Abstract
Noninvasive techniques to monitor temperature have numerous useful biomedical applications. However, MR thermometry techniques based on the chemical shift, relaxation rates, and molecular diffusion rate of the water ^1^H signal suffer from poor thermal resolution. The feasibility of MR thermometry based on the strong temperature dependence of the hyperfine‐shifted ^1^H signal from the paramagnetic lanthanide complex thulium‐1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetate (TmDOTA^–^) was recently demonstrated. The use of paramagnetic lanthanide complexes for MR thermometry can be further enhanced by improving the signal‐to‐noise ratio (SNR) of the observed signal. In this study, the use of lanthanide complexes of a methyl‐substituted analog of DOTA^4–^, 1,4,7,10‐tetramethyl 1,4,7,10‐tetra azacyclodoecane‐1,4,7,10‐tetraacetic acetate (DOTMA^4–^) was evaluated. DOTMA^4–^ complexes have 12 magnetically equivalent methyl protons, which provide an intense and sharper resonance compared to the corresponding DOTA^–^ complexes. Experiments with paramagnetic Pr^3+^, Yb^3+^, Tb^3+^, Dy^3+^, and Tm^3+^ complexes of DOTMA^4–^ showed that the Tm^3+^ complex is most favorable for MR thermometery because of the high temperature dependence of its chemical shift and its relatively narrow linewidth. The chemical shift of the methyl ^1^H signal from TmDOTMA^–^ was ∼60 times more sensitive to temperature than the water ^1^H shift and was insensitive to changes in concentration, pH, [Ca^2+^], or the presence of other ions and macromolecules. The application of TmDOTMA^–^ for measuring temperature in a subcutaneously implanted tumor model was demonstrated. Lastly, the feasibility of obtaining 3D images from the methyl ^1^H resonance of TmDOTMA^–^ was demonstrated in phantom and live animal experiments. Overall, TmDOTMA^–^ appears to be a promising probe for MR thermometry in vivo. Magn Reson Med 53:294–303, 2005. © 2005 Wiley‐Liss, Inc.