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.

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.…”

Controlled radio-frequency hyperthermia using an MR scanner and simultaneous monitoring of temperature and therapy response by1H,23Na and31P magnetic resonance spectroscopy in subcutaneously implanted 9L-gliosarcoma

“…exciting the nuclear spins. It monitors the tumour temperature from the 1 H chemical shift of TmDOTA, which is 50-100 times more sensitive to temperature than water 1 H shifts [17]. It maintains the tumour temperature within AE0.2 C of the target temperature with an integrated PID controller.…”

“…Normal breathing patterns were observed before, during and after the injection of TmDOTA À . The long-term effects of TmDOTA À on renal function or other measures of toxicity were not evaluated in the present study but the behaviour of TmDOTA À is expected to be similar to that of GdDOTA À because of the close chemical relationship between the two complexes [17]. Use of TmDOTA À in combination with water signal allows for in vivo absolute temperature measurements which is not possible with water signal alone [32].…”

“…Glickson, University of Pennsylvania, 2001). Among all the paramagnetic complexes proposed for MR thermometry, the macrocyclic complexes of thulium are most suitable for in vivo applications because of their high temperature sensitivity and high thermodynamic and kinetic stability [17].…”

“…The in-magnet RF HT technique controlled the heating using a proportional-integral-derivative (PID) feedback controller that was integrated into the MR system that adjusted the RF power level automatically to maintain the tumour temperature at a desired level during heating and MR data collection. Non-invasive temperature measurements based on the strong temperature dependence of the hyperfine chemical shift of a paramagnetic lanthanide complex 1,4,7,10-tetraazacyclodo-decane-1,4,7,10tetra-acetic acid (TmDOTA À ) were used to measure the tumour temperature during RF heating [16][17][18]. The use of paramagnetic complexes for MR thermometry using Ni-N,N-diaminotroponiminate was first suggested by Jack Roberts at the California Institute of Technology in the 1960s ( personal communication with J.D.…”