Zhipeng Cao1,2,3, Zhongliang Zu1,3, Kristin P. O'Grady1,3, Jun Ma2,3, Seth A. Smith1,2,3, William A. Grissom1,2,3, and John C. Gore1,2,3
1Radiology, Vanderbilt University, Nashville, TN, United States, 2Biomedical Engineering, Vanderbilt University, Nashville, TN, United States, 3Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States
Synopsis
A novel saturation pulse design method for ultra-high field human CEST imaging is presented. By alternating complementary saturation patterns using parallel transmission, the method achieves homogeneous CEST saturation in the whole brain volume.
Introduction
Chemical exchange saturation transfer (CEST) imaging is a molecular imaging method in which contrast is derived from the effects of exchange between protons of different chemical shifts. Although in principle CEST benefits from using higher main magnetic field strengths due to larger spectral separations, B1 field inhomogeneities pose a major challenge to achieving homogeneous CEST saturation at fields above 3T in human subjects. In recent years, a few methods have emerged to address this issue based on using alternating pulses with fixed coil modes [1,2] (Fig 1b), and parallel transmission (pTx) [3] (Fig 1c). In this report, we study the mathematical basis of the alternating pulsing method and demonstrate improved whole brain homogeneous saturation by jointly designing the pTx based saturation pulses (Fig 1d).
Theory
Based on Ref [3], pTx based CEST saturation pulses can be designed with a Gaussian envelope convolved with a train of basis pulses, each designed to achieve spatial homogeneous flip angle based on the small-tip-angle approximation [4], and their convolution with the Gaussian envelope ensures the desired spectral selectivity. Ref [3] demonstrated that convolving a typical 20ms Gaussian envelope with short (<1ms) basis pulses does not affect the pulse frequency behavior within +/-20ppm, while the common solutes of interest in CEST are within +/-5ppm.
Suggested by Ref [5], when the saturation effect of the solute dominates (due to short solute T2, fast exchange rate, or small saturation pulse power), a saturation pulse train with the same spatial average power may generate a homogeneous saturation distribution. Here, we first verify that the average power relationship holds for common solutes, and then demonstrate a novel alternating pTx pulsing method for improved saturation homogeneity, by jointly designing and alternating every $$$N_p$$$ ($$$N_p$$$=2,3...) saturation pulses. A minimization cost function can be formulated as: $$$\min_{b_i}{\Bigl\{\bigl\lvert \sum_{i=1}^{N_p}{|Ab_i|^2}-N_p|\theta|^2\bigl\lvert+\beta\sum_{i=1}^{N_p}{|b_i|^2}\Bigl\}}$$$, where A is the pTx system matrix, $$$b_i$$$ the $$$i$$$-th of all $$$N_p$$$ jointly-designed basis pulses, $$$\theta$$$ the saturation flip angle, and $$$\beta$$$ the regularization parameter of integrated RF power. The cost function is minimized by iteratively designing each individual basis pulse $$$b_i$$$ based on the flip angles of the rest $$$N_p-1$$$ basis pulses.
Method
The mathematical basis of the alternating saturation pulsing method was studied by performing 3-pool (water, solute, macromolecule) Bloch-McConnell simulations on three representative solutes at 9.4T: amide (1.5s T1, 2ms T2, fractional pool size (fs) 0.0015, exchange rate (ksw) = 50 Hz, offset = 3.5 ppm), creatine (1.5s T1, 10ms T2, 0.005 fs, 600Hz ksw, 2 ppm), and glutamate (1.5s T1, 10ms T2, 0.01 fs, 5000Hz ksw, 3ppm), and including macromolecular (1.5s T1, 0.015ms T2, 0.1 fs, 25Hz ksw, -2.34ppm) magnetization transfer (MT) effects and water relaxation (2.8s T1, 460ms T2). The peak B1 amplitude and duration of the saturation pulse were 1uT and 10ms for amide, 0.6uT and 20 ms for creatine, and 2uT and 20 ms for glutamate. Next, experiments were performed with same protocols on a creatine phantom and a glutamate phantom with homogeneous B1 field on a Varian 9.4T with a 38mm Litz RF coil. The phantoms were made by adding 50 mM creatine or glutamate in 1×PBS, with pH of the solutions titrated to 7 by using HCl or NaOH. All studies used the alternating saturation pulses scaled by different factors ($$$\alpha_1$$$, $$$\alpha_2$$$) (Fig 1b), with 100 gaussian pulses each with 90% duty cycle. Finally, the proposed alternating pTx saturation pulse design was demonstrated with B1 and B0 fields obtained from numerical simulation of an 8 channel transmit head array with a human head model at 7T. Each basis pulse is designed with 0.16 ms duration [3].
Results & Discussion
Fig2 shows that when saturation effects dominate, all three solutes in the presence of MT follow the average power relationship. Fig3 validates the average power relationship in experiments, albeit without MT effects. Fig4 shows the use of the average power relationship in designing parallel transmission pulses for CEST saturation that excite complementary flip angle distributions. Fig5 compares the volumetric saturation performance of the proposed method with the previously-published pTx based approach, showing the proposed method can overcome challenges from previous designs with short basis pulse durations (to keep side bands out of the frequency bandwidth of interest), that they were insufficient for homogeneous saturation in an extended brain volume.
Conclusion
A novel alternating pTx based CEST saturation pulse design method is proposed and demonstrated based on the metric of keeping constant average power for homogeneous saturation transfer for high field human MRI scanners. Ongoing work involves in vivo demonstration of the pulse design on a 7T Philips human MRI scanner.
Acknowledgements
NIH R01 EB 016695 & U01 EB 025162References
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