Ground-based investigations of a new biomedical diagnostic technology: nuclear magnetic resonance of laser polarized noble gas are addressed. The specific research tasks discussed are: (1) Development of a large-scale noble gas polarization system; (2) biomedical investigations using laser polarized noble gas in conventional (high magnetic field) NMR systems; and (3) the development and application of a low magnetic field system for laser polarized noble gas NMR

Walsworth, Ronald L.

English

NASA Technical Reports Server

;rant NAGW-5025
through 30 September 1997
Astrophysical Observatory !
member of the
Center for Astrophysics
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Specific aims of research and accomplishments during grant period
The present NASA grant (NAGW-5025) supports ground-based investigations of a new
biomedical diagnostic technology: nuclear magnetic resonance of laser polarized noble gas.
Large nuclear spin polarizations (> 10%) can be created in dense samples of the spin 1/2 noble
gases (3He and 129Xe) using the technique of spin-exchange optical pumping. Such large
Olarizations greatly enhance the nuclear magnetic resonance (NMR) detection sensitivity of
e and 129Xe, enabling fast, gas space magnetic resonance imaging (MRI), studies of gas
diffusion in porous media, and investigations of fluids using the soluble 129Xe species. Laser
polarized 3He and 129Xe can be benignly inhaled by humans with minimal loss of spin-
polarization (T1 - 5 to 50 seconds, depending on the organ and tissue) and then detected with
NMR. Potential biomedical apphcations include improved lung imaging (important for
emphysema diagnosis); the imaging of lipid membranes in the brain (useful in the diagnosis of
multiple sclerosis and in research on brain function); and better measurement of blood flow to
tissue (important for stroke and ischemia diagnosis, and also useful in research on
cardiopulmonary and brain function). In addition, noble gas laser polarization occurs external
to the body and does not require a large magnetic field for high sensitivity NMR detection--
unlike conventional NMR of 1H in liquid water, et al. which typically employs magnetic fields
of - 1 tesla to create thermally polarized nuclear spin polarizations of - 10 -5. Thus at low
magnetic fields (< 0.01 tesla), water NMR signals are not observable without extensive signal
averaging; whereas laser polarized noble gas NMR images can be obtained clearly and rapidly
in a single measurement. Low-field noble gas NMR may be practical in a small, low-power
device and enable both portable ground-based and practical space-based biomedical MRI
systems. Our biomedical investigations with laser polarized noble gas are in collaboration
with the Magnetic Resonance Division of the Brigham and Women's Hospital, headed by Dr.
Ferenc Jolesz.
The specific research aims of the present grant fall into three general areas:
(i) development of a large-scale noble gas laser polarization system; (ii) biomedical
investigations using laser polarized noble gas in conventional (high magnetic field) NMR
systems; and (iii) the development and application of a low magnetic field system for laser
polarized noble gas NMR.
Below is a description for each specific aim of what has been accomplished during the
tenure of NASA grant NAGW-5025 (4/1/96 to 9/30/97).
1. Development of a large-scale noble gas polarization system.
• Optimization of polarization chamber geometry.
Model calculations of the noble gas laser polarization process were performed. One of the
variables analyzed was polarization chamber geometry. Also, development was begun on a
low magnetic field noble gas NMR system (see specific aim 3 below). This low field system
will be used to investigate polarization chamber geometry, with the results to be compared
to the model calculations. The results of these studies will be used to improve the large-
scale noble gas polarization system.
• Optimization of polarization chamber gas pressures.
The optimization of polarization chamber gas pressures was also studied via model
calculations. Again, the results of these studies will be used to improve the large-scale
noble gas polarization system.
• Incorporation of large power diode laser arrays.
The large-scale noble gas polarization system incorporates four 15 watt diode laser arrays.
Each laser is fiber-coupled, and then the four fiber bundles are merged into a single meta-
fiber bundle that provides up to 60 watts of optical pumping hght onto the polarization
chamber.
• Optimization of laser optics (lenses, quarter wave plates, etc.).
A compact optics package has been developed that allows - 90% of the power from the 60
wattdiode laser array system to be circularly polarized and projected through the volume
of a polarization chamber up to - 0.5 m in length.
• Comparison of polarization system location in high or low magnetic field.
The large-scale noble gas polarization system allows operation in either high or low
magnetic field (resulting from the fringe field of an NMR magnet). Comparative tests of
system configuration have not yet been performed.
• Development of systems for cryogenic storage of polarized 129Xe.
The large-scale noble gas polarization system currently polarized 129Xe in the solid phase
at liquid nitrogen temperatures (- 77 K). At these temperatures we measured the 129Xe
polarization lifetime (T1) to be about 2.5 hours, in agreement with previous work.
2. High-field biomedical investigations using polarized noble gas NMR.
• Investigation of in vitro tissues.
We measured the polarization lifetime (T1) of laser polarized 129Xe dissolved in fresh
human blood in vitro. The T1 of 129Xe dissolved in the bloodstream is an important factor
in determining the polarization delivered to target tissues for in vivo NMR using inhaled,
laser polarized 129Xe. A blood-foam preparation was used to enhance the NMR signal of
129Xe dissolved in blood. We found that the dissolved 129Xe T 1 is significantly shorter in
oxygenated blood than in deoxygenated blood. To understand the oxygenation trend, T1
measurements were also made on plasma and hemoglobin preparations. Extrapolating our
blood foam results to in vivo oxygenation conditions, we estimate that the 129Xe T1 is 5-10
seconds in arterial blood and 15-25 seconds in venous blood. The measurement technique
using a polarized 129Xe gas-liquid exchange interface in a foam may also be generally
useful in studying foam coarsening and other liquid physical properties. A paper reporting
these results was published in the Journal of Magnetic Resonance.
• Investigation of ventilated animals.
We observed 129Xe NMR spectra in the thorax of living rats breathing the laser polarized
gas (see Fig. 1). We also obtained NMR images of laser polarized 129Xe gas inside the rat
lung (see Fig. 2). We observed three weD-resolved 129Xe tissue resonances, in addition to
the gas resonance in the lung gas space. We identified these resonances as 129Xe in solution
in pulmonary tissue, red blood ceils, and adipose tissue. Once xenon inhalation was
stopped, the three 129Xe tissue resonances were observed to decay with different time
constants ranging from 11 to 50 seconds-i.e, longer than the blood circulation time in the
animal. Thus it may be possible to perform dissolved-state 129Xe MRI in animals and
humans (and, in general, in complex fluid systems).
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Figure 1. 129Xe NMR spectra from a rat breathing the laser polarized gas. Spectral peaks A,
B, and C are 129Xe in solution in adipose tissue, pulmonary tissue, and red blood cells,
respectively. Polarization decay after cessation of breathing is shown at right.
Figure 2. Axial slice N-MR lung images of a living rat. (a) Temporal sequence of laser
polarized 129Xe NMR images from the lung gas space. (b) The summed image from the six
images shown in (a). (c) Conventional proton NMR image of a corresponding slice. Note the
complimentary nature of the noble gas and proton images.
• Development of laser polarized 129Xe MRI techniques.
We investigated gradient echo imaging strategies for laser polarized 129Xe MRI. We
performed experiments on the use of different gradient echo pulse sequences and found that
a variable flip angle approach can improve the 129Xe signal to noise ratio and eliminate
some typical image artifacts. We also demonstrated that although a constant signal
intensity can be obtained with such an approach, the maximum spatial resolution
achievable is constrained by the 129Xe polarization lifetime, T1. A paper reporting these
results was published in the Journal of Magnetic Resonance, Series B.
• Xenon uptake model calculations.
We developed the first model calculation of the build-up of inhaled, polarized 129Xe in
human tissues. This model assumes the steady inhalation of laser polarized 129Xe gas
mixed with air, and accounts for 129Xe depolarization in the lung, blood, and tissue of
interest. With the caveat that important parameters such as the 129Xe T1 times in blood
and tissues are not well known in vivo, we calculated that at 1.5 tesla the 129Xe NMR
signal-to-noise ratio in human brain tissues is ~ 1-10% of that from proton NMR in typical
water-rich tissue. At low field (< 0.01 tesla) the relative magnitudes of the 129Xe and
water proton NMR signal-to-noise ratios are expected to reverse.
3. Development and application of a low magnetic field MRI system.
• Development of a low-field solenoid and pulsed gradient coils.
A solenoid was constructed to provide a stable, homogeneous magnetic field < 0.01 tesla,
with first through fourth order static-gradient correction coils. Pulsed gradient coils for 2D
spectroscopy and imaging were also developed, providing up to ~ 10 -5 tesla/crn.
• Development of a low-RF system for magnetic resonance detection and excitation.
Sensitive low-RF (- 100 kHz) pulse and detection coils were developed to allow adiabatic
fast passage (AFP), free induction decay (FID), and spin echo detection of laser polarized
noble gas samples. Also, signal averaging techniques were developed to observe water
proton NMR at low magnetic fields.
• Development of techniques for low-field imaging.
A gradient echo signal was induced and detected from a cell containing laser polarized
129Xe gas at ~ 30 gauss, using the prototype low-field MRI system. Such gradient echoes
are important tools for low field imaging of laser polarized noble gas (with its finite
magnetization).
Relevant papers published during grant period
NMR of laser polarized 129Xe in blood foam.
C.H. Tseng, S. Peled, L. Nascimben, E. Oteiza, ILL Walsworth, and F.A. Jolesz, J.
Magn. Reson. 126, 79 (1997).
Gradient echo imaging considerations for hyperpolarized 129Xe MR.
L. Zhao, R. Mulkem, C.H. Tseng, D. Williamson, S. Patz, R. Kraft, ILL Walsworth,
F.A. Jolesz, and M.S. Albert, J. Magn. Reson., Series B 113, 179 (1996).
Demonstration of a two species noble gas maser.
R.E. Stoner, M.A. Rosenberry, J.T. Wright, T.E. Chupp, E.R. Oteiza, and ILL.
Walsworth, Phys. Rev. Lett. 77, 3971 (1996).
Determinants of tissue delivery for 129Xe magnetic resonance in humans.
S. Peled, F.A. Jolesz, C.H. Tseng, L. Nascimben, M.S. Albert, and ILL. Walsworth,
Magn. Reson. Med. 36, 340 (1996).
Temporal dynamics of hyperpolarized 129Xe resonances in living rats.
K. Sakai, A.M. Bilek, E. Oteiza, ILL Walsworth, D. Balamore, F.A. Jolesz, and M.S.
Albert, J. Magn. Reson., Series B 111, 300 (1996).
Relevant conference abstracts during grant period
NMR of laser polarized 129Xe in blood foam.
C.H. Tseng, S. Peled, L. Nascimben, G. Wong, ILL Walsworth, and F.A. Jolesz,
presented at the 1997 April American Physical Society Meeting, Washington, D.C., 18-
21 April 1997.
Large scale polarization of noble gas for use in medical imaging.
D. Hoffmann, G. Wong, C.H. Tseng, and R.L. Walsworth, presented at the 1997 April
American Physical Society Meeting, Washington, D.C., 18-21 April 1997.
Multiple echo techniques for hyperpolarized noble gas MRI.
L. Zhao, R. Mulkern, C.H. Tseng, D. WiUiamson, K. Oshio, H. Gubbjartsson, ILL
Walsworth, F.A. Jolesz, and M.S. Albert, presented at the Sixth Annual Meeting of the
International Society of Magnetic Resonance in Medicine (ISMRM), 12-18 April 1997.
Optimization of RF pulses for hyperpolarized noble gas MRI: the variable flip angle
approach.
L. Zhao, R. Mulkem, C.H. Tseng, D. Williamson, S. Patz, R. Kraft, ILL Walsworth,
F.A. Jolesz, and M.S. Albert, presented at the Sixth Annual Meeting of the
International Society of Magnetic Resonance in Medicine (ISMRM), 12-18 April 1997.
Projection-reconstruction imaging with hyperpolarized 129Xe.
D.F. Kacher, K. Shimizu, ILL Walsworth, F.A. Jolesz, and M.S. Albert, presented at
the Sixth Annual Meeting of the International Society of Magnetic Resonance in
Medicine (ISMRM), 12-18 April 1997.
NMR of laser polarized 129Xe in blood foam.
C.H. Tseng, S. Peled, L. Nascimben, G. Wong, ILL Walsworth, and F.A. Jolesz,
presented at the 1997 Experimental NMR Conference (ENC), Orlando, FL, 24-28 March
1997.
Optimal pulse sequences for hyperpolarized 129Xe MR.
L. Zhao, R. Mulkern, C.H. Tseng, D. WiUiamson, S. Patz, R. Kraft, ILL Walsworth,
F.A. Jolesz, and M.S. Albert, presented at Centre de Physique des Houches International
Workshop on Perspectives of MR Imaging Using Polarized Gases, Les Houches, France,
9-11 October 1996.
Temporal dynamics of hyperpolarized 129Xe resonances in living rats.
K. Sakai, A.M. Bilek, E. Oteiza, R.L. Walsworth, D. Balamore, F.A. Jolesz, and M.S.
Albert, presented at Centre de Physique des Houches International Workshop on
Perspectives of MR Imaging Using Polarized Gases, Les Houches, France, 9-11 October
1996.
Laser polarized 129Xe spectra and lifetimes in in vitro blood and blood derivatives.
C.H. Tseng, S. Peled, L. Nascimben, G. Wong, R.L. Walsworth, and F.A. Jolesz,
presented at Centre de Physique des Houches International Workshop on Perspectives
of MR Imaging Using Polarized Gases, Les Houches, France, 9-11 October 1996.
Biological studies with laser-polarized 129Xe.
C.H. Tseng, E.R. Oteiza, R.L. Walsworth, M.S. Albert, L. Nascimben, S. Peled, K.
Sakai, and F.A. Jolesz, presented at DAMOP Meeting of the American Physical
Society, Ann Arbor, MI, 15-18 May 1996.
Large-scale production of laser-polarized 129Xe: comparison of laser-diode-array and Ti-
sapphire optical pumping.
R.L. Walsworth, R.E. Stoner, C.H. Tseng, G.A. Wong, and E.R. Oteiza, presented at
DAMOP Meeting of the American Physical Society, Ann Arbor, MI, 15-18 May 1996.



Investigation of laser polarized xenon magnetic resonance

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