A multislice gradient echo pulse sequence for CEST imaging

Ward et al. (1) and Ward and Balaban (2) demonstrated that low-molecular-weight compounds with slowly exchanging –NH or –OH protons can alter tissue contrast via chemical exchange dependent saturation transfer (CEST) of chemically shifted, presaturated spins to bulk water. Images using CEST are typically generated by subtracting images obtained by applying a radiofrequency saturation pulse at the resonant frequency of the exchanging protons from images obtained by applying the saturation pulse at a control frequency. More recently, this CEST approach has been extended to exogenous paramagnetic lanthanide chelates with slow water exchange to produce MR contrast based on the paramagnetic CEST (PARACEST) effect (3,4). These PARACEST agents have advantages over more conventional T1-shortening agents because they are activated selectively by an excitation pulse applied at a specific frequency. Targeted CEST/PARACEST agents with different targets and different resonant frequencies for the exchanging protons may be injected together, yet imaged separately in a single examination (5). The CEST/PARACEST effect has been applied with responsive agents (6) to produce images sensitive to a variety of tissue parameters, including temperature (7), presence of enzymes (8), pH (2,9), and concentrations of glucose (10,11), lactate (12), and zinc (13). Also, since the relaxivities of these PARACEST agents are low, endogenous MR contrast is preserved until external radiofrequency saturation is applied and there is no interference with subsequent imaging with T1-shortening agents. In practice, the external radiofrequency saturation pulse is applied for a time longer than the T1 of the bulk water protons. Woessner et al. (14) have published numerical solutions to the Bloch equations that show that both CEST and PARACEST systems approach steady state under these conditions. As was recently pointed out by Liu et al. (15) and Sun et al. (16), the most straightforward acquisition schemes for PARACEST and CEST MRI involve collecting a single line of k-space data with radiofrequency irradiation and a control. This approach can lead to long acquisition times since this process can only be repeated with repetition times longer than the T1 of the tissue. They approached shorter acquisition times for PARACEST/CEST imaging with a fast imaging method like fast spin echo following a long presaturation period. The long presaturation period may contain many short saturation pulses rather than one long one, thereby placing less stress on the radiofrequency amplifier. In our alternate approach, short presaturation pulses are interleaved within an ordinary two-dimensional, multislice, gradient echo pulse sequence (Fig. 1), one short presaturation pulse before each excitation pulse. The shorter presaturation pulses, being spaced at much less than T1, have a cumulative effect on the magnetization. The flexibility in speed, coverage, and signal-to-noise ratio of ordinary gradient echo imaging is preserved (17). This note shows that multislice imaging with PARACEST/CEST agents is practical and that in a uniform phantom the same effect is seen in each slice. FIG. 1 Pulse sequence for two-dimensional, multislice, gradient-echo CEST, shown here for three slices. Saturation pulses are not spatially selective so the saturation pulse before each spatially selective observed pulse produces a CEST effect on all slices. ...