Noninvasive MR thermometry using paramagnetic lanthanide complexes of 1,4,7,10-tetraazacyclodoecane- α,α′,α′′,α′′′-tetramethyl-1,4,7,10-tetraacetic acid (DOTMA4-)

被引:44
作者
Hekmatyar, SK [1 ]
Hopewell, P [1 ]
Pakin, SK [1 ]
Babsky, A [1 ]
Bansal, N [1 ]
机构
[1] Indiana Univ, Sch Med, Dept Radiol, Indianapolis, IN 46202 USA
关键词
thermometry; lanthanide complexes; H-1 NMR spectroscopy; H-1 NMR imaging; paramagnetic shift; in vivo;
D O I
10.1002/mrm.20345
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
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 H-1 signal suffer from poor thermal resolution. The feasibility of MR thermometry based on the strong temperature dependence of the hyperfine-shifted H-1 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 Pr3+, Yb3+, Tb3+, Dy3+, and Tm3+ complexes of DOTMA(4-) showed that the TM3+ 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 H-1 signal from TmDOTMA(-) was similar to60 times more sensitive to temperature than the water H-1 shift and was insensitive to changes in concentration, pH, [Ca2+], 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 H-1 resonance of TmDOTMA(-) was demonstrated in phantom and live animal experiments. Overall, TmDOTMA- appears to be a promising probe for MR thermometry in vivo. (C) 2005 Wiley-Liss, Inc.
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收藏
页码:294 / 303
页数:10
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