Challenges in glucoCEST MR body imaging at 3 Tesla.

BACKGROUND: The aim of this study was to translate dynamic glucose enhancement (DGE) body magnetic resonance imaging (MRI) based on the glucose chemical exchange saturation transfer (glucoCEST) signal to a 3 T clinical field strength. METHODS: An infusion protocol for intravenous (i.v.) glucose was optimised using a hyperglycaemic clamp to maximise the chances of detecting exchange-sensitive MRI signal. Numerical simulations were performed to define the optimum parameters for glucoCEST measurements with consideration to physiological conditions. DGE images were acquired for patients with lymphomas and prostate cancer injected i.v. with 20% glucose. RESULTS: The optimised hyperglycaemic clamp infusion based on the DeFronzo method demonstrated higher efficiency and stability of glucose delivery as compared to manual determination of glucose infusion rates. DGE signal sensitivity was found to be dependent on T2, B1 saturation power and integration range. Our results show that motion correction and B0 field inhomogeneity correction are crucial to avoid mistaking signal changes for a glucose response while field drift is a substantial contributor. However, after B0 field drift correction, no significant glucoCEST signal enhancement was observed in tumour regions of all patients in vivo. CONCLUSIONS: Based on our simulated and experimental results, we conclude that glucose-related signal remains elusive at 3 T in body regions, where physiological movements and strong effects of B1 + and B0 render the originally small glucoCEST signal difficult to detect.

Optimization and repeatability of multipool chemical exchange saturation transfer MRI of the prostate at 3.0 T.

BACKGROUND: Chemical exchange saturation transfer (CEST) can potentially support cancer imaging with metabolically derived information. Multiparametric prostate MRI has improved diagnosis but may benefit from additional information to reduce the need for biopsies. PURPOSE: To optimize an acquisition and postprocessing protocol for 3.0 T multipool CEST analysis of prostate data and evaluate the repeatability of the technique. STUDY TYPE: Prospective. SUBJECTS: Five healthy volunteers (age range: 24-47 years; median age: 28 years) underwent two sessions (interval range: 7-27 days; median interval: 20 days) and two biopsy-proven prostate cancer patients were evaluated once. Patient 1 (71 years) had a Gleason 3 + 4 transition zone (TZ) tumor and patient 2 (55 years) had a Gleason 4 + 3 peripheral zone (PZ) tumor. FIELD STRENGTH: 3.0 T. Sequences run: T2 -weighted turbo-spin-echo (TSE); diffusion-weighted imaging; CEST; WASABI (for B0 determination). ASSESSMENT: Saturation, readout, and fit-model parameters were optimized to maximize in vivo amide and nuclear Overhauser effect (NOE) signals. Repeatability (intrasession and intersession) was evaluated in healthy volunteers. Subsequently, preliminary evaluation of signal differences was made in patients. Regions of interest were drawn by two post-FRCR board-certified readers, both with over 5 years of experience in multiparametric prostate MRI. STATISTICAL TESTS: Repeatability was assessed using Bland-Altman analysis, coefficient of variation (CV), and 95% limits of agreement (LOA). Statistical significance of CEST contrast was calculated using a nonparametric Mann-Whitney U-test. RESULTS: The optimized saturation scheme was found to be 60 sinc-Gaussian pulses with 40 msec pulse duration, at 50% duty-cycle with continuous-wave pulse equivalent B1 power (B1CWPE ) of 0.92 µT. The magnetization transfer (MT) contribution to the fit-model was centered at -1.27 ppm. Intersession coefficients of variation (CVs) of the amide, NOE, and magnetization transfer (MT) and asymmetric magnetization transfer ratio (MTRasym ) signals of 25%, 23%, 18%, and 200%, respectively, were observed. Fit-metric and MTRasym CVs agreed between readers to within 4 and 10 percentage points, respectively. DATA CONCLUSION: Signal differences of 0.03-0.10 (17-43%) detectable depending upon pool, with MT the most repeatable (signal difference of 17-22% detectable). LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1238-1250.

Differential inhibition of inducible T cell cytokine secretion by potent iron chelators.

Effector functions and proliferation of T helper (Th) cells are influenced by cytokines in the environment. Th1 cells respond to a synergistic effect of interleukin-12 (IL-12) and interleukin-18 (IL-18) to secrete interferon-gamma (IFN-gamma). In contrast, Th2 cells respond to interleukin-4 (IL-4) to secrete IL-4, interleukin-13 (IL-13), interleukin-5 (IL-5), and interleukin-10 (IL-10). The authors were interested in identifying nonpeptide inhibitors of the Th1 response selective for the IL-12/IL-18-mediated secretion of IFN-gamma while leaving the IL-4-mediated Th2 cytokine secretion relatively intact. The authors established a screening protocol using human peripheral blood mononuclear cells (PBMCs) and identified the hydrazino anthranilate compound 1 as a potent inhibitor of IL-12/IL-18-mediated IFN-gamma secretion from CD3(+) cells with an IC(50) around 200 nM. The inhibitor was specific because it had virtually no effect on IL-4-mediated IL-13 release from the same population of cells. Further work established that compound 1 was a potent intracellular iron chelator that inhibited both IL-12/IL-18- and IL-4-mediated T cell proliferation. Iron chelation affects multiple cellular pathways in T cells. Thus, the IL-12/IL-18-mediated proliferation and IFN-gamma secretion are very sensitive to intracellular iron concentration. However, the IL-4-mediated IL-13 secretion does not correlate with proliferation and is partially resistant to potent iron chelation.