Rapid dynamic R₁/R₂*/temperature assessment: A method with potential for monitoring drug delivery

Local drug delivery by hyperthermia-induced drug release from thermosensitive liposomes (TSLs) may reduce the systemic toxicity of chemotherapy, whilst maintaining or increasing its efficacy. Relaxivity contrast agents can be co-encapsulated with the drug to allow the visualization of the presence of liposomes, by means of R₂*, as well as the co-release of the contrast agent and the drug, by means of R_1, on heating. Here, the mathematical method used to extract both R₂* and R₁ from a fast dynamic multi-echo spoiled gradient echo (ME-SPGR) is presented and analyzed. Finally, this method is used to monitor such release events. R₂* was obtained from a fit to the ME-SPGR data. Absolute R₁ was calculated from the signal magnitude changes corrected for the apparent proton density changes and a baseline Look-Locker R₁ map. The method was used to monitor nearly homogeneous water bath heating and local focused ultrasound heating of muscle tissue, and to visualize the release of a gadolinium chelate from TSLs in vitro. R₂*, R₁ and temperature maps were measured with a 5-s temporal resolution. Both R₂*and R₁ measured were found to change with temperature. The dynamic R₁ measurements after heating agreed with the Look-Locker R₁ values if changes in equilibrium magnetization with temperature were considered. Release of gadolinium from TSLs was detected by an R₁ increase near the phase transition temperature, as well as a shallow R₂* increase. Simultaneous temperature, R₂* and R₁ mapping is feasible in real time and has the potential for use in image-guided drug delivery studies.