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

Abstract : 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 R 2 *, 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 R 2 * and R 1 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. R 2 * was obtained from a fit to the ME-SPGR data. Absolute R 1 was calculated from the signal magnitude changes corrected for the apparent proton density changes and a baseline Look–Locker R 1 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. R 2 *, R 1 and temperature maps were measured with a 5-s temporal resolution. Both R 2 *and R 1 measured were found to change with temperature. The dynamic R 1 measurements after heating agreed with the Look–Locker R 1 values if changes in equilibrium magnetization with temperature were considered. Release of gadolinium from TSLs was detected by an R 1 increase near the phase transition temperature, as well as a shallow R 2 * increase. Simultaneous temperature, R 2 * and R 1 mapping is feasible in real time and has the potential for use in image-guided drug delivery studies.
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Submitted on : Tuesday, August 29, 2017 - 12:07:05 PM
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Cyril Lorenzato, Chris Oerlemans, Alexandru Cernicanu, Mario Ries, Baudouin Denis de Senneville, et al.. Rapid dynamic R1/R2*/temperature assessment: a method with potential for monitoring drug delivery. NMR in Biomedicine, Wiley, 2014, 27 (11), pp.1267-1274. ⟨10.1002/nbm.3182⟩. ⟨hal-01578215⟩

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