MXPA00012644A

MXPA00012644A - Hyperpolarized gas transport device and associated transport method

Info

Publication number: MXPA00012644A
Application number: MXPA/A/2000/012644A
Authority: MX
Inventors: Kenton C Hasson; Geri T K Zollinger; David L Zollinger; Paul L Bogorad; Bradley A Wheeler
Original assignee: Paul L Bogorad; Kenton C Hasson; Magnetic Imaging Technologies Inc; Bradley A Wheeler; David L Zollinger; Geri T K Zollinger
Priority date: 1998-06-17
Filing date: 2000-12-15
Publication date: 2002-07-25

Abstract

A compact portable transport unit (10) 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 (20) in the transport unit (10). The solenoid (20) includes a plurality of coil segments and is sized and configured to receive the gas chamber of a container (30). The gas container (30) is configured with a valve (32), a spherical body (33), and an extending capillary stem (35) between the valve and the body. The gas container (30) 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.

Description

TRANSPORTATION DEVICE FOR HYPERPOLARIZED GAS AND ASSOCIATED TRANSPORTATION METHOD This invention was made with the support of the Government under the concession No. R43HL62756-01 of the National Institute of Health. The Government of the United States has certain rights in this invention.

RELATED REQUESTS This application claims the priority benefit of Provisional Application No. 60 / 089,692, issued on 6/17/98, entitled "Hyperpolarized Gas Containers and Associated Methods" and Provisional Application No. 60/121, 315, issued on April 23, 1998. / 2/99, entitled "Hyperpolarized gas containers, solenoids, and transportation and storage devices and associated transportation and storage methods". The contents of these applications are incorporated herein by reference as if they were fully mentioned herein.

FIELD OF THE INVENTION The present invention relates in general to the transport of hyperpolarized gases from one site to another, such as from a production site to a site for clinical use. Hypopolarized gases are particularly ^^? h? im ^ ná á? átimi mmm? amitittíit? aMkrfj | H | b¿ aÉÉjHtaü faith | Ki suitable for MR imaging and spectroscopy applications.

BACKGROUND OF THE INVENTION Imaging with inert gas ("IGI") using hyperpolarized noble gases is a promising recent advance in the technologies of Magnetic Resonance Imaging (MRI) and MR spectroscopy. 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 that have hitherto produced unsatisfactory images in this embodiment. It has been found that polarized Helium-3 ("3He") and Xenon-129 ("129Xe") are particularly suitable for this purpose. Unfortunately, as will be mentioned below, the polarized state of the gases is sensitive to driving conditions and environmental conditions and, the gases can undesirably decompose from the relatively fast polarized state. Various methods can be used to artificially increase the polarization of certain noble gas nuclei (such as 129Xe or 3He) over the natural or equilibrium levels, ie, the polarization of •• -. - - * • 'Boltzmann. Such an increase is desirable because it improves and increases the intensity of the MRI signal, allowing doctors to obtain better images of the substance in the body. See the patent of E.U.A. No. 5,545,396 to Albert et al., The disclosure of which is incorporated herein by reference as being fully mentioned herein. A decomposition time constant "TT" related to the longitudinal relaxation of the hyperpolarized gas is often used to characterize the time it takes for a gas sample to depolarize in a given situation.Hyperpolarized gas handling is critical due to the sensitivity of the gas. hyperpolarized state to environmental and management factors and therefore the undesirable decomposition potential of the gas from its hyperpolarized state before the planned final use, for example, supplying a patient for imaging Process, transport and store the hyperpolarized gases - thus how to deliver 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, interactions of hyperpolarized gas atoms with other nuclei, paramagnetic impurities, and the like. to minimize the decomposition n induced surface of the hyperpolarized state is presented in the U.S.A. patent No. 5,612,103 to Driehuys et al., Entitled "Coatings for production of hyperpolarized noble gases". Said in general, this patent describes the use of a modified polymer as a surface coating on ll l physical systems (such as a Pyrex ™ container) that come in contact with the hyperpolarized gas to inhibit the decomposition effect of the surface of the collection chamber or storage unit. Other methods for minimizing surface-induced or contact-induced decomposition are described in the U.S. patent application. co-pending and jointly assigned Series No. 09 / 163,721 of Zollinger et al., entitled "Methods of extraction of hyperpolarized noble gases, masking methods, and associated transport containers", and the Patent Application of E.U.A. co-pending and assigned jointly identified by Case 10 of Attorney No. 5770-12IP, entitled "Elastic containers for hyperpolarized gases and associated methods". The contents of these applications are incorporated herein by reference as if they were fully mentioned herein. However, other mechanisms of relaxation arise during the production, handling, storage, and transportation of hyperpolarized gas. These problems can be particularly troublesome when storing the gases (especially increased amounts) or transporting the hyperpolarized gas from a production site to a (far) use site. During transit, hyperpolarized gas can be exposed to many potentially depolarizing influences. In the past, a frozen amount of 129Xe (approximately 300cc-500cc) hyperpolarized was collected on a cold index and placed in a metal lined Dewar flask along with a small fork of permanent magnets arranged > M * m * v ** m **. , =; . , - > . -. . . . . . . *,. -, «,, - ^ - j ^ -y.,. to provide a magnetic retention field for it. The frozen gas was then taken to an experimental laboratory for supply to an animal subject. Unfortunately, the permanent magnet fork provided a relatively small magnetic field region (volume) 5 with a relatively low magnetic homogeneity associated therewith. In addition, the thawed sample produced a relatively small amount of useful hyperpolarized 129Xe (used for small animal subjects) that would not generally be sufficient for most patients with human dimensions. Accordingly, there is a need to provide improved ways to transport hyperpolarized gases so that the hyperpolarized gas is not unduly exposed to depolarizing effects during transportation. Improved storage and transportation methods and systems are desired for which hyperpolarized product can retain sufficient polarization and larger amounts to enable effective imaging in the supply when stored or transported longer transport distances under various environmental conditions (potentially depolarizing) ), and for longer periods from the initial polarization that has been previously feasible. ^^ e ^? OBJECTS AND BRIEF DESCRIPTION OF THE INVENTION Accordingly, an object of the present invention is to provide a transportation system that can protect gas products hyperpolarized potentially depolarizing environmental exposures during the movement of hyperpolarized gas products from a production site to a site of distant use. It is also an object of the present invention to configure a transportation unit that alternatively or additionally serves as a portable storage unit, to retain the polarized gases in their polarized state for longer periods including before shipment, or before shipment. supply even if the gases are not going to be shipped remotely. It is also an object of the present invention to provide a portable unit for storing or transporting an amount of hyperpolarized gas therein, which can substantially protect the hyperpolarized gas from the depolarizing effect or diffusion of gas atoms through magnetic field gradients. Another object of the present invention is to provide a unit portable for storing or transporting a hyperpolarized gas unit 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).

Aí ^ m m ?.

Another object of the present invention is to provide a method for protecting the hyperpolarized gas from the depolarizing effects of undesirable EMI at a frequency or scale of predetermined frequency. Another object of the present invention is to provide a relatively compact device,. gero, easily transportable that can provide enough protection for the hyperpolarized gas to allow the hyperpolarized gas to be transported successfully (as in a vehicle) from a production site to a site of distant use, so that the hyperpolarized gas retains a sufficient level polarization at the site of use to allow clinically useful images. Another object of the invention is to provide a hyperpolarized gas chamber with valve configured to inhibit polarization decomposition (i.e., has relatively long decomposition times) during transportation and / or storage. Another object of the invention is to configure a transportation unit to minimize external force related to impact, vibration, and other mechanical collisions that are introduced into or transmitted to the hyperpolarized gas container. Another object of the invention is to provide a protective compartment for a transportation unit which is configured in such a way that the hyperpolarized gas retained in an internally disposed hyperpolarized gas chamber can be directed out of or into the transportation unit (i.e. the gas chamber can be filled and / or emptied), without the need to remove the gas chamber from its protective housing. Another object of the invention is to configure a transportation unit with an easily accessible means for gas interrogation polarized retained within the gas chamber retained therein using nuclear magnetic resonance (NMR), in order to measure the polarization of the gas, or to measure the decomposition rate of the polarization. Another object of the invention is to provide a means for adjusting the magnetic field strength generated by a transport unit, in order to deflect the Larmor frequency of the spins related to the hyperpolarized gas, either for the purposes of NMR measurements, or to minimize the decomposition derived from electromagnetic interference at a frequency of interest. A further object of the present invention is to increase the protection effectiveness of the transportation units. Another object of the invention is to provide a way to transport hyperpolarized gases from a polarization site to a secondary and / or tertiary distribution site while maintaining a level of hyperpolarization sufficient to allow clinically useful images in the end-use site. These and other objects of the present invention are provided by the transportation (and / or storage) units of the present invention that are configured to protect hyperpolarized gas (and gas products). - l * »" ^ - and in a container or multiple containers) retained therein, thus minimizing depolarization losses introduced during the transportation of a hyperpolarized gas product from one place to another. of the invention is directed to a transportation unit used to transport hyperpolarized products therein The transportation unit comprises at least one gas chamber configured to retain a quantity of hyperpolarized product therein and at least one electromagnet that provides a magnetic field that defines at least one region of homogeneity.

The homogeneous magnetic field is dimensioned and configured to receive a main portion of the gas chamber (gas retention container) therein. The magnetic holding field is preferably provided primarily by a solenoid comprising at least one wire carrying current therein. In a In this embodiment, the gas chamber is defined by a single-dose or multiple-dose rigid body container. In an alternative embodiment, the gas chamber is defined by an elastic body container with an expandable gas chamber (preferably sized and configured to retain an individual dose of patient). In a preferred embodiment, a solenoid coil is configured to generate the magnetic retention field. Preferably, the solenoid coil is also dimensioned and configured to maximize the volume of the sufficiently homogeneous region provided by the Also, preferably the transport unit includes one or more layers of an electrically conductive metal around the compartment, as such, the compartment can provide protection from external electromagnetic radiation as well as mechanical support. and protection.The transportation unit may also include one or more layers of magnetically permeable materials, such as soft iron or mu metal, to provide additional electromagnetic protection, (including magnetic CD protection), or to act as a flow return. aspect of the present invention is a solenoid coil for providing a homogeneous magnetic field region in which the hyperpolarized gas is retained.The solenoid comprises a cylindrical body and a first coil segment having a first coil length and a first number of windings arranged in the cylindrical body The solenoid also includes a second and third coil segments having respective second and third coil lengths and respective second and third number of windings disposed in the cylindrical body. The first, second, and third coil segments are spatially separated and placed in the cylindrical body such that the second coil segment is between the first and third coil segments. In a preferred embodiment, the second coil length is larger than 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 favorably provide a sufficiently homogeneous retention region for the hyperpolarized gas within a relatively compact coil area, thus allowing the coil (as well as any related transportation unit) itself to be more compact while providing also a useful dose of the hyperpolarized gas that is to be contained and protected in it. Another aspect of the present invention is a hyperpolarized gas product container having a gas retention chamber and a capillary tube. The capillary tube has an internal diameter and length configured and dimensioned such that the capillary tube preferably inhibits the migration or diffusion exchange of the hyperpolarized gas product between the main body of the chamber and the upper portion of the gas container which Preference includes a valve. More specifically, the capillary tube is dimensioned in such a way that the ratio of the volume of the main body to the volume in the capillary tube, multiplied by the diffusion time for 3He to cross the length of the capillary, is greater than the Ti of a chamber sealed of the same material and dimensions. The exchange of gas product between the main body and the valve is undesirable since the valve is typically in a region of higher magnetic field gradients. Also, the valve may comprise materials that may undesirably introduce surface induced relaxation in the polarized gas. The container itself can be configured as a rigid body or elastic body. h-MfJjMáata-lltai-ÍM ^ -.- MI-_H "He '" * - - "*" - - * - * - ** - «--- Another aspect of the present invention is a transportation unit which includes at least one elastic container (and preferably a plurality of elastic containers) for retaining a quantity of hyperpolarized gas (or liquid) product therein.In operation, one or more of the elastic containers may be placed within a homogeneous region of a magnetic field produced by the transportation and / or storage unit Another aspect of the present invention is a system for distributing hyperpolarized gases, and preferably doses sized for patients with hyperpolarized gases. The system includes a first transportation unit which is dimensioned and configured to retain a multiple dose container therein. The system also includes at least a second transportation unit sized and configured to carry a plurality of individual dose containers therein. Preferably, the multi-dose container is a rigid body container and the individual dose containers are elastic baffles having expandable chambers to allow easy delivery or administration at a site of use. Similarly, in one embodiment, the dose container Multiple is transported to a pharmaceutical distribution point where the hyperpolarized gas in the multi-dose container can be formulated into the appropriate dosage or mixture according to the operation of the standard pharmaceutical industry. This may include solubilizing the gas, adjusting the concentration, prepare the mixture for injection or inhalation or other administration as specified by a physician, or by combining two different gases or liquids or other substances with the hyperpolarized gas transported. Then, the formulated hyperpolarized product, substance or mixture is preferably supplied in at least a second container, and preferably in a plurality of elastic containers of individual size that can be transported to a third site or tertiary site for use. In a preferred embodiment, the first transportation distance is such that the hyperpolarized gas moves at times or distances increased over conventional uses. Preferably, the transportation units and associated container of the present invention are configured such that during transportation and / or storage, the hyperpolarized gas (particularly 3 He) retains sufficient polarization after approximately 10 hours from polarization, and preference after at least 14 hours, and most preferably (especially for 3He) after about 30 hours. In other words, the transport units and associated containers of the present invention allow clinical use after a time elapsed of approximately 30 hours from the original polarization and after transportation to a second site (and even after a third). site or tertiary site). Conveyors and containers are preferably also configured to allow greater transit distances or longer transit times. In other words, the hyperpolarized product retains sufficient polarization after transport and longer time since polarization when placed in the transportation units to provide clinically useful images. This distribution system is in contrast to the conventional method, whereby the hyperpolarized gas is produced at a polarization site and quickly brought to a use site (which is typically close to the polarization site). A further aspect of the present invention is directed to a method for 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 diverting the resonant frequency of the hyperpolarized noble gas out of the predetermined electromagnetic interference frequency scale. Preferably, the method includes deflecting the normal resonance frequency related to the hyperpolarized gas at a frequency substantially outside the bandwidth of usual time-dependent fields produced by electrically powered equipment (such as computer monitors), vehicle engines, acoustic vibrations , and other sources. In a preferred embodiment, the resonant frequency of the hyperpolarized gas is deflected by applying a static magnetic field proximate to the hyperpolarized gas. For example, preferably for a hyperpolarized gas product comprising 3He, the applied static magnetic field is at least about 7 Gauss, while for hyperpolarized gas products comprising 129Xe, the applied magnetic field is at least about 20 Gauss. Another aspect of the present invention is directed to a system for preserving the polarization of the gas during transportation. The system includes the steps of introducing an amount of hyperpolarized gas product into a sealed 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 transportation unit that defines a magnetic retention region substantially homogeneous therein. The gas chamber is positioned within the homogeneous retention region and the hyperpolarized gas product is protected to minimize the depolarizing effects of external magnetic fields so that the hyperpolarized gas has a clinically useful polarization level at a site far away from the surface. Production site In a preferred embodiment, the step of providing the magnetic retention field is performed by electrically activating a longitudinally extending solenoid positioned in the transportation unit. The solenoid comprises a plurality of spatially separated coil segments, and the sealable container comprises a capillary tube in fluid communication with the gas chamber. The present invention is favorable because the transport unit can protect the hyperpolarized gas and minimize the depolarizing effects attributed to external magnetic fields, especially harmful oscillating fields, which can easily dominate other mechanisms of relaxation. The transport container is relatively compact and therefore, it is easily transported. Preferably, the transportation unit includes a homogeneous magnetic retention field next to the gas container so as to provide sufficient protection for the hyperpolarized state of the gas and facilitate transportation of the gas to an end-use site. In a preferred embodiment, the transportation unit includes a solenoid having at least one configuration of three coil segments with the central coil segment having a reduced number of layers of wire compared to the other two (opposite) coil segments. Stated differently, the opposite end segments have a greater number of wire layers that provide increased current density (current per unit length) in these areas. Advantageously, said coil segment design can extend the homogeneous region of the magnetic field generated by the solenoid while minimizing the size (length) of the solenoid itself. This relatively compact transportation unit can easily deliver a single dose of patient or a plurality of patient doses (combined or individual). In addition, the transportation unit is configured such that it can use an adjustable current to allow field adjustments, thus allowing correction for one or more electronic or mechanical drift, the type of gas transported, and severe exposure conditions. Also, the transportation unit can be used with more than one type of hyperpolarized gas, for example, 3He or 129Xe. In addition, the transportation unit can be configured so that the hyperpolarized gas can be released at the end-use site without removing the typically slightly brittle gas chamber from the transportation unit (when glass chambers are employed). This capability can protect the intermediate depolarizing handling gas and can also facilitate the safe release of the gas by protecting any users near the transport unit from exposure to the internal gas container (such as a glass sphere) that is typically under relatively high pressure. high. Alternatively, the transportation unit can protect gas containers elastically configured to provide products sized for individual doses easy to dispense. In addition, the gas container preferably includes a capillary tube and / or orifice isolation means that inhibits diffusion or movement of the hyperpolarized gas outside the main body, thereby helping to retain a majority of the hyperpolarized gas within the homogeneous retention region. and inhibiting the contact between the hyperpolarized gas and the potentially depolarizing materials in the sealing medium. Also, the walls of the compartment of the present invention are preferably configured so as to provide sufficient spatial separation of the gas container to increase the protection effectiveness of the transportation unit.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a front perspective view cut away of a transportation unit according to the present invention, the transportation unit comprising a gas chamber and solenoid. Figure 2 is an enlarged front view of the solenoid and gas chamber shown in Figure 1. Figure 2A is a perspective view of the solenoid shown in Figures 1 and 2. Figure 3 is a perspective view cut away of the solenoid. of Figure 2A illustrating the current direction and direction of the magnetic retention field and the highest homogeneity region in the solenoid. Figure 3A is a graph illustrating a preferred dvanado / current distribution in relation to the distance along the entire length of the solenoid, representing (2i) a current density that is twice that of the central coil segment (i), together with negligible current points between the coil segments. Figure 4 is a side view of a gas chamber configuration particularly suitable for use with the transportation unit according to the present invention. * * '> * - Figure 5 is a front perspective view of the transportation unit shown in Figure 1. Figures 6, 6A, and 6B are perspective views of transportation units configured to transport multiple containers of hyperpolarized gas products in accordance with alternate embodiments of the present invention. Figure 7 is a schematic illustration of a power monitoring and change circuit for use with a portable transportation unit in accordance with the present invention. Figure 8 is a schematic illustration of an operation circuit for use with a portable transportation unit related to a preferred embodiment of the present invention. Fig. 9 is a front perspective view of a calibration / anchoring station according to the present invention; Fig. 10 is a graphic representation of the normalized magnetic field generated by a solenoid embodiment of the present invention (bell-shaped curve); higher) compared to a coil having a uniform current density per unit length (lower bell curve). Figure 11 is a flow chart of a system for protecting hyperpolarized gas from the depolarizing effects attributed to external magnetic fields during transportation, thus preserving the polarized life of the gas.

Figure 12A is a partial or perspective cutaway view of a multiple transport distribution system.The distribution system provides a multi-dose container to a second site away from the polarization site. In the second site, the hyperpolarized product in the multiple dose container is divided, mixed or otherwise formulated into single use individual containers for delivery to a tertiary site (preferably a site of clinical use) in accordance with the present invention. Figure 12B is a schematic view of a drawer for facilitating the placement of a plurality of individual sized elastic containers in a single solenoid sized to house them Figure 13 is a partial cut-away perspective view of a distribution system that employs a plurality of magnetic retention field generators in the second transportation unit.Figure 14 is a flow chart of a distribution system according to the present invention.

DETAILED DESCRIPTION OF THE INVENTION The present invention will now be described with reference to the accompanying drawings, in which preferred embodiments of the invention are shown. However, this invention can take many forms and should not be construed as limited to the modalities set forth herein; rather, these modalities are provided so that this description is detailed and complete, and fully convey the scope of the invention to those skilled in the art. Similar numbers refer to similar elements in the present. In the figures, the layers and regions can be exaggerated for clarity. For ease of exposure, the term "hyperpolarized gas" is used to describe a hyperpolarized gas alone, or a hyperpolarized gas that is in contact with or combines with one or more components, be it gaseous, liquid, or solid. Thus, the hyperpolarized gas described herein can be a hyperpolarized gas composition / mixture (preferably non-toxic so as to be 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 in another liquid (such as a fluid vehicle) or processed in such a way that it becomes a substantially liquid state , i say, "a liquid polarized gas". In brief, as used herein, the term "gas" has been used in ain places to descriptively indicate a noble gas of hyperpolarized acid and which may include one or more components and which may be present in or further processed to be in one or more physical forms.

Background-Hyperpolarization Various techniques have been used to polarize, accumulate and capture polarized gases. For example, the patent of E.U.A. No. 5,642,625 to Cates et al. discloses a high volume hyperpolarizer for noble gas 5 polarized by spin and the US patent. No. 5,642,625 to Cates et al. describes a cryogenic accumulator for 129Xe polarized by spin. The descriptions of this patent and application are hereby incorporated by reference as if they were mentioned in their entirety herein. As used herein, the terms "hyperpolarize" and "polarize" are used interchangeably and mean to artificially increase the polarization of certain noble gas nuclei over natural or equilibrium levels. Such an increase is desirable since it allows stronger imaging signals corresponding to better MRI images of the substance in a target area of the body. As is known to those skilled in the art, hyperpolarization can be induced by spin exchange with an optically pumped alkaline metal vapor or alternatively by exchange of metastability. See the patent of E.U.A. 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 alkaline metals for this hyperpolarization technique include Sodium-23, Potassium-39, Rubidium-85, Rubidium-87, and Cesium-133.

- .-HE HAS-- . KOi? Lt * »*** - ** - A A A, A. *. **. ... .a a, .. .. - .. .. A. * .. .. * .. *. . , ...., * .... JJ, ..,. . ^^^ 0 ^ * ^.

Alternatively, noble gas can be hyperpolarized using metastability exchange. (See, for example, Schearer, LD, Phys Rev, 180: 83 (1969), Laloe, F., Nacher, PJ, Leduc, M., and Schearer LD, AIP ConfProx # 131 (Workshop on Polarized 3 Beams and Targets) (1984)). The metastability exchange technique involves direct optical pumping of, for example, 3He without the need for an alkaline metal intermediate. Because this process works best at low pressures (0-10 Torr), a compressor is typically used to compress 3He after the hyperpolarization step. Regardless of the hyperpolarization method used, once the active mechanism is no longer in effect, the polarization of the gas will inevitably decompose towards its equilibrium value term, which is essentially zero. The present invention is configured to operate with any hyperpolarization technique and, as will be understood by one skilled in the art, is not limited to working with any type of machine, method, or particular gas.

Polarized gas relaxation procedures Under most circumstances, the non-equilibrium polarization P (t) of a gas decomposes according to dPytydt-Pítyr-i 1.0 The total decomposition rate is equal to the sum of velocities of several mechanisms: 1 / T? - (1 / T?) Gas + (1 /?) surface + (1 /?) EMI + (1 / T- | gradient 2.0 Gas Interaction Relaxation The first decomposition term (1 / T?) Cas represents the depolarization of noble gas nuclei when they interact with each other and may also include interaction of the atoms with gaseous impurities such as oxygen. Therefore, careful preparation of the containment, transfer, and gas extraction systems is important in order to provide good polarization lives as will be mentioned below. Examples of suitable gas extraction methods and apparatus are described in the U.S. Patent Application. co-pending and jointly assigned Series No. 09 / 163,721, entitled "Methods of extraction of hyperpolarized noble gases, methods of masking, and associated transportation containers", identified by the Case of Attorney No. 5770-14, whose description is incorporated in the present by reference as if it were mentioned in its entirety herein. Even in the absence of other relaxation mechanisms, collisions between identical polarized gas atoms impose a fundamental upper limit on the feasible T-i life. For example, 3He atoms relax through a dipole-dipole interaction during 3He-3He collisions, while 129Xe atoms relax through the spin rotation interaction Nl where N is the molecular angular momentum and I designates nuclear spin rotation) during collisions 129Xe-1 '! 9Xe. In any case, because both procedures occur during noble gas-noble gas collisions, both resulting relaxation velocities are directly proportional to the number density (T-i is inversely proportional to number density). At a barium pressure, the theoretical maximum relaxation time T-i of 3He is approximately 750 hours, and for 129Xe the corresponding relaxation time is approximately 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 129Xe in Natural Xenon," 130 Phys Rev. p. 2302 (1963). 10 Unfortunately, other relaxation procedures such as surface relaxation, electromagnetic interference (EMI), and magnetic gradient relaxation can prevent the realization of these theoretical relaxation times. Consequently, each of these mechanisms is of interest when handling hyperpolarized gases and preferably is required to allow the total relaxation time to be large enough.

Surface-induced relaxation The term (1 / T-? Surface represents the mechanism of relaxation induced by surface. For example, historically it has been thought that collisions of gaseous 129Xe and 3He with container walls ("surface relaxation") dominate most relaxation procedures. For 3He, most of the longest known relaxation times have been - - - "" - • "* -" * »- achieved in special glass containers that have low helium permeability. See Fitzsimmons et al., "Nature of surface induced spin relaxation of gaseous He-3," 179 Phys. Rev., No. 1, p. 156 (1969). The patent of E.U.A. No. 5,612,103 to Driehuys et al. describes the use of coatings 5 to inhibit surface-induced nuclear spin relaxation of hyperpolarized noble gases, especially 129Xe. The content of this patent is hereby incorporated by reference as if it were mentioned in its entirety herein. Similarly, the patent application of E.U.A. co-pending and jointly assigned Series No. 09 / 126,448 of Deaton et al., and 0 their related request identified by Proxy Case No. 5770-12IP, describe preferred gas contact surface materials and related thicknesses, O-rings, and valve or seal materials and / or coatings that do not damage the polarized state of the gas, i.e., that can inhibit surface / contact induced relaxation mechanisms. The content of these applications is also incorporated herein by reference as if they were mentioned in their entirety herein.

Electromagnetic interference The relaxation mechanism expressed by the term (1 / T EMI is 0 the relaxation induced by electromagnetic fields dependent on time.

Indeed, EMI can potentially destroy the hyperpolarized gas state (EMI is particularly problematic if it is consistent in the MRI frequency). Unfortunately, the EMI can be generated ^^ ^ - - * • - '' by relatively common sources. For example, EMI is typically generated from a vehicle engine, high voltage lines, power stations and other current carrying entities. As such, transportation away from the hyperpolarized gas production site can expose the hyperpolarized gas to these undesirable sources of relaxation which, in turn, can dramatically reduce the polarization life of the transported gas. Fluctuating fields are particularly harmful if they are consistent in the frequency of magnetic resonance. For example, assuming the worst of the scenarios of a highly oscillating field consistent, the relaxation rate is expected to be comparable to the Rabi frequency: (1 T?) E i *? HAc / 2 2.10 Here, "?" is the gyromagnetic relation of the spins, "HAC" is the magnitude of the transverse fluctuating field. A resonant field HAc of only 1μG would cause relaxation on a time scale of the order of 100 seconds for 3He. On the other hand, if the field is fluctuating randomly, the relaxation rate is given by (1 / TI) EMI =? 2 < HAC2 > tc / (1+? 2t c2) 2.20 where V is the autocorrelation time of the fluctuations, "?" is the Larmor frequency of the spins, and "< HAc2 >" is the mean value of the square of the fluctuating transverse field component. In the case of random fluctuation, the velocity can be suppressed by increasing? (Which is proportional to the retention field strength), particularly if ? tc > 1. In either case, the relaxation rate can be suppressed by reducing the magnitude of the HAC interference.

Magnetic field gradients 5 Magnetic gradient relaxation expressed by the term (1 / T? Gradient) is related to the relaxation attributed to the exposure of hyperpolarized noble gases to heterogeneous static magnetic fields., as the polarized gas atoms diffuse or move through a heterogeneous magnetic field, they experience a time-dependent field, which can introduce depolarizing activity in the hyperpolarized atoms. For example, at typical pressures (ie approximately 1 barium), the relaxation rate attributed to a static magnetic field gradient can be expressed by the following equation: 15 (1 / T Gradient = D (| VBX | 2 + | VBy | 2) / Bz2 2.30 Here, "Bz" is the main component of the static magnetic field, "VBX" and "VBy" represent the gradients of the transversal field components, and "D" is the diffusion coefficient of the atoms polarized through the gas, for example, for pure 3He at 1 barium pressure, 20 the diffusion coefficient D «1.9 cm2 / s.In the earth's magnetic field (generally represented by a static magnetic field of approximately 0.5 G) , a transverse field gradient of 5 mG / cm causes a relaxation rate (1 / T? gradient of approximately 1.9 x 10" a ^ -a MtiHM tiAA.AMe. . ,. . . . . t -., .- - - > - - to - . • "-. , 4 -, • * '- - * í * ** > A.MMK? * ~.

V1 (ie, a Ti of 3He of approximately 1.5 hours). In contrast, in a 5 gauss field (as opposed to a 0.5 gauss field), the same gradient of 5mG / cm will typically produce a T-i of about 150 hours. Therefore a magnetic field homogeneity in the order of 10"5 3 cm" 1 is desirable to make the gradient relaxation tolerable at these pressures. Alternatively, higher gradients are acceptable if the 3He is pressurized at some pressure bars, or alternatively mixed with another gas such as nitrogen or argon to restrict diffusion, i.e., decrease the diffusion coefficient. As will be understood by those skilled in the art, during transportation, it is desirable to avoid heterogeneous magnetic fields, for example, to avoid nearby ferromagnetic objects. For example, it is desired to maximize as much as possible the spatial distance between the hyperpolarized gas and objects that can produce strong magnetic fields and / or magnetic field gradients. Protection The present invention recognizes that unless special precautions are taken, relaxation due to external magnetic fields (static and / or time-dependent) can dominate the other relaxation mechanisms. As mentioned above, both gradients in the static field and oscillating (low frequency) magnetic fields experienced by the hyperpolarized gas can cause significant relaxation.

In a favorable manner, the present invention employs a substantially static magnetic retention field applied (externally) "BH" to substantially protect the hyperpolarized gas from depolarizing effects attributed to one or more of EMI and gradient fields during transportation. The present invention employs a magnetic retention field that raises the Larmor frequency of the hyperpolarized gas above the noise region (1 / f), that is, the region where the ambient electromagnetic noise intensity is typically high (this noise is typically found below about 5 kHz). In addition, the field of The magnetic retention of the present invention is also preferably selected so as to raise the frequency of the hyperpolarized gas to a level which is above the frequencies related to large acoustic vibrations (these acoustic vibrations are typically less than about 20 kHz). As will be mentioned later, the frequency The increase associated with the favorably applied magnetic retention field allows a transportation unit to have greater electromagnetic protection effectiveness for a given housing thickness (the housing used to retain the hyperpolarized gas therein during transportation). The penetration depth "d" of a material protective conductor is inversely proportional to the square root of the frequency. Therefore, at 25 kHz, an example of penetration depth for aluminum is approximately 0.5 mm, compared to approximately 2.0 mm to 1.6 kHz. ,? it m * M ^ - -.

Preferably, the magnitude of the magnetic retention field of the present invention is selected such that any fluctuations related to the external field are small in magnitude compared to the field strength of the retention field; In this way, the retention field can reduce to a minimum the hyperpolarized gas response to relaxation induced by unpredictable external static field gradient. This can be achieved by applying hyperpolarized gas a magnetic retention field placed nearby that is sufficiently intense and homogeneous so as to minimize relaxation related to unpredictable static field during transportation. A sufficiently homogeneous retention field preferably includes (but is not limited to) a magnetic retention field having a homogeneity that is in the order of approximately at least 10"3 cm" 1 over the central part of the retention field. In the previous example, if a field homogeneous of approximately 10 G was applied, the same gradient of 5 pG cm "1 would result in Ti" 600 hr. Most preferably, the magnetic field retention homogeneity is approximately at least 5 x 10"4 cm" 1 about a region of interest (that is, the region of interest is the region related to the main volume of the gas hyperpolarized in the container (s)) in the transportation unit. Preferably, this volume is dimensioned and configured as a volume in the space representing approximately at least one sphere of 7.62 cm in diameter. In addition, the transportation unit 10 of this invention includes and provides a magnetic retention field that is positioned, sized, and configured relative to the hyperpolarized gas retained therein so as to also minimize the EMI or oscillating magnetic field depolarization effects therein. The depolarizing effect of EMI is preferably (substantially) blocked by applying the magnetic retention field (BH) close 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 usual time-dependent fields produced by sources powered by electric power. Alternatively, or additionally, protection from external interference can be achieved by placing 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 protection thickness is related to the spatial decomposition constant of an electromagnetic wave or penetration depth "d". The penetration depth d at an angular frequency "?", Given by "d = c / (2pμs?) 1/2", where "μ" is the magnetic permeability and "s" is the electrical conductivity of the material. At these frequencies, the wavelength of Larmor radiation is relatively long (-10 km), and is much larger than the size of the container. The effectiveness of protection therefore depends on the geometry of the container as well as the thickness of protection. For a thin spherical conductor of radius "a" and thickness "t", the protection factor for wavelengths "?" where? »a can be roughly represented by the following equation 5 Interestingly, the protection effectiveness increases as the size (radius) of the protection is increased. For the Accordingly, it is preferred that the metal compartment used to protect or surround the hyperpolarized gas be configured and dimensioned to define an internal volume and spatial separation relative to gas that is sufficient to provide increased protection effectiveness. In other words, it is preferred that the opposite walls of the compartment be separated by a predetermined distance relative to the position of the gas container r-held therein. Preferably, the walls define a minimum linear separation for the main volume of the container or chamber (the portion retaining a major portion of the gas or hyperpolarized product) so that there is approximately at least 3.81 cm. preferably at least 5.08 cm, and most preferably at least about 6.35 cm distance between the metal wall and the leading edge of the gas holding chamber on all sides. *,., - ** fe * - * ~ - • - • - As shown in Figure 1, the transportation unit 10 has a compartment 60 with a geometry in which the walls of the compartment are configured and sized to provide an internal volume 65 or geometry that is relatively large compared to the size of the gas container (s) 30 (30b, Figure 12). As shown also, the walls 63A, 63B, 63C, 63D are configured in such a way that the gas holding chamber 30, when in position in the compartment 60, is spaced a distance from the adjacent wall segments to provide sufficient space to facilitate the effectiveness of protection of the metal wall. That is, the opposite walls 63B, 63C and 63A, 63D (and preferably including the opposite upper and lower walls 63E, 60A) each have a minimum distance of separation preferably at least about 3.81 cm, and preferably at least 5.08 cm , and most preferably at least 6.35 cm in all directions from the main portion of the gas holding chamber 30. In a preferred configuration, the separation distances of the container 30 (30b, FIG. 12) as retained in the unit Transportation 10, have dimensions and geometric configuration to define a maximum separation ratio. That is, the separation ratio can be described as the linear distance from the center of the main volume of the container holding a volume of hyperpolarized gas to the edge thereof (i.e., the linear average width, or the radius of a gas chamber). spherical) at the minimum linear separation distance of each (or closest) wall from the leading edge of the portion of the gas holding chamber that retains the main volume of the gas. Preferably, the container and compartment are configured to provide a ratio that is less about 0.60. Alternatively, or additionally, the transport unit 10 may be configured with at least one layer formed of about 0.5 mm thick of magnetically permeable material, such as soft carbon steel of low carbon, or mu metals (by virtue of its greater magnetic permeability). However, these materials can significantly influence the static magnetic field and must be designed in conformity so as not to adversely affect the homogeneity. Regardless of the penetration depth of the materials (types of materials and number of layers) used to form the shipping container compartment, application of a homogeneous magnetic retention field close to the hyperpolarized gas can help by minimizing the depolarization of gas by virtue of decreasing the depth of penetration d, which is inversely proportional to the square root of the frequency. In addition, it helps by taking out the resonant frequency of gas from the bandwidth of common AC fields. It is preferred that the resonant frequency of the hyperpolarized gas be high so that it is above about 10 kHz, and most preferably high so that it is between about 20-30 kHz. Stated differently, it is preferred that for protection, the applied magnetic retention field has a field strength of about 2 to 35 gauss. HE A-M.Mblu.-Jk .. prefers even more than for 129Xe, the magnetic retention field is preferably at least about 20 Gauss; and for 3He, the magnetic retention field is preferably at least about 7 Gauss.

Transportation unit Referring now to Figure 1, a transportation unit 10 is illustrated according to a preferred embodiment of the present invention. As shown, the transportation unit 10 includes a magnetic field generator 20 'disposed therein, which provides a Magnetic holding field (BH) 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 transportation unit 10 also includes a power source 40 and operating circuitry 50 preferably provided on a printed circuit board 51 disposed internally. The transportation unit 10 preferably includes a substantially non-ferromagnetic metal cover or housing compartment 60 having a predetermined depth of penetration suitably sized to provide the desired protection, Y which includes a lower portion 60B and an upper portion 61 A (FIG. 5) that opens to facilitate access to the outlet orifice 31 and valve 32 of the gas chamber 30. It is preferred that the transportation unit 10 be configured with a minimum amount of ferromagnetic materials in or within the transportation unit 10 (i.e., is substantially free of ferromagnetic materials that are not designed to create the homogeneous retention field). Although to facilitate the disclosure, the term "transportation" is used to describe the unit, one skilled in the art will understand that the present invention can also be used to store a quantity of hyperpolarized gas product therein. As such, the term "transportation unit" includes a unit that can be used either as a storage unit, a transportation unit, or a storage or transportation unit. As shown in Figures 1 and 5, the upper portion 61 A of the housing is hinged to the lower part of the cover 60B, which defines a compartment volume 65. Preferably, as shown in Figure 1, the volume of compartment 65 is defined by a contiguous arrangement of four straight side walls 63A-63D (63D not shown) connected by a bottom wall 63E and an upper face plate 60A, 60A '. Therefore, the compartment 65 surrounds the gas chamber 30 and other internally mounted components (such as a power source 40 and operating circuitry 50). As shown in Figure 5, the upper portion 61 A preferably includes pawls 200A, 200B which engage the corresponding components 210A210B positioned on the outer wall of the lower portion of the cover 60B to fix the upper portion 61 A in the lower portion of the lower portion 60B where the upper portion 61 A is closed (ie, preferably during transportation). Preferably, the compartment 60 and, indeed, the entire transportation unit 10, is configured not to damage the polarization (substantially devoid of paramagnetic and ferromagnetic materials) in such a way that the transportation unit 10 does not introduce significant reductions in the level of polarization of the hyperpolarized gas in it. Stated generally, as the electromagnetic leak is proportional to the holes or openings in the housing 60, it is preferred, either when the upper part of the housing 61 A is closed or by forming the face plate 60A to attach to the lower part of the housing 60A. the cover 60B so that the outer walls of the housing 60 define a substantially continuous body (without openings) to minimize the entry of electromagnetic waves into the housing 60. Of course, the housing 60 may include openings as long as they are placed or formed in the housing 60 such that any leakage of electromagnetic interference is directed away from the solenoid core 33 where the gas chamber 30 resides and / or is configured with a protective cover or seal to provide sufficient housing integrity in order to reduce to a minimum the loss by polarization attributed to it. A suitable housing 60 is a relatively compact aluminum cover (having approximately a 1 mm wall thickness) manufactured by Zero Enclosures of Salt Lake City, Utah and modified to substantially remove the ferromagnetic physical components.

Preferably, the lower part of the cover 60B and the face plate 60A and / or upper portion 61A includes at least one layer of an electrically conductive metal therein, having a sufficient penetration depth to thereby provide one or more protection of external electromagnetic radiation, physical protection, and support of the gas container during transportation. Alternatively, or additionally, housing components 60 defining the compartment 65 (such as the walls and bottom portion 63A-63D, 63E and top portion 61A) include at least one layer of magnetically permeable material to provide either electromagnetic protection additional, magnetic CD protection, and / or a flow return. Preferably, as shown in Figure 1, the transportation unit 10 also comprises a metal face plate 60A, 60A * positioned over the opening defined by the upper surface of the cover when the upper portion 61A is open. As shown in FIGS. 1 and 5, the face plate 60A, 60A 'is configured to substantially surround the side walls and bottom of the housing to provide a compartment for the solenoid 20 when the upper portion 61A is open and also configured to allow a user to have access to a polarized gas chamber valve 32 and the hyperpolarized gas outlet orifice 31. In a preferred embodiment, after delivery to a desired location, the valve 32 is opened and the gas Hyperpolarized is released from the gas chamber 30 through the exit hole 31 while the gas chamber 30 itself remains inside the substantially enclosed housing 60. The inner housing 60 can add extra protection to the personnel in the gas release area. because the housing 60 surrounds a substantial portion of the gas chamber 30 therein, thus providing physical protection of any release unplanned or untimely breakage of the chamber itself (typically comprising an aluminosilicate glass) and which is typically transported under pressure. Further details of the preferred gas chamber 30 will be mentioned later.

Solenoid Switching to Figure 2, it is preferred that the transportation unit comprises an electromagnet to provide the magnetic retention field. Figure 2 illustrates a preferred embodiment of the electromagnet configured as a solenoid 20 comprising a plurality of electric coil segments to generate a substantially homogeneous static applied magnetic retention field 2 (BH). Of course, other configurations of electric wire (i.e., electromagnetic arrangements) can also be used as will be understood by one skilled in the art. As will also be understood by the person skilled in the art, other magnetic field generated ones such as permanent magnets (as long as they provide sufficient homogeneity) can also be used. Preferably, the solenoid 20 comprises at least three (3) electric coil segments 21, 22, 23 that 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 reel. The cylindrical spool may be formed of several preferably non-conductive materials such as polyvinyl chloride (PVC). Of course, the coil segments 21, 22, 23 can alternatively be placed in the cylindrical body. For example, the coil segments 21, 22, 23 may be wrapped on an intermediate layer of a cylindrical body (or even an inner layer) as will be understood by those skilled in the art. As shown in Figures 1, 2 and 3, the solenoid 20 is oriented such that it extends longitudinally from the opposite upper and lower ends of the transportation unit 10. The coil segments 2122, 23 are circumferentially wrapped around the respective portions of the cylindrical wall of the solenoid core 20a and preferably are configured such that the magnetic holding field BH (FIG. 3) is directed downwards so that preferably it is aligned with the predominant direction of the magnetic field of the earth (the field direction is generally indicated by the element 100). As such, the current in the solenoid coil segments 21, 22, 23 is directed clockwise when the solenoid is viewed from the top. This alignment with the direction of the earth can maximize the magnitude of the holding field with a given current. As shown in Figures 2 and 2A, the first and third coil segments 21, 23 are preferably placed close to the upper and lower part 20a, 20B of the solenoid, respectively. The second coil segment 22 is positioned between 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. Figure 1 shows a preferred embodiment wherein substantially the entire internal diameter of the solenoid 20 is covered with a layer of thin conductive material such as a metal film or tape 24. Figures 1 and 2 illustrate that the thin metal layer 24 acts to providing a separate column electrical protection 24a extending between the upper plate 60A and the upper surface of the lower part of the cover 63E. As shown, the shield 24a is formed as a thin metallic layer 24 which is disposed as a series of enveloped and overlapping layers of foil-thinned aluminum foil tape extending 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 metallic coating, metallic film or metal elastomer and the like.

Preferably, the protection 24th is configured so that at least the lower end 24b of the shield is in electrical contact with the cover 60. In a preferred embodiment, the lower end 24b is configured to be in electrical contact either directly or indirectly (that is, through other conductive components) with the cover. In this embodiment, the lower end 24b is configured such that the end defines a continuous electrical connection around the entire lower edge 24b. Of course, other components can be used to define an electrical bridge between the shield 24a and the cover. In another embodiment, both the upper edge 24c and the lower edge 24b of the shield 24a are arranged to define a continuous electrical contact with the respective adjacent portions of the cover 60. Furthermore, in a preferred embodiment, as illustrated in Figure 3A , the first and third coil segments 21, 23 are configured with an increased wire layers relative to the second coil segment 22. a preferred current distribution is also shown in figure 3A number. The increased number of layers related to the first and third coil segments 21, 23 relative to the second coil segment 22 acts to provide an additional current density in these segments and to extend the homogeneous region, as shown in Figure 3. Figure 10 illustrates a broader "flatter" field strength (Bz) than a solenoid having a plurality of winding segments can provide relative to a single-winding configuration of the same length having a current density uniform. Figure 10 illustrates the single-winding field as the lower "bell-shaped" graph. As such, a solenoid with a plurality of winding segments can increase the homogeneous retention region in the solenoid over a greater distance around the solenoid body (distance of "0" along the "z-position"). ). As shown in Figure 3A, the solenoid 20 is turned on its side (relative to the transit position shown in Figure 1) and A preferred current distribution in relation to each coil segment 21, 22, 23 is illustrated graphically. The first and third coil segments 21, 22 corresponds to a first value of current density (2i / l) and the intermediate segment coil or second coil segment corresponds to a value of lower current density, preferably approximately half of the final current density value (i.e., approximately (¡/ I)). (There is negligible current in 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 that is substantially the same, while the second segment of coil 22 has a current density value (i / l) which is approximately half that of the first and third coil segments 21, 23. As mentioned above, the additional current density X -ir ^ ORE X ^ l ^^ S is preferably provided by additional numbers of layers of wire in the first and third coil segments 21, 23. Preferably, the first and third coil segments 21, 23 are configured with a predetermined number of wire layers extending around a first and third longitudinal distances of solenoid. The second segmento22 is configured with about half the number of wire layers relative to the first and third coil segments 21, 23 and extends around a second longitudinal distance longer solenoid. Also, as illustrated in Figure 3A, preferably the first and third coil segments 21, 23 include approximately four layers of wire wrap (four layers in these segments are wrapped with wire, one layer on top of the other), each having a length of approximately 5.08 cm, while the second segment 22 includes approximately two layers of wire wrapping having a length of approximately 17.78 cm. The solenoid 20 is preferably sized to provide an internal diameter of approximately 15.24 cm. These dimensions are particularly suitable for a single dose amount of hyperpolarized gas which is retained in a spherical gas chamber 30 of 7.62 cm in diameter having a capillary tube 35 as shown in Figure 1. This gas chamber configuration 30 and solenoid 20 provides a radial separation of approximately 3.81 cm between the inner diameter of the solenoid and the external diameter of the gas chamber. Of course, other dimensions of solenoid 20 and coil segment configurations (lengths, number of layers, etc. and / or permanent magnet arrangements) can be used for containers 30 sized alternately and alternatively. In this preferred operating position, as shown in FIGS. 1 and 2, the gas chamber 30 is preferably arranged in the solenoid 20 so that the main spherical portion 33 of the gas chamber 30 is placed in the homogeneity area. increased within the solenoid 20 (for example, the center of the solenoid 20 and / or the center of the second coil segment 22). The positioning can be ensured by suspending the gas chamber 30 from the upper plate 60A '(figure 1) or by placing a platform or base or the like that does not damage the non-conducting gas under the gas chamber 30 (not shown). Preferably, as shown in the dotted line in Figure 2, the gas chamber 30 is disposed in the solenoid 20 so that it rests on the packing that does not damage the hyperpolarized gas which acts as a vibration damping material 50 for help isolate the gas chamber 30 from undue exposure to vibration during transportation. Also as shown, the packing material 50 extends securely and tightly around the capillary tube 35 to help cushion and isolate the container during shipment. In any case, it is preferred that the gas chamber 30 be well supported in the region of high homogeneity, since the homogeneity of the magnetic retention field is spatially determined (spatially variable) and the translation of the gas chamber 30 around the The same can result in the potential exposure of the hyperpolarized gas to a heterogeneous region, thus potentially reducing the polarized life of the hyperpolarized gas product. In any case, it is preferred that the coil segment configuration be such that each of the first and third coil segments 21, 23 provides an increased current density relative to the second coil segment or intermediate coil segment 22. In this In this embodiment, the solenoid coil segments 21, 22, 23 are dimensioned and configured with respect to the volume of the solenoid to provide adequate homogeneity of the magnetic field over a larger central volume and advantageously in this manner in a relatively compact form with respect to the previous designs of coil. Preferably, the three coils 21, 22, 23 are electrically connected in series and, as such, the terminal coil segments are electrically connected to the power source 40 (Figure 1). In effect, the current may alternatively be provided separately or otherwise electrically supplied to the coil segments 21, 22, 23. For example, as will be appreciated by those skilled in the art, a separate battery and associated circuitry (not shown) ) can drive the second coil 22, while a first battery is used to drive the first and third coils 21, 23.

In a preferred embodiment, the first and third coil segments have approximately 198 windings, while the second coil segment or central coil segment includes approximately 347 windings (i.e., the second coil segment 22 preferably has more than 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 approximately 743 windings therein. For this configuration, the field current: current ratio is approximately 23,059 G / A. In this way, the field strength at 300 mA is approximately 6,918 gauss, and the field strength at 320 mA is approximately 7,379 gauss. A suitable wire is HLM 18 gauge from MWS Wire Industries, Westlake Village, California. Preferably, for transit purposes, the power source 40 of the transportation unit is a 12V DC battery (such as that used to mechanically drive motorcycles). However, at anchor stations or at an end-use site, the transportation unit 10 may conveniently be plugged into an external power source to divert and preserve the battery charge. Also, the power source 40 of the transportation unit is configured by operation circuitry 50 to provide an adjustable current supply to the solenoid 20 from about 100 mA to about 2.0 A. In this manner, the solenoid 20 is preferably configured to provide a magnetic retention field of between approximately 2 to 40 gauss. The operation circuitry 50 of the transportation unit 10 will be described in more detail below.

Gas chamber Preferably, the gas chamber 30 is configured to provide a quantity of hyperpolarized gas which can be conveniently supplied to an end point in a dose volume that is favorably individual for the user (but in fact can also be configured to provide amounts of multiple or partial doses) of hyperpolarized gas. In a preferred embodiment, the gas chamber 30 is a spherical gas chamber of 100-200 cm 3. For 3He, it is preferred that the gas chamber 30 be pressurized to approximately 4 to 12 atmospheres of total pressure, and more preferably is pressurized to approximately 5 to 11 atmospheres of total pressure. The pressurization of a properly sized gas chamber can allow the hyperpolarized gas to be released through the outlet, since the pressure acts to match the ambient conditions. In this way, only by opening the valve 32, the hyperpolarized gas can be directed to a patient or a patient delivery system with minimal manipulation (and thus a potentially minimal depolarizing interaction). Alternatively, as shown in Figures 12A, 12B and 13, the hyperpolarized gas can be properly divided and diluted or sized at a polarization site or at a second site away from the polarization site in several bags sized for patient delivery with expandable cameras for (also) additional transportation and supply. The walls of the bags of the expandable chamber can be depressed to expel the gas mixture contained therein, requiring a minimum of extraction equipment. It should be noted that for hyperpolarized 3He at approximately 10 atmospheres of pressure, the theoretical T-i due to interactions with other hyperpolarized nuclei is approximately 75 hours. Substantially higher pressures allow more gaseous product to be sent into the container, and reduce the sensitivity of the hyperpolarized gas to the relaxation by gradient, but relaxation by gas-gas collision can become more frequent. In contrast, for 129Xe, it is preferred that the gas pressure be about 10 atmospheres or less, because higher pressures can dramatically reduce the expected relaxation time of the hipstropolated 129Xe (ie, at 10 atmospheres).; the Ti is 5.6 hours). In a preferred embodiment of the present invention, as shown in Figure 4, the gas chamber 30 includes a capillary tube that is dimensioned and configured to minimize the travel of the hyperpolarized gas atoms out of the spherical volume, and acts to remove most of the hyperpolarized gas from the valve 32. More specifically, the capillary is sized so that the ratio of the volume of the main body: the capillary volume, multiplied by the diffusion time of 3He (at filling pressure) to advance twice the length of the capillary, be greater than the T-, desired. As such, a significant 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 transportation. Preferably, the capillary tube 35 includes an inner diameter of about 1.0 mm and has a length, which is sufficient to allow proper positioning of the sphere within the homogeneity region in the solenoid 20. In the preferred embodiment of the solenoid 20 described above, the capillary tube 35 is approximately 10.16 cm in length. As such, for a gas chamber 30 with a sphere of 7.62 cm in diameter, the capillary tube 35 is preferably longer than that of the retention portion (body) of the sphere 33 of the gas chamber 30. Also preferably, the inner diameter of the capillary tube 35 is sufficiently small to retard the movement of the hyperpolarized atoms relative to the valve 32, thereby maintaining a substantial portion of the hyperpolarized gas in the spherical volume 33, and thus within the region of the field highly homogeneous Also as described above, even if the transportation unit 10 protects or protects the hyperpolarized gas from EMI and static magnetic gradients, the surface relaxation velocity associated with the container, the valves and other components that come into contact with it. hyperpolarized gas, can negatively affect the polarization life of hyperpolarized gas. As such, particularly for hyperpolarized 3He and for the multi-dose containers 30L (Fig. 12A, 13), it is preferred that the gas chamber 30 comprises primarily an aluminosilicate material. It has been shown that aluminosilicate materials have long surface relaxation times. The gas chamber 30 can be manufactured from GE180 ™ although, in effect, other aluminosilicates can be used. Typically, a transition glass is used to fix the borosilicate (32) valve 32 of the aluminosilicate gas chamber 30. Valves 32 suitable for use in the gas chambers 30 is the part number 826460-0004, which is available from Kimble Kontes, located in Vineland, NJ. The valves 32 may be further modified to cover or replace any paramagnetic or ferromagnetic impurities, or they may be treated or conditioned to remove or minimize the amount of impure or depolarizing materials that are present. located next to the hyperpolarized gas. A suitable transition glass includes uranium glass. Alternatively, other favorable polarization materials may be used, such as polymers or high purity metals with metallized surfaces, polymers, and the like. "High purity", as used in herein, means materials that are substantially free of paramagnetic or ferrous materials. Preferably, the metallic materials include less than 1 part per million of paramagnetic or ferrous impurities (such as iron, nickel, chromium, cobalt, and the like). In a - jjtaiWEh? .

Preferred alternative embodiment, as shown in Figures 12A and 13, the gas chamber may be an elastic bag 30b such as a single or multiple polymer layer bag having a metal film layer or inner surface, or surface layer which is formed of one or a combination of a high purity metal such as gold, aluminum, indium, zinc, tin, copper, bismuth, silver, niobium, and oxides thereof. Further descriptions of preferred hyperpolarization materials and containers, gaskets and the like, are included in copending United States patent application serial No. 09 / 126,448, entitled "Containers for Hyperpolarized Gases and Associated Methods" (and its related application), as described under the surface induced relaxation section described above. The elastic bag 30b may include a capillary tube (not shown) and / or means for isolating the fluid orifice to prevent the hyperpolarized gas from coming into contact with potentially depolarizing valves and fittings during transportation or storage. It is also preferred that the gas chamber 30 be configured as a sphere, since it has a geometry that minimizes the surface area / volume ratio, and thus the contact relaxation induced by the surface. In addition, since the solenoid 20 described above generates a region of high homogeneity which is typically typically spherical in shape, making the gas chamber spherical increases the volume of the gas chamber that adapts to the homogeneous region as much as possible. . In another preferred embodiment, the transportation 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 quantities (preferably, a plurality). of individual sized dosages) to facilitate dose distribution for individual use of hyperpolarized substances or formulations at far sites to retain enough polarization to allow useful clinical images on transport distances and longer times elapsed from the original polarization point. Figures 12A and 13 illustrate a multiple dose or bolus container 30L (i.e., a container of relatively large capacity), and a plurality of smaller elastic bag containers 30b (i.e., bags with expandable chambers). The bag container 30b may include a capillary tube similar to that used for the rigid container 30 described above (not shown). Similar to the gas chamber 30, the NMR coil 75 can be placed on an outer surface thereof to monitor polarization during transportation. More details regarding the configurations and preferred materials of the bag are described in the patent application of E.U.A. co-assigned and titled "Resilient Containers for Hyperpolarized Gases and Associated Methods", identified by attorney-in-fact case No. 5770-121 P, and the patent application of E.U.A. related series No. 09 / 126,448, incorporated herein by reference. The multi-bolus container 30L is used to deliver desired formulations, concentrations and / or mixtures of the hyperpolarized gas (with or without other substances, liquids, gases (such as nitrogen) or solids) at a distant site. The multi-dose container 30L may be the polarization chamber or the optical cell itself. The magnetic field generator is preferably a suitably sized solenoid 20, but can also be provided with permanent field magnets (not shown). In effect, an individual sized transportation unit (or even the transportation unit itself) can be used to transport the hyperpolarized gas to the second and third sites, that is, the second transportation unit 10 s can be sized and configured equally as the first transportation unit 10f, as necessary. Alternatively, the first transportation 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 placed for transportation from the second site. Figure 13 illustrates that the elastic bags 30b may each have a single magnetic field generator shown as a solenoid 20 operatively associated therewith. Figure 12A illustrates an alternative configuration with a single magnetic field generator (also shown as a solenoid 20) sized and configured to contain a plurality of bags 30b therein. As shown in Figure 12B, a drawer 630 can be used to contain a plurality of bags filled with hyperpolarized substance, and translated into the solenoid 20 'to place them in the desired region within the solenoid for effective protection as described above. Drawer 630 can also facilitate removal at a supply site. Preferably, the drawer is formed of non-conducting polarization materials. In fact, the drawer 630 can alternatively be configured, such as with compartments and means of sliding and latching or locking to locate the position of the bags in the affirmative, as well as a handle or extension means to allow central positioning. or depressed drawer and bags within the region of desired homogeneity.

Operation Circuitry Preferably, the transportation unit 10 includes an operation circuitry 50 that is operably associated with the solenoid 20 and the energy source 40. Preferably, the internal energy source 40 is a battery as described above, but it may also be operably associated to an external power source by an external power connection 141 (Figure 5). As shown schematically in Figure 8, the operation circuitry 50 preferably includes a switching and power monitoring circuit 125. As shown in Figure 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 in the solenoid 20. Advantageously, the energy monitoring circuitry 125 is preferably configured to switch automatically between the different energy sources (40, 140), without interruption of the current to the operating circuitry 50 or the solenoid 20. Preferably, the power switching and monitoring circuit 125 handles the power supply, so that the transportation unit 10 is mechanically driven from the internal power source 40 (battery) only when necessary. For example, when the transportation unit 10 is not easily connected to an external power source 140, the energy monitoring circuit 125 is coupled to the battery 40 to supply the power to the transportation unit 10. Preferably, the circuit energy monitoring 125 is then decoupled from the battery 40 when the transportation unit 10 is connected to a viable external power source 140 (such as a wall power outlet or vehicle) when the external connector hole 141 is connected to the external source 140. In a preferred embodiment, as shown in Figure 7, the power monitoring circuit 125 is operably associated with the recharging circuit 148 which allows the internal battery 40 to be recharged when the conveyor is mechanically driven from a external supply 140.

In effect, the operation circuit 50 may 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 is low. Preferably, as also shown in Figures 5 and 8, the transportation unit 10 includes a current reading 151 associated with the energy monitoring circuit 125. As shown, the current reading is an LCD display 151, which will allow the observer to visually affirm that the transportation unit is functioning properly, and will allow him to monitor the current traveling through the solenoid. As also shown in Figure 8, the operating circuitry 50 preferably includes current adjusting means 180 for increasing or decreasing the current supplied to the solenoid 20. In a preferred embodiment, the current adjusting means 180 is a rheostat operated by the current control knob 180 (figure 5). As described above, the adjustable current means are preferably adjustable to deliver between about 100mA to about 2.0A. The current adjustment allows the operating circuitry 50 to adjust the current in response to the needs of the transportation unit 10. For example, the current can be adjusted to provide a usual retention field corresponding to the type of hyperpolarized gas that is present. being transported. In addition, the current to the solenoid 20 can be adjusted to compensate for the electronic or mechanical variation of the system (i.e., battery discharge, electronic drift, coil resistance variability due to temperature), thereby maintaining the intensity of desired retention field. The operating circuitry preferably includes means for adjusting the magnetic field strength of the magnetic retention field, which preferably operates to deviate the Larmor frequency of the spins associated with the hyperpolarized gas. Said magnetic field adjustment is useful for carrying out NMR measurements, or for avoiding electromagnetic interference at a particular frequency or frequency scale. The NMR measurement system will be described in more detail below. As with all materials that come in contact with or are placed near or close to the hyperpolarized gas, it is preferred that the operating circuitry 50 contains magnetically active materials and minimum components such as iron transformers. However, if such materials or components are used, then it is preferred that they be placed at a sufficient distance from the gas chamber 30 and the solenoid 20, so as not to cause relaxation by undue gradient. In addition, it is preferred that the temperature sensitive components be removed from the operating circuitry 50 to provide a consistent and reliable circuit which can tolerate wide temperature ranges (inside and outside). In fact, operation circuitry 50 may be present in programs, equipment, or a combination of equipment and programs.

Portable monitoring (polarimetry / NMR coil) Preferably, the transportation 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 , said system can be used in a transitory evaluation site or in a desired evaluation site. For example, prior to the release of the gas from the transportation unit 10, the monitoring system can acquire a signal corresponding to the polarization level of the hyperpolarized gas in the transportation unit 10, and thus indicate the viability of the gas before of the supply, or in a receiving station at the point of use. This can confirm (reliably "inspect") the product, and ensure that it meets the acquisition specification before it is accepted on the site of use. The polarization monitoring system can also be used with the transportation unit 10 to evaluate the fluctuations of the magnetic retention field during transportation. In addition, the monitoring system can automatically adjust the current to compensate for detected fluctuations. Additional details of an adequate monitoring system, and methods to implement it, are described in the patent application of E.U.A. co-assigned and titled "Portable Hyperpolarized Gas Monitoring System, Computer Program Products, and Related Methods", identified by attorney-in-fact case No. 5770-17. The contents of this application are incorporated herein by reference. As shown in Figure 1, the transportation unit 10 preferably includes an NMR transmission / reception coil 75, which is positioned so that (safely or firmly) it comes into contact with the external wall of the storage chamber 30. The NMR coil 75 includes an input / output line 375 that is operably associated with an NMR polarimetry circuit and a computer (typically an external laptop device 500, as shown in FIG. 5). Preferably, the transportation unit 10 includes an access hole 300 to the computer, which is operably associated with the operation circuitry 50 and the NMR coil 75 via the coaxial BNC plug 275. The NMR coil 75 can be Use with the monitoring system to evaluate the polarization level of the hyperpolarized gas in a substantially non-destructive evaluation technique. In alternative form or in addition to the monitoring system (portable), the transportation unit 10 is preferably configured to be conveniently coupled to a (far) calibration station 500, as shown in Figure 9. Generally described as shown in Figure 9, the polarization detection is it can be carried out in a calibration station 500, which preferably uses a reduced field NMR spectrometer to transmit RF pulses to surface coils 75 located close to the hyperpolarized gas sample. The spectrometer then receives at least one return signal from the NMR coil 75 corresponding to the hyperpolarized gas. The processed and displayed signals 565 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 transportation unit 10). As shown, the calibration station 500 preferably includes a series of Helmholtz coils 552 (preferably approximately 60.96 cm in diameter) to provide the reduced magnetic field and another external NMR surface coil (not shown). The additional NMR surface coil is preferably sized and configured to approximately 2.54 cm in diameter, and with approximately 350 turns. The NMR surface coil is configured to be received on a non-metallic platform 170, and is arranged to be substantially flush with the upper surface of the platform to be able to come into contact with the delivery vessel of patient 575. Also, the RIVN coil is preferably located in the center of the Helmholtz coils 552. The The term "reduced field", as used herein, includes a magnetic field less than about 100 Gauss. Preferably, the calibration station 500 is configured with a field strength of approximately 5-40 Gauss, and more preferably a field strength of approximately 20 Gauss. Accordingly, the frequency scale of the 3He signal is about 16 kHz-128 kHz, with a preferred frequency of about 64 kHz. Similarly, the frequency scale of the 129Xe signal is approximately 5.9 kHz-47 kHz, with a preferred signal frequency of approximately 24 kHz. Preferably, the hyperpolarized gas is contained in a bag container for delivery to the patient 30, which is placed on the upper surface of the surface coil (not shown) and substantially at 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 within the transportation unit 10 via the 553 connection. In any case, the RF pulse frequency corresponds to the field strength of the magnetic field and gas in particular, examples of which were described above. This RF pulse generates an oscillating magnetic field that misaligns a small fraction of the hyperpolarized 3He or 129Xe nuclei of its static magnetic field alignment. The misaligned cores begin processing on their associated Larmour frequency (corresponding to the 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) in the computer, and the signal adapts a sinusoidal pattern that decays exponentially (as shows, the displayed signal 565 is the Fourier transformation of the received signal). The peak-to-peak peak voltage of this signal is directly proportional to the polarization (using a known calibration constant). The computer 500 'can then calculate the polarization level and generate calculated preferred usage data and times associated with the desired polarization levels. As will be recognized by those skilled in the art, other methods for determining the level of hyperpolarization or calibration may also be used, and still be within the methods of determination of expiration or use of the product or calibration and identification of the product contemplated by this invention. For example, by detecting the tiny magnetic field generated by the polarized 3He spins, it is possible to determine a level of polarization associated with them. In an alternative embodiment, the transportation units 10", 10 '" comprise a plurality of gas chambers 30 (figures 6, 6A) or 30b (figures 12A and 13), and each gas chamber 30 preferably includes an NMR coil individual 75 which is located adjacent to each gas chamber within the solenoids of the transportation unit 10", 10 '". It is further preferred that each gas chamber 30 be substantially electrically isolated from the other gas chambers 30, so that each gas chamber 30 is individually monitorable (individually excitable) for hyperpolarization level, and each is individually adaptable (intensity of field and adjustable coil current). In another alternative mode, as shown in Figure 6B, the transportation unit 10 '"can be configured with an individual coil 20' which is dimensioned and configured to surround a plurality of gas chambers 30 therein (see also Figure 12A). of the transport units (if the containers have necks or capillary tubes), either for individual or multiple gas containing units), the orientation of the neck or tube can take different directions, in addition, although the transportation units shown in the figures 6, 6A and 6B illustrate side-by-side gas containers, the present invention is not limited thereto For example, the transportation unit may be configured to comprise a plurality of units that are stacked longitudinally with capillary tubes that extend in the same directions or opposite directions Figure 12A illustrates an example, a plurality of bags 30b placed in the substantial linearity (either longitudinal or lateral). An NMR coil 75 can also be attached to each bag 30b contained for transportation or storage (not shown). Advantageously, a transport unit comprising a solenoid 20 has successfully withheld a Ti of 3 He of 45 hours (gas chamber with valve), while a gas chamber without a valve (sealed) (pressurized to approximately 2.2 atmospheres, not shown), has supported a Ti of 120 hours. These examples of Ti's were for 3He polarized at a production site and transported in transportation unit 10 for a travel time of approximately 30 hours (approximately 28 hours when the unit was physically removed from its "residence base" or polarizer), and where the unit was actually in transit for about 10 hours. The gas chambers 30 in the transportation unit 10 were exposed to environmental conditions while traveling to a use site in a vehicle.

Central Production Site and Far-Use Site The use of a far polarization production site typically requires longer Ti's compared to an on-site polarization apparatus to allow for adequate shipping and transportation times. However, a centrally located polarizer can reduce the equipment and maintenance costs associated with a plurality of units placed in situ at each imaging site, and the transportation units of the present invention can allow for increased transport times with Ti times. longer than conventionally achieved. In a preferred embodiment, a polarizing production unit (not shown) generates a polarized gas production site. The gas chamber 30 (or 30b) is in fluid communication with the polarizing unit, so that the polarizing unit produces and directs the polarized gas to the gas chamber 30. Preferably, the gas chamber 30 is maintained in the gas chamber 30. compartment 65 of the transportation unit (figure 1) (or individual compartment 65A-D, figures 6, 6A and 6B) during the filling step. More preferably, the container is placed in the transportation unit within the homogeneous retention field therein before the filling step. After a sufficient amount of hyperpolarized gas is captured in the gas chamber 30, the valve 32 is then closed (the gas chamber is sealed). In this way, the solenoid 20 in the transportation unit 10 is activated (preferably before the filling step, but can also be activated after the container is sealed), if the container is otherwise protected such as on board of the polarizing unit during filling. In operation, the power switch 161 (Fig. 5) in the transportation unit 10 is changed to the "on" position, and electric current is supplied to the solenoid 20, so that a magnetic retention field of about 7 is generated. Gauss as described above. The hyperpolarized gas is protected from parasitic magnetic gradients within the transportation unit 10 until and after delivery to a remote location. When desired, the hyperpolarized gas can be directed or released from the gas chamber 30, and delivered to a patient by means of a patient delivery system (temporarily imitated at its end-use time), so that the hyperpolarized state of the gas during delivery is sufficient to produce useful clinical images. Another aspect of the present invention is a system for distributing hyperpolarized gas products, so that doses of hyperpolarized gases sized for patients and for individual use have increased the storage life or useful polarization life. He A.-A * system includes a first transportation unit 10f (shown schematically by the dotted line box in Figure 12A), which is sized and configured to contain at least one multi-dose container 30L therein. The system also includes at least a second transportation unit 10s (shown schematically in Figure 12A) dimensioned and configured to carry a plurality of individual dose containers (such as those shown, for example, by 30 or 30b in the Figures 6A, 6B, 12A and 13, respectively) therein. Preferably, the multi-dose container is a rigid body container 30L, and the individual dose containers are elastic containers 30b having expandable chambers to allow easy administration or delivery at a site of use as described above. In a preferred distribution system, the hyperpolarized gas is collected in a multiple bolus container (such as that shown as container 30L in Figures 12A, 12B and 13) at the polarization site, and transported in a transportation unit 10f suitably sized to a site away from the first site. This 30L multi bolus container can be the optical cell itself, or another suitable container configuration as described above. In one embodiment, as shown in Figure 12A, the multi-dose container 30L is transported to a pharmaceutical distribution point, wherein the hyperpolarized gas in the multi-dose container 30L can be supplied or formulated in the appropriate dosage or mixture. according to the standard operation of pharmacy or drug manufacturer. For example, but not limited thereto, this supply or formulation activity may include solubilizing the gas in a liquid vehicle, adjusting the concentration, preparing the mixture for injection or inhalation, or other administration specified by a physician or manager of a regulatory agency. , or by combining one or more different gases or liquids or other substances with the hyperpolarized gas transported. Preferably, the materials used to form the product are suitable for administration to a subject in vivo (pharmaceutical grade substance). In any case, in the second site, the hyperpolarized gas maintained in the multi-bolus container 30L is preferably supplied in quantities or doses of hyperpolarized product for individual use, sized for application or prescribed in proportionally sized elastic containers 30b. As will be described later, suitable conditioning of the bag containers 30b is preferably observed. After the delivery step, the second container or subsequent container (preferably) sized for individual use can be delivered to a nearby use site (if the second site is near or part of a site for clinical use such as a hospital). Alternatively, in the second site, at least one bag 30b is placed in a second transportation unit 10 which is suitably sized and configured to contain the bag therein. Preferably, the transportation unit 10s is configured to contain a plurality of bags as shown in Figures 12A and 12B. In any case, one or more bags are placed in a second transportation unit 10s and delivered or transported to a third site or tertiary site, preferably the site of clinical use. Preferably, for bag containers, the transportation 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"3 cm" 1 over the volume occupied by the bags 30b. In a preferred embodiment, the first transportation distance is such that the hyperpolarized gas is moved at increased distances or times over conventional uses. Preferably, the transportation units and the associated container of the present invention are configured so that during transportation and / or storage, the hyperpolarized gas (particularly 3 He) retains sufficient polarization after approximately at least 10 hours of polarization, and more preferably of about at least 14 hours, and even more preferably more than about 30 hours after polarization, and when transported to a second site (and even then a third site or tertiary site). In addition, the transport unit and associated containers are preferably configured to allow longer transit distance times from the original polarization point in a way in which the hyperpolarized product retains sufficient polarization to provide images fe¡ ^^^^^ ¿^^^^^^^^^^ j ^ * ¡& amp; & amp; clinically useful. This distribution system contrasts with the conventional method, whereby the hyperpolarized gas is produced at a polarization site and sent rapidly to a use site (which is typically relatively close to the polarization site).

Preconditioning of the container Preferably, due to the susceptibility of the hyperpolarized gas to the paramagnetic oxygen as described above, the gas chamber 30 is preconditioned to remove contaminants. That is, it is processed to reduce or remove paramagnetic gases such as oxygen from inside the chamber and the walls of the container. For containers made of rigid substrates such as Pyrex ™, UHV vacuum pumps can be connected to the container to extract oxygen. Alternatively, for rigid and / or elastic containers (such as polymer bag containers), a roughing pump can be used which is typically more economical and easier to use than the UHV vacuum pump-based procedure. . Preferably, for elastic bag containers, the bag is processed with several purge / pump cycles. Preferably, this is achieved by pumping at 40 mtorr or less for one minute, and then directing clean gas (UHP) (such as nitrogen) into the container at a pressure of about one atmosphere or until the bag is substantially inflated. The partial pressure of oxygen is then reduced in the container. This can be done with a vacuum, but it is preferred that it be made with nitrogen. Once oxygen achieves imbalance of partial pressure through the walls of the container, it will extract the gas to restore equilibrium. The typical solubilities of oxygen are of the order of .01 -.05; in this way, 95-99% of the oxygen trapped in the walls will undergo transition to a gas phase. Before use, the container is evacuated, safely removing gaseous oxygen in this way. Unlike conventional rigid containers, polymer bag containers can continue to extract gas (trapped gases can migrate there due to pressure differentials between the outer surface and the inner surface), even after the initial flea cycles /pumping. In this way, care must be taken to minimize this behavior, especially when the final filling is not carried out temporarily with the preconditioning of the container. Preferably, a quantity of clean filler gas (grade 5 or UHP nitrogen) is directed into the bag (to substantially equalize the pressure between the chamber and the ambient conditions), and sealed for storage to minimize the amount of extraction of additional gas that can occur when the bag is stored and exposed to environmental conditions. This should substantially stabilize or minimize any further degassing of the polymer or materials from the wall of the container. In any case, the filler gas is preferably removed (evacuated) before final filling with the hyperpolarized gas. Advantageously, the container of the present invention can be reprocessed economically (purged, cleaned, etc.), / used again to transport additional quantities of hyperpolarized gases. It is also preferred that the bag container be sterilized before introducing the hyperpolarized product therein. As used herein, the term "sterilized" includes cleaning the containers and contact surfaces so 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 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 skilled in the art.

Examples of Hyperpolarized Gas Protection and Transportation System. Exhibit 11 illustrates a preferred system for protecting hyperpolarized (noble) gases (and hyperpolarized gas products in any form such as fluids, liquids, solids, and the like, including other liquid components). or gaseous in any way, as described above). An amount of hyperpolarized gas product is introduced into a sealable container comprising a gas chamber (and preferably a capillary tube) at a production site (block 800). An amount of hyperpolarized gas is captured in the gas chamber (block 810). A magnetic holding field is generated from a portable transportation unit, thereby defining a substantially homogeneous magnetic field retention region (block 820). The gas chamber is placed within the homogeneous retention region (block 830). Preferably (as indicated by the dotted line), the gas chamber is placed in the magnetic field retention region before filling. The hyperpolarized gas product is protected from parasitic magnetic fields to minimize the depolarizing effects attributed to them, so that the hyperpolarized gas retains a clinically useful polarization level at an end-use site, away from the production site ( block 840). Preferably, the magnetic retention field passage is provided by electrically activating a longitudinally extending solenoid located in the transportation unit. The solenoid comprises a plurality of spatially separated coil segments (block 821). It is also preferred that the protection step be carried out by changing the resonance frequency of the hyperpolarized gas in the container, at a predetermined frequency as described above (block 841). Figure 14 illustrates a method and / or system for distributing hyperpolarized gas products. The noble gas is polarized at a polarization site (block 900). An amount of hyperpolarized gas sufficient to provide multiple doses of hyperpolarized noble gas product is captured in a multi-dose container (block 910). The multiple dose container is located in a portable transportation unit which is configured to provide a homogeneous magnetic field to contain a main portion of the multiple dose container therein (block 920). The multiple dose container in the transportation unit is transported to a second site away from the first site or polarization site (block 930). In the second site, the hyperpolarized gas in the multi-dose container is distributed in separate multiple separate containers (preferably, reduced dose or sized containers for patients), and more preferably individual dose bags (block 940). Preferably, at the second site, and also preferably before the distribution step (block 940), multiple doses of gas are subdivided (block 941), and processed into at least one desired formulation to form a pharmaceutical grade product hyperpolarized suitable for in vivo administration (block 942). Preferably, the processing and subdivision steps 15 are carried out prior to the gas distribution in the secondary containers for transportation. In this way, the processing and / or distribution step in the second site can include the steps of formulating or otherwise processing the hyperpolarized gas into a sterile or non-toxic product, so that it is suitable for in vivo administration in humans. . Processing may include diluting the concentration, such as adding other inert gases (such as substantially pure nitrogen, at least grade 5), or vehicles or other liquids or substances. The processing may include manipulating the hyperpolarized gas from the g ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ which is formulated in the appropriate dosage or mixture according to the standard operation of the pharmaceutical industry. This may include solubilizing the gas, adjusting the concentration, preparing the mixture for injection or inhalation, or other administration specified by a physician, or combining one or more gases or liquids or other different substances with the hyperpolarized gas transported. Then, the formulated substance, mixture or hyperpolarized product is preferably supplied in at least a second container, and preferably in a plurality of elastic containers preferably for individual use, which can be transported to a third site or tertiary site. 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, near the second site (block 970), or located within a second transportation unit with a homogeneity region (block 950), and transported to a third site (preferably an imaging site) away from the second site (block 955). The supply of the product in a site close to the second site, is especially applicable for distribution - second oriented sites, which can be a clinic (such as the wing of a hospital). The hyperpolarized product can then be administered to a patient at the imaging site, or stored for future use (block 975). The hyperpolarized product administered is useful for obtaining clinical data associated with spectroscopy and magnetic resonance imaging procedures. The transportation units according to the present invention are configured so that during transport and / or storage of the gas, they have adequate protection as described herein. The foregoing is illustrative of the present invention, and should not be considered as limiting thereof. Although some examples of embodiments of this invention have been described, those skilled in the art will readily appreciate that many modifications to the embodiment examples are possible without departing materially from the teachings and novel advantages of this invention. Accordingly, it is intended that said modifications be included within the scope of this invention, as defined in the claims. In the claims, the clauses are intended to cover the structures described herein, carrying out the claimed function, and not only structural equivalents but also equivalent structures. Accordingly, it should be understood that the foregoing is illustrative of the present invention, and should not be considered to be limited to the specific embodiments described, and that modifications to the embodiments described as well as other embodiments are intended to be included within the scope of the invention. of the appended claims. The invention is defined by the following claims, with equivalents thereof included herein.

Claims

NOVELTY OF THE INVENTION CLAIMS 1. - A transportation unit for transporting hyperpolarized gas products therein, said transportation unit comprising: at least one gas chamber configured to contain a quantity of hyperpolarized gas product therein; and an electromagnet disposed in said transportation 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 gas chambers (for example, at least one) is dimensioned and configured to reside in said homogeneous region of the magnetic field.
2. The transport unit according to claim 1, further characterized in that it comprises at least one wire that has electric current, wherein said electrical wire (at least one) is configured to generate at least a portion of said magnetic retention field.
3. The transport unit according to claim 1, further characterized in that said electromagnet comprises at least one cylindrical solenoid. 4. - The transportation unit according to claim 3, further characterized in that said solenoid comprises a plurality of coil segments therein. 5. The transport unit according to claim 3, further characterized in that said transportation unit further comprises a metal compartment, wherein said solenoid is placed in said compartment so that it extends longitudinally therein. 6. The transport unit according to claim 5, further characterized in that said compartment includes at least one layer of an electrically conductive metal therein, thereby providing one or more protections against external electromagnetic radiation and structural support. during transportation. 7. The transport unit according to claim 5, further characterized in that said compartment includes at least one layer of magnetically permeable material to provide at least one additional electromagnetic protection, magnetic CD protection, or a flow return. 8. The transport unit according to claim 3, further characterized in that it comprises operating circuitry operably associated with said transportation unit, said operation circuitry including a direct current power supply operably associated with said solenoid. 9. - The transportation unit according to claim 8, further characterized in that said operating circuitry is configured to direct electric current to said solenoid to define the magnetic retention field having a field strength that 5 corresponds to the amount of current directed to said solenoid. 10. The transport unit according to claim 4, further characterized in that said operating circuitry is configured to allow an adjustable amount of current to said solenoid, thereby providing a retention field strength. 10 magnetic, adjustable. 11. The transport unit according to claim 3, further characterized in that said solenoid provides a homogeneous magnetic field retention volume defined with respect to the center of said solenoid, and wherein said container has a hyperpolarized product containing chamber 15 configured and dimensioned such that said containment chamber is maintained in said homogeneous field volume. 12. The transport unit according to claim 6, further characterized in that said solenoid is arranged in said transport unit, so that it extends longitudinally in said compartment, and defines a magnetic retention field that is substantially aligned with the magnetic field of the Earth. »Adft -'...- jhriftfr3 ' 13. - The transportation unit according to claim 4, further characterized in that said plurality of coil segments includes first, second and third spatially separated coil segments. 14. The transport unit according to claim 13, further characterized in that said second coil segment is disposed intermediate between said first and third coil segments, and wherein said second coil segment has a smaller number of electrical windings per unit length between said first and third coil segments. 15. The transport unit according to claim 14, further characterized in that said first and third coil segments extend a first longitudinal distance along said solenoid, and said second coil segment extends a second longitudinal distance to along said solenoid, and wherein said second distance is greater than said first and third distances. 16. The transport unit according to claim 1, further characterized in that said gas chamber includes a gas containment chamber having a main body portion with a first length and a capillary tube with a second length, said capillary tube it is in fluid communication with said gas containment chamber and having a capillary length and a capillary diameter, wherein said capillary length is greater than said length of the main body portion. 17. - The transportation unit according to claim 3, further characterized in that said solenoid and gas chamber (at least one of them) is a plurality of corresponding solenoids and gas chambers for the transportation of multiple doses of gas products hyperpolarized in them. 18. The transport unit according to claim 3, further characterized in that said gas chamber (at least one) is a plurality of separate gas chambers. 19. The transport unit according to claim 1, further characterized in that said gas chamber is defined at least by an elastic bag defining at least one expandable gas containment chamber. 20. The transport unit according to claim 19, further characterized in that said gas chamber (at least one) is a plurality of gas chambers defined by a plurality of elastic bags for the transportation of multiple separate doses of products. hyperpolarized in them. 21. The transport unit according to claim 20, further characterized in that it comprises a drawer for containing said plurality of bags, said drawer configured and sized to reside within said magnetic field generator. 22. A solenoid to provide protection for hyperpolarized gases to protect said gases from the magnetic field gradients of the drawer to minimize the depolarizing effects associated with them, characterized in that it comprises: 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 placed on said cylindrical body, so that said second The coil segment is intermediate between said first and third coil segments. 23. The solenoid according to claim 22, further characterized in that said second length is greater than said first and third lengths. 24. The solenoid according to claim 22, further characterized in that said first and third number of windings per unit length are greater than said second number of windings. 25. A container for hyperpolarized gas products having a gas containing chamber and a capillary tube, said capillary tube having an inner diameter length configured and dimensioned so that the capillary tube inhibits the movement of said hyperpolarized gas product of said gas containment chamber. 26. - The container according to claim 25, further characterized in that said length of capillary tube is greater than said length of the gas containment chamber. 27. The container according to claim 25, further characterized in that said container is pressurized to more than about 5 atmospheres pressure, and wherein said hyperpolarized gas product comprises hyperpolarized 3He. 28. A method for minimizing the relaxation of hyperpolarized noble gases due to external electromagnetic interference or magnetic fields of the drawer, characterized in that it comprises the steps of: capturing a quantity of hyperpolarized gas in a transportation unit comprising a gas chamber and operation circuitry; diverting the resonant frequency of the hyperpolarized noble gas out of the frequency scale of the predetermined electromagnetic interference during transportation; and transport the captured gas. 29. The method according to claim 28, further characterized in that said bypass step changes the resonant frequency of the hyperpolarized gas at a frequency substantially outside the bandwidth of prevailing time dependent fields associated with electrically driven equipment. 30. The method according to claim 28, further characterized in that said deflection step is carried out providing a substantially static magnetic field close to the * • * - *, ij «gas chamber containing the hyperpolarized noble gas with a sufficient field strength to change the resonant frequency of the hyperpolarized gas to a predetermined amount, thus minimizing the depolarization of the hyperpolarized gas attributed to the exposure to electromagnetic fields during transportation from a first site to a second site away from the first site. The method according to claim 28, further characterized in that it comprises providing a metal compartment around the hyperpolarized gas, the compartment having a predetermined penetration depth which is sufficient to substantially block the depolarizing effects of the predetermined electromagnetic interference or the fields of CA. 32. The method according to claim 28, further characterized in that said hyperpolarized gas comprises 3He, and said static magnetic field is at least about 7 gauss. 33. The method according to claim 28, further characterized in that said hyperpolarized gas comprises 129Xe, and said magnetic field is at least about 20 gauss. 34.- The method according to claim 28, further characterized in that said static magnetic field is substantially homogeneous around a region of the magnetic retention field. ^ ¡^ J ^ * ^ 35. - The method according to claim 28, further characterized in that said deviation step is applied generating an electromagnetic field close to the hyperpolarized gas during transportation, and wherein said electromagnetic field is adjustable during transportation. 36. A system for extending the polarization life of hyperpolarized gas during transportation, characterized in that it comprises the steps of: introducing a quantity of hyperpolarized gas product into a sealable gas chamber at a production site; capture a quantity of hyperpolarized gas product in the gas chamber; generating a magnetic retention field from a portable transportation unit, thereby defining a magnetic retention region substantially homogeneous therein; placing a larger portion of the gas chamber within the homogeneous retention region; transport the hyperpolarized gas captured in the gas chamber; and protecting the hyperpolarized gas product to minimize the depolarizing effects of external magnetic fields during said transport step, so that the hyperpolarized gas has a clinically useful polarization level at a site far away from the production site. 37.- A hyperpolarized gas protection system according to claim 36, further characterized in that said transportation unit comprises a metal compartment, and wherein said protection step is carried out by placing said gas chamber in jj ^? á! * *? & ^ the metal compartment, and electrically activating a solenoid disposed in the metal compartment. 38.- The hyperpolarized gas protection system according to claim 36, further characterized in that said protection step comprises diverting the normal resonant frequency of the hyperpolarized gas out of a predetermined frequency scale. 39.- The hyperpolarized gas protection system according to claim 36, further characterized in that the transportation unit is configured to contain a plurality of gas chambers separated therein. The method according to claim 36, further characterized in that the transportation step is carried out by transporting the gas chamber to a second site far from the production site. 41.- The method according to claim 40, further characterized in that the gas chamber is configured as a multi-gas container, and further comprising the step of distributing the hyperpolarized gas transported in the multi-dose container at the second site in a plurality of individual dose containers to provide an adequate amount of hyperpolarized gas product therein. The method according to claim 41, further characterized in that it comprises the steps of transporting said plurality of said individual dose containers to a third site far from the second site; administering the hyperpolarized product contained in at least one of said individual dose containers to a patient; and obtain a spectroscopy or MR image signal associated with them. 43.- A method for distributing hyperpolarized noble gas, characterized in that it comprises the steps of: polarizing noble gas at a polarization site; capturing a quantity of polarized gas in a multi-dose container, the amount of hyperpolarized gas being sufficient to provide a plurality of doses of a hyperpolarized product; placing the first multiple dose container within a portable transportation unit, the transportation unit configured to provide a homogeneous magnetic field proximate to a main portion of the multiple dose container contained therein; transporting the transport unit with the multiple dose container to a second site away from the polarization site; and distributing the hyperpolarized gas contained in the multiple dose container in multiple separate second containers in the second site. The method according to claim 43, further characterized in that said transportation step comprises protecting said hyperpolarized gas by activating an electromagnet in said portable transportation unit. 45. - The method according to claim 43, further characterized in that it comprises the steps of subdividing the hyperpolarized gas into the first multi-dose container at the second site; and processing the gas subdivided into at least one desired formulation to form a hyperpolarized pharmaceutical product suitable for in vivo administration, the processing step being carried out prior to said distribution step. 46. The method according to claim 45, further characterized in that it comprises the steps of: placing at least 10 one of the second multiple separated containers with the hyperpolarized gas product therein with a second transportation unit, the second transportation unit being configured to provide a region of homogeneity therefor; and transporting the second transportation unit with at least a second multiple separate container 15 to a third site. 47. The method according to claim 46, further characterized in that at least one of the second multiple separated containers comprises an elastic bag sized to deliver doses to the patient. The method according to claim 47, further characterized in that it comprises the steps of: administering said hyperpolarized pharmaceutical product in said second container to a patient; and get clinically useful data associated with the product • «hyperpolarized fafc administered by one or more of a spectroscopy or magnetic resonance imaging procedure. 49. The method according to claim 45, further characterized in that it comprises the steps of: placing a plurality of bags sized for the patient filled with the hyperpolarized pharmaceutical product in said second transportation unit; and transporting the plurality of bags sized for the patient to a third site away from the second site. The method according to claim 43, further characterized in that the hyperpolarized gas comprises 3He, and wherein the multi-bolus container is used to polarize a quantity of noble gas therein during said polarization step at the site of Polarization. 51.- A portable conveyor for transporting or storing a quantity of hyperpolarized gas product, characterized in that it comprises: a compartment having at least one wall with a penetration depth of a conductive protective material configured to provide protection for a quantity of hyperpolarized gas from electromagnetic interference externally generated during transportation from a polarization site to a site of use, said compartment defining a retention volume therebetween; at least one container of hyperpolarized gas located in said compartment, said gas container having a portion of retention volume of main gas, and a magnetic field source located in said compartment, said magnetic field source configured to provide a region of homogeneity near said hyperpolarized gas container; wherein the retention volume is dimensioned and configured to contain said hyperpolarized gas container so that the main volume of said hyperpolarized gas container is spatially separated a predetermined distance from adjacent portions of said wall (at least one), and in where said predetermined distance is sufficient to increase the protection efficiency of said compartment. 52. The portable transportation unit according to claim 51, further characterized in that said wall (at least one) comprises a pair of opposite walls that extend longitudinally. 53. The portable transportation unit according to claim 51, further characterized in that said magnetic field source is a solenoid. 54. The portable transportation unit according to claim 51, further characterized in that said predetermined separation distance is at least about 5.08 cm. The portable transportation unit according to claim 53, further characterized in that said solenoid comprises an interior surface of conductive material configured to provide protection. 56. The portable transportation unit according to claim 51, further characterized in that said gas container (at least one) is a plurality of gas containers. 57.- The portable transportation unit according to claim 51, further characterized in that said gas container (at least one) comprises a container which is also configured as an optical pumping cell for the hyperpolarized gas contained therein at a polarization site. 58.- The portable transportation unit according to claim 51, further characterized in that said predetermined separation distance provides a separation ratio of less than about 0.60, the separation ratio being expressed mathematically by the ratio of (a) half of the linear side width of the main volume portion of said gas container with respect to (b) the minimum linear separation distance of said wall (at least one). 59.- The portable transportation unit according to claim 51, further characterized in that said magnetic field source is a plurality of sources of electromagnetic field, at least each one for each of said containers (at least one) contained in that compartment. 60. - The portable transportation unit according to claim 51, further characterized in that said container (at least one) comprises a capillary tube.