Challenges in glucoCEST MR body imaging at 3 Tesla

Abstract

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.

Keywords: Glucose chemical exchange saturation transfer (glucoCEST), body magnetic resonance imaging (body MRI); clinical 3 T; field inhomogeneity; magnetization transfer ratio asymmetry (MTRasym).

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

2019 Quantitative Imaging in Medicine and Surgery. All rights reserved.

Figures

Figure 1

Timing of consecutive B0 map and glucoCEST acquisition. The CEST measurements consist of two reference scans without pre-saturation (S0) followed by multiple scans with pre-saturation (i.e., 6 pairs of positive and negative offset frequencies in an interleaved manner with 5 repetitions). In addition, B0 field maps were acquired in-between CEST scans to correct potential field drifts. Glucose infusion was performed without re-positioning the subjects for 30 minutes after 12 minutes of baseline scans. CEST, chemical exchange saturation transfer.

Figure 2

Optimum combination of parameters Δω and B1 for a range of T2 values, which produces the maximum sensitivity of glucoCEST at 3 T. For a given set of coordinates, the colour-map represents the required contrast-to-noise ratio (CNR: measured as the MTRasym/standard error) in order to differentiate an increase of 10 mM glucose concentration with 95% CI [reproduced from (26)]. This figure shows a simple way to optimise saturation power in a function of frequency offset and tissue T2 values. The calculated CNR values are indicative as they are simulated using a CW saturation pulse at equilibrium. MTRasym, magnetization transfer ratio asymmetry.

Figure 3

Glucose infusion profile (A,C,E) vs. MTRasym signal (B,D,F) in three patients with lymphoma (patient 1 = A and B, patient 2 = C and D, patient 3 = E and F) and a patient with prostate cancer (G for glucose infusion profile and H for MTRasym signal). Glucose infusion starting time is displayed in a vertical dotted line (B,D,F,H). The reference images on the rightmost column show ROIs for which the signal changes are displayed. MTRasym, magnetization transfer ratio asymmetry.

Figure 4

MTRasym signal as a function of infusion time before and after field drift correction. (A) MTRasym signal integrated in the range of 2–3ppm before WASABI correction shows field drifts both in tumour and contralateral regions of a patient with prostate cancer. It is worthwhile to note that the changes due to B0 drift are much larger in the body, due to the increased drift observed. In this case the B0 drifts across slice and entire scan duration were found to be 25 Hz (0.2 ppm) and 200 Hz (1.56 ppm), respectively. (B) After B0 correction, no significant enhancement in MTRasym signal is observed and the signal intensity is significantly reduced. MTRasym, magnetization transfer ratio asymmetry.

Figure S1

Representative glucose infusion profiles with (A) manual adjustment by the clinical team and (B) the DeFronzo method {i.e., using the glucose infusion rate formula described in eq. [2]}. Note that using the hyperglycaemic clamp, the time taken to reach the target plasma glucose is considerably shorter (12 min) following implementation of the DeFronzo method than that by manual adjustment (38 min).

Figure S2

Baseline T2-weighted mDixon images (in phase and out of phase) in 6 slices. (A) Patient 1 with Classical Hodgkin’s Lymphoma with tumour on the left cervical region; (B) Patient 2 with another classical Hodgkin’s lymphoma (bilateral cervical nodal involvement); (C) Patient 3 with a diffuse large B cell lymphoma patient with left cervical nodal involvement; (D) Patient 4 with a large Prostatic tumour.