Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis

Abstract

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) can probe tissue biochemistry in vivo with high resolution and sensitivity without requiring exogenous contrast agents. Applying CEST MRI at ultrahigh field provides advantages of increasing spectral resolution and improving sensitivity to metabolites with faster proton exchange rates such as glutamate, a critical neurotransmitter in the brain. Prior magnetic resonance spectroscopy and CEST MRI studies have revealed altered regulation of glutamate in patients with multiple sclerosis (MS). While CEST imaging facilitates new strategies for investigating the pathology underlying this complex and heterogeneous neurological disease, CEST signals are contaminated or diluted by concurrent effects (e.g., semi-solid magnetization transfer (MT) and direct water saturation) and are scaled by the T1 relaxation time of the free water pool which may also be altered in the context of disease. In this study of 20 relapsing-remitting MS patients and age- and sex-matched healthy volunteers, glutamate-weighted CEST data were acquired at 7.0 T. A Lorentzian fitting procedure was used to remove the asymmetric MT contribution from CEST z-spectra, and the apparent exchange-dependent relaxation (AREX) correction was applied using an R1 map derived from an inversion recovery sequence to further isolate glutamate-weighted CEST signals from concurrent effects. Associations between AREX and cognitive function were examined using the Minimal Assessment of Cognitive Function in MS battery. After isolating CEST effects from MT, direct water saturation, and T1 effects, glutamate-weighted AREX contrast remained higher in gray matter than in white matter, though the difference between these tissues decreased. Glutamate-weighted AREX in normal-appearing gray and white matter in MS patients did not differ from healthy gray and white matter but was significantly elevated in white matter lesions. AREX in some cortical regions and in white matter lesions correlated with disability and measures of cognitive function in MS patients. However, further studies with larger sample sizes are needed to confirm these relationships due to potential confounding effects. The application of MT and AREX corrections in this study demonstrates the importance of isolating CEST signals for more specific characterization of the contribution of metabolic changes to tissue pathology and symptoms in MS.

Evaluation of contributors to amide proton transfer–weighted imaging and nuclear Overhauser enhancement–weighted imaging contrast in tumors at a high magnetic field

“…Therefore, we used %s −1 as the unit for the AREX metric. It is worth noting that some previous publications have used Hertz as the unit for the AREX metric, which may make f s look like a dimensionless number 65–67 …”

“…It is worth noting that some previous publications have used Hertz as the unit for the AREX metric, which may make f s look like a dimensionless number. [65][66][67] Our experiments were performed on 9-L tumor models in rat brains. In other animal tumor models and human patients, the change in the sample parameters may be different.…”

Comprehensive 7 T CEST: A clinical MRI protocol covering multiple exchange rate regimes

“…The low B1 CEST saturation scheme ( ), for the detection of amide, rNOE, guanidine and the ssMT pool, was implemented according to 28 . Intermediate B1 saturation for amine and glutamate‐sensitive CEST ( ) was measured according to 29 . The CEST effect originating from endogenous, fast exchanging hydroxyl groups ( ) was prepared using the high B1 saturation method of Zaiss et al 2 as a template.…”

“…Other estimated behaviours for CEST effects with different B1 level are observed: with increasing B1 amplitude, the signal amplitude for the amide (Figure 3C) and rNOE (Figure 3G) labelling decreases, while for higher exchanging pools, like guanidine (Figure 3D) at 2.0 ppm, an increase can be observed. Fuelled by our simulation results and previous publications, 2,28,29 we propose a time-optimised measurement protocol and CEST saturation schedule for slow, intermediate and fast exchanging protons in the following section.…”

“…28 Intermediate B1 saturation for amine and glutamate-sensitive CEST ( ≈ 2 μT) was measured according to. 29 The CEST effect originating from endogenous, fast exchanging hydroxyl groups ( ≈ 4 μT) was prepared using the high B1 saturation method of Zaiss et al 2 as a template. The recovery time between offsets was 3 s for the intermediate/high B1 regime, while it was 1 s for the low B1 scheme.…”