Five-dimensional optoacoustic tomography for large-scale electrophysiology in scattering brains

用于散射脑大规模电生理学的五维光声断层扫描

• 批准号: 9055849
• 负责人: Daniel Razansky
• 金额: $ 20.62万
• 依托单位: TECHNICAL UNIVERSITY OF MUNICH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9055849
• 关键词: Action Potentials; Adult; Algorithms; BRAIN initiative; Blood; Brain; Brain region; Cell Culture Techniques; Cells; Cephalic; Data; Development; Diagnosis; Dyes; Electrophysiology (science); Ensure; Equipment; Fluorescence; Genetic; Geometry; Goals; Hippocampus (Brain); Image; Label; Lasers; Life; Light; Methods; Microscopy; Monitor; Mus; Neurons; Neurosciences; Optics; Organism; Pattern; Penetration; Performance; Physiological Processes; Population; Preparation; Process; Reporter; Resolution; Scanning; Signal Transduction; Staging; Stimulus; System; Techniques; Technology; Time; Validation; Variant; Zebrafish; base; brain metabolism; cranium; hemodynamics; image reconstruction; imaging modality; imaging system; millisecond; multi-photon; nervous system disorder; neuroimaging; novel; novel strategies; optical imaging; public health relevance; relating to nervous system; response; screening; spatiotemporal; temporal measurement; tomography; tool; two-photon; voltage

 DESCRIPTION (provided by applicant): Neuroscience has an essential requirement for large-scale neural recording technologies to ensure rapid progress in the understanding of brain function, diagnosis and treatment of neurological disorders. At present, a large gap exists between the localized optical microscopy studies looking at fast neuronal activities at single cell resolution level and the whole-brain observations of slow hemodynamics and brain metabolism provided by the macroscopic imaging modalities. The proposed two-year project is aimed at developing novel optoacoustic neuroimaging tool to volumetrically monitor activity of large distributed neuronal populations with unprecedented temporal resolution in the millisecond range. This goal will be accomplished by constructing a tomographic optoacoustic scanner to simultaneously record three- dimensional optoacoustic data in a spherical geometry. The high temporal resolution in volumetric recordings will make it possible to directly track action potentials using fast voltage-sensitive indicators. The resulting scanner will simultaneously record activity from large fields of view in scattering brains, potentially reaching the mouse hippocampus and beyond. Rapid tuning of the excitation laser wavelength will be further employed to enable simultaneous acquisition of five-dimensional (i.e. real-time volumetric multi- spectral) optoacoustic data, which will provide enhanced sensitivity in detecting rapid spectral variations of the activity reporters. The plan of action includes screening of several potential candidates for voltage imaging, including genetic indicators, using neuronal cell cultures. System validation will be subsequently performed in isolated scattering brains of adult zebrafish and mice, aiming at establishing sensitivity and spatiotemporal resolution metrics in detecting voltage signal transients due to spontaneous and stimulus- driven activity patterns. While the major importance of 3D optical microscopy techniques like two-photon imaging has been highlighted recently within the BRAIN initiative, they are generally limited to looking at small (~1mm3) superficially-located volumes with relatively slow temporal resolution, further requiring highly invasive cranial windows that can alter activity. In contrast, the proposed method is tailored for non-invasive deep brain observations and is ideal for simultaneous imaging of large fields of view at rapid volumetric frame rates and resolution approaching cellular scale. Furthermore, other optoacoustic approaches looked so far only at hemodynamic changes and blood oxygenation, slow and indirect indicators of brain activity. The proposed study will be the first to examine fast optoacoustic signatures of voltage-sensitive indicators, thus shattering the longstanding penetration barrier of optical microscopy in scattering brains.

 描述（由申请人提供）：神经科学对大规模神经记录技术有基本要求，以确保在理解脑功能、诊断和治疗神经系统疾病方面取得快速进展。目前，在单细胞快速神经元活动的局部光学显微镜研究之间存在很大的差距， 分辨率水平和由宏观成像模式提供的缓慢血流动力学和脑代谢的全脑观察。拟议的为期两年的项目旨在开发新型光声神经成像工具，以前所未有的毫秒范围内的时间分辨率对大型分布式神经元群体的活动进行体积监测。这一目标将通过构建一个断层光声扫描仪来实现，以同时记录三维光声数据在一个球形几何形状。容积记录中的高时间分辨率将使使用快速电压敏感指示器直接跟踪动作电位成为可能。由此产生的扫描仪将同时记录分散的大脑中大视野的活动，可能到达小鼠海马体和更远的地方。将进一步采用激发激光波长的快速调谐来实现五维（即实时体积多光谱）光声数据的同时采集，这将在检测活性报告物的快速光谱变化中提供增强的灵敏度。该行动计划包括利用神经元细胞培养物筛选几个电压成像的潜在候选者，包括遗传指标。随后将在成年斑马鱼和小鼠的分离散射脑中进行系统验证，旨在建立检测自发和刺激驱动活动模式引起的电压信号瞬变的灵敏度和时空分辨率指标。虽然像双光子成像这样的3D光学显微镜技术的重要性最近在BRAIN计划中得到了强调，但它们通常仅限于观察时间分辨率相对较低的小（约1mm3）表面体积，进一步需要高度侵入性的颅窗，可以改变活动。相比之下，所提出的方法是专为非侵入性的深部脑观察，是理想的同时成像的大视野在快速的体积帧速率和分辨率接近细胞规模。此外，到目前为止，其他光声方法只关注血液动力学变化和血氧，这是大脑活动的缓慢和间接指标。这项拟议中的研究将是第一个研究电压敏感指标的快速光声特征的研究，从而打破了光学显微镜在散射大脑中长期存在的渗透障碍。