Conventional chemical exchange saturation transfer (CEST) scans often sample pre-determined offsets, for example, only looking at creatine, or glutamate or amide^1-3, potentially missing tremendous amount of diagnostic information. To resolve metabolites at different chemical shift offsets, the saturation offset has to be varied from scan to scan so the complete Z-spectrum can be obtained, which is time consuming⁴. Moreover, this makes its temporal resolution quite poor, not suitable for capturing dynamic changes such as contrast agent enhanced pH MRI. To overcome this, we innovatively combined superfast Z-spectroscopy⁵ with chemical shift imaging (CSI) and developed Superfast CEST Spectral Imaging (SCSI). It obtained fast Z-spectral CEST information with spatial resolution. While conventional CSI measures dilute metabolites, the proposed SCSI exploits CEST mechanism to investigate the interaction between metabolites/contrast agents and tissue water, providing sensitivity enhanced characterizations of metabolites and pH, etc.In vitro CEST phantom with two vials of CuSO₄ doped creatine and nicotinamide solution at different concentrations was used. SCSI measurements were performed on a 4.7T Bruker scanner (Bruker Biospec, Billerica, MA) using a CSI sequence with PRESS localization. Figure 1 shows the pulse sequence of the proposed SCSI method. By applying a constant magnetic field gradient during the saturation period, the off-resonant data points in the Z-spectrum are generated by a gradient-induced change of the Larmor frequencies of the nuclei in the sample, such that they experience saturation with different off-resonance conditions depending on their position⁶. We acquired SCSI data without (B₁=0 µT) or with (B₁=1.0 µT) RF saturation, repetition time (TR)/saturation time (TS) = 5/2.5 s, 2 averages, FOV = 40x40 mm², slab thickness = 10mm, matrix = 8×8 (reconstructed to 32×32) and 128 spectral points over ±5 ppm. In vivo SCSI was performed on the kidneys of five adult Wistar rats with respiratory triggering after a CT contrast agent Iopamidol (Isovue370, 1.5 mg I/g) injection. The parameters of in vivo SCSI was similar to in vitro study except for TR/TS = 6/3 s, FOV = 22x16 mm², slab thickness = 4 mm and 128 spectral points from -2 to 8 ppm. Renal pH-weighted map was calculated using ratiometric analysis by taking the amplitude ratio of 5.5 and 4.3 ppm. Figure 2 shows that the proposed SCSI method can capture creatine and nicotinamide concentration differences (50 mM vs. 100 mM vs. background) with spatial information. Conventional proton CSI showed much lower sensitivity (data not shown) as it highly depends on the performance of water suppression. In practice, the residual water peak in conventional CSI is distorted and varies spatially in amplitude, which leads to substantial baseline variability that impairs metabolite quantification⁷. This can be overcome by our SCSI approach as it exploits CEST contrast to investigate the interaction between metabolites/contrast agents and tissue water so no water suppression is required. We further demonstrated the feasibility of the proposed SCSI approach for in vivo renal pH imaging after iopamidol injection. Figure 3 shows renal ratiometric CEST map obtained with this method, which is considered pH sensitive⁸, clearly resolved the differences among cortex, medulla and calyx. In conclusion, the proposed SCSI method allows us to integrate CSI with more sensitive CEST measurement, enabling fast Z-spectral imaging with good spatiotemporal resolution, which is highly desirable for monitoring dynamic processes.