Evaluating the feasibility of creatine‐weighted CEST MRI in human brain at 7 T using a Z‐spectral fitting approach

Abstract

The current study aims to evaluate the feasibility of creatine (Cr) chemical exchange saturation transfer (CEST)‐weighted MRI at 7 T in the human brain by optimizing the saturation pulse parameters and computing contrast using a Z‐spectral fitting approach. The Cr‐weighted (Cr‐w) CEST contrast was computed from phantoms data. Simulations were carried out to obtain the optimum saturation parameters for Cr‐w CEST with lower contribution from other brain metabolites. CEST‐w images were acquired from the brains of four human subjects at different saturation parameters. The Cr‐w CEST contrast was computed using both asymmetry analysis and Z‐spectra fitting approaches (models 1 and 2, respectively) based on Lorentzian functions. For broad magnetization transfer (MT) effect, Gaussian and Super‐Lorentzian line shapes were also evaluated. In the phantom study, the Cr‐w CEST contrast showed a linear dependence on concentration in physiological range and a nonlinear dependence on saturation parameters. The in vivo Cr‐w CEST map generated using asymmetry analysis from the brain represents mixed contrast with contribution from other metabolites as well and relayed nuclear Overhauser effect (rNOE). Simulations provided an estimate for the optimum range of saturation parameters to be used for acquiring brain CEST data. The optimum saturation parameters for Cr‐w CEST to be used for brain data were around B1rms = 1.45 μT and duration = 2 seconds. The Z‐spectral fitting approach enabled computation of individual components. This also resulted in mitigating the contribution from MT and rNOE to Cr‐w CEST contrast, which is a major source of underestimation in asymmetry analysis. The proposed modified z‐spectra fitting approach (model 2) is more stable to noise compared with model 1. Cr‐w CEST contrast obtained using fitting was 6.98 ± 0.31% in gray matter and 5.45 ± 0.16% in white matter. Optimal saturation parameters reduced the contribution from other CEST effects to Cr‐w CEST contrast, and the proposed Z‐spectral fitting approach enabled computation of individual components in Z‐spectra of the brain. Therefore, it is feasible to compute Cr‐w CEST contrast with a lower contribution from other CEST and rNOE.

Effect of offset‐frequency step size and interpolation methods on chemical exchange saturation transfer MRI computation in human brain

“…Modified Bloch‐McConnell equations‐based simulations were used to generate CEST data for different pools (glutamate, amide and creatine) with different saturation parameters (Table 1). The saturation parameters for Glu‐w, 33 APT‐w 34 and Cr‐w 4 CEST were considered as used in reported studies. For all the metabolites, the simulations were carried out over a limited offset‐frequency range (Table 1) at a step size of 0.05 ppm, assumed to be ideal, or reference CEST data without any B 0 field inhomogeneity effects.…”

“…The CEST MRI imaging parameters were slice thickness = 5 mm, GRE flip angle (FA) = 6 o , GRE readout TR/TE = 6/1. 4 The pulse sequence used in the current study for the acquisition of 2D APT-w MRI data has been reported previously. 2,8,34 The pulse comprised three sections: four blocks of RF saturation preparation pulses (each block with B 1rms = 2 μT, duration = 200 ms), each followed by a crusher gradient (duration = 10 ms, amplitude = 10 mT/m); lipid suppression (FA = 100 , duration = 17.…”

“…Chemical exchange saturation transfer (CEST) 1 MRI is an advanced non‐invasive imaging technique for the mapping of exogenous and endogenous molecules with higher temporal and spatial resolution compared with magnetic resonance spectroscopic imaging. Reported studies have shown the potential of CEST for in vivo mapping of molecules/metabolites such as endogenous cellular labile proteins and peptides, 2 glutamate, 3 creatine, 4 myo‐inositols 5 and glucose 6 …”

“…Chemical exchange saturation transfer (CEST) 1 MRI is an advanced non-invasive imaging technique for the mapping of exogenous and endogenous molecules with higher temporal and spatial resolution compared with magnetic resonance spectroscopic imaging. Reported studies have shown the potential of CEST for in vivo mapping of molecules/metabolites such as endogenous cellular labile proteins and peptides, 2 glutamate, 3 creatine, 4 myo-inositols 5 and glucose. 6 Amide-proton-transfer-weighted (APT-w) 2 MRI has shown a wide range of clinical applications 7 such as detection of tumors along with grading, 8,9 assessment of therapy response, 10 differentiating tumor recurrence from radiation necrosis 10 and detecting ischemic stroke.…”

“…11 The glutamate-weighted (Glu-w) 3 CEST imaging technique is used to estimate changes in glutamate levels and its clinical applications are being explored for better diagnosis of disorders such as spinal cord neuro-pathological disorders, 12 epilepsy, 13 brain tumors 14 and Alzheimer's disease. 15 Several other studies have reported the feasibility of mapping creatine, 4,16,17 myo-inositol, 5 glucose 6 and glycosaminoglycan 18 using CEST MRI along with some clinical/pre-clinical applications.…”