Abstract
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, has been difficult using 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 utilizes frequency-selective editing pulses to achieve homonuclear decoupled chemical shift encoding in each column of the acquired two-dimensional dataset, freeing up the entire row dimension for transverse relaxation encoding with J-refocusing. This results in increased spectral resolution, minimized background signals, and markedly broadened dynamic range for transverse relaxation encoding. The in vivo within-subject coefficients of variation for the transverse relaxation times of glutamate and glutamine, measured using the proposed method in the human brain at 7 T, were found to be approximately 4%. 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.