title: 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 R2 *, as well as the co-release of the contrast agent and the drug, by means of R1, 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.
authors.affiliation: University Medical Center Utrecht, Department of Radiology, Imaging Division, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands.
authors.forename: Cyril
authors.initials: C
authors.lastname: Lorenzato
authors.forename: Chris
authors.initials: C
authors.lastname: Oerlemans
authors.forename: Alexandru
authors.initials: A
authors.lastname: Cernicanu
authors.forename: Mario
authors.initials: M
authors.lastname: Ries
authors.forename: Baudouin
authors.initials: B
authors.lastname: Denis de Senneville
authors.forename: Chrit
authors.initials: C
authors.lastname: Moonen
authors.forename: Clemens
authors.initials: C
authors.lastname: Bos
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D003287:Contrast Media; D004337:Drug Carriers / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D004578:Electron Spin Resonance Spectroscopy; D005682:Gadolinium / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D006361:Heating / Q000295:instrumentation; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000032:analysis; D008081:Liposomes / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging / Q000379:methods*; D018482:Muscle, Skeletal / Q000033:anatomy & histology; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000032:analysis; D010316:Particle Size; D034421:Sus scrofa; D013552:Swine; D013696:Temperature; D062125:Thermometry / Q000379:methods*; D014018:Tissue Distribution; D014465:Ultrasonics
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D004337:Drug Carriers; D006571:Heterocyclic Compounds; D008081:Liposomes; D009942:Organometallic Compounds; C062402:gadoteridol; D005682:Gadolinium
keywords: MRI; apparent proton density; drug delivery system; focused ultrasound; high-intensity focused ultrasound; multi-echo spoiled gradient echo; relaxometry, R1, R2*; thermosensitive liposome