In-situ Ultrasonically Sculpted Virtual Light Paths for Steerable Neural Imaging and Stimulation

用于可操纵神经成像和刺激的原位超声雕刻虚拟光路

基本信息

批准号：
1935849
负责人：
Maysamreza Chamanzar
金额：
$ 33万
依托单位：
Carnegie-Mellon University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1935849&HistoricalAwards=false
关键词：
situ Ultrasonically Sculpted Virtual Light

项目摘要

Optical imaging of tissue is the gold standard of biomedical imaging, especially in the central nervous system for high throughput structural and functional imaging of brain activity. The key advantage of optical methods is that light interacts with tissue non-invasively. Existing optical imaging techniques, however, suffer from an inability to deliver and collect light deep into the tissue with high spatial resolution. Scattering of light in tissue limits the resolution and penetration depth, rendering such methods based on external optics limited to the superficial layers of biological tissues. Additionally, in the context of the central nervous system, which harbors widely distributed neural circuits, system-wide interrogation would require either fast optical beam-steering capability or simultaneous multi-site illumination. Recent techniques based on patterning of light from outside the brain cannot reach deep into the tissue, since as light propagates through tissue, it undergoes diffraction, scattering, and absorption; as a result, the beam widens and the intensity of light rapidly falls below the threshold of excitation of opsins and optical reporters. The proposed project aims to address these shortcomings of the optical methods by using high frequency sound waves (ultrasound) to form a virtual relay lens in the tissue to access deep tissue for optical imaging. In this technique, the tissue itself is turned into an optical lens that enables imaging deeper structures. This ultrasonically defined lens can be moved around without disturbing the tissue for steerable imaging. This multidisciplinary project provides a unique educational and training environment for graduate and undergraduate students to learn about contemporary concepts in photonics, ultrasonics, and neural technologies for applications in functional and structural imaging of brain. Students from underrepresented minority groups will be trained through this research program.In this interdisciplinary project, the researchers will develop a non-invasive alternative to endoscopic imaging of brain that usually involve implanting a graded-index (GRIN) lens into the brain. Non-invasive ultrasonic waves will be used to sculpt virtual optical relay lenses by confining and steering light deep into the tissue without having to insert physical GRIN lenses. The result of the proposed research on ultrasonic sculpting of virtual steerable optical lenses within the brain tissue for relay imaging will be a significant breakthrough to facilitate light-based methods for non-invasive imaging of brain tissue by addressing two unmet needs, i.e., noninvasive deep penetration and beam steering. This ultrasonically defined virtual lens can both deliver or collect light through the depth of the tissue. A phased array of ultrasonic transducers will be designed to form reconfigurable virtual relay lenses within the tissue. A model system in which to test and develop this technology is the mouse brain tissue. To further amplify the impact of the proposed project, the developed acousto-optic imaging technique will also be provided to different neurobiology labs for testing various neuroscience hypotheses using optical methods for brain imaging and stimulation. The proposed project advances frontiers of optical imaging by introducing a novel technique for non-invasive deep tissue penetration and real-time optical beam steering to enable targeted imaging of deep structures. This can potentially transform our ability to target specific pathways within the brain tissue in animal models. The results will have indirect clinical implications for humans.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

组织光学成像是生物医学成像的黄金标准，特别是在中枢神经系统中，用于大脑活动的高通量结构和功能成像。光学方法的主要优点是光与组织非侵入性地相互作用。然而，现有的光学成像技术无法以高空间分辨率将光传送和收集到组织深处。组织中的光散射限制了分辨率和穿透深度，使得这种基于外部光学的方法仅限于生物组织的表层。此外，在拥有广泛分布的神经回路的中枢神经系统中，全系统询问将需要快速光束控制能力或同时多站点照明。最近基于大脑外部光图案化的技术无法深入组织，因为当光在组织中传播时，它会经历衍射、散射和吸收；结果，光束变宽，光强度迅速降至视蛋白和光学报告基因的激发阈值以下。该项目旨在通过使用高频声波（超声波）在组织中形成虚拟中继透镜以进入深层组织进行光学成像，从而解决光学方法的这些缺点。在这项技术中，组织本身变成了光学透镜，可以对更深的结构进行成像。这种超声波定义的透镜可以在不干扰组织的情况下移动，以进行可操纵成像。这个多学科项目为研究生和本科生提供了一个独特的教育和培训环境，让他们了解光子学、超声波和神经技术的当代概念，以应用于大脑的功能和结构成像。来自代表性不足的少数群体的学生将通过该研究项目接受培训。在这个跨学科项目中，研究人员将开发一种非侵入性的大脑内窥镜成像替代方案，该成像通常涉及将渐变折射率（GRIN）透镜植入大脑。非侵入性超声波将用于通过将光限制和引导到组织深处来雕刻虚拟光学中继透镜，而无需插入物理梯度折射率透镜。拟议的脑组织内虚拟可操纵光学透镜超声雕刻用于中继成像的研究结果将是一个重大突破，通过解决两个未满足的需求，即非侵入性深部成像，促进基于光的脑组织非侵入性成像方法穿透和光束转向。这种超声波定义的虚拟透镜可以传输或收集穿过组织深度的光。超声换能器相控阵将被设计成在组织内形成可重新配置的虚拟中继透镜。测试和开发这项技术的模型系统是小鼠脑组织。为了进一步扩大拟议项目的影响，开发的声光成像技术还将提供给不同的神经生物学实验室，以使用光学方法进行脑成像和刺激来测试各种神经科学假设。该项目通过引入一种非侵入性深层组织穿透和实时光束控制的新技术来推进光学成像的前沿，从而实现深层结构的靶向成像。这可能会改变我们在动物模型中针对脑组织内特定通路的能力。结果将对人类产生间接的临床影响。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。