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

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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.