Slavka Carnicka1, Kathryn Keenan1, Elizabeth Mirowski2, Mark Brown3, Christopher Suiter4, Tara Fortin4, Hannah Erdevig1, Karl Stupic1, and Stephen Russek1
1Physical Measurement Laboratory, National Institute of Standards and Technology, Boulder, CO, United States, 2High Precision Devices Inc., Boulder, CO, United States, 3Department of Radiology, University of Colorado School of Medicine, Denver, CO, United States, 4Applied Chemicals and Materials Division, National Institute of Standards and Technology, Boulder, CO, United States
Synopsis
Phase-based magnetic resonance
thermometry is used for monitoring minimally invasive ablation therapies
like focused ultrasound therapy. MRT is prone to errors when applied in tissues
with high fat content (e.g. breast tissue, fatty liver) due to heat-induced
susceptibility changes. Therefore, there is a need for developing well
characterized adipose tissue mimics that could serve as standards for
validation of MRT techniques. In this study we showed that all measured adipose
tissue mimics are representative of human adipose tissue with similar chemical
spectra and thermal dependence of susceptibility shift and are reproducible
standards for human adipose tissue validation MRI techniques.
PURPOSE
Heat-induced susceptibility
changes occur when MR-thermometry (MRT) is applied to tissues with high fat content resulting in
errors in the temperature measurement.1 To improve accuracy of MRT in the human tissues, reliable
knowledge of fat temperature dependence is a prerequisite. There is a need for well-characterized fat tissue standards with chemical and MR properties similar
to human fat tissue (human-Fat).2 This study aims to evaluate several
potential human-Fat mimics, specifically examining the thermal dependence of their chemical
spectra and magnetic susceptibility.METHODS
1H-NMR
spectra of several human-Fat mimics, particularly oleic acid (Fat0;
most abundant fatty acid in human-Fat), three fat mimic samples
with different Fat0 content (High Precision Devices, Inc.; Fat 1;2;3;4), and their emulsions were measured at 20°C,37°C and 42°C. Absolute
value of magnetic susceptibility for all fat mimic samples was calculated from magnetic moments measured on a SQUID magnetometer at 7 and -7 Tesla with a temperature range of 3–55°C.Volume magnetic susceptibility, $$$\chi$$$, of Fat0 was calculated using sample density (vibrating tube densitometer) at temperatures from 20–70°C. Data for density were not obtained for samples Fat 1;2;3 due to their high
viscosity, mass magnetic susceptibility were calculated instead of $$$\chi$$$.
Volume susceptibility shift ($$$\Delta\chi$$$)
with temperature was calculated from MR phase images (3T; preclinical
MRI scanner). Water/fat phantom
with eight vials containing samples Fat1A;1B;2;3;4, Fat1-emulsion (E) and water-tissue
mimic (W; 3.2 mM CuSO4) oriented
parallel to $$$B_0$$$ (Fig.1) were imaged, using a gradient echo sequence with
TE from 10 to 80ms (ΔTE=10ms) at several
temperatures (11–49°C). Subsequently, MRI phase ($$$\phi$$$) images were used to
calculate $$$\Delta\chi$$$ relative to water for each temperature, according to the following
equation: $$$\Delta\chi=3\delta\phi/\gamma_pB_0TE$$$, where $$$\gamma_p$$$ is proton gyromagnetic ratio and $$$\delta\phi$$$ is the phase difference inside relative to
outside the vials. Fat1 was included in the phantom twice, and Fat4 was
excluded from analysis due to artifacts in the images.
RESULTS
Chemical spectra of fat mimics
and their emulsions were compared to human-Fat spectra. All
fat mimics have spectra similar
to reference human-Fat (Fat1 spectra shown in Fig.2).3 The locations of
the fat peaks do not change with temperature. The density and SQUID measured $$$\chi$$$ of Fat0 are temperature
dependent (Fig.3a), similar to human-Fat (Fig.3b).4 MRI
measurements revealed significant differences in thermal dependence of fat mimics $$$\Delta\chi$$$ and W solution $$$\Delta\chi$$$ (Fig.5). $$$\Delta\chi$$$
of fat samples rises with increasing temperature, while $$$\Delta\chi$$$ of water-tissue remained constant.The change
in $$$\chi$$$ in all fat samples correlated to oleic acid content. MR properties are similar to
human-Fat values (Fig.3b). A chemical shift artifact in the MR image is visible for fat samples (Fig.4), but not W solution.
DISCUSSION
NMR
spectra of all fat mimics are representative of human-Fat with
similar chemical spectra and thermal dependence of $$$\Delta\chi$$$ (Fig.2). Although, samples Fat1;2;3;4
reproduced human spectra more accurately than Fat0, small discrepancies between
proton resonant frequency peaks are within the range of variability of human-Fat composition.5 Locations
of fat peaks do not change with temperature, indicating that the resonant frequencies
of fat do not changing with temperature. Absolute value of $$$\chi$$$ of Fat0
is decreasing with temperature, indicating that fat becomes less diamagnetic with
temperature. Relative change in $$$\chi$$$ of Fat0 in our SQUID measurements is
0.00598ppm/°C, in
agreement with reported $$$\Delta\chi$$$ in human-Fat, ranging from 0.0039 to 0.0076ppm/°C.1 Relative change in
susceptibility has the same trend as relative change in density (Fig.3a) and can be
attributed to thermal expansion of the fat. Mass susceptibility of all
fat samples was temperature dependent, indicating temperature dependence of
their $$$\chi$$$.To confirm this, additional density measurements are planned in future.
MRI-measured $$$\Delta\chi$$$ increased with temperature for all fat samples and E. W solution had a nearly constant
$$$\Delta\chi$$$, in agreement with the theory, which predicts a weak Curie-law decrease in
susceptibility with temperature.The weak temperature dependence of the
susceptibility of the W is similar to that measured in water-based
tissue.1 Temperature dependence of $$$\Delta\chi$$$ for all fat samples was
related to their oleic acid content. There were limitations in our study: $$$\Delta\chi$$$
of repeated sample Fat1A and Fat1B had similar slopes, but the lines do not
overlap as expected. This is most likely due to partial volume distortion,
observed in vials Fat0 and Fat1A (the vials were on an angle with respect to $$$B_0$$$).CONCLUSION
The studied fat mimics are representative
of human-Fat, both in their spectral signature and temperature dependent
susceptibility, and can be used as standards for validation of MRT. Our
results
indicate that the impact of
heat-induced susceptibility changes of fat during thermal therapy in the
water/fat tissues cannot be neglected.Acknowledgements
No acknowledgement found.References
1. Sprinkhuizen
SM, Konings MK, van der Bom MJ, et al. Temperature-Induced Tissue
Susceptibility Changes Lead to Significant Temperature Errors I PRFS-Based MR
Thermometry during thermal interventions. Mag Res Med. 2010;64:1360-1372.
2. Keenan
KE, Wilmes LJ, Aliu SO, et al. Design of a breast phantom for quantitative MRI.
J Magn Reson Imaging. 2016;44: 610–619.
3. Heymsfield SB, Hu HH, Shen W, at al. Emerging Technologies and their
Applications in Lipid Compartment Measurement. Trend Endocrin Met. 2015;26(12):688–698.
4. Sprinkhuizen SM, Bakker ChJG, Ippel JH, et al. Temperature dependence
of the magnetic volume susceptibility of human breast fat tissue: an NMR study.
Magn Reson Matter Phy. 2012; 25: 33-39.
5. Malcom GT, Bhattacharyya AK, Velez-Duran M, et al. Fatty acid
composition of adipose tissue in humans: differences between subcutaneous
sites. Am J Clin Nutr. 1989;50(2):288-91.
6. Haynes WM. CRC Handbook of Chemistry and Physics, 96th Edition