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

Abstract

MR thermometry techniques based on the strong water ¹H signal provide high spatial and temporal resolution and have shown promise for applications such as laser surgery and RF ablation. However, these techniques have low temperature sensitivity for hyperthermia applications and are greatly influenced by local motion and susceptibility variations. ¹H NMR signals from paramagnetic lanthanide complexes of Pr³⁺, Yb³⁺ and Tm³⁺ show up to 300-fold stronger temperature dependence compared to the water ¹H signal. In addition, ¹H chemical shifts of many of these complexes are insensitive to other factors such as the concentration of the paramagnetic complex, pH, [Ca²⁺], and the presence of plasma macro-molecules and ions. Applications of lanthanide complexes for temperature measurement in intact animals and the feasibility of mapping temperatures in phantoms have been demonstrated. Among all the lanthanide complexes examined so far, thulium 1, 4, 7, 10-tetramethyl-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetate (TmDOTMA⁻) appears to be the most attractive for in vivo MR thermometry. The ¹H signal from the methyl groups on this complex is relatively intense because of 12 equivalent protons and provides high temperature sensitivity because of the large paramagnetic shifts induced by thulium. The possibility of imaging TmDOTMA²—in intact animals at physiologically safe concentrations has recently been demonstrated. Overall, MR thermometry methods based on hyperfine-shifted MR signals from paramagnetic lanthanide complexes appear promising for animal applications, but further studies relating to acceptable dose and signal-to-noise ratio are necessary before clinical use.

• Thermometry
• lanthanide complexes
• paramagnetic shift
• 1H MRS
• 1H MRI
• Abbreviation
• CHESS, chemical shift selective
• CSI, chemical shift imaging; C2T, coefficient of temperature dependence; |C2T|/FWHM, ratio of temperature coefficient and peak width at half maximum
• DOTMA24-, 1, 4, 7, 10-tetraazacyclododecane-α, α′, α′′, α′′′-tetramethyl-1, 4, 7, 10-tetraacetate
• EPSI, echo planar spectroscopic imaging
• FOV, field of view
• HT, hyperthermia
• NMR, nuclear magnetic resonance
• Pr[MOE-DO3A], praseodymium 10-(2-methoxyethyl)-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7-triacetate
• RF, radio frequency
• sc, subcutaneous
• SNR, signal-to-noise ratio
• TE, echo time
• TmDOTA−, thulium 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetate
• TmDOTP5−, thulium 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetrakis-(methylene phosphonate)
• TR, repetition time
• WSS, weighted signal summation