Perfusion has no effect on the in vivo CEST effect from Cr (CrCEST) in skeletal muscle

Abstract

Creatine, a key component of muscle energy metabolism, exhibits a chemical exchange saturation transfer (CEST) effect between its amine group and bulk water, which has been exploited to spatially and temporally map creatine changes in skeletal muscle before and after exercise. In addition, exercise leads to an increase in muscle perfusion. In this work, we determined the effects of perfused blood on the CEST effects from creatine in skeletal muscle. Experiments were performed on healthy human subjects (n = 5) on a whole-body Siemens 7T magnetic resonance imaging (MRI) scanner with a 28-channel radiofrequency (RF) coil. Reactive hyperemia, induced by inflation and subsequent deflation of a pressure cuff secured around the thigh, was used to increase tissue perfusion whilst maintaining the levels of creatine kinase metabolites. CEST, arterial spin labeling (ASL) and ³¹ P MRS data were acquired at baseline and for 6 min after cuff deflation. Reactive hyperemia resulted in substantial increases in perfusion in human skeletal muscle of the lower leg as measured by the ASL mean percentage difference. However, no significant changes in CrCEST asymmetry (CrCEST_asym ) or ³¹ P MRS-derived PCr levels of skeletal muscle were observed following cuff deflation. This work demonstrates that perfusion changes do not have a major confounding effect on CrCEST measurements.

Keywords: ASL; CEST; CrCEST; creatine; energy metabolism; muscle; perfusion.

Figure 1

CrCEST_asym maps of a healthy human leg at baseline and every 30 seconds during recovery following 3 minutes of blood flow occlusion induced by cuff inflation (total time post cuff release labeled). Color bar represents CrCEST_asym in percent.

Figure 2

ASL mean percent difference maps for 8 label/control pairs with a total temporal resolution of 32 seconds generated at baseline and recovery after 3 minutes of blood flow occlusion induced by cuff inflation (total time post cuff release labeled). Color bar represents mean percent difference.

Figure 3

(a) Stacked plot of every ³¹P MRS spectra acquired with a 12 second temporal resolution at baseline, during cuff inflation and following cuff release. (b) ³¹P MRS PCr signal integral as a function of time from ³¹P MRS spectra acquired with a temporal resolution of 12 seconds.

Figure 4

(a) CrCEST_asym, (b) ASL mean percent difference, and (c) relative PCr peak integral values at baseline, immediately following cuff deflation and 5 min post cuff deflation for each of the 5 subjects. (d) Anatomical image of the lower leg. CrCEST_asym and ASL mean percent difference measurements were calculated as an average from values in a region of interest (ROI) [outlined in white] for the gastrocnemius and soleus muscles chosen to correspond to the localization of the ³¹P surface coil which was away from any major vessels. Error bars represent the standard deviation in the CrCEST_asym and ASL mean percent difference in the ROI.