Chemical Exchange Saturation Transfer (CEST) imaging has emerged as an attractive alternative MRI contrast mechanism to T1 and T2 contrast (1-7). This lecture will cover the basic steps in generating CEST contrast maps, including acquisition, B0 map creation, and Post-processing of CEST MRI data.
Chemical Exchange Saturation Transfer (CEST) imaging has emerged as an attractive alternative MRI contrast mechanism to T1 and T2 contrast (1-7). The most common method to perform CEST experiments is through use of a long CW off resonance radiofrequency (RF) pulses to label solute molecules after which this labeling is transferred to the solvent. The change in longitudinal magnetization (z) of the water pool is then measured to characterize the effect. While using this approach which involves continuous transfer of partial saturation to bulk water can result in large water signal changes, it is often not possible to run CW-CEST based on amplifier droop, transmission coil and other scanner related considerations, especially on human MRI scanners. Consequently, a large percentage of CEST experiments on human subjects have used pulsed-CEST approaches (8-13). Pulsed-CEST approaches use frequency selective pulses for labeling which are typically inversion pulses. This labeling pulse is followed by a delay that allows labeled protons to exchange with bulk water. This whole process can be repeated many times to build up the fraction of labeled protons in bulk water. While it isn’t as efficient as CW saturation, it has advantages for selecting protons based on their exchange rate with water, as clearly exemplified by the Variable Delay Multi-Pulse (VDMP) sequence(14). Another approach is to use a binomial pair of excitation pulses to transfer signal to water with the chemical shift of exchanging solute molecules allowed to evolve between these pulses for frequency labeling, the Frequency Labeled Exchange approach (FLEX). The FLEX signal is collected as a function of the time variable (tevol) with this signal Fourier transformed to obtain a spectrum. This approach has several advantages which include a capability of simultaneously exciting multiple protons using the excitation pulses and an internal B0 reference which avoids the need to acquire additional B0 maps. Finally the short excitation pulses can efficiently label rapidly exchanging protons (15). However this approach can be more time intensive with the number of tevol’s required to transform the data.
Post-processing of CEST MRI data plays a crucial role in the generation of images. The first step after acquiring a set of CEST data over a range of frequency offsets is to correct the offsets spatially using a pre-acquired B0 map or by fitting the frequency dependence of the image intensity in each voxel to a line shape. Because of B0 inhomogeneity particularly for abdominal imaging studies, nominal offsets may present the contrast at other offsets, and, even worse, the magnitude of the error can vary spatially. For B0 map generation, the most common method is through Gradient echo phase imaging (16). This is an established technique to rapidly create such maps, however using phase-mapping methods may create complications when the CEST data collection uses a different pulse sequence. Another method, WAter Saturation Shift Referencing (WASSR) employs the same pulse sequence for B0 mapping as CEST data collection (17) but with a shorter, lower power saturation pulse to produce sharp maps of B0. For a number of studies when a relatively weak saturation field strength is used (i.e. < 2µT), one can directly fit the acquired z-spectral data to produce B0 corrected images. This is appropriate when MTC is negligible.
After B0 map generation, the next step is to extract the CEST contrast from other effects that could interfere with the accuracy of CEST quantification. There are two main approaches for separating CEST contrast: asymmetry analysis and curve fitting. For asymmetry analysis, the asymmetry of the magnetization transfer ratio (MTRasym) is calculated. This experimental MTRasym is assumed to be purely due to CEST contrast given the fact that Direct Saturation (DS) is symmetric with respect to the water resonance and magnetization transfer contrast (MTC) is assumed to be symmetric. While MTRasym is the most widely used metric to quantify CEST effects, it has several intrinsic weaknesses. As such, recently a number of groups have chosen to use curve fitting. One popular approach is to fit the experimental data to multiple lorentzians to retrieve the CEST contrast from experiment data (18-20). Another method which is relevant for FLEX studies is to fit the signal loss in the time domain to multi-exponential functions and then transform after fitting into the frequency dimension(15, 21). The fitting approaches can improve accounting for other sources of signal loss, but also generally require collection of more frequency data than asymmetry analysis and as a result require longer scanning times. Depending on the type of CEST agent to be detected and how many other background effects are present near the agent’s labile protons, curve fitting may be required.
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