Quantification of hydroxyl exchange of D‐Glucose at physiological conditions for optimization of glucoCEST MRI at 3, 7 and 9.4 Tesla

Abstract

Aims To determine individual glucose hydroxyl exchange rates at physiological conditions and use this information for numerical optimization of glucoCEST/CESL preparation. To give guidelines for in vivo glucoCEST/CESL measurement parameters at clinical and ultra‐high field strengths. Methods Five glucose solution samples at different pH values were measured at 14.1 T at various B1 power levels. Multi‐B1‐Z‐spectra Bloch‐McConnell fits at physiological pH were further improved by the fitting of Z‐spectra of five pH values simultaneously. The obtained exchange rates were used in a six‐pool Bloch‐McConnell simulation including a tissue‐like water pool and semi‐solid MT pool with different CEST and CESL presaturation pulse trains. In vivo glucose injection experiments were performed in a tumor mouse model at 7 T. Results and discussion Glucose Z‐spectra could be fitted with four exchanging pools at 0.66, 1.28, 2.08 and 2.88 ppm. Corresponding hydroxyl exchange rates could be determined at pH = 7.2, T = 37°C and 1X PBS. Simulation of saturation transfer for this glucose system in a gray matter‐like and a tumor‐like system revealed optimal pulses at different field strengths of 9.4, 7 and 3 T. Different existing sequences and approaches are simulated and discussed. The optima found could be experimentally verified in an animal model at 7 T. Conclusion For the determined fast exchange regime, presaturation pulses in the spin‐lock regime (long recover time, short yet strong saturation) were found to be optimal. This study gives an estimation for optimization of the glucoCEST signal in vivo on the basis of glucose exchange rate at physiological conditions.

Dynamic glucose‐enhanced (DGE) MRI in the human brain at 7 T with reduced motion‐induced artifacts based on quantitative R1ρ mapping

“…In contrast to the on‐resonant CESL approach utilized in this study at 7 T, the recent DGE‐MRI approach at 3 T by Herz et al used off‐resonant SL pulses in order to increase the contrast‐to‐noise ratio. This is particularly important at lower magnetic field strengths (e.g., 3 T) where the exchange weighting of glucose (i.e., the exchange‐dependent relaxation rate in the rotating frame R ex of glucose contributing to R 1ρ ) is considerably reduced . However, at ultrahigh fields (i.e., B 0 ≥ 7 T), the SNR as well as the exchange weighting were sufficient to use the more simplistic on‐resonant SL preparation.…”

“…The RF‐amplitude B 1 = 5 µT, TSL 1 = 50 ms, and parameters for the adiabatic hyperbolic secant half‐passage tipping pulses (maximal RF‐amplitude = 20 µT, duration t adia = 8 ms, adiabatic bandwidth = 1200 Hz, and adiabatic µ = 6) were set to the previously optimized values at 7 T . To further enhance the CESL contrast of glucose, the recovery time was slightly increased to t rec = 5 s in comparison to previous applications . Images with R 1ρ weighting (TSL 1 = 50 ms) and without R 1ρ weighting (TSL 2 = 0.2 ms) were acquired in an interleaved manner (Figure A).…”

“…The duration of image readout (t readout ) was approximately 2 s. Spin-lock (SL) preparation was achieved by an onresonant (frequency offset with respect to the water signal Δω = 0 ppm) adiabatically prepared SL pulse 16,17 ( Figure 1A). The RF-amplitude B 1 = 5 µT, TSL 1 = 50 ms, and parameters for the adiabatic hyperbolic secant half-passage tipping pulses (maximal RF-amplitude = 20 µT, duration t adia = 8 ms, adiabatic bandwidth = 1200 Hz, and adiabatic µ = 6) were set to the previously optimized values at 7 T. [16][17][18] To further enhance the CESL contrast of glucose, 27 the recovery time was slightly increased to t rec = 5 s in comparison to previous applications. [16][17][18] Images with R 1ρ weighting (TSL 1 = 50 ms) and without R 1ρ weighting (TSL 2 = 0.2 ms) were acquired in an interleaved manner ( Figure 1A).…”

“…This is particularly important at lower magnetic field strengths (e.g., 3 T) where the exchange weighting of glucose (i.e., the exchange-dependent relaxation rate in the rotating frame R ex of glucose contributing to R 1ρ ) 6 is considerably reduced. 6,7,27,31 However, at ultrahigh fields (i.e., B 0 ≥ 7 T), the SNR as well as the exchange weighting were sufficient to use the more simplistic on-resonant SL preparation. In addition, the off-resonant SL approach requires sampling of multiple frequency offsets for a retrospective compensation of B 0 -field inhomogeneities, whereas no such compensation is required in the on-resonant ΔR 1ρ approach used in this study (cf.…”

Non-invasive Investigation of Tumor Metabolism and Acidosis by MRI-CEST Imaging

“…Therefore, the idea of exploiting unlabeled D-glucose as an MRI contrast agent may represent a cheaper and potential alternative to FDG without involving ionizing radiations. Glucose molecules own five hydroxylic groups in fast exchange rate (500-6,000 Hz) with bulk water protons that can provide CEST contrast at 1-1.2 ppm from the water resonance (58,59). The feasibility of imaging glucose uptake with the CEST-MRI technique was demonstrated in colorectal tumor xenograft murine models, with glucose contrast (GlucoCEST) correlated to FDG accumulation as measured by autoradiography (60).…”