Wavefront sensor for deep imaging of the brain

用于大脑深度成像的波前传感器

基本信息

批准号：
9136863
负责人：
CHRIS XU
金额：
$ 24.15万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-03 至 2018-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): 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 strong tissue scattering, the penetration depth and imaging speed of optical microscopy in the mouse brain are very limited. The constraints in depth and speed make large scale, volumetric imaging of mouse brain activity, e.g., functional imaging of an entire mouse cortical column, out of reach of current imaging techniques. Adaptive optics (AO) have proven to be valuable for in vivo brain imaging, and will have even larger impact for deep brain 3-photon microscopy; however, existing AO techniques require iterative optimization using fluorescence signal when imaging deep within scattering mouse brains, which is incompatible with large scale, volumetric imaging over a large range of depth and field of view. This program will involve the development of a novel 2-photon Shack-Hartmann wavefront sensor (2P-SHWS) for direct measurement of optical wavefront deep within scattering mouse brain, followed by demonstration of the performance of the proposed 2P-SHWS for in vivo multiphoton imaging of mouse brain structure and function. This innovation is based on the realization that the physical principles for deep tissue imaging and deep tissue direct wavefront sensing are essentially the same because they both rely on the information carried by the ballistic photons, and they both require the suppression of the contributions from the scattered excitation photons. Therefore, parallel to the rationales behind multiphoton deep tissue imaging, deep tissue wavefront sensing should also benefit tremendously by the use of long wavelength and nonlinear excitation. The successful completion of this program will provide the unprecedented capability of direct wavefront measurement throughout the depth of the mouse neocortex (800 to 900 µm deep) and at an update rate of 1 to 10 Hz (depth dependent) during imaging. With its deep tissue wavefront sensing capability, high update rate, relatively simple implementation, and zero additional photobleaching and phototoxicity, 2P- SHWS is ideally positioned to transform our ability for large-scale, volumetric recording of mouse brain activity.

描述（适用提供）：光学成像在我们的努力中具有巨大的希望，可以理解大脑功能。光学脑成像的主要挑战是深度和速度。由于组织散射强，小鼠脑中光学显微镜的穿透深度和成像速度非常有限。深度和速度的约束使小鼠脑活动的体积成像，例如，整个小鼠皮层柱的功能成像，无法触及当前成像技术。事实证明，自适应光学器件（AO）对于体内脑成像很有价值，并且对深脑3光子显微镜的影响更大。但是，现有的AO技术需要使用荧光信号进行迭代优化，当在散射小鼠大脑内成像时，这与大规模的大规模不兼容，在大量深度和视野范围内进行体积成像。该程序将涉及开发一种新型的2光子Shack-Hartmann波前传感器（2P-SHWS），以直接测量小鼠大脑内部深处的光波叶，然后演示拟议的2P-SHW的性能，用于小鼠大脑结构和功能的体内多光子成像。这项创新是基于意识到，深层组织成像和深层组织直接波前传感器的物理原理本质上是相同的，因为它们都依赖弹道照片所携带的信息，并且他们都需要从散布的兴奋照片中抑制贡献。因此，与多光子深组织成像背后的理由平行，深层组织波前灵敏度也应通过使用长波长和非线性兴奋而极大地受益。该程序的成功完成将在整个小鼠新皮层深度（深度为800至900 µm）中，在成像过程中以1至10 Hz（深度）的更新速率提供直接波前测量的空前能力。 2p-SHW具有深层组织波前灵敏度能力，高更新速率，相对简单的实现以及零额外的光漂白和光毒性，理想的位置是改变我们对小鼠脑活动的大规模，体积记录的能力。