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Real-time Aberration Sensor for Large-Scale Microscopy Deep in the Mouse and Adult Zebrafish Brain

用于小鼠和成年斑马鱼大脑深处的大规模显微镜检查的实时像差传感器

基本信息

批准号：
10166305
负责人：
Steven Graham Adie
金额：
$ 198.23万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10166305
关键词：
Address Adult Algorithms Biological Biological Process Brain Brain Diseases Brain imaging Brain region Budgets Calibration Cells Cerebellum Consumption Financial compensation Fluorescence Goals Hybrids Image Imaging Techniques Imaging technology Individual Label Lasers Maps Methods Microscope Microscopy Modality Morphologic artifacts Motion Mus Neurons Neurosciences Neurosciences Research Noise Optical Coherence Tomography Optics Penetration Phase Photobleaching Photons Phototoxicity Physiologic pulse Population Positioning Attribute Procedures Pupil Research Resolution Sampling Shapes Signal Transduction Source Specificity Speed Structure System Techniques Technology Time Tissues Training Zebrafish adaptive optics awake base biological systems brain tissue data acquisition dentate gyrus digital imaging approach imaging study imaging system in vivo interest microscopic imaging mouse model multimodality multiphoton microscopy novel optical imaging parallel computer parallel processing programs relating to nervous system sensor spatiotemporal superior colliculus Corpora quadrigemina three photon microscopy two photon microscopy

项目摘要

ABSTRACT Optical imaging holds tremendous promise in our endeavor to understand brain functions. The major challenges for optical brain imaging are depth and speed. Due to optical aberrations and tissue scattering, the penetration depth and imaging speed of optical microscopy in the brains (e.g., mouse) is limited. The constraints in depth and speed make large-scale, deep imaging of mouse brain activity out of reach of current imaging techniques. Hardware adaptive optics (AO) has proven to be valuable for in vivo brain imaging with two-photon microscopy (2PM), and will have even larger impact for deep brain 3-photon microscopy (3PM); however, existing AO techniques require iterative optimization using multiphoton excited fluorescence signal. While adequate for imaging relatively shallow regions of the brain (< 1 mm deep), iterative optimization is impractical with ultra-deep imaging since the fluorescence signal deceases exponentially with imaging depth. The required integration time to obtain the necessary signal-to-noise ratio for iterative optimization becomes prohibitively long. In this program, we will leverage the advantages provided by computational adaptive optics (CAO) in optical coherence microscopy (OCM), specifically the strong OCT signal (from linear backscattering), and parallel computing on a high-end graphics processing unit (GPU), to provide orders of magnitude speed-up for the sensing of sample-induced aberrations throughout a volume of interest. A long-wavelength OCM system and CAO aberration sensor will be utilized to drive a hardware AO system to correct depth-dependent aberrations, push 3PM imaging depth beyond currently demonstrated limits, and increase imaging speed by at least one order of magnitude. Additionally, by combining with recently developed adaptive excitation laser technology, we will achieve approximately 300-fold increase in photon budget, which will enable truly unprecedented 3PM imaging speed and depth. Successful completion of this program will enable rapid aberration sensing at the depth range of 1 to 2 mm, and will open the exciting new opportunity of recording the neural activity of the dentate gyrus of adult mice through the intact brain. With its high-speed and deep-tissue aberration sensing capability, and zero additional photobleaching and phototoxicity, our novel method for real-time aberration sensing and correction is ideally positioned to transform our ability for large-scale, deep recording of mouse and adult zebrafish brain activity. This imaging approach will significantly extend the information available for neuroscience studies on individual cell-cell as well as circuit interactions that underlie normal and diseased brain function. The technology developed by this proposal will be applicable to imaging in other biological systems where large-scale, deep imaging at high spatiotemporal resolution is needed.

摘要光学成像在我们理解大脑功能的奋进中有着巨大的希望。的主要挑战最重要的是深度和速度由于光学像差和组织散射，脑中光学显微镜的深度和成像速度（例如，鼠标）是有限的。深度限制和速度使得对小鼠大脑活动的大规模深度成像超出了当前成像技术的范围。硬件自适应光学（AO）已被证明是有价值的在体脑成像与双光子显微镜 (2PM)，并将对深部脑3光子显微镜（3 PM）产生更大的影响;然而，现有的AO 这些技术需要使用多光子激发的荧光信号进行迭代优化。虽然足够用于对于脑的相对浅的区域（< 1 mm深）成像，迭代优化对于超深成像是不切实际的。因为荧光信号随成像深度呈指数衰减，所需的集成时间获得迭代优化所需的信噪比的时间变得过长。在这个节目中，我们将充分利用计算自适应光学（CAO）在光学相干方面的优势光学显微镜（OCM），特别是强OCT信号（来自线性后向散射），以及在高端图形处理单元（GPU），为传感提供数量级的加速，在整个感兴趣体积中的样品诱导的畸变。长波OCM系统和CAO 像差传感器将用于驱动硬件AO系统，以校正深度相关像差， 3 PM成像深度超过目前证明的限制，并将成像速度提高至少一个数量级大小此外，通过结合最近开发的自适应激发激光技术，我们将光子预算增加约300倍，这将实现真正前所未有的3 PM成像速度和深度。成功完成该计划将使在深度范围内的快速像差感测成为可能 1至2毫米，并将打开令人兴奋的新的机会，记录齿状回的神经活动，成年老鼠的完整大脑凭借其高速和深层组织像差传感能力，附加的光漂白和光毒性，我们的实时像差传感和校正的新方法，理想的定位是改变我们对小鼠和成年斑马鱼大脑进行大规模深度记录的能力活动这种成像方法将大大扩展神经科学研究的信息，单个细胞-细胞以及构成正常和患病脑功能基础的回路相互作用。技术该提案所开发的成像技术将适用于其他生物系统中的大规模，深需要高时空分辨率的成像。