Water diffusion-exchange effect on the paramagnetic relaxation enhancement in off-resonance rotating frame

The off-resonance rotating frame technique based on the spin relaxation properties of off-resonance T1rho can significantly increase the sensitivity of detecting paramagnetic labeling at high magnetic fields by MRI. However, the in vivo detectable dimension for labeled cell clusters/tissues in T1rho-weighted images is limited by the water diffusion-exchange between mesoscopic scale compartments. An experimental investigation of the effect of water diffusion-exchange between compartments on the paramagnetic relaxation enhancement of paramagnetic agent compartment is presented for in vitro/in vivo models. In these models, the size of paramagnetic agent compartment is comparable to the mean diffusion displacement of water molecules during the long RF pulses that are used to generate the off-resonance rotating frame. The three main objectives of this study were: (1) to qualitatively correlate the effect of water diffusion-exchange with the RF parameters of the long pulse and the rates of water diffusion, (2) to explore the effect of water diffusion-exchange on the paramagnetic relaxation enhancement in vitro, and (3) to demonstrate the paramagnetic relaxation enhancement in vivo. The in vitro models include the water permeable dialysis tubes or water permeable hollow fibers embedded in cross-linked proteins gels. The MWCO of the dialysis tubes was chosen from 0.1 to 15 kDa to control the water diffusion rate. Thin hollow fibers were chosen to provide sub-millimeter scale compartments for the paramagnetic agents. The in vivo model utilized the rat cerebral vasculatures as a paramagnetic agent compartment, and intravascular agents (Gd-DTPA)30-BSA were administrated into the compartment via bolus injections. Both in vitro and in vivo results demonstrate that the paramagnetic relaxation enhancement is predominant in the T1rho-weighted image in the presence of water diffusion-exchange. The T1rho contrast has substantially higher sensitivity than the conventional T1 contrast in detecting paramagnetic agents, especially at low paramagnetic agent volumetric fractions, low paramagnetic agent concentrations, and low RF amplitudes. Short pulse duration, short pulse recycle delay and efficient paramagnetic relaxation can reduce the influence of water diffusion-exchange on the paramagnetic enhancement. This study paves the way for the design of off-resonance rotating experiments to detect labeled cell clusters/tissue compartments in vivo at a sub-millimeter scale.