Purpose

Amide proton transfer (APT) is an important mechanism that may reflect changes in the physiological state. However, most CEST based methods have difficulty quantifying APT due to confounding asymmetric magnetization transfer (MT) and nuclear Overhauser effects (NOE). CERT¹ is a pulsed version of CEST that relies on the difference in the water signals when the solutes are rotated by π pulses (labeling scan) and 2π pulses (reference scan). Therefore, homogeneity of B₁ is crucial. In order to improve the robustness of CERT and further apply this method to the clinics, we propose a new method (Fig. 1), which replaces Gaussian pulses by adiabatic hyperbolic secant (HS) pulses during the saturation in CERT to obtain accurate rotations.

Methods

In order to demonstrate HS-CERT, the three-pool model composed by seven coupled Bloch equations were numerically simulated with the parameters of T_1w = 1.5 s, T_2w = 60 ms, T_1s = 1 s, T_2s = 20 ms, T_1m = 1 s, T_2m = 15 μs, f_s = 0.001, f_m = 0.1, k_sw = 50 Hz, and k_mw = 25 Hz, and the lineshape of macromolecule pool is depicted by a super-Lorentzian function. A 50 mM creatine phantom at pH = 6.7 was measured on a 9.4 T Varian small animal scanner at around 23˚C. The HS-CERT metric, named MTR_HS, is defined by the difference of the two scans with various pulse train time of repetition (PTR) at the same offset: $$$MTR_{HS}=( S(PTR_{short})-S(PTR_{long}))/S_0$$$. This definition is similar to the metric of conventional CERT, MTR_double: $$$MTR_{double}=(S(π)-S(2π))/S_0$$$.

Results

The three-pool model simulations of the HS-CERT Z-spectrum (Fig. 2A) show that the amount of saturation is related to PTR, likely due to T₁ effects during free recovery periods. We choose 200 ms PTR as the reference due to its small effects at the solute resonance, and we examine the effect of varying the PTR of the labeling scan in Fig. 2B. Experimental measurements of creatine using HS-CERT show similar results with long PTR leading to less saturation (Fig. 3A and 3B), and the comparisons with simulations agree with experiments (Fig. 3C). In the extreme cases, such as, 400 or 800 ms PTR, T₁ recovery strongly affects the equilibrium during the delays, and raises the baselines indicting that saturation is no longer purely a function of integrated power, which stays constant. These cases are excluded to avoid overestimations of APT. Fig. 3D shows that the contrasts of MTR_HS and MTR_double have comparable contrasts in this particular case. The simulations (Fig. 4) show that the contrasts of MTR_HS and MTR_double have 10% and 25~50% variations, respectively, when B₁ has +/- 20% errors. Similarly, the contrasts of MTR_HS and MTR_double have 10% and 20% variations, respectively, when B₀ has +/- 100 Hz errors.

Discussion

Even though MTR_HS and MTR_double have the same constant integrated power constraint and similar pulse sequences, the MTR_HS metric is based on the T₁ recovery during the interleaved delays instead of the rotation effect. In this study, we use 200 ms PTR as the reference scan; however, the optimal PTR is still unclear. MTR_HS and MTR_double are based on the assumption that constant integrated power leads to constant baseline saturation, which might not be true when the spins lose the memory due to the long delays. In this preliminary study, the pulse width of HS is 20 ms and β and μ are 529.83 rad/s and 1.78, respectively, which results in the excitation bandwidth of 300 Hz, and these values could be further optimized. Additionally, the pulse width and PTR are independent parameters in the adiabatic condition, which provides another degree of freedom affecting the interactions between pulse and proton exchange of solutes.

Conclusion

The preliminary results suggest that the robustness against B₁ and B₀ inhomogeneity can be improved by implementing adiabatic hyperbolic secant pulses during saturation, which is important to the clinical applications. It also shows that MTR_HS has comparable sensitivity to conventional MTR_double on the creatine phantom. However, the parameter constraints of MTR_HS are fundamentally different from those of MTR_double, and are not yet fully optimized.

Acknowledgements

No acknowledgement found.

References

1. Zu Z, Xu J, Li H, Chekmenev EY, Quarles CC, Does MD, Gore JC, Gochberg DF. Imaging amide proton transfer and nuclear overhauser enhancement using chemical exchange rotation transfer (CERT). Magn Reson in Med 2014;72(2):471-476.