Project Summary/Abstract: Networks of small nuclei in the meso and diencephalon (thalamus, hypothalamus, brainstem, etc.) and their connections to the cortex are critical to understanding consciousness and the onset of sedation during anesthesia. Yet despite their importance for daily survival, the functional connections among nuclei and between nuclei and cortex remain poorly understood. Ultra high field MRI at or above 7 Tesla (7T) provides several benefits for studying deep brain nuclei in humans, including improved image Signal to Noise Ratio (SNR) and improved contrast (CNR) for susceptibility based structural (SWI) and functional (BOLD) imaging as well as greater T1-dispersion. In addition to problems stemming from their small size, the study of nuclei at 7T is impeded by both static and dynamic variations in the background magnet field (B0) at these locations. These B0 variations cause image artifacts such as ghosting, signals voids, blurring, and geometric distortion. ΔB0 order and cannot compensate dynamic ΔB0. In the current project, we propose a comprehensive field Innovation: Standard B0 shim coils on commercial MRI scanners can only compensate static up to 2nd monitoring and control system to null high spatial order static and dynamic field variations at 7T. The system will use integrated RF-shim coil elements for maximum shimming and RF efficiency, NMR field probes for field monitoring, and feedback control for real-time shim updating. We are the first to combine these technologies in a unified system capable of largely overcoming the obstacle of ΔB0 in 7T MR imaging. Validation: We use the proposed system to (a.) reduce the standard deviation of B0 inhomogeneity on a slice-optimized basis over the whole brain; (b.) stabilize the phase of EPI time-series data; (c.) mitigate ghosting in multi-shot EPI; (d.) image and identify known functional networks between the brainstem and cortex in single subjects; and (e.) test a hypothesis based on animal models about the action of the anesthetic dexmedotomidine on a brainstem circuit involving three specific nuclei. Clinical benefit: By providing a new tool for studying the activity of brainstem nuclei during sedation, this project paves the way for future efforts to improve our understanding of neural circuits, develop safer site-specific anesthetic drugs, and potentially reduce post-operative delirium and cognitive impairment. Training: I am fortunate to be a part of the exceptionally rich neuroimaging environment at the MGH Martinos Center, one of the premier environments in the world for developing and validating the proposed field control technology. My K99/R00 proposal is designed to help me pivot from a MRI physicist into an independent investigator with enough background in neurobiology to ask clinically significant questions involving deep brain circuits and then develop targeted high-field MRI technology to answer them. To this end, I will require additional training, coursework, a...