MXPA00012737A - Resilient containers for hyperpolarized gases - Google Patents

Abstract

A resilient multi-layer container is configured to receive a quantity of hyperpolarized noble fluid such as gas and includes a wall with at least two layers, a first layer with a surface which minimizes contact-induced spin-relaxation and a first or second layer which is substantially impermeable to oxygen. The container is especially suitable for collecting and transporting 3He. The resilient container can be formed of material layers which are concurrently responsive to pressure such as polymers, deuterated polymers, or metallic films. The container can include a capillary stem and/or a port or valve isolation means to inhibit the flow of gas from the main volume of the container during transport. The resilient container can be configured to directly deliver the hyperpolarized noble gas to a target interface by deflating or collapsing the inflated resilient container. In addition, single layer resilient containers with T1's of above 4 hours for 129Xe and above 6 hours for 3He include materials with selected relaxivity values. In addition, a bag with a port fitting or valve member and one or more of a capillary stem and port isolation means is configured to minimize the depolarizing effect of the container valve or fitting(s). Also disclosed is a method for determining the gas solubility in an unknown polymer or liquid using the measured relaxation time of a hyperpolarized gas.

Description

FLEXIBLE CONTAINERS FOR HYPERPOLARIZED GASES This invention was made with government support under the AFOSR no. F41624-97-C9001 and NIH warranty no. 1 R43 HL59022-0. The government of the United States has the right to this invention.

RELATED REQUESTS This application claims priority of the provisional application in the United States no. 60 / 089,692, filed June 17, 1998. The related patent application Serial No. 09 / 126,448, filed July 30, 1998 is co-pending. The content of these documents is incorporated by reference as if they were fully set forth herein.

FIELD OF THE INVENTION The present invention relates to containers for processing, storage, transport and supply of hyperpolarized noble gases. ttimm? mumk - * - * < - ** > - •• '* BACKGROUND OF THE INVENTION Conventionally, magnetic resonance imaging ("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 from which they have been produced up to now with unsatisfactory images in this modality. It has been found that polarized helium-3 ("3He") and Xenon-129 ("129Xe") are particularly suitable for this purpose. Unfortunately, as will be discussed below, the polarized state of the gases makes them sensitive to handling and environmental conditions and, undesirably, can be decomposed from the polarized state relatively quickly. Hyperpolarizers are used to produce and accumulate polarized noble gases. Hyperpolarizers artificially improve the polarization of certain noble gas nuclei (eg 129Xe or 3H) over equilibrium or natural levels, ie, Boltzmann polarization. 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 U.S. Patent No. 5,545,396 to Albert et al., The disclosure of which is incorporated herein by reference as being fully disclosed herein.

To produce the hyperpolarized gas the noble gas is typically mixed with optically pumped alkaline metal vapors such as rubidium ("Rb"). These optically pumped metal vapors collide with the cores of the noble gas and hyperpolarize the noble gas through a phenomenon known as "spin exchange". The "optical pumping" of the alkali metal vapor is produced by irradiating the alkali metal vapor with circularly polarized light at the wavelength of the first major resonance for the alkali metal (for example 795 nm for Rb). As indicated in general, the atoms in ground state are excited, then decompose again to the ground state. Under a modest magnetic field (10 Gauss), the cycle of the atoms between the fundamental and excited states can produce almost 100% polarization of the atoms in a few microseconds. This polarization is generally carried out by the valence characteristics of alkali metal electrons. In the presence of noble gases of nuclear spin that is not zero, the alkali metal vapor atoms can collide with the noble gas atoms in a way where the polarization of the valence electrons is transferred to the noble gas nuclei to through a change of orientation of mutual spin "spin exchange". After completion of the spin exchange, the hyperpolarized gas is separated from the alkali metal before administration to a patient to form a non-toxic or sterile composition. Unfortunately, during and after collection, the hyperpolarized gas can deteriorate or decompose (lose its hyperpolarized state) relatively quickly and therefore must be managed, collected, transported and stored carefully. The decomposition constant "Ti" associated with the longitudinal relaxation time of the hyperpolarized gas with frequency 5 is used to describe the time a gas sample needs to depolarize in a given container. The handling of hyperpolarized gas is critical due to the sensitivity of the hyperpolarized state in relation to the environmental and management factors and the potential of the undesirable composition of the gas of its hyperpolarized state before its planned final use, ie the supply to a patient. The processing, transport and storage of hyperpolarized gases, as well as the supply of gas to the patient or end user, can expose the hyperpolarized gases to various relaxation mechanisms such as magnetic gradients, environmental and contact impurities, and the like. 15 Typically, hyperpolarized gases such as 129Xe and 3He have been collected in relatively old environments and transported in high specialty glass containers as rigid Pyrex ™ containers. However, to extract most of the gas from these rigid containers, it is typically necessary to use complex media gas extraction. The hyperpolarized gas such as 3He and 129Xe has also been temporarily stored in Tediar® and Teflon® single-layer flexible bags. However, these containers have produced relatively short relaxation times.

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One way to inhibit the decomposition of the hyperpolarized state is presented in U.S. Patent No. 5,612,103 to Driehuys et al. entitled "Coatings for Production of Hyperpolarized Noble Gases", in general, this patent describes the use of a modified polymer as a surface coating on physical systems (such as a Pyrex ™ container) that makes contact with the hyperpolarized gas to inhibit the effect of decomposition of the surface of the collection chamber or storage unit. However, there is still a need to resolve and reduce the dominant and sub-dominant relaxation mechanisms, and decrease the complexity of the physical systems required to deliver the hyperpolarized gas to a desired subject. Minimizing the effect of one or more of these factors can increase the life of the product by increasing the duration of the hyperpolarized state. Such an increase is desired so that the hyperpolarized product can retain enough polarization to allow effective imaging of the supply when it is transported over longer distances and / or is stored for longer periods from the initial polarization than it had been. previously possible.

BRIEF DESCRIPTION OF THE INVENTION In view of the foregoing, it is an object of the present invention to process and collect hyperpolarized gas in improved flexible containers. ii fiMÍS ^ áÍÍ ^ ri ^^^^ a ^ t ^ MW ^ MUÍÉiU ^^ MI? Mll ^ «^^ riUMu? ^? ^^^^^^^^^^ l ^^^^ bíhállM that are configured to inhibit the depolarization of collected polarized gas and provide Ti higher for 3He and 129Xe than has been achieved in the past. Another object of the present invention is to provide an improved container 5 that can be configured to function as a container for transportation and as a delivery mechanism to reduce the amount of handling or physical interaction required to deliver the hyperpolarized gas to a subject. Another objective of the present invention is to provide an improved, relatively non-complex and economical container 10 that can extend the polarization life of the gas in a container and reduce the amount of polarization lost during storage, transportation and supply. Another objective of the present invention is to provide methods, surface materials and containers that minimize the depolarizing effects of the hyperpolarized state of the gas (especially 3He) attributed to one or more of the paramagnetic impurities, oxygen exposure and surface relaxation. Another objective of the present invention is to provide a method for determining the solubility of the gas in polymers or liquids with respect to hyperpolarized 20 to 129Xe or 3He. These and other objectives are met by the present invention which is directed to flexible containers that are configured to reduce contact or surface-induced depolarization.

, MM ^ ttt! Lt --- ¡----- ll--? ---------------------------- forming an internal contact surface of a first material (of a predetermined thickness) that acts to minimize depolarization associated by surface or contact. In particular, a first aspect of the invention is directed to a container for receiving a quantity of hyperpolarized gas. The container includes at least one wall comprising internal and external layers configured to define a closed chamber for retaining a quantity of hyperpolarized gas. The inner layer has a predetermined thickness and an associated relaxation value which inhibits the contact-induced polarization loss of the hyperpolarized gas. The outer layer defines an oxygen cover that covers the inner layer. Of course, the two layers can be integrated into one, if the chosen material acts as a contact surface that does not damage the polarization and is also resistant to the introduction of oxygen molecules into the container chamber. The container also includes a quantity of hyperpolarized noble gas and a port attached to the wall in fluid communication with the chamber to capture and release the hyperpolarized gas through the port. Preferably, the container materials are selected so as to result in an effective Ti of more than 6 hours for 3He and more than about 4 hours for 129Xe due to the single material. It is also preferred that the oxygen cover be configured to reduce oxygen migration in the container to less than about 5 x 10'6 amgt / min, and most preferably to less than about 1 x 10"7 amgt / min. it further prefers that the thickness of the inner layer (W) be at least of a thickness equal to the scale of duration of the polarization decrease ("Lp") that can be determined by the equation: where Tp is the nuclear spin relaxation time of the noble gas in the polymer and Dp is the diffusion coefficient of the noble gas in the polymer. In a useful manner, using a contact surface having a thickness that is greater than the polarization decomposition duration scale can decrease or even prevent the hyperpolarized gas from penetrating the substrate (the underlying material of the first layer). In fact, for hyperpolarized gases that may have a high diffusion constant (such as 3He), surfaces with polymer coatings substantially thinner than the polarization decomposition duration scale may have a more harmful effect on polarization than surfaces that do not have such a coating This is because the polarized gas can be retained within the underlying material and interact with the substrate or underlying material for a longer time, potentially causing greater depolarization than if the thin coating were not present. A further aspect of the present invention is directed to a container with a wall formed of a layer or multiple layers of materials defining a chamber that can be expanded. The inner surface of the wall is formed of a material that has a low relaxation value for the hyperpolarized (non-toxic) fluid (hyperpolarized gas) «• * '•' - '- - * - - - - • - ** ~» -. * - which is at least partially dissolved or liquefied) contained therein. The wall is configured to define an oxygen protection to inhibit the migration of oxygen to the chamber. The Ti of the hyperpolarized fluid retained in the container is greater than about 6 hours. In a preferred embodiment, the container of the present invention is configured to receive hyperpolarized 3He and the inner layer has a thickness of at least 16-20 microns. In another preferred embodiment, the container is a polymer bag that can be expanded. Preferably, the polymer bag includes a metallized coating placed on the polymer that suppresses oxygen migration in the polymer and finally in the polarized gas contained in the gas holding chamber. In another preferred modality, a third layer is added to the metallized layer (opposite the polymer chamber) to provide puncture resistance. In a useful manner, the captured hyperpolarized gas can be supplied to the inhalation interface of a subject by exerting pressure on the bag so that the bag collapses and causes the gases to leave the chamber. At the time, this eliminates the requirement for a complementary supply mechanism. Additionally it is preferred that the container use seals as O-rings that substantially do not contain paramagnetic impurities. The close position of the seal with hyperpolarized gas can make this component a dominant factor in gas depolarization. In this way, it is preferred that the O-seals or rings be formed of substantially pure polyolefins such as polyethylene, polypropylene, copolymers and mixtures thereof. Of course, fillers that are compatible with hyperpolarization can be used (such as substantially pure carbon black and the like). Alternatively, the O-ring or seal may be coated with a surface material such as LDPE or deuterated HDPE or other material with low relaxivity and other properties and / or preferably materials having a low permeability for the hyperpolarized gas contained in the camera. In addition, the container can be configured such that once the gas is captured in the container to isolate a larger portion of the hyperpolarized gas in the container away from the potentially depolarizing components (such as fittings, valves and the like) during transportation and storage. Similar to the preferred embodiment discussed above, another aspect of the present invention is a flexible container of multiple layers for retaining hyperpolarized gas. The container comprises a first cap? of a first material configured to define a chamber that can be expanded to retain a quantity of hyperpolarized gas therein. Preferably, the first layer has a predetermined thickness sufficient to inhibit surface or contact depolarization of the hyperpolarized gas retained therein wherein the first layer of material has a "Y" relaxation value. It is also preferred that the "Y" relaxation value be less than about 0.0012 cm / min for 3He and less than about 0.01 cm / min for 129Xe. The container also includes a second layer of a • - * -'- «-" - ** • '• * - * - • -------------------- í - áÉ ---- --- a --- second placed material so that the first layer is between the second layer and the chamber, wherein the first and second layers respond concurrently to the application of pressure and one or both of the first and second layers act as a protection against oxygen to suppress the oxygen permeability in the chamber Additional layers of materials can be placed between the first and the second layer In a preferred embodiment, the hyperpolarized gas has a low relaxation value in the material of The first layer and the second layer preferably comprise a material that can protect against migration of oxygen to the first layer. In another preferred embodiment, the flexible container has a first layer formed of a metal film (which can act as a protection against oxygen and as a contact surface). In this modality it is preferred that the relaxation values be less than about 0.0023 cm / min and 0.0008 cm / min for 129Xe and 3He, respectively. In other words, it is preferred that the hyperpolarized gas has a high mobility on the metal surface or a low absorption energy relative to the metal contact surface so that the Ti of the gas in the container reaches > 50% of its theoretical limit. A further aspect of the present invention is directed to a The method for storing, transporting and supplying hyperpolarized gas to a target. The method includes introducing a quantity of hyperpolarized gas into a flexible multi-layer container. The container has a wall comprising at least one material that provides protection against ? á¡mti? ia ¿to oxygen (ie is resistant to oxygen transport in the container). Preferably, the container expands to capture a quantity of hyperpolarized gas. The container is sealed to retain the hyperpolarized gas therein. The container is transported to a site away from the hyperpolarization site. The hyperpolarized gas is supplied to a target by compressing the chamber and thus forcing the hyperpolarized gas out of it. Preferably, to maintain the hyperpolarized state, the container is substantially substantially protected and / or exposed to a homogeneous magnetic field that is kept close to protect it from unwanted external magnetic fields and / or field gradients from the time of polarization to delivery . It is preferred that the container be configured to be reused (after re-sterilization) to carry additional amounts of hyperpolarized gases. Similarly, another aspect of the present invention is to configure single-layer or multi-layer flexible bags as described above with a capillary rod. The capillary rod is configured to restrict the flow of hyperpolarized gas from the container when the valve is closed. The capillary rod is preferably positioned between the container port and a valve member and, as such, forms a portion of the hyperpolarized gas (liquid) inlet and outlet path. The capillary rod is preferably configured with an internal passage having the proper size and configured to inhibit the flow of the hyperpolarized gas and includes a gas contacting surface formed of a material compatible with polarization. The capillary rod preferably works in association with a valve so that the flexible container allows the gas to be captured so that it can be released and the gas is protected from any potential depolarization effect when the valve is closed. Similarly, another aspect of the present invention is the configuration of flexible single-ply or multi-ply bags as described above with an insulating means to direct the gas or fluid away from the pouch port during transport and storage. . In this way the isolation means inhibit a major portion of the gas or hyperpolarized fluid from making contact with selected components (accessories, valves, O-rings) operably associated with the bag. In a preferred embodiment, the isolation means are provided by a clip placed to compress the portion of the bag near the port and inhibit the movement of the gas thereon. A further aspect of the present invention is a method for preparing a storage container that can be expanded to receive a quantity of hyperpolarized gas. The method includes providing a quantity of substantially pure purge gas such as nitrogen or helium (preferably grade 5 or better) in the hyperpolarized gas container and expanding the hyperpolarized gas container. Then, the container collapses to remove the purge gas. The oxygen in the walls of the container is degassed by decreasing the partial pressure of oxygen within the container, thereby causing a substantial amount of oxygen trapped in the walls of the container to migrate to the container chamber in the gas phase in the container. where it can be eliminated. Preferably, after the degassing step, the container is filled with a quantity of storage gas as nitrogen (again, grade 5 or better is preferred). The gas is introduced into the container at a pressure that reduces the pressure differential between the walls of the container to inhibit further degassing of the container. Preferably, the The container is then stored for future use (some time after preconditioning). Storage nitrogen and degassed oxygen are removed from the container before filling it with an amount of hyperpolarized gas. Preferably, after removal from storage and before use, nitrogen is removed by evacuating the container before filling it with an amount of hyperpolarized gas. Another aspect of the present invention is directed to a method for determining the solubility of hyperpolarized gas (129Xe or 3He) in a polymer (unknown) or a particular fluid. The method includes the introduction of a first quantity of hyperpolarized noble gas in a container that has a known free volume and by measuring a first relaxation time of the hyperpolarized gas in the container. A substantially clean sample of the desired material is placed in the container and a second quantity of hyperpolarized noble gas is introduced into the container. It takes a second relaxation time of the second hyperpolarized gas in the container with the sample material. The solubility of the gas in the sample is determined based on the difference between the two relaxation times taken. The sample of material can be a structurally rigid sample (geometrically fixed) with an area / volume of known geometric surface that is inserted into the free volume of the chamber or container. Alternatively, the sample of material may be a liquid that partially fills the chamber. Utilitatively, the methods and containers of the present invention can improve the relaxation time (prolong Ti) of the hyperpolarized gas or liquid or combinations of what is contained therein. The containers are configured so that the surface that makes contact with the hyperpolarized gas (hyperpolarized gas contact surface) has a minimum depth or thickness of a material with low relaxation value in relation to the hyperpolarized noble gas. In addition, the containers are configured to also inhibit the migration of oxygen into the gas chamber of the container. In addition, the container can define the contact surface by forming the container of a flexible material such as a polymer or metal bag. Preferably, the bags are configured to inhibit the hyperpolarized gas from potentially contacting by depolarizing the components associated with the bag during transport or storage. The container is preferably a multi-layer container wherein each layer of material provides one or more of the properties of resistance, resistance to puncture and resistance to oxygen to the container. Additionally, at least the inner surface is configured to provide a contact surface compatible with polarization. The flexible configuration provides a relatively non-complex container and increased Ti and can be reused. The gas contact surface is preferably formed of a polymer or a high purity metal. Additionally, flexible or collapsible containers can be used to supply the gas in the patient interface no need for vehicles / additional supply equipment. This can reduce the exposure, handling and physical handling of the hyperpolarized gas that, in turn, can increase the polarization life of the hyperpolarized gas. Flexible containers with high purity contact surfaces can be extremely useful for 129Xe and 3He, as well as for other hyperpolarized gases; however, the expandable (polymer) container and coatings / layers are especially suitable for hyperpolarized 3He. In addition, the present invention preferably places the container with the hyperpolarized gas in a homogeneous magnetic field inside a transport container to protect the gas against fields magnetic, especially damaging oscillating fields that easily dominate other mechanisms of relaxation.

Additionally, the present invention can be used to determine the solubility of gas in polymers or fluids that in the past proved difficult and sometimes inaccurate, especially helium. One aspect of the present invention advantageously now provides a way to mold the predictable behavior of surface materials and is particularly suitable for determining the relaxation properties of polymers used as contact materials in physical systems used to collect, process or transport hyperpolarized gases. For example, the present invention satisfactorily provides relaxation properties of various materials (measured and / or calculated). These relaxation values can be used to determine the relaxation time (Ti) of hyperpolarized gas in containers corresponding to the gas solubility, the surface area of the contact material and the volume of free gas in the container. This information can be usefully used to extend the hyperpolarized life of gas in containers over those previously achieved in high volume production systems. The aforementioned and other objects and aspects of the present invention are explained in detail herein.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a schematic diagram of a 'descending spin station used to measure relaxation times in accordance with an aspect of the present invention. Figure 2 is a graph showing the polarization level of a gas associated with the distance x that the gas displaces to a polymer. Figure 3 is a graph showing the results of the relaxation times standardized in a graph in comparison with the solubility (measured and theoretical) for various materials (T? Cc representing the relaxation time for the hyperpolarized 129Xe gas in a sphere of a cubic centimeter). Figure 4 is a graph similar to Figure 3 showing the results of the standardized relaxation times for 3He. Figure 5 is a detailed table of values of experimental materials for xenon and helium. Figure 6 is a detailed table of predicted material values for xenon and helium. Figure 7 is a perspective view of a hyperpolarized gas container in accordance with one embodiment of the present invention in a deflated state. Figure 8 is a perspective view of the container of Figure 7 shown in an inflated state.

Figure 9 is a sectional view of an alternative embodiment of a container in accordance with the present invention. Figure 10 is an enlarged partial sectional view of the container wall in accordance with another embodiment of the present invention. Figure 11 is an enlarged partial sectional view of a further embodiment of a wall of the container in accordance with the present invention. Figure 12 is an enlarged partial sectional view of a further embodiment of a wall of the container in accordance with the present invention. Figure 13 is a perspective view of a preferred embodiment of a container with a seal in accordance with the present invention. Figure 14 illustrates the container of Figure 13 with an alternative external seal in accordance with a further embodiment of the present invention. Figure 15 illustrates another container with an alternative seal arrangement in accordance with another embodiment of the present invention. Figure 15A is a view with the separated parts of the container shown in Figure 15. -.-- ^ ------- ^ ------- «--- jBj ---- ^ -. .-, ... ,. - > . «-.- t -, - l" ---.-. .-- JJ._. . ... ._. -. - to--* . . .-. «..» .-, * -_ Figure 16 is a side perspective view of a transport container with protection configured to receive the container in accordance with a embodiment of the present invention. Figure 17 is a schematic illustration of the flexible container of Figure 13 shown attached to a user interface adapted to receive the container for supplying hyperpolarized gas thereto to the user in accordance with an embodiment of the present invention. Figure 18 shows the container of Figure 17 in a deflated condition after forces on the container cause the hyperpolarized gas to exit the container and enter the target. Figure 19 is a schematic illustration of the container of Figure 15 shown attached to a user interface in accordance with one embodiment of the present invention. Figure 20 is a block diagram of a method for determining the solubility of the gas in a polymer according to an embodiment of the present invention. The figures from 21 A to 21 C are perspective views of an alternative embodiment of a container with port isolation means in accordance with the present invention.

DETAILED DESCRIPTION OF THE PREFERRED MODALITIES In the following, the present invention will be described in greater detail with reference to the appended figures, in which the preferred embodiments of the invention are shown. However, this invention can be modalized in different ways and should not be construed as limited to the modalities set forth herein. Equal numbers refer to the same elements throughout the description. Layers and regions can be exaggerated for clarity. For a simpler analysis, the term "hyperpolarized gas" will be used to describe a hyperpolarized gas alone, or a hyperpolarized gas that makes contact with or combines with one or more other components, whether gaseous, liquid, or solid. In this way, the hyperpolarized gas described herein may be a composition / mixture of hyperpolarized gas (non-toxic so as to be suitable for in vivo introduction) so that the hyperpolarized noble gas can be combined with other noble gases and / or other inert or active components. Also, as used herein, the term "hyperpolarized gas" may include a product where the gas The hyperpolarized liquid is dissolved in another liquid (such as a vehicle) or processed so as to form in a substantially liquid state, ie "a liquid polarized gas". Thus, although the term includes the word "gas", this word is used to name and indicate descriptively the - ^ .. ^ -J-to- ^ -Aafc. » . ? ? . -, .. - »... . . . . .-- 2 gas produced by a hyperpolarizer to obtain a polarized "gas" product. In summary, as used herein, the term "gas" has been used in certain places to descriptively indicate a hyperpolarized noble gas which may include one or more components and which may be present in one or more physical forms. The preferred hyperpolarized noble gases (either alone or in combination) are listed in Table 1. This list was created with the intention of illustrating and not limiting.

TABLE 1 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 gases polarized by spin and the US patent. No. 5,809,801 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 fully set forth herein. How it is used 1 * * - in the present, the terms "hyperpolarize" and "polarize" are used interchangeably and mean to artificially improve the polarization of certain noble gas nuclei over the natural or equilibrium levels. Such an increase is desirable because it allows better image signals corresponding to better MRI images of the substance and a target area of the body. As is known to those skilled in the art, hyperpolarization can be induced by spin exchange with an alkaline metal vapor pumped 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. The alkali metals that are preferred for this hyperpolarization technique include sodium-23, potassium-39, rubidium-85, rubidium-87, and cesium-133. The isotopes of alkali metal, and their relative abundance and spins nuclear weapons are listed in table 2 below. This list was created to be illustrative and not restrictive.

TABLE 2 twenty ^ jg ^ »g * Alternatively, noble gas can be hyperpolarized using metastability exchange (see for example Schearer, L.D., Phys. Rev., 180: 83 (1969); Laloe, F. et al., AIP ConfProx # 131 (Workshop on Objectives and Rays of 3 He polarized) (1984))). The metastability exchange technique involves direct optical pumping, for example, 3He without the need for an alkaline metal intermediate. The metastability exchange method usually involves the excitation of the 3He atoms in ground state (11So) to a metastable state (23S-?) By a weak radiofrequency discharge. The 23S-atoms? they are then pumped optically using a circularly polarized light having a length of 1.08 μm in the case of 3 He. The light carries the transitions to 23P states, producing high polarizations in the metastable state in which the 23S atoms then decompose. The polarization of states 23S-? it is rapidly transferred to the ground state through metastability exchange shocks between the fundamental metastable state atoms. The optical pumping of metastability exchange will work in the same low magnetic fields where the spin exchange pump works. Similar polarizations can be achieved, but generally with lower pressures, for example, about 0-10 Torr. In general, for optically pumped systems with spin exchange, a gas mixture is introduced into the counterpolar hyperpolazir apparatus of the polarization chamber. Most xenon gas mixtures include a gas with a pH regulator as well as a -Ml ---------, --------------- É ----- I ---- II amount of gas support directed for hyperpolarization and preferably It occurs in a continuous flow system. For example, to produce hyperpolarized 129Xe, the premixed gas mixture is typically 85-89% He, about 5% or less 129Xe, and about 10% N2. In contrast, to produce hyperpolarized 3He, a mixture of 99.25% 3He and 0.75% N2 is pressurized to 8 atm (810 KPa) and heated and exposed to an optical laser light source in a batch mode system. In any case, once the hyperpolarized gas leaves the pumping chamber it goes to a collection or accumulation container. 10 An alignment field of 5-20 Gauss (0.5-2mT) is typically provided for optical Rb pumping for the polarization of 129Xe and 3He. The hyperpolarized gas is collected (as it is stored, transported and preferably supplied) in the presence of a magnetic field. It is preferred for solid (frozen) 129Xe that the field be of the order of at least 15 500 Gauss (0.05T), and typically about 2 kilo Gauss (0.2T), although larger fields may be used. Minor peers can potentially undesirably increase the relaxation rate or decrease the relaxation time of the polarized gas. With respect to 3He, the magnetic field is preferably of the order of at least 5-30 gauss (0.5-20mTm) although, again, larger (homogeneous) fields may be used. The magnetic field can be provided by electric or permanent magnets. In one embodiment, the magnetic field is provided by a plurality of permanent magnets placed near an apparatus lll m iilñ ll r - J ^ Ja? * a-tL - *** - • ^ ¿&JHSM ^ á ^ magnetic that is placed adjacent to the hyperpolarii gas collected. Preferably, the magnetic field is maintained homogeneously around the hyperpolarized gas to minimize field-induced degradation.

Polarized Gas Relaxation Procedures Once hyperpolarized, there is a theoretical upper limit on the relaxation time (Ti) of the polarized gas based on the relaxation by shock explained by fundamental physics, that is, the time it takes for a given sample to decompose or depolarizing due to the collisions of hyperpolarized gas atoms with each other, even without depolarizing factors. For example, 3He atoms relax through a dipole-dipole interaction during 3He-3He shocks, while 129Xe atoms relax through a spin rotation interaction Nl (where N is the molecular angular momentum and I designates nuclear spin rotation) during the 129Xe-129Xe crashes. In other studies, the angular momentum load associated with the change of orientation of the nuclear spin is conserved by absorbing the angular momentum of rotation of the colliding atoms. In any case, because both procedures occur during noble gas-noble gas shocks, both result in relaxation rates that are directly proportional to the gas pressure (Ti is inversely proportional to the pressure). At one atmosphere, the theoretical relaxation time (T,) of 3He is about 744 to 760 hours, while for 129Xe the corresponding relaxation time is about 56 hours. See Newbury et al, "Gaseous 3He-3He Magnetic Dipolar Spin Relaxation," 48 Phys. Rev. A., No. 6, p.4411 (1993); Hunt et al., Nuclear Magnetic Resonance of 129Xe in Natural Xenon, 130 Phyx. Rev. P. 2302 (1963). Unfortunately, other relaxation procedures prevent the realization of these theoretical relaxation times. For example, crashes of 129Xe and gaseous 3He with container walls ("surface relaxation") have historically dominated most relaxation procedures. For 3He, most of the longest known relaxation times have been achieved in special glass containers that have low helium permeability. In the past, a fundamental understanding of surface relaxation mechanisms has been difficult which hindered the associated prediction capacity of Ti. Patent of E.U.A. No. 5,612,103 to Driehuys et al. describes the use of coatings to inhibit surface-induced nuclear spin relaxation of the hyperporalized noble gases, especially * 29Xe. The contents of this patent are incorporated herein by reference as if fully set forth herein. Driehuys et al. recognized that nuclear spin relaxation of 129Xe in a surface coating of polydimethoxy siloxane ("PDMS") can be mastered by bipolar nuclear spin coupling of 129Xe with the protons in the polymer matrix. In this way, it was shown that paramagnetic contaminants (such as the presence of paramagnetic molecules such as oxygen) were not the dominant relaxation mechanism in such a system because the nuclear-dipole-dipole relaxation was found to dominate the system under investigation. This was by 129Xe substantially dissolved in the particular polymer matrix (PDMS) under investigation. See Bastiaan Driehuys et al., 5"Surface Relaxation Mechanisms of Laser-Polarized 129Xe," 74 Phys. Rev. Lett., No. 24, pp. 4943-4946 (1995). One aspect of the present invention now provides a more detailed understanding of the depolarization of noble gases in polymer surfaces. In fact, as will be explained below, the The solubility of noble gases in large numbers of polymer systems (not only PDMS) can cause an inter-nuclear dipole-dipole relaxation that dominates the rate of polarization decrease. Notably, this analysis now indicates that polymers can be especially effective for the suppression of 3 He relaxation. In addition, an explanation of prediction of The relaxation of noble gases on the polymer surfaces is described below. Utilizing, it is now possible to calculate and measure the relaxation properties of various materials. This information can be usefully used with other parameters such as free gas volume and surface area of the containers to provide more effective surface configurations and useful and characteristics of materials that can facilitate, preserve and further improve the polarization life of the noble gas. This is especially useful for providing containers that can perform reliable, repeatable and predictable production and maintenance of high volume polarization, which in the ^ ^ ^^^ A & ^^ j & The past had been difficult to achieve outside the primitive conditions of a low-production laboratory. In general, magnetic interactions can modify the preferred relaxation time constant as the longitudinal relaxation time (Ti), and typically occur when different atoms are found. In the case of hyperpolarized noble gases retained in containers, the magnetic magnetic moments of the gas atoms interact with the surface materials so that the gas returns to the equilibrium or non-hyperpolarized state. The magnetic moment resistance can be a determining factor in determining the relaxation rate associated with the surface material. Because different atoms and molecules have different magnetic moments, relaxation rates are material-specific.

Material relaxation capacity To compare information on the characteristics of certain materials that relate to the respective relaxing effects in hyperpolarized noble gases, the term "relaxation capacity" is used. As used herein, the term "relaxivity" ("Y") is used to describe a property of material associated with the deporalization rate ("1 / T |") of the hyperpolarized gas sample. For a container that has a chamber volume "Vc" capable of retaining a quantity of hyperpolarized gas and for a sample of material with a surface area "A" in the chamber of the container, each time a polarized gas atom makes contact With the surface of the container, there is the probability ("p") that it will depolarize. The depolarization rate (1 / T |) of this gas sample in the chamber can then be described at times p of the rate at which the gas atoms collide with the surface ("R").

- RP (2-1) T, The average surface (R) shock rate per gas atom is known from static mechanisms, R.Reif, Fundamentals of Statistical and Thermal Physics, McGraw-Hill, chapters 12-14, pp. 461-493 (1965); vA R = - (2.2) AV in this equation "v" is the average thermal velocity of the gas atoms. For the case of a sphere of one cubic centimeter ("1 cc") of129Xe the area is A = 4pr2 and the volume is V = 4pr3 / 3. In this way for v = 154 m / s, the Equation (2.2) produces a shock rate of R = 800 s' In other words, each atom of Xe makes contact with the surface of the sphere 800 times in a second. Thus, in accordance with equation (2.1) the longest Ti times must have a one minute probability of deporalization during each collision (p «1). The substitution of the equation (2.2) in equation (2.1) produces: 1 A? (2.3) 4V ---------------------------------- ^ ------ ^ - ^ ----- «--------- 111 Since the measurements for this study are made at ambient temperature, "v" will not vary. Therefore, the term capacity of Relaxation ("Y") that is defined as Y = vp / 4, results in: 1 A - = -Y (2.3) 5 T > V In this way, the capacity for relaxation ("Y") is a property of the material that can describe the deporalizing effect that a specific material has on a sample of hyperpolarized gas. When considering hyperpolarized gas containers, it is important to observe the relationship between the terms 1 / T? and A V in equation 2.4. In this way, the "A / V" relationship for a sphere that has a radius "r", the ratio is reduced to 3 / r. In this way, a one liter sphere (1000 cc, r = 6.2 cm) has a Ti that is 10 times longer than a sphere with a volume of one cubic centimeter (1cc, r = 0.62 cm) made of the same material.

Thus, preferably, in order to improve the Ti of the hyperpolarized gas in the containers, the containers are configured and sized to decrease the value of the A / V ratio; that is, to increase the relative volume with the container area, as will be discussed below in greater detail. 20 Determination of relaxation capacity Equation 2.4 can be used to calculate the gas relaxation capacity in case the surface relaxation is the effect single deporalizing (dominant) at the moment. This is not the case for studies of practical material. The surface of the test chamber, the seal of the chamber and other impurities also contribute to the relaxation of the gas. However, by using the relaxation time differences between the hyperpolarized gas in an empty test chamber and the hyperpolarized gas in the chamber containing a sample of material placed so as to make contact with the hyperpolarized gas, the capacity of the hyperpolarized gas can be determined. characteristic relaxation of the material. Note that the relaxation rates are additive in the following way: 1 1 1 1 - rp = - r a + - -T.fi + - r ... (v2.5) '- - J X \ In general, T? A can represent the relaxation effect of the surface of the test chamber Tb 'which can represent the effect of the hyperpolarized gas atoms colliding with each other. Assuming that surface relaxation is the dominant relaxation effect, the relaxation rate can be described by adding the surface effects of the material sample and the test chamber. 1 A Y A Y (2.6) V where Am and Ym describe the area and relaxation capacity respectively of the material sample and Ac and Ym correspond to the area and Relaxation capacity of the container or camera. "V" is the volume of free gas in the chamber. In this case V = Vc-Vm, where "Vc" is the volume of the chamber and "Vm" is the volume of the container occupied by the material sample. In studies of relaxation capacity for new materials (where the sample of material is small) the free volume "V" can be approximately equal to Vc that is, V = VC. Substituting again in (2.6): 1 A Y A Y (2.7) It should be noted that for the chamber without a sample of material this equation is reduced to -1 = 4 £ (2.8) where T | C is the characteristic relaxation rate of the empty container or chamber. Substituting (2.8) in (2.7) produces: = 4? + J_ (2.9)? VC Tlc Solving equation (2.9) gives an expression for the relaxation capacity Ym associated with a specimen of specific material with a Ti in a chamber with a known and observed volume T! C: rm ^ - (2-10) Am Al 1lc The capacity for relaxation of a given material can easily be translated back into a characteristic intuitive relaxation time. A comparison method, maintaining studies of relaxation rate of _ | _ * __ ¿-t- • ^ g ^ surface based, is to describe the relaxation rate as if there existed a spherical cell of 1 cc made of the material in question. Knowing the surface area and the volume of such cell (A = 4pr2, V = 4pr3, r = 62 cm) and substituting again in (2.8): "= Again, this container geometry is for illustration only and standardizes the relaxation term for comparison with the previous data. For reference, the Ti values observed from the 10 129Xe studies in the past showed Pyrex ultraclean with a single layer surface of Rb that has an associated time of T c C = 30 minutes.

Experimental determination of relaxation capacity The hyperpolarized gas samples were used in a material testing center known as the Spin Down Station. This apparatus was constructed to test several samples of material in a controlled environment. The system consists of a material testing chamber, a Pulse-NMR spectrometer, and a LabView user interface. The flexible system allows various cameras or bags to be cleaned and filled with 129Xe or 3He polarized. The Pulse-NMR system then traces the deterioration of the signal of these containers over time. ^ m a? ^^ t? t ^ ¿í? itd t ^ ri¡kaaj jMBb Equipment design Figure 1 is a schematic diagram of the Spin Down Station. This apparatus consists of a Helmholtz pair that generates a stable Helmholtz 151 magnetic field around the glass test chamber 5 labeled Spin Down Chamber 152. The frequency (f) of signal response is proportional to the applied magnetic field (B0) expressed by the equation f = YB0 / 2p. This ratio constant is known as the gyromagnetic ratio (YHe = 7400 s'1G "1, YXe = 26700 s" 1G "1) .If the applied magnetic field remains constant, the coil must be adapted to change between the Two gases: As an alternative to adapt again, the field strength was adjusted to obtain an equal frequency response for both gases: A current of 1.0 A (field 7 G) for 3He and 2.5 A (field 21 G) for 129Xe it was applied to the Helmholtz pair observed by the Helmholtz field shown in figure 1. 15 In the center of the Helmholtz field 151 was one of the two spinning 152 chambers used in these tests, both chambers had a valve to evacuate (Base pressure -30 milliTorr) and fill the chamber with hyperpolarized gas Each chamber can be opened to insert polymer samples (typically 10mmx20mmx1mm) As shown, the NMR 153 coil rests behind the camera in the center of the Helmholtz field 151. The first downward spin chamber is made of Pyrex ™ coated with demethyldichlorosilane (DMDCS) and used a rubber O-ring -MHI | BII¡ --- l-íl - lII-N - l ---- - * - - - - * • * - "" * "•" - "coated with Teflon ™ as the seal for vacuum This chamber exhibited a characteristic 110-minute T | C suitable for observing the surface relaxation effects of various polymer samples 154. Notably, after numerous tests, the Tc frequently decreased.A complete cleaning with high purity ethanol restored the camera to the baseline value Unfortunately, the T | C for the Pyrex ™ camera with 3He was not long enough to distinguish good materials from bad for 3He.The various glass tests in the Pyrex ™ down spin camera showed that a chamber made of 1724 aluminosilicate glass would have a T | C sufficiently long for 3 He.The 3He 1724 chamber was constructed with a base seal that required Apiezon ™ vacuum grease.The chamber exhibited a characteristic T | C of 12 On average, the Apiezon ™ grease used to Both the camera and the inlet valve caused the T! c of the camera to fluctuate significantly more than that of the Pyrex ™ camera. To reset the camera to T | C, baseline, the rasa was removed by cleaning the chamber with high purity hexane.

Test procedure Using a Spin Down Station, descent spin station, seven polymer samples were tested using 129Xe or hyperpolarized 3He. These polymers were obtained from Goodfellow, Inc. Berwyn, Pennsylvania.

. . .. .. . .... .. . .. . . . -. . - ...? . -. «E-at-ab» - ... - Sample supplied by DuPont.

The particular polymers were chosen to represent a wide range of solubilities for the 129Xe and 3He gases. Each polymer sample was cleaned with ethanol and cut into specific sizes and shapes to provide a known volume and surface area of the polymer sample (typically V = 2 cm3, SA = 42.6 cm2) for each study of T |. The following steps were taken for each measurement of material: 1. The pre-amp camera was cleaned 2. 129Xe or 3He was polarized 3. A Ti study was performed to establish the baseline of the camera (T | C) 4. The polymer sample was placed in chamber 5. 129Xe or 3He 6 was polarized. A Ti study was performed for the chamber containing a polymer sample (T | S) '«. - »w 7. T | C and Tis were used to discover the relaxation rate due to the specific polymer Polymer absorption model The ability to measure and calculate relaxation capacity can result in an understanding of the physical characteristics that differentiate materials. An initial study of a wide range of materials confirmed that conventional rigid glass containers are much better than containers made of materials that contain paramagnetic or ferrous materials such as stainless steel. Notably, this test also showed a wide range of relaxation capacity within different groups of materials. In particular, different polymer materials were observed through a margin of relaxation capacity. Important manufacturing points such as durability and reliability make polymer materials an excellent alternative to glass storage containers that are typically used for hyperpolarized gases. Scientifically, substantially pure samples of these materials allow relatively less complex models of surface relaxation. For analysis purposes, assume that a hyperpolarized gas polymer container exists in a homogeneous magnetic field. Since polymers are permeable materials, some amount of gas dissolves in the walls of the container. The only dominant relaxation mechanism in this system is that the hyperpolarized gas atoms interact with the protons or contaminants on the surface and volume of the polymer container. Driehuys et al. demonstrated that the relaxation of hyperpolarized 129Xe in a specially coated glass sphere was dominated by the dipolar coupling between protons on the surface and in the nuclear spin of 129Xe. See Driehuys et al., "High-volume production of laser-polarized 129Xe," 69 App. Phys. Lett. (12), p. 1668 (1996). Because the shocks of Xe-Xe have a Ti of 56 hours and the Ti times of typical conventional materials are of 2 hours or less, the relaxation rate of the free gas can be neglected. The gas dissolved in the container is in the form of a free gas. Therefore, the relaxation of this gas occurs through a continuous exchange between the free gas and that dissolved in the polymer. In material quantities, the rate of this gas exchange can be described by the "absorption parameters" - solubility ("S"), diffusion coefficient ("D"), and permeability ("P"). Permeability is the transmission of atoms or molecules through a polymer film. It depends on the chemical and physical structure of the material as well as the structure and physical characteristics of the permeating molecules. Permeability can be defined as the product of solubility and the diffusion coefficient ("P = SxD"). Solubility ("S") is a measure of how much permeable material can dissolve in a given material. The diffusion coefficient ("D") is a measure of the random mobility of the atoms in the polymer. The absorption parameters of the polymer can be used to characterize the relaxation of hyperpolarized gases in the presence of permeable surfaces.

Relaxation in the presence of polymer surfaces Magnetization ("M") is defined as the product of the gas polarization "P" and the density of the gas number "[G]", M = [G] P. The equation that governs the relaxation of magnetization in the presence of a surface diffusion - rM (x, t) (2.12) where ("M (x, t)") is the magnetization, ("D") is the diffusion coefficient of the gas in the surface material, and (T ") is the gas relaxation rate. Happer et al., Hyp. Int. 38, pp. 435-470 (1987) As usual, the solution is written as a product of time and space dependent components: M (x, t) = m (x) e (2.13) where ("m (x)") is the spatial distribution of the magnetization on the surface When replacing (2.15) in (2.13) the spatial equation is produced: ^. «(^ = 1 ^ -) m (x) (2.14) dx D T, This differential equation describes the spatial distribution of magnetization in the presence of diffusion and relaxation. The distribution of - .. -. _ ...- -. . .. -, -. . .. - ,. -. . . - - i-, --_ -,. , -, "., -. .--. ^ au ----. magnetization in a one-dimensional chamber is shown in figure 2. The chamber is a gas volume of width "2a" delimited on each side by infinite walls of polymer. The polarization of gas in this chamber has two specific regions of interest. In the free gas portion of the container, the polarization is relatively homogeneous with respect to the spatial variable x. In contrast, polarization decreases exponentially with distance x on the polymer surface. This profile reflects a much faster rate of relaxation within the polymer as opposed to free space. Equation (2.14) can be used to independently resolve the spatial magnetization of the gas and polymer regions.

For a gas phase with diffusion coefficient Dg and intrinsic relaxation velocity rg = 0, equation (2.14) results: d2 2 - mg (.?) = --mg (x) (region I) (2.15) The first-order symmetric solution to this equation is: m (x) = Acos (k?) = - (region I) Similarly, the polymer region has diffusion coefficient "Dp" and relaxation rate rp: ! lWp (*) = - (r, -!) «, (*) (region II) (2.16) ox J p 1. .m¿ ?? MM ^ aí A simplification premise is that the relaxation rate in the polymer is much faster than the relaxation rate observed (rp »1 / T?). Thus, by omitting the term 1 / T | In (2.16) a solution of the form is produced: (region II) These two solutions together with the appropriate boundary conditions can be used to resolve the observed Ti of the gas in the polymer chamber. The first boundary condition ("BC") maintains continuity of polarization through the polymer gas limit. Remember that magnetization is the product of polarization and gas number density produces: BC-i: SMg (a) = mp (a) where ("S") is defined as the ratio of gas number densities, or Ostwaid solubility "S = Np / Ng". The second boundary condition ("BC2") arises because the exchange of magnetization across the gas-polymer boundary is equal on both sides. This exchange, known as the magnetization current, is defined as Jm = -DVm (x), producing the boundary condition: BC2: D, ± m, M-D, j.m, W Applying the boundary conditions to the solutions for magnetization in each of the two regions produces the following transcendental equation: tan k = ^^ s (2.17) * A This equation can be solved numerically, although a reasonable approximation is that kga «1, so that kga = kga. In physical terms, this implies that the magnetization is spatially uniform across the gas phase. It also considers only the slowest of the multiple broadcast modes. In order for this premise to be false, the speed of relaxation in the walls would have to be rapid compared to the time it takes for the gas to diffuse through the chamber. Broadcast times are usually a few seconds, while common Ti values are several minutes. The application of this premise produces: The substitution in kg and kp of the solutions for (2.15) and (2.16) gives: The relaxation rate in terms of the polymer can be rewritten in terms of rp = 1 / T | P. The solution for the relaxation time Ti: This analysis can be extended in three dimensions, producing. where Vc is the internal volume of the chamber, A is the exposed surface area of the polymer and S is the solubility of gas in the polymer. The inverse relationship between Ti and S is a key observation of this development. Because the solubilities of He are usually many orders of magnitude lower than the corresponding solubilities of Xe, the times Ti for 3He must be significantly longer than for 129Xe. There is also an apparent inverse square root dependence on the diffusion coefficient Dp. Nevertheless, the relaxation time in the polymer 1 / TP also depends on Dp, canceling the global effect in T |. This leaves solubility as the dominant absorption characteristic when determining T |. In spite of canceling (2.21), the diffusion coefficient plays an important role in another quantity of interest, the duration scale of the gas and polymer interaction. The exponential decomposition duration scale of the polarization Lp = 1 / kp is given by solution a (2.16): L = JD TP p X¡ p X '\ i (2.22) , .-- -. ...., * -. - .. ». . .. - - ... . . .. .. . . * .... ^. j.

Importantly, this scale describes the depth in the polymer that the gas travels in the relaxation period. In order to compare theoretical predictions with experimental data, it is preferred that the material samples have at least a thickness of several length scales. This ensures that the surface model developed here, which assumes an infinite polymer thickness, is an accurate approximation of the diffusion process. As a reference, LPDE has a diffusion count of 6.90e-6 cm2 / s for helium gas and hyperpolarized 3He has a relaxation time in the polymer of approximately .601 s (T | p = 0.601 seconds). The resulting duration scale is about 20 μm, many times less than the 1 mm polymer samples used in the study described herein.

Predicting Ti values using the absorption model 15 Using equation (2.21) to predict Ti values for hyperpolarized gases in the presence of various polymer surfaces requires knowledge of the test environment (Vc, Ap), as well as parameters that connect the polymer and specific gas (T | p, S and D). Unfortunately, the solubility and diffusion data that bind gas and polymers are scattered and some 20 times do not exist. On the other hand, the test environment is usually known. Advantageously, these data can be used to calculate the T, p.

----? - Hi -------------- lj ---------? ^ Ad ^ WIÍÉM As previously discussed, the relaxation mechanism that dominates the relaxation of hyperpolarized gas in polymers is the interaction with the nuclear magnetic moments of the hydrogen nuclei (in hydrogen-based polymers). Established in a general way, in the absence of 5 paramagnetic contaminants, the 1H nuclei are the only source of magnetic dipoles to cause relaxation. Based on this interaction, Huang and Freed developed an expression for the gas relaxation velocity of V-. spin that diffuses through a polymer matrix. See L.P. Hwang et al., "Dynamic effects of pair correlation functions on spin relaxation by translational diffusion in liquids, "63 J. Chem. Phys. No. 9, pp. 4017-4025 (1975); J. H. Freed," Dynamic effects of correlation functions on spinning by translational diffusion in liquids. II. Finite jumps and independent Ti processes, "68 J. Chem. Phys. Vol. 9, pp. 4034-4037 (1978), and E. J. Cain et al," Nuclear Spin Relation Mechanism and Mobility of Gases in Polymers, "94 J.

Phys. Chem. No. 5, pp. 2128-2135 (1990). This results in the following expression in a low magnetic field of regime B (B < 1000 Gauss) (0.1 T). 405 DD "T, '= (2.23) 32p. S (s + y? 2Gy2Hh2Na? H \ 20 In this formula,? G is the gyromagnetic relation of the noble gas,? P is the gyromagnetic relation of the protons, s is the proton spin number (1/2), Na is the number of Avogadro, [1H] is the molar density of > _t - MÉte ---- u- -Éítaa «fi? ------ i protons in the matrix, and b is the distance of the closest approach of the noble gas to a proton. The dipole interaction equations have an inverse square dependence on the gyromagnetic relationships? G and? H. As mentioned before, substituting this form in equation (2.21) cancels Dp from the relaxation expression. This leaves only the solubility (S) to effect the Ti in various polymers. The other important factor in (2.23) is the dependence on [1H] "1. As such, because the protons in the polymer are the dominant relaxation mechanism, the high concentrations will adversely affect T? P. 10 I mplementar This expression for T? p requires the appropriate physical parameters in CGS units Table 2.1 shows an example of the approximate values used for this calculation performed for 129Xe relaxation in low density polyethylene (LDPE): TABLE 2.1: Sample data for Tr P d He «129 X? e in LDPE One of the few available literature values (Handbook of Polymer) ^ Mt & ^ kA Confirmation of the prediction model The development of the relaxation model based on absorption together with the experimental apparatus to test the relaxation capacity allows the comparison of a theoretical model of surface relaxation with experimental results. The confirmation of this model allows quantitative predictions of surface relaxation to select suitable and preferred materials to make contact with hyperpolarized gases. The descendant spin station was used to measure the relaxation effects of 7 different polymers in 129Xe and hyperpolarized 3He. In order to compare these experimental data with the theoretical data, the solubility of both gases in each polymer was measured. These absorption measurements are described below as well as a discussion of results from the 129Xe and 3He polymer studies.

Solubility measurements Solubility ("S") is the only thing that remains unknown in the formula to predict Ti of hyperpolarized gases in polymers (2.21). The equation is again exposed here as a reference: t, = A S D "20 Absorption data for several polymers are tabulated in sources such as the Polymer Handbook. S. Pauly, Permeability and Diffusion Data, The Polymer Handbook VI / 435. Unfortunately, while - ~ - - - "*" «* - * - * • - - - • - - - * - - • -» * .. »-,. . - »-. TO. that the data for helium is widely available (although prone to error), there has been no need to measure the absorption characteristics of Xe in different polymers. The lack of published xenon solubilities resulted in a search for equipment to measure these quantities. The polymer group at the Department of Chemical Engineering at North Carolina State University measured the solubility of xenon and helium gases in 7 polymers that would be used to verify the theory of polymer relaxation. The results of the solubility measurements of helium and xenon are compared with the literature values available in the Table 4.1 below (note that some data were not available).

TABLE 4.1: Results of solubility measurements fifteen Literature value for Nylon 11.

The measurements were obtained by placing polymer samples in an evacuated chamber. Then a known gas pressure was introduced into ^^ ffi? ^^^ ----------------- tl-l ------ k ------ < the camera. As the gas dissolved in the polymer, the decrease in chamber pressure was recorded. By knowing the volume of the test chamber and carefully maintaining the temperature of the apparatus, the solubility of the gas in the polymer can be calculated from the pressure versus time data. However, there are many intrinsic difficulties in polymer absorption measurements. Due to the low diffusion coefficients in some polymers such as polyimide, it can take a long time for the gas to penetrate the entire sample and establish an equilibrium. Even the thinnest available samples should be allowed to remain in the chamber for several days. Another problem, evident in measurements of He, that the differences in pressure observed for materials with low solubilities are extremely small, resulting in significant measurement uncertainty. In addition to these problems, density values play an important role in the calculation of solubility. Although the manufacturer provides density estimates for material samples, laboratory measurements indicated that these values are often not accurate. This discrepancy may be responsible for drastic changes in the final solubility value. Therefore, it should be noted that with regard to absorption measurements, more reliable results can be obtained. However, the values provided are sufficient to confirm the relaxation theory based on solubility.

Study of 129Xe materials Most of the study of these materials was performed using hyperpolarized 129Xe. A much larger sensitivity of 129Xe for surface effects resulted in shorter Ti times and 5 allowed a faster material test. The most drastic relaxation effects eliminated the need for an extremely long Ti camera as is the case for 3He studies. This single fact yields more reliable results for 129Xe material testing. Figure 3 is a graph of Ti00 against the product S [1 H] 5, which represents the two significant terms in the expression for Ti (2.21) developed in the polymer absorption relaxation model. For the experimental data points, the error bars and in the graph represent the cumulative error in the relaxation measurement. The error bars x are associated with the solubility measurements described above. The data confirm that solubility can be used to predict Ti for hyperpolarized 129Xe on polymer surfaces. Although the experimental data points follow the trend predicted by the theoretical model remarkably well, certain discrepancies warrant further discussion. The Ti measurements lower than predicted as in the silicone case 20 can be explained in different ways. Paramagnetic impurities in the sample material or test chamber are the main suspects. It should be remembered that only the protons assumed to have a depolarizing effect on the hyperpolarized gas. With the final purpose -MaA-tt ----- - ^ i ^^^^ to keep this premise true, the composition of the material sample should have been extremely pure. For example, since the gyromagnetic ratios of Fe and protons are related YFT ~ 1000 Y-IH, a presence of one part per thousand of Fe in the material sample can double the rate of relaxation. Although the sample surfaces were cleaned with high purity ethanol prior to testing at the Spin Off Station, the paramagnetic impurities can be trapped in the polymer matrix during the cure process. A possible contaminant is Pt metal (which is paramagnetic) that can be used in the mold that forms the silicone polymers. When considering factors that cause the measured results of Ti to be higher than predicted as in the case of polyimide (Pl) and PTFE, the diffusion coefficient becomes an important parameter. For polyimide, the diffusion of Xe in the polymer is so slow that it takes weeks for the Xe to fully equilibrate. This time scale is much larger than the 1-2 hour time scale of relaxation measurements. Because T? P of 129Xe in Pl is in the order of 100 ms (based on LDPE), 129Xe atoms only sample a tiny layer (~ 5 μm, based on a D-10 diffusion coefficient). "8 cm2 / s) of the surface of the polymer sample This surface layer may have different absorption characteristics than the massive polymer that was used in the solubility measurements, although normally the solubility can only be measured for the sample mass, the region of interest is only 0.5 μm between 1 mm, or 0.5x10_6 / 1.0x10-3 (approximately 1/2000) of the real sample, and a summary comparison of the predicted and measured results is presented in Table 4.2. for 129Xe In figures 5 and 6 more detailed results of the theoretical and experimental calculations are tabulated.

TABLE 4.2 Results of polymer relaxation study for 129Xe He material studies The study of 3He surface relaxation in polymers is much more challenging than the 129Xe study. Figure 4 shows the results of this study in the form T? P vs. S [1 H] 5 as discussed for the 129Xe presented in Figure 3. The various errors associated with the study of 3He make a direct comparison with the difficulty of 129Xe. However, there are trends that link the two studies that deserve to be mentioned.

The results for LDPE and PTFE agree extremely well with the theory. However, the other materials in the 3He study do not reach the predicted times of T | relaxation. Of these materials, silicone, PP and HDPE are consistent with the short results observed in the 129Xe study. This trend indicates paramagnetic impurities in the material samples. These contaminants can include dust, fingerprints, Apiezon grease, and ferrous impurities that can be trapped in the polymer material. Unfortunately, higher diffusion coefficients for He result in much larger length scales (~ 20 μm 3He vs. -1 μm 129Xe, equation 2.23) for polymer gas interaction. The greater mobility of gas atoms in the polymer results in a much deeper sampling of the polymer. This sampling can increase significantly the probability of interaction with paramagnetic impurities if its distribution in the polymers is not uniform. For example, the silicone gas has a high diffusion coefficient (DHe ~ 4e, DXe ~ 5e, 6) in relation to other polymers in the study. Although the Ti measured for silicone, PP, and HDPE was lower than predicted in both 129Xe and 3He studies, the 3He has a duration scale of approximately 3 times that of 129Xe. This issue of contaminants increases the importance of sample preparation in the study of surface effects, as well as the preparation of containers used for hyperpolarized gases. As discussed with the 129Xe study, the sample preparation included only ^ Surface cleaning, leaving no contaminants contained within the polymer matrix. An alternative may be to use acid baths to clean containers or container materials to remove or minimize at least surface impurities and near subsurface potentially embedded in the polymer matrix. Of the remaining polymers in the 3He study, only polyimide (Pl) and nylon 6 showed markedly different results between the two studies. One distinction that could explain this result is the difference between amorphous and semi-crystalline polymers. LDPE, HDPE and PP are amorphous polymers that must show uniform solubility. Alternatively, semicrystalline polymers, such as PTFE, nylon 6, and Pl can show spatial diffusion and thus show regional solubilities that differ from the volumetric solubility measured in the polymer laboratory. 15 Table 4.3 presents a summary comparison of the predicted and measured results for 3He. (Detailed results in figures 5 and 6).

TABLE 4.3: Results of polymer relaxation study for 3He Pollution by O? Impurities introduced into the test environment can also explain measurement errors. Dust, fingerprints and other contaminants can be introduced into the test chamber when the chamber is open to insert the sample. All these contaminants 15 have a depolarizing effect that is not included in the absorption model. The most important confirmed contaminant in the test environment is the presence of 02 in the test chamber. Because 02 has a magnetic moment, it can relax hyperpolarized gases in the same way as protons. Although 20 02 affects 129Xe and 3He in a similar way, the T times (longer associated with the 3He study increase any O2 contamination.) For example, 1 Torr of O2 in the chamber would not usually be noticed in the study time scale. of 129Xe but it would have a radical impact on studies of -ri-tf ^ tf-tltttrii - Ml ------ a ---- ia ----- l -------------- fa ------ -i -I & - Í ------ I 3He. On different occasions the effect of 02 was observed in the test chamber. It resulted in a non-exponential decomposition rate many times faster than the predicted Ti of the sample. Even in storage, the oxygen in the atmosphere diffuses and is absorbed in the polymer sample. In order to remove this 02 from the polymer, preferably the sample is left under vacuum for a period before testing. The period necessary for this degassing to occur can be calculated if diffusion coefficients are available. Table 4.5 shows the degassing calculations for 1 mm polymer samples thick with diffusion coefficients of 02 available, assuming that t ~ (Z) 2 / D (Z = sample thickness).

TABLE 4.5: O2 degassing time for relaxation studies 3He 15 no S (02) available for PP -------- a When determining the relaxation time (Ti) of a noble hyperpolarized gas in a polymer container, Equation 2.21 can be restated as: where "V" is the volume of the container, "A" is the surface area of the container, "S" is the Ostwaid solubility of the noble gas in the polymer, "T? P" is the relaxation time of the dissolved noble gas in the polymer matrix and "DP" is the diffusion coefficient of the noble gas in the polymer. This quantitative analysis reveals that the relaxation time of the noble gas is inversely proportional to the solubility of noble gas in the polymer. In fact, and surprisingly, as mentioned above, it is considered that the surface induced relaxation time is proportional to the square root of the relaxation time of the noble gas in the polymer matrix. Exposing again the multiple constants of equation 2.23 in a factor "C" results in: C = 32ph2Na5- (2.23a) 4.05x105 In this way, the relaxation rate of a noble gas in the polymer can be expressed as set out in 1 C? ? lKI + \) (2.23b) T, p bDP M equation (2.23b (1 = proton spin)). Inserting this relaxation velocity expression in equation (2.2T) shows that the dependence on the diffusion coefficient disappears and results in a surface relaxation time "Ti" which can be expressed by the equation (2.23c). ).

This expression can be used to predict the relaxation time of hyperpolarized noble gases such as 3He or 129Xe on any polymer surface. As noted in the patent of E.U.A. No. 5,612,103, the perdeuteration of the polymer should lead to an improvement in the noble gas ratio time. However, this improvement seems to be lower than previously predicted. The gyromagnetic or deuterium ratio is 6.5 times smaller than for hydrogen, and the spin "I" is 1. A comparison of the ratio time of the noble gas in the perdeuterated polymer matrix with its normal intraparticle c shows the following: rp () = (l / 2? i / 2 + l) (26750) 2 _ 15 9 TP (H) (i? i + l) (4106) 2 However, this improvement in Tp translates into a global improvement in relaxation time of approximately 4 (the square root of 15.9). In this way, deuteration is still desired but maybe it is not as impressive as previously expected.

Now we can make a relaxation comparison of 3He with 129Xe relaxation in a given polymer surface using equation (2.23c) assuming that "b" does not vary substantially for the two gases as expressed in equation (2.31.). 5 T. (3He) _ SXey? Xe rl29 - (2.31) T rXe) SHe? He For example, in low density polyethylene ("LDPE"), the solubility ratio of xenon to helium solubility is 107 and the ratio of ?? e /? He = 0.37. In this way, the relaxation time of 3He in one LDPE surface will be almost 40 times larger than for 129Xe. In addition, as mentioned above, the level of noble gas polarization is not spatially uniform in the polymer. The polarization is constant for the gas phase but decreases exponentially with distance in the polymer. 15 Therefore, it is important to mention that especially in the case of copolymer coatings, the thickness of the coating preferably exceeds the polarization decomposition duration scale "LP" (equation 2.22) in order that the depolarization time of The gas depends on the polymer properties in a predictable manner. For a coating thickness less than "Lp", the polarized gas can penetrate the substrate below the polymer, and potentially experience rapid unwanted relaxation. Because "TP" also depends linearly on "DP", the depolarization duration scale is proportional to the | g | || HMi || MIÉitlMIM ^ a ^^^^ Ba ^^^ aÉÍMM ^^ ÉJÍ ^^ i,, - i i i im gas diffusion coefficient. Thus, especially for 3He, which tends to have a high diffusion constant, the contact layer of the polymer, or the thickness of the coating or film is preferably several times the scale of critical duration. Preferably, the thickness is more than about 16 micrometers and preferably at least 100-200 micrometers thick in order to be effective. In fact, coatings that are substantially thinner than "LP" can be more harmful than having no coating, because the mobility of the noble gas is reduced once in the coating. As such, a noble gas dissolved in a thin coating can interact with the lower surface for a much longer time than if the coating were not present. In fact, the probability of depolarization seems to increase as the square of the interaction time. Relatively long relaxation times achievable with Polymers (coatings or container materials) make it necessary to develop ppo polymer storage bags of hyperpolarized gas. In addition, the bags are a desirable storage and delivery device for magnetic resonance imaging using inhaled hyperpolarized 3He because the gas can be completely extracted. when the bag collapses. In contrast, a rigid container usually requires a more sophisticated gas extraction mechanism. ll-tfHliililMh ^ W ^^ MWtata Relaxation induced by O? When bags with long surface relaxation times are used, other relaxation mechanisms become important. One of the most important additional relaxation mechanisms is due to collisions of the noble gas with paramagnetic oxygen as mentioned above. Saam et al., Have shown that the 3H relaxation time due to collisions with paramagnetic oxygen can be expressed as established in equation (2.32).

? L 2 j ß (2 32) (Note that amagat is abbreviated as "amgt") (1 amagat = 2.689x1019 atoms / cm3, the density of an ideal gas at 273K and 1 atm). See B. Saam et al., "Nuclear relaxation of 3He in the presence of 02" Phys. Rev. A. 52, p. 862 (1995). In this way, an oxygen pressure as small as 1/1000 of an atmosphere can result in a relaxation time of 3H of only 38 minutes even with perfect surfaces. Given this problem, great care must be taken to reduce the oxygen content in the storage container through careful preconditioning of the container, such as by pure gas pumping and purging methods. However, even with preconditioning, a bag is susceptible to oxygen permeability through the polymer which can unfavorably create substantial oxygen concentration over time. The volume of oxygen transmitted to ^ jg ^ and through the polymer material depends on several factors, which include the specific polymer oxygen permeability coefficient "Q02". For small amounts of oxygen transfer, the rate of oxygen concentration created in the bag is almost constant and can be expressed by equation (2.23). "[02]" is the concentration of oxygen in the bag, "A" is the polymer surface area, "? P02" is the difference in oxygen pressure across the surface of the bag, "Vbag" is the volume of the bag, "? x" is the thickness of the polymer and "Q02" is the coefficient of oxygen permeability. When using equation (2.33) and a bag that has the following characteristics (area = 648 cm2, volume = 1000 cm3,? X = 0.01 cm, P = .2x105Pa, Q02 (LDPE) = 2.2 x 10'13 cm2 / s Pa) gives a value d / dt (02) of approximately 2.8 x 10"7 amgt / s In this way, a duration of one hour (3600 seconds) will give 1 x 10'3 amgt, which corresponds to a Ti of Approximately 38 minutes For Fedlar ™, oxygen permeability is smaller (0.139 x 10-13 cm2 / s Pa- 158 times less permeable than LDPE) Thus, in this material, one hour of permeability will give a Ti induced by 02 of approximately 99 hours, but after 10 hours the Ti decreases only to 10 hours.So, as an alternative to a protection of 02 placed on the inner layer, the same contact surface layer can be formed as a polymer having permeability reduced for 02 and / or increased thickness? x.

Accordingly, oxygen-induced relaxation can quickly dominate surface relaxation even when careful gas management techniques are used. Therefore, to make the polymer bags a viable storage medium, preferably another layer of material is used to suppress oxygen permeability. As long as the thickness of the polymer in contact with the polarized gas is greater than LP, the second material used for suppression of oxygen permeability need not be non-depolarizing. A metal film such as aluminum can be very effective in such an application.

Materials A comparison of the relaxation times measured experimentally with the theoretical values reveals a remarkable agreement for the polymer systems for which the solubilities of 129Xe are known. The theoretical relaxation times are also calculated for 3He in a variety of surfaces / polymer systems. The summary results e;? Figures 5 and 6. The relaxation times have been scaled to a 1 cm3 spherical container. Note that the results for 129Xe in the PTFE fluoropolymer (Teflon ™) are also shown in Figures 5 and 6. For this case, for a spherical container of one cubic centimeter ("cm3"), the calculated Ti was . 65 min and the observed relaxation time was 8.3 min. The calculations are identical to those previously discussed, except for the substitutions in the equations and a slight change in "b" due to the larger size of the fluorine atom compared to the hydrogen atom. The composition of the atomic structure of the material is different (ie, fluorine against a hydrogen atom). In fact, with the possible exception of Tediar ™ (5 polyvinyl fluoride), most fluoropolymers are not preferred for the preservation of hyperpolarization of 3 He. For example, the Ti predicted for 3He in PTFE is only 13.1 minutes in a sphere of 1 cm3. This is due to a relatively high solubility of helium in most fluoropolymers due to that large empty space in the polymer resulting from large fluorine atoms. Moreover, most common joint materials, such as Viton ™, Kel-F ™, and Kalrez ™, are fluoropolymers with fillers and can potentially substantially depolarize 3He compared to pure hydrocarbon gaskets such as those containing polyolefins. . Examples of preferred sealing materials include polyolefin such as polyethylene, polypropylene and copolymers and combinations thereof. Since the shape of the container (the area of the chamber that holds the gas) can impact the rate of depolarization, it is preferred that the configurations of the container be selected to maximize the volume of the container. gas-free container (V) and at the same time minimize the surface area (A) which makes contact with the hyperpolarized gas (that is, decrease the value of the A / V ratio). Most preferably, the container is dimensioned and configured to provide an A / V ratio of approximately less than 1.0 m / g ßM mm i * ^ cm -1, and even preferably less than about 0.75 cm -1. In one embodiment, the container is substantially spherical, such as a round container similar to a balloon. Preferred polymers for use in the inventions described herein include materials which have a reduced solubility for the hyperpolarized gas. For the purposes of the inventions herein, the term "polymer" is broadly construed to include homopolymers, copolymers, terpolymers, and the like. Likewise, the term "combinations and mixtures thereof" include both immiscible and miscible combinations and mixtures. Examples of suitable materials include, but are not limited to, polyolefins (eg, polyethylenes, polypropylenes), polystyrenes, polymethacrylates, polyvinyls, polydienes, polyesters, polycarbonates, polyamides, polyimides, polynitriles, cellulose and cellulose derivatives and combinations and mixtures thereof. It is preferred that the coating or surface of the container comprises one or more of a high density polyethylene, low density polyethylene, polypropylene of approximately 50% crystallinity, polyvinyl chloride, polyvinyl fluoride, polyamide, polyimide, or cellulose and combinations and mixtures thereof. Of course, the polymers can be modified. For example, by using halogen as a substituent or by placing the polymer in deuterated (or partially deuterated) form (replacement of hydrogen protons with deuterons) the relaxation rate associated with them can be reduced. Methods for deuterating polymers are known in the art. For example, the deuteration of hydrocarbon polymers is described in the U.S.A. Nos. 3,657,363, 3,966,781 and 4,914,160, the disclosures of which are incorporated herein by reference. Normally, 5 these methods use catalytic replacement of deuterons by protons. Preferred deuterated hydrocarbon copolymers and polymers include deuterated paraffins, polyolefins and the like. Such polymers and copolymers and the like can also be entangled according to known methods. It is further preferred that the polymer be substantially free of paramagnetic contaminants or impurities such as color centers, free electrons, dyes, other fillers and the like. Any plasticizer or filler used must be selected to minimize any magnetic impurity that has contact or that is placed next to the hyperpolarized noble gas. Alternatively, the first layer or contact surface can be formed with a metal surface of high purity (and preferably non-magnetic) such as a metal film. The high purity metal surface can advantageously provide surfaces resistant to depolarization / low relaxation capacity in relation to noble gases hyperpolarized. The preferred modalities will be discussed below. Of course, the high purity metal film can be combined with the materials discussed above or can be used with other materials to ^ _i ^ __? - ái ----- i form one or more layers to provide a surface or region of absorption that is resistant to contact-induced depolarization interactions. As mentioned above, any of these materials can be provided as a surface coating on an underlying substrate or can be formed as a layer of material to define a contact surface compatible with polarization. If used as a coating, the coating can be applied by any number of techniques as will be appreciated by those skilled in the art (e.g., by solution coating, chemical vapor deposition, melt-bonding, sintering with powder and the like) . The hydrocarbon grease can also be used as a coating. As mentioned above, the storage container or container can be rigid or flexible. Rigid containers can be formed of Pyrex ™ glass, aluminum, plastic, PVC or similar. Flexible containers are preferably formed as collapsible bags, preferably collapsible multiple layer bags comprising several layers of secured material. The multiple layer configuration can employ layers of material formed from different materials, i.e., the layers of material can be selected and combined to provide a collapsible bag which is oxygen resistant, moisture resistant, puncture resistant and which have a contact surface with gas which inhibits contact-induced depolarization. As used herein, the term "oxygen resistant" means that the bag is configured to inhibit oxygen migration in the portion of the bag that retains the gas. Preferably, the bag is configured to provide an oxygen leak rate or oxygen permeability rate of less than about 5 x 10"6 amgt / min, preferably less than 5.2 x 10'7 amgt / min, and preferably less about 1 x 10'7 amgt min in a pressure atmosphere.

Containers Returning again to the drawings, Figures 7 and 8 illustrate a preferred embodiment of a flexible container 10 for hyperpolarized gas according to the present invention. Figure 7 shows the container 10 in the collapsed position (empty or hollow) and figure 8 shows the container 10 inflated (full). As shown, the container 10 includes a front wall 12 and a rear wall 13 and a chamber that retains the gas (or liquid) 14 formed between the walls 12, 13. As shown, the walls 12, 13 are joined by a perimeter seal 15. As shown in Figure 7, in a preferred embodiment, the container 10 includes an outwardly extending port connector 20 in fluid communication with the port 22. The port connector 20 is preferably fixed to the container 10 through an accessory 28. The accessory 28 can be heat sealed to the interior of the wall 12 to secure the accessory 28 to the interior of the container wall 12 in an airtight manner. Alternatively, as shown in Figure 7, a gasket or ring-27 may be used to seal the accessory 28 to the container 10.

As shown in Figure 9, the fitting 28 extends through the wall of the container 12 and is secured against the exterior of the wall of the container 12 through an understanding with a nut engaging element 27 and a ring. 0 placed intermediate 27a. As also shown, the nut coupling element 27 is positioned on the opposite side of the wall of the multilayer container 12 and is configured in such a way that it includes an opening with internal threads which is placed on and threadably engages the external threads of accessory 28c. Again, the seal provided by the element of nut coupling 27, the associated 0-ring 27a and the fitting 28 are preferably configured to withstand about 3 atm of pressure and are also preferably configured to provide a vacuum tight seal. In the embodiment shown in Figures 7 and 13, the port connector 20 is configured to define a flow path portion. of fluid 22f. In Figure 9, an alternate modality is shown. In this embodiment, the port connector 20 'is configured to operate as a second upper coupling nut which engages in a threaded manner with the accessory 28 separated from the coupling element of nut 27. As shown, the port connector 20 'includes a ring-0 20a placed in the middle of a lower portion of the port connector 20b and a portion of the accessory 28b. As before, it is preferred that this seal between the accessory 28 and the port connector 20 'is also configured in a "» * "- -" - - < - - - - "- hermetic arrangement and is configured to withstand pressures of more than about 3 atm (and preferably leak tight at vacuum pressures used to condition the container, as will discuss later). In a preferred embodiment, the container 10 includes a capillary rod 26s and a valve member 26. As shown in Figure 9, the port connector 20 'is configured to mesh with the capillary rod 26s which extends away from the the chamber of the container 14 and which is in fluid communication with the valve element 26. The valve element 26 is operably associated with the chamber 14 so that it freely controls the intake and release of the fluid. That is, in operation, the valve 26 opens and the hyperpolarized gas (or liquid) is directed through the outlet 29 through the valve body 26 and through the capillary rod 26s to the chamber 14, thereby forcing the container 10 expand (figure 8) and capture the hyperpolarized gas (or liquid). The capillary rod 26s can be formed as a p? integral of the valve element 26 or as a separate component. For example, the valve member 26 may include a body portion formed of glass such as Pyrex or the like, and the capillary rod 26s may be formed directly on an end portion of the body. same as a glass such as Pyrex or an aluminosilicate, or other material to extend as a continuous body attached to the lower portion of the valve member 26. The valve illustrated in Figure 9 includes a connecting portion 26p with a 0-ring 26th which moves longitudinally to MHÉ IMttafitf --- l --fa ------- it-ha --------- i --- engage with the end of the lower nozzle of the valve chamber 26n to close the path of flow 22f in the closed position of the valve. In contrast, the valve connection 26p moves away from the nozzle end 26n to allow gas to flow through the port 22, the capillary rod 5 26s and the valve body 26b and into (or out of) the outlet of the valve 26b. valve 29. Operationally, still referring to Figure 9, the capillary rod 26s is configured such that a large portion of the hyperpolarized gas, once in the chamber 14, remains there when the valve member 26 is closed. That is, the dimensions and form of capillary rod 26s are such that the diffusion of the hyperpolarized gas away from the chamber of the container 14 is inhibited. Thus, the capillary rod 26s can reduce the exposure amount for a large part of the hyperpolarized gas with the valve 26 and any component potentially depolarizing associated operably with it. In addition, the capillary rod 26s also provides a portion of the gas flow path 22f therethrough. In such a case, the capillary rod 26s includes an internal passage which is preferably dimensioned and configured in such a way that it inhibits the flow of gas from the chamber during storage or transport and at the same time, also allows the gas to leave the chamber 14 to its final destination without undue or significant impedance. Preferably, as discussed above, the capillary rod 26s is operably associated with the valve member 26 and is configured to retain a large portion of the gas in the baghouse.

The valve body 14, and away from the valve body 26b when the valve member 26 is closed. On the contrary, when the valve element 26 is open, the gas leaves the chamber 14 in the flow path 22f towards the outlet 29. Thus, in operation, when the valve element 26 is closed, the capillary rod 26s helps to maintain a large portion of the hyperpolarized gas away from the valve element 26 (as, for example, retained at least below the 0-ring at the nozzle end of the valve designated by the step-down portion of the valve body in Figure 9 ) to thereby inhibit any contact-induced depolarization that can be attributed in this respect. In one embodiment, the capillary rod 26s has a length, which is at least about 5.1cm with an internal diameter of 0.3cm and an outer diameter of 0.5cm. For a bag container of 18 cm x 18 cm (or approximately one liter), this length is greater than about 20% the length or width of the container 10. As shown in Figure 9, the valve member 26 includes a knob externally adjustable fitment 26a which rotates to open and close the valve element 26. As also shown, the valve member 26 includes a plurality of O-rings 26o therein. A suitable glass valve is available at Kimble Kontes Valves located in Vineland, NJ. As also shown in Figure 9, the capillary stem 26s is positioned in the middle of the valve member 26 and the container chamber 14 to inhibit the migration of the hyperpolarized substance to the valve member 26 to reduce exposure to any potentially material. depolarizing therein (which potentially includes one or more of the O-rings 26o). Preferably, all of the structural and sealing materials associated with the container 10 and other components of container assemblies which are in contact with the hyperpolarized gas are selected or formed of materials which are preferably substantially non-depolarizing. Preferably, the capillary rod 26s is formed with a substantially rigid body. As used herein, the term "rigid" means that it can structurally assist in supporting the weight of a valve element 26 when assembled to the container 10 to minimize the stress / strain that can be introduced to the attachment of the fitting. 28. For example, the rigid body of the capillary rod 26s can be provided by a rigid substrate, such as a plastic, a PVC material, a glass, Pyrex, or silicate aluminum material, a metal and the like. Of course, the surfaces that contact the gas or hyperpolarized fluid of the capillary rod 26s, preferably are formed with a material or coating which is substantially non-depolarizing to the liquid or hyperpolarized gas retained therein (low relaxation capacity and / or solubility for the hyperpolarized gas). It should also be noted that as shown, the capillary rod 26s is a prolonged cylindrical rod, but other configurations are also possible. Preferably, whatever the configuration, the internal passage (shown as a diameter) of the capillary rod 26s is configured to inhibit or restrict the flow of fluid from the chamber of the bag 14 when the valve member 26 is closed. Referring again to Figure 9, the valve element 26 is configured with an end portion which retains the outlet 29 away from the capillary rod 26s which forms the port of entry and exit of the hyperpolarized gas. Preferably, the outlet 29 is configured with a sealing means 25 that allows the container to coincide and mesh with an external device at the final destination or supply point (in an airtight manner) to facilitate the supply of the gas or liquid without exposure to the atmosphere. As shown, this sealing means 25 includes an O-ring 25a which is configured to engage sealingly with the external device. In operation, the sealing means 25 compresses the o-ring 25a to mesh uniformly with the supply or inlet device (not shown). As such, the container chamber 14, the accessory 28, the capillary rod 26s, a portion of the valve member 26 and the end portion of the valve member 29 define the hyperpolarized fluid path 22f. Thus, in the embodiment shown in Figure 9, when the valve member 26 is open, the fluid flow path 22f extends from the chamber of the container 14 through the capillary rod 26s to an external device or source, such as a hyperpolarizer delivery port (such as during filling) or patient delivery interface (such as at a point of clinical use of gas supply). That is, a clinician or doctor can simply turn the knob 26a to It is necessary to open the valve element 26 and compress the walls of the bag to release or expel the hyperpolarized gas from the chamber 14. In a preferred embodiment, as shown in Figures 16-19, the chamber 14 is coupled with a target interface. As shown, the container 10, when compressed, expels the gas directly to the contact mask with the patient 90, so that a patient can inhale or breathe the gas therefrom. Of course, other flow path configurations (with or without the capillary rod 26s and / or valve element 26) can be used so that the hyperpolarized fluid flow path 22f is defined by other components, such as tube or conduit intermediate, distal or proximal (in relation to the camera of the bag). An example of the use of conduit 70 without a capillary rod 26s is illustrated in Figure 17. For conduit or tube mode, various materials can be used for the conduit. An example of a suitable material alternative is polymer tubing attached to accessory 28 and / or connector 20 and in fluid communication with chamber 14. F tube is formed in such a way that at least the inner surface comprises a material compatible with polarization with an adequate relaxation or solubility value to provide a sufficiently long Ti and the outer layer material comprises a mechanically stable (ie, independent) polymer matrix, resistant to oxygen and flexible. Of course, depending on the material selection, the tube can be formed as a unitary single layer body where the inner surface and the outer layer material are the same, or the tube can include a coated inner surface and an outer surface or wall layer of different material. Figures 21 A, 21 B and 21 C illustrate another preferred embodiment of a container 10. As shown, this embodiment is similar to that shown in Figure 7, except that the accessory 28 can be subsequently isolated from the main volume of the container. gas (or liquid) retained in chamber 14 as shown in figure 21 b. As shown, the container is configured to place the port 22 on an edge portion of the body of the container. In addition, it is also preferred that an insulation means 31 be placed between the port and the main volume of the chamber to isolate port 22 and port 28 accessories or other components of the gas or liquid in the container during transport and storage. As such, exposure of the gas or liquid to port 22 or port 28 accessories is reduced. In operation, the container is in an empty (deflated) position as shown in Figure 21a. As shown in Figure 21 b, a flexible tube such as tygon® is attached to the container. It is also preferred that the tube be operably associated with the sealing means such as a clip, valve or the like as discussed herein for other embodiments. As shown in Figure 21b, a quantity of hyperpolarized gas or fluid is directed to the container through the opening 22a as schematically shown by the arrows. As shown in Figure 21c, when the flexible container is sufficiently full (but below its full capacity), an insulation means 31 i is fixed or formed in the bag to contract or enclose the bag portion with the port 22 and / or accessory 28 in a manner which will inhibit contact of the main volume of the hyperpolarized gas or liquid with this region of the bag or container. As shown, the insulating means 31 i is a clip having opposing fastening bars 31, 32, compressed together by a fastener 33. Of course, other insulating means such as heat sealing, fastening can also be used. , restrictive contraction with configurations or bag support attachments and the like. For example, the bag container can be sized and configured with the port on an edge portion, preferably, close to a corner and the partially filled container, so that the corner can be bent against the body of the container and held in place simply by fixing a portion of the outer wall to an opposite wall, such as through of a means of adhesive fixation, sailboat ™, hook and the like. The fold line acts to "contract" the main chamber of the port container (not shown) in a manner that is substantially hermetic. Of course, a bending bar or other device can be used to facilitate a narrow bending line between the port region and the bulk of the bag. A multi-layer flexible container (3 sheets) 10 having a capillary rod 26s and a valve member 26, as shown in Figure 9, can provide a corrected Ti (considering material properties) for hyperpolarized 3He gas at less about 450 minutes (7.5 hours), and preferably a corrected Ti of at least 7 about 600 minutes (10 hours) and an associated oxygen permeability rate of approximately 5.2 x 10'7 amgt / min (in a pressurized atmosphere). In a preferred embodiment, as shown in Figure 12, the walls 12, 13 are configured with two layers 41, 44. The first layer 41 includes the internal contact surface 12a of the retaining chamber 14 and thus, makes contact with hyperpolarized gas. As such, the hyperpolarized noble gas is susceptible to contact-induced depolarization depending on the type of material and the depth of the material used to form this layer. Thus, preferably, this surface is formed by a coating or a layer of material of sufficient thickness to prevent the hyperpolarized gas from penetrating the underlying substrate. In addition, the surface must have a low relaxation capacity in relation to hyperpolarized gas. As such, both the material and the thickness are selected and configured to inhibit depolarization of the surface induced gas. With respect to the thickness, it is preferred that the thickness is greater than the critical decomposition scale length Lp and preferably greater than a plurality of the decay duration scale. For example, for 3He and HDPE, the critical duration scale is about 8 μm, so a preferred material layer depth is greater than about 16-20 μm. Furthermore, with respect to "low relaxation capacity", it is preferred that for 3H, the material has a relaxation value of less than about 0.0013 cm / min and preferably less than 0.0008 cm / min. For 129Xe, it is preferred that the material have a relaxation value of less than about 12 cm / min and preferably less than 0.0023 cm / min. "Reduced solubility" is intended to describe materials for which the hyperpolarized gas has a reduced solubility. Preferably, with respect to 129Xe, the solubility is less than about 0.75, and preferably less than 0.4. For 3He, the solubility is preferably less than 0.03, and preferably less than 0.01. The second layer 44 includes the outer surface 12b that is exposed to air which includes components which can potentially degrade the hyperpolarized gas in the chamber. For example, as discussed above, paramagnetic oxygen can cause depolarization of the gas if it migrates to the contact surface 12a or chamber 14. As such, it is preferred that the second layer 44 be configured to suppress oxygen migration. The second layer 44 may be formed as an oxygen resistant substrate, a metal layer, or metallized deposit or coating formed on another layer. Preferably the second layer 44 (alone or in combination with other layers) prevents demagnetizing amounts of 02 from entering the chamber at a rate of more than 5 x 10"6 amgt / min, and most preferably at a rate that is less than about 1x10-7 amgt / min. Most preferably, for a desired Ti of about 24 hours and after 24 hours of permeability, it is preferred that the concentration of 02 is less than about 2.6x10-5 amgt. , at 1 atm, for a one liter bag, it is preferred that the container be configured to maintain the concentration of 02 in the chamber below .003% of the total gas concentration.Of course, the second layer can be selected or configured alternatively to protect other environmental contaminants such as moisture, for example, in this embodiment, a first layer may have a very low permeability for 02 but may be sensitive to moisture.The second layer 44 may be configured with a r polyethylene protective coating to compensate for this property and provide an improved T-i container. In another alternative embodiment, the inner surface 12a can be configured as a high purity (non-magnetic) metal film applied to an underlying substrate, polymer, or other container material. High purity metal surfaces can provide even greater protection against depolarization relative to other surfaces. Because the hyperpolarized gas has contact with the metal, the underlying material does not require to have a low solubility for the hyperpolarized gas. In a preferred embodiment, the container has a flexible configuration as a bag that can be collapsed with the inner surface 12a formed from a high purity metal film (preferably a thickness within the range of about 10 nm to about 10 microns). ). As such, in this embodiment, the first layer 41 is the metallized layer and can provide oxygen resistance / protection as well as protection against contact depolarization. Preferred metals include those that are BÉKÜ ^ HÉIM- - ^ 1 ^^ - ^^^^^^ J- < They are substantially pure in a paramagnetic way (that is, they do not introduce magnetic moments) and flexible to the depolarization by contact of the hyperpolarized gases. selected to minimize the time of gas adsorption on the metal surface, ie, for the noble gas to have a low adsorption energy on the metal surface Examples of suitable materials include, but are not limited to, aluminum , gold, silver, indium, beryllium copper, copper, and mixtures and combinations thereof As used herein, "high purity" includes materials having less than 1 ppm of ferrous or paramagnetic impurities and most preferably less than 1 ppb of ferrous or paramagnetic impurities In a further embodiment, the inner surface 12a can be formed as a hybrid surface (a combination or side-by-side disposition of metal film of high purity and polymer) or as a high purity metal formed on a polymer substrate. As such, a metal film may be layered on a polymer with good relaxability properties to compensate for cracks or gaps that may develop in the metal film layer. In another preferred embodiment, as shown in Figure 12, the inner surface 12a is formed directly by the inner wall of a polymer bag and the outer or intermediate surface is formed of a metallized material or coating placed on and directly in contact with the polymer bag. However, as illustrated in Figures 10 and 11, the intermediate layers 42, 43 placed between the inner layer 41 and the outer layer 44 can also be used. For example, in a preferred embodiment, the container has three layers 41, 42, 44. The first layer 41 is 0.004"linear LDPE, the second layer 42 is 0.0005" aluminum sheet and the third layer 44 is gauge polyester. 48. Advantageously, the first layer of LPDE provides a surface that is compatible with polarization with a relatively long Tt, the second layer of aluminum sheet inhibits oxygen permeation, and the polyester layer provides strength and resistance to breakage . The outer layers 41 and 44 are joined to the middle layer 42 with urethane adhesive. Typically, the layers are cemented or bonded together but other fixing or joining means may also be used as will be recognized by those skilled in the art. It has been observed that a container 10 with this three-layer configuration has a corrected Ti (due only to the material) for 3He of approximately 490 minutes (more than 8 hours) and an oxygen leakage rate of about 3.9 x 10". amgt / min This Ti is different from the one in the single-ply bag used in the past, for example Ti for 3He in a conventional one-liter single-layer Tediar® bag (pre-conditioned as described below) has been estimated in less than 4 hours In figure 10, container 10 has four layers 41, 42, 43, 44. As shown, the inner layer 41 is not a coating but is defined by the expandable polymer bag (or modified polymer) having a thickness sufficient to inhibit contact depolarization. In this embodiment, the intermediate layers may be formed of any number of alternative materials, preferably flexible materials for contracting and expanding with the inner layer 41. In a preferred embodiment, the inner layer 41 is about 0.0025"(inches) (6.4 x 10"3 cm) of linear LDPE (LLDPE); the second layer 42 is about 0.003 inches (8 x 10"3 cm) of Al, the third layer 43 is PE of 7 Ib, and the outer layer 44 is 48-gauge PET. A bag container with this configuration of Multiple layers have been shown to have a corrected Ti (due only to the material) of around 14 hours and an oxygen leak rate substantially less than about 3x10-8 amgt / min at one atmosphere (101 KPa). shown) a bag with five layers is used: the first layer is 35 μm of HDPE; the second layer 42 is 35 μm polyamide; the third layer 43 is 1 μm of aluminum; the fourth layer 44 is 35 μm of polyvinylidene chloride; and the fifth layer (not shown) is 35 μm polyester. Advantageously, the multiple layers can provide strength and / or resistance to further breakage and pressure. Of course, alternate layer materials and numbers may also be employed according to the present invention. In one embodiment (not shown), a coating can be placed on the inner surface 12a of the polymer bag to define the appropriate depth of the contact layer either alone or in combination with the thickness of the polymer bag. Of course, the two layers can be formed as a single layer if the container material employed has a low relaxation capacity for the hyperpolarized gas and if the material is sufficiently impermeable to environmental contaminants such as 02. Examples of such materials include but are not they are limited to PET (polyethylene terephthalate), PVDC (polyvinylidene dichloride), cellophane and polyacrylonitrile. As shown in Figures 9 and 13-15, the container 10 also includes a sealing means that is operatively associated with the inlet port 22 and is used to capture the hyperpolarized gas within the chamber 30. Described in general terms, the sealing means closes the passage 22a in communication with the entrance port of the bag 22 (Figure 7), thus retaining the hyperpolarized gas substantially within the chamber 14 of the container. The sealing means can be configured in numerous ways, either with valves integral with the bag (Figure 9) and / or with clips or other devices that are placed in the flow path of the container. In the configuration shown in Fig. 13, the coupling element 20 includes a conduit 70 extending to J outside the flow path, and the sealing means is a loop or hot seal applied to the conduit. Examples of suitable sealing means include, but are not limited to, a clip 72 (FIG. 13) a hot seal 74 (FIG. 14) and a membrane seal 76 (FIG. 15). Alternatively, the valve 26 (Figure 9), a stopcock and other fittings and / or seals (gaskets, hydrocarbon grease, O-rings) (not shown) can be used to control the release of the hyperpolarized gas. Preferably, you must ensure carefully ÜÉÉ ^ É ^ IÉ ^^ iii ^^ aM ^^^^^^^^^ ÉÉÉÜÉ l l? ? . It is important that all accessories, seals and the like that are in contact with hyperpolarized gas or are located relatively close to it are made of materials that are compatible with polarization or that do not substantially degrade the polarized state. of hyperpolarized gas. For example, as stated above, various commercially available seals include fluoropolymers or fillers and the like which are not particularly good for the preservation of hyperpolarized 3He gases due to the solubility of the material with the hyperpolarized gas. Because several common joint materials are fluoropolymers or contain undesirable fillers, they can potentially have a substantially depolarizing effect on the gas. This is especially acute with respect to 3 He. This can be attributed to a relatively high solubility of helium in most fluoropolymers due to a larger empty space in the polymer that is attributed to the large fluorine atoms. In fact, preliminary evidence indicates that common O-ring materials (such as Vit n ™, Kel-F ™, ethylene-propylene, Buna-N ™, and silicone) exhibit poorer relaxation properties than is expected from relaxation speed of pure polymers. Most conventional O-rings are so depolarizing that they can dominate the relaxation of a complete hyperpolarized gas chamber. In fact, commercial ethylene-propylene O-rings have 1 / 3-1 / 2 relaxation time compared to pure LDPE with 129Xe. The faster rate of relaxation can be explained because the magnetic impurities in the O-rings can be introduced by dyes and fillers and the like. Therefore, it is preferred that the containers of the present invention employ seals, O-rings, joints and the like with substantially pure hydrocarbon materials (substantially free of magnetic impurities) such as those containing polyolefins. Examples of suitable polyolefins include polyethylene, polypropylene, copolymers, and combinations thereof that have been modified to minimize the amount of magnetically impure fillers used therein. Suitable additional seals include hydrocarbon grease and hydrocarbon seals and O-rings made of polyethylene and the like. Therefore, if a valve is used to contain the gas in the chamber 30, it is preferably configured with a magnetically pure ring-0 and / or hydrocarbon grease (at least the surface). Of course, because fillers and plasticizers are employed, it is preferred that they be selected to minimize magnetic impurities such as substantially pure carbon black. In an alternative embodiment, the ring-0 seal can be configured with the exposed surface coated with a high purity metal as discussed for the surface of the container. Similarly, the O-ring or seal can be coated or formed with an outer exposed layer of a polymer of at least "Lp" thick. For example, a layer of pure polyethylene can be placed on a commercially available ring-0. A preferred commercially available ring-0 material for 129Xe is a rubber O-ring coated with Teflon ™ or a polymer of low relaxivity as described above. The empty spaces in Teflon ™, unlike a fluoropolymer, do not affect 129Xe as much as 3He does because 129Xe act is larger than fluorine, which is larger than 3He. As previously discussed, fluoropolymers can be used as seals with 129Xe but are not preferred for use with arrangements where the seal can have contact with the hyperpolarized 3He. In operation, after supplying to a use site, the technician or patient can open the valve member 26 (Figure 9) and breathe, or stop the flow by placing a temporary clip 72 in the conduit 20 (Figure 13). Figures 13 and 14 illustrate preferred embodiments of a seal arrangement used to transport or store the filled container. Each acts to seal the fluid passage 22a by contracting the closed conduit 70 in at least one position. Fig. 13 shows the use of an external clip 72 and Fig. 14 shows the use of a r'3 redundant heat seal 74. In operation, each is easily employed with little impact on the polarization of the gas in the container 10. For example, for the embodiment shown in Figure 14, after the container 10 is filled with hyperpolarized gas, a loop in process (not shown) ) is inserted over the duct 70 so that it closes the passage 22a. Heat is applied to the duct 70 as the wall of the duct collapses to provide a heat seal 74 to at least one side of the loop in process. The bag is ^ -J ^ ready to be transported. Once at the desired delivery location site, the heat seal 74 can be removed and a temporary loop placed over the conduit 70. As shown in Figure 17, the conduit 70 can be fixed directly with a breathing apparatus or air interface. patient 90. As illustrated in Figure 18, the hyperpolarized gas can be forced out of the bag and into the interface 90 by external depression / compression of the walls of the container 10. Alternatively, the patient 92 can inhale by simply directing the gas 100 to the inhalation path 105. Now with reference to FIG. 15, in another embodiment, a membrane seal 76 is placed directly on the outside portion of the inlet port 22. The membrane seal 76 may be joined by heat, or by a fastener such as a polymer washer attached to the peripheral portion of the coupling element 22, preferably leaving the central portion 76a externally and accessible In this embodiment, as shown in Figure 19, the container 10 can be transported to the site of use and inserted directly into the patient interface 90 '. Preferably, the membrane seal 76 is inserted into the interface 90 'so that it is positioned internally to the air-tight coupling provided by the seal 130 between the coupling element 20 and the interface 90'. Advantageously, the interface 90 'may include a bore 79 within the receiving area for opening the central portion of the membrane seal 76 after the coupling element 20 forms the outer seal 120 so that the container is sealed to the interface 90. ' This allows the gas in the container to be easily released and directed to the patient. The gas can be easily removed or removed from the container 10 by pressing the walls 12, 13 of the container 10 or through inhalation. Advantageously, said configuration eliminates the requirement of sophisticated or relatively complex gas extraction mechanisms and also reduces the amount of physical manipulation and / or interfaces required to supply the gas to the subject. As shown in Figure 16, a transport box 80 is preferably used to hold the bag 10 during transport. This can help protect the bag from physical damage. Furthermore, it is preferred that the box 80 include magnetic means to provide a desired static (substantially homogeneous) magnetic field around the hyperpolarized gas. In addition, or alternatively, the box 80 can be configured to form a shield from the undesirable magnetic fields as will be discussed later. In brief, the present invention provides containers that improve the relaxation time of the hyperpolarized gas. Preferably, the container has such a configuration and size and the contact surface is formed from a suitable material, that the hyperpolarized gas in the container has a relaxation time of more than about 6 hours and most preferably more than about 10 hours. 20 hours for 3 He. Similarly, the container has such a configuration and such size and the contact surfaces are formed of a suitable material that the hyperpolarized gas ^ g * ^ 129Xe in the container has a relaxation time of more than about 4 hours, preferably more than about 6 hours, and most preferably more than about 8 hours.

Protection The present invention recognizes that unless special precautions are taken, relaxation due to external magnetic fields (static and / or time-dependent) can dominate all other relaxation mechanisms. Both gradients in the static field and (low frequency) oscillating magnetic fields experienced by the hyperpolarized gas can cause significant relaxation. Advantageously, a substantially static magnetic retention field applied (externally) "BH" can substantially protect the hyperpolarized gas from depolarizing effects attributed to one more EMI and gradient fields during transportation. The present invention employs a magnetic retention field that elevates the Larmor frequency of the hyperpolarized gas over the noise region (l / f), ie the region where the ambient electromagnetic noise intensity is typically high (this noise is typically less than 5 kHz). In addition, a magnetic retention field is also preferably selected to raise the frequency of the hyperpolarized gas to a level that is above the frequencies associated with the large acoustic vibrations (these acoustic vibrations are typically less than about 20 kHz).

As will be discussed later, the increased frequency associated with the applied magnetic retention field advantageously allows a transport unit (Figure 16) to have a higher electromagnetic shielding effectiveness for a given housing thickness (the housing used to retain the hyperpolarized gas in the same during transport and / or storage). The depth of the cover "d" of a conductive protective material is inversely proportional to the square root of the frequency. Therefore, at 25 kHz, an exemplary cover depth for aluminum is about 0.5 mm, compared to about 2.0 mm at 1.6 kHz. Preferably, the magnetic retention field of the present invention is selected in such a way that any fluctuation related to the external field is smaller in magnitude compared to the field strength of the retention field; in this way the retention field can minimize the response of the hyperpolarized gas to relaxation induced by external predictable static field gradient. This can be achieved by applying a closely placed magnetic retention field to the hyperpolarized gas that is sufficiently strong and homogeneous to minimize the relaxation related to the unpredictable static field during transport and storage. A sufficiently homogeneous retention field preferably includes (but is not limited to) a magnetic retention field having homogeneity in the scale of at least 10"3 cm-1 over the central part of the retention field (i.e. the part where the gas resides.) Most preferably, the homogeneity of the magnetic retention field is at least 5 x 10"4 cm -1. In addition, the magnetic retention field should be placed, and configured in relation to the hyperpolarized gas so that it also minimizes the EMI or oscillating magnetic field depolarization effects. The depolarizing effect of EMI is preferably (substantially) decreased by applying the magnetic retention field (BH) close to the gas so that the resonant frequency of the hyperpolarized gas is preferably above or outside the bandwidth of the prevailing time-dependent fields. produced by supplied or electrically driven sources. Alternatively, or additionally, external interference can be protected by placing a substantially continuous shield or a transport 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 constant spatial decomposition of an electromagnetic wave or cover depth d. The depth of cover d at an angular frequency? it is 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 the Larmor radiation is long (-10 km), and is much longer than the size of the container. The effectiveness of the protection therefore depends on the geometry of the container as well as the thickness of the protection. For a thin spherical conductor of radius a and thickness t, the protection factor for wavelengths A is given approximately by F = (1+ (2 a / 3d2) 2) 1/2 Interestingly, the protection effectiveness increases as the size (radius) of the protection increases. Therefore, it is preferred that a metal closure used to protect or surround the hyperpolarized gas be configured to define an internal volume that is sufficient to provide increased protection effectiveness. In other words, it is preferred that the closure walls are spaced a predetermined distance relative to the position of the gas container. Alternatively, or additionally, a transport unit can be configured with at least one layer formed of about 0.5 mm thick of magnetically permeable material, such as mild iron of ultra low carbon steel, or mu metals (by virtue of its high magnetic permeability). However, these materials can influence sign. The static magnetic field must be designed and must be designed so as not to adversely affect homogeneity. With respect to the depth of cover of the materials (types of materials and number of layers) used to form a transport container closure, the application of a homogeneous magnetic retention field close to the hyperpolarized gas can help to minimize depolarization of gas under the roof depth decrease d, which is inversely proportional to the square root of the frequency. In addition, it helps by pushing the resonant frequency of the gas out of the bandwidth of common AC fields. It is preferred that the resonant frequency of the hyperpolarized gas be raised to be above 10 kHz, and most preferably increased to be between about 20-30 kHz. In other words, it is preferred that for protection, the applied magnetic retention field has a field strength of approximately 2 to 35 Gauss (0.2-3.5 mT). It is preferred that for 129Xe, the magnetic retention field is preferably at least 20 Gauss; and for 3He, the magnetic retention field is preferably at least 7 Gauss (0.7 mT). See the application of E.U.A. co-pending and co-assigned provisional number 60/121, 315 for additional details of protection method and preferred transport unit configurations. The content of this document is incorporated herein by reference.

Preconditioning of the preferred sea container, due to the susceptibility of hyperpolarized to paramagnetic oxygen as stated above, storage container 10 is preconditioned to remove contaminants. That is, it has a method for reducing or removing paramagnetic gases such as oxygen within the chamber and walls of the container. For containers made with rigid substrates, such as Pyrex ™, UHV vacuum pumps can be connected to the container to extract oxygen. However, a roughing pump can also be used and is typically cheaper and easier to use than the UHV vacuum pump-based process for both flexible and non-flexible containers. Preferably, the bag is processed with different purge / pump cycles, for example, pumping at or below 20 mtorr (2.7 Pa) for one minute, and then directing the regulating cleaning gas (such as grade 5 or better nitrogen) in the container at a pressure of about one atm (101 KPa) or until the bag is substantially inflated. The partial pressure of oxygen is reduced in the container. This can be done with vacuum but it is preferred that it be done with nitrogen. Once the oxygen performs partial pressure imbalance through the walls of the container, it will degas to restore equilibrium. In other words, oxygen in the walls of the container is degassed by decreasing the partial pressure inside the container chamber. The typical oxygen solubilities are on the scale of .01-.05; therefore, 95-99% of the oxygen trapped in the walls will pass into a gas phase. Before using or filling the container is evacuated, thus removing gaseous oxygen. Unlike conventional rigid containers, polymer bag containers can continue to degas (trapped gases can migrate to the chamber due to pressure differences between the outer surface and the inner surface) even after the initial purge and pumping cycles . Therefore, care should be taken to minimize this behavior especially when the final refill is not carried out temporarily with the preconditioning of the container. Preferably, a quantity of cleaning filler gas (such as grade 5) is directed to the bag (to substantially equalize the pressure between the chamber and ambient conditions) and sealed for storage in order to minimize the amount Additional degassing that can occur when the bag is stored and exposed to environmental conditions. This should substantially stabilize or minimize any 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 (purge, clean, etc.) and reused to transport additional amounts of hyperpolarized gases. It is also preferred that the container or bag be sterilized before introducing the hyperpolarized product therein. As used herein the term "sterilized" includes cleaning containers and contact surfaces so that the container is clean enough to inhibit contamination of the product and is suitable for medical and medicinal purposes. In this way, the sterilized container allows a substantially sterile and non-toxic hyperpolarized product supplied for in vivo introduction into the patient. Proper stabilization and cleaning methods are well known to those skilled in the art. 9 Measuring the solubility of gas in a polymer or liquid In the past, the measurement of gas solubility of most polymers has been slow and difficult, and in the case of helium, usually inaccurate. Nevertheless, as discussed previously, the relaxation time of the hyperpolarized gas, T-i, is now determined as proportional to the gas solubility. Advantageously, due to the recognition and determination of the relationships discussed above, the hyperpolarized noble gases such as 3He and 129Xe can be used to determine or measure the solubility of gas in a polymer or liquid. This information can be useful for quickly evaluating polymer structures. In addition, a given polymer sample can be evaluated using both 129Xe and 3He gases, because each has complementary information. For example, 3He will show a greater depth of the polymer based on its higher diffusion coefficients. Preferably, as shown in FIG. 20, a first quantity of a hyperpolarized gas is introduced into a container (block 300). A first relaxation time is measured from the hyperpolarized gas in the container (block 310). A sample of selected material is placed in the container (block 320). A second quantity of a hyperpolarized noble gas is introduced into the container (block 330). A second relaxation time is measured associated with the sample and the gas in the container (block 340). The gas solubility is determined based on the difference between the two relaxation times (block 350). Preferably, this is determined in accordance with equation (2.23c). The sample of material can be a physical or solid sample or a liquid as described above. Although the previously used sample was a geometrically fixed polymer sample, the method can also be used to determine gas solubilities in liquids or fluids. For example, instead of placing a polymer sample in the chamber, a liquid can be introduced. The liquid will preferably be introduced in an amount that is less than the free volume of the chamber since it will adapt to the shape of the chamber to define an associated volume and a surface area. The polarized gas can be directed into the chamber with the liquid and the rate of relaxation determined due to the specific liquid. This can especially help to formulate carrier substances for hyperpolarized 129Xe and 3He injection formulations.

EXAMPLES In the examples provided below, it is assumed that the polymer interface is present at a depth corresponding to a plurality of critical length scales as discussed above. iÜilHiMÉÉkiM EXAMPLE 1 Bag of LDPE / HDPE 3He An exemplary one liter patient delivery bag, such as that shown in Figure 7, is 7 x 7 inches squared. The expected T-i for 3He can be determined using (equation 2.4) and the theoretical relaxation capacity of LDPE for 3He cited in Table 4.3. The associated area (A = 2 * 18cm * 18cm) is 648cm2, the volume of 1000cm3 and the relaxation capacity is 0.0012 cm / min. Equation 2.4 leads to a Ti of about 1286 min or 21.4 hours for a LDPE bag configured as previously stated (absence of other relaxation mechanisms). For a bag made of HDPE, which has a relaxation capacity value of less than about 0.0008 cm / min (attributed to the lower solubility of 3 He), the Ti is estimated at 32 hours. In deuterated HDPE, the T-i is expected to be 132 hours.

EXAMPLE 2 LDPE / Nylon bag of 129Xe The same one-liter LDPE patient delivery bag as described in Example 1 contains hyperpolarized 129Xe. The volume and the surface area are equal but the theoretical relaxation capacity is 0.0419 cm / min (Table 4.2) for 129Xe in LDPE. The relaxation capacity is greater due to the higher solubility of 129Xe in LDPE compared to He (Sxe = 0.68 vs SHe = 0.006). For this configuration, Ti is estimated at 36.8 minutes. Similarly, for the measured relaxation capacity for Nylon-6 of 0.0104 cm / min, the expected Ti is believed to be around 148 min or about 2.4 hours. This value is close to that which has been measured for the Tediar ™ bags currently used.

EXAMPLE 3 Surface of metal film In this example, metal film coatings are used as the contact surface. The bag of 7 inches x 7 inches squared (18 cm x 18 cm) described in example 1 is used but this time coated or formed with high purity aluminum on its internal contact surface (the surface in contact with the hyperpolarized gas). ). The relaxation capacity of high purity aluminum for 129 < e has been recently measured at approximately 0.00225 cm / min. (A readily available material suitable for use is Reynold's ™ heavy-load freezing aluminum). When performing the calculation, a container with a prolonged Ti for xenon of approximately 11.43 hours can be obtained. This is a great improvement on T-i for Xe. Similarly, the use of such metal film surfaces for 3He can generate Ti's on the scale of thousands of hours (the container is no longer a limiting factor because these Ti's are above the theoretical collision relaxation time). described previously). The metals other than aluminum can be used including indium, gold, zinc, tin, copper, bismuth, silver, niobium, and oxides thereof. Preferably, "high purity" metals (ie, metals that are substantially free of paramagnetic or ferrous impurities) are used because even small amounts of undesirable materials or contaminants can degrade the surface. For example, another sample of high purity aluminum evaluated has a relaxation capacity of approximately 0.049 cm / min, 22 times worse than the sample cited above. This is mainly due to the presence of ferrous or paramagnetic impurities such as iron, nickel, cobalt, chromium and the like. Preferably, the metal is selected to be below 1 ppm in content of ferrous or paramagnetic impurities.

EXAMPLE 4 Multiple materials Using the bag configured as stated in example 1, the effects of the addition of multiple materials can be determined. For example, a 5 cm2 silicone gasket placed in a deuterated 1 liter HDPE bag (described in Example 1 (for 3 He)) with a starting T-i of 132 hours will reduce the relaxation time associated with the container. As stated in equations 2.5, 2.6, the relaxation scales can be added. Therefore, in order to properly determine the relaxation time of the container or equipment, the relaxation capacities and corresponding surface areas of all materials adjacent to the free volume should be evaluated. The hypothetical silicon seal, with an exemplary area "A" of 5 cm2, the measured relaxation capacity of 0.0386 cm / min (Table 4.3), and the free volume still in 1000 cc, gives a relaxation rate of approximately l. ? xIO ^ / min. Adding the speed due to the bag itself (I.SxIO ^ / min) produces a total velocity of approximately 3.2x10 '4 / min which is inverted in order to obtain a T-i of approximately 52 hours. Therefore, it is evident that adding a small surface area of a scarce material can drastically shorten the T-i despite the fact that most of the container material is good. Therefore, many commercially used ring-0 materials may have relaxation capacities in the order of magnitude greater than that described, further worsening the situation. Therefore, it is important to use substantially pure materials (free of impurities). The relaxation capacity for a silicone ring-0 available "off the shelves" for 129Xe was measured at approximately 0.2-0.3 cm / min. For example, using the 29Xe relaxation capacity numbers measured for the deuterated 3He HDPE container will reduce the bag from 132 hours to only 15 hours (a full order of magnitude deterioration). The key is that each joint, coupling, valve, tube or other complement that is added to the bag or container (especially those that are in fluid communication with 4 hyperpolarized gas) are preferably made of the most compatible material possible in relation to the hyperpolarized state.

EXAMPLE 5 Measurement of specific material properties The measurement of specific material properties such as the relaxation capabilities of the materials is described above. For example, as stated in equation 2.5, the relaxation rates attributed to various relaxation mechanisms are additive. Therefore, in order to measure the property of specific material, a spin-down chamber such as the one described here can be used to determine two relaxation times for a hyperpolarized gas. Using the chamber consisting of two hemispheres sealed with an O-ring, the chamber is closed, HP ("hyperpolarized gas") is introduced into it and the Ti relaxation time is measured. After the chamber is opened, a sample of the known surface area is inserted, and the procedure is repeated to measure a new T-i. The new T-i will be smaller than the previous one because the new relaxation surface has been added while maintaining the free volume almost in the same. The difference between the two relaxation times is attributed to the relaxation capacity of the specimen of aggregate material. In this way, the difference can be used to calculate the relaxation capacity of the material using equation (2.10). j ^^^^^^^ Ú ^ -ttiu EXAMPLE 6 Validation of the absorption model Figures 4.1 and 4.2 show the experimental and calculated TT values for 129Xe and 3He, respectively, in a 1 cc sphere for different surface materials as set out in graphs against the solubility product (S) and the square root of the molar density of the protons in the matrix of the material [1 H] '5. The value of the 1 cc sphere incorporates both the volume and the surface area and is a useful metric Ti corresponding to conventional evaluations, and as such is typically more easily described than the relaxation capacity parameters described herein. The value of Ti according to equation (2.23c) depends on the number of fixed constants and then inversely depends on the gas solubility and the square root of the proton concentration. The experimental values of Ti (T? 8) of the sphere of a cubic centimeter measured for all polymers are also placed in graphs and show a substantial agreement between the theory and the experiment, thus validating the absorption model described in the present. The foregoing illustrates the present invention and is not constructed as a limitation thereof. Although some exemplary embodiments of the invention have been described, those skilled in the art will readily appreciate that many modifications to the modalities of the examples are possible without departing materially from the teachings and advantages.

HBMM novel of the invention. Also, all such modifications attempt to be included within the scope of the invention as defined in the claims. In these claims, the more functioning means clauses attempt to cover the structures described herein by performing the aforementioned function and not only structural equivalents but equivalent structures. Therefore, it should be understood that the foregoing illustrates the present invention and is not intended to be limited to the specific embodiments described, and that modifications to the embodiments described, as well as other embodiments, attempt to be included within the scope of the appended claims. The invention is defined by the following claims, with equivalents of the claims included therein.

Claims (54)

NOVELTY OF THE INVENTION CLAIMS

1. - A flexible container for retaining hyperpolarized gas products, comprising: (a) a compressible body comprising at least one collapsible wall and an internal gas retention chamber, wherein said wall changes its shape in response to the introduction of gas into and out of said internal chamber so that said wall has a collapsed configuration associated with the absence of a gas retained in said internal chamber and an expanded configuration associated with the presence of a sufficient amount of gas retained in said internal chamber , and wherein said wall comprises a material forming an internal surface thereof having a low value of relaxation capacity for the gas retained therein associated therewith, and wherein said wall comprises a material having a permeability to oxygen that is sufficient to inhibit the entry of oxygen into said chamber, so that, at atmospheric pressure, oxygen enters said chamber. camera at a speed which is less than about 1x10'7 AMGT / min; (b) a port placed in said wall in fluid communication with said internal chamber for directing gas in and out of said internal gas retention chamber; (c) a sealing means operably associated with said port for controlling the flow of gas in and out of said internal gas holding chamber; and (d) a quantity of hyperpolarized gas placed in said internal gas retention chamber, wherein said wall is configured so that said low relaxation capacity value and said oxygen permeability are sufficient to provide a Ti, for said hyperpolarized gas retained in said container that is more than about 6 hours, and wherein the Ti for said hyperpolarized fluid retained in said container is influenced by loss of polarization and migration of oxygen induced by contact in said chamber.

2. A flexible container according to claim 1, further characterized in that at least one wall comprises a first layer of a first material configured to define said internal surface of said internal chamber and a second layer of a second material fixed and placed on said first layer so that the first layer is between said second layer and said internal chamber.

3. A flexible container according to claim 2, further characterized in that said first and second layers are formed of different materials.

4. A flexible container according to claim 2, further comprising a third layer of a third material placed on said second layer away from the first layer, wherein at least one of said first, second and third layers respond concurrently to the application of pressure to said compressible body and wherein at least one of said first, second and third materials is of a different material than the other layers of materials.

5. A container according to claim 3, further characterized in that it comprises a quantity of hyperpolarized fluid 3He retained in said expandable chamber, and wherein said internal layer has a thickness of at least 16 microns.

6. A container according to claim 4, further characterized in that said wall comprises aclicionally a fourth layer of underlying material and secured to said third layer of material opposite said second layer of material.

7. A container according to claim 4, further characterized in that at least one of said second and third layers of material is formed of an oxygen protection material.

8. A container according to claim 2, further characterized in that said first layer of material comprises a high purity metal that is substantially free of ferrous and paramagnetic impurities.

9. A container according to claim 4, further characterized in that at least one of said second and third layers of material comprises a metal film.

10. A container according to claim 2, further characterized in that said first layer of material comprises a material selected from the group consisting of polyolefin, polystyrene, polymethacrylate, polyvinyl, polydiene, polyester, polycarbonate, polyamide, polyimide, polynitriles, cellulose and cellulose derivatives, and mixtures thereof.

11. A container according to claim 2, further characterized in that said first layer of material comprises a material selected from the group consisting of high density polyethylene, low density polyethylene, polypropylene having approximately 50% crystallinity, polyvinyl fluoride, polyamide, polyimide, polynitriles and cellulose, and combinations and mixtures thereof.

12. A flexible container in accordance with the claim 10, further characterized in that said first material is perdeuterated or partially perdeuterated.

13. A flexible container according to claim 2, further characterized in that said first material comprises a copolymer.

14. A lexible container according to claim 2, further characterized in that said first material is perdeuterated or partially perdeuterated.

15. A flexible container according to claim 4, further characterized in that said first layer comprises a high purity metal.

16. A flexible container according to claim 8 or 15, further characterized in that said first layer comprises a material selected from the group consisting of aluminum, indium, gold, zinc, tin, bismuth copper, silver, niobium, and oxides of the same.

17. A container according to claim 1, further characterized in that said container has an internal volume (V) and an internal surface area (A), wherein said container has such a size that the ratio A / V is less of approximately .75 cm'1.

18. A container according to claim 1, further characterized in that said container also includes a plurality of O-rings operably associated therewith, and wherein at least one of said O-rings is configured in a way that is substantially non-depolarizing to the hyperpolarized gas retained in said container.

19. A container according to claim 18, further characterized in that one of said O-rings is coated with a material that inhibits contact-induced relaxation of said hyperpolarized gas.

20. A container according to claim 18, further characterized in that said O-rings are formed in such a way that they are substantially free of depolarizing filler materials.

21. A container according to claim 1, further characterized in that said hyperpolarized gas comprises gas 3He, and wherein said internal surface material has a value of relaxation capacity of less than about 0.0013 cm / min.

22. - A container according to claim 1, further characterized in that said hyperpolarized gas comprises gas 129Xe, and wherein said internal surface material has a value of relaxation capacity of less than about 0.012 cm / min.

23. A container according to claim 1, further characterized in that said hyperpolarized gas is in the gaseous state.

24. A container according to claim 20, further characterized in that said hyperpolarized gas comprises hyperpolarized 3He, and wherein said container is configured in such a manner that said hyperpolarized gas 3He in said container is configured to provide a greater relaxation time of approximately 14 hours.

25. A container according to claim 23, further characterized in that said hyperpolarized gas comprises hyperpolarized 129Xe.

26. A container according to claim 1, further characterized in that it comprises a capillary rod having first and second opposite end portions, wherein said second end portion is in fluid communication with said container port.

27.- A container according to claim 26, further characterized in that said sealing means comprises a valve, and wherein said capillary rod is placed intermediate to said port and said valve.

28. A container according to claim 1, further characterized in that said container includes a means of isolation of port operably associated with said expandable chamber to isolate said port from a portion greater than said expandable chamber.

29. A container according to claim 28, further characterized in that said container includes a perimeter, and wherein said port is arranged in said container so that it is close to a portion of said perimeter, and wherein said insulation means is placed intermediate said port and a larger portion of said expandable chamber.

30. A container according to claim 28, further characterized in that said insulation means is an externally applied clip 15.

31.- A container according to claim 29, further characterized in that said insulation means is defined by folding the perimeter portion of said container with said port towards the main volume of said expandable chamber.

32. A method according to claim 4 or 6, further characterized in that said layers of material are formed of different materials. --fÉ-UMÉÉ-ill ^ -i

33. - A flexible container according to claim 27, further characterized in that said capillary rod is formed in a portion of said valve to define a continuous body.

34. A flexible container according to claim 27, further characterized in that said valve comprises a glass body.

35.- A flexible container in accordance with the claim 26, further characterized in that said capillary rod is substantially rigid and has an internal surface having a low solubility for said hyperpolarized gas which inhibits depolarization of the hyperpolarized gas induced by contact.

36.- A flexible container in accordance with the claim 27, further characterized in that said valve has a first open position and a second closed position, and wherein said capillary rod has an internal length and width of such size and configuration to inhibit the passage of hyperpolarized gas from said container chamber hac ' 3 said valve when said valve is in closed position.

37.- A method for storing, transporting and supplying hyperpolarized gas to a target, comprising the steps of: hyperpolarizing a noble gas quantity with spin exchange with an alkali metal; introducing a quantity of hyperpolarized gas into an expandable multilayer container having opposite walls defined by multiple layers of materials, wherein the multiple layers of container walls securely join so as to be in concurrent response to the application of pressure to them, and wherein said multiple layers are formed of materials that provide a sufficient oxygen permeability rate to inhibit the oxygen migration in the container, the oxygen permeability rule, at atmospheric pressure being less than about 1 x 10'7 amgt / min, wherein the hyperpolarized gas is processed to be non-toxic and substantially free of alkali metal and therefore suitable for in vivo administration, and wherein said walls have an internal surface formed of material having a low relaxation capacity for the hyperpolarized gas retained in said container; sealing the container to retain the hyperpolarized gas within it; transport the container to a remote site of the hyperpolarization site; and compressing the container to collapse the chamber and force the hyperpolarized gas out of it, thereby supplying the hyperpolarized gas to a target.

38. A method according to claim 37, further characterized in that it comprises the step of inhibiting the circulation of a larger portion of the gas retained in the container towards the opening of the port in the container during storage and transportation.

39.- A method according to claim 38, further characterized in that said step of inhibiting is carried out by placing a capillary flow passage in communication with the container port.

40. A method according to claim 38, further characterized in that said step of inhibition is carried out by substantially isolating a smaller portion of the container from the main volume of the container.

41. A method according to claim 40, further characterized in that said isolation step is carried out by pressing a portion of the opposite walls of the container together.

42. A method according to claim 40, further characterized in that said isolation step is carried out by bending the smaller portion of the container towards the main volume of the container in order to contract together the opposite wall segments between them.

43.- A method according to claim 37, further characterized in that said hyperpolarized gas is 3He, and wherein said container walls include a first internal layer that defines the internal surface that inhibits the interaction by depolarizing contact of the hyperpolarized gas so that the hyperpolarized gas has a relaxation time influenced by contact-induced loss of polarization and oxygen migration in said chamber which is more than about 6 hours.

44.- A method according to claim 37, further characterized in that the walls include a first layer of material comprising a high purity metal.

45. A method according to claim 38, further characterized in that the walls include a first layer of material comprising a polymer and a second layer of material comprising a metal, the second layer of metal defining a protection against oxygen that underlies the first layer.

46.- A method according to claim 38, further characterized in that the multiple layers of materials defining said walls include at least two layers that are formed of a different material, the materials selected to suppress the oxygen migration in said chamber .

47. A method according to claim 38, further characterized in that said introduction and transport sealing steps are repeated.

48. A method according to claim 37, further characterized in that said container walls comprise at least three layers of three different materials.

49. A method according to claim 37, further characterized in that said hyperpolarized gas is 3Helio, and wherein said expandable multi-layer container comprises an inner gas contact surface formed of a material having a relaxation capacity value less than about .0013 cm / min.

50. A method according to claim 37, further characterized in that said hyperpolarized gas is 29Xe, and wherein said expandable multi-layer container comprises an internal gas contact surface formed of a material having a relaxation capacity value of less than about .012 cm / min.

51.- A method of preparing a container for expandable storage to receive a quantity of hyperpolarized gas, comprising the steps of: providing a quantity of purge gas in the hyperpolarized gas container; expanding the hyperpolarized gas container by directing a quantity of purge gas therein; collapse the hyperpolarized gas container by removing the purge gas from it; degassing the oxygen in the walls of the container decreasing the partial pressure of oxygen in the container thus causing a substantial amount of the oxygen trapped in the walls of the container to migrate towards the chamber of the container in the gas phase; filling a container with an amount of storage nitrogen after said degassing step at a pressure that minimizes the differential pressure through the walls 15 of the container to minimize further degassing of the container; store the container for future use; and removing the degassed oxygen and storage nitrogen from the container before filling with an amount of hyperpolarized gas.

52. A method for determining the solubility of hyperpolarized gas in a material such as a polymer or fluid, comprising the steps of: introducing a first quantity of hyperpolarized gas into a container; measuring a first longitudinal spin relaxation rate of hyperpolarized gas in the container; place a sample of a material i ^^ mtámit? l ^ ^^^^^^^ mt ^^ i? ^^ ??? M? M? ^ mi?, l,,,!, ,, i, km,, ii ii. • my . - t .M «.« i. .niiiiiii-ri niMi.i desired in the container; introduce a second amount of hyperpolarized noble gas into the container; measuring a second longitudinal spin relaxation velocity of the hyperpolarized gas in the container; and determining the solubility of the gas in the sample based on the difference between the first and second relaxation velocities.

53. A method according to claim 52, further characterized in that said sample is a structurally fixed sample having a known geometric shape with a surface formed of the desired material. 54.- A method according to claim 52, further characterized in that said sample is a quantity of fluid that fills a portion of the free volume in the container. ^^ gM ^ iÜHÉIIU SUMMARY OF THE INVENTION A flexible multi-layer container is described which is configured to receive a quantity of hyperpolarized noble fluid such as a gas and includes a wall with at least two layers, a first layer with a surface that minimizes the induced spin relaxation. by contact and a first or second layer that is substantially impermeable to oxygen; the container is especially suitable for picking up and transporting 3He; The flexible container can be formed of layers of material 10 which are concurrently in response to pressure such as polymers, deuterated polymers, or metallic films; the container may include a capillary rod and / or a port or valve isolation means to inhibit the flow of gas from the main volume of the container during transport; the flexible container can be configured to directly supply the gas 15 hyperpolarized noble to a target interface deflating or collapsing the inflated flexible container; In addition, single-layer flexible containers with Ti's of more than 4 hours for 129Xe and more than 6 hours for 3He include materials with selected relaxation capacity values; In addition, a bag with a port accessory or valve element and one or 20 more than one capillary rod and port isolation means are configured to minimize the depolarization effect of the valve or accessory (s) of the container; Also disclosed is a method for determining the solubility of gas in an unknown polymer or liquid using the measured relaxation time of a hyperpolarized gas. HL / MC / PG / all P00 / 1741F