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 requirements
1. 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 line
2.
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
inhomogeneity
3. 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 0
oC to 60
oC at
different magnetic fields using a SQUID magnetometer to find Curie temperature
(T
c) 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, T
C was found to be around 19
oC.
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 21.1
oC
to 49.6
oC 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 ±1.8
oC, at 37
oC.
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
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