  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.
