U.S. patent application number 09/846720 was filed with the patent office on 2001-10-04 for hyperpolarized gas containers, solenoids, transport and storage devices and associated transport and storage methods.
Invention is credited to Bogorad, Paul L., Hasson, Kenton C., Wheeler, Bradley A., Zollinger, David L., Zollinger, Geri T.K..
Application Number | 20010025493 09/846720 |
Document ID | / |
Family ID | 26780848 |
Filed Date | 2001-10-04 |
United States Patent
Application |
20010025493 |
Kind Code |
A1 |
Hasson, Kenton C. ; et
al. |
October 4, 2001 |
Hyperpolarized gas containers, solenoids, transport and storage
devices and associated transport and storage methods
Abstract
A compact portable transport unit for shipping hyperpolarized
noble gases and shielding same from electromagnetic interference
and/or external magnetic fields includes a means for shifting the
resonance frequency of the hyperpolarized gas outside the bandwidth
of typical frequencies associated with prevalent time-dependent
fields produced by electrical sources. Preferably the transport
unit includes a magnetic holding field which is generated from a
solenoid in the transport unit. The solenoid includes a plurality
of coil segments and is sized and configured to receive the gas
chamber of a container. The gas container is configured with a
valve, a spherical body, and an extending capillary stem between
the valve and the body. The gas container or hyperpolarized product
container can also be formed as a resilient bag. The distribution
method includes positioning a multi-bolus container within the
transport unit to shield it and transporting same to a second site
remote from the first site and subsequently dispensing into smaller
patient sized formulations which can be transported (shielded) in
another transport unit to yet another site.
Inventors: |
Hasson, Kenton C.; (Durham,
NC) ; Zollinger, Geri T.K.; (Chapel Hill, NC)
; Zollinger, David L.; (Chapel Hill, NC) ;
Bogorad, Paul L.; (Hillsborough, NC) ; Wheeler,
Bradley A.; (Raleigh, NC) |
Correspondence
Address: |
Myers Bigel Sibley & Sajovec, P.A.
Post Office Box 37428
Raleigh
NC
27627
US
|
Family ID: |
26780848 |
Appl. No.: |
09/846720 |
Filed: |
May 1, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09846720 |
May 1, 2001 |
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09333571 |
Jun 16, 1999 |
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6269648 |
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60089692 |
Jun 17, 1998 |
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60121315 |
Feb 23, 1999 |
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Current U.S.
Class: |
62/3.1 |
Current CPC
Class: |
F17C 2203/0607 20130101;
F17C 2250/0491 20130101; F17C 2260/026 20130101; F17C 2205/0352
20130101; F17C 1/00 20130101; F17C 2227/041 20130101; F17C
2250/0404 20130101; F17C 2203/0636 20130101; F17C 3/00 20130101;
Y10S 62/914 20130101; G01R 33/282 20130101; F17C 2203/0697
20130101; F17C 2201/0128 20130101; F17C 2201/0176 20130101; A61K
49/1815 20130101; F17C 2260/03 20130101; F17C 2203/0629 20130101;
F17C 2203/0685 20130101; F17C 2223/0123 20130101; F17C 2223/035
20130101; F17C 2205/035 20130101; F17C 13/002 20130101; F17C
2203/0604 20130101; F17C 2260/012 20130101; F17C 2225/0123
20130101; F17C 2250/032 20130101; F17C 2205/0134 20130101; F17C
2201/058 20130101; F17C 2203/066 20130101; F17C 13/005 20130101;
F17C 2221/07 20130101; F17C 2205/0382 20130101; F17C 2227/044
20130101; F17C 2270/02 20130101; F17C 2225/035 20130101; F17C
2205/0323 20130101; F17C 2203/0646 20130101; F17C 2270/0536
20130101 |
Class at
Publication: |
62/3.1 |
International
Class: |
F25B 021/00 |
Goverment Interests
[0002] This invention was made with Government support under
National Institute of Health Grant No. R43HL62756-01. The United
States Government has certain rights in this invention.
Claims
That which is claimed is:
1. A transport unit for transporting hyperpolarized gas products
therein, said transport unit comprising: at least one gas chamber
configured to hold a quantity of hyperpolarized gas product
therein; and an electromagnet disposed in said transport unit, said
electromagnet configured and sized to define a magnetic holding
field having at least one region of homogeneity therein, wherein a
major portion of each of said at least one gas chamber is sized and
configured to reside in said magnetic field homogeneous region.
2. A transport unit according to claim 1, further comprising at
least one electrical current carrying wire, wherein said at least
one electrical wire is configured to generate at least a portion of
said magnetic holding field.
3. A transport unit according to claim 1, wherein said
electromagnet comprises at least one cylindrical solenoid.
4. A transport unit according to claim 3, wherein said solenoid
comprises a plurality of coil segments thereon.
5. A transport unit according to claim 3, said transport unit
further comprising a metallic enclosure, wherein said solenoid is
positioned in said enclosure such that it extends longitudinally
therein.
6. A transport unit according to claim 5, wherein said enclosure
includes at least one layer of an electrically conducting metal
thereon, thereby providing one or more of shielding from external
electromagnetic radiation and structural support during
transport.
7. A transport unit according to claim 5, wherein said enclosure
includes at least one layer of magnetically permeable material to
provide at least one of additional electromagnetic shielding, DC
magnetic shielding, or a flux return.
8. A transport unit according to claim 3, further comprising
operating circuitry operably associated with said transport unit,
said operating circuitry including a direct current power supply
operably associated with said solenoid.
9. A transport unit according to claim 8, wherein said operating
circuitry is configured to direct electrical current to said
solenoid to define the magnetic holding field having a field
strength corresponding to the amount of current directed to said
solenoid.
10. A transport unit according to claim 4, wherein said operating
circuitry is configured to allow an adjustable amount of current to
said solenoid thereby providing an adjustable magnetic holding
field strength.
11. A transport unit according to claim 3, wherein said solenoid
provides a homogeneous magnetic holding field volume defined
relative to the center of said solenoid, and wherein said container
has a hyperpolarized product holding chamber configured and sized
such that said holding chamber is held in said homogeneous field
volume.
12. A transport unit according to claim 6, wherein said solenoid is
disposed in said transport unit such that it longitudinally extends
in said enclosure and defines a magnetic holding field which is
substantially aligned with the earth's magnetic field.
13. A transport unit according to claim 4, wherein said plurality
of coil segments includes spatially separated first, second, and
third coil segments.
14. A transport unit according to claim 13, wherein said second
coil segment is disposed intermediate said first and third coil
segments, and wherein said second coil segment has a lower number
of electrical windings per unit length then said first and third
coil segments.
15. A transport unit according to claim 14, wherein said first and
third coil segments extend a first longitudinal distance along said
solenoid and said second coil segment extends a second longitudinal
distance along said solenoid, and wherein said second distance is
greater than said first and third distance.
16. A transport unit according to claim 1, wherein said gas chamber
includes a gas holding chamber having a major body portion with a
first length and a capillary stem with a second length, said
capillary stem is in fluid communication with said gas holding
chamber and having a capillary length and a capillary diameter,
wherein said capillary length is greater than said major body
portion length.
17. A transport unit according to claim 3, wherein said at least
one solenoid and gas chamber is a plurality of corresponding
solenoids and gas chambers for transporting multiple doses of
hyperpolarized gas products therein.
18. A transport unit according to claim 3, wherein said at least
one gas chamber is a plurality of separate gas chambers.
19. A transport unit according to claim 1, wherein said gas chamber
is defined by at least one resilient bag defining at least one
expandable gas holding chamber.
20. A transport unit according to claim 19, wherein said at least
one gas chamber is a plurality of gas chamber s defined by a
plurality of resilient bags for transporting multiple separate
doses of hyperpolarized products therein.
21. A transport unit according to claim 20, further comprising a
tray for holding said plurality of bags, said tray configured and
sized to reside within said magnetic field generator.
22. A solenoid for providing a shield for hyperpolarized gases to
protect said gases from stray magnetic field gradients to minimize
the depolarization affects associated therewith, comprising: a
cylindrical body; a first coil segment having a first coil length
and a first number of windings disposed on said cylindrical body; a
second coil segment having a second coil length and a second number
of windings disposed on said cylindrical body; and a third coil
segment having a third coil length and a third number of windings
disposed on said cylindrical body, wherein said first, second, and
third coil segments are spatially separated and positioned on said
cylindrical body such that said second coil segment is intermediate
said first and third coil segments.
23. A solenoid according to claim 22, wherein said second length is
greater than said first and third lengths.
24. A solenoid according to claim 22, wherein said first and third
number of windings per unit length are greater than said second
number of windings.
25. A hyperpolarized gas product container having a gas holding
chamber and a capillary stem, said capillary stem having an inner
diameter and length configured and sized such that said capillary
stem inhibits the movement of said hyperpolarized gas product from
said gas holding chamber.
26. A container according to claim 25, wherein said capillary stem
length is greater than said gas holding chamber length.
27. A container according to claim 25, wherein said container is
pressurized to above about 5 atmospheres of pressure, and wherein
said hyperpolarized gas product comprises hyperpolarized
.sup.3He.
28. A method of minimizing relaxation of hyperpolarized noble gases
due to external electromagnetic interference or stray magnetic
fields, comprising the steps of: capturing a quantity of
hyperpolarized gas in a transport unit comprising a gas chamber and
operating circuitry; shifting the resonant frequency of the
hyperpolarized noble gas out of the frequency range of
predetermined electromagnetic interference during transport; and
transporting the captured gas.
29. A method according to claim 28, wherein said shifting step
shifts the resonant frequency of the hyperpolarized gas to a
frequency substantially outside the bandwidth of prevalent
time-dependent fields associated with electrically powered
equipment.
30. A method according to claim 28, wherein said shifting step is
performed by providing a substantially static magnetic field
proximate to the gas chamber holding the hyperpolarized noble gas
with a field strength sufficient to shift the resonant frequency of
the hyperpolarized gas a predetermined amount, thereby minimizing
the depolarization of the hyperpolarized gas attributed to exposure
to electromagnetic fields during transport from a first site to a
second site remote from the first site.
31. A method according to claim 28, further comprising providing a
metal enclosure around the hyperpolarized gas, the enclosure having
a predetermined skin depth which is sufficient to substantially
block the depolarizing effects of predetermined electromagnetic
interference or AC fields.
32. A method according to claim 28, wherein said hyperpolarized gas
comprises .sup.3He said static magnetic field is at least about 7
gauss.
33. A method according to claim 28, wherein said hyperpolarized gas
comprises .sup.129Xe and said magnetic field is at least about 20
gauss.
34. A method according to claim 28, wherein said static magnetic
field is substantially homogeneous about a magnetic holding field
region.
35. A method according to claim 28, wherein said shifting step is
applied by generating an electromagnetic field proximate to the
hyperpolarized gas during transport, and wherein said
electromagnetic field is adjustable during transport.
36. A system of extending the polarization lifetime of
hyperpolarized gas during transport, comprising the steps of:
introducing a quantity of hyperpolarized gas product into a
sealable gas chamber at a production site; capturing a quantity of
hyperpolarized gas product in the gas chamber; generating a
magnetic holding field from a portable transport unit, thereby
defining a substantially homogeneous magnetic holding region
therein; positioning a major portion of the gas chamber within the
homogeneous holding region; transporting the captured
hyperpolarized gas in the gas chamber; and shielding the
hyperpolarized gas product to minimize the depolarizing effects of
external magnetic fields during said transporting step such that
the hyperpolarized gas has a clinically useful polarization level
at a site remote from the production site.
37. A hyperpolarized gas protection system according to claim 36,
wherein said transport unit comprises a metallic enclosure, and
wherein said step of shielding is performed by positioning said gas
chamber in the metallic enclosure and electrically activating a
solenoid disposed in the metallic enclosure.
38. A hyperpolarized gas protection system according to claim 36,
wherein said shielding step comprises shifting the normal resonant
frequency of the hyperpolarized gas outside a predetermined
frequency range.
39. A hyperpolarized gas protection system according to claim 36,
wherein the transport unit is configured to hold a plurality of
separate gas chambers therein.
40. A method according to claim 36, wherein the transporting step
is performed by transporting the gas chamber to a second site
remote from the production site.
41. A method according to claim 40, wherein the gas chamber is
configured as a multi-dose container, and further comprising the
step of distributing the transported hyperpolarized gas in the
multi-dose container at the second site into a plurality of
single-dose containers to provide a suitable amount of
hyperpolarized gas product therein.
42. A method according to claim 41, further comprising the steps of
transporting said plurality of said single dose containers to a
third site remote from the second site; administering the
hyperpolarized product held in at least one of said single dose
containers to a patient; and obtaining an MR imaging or
spectroscopy signal associated with same.
43. A method for distributing hyperpolarized noble gas, comprising
the steps of: polarizing noble gas at a polarization site;
capturing a quantity of polarized gas in a multi-dose container,
the quantity of hyperpolarized gas being sufficient to provide a
plurality of doses of a hyperpolarized product; positioning the
first multi-dose container within a portable transport unit, the
transport unit configured to provide a homogeneous magnetic field
proximate to a major portion of the multi-dose container held
therein; transporting the transport unit with the multi-dose
container to a second site remote from the polarization site; and
distributing the hyperpolarized gas held in the multi-dose
container into multiple separate second containers at the second
site.
44. A method according to claim 43, wherein said transporting step
comprises shielding said hyperpolarized gas by activating an
electromagnet in said portable transport unit.
45. A method according to claim 43, further comprising the steps of
sub-dividing the hyperpolarized gas in the first multi-dose
container at the second site; and processing the sub-divided gas
into at least one desired formulation to form a hyperpolarized
pharmaceutical product suitable for in vivo administration, the
processing step being performed prior to said distributing
step.
46. A method according to claim 45, farther comprising the steps
of: positioning at least one of the multiple separate second
containers with the hyperpolarized gas product therein into a
second transport unit, the second transport unit being configured
to provide a region of homogeneity therefor; and transporting the
second transport unit with the at least one multiple separate
second container to a third site.
47. A method according to claim 46, wherein at least one of the
multiple separate second containers comprises a patient dose sized
resilient bag.
48. A method according to claim 47, further comprising the steps
of: administering said hyperpolarized pharmaceutical product in
said second container to a patient; and obtaining clinically useful
data associated with the administered hyperpolarized product via
one or more of an Magnetic Resonance Imaging or Spectroscopy
procedures.
49. A method according to claim 45, further comprising the steps
of: positioning a plurality of patient-sized bags filled with the
hyperpolarized pharmaceutical product in said second transport
unit; and transporting the plurality of patient sized bags to a
third site remote from the second site.
50. A method according to claim 43, wherein the hyperpolarized gas
comprises .sup.3He, and wherein the multi-bolus container is used
to polarize a quantity of noble gas therein during said polarizing
step at the polarization site.
51. A portable transporter for transporting or storing a quantity
of hyperpolarized gas product, comprising: an enclosure having at
least one wall with a skin depth of a conductive shielding material
configured to provide a shield for a quantity of hyperpolarized gas
from externally generated electromagnetic interference during
transport from a polarization site to a use site, said enclosure
defining a holding volume therebetween; at least one hyperpolarized
gas container positioned in said enclosure, said gas container
having a major gas holding volume portion, and a magnetic field
source positioned in said enclosure, said magnetic field source
configured to provide a region of homogeneity proximate to said
hyperpolarized gas container; wherein the holding volume is sized
and configured to hold said hyperpolarized gas container such that
the major volume of said hyperpolarized gas container is spatially
separated a predetermined distance from adjacent portions of said
at least one wall, and wherein said predetermined distance is
sufficient to increase the shielding effectiveness of said
enclosure.
52. A portable transporter according to claim 51, wherein said at
least one wall comprises a pair of opposing longitudinally
extending walls.
53. A portable transport unit according to claim 51, wherein said
magnetic field source is a solenoid.
54. A portable transport unit according to claim 51, wherein said
predetermined separation distance is at least about 2.0 inches.
55. A portable transport unit according to claim 53, wherein said
solenoid comprises a conductive material inner surface configured
to provide shielding.
56. A portable transport unit according to claim 51, wherein said
at least one gas container is a plurality of gas containers.
57. A portable transport unit according to claim 51, wherein said
at least one gas container comprises a container which is also
configured as an optical pumping cell for the hyperpolarized gas
held therein at a polarization site.
58. A portable transport unit according to claim 51, wherein said
predetermined separation distance provides a separation ratio of
less than about 0.60, the separation ratio being mathematically
expressed by the ratio of (a) the linear lateral half-width of the
major volume portion of said gas container to (b) the linear
minimum separation distance of said at least one wall.
59. A portable transport unit according to claim 51, wherein said
magnetic field source is a plurality of electromagnetic field
sources, at least one each for each of said at least one containers
held in said enclosure.
60. A portable transport unit according to claim 51, wherein said
at least one container comprises a capillary stem.
Description
RELATED APPLICATIONS
[0001] This application claims the benefit of priority from
Provisional Application No. 60/089,692, filed Jun. 17, 1998,
entitled "Containers for Hyperpolarized Gases and Associated
Methods" and Provisional Application No. 60/121,315, filed Feb. 23,
1999, entitled "Hyperpolarized Gas Containers, Solenoids, and
Transport and Storage Devices and Associated Transport and Storage
Methods." The contents of these applications are hereby
incorporated by reference as if recited in full herein.
FIELD OF THE INVENTION
[0003] The present invention relates generally to the transport of
hyperpolarized gases from one site to another, such as from a
production site to a clinical use site. The hyperpolarized gases
are particularly suitable for MR imaging and spectroscopy
applications.
BACKGROUND OF THE INVENTION
[0004] Inert gas imaging ("IGI") using hyperpolarized noble gases
is a promising recent advance in Magnetic Resonance Imaging (MRI)
and MR spectroscopy technologies. Conventionally, MRI has been used
to produce images by exciting the nuclei of hydrogen molecules
(present in water protons) in the human body. However, it has
recently been discovered that polarized noble gases can produce
improved images of certain areas and regions of the body which have
heretofore produced less than satisfactory images in this modality,
Polarized Helium-3 (".sup.3He") and Xenon-129 (".sup.129Xe") have
been found to be particularly suited for this purpose.
Unfortunately, as will be discussed further below, the polarized
state of the gases is sensitive to handling and environmental
conditions and can, undesirably, decay from the polarized state
relatively quickly.
[0005] Various methods may be used to artificially enhance the
polarization of certain noble gas nuclei (such as .sup.129Xe or
.sup.3He) over the natural or equilibrium levels, i.e., the
Boltzmamn polarization. Such an increase is desirable because it
enhances and increases the MRI signal intensity, allowing
physicians to obtain better images of the substance in the body.
See U.S. Pat. No. 5,545,396 to Albert et al., the disclosure of
which is hereby incorporated by reference as if recited in full
herein.
[0006] A "T.sub.1" decay time constant associated with the
longitudinal relaxation of the hyperpolarized gas is often used to
characterize the length of time it takes a gas sample to depolarize
in a given situation. The handling of the hyperpolarized gas is
critical because of the sensitivity of the hyperpolarized state to
environmental and handling factors and thus the potential for
undesirable decay of the gas from its hyperpolarized state prior to
the planned end use, e.g., delivery to a patient for imaging.
Processing, transporting, and storing the hyperpolarized gases--as
well as delivering the gas to the patient or end user--can expose
the hyperpolarized gases to various relaxation mechanisms such as
magnetic field gradients, surface-induced relaxation,
hyperpolarized gas atom interactions with other nuclei,
paramagnetic impurities, and the like.
[0007] One way of minimizing the surface-induced decay of the
hyperpolarized state is presented in U.S. Pat. No. 5,612,103 to
Driehuys et al. entitled "Coatings for Production of Hyperpolarized
Noble Gases." Generally stated, this patent describes the use of a
modified polymer as a surface coating on physical systems (such as
a Pyrex.TM. container) which contact the hyperpolarized gas to
inhibit the decaying effect of the surface of the collection
chamber or storage unit, Other methods for minimizing surface or
contact-induced decay are described in co-pending and co-assigned
U.S. patent application Ser. No. 09/163,721 to Zollinger et al.,
entitled "Hyperpolarized Noble Gas Extraction Methods, Masking
Methods, and Associated Transport Containers," and co-pending and
co-assigned U.S. Patent Application identified by Attorney Docket
No. 5770-12IP, entitled "Resilient Containers for Hyperpolarized
Gases and Associated Methods." The contents of these applications
are hereby incorporated by reference as if recited in full
herein.
[0008] However, other relaxation mechanisms arise during
production, handling, storage, and transport of the hyperpolarized
gas. These problems can be particularly troublesome when storing
the gases (especially increased quantities) or transporting the
hyperpolarized gas from a production site to a (remote) use site.
In transit, the hyperpolarized gas can be exposed to many
potentially depolarizing influences. In the past, a frozen amount
of hyperpolarized .sup.129Xe (about 300cc-500cc's) was collected in
a cold finger and positioned in a metallic coated dewar along with
a small yoke of permanent magnets arranged to provide a magnetic
holding field therefor. The frozen gas was then taken to an
experimental laboratory for delivery to an animal subject.
Unfortunately, the permanent magnet yoke provided a relatively
small magnetic field region (volume) with a relatively low magnetic
homogeneity associated therewith. Further, the thawed sample
yielded a relatively small amount of useful hyperpolarized
.sup.129Xe (used for small animal subjects) which would not
generally be sufficient for most human sized patients.
[0009] There is, therefore, a need to provide improved ways to
transport hyperpolarized gases so that the hyperpolarized gas is
not unduly exposed to depolarizing effects during transport.
Improved storage and transport methods and systems are desired so
that the hyperpolarized product can retain sufficient polarization
and larger amounts to allow effective imaging at delivery when
stored or transported over longer transport distances in various
(potentially depolarizing) environmental conditions, and for longer
time periods from the initial polarization than has been viable
previously.
OBJECTS AND SUMMARY OF THE INVENTION
[0010] It is therefore an object of the present invention to
provide a transport system that can protect hyperpolarized gas
products from potentially depolarizing environmental exposures
during movement of the hyperpolarized gas products from a
production site to a remote use site.
[0011] It is also an object of the present invention to configure a
transport unit to serve alternatively or in addition as a portable
storage unit, to hold polarized gases in their polarized state for
longer periods including prior to shipment, or prior to delivery
even if the gases are not intended to be remotely shipped.
[0012] It is also an object of the present invention to provide a
portable unit for storing or transporting a quantity of
hyperpolarized gas therein, which can substantially protect the
hyperpolarized gas from the depolarizing effect of diffusion of the
gas atoms through magnetic field gradients.
[0013] It is another object of the present invention to provide a
portable unit for storing or transporting a quantity of
hyperpolarized gas therein, which can substantially protect the
hyperpolarized gas from the depolarizing effects of one or more of
oscillating magnetic fields, electromagnetic noise, and
electromagnetic interference (EMI).
[0014] It is another object of the present invention to provide a
method of protecting the hyperpolarized gas from the depolarizing
effects of undesirable EMI at a predetermined frequency or
frequency range.
[0015] It is another object of the invention to provide a
relatively compact, lightweight, easily transportable device which
can provide sufficient protection for the hyperpolarized gas to
allow the hyperpolarized gas to be successfully transported (such
as in a vehicle) from a production site to a remote use site, such
that the hyperpolarized gas retains a sufficient level of
polarization at the use site to allow for clinically useful
images.
[0016] It is another object of the invention to provide a valved
hyperpolarized gas chamber configured to inhibit polarization decay
(i.e., has relatively long decay times) during transport and/or
storage.
[0017] It is another object of the invention to configure a
transport unit to minimize the external force associated with
shock, vibration, and or other mechanical collisions that are input
into or transmitted to the hyperpolarized gas container.
[0018] It is another object of the invention to provide a
protective enclosure for a transport unit which is configured such
that the hyperpolarized gas held in an internally disposed
hyperpolarized gas chamber may be directed out of or into the
transport unit (i.e., the gas chamber may be filled and/or
emptied), without the need to remove the gas chamber from its
protective housing.
[0019] It is another object of the invention to configure a
transport unit with an easily accessible means for interrogating
the polarized gas held within the gas chamber held therein using
nuclear magnetic resonance (NMR), in order to measure the
polarization of the gas, or to measure the decay rate of the
polarization.
[0020] It is another object of the invention to provide a means of
adjusting the magnetic field strength generated by a transport
unit, in order to shift the Larmor frequency of the spins
associated with the hyperpolarized gas, either for purposes of NMR
measurements, or to minimize decay from electromagnetic
interference at a frequency of interest.
[0021] It is an additional object of the present invention to
increase the shielding effectiveness of transport units.
[0022] It is still another object of the invention to provide a way
to transport hyperpolarized gases from a polarization site to a
secondary and/or tertiary distribution site while maintaining a
sufficient level of hyperpolarization to allow clinically useful
images at the ultimate use site.
[0023] These and other objects of the present invention are
provided by the transport (and/or storage) units of the instant
invention which are configured to protect hyperpolarized gas (and
gas products and in one or multiple containers) held therein,
thereby minimizing depolarizing losses introduced during transport
of a hyperpolarized gas product from one place to another. In
particular, a first aspect of the invention is directed toward a
transport unit used to transport hyperpolarized products therein.
The transport unit comprises at least one gas chamber configured to
hold a quantity of hyperpolarized product therein and at least one
electromagnet providing a magnetic holding field defining at least
one region of homogeneity. The homogeneous region of the magnetic
holding field is sized and configured to receive a major portion of
the gas chamber (gas holding container) therein. The magnetic
holding field is preferably primarily provided by a solenoid
comprising at least one current carrying wire thereon. In one
embodiment, the gas chamber is defined by a rigid body single or
multi-dose container. In an alternative embodiment, the gas chamber
is defined by a resilient body container with an expandable gas
chamber (preferably sized and configured to hold a single patient
dose).
[0024] In one preferred embodiment, a solenoid coil is configured
to generate the magnetic holding field. Preferably the solenoid
coil is also sized and configured to maximize the volume of the
sufficiently homogeneous region provided thereby. Also preferably,
the transport unit preferably includes one or more layers of an
electrically conducting metal about the enclosure. As such, the
enclosure can provide shielding from external electromagnetic
radiation as well as mechanical support and protection. The
transport unit may also include one or more layers of magnetically
permeable materials, such as soft iron or mu-metal, to provide
additional electromagnetic shielding, (including DC magnetic
shielding), or to act as a flux return.
[0025] A further aspect of the present invention is a solenoid coil
for providing a homogeneous magnetic field region in which the
hyperpolarized gas is held. The solenoid comprises a cylindrical
body and a first coil segment having a first coil length and a
first number of windings disposed on the cylindrical body. The
solenoid also includes second and third coil segments having
respective second and third coil lengths and respective second and
third number of windings disposed on the cylindrical body. The
first, second, and third coil segments are spatially separated and
positioned on the cylindrical body such that the second coil
segment is intermediate the first and third coil segments. In a
preferred embodiment, the second coil length is greater than both
of the first and third coil lengths and the first and third
windings are configured with a greater number of layers relative to
the second winding. This coil configuration can advantageously
provide a larger sufficiently homogeneous holding region for the
hyperpolarized gas within a relatively compact coil area, thereby
allowing the coil (as well as any associated transport unit) itself
to be more compact while also providing for a useful dose of the
hyperpolarized gas to be contained and protected therein.
[0026] Another aspect of the present invention is a hyperpolarized
gas product container having a gas holding chamber and a capillary
stem. The capillary stem has an inner diameter and length
configured and sized such that the capillary stem preferably
inhibits the migration or diffuisional exchange of the
hyperpolarized gas product between the main body of the chamber and
the upper portion of the gas container which preferably includes a
valve. More specifically, the capillary stem is sized such that the
ratio of the main body volume to the volume in the capillary stem,
multiplied by the diffusion time for .sup.3He to traverse the
length of the capillary, is greater than the T.sub.1 of a sealed
chamber of the same material and dimensions. Exchange of gas
product between the main body and the valve is desirable because
the valve is typically in a region of higher magnetic field
gradients. Further, the valve may comprise materials that can
undesirably introduce surface-induced relaxation into the polarized
gas. The container itself may be configured as a rigid body or
resilient body.
[0027] Yet another aspect of the present invention is a transport
unit including at least one resilient container (and preferably a
plurality of resilient containers) for holding a quantity of
hyperpolarized gas (or liquid) product therein. In operation, one
or more of the resilient containers are positionable within a
homogeneous region of a magnetic field produced by the transport
and/or storage unit.
[0028] Another aspect of the present invention is a system for
distributing hyperpolarized gases, and preferably patient sized
doses of hyperpolarized gases. The system includes a first
transport unit which is sized and configured to hold a large
multi-dose container therein. The system also includes at least one
second transport unit sized and configured to carry a plurality of
single dose containers therein. Preferably, the multi-dose
container is a rigid body container and the single dose containers
are resilient containers having expandable chambers to allow easy
delivery or administration at a use site.
[0029] Similarly, in one embodiment, the multi-dose container is
transported to a pharmaceutical distribution point where the
hyperpolarized gas in the multi-dose container can be formulated
into the proper dosage or mixture according to standard
pharmaceutical industry operation. This may include solubilizing
the gas, adjusting the concentration, preparing the mixture for
injection or inhalation or other administration as specified by a
physician, or combining two different gases or liquids or other
substances with the transported hyperpolarized gas. Then, the
formulated hyperpolarized product, substance, or mixture is
preferably dispensed into at least one second container, and
preferably into a plurality of preferably a single use size
resilient containers which can be transported to a third or
tertiary site for use. In a preferred embodiment, the first
transport distance is such that the hyperpolarized gas is moved at
increased times or distances over conventional uses. Preferably,
the transport units and associated container of the present
invention are configured-such that during transport and/or storage,
the hyperpolarized gas (particularly .sup.3He) retains sufficient
polarization after about 10 hours from polarization, and preferably
after at least 14 hours, and still more preferably (especially for
.sup.3He) after about 30 hours. Stated differently, the transport
units and associated containers of the instant invention allow
clinical use after about 30 hours elapsed time from original
polarization and after transport to a second site (and even then a
third or tertiary site). The transporters and containers are also
preferably configured to allow greater transit distances or greater
transit times. Stated differently, the hyperpolarized product
retains sufficient polarization after transport and greater elapsed
time from polarization when positioned in the transport units to
provide clinically useful images. This distribution system is in
contrast to the conventional procedure, whereby the hyperpolarized
gas is produced at a polarization site and rushed to a use site
(which is typically relatively close to the polarization site).
[0030] An additional aspect of the present invention is directed
toward a method of minimizing the relaxation rate of hyperpolarized
noble gases due to external electromagnetic interference. The
method includes the steps of capturing a quantity of hyperpolarized
gas in a transportable container and shifting the resonant
frequency of the hyperpolarized noble gas out of the frequency
range of predetermined electromagnetic interference. Preferably,
the method includes shifting the normal resonance frequency
associated with the hyperpolarized gas to a frequency substantially
outside the bandwidth of prevalent time-dependent fields produced
by electrically powered equipment (such as computer monitors),
vehicular engines, acoustic vibrations, and other sources. In a
preferred embodiment, the resonant frequency of the hyperpolarized
gas is shifted by applying a static magnetic field proximate to the
hyperpolarized gas. For example, preferably for a hyperpolarized
gas product comprising .sup.3He, the applied static magnetic field
is at least about 7 Gauss, while for hyperpolarized gas products
comprising .sup.129Xe, the applied magnetic field is at least about
20 Gauss.
[0031] Yet another aspect of the present invention is directed
toward a system for preserving the polarization of the gas during
transport. The system includes the steps of introducing a quantity
of hyperpolarized gas product into a sealable container comprising
a gas chamber at a production site and capturing a quantity of
hyperpolarized gas product in the gas chamber. A magnetic holding
field is generated by a portable transport unit defining a
substantially homogeneous magnetic holding region therein. The gas
chamber is positioned within the homogeneous holding region and the
hyperpolarized gas product is shielded to minimize the depolarizing
effects of external magnetic fields such that the hyperpolarized
gas has a clinically useful polarization level at a site remote
from the production site.
[0032] In a preferred embodiment, the step of providing the
magnetic holding field is performed by electrically activating a
longitudinally-extending solenoid positioned in the transport unit.
The solenoid comprises a plurality of spatially separated coil
segments, and the sealable container comprises a capillary stem in
fluid communication with the gas chamber.
[0033] The present invention is advantageous because the transport
unit can protect the hyperpolarized gas and minimize the
depolarizing effects attributed to external magnetic fields,
especially deleterious oscillating fields, which can easily
dominate other relaxation mechanisms. The transport container is
relatively compact and is, thus, easily portable. Preferably, the
transport unit includes a homogeneous magnetic holding field
positioned proximate to the gas container so that it provides
adequate protection for the hyperpolarized state of the gas and
facilitates the transport of the gas to an end use site. In a
preferred embodiment, the transport unit includes a solenoid having
at least a three-coil segment configuration with the central coil
segment having a reduced number of wire layers compared to the
other (opposing) two coil segments. Stated differently, the
opposing end segments have a greater number of wire layers
providing increased current density (current per unit length) in
these areas. Advantageously, such a coil segment design can enlarge
the homogeneous region of the magnetic field generated by the
solenoid while minimizing the size (length) of the solenoid itself.
This relatively compact transport unit can easily deliver a single
patient dose or a plurality of patient doses (combined or
individual).
[0034] Further, the transport unit is configured such that it can
use an adjustable current to allow field adjustments, thereby
enabling correction for one or more of electronic or mechanical
drift, the type of gas transported, and severe exposure conditions.
In addition, the transport unit can be employed with more than one
type of hyperpolarized gas, for example, .sup.3He or .sup.129Xe. In
addition, the transport unit can be configured such that the
hyperpolarized gas can be released at the end use site without
removing the typically somewhat fragile gas chamber from the
transport unit (when glass chambers are employed). This capability
can protect the gas from intermediate depolarizing handling and can
also facilitate the safe release of the gas by shielding any users
proximate to the transport unit from exposure to the internal gas
container (such as a glass sphere) which is typically under
relatively high pressure. Alternatively, the transport unit can
shield resiliently configured gas containers to provide easy to
dispense single dose sized products. In addition, the gas container
preferably includes a capillary stem and/or a port isolation means
which inhibits the diffusion or movement of the hyperpolarized gas
out of the main body, thereby helping to retain a majority of the
hyperpolarized gas within the homogeneous holding region and
inhibiting contact between the hyperpolarized gas and the
potentially depolarizing materials in the sealing means. Further,
the enclosure walls of the instant invention are preferably
configured such that they provide adequate spatial separation from
the gas container to increase the shielding effectiveness of the
transport unit.
BRIEF DESCRIPTION OF THE DRAWINGS
[0035] FIG. 1 is a cutaway front perspective view of a transport
unit according to the present invention, the transport unit
comprising a gas chamber and solenoid.
[0036] FIG. 2 is an enlarged cutaway front view of the solenoid and
gas chamber shown in FIG. 1.
[0037] FIG. 2A is a perspective view of the solenoid shown in FIGS.
1 and 2.
[0038] FIG. 3 is a cutaway perspective view of the solenoid of FIG.
2A illustrating the current direction and the magnetic holding
field direction and the region of highest homogeneity in the
solenoid.
[0039] FIG. 3A is a graph that illustrates a preferred
winding/current distribution relative to the distance along the
length of the solenoid, with (2i) representing a current density
which is twice that of the center coil segment (i), along with
points of negligible current between the coil segments.
[0040] FIG. 4 is a side view of a gas chamber configuration
particularly suitable for use with the transport unit according to
the present invention.
[0041] FIG. 5 is a front perspective view of the transport unit
shown in FIG. 1.
[0042] FIGS. 6, 6A, and 6B are perspective views of transport units
configured to transport multiple containers of hyperpolarized gas
products according to alternate embodiments of the present
invention.
[0043] FIG. 7 is a schematic illustration of a power monitoring and
switching circuit for use with a portable transport unit according
to the present invention.
[0044] FIG. 8 is a schematic illustration of an operating circuit
for use with a portable transport unit associated with a preferred
embodiment of the present invention.
[0045] FIG. 9 is a front perspective view of a calibration/docking
station according to the present invention.
[0046] FIG. 10 is a graphical representation of the normalized
magnetic field generated by an embodiment of the solenoid of the
instant invention (top bell-shaped curve) compared to a coil having
uniform current density per unit length (bottom bell-shape
curve).
[0047] FIG. 11 is a flow chart of a system for shielding
hyperpolarized gas from the depolarizing effects attributed to
external magnetic fields during transport, thereby preserving the
polarized life of the gas.
[0048] FIG. 12A is a perspective partial cutaway view of a
multi-transport distribution system. The distribution system
delivers a multi-dose container to a second site remote from the
polarization site. At the second site, the hyperpolarized product
in the multi-dose container is divided, mixed, or otherwise
formulated into resilient single use containers for delivery to a
teritary (preferably clinical use site) according to the present
invention.
[0049] FIG. 12B is an exploded view of a tray for facilitating
positioning of a plurality of single-sized resilient containers in
a single solenoid sized to accommodate same.
[0050] FIG. 13 is a perspective partial cutaway view of a
distribution system which employs a plurality of magnetic holding
field generators in the second transport unit.
[0051] FIG. 14 is a flow chart of a distribution system according
to the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0052] The present invention now will be described more fully
hereinafter with reference to the accompanying drawings, in which
preferred embodiments of the invention are shown. This invention
may, however, be embodied in many different forms and should not be
construed as limited to the embodiments set forth herein; rather,
these embodiments are provided so that this disclosure will be
thorough and complete, and will fully convey the scope of the
invention to those skilled in the art, Like numbers refer to like
elements throughout. In the figures, layers and regions may be
exaggerated for clarity.
[0053] For ease of discussion, the term "hyperpolarized gas" is
used to describe a hyperpolarized gas alone, or a hyperpolarized
gas that contacts or combines with one or more other components,
whether gaseous, liquid, or solid. Thus, the hyperpolarized gas
described herein can be a hyperpolarized gas composition/mixture
(preferably non-toxic such that it is suitable for in vivo
administration) such that the hyperpolarized gas can be combined
with other gases and/or other inert or active substances or
components. Also, as used herein, the term "hyperpolarized gas" can
include a product in which the hyperpolarized gas is dissolved into
another liquid (such as a carrier fluid) or processed such that it
transforms into a substantially liquid state, i.e., "a liquid
polarized gas". In summary, as used herein, the term "gas" has been
used in certain places to descriptively indicate a noble gas which
has been hyperpolarized and which can include one or more
components and which may be present in or farther processed to be
in one or more physical forms.
BACKGROUND--HYPERPOLARIZATION
[0054] Various techniques have been employed to polarize,
accumulate and capture polarized gases. For example, U.S. Pat. No.
5,642,625 to Cates et al. describes a high volume hyperpolarizer
for spin-polarized noble gas and U.S. Pat. No. 5,642,625 to Cates
et al. describes a cryogenic accumulator for spin-polarized
.sup.129Xe. The disclosures of this patent and application are
hereby incorporated herein by reference as if recited in full
herein. As used herein, the terms "hyperpolarize" and "polarize"
are used interchangeably and mean to artificially enhance the
polarization of certain noble gas nuclei over the natural or
equilibrium levels. Such an increase is desirable because it allows
stronger imaging signals corresponding to better MRI images of the
substance in a targeted area of the body. As is known by those of
skill in the art, hyperpolarization can be induced by spin-exchange
with an optically pumped alkali-metal vapor or alternatively by
metastability exchange. See U.S. Pat. No. 5,545,396 to Albert et
al. The alkali metals capable of acting as spin exchange partners
in optically pumped systems include any of the alkali metals,
Preferred alkali metals for this hyperpolarization technique
include Sodium-23, Potassium-39, Rubidium-85, Rubidium-87, and
Cesium-133.
[0055] Alternatively, the noble gas may be hyperpolarized using
metastability exchange. (See e.g., Schearer, L. D., Phys Rev,
180:83 (1969); Laloe, F., Nacher, P. J., Leduc, M., and Schearer L.
D., AIP ConfProx #131 (Workshop on Polarized .sup.3He Beams and
Targets) (1984)). The technique of metastability exchange involves
direct optical pumping of, for example, .sup.3He without the need
for an alkali metal intermediary. Since this process works best at
low pressures (0-10 Torr), a compressor is typically used to
compress the .sup.3He after the hyperpolarization step.
[0056] Regardless of the hyperpolarization method used, once the
active mechanism is no longer in effect, the polarization of the
gas will inevitably decay toward its thermal equilibrium value,
which is essentially zero. The present invention is configured to
work with any hyperpolarization technique and, as will be
appreciated by one of skill in the art, is not limited to working
with any one type of machine, method, or particular gas.
[0057] Polarized Gas Relaxation Processes
[0058] Under most circumstances, the non-equilibrium polarization
P(t) of a gas decays according to
dP(t)/dt=-P(t)/T.sub.1 1.0
[0059] The overall decay rate is equal to the sum of rates from
various mechanisms:
1/T.sub.1=(1/T).sub.Gas+(1/T.sub.1).sub.Surface+(1/T.sub.1).sub.EMI+(1/T.s-
ub.1).sub.Gradient 2.0
[0060] Gas Interaction Relaxation
[0061] The first decay term (1/T.sub.1).sub.Gas represents the
depolarization of the noble gas nuclei when interacting with each
other and can also include interaction of the atoms with gaseous
impurities such as oxygen. Thus, careful preparation of gas
containment, transfer, and extraction systems is important for
providing good polarization lifetimes as will be discussed further
below. Examples of suitable gas extraction methods and apparatus
are described in co-pending and co-assigned U.S. patent application
Ser. No. 09/163,721, entitled "Hyperpolarized Noble Gas Extraction
Methods, Masking Methods, and Associated Transport Containers,"
identified by Attorney Docket No. 5770-14, the disclosure of which
is hereby incorporated by reference as if recited in full
herein.
[0062] Even in the absence of all other relaxation mechanisms,
collisions between identical polarized gas atoms impose a
fundamental upper limit to the achievable T.sub.1 lifetime. For
example, .sup.3He atoms relax through a dipole-dipole interaction
during .sup.3He-.sup.3He collisions, while 129Xe atoms relax
through N.multidot.I spin rotation interaction (where N is the
molecular angular momentum and I designates nuclear spin rotation)
during .sup.129Xe-.sup.129Xe collisions. In any event, because both
processes occur during noble gas-noble gas collisions, both
resulting relaxation rates are directly proportional to number
density (T.sub.1 is inversely proportional to number density). At
one bar pressure, the theoretical maximum relaxation time T.sub.1
of .sup.3He is about 750 hours, and for .sup.129Xe the
corresponding relaxation time is about 56 hours. See Newbury et
al., "Gaseous 3He-3He Magnetic Dipolar Spin Relaxation," 48 Phys.
Rev. A., No. 6, p. 4411 (1993); Hunt et al., "Nuclear Magnetic
Resonance of .sup.129Xe in Natural Xenon," 130 Phys Rev. p. 2302
(1963).
[0063] Unfortunately, other relaxation processes such as surface
relaxation, electromagnetic interference (EMI), and magnetic
gradient relaxation can prevent the realization of these
theoretical relaxation times. Accordingly, each of these mechanisms
are of concern when handling hyperpolarized gases and are
preferably addressed so as to allow for the overall relaxation time
to be sufficiently large.
[0064] Surface-induced Relaxation
[0065] The (1/T.sub.1).sub.Surface term represents the
surface-induced relaxation mechanism. For example, the collisions
of gaseous 129Xe and .sup.3He with container walls ("surface
relaxation") have historically been thought to dominate most
relaxation processes. For .sup.3He, most of the known longer
relaxation times have been achieved in special glass containers
having a low permeability to helium. See Fitzsimmons et al.,
"Nature of surface induced spin relaxation of gaseous He-3," 179
Phys. Rev., No. 1, p. 156 (1969). U.S. Pat. No. 5,612,103 to
Driehuys et al. describes using coatings to inhibit the
surface-induced nuclear spin relaxation of hyperpolarized noble
gases, especially .sup.129Xe. The contents of this patent are
hereby incorporated by reference as if recited in full herein.
Similarly, co-pending and co-assigned U.S. patent application Ser.
No. 09/126,448 to Deaton et al., and its related application
identified by Attorney Docket No. 5770-121P, describe preferred
gas-contact surface materials and associated thicknesses, O-rings,
and valve or seal materials and/or coatings which are friendly to
the polarized state of the gas, i.e., which can inhibit
surface/contact-induced relaxation mechanisms. The content of these
applications are also hereby incorporated by reference as if
recited in full herein.
[0066] Electromagnetic Interference
[0067] The relaxation mechanism expressed by the term
(1/T.sub.1).sub.EMI is the relaxation induced by time-dependent
electromagnetic fields. Indeed, EMI can potentially destroy the
hyperpolarized state of the gas (EMI is particularly problematic if
coherent at the magnetic resonance frequency). Unfortunately, EMI
can be generated by relatively common sources. For example, EMI is
typically generated from a vehicle's engine, high voltage lines,
power stations and other current carrying entities. As such,
transport away from the hyperpolarized gas production site can
expose the hyperpolarized gas to these undesirable relaxation
sources that, in turn, can dramatically reduce the polarization
lifetime of the transported gas.
[0068] Fluctuating fields are particularly deleterious if they are
coherent at the magnetic resonance frequency. For example, assuming
a generally worst case scenario of a highly coherent oscillating
field, it is expected that the relaxation rate is comparable to the
Rabi frequency:
(1/T.sub.1).sub.EMI.apprxeq..gamma.H.sub.AC/2 2.10
[0069] Here, ".gamma." is the gyromagnetic ratio of the spins, and
"H.sub.AC" is the magnitude of the transverse fluctuating field. A
resonant field H.sub.AC of only 1 .mu.G would cause relaxation on a
time scale of order 100 seconds for .sup.3He. On the other hand, if
the field is randomly fluctuating, the relaxation rate is given
by
(1/T.sub.1).sub.EMI=.gamma..sup.2<H.sub.AC.sup.2>.tau..sub.c/(1+.ome-
ga..sup.2.tau..sub.c.sup.2) 2.20
[0070] where ".tau..sub.c" is the autocorrelation time of the
fluctuations, ".omega." is the Larmor frequency of the spins, and
"<H.sub.AC.sup.2>" is the mean value of the square of the
fluctuating transverse field component. In the random fluctuation
case, the rate can be suppressed by increasing .omega., (which is
proportional to the holding field strength), particularly if
.omega..tau..sub.c>1. In either case, the relaxation rate can be
suppressed by reducing the magnitude of the interference
H.sub.AC.
[0071] Magnetic Field Gradients
[0072] Magnetic gradient relaxation expressed by the term
(1/T.sub.1).sub.Gradient is associated with the relaxation
attributed to the exposure of the hyperpolarized noble gases to
inhomogeneous static magnetic fields. Generally stated, as the
polarized gas atoms diffuse or move through an inhomogeneous
magnetic field, they experience a time-dependent field, which can
introduce depolarizing activity onto the hyperpolarized atoms. For
example, at typical pressures (i.e., about 1 bar), the relaxation
rate attributed to a static magnetic field gradient can be
expressed by the following equation: 1 ( 1 / T 1 ) Gradient = D ( B
x 2 + B y 2 ) / B z 2 2.30
[0073] Here, "B.sub.z" is the primary component of the static
magnetic field, "{overscore (V)}B.sub.x" and "{overscore
(V)}B.sub.y" represent the gradients of the transverse field
components, and "D" is the diffusion coefficient of the polarized
atoms through the gas. For example, for pure .sup.3He at 1 bar
pressure, the diffusion coefficient D.apprxeq.1.9 cm.sup.2/s. In
the earth's magnetic field (generally represented by a static
magnetic field of about 0.5 G), a 5 mG/cm transverse field gradient
causes a relaxation rate (1/T.sub.1).sub.Gradient of about
1.9.times.10.sup.-4s.sup.-1 (i.e..sub.1 a .sup.3He T.sub.1 of about
1.5 hours). In contrast, in a 5 gauss field (as opposed to a 0.5
gauss field), the same 5 mG/cm gradient will typically yield a
T.sub.1 of about 150 hours. Thus a magnetic field homogeneity on
the order of 10.sup.-3 cm.sup.-1 is desirable to make gradient
relaxation tolerable at these pressures. Alternatively, higher
gradients are acceptable if the .sup.3He is pressurized to at least
several bars of pressure, or alternatively mixed with another gas
such as nitrogen or argon to restrict diffusion, i.e., lower the
diffusion coefficient. As will be appreciated by those of skill in
the art, during transport, it is desirable to avoid inhomogeneous
magnetic fields, e.g., to avoid nearby ferromagnetic objects. For
example, it is desired to maximize to the extent possible the
spatial distance between the hyperpolarized gas and objects that
can produce strong magnetic fields and/or magnetic field
gradients.
[0074] Shielding
[0075] The present invention recognizes that unless special
precautions are taken, relaxation due to external magnetic fields
(static and/or time dependent) can dominate all other relaxation
mechanisms. As discussed above, both gradients in the static field
and (low frequency) oscillating magnetic fields experienced by the
hyperpolarized gas can cause significant relaxation.
[0076] Advantageously, the instant invention employs an
(externally) applied substantially static magnetic holding field
"B.sub.H" to substantially protect the hyperpolarized gas from
depolarizing effects attributed to one or more of the EMI and
gradient fields during transport. The instant invention employs a
magnetic holding field which raises the Larmor frequency of the
hyperpolarized gas above the region of noise (1/f), i.e., the
region where the intensity of ambient electromagnetic noise is
typically high (this noise is typically under about 5 kHz).
Further, the magnetic holding field of the instant invention is
also preferably selected such that it raises the frequency of the
hyperpolarized gas to a level which is above those frequencies
associated with large acoustic vibrations (these acoustic
vibrations are typically less than about 20 kHz). As will be
discussed below, the increased frequency associated with the
applied magnetic holding field advantageously allows a transport
unit to have greater electromagnetic shielding effectiveness for a
given housing thickness (the housing used to hold the
hyperpolarized gas therein during transport). The skin depth
".delta." of a conductive shielding material is inversely
proportional to the square root of the frequency. Thus, at 25 kHz,
an exemplary skin depth for aluminum is about 0.5 mm, as compared
to about 2.0 mm at 1.6 kHz.
[0077] Preferably, the magnitude of the magnetic holding field of
the instant invention is selected so that any external
field-related fluctuations are small in magnitude compared to the
field strength of the holding field; in this way the holding field
can minimize the hyperpolarized gas's response to unpredictable
external static field gradient-induced relaxation. This can be
accomplished by applying to the hyperpolarized gas a proximately
positioned magnetic holding field which is sufficiently strong and
homogeneous so that it minimizes the unpredictable static
field-related relaxation during transport. A sufficiently
homogeneous holding field preferably includes (but is not limited
to) a magnetic holding field which has homogeneity which is on the
order of about at least 10.sup.-3 cm.sup.-1 over the central part
of the holding field. In the previous example, if a homogeneous
field of about 10 G were applied, the same 5 mG cm.sup.-1 gradient
would instead result in T.sub.1.apprxeq.600 hr. More preferably,
the magnetic holding field homogeneity is about at least
5.times.10.sup.-4 cm.sup.-1 over about a region of interest (i.e.,
the region of interest is region associated with the major volume
of the hyperpolarized gas in the container(s)) in the transport
unit. Preferably this volume is sized and configured as a volume in
space representing about at least a three-inch diameter sphere.
Further, the transport unit 10 of the instant invention includes
and provides a magnetic holding field which is positioned, sized,
and configured relative to the hyperpolarized gas held therein such
that it also minimizes the EMI or oscillating magnetic field
depolarization effects on same. The depolarizing effect of EMI is
preferably (substantially) blocked by applying the magnetic holding
field (B.sub.H) proximate to the gas so that the resonant frequency
of the hyperpolarized gas is adjusted to a predetermined frequency.
Preferably, the predetermined frequency is selected such that it is
above or outside the bandwidth of prevalent time-dependent fields
produced by electrically powered or supplied sources.
[0078] Alternatively, or additionally, the external interference
can be shielded by positioning a substantially continuous shield or
shipping container having at least one layer formed of a conductive
material, such as metal, around the hyperpolarized gas in the
container. The preferred shielding thickness is related to the
spatial decay constant of an electromagnetic wave or skin depth
".delta.". The skin depth .delta. at an angular frequency
".omega.", given by ".delta.=c/(2.pi..mu..sigma..ome-
ga.).sup.1/2", where ".mu." is the magnetic permeability and
".sigma." is the electrical conductivity of the material. At these
frequencies, the Larmor radiation wavelength is relatively long
(.about.10 km), and is much larger than the container size. The
shielding effectiveness is therefore dependent upon the container
geometry as well as the shielding thickness. For a thin spherical
conductor of radius "a" and thickness "t", the shielding factor for
wavelengths ".lambda." where .lambda.>> a can be
approximately represented by the following equation
F=(1+(2at/3.delta..sup.2).sup.2).sup.1/2 2.4
[0079] Interestingly, the shielding effectiveness increases as the
size (radius) of the shield is increased. It is therefore preferred
that the metallic enclosure used to shield or surround the
hyperpolarized gas be configured and sized to define an internal
volume and spatial separation relative to the gas which is
sufficient to provide increased shielding effectiveness. Stated
differently, it is preferred that the opposing walls of the
enclosure are spaced apart a predetermined distance relative to the
position of the gas container held therein. Preferably, the walls
define a minimum linear separation for the major volume of the
container or chamber (the portion holding a major portion of the
hyperpolarized gas or product) such that there is about at least
1.5 inches, and more preferably at least about 2.0 inches, and even
more preferably at least about 2.5 inches of distance between the
metallic wall and the leading edge of the gas holding chamber on
all sides.
[0080] As shown in FIG. 1, the transport unit 10 has an enclosure
60 with a geometry in which the walls of the enclosure are
configured and sized to provide an internal volume 65 or geometry
which is relatively large in comparison to the size of the gas
container(s) 30 (30b, FIG. 12). As is also shown, the walls 63A,
63B, 63C, 63D are configured such that the gas holding chamber 30,
when in position in the enclosure 60, is spaced apart a distance
from the adjacent wall segments to provide sufficient spacing to
facilitate the shielding effectiveness of the metallic wall. That
is, the opposing walls 63B, 63C and 63A, 63D (and preferably
including the opposing top and bottom walls 63E, 60A) each have a
minimum separation distance of preferably at least about 1.5
inches, and more preferably at least 2.0 inches, and still more
preferably at least about 2.5 inches in all directions from the
major portion of the gas holding chamber 30. In a preferred
configuration, the separation distances of the container 30 (30b,
FIG. 12) as held in the transport unit 10, is sized and
geometrically configured to define a maximum separation ratio. That
is, the separation ratio can be described as the linear distance
from the center of the major volume of the container holding a
volume of hyperpolarized gas to the edge thereof (i.e., the linear
half width, or the radius of a spherical gas chamber) to the
minimum linear separation distance of each (or the closest) wall
from the leading edge of the portion of the gas holding chamber
holding the major volume of the gas. Preferably, the container and
enclosure are configured to provide a ratio which is less than
about 0.60.
[0081] Alternatively, or additionally, the transport unit 10 can be
configured with at least one layer formed from about 0.5 mm thick
of magnetically permeable material, such as ultra low carbon steel
soft iron, or mu-metals (by virtue of their greater magnetic
permeability). However, these materials may significantly influence
the static magnetic field and must be designed accordingly not to
affect the homogeneity adversely.
[0082] Irrespective of the skin depth of the materials (types of
materials and number of layers) used to form the shipping container
enclosure, application of a homogeneous magnetic holding field
proximate to the hyperpolarized gas can help minimize the gas
depolarization by virtue of decreasing the skin depth .delta.,
which is inversely proportional to the square root of the
frequency. Further, it helps by pushing the resonant frequency of
the gas outside the bandwidth of common AC fields. It is preferred
that the resonant frequency of the hyperpolarized gas be raised
such that it is above about 10 kHz, and more preferably be raised
such that it is between about 20-30 kHz. Stated differently, it is
preferred that for shielding, the applied magnetic holding field
have a field strength of about 2 to 35 gauss. It is more preferred
that for .sup.129Xe, the magnetic holding field is preferably at
least about 20 Gauss; and for .sup.3He, the magnetic holding field
is preferably at least about 7 Gauss.
[0083] Transport Unit
[0084] Referring now to FIG. 1, a transport unit 10 is illustrated
according to a preferred embodiment of the instant invention. As
shown, the transport unit 10 includes a magnetic field generator
20' disposed therein, which provides a magnetic holding field
(B.sub.H) for the gas. As shown, the magnetic field generator is a
solenoid 20, which is configured and sized to receive a
hyperpolarized gas storage chamber 30 therein. The transport unit
10 also includes a power source 40 and operating circuitry 50
preferably provided on an internally disposed printed circuit board
51. The transport unit 10 preferably includes a substantially
non-ferromagnetic metallic case or housing enclosure 60 having a
predetermined skin depth appropriately sized to provide desired
shielding, and which includes a bottom portion 60B and a top 61A
(FIG. 5) that open to facilitate easy access to the exit port 31
and valve 32 of the gas chamber 30. It is preferred that the
transport unit 10 be configured with a minimal amount of
ferromagnetic materials on or inside the transport unit 10 (i.e.,
is substantially free of ferromagnetic materials that are not
intended for creating the homogeneous holding field). Although for
ease of discussion, the term "transport" is used to describe the
unit, it will be appreciated by one of skill in the art, that the
instant invention may also be used to store a quantity of
hyperpolarized gas product therein. As such, the term "transport
unit" includes a unit that can be used as either a storage unit, a
transport unit, or both a storage and transport unit.
[0085] As shown in FIGS. 1 and 5, the top 61A of the housing is
hinged to the bottom of the case 60B, which defines an enclosure
volume 65. Preferably, as shown in FIG. 1, the enclosure volume 65
is defined by a contiguous arrangement of four upstanding sidewalls
63A-63D (63D not shown) connected by a bottom wall 63E and a top
face-plate 60A, 60A'. Thus, the enclosure 65 surrounds the gas
chamber 30 and other internally mounted components (such as a power
source 40 and operating circuitry 50).
[0086] As shown in FIG. 5, the top portion 61A preferably includes
latches 200A, 200B which engage with corresponding components 210A,
210B positioned on the outside wall of the bottom portion of the
case 60B to secure the top 61A to the bottom to the bottom 60B when
the top 61A is closed (i.e., preferably during transport).
Preferably, the enclosure 60 and, indeed, the entire transport unit
10, is configured to be polarization-friendly (substantially devoid
of paramagnetic and ferromagnetic materials) such that the
transport unit 10 does not introduce significant reductions in the
polarization level of the hyperpolarized gas therein.
[0087] Generally stated, as electromagnetic leakage is proportional
to holes or openings in the housing 60, it is preferred, either
when the top of the housing 61A is closed or by configuring the
face plate 60A to attach to the bottom of the case 60B such that
the exterior walls of the housing 60 define a substantially
continuous body (without openings) to minimize the entry of
electromagnetic waves inside the housing 60. Of course, the housing
60 can include apertures as long as they are positioned or formed
on the housing 60 such that any electromagnetic interference
leakage is directed away from the solenoid core 33 where the gas
chamber 30 resides and/or are configured with a protective covering
or seal to provide sufficient housing integrity to minimize
polarization loss attributed thereto. One suitable housing 60 is a
relatively compact aluminum case (having about a 1 mm wall
thickness) manufactured by Zero Enclosures of Salt Lake City, Utah
and was modified to substantially remove ferromagnetic
hardware.
[0088] Preferably, the bottom of the case 60B and the face plate
60A and/or top 61A includes at least one layer of an electrically
conducting metal thereon, having a sufficient skin depth to thereby
provide one or more of shielding from external electromagnetic
radiation, physical protection, and support of the gas container
during transport. Alternatively, or additionally, the components of
the housing 60 which define the enclosure 65 (such as the walls and
bottom 63A-63D, 63E and top 61A) include at least one layer of
magnetically permeable material to provide either additional
electromagnetic shielding, DC magnetic shielding, and/or a flux
return.
[0089] Preferably, as shown in FIG. 1, the transport unit 10 also
comprises a metal face plate 60A, 60A' positioned over the opening
defined by the upper surface of the case when the top 61A is
opened. As shown in FIGS. 1 and 5, the face plate 60A, 60A' is
configured to substantially enclose the side walls and bottom of
the housing to provide an enclosure for the solenoid 20 when the
top 61A is open and yet also configured to allow a user access to a
polarized gas chamber valve 32 and the hyperpolarized gas exit port
31.
[0090] In a preferred embodiment, after delivery to a desired
location, the valve 32 is opened and the hyperpolarized gas is
released from the gas chamber 30 through the exit port 31 while the
gas chamber 30 itself remains captured in the substantially
enclosed housing 60. The bottom housing 60 can add extra protection
to personnel in the gas release area because the housing 60
surrounds a substantial portion of the gas chamber 30 therein,
thereby providing a physical shield from any unplanned release or
untimely breakage of the chamber itself (typically comprising an
alumnosilicate glass) and which is typically transported under
pressure. Further details of the preferred gas chamber 30 will be
discussed below.
[0091] Solenoid
[0092] Turning to FIG. 2, it is preferred that the transport unit
comprise an electromagnet for providing the magnetic holding field.
FIG. 2 illustrates a preferred embodiment of the electromagnet
configured as a solenoid 20 comprises a plurality of electrical
coil segments for generating a substantially homogeneous static
applied magnetic holding field (B.sub.H). Of course, other
electrical wire configurations (i.e., electromagnetic arrangements)
can also be used as will be appreciated by one of skill in the art.
As will also be appreciated by one of skill in the art, other
magnetic field generators can also be employed such as permanent
magnets (so long as they provide sufficient homogeneity).
Preferably, the solenoid 20 comprises at least three (3) electrical
coil segments 21, 22, 23 which are wrapped around an outer surface
of the cylindrical wall of the solenoid body or core 20A. During
fabrication, this outer surface placement of the coil segments 21,
22, 23 allows the outer wall of the solenoid core 20A to act as the
wrapping spool. The cylindrical spool can be formed of various
preferably non-conducting materials such as polyvinyl chloride
(PVC). Of course, the coil segments 21, 22, 23 can be alternatively
positioned on the cylindrical body. For example, the coil segments
21, 22, 23 can be wrapped onto an intermediate layer of a
cylindrical body (or even an inner layer) as will be appreciated by
those of skill in the art.
[0093] As shown in FIGS. 1, 2 and 3, the solenoid 20 is oriented
such that it extends longitudinally from the opposing top and
bottom ends of the transport unit 10. The coil segments 21, 22, 23
are circumferentially wrapped around the respective portions of the
cylindrical wall of the solenoid core 20a and are preferably
configured such that the magnetic holding field B.sub.H (FIG. 3) is
directed downward such that it preferably aligns with the
predominant direction of the earth's magnetic field (the field
direction is generally indicated by element 100). As such, the
current in the solenoid coil segments 21, 22, 23 is directed
clockwise when viewing the solenoid from the top. This earthly
directional alignment can maximize the magnitude of the holding
field with a given current.
[0094] As shown in FIGS. 2 and 2A, the first and third coil
segments 21, 23 are preferably positioned proximate to the top and
bottom 20A, 20B of the solenoid, respectively. The second coil
segment 22 is positioned intermediate the first and third coil
segments 21, 23. As shown, the second segment 22 is spatially
separated by a separation distance 22A, 22B from the first and
third coil segments 21, 23.
[0095] FIG. 1 shows a preferred embodiment wherein substantially
the entire inner diameter of the solenoid 20 is covered with a thin
conductive material layer such as a metallic film or tape 24. FIGS.
1 and 2 illustrate that the thin metallic layer 24 acts to provide
a separate columnated electrical shield 24a which extends between
the top plate 60A and the top surface of the bottom of the case
63E. As shown, the shield 24a is formed as a thin metallic layer 24
which is arranged as a series of wrapped and overlapping layers of
aluminum foil tape which extends from the top to the bottom of the
solenoid 20. This thin metallic layer 24 can also be provided by
other metallic finishes, such as by a metallic coating, metallic
film or metallic elastomer and the like.
[0096] Preferably the shield 24a is configured such that at least
the bottom end 24b of the shield is in electrical contact with the
case 60. In a preferred embodiment, the bottom end 24b is
configured to be in electrical contact either directly or
indirectly (i. e., via other conductive components) with the case.
In this embodiment, the bottom end 24b is configured such that the
end defines a continuous electrical connection around the entire
bottom edge 24b. Of course, other components can be used to define
an electrical bridge between the shield 24a and the case.
[0097] In another embodiment, both the top edge 24c and the bottom
edge 24b of the shield 24a are arranged to define a continuous
electrical contact with the respective adjacent portions of the
case 60.
[0098] Further, in a preferred embodiment, as illustrated in FIG.
3A, the first and third coil segments 21, 23 are configured with an
increased number of wire layers relative to the second coil segment
22. A preferred current distribution is also illustrated in FIG.
3A. The increased number of layers associated with the first and
third coil segments 21, 23 relative to the second coil segment 22
acts to provide additional current density in these segments and to
enlarge the homogeneous region, as shown in FIG. 3. FIG. 10
illustrates a broader "flatter" field strength (Bz) which a
solenoid having a plurality of winding segments can provide
relative to a single winding configuration of the same length
having a uniform current density. FIG. 10 illustrates the single
winding field as the bottom "bell-shaped" graph. As such, a
solenoid with a plurality of winding segments call increase the
homogeneous holding region in the solenoid along a greater distance
about the center of the solenoid body (distance from "0" along the
"z-position").
[0099] As shown in FIG. 3A, the solenoid 20 is turned on its side
(relative to the transit position shown in FIG. 1) and a preferred
current distribution relative to each coil segment 21, 22, 23 is
graphically illustrated. The first and third coil segments 21, 23
correspond to a first current density value (2i/l) and the
intermediate or second coil segment corresponds to a lesser current
density value, preferably about half the end current density value
(i.e., about (i/l)). (There is negligible current in the gaps 21A,
22A, 22B and 23A). As shown, it is preferred that each of the first
and third coil segments 21, 23 have a current density value which
is substantially the same, while the second coil segment 22 has a
current density value (i/l) which is about half of that of the
first and third coil segments 21, 23. As noted above, the
additional current density is preferably provided by additional
numbers of wire layers in the first and third coil segments 21,
23.
[0100] Preferably, the first and third coil segments 21, 23 are
configured with a predetermined number of wire layers that extend
about a first and third solenoid longitudinal distance. The second
segment 22 is configured with about half of the number of wire
layers relative to the first and third coil segments 21, 23 and
extends about a longer second solenoid longitudinal distance. Also,
as illustrated in FIG. 3A, preferably the first and third coil
segments 21, 23 include about four wire wrap layers (wire is
wrapped in four layers in these segments, one layer on top of the
other), each having about a 2.0 inch length, while the second
segment 22 includes about two wire wrap layers having about a 7.0
inch length. The solenoid 20 preferably is sized to provide about a
6.0 inch inner diameter. These dimensions are particularly suitable
for a single dose quantity of hyperpolarized gas that is held in a
3 inch diameter spherical gas chamber 30 having a capillary stem 35
as shown in FIG. 1. This gas chamber 30 and solenoid 20
configuration provides about a 1.5 inch radial separation between
the solenoid inner diameter and the gas chamber outer diameter. Of
course, other solenoid 20 dimensions and coil segment
configurations (lengths, numbers of layers etc., and/or permanent
magnet arrangements) can be used for alternatively sized and shaped
containers 30.
[0101] In its preferred operative position, as shown in FIGS. 1 and
2, the gas chamber 30 is preferably disposed in the solenoid 20
such that the spherical or major portion 33 of the gas chamber 30
is positioned the area of increased homogeneity within the solenoid
20 (e.g., the center of the solenoid 20 and/or the center of the
second coil segment 22). The positioning can be secured by
suspending the gas chamber 30 from the top plate 60A' (FIG. 1) or
by positioning a non-conducting gas friendly platform or base or
the like under the gas chamber 30 (not shown). Preferably, as shown
in dotted line in FIG. 2, the gas chamber 30 is disposed in the
solenoid 20 such that it rests on hyperpolarized gas friendly
packaging which acts as vibration damping material 50 to help
insulate the gas chamber 30 from undue exposure to vibration during
transport. Also as shown, the packing material 50 extends securely
and snugly around and about the capillary stem 35 to help cushion
and insulate the container during shipment. In any event, it is
preferred that the gas chamber 30 be well supported in the high
homogeneity region, as the magnetic holding field's homogeneity is
spatially determined (spatially variable) and translation of the
gas chamber 30 thereabout can result in the hyperpolarized gas
being potentially exposed to an inhomogeneous region, thereby
potentially reducing the polarized life of the hyperpolarized gas
product.
[0102] In any event, it is preferred that the coil segment
configuration is such that each of the first and third coil
segments 21, 23 provides an increased current density relative to
the second or intermediate coil segment 22. In this configuration,
the solenoid electrical coil segments 21, 22, 23 are sized and
configured with respect to the solenoid volume to provide adequate
magnetic field homogeneity over a larger central volume and
advantageously do so in a relatively compact manler relative to
previous coil designs. Preferably, the three coils 21, 22, 23 are
electrically connected in series and, as such, the end coil
segments are electrically connected to the power source 40 (FIG.
1). Of course, the current can alternatively be separately provided
or otherwise electrically supplied to the coil segments 21, 22, 23.
For example, as will be appreciated by those of skill in the art, a
separate battery and associated circuitry (not shown) can supply
the second coil 22 while a first battery is used to power the first
and third coils 21, 23.
[0103] In a preferred embodiment, the first and third coil segments
have about 198 windings while the second or central coil segment
includes about 347 windings (i.e., the second coil segment 22
preferably has above about 1.5 times the number of windings of the
first and third coil segments 21, 23). Thus, in a preferred
embodiment, the solenoid 20 is configured with about 743 windings
thereon. For this configuration the ratio of field strength to
current is about 23.059 G/A. Thus, the field strength at 300 mA is
about 6.918 gauss and the field strength at 320 mA is about 7.379
gauss. A suitable wire is 18 gauge HML from MWS Wire Industries,
Westlake Village, Calif.
[0104] Preferably, for transit purposes, the transport unit power
source 40 is a 12V DC battery (such as those used to power
motorcycles). However, at docking stations or an end-use site, the
transport unit 10 can be conveniently plugged into an exterior
power source to bypass and preserve the battery charge. Also the
transport unit power source 40 is configured via operating
circuitry 50 to provide an adjustable current supply to the
solenoid 20 of about 100 mA to about 2.0 A. Thus, the solenoid 20
is preferably configured to provide a magnetic holding field of
between about 2 to 40 gauss. The operating circuitry 50 of the
transport unit 10 will be discussed further below.
[0105] Gas Chamber
[0106] Preferably, the gas chamber 30 is configured to provide a
quantity of hyperpolarized gas which can be conveniently delivered
to an end point in a user-friendly single dose volume (but of
course can also be configured to provide multiple or partial dose
quantities) of hyperpolarized gas. In a preferred embodiment, the
gas chamber 30 is a 100-200 cm.sup.3 gas spherical chamber. For
.sup.3He, it is preferred that the gas chamber 30 is pressurized to
about 4-12 atmospheres of total pressure, and more preferably it is
pressurized to about 5-11 atmospheres of total pressure. Pressuring
an appropriately sized gas chamber can allow the hyperpolarized gas
to be released through the exit as the pressure acts to equalize
with ambient conditions. Thus, by merely opening the valve 32, the
hyperpolarized gas can be directed to a patient or a patient
delivery system with minimal handling (and thus minimal potentially
depolarizing interaction). Alternatively, as shown in FIGS. 12A,
12B, and 13 the hyperpolarized gas can be divided and diluted or
appropriately sized either at a polarization site or at a second
site remote from the polarization site into several patient
delivery sized bags with expandable chambers for (further)
transport and delivery. The walls of the expandable chamber bags
can be depressed to expel the gas mixture held therein with a
minimum of extraction equipment required.
[0107] It should be noted that for hyperpolarized .sup.3He, at
about 10 atm of pressure, the theoretical T.sub.1 due to
interactions with other hyperpolarized nuclei is about 75 hours.
Substantially higher pressures allow more gas product to be shipped
in the container and reduces the sensitivity of the hyperpolarized
gas to gradient relaxation, but the gas-gas collision relaxation
can become more prevalent. In contrast, for .sup.129Xe, it is
preferred that the gas pressure be about 10 atm or less, because
higher pressures can dramatically reduce the expected relaxation
time of the hyperpolarized .sup.129Xe (i.e., at 10 atm, the T.sub.1
is 5.6 hours).
[0108] In a preferred embodiment of the instant invention, as shown
in FIG. 4, the gas chamber 30 includes a capillary stem 35 which is
sized and configured to minimize the travel of hyperpolarized gas
atoms out of the spherical volume and acts to keep most of the
hyperpolarized gas away from the valve 32. More specifically, the
capillary is dimensioned such that the ratio of the main body
volume to the capillary volume, multiplied by the diffusion time of
.sup.3He (at fill pressure) to go twice the length of the
capillary, is greater than the desired T.sub.1. As such, a major
portion of the hyperpolarized gas remains in the region of highest
homogeneity within the solenoid 20 where it is best protected from
depolarizing effects during transport. Preferably, the capillary
stem 35 includes about a 1.0 mm inside diameter and has a length,
which is sufficient to allow proper positioning of the sphere
within the region of homogeneity in the solenoid 20. In the
preferred embodiment of the solenoid 20 described above, the
capillary stem 35 is approximately 4 inches long. As such, for a
gas chamber 30 with a three inch diameter sphere, the capillary
stem 35 is preferably longer than the than the sphere holding
(body) portion 33 of the gas chamber 30. Also preferably, the inner
diameter of the capillary stem 35 is sufficiently small as to slow
movement of the hyperpolarized atoms relative to the valve 32,
thereby keeping a substantial portion of the hyperpolarized gas in
the spherical volume 33 and thus within the high-homogeneous field
region.
[0109] As also discussed above, even if the transport unit 10
shields or protects the hyperpolarized gas from EMI and static
magnetic field gradients, the surface relaxation rate associated
with the container, the valve(s), and other hyperpolarized gas
contacting components can deleteriously affect the polarization
lifetime of the hyperpolarized gas. As such, particularly for
hyperpolarized .sup.3He, and for multi-dose containers 30L (FIG.
12A, 13) it is preferred that the gas chamber 30 primarily comprise
an aluminosilicate material. Aluminosilicate materials have been
shown to have long surface relaxation times. The gas chamber 30 may
be manufactured from GE180.TM., although, of course, other
aluminosilicates may be used. Typically a transition glass is used
to attach the borosilicate (Pyrex.RTM.) valve 32 of the
aluminosilicate gas chamber 30. Suitable valves 32 for use in the
gas chambers 30 is part number 826460-0004 which is available from
Kimble Kontes, located in Vineland, N.J. The valves 32 can be
further modified to coat or replace any paramagnetic or
ferromagnetic impurities, or may be treated or conditioned to
remove or minimize the amount of impure or depolarizing materials
that are positioned proximate to the hyperpolarized gas. Suitable
transition glass includes uranium glass.
[0110] Alternatively, other polarization-friendly materials can be
used, such as high purity metals or polymers with metallized
surfaces, polymers and the like. "High purity" as used herein means
materials that are substantially free of paramagnetic or ferrous
materials. Preferably, the metallic materials include less than 1
part per million paramagnetic or ferrous impurities (such as iron,
nickel, chromium, cobalt and the like). In an alternate preferred
embodiment, as shown in FIGS. 12A and 13, the gas chamber can be a
resilient bag 30b such as a single or multiple polymer layer bag
having a metallic film layer or inner surface or surface layer
which is formed from one or a combination of a high purity metal
such as gold, aluminum, indium, zinc, tin, copper, bismuth, silver,
niobium, and oxides thereof. Additional descriptions of preferred
hyperpolarization materials and containers, O-rings and the like
are included in co-pending U.S. patent application Ser. No.
09/126,448 entitled "Containers for Hyperpolarized Gases and
Associated Methods" (and its related application) as discussed
under the Surface-induced Relaxation section hereinabove. The
resilient bag 30b may include a capillary stem (not shown) and/or a
fluid port isolation means to inhibit the hyperpolarized gas from
contacting potentially depolarizing valves and fittings during
transport or storage.
[0111] It is also preferred that the gas chamber 30 be configured
as a sphere because it has a geometry that minimizes the surface
area/volume ratio and thus the surface-induced contact relaxation.
Further, since the solenoid 20 described above generates a region
of high homogeneity that is typically generally spherical in shape,
making the gas chamber spherical in shape maximizes the volume of
the gas chamber that fits the homogeneous region.
[0112] In another preferred embodiment, the transport unit 10 is
configured in at least two different sizes, a first size for
transporting large quantities of gas in a single container, and a
second size for transporting one or more (preferably a plurality of
single-sized dosages) for facilitating distribution of single-use
doses of hyperpolarized substances or formulations at remote sites
to retain sufficient polarization to allow clinical useful images
over longer transport distances and elapsed times from original the
original point of polarization. FIGS. 12A, and 13 illustrate a
multi-bolus or dose container 30L (i.e., a relatively large
capacity container) and a plurality of smaller resilient bag 30b
containers (i.e., bags with expandable chambers). The bag container
30b may include a capillary stem similar to that used for the rigid
container 30 discussed above (not shown). Similar, to the gas
chamber 30, the NMR coil 75 can be positioned on an outer surface
thereof to monitor polarization during transport.
[0113] Further details regarding preferred bag materials and
configurations are discussed in co-pending and co-assigned U.S.
Patent Application entitled, "Resilient Containers for
Hyperpolarized Gases and Associated Methods," identified by
Attorney Docket No. 5770-12IP and related U.S. patent application
Ser. No. 09/126,448, incorporated by reference herein.
[0114] The multi-bolus container 30L is used to dispense desired
formulations, concentrations, and/or mixtures of the hyperpolarized
gas (with or without other substances, liquids, gases (such as
nitrogen), or solids) at a remote site. The multi-dose container
30L may be the polarization chamber or optical cell itself. The
magnetic field generator is preferably a correspondingly sized
solenoid 20, but can also be provided by permanent field magnets
(not shown). Of course, a single sized transport unit (or even the
same transport unit) can be used to transport the hyperpolarized
gas to the second and third sites, i.e., the second transport unit
10s may be sized and configured the same as the first transport
unit 10f as needed. Alternatively, the first transport unit may be
larger than the second or the second may be larger than the first
depending on how the hyperpolarized gas is distributed and the
shape and size and number of the second containers positioned for
transport from the second site.
[0115] FIG. 13 illustrates that the resilient bags 30b can each
have an individual magnetic field generator shown as a solenoid 20
operatively associated therewith. FIG. 12A illustrates one
alternate configuration with a single magnetic field generator
(also shown as a solenoid 20) sized and configured to hold a
plurality of bags 30b therein. As shown in FIG. 12B, a tray 630 can
be used to hold a plurality of hyperpolarized substance filled bags
and translated into the solenoid 20' to position them in the
desired region within the solenoid for effective shielding as
discussed above. The tray 630 can also facilitate removal at a
delivery site. Preferably, the tray is formed of non-conductive
polarization friendly materials. Of course, the tray 630 can be
alternatively configured such as with compartments and sliding and
locking means which ratchet or lock for positionally affirmatively
locating the bags, as well as a handle or extension means to allow
central or recessed positioning of the tray and bags within the
desired region of homogeneity.
[0116] Operating Circuitry
[0117] Preferably, the transport unit 10 includes operating
circuitry 50 that is operably associated with the solenoid 20 and
the power source 40. Preferably, the internal power source 40 is a
battery as described above, but can also be operably associated
with an external power source via an external power connection 141
(FIG. 5). As shown schematically in FIG. 8, the operating circuitry
50 preferably includes a power monitoring switching circuit 125. As
shown in FIG. 7, the power monitoring and switching circuit 125
includes a relay switch 145, a current monitor 150 and an on/off
switch output 160 which is connected to the input of the current
load into the solenoid 20. Advantageously, the power monitoring
circuitry 125 is preferably configured to automatically switch
between the different power sources (40, 140) without interruption
of the current to either the operating circuitry 50 or the solenoid
20. Preferably, the power monitoring switching circuit 125 manages
the power supply such that the transport unit 10 is powered from
the internal power source 40 (battery) only when needed. For
example, when the transport unit 10 is not easily connected to an
external power source 140, the power monitoring circuit 125 engages
the battery 40 to supply the power to the transport unit 10.
Preferably, the power monitoring circuit 125 then disengages the
battery 40 when the transport unit 10 is connected to a viable
external power source 140 (such as a wall or vehicle power outlet)
when the external connector port 141 is connected to the external
source 140. In a preferred embodiment, as shown in FIG. 7, the
power monitoring circuit 125 is operably associated with recharging
circuit 148 which allows the internal battery 40 to be recharged
when the transporter is powered from an external supply 140.
[0118] Of course, the operating circuit 50 can also include other
components and circuits such as a battery monitor 171 (FIG. 5) and
an audible and or visual alarm (not shown) to indicate when the
battery 40 is low. Preferably, as also shown in FIGS. 5 and 8, the
transport unit 10 includes a current readout 151 associated with
the power monitoring circuit 125. As shown, the current readout is
a LCD display 151, which will allow a custodian to visually affirm
that the transport unit is functioning properly and enable him to
monitor the current running through the solenoid. Also as shown in
FIG. 8, the operating circuitry 50 preferably includes a current
adjustment means 180 for increasing or decreasing the current
delivered to the solenoid 20. In a preferred embodiment, the
current adjustment means 180 is a rheostat operated by the current
control knob 180 (FIG. 5). As discussed above, the adjustable
current means preferably is adjustable to supply between about 100
mA to about 2.0 A.
[0119] The current adjustment allows the operating circuitry 50 to
adjust the current in response to the needs of the transport unit
10. For example, the current can be adjusted to provide a custom
holding field corresponding to the type of hyperpolarized gas being
transported. Additionally, the current to the solenoid 20 can be
adjusted to compensate for electronic or mechanical system
variation (i.e., battery drainage, electronic drift, coil
resistance variability due to temperature), thereby maintaining the
desired holding field strength. The operating circuit preferably
includes a means for adjusting the magnetic field strength of the
magnetic holding field, which preferably operates to shift the
Larmor frequency of the spins associated with the hyperpolarized
gas, Such magnetic field adjustability is useful for performing of
NMR measurements, or to avoid electromagnetic interference at a
particular frequency or frequency range. The NMR measurement system
will be discussed further below.
[0120] As with all materials that contact, or are positioned near
or proximate to the hyperpolarized gas, it is preferred that the
operating circuitry 50 contain minimal magnetically active
materials and components such as iron transformers. However, if
such materials or components are used, then it is preferred that
they be positioned a sufficient distance from the gas chamber 30
and the solenoid 20 so that they do not cause undue gradient
relaxation. Further, it is preferred that temperature sensitive
components be removed from the operating circuit 50 in order to
provide a reliable, consistent circuit which can tolerate broad
temperature ranges (inside and outside). Of course the operating
circuitry 50 may be present in hardware, software, or a combination
of software and hardware.
[0121] Portable Monitoring (NMR Coil/Polarimetry)
[0122] Preferably, the transport unit 10 is operably associated
with a polarization monitoring system that is configured to monitor
the polarization level of the hyperpolarized gas in the gas chamber
30. Advantageously, such system can be used in transit or at a
desired evaluation site. For example, prior to release of the gas
from the transport unit 10, the monitoring system can acquire a
signal corresponding to the polarization level of the
hyperpolarized gas in the transport unit 10 and thus indicate the
viability of the gas prior to delivery or at a receiving station at
the point of use. This can confirm (reliably "inspect") the product
and assure that the product meets purchase specification prior to
acceptance at the use site.
[0123] The polarization monitoring system can also be used with the
transport unit 10 to evaluate magnetic holding field fluctuations
during transport. Further, the monitoring system can automatically
adjust the current to compensate for detected fluctuations.
Additional details of a suitable monitoring systems and methods for
implementing same are discussed in co-pending and co-assigned U.S.
patent application, entitled "Portable Hyperpolarized Gas
Monitoring System, Computer Program Products, and Related Methods,"
identified by Attorney Docket No. 5770-17. The contents of this
application are hereby incorporated by reference as if recited in
full herein.
[0124] As shown in FIG. 1, the transport unit 10 preferably
includes a NMR transmit/receive coil 75, which is positioned such
that it (securely or firmly) contacts the external wall of the
storage chamber 30. The NMR coil 75 includes an input/output line
375 that is operably associated with a NMR polarimetry circuit and
a computer (typically an external portable computer device 500, as
shown in FIG. 5). Preferably, the transport unit 10 includes a
computer access port 300 which is operably associated with the
operating circuitry 50 and the NMR coil 75 via the coaxial BNC
bulkhead 275. The NMR coil 75 can be used with the monitoring
system to evaluate the polarization level of the hyperpolarized gas
in a substantially nondestructive evaluation technique.
[0125] Alternatively, or in addition to the (portable) monitoring
system, the transport unit 10 is preferably configured to
conveniently dock into a (remote) site calibration station 500, as
shown in FIG. 9. Generally described, as shown in FIG. 9, the
polarization detection can be carried out at a calibration station
500 which preferably uses a low-field NMR spectrometer to transmit
RF pulses to surface coils 75 positioned proximate to the
hyperpolarized gas sample. The spectrometer then receives at least
one signal back from the NMR coil 75 corresponding to the
hyperpolarized gas. The signal is processed and displayed 565 to
determine the polarization level of the hyperpolarized gas
(preferably this reading is taken while the gas is contained in the
gas chamber 30 within the transport unit 10).
[0126] As shown, the calibration station 500 preferably includes a
set of Helmholtz coils 552 (preferably of about 24 inches in
diameter) to provide the low magnetic field and another external
NMR surface coil (not shown). The additional NMR surface coil is
preferably sized and configured at about 1 inch in diameter and
with about 350 turns. The NMR surface coil is configured to be
received into a non-metallic platform 170 and is arranged to be
substantially flush with the upper surface of the platform to be
able to contact the patient delivery vessel 575. Also, the NMR coil
is preferably positioned in the center of the Helmholtz coils 552.
The term "low field" as used herein includes a magnetic field under
about 100 Gauss. Preferably, the calibration station 500 is
configured with a field strength of about 5-40 Gauss, and more
preferably a field strength of about 20 Gauss. Accordingly, the
corresponding .sup.3He signal frequency range is about 16 k Hz-128
kHz, with a preferred frequency of about 64 kHz. Similarly, the
.sup.129Xe signal frequency range is about 5.9 kHz-47 kHz, with a
preferred signal frequency of about 24 kHz.
[0127] Preferably, the hyperpolarized gas is contained in a patient
delivery bag container 30b which is positioned on the top surface
of the surface coil (not shown) and substantially in the center of
the Helmholtz coils 552. Generally described, in operation, a
selected RF pulse (of predetermined frequency, amplitude, and
duration) is transmitted from the NMR device 501 to the surface
coil (not shown). Alternatively, the calibration station 500 can be
used to transmit the selected RF pulse inside the transport unit 10
via connection 553. In any event, the RF pulse frequency
corresponds to the field strength of the magnetic field and the
particular gas, examples of which are noted above. This RF pulse
generates an oscillating magnetic field which misaligns a small
fraction of the hyperpolarized .sup.3He or .sup.129Xe nuclei from
their static magnetic field alignment. The misaligned nuclei start
processing at their associated Larmour frequency (corresponding to
pulse frequency). The processing spins induce a voltage in the
surface coil that can be processed to represent a signal 565. The
voltage is received back (typically amplified) at the computer and
the signal fits an exponentially decaying sinusoid pattern. (As
shown, the displayed signal 565 is the Fourier transform of the
received signal). The initial peak-to-peak voltage of this signal
is directly proportional to polarization (using a known calibration
constant). The computer 500' can then calculate the polarization
level and generate calculated preferred use dates and times
associated with desired polarization levels. As will be recognized
by those of skill in the art, other calibration or
hyperpolarization level determination methods can also be employed
and still be within the product identification and calibration or
product-use or expiration determination methods contemplated by the
present invention. For example, by detecting the minute magnetic
field generated by the polarized .sup.3He spins, one can determine
a polarization level associated therewith.
[0128] In an alternate embodiment, the transport units 10", 10"'
comprise a plurality of gas chambers 30 (FIGS. 6, 6A) or 30b (FIG.
12A and 13) and each gas chamber 30 preferably includes an
individual NMR coil 75 which is positioned adjacent each gas
chamber within the solenoids of the transport unit 10", 10"'. It is
further preferred that each gas chamber 30 be substantially
electrically isolated from the other gas chambers 30 such that each
gas chamber 30 is individually monitorable (individually excitable)
for hyperpolarization level and each is individually tunable
(adjustable field strength and coil current). In another alternate
embodiment, as shown in FIG. 6B, the transport unit 10"" can be
configured with a single coil 20' which is sized and configured to
surround a plurality of gas chambers 30 therein (see also FIG.
12A). When positioning the containers 30 within the transport units
(if the containers have necks or capillary stems, whether for
single or multiple gas container units), neck or stem orientation
can be oriented in different directions. Further, although the
transport units shown in FIGS. 6, 6A, and 6B illustrate side by
side gas containers, the present invention is not limited thereto.
For example, the transport unit can be configured to comprise a
plurality of units that are stacked longitudinally with capillary
stems extending in the same or opposing directions. FIG. 12A
illustrates one example, a plurality of bags 30b positioned in
substantial linear alignment (whether longitudinal or lateral). An
NMR coil 75 can also be attached to each bag 30.sub.b held for
transport or storage (not shown).
[0129] Advantageously, a transport unit comprising a solenoid 20
has successfully supported a T.sub.1 of .sup.3He of 45 hours
(valved gas chamber) while an tuivalved model (sealed) gas chamber
(pressurized to about 2.2 atm, not shown) has supported a T.sub.1
of 120 hours. These exemplary T.sub.1's were for .sup.3He polarized
at a production site and transported in the transport unit 10 for a
travel time of about 30 hours (approximately 28 hours where the
unit was physically removed from its "home-base" or polarizer) and
where the unit was actually in transit for approximately 10 hours.
The gas chambers 30 in the transport unit 10 were exposed to
environmental conditions while traveling to a use site in a
vehicle.
[0130] Central Production Site; Remote Use Site
[0131] Use of a remote polarization production site typically
requires longer T.sub.1's relative to an on-site polarization
apparatus to allow adequate shipping and transport times. However,
a centrally stationed polarizer can reduce equipment and
maintenance costs associated with a plurality of on-site units
positioned at each imaging site and the transport units of the
instant invention can allow increased transport times with longer
T.sub.1 times over those conventionally achieved. In a preferred
embodiment, a production polarizer unit (not shown) generates the
polarized gas a production site. The gas chamber 30 (or 30b) is in
fluid communication with the polarizer unit such that the polarizer
unit produces and directs the polarized gas to the gas chamber 30.
Preferably, the gas chamber 30 is held in the transport unit
enclosure 65 (FIG. 1) (or individual enclosure 65A-D, FIGS. 6, 6A,
and 6B) during the filling step. More preferably, the container is
positioned in the transport unit within the homogeneous holding
field therein prior to the filling step. After a sufficient
quantity of hyperpolarized gas is captured in the gas chamber 30,
the valve 32 is then closed (the gas chamber is sealed). Thus, the
solenoid 20 in the transport unit 10 is activated (preferably prior
to the filling step, but can also be activated after the container
is sealed, if the container is otherwise protected such as on-board
the polarizer unit during fill. In operation, the power switch 161
(FIG. 5) on the transport unit 10 is turned to the "on" position
and electrical current is supplied to the solenoid 20 such that
about a 7 Gauss magnetic holding field is generated as discussed
above. The hyperpolarized gas is shielded from stray magnetic
gradients within the transport unit 10 until and after delivery to
a remotely located site. When desired, the hyperpolarized gas can
be directed or released from the gas chamber 30 and dispensed to a
patient via some patient delivery system (temporally limited to its
end use time) such that the hyperpolarized state of the gas at
delivery is sufficient to produce useful clinical images.
[0132] Another aspect of the present invention is a system for
distributing hyperpolarized gas products such that single use or
patient sized doses of hyperpolarized gases have increased shelf
life or useful polarization life. The system includes a first
transport unit 10f (schematically shown by dotted line box in FIG.
12A) which is sized and configured to hold at least one multi-dose
container 30L therein. The system also includes at least one second
transport unit 10s (schematically shown in FIG. 12A)sized and
configured to carry a plurality of single dose containers (such as
for example shown by 30 or 30b in FIGS. 6A, 6B, and 12A, 13,
respectively) therein. Preferably, the multi-dose container is a
rigid body container 30L and the single dose containers are
resilient containers 30b having expandable chambers to allow easy
delivery or administration at a use site as described above. In a
preferred distribution system, the hyperpolarized gas is collected
in a multi-bolus container (such as that shown as container 30L in
FIGS. 12A, 12B, and 13) at the polarization site and transported in
a suitably sized transport unit 10f to a second site remote from
the first site. This multi-bolus container 30L can be the optical
cell itself, or other suitable container configuration such as
those discussed above.
[0133] In one embodiment, as shown in FIG. 12A, the multi-dose
container 30L is transported to a pharmaceutical distribution point
where the hyperpolarized gas in the multi-dose container 30L can be
dispensed or formulated into the proper dosage or mixture according
to standard pharmacy or drug manufacturer operation. For example,
but not limited to, this dispensing or formulation activity may
include solubilizing the gas in a carrier liquid, adjusting the
concentration, preparing the mixture for injection or inhalation or
other administration as specified by a regulatory agency directive
or physician, or combining one or more different gases or liquids
or other substances with the transported hyperpolarized gas.
Preferably, the materials used to form the product are suitable for
administration to an in vivo subject (pharmaceutical grade
substance). In any event, at the second site, the hyperpolarized
gas held in the multi-bolus container 30L is preferably dispensed
into single use, application-sized, or prescripted amounts or doses
of hyperpolarized product into proportionately sized resilient
containers 30b. Proper conditioning of the bag containers 30b is
preferably observed as will be discussed further below.
[0134] Subsequent to the dispensing step, the second or subsequent
(preferably) single-use sized container can be delivered to a
proximately located use site (if the second site is proximate or
part of a clinical use site such as a hospital). Alternatively, at
the second site, at least one bag 30b is positioned in a second
transport unit 10 which is suitably sized and configured to hold
the bag therein. Preferably, the transport unit 10s is configured
to hold a plurality of bags as shown in FIGS. 12A, 12B . In any
event, one or more bags are positioned in a second transporting
unit 10s and delivered or transported to a third or tertiary site,
preferably the clinical use site. Preferably, for bag containers,
the transport unit 10s includes a magnetic field generator with a
region of high homogeneity. Preferably, the high homogeneity is
such that the gradients are less than about 10.sup.-3 cm.sup.-1
over the volume occupied by the bags 30b.
[0135] In a preferred embodiment, the first transport distance is
such that the hyperpolarized gas is moved at increased times or
distances over conventional uses. Preferably, the transport units
and associated container of the present invention are configured
such that during transport and/or storage, the hyperpolarized gas
(particularly .sup.3He) retains sufficient polarization after about
at least 10 hours from polarization, and more preferably after
about at least 14 hours, and even more preferably greater than
about 30 hours after polarization and when transported to a second
site (and even then a third or tertiary site). Further, the
transport unit and associated containers are preferably configured
to allow greater transit distances or times from the original
polarization point in a manner in which the hyperpolarized product
retains sufficient polarization to provide clinically useful
images. This distribution system is in contrast to the conventional
procedure, whereby the hyperpolarized gas is produced at a
polarization site and nished to a use site (which is typically
relatively close to the polarization site).
[0136] Preconditioning the Container
[0137] Preferably, due to susceptibility of the hyperpolarized gas
to paramagnetic oxygen as noted above, the gas chamber 30 is
preconditioned to remove contaminants. That is, it is processed to
reduce or remove the paramagnetic gases such as oxygen from within
the chamber and container walls. For containers made with rigid
substrates, such as Pyrex.TM., UHV vacuum pumps can be connected to
the container to extract the oxygen. Alternatively, for rigid
and/or resilient containers (such as polymer bag containers), a
roughing pump can be used which is typically cheaper and easier
than the UHV vacuum pump based process. Preferably, for resilient
bag containers, the bag is processed with several purge/pump
cycles. Preferably this is accomplished by pumping at or below 40
mtorr for one minute, and then directing clean (UHP) buffer gas
(such as nitrogen) into the container at a pressure of about one
atmosphere or until the bag is substantially inflated. The oxygen
partial pressure is then reduced in the container. This can be done
with a vacuum but it is preferred that it be done with nitrogen.
Once the oxygen realizes the partial pressure imbalance across the
container walls, it will outgas to re-establish equilibrium.
Typical oxygen solubilities are on the order of 0.01-0.05; thus,
95-99% of the oxygen trapped in the walls will transition to a gas
phase. Prior to use, the container is evacuated, thus harmlessly
removing the gaseous oxygen. Unlike conventional rigid containers,
polymer bag containers can continue to outgas (trapped gases can
migrate therein because of pressure differentials between the outer
surface and the inner surface) even after the initial purge/pump
cycles. Thus, care should be taken to minimize this behavior,
especially when the final filling is not temporally performed with
the preconditioning of the container. Preferably, a quantity of
clean (UHP or Grade 5 nitrogen) filler gas is directed into the bag
(to substantially equalize the pressure between the chamber and
ambient conditions) and sealed for storage in order to minimize the
amount of further outgassing that may occur when the bag is stored
and exposed to ambient conditions. This should substantially
stabilize or minimize any further outgassing of the polymer or
container wall materials. In any event, the filler gas is
preferably removed (evacuated) prior to final filling with the
hyperpolarized gas. Advantageously, the container of the instant
invention can be economically reprocessed (purged, cleaned, etc.)
and reused to ship additional quantities of hyperpolarized
gases,
[0138] It is also preferred that the container or bag be sterilized
prior to introducing the hyperpolarized product therein. As used
herein, the term "sterilized" includes cleaning containers and
contact surfaces such that the container is sufficiently clean to
inhibit contamination of the product so that it is suitable for
medical and medicinal purposes. In this way, the sterilized
container allows for a substantially sterile and non-toxic
hyperpolarized product to be delivered for in vivo introduction
into the patient. Suitable sterilization and cleaning methods are
well known to those of skill in the art.
[0139] Hyperpolarized Gas Transport Protection System Examples
[0140] FIG. 11 illustrates a preferred system for protecting
hyperpolarized (noble) gases (and hyperpolarized gas products in
whatever form such as fluids, liquids, solids, and the like
including other gas or liquid components in whatever form as noted
earlier). A quantity of hyperpolarized gas product is introduced
into a sealable container comprising a gas chamber (and preferably
a capillary stem) at a production site (Block 800). A quantity of a
hyperpolarized gas is captured in the gas chamber (Block 810). A
magnetic holding field is generated from a portable transport unit
thereby defining a substantially homogeneous magnetic holding field
region (Block 820). The gas chamber is positioned within the
homogeneous holding region (Block 830). Preferably, (as indicated
by dotted line) the gas chamber is positioned in the magnetic field
holding region prior to filling. The hyperpolarized gas product is
shielded from stray magnetic fields to minimize the depolarizing
effects attributed thereto such that the hyperpolarized gas retains
a clinically useful polarization level at an end use site remote
from the production site (Block 840). Preferably, the magnetic
holding field step is provided by electrically activating a
longitudinally extending solenoid positioned in the transport unit.
The solenoid comprises a plurality of spatially separated coil
segments (Block 821). It is also preferred that the shielding step
be performed by shifting the resonance frequency of the
hyperpolarized gas in the container to a predetermined frequency as
discussed above (Block 841).
[0141] FIG. 14 illustrates a method and/or system for distributing
hyperpolarized gas products. Noble gas is polarized at a
polarization site (Block 900). A quantity of hyperpolarized gas
sufficient to provide multiple doses of hyperpolarized noble gas
products are captured in a multi-dose container (Block 910). The
multi-dose container is positioned in a portable transport unit
which is configured to provide a homogeneous magnetic field for
holding a major portion of the multi-dose container therein (Block
920). The multi-dose container in the transport unit is transported
to a second site remote from the first or polarization site (Block
930). At the second site, the hyperpolarized gas in the multi-dose
container is distributed into multiple separate second containers
(preferably reduced or patient sized dose containers), and more
preferably single dose bags (Block 940).
[0142] Preferably, at the second site, and also preferably prior to
the distribution step (Block 940), the multi-doses of gas are
subdivided (Block 941) and processed into at least one desired
formulation to form a hyperpolarized pharmaceutical grade product
suitable for in vivo administration (Block 942). Preferably, the
processing and subdividing steps are performed prior to the
distribution of the gas into the secondary containers for
transport. Thus, the processing and/or distribution step at the
second site can include the steps of formulating or otherwise
processing the hyperpolarized gas into a sterile or non-toxic
product such that it is suitable for in vivo human administration.
The processing can include diluting concentration such as by adding
other inert gases (such as substantially pure, at least grade 5,
nitrogen), or carrier or other liquids or substances. The
processing can include manipulating the hyperpolarized gas from the
multi-dose container such that it is formulated into the proper
dosage or mixture according to standard pharmaceutical industry
operation. This may include solubilizing the gas, adjusting the
concentration, preparing the mixture for injection or inhalation or
other administration as specified by a physician, or combining one
or more different gases or liquids or other substances with the
transported hyperpolarized gas. Then, the formulated hyperpolarized
product, substance, or mixture is preferably dispensed into at
least one second container, and preferably into a plurality of
preferably single use size resilient containers which can be
transported to a third or tertiary site.
[0143] From the second site, at least one of the second containers
(preferably a single dose bag container) can be used to deliver a
hyperpolarized product to a user proximate to the second site
(Block 970) or positioned within a second transport unit with a
region of homogeneity (Block 950) and transported to a third site
(preferably an imaging site) remote from the second site (Block
955). The delivery of the product at a site proximate to the second
site is especially applicable for distribution-oriented second
sites which are clinics (such as a wing of the hospital). The
hyperpolarized product can then be administered to a patient at the
imaging site or stored for futures use (Block 975). The
administered hyperpolarized product is useful for obtaining
clinical data associated with Magnetic Resonance Imaging and
Spectroscopy procedures. The transport units according to the
present invention are configured such that during transport and/or
storage the gas has proper shielding as described herein.
[0144] The foregoing is illustrative of the present invention and
is not to be construed as limiting thereof. Although a few
exemplary embodiments of this invention have been described, those
skilled in the art will readily appreciate that many modifications
are possible in the exemplary embodiments without materially
departing from the novel teachings and advantages of this
invention, Accordingly, all such modifications are intended to be
included within the scope of this invention as defined in the
claims. In the claims, means-plus-function clauses are intended to
cover the structures described herein as performing the recited
function and not only structural equivalents but also equivalent
structures. Therefore, it is to be understood that the foregoing is
illustrative of the present invention and is not to be construed as
limited to the specific embodiments disclosed, and that
modifications to the disclosed embodiments, as well as other
embodiments, are intended to be included within the scope of the
appended claims. The invention is defined by the following claims,
with equivalents of the claims to be included therein.
* * * * *