High-resolution glutamate-weighted mapping of in vivo mouse brain across age with chemical exchange saturation transfer MRI

Aging in the mammalian brain involves significant structural, functional, and metabolic changes, including a decrease in glutamate concentration. Glutamate-weighted chemical exchange saturation transfer (gluCEST) MRI provides a non-invasive method for mapping glutamate distribution with high spatial resolution. Collecting data from a large cohort of healthy mice aged 2 to 23 months, scanned in vivo at 17.2 T, we demonstrate that gluCEST can differentiate multiple brain regions, and introduce a gluCEST template for the mouse mid-rostrocaudal brain from Bregma -0.5 to -4 mm approximately. Our findings reveal significant age-related decreases in gluCEST values in the hippocampus, thalamus, and hypothalamus. These decreases did not correlate with volume reductions of these regions, except in the hippocampus, indicating gluCEST as a complementary neuroimaging approach to overall anatomical changes. Our study also demonstrates gluCEST's potential to monitor age-related changes in smaller brain subregions, such as cortical and hippocampal layers, providing a valuable tool for longitudinal investigations into aging and neurodegenerative diseases. The high spatial resolution and sensitivity offered by ultra-high magnetic field MR scanners enhance the precision of these measurements, paving the way for future preclinical and clinical applications.