In vivo chemical exchange saturation transfer imaging of creatine (CrCEST) in skeletal muscle at 3T

Abstract

Purpose To characterize the chemical exchange saturation transfer (CEST) based technique to measure free creatine (Cr), a key component of muscle energy metabolism, distribution in skeletal muscle with high spatial resolution before and after exercise at 3T. Methods CrCEST saturation parameters were empirically optimized for 3T. CEST, T2, magnetization transfer ratio (MTR) and 31P magnetic resonance spectroscopy (MRS) acquisitions of the lower leg were performed before and after mild plantar flexion exercise on a 3T whole-body MR scanner on 6 healthy volunteers. Results The feasibility of imaging Cr changes in skeletal muscle following plantar flexion exercise using CrCEST was demonstrated at 3T. This technique exhibited good spatial resolution and was able to differentiate differences in muscle utilization among subjects. CrCEST results were compared with 31P MRS results showing good agreement in the Cr and PCr recovery kinetics. A relationship of 0.45 % CrCESTasym/mM Cr was observed across all subjects. Conclusion Demonstrated the CrCEST technique could be applied at 3T to measure dynamic changes in creatine in in vivo muscle. The widespread availability and clinical applicability of 3T scanners has the potential to clinically advance this method.

Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders

“…This pilot study was performed at 3T because MRI scanners at this field strength are more widely available, and thus may be used for future, larger studies and/or adapted for clinical use. In addition, the feasibility of CrCEST imaging at 3T has already been demonstrated (14). As this separate study reflected a sample of convenience, it did not include standardized clinical factors including fasting status, previous exercise, or time of day.…”

“…Image processing was performed using in-house MATLAB scripts (49,50). Water saturation shift referencing (51) maps and B 1 maps were acquired before and after exercise, and used to generate corrected CrCEST images as described for previous studies (14,50). CrCEST contrast was computed by subtracting the normalized magnetization signal at the creatine proton frequency (Δω = +1.8 ppm), from the magnetization at the corresponding reference frequency on the opposite side of the water resonance (-Δω) (52).…”

“…The subsequent decrease in the water signal results in contrast that reflects the concentration dependence of the metabolite, with high spatial resolution. With CEST, the creatine content can be simultaneously measured in every muscle of a leg in vivo (13,14). Recent studies in healthy humans have demonstrated that CEST imaging of free creatine can readily provide muscle group-specific information about OXPHOS capacity.…”

“…Recent studies in healthy humans have demonstrated that CEST imaging of free creatine can readily provide muscle group-specific information about OXPHOS capacity. CrCEST is used to determine the exponential time constant for the decline in Cr after exercise (τCr), which corresponds inversely to the exponential time constant for the recovery of PCr after exercise (τPCr) observed with 31 P-MRS (13,14). The objective of this proof-of-principle study was to determine whether CrCEST-derived measurements of postexercise exponential decline in free creatine were prolonged in individuals with primary genetic-based mitochondrial diseases, as compared with matched healthy volunteers.…”

Potential of PET-MRI for imaging of non-oncologic musculoskeletal disease

“…T2 and T1rho relaxometry as well as magnetization transfer techniques provide information about cartilage biochemistry and have been shown to have significant prognostic value (20,21). Further, arterial spin labeling (ASL) (22) and chemical exchange saturation transfer (CEST) (23,24) techniques are able to assess muscle perfusion and energetics, respectively. Although MRI is not typically associated with bone imaging, tissue diffusion (25) and ultra-short echo time (uTE) (26,27) methods are able to provide important information about bone strength and fracture risk.…”