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.

组织的光学成像是生物医学成像的金标准，尤其是在中枢神经系统中，用于高通量的脑活动的高吞吐结构和功能成像。光学方法的主要优点是光无创地与组织相互作用。然而，现有的光学成像技术无法通过高空间分辨率将光线输送到组织深处。在组织中光的散射限制了分辨率和渗透深度，从而基于限制于生物组织表层的外部光学元件来渲染此类方法。此外，在中枢神经系统的背景下，该系统具有广泛分布的神经回路，系统范围的询问将需要快速的光束传动能力或同时的多站点照明。基于大脑外部光的光的最新技术无法深入组织，因为当光通过组织传播时，它会经历衍射，散射和吸收。结果，光束扩大，光的强度迅速降至Opsins和Optical Reporter的激发阈值以下。拟议的项目旨在通过使用高频声波（超声）在组织中形成虚拟继电器镜头来访问深层组织以进行光学成像，以解决光学方法的这些缺点。在这种技术中，组织本身变成了光学镜头，可以使成像更深的结构成像。这种超声定义的镜头可以四处移动，而不会干扰组织以进行可通的成像。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，以了解光子学，超声波和神经技术在大脑功能和结构成像中的应用中的当代概念。来自代表性不足的少数群体的学生将通过该研究计划进行培训。在这个跨学科项目中，研究人员将开发出一种非侵入性替代方案，用于对大脑的内窥镜成像，通常涉及将分级折射率（Grin）镜头植入大脑。非侵入性超声波将通过将光线限制在组织深处而无需插入物理咧嘴透镜的情况下，用于雕刻虚拟光继电器镜片。拟议的关于对脑组织内虚拟可传动光透镜进行超声波雕刻进行超声波雕刻的研究的结果将是一个重大突破性的突破性突破性，可以通过满足两种未满足的需求，即非侵入性深度渗透和横向转向和光束转向和光束转向，从而促进基于光的基于光的方法。这种超声定义的虚拟镜头可以通过组织深度传递或收集光。将设计一组超声波传感器的阶段阵列，以形成组织内的可重构虚拟继电器透镜。测试和开发该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，还将向不同的神经生物学实验室提供开发的声学成像技术，以使用光学方法来测试各种神经科学假设，以进行脑成像和刺激。拟议的项目通过引入一种用于非侵入性深层组织穿透和实时光束转向的新技术来推进光学成像的前沿，从而实现了深层结构的靶向成像。这可能会改变我们在动物模型中靶向脑组织内特定途径的能力。结果将对人类有间接的临床影响。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点评估和更广泛影响的评论标准来支持的。