Chemical exchange rotation transfer imaging of phosphocreatine in muscle

Abstract

In chemical exchange saturation transfer (CEST) imaging, the signal at 2.6 ppm from the water resonance in muscle has been assigned to phosphocreatine (PCr). However, this signal has limited specificity for PCr since the signal is also sensitive to exchange with protein and macromolecular protons when using some conventional quantification methods, and will vary with changes in the water longitudinal relaxation rate. Correcting for these effects while maintaining reasonable acquisition times is challenging. As an alternative approach to overcome these problems, here we evaluate chemical exchange rotation transfer (CERT) imaging of PCr in muscle at 9.4 T. Specifically, the CERT metric, AREX_double,cpw at 2.6 ppm, was measured in solutions containing the main muscle metabolites, in tissue homogenates with controlled PCr content, and in vivo in rat leg muscles. PCr dominates CERT metrics around 2.6 ppm (although with nontrivial confounding baseline contributions), indicating that CERT is well-suited to PCr specific imaging, and has the added benefit of requiring a relatively small number of acquisitions.

Keywords: CERT; CEST; creatine; muscle; phosphocreatine.

Fig. 1:

Measured MTR_double,cpw and AREX_double,cpw spectra from solutions containing the main metabolites in muscle. T_1obs are around 4 s for all samples.

Fig. 2:

CW Z-spectra (a), CERT Z-spectra (b), MTR_asym spectra using CW CEST data (c), MTR_{double, cpw} spectra (d), and AREX_{double, cpw} spectra (e) for sample 1 homogenate, and sample 2 homogenate + PCr. Arrows indicate the CEST signals from PCr at around 2.6ppm. T_1obs are 3.7 s and 3.5 s for sample 1 and sample 2, respectively. Note that the 2π spectra in figure (b) serve as baselines with no rotation-exchange effects in the CERT approach.

Fig. 3:

Experimental CW and CERT_cpw Z-spectra (a), MTR_asym spectrum (b), MTR_double,cpw spectrum (c), and AREX_double,cpw spectrum (d) from rat legs (N=5). Arrows indicate the CEST signals from PCr at around 2.6ppm. T_1obs is 2 ± 0.07 s.

Fig. 4:

Maps of tissue anatomy (a), AREX_{double, cpw} at 2 ppm (b), and AREX_{double, cpw} at 2.6 ppm (c) from a representative healthy rat leg. ROI was drawn from region where shimming is good (the root mean square deviation of B₀ field map was < 60 Hz). Anatomy image was from the control scan in the CEST experiment, and was cropped to match the PCr image and to avoid an aliasing artifact at the edge of the image.