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.

Materials and methods: CrCEST saturation parameters were empirically optimized for 3T. CEST, T2 , magnetization transfer ratio (MTR), and (31) P 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 six 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 use among subjects. The CrCEST results were compared with (31) P 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: It is demonstrated that the CrCEST technique could be applied at 3T to measure dynamic changes in creatine in muscle in vivo. The widespread availability and clinical applicability of 3T scanners has the potential to clinically advance this method.

Keywords: CrCEST; chemical exchange; creatine; endogenous contrast; muscle.

© 2013 Wiley Periodicals, Inc.

Figures

Figure 1

The data (crosses) fitted z-spectra (solid lines) and corresponding asymmetry plots for the soleus muscle at baseline for (a,b) varying saturation amplitudes [B1rms = 0.72 μT, 1.44 μT, 2.16 μT, 2.87 μT, and 3.59 μT] and constant 500 ms duration as well as (c,d) varying saturation durations [tsat = 250ms, 500ms, 1000 ms and 1500 ms] at a saturation amplitude of B1rms = 2.15 μT. CrCESTasym at Δω=1.8 ppm is indicated with a dotted line.

Figure 2

CrCESTasym maps of a human calf muscle before and every 24 seconds after (in order by number) 2 minutes of mild plantar flexion exercise. Color bar represents CrCESTasym in percent. The segmented anatomical image is displayed in the bottom left.

Figure 3

Plot of the average CrCESTasym as function of time in 3 different muscles of the calf [Soleus, Medial Gastrocnemius (MG) and Lateral Gastrocnemius (LG)] segmented from anatomical images (Top Right). Error bars represent the standard deviation in the CrCESTasym in each region.

Figure 4

(a) MTR and (b) T2 maps before and every 28 seconds after (in order by number) the 2 minutes of mild plantar flexion exercise.

Figure 5

(a) Stacked plot of every alternate 31P MRS spectra acquired 2 minutes before and 8 minutes after exercise with a 12 second temporal resolution. (b) Comparison between the CrCESTasym from the area of the gastrocnemius muscles equal to that of the 31P surface coil excitation and 31P MRS PCr signal as a function of time at an equal temporal resolution of 24 seconds.

Figure 6

CrCESTasym and 31P MRS data across subjects. (a) 31P MRS PCr peak integral as a function of time. (b) Mean CrCESTasym corresponding to the 31P MR Signal is plotted as a function of time for each subject. For each subject, good agreement is seen between the two figures in the rate and shape at which they recover back to baseline following exercise

Figure 7

Plot of the average change in the CESTasym corresponding to the 31P MR Signal as a function of the calculated change in Cr concentration across all subjects. The % decrease in the PCr signal following exercise was used to determine the decrease in PCr based on a 33 mM PCr baseline concentration (19). As the total Cr remains constant, the decrease in PCr concentration was equated to an equivalent increase in Cr concentration. This produces a slope of 0.45 % CrCESTasym/mM Cr with an R2 value 0.65 with the y-intercept set to zero.