Brain H2D MRS: Implemation and Initial Applications

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DESCRIPTION (provided by applicant) The long-term objective is to apply 2D 1H magnetic resonance spectroscopy (MRS) techniques in studies of pediatric neurological disorders. 1H MRS is valuable for evaluating neurological brain diseases. However, there are limitations in current clinical 1H MRS examinations. Most peaks are crowded in a narrow aliphatic spectral window, and numerous low concentration metabolites are overshadowed by a few metabolites present in higher levels, and much valuable information is lost. Most metabolites have coupled spins, and 2D MRS separates the peaks in a second frequency dimension, greatly increasing the information content of the data. Application of 2D MRS in clinical examinations will enhance the abilities for diagnoses and patient management, and improve the understanding of disease processes. The specific aims are: (1) to implement 2D spin-echo double-quantum MRS pulse sequences for in vivo measurement of brain metabolites in 1.5T clinical scanners: (1a) to implement a localized pulse sequence optimized for GABA measurement; (1b) to implement localized pulse sequences for general detection of metabolites; (1c) to implement whole-brain measurement pulse sequences for general detection of metabolites. (2) to assign and evaluate peaks detected in the normal brain: (2a) to acquire spectra from metabolite solutions; (2b) to acquire brain spectra and baselines due to macromolecules in a group of adult normal volunteers; (2c) to assign the in vivo peaks and measure metabolite levels, and to determine optimal pulse sequences for studies of Aim 3; (2d) to acquire age-matched control spectra from normal children. (3) to explore the utility of the 2D MRS techniques in patients between the ages of 7 and 11 years: (3a) to study the effects of the ketogenic diet (KD) on brain GABA levels in seizure patients; (3b) to measure the brain?s level of branched chain amino-acids (BCAA) and keto-acids (BCKA) in maple syrup urine disease (MSUD); (3c) to test the hypothesis that low levels of brain galactitol are present even under a lactose restrictive diet; (3d) to study unassigned, unusual spectral peaks found in routine clinical MRS examinations. A localized 1D double-quantum filtered MRS pulse sequence will be modified into several 2D double quantum MRS pulses for localized and whole brain measurement. Different pulse parameters will be used for different types of spin systems. A frequency selective coherent transfer pulse will be used for optimal detection of GABA, and a broadband coherent transfer pulse will be used for all other 2D pulse sequences. The measurement procedures will be applied to normal subjects first. MRS measured GABA level before and after initiation of KD therapy will be compared in seizure patients and correlated with response. The MRS measurement of BCAAs and BCKAs will be conducted during metabolic crisis and in normal conditions in MSUD and correlated with clinical condition and serum BCAA and urine BCKA. In galactosemia, 2D MRS will be used to look for low levels of galactitol, and the MRS results will be correlated with the urine galactitol levels. 2D MRS will also be used to characterize unusual peaks found in clinical practice.