High-Resolution Multiplexed MRI at Ultrahigh Field - PROJECT SUMMARY Magnetic resonance imaging (MRI) has revolutionized diagnostic radiology and medicine over the last five decades operating at field strengths from 0.5T to 3T. Ultra-high-field (UHF) MRI offers increased signal-to-noise ratio and chemical shift dispersion, which provide unique opportunities to further enhance the clinical impact of MRI, particularly for diagnosis of diseases with invisible structural lesions at lower field strengths, such as epilepsy, multiple sclerosis, and neurodegenerative disorders. Over the last two decades, especially after the US Food and Drug Administration (FDA) approved the Siemens Magnetom 7T Terra for clinical use in 2017, significant progress has been made in improving UHF MRI technology for research and clinical applications, The primary goal of this project is to develop a novel UHF MRI technology to provide an unprecedented capability for ultrafast, high-resolution multiplexed imaging of multiple molecules. The proposed technology is based on our recent breakthrough in 1H-MR spectroscopic imaging without water suppression at 3T and leverages the unique advantages of 7T MRI to improve the mapping of overlapping metabolite resonances and subtle tissue property changes. By utilizing the unsuppressed water spectroscopic signals, the technology will generate quantitative tissue property maps, including T1, T2, T2’, spin density, myelin water fraction, and magnetic susceptibility at 0.7×0.7×0.7 mm3 resolution. The technology will also simultaneously measure and quantify multiple endogenous metabolites and neurotransmitters, including N- acetylaspartate, myo-inositol, choline, creatine, glutamate, glutamine, lactate, γ-aminobutyric acid, glutathione, taurine, and N-acetylaspartylglutamate at 1.8×1.8×1.8 mm3 resolution. The technology will also have built-in mechanisms to correct the effects of system imperfections at 7T, including B0 inhomogeneity and drift, B1 inhomogeneity, as well as subject motion, ensuring accurate and robust biomarker quantification under practical imaging conditions. The specific aims of the proposed project are: a) to develop a novel data acquisition sequence to enable ultrafast high-resolution multiplexed MRI at 7T, b) to build an AI-powered data processing pipeline for reconstruction and quantification of all the molecular and tissue property biomarkers, and c) to evaluate the performance of the proposed technology through a multi-site experimental study on phantoms and human subjects. When fully developed, the proposed technology will deliver an unprecedented imaging capability that can provide quantitative structural, physiological and molecular biomarkers for multifaceted tissue characterization. Such a capability will greatly enhance our ability to characterize tissues in normal and diseased states and address an urgent unmet need in precision healthcare of neurodegenerative diseases.