MR thermometry with paramagnetic lanthanide complexes and its applications at 9.4-Tesla and development of clinical sodium (sodium-23) MRI at 3-Tesla

Judy Rose James, Purdue University

Abstract

Magnetic resonance (MR) thermometry based on the water 1H signal provides high temporal and spatial resolution but has low temperature sensitivity (∼0.01 ppm/°C) and requires monitoring of another weaker signal for absolute temperature measurements. The use of the paramagnetic lanthanide complex, thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraacetate (TmDOTMA-), which is ∼60 times more sensitive to temperature than the water 1H signal, is advanced to image absolute temperatures in vivo using water signal as a reference. The temperature imaging technique was developed using gradient echo and asymmetric spin echo imaging sequences on 9.4 T horizontal and vertical MR scanners. A comparison of regional temperatures measured with TmDOTMAy1 and fiber-optic probes showed that the accuracy of imaging temperature is <0.3°C. The temperature imaging technique was found to be insensitive to the main magnetic field inhomogeneities. The feasibility of imaging absolute temperature of intact rats with ∼1 mm spatial resolution in only 3 min is demonstrated with physiologically safe concentrations (∼1.4 mmol/kg dose). TmDOTMA- should prove useful for imaging absolute temperatures in deep-seated organs in numerous biomedical applications such as controlled hyperthermia. The application of MR thermometry was taken to a new level to treat sc-implanted tumors by developing a non-invasive magnetic resonance (MR) technique that produced controlled radio-frequency (RF) hyperthermia (HT). The method used the 1H chemical shift of a different paramagnetic lanthanide complex, TmDOTA- to monitor tumor temperature non-invasively. The desired HT temperature was achieved and maintained using a feedback loop mechanism that uses a proportional-integral-derivative (PID) controller. The RF HT technique was able to heat the tumor from 33 to 45°C in ∼ 10 min and maintain the tumor temperature within ±0.2°C of the target temperature without affecting the overall body temperature. The in-magnet PID based RF HT was then interleaved with simultaneous 23Na and 31P MRS data collection to investigate the effects of HT on total and intracellular Na+ measured by single-quantum (SQ) and multiple-quantum-filtered (MQF) 23Na MRS, and cellular energy status (ATP/Pi), and intra- and extra-cellular pH (pH i and pHe, respectively) by 31P MRS in sc-implanted 9L-glioma in rats. Simultaneous monitoring of metabolic changes with RF HT showed a significant increase in total (12%, p ≤ 0.05) and intra-cellular (30-40%, p ≤ 0.05) sodium and a significant decrease in cellular bio-energetics (60%, p ≤ 0.05), pHi and pHe (0.2 and 0.17 pH units decrease respectively, p ≤ 0.05). The developed RF HT technique in combination with simultaneous MR measurements of sodium and cellular energetics during HT treatment show that 23Na and 31P will prove useful for monitoring therapy response during the treatment and may prove valuable in designing methods to improve therapeutic efficiency. Clinical 23Na magnetic resonance imaging (MRI) of the human torso using an 8-channel dual tuned 23Na and 1H transmit/receive coil for various body applications was developed, optimized and characterized at 3 T. The 23Na MR images of the human torso were acquired with 0.3 cm spatial resolution and ∼ 20 signal-to-noise ratio (SNR) in ∼15 min. These images were acquired with optimized pulse sequence and imaging parameters under specific absorption rate limit for human scans. A mathematical algorithm based on exponential signal decay was used for RF inhomogeneity correction in the 23Na images caused by the four opposing phased-array coils. Tissue sodium concentration (TSC) of 20.8 ± 1.2 mM was calculated from the inhomogeneity corrected 23Na MR images of healthy livers (n = 6). The reproducibility of TSC measurements was evaluated in healthy volunteers and compared with the water apparent diffusion coefficient (ADC) measurements (respiratory-gated and free-breathing). Among all the liver measurements evaluated, TSC values from the 23 Na MR images were the most reproducible parameter with a minimal inter-volunteer (4.2%) and intra-volunteer variability (4.4%) even without cardiac or respiratory gating. It is likely that this developed 23Na MRI technique can yield useful information to study normal and abnormal physiology because of the immense physiological significance of trans-membrane sodium gradient. The ability to perform 23Na MRI of the torso in clinical settings will prove useful to non-invasively detect and diagnose a number of diseases in various body organs and will greatly aid in monitoring therapy response.

Degree

Ph.D.

Advisors

Dydak, Purdue University.

Subject Area

Biomedical engineering|Medical imaging

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