Time-Reversal Optical Focusing for Noninvasive Optogenetics

 描述（由申请人提供）：我们的身体呈现光学不透明，因为生物组织强烈散射光。尽管诸如多光子激发的进步已经通过选通散射光实现了对光学成像的更深入的访问，但是这些策略仍然是不可行的。 基本上限于浅表深度（~ 1 mm）。加州理工学院的Yang团队率先将光学散射的时间反演对称性作为“关闭”组织散射的直接策略。2012年，Yang的团队展示了一种基于数字光学相位共轭的时间反转超声编码（TRUE）聚焦策略，以灵活可控地提供 离体组织中的高光功率。在这里，我们提出了实现一个数字真聚焦在体内与快速波前传感和波前调制。如果成功，这种新方法将使光聚焦到活体啮齿动物大脑中4 mm的深度，焦点最小宽度接近单细胞水平（30 m）。这种在生物组织内产生紧密激光焦点的能力可以转化为功能成像和大脑操纵的强大新方法。我们可以扫描焦点来执行荧光、拉曼和其他类型的成像。我们还可以使用焦点以高精度选择性地消融组织。该技术还将实现光遗传学的非侵入性聚焦光传输-这是我们拟议研究的重点。数字TRUE的使用将使光遗传学技术能够扩展到脑深部，实现非侵入性、空间特异性的激发/抑制。在这个项目中，我们将通过体内麻醉记录，利用实时回路活动反馈来补充定义的脑回路的光遗传学控制的力量，以建立数字TRUE作为光遗传学研究的新的非侵入性光学工具。 这项拟议的工作代表了光遗传学的一项强大的使能技术-可能为光遗传学开辟新的应用和新的方法。除了光遗传学，数字TRUE还有望对生物医学研究和诊断产生更广泛的影响。Digital TRUE在深层组织中聚焦光的独特能力在体内深层组织光学成像和生化分析方面具有巨大潜力。虽然有重大的技术挑战要解决，我们提出的项目是一个重要的和必要的一步，在推进TRUE发挥其全部潜力。

 DESCRIPTION (provided by applicant): Our bodies appear optically opaque because biological tissue scatters light strongly. Although advances such as multiphoton excitation have enabled deeper access for optical imaging by gating out scattered light, these strategies are still fundamentally limited to superficial depths (~ 1 mm). Yang's group at Caltech has pioneered time-reversal symmetry of optical scattering as a direct strategy to 'turn off' tissue scattering. n 2012, Yang's group demonstrated a time-reversal ultrasound-encoded (TRUE) focusing strategy based on the use of digital optical phase conjugation to flexibly and controllably deliver high optical power in ex vivo tissues. Here we propose to realize a digital TRUE focusing in vivo with rapid wavefront sensing and wavefront modulation. If successful, this novel approach will enable light focusing up to a depth of 4 mm in a living rodent brain, with a focal minimal width close to single-cell level (30 ¿m). This ability to render a tight laser focus within biological tissues can be translated into powerful new methods for functional imaging and manipulation of the brain. We can scan the focus spot to perform fluorescence, Raman, and other types of imaging. We can also use the focus spot to selectively ablate tissues with high precision. This technology will also enable non-invasive focused light delivery for optogenetics - a key application area that is the focus of our proposed research. The use of digital TRUE would enable the extension of optogenetic techniques to the deep brain for non-invasive, spatially specific, excitation/inhibition. For this project, we will complement the power of optogenetic control of defined brain circuits with real-time circuit activity feedback, via in vivo anaesthetizd recordings, to establish digital TRUE as a new, noninvasive optical tool for optogenetic studies. This proposed work represents a powerful enabling technology for optogenetics - potentially opening up new applications and new methods for optogenetics. In addition to optogenetics, digital TRUE promises broader impacts on biomedical research and diagnosis. Digital TRUE's unique capability to focus light in deep tissues holds tremendous potential in enabling in vivo deep tissue optical imaging and biochemical analysis. Although there are significant technical challenges to be tackled, our proposed project is an important and necessary step in advancing TRUE to reach its full potential.