text:
A transport unit includes a plurality of permanent magnets arranged to provide a magnetic holding field for protecting hyperpolarized gas during storage and/or transport. The permanent magnets are configured in a relatively light weight manner to project a substantially cylindrical magnetic holding field or spherical holding field in space. The magnet arrangements can include primary magnets and field shaping secondary magnets which act to enlarge the region of homogeneity. The permanent magnet arrangement can also be provided with a cylindrical shaped flex sheet magnetically activated to provide the magnetic holding field. The permanent magnet arrangements do not require disassembly to insert or remove one or more containers of hyperpolarized gas in or out of the transport unit.
1. A transport unit for holding a quantity of hyperpolarized gas therein comprising:
at least one container for holding hyperpolarized gas;
a flexible sheet material layer having an applied magnetization, wherein said flexible layer is configured as a cylinder such that opposed ends of the sheet brought adjacent to each other in the cylindrical configuration do not overlap, wherein said flexible material layer has magnetic north and south poles thereon, and a magnetic field strength associated therewith, wherein said flexible material layer defines a homogeneous magnetic holding field operably associated with said gas container; and
a housing configured to receive said flexible material cylinder and said gas container therein.
2. A transport unit according to
3. A transport unit according to
4. A transport unit according to
5. A transport unit according to
wherein each point on said flexible cylinder has a direction of magnetic north associated therewith;
wherein each of said plurality of points has a first vertical axis associated therewith which intersects said point;
wherein said flexible cylinder has a second vertical axis associated therewith which diametrically extends to bisect opposing top and bottom surfaces of the cylinder; and
wherein said flexible cylinder is configured such that at any point, a first angle between said magnetic north direction and said first vertical axis is about twice the magnitude of a second angle between said second vertical axis and a line to said point from the center of said second diametrical axis.
This application is a division of U.S. application Ser. No. 10/668,518 filed Sep. 23, 2003, now U.S. Pat. No. 7,066,319, which is a division of U.S. application Ser. No. 09/583,663 filed May 30, 2000, now U.S. Pat. No. 6,648,130 which claims the benefit of priority from Provisional application Ser. No. 60/148,359 filed Aug. 11, 1999, entitled "Hyperolarized Gas Transport and Storage Devices and Associated Transport and Storage Methods Using Permanent Magnets"
This invention was made with Government support under National Institute of Health Grant number R43HL62756-01. The United States Government has certain rights in this invention.
The present invention relates generally to the transport of hyperpolarized gases from one site to another, such as from a production site to a clinical use site. The hyperpolarized gases are particularly suitable for MR imaging and spectroscopy applications.
Inert gas imaging ("IGI") using hyperpolarized noble gases is a promising recent advance in Magnetic Resonance Imaging (MRI) and MR spectroscopy technologies. Conventionally, MRI has been used to produce images by exciting the nuclei of hydrogen molecules (present in water protons) in the human body. However, it has recently been discovered that polarized noble gases can produce improved images of certain areas and regions of the body which have heretofore produced less than satisfactory images in this modality. Polarized Helium-3 ("3He") and Xenon-129 ("129Xe") have been found to be particularly suited for this purpose. Unfortunately, as will be discussed further below, the polarized state of the gases is sensitive to handling and environmental conditions and can, undesirably, decay from the polarized state relatively quickly.
Various methods may be used to artificially enhance the polarization of certain noble gas nuclei (such as 129Xe or 3He) over the natural or equilibrium levels, i.e., the Boltzmann polarization. Such an increase is desirable because it enhances and increases the MRI signal intensity, allowing physicians to obtain better images of the substances in the body. See U.S. Pat. No. 5,545,396 to Albert et al., the disclosure of which is hereby incorporated by reference as if recited in full herein.
A "T1" decay time constant associated with the hyperpolarized gas' longitudinal relaxation is often used to characterize the length of time it takes a gas sample to depolarize in a given situation. The handling of the hyperpolarized gas is critical because of the sensitivity of the hyperpolarized state to environmental and handling factors and thus the potential for undesirable decay of the gas from its hyperpolarized state prior to the planned end use, e.g., delivery to a patient for imaging. Processing, transporting, and storing the hyperpolarized gases—as well as delivering the gas to the patient or end user—can expose the hyperpolarized gases to various relaxation mechanisms such as magnetic field gradients, surface-induced relaxation, hyperpolarized gas atom interactions with other nuclei, paramagnetic impurities, and the like.
One way of reducing the surface-induced decay of the hyperpolarized state is presented in U.S. Pat. No. 5,612,103 to Driehuys et al. entitled "Coatings for Production of Hyperpolarized Noble Gases." Generally stated, this patent describes the use of a modified polymer as a surface coating on physical systems (such as a Pyrex™ container) which contact the hyperpolarized gas to inhibit the decaying effect of the surface of the collection chamber or storage unit. Other methods for reducing surface-induced decay are described in co-pending and co-assigned U.S. patent application Ser. No. 09/163,721 to Zollinger et al., entitled "Hyperpolarized Noble Gas Extraction Methods, Masking Methods, and Associated Transport Containers."
However, other relaxation mechanisms arise during production, handling, storage, and transport of the hyperpolarized gas. These problems can be particularly troublesome when storing the gases or transporting the hyperpolarized gas from a production site to a (remote) distribution and/or use site. In transit, the hyperpolarized gas can be exposed to many potentially depolarizing influences. There is, therefore, a need to provide improved ways to transport hyperpolarized gases so that the hyperpolarized gas is not unduly exposed to depolarizing effects during transport. Improved storage and transport methods and systems are desired so that the hyperpolarized product can retain sufficient polarization to allow effective imaging at delivery when stored or transported over longer transport distances in various (potentially depolarizing) environmental conditions, and for longer time periods from the initial point of polarization than has been viable previously.
One design used to provide a homogeneous field in a unit for transporting and storing hyperpolarized gas products is proposed by Hasson et al. in U.S. patent application Ser. No. 09/333,571 entitled "Hyperpolarized Gas Containers, Solenoids, Transport and Storage Devices and Associated Transport and Storage Methods." This technique comprises a durable, safe, and convenient transport unit. However, a magnetic field generator within the transport unit used for generating the hyperpolarized gas magnetic holding field requires power to operate it. During transport or in storage, a convenient source of power may be difficult to find. Additionally, batteries with lengthy lifetimes suitable for hyperpolarized gas transport and storage can be heavy and are often large.
Another alternative is proposed by Aidam et al. in WO 99/17304. This reference proposes configuring a magnetically shielded container using opposing pole shoes to provide a unit for holding and transporting a chamber of polarized gas. Unfortunately, the shielded container is designed so as to require removal of one of the pole shoes to remove the gas chamber, thereby potentially sacrificing the homogeneity of the field. Additionally, the pole shoes can be dented or permanently magnetized during transport and storage. Physical deformation of the pole shoes which occurs during transport or normal use can unfortunately permanently destroy the homogeneity of the magnetic field. Furthermore, the pole shoes (which as described by Aidam et al. comprise mu metal or soft iron) can display hysteresis characteristics. This hysteresis can cause the pole shoes to be permanently magnetized if placed next to a magnetic field source, thereby acting as its own magnet and potentially deleteriously affecting the homogeneity of the resulting permanent magnet field.
A third alternative is proposed in U.S. patent application Ser. Nos. 08/989,604 and 09/210,020 to Driehuys et al. In these two patent applications, a magnetic field generator is described for the transport of hyperpolarized frozen xenon. The embodiment proposed by Driehuys et al. comprises a relatively small magnet yoke and two permanent magnets mounted opposite one another on the magnet yoke. This configuration produces a magnetic field with high field strength but relatively low homogeneity. While high magnetic field strength alone can generally maintain a highly hyperpolarized state in a solid hyperpolarized gas product, thawing prior to use produces a gaseous xenon product, which then typically requires that the field be homogeneous to reduce the likelihood of rapid depolarization due to gradient-induced relaxation.
It is therefore an object of the present invention to provide a transport unit which can hold quantities of hyperpolarized gas for extended periods of time, such that the hyperpolarized gas is sufficiently viable to produce clinically useful images at a spatially and/or temporally separated point in time from the point of polarization.
It is also an object of the present invention to configure a transport unit such that it can be used to transport gas in a commercial shipping vehicle and/or store gas over relatively long periods of time (the latter particularly for when the polarized gas is not intended to be remotely shipped).
Another object of the present invention is to shield a quantity of hyperpolarized gas from deleterious environmentally-induced depolarizing events during transport and/or storage.
An additional object of the present invention is to configure a transport unit with permanent magnets which does not require disassembly to dispense the hyperpolarized gas therefrom or to insert hyperpolarized gas in containers therein.
It is also an object of the present invention to create a transport unit which is lightweight, compact, and easily transportable to facilitate ease of transport and storage.
An additional object of the present invention is to provide a magnetic field generator or source which does not require external power.
It is another object of the present invention to configure a transport unit to reduce the external force associated with shock, vibration, and/or other mechanical collisions that are input into or transmitted to containers of hyperpolarized gas held within the transport unit.
It is also an object of the present invention to provide a portable unit for storing or transporting hyperpolarized gas held in a plurality of separate containers therein.
It is another object of the present invention to size and configure a transport unit to provide a suitable environment for storing and transporting large pressurized multi-bolus containers of hyperpolarized gas.
An additional object of the present invention is to configure a transport unit with an easily accessible means for interrogating the polarized state of the polarized gas held therein using nuclear magnetic resonance (NMR), in order to measure the polarization of the gas, or to measure the decay rate of the polarization.
An additional object of the present invention is to reduce hyperpolarization relaxation due to gas-gas relaxation and/or gradient relaxation by diluting the hyperpolarized gas with a buffer gas.
These and other objects are satisfied by the present invention by configuring a transport unit with a series of relatively lightweight permanent magnets arranged to provide a region of homogeneity for a quantity of hyperpolarized gas held therein. In particular, a first aspect of the present invention is directed to a transport unit which includes a housing and at least four discrete spaced-apart permanent magnets which are configured such that they are arranged in spaced-apart relationship about a longitudinally extending axis defining a center therebetween. The permanent magnets provide a magnetic field with a region of homogeneity substantially centered with respect to the longitudinal axis and the magnets are oriented such that the field direction they produce are substantially perpendicular to the longitudinal axis. Additionally, the transport unit includes at least one container, sized and configured to hold a quantity of hyperpolarized gas, positioned proximate to the region of homogeneity.
In one preferred embodiment, the spaced-apart permanent magnets are elongated and positioned in spaced-apart circumferential relationship to longitudinally extend a distance sufficient to define a substantially cylindrical volume projected in space. In another preferred embodiment, the spaced-apart permanent magnets are positioned in spaced-apart circumferential relationships to define a spherical volume projected in space.
Another aspect of the present invention is directed toward a transport unit for transporting containers of hyperpolarized gas products. This transport unit includes first and second spaced-apart opposing end plates and a plurality of spaced-apart elongated permanent magnets having opposing first and second ends. Each of the permanent magnets are positioned to extend substantially linearly between the first and second opposing end plates to provide a magnetic field with a region of homogeneity therebetween. Additionally, a chamber (configured to hold a quantity of hyperpolarized gas) is preferably positioned between the first and second end plates within the region of homogeneity.
Preferably, the spaced-apart elongated permanent magnets are positioned in a spaced-apart circumferential relationship to define a cylinder projected in space. In one preferred embodiment, the plurality of permanent magnets are rubber strip magnets and each magnet is structurally secured to a longitudinally extending support member which is attached to each of the opposing end plates. Preferably, the magnets are configured to remain fixedly attached to the end plates via the support members during installation and removal of the gas container(s) into and out of the transport unit. It is also preferred that the permanent magnets be substantially circumferentially spaced apart about a circle with a center coincident with a longitudinal center axis extending therethrough. The center of the longitudinal center axis defines the center of a holding volume in the transport unit, and a vertical diametrical line drawn through the center of the circle between the upper and lower parts thereof defines a first vertical axis. In this preferred embodiment, the elongated magnets are oriented such that the magnetic north pole surface is in a fixed angular relationship with the first vertical axis. Additionally, a plurality of supplementary magnets can be positioned on end portions of selected elongated magnets enlarge the region of homogeneity therein.
Another aspect of the present invention is directed toward a transport unit for transporting hyperpolarized gas using discrete magnets. The unit includes at least one gas chamber configured to hold a quantity of hyperpolarized gas therein, a first upstanding end wall comprising a first set of spaced-apart discrete permanent magnets positioned thereon, and a second upstanding end wall positioned in the transport unit spaced apart from and opposing the first wall to define a gas enclosure volume for holding the gas chamber therebetween. The second upstanding wall comprises a second set of spaced-apart discrete permanent magnets positioned thereon. Additionally, the first and second magnet sets are circumferentially arranged about two corresponding circles with corresponding first diameters and aligned centers on the first and second walls, respectively, and each of the discrete permanent magnets has a magnetic north and south pole associated therewith. Furthermore, the first magnet set is arranged on the first wall such that the magnetic north pole of each magnet in the first magnet set is directed toward the center of the circle that the first magnet set is arrange thereabout, and the magnetic south pole of each magnet in the second magnet set is directed toward the center of the circle around which the second magnet set is arranged. Each of the permanent magnets in each of the first and second magnet sets are arranged to laterally extend toward the other a minor distance to define a central free space with a magnetic holding field having a region of homogeneity therebetween.
Preferably, the transport unit also includes a housing, where the housing is spaced apart a predetermined separation distance (preferably at least about 2 inches) from the perimeter of the gas chamber holding a major volume of the hyperpolarized gas therein. The transport unit also preferably includes a third supplementary set of magnets arranged to be circumferentially spaced apart about a third circle having a second diameter, wherein the set of supplementary magnets is positioned intermediate the first and second magnet sets. Preferably, the second diameter is larger than the first diameter. The magnets in the supplementary set of magnets have a north pole and a south pole, and the north pole of the supplementary magnets are oriented to point normal to the plane defined by the third circle and in the direction of a plane defined by the first circle.
Another aspect of the present invention is directed toward a method of fabricating a cylindrically shaped magnetic field volume. This method involves rolling a flexible magnetic sheet into a first hollow cylinder such that the ends abut. Then, a magnetic field is applied to the cylindrically configured flexible magnetic sheet which is then unrolled. Finally, the flexible magnetic sheet is rerolled into a second hollow cylinder such that the ends abut, and such that the sides are reversed, i.e., the side that was inside the first hollow cylinder is positioned to define the outer side of the second hollow cylinder.
An additional aspect of the present invention is directed toward a transport unit for transporting a quantity of hyperpolarized gas using a magnetic hollow cylinder to generate a holding field for a chamber of hyperpolarized gas. The transport unit includes at least one container for holding hyperpolarized gas, a flexible material layer having an applied magnetization, wherein the flexible layer is configured as a cylinder having magnetic north and south poles and a magnetic field strength. The flexible material layer defines a homogenous magnetic holding field for the container and fits inside a housing.
Preferably, the housing is configured and sized to be at least 2 inches away from the walls of the gas container. Furthermore, the flexible material is magnetized such that the direction of the magnetic north varies about the circumference of the cylinder. The cylinder also includes a continuous surface represented by a plurality of adjacent points drawn in space. At each point on the flexible cylinder, there is a direction of magnetic north and a first vertical axis which intersects the point. Additionally, each point has a second vertical axis associated with it which diametrically extends to bisect opposing top and bottom surfaces of the cylinder. The flexible cylinder is preferably configured such that at any point, a first angle between the magnetic north direction and the first vertical axis is twice the magnitude of a second angle between the second vertical axis and a line to the point from the center of the second diametrical axis.
The present invention is advantageous because it enables hyperpolarized gas to withstand travel from a production site to a remote use site in a hyperpolarized state which is still capable of producing clinically useful images at the remote site. To do this, the present invention shields the gas from deleterious ambient external magnetic fields while creating its own internal holding field for the hyperpolarized gas without requiring an external or internal power source. Advantageously, this holding field comprises permanent magnets, which are lightweight and easy to manufacture. Additionally, the magnetic holding field does not need to be disturbed to insert or remove a gas chamber, which advantageously allows the magnetic holding field to carry several gas chambers at one time without deleterious affects on the remaining chambers in the holding field when one is removed therefrom.
FIGS. 13 and 13A-C are perspective views of a flexible magnet sheet magnetized and configured to provide a cylindrical magnetic holding field according to the present invention.
The present invention now will be described more fully hereinafter with reference to the accompanying drawings, in which preferred embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Like numbers refer to like elements throughout. In the figures, layers and regions may be exaggerated for clarity.
For ease of discussion, the term "hyperpolarized gas" will be used to describe a hyperpolarized gas alone, or a hyperpolarized gas that contacts or combines with one or more other components, whether gaseous, liquid, or solid. Thus, the hyperpolarized gas described herein can be a hyperpolarized gas composition/mixture (preferably non-toxic such that it is suitable for in vivo introduction) such that the hyperpolarized gas can be combined with other gases and/or other inert or active components. Also, as used herein, the term "hyperpolarized gas" can include a product in which the hyperpolarized gas is dissolved into or combined with another liquid or gas (such as a carrier fluid) or processed such that it transforms into a substantially liquid state, i.e., "a liquid polarized gas". Thus, although the term "hyperpolarized gas" includes the word "gas", this word is used to name and descriptively track the noble gas which is polarized via 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 gas which can include one or more components and which may be present in one or more physical forms.
Various techniques have been employed to polarize, accumulate and capture polarized gases. For example, U.S. Pat. No. 5,642,625 to Cates et al. describes a high volume hyperpolarizer for spin-polarized noble gas and U.S. Pat. No. 5,809,801 to Cates et al. describes a cryogenic accumulator for spin-polarized 129Xe. The disclosures of these patents are hereby incorporated herein by reference as if recited in full herein. As used herein, the terms "hyperpolarize" and "polarize" are used interchangeably and mean to artificially enhance the polarization of certain noble gas nuclei over the natural or equilibrium levels. Such an increase is desirable because it allows stronger imaging signals corresponding to better MRI images of the substance in a targeted area of the body. As is known by those of skill in the art, hyperpolarization can be induced by spin-exchange with an optically pumped alkali-metal vapor, or alternatively by metastability exchange. See U.S. Pat. No. 5,545,396 to Albert et al. The alkali metals capable of acting as spin exchange partners in optically pumped systems include any of the alkali metals. Preferred alkali metals for this hyperpolarization technique include Sodium-23, Potassium-39, Rubidium-85, Rubidium-87, and Cesium-133.
Alternatively, the noble gas may be hyperpolarized using metastability exchange. (See e.g., Schearer, L. D., Phys Rev, 180:83 (1969); Laloe, F., Nacher, P. J., Leduc, M., and Schearer L. D., AIP ConfProx #131 (Workshop on Polarized 3He Beams and Targets) (1984)). The technique of metastability exchange involves direct optical pumping of, for example, 3He without the need for an alkali metal intermediary. Since this process works best at low pressures (0-10 Torr), a compressor is typically used to compress the 3He after the hyperpolarization step.
Regardless of the hyperpolarization method used, once the active mechanism is no longer in effect, the polarization of the gas will inevitably decay toward its thermal equilibrium value, which is essentially zero. The present invention is configured to work with any hyperpolarization technique and is not limited to working with any one machine, method, or particular gas.
Polarized Gas Relaxation Processes
Under most circumstances, the non-equilibrium polarization "P(t)" of a gas decays according to
The first decay term "(1/T1)Gas" represents the depolarization of the noble gas nuclei when interacting with each other and can also include interaction of the atoms with gaseous impurities such as oxygen. Thus, careful preparation of gas containment, transfer, and extraction systems is important for providing good polarization lifetimes as will be discussed further hereinbelow. Examples of suitable gas extraction methods and apparatus are described in co-pending and co-assigned U.S. patent application Ser. No. 09/163,721, entitled "Hyperpolarized Noble Gas Extraction Methods, Masking Methods, and Associated Transport Containers," the disclosure of which is hereby incorporated by reference as if recited in full herein.
Even in the absence of all other relaxation mechanisms, collisions between identical polarized gas atoms impose a fundamental upper limit to the achievable T1 lifetime. For example, 3He atoms relax through a dipole-dipole interaction during 3He—3He collisions, while 129Xe atoms relax through N•I spin rotation interaction (where N is the molecular angular momentum and I designates nuclear spin rotation) during 129Xe—129Xe collisions. In any event, because both processes occur during noble gas-noble gas collisions, both resulting relaxation rates are directly proportional to number density (T1 is inversely proportional to number density). At one bar pressure, the theoretical maximum relaxation time T1 of 3He is about 750 hours, and 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 129 Xe in Natural Xenon, 130 Phys Rev. p. 2302 (1963).
However, relatively small amounts of hyperpolarized gas diluted with buffer gases of low magnetic moment (such as nitrogen or argon) can significantly increase the T1 of the mixture (compared to the T1 of the pure hyperpolarized gas at the same pressure) despite high pressures. This is because the buffer gas has a low magnetic moment and therefore does not substantially contribute to gas-gas relaxation mechanisms. The buffer gas additionally acts to decrease the interaction of potentially depolarizing hyperpolarized gas nuclei by decreasing the concentration of (diluting) the hyperpolarized gas. Furthermore, as described below, packaging small quantities of hyperpolarized gas with buffer gas(es) at high total pressures (due to buffer gas dilution) can additionally decrease the diffusion of the hyperpolarized gas atoms, thereby decreasing the effects of magnetic gradient relaxation due to magnetic field inhomogeneities.
Unfortunately, other relaxation processes such as surface relaxation, electromagnetic interference (EMI), and magnetic gradient relaxation can also prevent the realization of the theoretical relaxation times. Accordingly, each of these mechanisms are of concern when handling hyperpolarized gases and each is preferably addressed so as to extend the overall relaxation time to allow for consistently longer storage or transit times for successful transport and commercialization of hyperpolarized gases.
Surface-Induced Relaxation
The (1/T1)Surface term in equation 2.0 represents the surface-induced relaxation mechanism. For example, the collisions of gaseous 129Xe and 3He with container walls ("surface relaxation") historically have been thought to dominate most relaxation processes. For 3He, most of the known longer relaxation times have been achieved in special glass containers having a low permeability to helium and low iron content. See e.g. Fitzsimmons et al., Nature of surface induced spin relaxation of gaseous He-3, 179 Phys. Rev., No. 1, p. 156 (1969). U.S. Pat. No. 5,612,103 to Driehuys et al. describes using coatings to inhibit the surface-induced nuclear spin relaxation of hyperpolarized noble gases, especially 129Xe. The contents of this patent are hereby incorporated by reference as if recited in full herein. Similarly, co-pending and co-assigned U.S. patent application Ser. No. 09/126,448 to Deaton et al. and its related U.S. patent application Ser. No. 09/334,400 by Zollinger et al. describe preferred gas-contact surface materials and associated thicknesses, o-ring, valve or seal materials and/or coatings which are friendly to the polarized state of the gas, i.e., which can inhibit surface/contact-induced relaxation mechanisms. The contents of these applications are also hereby incorporated by reference as if recited in full herein.
Electromagnetic Interference
The relaxation mechanism expressed by the term (1/T1)EMI is the relaxation induced by time-dependent electromagnetic fields. Indeed, EMI can potentially destroy the hyperpolarized state of the gas (EMI is particularly problematic if coherent at the magnetic resonance frequency). Unfortunately, EMI can be generated by relatively common sources. For example, EMI is typically generated from a vehicle's engine, high voltage lines, power stations and other current carrying entities. As such, transport away from the hyperpolarized gas production site can expose the hyperpolarized gas to these undesirable relaxation sources that, in turn, can dramatically reduce the polarization lifetime of the transported gas.
Fluctuating fields are particularly deleterious if they are coherent at the magnetic resonance frequency. For example, assuming a severe scenario of a highly coherent oscillating field, the relaxation rate can be comparable to the Rabi frequency:
Magnetic gradient relaxation expressed by the term (1/T1)Gradient is associated with the relaxation attributed to the exposure of the hyperpolarized noble gases to inhomogeneous static magnetic fields. Generally stated, as the polarized gas atoms diffuse or move through an inhomogeneous magnetic field, they experience a time-dependent field, which can depolarize the hyperpolarized atoms. For example, at typical pressures (i.e., about 1 bar), the relaxation rate attributed to a static magnetic field gradient can be expressed by the following equation:
The present invention recognizes that unless special precautions are taken, relaxation due to external magnetic fields (static and/or time dependent) can dominate all other relaxation mechanisms. As discussed above, both gradients in the static field and (low frequency) oscillating magnetic fields experienced by the hyperpolarized gas can cause significant relaxation.
Advantageously, the instant invention employs an (externally) applied static magnetic holding field to substantially protect the hyperpolarized gas from depolarizing effects attributed to one or more of the EMI and field gradients during transport. The instant invention employs a magnetic holding field which raises the Larmor frequency of the hyperpolarized gas above the region of noise (1/f), i.e., the region where the intensity of ambient electromagnetic noise is typically high (this noise is typically under about 5 kHz). Further, the magnetic holding field of the instant invention is also preferably selected such that it raises the frequency of the hyperpolarized gas to a level which is above those frequencies associated with large acoustic vibrations (these acoustic vibrations are typically less than about 20 kHz). As will be discussed below, the increased frequency associated with the applied magnetic holding field advantageously allows a transport unit to have greater electromagnetic shielding effectiveness for a given housing thickness (the housing used to hold the hyperpolarized gas therein during transport). The skin depth "δ" of a conductive shielding material is inversely proportional to the square root of the frequency. Thus, at 25 kHz, an exemplary preferred skin depth for aluminum is about 0.5 mm, as compared to about 2.0 mm at 1.6 kHz.
Preferably, the magnetic holding field of the instant invention is selected so that any external field-related fluctuations are small in magnitude compared to the field strength of the holding field; in this way the holding field can minimize the hyperpolarized gas's response to unpredictable external static field gradient-induced relaxation. This can be accomplished by applying to the hyperpolarized gas a proximately positioned magnetic holding field which is sufficiently strong and homogeneous so that it minimizes the unpredictable externally-applied static field-related relaxation during transport. A sufficiently homogeneous holding field preferably includes (but is not limited to) a magnetic holding field which has a homogeneity on the order of about at least 10−3 cm−1 over the central part of the holding field (i.e., the part of the field extending about a major volume of the hyperpolarized gas). In the previous example, if a homogeneous field of even 10 G were applied, the same 5 mG cm−1 gradient would instead result in T1≈600 hr. More preferably, the magnetic holding field homogeneity is about at least 5�10−4 cm−1 over about a region in space which approximates a three-inch diameter sphere. Further, the transport unit 10 of the instant invention includes and provides a magnetic holding field which is positioned, sized, and configured relative to the hyperpolarized gas such that it also minimizes the EMI or oscillating magnetic field depolarization effects. The depolarizing effect of EMI is preferably (substantially) blocked by applying the magnetic holding field proximate to the gas so that the resonant frequency of the hyperpolarized gas is shifted to a predetermined frequency. Preferably, the predetermined frequency is selected such that it lies above or outside the bandwidth of prevalent time-dependent fields produced by electrically powered or supplied sources.
Alternatively, or additionally, the external interference can be shielded by positioning a substantially continuous metallic shield or shipping container having at least one layer formed of a conductive material such as metal around the container of hyperpolarized gas. The preferred shielding thickness is related to the spatial decay constant of an electromagnetic wave or skin depth "δ". The skin depth "δ" at an angular frequency "ω" is given by δ=c/(2πμσω)1/2, where "μ" is the magnetic permeability and "σ" is the electrical conductivity of the material. At preferred operating frequencies (about 24 kHz), the Larmor radiation wavelength is long (˜10 km), and is much larger than the container size.
The shielding effectiveness is also dependent upon the container geometry as well as the shielding thickness. For a thin spherical conductor of radius "a" and thickness "t", the shielding factor "F" for wavelengths λ>>a is given approximately by
Interestingly, the shielding effectiveness increases as the size (typically radius) of the shield is increased. It is therefore preferred that the shipping container or metallic housing used to shield or surround the hyperpolarized gas be configured to define an internal volume which is sufficient to provide increased shielding effectiveness. Stated differently, as shown in
Alternatively, or additionally, the transport unit can be configured with at least one layer formed from about 0.5 mm thick of magnetically permeable material, such as ultra low carbon steel, soft iron, or mu-metals (by virtue of their greater magnetic permeability). However, these materials may significantly influence the static magnetic field and, as will be appreciated by one of skill in the art, must be designed accordingly not to affect the homogeneity adversely.
Irrespective of the skin depth of the materials used to form the shipping container housing (types of materials and number of layers), application of a homogeneous magnetic holding field proximate to the hyperpolarized gas can help minimize the gas depolarization by virtue of decreasing the skin depth δ, which is inversely proportional to the square root of the frequency. Further, it helps by pushing the resonant frequency of the gas outside the bandwidth of common AC fields. It is preferred that the resonant frequency of the hyperpolarized gas be raised such that it is above about 10 kHz, and more preferably be raised such that it is between about 20-30 kHz. Stated differently, it is preferred that for shielding, the applied magnetic holding field has a field strength of about 2 to 35 Gauss. It is more preferred that for 129Xe, the magnetic holding field is preferably at least about 20 Gauss; and for 3He, the magnetic holding field is preferably at least about 7 Gauss.
Transport Unit
Referring to
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Generally stated, as electromagnetic leakage is proportional to holes or openings in the housing 60, it is preferred that (as shown in
Preferably, the bottom and top of the case 60B, 61A include at least one layer of an electrically conducting metal having a sufficient skin depth to thereby provide one or more of shielding from external electromagnetic radiation, physical protection, and support of the gas container during transport. Alternatively, or additionally, the components of the housing 60 which define the enclosure volume 65 (such as the walls and bottom 63A-63E and top 61A) include at least one layer of magnetically permeable material to provide either additional electromagnetic shielding, DC magnetic shielding, and/or a flux return. Advantageously, when multiple transport units are positioned adjacent to one another (in storage, for example), a flux return around the magnetic field generator minimizes deleterious effects to the internal magnetic holding field BH (and therefore the hyperpolarized gas) caused by the magnetic holding field in any neighboring transport unit 10.
Preferably, as shown in
In a preferred embodiment, after delivery to a desired location, the valve 32 is opened and the hyperpolarized gas is released from the gas chamber 30 through the exit port 31 while the gas chamber 30 itself remains captured in the substantially enclosed housing 60 (
In its preferred operative position, as shown in
In another preferred embodiment, a tray 630 as shown in
Preferably, as shown in dotted lines in
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Turning to
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Further, in a preferred embodiment, as shown in
In another preferred embodiment, shown in
As shown in
In another preferred embodiment, as shown in
Preferably, the magnetic field strength of each of the aforementioned secondary strips 28A-28P is also substantially less than that of the primary strips 21A-21H. Preferably, the secondary strips 28A-28P have a magnetic field strength of less than about 50% of the primary strips 21A-21H. More preferably, the secondary strips 28A-28P have less than about 35% of the magnetic field strength of the primary strips 21A-21H. Most preferably, the secondary strips 28A-28P have about 25% or less of the magnetic field strength of the primary strips 21A-21H.
As shown in
As will be appreciated by one of skill in the art, additional magnets (tertiary, quaternary, etc.) can be further added to the permanent magnet assembly 20 to further increase the region of homogeneity 21M. Additional magnets, in a preferred embodiment, are shorter in length and of smaller magnetic field strength than both the primary 21A-21H and secondary magnets 28A-28P.
Additionally, as appreciated by one of skill in the art and shown in
In a preferred embodiment, the primary magnets 21A-21H are arranged as shown in
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In the embodiment shown in
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In another preferred embodiment, as shown in
As shown in
Materials and structural elements are preferably chosen such that transport unit's 10 weight and any depolarizing affect on the hyperpolarized gas held in the gas chamber 30 is minimized. As such, the bars 26A-26D (
The net magnetic field BH from the permanent magnet assembly 20 is preferably configured to predominantly coincide with the earth's magnetic field. Because reversing field direction adversely affects the state of the hyperpolarized gas (i.e. depolarization occurs), this orientation can significantly prolong the lifetime of the hyperpolarized gas. Orienting the net magnetic field to coincide predominantly with the earth's magnetic field minimizes the adverse effects to the hyperpolarized gas when removing it from or inserting it into the transport unit 10.
Additionally, to further prevent unnecessary depolarization of the gas due to changes in magnetic field direction, end access ports 29 such as those shown in
Alternative configurations for permanent magnets arranged to provide a magnetic holding field BH approximating a cylindrical volume projected in space are also possible substantially maintaining the θ=2φ relationship described above. For example, as shown in
While the cylindrical arrangements of permanent magnets described above is very effective at producing a homogeneous magnetic field, other permanent magnet arrangements can also provide a magnetic field with sufficient homogeneity to transport and store hyperpolarized gas. One such arrangement involves approximating a spherical shell geometry with discrete magnets.
As shown by Coey, J. M. D., in Rare-earth Iron Permanent Magnets, the magnetic field produced by a continuous magnetized shell (i.e., a hollow sphere magnet) can be analyzed. For a spherical shell with outer diameter "b" and inner diameter "a", inside the shell, the magnetic field B is homogeneous with a magnitude of
However, hyperpolarized gas cannot be easily placed into a spherical shell without substantially deleteriously affecting the magnetic field inside the shell. Additionally, manufacturing such a magnetized shell can be difficult and expensive. Alternatively, however, it is possible to approximate a spherical shell using discrete permanent magnets. Designs based on spherical geometry approximations are more advantageous than the magnetized spherical shell because spherical shell approximations can be easier to manufacture and can allow insertion and removal of a chamber filled with hyperpolarized gas without affecting the magnetic field.
Additionally, for "2n" rings the mean magnetic potential "Φ" per magnet, as "n" approaches infinity is
In one preferred embodiment, as shown in
Furthermore, as shown in
In a preferred embodiment, the chamber 30 is also supported in the region of homogeneity 21M by vibration isolation packing material 50 shown by the dotted line in
In one preferred embodiment, the transport unit 10′ further includes shielding means. Structural plates 226, 227, 292, and 293 can act as a magnetic shield if configured, sized, and/or positioned appropriately as described in the shielding section hereinabove. However, additional shielding can also be added, such as a high permeability metal which can also act as a flux return. The addition of high permeability metal may also compensate for the edge effects of the permanent magnet field, if designed properly as will be appreciated by one of skill in the art. Advantageously, with the design depicted in
As shown in
In one preferred embodiment, two opposing magnet sets 226S, 227S of eight magnets are arranged around 12 inch diameter circles. The opposing magnet sets are preferably spaced about 15⅛″ apart and the poles are oriented as described above. Additionally, a third set of sixteen magnets is placed on an equatorial circle (i.e., directly transversely centered between the first two magnet sets) whose radius is approximately 9⅜ inches. The equatorial magnets are oriented parallel to the end plates (perpendicular to the non-equatorial magnets), with the fields oriented as shown in
Of course, the design described hereinabove can be sized and configured to create a magnetic holding field with a region of homogeneity to substantially encompass one or more chamber(s) which are transported and/or stored. Additional magnets (both more rings and/or more magnets per ring) can make the generated field BH more homogeneous, while fewer magnets can reduce the size of the region of homogeneity 21M. Preferably, when configuring the spherical magnet approximation, the design is arranged such that it includes rings with an equal number of magnets per ring 226S, 227S (except for equatorial rings, as described hereinabove) positioned at angles θk and tipped at an angle 2θk away from the axis of symmetry represented by a line drawn central and parallel to the walls 226, 227 holding the magnet rings thereon.
As noted above, the materials of the device must be chosen such that it minimizes depolarizing activity to the gas. Therefore, all the plates 226, 227, 292, 293, 380, etc., the chamber holder 290, and the magnet holders 250-257 and 260-267 are preferably composed of a non-magnetic material such as aluminum or plastic. Preferably, to minimize weight, a low density, high strength material should be chosen for these components.
Gas Chamber
Preferably, the gas chamber 30 is configured to provide a clinically useful quantity of hyperpolarized gas which can be conveniently delivered to an end point in a user-friendly single dose volume (but of course can also be configured to provide multiple or partial dose quantities) of hyperpolarized gas. In a preferred embodiment, the gas chamber 30 is a 100-200 cm3 gas spherical chamber. For 3He it is preferred that the gas chamber 30 be pressurized to about 4-12 atmospheres of total pressure, and more preferably it is pressurized to about 5-11 atmospheres of total pressure. Pressuring an appropriately sized gas chamber can allow the hyperpolarized gas to be released through the exit port 31 as the pressure acts to equalize with ambient conditions. Thus, by merely opening the valve 32, the hyperpolarized gas can be directed to a patient or a patient delivery system with minimal handling (and thus minimal potentially depolarizing interaction). Alternatively, the hyperpolarized gas can be divided and/or diluted either at a polarization site or at a second site remote from the polarization site into several patient delivery bags with expandable chambers for (further) transport and delivery. The walls of the expandable chamber bags can be depressed to expel the gas mixture held therein with a minimum of extraction equipment required.
It should be noted that for hyperpolarized 3He, at about 10 atm of pressure, the theoretical T1 due to interactions with other hyperpolarized nuclei is about 75 hours. Substantially higher pressures allow more gas product to be shipped in the container and reduces the sensitivity of the hyperpolarized gas to gradient relaxation, but the gas-gas collision relaxation can become more prevalent. In contrast, for 129Xe, it is preferred that the gas pressure be about 10 atm or less, because higher pressures can dramatically reduce the expected relaxation time of the hyperpolarized 129Xe (i.e., at 10 atm, the T1 is 5.6 hours). However, as described above, diluting the hyperpolarized noble gas with a second substance of low magnetic moment can significantly decrease the relaxation rate due to gas-gas interactions at high pressures.
In a preferred embodiment of the instant invention, as shown in
As also discussed above, even if the transport unit 10 shields or protects the hyperpolarized gas from EMI and static magnetic field gradients, the surface relaxation rate associated with the container, the valve(s), and other hyperpolarized gas contacting components can deleteriously affect the polarization lifetime of the hyperpolarized gas. As such, particularly for hyperpolarized 3He, it is preferred that the gas chamber 30 primarily comprise an aluminosilicate material. Aluminosilicate materials have been shown to have long surface relaxation times. The gas chamber 30 may be manufactured from GE180™, although, of course, other aluminosilicates may be used. Typically a transition glass is used to attach the borosilicate (Pyrex�) valve 32 to the aluminosilicate gas chamber 30. A suitable valve 32 for use in the gas chambers 30 is part number 826460-0004 which is available from Kontes, of Vineland, N.J. The valves 32 can be further modified to coat or replace any paramagnetic or ferromagnetic impurities, or may be treated or conditioned to remove or minimize the amount of impure or depolarizing materials that are positioned proximate to the hyperpolarized gas. Suitable transition glass includes uranium glass. Alternatively, other polarization-friendly materials can be used, such as high purity metals or polymers with metallized surfaces, polymers and the like. "High purity" as used herein means materials that are substantially free of paramagnetic or ferrous materials. Preferably, the metallic materials include less than 1 part per million paramagnetic or ferrous impurities (such as iron, nickel, chromium, cobalt and the like). In an alternate preferred embodiment, the gas chamber 30 can be a resilient bag having a metallic film surface or surface layer which is formed from one or a combination of a high purity metal such as gold, aluminum, indium, zinc, tin, copper, bismuth, silver, niobium, and oxides thereof. Additional descriptions of preferred hyperpolarization materials and containers, o-rings and the like are included in co-pending U.S. patent application Ser. No. 09/126,448 entitled "Containers for Hyperpolarized Gases and Associated Methods" and the related co-pending and co-assigned U.S. patent application Ser. No. 09/334,400, as discussed under the Surface-Relaxation section hereinabove. The contents of these applications are hereby incorporated by reference as if recited in full herein.
It is also preferred that the gas chamber 30 be configured as a sphere because it has a geometry that minimizes the surface area/volume ratio and thus the surface-induced contact relaxation. Furthermore, a spherical shape generally maximizes the ratio of chamber volume to region of high magnetic field homogeneity.
In another preferred embodiment, the transport unit 10 and corresponding permanent magnet assembly 20 are configured in at least two different sizes. A first size is designed for transporting large quantities of gas in a single gas chamber 30 configured to hold multiple dosages of hyperpolarized gas or fluid therein ("multi-bolus container") (
The multi-bolus container is used to dispense desired formulations, concentrations, and/or mixtures of the hyperpolarized gas (with or without other substances, liquids, gases (such as nitrogen), or solids) at a remote site. The multi-dose container may be the polarization chamber or optical polarization cell itself. Of course, a single sized transport unit (or even the same transport unit) can be used to transport the hyperpolarized gas to the second and third sites, i.e., the second transport unit may be sized and configured the same as the first transport unit if desired. Alternatively, the first transport unit may be larger than the second or the second may be larger than the first depending on how the hyperpolarized gas is distributed and the shape, size, and number of the second containers positioned for transport from the second site.
In another preferred embodiment, the gas chamber 30 in the middle of the magnetic holding field is the same chamber used to hyperpolarize the gas. With this embodiment, the preferred method of obtaining the gas would be to hyperpolarize gas on a polarizer in an optical chamber, detach the optical chamber from the polarizer, place the optical polarization chamber in the homogeneous region of the magnetic field 21M, transport and/or store the hyperpolarized gas in the transport unit 10, dispense (and dilute if necessary) the hyperpolarized gas from the chamber 30, and use as desired. It is preferable to use the polarization chamber as a chamber during transport because the process can provide improved hyperpolarized gas yields.
Portable Monitoring (NMR Coil/Polarimetry)
Preferably, the transport unit 10 is operably associated with a polarization monitoring system that is configured to monitor the polarization level of the hyperpolarized gas in the gas chamber 30. Advantageously, such system can be used in transit or at a desired evaluation site. For example, prior to release of the gas from the transport unit 10, the monitoring system can acquire a signal corresponding to the polarization level of the hyperpolarized gas in the transport unit 10 and thus indicate the viability of the gas prior to delivery or at a receiving station at the point of use. This can confirm (reliably "inspect") the product and assure that the product meets purchase specification prior to acceptance at the use site.
The polarization monitoring system can also be used with the transport unit 10 to evaluate magnetic holding field fluctuations during transport. Furthermore, the monitoring system can compensate for sub-optimal polarization measurements obtained due to external or internal conditions. This is very important for permanent magnet configurations, because the magnitude of the response of hyperpolarized gas to an RF pulse is frequency-dependent (i.e. dependent on the frequency of the hyperpolarized gas's response). Furthermore, the frequency of the response of the hyperpolarized gas is field strength-dependent. Since the strength of the magnetic field generated from permanent magnets cannot easily be changed to compensate for changes imposed from external sources, this alternative compensation technique is crucial to obtain accurate polarization measurements of the hyperpolarized gas in the transport unit 10. Additional details of a suitable monitoring system and methods for implementing same are discussed in co-pending and co-assigned U.S. patent application Ser. No. 09/334,341, entitled "Portable Hyperpolarized Gas Monitoring System, Computer Program Products, and Related Methods." The contents of this application are hereby incorporated by reference as if recited in full herein.
As shown in
Alternatively or in addition to the (portable) monitoring system, the transport unit 10 is preferably configured to conveniently dock into a (remote) site calibration station 500, as shown in
As shown, the calibration station 500 preferably includes a set of Helmholtz coils 552 (preferably of about 24 inches in diameter) to provide a low magnetic field and another external NMR surface coil (not shown). The additional NMR surface coil is preferably sized and configured at about 1 inch in diameter and with about 350 turns. The NMR surface coil is configured to be received into a non-metallic platform 170 and is arranged to be substantially flush with the upper surface of the platform to be able to contact a patient delivery vessel 575. Also, the NMR coil is preferably positioned in the center of the Helmholtz coils 552. The term "low field" as used herein includes a magnetic field under about 100 Gauss. Preferably, the calibration station 500 is configured with a field strength of about 5-40 Gauss, and more preferably a field strength of about 20 Gauss. Accordingly, the corresponding 3He signal frequency range is about 16 kHz-128 kHz, with a preferred frequency of about 24 kHz. Similarly, the 129Xe signal frequency range is about 5.9 kHz-47 kHz, with a preferred signal frequency of about 24 kHz.
Preferably, after being released from the chamber 30, the hyperpolarized gas is contained in a patient delivery container 575 which is positioned on the top surface of the surface coil (not shown) and substantially in the center of the Helmholtz coils 552. Generally described, in operation, a selected RF pulse (of predetermined frequency, amplitude, and duration) is transmitted from the NMR device 501 to the surface coil (not shown). Alternatively, the calibration station 500 can be used to transmit the selected RF pulse inside the transport unit 10 via a cable 553. In any event, the RF pulse frequency corresponds to the field strength of the magnetic field and the particular gas, examples of which are noted above. This RF pulse generates an oscillating magnetic field which misaligns a small fraction of the hyperpolarized 3He or 129Xe nuclei from their static magnetic field alignment. The misaligned nuclei start precessing at their associated Larmour frequency (corresponding to pulse frequency). The precessing spins induce a voltage in the surface coil that can be processed to represent a signal 565. The voltage is received back (typically amplified) at the computer and the signal fits an exponentially decaying sinusoid pattern. As shown, the displayed signal 565 is the Fourier transform of the received signal. The initial peak-to-peak voltage of this signal is directly proportional to polarization (using a known calibration constant). The computer 500′ can then calculate the polarization level and generate calculated preferred use dates and times associated with desired polarization levels. As will be recognized by those of skill in the art, other calibration or hyperpolarization level determination methods can also be employed and still be within the product identification and calibration or product-use or expiration determination methods contemplated by the present invention. For example, by detecting the minute magnetic field generated by the polarized 3He spins, one can determine a polarization level associated therewith.
In an alternate embodiment, the transport units 10, 10′ comprise a plurality of gas chambers 30, 30′ (
Central Production Site; Remote Use Site
Use of a remote polarization production site typically requires longer T1's relative to an on-site polarization apparatus to allow adequate shipping and transport times. However, a centrally stationed polarizer can reduce equipment and maintenance costs associated with a plurality of on-site units positioned at each imaging site and the transport units of the instant invention can allow increased transport times with longer T1 times over those conventionally achieved. In a preferred embodiment, a production polarizer unit (not shown) generates the polarized gas at a production site. The gas chamber 30 is in fluid communication with the polarizer unit such that the polarizer unit produces and directs the polarized gas to the gas chamber 30. Preferably, the gas chamber 30 is held in the transport unit housing 60 (
Preconditioning the Container
Preferably, due to susceptibility of the hyperpolarized gas to paramagnetic oxygen as noted above, the gas chamber 30 is preconditioned to remove contaminants. That is, it is processed to reduce or remove the paramagnetic gases such as oxygen from within the chamber and container walls. For containers made with rigid substrates, such as Pyrex™, UHV vacuum pumps can be connected to the container to extract the oxygen. Alternatively, for rigid and/or resilient containers (such as polymer bag containers), a roughing pump can be used which is typically cheaper and easier than the UHV vacuum pump based process. Preferably, for resilient bag containers, the bag is processed with several purge/pump cycles. Preferably this is accomplished by pumping at or below 40 mtorr for one minute, and then directing clean (UHP) buffer gas (such as Grade 5 nitrogen) into the container at a pressure of about one atmosphere or until the bag is substantially inflated. The oxygen partial pressure is then reduced in the container. This can be done with a vacuum but it is preferred that it be done with nitrogen. Once the oxygen realizes the partial pressure imbalance across the container walls, it will outgas to re-establish equilibrium. Typical oxygen solubilities are on the order of 0.01-0.05; thus, 95-99% of the oxygen trapped in the walls will transition to a gas phase. Prior to use, the container is evacuated, thus harmlessly removing the gaseous oxygen. Unlike conventional rigid containers, polymer bag containers can continue to outgas (trapped gases can migrate therein because of pressure differentials between the outer surface and the inner surface) even after the initial purge/pump cycles. Thus, care should be taken to minimize this behavior, especially when the final filling is not temporally performed with the preconditioning of the container. Preferably, a quantity of clean (UHP) filler gas is directed into the bag (to substantially equalize the pressure between the chamber and ambient conditions) and sealed for storage in order to minimize the amount of further outgassing that may occur when the bag is stored and exposed to ambient conditions. This should substantially stabilize or minimize any further outgassing of the polymer or container wall materials. In any event, the filler gas is preferably removed (evacuated) prior to final filling with the hyperpolarized gas. Advantageously, the container of the instant invention can be economically reprocessed (purged, cleaned, etc.) and reused to ship additional quantities of hyperpolarized gases.
It is also preferred that the container or bag be sterilized prior to introducing the hyperpolarized product therein. As used herein, the term "sterilized" includes cleaning containers and contact surfaces such that the container is sufficiently clean to inhibit contamination of the product so that it is suitable for medical and medicinal purposes. In this way, the sterilized container allows for a substantially sterile and non-toxic hyperpolarized product to be delivered for in vivo introduction into the patient. Suitable sterilization and cleaning methods are well known to those of skill in the art.
With the invention described hereinabove, a noble gas can be hyperpolarized at one site in large quantities and distributed to and diluted at remote sites while still preserving clinically useful levels of polarization for the gas at an imaging site. Advantageously, this invention is lightweight, compact, and does not require power or any other outside input, which makes it more suitable for transport and storage. Further advantageously, the transport unit described in this invention does not require disassembly (thereby potentially compromising the homogeneity) of the magnetic field to insert and/or remove a gas chamber to and from the field. This characteristic is advantageous for transporting multiple doses of gas, during which disassembly of the magnetic field to remove a single dose could deleteriously affect the doses remaining in the magnetic field.
The foregoing is illustrative of the present invention and is not to be construed as limiting thereof. Although a few exemplary embodiments of this invention have been described, those skilled in the art will readily appreciate that many modifications are possible to the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of this invention as defined in the claims. In the claims, means-plus-function clauses are intended to cover the structures described herein as performing the recited function and not only structural equivalents but also equivalent structures. Therefore, it is to be understood that the foregoing is illustrative of the present invention and is not to be construed as limited to the specific embodiments disclosed, and that modifications to the disclosed embodiments, as well as other embodiments, are intended to be included within the scope of the appended claims. The invention is defined by the following claims, with equivalents of the claims to be included therein.
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Below is the poem entitled W-My Teacher - the Master of simplification which was written by poet
Mehta. Please feel free to comment on this poem. However, please remember, PoetrySoup is a place of encouragement and growth.
Read Poems by
Dr.Ram Mehta
The result of my last year high school was out
And was sad, dejected as I got the second top
Losing the scholarship for further study scope
As my dad had no means for college no doubt.
As entered my house, saw my teacher with dad
Both of them chatting laughing in a happy mood
The teacher said, "Get prepared for college soon"
You got the scholarship though you second stand.
After my door opener left, dad told me the story
The teacher knew about the top ranker's wish
For not going further for the college education.
As a result, the teacher approached the committee.
Proving the teacher is more important than teach
An enemy of simplism but master of simplification.
* The Italian sonnet with abba, abba, cdecde rhymescheme
Full based on a true event of 1954:
A tribute to my late teacher Shri Damodar Dave of N.D.H.High School, Dwarka,
Gujarat, India.
Reposted on 912-13
First place win
Contest: Your old favourite poem by Judy Connos
Dr. Ram Mehta,
July 13, 2011
First Place win in:
Contest: "The Right Time" sponsored by Michael J. Falotico

subset: commoncrawl


text:
In honor of Professor Charles Moureu, Technical Advisor to the French delegation to the Conference for the Limitation of Armaments of Washington, the Chemical Colloquium will hold a special meeting in Boylston 9 at 4.45 o'clock this afternoon. Professor Mouren is President of the International Union of Pure and Applied Chemistry, a member of the French Institute and of the Academy of Medicine
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Today is officially "Read the Constitution Day" here in Wisconsin, and one group on the UW-Oshkosh campus is working to convince students to do just that.
The UW-Oshkosh Pre-Law Society handed out pocket constitutions, and cupcakes to students.
Group members say they're working to remind students about the basic freedoms people living the U.S. are entitled to.
Copyright 2013 WFRV and WJMN Television Station, Inc.. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.


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Well probably the most eccentric owner in the NBA, Mark Cuban was not so much as the NBA Slam Dunk Contest came early this year in the form of a 112-90 rout of Cuban's Dallas Mavericks.
Once the guys on the Clippers get out in the open floor, WATCH OUT! Probably the last thing Cuban wants to see as his team is going through a rough patch without Dirk and possibly going through their first rebuilding year under Cuban.
Well just look at Cuban's face after watching two consecutive turnovers get turned into fast break alley oops. He looks beyond sick to his stomach.
Andrew Alvez | Elite.
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3 named Duke undergraduate Young Trustee finalists
Three students have been named undergraduate Young Trustee finalists.
Seniors Ashley Alman, Gurdane Bhutani and Chris Brown, named finalists by the Young Trustee Nominating Committee Sunday night, will compete in a Feb. 7 election open to the entire student body.
The process concluded this weekend following interviews with all eight semifinalists. Campaigning starts Thursday.
"We want them to have presence in the Board of Trustees," said junior Dan Pellegrino, chair of the YTNC. "We want someone who's not gonna be intimidated and who'll have their voice heard."
Alman is an undergraduate admissions blogger, a member of the First Year Advisory Council board and vice president of external affairs for Duke University Union.
Bhutani, an A.B. Duke Scholar, is the president of the Council for Collaborative Action. He served as executive vice president for Duke Student Government as a junior.
Brown is a current member of The Chronicle's independent editorial board. He is also an undergraduate representative on the Board's Business and Finance Committee. He was formerly the external chief of staff for DSG.
YTNC is independent from DSG to improve objectivity, Pellegrino noted. But there are five current DSG vice presidents and four senators on the committee, composed of 14 students.


text:
Nikon MH-22 Battery Charger + EN-EL4a Battery + Kit for D300, D300s, D700 D3, D3s & D3x Cameras - 25375-38603-Kit
|The Nikon Dual Quick Charger MH-22 recharges two (2) EN-EL4/EN-EL4a Lithium Ion batteries. The MH-22 is equipped with a battery calibration feature and charge lamp that glows blinks or turns off according to the battery charge state. The approximate charging time for a fully discharged EN-EL4/EN-EL4a is approximately 100 minutes.


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I am more than happy that we are getting your help with this. It is refreshing to find an organisation that responds so quickly and positively.
Andrew Fowler,
BAM Rail
We can produce audio recordings of written materials in a range of foreign languages. These can be used by people with reading difficulties, visual impairment or the elderly. They facilitate access to your resources to groups of people who are not able to read materials, even if translated into their own languages.
To produce an audio recording version of a written document is a four stage process involving:
The adaptation is usually carried out by our project managers and the translation by our translators. The recordings are made by voice over artists who are native speakers of the languages required. We use professional recording equipment with the services of a recording engineer to create each recording.
Recordings can be provided in any or all of these formats:
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If you would like further information about audio recordings or would like to discuss your requirements with us, please contact us.


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Voyager Academy, inaugural coach Patrick Walton, part ways
The only head coach the Voyager Academy basketball program has ever had has been removed from the Vikings' bench despite four successive years of improved win totals since the program began with junior-varsity freshmen in 2010-11.
"I enjoyed my four years there at Voyager Academy. It was a unique experience," Patrick Walton said.
"First of all, Coach Walton was a great person for this program," Voyager athletics director Mike Germino said. "We told him that his contract would not be renewed moving forward after this (past) season."
Germino said personnel rules prevent him from commenting further.
"I decided, with the support of administration, that we had gone as far as we thought that we could go, and we decided that this year was a time that we were just going to go in a different direction," Germino said. "At no point did Coach Walton do anything wrong during his time here."
Walton did a number of things right, including leading the Vikings to their first regular-season title in the 1-A North Central Athletic Conference this season, repeating as NCAC Tournament champion and returning to the state playoffs for the second straight year.
"He's done a lot for the program. Basically, we started from the bottom and basically have worked our way up," Germino said.
Walton said his four seasons with Voyager included a junior-varsity campaign in 2010-11, the year the charter school opened to high school students. That Vikings team had freshmen only and went 2-17, he said.
But those guys moved up to the varsity level and followed with seasons of 8-18, 16-10 and 20-10, losing in the first round of the state playoffs each of the last two years.
Voyager assistant coach Mike Huff is in charge of the team until a new coach is named, Germino said. Huff and assistant coach Melvin Scott, who played at North Carolina, have been overseeing the Vikings' offseason workouts.
Scott and Huff are among 52 applicants to become Voyager's new coach, Germino said. Both teach physical education at the school. Walton did not teach at Voyager.
Voyager has closed the application process for its next basketball coach, Germino said.
"We are looking to take our basketball program to the next step," Germino said, adding that the next coach at Voyager will need to be skilled both in player development and Xs and Os, Germino said.
Huff played professional basketball overseas before becoming coordinator of sports performance at the Michael W. Krzyzewski Human Performance Lab at Duke University.
Scott played pro ball overseas and was on the UNC squad that won the national championship in 2005.
"What Coach Walton did over the last four years was tremendous," Germino said. "We are looking to make a bigger step."
Voyager's next coach will inherit an experienced core that includes Diante Parker, Christopher Sause and Gary Ford Jr. All of them started as juniors at some point this season.
The best player for Voyager next season likely will be 6-8 Jay Huff, a player with length and a knack for stuffing other shooters' shots and sinking his own 3-pointers. He's the son of Mike Huff.
Walton said he still wants to coach, adding that it's too soon to say whether he'll be able to bring himself to sit in the stands and watch Ford bring the ball up the floor and get it to Sause, Huff and Parker.
"Being able to build a program and watch it come from barely winning any games to being a championship-caliber type program, all that was great," Walton said about his time at Voyager. "They wanted to move in a different direction."


text:
SOS of Ohio Spay and Neuter Clinic, also known as Shelter Outreach Services of Ohio, focuses on the low cost spay and neuter of feral and owned cats, dogs and rabbits.
It is our goal to affordably provide these high-quality services to low-income Columbus area residents, nonprofit animal rescue groups and humane societies alike.
To see if you qualify for one of SOS of Ohio's Program, go to our program page or please call the clinic at 614-396-8707.


text:
From CNN's February 25 live coverage of the health care summit:
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In addition to reviewing print and online media, Media Matters monitors at least 150 hours of television and radio each week. This section features highlights (or low-lights) from our monitoring efforts, other noteworthy clips as well as original videos.
Fox News CEO Roger Ailes reportedly told network host Eric Bolling to defend Republican presidential candidate Donald Trump on air. Bolling has repeatedly gone to bat for Trump, praising him as someone who "means business" and defending his controversial remarks.
The New York Times was forced to issue two corrections after relying on Capitol Hill anonymous sourcing for its flawed report on emails from former Secretary of State and Democratic presidential candidate Hillary Clinton. The Clinton debacle is the latest example of why the media should be careful when relying on leaks from partisan congressional sources -- this is far from the first time journalists who did have been burned.
Several Fox News figures are attempting to shift partial blame onto Samuel DuBose for his own death at the hands of a Cincinnati police officer during a traffic stop, arguing DuBose should have cooperated with the officer's instructions if he wanted to avoid "danger."


text:
Ban Joins Morikawa At U.S. Amateur
Cal senior qualifies by sharing individual medalist honors at sectional qualifier.
Incoming Frosh Collin Morikawa Wins Trans-Miss Title
KK Limbhasut Takes Third
2015 Cal Golf Tournament
September 28 - TPC Stonebrae
Shotaro Ban Cal Am Champion
Senior Becomes First Current Cal Player To Win Event
Shotaro Ban Reaches Cal Am Finals
Senior Becomes First Cal Player To Get To Championship Match
Shotaro Ban Advances To Quarterfinals At Cal Am
Ban Knocks Off Fellow Cal Senior Keelan Kilpatrick
Three Cal Golfers Advance To Round Of 16 At Cal Am
Ban, Kilpatrick And Limbhasut Win Wednesday Matches
Four Cal Golfers Advance To Match Play At Cal Am
Limbhasut, Doyle, Kilpatrick And Ban In Round Of 32
U.S. Open Ends For Byeong-Hun An And Brandon Hagy
Both first-time participants fail to make the cut.
Byeong-hun An And Brandon Hagy Make U.S. Open Debuts
An Fires 73, While Hagy Shoots 74
Brandon Hagy Qualifies For First U.S. Open
Hagy Joins Former Cal Teammate Ben An In 2015 Field
Seven Cal Affiliates In U.S. Open Sectional Qualifying Monday
List Includes Cheatham, Hagy, Hahn, Homa, Weaver, Wi And Yoon


text:
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text:
By Douglas J. GillertAmerican Forces Press Service
CAMP H. M. SMITH, Hawaii, April 28, 1997 Adm. Joseph Prueher had just gotten back from a visit to Vietnam, where he accompanied a Joint Task Force Full Accounting team to the 1967 crash site of an American B-52.
"There were about 20 joint task force people and 300 Vietnamese out in the field, digging through the mud for little fragments and putting together the picture," said Prueher (pronounced "Preer"), commander in chief of U.S. Pacific Command. "The commitment our nation has to accounting for all these people is very strong. But the irony is, working with the Vietnamese ends up being a bonding experience. Vietnam is going to be a big and important part of the mosaic out here."
The phenomenal growth of post-World War II Japan has been followed by the burgeoning economies of the Republic of Korea, Hong Kong, Singapore, Thailand and Taiwan, as well as Australia and New Zealand to the south and India to the west. According to the World Bank, the area's rapid growth will continue to effect the global economy and serve as an important source of stability for the rest of the world.
Underwriting the Pacific Rim's prosperity, said America's senior military leader in the region, is security provided by a large U.S. military presence and capability.
"Anyone who looks at the U.S. engagement in the Pacific is intellectually persuaded that it's important for us to be here," Prueher said. "The security brokered by the United States and its allies creates the conditions necessary for prosperity."
A strategy of cooperative engagement governs America's military presence in the Pacific theater. This strategy, Prueher said, has three components: peacetime engagement, or preventive defense; the ability to respond to crises; and the ability to fight and win a major conflict, should one arise.
"There's a circular logic associated with this," Prueher said. "The ability to fight and win a major conflict allows us to operate in the lower spectrum of peacetime engagement.
"Our forward-based forces allow us to interact with other nations and create stability. We have no territorial desires in the area, and I think we're largely seen as an honest broker." America's allies in the region understand U.S. objectives, the admiral said. "Everywhere I go," he said, "the United States is welcomed."
When Prueher arrived at his command last year, one group of people -- Japanese citizens of Okinawa -- weren't so sure they wanted the Americans on their soil. Negative publicity over the rape of an island school girl, and ongoing complaints about the noise American jets created, led the Okinawan governor to call for an end to the American presence there.
Prueher's thrust has been to deal straightforwardly with Okinawans. "We have tried to act as if the Okinawans had a congressman and U.S. mayors that would beat on our door, then behave responsibly toward them and reduce intrusion where we could." For example, the United States agreed to return 20 percent of the land occupied by American bases and halted Marine marches down Okinawan roads. Futenma Marine Corps Air Station will close once a suitable location is found elsewhere. And training flight schedules and routes were altered to reduce noise over schools and neighborhoods.
"Strategically, Japan and we have agreed we need the forces there, agreed on the security arrangements and are trying to work it in the most nonobtrusive way we can," the admiral said.
"Anytime we put our soldiers, sailors, airmen and Marines on another nation's soil, attendant with the responsibility of going there to work for security is the responsibility to be a good neighbor." Awareness and sensitivity training for service members and community relations programs bolstered base-community ties to where now, the admiral said, "our military people are quite welcome there."
Although the United States isn't solely responsible for security in the Pacific region, it doesn't enjoy the same multilateral cooperation present in Europe under NATO. "We don't have anything like NATO out here," Prueher said. "The nations here are largely unwilling to tie themselves security-wise to come to the aid of another nation under any circumstance. Instead, we have a series of bilateral relationships in the Asian Pacific."
Nations in this region willingly train and exercise with DoD forces, the admiral said. Also, Japan outlays more than $5 billion annually to subsidize U.S. bases there, and the Republic of Korea also contributes financially to a U.S. presence in that country.
"With Japan and Korea we have alliances," Prueher said. "We also have training agreements with them, as well as with Australia. We do lower levels of training with other nations -- Thailand, for example. The Thais train us in jungle warfare."
Every nation in the region has some military capability, but none could project military influence on its own, Prueher said. "The nations of the Asian Pacific region largely have emerging economies, which allows them to afford and modernize their militaries, and they're doing that. This modernization, in my view, is not an arms race but [is done] for legitimate protection."
Because of the presence of 37,000 Americans on Korean soil, most Asian-Pacific nations aren't threatened by the tenuous political and economic situation in North Korea, the admiral said. They're more concerned about China.
"China has a burgeoning economy and 1.25 billion people. It's a huge nation [that] is and will be increasingly influential in the region," Prueher said. "As China starts to modernize its military, the Asian-Pacific nations are very concerned, because they'd like to know China's intentions. In our relationship and discussions with China, we encourage them to be more transparent about what they intend to do, what they're doing with their military -- and the importance of mutual confidence among nations."
The Pacific Command's area of operations also extend to central Asia, home of the world's largest democracy, India. "We think India will surpass China in population around the middle of the next century," Prueher said. "They're also becoming a very strong economic power."
Overseeing security for such a broad area requires close teamwork among the command's components, Prueher said. The Army, Navy, Air Force and Marine elements work well together, he added. The admiral hosts frequent component commander conferences where they resolve common problems and challenges, looking beyond sometimes divisive budget concerns to deal with the joint maintenance of operational readiness.
"Our joint efforts are at a level you don't see in other militaries of the world," Prueher said. "I've spent time in Europe, where the armies, navies and air forces work separately. We provide an example on how to work together. We are so far down the joint path, we could not work well independently. Any major chore we take on, we need each other."
Troop quality also sets America apart, the admiral said. "Our enlisted members are as smart as they've ever been. I'm impressed, wherever I go, with our people. What really sets us apart from militaries of other nations are our NCO corps and senior enlisted people who are so responsible and capable. It waters the eyes of our allies, friends and foes to see how capable these young men and women are."
Already having on his team what he considers the best troops in the world, Prueher would like to go shopping for some new equipment.
"We CinCs get accused all the time of caring only about day-to-day readiness and not caring too much about modernization," he said. "I don't think that's a fair rap. Modernization means future readiness. My successor, two or three times removed, is going to need modern equipment, so we need to modernize now."
What's needed in the Pacific? "Theater missile defense -- particularly in Korea but also on ships where we can move it around -- is a key element," the admiral said. "We watch carefully what's going on with the Army at the National Training Center, where they're testing a digitized battlefield and comprehensive information awareness. That's something we would like to eventually have in this theater, because it will make our soldiers much more effective."
Closer to home, the Pacific Fleet is testing a multilayered information web that would link Pacific Command with all of its components and joint task force commanders. Called IT-21 (information technology for the 21st century), the system uses commercial off-the-shelf technology.
"IT-21 can help tie us together and have the effect of a multiplier on our capability to move information and do research," Prueher said. "It could eventually reduce the number of people we need on the staff."
Future equipment needs aside, Prueher said U.S. forces in the Pacific are ready now for any contingency. "Our equipment works well and our young men and women are tremendous.
"We have to look at what's going on in the area -- our area of responsibility is quite big -- and try to make sure we're not mal-positioned should a crisis arise. That's what we do. We're always watching, trying to be in the right place at the right time."


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You want to know what progress looks like in Iraq? It's when the front page of the New York Times features an article not about Iraq's security situation, but about its politics. The focus of the piece, by Alissa J. Rubin, is on fears among Iraqi politicos that Prime Minister Nouri al Maliki may be amassing too much power. That, too, counts as progress.
I vividly recall visiting Iraq in 2007 and early 2008 and hearing from all concerned — Iraqis as well as Americans — how weak and ineffectual Maliki was. Up until mid-2007 the security situation was dire and the prime minister seemed helpless to turn things around. There was widespread talk that the parliament would oust him — something that probably would have happened if only the political parties could have agreed on a consensus candidate to replace him.
The perception of Maliki's weakness changed dramatically in the spring of 2008 when he made the gutsy decision to send the Iraqi security forces to clean out first Basra, then Sadr City. Those were pivotal events that, along with the surge, dealt crippling blows to Moqtada al Sadr's thuggish militia and helped to set off a virtuous spiral of security improvements.
It's pretty clear that stronger central government results in better security. Of course, Iraqi politicos, still understandably traumatized by the Saddam Hussein years, cannot help thinking that their government can become so strong as to repress them. That is a legitimate concern in the future but for now, with 140,000 U.S. troops still in the country, there is a powerful outside guarantee that no faction in Iraqi politics can override the constitution and oppress everyone else. That, by the way, is another argument for keeping a substantial U.S. force presence in the country for years to come. In the meantime, I'd rather have the Iraqi political class fretting that their prime minister is too strong rather than too weak.


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Hey everyone,
I am having troubles moving my PetroWest image that is in the footer over to the right. It will not go any farther than that. Any ideas on what to do?
Here is a link to the site: http://quigleycontracting.squarespace.com/
It's currently being absolutely positioned FROM the right side by 200px. If you change the 200 to 0, it'll go all the way over to the right.
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- 2
- people in the U.S. have this name View Irvin Scherer on Whitepages
Meaning & Origins
Mainly U.S.: variant of Irvine or Irving.
|1,311th in the U.S.
German and Jewish (Ashkenazic): occupational name for a sheepshearer or someone who used scissors to trim the surface of finished cloth and remove excessive nap, from German Scherer, Yiddish sherer, agent derivatives of Middle High German scheren 'to shear'.
|2,531st in the U.S.
Nicknames & variations
Irving, Irvine, Irvina, Irvinia, Irvian, Irvim, Irvinne, Irfan, Irviana, Irvien
Schell, Schenk, Schenck, Scheer, Scheffler, Scheel, Scheller, Scheid, Schermerhorn, Schechter