T2* Based MRI Temperature Contrast
Janusz Henryk Hankiewicz1, Jason Nobles1, Zbigniew Celinski1, Karl Stupic2, and Robert Camley1

1UCCS Center for Biofrontiers Institute, University Colorado Colorado Springs, Colorado Springs, CO, United States, 2National Institute of Standards and Technology, Boulder, CO, United States

Synopsis

The aim of this study was to develop a novel temperature-sensitive MRI contrast agent based on temperature changes of the magnetic moment of magnetic particles. Gadolinium was used to test the hypothesis that magnetic particles will create a temperature-dependent local dipole magnetic field. This effect was locally visible as a temperature dependent darkening on gradient-echo MRI images. Shades of gray within the images can then be calibrated to map the local temperatures in specific areas of tissue during medical procedures. The estimated accuracy of temperature determination deep in the phantom using MR image intensity is ±1.8oC, at 37oC.

Purpose

Precise determination of tissue temperature deep in the body is important in different medical diagnosis and interventional procedures. A minimally invasive MRI thermometry that produces high thermal, spatial and temporal resolution temperature maps superimposed on anatomical images within the targeted tissue would address these requirements1. We hypothesize that magnetic particles embedded in the tissue will create a temperature-dependent local dipole magnetic field that will modulate the static magnetic field of the MRI scanner and broaden the nuclear magnetic resonance line2. Consequently, the effective nuclear spin-spin relaxation time (T2*) of the tissue near the magnetic particle will be shortened. The effect can be measured directly with image guided localized NMR spectroscopy as linewidth broadening and can also be visible as a darker area on MRI images acquired with the gradient echo method, which is very sensitive for local magnetic field inhomogeneity3. In this report, we present the use of particles made of gadolinium because of its phase transition from the ferromagnetic to a paramagnetic state with rapid changes in magnetization near the body temperature range

Methods

To test the hypothesis, gadolinium particles of 6 μm diameter and 2 μm thickness were prepared using standard photolithography with deposition by a magnetron sputtering system. The magnetic properties of the Gd particles were measured in the range of 0oC to 60oC at different magnetic fields using a SQUID magnetometer to find Curie temperature (Tc) and to determine the temperature dependence of the magnetic moment. The temperature effect of the Gd particles on the 1H NMR line broadening and MRI image intensity was determined using Gd particles suspended in a 1% agar-Ringer’s solution gel, to create an isotonic solution similar to the bodily fluids of an animal. For NMR (364 mT) and MRI (1.5 T, 30 cm bore, preclinical scanner) temperature measurements, a mixture containing 6 ml of 1% agar-Ringer’s solution and 1.1 mg of Gd particles was prepared. The above concentration was diluted with 1% agar-Ringer’s solution to obtain an additional mixture of 50% concentration.

Results

Fig.1 shows the temperature dependent magnetization results for the Gd particles obtained from the SQUID. Different values of the magnetic field in SQUID were used to match the fields of the NMR spectrometer and of commercially available clinical MRI scanners. From ultra-low field measurements, TC was found to be around 19oC. The thermal dependence of the NMR linewidth broadening due to the presence of Gd particles at two concentrations is presented in Fig. 2. This was obtained by subtracting the NMR linewidth at full width at half maximum (FWHM) in pure agar gel from the linewidth at FWHM in agar gel with suspended Gd particles. Fig. 3 shows an example of gradient-echo MRI images of phantoms at different temperatures: The top row is undoped agar gel. The bottom shows the agar gel doped with the highest content of Gd particles (100%). Imaging parameters: gradient echo, FOV=3x3 cm, matrix 64x64, slice thickness=4 mm, TE=2.5 ms, TR=15.0 s. Objects on axial images are 10 mm across

Discussion

The results obtained from low-field NMR and 1.5 T MRI show that the 1H NMR linewidth and the intensity of the MRI gradient echo images are strongly affected by the presence of the Gd particles. They are also temperature dependent. Fig. 4 shows quantitative analysis of image intensities over the entire phantom’s cross-section as a function of temperature. Analysis of SQUID and MRI data for 100% Gd concentration at 1.5 T shows a strong correlation between magnetization and the MRI images intensity ratios ( Pearson r=0.98). The linear part of ratios of MR images intensity in temperature range from 21.1oC to 49.6oC on Fig. 4 for 100% concentration of gadolinium was statistically analyzed using regression of means. Results show that images intensity ratios are strongly negatively correlated with temperature (Pearson r=-0.98, slope of -0.025 +/- 0.002). From the regression’s 95% confidence bands, we estimate accuracy of temperature determination in the phantom using MR image intensity ±1.8oC, at 37oC.

Conclusion

The results show that Gd is a promising model material as an MRI temperature contrast agent. We conclude that shades of gray in images taken with Gd particles present can be calibrated to obtain a temperature or to report the achievement of a certain temperature. Studies to replace gadolinium by more bio-compatible magnetic alloys and heterogeneous structures as temperature sensitive MRI contrast are under the way.

Acknowledgements

This work was supported by the State of Colorado Bioscience Discovery Evaluation Grant (14BGF- 22).

References

1. Rieke V and Pauly KB. MR Thermometry. J. Magn. Reson. Imaging. 2008;27(2): 376-390.

2. Settecase F, Sussman MS, and Roberts TPL. A new Temperature-Sensitive Contrast Mechanism for MRI: Curie Temperature Transition-Based Imaging. Contrast Media Mol. Imaging. 2007;2(1): 50-54.

3. Bernstein MA, King KF, and Zhou XJ. Handbook of MRI pulse sequences. Ch.14 (Elsevier, Amsterdam, 2004).

Figures

Temperature dependence of the magnetic moment in gadolinium for selected magnetic fields in SQUID. The 1.5 T field (typical of those in MRI scanners) shows a substantial change in magnetization near body temperature.

Temperature changes of 1H NMR line broadening in agar-Ringer’s solution gel with suspended Gd powder.

An example of axial gradient-echo MRI images of phantoms at different temperatures. Top: agar gel, bottom: agar gel doped with the highest content of Gd particles (100%). Note that the image of the agar gel with the Gd particles shows brightening as the temperature is increased.

Thermal variation ratios of images intensity of pure agar gel to agar gel with Gd particles for two different Gd concentrations.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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