Brain temperature by Biosensor Imaging of Redundant Deviation in Shifts (BIRDS): comparison between TmDOTP5−and TmDOTMA−

Abstract

Chemical shifts of complexes between paramagnetic lanthanide ions and macrocyclic chelates are sensitive to physiological variations (of temperature and/or pH). Here we demonstrate utility of a complex between thulium ion (Tm(3+)) and the macrocyclic chelate 1,4,7,10-tetramethyl 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (or DOTMA(4-)) for absolute temperature mapping in rat brain. The feasibility of TmDOTMA(-) is compared with that of another Tm(3+)-containing biosensor which is based on the macrocyclic chelate 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetrakis(methylene phosphonate) (or DOTP(8-)). In general, the in vitro and in vivo results suggest that Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) which originate from these agents (but exclude water) can provide temperature maps with good accuracy. While TmDOTP(5-) emanates three major distinct proton resonances which are differentially sensitive to temperature and pH, TmDOTMA(-) has a dominant pH-insensitive proton resonance from a -CH(3) group to allow higher signal-to-noise ratio (SNR) temperature assessment. Temperature (and pH) sensitivities of these resonances are practically identical at low (4.0T) and high (11.7T) magnetic fields and at nominal repetition times only marginal SNR loss is expected at the lower field. Since these resonances have extremely short relaxation times, high-speed chemical shift imaging (CSI) is needed to detect them. Repeated in vivo CSI scans with BIRDS demonstrate excellent measurement stability. Overall, results with TmDOTP(5-) and TmDOTMA(-) suggest that BIRDS can be reliably applied, either at low or high magnetic fields, for functional studies in rodents.