Deep and fast imaging using adaptive excitation sources

使用自适应激励源进行深度快速成像

• 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
• 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

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.

摘要