DESCRIPTION (provided by applicant): Magnetic resonance (MR) imaging (MRI) and in vivo MR spectroscopy (MRS) techniques have become indispensable tools for imaging brain structure, function, connectivity, neurochemistry and neuroenergetics, and for investigating neurological disorders. However, it remains a challenge to achieve superior MRI/MRS detection sensitivity, spatial and temporal imaging resolutions adequate for addressing fundamental and challenging neuroscience questions even with the most advanced technology. The prevailing paradigms for improving MRI/MRS performance largely invoke increasing the magnetic field strength, which may have reached practically achievable limits for human studies due to many technological and safety (i.e., high specific absorption rate (SAR)) concerns, and increasing the receiver channel count which is also ultimately limited due to noise characteristics of coils of decreasing size. To alleviate these major limitations, this R24 proposal relies on the interdisciplinary research efforts and expertise of leading experts across two institutions to pioneer an entirely innovative engineering solution that uses the ultra-high dielectric constant (uHDC) material incorporated with ultrahigh-field MRI/MRS techniques for synergistically increase signal-to-noise ratio and concurrently reduce RF power demand, and for achieving unprecedented improvements in spatial/temporal resolution over the current state-of-the-art MR technologies. We will develop and optimize prototypes of uHDC material for human brain studies using 7 Tesla (T) and 10.5T whole-body human scanners. Moreover, we will exploit and assess the new utility and capability of the innovative uHDC-MR technology for cutting-edge neuroscience research. One pilot study is the functional mapping of neural circuits and resting-state connectivity at the level of columns and cortical layers in the human visual cortex with ultrahigh spatial resolution 1H MRI at 7T, complemented with anatomical connectivity derived from diffusion weighted images for tractography. The other one is to combine the uHDC technique with newly developed in vivo 31P and 17O MRS techniques for noninvasively and reliably imaging the cerebral metabolic rates of oxygen consumption and ATP, cerebral blood flow, oxygen extraction fraction and nicotinamide adenine dinucleotide (NAD) redox state in the human brain at resting and activated states. The proposed research will shift the current paradigm of neuroimaging development towards an efficient, cost-effective engineering solution that will attain multiplicative gains from uHDC and ultrahigh fields, and lead to next generation o MRI/MRS technology and instrument. Such advancement will accelerate human brain imaging and neuroscience research beyond what can be achieved through existing technology, promote new research directions, and transform our understanding regarding the human brain function and dysfunction.

PUBLIC HEALTH RELEVANCE: The proposed research will overcome the current technical barriers, and significantly reinvigorate MRI and in vivo MRS imaging technologies at ultrahigh field. This advancement will open new opportunities to perform cutting-edge research for addressing challenging neuroscience questions in the perspective of brain functionality at the level of elementary computational units and neuroenergetics at the cellular level with unprecedented imaging capability, and ultimately for understanding human brain physiology and function, neural circuitry and network under various brain states. Although, this proposal focuses on pushing the limit of human brain imaging at ultrahigh field, the same technology could be applied to clinical MRI scanners at 1.5T and 3T for brain and other organs, thus, translational research and clinical diagnosis can also benefit from much improved imaging sensitivity, spatial/temporal resolution, reliability and reproducibility that are essential for improving individualized medicine in disease diagnosis and treatment monitoring.