Time-Reversal Optical Focusing for Noninvasive Optogenetics

 描述(申请人提供)：我们的身体看起来不透明，因为生物组织强烈地散射光线。尽管诸如多光子激发之类的技术进步使得光学成像能够通过选通散射光更深入地获取，但这些策略仍然是 基本上仅限于浅层深度(~1毫米)。加州理工大学的杨的团队开创了光学散射的时间反转对称性，将其作为一种直接关闭组织散射的策略。2012年，杨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，以灵活且可控地传递 体外组织中的高光功率。在这里，我们提出了利用快速波前传感和波前调制来实现活体数字真聚焦。如果成功，这种新的方法将使光在活的啮齿动物大脑中聚焦到4毫米的深度，焦点的最小宽度接近单细胞水平(30？m)。这种在生物组织内呈现紧密激光焦点的能力可以转化为强大的新方法，用于大脑的功能成像和操作。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来高精度地选择性地消融组织。这项技术还将使光遗传学的非侵入性聚焦光传输成为可能--这是我们拟议研究的一个关键应用领域。数字TRUE的使用将使光遗传技术能够扩展到大脑深处，以实现非侵入性的、空间上特定的兴奋/抑制。在这个项目中，我们将通过活体麻醉记录，通过实时电路活动反馈来补充定义的大脑电路的光遗传控制的能力，以建立数字TRUE作为光遗传学研究的一种新的、非侵入性的光学工具。这项拟议的工作代表了光遗传学的一项强大的使能技术-潜在地为光遗传学开辟了新的应用和新的方法。除了光遗传学，Digital 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线的独特能力在实现体内深层组织光学成像和生化分析方面具有巨大的潜力。尽管有重大的技术挑战需要解决，但我们提议的项目是推动TRUE充分发挥其潜力的重要和必要的一步。

 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.