US20140123681A1 - Method and apparatus to hyperpolarize materials for enhanced mr techniques - Google Patents
Method and apparatus to hyperpolarize materials for enhanced mr techniques Download PDFInfo
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- US20140123681A1 US20140123681A1 US14/103,294 US201314103294A US2014123681A1 US 20140123681 A1 US20140123681 A1 US 20140123681A1 US 201314103294 A US201314103294 A US 201314103294A US 2014123681 A1 US2014123681 A1 US 2014123681A1
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- G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
- G01R33/282—Means specially adapted for hyperpolarisation or for hyperpolarised contrast agents, e.g. for the generation of hyperpolarised gases using optical pumping cells, for storing hyperpolarised contrast agents or for the determination of the polarisation of a hyperpolarised contrast agent
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- G01R33/60—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using electron paramagnetic resonance
Definitions
- the invention relates generally to a method and apparatus for polarizing samples for use in magnetic resonance imaging (MRI).
- MRI magnetic resonance imaging
- the present invention relates to nuclear magnetic resonance (NMR) analysis, particularly to nuclear magnetic resonance imaging (MRI) and analytical high-resolution NMR spectroscopy.
- NMR nuclear magnetic resonance
- MRI nuclear magnetic resonance imaging
- spectroscopy is routinely used in the determination of molecular structure.
- MRI and NMR spectroscopy lack some degree of sensitivity due to the normally very low polarization of the nuclear spins of the contrast agents typically used.
- hyperpolarization techniques a sample of an imaging agent, for example but not limited to 13 C 1 -Pyruvate or another agent, is introduced or injected into the subject being imaged. Hyperpolarization is not limited to 13 C 1 -Pyruvate or any specific compound (metabolically active or not).
- the term “polarize” refers to the alignment of the nuclear spins of an agent for further use in MRI.
- hypopolarized refers to polarized to a level over that found at room temperature and at 1 T, which is further described in U.S. Pat. No. 6,466,814.
- the imaging agent undergoes this hyperpolarization in an apparatus in close proximity to its end use. This is due to the normally short life time (longitudinal relaxation time T 1 ) of the polarization causing the spins to relax back to the thermal equilibrium polarization.
- One such technique to polarize nuclear spins uses Dynamic Nuclear Polarization to polarize the spins in the solid state.
- the apparatus used to produce the hyperpolarized samples is provided with a low temperature space that is in a magnetic field.
- the apparatus is equipped with a flow cryostat that includes a vacuum insulated chamber inserted into the bore of a magnet. The cryostat is cooled by way of a stream of a cold cryogen provided by an external cryogen supply through a transfer line and pumping device, and the flow of cryogen into the flow cryostat cools the bore of the magnet and forms the low temperature space.
- the pumping devices currently used to provide the stream of cold cryogen are open cycle pumping systems that are undesirable for use in a clinical setting for numerous reasons.
- the open cycle pumping systems are large and generate high levels of noise.
- the open cycle pumping systems are expensive and cumbersome to operate because of the large quantity of cryogen that is consumed in the pumping process. That is, in order to provide a stream of cold cryogen to the flow cryostat, a sizable portion of the liquid cryogen is evaporated. In an open cycle pumping system, a large measure of this evaporated cryogen is not reclaimable. Thus, a large amount of cryogen is needed to hyperpolarize a sample, which adds significantly to the cost of operating the system.
- hyperpolarization systems are inefficient and expensive to operate.
- the present invention overcomes the aforementioned drawbacks by providing an apparatus and method for producing hyperpolarized samples for use in magnetic resonance systems.
- a sorption pump is incorporated into the apparatus to create a closed system for hyperpolarizing. Being a closed system, the apparatus and system loses no cryogen to atmosphere such that there is no need to replenish cryogen in the system.
- an apparatus comprises a cooling container containing a cryogenic refrigerant therein, configured to hyperpolarize a plurality of samples therein; a refrigeration system comprising: a refrigerator; and a helium condenser, wherein the helium condenser is separate and positioned exterior to and apart from the cooling container; a sorption pump connected to the cooling container, wherein the sorption pump is separate and spaced apart from the cooling container; a thermal switch configured to connect and disconnect the refrigeration system from the sorption pump; a heater disposed adjoining the sorption pump, configured to heat the sorption pump and promote molecular desorption therein; a single magnetic field producing device in thermal communication with the refrigeration system, wherein the single magnetic field producing device is configured to maintain a selected magnetic field in the apparatus, wherein the single magnet field producing device comprises: a superconducting magnet having a bore therethrough positioned about the cooling container; a magnet vessel to enclose the superconducting magnet, the magnet containing liquid cryogen there
- a polarizing subsystem comprises: a container having a liquid helium bath configured to receive a material to be polarized; a sorption pump to reduce a pressure in the container, thereby to vaporize a portion of the liquid helium bath, the sorption pump comprising: a sorb can configured separate, spaced apart, and exterior to the container; a cooling system comprising: a magnet condenser configured separate, spaced apart, and exterior to the container, configured to recondense liquid helium boiled off therefrom and cool the sorption pump and promote molecular adsorption therein; a thermally conductive link that selectively connects the sorption pump and the cooling system to provide selective cooling to the sorption pump; a heater disposed adjoining the sorption pump, the heater configured to heat the sorption pump and promote molecular desorption therein; a single magnetic field producing device configured to maintain a selected magnetic field for polarizing the material in the apparatus, wherein the single magnetic field producing device is cooled
- a method for producing a hyperpolarized material comprises: placing a material sample in a vessel containing a liquid helium bath; reducing a temperature of the liquid helium bath with a sorption pump and a refrigeration system, wherein the sorption pump comprises: a sorb can configured separate from and exterior to and spaced apart from the vessel, wherein the refrigeration system comprises: a helium condenser configured separate from and exterior to and spaced apart from the vessel; refilling the liquid helium bath by heating the sorption pump with a heater, the heater being disposed adjoining the sorption pump; positioning a single magnetic field producing device adjacent the vessel, wherein the single magnetic field producing device is configured to product a high homogeneity magnetic field and a fringe magnetic field offset from the high homogeneity field; and polarizing the material sample when the liquid helium bath has been sufficiently cooled by the single magnetic field producing device
- a polarizer system comprises: a refrigerator; a magnet condenser; a helium condenser; a thermal bus permanently linking the refrigerator, the magnet condenser, and the helium condenser; a sorption pump selectively linked through a thermal switch to the thermal bus; a heater adjoining the sorption pump; a container containing a cryogenic refrigerant therein, configured to receive a plurality of samples for polarizing therein; a magnetic field producing device in a magnet vessel surrounding the container; wherein the polarizing system is further configured to operate in three separate modes, wherein: a first mode comprises: heating the sorption pump with the heater, thereby releasing helium gas to be cooled and liquefied by the helium condenser, wherein the released helium gas heats the thermal bus, thereby isolating the magnet vessel due to a thermal diode effect at the magnet condenser; a second mode comprises: upon completion of condensation
- FIG. 1 is a block diagram and schematic of an apparatus to hyperpolarize materials according to an embodiment of the current invention.
- FIG. 2 is a cross-sectional view of a sample path and holding container arrangement according to an embodiment of the current invention.
- FIG. 3 is a cross-sectional view of a sample path and holding container arrangement according to another embodiment of the current invention.
- FIG. 4 is a cross-sectional view of a sample path and holding container arrangement according to another embodiment of the current invention.
- FIG. 5 is a cross-sectional view of a sorption pump according to an embodiment of the current invention.
- FIG. 6 is a 24-hour cycle pie-type chart showing the various modes of operation of the system according to an embodiment of the current invention.
- FIG. 7 is a graph comparing temperature of various elements of the system and magnet pressure over time of an embodiment of the current invention.
- the polarizer system 10 is a closed cyclical thermal system configured to hyperpolarize a sample of an imaging agent for use in MRI.
- the sample can be composed of 13 C 1 -Pyruvate or another agent that can be polarized.
- the system 10 is a closed system.
- the term “closed system” as used herein means that the system does not lose cryogen to the atmosphere. As such, there is no requirement or need to replenish the system periodically with additional cryogen.
- Polarizer system 10 is formed in part by a vacuum chamber 12 that surrounds the internal components of the system.
- Polarizer system 10 also includes a thermal shield 16 within the vacuum chamber 12 .
- Thermal shield 16 surrounds the main components of the polarizer system 10 and functions to reduce the radiative heat load to those components.
- the thermal shield 16 is composed of aluminum and is insulated with twenty or more layers of a highly insulative material, such as multilayer insulation (MLI).
- MLI multilayer insulation
- a refrigerator 14 that functions as a cooling system for the polarizer system is also included and can be selected from a number of refrigerators (cold-heads or cryo-coolers) that are known and are commonly used on MRI magnets.
- the refrigerator 14 is positioned, at least in part, externally from vacuum chamber 12 . Such a configuration allows any heat generated by the refrigerator 14 to be exhausted in the ambient environment rather than into the interior of vacuum chamber 12 .
- refrigerator 14 is a closed cycle refrigerator capable of providing low temperature environments below 10 K.
- a separate vacuum enclosure 18 is provided for the refrigerator 14 .
- the refrigerator itself is mounted in a vertical orientation within a mobile sleeve 20 to allow for vertical movement of the refrigerator 14 therein.
- the refrigerator 14 is further characterized in being field serviceable. That is, the cryostat design is such that the refrigerator 14 can be switched off and removed for a time that will allow a service engineer to replace or service the refrigerator.
- the polarizer system 10 is immune to such a procedure and is configured to continue operation for a period of time while refrigerator is shut off.
- the substance or material to be polarized (e.g., 13 C 1 -pyruvate), hereafter referred to as sample 22 ) is positioned within vacuum chamber 12 for hyperpolarization.
- the sample is placed in container 24 having a cryogenic refrigerant 26 therein.
- the sample(s) 22 are placed in a holding container 44 that is, in turn, at least partially immersed in the liquid helium bath 26 of the container 24 .
- the cryogenic refrigerant is in the form of a liquid helium bath 26 into which the sample 22 is at least partially immersed.
- Container 24 is sealable and can be evacuated to low pressures (e.g.
- the temperature of liquid helium bath 26 is lowered to a suitable temperature, e.g. temperatures below 4.2 K and preferably below 1.5 K.
- the sample 22 is then placed in a suitable magnetic field by magnetic field producing device 28 positioned about container 24 to achieve hyperpolarization.
- the samples 22 are introduced into the polarizer system 10 by way of a sample path 30 that passes through an ante chamber 32 (i.e., air lock).
- the purpose of the ante chamber 32 is to prevent contamination of the sample path 30 during introduction of the samples 22 and also to eliminate the need of breaking the vacuum on the sample path 30 .
- the sample path is pressurized to atmospheric pressure with helium gas; however, this is a major limitation of existing polarizers since bringing the sample path pressure to atmospheric pressure constitutes a significant heat load to the liquid helium bath and also transiently raises the temperature of the bath, i.e. reduces the throughput.
- the ante chamber 32 is isolated from vacuum chamber 12 by a gate valve 34 and from the atmosphere by a sealing cap 36 .
- the ante chamber 32 can then, once the sample 22 has been introduced, be evacuated and flushed with helium gas in several cycles to eliminate and evacuate any air (and moisture).
- ante chamber 32 reduces the heat load to the liquid helium bath 26 .
- the specific design of the ante chamber 32 will vary based on the geometry of the sample 22 and can be designed accordingly in a way known to one skilled in the art.
- the sample path 30 and the internal surfaces thereof exposed to the sample 22 , are made from materials that are routinely used for pharmaceutical equipment and should follow such industry standards.
- a portion of the sample path 30 can be filled with liquid helium dispensed through a sterile filter to further minimize the bio-burden in this area.
- the sample path 30 is further characterized in having an equilibrator 38 that serves the purpose of leading the heat of the samples 22 to the refrigerator 14 before the sample 22 is introduced into the helium bath 26 .
- the latent heat of the sample 22 would constitute a very large heat load to the helium bath 26 significantly reducing the hold time of the system.
- the time required to sit in the equilibrator 38 will depend on the rate of heat conduction in the sample 22 , from the sample to the equilibrator 38 , and on the rate of heat conduction away from the equilibrator 38 .
- An optimized design can be made based on the above parameters and the temperature at which the sample 22 is allowed to enter the bath 26 .
- the equilibrator 38 can be designed in several ways by a person skilled in the art. The main characteristics are low conductivity to the bath 26 and good conductivity from the sample 22 to the refrigerator 14 .
- the good conductivity from the sample 22 can be obtained by good physical contact between the sample 22 and a high conductivity material, but in many cases the helium gas present in the sample path 30 will act as a sufficient exchange gas and efficiently conduct the heat from the sample 22 to the walls of the equilibrator 38 .
- the sample path 30 can also be equipped with a means of providing heat to the sample during a dissolution process or a means to mechanically agitate the sample during the dissolution.
- a means of providing heat to the sample during a dissolution process or a means to mechanically agitate the sample during the dissolution.
- the sample is dissolved by way of a heated solvent flowing thru sample 22 and is removed from the polarizer system 10 via the sample path 30 to a desired location/user.
- the means for mechanically agitating the sample 22 is an ultrasound transmitter 40 that vigorously agitates the solvent and facilitates the dissolution.
- An ultrasonic burst is carried down the sample path 30 and into the sample by way of a sonicator probe 42 to break the solid sample and pressurize the surrounding environment to force the dissolved sample and solvent back up the sample path 30 .
- the ultrasound would at the same time dissipate heat in the solution. While a heated solvent and ultrasound have been described as a means of providing energy to the sample, it is also envisioned that other methods/mechanisms for providing energy could also be implemented, such as infrared radiation or microwave energy.
- the sample 22 is ultimately positioned in a holding container 44 that is in thermal contact with liquid helium bath 26 of container 24 .
- the sample 22 is separated from liquid helium bath 26 by placing it inside the holding container 44 .
- This placement of sample 22 into holding container 44 increases the longevity of the polarizer system 10 and improves system efficiency, as the sample loading inevitably introduces contamination into the polarizer system 10 , which would in turn effect operation of a sorption pump 46 in the polarizer system.
- the sorption pump 46 is sensitive to contamination and cannot easily be restored, and thus, placement of sample 22 in the holding container 44 helps to prevent these contaminants from entering into liquid helium bath 26 .
- the holding container 44 is in thermal contact with liquid helium bath 26 by a common wall 47 with high thermal conductivity that minimizes the thermal gradient. If holding container 44 is not immersed in liquid helium bath 26 , it also can be placed in thermal contact therewith by way of copper tails or fins 49 that extend down from the holding container 44 into the bath 26 .
- the holding container 44 can also be filled in part with liquid helium. In such a configuration, the liquid helium acts as a good heat conductor from sample 22 to the walls of the holding container 44 and finally into the helium bath 26 of container 24 .
- the superfluid helium which has very high heat conductivity, also serves to conduct dissipated microwave energy away from sample 22 that is directed thereto by a microwave irradiation system (not shown).
- liquid helium within holding container 44 is optional and will depend on the design of the microwave irradiation system, the sample properties, and the thermal contact to the sample 22 . Rather that being filled with liquid helium, it is also envisioned that holding container 44 be filled with helium gas.
- the use of helium gas within holding container 44 for cooling sample 22 is desirable since this volume of helium may occasionally be evaporated and recondensed from, for example, a helium gas cylinder. Additionally, the helium gas can lead to improvement in the cryogenic performance of the polarizer system 10 by reducing the film flow from the helium bath if operated above the lambda point of helium.
- the holding container 44 contains a microwave confining arrangement that includes a waveguide 48 and optionally a sample cup 50 .
- waveguide 48 shown in FIG. 1 microwaves are transmitted into the sample by waveguide 48 , which extends down around sample path 30 and joins with holding container 44 to irradiate the sample 22 . As shown in FIG.
- waveguide 48 and conical horn 52 form with sample cup 50 to irradiate sample 22 .
- the waveguide 48 contains a vacuum-tight seal 54 therein, which can be constructed of a polymer, quartz, or sapphire window, and also contains baffles 56 at appropriate positions within the sample path 30 to reduce heat transfer down the sample path and into the holding container 44 .
- the waveguide 48 is removable from the sample path 30 after hyperpolarization of the sample 22 has been achieved and before a desired dissolution of the sample is carried out.
- the waveguide 48 joins with sample cup 50 at the lower end thereof to guide microwaves into the sample 22 .
- the sample cup 50 has a thin layer metal wall 57 and bottom surface that confines these microwaves to the sample.
- the sample cup is comprised of a titanium or gold, or another metallic material that will not react with the pyruvic acid of the sample or with the solvent used to dissolve the sample during dissolution. It is also envisioned that a plastic inner shell 58 could be included inside the metallic sample cup 57 to prevent contact between the sample and metal.
- the plastic inner shell 58 would also dictate heat conductivity of the sample cup 50 , and thus inclusion of the inner plastic shell 58 may also depend on the selection of liquid or gaseous helium within holding container 44 and the desired amount of heat transfer between the sample cup and the helium.
- the waveguide 48 and sample cup 50 arrangement is designed to minimize losses and deliver a maximum of the microwave energy to the sample, as a higher loss in the microwave delivery system would require a more powerful microwave source. It is also envisioned that the microwave delivery system is part of the sample 22 to confine the microwave entirely to the sample 22 .
- a NMR coil 60 is also included in the overall structure of the holding container 44 .
- the NMR coil 60 is optional, but provides a means of measuring the nuclear polarization during and after the DNP polarization process by producing RF pulses that measure the polarization level of the sample 22 .
- a number of arrangements for an NMR coil 60 are known in the art, and in a preferred embodiment, the NMR coil 60 is positioned outside the microwave confining arrangement.
- the NMR coil 60 can be a saddle coil, Helmholz coil, birdcage coil, or any other known design.
- the NMR coil 60 is connected to the outside of vacuum chamber 12 by, for example, a coaxial cable 62 or other suitable radio frequency cabling.
- the NMR coil 60 is positioned inside of the holding container 44 , although it is envisioned that NMR coil 60 could also be positioned outside of the holding container 44 .
- the walls of the holding container 44 can be slit in such a way as to minimize losses and ensure radio frequency penetration. That is, the holding container 44 could, in part, be formed of copper and slit as desired to allow RF signals to penetrate therethrough and include a plastic inner shell 64 to provide a sealed holding container 44 . To also allow the RF signals to penetrate into the sample 22 , the thickness of the sample cup 50 walls is kept within a desired range such that the RF waves are not severely attenuated by the metallic sample cup.
- sample path 30 is configured to be removable in the field without de-energizing the magnet and breaking the cryostat vacuum. This allows for regular field service of the polarizer system 10 while causing minimal disruption to the operation thereof.
- the sample path 30 can require field service for a number of reasons, such as failure of the NMR coil 60 or waveguide 48 transmission systems (shown in FIG. 1 ) for electrical or mechanical reasons, contamination of the sample path 30 by ingression of air that cannot be removed by a standard operation procedure, or failure of the sample 22 at any stage of the process.
- Detachable sample path 30 is mounted in a stainless steel sleeve 66 that isolates the sample path vacuum from the remaining cryostat vacuum 12 and is sealed to holding container 44 via an indium gasket 68 to allow for evacuation of the sleeve 66 . This would allow the sample path vacuum to be broken without disrupting operation of the rest of the polarizer system 10 and for removal of the sample path 30 .
- the sample path 30 also includes a bolted room temperature flange (not shown) sealed by standard vacuum techniques. It is also envisioned that other configurations could be implemented for the detachable sample path 30 .
- Magnetic field producing device 28 is shown positioned about container 24 and the liquid helium bath 26 .
- Magnetic field producing device 28 is a superconducting magnet having a bore therethrough in which container 24 is placed.
- Superconducting magnet 28 is capable of creating a magnetic field strength that is sufficiently high, e.g. between 1-25 T or more, for example 5.0 T, for hyperpolarization of the sample 22 to take place.
- the magnet is enclosed in a vessel 70 containing liquid helium to provide cooling.
- the liquid helium is in turn cooled by refrigerator 14 that is connected to magnet 28 by way of thermal bus 72 , 90 .
- the magnet 28 is connected to the thermal bus 72 , 90 through a condenser 74 , which is a standard configuration for superconducting magnets cooled by a refrigerator.
- the condenser 74 e.g., also referred to as magnet condenser, recondenser, and/or first condenser herein
- the condenser 74 re-condenses into the magnet vessel 70 any helium gas that evaporates due to the heat load to the magnet 28 .
- the thermal bus 72 , 90 will warm up.
- the condenser 74 is isolated from the magnet 28 thereby maximizing the time that the magnet 28 will survive not being cooled by the refrigerator 14 and preventing quench or loss of cryogen.
- magnet 28 could be dry (i.e., no liquid helium), but the magnet would then only maintain its superconducting properties for a short time (i.e., until the magnet warms above its superconducting temperature) in case of the refrigerator 14 being turned off.
- the magnet 28 can favorably be operated sub-atmospheric to minimize the heat load to the refrigerator 14 from the magnet. If the magnet 28 is operated sub-atmospheric, a protective buffer helium volume can be added to any safety exhaust ports on the polarizer system 10 to prevent ingression of air and contamination of the magnet or sorption pump.
- the magnet 28 is designed such as to provide a high magnetic fringe field region away from the very low temperature container 24 .
- This high field region e.g. 1-25 T or more, for example 5 T, is required in many instances during the dissolution of the sample 22 . That is, as the dissolved sample is transferred out from container 24 via the sample path 30 and outside the volume of the vacuum chamber 12 , a fringe magnetic field is desirable to maintain the hyperpolarized state of the sample 22 .
- the magnet 28 can be designed in way that the fringe field is axially contained via active or passive shielding.
- the magnetic field is preferably high, at least to an extent that the relaxation of the sample polarization is minimized at all steps of the dissolution process. Depending on the properties of the sample 22 , this fringe magnetic field can be adjusted in intensity and coverage area as needed.
- the magnet 28 and cryostat are also designed in such a way as to minimize or tolerate the interaction with an imaging magnet (not shown).
- an imaging magnet not shown
- MR magnetic resonance
- magnetic field homogeneity and magnetic forces need to be carefully controlled on both magnets in order to minimize interference of the two magnetic fields and maintain homogeneity of the MR imaging field.
- container 24 is sealable and can be evacuated to low pressures. Evacuation of container 24 to a low pressure in turn reduces the temperature of liquid helium bath 26 by vaporizing a portion of liquid helium and moving the state point down the helium saturation curve. That is, the boiling temperature of liquid helium (4.2 K) is a function of its vapor pressure. By reducing the pressure on the liquid helium bath 26 , it is possible to cool it, and the sample 22 therein, to about 1 K without any further complications. This low temperature then allows for transformation of the sample 22 to a high fractional polarization state that is desired.
- sorption pump 46 is fluidly connected to container 24 by way of a pumping line 76 .
- Sorption pump 46 is configured to lower pressure in container 24 by adsorbing the gas that evaporates from liquid helium bath 26 .
- Sorption pump 46 operates in this sorption mode (i.e., polarization/pumping phase) when the pump is lowered to a cryogenic temperature. That is, when sorption pump 46 is cooled to a temperature of ⁇ 10 K or below, helium gas will evaporate from liquid helium bath 26 and be adsorbed by sorption pump 46 forming a monolayer or two on a sorbent material therein.
- sorption pump 46 includes a pump enclosure 78 containing a sorbent material 80 therein.
- Pump enclosure 78 is preferably in the form of a cylinder, although other suitable constructions may also be implemented.
- Sorbent material 80 is formed of a material having a high rate of adsorption at low temperatures.
- sorbent material 80 is composed of activated charcoal, which has a high rate of adsorption due to its large total surface area, which is in the range of tens of square meters per gram (e.g., >1000 m 2 /g).
- Dispersed within sorbent material 80 are cooling fins 82 that cool the material.
- Cooling fins 82 promote uniform cooling of sorbent material 80 to improve the adsorption efficiency during a pumping or sorption cycle/phase.
- cooling fins 82 are comprised of copper tubing so as to provide a medium having good thermal conductivity for quick cooling of the sorbent material 80 .
- the cooling structure 82 can be arranged in many ways depending on the geometry of the enclosure 78 to provide quick cooling of the sorbent material 80 .
- aspects of the present invention offer advantages over previous polarizing art includes the practical usage of this system in a clinical environment, and not merely in a limited research environment.
- Prior attempts with polarizing suffer in that temperature constraints of the systems limit the rate heat can be extracted from the sorption pump, which ultimately impacts the practical usage of these earlier polarizing systems. For example, in these systems when the sorb can is heated to release adsorbed helium, the magnet will not quench and the helium in the helium can is recondensed despite the excess heat load on the thermal bus during this time.
- various elements in the system 10 are separate positioned exterior to and/or apart from other elements of the system 10 . These elements include, but are not limited to, the condensers 74 , 88 , cooling container 24 , and sorption pump 46 . Note too that the system 10 only requires a single magnetic field producing device 28 .
- Advantages of the system and apparatus, depicted in FIG. 1 include directing heat to the shared refrigerator 14 that is permanently linked to the two independent condensers 74 , 88 , and temporarily, or selectively, linked to the sorption pump 46 through the thermal switch 84 .
- the novel structure of the system 10 enables for the operation of three distinct modes, or phases, of operation.
- a first mode can be termed a condensing, or desorption, mode
- a second mode can be termed a cooling mode
- the third mode can be termed a polarizing, or sorption pumping, mode.
- the components of the polarizer 10 are optimized and matched to work as a cryogenically closed system (i.e., without release of helium to the environment) with specific operating modes and optimized thermal budget that other systems do not follow (See e.g., FIG. 7 ).
- sorption pump 46 can be switched to condensing mode (i.e., reheating/desorption phase) to allow for the helium molecules adsorbed in sorbent material 80 to recondense and transfer back to container 24 to refill the liquid helium bath 26 .
- condensing mode the temperature of sorption pump 46 is raised to a temperature such that helium molecules are desorbed from the sorbent material 80 and released therefrom.
- thermal switch 84 is positioned to disconnect the refrigerator 14 and thermal bus 72 , 90 from sorption pump 46 .
- the temperature of sorption pump 46 When disconnected from refrigerator 14 , the temperature of sorption pump 46 is elevated by turning on heater 86 , and enters desorption phase upon reaching a temperature of, for example, 30-40 K, wherein helium molecules escape from the sorbent material 80 and exit the sorption pump 46 via the pumping line 76 .
- sorption pump 46 is also allowed to enter a regeneration phase where the sorbent material 80 can be heated by heater 86 to a higher temperature to drive off water vapor collected therein that does not desorb at room temperature.
- This regeneration (or fourth) phase can take up to two hours, and as such, would be performed during periods when use of the polarizer system 10 is not required.
- the heating profile and desorption/regeneration temperatures are chosen to give the most optimal cryogenic performance.
- helium gas molecules that had previously been vaporized are allowed to recondense in the condensing/desorption phase.
- This recondensing is achieved by way of a condenser 88 (e.g., also referred to as helium condenser, container condenser, and/or second condenser herein) that is connected to sorption pump by way of pumping line 76 .
- Helium gas released from sorbent material 80 during the desorption phase exits sorption pump 46 by way of the pumping line 76 and is carried to helium condenser 88 .
- Helium condenser 88 functions to cool the helium gas to a temperature necessary to place the helium in a liquid state.
- Helium condenser 88 is cooled by refrigerator 14 through connection thereto formed by common thermal bus 90 .
- a thermal bus 90 is connected to refrigerator 14 by way of another thermal bus 72 .
- Thermal bus 90 then is connected to helium condenser 88 to allow for recondensing of the helium gas that enters into the condenser 88 .
- FIG. 1 shows two connected thermal buses 72 , 90 , it is also envisioned that thermal bus 90 and thermal bus 72 can be formed as a single thermal bus or as a plurality of buses.
- the sorption pump 46 In the first mode (i.e., condensing/desorption) of operation, the sorption pump 46 is directly and aggressively heated with the heater 86 adjoined thereto. This heating enables a rapid temperature rise in the large sorbent mass (e.g., >5 kg) in the sorption pump 46 and a release of large quantities of helium gas. The released helium gas is cooled and liquefied at condenser 88 . The warm gas from the sorption pump 46 heats the thermal bus 72 , 90 and effectively isolates the magnet vessel 70 due to a thermal diode “effect” experience at the magnet condenser 74 . Thus, the heat related to the condensation of helium gas from the sorption pump 46 can be wholly and efficiently directed to the refrigerator 14 without negatively impacting the magnet 28 .
- the large sorbent mass e.g., >5 kg
- FIG. 6 demonstrates an example of the temporal cycle of an apparatus 10 enabled by the cryogenic system disclosed in this document.
- FIG. 7 shows representative temperature and pressure profile for specific components of the apparatus 10 during this cycle.
- the apparatus 10 is capable of progressing through three modes during a 24 hour period.
- the thermal switch 84 is opened to enable the sorption pump 46 to be heated while minimizing the impact on the remaining components of the apparatus 10 .
- the thermal switch 84 effectively isolating the sorption pump 46 from the remainder of the system 10 , the cooling power of the refrigerator 14 shared on the thermal bus 72 , 90 by the magnet condenser 74 and helium condenser 88 .
- Helium gas adsorbed in the sorption pump 46 is liberated and transported through the pumping line 76 to the condenser 88 , resulting in the temperature of the thermal bus 72 , 90 to rise.
- the rise in temperature at the thermal bus 72 , 90 causes helium gas in the magnet vessel 70 and condenser 74 to stratify and effectively isolate the magnets vessel 70 from the remainder of the apparatus 10 .
- the majority of the cooling power of the refrigerator 14 is directed to the helium condenser 88 enabling the rapid and efficient condensation of helium gas to liquid, which is collected in the container 24 .
- greater than 3 L of liquid helium can be collected in the container 24 during a 10 hour condensation period.
- FIG. 7 shows that during this first mode of operation the sorption pump temperature is rapidly elevated resulting in a corresponding increase in the helium gas pressure in the sorption pump 46 .
- the rate of heating is decreased to maintain a constant pressure while helium is expelled from the sorption pump 46 and condensed into the helium container.
- the thermal bus 72 , 90 and holding container 44 reflect the increased temperature associated with the elevated pressure of the helium being condensed.
- the magnet vessel 70 pressure slowly increases as the magnet 28 is isolated from the refrigerator 14 . Due to the large thermal mass of the liquid helium contained in the magnet vessel 70 , this pressure and corresponding temperature increase is relatively minor, on the order of 2-4 pounds per square inch.
- the sorption pump heater 86 is turned off and the system 10 is allowed to equilibrate. Once the thermal bus temperature is sufficiently low the magnet condenser 74 will again receive cooling power from the thermal bus 72 , 90 and the magnet vessel pressure and temperature will be reduced.
- cooling fins 82 are attached to a thermal switch 84 that connects and disconnects sorption pump 46 from refrigerator 14 according to operator commands.
- refrigerator 14 is connected to sorption pump 46 by way of thermal bus 72 , 90 (i.e., thermally conductive link) and thermal switch 84 .
- Thermal bus 72 , 90 provides a link for refrigerator 14 to cool sorption pump 46 and the sorbent material 80 therein to a cryogenic temperature to allow the pump 46 to operate in sorption mode.
- the conductive link provided by thermal bus 72 , 90 is selectively connected and disconnected from sorption pump 46 by way of thermal switch 84 , thus allowing for the pump 46 to also exit sorption mode when desired.
- both condensers 74 , 88 experience the thermal diode “effect” and isolate the magnet 28 and helium vessel 24 from the thermal bus 72 , 90 .
- This isolation of the magnet 28 allows the thermal bus 72 , 90 to thereby achieve temperature greater than about 20K without impacting or affecting the magnet 28 and its temperature. In this manner, the higher temperatures achieved by the thermal bus 72 , 90 allows the refrigerator 14 to achieve greater efficiency (e.g., 10 ⁇ ), thereby accelerating the rate of heat extraction from the heat pump 46 .
- FIG. 6 shows the second mode of operation, cooling, commencing at 5:00AM.
- the thermal switch 84 is closed connecting the hot sorption pump 46 to the thermal bus 72 , 90 .
- This connection results in a rapid rise in the thermal bus 72 , 90 temperature, effectively turning off the magnet condenser 74 and the helium condenser 88 .
- Removal of liquid helium thermal masses in the magnet vessel 70 and helium container enables the thermal bus temperature to achieve values in excess of 15 K, where the refrigerator's cooling power is greatly increased. This increased cooling power rapidly cools the sorption pump 46 reducing the pressure within the sorption pump 46 .
- FIG. 7 shows that during this second mode of operation the thermal bus temperature rapidly rises and then falls as the heat is extracted by the refrigerator 14 .
- the sorption pump 46 and helium container temperature show a corresponding rapid decrease in temperature.
- the magnet 28 experiences an increase in pressure during this mode of operation. Again, due to the high thermal mass of the liquid helium in the magnet vessel 70 , this increase in pressure is relatively minor.
- the sorption pump 46 and connected pumping line 76 are designed to create a high pumping capacity. This high pumping capacity is needed to obtain a low base temperature in the liquid helium bath 26 in a reasonable time. Upon adsorption of a sufficient number of molecules to reduce the temperature of liquid helium bath 26 to a desired temperature for hyperpolarization of the sample 22 , the sorption pump 46 is configured to maintain the low temperature of the liquid helium bath 26 for an extended time during which hyperpolarization can occur. The exact capacity of the sorption pump 46 to absorb helium and the volume of liquid helium in bath 26 can be designed and optimized to give the desired hold time of the low temperature for hyperpolarization.
- the helium container or vessel 24 and sorption pump 46 are cold relative to the magnet 28 , thereby eliminating any thermal diode “effect” from the condenser 74 . This allows for the effective cooling of the magnet 28 .
- FIG. 6 shows the third mode of operation, polarize, commencing at 8:00 AM. At this point the sorption pump 46 and helium container 24 temperatures have achieved stabile and minimum temperatures. The reduced thermal bus temperature once again enables the magnet condenser 74 to cool the magnet 28 and reduce the pressure in the magnet vessel 70 .
- FIG. 7 shows this cooling of the magnet pressure continues throughout the remainder of the cryogenic cycle, preparing the magnet 28 for the next period of loss of cooling.
- the functioning of the polarizer system 10 as a closed system operating in a cyclical thermal cycle provides for an efficient system for hyperpolarizing the sample 22 . Additionally, the amount of liquid helium consumed during hyperpolarization is reduced essentially to zero because of the sorption pump 46 and condenser 88 arrangement, thus reducing maintenance on the polarizer system 10 as no liquid cryogens need to be filled and no mechanical pumps need to be serviced.
- the polarizer system 10 heretofore described includes an adsorption pump 46 (i.e., sorption pump). While adsorption pumps have been used in a number of cryogenic applications, sorption pump 46 provides the unique benefits of having a very high adsorption capacity that translates into a high pumping capacity and long hold time.
- the polarizer system 10 also provides a single common refrigerator 14 that is configured to cool both the superconducting magnet 28 and the sorption pump 46 .
- the superconducting magnet cryogenic system i.e., refrigerator 14 and liquid helium contained in magnet vessel 70 ) is designed in such a way to be insensitive to the thermal cycle of sorption pump 46 .
- the sorption pump 46 is capable of reaching temperatures well below any currently available refrigerator.
- polarizer system 10 implements sorption pump 46
- a refrigerator with sufficient capacity and base temperature can provide an environment having cryogenic temperatures in the range of 1.5 K that are suitable for hyperpolarization, such as an Adiabatic Demagnetization Refrigerator (ADR), which has also been successfully operated in low temperature physics applications.
- ADR Adiabatic Demagnetization Refrigerator
- the system 10 intentionally isolates the magnet vessel 70 (and magnet 28 ) during cooling of the sorption pump 46 or its emitted gas.
- the system 10 exploits the large thermal mass of the magnet 28 so as to enable the magnet 28 to “ride” through a period when the magnet 28 is not receiving any supplemental cooling from the refrigerator 14 .
- This intentional isolation allows the refrigerator 14 and its limited cooling power to be more efficiently utilized.
- the magnet 28 is thereby “insensitive” to the thermal cycle of the sorption pump 46 , which ultimately enables the system 10 to operate more optimally in practical uses, including clinical applications.
- FIGS. 6 and 7 demonstrate how the novel combination of multiple condensers and a thermal switch on a shared thermal bus enables specific components of the apparatus to be isolated during certain modes of operation and therefore increasing the efficiency of the entire system.
- the ability to isolate the magnet and sorption pump from the thermal bus during the condensation mode enables rapid and efficient condensation of practical and useful volumes of liquid helium during a minimized period.
- the ability to isolation the magnet and helium container from the thermal bus during cooling enables the thermal bus temperature to rapidly elevate to levels where the refrigerators cooling power is enhanced, accelerating the cooling process.
- the ability to reconnect the magnet to the refrigerator during the low thermal load polarization mode enables the magnet to recover and reset the system's thermal balance for the next cycle.
- polarizer system 10 has been described above as a self-contained system, it is also envisioned that the system be integrated with a MR imaging system.
- an MR magnet functions to create the fringe magnetic field. With some local optimization of the strength and homogeneity of this fringe field, a sufficient DNP polarizing field needed for hyperpolarization of the 13 C 1 -pyruvate sample can be created.
- a helium reservoir of the MR imaging system used to cool the imaging magnet could also be used to provide liquid helium to the container surrounding the sample to be polarized.
- One implementation would be to connect the main helium reservoir to the container/sample space of the polarizer system via a capillary with a needle valve and controlling inflow of liquid helium to the container by way of the valve.
- the integration of the polarizer system with a MR imaging system would lead to a more compact and cheaper overall design.
- the sample space (containing a bath of liquid helium) may be pumped on constantly by a sorption pump, which will result in a reduction of the helium's vapour pressure and consequently in a lower operating temperature.
- the use of the MR imaging magnet for hyperpolarization would facilitate maintenance, as liquid helium re-filling would be performed on only the one integrated system rather than at different times for the two separate magnets.
- the integrated system would also take advantage of the existing cryogenic safety features of the MR scanner and make use of MR scanner electronics to monitor the increasing NMR signal from the sample while the polarization process is on-going.
- an apparatus comprises a cooling container containing a cryogenic refrigerant therein, configured to hyperpolarize a plurality of samples therein; a refrigeration system comprising: a refrigerator; and a helium condenser, wherein the helium condenser is separate and positioned exterior to and apart from the cooling container; a sorption pump connected to the cooling container, wherein the sorption pump is separate and spaced apart from the cooling container; a thermal switch configured to connect and disconnect the refrigeration system from the sorption pump; a heater disposed adjoining the sorption pump, configured to heat the sorption pump and promote molecular desorption therein; a single magnetic field producing device in thermal communication with the refrigeration system, wherein the single magnetic field producing device is configured to maintain a selected magnetic field in the apparatus, wherein the single magnet field producing device comprises: a superconducting magnet having a bore therethrough positioned about the cooling container; a magnet vessel to enclose the superconducting magnet, the magnet containing liquid cryogen there
- a polarizing subsystem comprises: a container having a liquid helium bath configured to receive a material to be polarized; a sorption pump to reduce a pressure in the container, thereby to vaporize a portion of the liquid helium bath, the sorption pump comprising: a sorb can configured separate, spaced apart, and exterior to the container; a cooling system comprising: a magnet condenser configured separate, spaced apart, and exterior to the container, configured to recondense liquid helium boiled off therefrom and cool the sorption pump and promote molecular adsorption therein; a thermally conductive link that selectively connects the sorption pump and the cooling system to provide selective cooling to the sorption pump; a heater disposed adjoining the sorption pump, the heater configured to heat the sorption pump and promote molecular desorption therein; a single magnetic field producing device configured to maintain a selected magnetic field for polarizing the material in the apparatus, wherein the single magnetic field producing device is cooled
- a method for producing a hyperpolarized material comprises: placing a material sample in a vessel containing a liquid helium bath; reducing a temperature of the liquid helium bath with a sorption pump and a refrigeration system, wherein the sorption pump comprises: a sorb can configured separate from and exterior to and spaced apart from the vessel, wherein the refrigeration system comprises: a helium condenser configured separate from and exterior to and spaced apart from the vessel; refilling the liquid helium bath by heating the sorption pump with a heater, the heater being disposed adjoining the sorption pump; positioning a single magnetic field producing device adjacent the vessel, wherein the single magnetic field producing device is configured to product a high homogeneity magnetic field and a fringe magnetic field offset from the high homogeneity field; and polarizing the material sample when the liquid helium bath has been sufficiently cooled by the single magnetic field producing device.
- a polarizer system comprises: a refrigerator; a magnet condenser; a helium condenser; a thermal bus permanently linking the refrigerator, the magnet condenser, and the helium condenser; a sorption pump selectively linked through a thermal switch to the thermal bus; a heater adjoining the sorption pump; a container containing a cryogenic refrigerant therein, configured to receive a plurality of samples for polarizing therein; a magnetic field producing device in a magnet vessel surrounding the container; wherein the polarizing system is further configured to operate in three separate modes, wherein: a first mode comprises: heating the sorption pump with the heater, thereby releasing helium gas to be cooled and liquefied by the helium condenser, wherein the released helium gas heats the thermal bus, thereby isolating the magnet vessel due to a thermal diode effect at the magnet condenser; a second mode comprises: upon completion of condensation
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Abstract
An apparatus, system, and method for producing hyperpolarized samples for use in magnetic resonance systems. A sorption pump is incorporated into the apparatus to create a closed system for hyperpolarizing. Being a closed system, the apparatus and system loses no cryogen to atmosphere such that there is no need to replenish cryogen in the system. Under the method, the apparatus is able to operate in three distinct modes.
Description
- This Continuation-In-Part (C.I.P.) application claims the benefit of the Apr. 2, 2007 filing date of U.S. application Ser. No. 11/695,411 (Entitled: METHOD AND APPARATUS TO HYPERPOLARIZE MATERIALS FOR ENHANCED MR TECHNIQUES, attorney docket no. 205265-1). The aforementioned application is incorporated herein by reference in its entirety.
- The invention relates generally to a method and apparatus for polarizing samples for use in magnetic resonance imaging (MRI).
- The present invention relates to nuclear magnetic resonance (NMR) analysis, particularly to nuclear magnetic resonance imaging (MRI) and analytical high-resolution NMR spectroscopy. MRI is a diagnostic technique that has become particularly attractive to physicians as it is non-invasive and does not involve exposing the patient under study to potentially any such as from X-rays. Analytical high resolution NMR spectroscopy is routinely used in the determination of molecular structure.
- MRI and NMR spectroscopy lack some degree of sensitivity due to the normally very low polarization of the nuclear spins of the contrast agents typically used. A number of techniques exist to improve the polarization of nuclear spins. These techniques are known as hyperpolarization techniques and lead to an increase in sensitivity. In hyperpolarization techniques, a sample of an imaging agent, for example but not limited to 13C1-Pyruvate or another agent, is introduced or injected into the subject being imaged. Hyperpolarization is not limited to 13C1-Pyruvate or any specific compound (metabolically active or not). As used herein, the term “polarize” refers to the alignment of the nuclear spins of an agent for further use in MRI. Further, as used herein, the term “hyperpolarized” refers to polarized to a level over that found at room temperature and at 1 T, which is further described in U.S. Pat. No. 6,466,814.
- In many instances, the imaging agent undergoes this hyperpolarization in an apparatus in close proximity to its end use. This is due to the normally short life time (longitudinal relaxation time T1) of the polarization causing the spins to relax back to the thermal equilibrium polarization. One such technique to polarize nuclear spins uses Dynamic Nuclear Polarization to polarize the spins in the solid state. The apparatus used to produce the hyperpolarized samples is provided with a low temperature space that is in a magnetic field. As typically constructed, the apparatus is equipped with a flow cryostat that includes a vacuum insulated chamber inserted into the bore of a magnet. The cryostat is cooled by way of a stream of a cold cryogen provided by an external cryogen supply through a transfer line and pumping device, and the flow of cryogen into the flow cryostat cools the bore of the magnet and forms the low temperature space.
- The pumping devices currently used to provide the stream of cold cryogen are open cycle pumping systems that are undesirable for use in a clinical setting for numerous reasons. First, the open cycle pumping systems are large and generate high levels of noise. Furthermore, the open cycle pumping systems are expensive and cumbersome to operate because of the large quantity of cryogen that is consumed in the pumping process. That is, in order to provide a stream of cold cryogen to the flow cryostat, a sizable portion of the liquid cryogen is evaporated. In an open cycle pumping system, a large measure of this evaporated cryogen is not reclaimable. Thus, a large amount of cryogen is needed to hyperpolarize a sample, which adds significantly to the cost of operating the system.
- In addition to adding cost to the operation of the pumping system, the failure to reclaim the evaporated cryogen in an open cycle pumping system also leads to overall system inefficiency. That is, continuous operation of an open cycle pumping system is not possible because of the cryogen loss associated with the hyperpolarization of each imaging agent sample. Therefore, continuous operation for the open cycle systems is only obtained by regular cryogen filling in intermediate reservoirs.
- Thus, current hyperpolarization systems are inefficient and expensive to operate. A need therefore exists for a hyperpolarization system that minimizes or eliminates cryogen consumption and is energy efficient. It is also desirable that an improved hyperpolarization system be designed to operate in a manner that minimizes disruption to the surrounding environment and allow for more continuous operation, without the requirement of the operator to handle liquid cryogens, to increase production of hyperpolarized imaging agent samples.
- The present invention overcomes the aforementioned drawbacks by providing an apparatus and method for producing hyperpolarized samples for use in magnetic resonance systems. A sorption pump is incorporated into the apparatus to create a closed system for hyperpolarizing. Being a closed system, the apparatus and system loses no cryogen to atmosphere such that there is no need to replenish cryogen in the system.
- Therefore, according to one embodiment of the present invention, an apparatus comprises a cooling container containing a cryogenic refrigerant therein, configured to hyperpolarize a plurality of samples therein; a refrigeration system comprising: a refrigerator; and a helium condenser, wherein the helium condenser is separate and positioned exterior to and apart from the cooling container; a sorption pump connected to the cooling container, wherein the sorption pump is separate and spaced apart from the cooling container; a thermal switch configured to connect and disconnect the refrigeration system from the sorption pump; a heater disposed adjoining the sorption pump, configured to heat the sorption pump and promote molecular desorption therein; a single magnetic field producing device in thermal communication with the refrigeration system, wherein the single magnetic field producing device is configured to maintain a selected magnetic field in the apparatus, wherein the single magnet field producing device comprises: a superconducting magnet having a bore therethrough positioned about the cooling container; a magnet vessel to enclose the superconducting magnet, the magnet containing liquid cryogen therein to cool the superconducting magnet; and a magnet condenser configured to recondense helium gas that evaporates due to a heat load to the superconducting magnet, wherein the superconducting magnet is configured to produce a primary magnetic field region about the cooling container for hyperpolarization of the plurality of samples and a secondary magnetic field region offset from the primary magnetic field region that extends axially out from the superconducting magnet, wherein the superconducting magnet is further configured to operate without quench or loss of liquid helium when disconnected from the refrigeration system; and at least one thermal bus connecting the refrigeration system, the helium condenser, the magnet condenser, and the thermal switch, further wherein the apparatus comprises a closed system.
- In accordance with another embodiment of the present invention, a polarizing subsystem comprises: a container having a liquid helium bath configured to receive a material to be polarized; a sorption pump to reduce a pressure in the container, thereby to vaporize a portion of the liquid helium bath, the sorption pump comprising: a sorb can configured separate, spaced apart, and exterior to the container; a cooling system comprising: a magnet condenser configured separate, spaced apart, and exterior to the container, configured to recondense liquid helium boiled off therefrom and cool the sorption pump and promote molecular adsorption therein; a thermally conductive link that selectively connects the sorption pump and the cooling system to provide selective cooling to the sorption pump; a heater disposed adjoining the sorption pump, the heater configured to heat the sorption pump and promote molecular desorption therein; a single magnetic field producing device configured to maintain a selected magnetic field for polarizing the material in the apparatus, wherein the single magnetic field producing device is cooled by the cooling system, wherein the polarizer system operates in a closed cyclical thermal cycle alternating between a polarizing phase and a reheating phase based on the thermally conductive link of the sorption pump to the cooling system.
- In accordance with yet another embodiment of the present invention, a method for producing a hyperpolarized material comprises: placing a material sample in a vessel containing a liquid helium bath; reducing a temperature of the liquid helium bath with a sorption pump and a refrigeration system, wherein the sorption pump comprises: a sorb can configured separate from and exterior to and spaced apart from the vessel, wherein the refrigeration system comprises: a helium condenser configured separate from and exterior to and spaced apart from the vessel; refilling the liquid helium bath by heating the sorption pump with a heater, the heater being disposed adjoining the sorption pump; positioning a single magnetic field producing device adjacent the vessel, wherein the single magnetic field producing device is configured to product a high homogeneity magnetic field and a fringe magnetic field offset from the high homogeneity field; and polarizing the material sample when the liquid helium bath has been sufficiently cooled by the single magnetic field producing device
- In accordance with yet another embodiment of the present invention, a polarizer system comprises: a refrigerator; a magnet condenser; a helium condenser; a thermal bus permanently linking the refrigerator, the magnet condenser, and the helium condenser; a sorption pump selectively linked through a thermal switch to the thermal bus; a heater adjoining the sorption pump; a container containing a cryogenic refrigerant therein, configured to receive a plurality of samples for polarizing therein; a magnetic field producing device in a magnet vessel surrounding the container; wherein the polarizing system is further configured to operate in three separate modes, wherein: a first mode comprises: heating the sorption pump with the heater, thereby releasing helium gas to be cooled and liquefied by the helium condenser, wherein the released helium gas heats the thermal bus, thereby isolating the magnet vessel due to a thermal diode effect at the magnet condenser; a second mode comprises: upon completion of condensation of helium from the sorption pump, turning off the heater and cooling the sorption pump by closing the thermal switch, thereby creating a thermal linkage of the sorption pump, the thermal bus and the refrigerator, and thermally isolating the magnetic field producing device from the thermal bus; and, a third mode comprises: cooling the magnetic field producing device, thereby eliminating a thermal diode effect of the magnet condenser.
- Various other features and advantages of the present invention will be made apparent from the following detailed description and the drawings.
- The drawings illustrate an embodiment presently contemplated for carrying out the invention.
- In the drawings:
-
FIG. 1 is a block diagram and schematic of an apparatus to hyperpolarize materials according to an embodiment of the current invention. -
FIG. 2 is a cross-sectional view of a sample path and holding container arrangement according to an embodiment of the current invention. -
FIG. 3 is a cross-sectional view of a sample path and holding container arrangement according to another embodiment of the current invention. -
FIG. 4 is a cross-sectional view of a sample path and holding container arrangement according to another embodiment of the current invention. -
FIG. 5 is a cross-sectional view of a sorption pump according to an embodiment of the current invention. -
FIG. 6 is a 24-hour cycle pie-type chart showing the various modes of operation of the system according to an embodiment of the current invention. -
FIG. 7 is a graph comparing temperature of various elements of the system and magnet pressure over time of an embodiment of the current invention. - Referring to
FIG. 1 , an apparatus for hyperpolarizing a material for use in nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) is shown. Thepolarizer system 10 is a closed cyclical thermal system configured to hyperpolarize a sample of an imaging agent for use in MRI. For example, the sample can be composed of 13C1-Pyruvate or another agent that can be polarized. Further, thesystem 10 is a closed system. The term “closed system” as used herein means that the system does not lose cryogen to the atmosphere. As such, there is no requirement or need to replenish the system periodically with additional cryogen. Polarizersystem 10 is formed in part by avacuum chamber 12 that surrounds the internal components of the system. Polarizersystem 10 also includes athermal shield 16 within thevacuum chamber 12.Thermal shield 16 surrounds the main components of thepolarizer system 10 and functions to reduce the radiative heat load to those components. In one embodiment, thethermal shield 16 is composed of aluminum and is insulated with twenty or more layers of a highly insulative material, such as multilayer insulation (MLI). - A
refrigerator 14 that functions as a cooling system for the polarizer system is also included and can be selected from a number of refrigerators (cold-heads or cryo-coolers) that are known and are commonly used on MRI magnets. Therefrigerator 14 is positioned, at least in part, externally fromvacuum chamber 12. Such a configuration allows any heat generated by therefrigerator 14 to be exhausted in the ambient environment rather than into the interior ofvacuum chamber 12. - In one embodiment,
refrigerator 14 is a closed cycle refrigerator capable of providing low temperature environments below 10 K. Aseparate vacuum enclosure 18 is provided for therefrigerator 14. The refrigerator itself is mounted in a vertical orientation within amobile sleeve 20 to allow for vertical movement of therefrigerator 14 therein. Therefrigerator 14 is further characterized in being field serviceable. That is, the cryostat design is such that therefrigerator 14 can be switched off and removed for a time that will allow a service engineer to replace or service the refrigerator. Thepolarizer system 10 is immune to such a procedure and is configured to continue operation for a period of time while refrigerator is shut off. - Referring still to
FIG. 1 , the substance or material to be polarized (e.g., 13C1-pyruvate), hereafter referred to assample 22, is positioned withinvacuum chamber 12 for hyperpolarization. To allow for hyperpolarization of thesample 22, the sample is placed incontainer 24 having a cryogenic refrigerant 26 therein. In an embodiment, the sample(s) 22 are placed in a holdingcontainer 44 that is, in turn, at least partially immersed in theliquid helium bath 26 of thecontainer 24. In one embodiment, the cryogenic refrigerant is in the form of aliquid helium bath 26 into which thesample 22 is at least partially immersed.Container 24 is sealable and can be evacuated to low pressures (e.g. pressures of the order of 1 mbar or less) as will be explained in greater detail below. To allow for hyperpolarization of thesample 22, the temperature ofliquid helium bath 26 is lowered to a suitable temperature, e.g. temperatures below 4.2 K and preferably below 1.5 K. Thesample 22 is then placed in a suitable magnetic field by magneticfield producing device 28 positioned aboutcontainer 24 to achieve hyperpolarization. - The
samples 22 are introduced into thepolarizer system 10 by way of asample path 30 that passes through an ante chamber 32 (i.e., air lock). The purpose of theante chamber 32 is to prevent contamination of thesample path 30 during introduction of thesamples 22 and also to eliminate the need of breaking the vacuum on thesample path 30. In existing polarizer systems in the art, the sample path is pressurized to atmospheric pressure with helium gas; however, this is a major limitation of existing polarizers since bringing the sample path pressure to atmospheric pressure constitutes a significant heat load to the liquid helium bath and also transiently raises the temperature of the bath, i.e. reduces the throughput. In one embodiment of the present invention, theante chamber 32 is isolated fromvacuum chamber 12 by agate valve 34 and from the atmosphere by a sealingcap 36. Theante chamber 32 can then, once thesample 22 has been introduced, be evacuated and flushed with helium gas in several cycles to eliminate and evacuate any air (and moisture). Thus,ante chamber 32 reduces the heat load to theliquid helium bath 26. The specific design of theante chamber 32 will vary based on the geometry of thesample 22 and can be designed accordingly in a way known to one skilled in the art. - Referring also now to
FIG. 2 , thesample path 30, and the internal surfaces thereof exposed to thesample 22, are made from materials that are routinely used for pharmaceutical equipment and should follow such industry standards. A portion of thesample path 30 can be filled with liquid helium dispensed through a sterile filter to further minimize the bio-burden in this area. Thesample path 30 is further characterized in having an equilibrator 38 that serves the purpose of leading the heat of thesamples 22 to therefrigerator 14 before thesample 22 is introduced into thehelium bath 26. The latent heat of thesample 22 would constitute a very large heat load to thehelium bath 26 significantly reducing the hold time of the system. Depending on the heat capacity properties of thesample 22, this energy is easily predictable and/or measured, and the time required to sit in theequilibrator 38 will depend on the rate of heat conduction in thesample 22, from the sample to theequilibrator 38, and on the rate of heat conduction away from theequilibrator 38. An optimized design can be made based on the above parameters and the temperature at which thesample 22 is allowed to enter thebath 26. Theequilibrator 38 can be designed in several ways by a person skilled in the art. The main characteristics are low conductivity to thebath 26 and good conductivity from thesample 22 to therefrigerator 14. The good conductivity from thesample 22 can be obtained by good physical contact between thesample 22 and a high conductivity material, but in many cases the helium gas present in thesample path 30 will act as a sufficient exchange gas and efficiently conduct the heat from thesample 22 to the walls of theequilibrator 38. - The
sample path 30 can also be equipped with a means of providing heat to the sample during a dissolution process or a means to mechanically agitate the sample during the dissolution. In one embodiment, once thesample 22 has been hyperpolarized to a desired state, the sample is dissolved by way of a heated solvent flowing thrusample 22 and is removed from thepolarizer system 10 via thesample path 30 to a desired location/user. Referring now toFIG. 2 , in another embodiment, the means for mechanically agitating thesample 22 is anultrasound transmitter 40 that vigorously agitates the solvent and facilitates the dissolution. An ultrasonic burst is carried down thesample path 30 and into the sample by way of asonicator probe 42 to break the solid sample and pressurize the surrounding environment to force the dissolved sample and solvent back up thesample path 30. The ultrasound would at the same time dissipate heat in the solution. While a heated solvent and ultrasound have been described as a means of providing energy to the sample, it is also envisioned that other methods/mechanisms for providing energy could also be implemented, such as infrared radiation or microwave energy. - Referring again to
FIG. 1 , thesample 22 is ultimately positioned in a holdingcontainer 44 that is in thermal contact withliquid helium bath 26 ofcontainer 24. Thesample 22 is separated fromliquid helium bath 26 by placing it inside the holdingcontainer 44. This placement ofsample 22 into holdingcontainer 44 increases the longevity of thepolarizer system 10 and improves system efficiency, as the sample loading inevitably introduces contamination into thepolarizer system 10, which would in turn effect operation of asorption pump 46 in the polarizer system. Thesorption pump 46 is sensitive to contamination and cannot easily be restored, and thus, placement ofsample 22 in the holdingcontainer 44 helps to prevent these contaminants from entering intoliquid helium bath 26. - Referring now to
FIG. 3 , the holdingcontainer 44 is in thermal contact withliquid helium bath 26 by acommon wall 47 with high thermal conductivity that minimizes the thermal gradient. If holdingcontainer 44 is not immersed inliquid helium bath 26, it also can be placed in thermal contact therewith by way of copper tails orfins 49 that extend down from the holdingcontainer 44 into thebath 26. The holdingcontainer 44 can also be filled in part with liquid helium. In such a configuration, the liquid helium acts as a good heat conductor fromsample 22 to the walls of the holdingcontainer 44 and finally into thehelium bath 26 ofcontainer 24. In one embodiment, the superfluid helium, which has very high heat conductivity, also serves to conduct dissipated microwave energy away fromsample 22 that is directed thereto by a microwave irradiation system (not shown). - The need for liquid helium within holding
container 44 is optional and will depend on the design of the microwave irradiation system, the sample properties, and the thermal contact to thesample 22. Rather that being filled with liquid helium, it is also envisioned that holdingcontainer 44 be filled with helium gas. The use of helium gas within holdingcontainer 44 for coolingsample 22 is desirable since this volume of helium may occasionally be evaporated and recondensed from, for example, a helium gas cylinder. Additionally, the helium gas can lead to improvement in the cryogenic performance of thepolarizer system 10 by reducing the film flow from the helium bath if operated above the lambda point of helium. - To focus and confine the microwaves to sample 22, so as to provide for efficient polarization thereof, the holding
container 44 contains a microwave confining arrangement that includes awaveguide 48 and optionally asample cup 50. The microwave confining arrangement is designed in a way to deliver the microwave energy (microwave magnetic field) required for the DNP process. For example, if the magnetic field for polarization is chosen in the range 1-20 T, the microwave field would be in the range 3-560 GHz for a g=2 paramagnetic agent. In the embodiment ofwaveguide 48 shown inFIG. 1 , microwaves are transmitted into the sample bywaveguide 48, which extends down aroundsample path 30 and joins with holdingcontainer 44 to irradiate thesample 22. As shown inFIG. 3 , in another embodiment,waveguide 48 andconical horn 52 form withsample cup 50 to irradiatesample 22. Thewaveguide 48 contains a vacuum-tight seal 54 therein, which can be constructed of a polymer, quartz, or sapphire window, and also containsbaffles 56 at appropriate positions within thesample path 30 to reduce heat transfer down the sample path and into the holdingcontainer 44. InFIG. 3 , thewaveguide 48 is removable from thesample path 30 after hyperpolarization of thesample 22 has been achieved and before a desired dissolution of the sample is carried out. - Referring still to
FIG. 3 , thewaveguide 48 joins withsample cup 50 at the lower end thereof to guide microwaves into thesample 22. Thesample cup 50 has a thinlayer metal wall 57 and bottom surface that confines these microwaves to the sample. Preferably, the sample cup is comprised of a titanium or gold, or another metallic material that will not react with the pyruvic acid of the sample or with the solvent used to dissolve the sample during dissolution. It is also envisioned that a plasticinner shell 58 could be included inside themetallic sample cup 57 to prevent contact between the sample and metal. The plasticinner shell 58 would also dictate heat conductivity of thesample cup 50, and thus inclusion of the innerplastic shell 58 may also depend on the selection of liquid or gaseous helium within holdingcontainer 44 and the desired amount of heat transfer between the sample cup and the helium. Thewaveguide 48 andsample cup 50 arrangement is designed to minimize losses and deliver a maximum of the microwave energy to the sample, as a higher loss in the microwave delivery system would require a more powerful microwave source. It is also envisioned that the microwave delivery system is part of thesample 22 to confine the microwave entirely to thesample 22. - In one embodiment, a
NMR coil 60 is also included in the overall structure of the holdingcontainer 44. TheNMR coil 60 is optional, but provides a means of measuring the nuclear polarization during and after the DNP polarization process by producing RF pulses that measure the polarization level of thesample 22. A number of arrangements for anNMR coil 60 are known in the art, and in a preferred embodiment, theNMR coil 60 is positioned outside the microwave confining arrangement. TheNMR coil 60 can be a saddle coil, Helmholz coil, birdcage coil, or any other known design. TheNMR coil 60 is connected to the outside ofvacuum chamber 12 by, for example, acoaxial cable 62 or other suitable radio frequency cabling. In one embodiment, theNMR coil 60 is positioned inside of the holdingcontainer 44, although it is envisioned thatNMR coil 60 could also be positioned outside of the holdingcontainer 44. The walls of the holdingcontainer 44 can be slit in such a way as to minimize losses and ensure radio frequency penetration. That is, the holdingcontainer 44 could, in part, be formed of copper and slit as desired to allow RF signals to penetrate therethrough and include a plasticinner shell 64 to provide a sealed holdingcontainer 44. To also allow the RF signals to penetrate into thesample 22, the thickness of thesample cup 50 walls is kept within a desired range such that the RF waves are not severely attenuated by the metallic sample cup. - Referring now to
FIG. 4 , according to one embodiment,sample path 30 is configured to be removable in the field without de-energizing the magnet and breaking the cryostat vacuum. This allows for regular field service of thepolarizer system 10 while causing minimal disruption to the operation thereof. Thesample path 30 can require field service for a number of reasons, such as failure of theNMR coil 60 orwaveguide 48 transmission systems (shown inFIG. 1 ) for electrical or mechanical reasons, contamination of thesample path 30 by ingression of air that cannot be removed by a standard operation procedure, or failure of thesample 22 at any stage of the process.Detachable sample path 30 is mounted in astainless steel sleeve 66 that isolates the sample path vacuum from the remainingcryostat vacuum 12 and is sealed to holdingcontainer 44 via anindium gasket 68 to allow for evacuation of thesleeve 66. This would allow the sample path vacuum to be broken without disrupting operation of the rest of thepolarizer system 10 and for removal of thesample path 30. Thesample path 30 also includes a bolted room temperature flange (not shown) sealed by standard vacuum techniques. It is also envisioned that other configurations could be implemented for thedetachable sample path 30. - Referring again to
FIG. 1 , one embodiment of magneticfield producing device 28 is shown positioned aboutcontainer 24 and theliquid helium bath 26. Magneticfield producing device 28 is a superconducting magnet having a bore therethrough in whichcontainer 24 is placed.Superconducting magnet 28 is capable of creating a magnetic field strength that is sufficiently high, e.g. between 1-25 T or more, for example 5.0 T, for hyperpolarization of thesample 22 to take place. To ensure efficient operation ofsuperconducting magnet 28, the magnet is enclosed in avessel 70 containing liquid helium to provide cooling. The liquid helium is in turn cooled byrefrigerator 14 that is connected tomagnet 28 by way of 72, 90. Thethermal bus magnet 28 is connected to the 72, 90 through athermal bus condenser 74, which is a standard configuration for superconducting magnets cooled by a refrigerator. The condenser 74 (e.g., also referred to as magnet condenser, recondenser, and/or first condenser herein) re-condenses into themagnet vessel 70 any helium gas that evaporates due to the heat load to themagnet 28. In the event thatrefrigerator 14 is disconnected for servicing or there is an electrical power failure, the 72, 90 will warm up. In response, thethermal bus condenser 74 is isolated from themagnet 28 thereby maximizing the time that themagnet 28 will survive not being cooled by therefrigerator 14 and preventing quench or loss of cryogen. It is also envisioned thatmagnet 28 could be dry (i.e., no liquid helium), but the magnet would then only maintain its superconducting properties for a short time (i.e., until the magnet warms above its superconducting temperature) in case of therefrigerator 14 being turned off. - The
magnet 28 can favorably be operated sub-atmospheric to minimize the heat load to therefrigerator 14 from the magnet. If themagnet 28 is operated sub-atmospheric, a protective buffer helium volume can be added to any safety exhaust ports on thepolarizer system 10 to prevent ingression of air and contamination of the magnet or sorption pump. - The
magnet 28 is designed such as to provide a high magnetic fringe field region away from the verylow temperature container 24. This high field region, e.g. 1-25 T or more, for example 5 T, is required in many instances during the dissolution of thesample 22. That is, as the dissolved sample is transferred out fromcontainer 24 via thesample path 30 and outside the volume of thevacuum chamber 12, a fringe magnetic field is desirable to maintain the hyperpolarized state of thesample 22. Furthermore, themagnet 28 can be designed in way that the fringe field is axially contained via active or passive shielding. Along thesample path 30, the magnetic field is preferably high, at least to an extent that the relaxation of the sample polarization is minimized at all steps of the dissolution process. Depending on the properties of thesample 22, this fringe magnetic field can be adjusted in intensity and coverage area as needed. - The
magnet 28 and cryostat are also designed in such a way as to minimize or tolerate the interaction with an imaging magnet (not shown). In some circumstances, it is preferable to position thepolarizer system 10 as close as possible to a magnetic resonance (MR) system (not shown) and the imaging magnet contained therein. In such an arrangement, magnetic field homogeneity and magnetic forces need to be carefully controlled on both magnets in order to minimize interference of the two magnetic fields and maintain homogeneity of the MR imaging field. - Referring still to
FIG. 1 ,container 24 is sealable and can be evacuated to low pressures. Evacuation ofcontainer 24 to a low pressure in turn reduces the temperature ofliquid helium bath 26 by vaporizing a portion of liquid helium and moving the state point down the helium saturation curve. That is, the boiling temperature of liquid helium (4.2 K) is a function of its vapor pressure. By reducing the pressure on theliquid helium bath 26, it is possible to cool it, and thesample 22 therein, to about 1 K without any further complications. This low temperature then allows for transformation of thesample 22 to a high fractional polarization state that is desired. - To achieve this reduction in pressure on
liquid helium bath 26,sorption pump 46 is fluidly connected tocontainer 24 by way of apumping line 76.Sorption pump 46 is configured to lower pressure incontainer 24 by adsorbing the gas that evaporates fromliquid helium bath 26.Sorption pump 46 operates in this sorption mode (i.e., polarization/pumping phase) when the pump is lowered to a cryogenic temperature. That is, when sorption pump 46 is cooled to a temperature of ˜10 K or below, helium gas will evaporate fromliquid helium bath 26 and be adsorbed bysorption pump 46 forming a monolayer or two on a sorbent material therein. - As shown in
FIG. 5 ,sorption pump 46 includes apump enclosure 78 containing asorbent material 80 therein.Pump enclosure 78 is preferably in the form of a cylinder, although other suitable constructions may also be implemented.Sorbent material 80 is formed of a material having a high rate of adsorption at low temperatures. In one embodiment,sorbent material 80 is composed of activated charcoal, which has a high rate of adsorption due to its large total surface area, which is in the range of tens of square meters per gram (e.g., >1000 m2/g). Dispersed withinsorbent material 80 are coolingfins 82 that cool the material. Coolingfins 82 promote uniform cooling ofsorbent material 80 to improve the adsorption efficiency during a pumping or sorption cycle/phase. In one embodiment, coolingfins 82 are comprised of copper tubing so as to provide a medium having good thermal conductivity for quick cooling of thesorbent material 80. The coolingstructure 82 can be arranged in many ways depending on the geometry of theenclosure 78 to provide quick cooling of thesorbent material 80. - Continuing to refer to
FIG. 1 , aspects of the present invention offer advantages over previous polarizing art includes the practical usage of this system in a clinical environment, and not merely in a limited research environment. Prior attempts with polarizing suffer in that temperature constraints of the systems limit the rate heat can be extracted from the sorption pump, which ultimately impacts the practical usage of these earlier polarizing systems. For example, in these systems when the sorb can is heated to release adsorbed helium, the magnet will not quench and the helium in the helium can is recondensed despite the excess heat load on the thermal bus during this time. - As
FIG. 1 illustrates, various elements in thesystem 10 are separate positioned exterior to and/or apart from other elements of thesystem 10. These elements include, but are not limited to, the 74, 88, coolingcondensers container 24, andsorption pump 46. Note too that thesystem 10 only requires a single magneticfield producing device 28. - Advantages of the system and apparatus, depicted in
FIG. 1 , include directing heat to the sharedrefrigerator 14 that is permanently linked to the two 74, 88, and temporarily, or selectively, linked to theindependent condensers sorption pump 46 through thethermal switch 84. The novel structure of thesystem 10 enables for the operation of three distinct modes, or phases, of operation. A first mode can be termed a condensing, or desorption, mode; a second mode can be termed a cooling mode; and, the third mode can be termed a polarizing, or sorption pumping, mode. The components of thepolarizer 10 are optimized and matched to work as a cryogenically closed system (i.e., without release of helium to the environment) with specific operating modes and optimized thermal budget that other systems do not follow (See e.g.,FIG. 7 ). - Upon completion of a desired polarizing, or sorption pumping, phase in which
samples 22 have been polarized,sorption pump 46 can be switched to condensing mode (i.e., reheating/desorption phase) to allow for the helium molecules adsorbed insorbent material 80 to recondense and transfer back tocontainer 24 to refill theliquid helium bath 26. Referring still toFIG. 1 , in condensing mode, the temperature ofsorption pump 46 is raised to a temperature such that helium molecules are desorbed from thesorbent material 80 and released therefrom. To achieve this higher temperature,thermal switch 84 is positioned to disconnect therefrigerator 14 and 72, 90 fromthermal bus sorption pump 46. When disconnected fromrefrigerator 14, the temperature ofsorption pump 46 is elevated by turning onheater 86, and enters desorption phase upon reaching a temperature of, for example, 30-40 K, wherein helium molecules escape from thesorbent material 80 and exit thesorption pump 46 via thepumping line 76. In addition, for example during service operations, ifnecessary sorption pump 46 is also allowed to enter a regeneration phase where thesorbent material 80 can be heated byheater 86 to a higher temperature to drive off water vapor collected therein that does not desorb at room temperature. This regeneration (or fourth) phase can take up to two hours, and as such, would be performed during periods when use of thepolarizer system 10 is not required. The heating profile and desorption/regeneration temperatures are chosen to give the most optimal cryogenic performance. - As mentioned above, helium gas molecules that had previously been vaporized are allowed to recondense in the condensing/desorption phase. This recondensing is achieved by way of a condenser 88 (e.g., also referred to as helium condenser, container condenser, and/or second condenser herein) that is connected to sorption pump by way of pumping
line 76. Helium gas released fromsorbent material 80 during the desorption phase exitssorption pump 46 by way of thepumping line 76 and is carried tohelium condenser 88.Helium condenser 88 functions to cool the helium gas to a temperature necessary to place the helium in a liquid state. Once the helium has been recondensed into a liquid state, it re-enterscontainer 24 andliquid helium bath 26 is refilled.Helium condenser 88 is cooled byrefrigerator 14 through connection thereto formed by commonthermal bus 90. As shown inFIG. 1 , athermal bus 90 is connected torefrigerator 14 by way of anotherthermal bus 72.Thermal bus 90 then is connected tohelium condenser 88 to allow for recondensing of the helium gas that enters into thecondenser 88. WhileFIG. 1 shows two connected 72, 90, it is also envisioned thatthermal buses thermal bus 90 andthermal bus 72 can be formed as a single thermal bus or as a plurality of buses. - In the first mode (i.e., condensing/desorption) of operation, the
sorption pump 46 is directly and aggressively heated with theheater 86 adjoined thereto. This heating enables a rapid temperature rise in the large sorbent mass (e.g., >5 kg) in thesorption pump 46 and a release of large quantities of helium gas. The released helium gas is cooled and liquefied atcondenser 88. The warm gas from thesorption pump 46 heats the 72, 90 and effectively isolates thethermal bus magnet vessel 70 due to a thermal diode “effect” experience at themagnet condenser 74. Thus, the heat related to the condensation of helium gas from thesorption pump 46 can be wholly and efficiently directed to therefrigerator 14 without negatively impacting themagnet 28. - Referring now to both
FIGS. 6 and 7 ,FIG. 6 demonstrates an example of the temporal cycle of anapparatus 10 enabled by the cryogenic system disclosed in this document.FIG. 7 shows representative temperature and pressure profile for specific components of theapparatus 10 during this cycle. Theapparatus 10 is capable of progressing through three modes during a 24 hour period. - In the first mode (desorption/condense), shown to begin at 8:00 pm in this example, the
thermal switch 84 is opened to enable thesorption pump 46 to be heated while minimizing the impact on the remaining components of theapparatus 10. With thethermal switch 84 effectively isolating thesorption pump 46 from the remainder of thesystem 10, the cooling power of therefrigerator 14 shared on the 72, 90 by thethermal bus magnet condenser 74 andhelium condenser 88. Helium gas adsorbed in thesorption pump 46 is liberated and transported through thepumping line 76 to thecondenser 88, resulting in the temperature of the 72, 90 to rise. The rise in temperature at thethermal bus 72, 90 causes helium gas in thethermal bus magnet vessel 70 andcondenser 74 to stratify and effectively isolate themagnets vessel 70 from the remainder of theapparatus 10. At this point the majority of the cooling power of therefrigerator 14 is directed to thehelium condenser 88 enabling the rapid and efficient condensation of helium gas to liquid, which is collected in thecontainer 24. Through this procedure greater than 3 L of liquid helium can be collected in thecontainer 24 during a 10 hour condensation period. -
FIG. 7 shows that during this first mode of operation the sorption pump temperature is rapidly elevated resulting in a corresponding increase in the helium gas pressure in thesorption pump 46. When the desired condensation pressure is achieved, for example 1100 Torr, the rate of heating is decreased to maintain a constant pressure while helium is expelled from thesorption pump 46 and condensed into the helium container. The 72, 90 and holdingthermal bus container 44 reflect the increased temperature associated with the elevated pressure of the helium being condensed. During this period themagnet vessel 70 pressure slowly increases as themagnet 28 is isolated from therefrigerator 14. Due to the large thermal mass of the liquid helium contained in themagnet vessel 70, this pressure and corresponding temperature increase is relatively minor, on the order of 2-4 pounds per square inch. When the desired amount of liquid helium is condensed in the helium container, shown at 2:00 AM inFIG. 7 , thesorption pump heater 86 is turned off and thesystem 10 is allowed to equilibrate. Once the thermal bus temperature is sufficiently low themagnet condenser 74 will again receive cooling power from the 72, 90 and the magnet vessel pressure and temperature will be reduced.thermal bus - In order to cool the
sorbent material 80, during the cooling phase, as described above, coolingfins 82 are attached to athermal switch 84 that connects and disconnects sorption pump 46 fromrefrigerator 14 according to operator commands. Referring back toFIG. 1 ,refrigerator 14 is connected to sorption pump 46 by way ofthermal bus 72, 90 (i.e., thermally conductive link) andthermal switch 84. 72, 90 provides a link forThermal bus refrigerator 14 to coolsorption pump 46 and thesorbent material 80 therein to a cryogenic temperature to allow thepump 46 to operate in sorption mode. The conductive link provided by 72, 90 is selectively connected and disconnected fromthermal bus sorption pump 46 by way ofthermal switch 84, thus allowing for thepump 46 to also exit sorption mode when desired. - In the second mode of operation (i.e., cooling), upon completion of the condensation of helium gas from
sorption pump 46,heater element 86 is turned off and thesorption pump 46 is cooled by closingthermal switch 84, thereby creating a thermal linkage between thesorption pump 46, the 72, 90, andthermal bus refrigerator 14. During operation of the second mode, both 74, 88 experience the thermal diode “effect” and isolate thecondensers magnet 28 andhelium vessel 24 from the 72, 90. This isolation of thethermal bus magnet 28, in particular, allows the 72, 90 to thereby achieve temperature greater than about 20K without impacting or affecting thethermal bus magnet 28 and its temperature. In this manner, the higher temperatures achieved by the 72, 90 allows thethermal bus refrigerator 14 to achieve greater efficiency (e.g., 10×), thereby accelerating the rate of heat extraction from theheat pump 46. -
FIG. 6 shows the second mode of operation, cooling, commencing at 5:00AM. During this mode thethermal switch 84 is closed connecting thehot sorption pump 46 to the 72, 90. This connection results in a rapid rise in thethermal bus 72, 90 temperature, effectively turning off thethermal bus magnet condenser 74 and thehelium condenser 88. Removal of liquid helium thermal masses in themagnet vessel 70 and helium container enables the thermal bus temperature to achieve values in excess of 15 K, where the refrigerator's cooling power is greatly increased. This increased cooling power rapidly cools thesorption pump 46 reducing the pressure within thesorption pump 46. As the pressure in thesorption pump 46 is reduced, liquid helium in the helium container is evaporated and the gas is returned thesorption pump 46. This process rapidly cools the helium container to less than 1 K, typically in less than 2 hours.FIG. 7 shows that during this second mode of operation the thermal bus temperature rapidly rises and then falls as the heat is extracted by therefrigerator 14. Thesorption pump 46 and helium container temperature show a corresponding rapid decrease in temperature. Themagnet 28 experiences an increase in pressure during this mode of operation. Again, due to the high thermal mass of the liquid helium in themagnet vessel 70, this increase in pressure is relatively minor. - The
sorption pump 46 and connected pumpingline 76 are designed to create a high pumping capacity. This high pumping capacity is needed to obtain a low base temperature in theliquid helium bath 26 in a reasonable time. Upon adsorption of a sufficient number of molecules to reduce the temperature ofliquid helium bath 26 to a desired temperature for hyperpolarization of thesample 22, thesorption pump 46 is configured to maintain the low temperature of theliquid helium bath 26 for an extended time during which hyperpolarization can occur. The exact capacity of thesorption pump 46 to absorb helium and the volume of liquid helium inbath 26 can be designed and optimized to give the desired hold time of the low temperature for hyperpolarization. - In the third mode of operation (i.e., polarizing), the helium container or
vessel 24 and sorption pump 46 are cold relative to themagnet 28, thereby eliminating any thermal diode “effect” from thecondenser 74. This allows for the effective cooling of themagnet 28. -
FIG. 6 shows the third mode of operation, polarize, commencing at 8:00 AM. At this point thesorption pump 46 andhelium container 24 temperatures have achieved stabile and minimum temperatures. The reduced thermal bus temperature once again enables themagnet condenser 74 to cool themagnet 28 and reduce the pressure in themagnet vessel 70.FIG. 7 shows this cooling of the magnet pressure continues throughout the remainder of the cryogenic cycle, preparing themagnet 28 for the next period of loss of cooling. - The functioning of the
polarizer system 10 as a closed system operating in a cyclical thermal cycle provides for an efficient system for hyperpolarizing thesample 22. Additionally, the amount of liquid helium consumed during hyperpolarization is reduced essentially to zero because of thesorption pump 46 andcondenser 88 arrangement, thus reducing maintenance on thepolarizer system 10 as no liquid cryogens need to be filled and no mechanical pumps need to be serviced. - The
polarizer system 10 heretofore described includes an adsorption pump 46 (i.e., sorption pump). While adsorption pumps have been used in a number of cryogenic applications,sorption pump 46 provides the unique benefits of having a very high adsorption capacity that translates into a high pumping capacity and long hold time. Thepolarizer system 10 also provides a singlecommon refrigerator 14 that is configured to cool both thesuperconducting magnet 28 and thesorption pump 46. The superconducting magnet cryogenic system (i.e.,refrigerator 14 and liquid helium contained in magnet vessel 70) is designed in such a way to be insensitive to the thermal cycle ofsorption pump 46. Thesorption pump 46 is capable of reaching temperatures well below any currently available refrigerator. While the embodiment ofpolarizer system 10 described aboveimplements sorption pump 46, it is also envisioned that a refrigerator with sufficient capacity and base temperature can provide an environment having cryogenic temperatures in the range of 1.5 K that are suitable for hyperpolarization, such as an Adiabatic Demagnetization Refrigerator (ADR), which has also been successfully operated in low temperature physics applications. - In this manner, the
system 10 intentionally isolates the magnet vessel 70 (and magnet 28) during cooling of thesorption pump 46 or its emitted gas. Thesystem 10 exploits the large thermal mass of themagnet 28 so as to enable themagnet 28 to “ride” through a period when themagnet 28 is not receiving any supplemental cooling from therefrigerator 14. This intentional isolation allows therefrigerator 14 and its limited cooling power to be more efficiently utilized. Themagnet 28 is thereby “insensitive” to the thermal cycle of thesorption pump 46, which ultimately enables thesystem 10 to operate more optimally in practical uses, including clinical applications. - Together
FIGS. 6 and 7 demonstrate how the novel combination of multiple condensers and a thermal switch on a shared thermal bus enables specific components of the apparatus to be isolated during certain modes of operation and therefore increasing the efficiency of the entire system. The ability to isolate the magnet and sorption pump from the thermal bus during the condensation mode enables rapid and efficient condensation of practical and useful volumes of liquid helium during a minimized period. The ability to isolation the magnet and helium container from the thermal bus during cooling enables the thermal bus temperature to rapidly elevate to levels where the refrigerators cooling power is enhanced, accelerating the cooling process. Finally, the ability to reconnect the magnet to the refrigerator during the low thermal load polarization mode enables the magnet to recover and reset the system's thermal balance for the next cycle. - While
polarizer system 10 has been described above as a self-contained system, it is also envisioned that the system be integrated with a MR imaging system. In such a configuration, an MR magnet functions to create the fringe magnetic field. With some local optimization of the strength and homogeneity of this fringe field, a sufficient DNP polarizing field needed for hyperpolarization of the 13C1-pyruvate sample can be created. Additionally, a helium reservoir of the MR imaging system used to cool the imaging magnet could also be used to provide liquid helium to the container surrounding the sample to be polarized. One implementation would be to connect the main helium reservoir to the container/sample space of the polarizer system via a capillary with a needle valve and controlling inflow of liquid helium to the container by way of the valve. The integration of the polarizer system with a MR imaging system would lead to a more compact and cheaper overall design. - As discussed earlier with regard to the stand alone polarizer system, it is often desirable to lower the temperature of the sample during polarization beyond the boiling point of helium at atmospheric pressure (4.2 K) in order to achieve high nuclear polarization of the sample. To reach these lower temperatures, the sample space (containing a bath of liquid helium) may be pumped on constantly by a sorption pump, which will result in a reduction of the helium's vapour pressure and consequently in a lower operating temperature. In light of the integration of the polarization system and the MRI imaging system, it is favourable to re-circulate the cold helium gas that is pumped out of the sample space to add to the cooling effect of the MR imaging magnet to provide additional cooling capacity (resulting in a longer helium hold time and obliterating the implementation of a liquid nitrogen reservoir) and to have an advantageous effect on cryogenic hold-time.
- In general, the use of the MR imaging magnet for hyperpolarization would facilitate maintenance, as liquid helium re-filling would be performed on only the one integrated system rather than at different times for the two separate magnets. The integrated system would also take advantage of the existing cryogenic safety features of the MR scanner and make use of MR scanner electronics to monitor the increasing NMR signal from the sample while the polarization process is on-going.
- Therefore, according to one embodiment of the present invention, an apparatus comprises a cooling container containing a cryogenic refrigerant therein, configured to hyperpolarize a plurality of samples therein; a refrigeration system comprising: a refrigerator; and a helium condenser, wherein the helium condenser is separate and positioned exterior to and apart from the cooling container; a sorption pump connected to the cooling container, wherein the sorption pump is separate and spaced apart from the cooling container; a thermal switch configured to connect and disconnect the refrigeration system from the sorption pump; a heater disposed adjoining the sorption pump, configured to heat the sorption pump and promote molecular desorption therein; a single magnetic field producing device in thermal communication with the refrigeration system, wherein the single magnetic field producing device is configured to maintain a selected magnetic field in the apparatus, wherein the single magnet field producing device comprises: a superconducting magnet having a bore therethrough positioned about the cooling container; a magnet vessel to enclose the superconducting magnet, the magnet containing liquid cryogen therein to cool the superconducting magnet; and a magnet condenser configured to recondense helium gas that evaporates due to a heat load to the superconducting magnet, wherein the superconducting magnet is configured to produce a primary magnetic field region about the cooling container for hyperpolarization of the plurality of samples and a secondary magnetic field region offset from the primary magnetic field region that extends axially out from the superconducting magnet, wherein the superconducting magnet is further configured to operate without quench or loss of liquid helium when disconnected from the refrigeration system; and at least one thermal bus connecting the refrigeration system, the helium condenser, the magnet condenser, and the thermal switch, further wherein the apparatus comprises a closed system.
- In accordance with another embodiment of the present invention, a polarizing subsystem comprises: a container having a liquid helium bath configured to receive a material to be polarized; a sorption pump to reduce a pressure in the container, thereby to vaporize a portion of the liquid helium bath, the sorption pump comprising: a sorb can configured separate, spaced apart, and exterior to the container; a cooling system comprising: a magnet condenser configured separate, spaced apart, and exterior to the container, configured to recondense liquid helium boiled off therefrom and cool the sorption pump and promote molecular adsorption therein; a thermally conductive link that selectively connects the sorption pump and the cooling system to provide selective cooling to the sorption pump; a heater disposed adjoining the sorption pump, the heater configured to heat the sorption pump and promote molecular desorption therein; a single magnetic field producing device configured to maintain a selected magnetic field for polarizing the material in the apparatus, wherein the single magnetic field producing device is cooled by the cooling system, wherein the polarizer system operates in a closed cyclical thermal cycle alternating between a polarizing phase and a reheating phase based on the thermally conductive link of the sorption pump to the cooling system.
- In accordance with yet another embodiment of the present invention, a method for producing a hyperpolarized material comprises: placing a material sample in a vessel containing a liquid helium bath; reducing a temperature of the liquid helium bath with a sorption pump and a refrigeration system, wherein the sorption pump comprises: a sorb can configured separate from and exterior to and spaced apart from the vessel, wherein the refrigeration system comprises: a helium condenser configured separate from and exterior to and spaced apart from the vessel; refilling the liquid helium bath by heating the sorption pump with a heater, the heater being disposed adjoining the sorption pump; positioning a single magnetic field producing device adjacent the vessel, wherein the single magnetic field producing device is configured to product a high homogeneity magnetic field and a fringe magnetic field offset from the high homogeneity field; and polarizing the material sample when the liquid helium bath has been sufficiently cooled by the single magnetic field producing device.
- In accordance with yet another embodiment of the present invention, a polarizer system comprises: a refrigerator; a magnet condenser; a helium condenser; a thermal bus permanently linking the refrigerator, the magnet condenser, and the helium condenser; a sorption pump selectively linked through a thermal switch to the thermal bus; a heater adjoining the sorption pump; a container containing a cryogenic refrigerant therein, configured to receive a plurality of samples for polarizing therein; a magnetic field producing device in a magnet vessel surrounding the container; wherein the polarizing system is further configured to operate in three separate modes, wherein: a first mode comprises: heating the sorption pump with the heater, thereby releasing helium gas to be cooled and liquefied by the helium condenser, wherein the released helium gas heats the thermal bus, thereby isolating the magnet vessel due to a thermal diode effect at the magnet condenser; a second mode comprises: upon completion of condensation of helium from the sorption pump, turning off the heater and cooling the sorption pump by closing the thermal switch, thereby creating a thermal linkage of the sorption pump, the thermal bus and the refrigerator, and thermally isolating the magnetic field producing device from the thermal bus; and, a third mode comprises: cooling the magnetic field producing device, thereby eliminating a thermal diode effect of the magnet condenser.
- The present invention has been described in terms of the preferred embodiment, and it is recognized that equivalents, alternatives, and modifications, aside from those expressly stated, are possible and within the scope of the appending claims.
Claims (21)
1. An apparatus comprising:
a cooling container containing a cryogenic refrigerant therein, configured to hyperpolarize a plurality of samples therein;
a refrigeration system comprising:
a refrigerator; and
a helium condenser, wherein the helium condenser is separate and positioned exterior to and apart from the cooling container;
a sorption pump connected to the cooling container, wherein the sorption pump is separate and spaced apart from the cooling container;
a thermal switch configured to connect and disconnect the refrigeration system from the sorption pump;
a heater disposed adjoining the sorption pump, configured to heat the sorption pump and promote molecular desorption therein;
a single magnetic field producing device in thermal communication with the refrigeration system, wherein the single magnetic field producing device is configured to maintain a selected magnetic field in the apparatus, wherein the single magnet field producing device comprises:
a superconducting magnet having a bore therethrough positioned about the cooling container;
a magnet vessel to enclose the superconducting magnet, the magnet containing liquid cryogen therein to cool the superconducting magnet; and
a magnet condenser configured to recondense helium gas that evaporates due to a heat load to the superconducting magnet,
wherein the superconducting magnet is configured to produce a primary magnetic field region about the cooling container for hyperpolarization of the plurality of samples and a secondary magnetic field region offset from the primary magnetic field region that extends axially out from the superconducting magnet,
wherein the superconducting magnet is further configured to operate without quench or loss of liquid helium when disconnected from the refrigeration system; and
at least one thermal bus connecting the refrigeration system, the helium condenser, the magnet condenser, and the thermal switch,
further wherein the apparatus comprises a closed system.
2. The apparatus of claim 1 wherein the superconducting magnet is further configured to operate in proximity to a magnetic resonance (MR) imaging field without degrading a homogeneity thereof.
3. The apparatus of claim 1 wherein the sorption pump operates in a sorption mode when the thermal bus is connected to the thermal switch and operates in a desorption mode when the thermal bus is disconnected from the thermal switch.
4. The apparatus of claim 3 wherein the sorption pump is configured to reduce pressure in the cooling container and vaporize a portion of the cryogenic refrigerant therein when operating in sorption mode.
5. The apparatus of claim 4 wherein the helium condenser is configured to recondense the vaporized cryogenic refrigerant when the sorption pump is operating in desorption mode.
6. The apparatus of claim 5 further comprising a pumping line to transfer the vaporized cryogenic refrigerant from the sorption pump to the helium condenser.
7. The apparatus of claim 1 wherein the sorption pump further comprises:
a pump enclosure;
a sorbent material housed within the pump enclosure; and
cooling fins interspersed within the sorbent material and connected to the thermal switch, wherein the cooling fins cool the sorbent material when the sorption pump is in sorption mode.
8. The apparatus of claim 1 further comprising a vacuum chamber that encloses the apparatus.
9. The apparatus of claim 8 further comprising an ante-chamber attached to the vacuum chamber to maintain a vacuum in the vacuum chamber when loading the substance to be polarized into the cooling chamber.
10. The apparatus of claim 1 further comprising:
a waveguide positioned to transmit microwaves to the substance to be polarized; and
a nuclear magnetic resonance (NMR) coil positioned within the cooling container and about the substance to be polarized, wherein the NMR coil is configured to detect a level of polarization of the substance.
11. The apparatus of claim 1 wherein the cryogenic refrigerant is liquid helium.
12. The apparatus of claim 1 wherein the substance to be polarized is 13C1-pyruvate.
13. A polarizing subsystem comprising:
a container having a liquid helium bath configured to receive a material to be polarized;
a sorption pump to reduce a pressure in the container, thereby to vaporize a portion of the liquid helium bath, the sorption pump comprising:
a sorb can configured separate, spaced apart, and exterior to the container;
a cooling system comprising:
a magnet condenser configured separate, spaced apart, and exterior to the container, configured to recondense liquid helium boiled off therefrom and cool the sorption pump and promote molecular adsorption therein;
a thermally conductive link that selectively connects the sorption pump and the cooling system to provide selective cooling to the sorption pump;
a heater disposed adjoining the sorption pump, the heater configured to heat the sorption pump and promote molecular desorption therein;
a single magnetic field producing device configured to maintain a selected magnetic field for polarizing the material in the apparatus, wherein the single magnetic field producing device is cooled by the cooling system,
wherein the polarizer system operates in a closed cyclical thermal cycle alternating between a polarizing phase and a reheating phase based on the thermally conductive link of the sorption pump to the cooling system.
14. The polarizer system of claim 13 further comprising a thermal switch to connect and disconnect the thermally conductive link from the sorption pump.
15. The polarizer system of claim 14 wherein the thermal switch connects the thermally conductive link to the sorption pump during the polarizing phase and disconnects the thermally conductive link from the sorption pump during the reheating phase.
16. The polarizer system of claim 13 further comprising a helium condenser to recondense the vaporized helium when the polarizer system is in the reheating phase.
17. The polarizer system of claim 13 wherein the cooling system is configured as a closed cycle refrigerator to produce cryogenic temperatures.
18. A method for producing a hyperpolarized material comprising:
placing a material sample in a vessel containing a liquid helium bath;
reducing a temperature of the liquid helium bath with a sorption pump and a refrigeration system, wherein the sorption pump comprises:
a sorb can configured separate from and exterior to and spaced apart from the vessel,
wherein the refrigeration system comprises:
a helium condenser configured separate from and exterior to and spaced apart from the vessel;
refilling the liquid helium bath by heating the sorption pump with a heater, the heater being disposed adjoining the sorption pump;
positioning a single magnetic field producing device adjacent the vessel, wherein the single magnetic field producing device is configured to product a high homogeneity magnetic field and a fringe magnetic field offset from the high homogeneity field; and
polarizing the material sample when the liquid helium bath has been sufficiently cooled by the single magnetic field producing device.
19. The method of claim 18 wherein reducing a temperature further comprises:
lowering a pressure in the vessel by way of the sorption pump; and
vaporizing a portion of the liquid helium bath at the lowered pressure.
20. The method of claim 19 further comprising recondensing the vaporized helium by way of a magnet condenser to refill the vessel with liquid helium.
21. A polarizer system comprising:
a refrigerator;
a magnet condenser;
a helium condenser;
a thermal bus permanently linking the refrigerator, the magnet condenser, and the helium condenser;
a sorption pump selectively linked through a thermal switch to the thermal bus;
a heater adjoining the sorption pump;
a container containing a cryogenic refrigerant therein, configured to receive a plurality of samples for polarizing therein;
a magnetic field producing device in a magnet vessel surrounding the container;
wherein the polarizing system is further configured to operate in three separate modes, wherein:
a first mode comprises:
heating the sorption pump with the heater, thereby releasing helium gas to be cooled and liquefied by the helium condenser, wherein the released helium gas heats the thermal bus, thereby isolating the magnet vessel due to a thermal diode effect at the magnet condenser;
a second mode comprises:
upon completion of condensation of helium from the sorption pump, turning off the heater and cooling the sorption pump by closing the thermal switch, thereby creating a thermal linkage of the sorption pump, the thermal bus and the refrigerator, and thermally isolating the magnetic field producing device from the thermal bus; and,
a third mode comprises:
cooling the magnetic field producing device, thereby eliminating a thermal diode effect of the magnet condenser.
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| Application Number | Priority Date | Filing Date | Title |
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| US14/103,294 US20140123681A1 (en) | 2007-04-02 | 2013-12-11 | Method and apparatus to hyperpolarize materials for enhanced mr techniques |
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| Application Number | Priority Date | Filing Date | Title |
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| US11/695,411 US20080242974A1 (en) | 2007-04-02 | 2007-04-02 | Method and apparatus to hyperpolarize materials for enhanced mr techniques |
| US14/103,294 US20140123681A1 (en) | 2007-04-02 | 2013-12-11 | Method and apparatus to hyperpolarize materials for enhanced mr techniques |
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| US11/695,411 Continuation-In-Part US20080242974A1 (en) | 2007-04-02 | 2007-04-02 | Method and apparatus to hyperpolarize materials for enhanced mr techniques |
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