In Vivo Magnetic Resonance Spectroscopy by J-Locked Chemical Shift Encoding for Determination of Neurochemical Concentration and Transverse Relaxation Time

Cell pathology in neuropsychiatric disorders has mainly been accessible by analyzing postmortem tissue samples. Although molecular transverse relaxation informs local cellular microenvironment via molecule-environment interactions, precise determination of the transverse relaxation times of molecules with scalar couplings (J), such as glutamate and glutamine, is difficult using current in vivo magnetic resonance spectroscopy (MRS) technologies, whose approach to measuring transverse relaxation has not changed for decades. We introduce an in vivo MRS technique that achieves chemical shift encoding with selectively locked J-couplings in each column of the acquired two-dimensional dataset, freeing up the entire row dimension for transverse relaxation encoding. This results in increased spectral resolution, minimized background signals, and markedly broadened dynamic range for transverse relaxation encoding. This technique enables determination of the transverse relaxation times of glutamate and glutamine in vivo with unprecedented high precision. Since glutamate predominantly resides in glutamatergic neurons and glutamine in glia in the brain, this noninvasive technique provides a way to probe cellular pathophysiology in neuropsychiatric disorders for characterizing disease progression and monitoring treatment response in a cell type-specific manner in vivo.