CAREER: Super-resolution Ultrasound Imaging for High-resolution Functional Mapping of the Brain

大脑是人体中最复杂的器官。大脑是如何工作的仍然是人类最具挑战性的科学问题之一。几十年来，科学家和工程师不断开发和完善新的方法和技术，以推进我们对大脑的理解。在这些工具中，成像对于破译大脑至关重要，因为它使我们能够直接可视化和研究复杂的大脑组织及其组织和功能网络。然而，即使目前有大量可用的脑成像技术，我们探测大脑皮层以外的深层脑组织的能力仍然有限。这种限制在很大程度上可以归因于成像的物理学，这决定了我们可以看到的物体有多小和我们可以看到的物体有多深之间不可避免的权衡。这个缺点最终限制了我们探索大脑表层组织之外的能力，限制了我们理解人类大脑是如何整体工作的。因此，本CAREER提案的长期目标是通过开发一种新的超声成像技术来克服这一缺点，该技术可以在微观空间分辨率下探测大脑深部功能神经活动。我们的技术利用深度学习和超快超声成像的力量，打破了传统超分辨率超声成像速度的障碍。如果成功，这项革命性的新技术将成为一种范式转换成像工具，提供比以往任何时候都更精细的空间分辨率和更深入、更广泛的大脑功能映射。这种新成像技术的独特能力也将为基础神经科学研究和许多神经系统疾病应用中许多尚未开发的机会打开新的大门。CAREER计划的目标是开发一种新的、革命性的功能性脑成像技术，通过完整的头骨，在微米尺度上连续、实时地监测整个大脑的神经活动。推力1将侧重于通过开发基于深度学习的超分辨率成像技术来提高传统超分辨率超声成像的时间分辨率。Thrust 2将通过开发基于现代高速fpga的新型超快超声系统来解决与超声图像重建相关的计算挑战。推力3将专注于开发基于深度学习和新型3D超快成像技术的相位像差校正方法，以实现全脑的鲁棒完整颅骨成像。体内小鼠脑成像研究将在整个技术推力中进行，以评估和验证新开发的超分辨率成像技术的性能。如果成功，这项工作将产生一种新的、无辐射的、低成本的、可广泛使用的功能性脑成像技术，这将是第一个能够以高时空分辨率对体内深部脑神经活动进行无创探测的技术。除了技术上的推动外，这个CAREER方案还包括教育和推广项目，旨在向新一代学生灌输提高医疗保健标准的愿望，使所有患者都能获得最先进的治疗、诊断和筛查选择。通过提供研究机会，创建超声工程实验室，开发创新的教学策略，并建立新的课程，该职业建议将为这些学生提供必要的知识和工具，以在提供的机会中创造可操作的变化。该奖项反映了美国国家科学基金会的法定使命，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。

The brain is the most complex organ in the human body. How does the brain work remain one of the most challenging scientific problems for humanity. For decades, scientists and engineers continually develop and refine new methods and techniques to advance our understanding of the brain. Out of these tools, imaging is essential for deciphering the brain because it allows us to directly visualize and investigate the complex brain tissues and their organizations and functional networks. However, even with the multitude of brain imaging technologies that are currently available, our ability to probe deep brain tissues beyond the cerebral cortex is still limited. This limitation can largely be attributed to the physics of imaging, which dictate the inevitable trade-off between how small of an object we can see and from how deep we can see them. This shortcoming ultimately limits our ability to explore beyond the superficial tissues of the brain and to understand how the human brain works in its entirety. The long-term objective of this CAREER proposal, therefore, is to overcome this shortcoming by developing a new ultrasound imaging technology that can probe deep brain functional neural activities at a microscopic spatial resolution. Our technique leverages the power of deep learning and ultrafast ultrasound imaging to break the barrier of imaging speed for conventional super-resolution ultrasound. If successful, this transformative new technology will become a paradigm-shifting imaging tool that provides functional brain mapping at a much finer spatial resolution with a much deeper and wider territory than ever before. The unique capabilities of this new imaging technology will also open new doors for many under-explored opportunities in both basic neuroscience research and in many neurological disease applications. The goal of this CAREER proposal is to develop a new and transformative functional brain imaging technology that allows continuous, real-time monitoring of neural activities of the entire brain at a micron-scale through intact skull. Thrust 1 will focus on improving the temporal resolution of conventional super-resolution ultrasound imaging by developing deep learning-based super-resolution imaging techniques. Thrust 2 will address the computational challenges associated with ultrasound image reconstruction by developing a new ultrafast ultrasound system based on modern high-speed FPGAs. Thrust 3 will concentrate on developing phase aberration correction methods based on deep learning and novel 3D ultrafast imaging techniques to achieve robust intact skull imaging of the whole brain. In vivo mouse brain imaging studies will be conducted throughout the technical thrusts to evaluate and validate the performance of the newly developed super-resolution imaging techniques. If successful, the proposed work will result in a new, radiation-free, low-cost, and widely accessible functional brain imaging technique that will be the first to enable noninvasive probing of in vivo, deep-brain neural activities with high spatiotemporal resolution. In addition to the technical thrusts, this CAREER proposal also includes educational and outreach programs aimed to instill in the new generation of students the desire to improve the standard of healthcare such that all patients have access to state-of-the-art treatment, diagnostic, and screening options. By providing research opportunities, creating ultrasound engineering labs, developing innovative teaching strategies, and establishing new courses, this CAREER proposal will provide these students with the knowledge and tools necessary to create actionable changes within the opportunities presented.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.