In Vivo Detection of PARACEST Agents With Relaxation Correction

Several pulse sequences have been used to detect paramagnetic chemical exchange saturation transfer (PARACEST) contrast agents in animals to quantify the uptake over time following a bolus injection. The observed signal change is a combination of relaxation effects and PARACEST contrast. The purpose of the current study was to isolate the PARACEST effect from the changes in bulk water relaxation induced by the PARACEST agent in vivo for the fast low-angle shot pulse sequence. A fast low-angle shot-based pulse sequence was used to acquire continuous images on a 9.4-T MRI of phantoms and the kidneys of mice following PARACEST agent (Tm(3+)-DOTAM-Gly-Lys) injection. A WALTZ-16 pulse was applied before every second image to generate on-resonance paramagnetic chemical exchange effects. Signal intensity changes of up to 50% were observed in the mouse kidney in the control images (without a WALTZ-16 preparation pulse) due to altered bulk water relaxation induced by the PARACEST agent. Despite these changes, a clear on-resonance paramagnetic chemical exchange effect of 4-7% was also observed. A four-pool exchange model was used to describe image signal intensity. This study demonstrates that in vivo on-resonance paramagnetic chemical exchange effect contrast can be isolated from tissue relaxation time constant changes induced by a PARACEST agent that dominate the signal change.