Noninvasive MR thermometry using paramagnetic lanthanide complexes of 1,4,7,10-tetraazacyclodoecane-alpha,alpha',alpha'',alpha'''-tetramethyl-1,4,7,10-tetraacetic acid (DOTMA4-).
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 1H signal suffer from poor thermal resolution. The feasibility of MR thermometry based on the strong temperature dependence of the hyperfine-shifted 1H 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 DOTA4-, 1,4,7,10-tetramethyl 1,4,7,10-tetra azacyclodoecane-1,4,7,10-tetraacetic acetate (DOTMA4-) was evaluated. DOTMA4- 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 DOTMA4- 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 1H signal from TmDOTMA- was approximately 60 times more sensitive to temperature than the water 1H 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 1H resonance of TmDOTMA- was demonstrated in phantom and live animal experiments. Overall, TmDOTMA- appears to be a promising probe for MR thermometry in vivo.
Hekmatyar
S K
SK
Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5181, USA.
Hopewell
Paige
P
Pakin
Sait Kubilay
SK
Babsky
Andriy
A
Bansal
Navin
N
D000465:Algorithms; D000818:Animals; D045744:Cell Line, Tumor; D005240:Feasibility Studies; D005354:Fibrosarcoma / Q000175:diagnosis*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D028581:Lanthanoid Series Elements; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008280:Magnetics; D051379:Mice; D008809:Mice, Inbred C3H; D019047:Phantoms, Imaging; D011522:Protons; D000644:Quaternary Ammonium Compounds; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013817:Thermography / Q000379:methods*
D028581:Lanthanoid Series Elements; D011522:Protons; D000644:Quaternary Ammonium Compounds; C054005:N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium