Transcranial Functional Ultrasound in Adult Humans - The World Health Organization characterizes neurological disorders as one of the greatest threats to public health, a leading contributor to disability-adjusted life years, and the second leading cause of global deaths. Across the world, mental disorders represent 10% of global disease burden, impacting an estimated 1 billion people. These disorders carry a huge economic burden, and while estimates and projections of total costs vary wildly, mental health carries a cost in the United States of at least $200 billion annually. This significant burden motivates improvements in understanding of disease etiology, diagnosis, prevention, and treatment. Many tools exist to examine such issues, but there is still a need for a functional imaging tool that is low-cost while maintaining high-spatial and temporal resolution. This need can be met with transcranial functional ultrasound imaging. Here, we build off new functional ultrasound imaging techniques demonstrated in rodent models, human neonates and in adult humans with exposed brains, to develop fully non-invasive, functional ultrasound for adult humans. Translating functional ultrasound to humans in a broadly useful way has been difficult because transcranial imaging requires lower imaging frequencies to better penetrate the skull, but this in turn reduces the sensitivity to small changes in blood flow-the source of the functional ultrasound's signal. New signal processing and machine learning techniques-developed by our group and others-enhance the performance of low velocity blood flow imaging, particularly in the high clutter and noise environments encountered transcranially, and using some of these methods, our preliminary data provides the first ever demonstration of transcranial functional ultrasound in adults. Additionally, because transcranial ultrasound struggles with establishing precise anatomical orientation and general localization, we will integrate image-to-physical tracking and a two-sided, dual-transducer imaging configuration with our advanced imaging methods to turn transcranial functional ultrasound into a broadly useful tool. We hypothesize that our advanced techniques integrated with tracking and multiple transducers will enable reliable ultrasound-based functional assessment in nearly all subjects.
