We review the mechanisms by which liposomal contrast agents-solutions of liposomes that entrap and deliver (usually paramagnetic) contrast agent into specific tissues-cause a desired enhancement of the bulk relaxation rate in tissues. The relaxation-enhancing action for transverse magnetization can be most generally explained by exchange (inner sphere relaxation) and diffu-sional dephasing (outer sphere relaxation). Simple analytic expressions for inner and outer sphere relaxation mechanisms are presented. At typical MRI field strengths (≤ 1T) longitudinal magnetization is affected only by inner sphere relaxation. For typical liposomal preparations the transverse magnetization relaxation is also dominated by the inner sphere mechanism. For rather low effective concentrations (2mM) of Gd(DTPA)2-, a relaxation rate enhancement of several Hertz is typically achieved, and the rate increases linearly with the concentration of liposomes. The inner sphere model presented here is similar to recent descriptions which significantly generalize earlier models which have not taken into account the finite lifetime of water inside the liposomes. The present model describes how the permeability, the relative size and the relax-ivity of the entrapped contrast agent affect the bulk relaxivity of the tissue to which liposomal contrast agents have been introduced. Outer sphere relaxation plays a minor role and is comparable to inner sphere relaxation only for larger (diameters ≤ 500 nm), reasonably impermeable (Pd≤ < 10-3 cm/s) liposomes for which the bulk rate enhancement is rather low-about one Hertz. A notable exception occurs for giant (diameters ≤ 10μm), multivesicular liposomes where the bulk rates can be many times higher. Simulations have been carried out for the purpose of investigating the simultaneous action of inner and outer sphere relaxation. The simulations reveal the expected dependence of outer sphere relaxation time on the echo time, but they consistently predict a relaxation rate about twice as high as what the outer sphere theory predicts. In the realm of liposomes studied here, the simulations imply an independence of the inner and outer sphere relaxation mechanisms; i. e., relaxation enhancements can be calculated independently and simply added.
ASJC Scopus subject areas
- Pharmaceutical Science