d-glucose weighted chemical exchange saturation transfer (glucoCEST)-based dynamic glucose enhanced (DGE) MRI at 3T: early experience in healthy volunteers and brain tumor patients

Abstract

Purpose: Dynamic glucose enhanced (DGE) MRI has shown potential for imaging glucose delivery and blood-brain barrier permeability at fields of 7T and higher. Here, we evaluated issues involved with translating d-glucose weighted chemical exchange saturation transfer (glucoCEST) experiments to the clinical field strength of 3T.

Methods: Exchange rates of the different hydroxyl proton pools and the field-dependent T₂ relaxivity of water in d-glucose solution were used to simulate the water saturation spectra (Z-spectra) and DGE signal differences as a function of static field strength B₀ , radiofrequency field strength B₁ , and saturation time t_sat . Multislice DGE experiments were performed at 3T on 5 healthy volunteers and 3 glioma patients.

Results: Simulations showed that DGE signal decreases with B₀ , because of decreased contributions of glucoCEST and transverse relaxivity, as well as coalescence of the hydroxyl and water proton signals in the Z-spectrum. At 3T, because of this coalescence and increased interference of direct water saturation and magnetization transfer contrast, the DGE effect can be assessed over a broad range of saturation frequencies. Multislice DGE experiments were performed in vivo using a B₁ of 1.6 µT and a t_sat of 1 second, leading to a small glucoCEST DGE effect at an offset frequency of 2 ppm from the water resonance. Motion correction was essential to detect DGE effects reliably.

Conclusion: Multislice glucoCEST-based DGE experiments can be performed at 3T with sufficient temporal resolution. However, the effects are small and prone to motion influence. Therefore, motion correction should be used when performing DGE experiments at clinical field strengths.

Keywords: CEST; T2 relaxation; Z-spectrum; d-glucose; fast exchange; glioma; glucoCEST; motion correction.

Figure 1.

Simulations of the DGE difference Z-spectrum as a function of static field strength (11.7 T, 7.0 T and 3.0 T) in different tissue compartments. Four different RF powers from 0.4 to 2.0 μT are simulated for a saturation time of 1 s. The simulation assumes that blood glucose concentration increase from 5 mM to 15 mM after infusion and the glucose in other tissue compartments is ¼ of the blood concentration. The plots for the gray and white matter are enlarged in the black box below. Parameters are listed in Table 1.

Figure 2.

Simulated glucoCEST signal at 2 ppm as a function of saturation time and power in different tissue compartments at 3 T. Parameters are listed in Table 1.

Figure 3.

Illustration of a DGE study in a healthy volunteer. (a) The dynamic difference images; (b) the DGE signal as a function of infusion time in the brain as a whole, gray matter, white matter and CSF; (c) the mean AUC during glucose infusion (0-2 min); and (d) the mean AUC 5 min post glucose infusion (2-7 min) of a healthy volunteer.

Figure 4.

Mean AUC_0-2min and AUC_2-7min in the WM, GM, and CSF tissue compartments. One-sample t-tests were performed for comparing each mean AUC to the average baseline (0 by definition). Paired t-test were performed when comparing AUC_0-2min and AUC_2-7min. * denotes a p-value < 0.05, for the t-tests.

Figure 5.

DGE MRI of a patient previously diagnosed with an IDH mutant anaplastic oligodendroglioma (WHO Grade III) at the time point of 18 months post-surgery (Patient 1), (a) without motion correction. (b) shows the translation and rotation motion correction profile leading to the dynamic images in (c).

Figure 6.

Multi-contrast images for Patient 1: (a) the post Gd T1 MPRAGE, T2 FLAIR, mean DGE AUC_0-2min image, mean DGE AUC_2-7min image; and (b) the DGE signal as a function of infusion time in the Gd-enhanced, FLAIR hyperintense and posterior normal appearing white matter.

Figure 7.

DGE MRI of a patient previously diagnosed with an IDH mutant glioblastoma at the time point of 3 months post-surgery (Patient 2). The dynamic difference images before (a) and after (c) motion correction. b) The translation and rotation profile before the motion correction. The color scale for this patient differs from the one from Patient 1.

Figure 8.

Multi-contrast images for Patient 2: (a) the post Gd T1 MPRAGE, T2 FLAIR, mean DGE AUC_0-2min image, mean DGE AUC_2-7min image; and (b) the DGE signal as a function of infusion time in the Gd-enhanced, FLAIR hyperintense and posterior normal appearing white matter. The color scale for this patient differs from the one from Patient 1.