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

描述（由申请人提供）：在此，我们提出开发一种用于体内内窥镜成像的多功能纳米移液管（NP），结合来自深层皮质层或深层脑结构的电生理记录。 使用这个NP，我们计划研究神经元的信息处理机制，跨皮层层和脑深部核。 如今，大鼠桶状皮质和有行为的猴子视觉皮质中的功能地图已经非常成熟，并且可以使用功能成像技术（例如具有高空间分辨率的内在信号光学成像（OI-IS）或电压敏感染料成像）以2D方式进行演示。具有高时空分辨率的染料成像（VSDI）。 然而，由于现代体内成像技术无法以高时空分辨率从大脑皮层深层解析神经元活动，因此3D成像功能图尚未完全实现。 出于同样的原因，目前还不可能使用VSDI或OI-IS对深部脑结构进行成像。 在这里，我们建议解决这个问题，结合在纳米技术领域的最新发展，并在体内的真实的时间成像技术。 最近，Zeev Zalevsky教授和他的实验室开发了一种技术，可以生成类似于光子晶体光纤（PCF）的光纤，具有内部金属线。 这些纤维是通过使具有所需横截面的二氧化硅预成型件变细而产生的，其中预先插入导线。 这种预成型体的锥形化，在不失去其内部几何形状的情况下获得，产生短而薄的纳米移液管，其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中固有的低分辨率。 利用这种技术和专业知识，结合Hamutal Slovin博士的成像专业知识，我们建议制造一种含有光纤和电纤维的锥形预制件（具体目标#1），并测试其在体外和体内小型人造目标上的适用性（具体目标#2）。 最后，我们将通过功能成像，即OI-IS和VSDI（特定目标#3），在麻醉大鼠的桶皮质和脑深部核团上进行体内测试，以确定该设备是否可用于脑成像。 如果成功的话，我们的纳米移液管有望彻底改变现有的成像能力，并将使人们对视觉感知和高级认知功能的神经机制有新的认识。 公共卫生相关性：我们建议开发一种纳米移液管（探针），将其插入大脑皮层表面，并能够从深层皮层或深层脑核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，并将使人们对视觉感知和高级认知功能的神经机制有新的认识。

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.