functional maps in 3D has not yet been fully achieved due to the inability of modern in vivo imaging techniques to resolve neuronal activity at high spatio-temporal resolution from deep layers of the cerebral cortex. For the same reasons, imaging from deep brain structures using VSDI or OI-IS is not possible currently. Here we propose to address this problem by combining recent developments in the field on nanotechnology and in real time imaging techniques in vivo. Recently, Prof. Zeev Zalevsky and his laboratory have developed the technology that enables generation of fibers similar to photonic crystal fibers (PCF), having internal metal wires. Those fibers are generated by tapering silica pre-forms with desired cross section into which the wires are pre-inserted. This tapering of the pre-form, obtained without losing its internal geometry, produces short, thin nano-pipettes that transmit light and electrical signals to appropriate sensors. Furthermore, the Zalevsky laboratory has developed algorithms to amplify the low resolution inherent in such a system. Using this technology and expertise, in combination with Dr. Hamutal Slovin's imaging expertise, we propose to fabricate a tapered pre-form containing optical and electrical fibers (Specific Aim #1) and test its applicability on small artificial targets in vitro and in vivo (Specific Aim #2). Finally, we will determine whether this device can be used for brain imaging by testing it in vivo on the barrel cortex and deep brain nuclei of anesthetized rats through functional imaging, namely OI-IS and VSDI (Specific Aim #3). If successful, our nano-pipette is expected to revolutionize existing imaging capabilities and will enable new insights into the neural mechanisms underlying visual perception and higher cognitive functions. PUBLIC HEALTH RELEVANCE: We propose to develop a nanopipette (probe), which will be inserted into the cortical surface of the brain and will enable simultaneous imaging and electrophysiological recording from deep cortical layers or deep brain nuclei. If successful, the outcomes of this project will revolutionize existing imaging capabilities and will enable new insights into the neural mechanisms underlying visual perception and higher cognitive functions.

描述（由申请人提供）：在这里，我们建议开发一种多功能纳米移液器（NP），用于体内内窥镜成像，结合皮层深层或脑深部结构的电生理记录。利用这个NP，我们计划研究跨皮质层和来自脑深部核的信息处理的神经元机制。目前，大鼠桶状皮层和行为猴视觉皮层的功能图谱已经建立，并且可以利用高空间分辨率的内在信号光学成像（OI-IS）或高时空分辨率的电压敏感染料成像（VSDI）等功能成像技术在二维上进行展示。然而，由于现代体内成像技术无法从大脑皮层深层以高时空分辨率解析神经元活动，因此尚未完全实现3D成像功能图。出于同样的原因，目前还不可能使用VSDI或OI-IS对大脑深部结构进行成像。在这里，我们建议通过结合纳米技术和体内实时成像技术的最新发展来解决这个问题。最近，Zeev Zalevsky教授和他的实验室开发了一种技术，可以产生类似光子晶体光纤（PCF）的光纤，内部有金属线。这些纤维是通过逐渐变细的二氧化硅预成型而产生的，该预成型具有所需的横截面，电线被预先插入其中。在不失去其内部几何形状的情况下，预成型的这种锥形产生了短而薄的纳米移液管，可以将光和电信号传输到适当的传感器。此外，Zalevsky实验室已经开发出算法来放大这种系统固有的低分辨率。利用这项技术和专业知识，结合Hamutal Slovin博士的成像专业知识，我们建议制造一个包含光学和电气纤维的锥形预成型（特定目标#1），并测试其在体外和体内小型人造目标上的适用性（特定目标#2）。最后，我们将通过功能成像，即OI-IS和VSDI，在麻醉大鼠的脑桶皮质和脑深部核上进行活体测试，以确定该装置是否可以用于脑成像（Specific Aim #3）。如果成功，我们的纳米移液器有望彻底改变现有的成像能力，并将为视觉感知和更高认知功能的神经机制提供新的见解。公共卫生相关性：我们建议开发一种纳米吸管（探针），将其插入大脑皮层表面，并将实现皮层深层或脑深部核的同步成像和电生理记录。如果成功，该项目的成果将彻底改变现有的成像能力，并将为视觉感知和高级认知功能的神经机制提供新的见解。