This invention was made with Government support under Grant Nos. DAAH04-94-G-0204,
DAMD1794J4469, and F49620-94-0466. The Government may have rights in this invention.
BACKGROUND OF THE INVENTION
The invention relates to apparatus and methods for hyperpolarizing
noble gases. Specifically, the invention relates to methods and apparatus for producing
significant quantities of hyperpolarized noble gases in a continuous manner.
Nuclear magnetic resonance (NMR) is a phenomenon which can be induced
through the application of energy against an atomic nucleus being held in a magnetic
field. The nucleus, if it has a magnetic moment, can be aligned within an externally
applied magnetic field. This alignment can then be transiently disturbed by application
of a short burst of radio frequency energy to the system. The resulting disturbance
of the nucleus manifests as a measurable resonance or wobble of the nucleus relative
to the external field.
For any nucleus to interact with an external field, however, the nucleus
must have a magnetic moment, i.e., non-zero spin. Experimental nuclear magnetic
resonance techniques are, therefore, limited to study of those target samples which
include a significant proportion of nuclei exhibiting non-zero spin. A highly preferred
such nucleus is the proton (1H), which is typically studied by observing
and manipulating the behavior of water protons (1H2O) in magnetic
fields. Other nuclei, including certain noble gas nuclei such as 3He
and 129Xe, are in principle suited to study via NMR. However, the low
relative natural abundance of these isotopes, their small magnetic moments, and
other physical factors have made NMR study of these nuclei difficult if not impossible
One important consideration in studying noble gas nuclei via NMR is
that they normally yield only a very low NMR signal intensity. It is known, however,
that the spin polarization of such noble gases as 3He and 129Xe
can be increased over natural levels, i.e., populations of these isotopes can be
artificially "hyperpolarized", to provide a much larger NMR signal. One preferred
hyperpolarization technique is known as spin exchange hyperpolarization. Without
describing this technique in exhaustive detail, in this scenario a noble gas is
hyperpolarized via interaction with an alkali-metal vapor, such as rubidium, which
itself has been polarized by absorption of laser energy of an appropriate wavelength.
The polarized rubidium transfers its polarization to the noble gas through a phenomenon
known as spin exchange transfer. The end result is that the noble gas becomes "hyperpolarized",
i.e., more polarized than it would otherwise be. Details of the theory underlying
the spin exchange hyperpolarization technique are available in the literature.
While well established as a theoretical phenomenon, the actual practice
of spin exchange hyperpolarization has proven to be something of an art. The production
and handling of hyperpolarized noble gases is not only logistically difficult, it
is expensive as well. Moreover, due to the experimental nature of spin exchange
studies, the production of hyperpolarized noble gases has typically been undertaken
only on a small scale. Exquisite craftsmanship is typically required, involving
expertise in a variety of fields including lasers, electronics, glass-blowing, ultra-high
vacuum pump operation, high-purity gas handling as well as nuclear magnetic resonance
For example, the production of a single sample of hyperpolarized noble
gas has typically involved the fabrication of a single-use sealed glass cell with
a volume capacity of only a few tens to a few hundred cubic centimeters. Such cells
have required delicacy in manufacture, yet their quality, as measured by their tendency
to depolarize the noble gas, has not always been predictable. Moreover, use of such
cells for spin exchange requires that they be sealed with the alkali metal present
therein. This has meant that care must be taken to remove impurities which can cause
oxidation of the metal and consequent ruination of the cell. Other problems arise
in the glass itself which can depolarize the noble gas faster than it can be polarized.
For study of polarized noble gas by nuclear magnetic resonance (NMR) techniques,
the sealed cell must be opened or destroyed to release the hyperpolarized gas into
the NMR spectrometer. Proceeding to the next sample has required repeating all of
these steps, including fabricating and filling a new glass cell, which might or
might not have similar qualities, resulting in a tedious and often unpredictable
Middleton established for the first time the possibility of making
sealed cells capable of containing larger quantities of a noble gas for hyperpolarization
by the spin exchange technique. Middleton H., The Spin Structure of the Neutron
Determined Using a Polarized3He Target. Ph.D. Dissertation. Princeton
University. (1994). Even so, the reliability of the procedures described in this
publication has not proven to be suited to routine use, in that sample-to-sample
variability has remained a problem. Moreover, there is no disclosure in this document
of any method of making refillable cells or cells which could be used on a continuous
or flowing basis without significant rehabilitation. Accordingly, while progress
in cell manufacture has occurred, the art has not provided means for making refillable
or continuous flow spin exchange pumping cells.
A publication by Becker et al., Nucl. Inst. &
Meth. in Phys. Res. A. 346:45-51 (1994) describes a method for producing
hyperpolarized 3He by a distinctly different polarization method known
as metastability exchange. This approach requires the use of extremely low pressures
of 3He, i.e., about 0.001 atm to about 0.01 atm, and does not involve
the use of an alkali metal. Significant accumulation of hyperpolarized gas is limited
by the necessity of using huge pumping cells (i.e., about 1 meter long) and then
compressing the gas to a useful level. The Becker et al. publication discloses an
ingenious but technically difficult approach which employs large volume compressors
made of titanium for compressing the gas to about atmospheric pressure. Unfortunately,
manufacture and operation of such a system requires great engineering skill, limiting
the reproducibility and operability of the system on a routine basis. The apparatus
described by Becker, et al. also requires significant amounts of floor space and
cannot be moved. The Becker et al. paper also avoids the use of alkali metals in
the pumping cells, and does not disclose any method of producing hyperpolarized
noble gas by spin exchange. Hence, the Becker et al. paper does not resolve the
complexity of manufacturing pumping cells in which an alkali metal is employed.
As a result, this publication does not describe or suggest any method or apparatus
related to the production and delivery of arbitrarily large or small quantities
of hyperpolarized noble gas by spin exchange.
It was recently demonstrated that hyperpolarized noble gases can be
imaged by nuclear magnetic resonance imaging (MRI) techniques. See U.S. patent application
Serial No. 08/225,243. In addition, because the noble gases as a group are inert
and non-toxic, it was found that hyperpolarized noble gases can be used for MRI
of human and animal subjects. As a result, there exists a growing need for the generation
of larger quantities of hyperpolarized noble gases. Moreover, because of medical
and veterinary concerns, controlled uniformity and reliability in the purity of
the gases and the amount of hyperpolarization have become necessary. Also, the need
for convenient and reliable generation of these hyperpolarized gases has become
important for use in a clinical setting in which technicians. having little or no
specific training in the laboratory techniques described above, are still able to
provide discrete or continuous hyperpolarized noble gas samples to subjects undergoing
In view of the above considerations, it is clear that the apparatus
and methods in use in the existing art are limited in a number of ways. For example,
the existing art does not provide any practical means for refilling a spin exchange
polarization chamber (cell) once it has been used. Most current chambers are either
permanently sealed after the first filling or have been refilled with at best unsatisfactory
results. Thus, it would be of benefit to develop means for effectively refilling
a pumping chamber, or even for optically pumping in a continuous flow mode in the
same chamber, so as to decrease costs of materials and personnel.
Moreover, even successful fills for the permanently sealed cells used
previously were accomplished via a significantly different system. In the past,
an expensive ultra-high vacuum system, with either oil-free pumps or cryotrapped
oil-containing pumps, has been required in order to produce a sufficiently clean
apparatus for filling high quality polarization chambers. Such a system is expensive
(about $30,000), not very compact (3 ft by 6 ft footprint), and requires high maintenance
by a trained vacuum technician. A new system, requiring only minimal maintenance
and capable of being operated without specialized knowledge of vacuum technology,
would be desirable. Also, a system having a more convenient size would be useful
in clinical settings.
In addition, there has been no practical way to produce hyperpolarized
gas in a continuous fashion. For each spin exchange hyperpolarization procedure
a new sealed sample has had to be prepared and introduced into the hyperpolarization
apparatus. It would, therefore, be desirable to develop a system which overcomes
this limitation to provide means for continuous hyperpolarization of flowing noble
Systems for producing hyperpolarized gases have also been quite bulky,
typically requiring separate rooms for their installation. Such systems are not
transportable. Thus, small, convenient hyperpolarizers would be advantageous. Also
transportable systems would be of benefit in situations where space is a critical
Also, there has previously been no convenient way to store substantial
quantities of hyperpolarized noble gases for later distribution in discrete quantities
of arbitrary amount (up to liters of gas at atmospheric pressure). It would be important
to overcome this limitation as well, to provide apparatus for continuous accumulation
of a hyperpolarized noble gas. as well as storage and controlled release of the
hyperpolarized gas on an as-needed basis, while still retaining substantial quantities
SUMMARY OF THE INVENTION
Accordingly, as a result ofthe invention, there is now provided an
improved apparatus and method for producing hyperpolarized noble gases. In particular,
there is provided self-contained apparatus for producing and delivering large quantities
of high purity hyperpolarized noble gases for use in magnetic resonance imaging.
In one embodiment, the apparatus includes a high capacity hyperpolarizer,
in which a flowing noble gas, preferably xenon-129 or helium-3, can be hyperpolarized
in substantially larger quantities than has been possible in the past. This hyperpolarizer
includes means for hyperpolarizing a flowing noble gas in a continuous or batch
mode. For example, the noble gas may be flowed through the hyperpolarizer's polarization
chamber in a continuous mode, such that the rate of flow permits a substantial fraction
of the nuclei to be hyperpolarized during their passage through the polarization
chamber. This continuous flow approach is particularly well adapted to a noble gas
having a relatively short polarization time, such as129Xe. Alternatively,
in a semi-continuous approach, the flow of the noble gas may be isolated or temporarily
interrupted to enable hyperpolarization of the noble gas in discrete volumes. In
this. semi-continuous mode, a quantity or volume of the noble gas is hyperpolarized
in the polarization chamber and thereafter the flow is resumed to deliver a discrete
quantity or pulse of a noble gas. Also, subsequent volumes of the flowing gas can
then be treated to provide episodic or periodic pulses of hyperpolarized gas. Helium-3
has a relatively long polarization time, i.e., up to several hours, and is preferably
polarized using this episodic flow approach.
In this apparatus the polarization chamber permits flow-through of
the nobie gas, either on a continuous or semi-continuous basis. Hence, the generation
of relatively large quantities of the hyperpolarized noble gas is not impeded or
otherwise limited by the need to prepare new hyperpolarization cells for each and
In another embodiment, the hyperpolarizer apparatus of the invention
further includes means for accumulating hyperpolarized 129Xe in a continuous
or semi-continuous mode. This system enables hyperpolarized xenon to be flowed from
the polarization chamber through a cryotrapping reservoir and trapped efficiently
and selectively as frozen xenon. The accumulator permits xenon flowing within the
reservoir to deposit on top of previously deposited xenon, thereby permitting the
accumulation of the xenon ice. Because the solid form of hyperpolarized
129Xe has a much longer polarization lifetime than the gaseous form,
the accumulator can serve as a storage device, allowing the accumulation of significant
quantities of hyperpolarized gas for use at a later time.
The invention further includes a method of hyperpolarizing a noble
gas in which a gas mixture of 129Xe is hyperpolarized. The gas mixture
includes a minor quantity of xenon, a minor quantity of a fluorescence-quenching
gas such as nitrogen or hydrogen, and a major quantity of a buffer gas. It has now
been observed that the hyperpolarization of high partial pressures of xenon is not
as efficient as desired, i.e., high pressure xenon can inhibit its own hyperpolarization
by depolarizing the alkali metal too efficiently. Low pressure hyperpolarization
therefore, has been the requisite norm. A new method of improving the efficiency
of xenon hyperpolarization according to the invention, however, includes using a
buffer gas to broaden the absorption of laser energy, thereby enhancing the efficiency
of the hyperpolarization process. One preferred buffer gas is helium, although hydrogen
can also be used. Accordingly, the invention includes the use of a buffer gas different
from the quenching gas, to solve the problem that certain quenching gases cause
depolarization of the alkali-metal vapor at high pressures of the quenching gas.
Accordingly, a preferred gas mixture includes a minor amount of 129Xe,
a minor amount of a fluorescence quenching gas, and the balance helium. More preferably,
the mixture includes from about 0.1 % to about 5%129Xe, from about 0.1
% to about 30% of a quenching gas such as nitrogen or hydrogen, and the balance
helium. Most preferably, the mixture includes about 1% 129Xe, about 1%
nitrogen, with the balance being helium. Alternatively, the mixture can include
from about 0.1% to about 5% 129Xe, with the balance being hydrogen, wherein
hydrogen performs quenching and pressure-broadening functions.
Accordingly, the invention provides a method for hyperpolarizing a
flowing noble gas. The method includes:
thereby providing a flowing hyperpolarized noble gas.
- a) flowing a target gas, which includes a noble gas, through a pumping chamber;
- b) hyperpolarizing the flowing noble gas in the pumping chamber by spin exchange
with alkali metal atoms;
The method preferably involves flowing the target gas through the
pumping chamber at a rate which provides an average atom residence time of the noble
gas of from about 0.5 to about 5 times the spin exchange time τSE
between atoms of the alkali metal and the noble gas. More preferably, the flow rate
provides an average atom residence time of the noble gas of from about 1 to about
3 times the spin exchange time τSE between atoms of the alkali
metal and the noble gas.
The method can be performed such that the target gas is continuously
flowed through the pumping chamber during the hyperpolarizing. This mode is preferred
for noble gases such as 129Xe, having relatively short polarization times.
Alternatively, the method can include temporarily disrupting (reducing or halting)
the flow to isolate a discrete quantity of the target gas in the pumping chamber
to permit hyperpolarizing of a quantity of noble gas. Flow of the gas is restored
or increased once the desired quantity of the noble gas has been hyperpolarized
to the desired degree. Noble gases, such as 3He, having longer polarization
times are preferably polarized using this mode. In an episodic or periodic approach,
this method is preferably performed at least twice, to provide two or more discrete
quantities of the hyperpolarized noble gas to provide semi-continuous flowing delivery.
The method of the invention involves hyperpolarizing the noble gas
by spin exchange with alkali metal atoms. A preferred alkali metal is rubidium,
preferably including rubidium-85 and/or rubidium-87. Rubidium atoms have been found
to be suitable for polarizing both 129Xe and 3He. In other
applications, however, cesium (preferred for 129Xe) or potassium (preferred
for 3He) may be desirable. Other alkali metals may be employed as needed.
The noble gas preferably includes a polarizable amount of a noble
gas isotope having nuclear spin. Preferred noble gases include xenon, including
129Xe, and helium, including3He. Other noble gases may be
employed as required. Preferably, the isotope having non-zero spin is present in
the noble gas in at least natural isotopic abundance. Enriched noble gases, i.e.,
having substantially greater proportions of the desired isotope than are found in
nature are more preferred. Helium-3, in particular, has a natural abundance in helium
which is so low (i.e., 10-6) as to make enrichment necessary. Useful
amounts of 3He (e.g., at least about 10%, preferably more than about
50% 3He) can be obtained by harvesting the 3He produced by
the radioactive decay of tritium, and helium gas containing up to 100%
3He is commercially avaliable.
In a preferred scenario, the target gas includes not only the noble
gas, but further includes a quenching gas, which acts to suppress fluorescence by
the alkali metal atoms during hyperpolarizing. Preferred quenching gases include
nitrogen gas (N2) and hydrogen gas (H2).
A particularly preferred method involves using a target gas in which
the noble gas includes 129Xe. In this case, the target gas includes a
quenching gas, as well as a buffer gas which causes pressure broadening of the optical
absorption spectrum at which the alkali metal atoms absorb suitable hyperpolarizing
radiation. A highly preferred buffer gas is helium, which is substantially
4He. Hence, a useful target gas according to this embodiment includes
a minor amount of 129Xe, a minor amount of nitrogen or hydrogen as the
quenching gas, and a major amount of helium. More preferably, the target gas includes
from about 0.1% to about 5% 129Xe, from about 0.1% to about 30% of the
quenching gas, with the balance being helium. Still more preferably, the target
gas includes about 1% 129Xe, about 1% nitrogen, with the balance being
helium. Thus, the invention includes three-part target gases, in which the quenching
gas and the buffer gas are different. However, target gases can include hydrogen
as both a quenching gas and a buffer gas, e.g., about 0.1% to about 5%
129Xe, with the balance hydrogen.
In another embodiment, the hyperpolarization method further includes
accumulating the hyperpolarized noble gas flowing from the pumping chamber. In the
case of 3He, a large amount of 3He can be accumulated (at
or above atmospheric pressure) in a gas storage reservoir. In the case of
129Xe, preferred accumulating means includes a cryotrapping reservoir
which permits flow-through of gas, with the accumulation of 129Xe in
frozen form. while limiting the accumulation of other gases, such as quenching and
buffer gases initially present in the target gas mixture.
The method advantageously includes flowing the noble gas under hyperbaric
or supra-atmospheric conditions. Preferably, the gas is flowed at a pressure of
from about 1 atmospheres (atm) to about 30 atm. A presently preferred pressure is
about 10 atm.
In a particularly advantageous approach, the noble gas (or target
gas) flowed through the pumping chamber is substantially free of impurities which
can interfere with the hyperpolarizing process. Thus, impurities such as alkali-metal-reactive
impurities and impurities which would otherwise cause the alkali metal to deposit
in solid phase in the pumping chamber should be removed. Also, particularly in the
case of 3He, impurities which can depolarize the noble gas should be
removed. Preferably, the purifying means removes (e.g., getters) impurities such
as water vapor and oxygen introduced during gas manufacture or mixing prior to the
The hyperpolarizing method of the invention is enhanced by heating
the pumping chamber and its contents during hyperpolarizing to increase the efficiency
of the process. In addition, the various aspects and parameters of the process are
desirably monitored and controlled by central control means, typically including
In a preferred embodiment, the invention also provides a method of
hyperpolarizing129Xe in a target gas. The target gas includes
129Xe, as well as a quenching gas for quenching fluorescence of alkali
metal atoms during hyperpolarizing, and a buffer gas for pressure-broadening the
optical absorption band of the alkali metal atoms, and the hyperpolarizing is performed
under conditions sufficient to induce hyperpolarization of the129Xe by
spin exchange with alkali metal atoms, thereby providing hyperpolarized
129Xe. The buffer gas and the quenching gas are preferably different.
Preferably, the quenching gas is nitrogen or hydrogen. The buffer gas is preferably
helium or hydrogen. More preferably, the target gas includes from about 0.1 % to
about 5% 129Xe, from about 0.1 % to about 30% of the quenching gas, with
the balance being helium. Still more preferably, the target gas includes about 1%
129Xe, about 1% nitrogen, with the balance being helium.
In another embodiment, the invention includes apparatus for hyperpolarizing
a flowing noble gas. In this embodiment, the apparatus includes:
- a) a target gas delivery system adapted to deliver a flowing noble gas;
- b) a pumping chamber for hyperpolarizing the flowing noble gas by-spin exchange
with alkali metal atoms; and
- c) hyperpolarization means for hyperpolarizing the flowing noble gas in the
The target gas delivery system in this embodiment preferably includes
a gas container capable of maintaining the noble gas under compression prior to
flowing the gas through the pumping chamber. A high pressure gas canister or bottle
or other such device may be employed for this purpose. Moreover, the delivery system
should be able to deliver the target gas under hyperbaric conditions. The remaining
parts of the target gas delivery system are preferably sealed to maintain the gas
under hyperbaric conditions of from about 1 atm to about 30 atm, more preferably
about 10 atm. Indeed, all of the parts of the apparatus of the invention which contact
the gas, including the pumping chamber associated conduits and valves, should be
operable using hyperbaric gas pressures, preferably from about 1 atm to about 30
atm. The target gas delivery system also preferably includes means for removing
impurities, such as alkali-metal-reactive impurities and depolarizing impurities,
from the flowing target gas prior to flow of the gas through the pumping chamber.
The pumping chamber in the apparatus is preferably adapted to admit
hyperpolarizing radiation, i.e., radiation of a.wavelength and energy sufficient
to permit polarization of the noble gas by spin exchange with alkali metal atoms.
Thus, at least one irradiation window is included in the pumping chamber. In situations
in which irradiation is employed from more than one position or direction, additional
irradiation ports can be included.
The apparatus also can include a receiving reservoir adapted to receive
hyperpolarized noble gas flowing from the pumping chamber. For 129Xe,
a highly preferred receiving reservoir includes a cryotrapping accumulator for accumulating
129Xe in a frozen state.
In a preferred embodiment, the apparatus is adapted to permit continuous
flow of the target gas through the pumping chamber during hyperpolarizing. Alternatively,
the apparatus should permit controllable isolation of a discrete quantity of the
flowing noble gas in the pumping chamber during hyperpolarizing. For example, the
apparatus may be valved to permit control of the flow rate so as the reduce or halt
the flow temporarily, while permitting resumption or increase of the flow when desired.
The apparatus should be adapted to deliver the target gas through
the pumping chamber at a rate sufficient to provide an average atom residence time
of the noble gas in the pumping chamber of from about 0.5 to about 5 times, more
preferably from about 1 to about 3 times, the spin exchange time τSE
between atoms of the alkali metal and the noble gas.
The hyperpolarizing means in the apparatus of the invention preferably
includes a laser system capable of delivering into the pumping chamber radiation
sufficient for hyperpolarizing the noble gas via spin exchange with alkali metal
atoms, such as atoms of rubidium, cesium, or potassium. While conventional types
of lasers are compatible with the invention, it is preferred that the laser system
employs at least one laser diode array. In a preferred apparatus according to the
invention, the laser system includes two laser sources in opposing arrangement along
a single optical axis, with the pumping chamber adapted to admit radiation from
both lasers. Each of the two laser sources preferably includes at least one laser
diode array. Two dimensional, or stacked, laser diode arrays are preferred, and
can deliver substantial output power into the pumping chamber. The laser system
of any of these embodiments preferably includes radiation focusing means to collimate,
and more preferably focus, radiation emitted from the laser system. Such focusing
means preferably includes a Fresnel lens.
. The pumping chamber itself should admit hyperpolarizing radiation
from the laser source(s). Preferred structures of the chamber include conical or
truncated conical (frustoconical) structures, although in certain configurations
a cylindrical cell is suitable. Preferably, the chamber is designed in conjunction
with the laser system to maximize light delivery into the chamber and throughout
its interior, to maximize the efficiency of the hyperpolarizing procedure.
Other apparatus is advantageously incorporated with the laser and
pumping chamber, For example, the apparatus preferably also includes heating means
for heating the pumping chamber during the hyperpolarizing procedure. Also, the
apparatus desirably includes.means for monitoring hyperpolarization in the pumping
chamber, such as by NMR polarimetry. In addition, the pumping chamber preferably
includes a fluorescence observation window, as well as fluorescence monitoring means
for monitoring fluorescence through the fluorescence observation window.
Moreover, in continuously flowing systems, the apparatus preferably
includes an alkali-metal vaporizer to provide sufficient alkali-metal vapor density
in a flowing target gas to maintain good efficiency of the hyperpolarization process.
In addition, the pumping chamber is desirably equipped with alkali-metal refluxing
means to recover alkali metal vapor which might ordinarily leave the chamber with
the flowing gas following hyperpolarizing. The vaporizer and the refluxing means
can operate together to provide a continuous recirculation of the alkali-metal vapor
through the pumping chamber. In preferred cases, the apparatus includes an amount
of an alkali metal to permit maintenance of sufficient alkali-metal vapor density
during a hyperpolarization procedure.
In another embodiment, the invention provides apparatus for hyperpolarizing
a noble gas, most preferably 3He. which apparatus includes:
In this embodiment, the replaceable polarization unit is configured such that the
unit is capable of engaging with and operating in conjunction with the hyperpolarization
means so that the pumping chamber is oriented to transmit light energy from the
laser source into the pumping chamber for hyperpolarization of the noble gas. Preferably,
the apparatus is adapted to enable hyperpolarization by means of spin exchange between
atoms of the noble gas and an alkali metal.
- a) hyperpolarization means, including:
- 1) a laser system capable of delivering hyperpolarizing radiation, and
- 2) a computer system enabling control and monitoring of a hyperpolarization
- b) a replaceable polarization unit, including:
- 1) a target gas delivery system for maintaining and delivering a target gas
including a noble gas, preferably 3He, at a hyperbaric pressure, and
- 2) a pumping chamber in fluid communication with the target gas delivery system.
One desirable feature of the apparatus which involves a replaceable
polarization unit is that a quantity of the target gas can be flowed into the pumping
chamber, the quantity of noble gas can be hyperpolarized, and then the polarization
unit can be removed from the hyperpolarization means to permit flowing delivery
of the quantity of gas as desired, e.g., to a patient undergoing MRI. Immediately,
another replaceable unit can be installed into the hyperpolarization means, to begin
the flowing hyperpolarization of another quantity of gas. This mode of operation
is particularly desirable with 3He, which requires relatively long polarization
In a further embodiment, the invention provides apparatus for use
in hyperpolarizing a flowing noble gas, most preferably 3He, including:
The polarization unit in this embodiment is adapted to removably engage and operate
with a hyperpolarizing system including a laser system capable of delivering hyperpolarizing
radiation into the pumping chamber when the polarization unit is engaged therewith.
Apparatus according to this embodiment preferably enables spin exchange hyperpolarization
of the noble gas.
- a removable polarization unit, including:
- a pumping chamber adapted to permit flow-through of a noble gas, and permissive
to hyperpolarizing radiation for hyperpolarizing a flowing noble gas.
This embodiment of the invention further provides apparatus; in which
the removable polarization unit further includes a target gas delivery system, for
maintaining and flowing through the pumping chamber a target gas including a noble
gas to be hyperpolarized. The target gas delivery system preferably includes such
a target gas, which includes the noble gas to be hyperpolarized.
Also in this embodiment, the pumping chamber can further include an
amount of an alkali metal sufficient to maintain an alkali-metal vapor during a
Other features of the apparatus of the invention described elsewhere
herein can be incorporated into this embodiment. For example, the apparatus can
include a removable polarization unit which further includes a heating system for
heating the pumping chamber. Also, the target gas delivery system can further includes
a target gas purifier for removing alkali metal-reactive impurities from the target
gas prior to flow of the target gas through the pumping chamber. Alkali metal vaporizer
means and refluxing means can also be included.
The polarization unit, including the elements of the target gas delivery
system and the polarization chamber are preferably operable under conditions in
which the target gas is under hyperbaric pressure, e.g., from about 1 atm to about
The invention also provides, in a further embodiment, apparatus for
hyperpolarizing a flowing noble gas, preferably 3He, including:
In this embodiment, the hyperpolarizing system is adapted to removably engage and
operate with a removable polarization unit having a multi-use pumping chamber adapted
to permit flow-through of a noble gas, and to permit delivery of hyperpolarizing
radiation into the pumping chamber when the polarization unit is engaged therewith.
The hyperpolarizing system preferably enables spin exchange polarization of the
- a hyperpolarizing system, including:
- a laser system for delivering hyperpolarizing radiation sufficient to enable
hyper-polarization of a flowing noble gas.
The hyperpolarizing system preferably further includes a hyperpolarization
monitoring system, e.g., an NMR polarimetry system, for monitoring the status of
a hyperpolarization procedure. Moreover, the system can include a heating system
for heating a pumping chamber of the removable polarization unit when such a unit
is engaged therewith.
This type of hyperpolarizing system can further include an reservoir
means for accumulating a flowing hyperpolarized noble gas. In this case, the accumulator
is adapted to permit fluid communication with the pumping chamber when the removable
polarization unit is engaged therewith. The reservoir means preferably permits flow-through
of a target gas. In the preferred case involving 3He, the reservoir permits
hyperbaric accumulation of the hyperpolarized 3He. Alternatively, hyperpolarized
129Xe can be accumulated in frozen form via selective cryotrapping of
the hyperpolarized 129Xe gas.
In this embodiment, also, the laser system includes at least one,
and preferably two, laser sources. When two laser sources are provided, they are
preferably positioned in opposed arrangement along a single optical axis, such that
hyperpolarizing radiation can be delivered from opposing directions into the pumping
chamber when the polarization unit is engaged with the hyperpolarizing system. Whether
one or more laser sources is employed, each laser source is preferred to include
at least one laser diode array. As with other apparatus according to the invention,
when two or more laser diode arrays are used, they are preferably held is a stacked
These and other advantages of the present invention will be appreciated
from the detailed description and examples which are set forth herein. The detailed
description and examples enhance the understanding of the invention, but are not
intended to limit the scope of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
Preferred embodiments of the invention have been chosen for purposes
of illustration and description, but are not intended in any way to restrict the
scope of the invention. The preferred embodiments of certain aspects of the invention
are shown in the accompanying drawings, wherein:
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
- Figure 1 is a block diagram illustrating the general configuration of a hyperpolarizer
unit according to the invention;
- Figure 2 is a schematic diagram illustrating a flowing hyperpolarizer and accumulator
apparatus according to the invention;
- Figure 3 is a schematic diagram of a continuous or episodic flow polarization
cell according to the invention, including certain associated apparatus;
- Figure 4 is a schematic diagram of a hyperpolarizer unit of the invention, indicating
the structures of single and dual laser systems according to the invention;
- Figure 5 is an illustration of a transportable hyperpolarizer system according
to the invention; and
- Figure 6 is a schematic diagram of a removable polarization unit according to
In general terms, Figure 1 shows a schematic block diagram of an integrated
hyperpolarizer system useful for generating and accumulating large quantities of
a flowing hyperpolarized noble gas according to the invention. In Figure 1, a hyperpolarizer
unit is shown which includes several major subsystems, including an MRI gas delivery
subsystem through which the flowing polarized gas can be delivered as needed for
The pumping chamber shown in the diagram is the chamber in which the
alkali metal optical pumping and alkali-noble gas spin exchange take place. Initially,
unpolarized gas enters from the high purity gas handling subsystem and exits to
the polarized gas storage chamber which accumulates the hyperpolarized gas.
The gas handling subsystem provides the proper supply of gases to
the polarization chamber while generating and/or maintaining the gas purity required
for the hyperpolarization process.
After having been polarized in the polarization chamber, the hyperpolarized
gas may be flowed into the polarized gas storage chamber where it is accumulated
and stored until use. The polarization chamber and the polarized gas storage chamber
generally must be carefully prepared so as to maintain the gas polarization and
may also function to separate the hyperpolarized noble gas from an inert buffer
gas. When needed, the hyperpolarized gas will be flowed from this chamber to the
MRI delivery subsystem.
The MRI delivery subsystem shown in Figure 1 encompasses all the equipment
required for respirating a subject on the hyperpolarized gas either from the polarized
gas storage chamber or directly from the polarization chamber. This may include
devices and systems to perform a variety of desirable functions, preferably including
pressure regulation, virus filtration (HEPA, etc.), gas mixing to include oxygen,
an appropriate MR-compatible breathing mask, etc. Typically, exhaled air is collected
by the same mask and directed to the gas recovery subsystem. After being used for
a subject, the gas is collected by the gas recovery subsystem so that it can be
recycled for future use. The collected gas can be periodically shipped back to a
central reprocessing location for purification and/or sterilization.
The polarimetry subsystem shown in Figure 1 monitors the level of
polarization of the gas in the polarization chamber or the gas storage chamber.
Also as shown in Figure 1, the laser subsystem supplies the necessary
photons (hyperpolarizing radiation) for the optical pumping process. The output
beam of this system is directed into the polarization chamber.
The control subsystem is a unified computer-software and hardwired
subsystem which controls and monitors the different processes occurring in the various
Figure 2 illustrates in somewhat greater detail an integrated hyperpolarizer
system useful for generating and accumulating large quantities of a flowing hyperpolarized
noble gas according to the invention.
In Figure 2, a laser diode array 1, has an output power of from about
100 W to about 500 W and emits radiation of wavelength λ suitable for absorption
by alkali metal atoms. The wavelength spread Δλ is about 2nm FWHM,
with a linear polarization of about 95% or greater. Because of the large spread
in wavelength, this type of laser is referred to herein as a "broad-band'' laser.
In an alternative embodiment, two lasers pumping from opposite sides of the pumping
cell 4 can be used, with appropriate redesign of the cell 4 and the optical diagnostics
An aspheric Fresnel lens 2 (typically plastic) directs most of the
light from the diode laser array 1 into the optical pumping cell 4. An image of
the diode face is formed just beyond the end of the optical pumping cell 4. Although
the Fresnel lens is inexpensive and well adapted to currently available diode laser
arrays, different optics may be more appropriate for future lasers which may have
higher intrinsic brightness than those available today.
Quarter wave plate 3 converts linearly polarized light from the diode
laser array to circularly polarized light. As shown, a plastic quarter wave plate
is positioned just past the Fresnel lens 2 where the laser beam has expanded so
much that heating of the lens and the wave plate is not a problem. The light from
the laser 1, which is already linearly polarized to a high degree, can be passed
through a linear polarizer (not shown) before it reaches the quarter wave plate
3 if the natural linear polarization is not sufficient.
Optical pumping cell 4 is shown, provided with saturated alkali-metal
vapor, e.g., Rb or Cs, and an optimum gas mixture of 129Xe, N2
and He, as described below in connection. with the premixed gas tank 11. The cell
4 has the shape of a truncated cone to accommodate the converging light from the
lens 2. Refluxed alkali metal from the exit pipe 6 drops back through the cell and
collects in the vaporizer 5. The cell and associated piping must withstand the high
pressure of premixed gas, typically from above about 1 atmosphere to about 30 atmospheres.
High gas pressure inside the cell is important to permit efficient absorption of
the broad-band light from a diode laser.
A vaporizer 5 is provided, in this case, upstream of the pumping cell
4 for loading the flowing gas mixture with alkali-metal vapor prior to the gas's
entry into the cell. The vaporizer 5 can be made of crumpled wires of copper or
other non-magnetic metal or sintered metal that is readily wetted by liquid alkali
metals (e.g., a metallic sponge). The vaporizer 5 is soaked with liquid alkali metal,
and stuffed into a receptacle of appropriate materials and dimensions to ensure
full loading of the gas with vapor. The flow velocity of the gas, the distance through
which it flows, and the pore diameter of the "sponge" are adjusted to ensure that
the gas is fully saturated with alkali-metal vapor before it enters the optical
pumping cell. The vaporizer eliminates problems of small surface area of the alkali-metal
droplets in the optical pumping cell. which often causes the gas to be undersaturated
with vapor in the optical pumping cell.
It should be noted that other means can be used for loading the noble
gas with alkali-metal vapor. For example, a mixing chamber can be employed having
means for providing alkali-metal vapor to a relatively static quantity of gas prior
to infusion into the polarization chamber. Such an approach would be advantageous
in systems and methods in which the flow is modulated or interrupted.
The vaporizer 5 illustrated in Figure 2 is replenished by gravity
flow of condensed alkali metal from a refluxing outlet pipe 6, which leaves the
cell in a substantially vertical orientation. The refluxing outlet pipe 6 causes
the alkali-metal vapor in the gas exiting the cell to condense on the walls of the
pipe. The dimensions and flow velocity are adjusted to ensure that most of the alkali
metal condenses and drips back into the optical pumping cell by gravity flow, eventually
returning to the vaporizer. Thus, the vaporizer and reflux condenser together act
as a recirculating alkali-metal supply system for flowing hyperpolarizers according
to the invention.
A fluorescence monitoring detector 7, e.g., including a charge-coupled-device
(CCD) camera and appropriate filters, is provided to observe the weak, unquenched
D2 fluorescence from the optically pumped alkali-metal vapor. The fluorescence
monitoring arrangement can be adjusted for use with two lasers pumping from either
side of the cell.
Insulating window 8 is provided to permit pumping light to enter the
oven 9 and the optical pumping cell 4. This window and other light-transmitting
surfaces may be provided with an antireflection coating. Similar windows are provided
for the fluorescence monitor 7 and the optical multichannel analyzer (OMA) 10.
Oven 9 is provided to keep the optical pumping cell at a temperature
appropriate for absorbing most of the useful light from the diode laser. Typical
operating temperatures for rubidium are from about 100 °C to about 200 °C. Somewhat
lower temperatures are appropriate for cesium which is more easily volatilized.
The oven can be heated by flowing hot air or by internal, non-magnetic electrical
Optical multichannel analyzer (OMA) 10 for measuring the efficiency
of absorption of light from the broad-band diode laser array. A different arrangement
of the OMA is required if the cell is pumped from both sides. OMA systems suitable
for use in the apparatus of the invention are commercially available.
A high-pressure tank 11 is included to maintain a premixed target
gas at a pressure of several hundred atmospheres. Preferred target gas constituents,
by partial pressure, are:
- a. from about 0.1 % to about 5% 129Xe (or xenon of at least about
natural isotopic composition) for hyperpolarization in the optical pumping cell
4 and accumulation in the xenon accumulator 17;
- b. from about 1% to about 3% N2 for quenching fluorescence in the
optical pumping cell 4. H2 may be used at somewhat higher partial pressures
(e.g., from about 1% to about 30%) in place of N2 to take advantage of
the smaller spin depolarization cross-sections of alkali-metal atoms in H2
gas compared to N2 gas;
- c. the balance of the gas is a buffer gas, preferably He, for pressure broadening
the optical absorption lines of the alkali-metal atoms in the optical pumping cell
4. The He gas pressure is adjusted to ensure that it causes negligible spin depolarization
compared to the xenon. Other gas mixtures may be employed impart quenching and pressure-broadening
qualities to the target gas.
A pressure regulator 12 is employed to reduce the very high pressure
of the premixed gas in the storage tank 11 to a pressure appropriate for the optical
pumping cell 4. This is typically from about 10 to about 30 atmospheres, depending
on how much pressure broadening is needed for optimum use of the broad-band laser
Gas purifier (getter) 13 is used to remove trace impurities, mainly
water vapor, from the premixed target gas stream.
As shown in Figure 2, the accumulation reservoir 17 for accumulating
xenon includes a counterflow cold trap -- cooled by liquid nitrogen or some other
cryogen in a Dewar vessel. Closed-cycle refrigerators can also be used for cooling.
Such systems would not be included in apparatus dedicated to 3He.
Detachment point 15, together with.the detachment point 20, permits
the removal of the accumulation reservoir 17. Valve 14 isolates the optical pumping
cell 4 from the detachment point 15, and controls flow therebetween. Valve 16 is
used to isolate the accumulation reservoir 17 from detachment point 15.
A permanent magnet 18 is provided to produce a static field of greater
than about 500 Gauss (0.05 T) at the location of the frozen xenon in the accumulator
reservoir. A field this large is adequate to obtain the longest possible spin-lattice
relaxation times (e.g., about 3 hours at liquid nitrogen temperatures). For lower
condensation temperatures, where much longer spin-lattice relaxation times are attainable,
larger magnetic fields are needed. The magnet may also be contained inside the cryogenic
assembly and kept cool along with xenon accumulation reservoir.
Valve 19 is employed to isolate the xenon condenser 17 from the detachment
point 20, which together with detachment point 15 permits removal of the xenon condenser
Valve 21 is used to release sublimed hyperpolarized 129Xe
gas to transfer bag 22 or to any other container for transport of hyperpolarized
129Xe gas at atmospheric pressure for various uses, e.g., MRI of patients,
non-destructive evaluation, etc. Hard-walled containers can be used to transport
the hyperpolarized 129Xe gas at other pressures.
Valve 23 isolates the xenon accumulator 17 during sublimation of the
condensed xenon and gas transfer to the bag or other receptacle 22.
Glass-to-metal seal 24 is provided, with the piping on the pump side
of the seal preferably being stainless steel or other metal. On the xenon-condenser
side of the seal, the piping is glass. Similar glass-to-metal seals on the input
side of the gas flow and appropriate stress-relieving bellows are not shown, but
are normally to be preferred.
Pressure gauge 25 is used to monitor and control pressure during the
Pump 27, isolated by valve 26, is used for evacuating any remaining
He and N2 from the xenon condenser 17 at the end of the accumulation
A needle valve 28 or other flow control device is included to permit
waste He and N2 gas to vent to the room or to a recovery container for
reuse. This valve 28 controls the flow rate through the optical pumping cell 4.
The venting rate is adjusted to optimize the preparation of hyperpolarized
129Xe according to principles we have developed. Flow of the gas is monitored
by flow meter 29.
A vent 30 is provided, leading to the atmosphere or to a collection
receptacle for spent buffer gas (e.g., He) and quenching gas (e.g., N2
Port 31 is included for purging the gas lines with clean gas (e.g.
argon, helium or nitrogen) through the vent 24 after the tank of premixed gas is
attached. Vent 33 permits release of the purging gas introduced at the port 31.
Attachment point 32 is supplied for connecting the premixed gas supply
to the optical pumping cell. Valve 34 isolates the optical pumping cell during purging
ofthe gas-supply piping.
A nuclear magnetic resonance pickup coil 35 is also included to monitor
129Xe polarization in the pumping chamber, which is useful for optimizing
the gas flow rate.
Temperature sensor 36, e.g., a resistive temperature device (RTD),
is employed to monitor the temperature of the oven.
A static magnetic field 37 is also illustrated. The source is not
shown, but we have successfully used either Helmholtz coils or the fringing fields
of a magnetic resonance imaging magnet or a combination of the two.
A control subsystem (not shown) is generally desirable as a unified
computer-software and hardwired subsystem which is used to control and monitor the
different processes occurring in the various subsystems.
Figure 3 illustrates one configuration of a hyperpolarization system
according to the invention, including additional details concerning certain components
of the polarization chamber. The drawing shows a polarization chamber (cell) 4,
an oven 9 in which the cell 4 is housed, and heating and control apparatus 40a-f
necessary to maintain the oven 4 at a chosen temperature.
One implementation of a polarization chamber is shown in Figure 3.
As the chamber in which the optical pumping and spin exchange takes place it must
satisfy a number of requirements. For example, the pumping chamber must hold an
appropriate amount of polarizable gas in a substantially leak-tight environment.
The gas pressure in the chamber is maintained according to the requirements of the
apparatus, preferably being maintained at a pressure above atmospheric pressure
(also designated herein "hyperbaric") up to about 30 atm, and more preferably from
about 8 atm to about 12 atm for a glass cell. The gas pressure may be outside (above
or below) this range, as required. A presently preferred pressure is about 10 atm;
which reflects the structural limitations of glass, the material most typically
used in the manufacture of polarization chambers. Higher pressure or gas density
could be used in other polarization chamber structures.
The pumping chamber 4 shown in Figure 3 is a preferred embodiment
having two light ports or windows (4a and 4b) for admitting hyperpolarizing radiation
(arrows 41 and 42) into the cell from two lasers (not shown) arranged to emit along
the same axis but from opposite directions. Regardless of whether one or more than
one light port is employed, the ports are preferably at least substantially transparent
to light at and/or near the wavelength of the optical pumping transition line of
the alkali metal being used (i.e., "hyperpolarizing radiation"). For example, the
wavelength of the D1 transition in rubidium is 794.7 nm, and the
light ports suitable for use with rubidium should be at least substantially transparent
to light at this wavelength. Other alkali metals are hyperpolarized using other
wavelengths, and the light ports should be transparent to the appropriate wavelength.
Optimization of pumping efficiency would require that the light ports be as transparent
as possible to light of the requisite wavelength, i.e., absorption of the hyperpolarizing
radiation should be minimized. They may be antireflection-coated to maximize light
The volume-averaged relaxation time ofthe nuclear polarization of
a gas in the pumping chamber must be sufficiently slow compared to the spin-exchange
rate between the alkali-metal atom and the noble-gas nucleus to allow the desired
level of polarization in the cell to be attained. The materials and design of the
polarization chamber must therefore be selected with care. For example, the pumping
chamber should be chemically compatible with alkali metals, preferably being compatible
with alkali metals at temperatures appropriate for optical pumping (e.g., up to
about 200 °C or more). In addition, if an NMR polarimetry system is used to monitor
the hyperpolarization procedure, it is preferred that.the pumping chamber walls
not interfere substantially with the rf field required for polarimetry.
The particular implementation of the pumping chamber will depend on
the type of gas being polarized. As noted above, polarization chambers useful according
to the invention can be made of glass. The glass should be resistant to the alkali
metal(s) employed in the spin exchange process. For 3He, moreover, the
pumping chamber is preferably made from a glass having a limited permeability to
helium. More preferably, the glass has a helium permeability which is smaller than
that of Coming 7704 (Pyrex®). Such glasses are exemplified by aluminosilicate
glasses (such as Coming 1720), or metal-sealing borosilicate glasses (such as Corning
7052 or Schott 8502). For 129Xe, on the other hand, there is no stringent
need for limited permeability since xenon is a substantially larger atom, and permeability
is not a significant problem. Another useful glass is glass which is prepared to
be substantially free of iron. For lower temperature applications, standard borosilicate
laboratory glassware, e.g., Pyrex®, Duran®, can be used.
The pumping chamber preferably has a conical or truncated conical
(frustoconical) shape, to provide a gas volume which conforms substantially to a
converging beam of hyperpolarizing radiation. By focusing (converging) the laser
radiation into a cell with decreasing diameter along the optical axis, the light
intensity at regions of the cell distal to the laser is effectively increased to
at least partially offset the decrease in intensity which occurs due to absorption
of the light in the proximal regions. Nonetheless, cylindrical pumping cells may
be desirable in certain implementations. Hourglass-shaped cells (i.e., cells resembling
two cones opposed at their apices) can be desirable to implement and maximize the
efficiency of opposed laser systems.
Presently, the pumping cells are made of glass. Other pumping chamber
designs, capable of higher pressure operation, can be employed. Cells with pressures
in excess of 10 atmospheres can be readily made by using metal walls and piping
with appropriate optical windows to admit the light. It is also possible to design
glass optical pumping cells contained within a high-pressure surrounding gas or
a transparent liquid (e.g., pump oil), in an external cell with appropriate windows.
Then the pressure differential across the inner cell walls is minimized, and there
is no danger of breakage.
Previously, sealed cells have retained the hyperpolarization gas in
contact with the walls of the cell for extended periods, providing ample opportunity
for the gas to relax by interacting with iron and other paramagnetic impurities.
An advantage of the continuous or semi-continuous hyperpolarization system of the
invention, however, is that the hyperpolarized noble gas need not be in contact
with glass for any prolonged period. We have found that because of this feature,
the need for removing paramagnetic impurities in the glass is reduced, permitting
use of less expensive materials.
The pumping chamber 4 also desirably has separate resealable inlet
and outlet ports, such as o-ring valves, which allow continuous or episodic removal
and replacement of the gas being polarized. Any suitable gas ports permitting flow
control can be employed. The chamber 4 can have a single gas port through which
gas is flowed into and out of the cell episodically. However, for flowing gas in
a continuous fashion, two gas ports are required. Such an arrangement is shown in
Figure 3, in which inlet port 43 and outlet port 44 are shown. The remainder of
the gas handling system is not shown in this drawing.
The resealable gas ports include valve means for controlling the flow
of gas. Typically, these valves have Pyrex® glass bodies and stems, and are
fitted with flexible and elastic seals which are also resistant to alkali metals.
Such seals are typically o-rings, and can be made of various polymeric materials.
A preferred o-ring material, which has shown virtually no susceptibility to alkali
attack, is a copolymer of ethylene and propylene. Other polymers which may be suitable
include silicone polymers. Fluoroelastomers such as Viton™, Teflon®, etc.,
are relatively less resistant to alkali attack, and are therefore less desirable,
albeit suitable for short term use. Resistance of the o-rings to alkali attack is
an important characteristic since oxidation of the pumping chamber can occur should
oxygen enter the chamber through failed o-rings.
The valves in the resealable gas inlet and outlet apparatus are separated
from the main body of the pumping chamber by conduits, preferably tubes made from
glass similar to that used for the polarization chamber. See conduits 43 and 44
in Figure 3. These tubes allow the heat sensitive o-ring materials to be thermally
separated from the main body of the cell and the oven surrounding the cell, which,
during the polarization process, is often heated to above the o-ring's limit. The
tubes also help limit the net polarization relaxation due to interaction of the
hyperpolarized noble gas with the valve body. This is believed to be related to
the use of high operating gas pressures, at which pressures diffusion down the length
of the tubes is slow compared to the depolarization time constant of the bulk volume
(which is dependent upon the ratio of tube volume to total volume). Also, capillary
tubes limit the degree to which the hyperpolarized gas, particualrly 3He,
can contact (diffuse into) and be depolarized by the valve seals. Valves constructed
of non-ferrous metals could also be used.
We have found that the pumping cell will have a longer 3He
polarization lifetime if the stock glass tubing is entirely reblown during the fabrication
of the cell. Reblowing means that every interior surface is made molten and reformed
during fabrication. An acid rinse with a strong acid, such as HNO3 or
HCl, can also be used to improve polarization lifetime, but alone is not as effective
When the interior surfaces of the glass are sufficiently clean and
the chamber is fabricated according to the procedures described herein, no significant
relaxation of the noble gas polarization occurs relative to the time scale of the
spin-exchange process. A detailed description of such procedures is found in Middleton,
H.L., The Spin Structure of the Neutron Determined Using a Polarized
3He Target, Ph.D. Dissertation, Chapter 5, Princeton University,
(1994). This description is incorporated herein by reference. Briefly, the interior
cell walls are cleaned by baking them at up to 500 °C, either while the cell is
under vacuum or while it is being purged with a pure buffer gas. A radio frequency
(rf) discharge may also be run inside the cells to assist in driving contaminants
from the surface. After being cleaned, the cells are not exposed to the atmosphere
but are either kept under vacuum or kept filled with the pure purge gas until the
alkali-metal and the noble gas are introduced. Since the alkali metal is typically
driven into the cells by heating a reservoir of the metal, all of the connecting
gas/vacuum lines between the cell and the reservoir must be alkali metal-resistant
and cleaned of volatile adsorbed species in a manner similar to the cell cleaning
method. After the alkali metal is loaded into the cell, the desired amount of the
target gas is introduced and the cell is sealed off, at which point it is ready
to be polarized.
Other improvements in reduction of gas depolarization can be advantageously
incorporated into the apparatus of the invention. For example, metal-film coatings
(gold, alkali-metals, etc.) may improve polarization lifetimes and reduce the effort
required in cleaning and fabricating cells. We have found, for instance, that gold
does not induce any significant relaxation of the nuclear polarization and can thus
serve a good wall coating material. Polymeric coatings such as those described in
U.S. patent application Serial No. 08/478,276, filed June 7, 1995, can also be employed
Another method of improving the cleaning process includes employing
a low pressure gas purge concurrent with an rf discharge.
A third alternative method includes fabricating the cells from machinable,
non-ferrous metals to allow for high gas pressures. Such an interior surface may
require coating with an appropriate metal or polymer film. Moreover, laser ports
would then have to be added to allow the introduction of laser light into the cell.
Since the radio frequency used for the NMR polarimetry is only tens of kHz, the
skin depth of the metal may be such that the metal walls will not interfere with
the NMR. Alternatively, the polarimetry can be omitted, performed in a separate
storage chamber, or accomplished optically by measuring the frequency shift of the
alkali EPR frequency due the presence of the polarized 3He.
A fourth approach would be to fit the cells with an alkali metal ampule
having a mechanical seal that could be opened after the remainder of the cell is
cleaned. For instance, a thin glass window could be broken by a small glass bead
or by the noble gas pressure when the cell is filled. Such a system would reduce
the amount of handling of alkali-metal required during the cell-filling process.
Still another advantageous technique includes manufacturing the storage
chambers for previously polarized noble gas so as to be substantially identical
to the polarization chamber, except that the requirements of alkali-metal chemical
resistance and transparency to the optical-pumping laser light may be relaxed. This
becomes of especial importance in the accumulator reservoirs useful according to
the invention. We have unexpectedly found that, because the relaxation of the hyperpolarized
129Xe is so efficiently depressed in the frozen state, the quality of
manufacture of the walls of the reservoir is of lesser importance. This feature,
therefore, enables lower quality standards to be observed, with concomitant cost
We find that alkali-metal vapor tends to be lost from a flowing gas
polarization chamber during even modest gas flows (10-20 cm3/min) if
significant precautions are not taken. This has previously been a substantial impediment
to the development of refillable or continuous flow cells. We have observed, for
example, that the rubidium absorption resonance and D2 resonance
can completely disappear under unfavorable conditions. Our study indicates that
the major source of rubidium loss in a flowing gas system is due to gettering of
impurities (presumably H2O and O2) by the rubidium vapor.
Small amounts of hese impurities in the supply gas would ordinarily have only a
vanishingly small effect on he rubidium in a sealed cell. Flow of gas, however,
appears to provide a continual fresh supply of such alkali-reactive impurities into
the polarization chamber, resulting in continuing and substantial diminution of
available alkali vapor. Our present understanding is based on our finding that this
loss of rubidium vapor can be substantially prevented by installing an in-line gas
purifier, such as one of the nitrogen purifiers (getters) available from Ultra-Pure
Systems, Inc. Such purifiers have been found to clean the feed gas sufficiently
so that rubidium vapor loss is virtually eliminated at a wide range of flow rates.
Such purifiers are typically designed for the purification of nitrogen, but they
also pass the noble gases without problem, and have been found to be ideally suited
for purification of, for example, a He:Xe:N, mixture preferably employed according
to the method of the invention.
Another, less significant, loss of rubidium occurs as the rubidium
leaves the cell as gas is flowed through the cell. We have overcome this problem
in several ways. First, rubidium loss can be limited by ensuring that the temperature
of the conduit leading away from the pumping cell is low enough to secure the deposition
of the rubidium on the conduit walls. Room temperature is normally adequate. No
additional filter or trap is required, although a cold trap may be employed to ensure
complete rubidium removal in medical applications. Second, and more preferably,
refluxing apparatus can be used. For example, a refluxing outlet pipe may be used
to condense the alkali-metal vapor. The dimensions of the pipe and the gas flow
velocity can be adjusted to ensure that most of the alkali metal condenses and drips
back into the pumping cell by gravity flow. Accordingly, an outlet conduit leaving
the pumping chamber in a substantially vertical orientation will take advantage
of such gravity flow. this configuration is illustrated in Figure 2. In non-flowing
systems such as the sealed cells commonly used previously, such reflux is clearly
unnecessary since the alkali metal cannot escape from such sealed cells.
Nonetheless, despite such precautions, the alkali metal in the pumping
chamber will eventually become oxidized or used up. In that event, the pump chambers
themselves can be easily recycled. Current procedure is to rinse the chamber with
warm water, and then dry in an oven. The cell can the be recoated with a coating
agent such as dimethyldichlorosilane and reattached to a manifold. The cell can
then be baked out overnight, and a vacuum drawn. It is then ready for reinstallation
on the hyperpolarizer. Cells can be recycled in this manner numerous times without
detectable degradation in performance.
As mentioned briefly above, Figure 3 also shows the oven 9 which houses
the polarization chamber 4. The optical pumping oven operates in a temperature range
which is limited by loss of alkali-metal vapor polarization at unduly high temperatures.
Maximizing the temperature without sacrificing rubidium polarization maximizes the
spin exchange rate, allowing for faster accumulation of polarized noble gas. Typically,
the temperature range for the oven is from about 80 °C to about 200°C. A preferred
temperature is in the range of from about 105 °C to about 150 °C. For example, a
temperature of about 150 °C provides a Rb-129Xe spin exchange time of
about 22 s, and an average rubidium polarization of about 50%. About 20-30% of the
laser light is absorbed by the rubidium at this temperature. A temperature of about
130 °C may be preferred since the 129Xe NMR signal drops precipitously
at higher temperatures. At 130 °C. the Rb-129Xe spin exchange time is
about 65 s, roughly a factor of three lower than the time at 150 °C. Accordingly,
flow rates would have to be lower at lower temperatures, resulting in lower yields
of polarized 129Xe, It has also been found that laser-induced heating
causes a higher (∼20 °C higher) effective cell temperature (and thus a higher
rubidium number density ([Rb])) than is reflected by the oven thermometer.
By controlling gas flow rate and temperature in the polarization chamber,
the degree of polarization and total volume of the hyperpolarized gas produced can
be adjusted. For a given available laser power and bandwidth, the temperature of
the pumping chamber will be set as high as possible without significant sacrifice
to the volume-averaged polarization of the alkali-metal vapor. This optimization
determines the spin-exchange rate γSE at which polarization is
transferred to the noble gas. The flow rate will preferably then be adjusted so
that a noble gas atom spends on average about 1-3 spin exchange time constants (1/γSE)
in the polarization chamber. A hotter chamber will result in faster spin exchange,
thus allowing higher flow rates of the gas. Flow settings can be verified by comparing
the noble gas NMR signal against the flow rate. If the flow is too fast, the noble
gas signal will drop because the sample does not have a chance to fully polarize.
The oven should be constructed so as to minimize the creation of magnetic-field
gradients capable of inducing nuclear relaxation in the noble gas. Preferably, the
oven is constructed of materials that do not create gradients sufficient to induce
significant nuclear relaxation in the noble gas. The oven materials should also
retain substantial structural integrity at temperatures up to at least about 250
°C. High temperature plastics or aluminum are suitable choices. Ferromagnetic materials
such as steel generate magnetic field gradients which can rapidly depolarize the
noble gas, and are therefore less desirable materials. A discussion of this effect
may be found in the Middleton dissertation, referred to elsewhere herein.
As noted above in reference to Figure 3, the illustrated oven 9 is
provided with two or more laser windows 8a and 8b positioned to which permit laser
light (arrows 41 and 42) to pass into and out of the oven along the optical axis
of the system. (The optical axis is defined as the path, containing the laser, optics,
and the cell, along which the laser light travels.) The oven is preferably oriented
so that the optical axis is aligned with the direction of the applied magnetic field
necessary for optical pumping. Preferably, the oven windows 8a and 8b do not significantly
impair the transmission of the laser light through reflection and/or absorption.
They may be antireflection-coated to maximize light transmission.
Again referring to Figure 3, the oven may also be equipped with a
fluorescence observation window 7d. Preferably, the observation window is oriented
to permit visualization of the polarizing chamber from a position substantially
perpendicular to the optical axis. This window 7d allows the observation of
D2 resonant fluorescence resulting from optical pumping of an
alkali-metal vapor. Figure 3 further illustrates fluorescence visualization means,
Typically, such means includes a video camera 7a and monitor 7c, equipped with a
D2 filter 7b, for observing the fluorescence. The image can be
used to tune the laser wavelength, to optimize the optical pumping temperature,
as well as to align the laser.
The oven should be heated by means of materials and in a manner that
satisfy the same conditions for minimizing magnetic-field gradients as described
above. As shown in Figure 3, in a preferred embodiment, compressed air in conduit
45a is passed over a filament heater 45b situated several feet away from the oven
9. (The heater is placed at a distance to minimize the field gradients created by
the current running through it.) The hot air is then flowed through the oven 9 via
inlet 45c to attain the desired temperature. A temperature controller 45d actuates
the heater based on the reading of a temperature sensor 45e inside the oven. Hot
air is vented through outlet 45f. The sensor 45e should be non-ferromagnetic to
avoid the generation of field gradients. In an alternative approach, a high rf electrical
heater may be used to heat the chamber. Use of such high frequency rf power is inherently
devoid of the types of gradients which might interfere with the polarization.
In a preferred embodiment of the apparatus of the invention, the pumping
chamber's valve assembly remains outside of the oven. This reduces both deterioration
of temperature sensitive o-rings, and limits the migration of potentially harmful
alkali metal toward the valve.
The gas handling and purification system can incorporate numerous
features. The system introduces a controllable mixture of gases into the polarization
chamber while simultaneously insuring sufficient purity in the gas stream to prevent
significant degradation of the quality of the polarization chamber. The polarization-chamber
quality is determined by the T1 (polarization lifetime) of the hyperpolarized
gas within it. It is known that the polarization chamber quality is affected both
by gaseous impurities and by contaminants on the walls.
The polarization process requires both the polarizable noble gas (typically
anywhere from 0.1 atm to tens of atm) and a small amount (generally 10 to 100 Torr)
of a quenching gas (usually nitrogen, but perhaps hydrogen or others). The quenching
gas improves the efficiency of the optical pumping process. For hyperpolarizing
129Xe, it is preferred to also include a large amount of a buffer gas
(generally from about 1 atm to a few tens of atm), which acts to broaden the alkali-metal
absorption line and to improve the polarization efficiency. See below for greater
detail concerning the buffer gas.
One type of plumbing-design implementation for the target gas handling
system includes separate pathways for introducing the low-pressure (nitrogen) and
high-pressure gases. In this way a separate low-range pressure gauge may be isolated
from the high-pressure gasses in order to prevent its rupture. It has been found
that chemical or cryogenic getters should be placed in the gas flow lines as needed
to increase the gas purity. Since varying purities of gas are available, the amount
of additional purification will be established based on measurements of the polarization-chamber
degradation vs. either. number of times refilled (if discrete charges are used)
or total operating time (if a continuous-flow system is used). Even high purity
gases however, have been found to contain enough impurities, such as O2
and H2O, to cause significant degradation of the cells within a relatively
short period of flow or after a few refills.
With a multiple-gas handling system, the filling of a cell proceeds
as follows to get discrete charges of polarized gas. First, any residual inert buffer
gas in the system is evacuated using the roughing pump. Second, the small amount
of nitrogen required is introduced into the polarization chamber and the low-range
pressure gauge valved off. Next, the gas to be polarized and any additional high-pressure
buffer gases are introduced and the polarization chamber is valved off once the
desired pressures are attained.
A continuous flow into the pumping chamber can be accomplished by
inserting metering valves into the different gas flow lines and using a flow meter
on the exhaust port of the polarization chamber to calibrate flow vs. pressure-gradient
and metering valve setting. Since only a small amount of nitrogen is required, it
may be difficult to set its flow rate given the much larger flow rates of the other
gases. Since the nitrogen strongly affects the fluorescence coming from the polarization
chamber during optical pumping, this can be overcome by calibrating the nitrogen
flow rate vs. the total fluorescence coming from the chamber during optical pumping.
While the multiple-gas handling approach is workable, and has the
advantage of permitting adjustment of the gas mixture on a continuing basis, it
is more preferred to employ premixed gases. In a highly preferred embodiment, a
premixed gas is supplied directly to the polarization chamber from a single reservoir
without need for adjusting relative flow rates. This simplifies the operation of
the system, and renders the polarization process more reproducible and consistent.
For example, the proportions of the gases in the mixture are invariant over time
and between hyperpolarization procedures. Suitable gas mixtures are discussed elsewhere
herein, and may be obtained from commercial sources.
It should be understood that because the hyperpolarizing apparatus
of the invention permits hyperpolarization of a noble gas on a continuing basis,
the gas delivery system is preferably configured to permit easily controlled and
consistent gas mixtures to the pumping chamber. In larger scale systems, a single
gas handling system can be used to supply the target gas, serially or simultaneously,
to two or more polarizing systems. Separate control means can be provided to allow
individual control-of gas flow to each of the pumping cells.
In any case, all of the gas handling plumbing lines must have their
interiors cleaned prior to filling a polarization chamber. This prevents contaminants
from evolving off of the interior surfaces and being carried into the polarization
chamber, where they could degrade its surface. This cleaning may be accomplished
through moderate heating of the plumbing lines to about 100 °C while purging the
lines with an appropriate, high-purity inert buffer gas and or evacuating the lines.
If a combination of purging and evacuating is performed, these methods may be performed
in simultaneous or sequential combination.
Once the gas is flowing into the polarization chamber and the hyperpolarizing
is begun, the procedure should be monitored. In particular, the condition of the
gas contents in the chamber should be determine as the hyperpolarization proceeds.
NMR polarimetry is a preferred method for monitoring the gas polarization in the
polarization chamber (cell). The system is preferably able to operate in applied
magnetic fields of order 10 G, corresponding to NMR frequencies of tens of kHz for
129Xe. Generation of an NMR signal is accomplished by placing an inductive
coil near the cell. The coil is part of a tuned circuit which resonates near the
NMR frequency. Because of the low frequencies involved, tuning can be done in a
separate tuning box well away from the coil and connected to it through coaxial
The polarimetry subsystem functions according to typical NMR principles.
There are two stages in generating an NMR signal: radio-frequency (rf) excitation
and signal acquisition. A single rf pulse is delivered to the coil at or near the
Larmor-frequency to excite a small fraction of the spins, which subsequently precess
about the applied magnetic field. The precession is detected as it generates a small
voltage in the same coil. The signal-voltage is amplified, heterodyned, filtered,
and digitized for analysis and display on a computer. Other circuit components serve
both to shut off important detection components during rf excitation (muting mixer)
and to prevent leakage rf from reaching the coil during signal acquisition (isolation
mixers and diode gate).
To effectively monitor the polarization, the size of the signal should
be directly proportional to the polarization of the gas. This is accomplished without
significant depolarization of the sample by using a small excitation (flip) angle
in conjunction with a surface coil, which excites only a small fraction of the nuclei.
Although the process of generating the signal effectively destroys polarization,
the number of nuclei affected is negligible compared to the entire sample. Yet this
small fraction of spins typically generates a sufficiently strong NMR signal if
the gas is hyperpolarized. If the rf excitation is executed reproducibly, the signal
generated in this small fraction of nuclei is proportional to the polarization of
the entire sample. The system is calibrated to yield an absolute value of the polarization
(0-100%) by comparing the polarized gas signals to those of a water sample having
the same geometry, for which the thermal-equilibrium polarization can be calculated.
The method of low-field pulsed-NMR to do polarimetry is a significant advance over
the prior art of Adiabatic Fast Passage (AFP), particularly as it becomes more desirable
to polarize larger and larger volumes. because AFP requires a strong rf excitation
of the entire sample volume.
Alternatively, a separate outlet bulb can be fined to the polarization
chamber to permit accumulation of a test sample of the polarized gas. The bulb can
be measured in an Adiabatic Fast Passage (AFP) apparatus, which can yield much better
NMR signals than pulsed NMR on the pump chamber. This apparatus can be calibrated
to provide an experimental measurement of the gas polarization, which can be used
to further refine the adjustment of the accumulation parameters.
In a preferred embodiment, the entire hyperpolarization system can
be run from a desktop computer equipped with a few special circuit boards. One such
board generates the necessary radio frequency pulses through Direct Digital Synthesis
(DDS). Another desirable circuit board is an analog-to-digital converter (ADC board),
which digitizes the signal. The latter circuit board also generates the (TTL) gating
pulses which switch the muting and isolation mixers.
The laser subsystem of the hyperpolarization apparatus supplies the
photons (hyperpolarizing radiation) necessary to the optical pumping process. Preferably,
the photons are supplied by one or more laser-diode arrays producing continuous
wave (cw) power. However, any laser system that provides sufficient power at the
alkali-metal D1 or D2 lines may be acceptable.
High pressure operation such as that described herein, however, has been found to
require lasers capable of delivering more than 10 W, and preferably more than 50
W of power. Conventional lasers capable of delivering such power are prohibitively
expensive to purchase and operate. Moreover, such lasers are bulky and require expensive
and more or less permanent installation. For transportable or integrated hyperpolarization
units, such lasers. are too unwieldy. In such embodiments, the laser-diode arrays
become highly preferred because of their compactness and efficiency, as well as
their relative cheapness to acquire and operate.
Figure 4 is a schematic illustration of a laser subsystem suited for
use in the apparatus of the invention. The top part of Figure 4 shows an optical
arrangement for the laser diode(s), while the bottom part of the figure shows the
electrical configuration. The arrangement of optical elements, shown in the dashed
box, represents one of several ways to prepare the emitted light. The light travels
along the optical axis, substantially parallel to an applied magnetic field, through
the oven windows and into the cell. The optics are adjusted to maximize the volume
within the cell absorbing the light. As noted above, a converging or focused beam
is preferred, together with a converging cell structure, to maximize the absorption
of the hyperpolarizing radiation along the axis of the cell. Optionally, a second
similar laser and set of optics directs light into the cell along the same optical
axis, but from the opposite direction. The electrical configuration consists of
a power supply and several circuit elements necessary for monitoring and protection
of the laser diode(s).
Unlike conventional lasers which emit coherent light of a single wavelength
(extremely narrow profile), diode array lasers are broad-band devices whose emissions
have a spectral width. i.e., typically emitting light at a continuous band of wavelengths.
Normally, this spectral width is relatively narrow, appearing as a broadening around
some principal wavelength, and being only about 1-5 nm wide. Lower power GaAlAs
diode arrays have been employed for spin exchange polarization of 3He.
Chupp et al., Phys. Rev. A 40(8):4447-4454 (1989) describes the use
of an approximately 1-W diode array, and Cummings et al., Phys. Rev. A 51(6)4842-4851
(1995) describes a 20-W diode array. For the method and apparatus of the
present invention, the power of the diode arrays is preferably significantly larger,
being above about 50 W, and more preferably above about 100 W.
The choice of laser emission wavelength λ is determined by
the choice of the alkali metal used for spin exchange. As noted, the laser should
emit at about the D1 (or D2) transition line
of the desired alkali metal. For rubidium, λ is preferred to be about 795
nm, while for cesium, λ is preferred be about 894 nm. Thus, for rubidium,
the laser can be a GaAlAs laser. The use of cesium rather than rubidium metal, however,
permits the use of more reliable, aluminum-free diode laser arrays (e.g., InGaAsP
lasers), lower operating temperatures, and 13% more photons per watt because of
the longer resonance wavelength for Cs. A currently preferred laser diode array
(available from Opto Power, of Tucson, Arizona) is a GaAlAs laser diode array, comprising
10 bar diodes in a stacked arrangement, which develops about 125 W of continuous
wave (cw) power, can be tuned to a peak wavelength of 794.44 nm, and exhibits about
2 nm full spectral width at half maximum (FWHM).
Should lasers with narrower bandwidths become competitive (efficiency,
cost, etc.) with conventional arrays in the future, less line-broadening buffer
gas would be needed than for the presently available lasers mentioned above. This
would permit use of higher proportions of xenon in the target gas mixture, which
in turn would improve the yield of the accumulator apparatus. Lower pressure operation
would also simplify some engineering problems with respect to the hyperpolarizer.
Also unlike conventional lasers, diode laser emissions are typically
highly divergent, requiring optical correction to concentrate the light at a desired
focus. The optical elements illustrated in Figure 4 include, inter alia, a laser
diode array 51, one or more (cylindrical or aspheric) lenses 52a-52d, a polarizing
beam-splitter cube 53, and a quarter-wave plate 54. The lenses 52a-52d collimate
and/or focus the laser light through window 8a to a beam size generally conforming
to the dimensions of the polarizing cell 4 within oven 9. Depending upon application,
the optics at least substantially reduce the divergence of the beam, rendering the
beam collimated or more preferably providing a converging beam. We have found that
circularly polarized converging light with angles as large as 30° from the magnetic
field direction can efficiently spin-polarize alkali-metal atoms. The lenses are
divided into two sets: one set each for independent horizontal (52a and 52c) and
vertical (52b and 52d) movement and focusing of the light. Figure 4 also illustrates
indirectly a preferred, optional, laser system in which a second laser is employed
to direct hyperpolarizing radiation into the cell 4 via window 8b in oven 9. The
optional second laser system is identified as the dashed box II at the right side
of the drawing, and should include substantially the same elements included within
the dashed box I at the left side of the drawing.
We have unexpectedly found that simple aspheric Fresnel lenses can
be used to focus the light from the diode arrays. These inexpensive lenses do converge
transmitted light, but do not normally provide focus sufficient to generate a crisp
image: This lack of focus, however, is not a significant limitation, and the use
of such lenses helps reduce the cost of the hyperpolarizer over other types of installations
which employ substantially more expensive cylindrical lenses. Other light collection
arrangements are also possible, for example, microlenses on the diode array, or
combinations of mirrors and lenses.
The beam-splitter cube 53 divides the incoming light into its two
separate orthogonal linear polarizations. One polarization is reflected at 90 degrees
to the optical axis and absorbed by a beam-block (not shown). The other polarization
passes through to the quarter-wave plate 54, which converts the linearly polarized
light to the circularly polarized light necessary for optical pumping.
As shown in Figure 4, the laser-diode arrays 51 are each mounted to
a brass cooling block 55, through which water flows to and from a heat exchanger
56 via cooling fluid conduits 57, and valves 58 and 59. The heat exchanger 56 may
be anything from a recycling chiller with a secondary water circuit to a simple
radiator, depending on laser power. Also as shown in Figure 4, in a multi-laser
setup, a single heat-exchanger unit can be used to supply both lasers, with valves
or separate heater units on each set of water lines to control the temperature of
each laser independently. Alternatively, each laser may be provided with its own
The laser-diode array is electrically driven by the circuit also diagramed
in Figure 4, or by another circuit equivalent thereto. The precise rating of the
power supply 61 depends on the number of laser diodes and whether they are arranged
in series or in parallel. For a single laser, for example, the power supply can
be a DC supply rated at about 20-40 V, and about 20-40 A. Again referring to Figure
4, the 200-ohm shunt resistor 62 reduces the intensity of any voltage spikes coming
from the supply 61. The 0.1 ohm series resistor 63 and the DC voltmeter 64 are used
to monitor the current through the laser diode 65. The parallel reverse-biased Schottky
diode 66 protects against aninadvertent wrong-polarity connection of the laser diode
65. The current is adjusted and the current limit is set using the controls on the
power supply 61. A thermocouple 67 mounted directly to the cooling block 55 monitors
its temperature. In the event that this temperature exceeds a set point, a high-limit
temperature detector 68 trips a manual-reset relay switch 69 and shuts down the
One feature of spin exchange hyperpolarization of helium is that it
can be performed at relatively high gas pressures, something which is not possible
with metastability exchange methods. This provides an advantage over metastability
exchange inasmuch as it is inherently less work to decompress a gas than to compress
it. As noted hereinabove, complex apparatus is necessary to compress 3He
produced by metastability exchange by up to two orders of magnitude to obtain usable
pressures (∼1 atm) of the gas.
Previously, it has been recognized that hyperpolarized 3He
can be produced at high polarizations by means of spin exchange at high pressures
(∼10 atm). We have found however, that this is not possible when using high
pressures of 129Xe. Specifically, the efficiency with which xenon depolarizes
rubidium vapor is surprisingly high. We estimate that neglecting molecular contributions,
0.1 atm of xenon has about the same spin destructive effect as 270 atm of helium.
As result, it is now believed that xenon pressures in excess of about 1 arm will
result in very low rubidium polarizations for all but the most intense (i.e.. thousands
of watts) pump lasers.
For example, for a diode laser, a laser intensity of about 20 W/cm2
(or 100 W/5 cm2) would result in a Rb electronic polarization of only
about 25% at the front of a chamber containing 10 atm of xenon. This polarization
level only decreases toward the back of the chamber so that only small polarization
volumes can be tolerated, with correspondingly small yields of polarized
The use of lower pressures of xenon can result in higher Rb polarizations,
but at a substantial penalty. Low gas pressures give narrow Rb D1
resonance lines and thus allow only a tiny fraction of the broad spectral output
of the diode array (2 nm FWHM) to be used. Furthermore, the spectral hole burning
that results from a narrow D1 resonance again means that only
very small volumes of Rb can be polarized, yielding small quantities of polarized.129Xe.
For example, a 20 cm3 cell containing 0.5 atm of xenon, and having a
wall relaxation of time of 1000 s will at optimum give a 129Xe polarization
of 56%, while using only 2.3, W of 100 W incident on the cell. The resulting 10
cm3 of polarized gas (at 1 atm) is not sufficient for most applications
In typical hyperpolarization procedures, unpolarized 129Xe
is placed in a sealed pumping cell along with a few tens of Torr of a gas (often
nitrogen) which quenches the fluorescence of laser-excited rubidium atoms, thereby
aiding the optical pumping process. We have unexpectedly found, however, that a
buffer gas can be added to the sample to broaden the alkali metal resonance line,
allowing for more efficient absorption of the broad spectral output of current high-power
laser diode arrays. Without this high-pressure buffer gas, very little (about 1%)
of the light from the diode laser can be absorbed because of the broad spectral
bandwidth of the diode laser array (2 nm or more) and the very narrow (0.01 nm)
absorption bandwidth of alkali metal atoms at low pressure. To achieve this effect,
the buffer gas should not induce significant spin destruction of either the alkali-metal
vapor or the129Xe during optical pumping. A highly preferred buffer gas
is helium, naturally having an isotopic abundance of 99+% 4He, but other
gases having similar properties may be employed.
We have observed that increased buffer gas pressures induce the absorption
band of rubidium to broaden, and that gas pressures of order 10 atm or more are
preferred to achieve the desired broadening. Due to xenon s inherent capacity to
destroy alkali-metal polarization, however, it is believed that samples containing
10 atm or more of pure xenon would not be usable. By contrast, it has been found
that helium is quite non-destructive to the polarized alkali-metal spins and can
be used as a line-broadening agent without penalty. Hydrogen can serve both as a
quenching gas and a buffer gas to broaden the optical absorption line. Nitrogen
is not as good a gas for this purpose as hydrogen or helium, because it causes substantial
spin depolarization of the alkali metal atoms.
Accordingly, preferred gas mixtures for hyperpolarization of
129Xe according to the method of the invention would include a substantial
proportion of the buffer gas, e.g., helium, with a minor but significant amount
of 129Xe. For example, the mixture can include from about 0.1 % to about
5% of xenon containing at least a natural isotopic abundance of 129Xe,
from about 0.1% to about 3% of N2, with the balance being helium. Most
preferably, the mixture includes about 1% of 129Xe, about 1% of N2,
and about 98% helium. Alternatively, if the quenching gas is hydrogen, from about
1% to about 30% of the gas mixture should be hydrogen, with a corresponding reduction
in the net proportion of helium. For helium, the gas mixture is simpler, since no
benefit is gained from including a buffer gas. As for 129Xe, however,
helium gas mixtures preferably include an amount of nitrogen or hydrogen as a quenching
gas comparable to the amount used for 129Xe.
The low partial pressures of Xe used in the preferred method give
rise to several problems. First, polarized 129Xe must be separated from
the helium to attain useful concentrations of 129Xe. Second, the polarized
129Xe must be pressurized so that it can be extracted from the polarization
apparatus. Third, while high 129Xe polarizations are attained on very
short timescales, the yield of polarized gas from the pump chamber is very small.
We have now found that freezing the polarized 129Xe into a solid (T≤
160 K) solves all three of these problems.
To produce laser-polarized 129Xe in significant quantities,
we have taken advantage of the extremely long spin-lattice-relaxation times T1
of solid 129Xe. It has been demonstrated that once polarized,
129Xe can be frozen into a solid with little loss of polarization. As
detailed in Gatzke et al., Phys. Rev. Lett., 70(5):690-693 (1993), relaxation
times are much longer in the solid phase than those which have been achieved thus
far in the gaseous phase.
It is now possible, by means of cryotrap accumulator apparatus. to
take advantage of the properties of xenon ice. Specifically, it is now recognized
that the three-hour relaxation time of 129Xe in ice at liquid nitrogen
temperatures permits the pumping and continuous accumulation of polarized
129Xe for up to three hours at a time. The use of even lower temperatures
can extend the potential accumulation period further.
Once the flowing target gas is hyperpolarized, the entire gas stream
(129Xe, helium, and nitrogen) can be flowed through an accumulator. Details
of an especially preferred accumulator for 129Xe. are described in copending
patent application Serial No. 08/XXX,XXX, entitled "Cryogenic Accumulator for Spin-Polarized
Xenon-129", filed on even date herewith, the entire disclosure of which is incorporated
herein by reference. The accumulator includes a cryostat, preferably operating in
the temperature range of from about 4.2 K to about 157 K. A temperature of about
77 K is preferred due its convenience, i.e., about the temperature of liquid nitrogen
(b.p. = 77 K) which is a readily available refrigerant. However, lower temperatures
are generally preferred, since longer polarization lifetimes can be obtained as
the temperature of accumulation and storage are decreased.
In any event, polarized 129Xe passing through the cryostat
immediately freezes due to its melting point being 157 K. At low enough temperatures,
the nitrogen may also freeze, but this should have no deleterious effect on the
129Xe polarization and long T1. Hydrogen may be substituted
as the quenching gas to avoid this problem. The bulk of the gas, i.e., the helium,
simply passes through the cryostat and out through the exit port. Hence, a useful
feature of this method is that it can be used to effectively separate the hyperpolarized
xenon from the other, unwanted, components ofthe target gas mixture.
Because the relaxation time T1 of frozen 129Xe
is significantly longer when maintained in an applied magnetic field, the cryostatic
accumulator is preferably fitted with a small permanent magnet capable of such magnetic-field
strengths in order to improve holding times. The primary consideration in choosing
the strength of the applied field is that the field should enable accumulation and/or
storage for a period of about the maximum possible spin-lattice relaxation time
at the accumulation/storage temperature. Accordingly, the applied field should be
at least about 500 G (0.05 T) at liquid nitrogen temperatures. We observe, however,
that the selection of field strength is dependent upon the temperature at which
the129Xe is being accumulated or stored. Specifically, lower temperature
accumulation and/or storage benefits from the use of higher field strength.
The apparatus described herein is capable of integration with MRI
imaging systems consistent with the systems described in U.S. patent application
Serial No. 08/225,243. Typical of such systems is a commercially available MR imaging
unit including a 2-Tesla, 30-cm horizontal Omega CSI magnet (G.E. NMR Instruments,
Fremont, CA) and associated apparatus, described in greater detail in Middleton
et al., Magn. Reson, in Med 33:271-275 (1995). The ability to produce large
quantities of hyperpolarized noble gas can now be employed beneficially to permit
the accumulation and storage of sufficient gas prior to imaging that no additional
hyperpolarizing need be undertaken during the imaging itself. Thus, one or more
subjects can now be imaged in a clinical setting using a single source of previously
accumulated xenon. Alternatively, imaging can now be undertaken in which a continuous
hyperpolarization procedure generates a continuing source of hyperpolarized gas
supplied to a subject for study of respiration or other physiological processes
enabled by the extraordinary properties of the noble gases. Previously, imaging
of this sort was either impossible or extremely impractical due to the small amounts
of hyperpolarized gases available for use.
In one preferred embodiment, the hyperpolarizer apparatus of the invention
is a freestanding integrated unit, which is substantially self-contained and convenient
to use. For example, the apparatus can be configured into a movable cart system
with a footprint of about 2 feet by 6 feet. In this embodiment, the unit includes
the laser system, a gas source, a polarizing cell, NMR polarimetry systems, power
supplies, and a computer which is programmed to control and monitor most or all
of the systems.
The laser subsystem of the hyperpolarizer system unit preferably includes
one or more high power diode laser arrays, a power supply for the lasers, protection
circuitry, a cooling unit and assorted optics for controlling and directing the
The control subsystem includes a computer system, such as a personal
microcomputer or workstation, components for monitoring the polarization by NMR
as the procedure is performed, and components for monitoring and maintaining the
cell temperature during the procedure. For example, the rf for the polarimetry can
be provided using direct digital synthesis, as described elsewhere herein.
Ideally, the hyperpolarizer system also includes a number of safety
systems, including interlocks, limit switches, non-computer controlled relays, etc.
Preferably, the integrated polarization system includes a replaceable
polarization cartridge unit, which includes all of the components with which the
gas has contact during the polarization procedure. Thus, the polarization unit can
include a high pressure gas bottle containing enough gas to provide a substantial
hyperbaric flow of gas during the hyperpolarization. The polarization unit further
includes the pumping cell. Inlet and outlet conduits, respectively leading to and
from the pumping cell, are included. These include valves for controlling the flow
of gas into and out of the cell. For convenience, the polarization cartridge can
also include some or all elements of the pumping oven, as well as the polarimetry
probes. Other elements such as pressure transducers, regulators, and gas purifiers
can also be included as desired.
The polarization unit is designed to permit easy its straightforward
insertion into and removal from the hyperpolarizer system unit. The cartridge should
be of a size and weight so as to promote ease of handling and installation. Applicants
believe that a suitable polarization unit can be approximately 30 cm by 50 cm by
10 cm or roughly equivalent thereto. At this size the essential components can be
included without unduly impairing handling of the unit. One structure capable of
satisfying these various design requirements is described in detail below.
Another convenient feature of the replaceable polarization unit is
that the target gas is preferably supplied premixed in a single bottle. This permits
formulation and use consistent target gas mixtures, and avoids the necessity of
having the operator of the unit control the gas mixture, thereby simplifying operation
of the unit. Nonetheless, the polarization unit can, alternatively, include separate
bottles for each gas to be mixed into the target gas.
Figure 5 illustrates one embodiment of a transportable hyperpolarizer
system unit according to the invention. In this embodiment, two laser diode arrays
100a and 100b are mounted on the top of a wheeled cart 101. Optics subsystems 102a
and 102b are provided to collimate the laser energy, directing the energy to a focus
at the pumping cell 103. The pumping cell can be mounted separately or as part of
a replaceable polarization unit subsystem, described below. In Figure 5, the pumping
cell 103 is shown as part of such a polarization unit 110. Accordingly, the hyperpolarizer
may be viewed as a docking station into which the polarization cartridge can be
inserted to engage and operate with the systems on the hyperpolarizer. The hyperpolarizer
system further includes a power subsystem including a power supply 120, a main power
safety 121 and other protection circuitry 122, each having controls and displays
as necessary. A cooler system 125 is provided to modulate the operating temperature
of the lasers. A shelf 127 provides an emplacement for a microcomputer (not shown)
for controlling and monitoring the polarization process. The cart 101 further includes
a cover 105 to confine the laser light. Similar systems may be permanently or sem-permanently
installed in, for example, a wall mount or a fixed electrical rack system. Other
configurations are within the scope of the invention. Preferably, each of the main
systems and subsystems are easily replaceable, such as being integrated into the
unit via plug and jack connections.
Figure 6 provides a schematic illustration of one embodiment of a
replaceable polarization unit according to the invention. A gas bottle 201 is provided
which contains the target gas including a noble gas such as 3He or
129Xe. Suitable gas mixtures, as described herein, are available from
gas suppliers, such as Isotec, Inc. Miamisburg, OH. The gas bottle is capable of
maintaining the target gas under high pressure, and includes enough gas to permit
several high pressure fills of a pumping chamber 221 or which permits high pressure
continuous flow through the chamber sufficient to produce the requisite amount of
hyperpolarized noble gas. An important advantage of the polarization unit is that
it can be replaced easily when the gas supply is exhausted. Moreover, replacement
polarization units can be manufactured and shipped fully configured for installation
into a hyperpolarizer system, and can be stored indefinitely in reserve.
The gas bottle 201 is in fluid communication with a pressure regulator
203 via conduits 205 and 206, controlled by valve 207. The pressure regulator 203
controls the gas flow, and is preferably a high purity regulator such as a stainless
steel two stage ultra-high purity (UHP) regulator (e.g., Model E99-OLRC available
from Air Products). Valve 207 and other valves in the cartridge which contact the
gas should be operable under high pressure. Suitable valves include all metal Nupro
valves Model SS-4BG-VCR available from Penn Valve & Fitting Co., Willow Grove,
Conduit 209 leads from the regulator 203 to a flow-through pressure
transducer 211, and flow is controlled by valve 213. Valve 213 is used to regulate
flow when filling the cell with a new gas charge. Cell pressure is monitored by
the now-through pressure transducer 211. The transducer 211 is preferably-bakeable
to about 200 °C. Suitable transducers include, for example. Model HS-10S available
from Hastings NALL Mass Flow-meters or Model 212FT available from Setra Systems,
Inc., Acion MA.
Transducer 211 is in fluid communication with gas purifier 215 via
conduit 217. The purifier 215 is desirable for removing water vapor and other impurities
from the target gas, since such impurities can interfere with the polarization process.
The purifier 215 is preferably a getter device, such as the mini purifier vessel
available from Ultra-Pure Systems. Inc., Colorado Springs, CO. Typically, such devices
are heated to improve purification, e.g., by an external band heater with a thermocouple
(e.g. available from Ultra-Pure Systems, Inc.)
Conduits 219 and 220 connect the purifier 215 to the pumping cell
221, and is controlled by valve 223. The pumping cell 221 is manufactured as described
elsewhere herein and has a volume of about 10 cm3 to about 100 cm3,
preferably about 30 cm3. Pumping cell 221 also includes an outlet vent
225, which is controlled by a valve 227.
Conduit 219 branches to provide conduit 220 to the pumping cell and
conduit 229 to valve 231. Then conduit 233 leads from valve 231 and branches to
provide conduit 235 leading to diaphragm pump 237 (controlled by valve 239) and
conduit 241 leading to a purge outlet 243 and controlled by valve 245.
This gas delivery configuration permits convenient purging of the
system, which is important to maintaining the efficiency of the hyperpolarization
procedure. A purging protocol can proceed as follows: First, a hot clean purge gas
is injected into the purge inlet 247, traveling through conduit 249, controlled
by valve 251. Next, the purge gas passes through the regulator 203, the pressure
transducer 211, and the purifier 215. By opening valves 231 and 245, the purge gas
can be vented through the purge outlet 243. In principle, valves 223 and 227 can
be used to purge the cell, however, it is believed that this will not be necessary
as a routine matter. Finally, the diaphragm pump 237 can be used to remove residual
purge gas through valve 239 following the purge.
The following examples are provided to assist in a further understanding
of the invention. The particular materials and conditions employed are intended
to be further illustrative of the invention and are not limiting upon the reasonable
scope thereof. In particular, certain considerations applicable to polarization
of noble gases according to the invention are exemplified herein with reference
to polarization of flowing 129Xe by spin exchange with rubidium atoms.
However, this description should not be understood as limiting the scope of the
invention. Such considerations apply in the polarization of 3He, such
as in a semi-continuous flowing mode, as well as in the use of other alkali metals,
such as cesium and potassium. Exceptions and variations to these generalizations,
such as they are known, are noted herein where relevant, without taking away from
the general applicability of the invention.
A continuous flow polarization apparatus according to the invention
has been constructed generally in accord with the structure illustrated in Figure
2, described above. The pumping chamber is a glass cylinder 6 cm long and having
a volume of about 30 cm3. The optical axis is collinear with the longitudinal
axis of the chamber.
We have found that the optimal flow through the pumping chamber is
dependent upon temperature. For the hyperpolarization of 129Xe (3% in
96% helium; 10 atm) in this 30 cm3 chamber, the flow rate can be in the
range of from about 300 cm3/min to about 600 cm3/min at 150
°C. Modeling indicates that from about 20% to about 30% of the laser light is absorbed
at 150 °C, corresponding to a spin exchange time (τSE) of 22 s, and
an average rubidium polarization of about 50%.
A gas mixture of 3% Xe having a natural isotopic composition of about
26% 129Xe, 1 % nitrogen, and 96% helium was polarized using the apparatus
described in Example 1. In addition, a cryotrapping accumulator according to the
invention was used to accumulate the gas leaving the pumping chamber. Using liquid
nitrogen as a refrigerant for a glass cold finger, 120 cm3 of frozen
hyperpolarized 129Xe was accumulated in 0.5 hr. The nominal flow rate
of the target gas during accumulation was 80-100 cm3/min at STP. Since
the gas mixture was only 3% Xe, this permitted a xenon accumulation rate of up to
about 3 cm3/min at STP. Upon subliming, the 129Xe was allowed
to expand back into the pumping chamber, which was equipped with a pulsed NMR coil.
The NMR signal strength was determined to be about 1/4 of the largest saturation
even seen from the He:Xe:N2 gas mixture in a sealed pump chamber. From
computer modeling, it is believed that the saturation polarization of
129Xe during an optical pumping procedure is about 75%. The pressure
of the sublimed xenon was measured with a capacitance manometer to be 1.21 atm compared
to 0.27 atm of xenon in the gas mixture during pumping. Given the ratio of pressures
and NMR signals. we arrived at a rough polarization of the accumulated
129Xe of 5%.
The net polarization obtained in this experiment was within an order
of magnitude of the theoretical maximum polarization. Thus, while it must be recognized
that this procedure was not optimized, it is shown that the continuous production
of hyperpolarized 129Xe is possible using the method and apparatus of
the invention. Moreover, the production and accumulation process preserved a significant
amount of the polarization of the xenon. Based on this study, we expect improvements
in yield for the sublimed gas.
A significant feature of the method and apparatus of the invention
is that substantially larger amounts of hyperpolarized xenon can now be produced
than were possible using substantially pure xenon as a target gas. That is, the
yield of hyperpolarized xenon as a function of time is substantially increased,
notwithstanding the fact that the xenon is present as only a small fraction when
the target gas is 90% or more of a buffer gas.
Clearly, the volumes of hyperpolarized 129Xe obtained using
the apparatus of the invention permit the generation of volumes of hyperpolarized
noble gases on the order of at least tens of liters per day. Accordingly, the invention
now enables, for the first time, the production of sufficient polarized noble gases
to enable clinical ventilation studies of human lung by MRI.
Thus, while there have been described what are presently believed
to be the preferred embodiments of the present invention, those skilled in the art
will realize that other and further embodiments can be made without departing from
the spirit of the invention, and it is intended to include all such further modifications
and changes as come within the true scope of the claims set forth herein.