Le Zhang1,2, Alex Burant2,3, Andrew McCallister2,3, Karl Koshlap4, Simone Degan5, Michael Antonacci2,3, and Rosa Tamara Branca2,3
1Department of Applied Physical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 2Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 3Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 4Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 5Center for Molecular and Biomolecular Imaging, Duke University, Durham, NC, United States
Synopsis
A
new thermometry method based on the temperature dependence of lipid-dissolved 129Xe
was proposed, while its accuracy was assessed by direct comparison with Proton
Resonance Frequency (PRF) based MR thermometry methods. The temperature
dependences of chemical shifts of lipid-dissolved 129Xe, water and
methylene spins were first measured in
vitro with high accuracy on various fat-rich tissues. The results were then
used to obtain relative temperature maps in
vivo in mice acclimated at different temperatures. Lipid-dissolved 129Xe
based MR thermometry demonstrated superior accuracy in both in vivo and in vitro results when compared to PRF based MR thermometry in fatty
tissues.Purpose
Most
MRI
thermometry methods take advantage of the linear temperature dependence of the Proton Resonance Frequency (PRF)
1 to measure temperature
in vivo. However, the effect of
temperature on PRF can be easily overshadowed by field drift as well as
macroscopic and microscopic magnetic susceptibility gradients
2. In
fatty tissues, to partially remove the effect of field drift and macroscopic
field inhomogeneities, the temperature-independent resonance frequency of
methylene protons is often used as an internal reference
3. However,
as water and methylene spins reside in different tissue compartments,
microscopic susceptibility gradients cannot be completely removed and can still
produce large inaccuracies
4. Recently, a strong linear temperature
dependence of the chemical shift of Lipid-Dissolved
129Xe (LDX) was
found in mice
5. Being highly lipophilic, LDX spins reside in the same tissue compartment
as methylene spins. As a result, methylene-referenced LDX based MR thermometry should provide
more accurate temperature measurements. In this study, the accuracy of
referenced and unreferenced PRF and LDX was evaluated both
in vitro and
in vivo.
Methods
In vitro
high-resolution NMR experiments were performed on fatty tissues excised from
rats and human cadavers on a Varian Inova 500MHz NMR Spectrometer by using a
broadband probe. Samples were degassed and filled with isotopically enriched
129Xe
(>85%) at desired pressures. A Varian biopack temperature control unit,
calibrated using a 100% methanol sample, ensured a temperature accuracy of
0.1°C. For
in vivo experiments, four obese
(ob/ob) mice were scanned on a Bruker BioSpec 9.4T scanner using a xenon surface
coil (1cm diameter) inserted in a
1H volume coil. The animals were
anesthetized and mechanically ventilated with 75-vol% hyperpolarized (polarization ~15%, Polarean,
Inc., Durham, NC)
129Xe (natural isotopic abundance) and 25-vol%
oxygen. Body temperatures were allowed to equilibrate at set bore temperatures
for 0.5h before
129Xe and
1H CSI maps were acquired. From
these maps,
129Xe, water and methylene resonance frequencies were
obtained, while temperature maps were derived by using a temperature
coefficient of ‑0.01ppm/°C and -0.209ppm/°C for water and LDX, respectively.
Results
Fig.
1 shows the chemical shift temperature dependence of both unreferenced and
methylene-referenced PRF and LDX. The temperature coefficient of PRF (1A) averaged
to ‑0.012ppm/°C, in agreement with literatures
1, with a maximal
variation of 0.002ppm/°C across four samples. The temperature coefficient of
LDX (1C) averaged to ‑0.209ppm/°C, with a variation of 0.05ppm/°C across the
samples. When referenced to the chemical shift of the methylene peak, the
average temperature coefficient of PRF method (1B) became ‑0.008ppm/°C, with a
variation of 0.04ppm/°C, while that of LDX (1D) became ‑0.212ppm/°C, with a
variation of 0.01ppm/°C. For a given temperature (25°C), the water-methylene resonance
frequency difference showed a variation of 0.3ppm among the samples analyzed,
whereas the LDX-methylene resonance frequency difference showed a variation of 0.4ppm.
Fig. 2 shows the referenced and unreferenced PRF and LDX frequency distribution
(2A) across the abdomen of an obese mouse acclimated at two different
temperatures as well as the calculated relative temperature change (2B) obtained
from these maps by using a temperature coefficient of ‑0.01ppm/°C for PRF and a
temperature coefficient of ‑0.209ppm/°C for LDX. The relative temperature
distribution at 29°C calculated by using the LDX-methylene resonance frequency
difference is also shown in Fig. 2C. Fig. 3 shows the absolute value of the LDX-methylene
resonance frequency difference obtained
in
vitro and
in vivo for all animals
and rWAT samples analyzed.
Discussion
For
a given temperature, the water chemical shift and its temperature coefficient displayed a large variation across the samples, even when the methylene spins were used
as reference. On the other end, the
LDX temperature coefficient was close to what we previously found
in vivo5 and with a small difference
among all samples. In addition, the
use of methylene spins as an internal reference for the LDX further reduced
this difference to 0.01ppm/°C. The superior accuracy of LDX-based thermometry
was also evident in the
in vivo
studies. The temperature distribution obtained using LDX frequency as a
temperature probe was quite homogenous, with a variation of less than 1°C
across the entire mouse abdomen. On the other hand, PRF-based MR thermometry
yielded a temperature variation across the same area of more than 10°C. More
interestingly, Fig. 3 shows the methylene-referenced LDX frequency could be
used to accurately predict absolute temperature with an accuracy of better than
1°C in all four mice.
Conclusion
By
utilizing the strong linear temperature dependence of lipid-dissolved
129Xe
chemical shift and referencing it to the chemical shift of neighboring lipid
spins, a novel MR thermometry method, more accurate and precise than PRF, is
proposed.
Acknowledgements
No acknowledgement found.References
[1]
Venkatesh AK, Kacher DF, Kuroda K, et al. Temperature Measurement Using the 129Xe
Chemical Shift. Proc ISMRM, Glasgow, Scotland. 2001 [2] Bolan PJ, Henry P-G,
Baker EH, et al. Measurement and correction of respiration-induced B0
variations in breast 1H MRS at 4 Tesla. MRM 2004;52(6):1239-1245 [3]
Hofstetter LW, Yeo DTB, Dixon WT, et al. Fat-referenced MR thermometry in the
breast and prostate using IDEAL. JMRI 2012;36(3):722-732 [4] Szczepaniak LS,
Dobbins RL, Stein DT, et al. Bulk magnetic susceptibility effects on the
assessment of intra- and extramyocellular lipids in vivo. MRM 2002;47(3):607-610 [5] Branca RT, He T, Zhang L, et
al. Detection of brown adipose tissue and thermogenic activity in mice by
hyperpolarized xenon MRI. PNAS 2014;111(50):18001-18006