Toward quantitative CEST imaging of glutamate in the mouse brain using a multi‐pool exchange model calibrated by 1H‐MRS

Purpose To develop a CEST quantification model to map glutamate concentration in the mouse brain at 11.7 T, overcoming the limitations of conventional glutamate‐weighted CEST (gluCEST) contrast (magnetization transfer ratio with asymmetric analysis). Methods 1H‐MRS was used as a gold standard for glutamate quantification to calibrate a CEST‐based quantitative pipeline. Joint localized measurements of Z‐spectra at B1 = 5 μT and quantitative 1H‐MRS were carried out in two voxels of interest in the mouse brain. A six‐pool Bloch‐McConnell model was found appropriate to fit experimental data. Glutamate exchange rate was estimated in both regions with this dedicated multi‐pool fitting model and using glutamate concentration determined by 1H‐MRS. Results Glutamate exchange rate was estimated to be ˜1300 Hz in the mouse brain. Using this calibrated value, maps of glutamate concentration in the mouse brain were obtained by pixel‐by‐pixel fitting of Z‐spectra at B1 = 5 μT. A complementary study of simulations, however, showed that the quantitative model has high sensitivity to noise, and therefore, requires high‐SNR acquisitions. Interestingly, fitted [Glu] seemed to be overestimated compared to 1H‐MRS measurements, although it was estimated with simulations that the model has no intrinsic fitting bias with our experimental level of noise. The hypothesis of an unknown proton‐exchanging pool contributing to gluCEST signal is discussed. Conclusion High‐resolution mapping of glutamate in the brain was made possible using the proposed calibrated quantification model of gluCEST data. Further studying of the in vivo molecular contributions to gluCEST signal could improve modeling.