SWIFT-CEST: A new MRI method to overcome T₂ shortening caused by PARACEST contrast agents

The exchange of water molecules between the inner sphere of a paramagnetic chemical exchange saturation transfer (PARACEST) contrast agent and bulk water can shorten the bulk water T₂ through the T₂-exchange (T_2ex) mechanism. The line-broadening T_2ex effect is proportional to the agent concentration, the chemical shift of the exchanging water molecule, and is highly dependent on the water molecule exchange rate. A significant T_2ex contribution to the bulk water linewidth can make the regions of agent uptake appear dark when imaging with conventional sequences like gradient-echo and fast spin-echo. The minimum echo times for these sequences (1-10 ms) are not fast enough to capture signal from the regions of shortened T₂. This makes "Off" (saturation at -ΔIω) minus "On" (saturation at +ΔIω) imaging of PARACEST agents difficult, because the regions of uptake are dark in both images. It is shown here that the loss of bulk water signal due to T _2ex can be reclaimed using the ultrashort echo times (<10 μs) achieved with the sweep imaging with Fourier transform pulse sequence. Modification of the sweep imaging with Fourier transform sequence for PARACEST imaging is first discussed, followed by parameter optimization using in vitro experiments. In vivo PARACEST studies comparing fast spin-echo to sweep imaging with Fourier transform were performed using EuDOTA-(gly) 4- uptake in healthy mouse kidneys. The results show that the negative contrast caused by T _2ex can be overcome using the ultrashort echo time achieved with sweep imaging with Fourier transform, thereby enabling fast and sensitive in vivo PARACEST imaging.