Deep and fast imaging using adaptive excitation sources

使用自适应激励源进行深度快速成像

基本信息

批准号：
10516870
负责人：
CHRIS XU
金额：
$ 55.83万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10516870
关键词：
3-Dimensional Amplifiers Animal Model Behavior Brain Brain imaging Budgets Calcium Chronic Cortical Column Data Detection Development Fiber Fluorescence Frequencies Gases Gaussian model Generations Genetic Goals Image Imaging Device Imaging technology Institution Lasers Measurement Methods Microscope Mus Nervous system structure Neurons Neurosciences Noise Optics Penetration Performance Photons Physiologic pulse Population Process Pulse Rates Research Research Personnel Research Proposals Resolution Resource Sharing Sampling Scanning Signal Transduction Site Source Speed Structure Synapses System Technology Testing TimeLine Tissue imaging Tissues Training Trees Work base brain tissue cell type commercialization design diversity and equity experimental study feeding fly imaging software improved in vivo in vivo imaging industry partner innovation interest member multiphoton imaging multiphoton microscopy novel strategies optical imaging outreach programs relating to nervous system second harmonic temporal measurement three photon microscopy trend two photon microscopy two-photon voltage

项目摘要

Abstract Optical recordings of activity are critical to probe neural systems because they provide high-resolution, non-invasive measurements, ranging from single neurons to entire populations in intact nervous systems, and are readily combined with genetic methods to provide cell type-specific recordings. Nevertheless, the limited penetration depth, spatial scale and temporal resolution remain major challenges for optical imaging. Cellular- resolution imaging in scattering brains is typically achieved with multiphoton microscopy (MPM). Because of the nonlinear excitation process, the development of multiphoton imaging depends critically on ultrafast technologies, particularly femtosecond sources. From the first demonstrations of second harmonic generation (SHG) and 2- photon fluorescence (ruby laser), the first 2-photon imaging (mode-locked femtosecond laser), to the deepest 3- photon imaging so far (long wavelength optical parametric amplifiers), advances in multiphoton imaging have been largely propelled by the innovations in laser technologies. This research proposal aims to continue this trend. We will develop and disseminate a new generation of ultrafast lasers and multiphoton imaging tools that will enable deep, fast, and large-scale imaging of structure and function with cellular and subcellular resolution. To approach the fundamental limits defined by the “photon budget”, we will develop an adaptive excitation source (AES) at 1300 nm for deep tissue 3-photon microscopy (3PM). By feeding the structural information of the sample to the laser source, the AES generates on-demand pulses only within regions of interest (ROIs) and transforms a conventional multiphoton microscope into a “random-access” microscope for the ROIs. We will integrate the AES with high speed scanners and optimize the photon budget and scanning systems. We will further test and validate the performance of the new imaging technology in three proof-of-concept experiments in animal models. The research involves close interactions between the PI (Chris Xu) and Co-investigators (Alex Kwan, Frank Wise, Nilay Yapici, and Rafael Yuste). Furthermore, we will work with industry partners to explore commercialization of the technology, which will provide a direct path to broad dissemination. The combination of 1300 nm AES and 3PM will transform our ability to image deep and fast and will have a broad impact on neuroscience where high- resolution, high speed imaging deep within an intact brain is required. The team members are active proponents of diversity, equity and inclusion (DEI) in their institutions, and will integrate the goals of this research program with advancing DEI.

抽象的活动的光学记录对于探测神经系统至关重要，因为它们提供高分辨率、非侵入性测量，范围从单个神经元到完整神经系统中的整个群体，以及然而，这些方法很容易与遗传方法结合以提供细胞类型特异性记录。穿透深度、空间尺度和时间分辨率仍然是光学成像的主要挑战。由于散射脑的分辨率成像通常是通过多光子显微镜（MPM）来实现的。非线性激发过程，多光子成像的发展关键取决于超快技术，特别是从二次谐波产生 (SHG) 和 2- 的首次演示开始。光子荧光（红宝石激光）、首创2光子成像（锁模飞秒激光）、至最深3光子到目前为止，光子成像（长波长光学参量放大器），多光子成像的进展已经这项研究计划在很大程度上是由激光技术的创新推动的。我们将开发和传播新一代超快激光器和多光子成像工具。将能够以细胞和亚细胞分辨率对结构和功能进行深度、快速和大规模成像。为了接近“光子预算”定义的基本极限，我们将开发一种自适应激发源 (AES) 在 1300 nm 下进行深层组织 3 光子显微镜 (3PM) 通过提供样品的结构信息。对于激光源，AES 仅在感兴趣区域 (ROI) 内生成按需脉冲并转换我们将把传统的多光子显微镜集成到用于 ROI 的“随机访问”显微镜中。我们将进一步测试和优化带有高速扫描仪的 AES 光子预算和扫描系统。在动物模型的三个概念验证实验中验证新成像技术的性能。该研究涉及 PI（Chris Xu）和联合研究者（Alex Kwan、Frank Wise、此外，我们将与行业合作伙伴合作探索商业化。该技术的发展将为 1300 nm AES 和 AES 的广泛传播提供直接途径。 3PM 将改变我们深度、快速成像的能力，并对神经科学产生广泛影响，其中高完整大脑深处需要高分辨率、高速成像，该团队成员是积极的支持者。其机构中的多样性、公平性和包容性（DEI），并将整合该研究计划的目标随着DEI的推进。