PROJECT SUMMARY Detection of disease progression as well as evaluation of therapeutical interventions are important in the management of many neurological disorders. Metabolic alterations such as altered glucose metabolism often play a crucial role in conditions such as Alzheimer's and Parkinson's disease, and brain tumors. Magnetic Resonance Imaging (MRI) is commonly used to monitor neurological diseases due to its high sensitivity and excellent soft tissue image contrast. However, MRI has very limited capabilities to image active tissue metabolism. MR spectroscopic methods such as 1H, 13C, hyperpolarized 13C and 31P MR spectroscopic imaging (MRSI) are important MR research tools that can detect metabolism non-invasively in vivo. Unfortunately, none of these methods have reached clinical significance because of technical complexity, lack of robustness and/or low sensitivity. Deuterium metabolic imaging (DMI) is a new, MR-based method that can map active metabolism of deuterated substrates non-invasively in vivo. DMI is unique in that it is extremely robust, while providing good sensitivity and information content, and thus has great promise to be integrated in the clinic. The clinical potential of DMI has sparked rapid adoption by research groups worldwide, whereby DMI has primarily been implemented on (ultra)-high-field MR research scanners. However, such MR scanners (≥ 7T) are only available at specialized research sites and represent only ~1% of the broadly available 3T MR scanner base, and thus severely limit the availability of DMI. Our main goal is to assist DMI to become an accessible method to study larger, diverse patient populations and establish its added value to neuroimaging by increasing the spatial resolution of DMI and implement and validate the technique on a standard 3T MR scanner. The RF coil is one of the primary determinants of the sensitivity and overall performance of MRI and DMI. Aim 1 is dedicated to the design, optimization and construction of a multi-element 1H/2H RF coil for high-quality DMI and MRI of human brain. Emphasis is placed on high-sensitivity, whole-brain coverage for DMI while retaining clinical MRI quality and acceleration potential. Aim 2 is focused on novel acquisition and processing methods to provide robust 2H-based metabolic maps of cerebral glucose metabolism with increased sensitivity at 3T. Improved detection sensitivity is pursued through balanced steady-state free precession and proton decoupling. A complete processing pipeline will be developed for reproducible generation of 2H-based metabolic maps, cumulating in a user-friendly graphical user interface. Aim 3 is centered on establishing the reproducibility of DMI at 3T with test-retest scans on healthy subjects. Also, patients with brain tumors are studied to demonstrate the clinical applicability of DMI. Upon successful completion, this project will deliver the hardware (RF coil) and software (sequences, processing) necessary to achieve robust and reproducible DMI at clinical 3T MR scanners. These technical developments will drastically improve access to DMI and drive its further development and validation via use in larger, diverse patient populations in multi-site imaging trials.

PROJECT NARRATIVE Deuterium metabolic imaging (DMI) is a novel 3D method to image metabolism of deuterium-labeled substrates in healthy or diseased human brain and has shown great clinical potential to detect aberrant metabolism in patients with high grade brain tumors. To establish the clinical value of DMI on larger patient populations and different neurological diseases, the method must migrate from dedicated (ultra)-high-field research MR scanners to the more commonly available clinical field strength of 3T. Successful development of the technical innovations in this proposal will guarantee an optimal implementation of DMI at 3T, thereby driving its further development and validation via use in larger, diverse patient populations.