PURPOSE

The molecular CEST imaging previously has been shown sensitive to the glucose and glutamate by measuring the exchangeable protons from the hydroxyl and amine group respectively for targeting glucose metabolism and inflammation¹. The current study investigated the feasibility of CEST imaging for a simultaneous detection on the proton transfer for glucose (glucoCEST) and glutamate (gluCEST). The CEST imaging parameters were optimized on a test phantom consisting of glucose (Glc) and glutamate (Glu), together with other concentrated molecules in the brain: myo-inositol (MI), lactate (Lac), N-Acetylaspartic acid (NAA), and a mixture of them to test the sensitivity and specificity of glucose and glutamate detection by CEST. A preliminary in vivo experiment was performed on a rat brain with injury and compared to the ¹⁸F-FDG positron emission tomography (PET) detecting the glucose uptake and ¹⁸F-DPA for imaging microglial activation in vivo.

METHODS

The phantom experiments were done using a Doty radiofrequency quadrature coil (Doty Scientific, Inc., SC) on a Bruker 9.4T scanner (Bruker Corp., MA). The CEST data were acquired by 2D Rapid Acquisition with Relaxation Enhancement (RARE) sequence with (SMT) and without (S0) magnetization transfer (MT) preparation pulses: TR 3.10s, TE 10.39ms; RARE factor 4; in plane resolution 200μm2, slice thickness 0.8mm. The effect of varying MT preparation pulses on the sensitivity and specificity for glucose detection were investigated by arraying the saturation power from 0.5μT to 7μT and saturation duration from 0.5s to 3s. The CEST Z-spectrum were acquired from the MT frequency offsets (Δω) from −2.0kHz to +2.0kHz with 50Hz frequency stepping, as a result, 81 points were sampled to delineate the entire Z-Spectrum from -5 part per million (ppm) to +5ppm. CEST data were corrected for B0/B1 field inhomogeneity using WASSR water referencing²: 0.2 μT for saturation power and 0.1s for saturation duration, Δω −0.4kHz to +0.4kHz with 10Hz frequency stepping. The asymmetry of magnetization transfer ratio (MTRasym) maps were derived for glucoCEST (1.2, 2.1, 2.9ppm) and gluCEST (3ppm) maps by calculating the area under the curve at the related chemical shifts. A focal injured rat brain was scanned using the same imaging parameters with the optimized MT saturation pulses (2μT, 2s). ¹⁸F-FDG and ¹⁸F-DPA PET were performed 24 and 48 hours after MRI scans, respectively, using Siemens micro-PET/CT scanner. Standardized uptake values were calculated for the PET data.

RESULTS

The MTRasym of the Glc phantom by saturation power 2μT, and duration 2s showed peaks at 1.2, 2.1, 2.9ppm, and that of Glu phantom exhibited a broad coverage of peaks from 1 to 3.5 ppm (Fig. 1). The glucoCEST map showed the most contrast to Glc, while the gluCEST displayed predominant contrast to the Glu. The CEST Z-spectrum and MTRasym of the rat brain showed different patterns between the normal and injured tissue (Fig. 2). The injured tissue comparing to the normal tissue exhibited decreased MTRasym at the hydroxyl chemical shifts, where the increased MTRasym was seen for the amine chemical shift range at 3ppm. Comparable results are seen in the assessment of glucose uptake between the glucoCEST and ¹⁸F-FDG PET (Fig. 3A), and for the inflammation markers between gluCEST and ¹⁸F-DPA PET (Fig. 3B).

DISCUSSION

CEST imaging has been previously shown sensitive to detect glucose uptake in tumor³ and neuroinflammation in Alzheimer's disease⁴ by selectively mapping the chemical shifts of the hydroxyl and amine group. In the current study, we further demonstrated the possibility to simultaneously detecting the glucose and glutamate content by optimized CEST acquisition parameters to show the decreased glucose metabolism and increased inflammation at the same time. The current finding suggests that the CEST technique has strong potentials for the simultaneous detection of the glucose and glutamate, without using radioactive isotopes, for repetitively monitoring the metabolism and inflammation in the TBI.

Acknowledgements

No acknowledgement found.