CAREER: All-Acoustic Image-Guided Implantable Microscopic Ultrasound Neuromodulation

职业：全声图像引导植入式显微超声神经调节

• 批准号: 1942839
• 负责人: Mehdi Kiani
• 金额: $ 50万
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1942839&HistoricalAwards=false
• 关键词: CAREER; Acoustic; Image; Guided; Implantable

Neuromodulation has the potential to map neural functions; enhance our perceptual, motor, and cognitive capabilities; and restore sensory and motor functions lost through injury or disease. Despite several decades of research and development, state-of-the-art noninvasive neuromodulation techniques still suffer from poor spatial resolution (more than several millimeters), while implantable electrical and optical methods with finer spatial resolution only provide a limited coverage of hundreds to thousands of neurons through extremely invasive parenchymal implantation. These limitations are fundamental, and further optimization of these technologies cannot simultaneously meet the critical requirements of minimal invasiveness, microscopic spatial resolution (hundreds of micrometers and below), and whole brain coverage. This program includes scientific research in a radical approach that explores ultrasound, which has already been effective in transcranial neuromodulation with sub-centimeter resolution, as a minimally invasive implantable means for unprecedented microscopic-resolution neuromodulation at large scale. The proposed research will yield a unique building block for a comprehensive set of minimally invasive neural interfaces. It will open new opportunities in neuroscience with significant improvements in spatial resolution and coverage of neuromodulation of the brain, initially in animals. Ultimately, it will also have huge translational potential for many clinical applications in humans, such as the treatment of neurological and psychiatric disorders and brain-machine interfaces. Leveraging the multidisciplinary nature of the research, this program also includes an integrated outreach and educational component created around a "Troubleshooting and Inquiry-based Learning (TIL) Framework" to enhance students' learning of principles and research skills at different education levels. Transforming an undergraduate circuit course with the TIL framework will enhance the research skills, problem solving, and creative thinking of many undergraduate students. An annual week-long summer workshop for teachers with educational TIL-based hands-on and in-class computer-game-based modules will educate K-12 teachers and their students from districts underrepresented in the science, technology, engineering, and mathematics (STEM) fields in this research. A TIL-based "Ultrasonically Transferred Song" hands-on module for pre-college female students will attract them to the engineering profession and educate them in this research. A new medical-device course will educate graduate students in this field.This program will explore implantable microscopic ultrasound stimulation (IuUS) with minimally invasive modulation of the whole brain with the spatial resolution of hundreds of micrometers and below. This program will establish the fundamental basis for IuUS, in which an ultrasound transducer array is implanted on the brain surface (partially removed skull) with no parenchymal penetration to electronically steer highly focused ultrasound beams towards different neural targets. Such a system can be utilized in basic neuroscience experiments to address the most fundamental scientific questions in ultrasound neuromodulation: underlying mechanism, efficacy, and safety. This work will explore and establish vibro-acoustography for high energy efficiency in IuUS. It will investigate fundamental limits of spatial resolution and coverage as well as energy efficiency in IuUS by developing numerical and computational models based on wave equations to explore effects of different transducer geometries, frequencies, and configurations as well as their interactions with tissue and electronics. To manage post-implantation uncertainties (e.g. micromotions), this work will explore and create a learning-based all-acoustic image-guided system for accurate anatomical targeting. An on-chip machine-learning model with offline training will be developed to dynamically map changes in the profile of acoustic beams to micromotions and tissue changes in a fast and accurate fashion. An inductively interrogated closed-loop (recording and stimulation) system-on-chip with novel circuitry will also be developed for IuUS. Finally, a system-level demonstration will establish the fundamental basis for IuUS.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.

神经调节具有映射神经功能的潜力;增强我们的感知，运动和认知能力;并恢复因损伤或疾病而失去的感觉和运动功能。尽管经过了几十年的研究和开发，最先进的非侵入性神经调节技术仍然存在空间分辨率差（超过几毫米）的问题，而具有更精细空间分辨率的可植入电学和光学方法通过极侵入性实质植入仅提供数百至数千个神经元的有限覆盖。这些限制是根本性的，这些技术的进一步优化无法同时满足微创、微观空间分辨率（数百微米及以下）和全脑覆盖的关键要求。该计划包括以激进的方法探索超声的科学研究，超声在亚厘米分辨率的经颅神经调节中已经有效，作为一种微创植入式手段，用于大规模前所未有的显微分辨率神经调节。拟议的研究将为一套全面的微创神经接口提供一个独特的构建模块。它将为神经科学开辟新的机会，首先在动物中显着提高空间分辨率和大脑神经调节的覆盖率。最终，它还将在人类的许多临床应用中具有巨大的转化潜力，例如治疗神经和精神疾病以及脑机接口。利用研究的多学科性质，该计划还包括围绕“故障排除和基于探究的学习（TIL）框架”创建的综合推广和教育组件，以提高学生在不同教育水平上对原则和研究技能的学习。用TIL框架改造本科电路课程将提高许多本科生的研究技能、解决问题能力和创造性思维。一年一度的为期一周的暑期研讨会，为教师提供基于教学实践和课堂计算机游戏的模块，将教育K-12教师和他们的学生，他们来自科学，技术，工程和数学（STEM）领域。一个基于TIL的“超声波传输的歌曲”动手模块，为大学前的女学生将吸引他们到工程专业，并在这项研究中教育他们。一个新的医疗设备课程将培养该领域的研究生。该计划将探索植入式显微超声刺激（IuUS），其具有数百微米及以下的空间分辨率，可对整个大脑进行微创调制。该计划将为IuUS奠定基础，其中超声换能器阵列被植入脑表面（部分切除的颅骨），没有实质穿透，以电子方式将高度聚焦的超声波束转向不同的神经靶点。这样的系统可以在基础神经科学实验中使用，以解决超声神经调节中最基本的科学问题：潜在的机制，有效性和安全性。这项工作将探索和建立IuUS的高能量效率的振动声图。它将通过开发基于波动方程的数值和计算模型来研究IuUS中空间分辨率和覆盖范围以及能量效率的基本限制，以探索不同换能器几何形状，频率和配置的影响以及它们与组织和电子器件的相互作用。为了管理植入后的不确定性（例如微动），这项工作将探索和创建一个基于学习的全声学图像引导系统，用于精确的解剖定位。将开发具有离线训练的片上机器学习模型，以快速准确地将声束轮廓的变化动态映射到微动和组织变化。还将为IuUS开发具有新型电路的感应询问闭环（记录和刺激）片上系统。最后，系统级演示将为IuUS奠定基础。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

A 16-Channel High-Voltage ASIC with Programmable Delay Lines for Image-Guided Ultrasound Neuromodulation

• DOI: 10.1109/biocas54905.2022.9948689
• 发表时间: 2022-10
• 期刊: 2022 IEEE Biomedical Circuits and Systems Conference (BioCAS)
• 作者: Ardavan Javid;Chenyuan Zhao;M. Kiani