Rohan S. Virgincar1, Scott H. Robertson2, Simone Degan3, Geoffry Schrank4, Mu He5, John Nouls4, and Bastiaan Driehuys4
1Biomedical Engineering, Duke University, Durham, NC, United States, 2Medical Physics Graduate Program, Duke University, Durham, NC, United States, 3Center for Molecular and Biomolecular Imaging, Duke University, Durham, NC, United States, 4Radiology, Duke University, Durham, NC, United States, 5Electrical and Computer Engineering, Duke University, Durham, NC, United States
Synopsis
Inhaled 129Xe exhibits chemical shifts which carry useful
information about the underlying physiology. However, their resonant
frequencies have been reported with a variability of 2-3 ppm likely
attributable to using simplistic peak finding methods and inconsistent reference
frequencies. In this work, we use robust non-linear curve fitting of the
complex dissolved-phase spectrum in mice to identify resonances, and report
shifts relative to an accurate reference frequency. At short 129Xe
replenishment times curve fitting identified two peaks at 197.4±0.9 and
193.0±0.7 ppm, but as replenishment time was increased, five distinct peaks
became apparent at 198.4±0.4, 195.5±0.4, 193.9±0.2, 191.3±0.2, and 190.7±0.3 ppm.Purpose
129Xe readily interacts with biological media and exhibits chemical shifts
that reflect the local tissue microenvironment. These shifts have been
extensively studied
in vitro, and to
a limited extent
in vivo in mice,
rats and humans. Previously,
in vivo 129Xe
spectra have been processed by simply phasing the spectrum, identifying
frequencies at which peaks occur, and calculating shifts relative to the
readily available gas-phase resonance originating mostly from pulmonary
airspaces. This practice has shortcomings. First, the rapid exchange of
129Xe
between compartments may lead to broad and overlapping resonances that are
often difficult to fully phase and isolate. Second, the
in vivo 129Xe gas-phase resonance, used as a reference,
also exhibits a shift
1 due to bulk magnetic susceptibility (BMS) causing
a bias in the reported dissolved-phase shifts. In this study, we identify
individual resonances in the dissolved-phase
129Xe spectrum of the
mouse lung by fitting the complex time domain signal to a series of
exponentially decaying signals, and then report chemical shifts relative to an
accurate gas-phase reference frequency adjusted for BMS shifts
2. Additionally,
we present spectra at increasingly long
129Xe replenishment times,
and show that the spectra become progressively richer as
129Xe reaches
downstream compartments within the thoracic cavity.
Methods
5 Balb/c mice were ventilated on an HP gas-compatible ventilator and
underwent respiratory gated hyperpolarized
129Xe dissolved-phase
spectroscopy in a quadrature
129Xe coil at 2T with the following
parameters: frequency-selective 1.2-ms sinc pulse centered on the dissolved
phase, TR/TE = 100-8000/1.2 ms, 2048 points, BW = 8.06 kHz, α = 90°, and 11 averages.
Using an in-house MATLAB fitting tool, spectra were then interactively
decomposed by least squares fitting the complex free induction decay signal to
a sum of exponentially decaying signals. The software then reports the
intensity, frequency, phase and decay rate of each individual peak in the
spectrum.
Results and Discussion
At the shortest TR of 100 ms,
129Xe is limited to the
gas-exchange region and exhibits two broad resonances at 197.4±0.9 and 193.0±0.7
ppm (n = 2). Increasing TR revealed additional peaks developing as
129Xe
moved into downstream compartments. At the longest TR (8 s), five robust peaks
were identified at 198.4±0.4, 195.5±0.4, 193.9±0.2, 191.3±0.2, and 190.7±0.3
ppm in all of the five mice. Based on the signal dynamics in our time series
spectra, and comparing with the limited literature on
in vivo 129Xe spectroscopy in mice, we can postulate the
origins of these peaks. We suggest that the 198.4 ppm peak originates from blood
1,3,
while the 195.5 and 193.9 ppm peaks arise from aqueous media. They contain signal
contributions from the pulmonary-capillary barrier tissue, plasma, and possibly
also from the myocardium. The remaining upfield peaks (<192 ppm), only
appear at long TRs, and likely arise from the slowly perfused and distal
epicardial fat
4. Using these improved fitting techniques and
accurate frequency referencing should facilitate standardized comparison across
sites, and aid in advancing the use of
129Xe spectroscopy and
imaging to detect pathology.
Acknowledgements
R01-CA-142842,
R01HL105643, and P41 EB015897References
1. Wagshul ME et al. In vivo MR imaging and spectroscopy using hyperpolarized Xe-129. Magn. Reson. Med. 1996, 36(2):183-191
2. Virgincar RS et al. Establishing an accurate reference frequency for in vivo 129Xe spectroscopy. International Society for Magnetic Resonance in Medicine 24th Annual Meeting. 2016, Abstract ID 5540, submitted
3. Narazaki M et al. Origin of dissolved-phase hyperpolarized Xe-129 signal in the mouse chest based on experimental evidence from extensive magnetic resonance measurements. Mag. Reson. Med. Sci.
2011, 10(3):149-154
4. Swanson SD et al. Distribution and dynamics of laser-polarized 129Xe magnetization in vivo. Magn. Reson. Med. 1999, 42(6):1137-1145