Investigation of metabolite correlates of CEST in the human brain at 7 T

Metabolite-weighted chemical exchange saturation transfer MRI can be used to indirectly image metabolites such as creatine and glutamate. This study aims to further explore the contrast of CEST at 2 ppm in the human brain at 7T and investigate the metabolite correlates of CEST at 2 ppm via correlations with magnetic resonance spectroscopy (MRS). Simulations were performed to establish the optimal acquisition parameters, such as total saturation time (tsat) and B1 root mean squared (B1rms) for CEST at 2 ppm in the human brain. Parameters were validated via in vitro phantom studies at 7T using concentrations, pH and temperature comparable to what is found in the human brain. Finally, 10 healthy volunteers were scanned at 7T for comparison with MRS. Our results show that the optimal parameters to acquire CEST at 2 ppm images are: B1rms = 2.14 mu T & tsat = 1500 ms, respectively. Comparison with MRS showed no significant correlation between CEST at 2 ppm and total Creatine measured by MRS (R = 0.19; p-value = 0.273). However, a significant correlation was found between CEST at 2 ppm and Glu (R = 0.39; p-value = 0.033), indicating the broad Glutamate-weighted CEST as the main measurable contributor to CEST at 2 ppm. We identified and confirmed optimal CEST at 2 ppm sequence parameters and validated CEST at 2 ppm measurements in a controlled in vitro environment. Our findings suggest that glutamate is a substantial contributor to the CEST at 2 ppm contrast observed in the human brain, whereas the creatine contribution to CEST at 2 ppm in the brain did not show a measurable contribution. CEST can be used to indirectly image in vivo amine protons, such as those in creatine and glutamate. CEST at 2 ppm was measured in the human gray and white matter (A) and correlated with MRS concentrations of total creatine and glutamate of the same regions (B). A significant correlation was found between CEST at 2 ppm and glutamate (C), suggesting glutamate to substantially contribute to CEST contrast at 2 ppm in the human brainimage