Non-invasive temperature imaging with thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraacetic acid (TmDOTMA−)

Abstract

Non-invasive thermometry using hyperfine-shifted MR signals from paramagnetic lanthanide complexes has attracted attention recently because the chemical shifts of these complexes are many times more sensitive to temperature than the water 1H signal. Among all the lanthanide complexes examined thus far, thulium tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (TmDOTMA-) appears to be the most suitable for MR thermometry. In this paper, the feasibility of imaging the methyl 1H signal from TmDOTMA- using a frequency-selective radiofrequency excitation pulse and chemical shift-selective (CHESS) water suppression is demonstrated. A temperature imaging method using a phase-sensitive spin-echo imaging sequence was validated in phantom experiments. A comparison of regional temperature changes measured with fiber-optic probes and the temperatures calculated from the phase shift near each probe showed that the accuracy of imaging the temperature with TmDOTMA- is at least 0.1-0.2 degrees C. The feasibility of imaging temperature changes in an intact rat at 0.5-0.6 mmol/kg dose in only a few minutes is demonstrated. Similar to commonly used MRI contrast agents, the lanthanide complex does not cross the blood-brain barrier. TmDOTMA- may prove useful for temperature imaging in many biomedical applications but further studies relating to acceptable dose and signal-to-noise ratio are necessary before clinical applications.

MR thermometry

“…These complexes have chemical shifts many times more sensitive than the water 1 H shift, eg, TmDOTMA Ϫ has a temperature coefficient of 0.57 ppm/°C, which is nearly 60 times that of water. In order to image the methyl 1 H signal from TmDOTMA Ϫ , excellent water suppression is necessary, resulting in imaging times of several minutes (72,73). Limitations for in vivo applications are the required concentration of the agent and low SNR.…”

Noninvasive thermometry using hyperfine-shifted MR signals from paramagnetic lanthanide complexes

“…The authors have demonstrated and validated the capability of imaging temperature with sub-degree resolution with TmDOTMA À in phantoms [31]. Phase-sensitive spin-echo images of a 20-mm MR tube filled with 4 mM TmDOTMA À were acquired continuously during a heating experiment on a 9.4 T vertical bore MR system.…”

“…Tm 3þ , Tb 3þ and Dy 3þ induce the largest paramagnetic shifts [33]. The agents that have been suggested for MR thermometry include praseodymium 10-(2-methoxyethyl)-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7-triacetate (Pr[MOE-DO3A]) (16)(17)(18)(19)(20)(21)(22), thulium 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetrakis-(methylene phosphonate) (TmDOTP 5À ) [23][24][25][26], thulium 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetate (TmDOTA À ) [27,28] and Yb 3þ , Pr 3þ , Tm 3þ , Tb 3þ and Dy 3þ complexes of 1, 4, 7, 10-tetraazacyclododecane-, 0 , 00 , 000 -tetramethyl-1, 4, 7, 10-tetraacetate (DOTMA 4À ) [29][30][31]. The chemical structures and some of the important features of these complexes are listed in Table I.…”

“…The feasibility of MR thermometry based on the strong temperature dependence of the hyperfine chemical shifts of many paramagnetic complexes has been explored [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. The observed chemical shift, obs , of a nucleus in a paramagnetic complex is composed of contributions from a diamagnetic term, dia , a paramagnetic contact term, con , and a paramagnetic dipole term, dip [32]:…”

“…These images clearly show heterogeneity in the temperature changes. The temperature imaging method has been validated by comparing the image phase data with global temperature changes measured by spectroscopy and with regional temperature changes measured by fibre-optic probes [31].…”