Project Summary/Abstract Neurologic diseases affect as many as one billion people worldwide and are a major cause of disability and human suffering. Current standard of care imaging (contrast-enhanced MRI) is extremely limited to detect many neurological and neurodegenerative diseases. MR spectroscopic imaging (MRSI) has a great potential to supplement routine clinical MRI for clinical conditions including brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating diseases, and infectious brain lesions. Gadolinium contrast agents have incomplete clearance, and repeated use of contrast-enhanced imaging has recently received an FDA warning due to brain accumulation. MRSI does not use contrast material and has no/minimal risk for patients. 3D encoded MRSI methods provide high sensitivity per unit time and unit volume. Presurgical and radiation treatment planning will greatly benefit from full 3D information, ideally with isotropic resolution. Echo-planar spectroscopic imaging (EPSI) based 3D whole-brain MRSI have been on most scanner platforms, and are probably the most commonly used fast MRSI techniques to date. The primary limitation of 3D MRSI has been magnetic B0 field inhomogeneity, which broadens lineshapes and diminishes spectral quality in about 40% of the brain (e.g., mesial temporal lobe, inferior frontal cortex, medial frontal gyrus, brainstem, and cerebellum). This limits the ability to evaluate critical brain regions such as mesial temporal lobe (MTL) and orbitofrontal cortex (OFC), which have pivotal roles across neurologic disorders. Recently, we introduced a radically novel concept called Unified Coil (UNIC), which includes innovative decoupling methods to bring the distance between separate shim and RF loops to zero millimeters. Both RF and shim coils are at a close proximity to the target organ for maximized RF SNR and shimming. Physical law implies that the only effective way to shim local inhomogeneous field (as in MTL/OFC) is by placing size-matched shim coils which generate opposite high-order field to counteract the inhomogeneous field. Our hypothesis is that UNIC will dramatically increase brain volume coverage and allow true metabolic evaluation of the entire brain using 3D MRSI. This will enable broader applications in patient management with various neurological disorders. The proposed study will prototype the first UNIC head coil (Aim 1), optimize the technique in shimming performance and hardware complexity (Aim 2), and assess the technique quantitatively in improving brain coverage of 3D MRSI (Aim 3). Successful completion of this study will largely resolve the longstanding B0 inhomogeneity issue in whole brain. Such coils can be widely used to benefit the entire MRSI community by advancing B0 shimming technology. It will help catalyze the widespread clinical acceptance of MRSI.