Optimized MRI contrast for on-resonance proton exchange processes of PARACEST agents in biological systems

Image contrast associated with paramagnetic chemical exchange saturation transfer agents can be generated by off-resonance irradiation of agent-bound water or amide protons or on-resonance irradiation of bulk water. Previously, a four-pool model was developed to describe an in vivo system. The model incorporated the magnetization transfer effect from macromolecules when using off-resonance irradiation. In the current study, this four-pool model is modified to describe the in vivo system when using on-resonance irradiation. The influences of pulse power, pulse duration, the chemical shift of bound water, the proton exchange rate between bulk water and bound water, and agent concentration on the on-resonance paramagnetic agent chemical exchange effects were simulated using a WALTZ-16 pulse train in the absence and presence of the macromolecule pool. The results demonstrated that while contrast increases with pulse duration in aqueous solution, there is an optimal pulse duration that maximizes on-resonance paramagnetic agent chemical exchange effects contrast in vivo. This predication was verified by experimental spectroscopic and imaging results from aqueous solution, bovine serum albumin phantoms, and a tissue phantom containing thulium-DOTAM (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetamide)-glycine-lysine. This model can be used to optimize sequence parameters to maximize in vivo on-resonance paramagnetic agent chemical exchange effects contrast.