WO2013068448A1

WO2013068448A1 - Improved production of laser-polarized xenon

Info

Publication number: WO2013068448A1
Application number: PCT/EP2012/072114
Authority: WO
Inventors: Leif SCHRÖDER; Christopher Witte; Martin KUNTH; Federica ROSELLA; Jörg DÖPFERT
Original assignee: Forschungsverbund Berlin E.V.
Priority date: 2011-11-09
Filing date: 2012-11-08
Publication date: 2013-05-16

Abstract

The invention describes a polarizing cell comprising an inner enclosure (1) having a side wall defining an interior with at least one pair of openings including a gas entrance (6) and exit (7) to allow a gas mixture to pass through the interior, and at least one window transparent to laser light (9); contained within an outer enclosure (2) with at least one partitioning device to divide the volume outside the above mentioned inner enclosure into two or more compartments (3,4) that are maintained at different temperature.

Description

Improved production of laser-polarized xenon

DESCRIPTION

The invention concerns a polarizing cell for spin exchange optical pumping contained within an outer enclosure, wherein the outer enclosure generates two compartments, namely one hot and one cooled compartment.

BACKGROUND OF THE INVENTION

Magnetic resonance imaging (MRI) is an imaging technique used to visualize detailed internal structures. MRI depends on the generation of strong and uniform magnetic fields. MRI being a modality of choice for an increasing number of specialists for both structural anatomical and functional human MRI imaging. The basic components of a typical magnetic resonance system for producing images for human studies include a main magnet (usually a superconducting magnet which produces the substantially homogeneous magnetic field, one or more sets of shim coils, a set of gradient coils, and one or more radio-frequency (RF) coils.

MRI generates 2 dimensional and 3 dimensional images of objects using nuclear magnetic resonance (NMR). The process begins with positioning the object to be imaged in a strong, uniform magnetic field, which polarizes the nuclear magnetic moments of any NMR active nuclei by forcing their spins into one of two possible orientations upon measurement. Then an appropriately polarized RF field, applied at resonant frequency, forces spin transitions between orientations. As these spins recover to their equilibrium, they create a signal that can be detected by a receiving coil.

An MRI scanner applies the RF field as finely crafted pulses, which usually only excite protons whose resonant frequencies fall within a fairly narrow range. Applying magnetic-field gradients during the radio-frequency pulse creates resonant conditions for only the protons that are located in a thin, predetermined slice of the body. Orientation and thickness of this slice can be selected arbitrarily. The NMR signal encodes positional information across the slice by using a method known as the "spin warp" and a two-dimensional Fourier transform extracts that positional information. The process creates a data matrix in which each element represents an NMR signal from a single, localized volume element, or voxel, within the imaged slice. A two-dimensional display of this matrix's contents creates a human-readable image of the selected slice. Each image element, or pixel, represents the NMR signal strength that was recorded for its corresponding voxel. MRI can be used for various medical applications. For example MRI of the lung, using hyperpolarized xenon instead of water protons, yields important information about ventilation or perfusion of the organ without using any ionizing radiation and at superior temporal and spatial resolution compared to szintigraphic imaging. The technique is based on an increased magnetization of the noble gas xenon, produced by converting laser light polarization into xenon nuclear spin polarization. The noble gas serving as the contrast agent is therefore also called laser-polarized xenon. The term "hyperpolarized gas" describes a non-zero nuclear spin gas in which nuclei spins are artificially aligned along the quantization axis defined by a uniform magnetic field beyond the thermal equilibrium value.

However, to become a competitive diagnostic tool, data acquisition must be accomplished during a breath-hold period that is of an acceptable short duration. Hence, production of a sufficiently large volume of the noble gas with high spin polarization is the key to improve the signal-to-noise ratio for fast image encoding. The polarization process needs high photon densities in an extended volume for polarization build-up. Modern lasers provide good preconditions to achieve this but problems of ensuring homogeneous illumination inside the polarization apparatus have been repeatedly reported and limit the benefits that can be drawn from powerful lasers.

Xenon is a chemical element with the symbol Xe and atomic number 54. Naturally occurring xenon consists of nine stable isotopes. Besides these stable forms, there are over 40 unstable isotopes that have been discovered. Nuclei of two of the stable isotopes of xenon, ¹²⁹Xe and ¹³ Xe, have non-zero intrinsic angular momenta (nuclear spins, suitable for nuclear magnetic resonance). The nuclear spins can be aligned beyond ordinary polarization levels by means of circularly polarized light and rubidium vapor. The resulting spin polarization of xenon nuclei can surpass 50% of its maximum possible value, greatly exceeding the equilibrium value dictated by the Boltzmann distribution (typically 0.001 % of the maximum value at room temperature). Such non-equilibrium alignment of spins is a temporary condition, and is called hyperpolarization. The process of hyperpolarizing the xenon is called spin exchange optical pumping (SEOP).

This method which has become standard for polarizing noble gases makes use of optical pumping of alkali metals (rubidium (Rb) in most cases) followed by polarization transfer (spin exchange) to the noble gas nucleus during collisions. A polarization degree of ~10% -20% is currently standard for Xe polarizers using optical pumping of Rb and spin exchange, with an output close to 11/h. Spin exchange optical pumping is a well established method to produce hyperpolarized (hp) noble gases such as helium or xenon for NMR and MRI applications with a ~10,000-fold increased sensitivity. The technique is based on using circular polarized laser light at ca. 795 nm to pump the D1 transition of rubidium vapour in a static magnetic field. This can achieve almost complete Rb electron spin polarization which is then transferred onto, e.g., xenon (Xe) nuclear spins through spin-spin interactions. Setups for animal or clinical applications are available through Polarean (formerly GE Medical, formerly

MITI/Nycomed Amersham) or XeMed. This method takes advantage of the fact that the photons of circularly polarized light have angular momentum with a well-defined projection on the direction of motion (helicity). The interaction of polarized photons with alkali atoms placed in a magnetic field leads to a non-equilibrium population of such atoms of the ground state (optical pumping).

Schematically, the components of a polarizer are: (a) a cell with specially prepared surface; (b) gas mixture consisting of the vapour of the alkali metal (usually rubidium ), the noble gas to be polarized and buffer gas consisting of nitrogen or nitrogen and ⁴He; and (c) the laser system. The cell is placed in a magnetic field, parallel to the direction of propagation of the laser light, with strength ranging from a few tens of Gauss produced by Helmholtz coils, to a few hundred Gauss in the fringe fields of NMR magnets or inside solenoid coils. Each component has to be carefully optimized, resulting in a rather complicated, multiparametric problem. The laser power is chosen such that the polarization of the Rb atoms is maintained to a high degree by optical pumping. The dimensions of the polarizing vessel should ensure that for the laser power used a nearly homogenous illumination is attained, resulting in a nearly uniform Rb polarization. Special coating of the glass is needed since wall surface relaxation is an important factor in polarization loss. The alkali vapour and gas mixture are kept at constant temperature by an oven. The temperature also has to be optimized, since most quantities which influence the degree of polarization depend on it. A value of 120° C is found to ensure a high Rb polarization as well as its uniform distribution over the cell, for a typical xenon polarizer. Rb is usually chosen since its high vapour pressure allows operation at relatively low temperature, avoiding chemical corrosion of the cell and reducing diffusion- mediated wall relaxation.

Polarizers can operate in either batch or continuous flow mode. In order to obtain the rather large quantities needed for medical applications several batches have to be accumulated. The polarized xenon is stored as ice in a cold finger kept at liquid nitrogen temperature.

At high Xe concentrations (i.e., typically beyond ca. 2% partial pressure of a He/N2/Xe gas mixture) the Rb polarization is reduced, in turn this reduces the fraction of Xe that is polarised. Increasing the photon density (through increased laser power) can improve the Rb polarisation and hence the Xe polarization while increasing the Xe fraction. A deleterious side effect is that higher photon density comes with amplified heat production inside the pumping cell which in return often yields higher Rb vapour density in designs where an amount of Rb (for example a droplet) is located directly inside the pumping volume as the source of Rb vapour. The observable chain reaction with more and more Rb vapour is called rubidium runaway. It generates areas of dense, highly absorptive Rb clouds (often at the entrance window where the laser beam enters the pumping cell), leading to inhomogeneous cell illumination and, consequently, poor Xe polarization.

Several polarizers are described in the prior art to address the problem.

A design proposed by the University of New Hampshire (UNH)/XeMed aims to solve this problem by separating the area of Rb vaporization from the pumping volume to enable high laser transmission throughout the cell. It also uses strong cooling of the pumping cell entrance window. However, the main purpose of this cooling jacket is to completely condense any remaining Rb in order to prevent alkali metal impurities outside the pumping cell. This UNH design requires a relative large pumping cell (ca. 180 cm overall length, 4 cm diameter) and a water cooling jacket (operated at 10°C) which can be a safety issue in terms of direct proximity to the glass apparatus containing the alkali metal. Moreover, the system is optimized for low gas pressures to benefit from better Rb-Xe spin transfer rates. This type of polarizer usually aims to produce large amounts of polarized xenon that is frozen out in a cold trap located behind the pumping cell in the direction of gas travel. It represents a suitable system for MRI applications with Xe in gas phase such as lung imaging where one batch of Xe ice is produced, sublimated and used for a relative short series of experiments.

In US 7,495,435 B2 an apparatus for hyperpolarizing atomic nuclei through optical pumping is depicted. The apparatus has a cylindrical optica! pumping cell having an inlet and an outlet spaced therefrom. A supply of a mixture of optically pumpable species and hyperpolarizable nuclei is connected to the inlet of the cell. A nozzle at an inlet of the optical pumping cell forms and injects a jet flow of the mixture into the optical pumping cell. It is then drawn out through the outlet such that the mixture touches the inner walls of the optical pumping cell only adjacent the outlet.

Furthermore, WO 2008/036369 A2 discloses a polarizing apparatus that has a thermally conductive partitioning system inside a polarizing cell. In the polarizing region, this thermally conductive partitioning system serves to prevent the elevation of the temperature of the polarizing cell where laser light is maximally absorbed to perform the polarizing process. By employing this partitioning system, increases in laser power of factors of ten or more can be beneficially utilized to polarize xenon. Accordingly, the polarizing apparatus and the method of polarizing ²⁹Xe achieves higher rates of production. A number of potential drawbacks of this approach are as follows: The dramatically larger surface area increases the overall contribution of the layer of depolarized rubidium lining the surface. This will increase laser absorption along the surfaces. There will also be a depolarizing effect of copper on the ²⁹Xe. Another disadvantage of the prior art is, that the various polarizers are physically large, which makes them difficult to move or transport.

Other polarizers of the prior art usually have a small pumping cell volume and work at increased gas pressure to ensure better laser light absorption. However, the spin transfer rate is worse at higher pressure, so the system has to be optimized such that the inflowing xenon picks up polarization as fast as possible. This is achieved by high densities of rubidium vapour, which speed up the dynamics of xenon polarization build-up. This requires high laser power that usually comes with the deleterious side effect already mentioned, rubidium runaway. This causes the polarization process to collapse after warm-up.

SUMMARY OF THE INVENTION

In light of the prior art, the technical problem underlying the present invention is to provide a polarizer that yields large volumes of hyperpolarized noble gas without uncontrollable high concentrations of alkali metal vapor and to overcome the disadvantages of the prior art. This includes a setup for stable flow of the Xe gas mix through the cell and consistent delivery of hyperpolarized xenon into solutions when operating in continuous flow mode.

This problem is solved by the features of the independent claims. Preferred embodiments of the present invention are provided by the dependent claims.

Therefore, a polarizing cell is provided, comprising an inner enclosure having a side wall defining an interior with at least one pair of openings including a gas entrance and exit to allow a gas mixture to pass through the interior, and at least one window transparent to laser light. The polarizing cell is contained within an outer enclosure with at least one partitioning device to divide the volume outside the above mentioned inner enclosure into two or more compartments, that are preferably maintained at different temperature.

It is further preferred, that the partitioning device of the outer enclosure is fitting around the cross sectional shape of the inner enclosure, wherein

a. one compartment is for heating at least one section of the inner enclosure, preferably including a feed-through for the gas entrance/exit that leads into this heated part of the inner enclosure;

b. one compartment is for cooling, especially actively cooling another section of the inner enclosure, preferably including a feed-through for the gas exit/entrance that leads out of the inner enclosure and at least one opening transparent to laser light;

c. these two compartment work to maintain a temperature differential across the polarizing cell. The cell is preferably structured, that the inner enclosure contains at least one alkali metal (preferably a small amount or droplet of a liquid or solid alkali metal) residing in that area of the inner enclosure that protrudes into the heated compartment. The wording "a small amount" is not ambiguous for a person skilled in the art, as the skilled person is able to simply calculate the amount of alkali metal needed to generate the preferred amount of hyperpolarised xenon.

In a preferred embodiment, the part of the outer enclosure defining the cooled compartment comprises a method for cooling the polarizing cell in this region, preferably a feed-through for a nozzle to pump in a coolant medium to reduce the temperature in this volume. This compartment is built to be not pressure tight in order to release the warm coolant while delivering fresh coolant.

In another preferred embodiment, the temperature of the cooled section of the polarizing cell, preferably by adjusting the flow through the nozzle, is controlled by:

a. a device to read the surface temperature of the inner enclosure in the cooled compartment and to use this value as an input for

b. a method of adjusting the cooling apparatus to maintain a constant, desired temperature as measured by the device of a.

Further preferred is a controller, preferably an electronic proportional-integral-differential (PID) controller that adjusts the coolant flow through the above mentioned nozzle via a device for adjusting the flow (for example a mass flow controller) for matching the surface temperature with the set point for the cooled compartment.

Therefore, the preferred cell allows adjusting the ambient temperature of the inner enclosure in the cooled compartment by regulating the coolant flow through the nozzle.

The invention also relates to a computer-controlled user interface to select the set value for the cooling process and to monitor the process value of the controller circuit (i. e. PID) and the amount of coolant flow through the mass flow controller.

Furthermore, the invention concerns a polarizing apparatus comprising:

a. a polarizing cell setup of claim 1 located in a sufficiently uniform magnetic field, preferably located in a compact set of magnetic field coils, arranged around the outer enclosure of the cell, not necessarily in the Helmholtz configuration;

b. laser light, at the absorption wavelength of the alkali metal vapor, propagating through at least one transparent window into the outer and inner enclosure of the cell; c. an optical arrangement to cause the laser light to be substantially circularly polarized.

The polarizing apparatus preferably comprises:

a. a gas mixture containing at least a polarizable nuclear species, at least one alkali metal vapor generated by at least one alkali metal and at least one gas for quenching optical transition of the alkali metal(s);

b. a heating device to cause the surface temperature of the inner enclosure to be elevated in the non-cooled compartment to induce partial vaporization of at least one alkali metal.

Furthermore, the polarizing apparatus comprises preferably:

a. a nonferrous inner enclosure with an interior and at least two openings for flowing gas to pass through; and

b. the window of the inner and outer enclosure allowing laser light to at least partially illuminate the interior of the inner enclosure, preferably the windows are maintained at (not necessarily identical) temperatures substantially lower than the heated part of the inner enclosure.

It is preferred, that the inner enclosure is more than two times greater in length than in diameter.

Furthermore, it is preferred that the surface temperature of the inner enclosure in the heated compartment is more than 1 10°C.

In a preferred embodiment, the surface temperature of the inner enclosure in the cooled compartment is more than 100°C and at least 10°C colder than the surface temperature of the inner enclosure in the heated compartment.

The invention also concerns a magnetic field generator or apparatus that provides a uniformly oriented, preferably homogeneous, magnetic field over the entire range of the inner enclosure.

The invention also relates to a gas flow control apparatus for hyperpolarized species generated with a polarizing apparatus comprising:

a. tubing connecting the outlet of the polarizing apparatus with the inlet of a test volume (for example a test tube) inside a setup capable of performing NMR and/or MRI experiments;

b. tubing connecting the outlet of this very test volume to vent gas out of NMR/MRI setup; c. a flow control unit before or after the test volume.

Preferably, the gas flow control apparatus, wherein the gas flow through the pumping cell and hence the test tube/volume is stabilized and can be adjusted to a setpoint and the flow through the cell and the inlet tubing is maintained constant even if the flow through the test volume is temporarily stopped.

It is preferred, that the inlet tubing bifurcates closely to the test volume inlet into another tubing that directs gas out of the NMR/MRI setup while flow through the test volume is stopped.

In a preferred embodiment, the gas flow through the tubes is controlled via mass flow controllers that can be triggered by signals from the NMR/MRI setup while executing a NMR/MRI pulse sequence.

The invention also concerns a computer-controlled user interface to control the polarizing apparatus to select the set value for the cooling process and to monitor the process value of a controller circuit and the amount of gas flow through a device for adjusting the flow, especially a mass flow controller. In another preferred embodiment, the mass flow controllers are operated through a computer-controlled user interface or a manual interface. The computer-controlled user interface preferably controls the apparatus to select the set value for the cooling process and to monitor the process value of a controller circuit and the amount of gas flow through a device for adjusting the flow, especially a mass flow controller.

DETAILED DESCRIPTION OF THE INVENTION

The polarizing cell provided ensures a high production rate of hyperpolarized noble gas, preferably xenon in a compact and moveable cell. A currently commercially available system can produce approximately 0.16 L/hour of ¹²⁹Xe with a polarization of approximately 5%. The polarizer according to the invention allows the production of especially 0.55 L/hour of xenon with a polarization of 16%. The polarizing cell converts more photon polarization into usable xenon spin polarization with applications like more efficient lung imaging and earlier disease detection of, e. g. chronic obstructive pulmonary disease (COPD).

Several recent applications that use hyperpolarized (in the sense of the invention also described as "hp") xenon as a functionalized contrast agent in solution state require a continuous production of hp gas without a freezing step. Such experiments are based on the idea that the Xe gas mixture is used directly from the pumping cell and transferred into the test solution over longer periods of time to acquire dataset series with constant fresh Xe delivery. This is especially true for the Hyper-CEST technique, where signal variations in arrays of spectra are observed. Many existing polarizers only have small pumping cell volumes (< 0.5 L) and when used for solution state experiments, such systems work at increased pressure (ca. 3-5 bar abs) to increase the amount of dissolved Xe and ensure better laser absorption due to pressure broadening. Unfortunately, the spin transfer rate is worse at higher pressure, so the system has to be optimized such that the inflowing Xe picks up polarization as fast as possible when operated in continuous flow mode. This can be achieved by high alkali metal densities (requiring relative high operating temperatures) which speed up the dynamics of Xe polarization build-up. However, the laser must be strong enough to maintain the high polarisation of the alkali metal spin pool while at the same time the setup must prevent the effect know as rubidium runaway (which can also occur with other alkali metals) to ensure sufficient cell illumination.

For experiments with functionalized xenon (i.e. ²⁹Xe trapped in molecular cages that have a specific targeting moiety) in solution state, a polarizing cell is provided for optimized production of hp Xe that prevents rubidium runaway in a relative small pumping cell for a more compact polarizer setup. For the polarization of rubidium, it is preferred to use a 150 W laser, however, it is also possible to use other laser energies.

The invention can especially be described as a dual compartment housing for a pumping cell, includes a simple, moderate cooling mechanism preferably based on a regulated air flow around the entrance window. For this purpose, the cell is placed inside a box, which is described in the sense of the invention as an outer enclosure, with a separation wall (or partitioning device). The partitioning device is preferably a part of the outer enclosure (e. g. a wall) and divides the volume outside the inner enclosure into two compartments. Therefore, the polarizing cell comprises preferably an inner enclosure and is contained within an outer enclosure, wherein the outer enclosure is divided into two compartments, namely a heated and a actively cooled compartment. A hot and a cold section on the outside of the cell are defined (see e. g. Fig. 1 ).

Heating of the heated compartment is preferably achieved by a silicon strip heater underneath the alkali metal (for example Rb droplet) in the rear part of the cell. However, alternative heating means can also be applied to the polarizing cell. The person skilled in the art is familiar with various heating techniques or methods that can be used for the polarizing cell. The heating or hot compartment can also be heated by, for example, hot air or a heated oil bath surrounding the hot part of the inner cell.

The heater is preferably kept at a temperature of approximately 180°C, wherein a thermocouple on top of the cell reads approximately 160°C while the laser is emitting. The front part of the outer enclosure, where the laser entrance window is located, inside the compartment contains an air nozzle connected to a compressed air supply (preferably at room temperature) and a mass flow controller (MFC). However, cooling of the cold compartment might also be achieved by other devices. A temperature sensor, preferably a thermocouple, that is preferably attached close to the entrance window monitors the temperature in this area and serves as an input for a controller, preferable a PID controller (proportional-integral-derivative controller), that controls the flow of coolant, in this case compressed air, through the regulator.

A diode laser combined with polarization optics and a beam expander produce to illuminate the whole pumping volume which can deliver circularly polarized light at the alkali metal excitation wavelength with a power of preferably greater than 100 W into the pumping cell. Without the active cooling, when switching the laser from medium to full power output, the Xe polarization transiently increases and then rapidly drops significantly by > 50% . This is due to the onset of rubidium runaway, producing temperatures >190°C around the entrance window and an opaque alkali metal atmosphere. High polarization with the benefit from full laser power can be recovered when activating the cooling mechanism and adjusting the cooling setpoint of the PID unit to preferably 130°C while the rear part of the cell remains preferably at ca. 160°C. This ensures improved cell illumination and better polarization transfer to the flowing Xe gas.

Contrary to the UNH design with its long pumping cell, where the temperature management is within the cell, the preferred polarizing cell controls the rubidium runaway although the alkali metal vaporization takes place directly inside the pumping volume by using a cooling mechanism. This allows working with a more compact design. Excessive cooling to temperatures <100° on the cell entrance surface as shown for the UNH setup is counter productive since this will reduce the overall cell temperature in a short pumping cells. The resulting reduced alkali metal vapour density comes with unwanted deceleration of the Xe polarization build-up.

The preferred polarizing cell can both prevent Rb runaway and preferably helps to condense the alkali metal near the gas exit. Moreover, using air as the coolant eliminates potential hazards represented by using water in direct proximity to the Rb apparatus.

Cooling at least one section of the inner enclosure is especially useful for the increased production of hp Xe. Common gas mixtures for SEOP contain 1-2% of Xe (remaining components: nitrogen and helium). A larger Xe fraction usually decreases the spin polarization and is only useful if the concentration increase at least outweighs this polarization loss. We observed that a powerful laser like a 120 W laser can in principle guarantee a high Rb polarization that serves an increased pool of Xe atoms. However, the additional Rb-Xe spin transfer causes more light absorption and eventually also more heat production inside the pumping cell. Increasing the Xe fraction from 2% to 5% makes the cooling device (in the sense of the invention the cooled or cold compartment of the inner enclosure can also be defined as cooling device) to operate at higher air flow rates. This compensates the additional heat production and even at the higher Xe concentration almost the same polarisation can be maintained (the polarisation drops from 16.8% to 15.8%). Without the cooling device, the deleterious Rb runaway effect would be even more intense at high Xe partial pressures.

An additional component that is preferred when running the polarizing cell or the preferred polarizing apparatus in continuous flow mode is a gas delivery apparatus for hyperpolarized species generated with a polarizing cell or apparatus comprising:

a. tubing connecting the outlet of the polarizing apparatus with the inlet of a test volume inside a setup capable of performing NMR and/or MRI experiments b. tubing connecting the outlet of this very test volume to vent gas out of

NMR/MRI setup;

c. a flow control unit before or after the test volume

Therefore, the gas delivery apparatus ensures stable flow and temperature conditions in the pumping cell and consistent delivery of hyperpolarized Xe although the flow into the sample is temporarily stopped for each NMR data acquisition. The gas flow through the pumping cell as well as transfer close to the sample is preferably kept constant. A bifurcation of the delivery line directly in front of the sample enables to divert the flow into a bypass line when gas delivery into the sample is not desired (see e. g. Fig. 2). Both the outlet coming from the sample and the bypass line are regulated through mass flow controllers (MFCs).

Software or hardware respectively processes the trigger pulses from the NMR spectrometer and controls the opening and closing of the MFCs as well as adjusting the flow rates. Behind the sample in the direction of the gas flow sits a valve connecting the sample and bypass lines. This valve is preferably closed during the normal operation of the gas delivery system but is opened during pressurisation or depressurisation to ensure the pressure is the same on either side of the sample. With preferred parameters of 0.03-0.5 SLM, a high signal stability of dissolved Xe for repetitive gas delivery is ensured (variations < 1 %).

FIGURES

The invention is further described by the figures. These are not intended to limit the scope of the invention.

Brief description of the figures: Fig. 1 Schematics of the preferred optical pumping cell with heating and cooling devices

Fig. 2 Schematics of the preferred flow control system

Fig. 3 Temperature profile of a preferred cell

Detailed description of the figures:

Fig. 1 shows schematics of the preferred optical pumping cell with heating and cooling devices. The outer enclosure (2) is preferably divided into a hot compartment (4) and a cooled compartment (3) to maintain a temperature differential across the polarizing cell (1 ). The laser light (8) enters the optical cell from the left passing through two windows transparent to the laser light (9). A heater (16) is preferably used to heat rubidium (for example a droplet) and create a rubidium vapour (5). The xenon gas mixture (15, 5 % natural abundance xenon, 10 % nitrogen and 85 % helium) flows counter to the direction of laser propagation from the gas mix inlet (6) to the gas mix outlet (7). Temperature sensors (14) monitor the temperature of the polarizing cell in the cooled section and heated

compartments. The output from temperature sensor in the cooled is fed into a controller (10, preferable an PID controller) which changes the flow of room temperature air (13) using a mass flow controller (1 1 ) ensuring a stable temperature. A temperature regulator (12) keeps the heated side of the polarizing cell at a constant elevated temperature using input from the temperature sensor and the heating device (16).

Fig. 2 shows schematics of the preferred flow control apparatus. The preferred gas delivery apparatus ensures a continuous and stable flow through the pumping cell and batch-wise delivery of Xe into the sample, triggered by the NMR spectrometer. The hyperpolarized gas (23) flows out of the polarizer (28) and into a line that bifurcates close to the sample (24). Gas flow to (26) and from (27) the sample is controlled by a mass flow controller (19) situated either before or behind the sample, preferably behind to prevent loss of polarisation. Gas flow through the bypass line (25) is also controlled by a mass flow controller (20).

Trigger signals (18) from the NMR control unit (17) alternately direct the gas flow either through the gas bypass or through the sample. A control computer (21 ) sets the flow setpoints (29) of the two mass flow controllers, preferably to the same value thus ensure a constant flow through the polarizer.

Fig 3. Plot depicting effect of changes in temperature on the Xe polarization. Three thermocouples are preferably used to monitor the temperature throughout the cell, which can be used to observe the process of rubidium runaway. Initially the laser power was especially set to 100 W and the cell was allowed to stabilise. At time 0 the laser power was increased to 150 W while continuously monitoring the xenon polarisation in terms of detectable signal of the gas flowing directly from the polarizer into an NMR spectrometer. As can been seen in Fig 3, initially the xenon polarisation drops as the laser wavelength depends on the power output. After a few minutes the laser wavelength has re-stabilized. As the temperature increases due to increased laser absorption, so does the xenon polarisation, indicating that the laser is strong enough to maintain the polarisation of the rubidium at higher rubidium densities. After approximately 25 minutes the temperature at the exit of the cell stabilises, indicating that the laser light is no longer penetrating to this area and heating it. At approximately 62 minutes there is a rapid heating of the laser entrance of the cell with a decrease in the temperature of the centre and exit of the cell. Due to the high temperature the rubidium density at the entrance rapidly increases, and the laser no longer penetrates through the cell. This is followed by a rapid loss of xenon polarisation due to the poor illumination of the cell. At 69 minutes the temperature at the entrance of the cell is actively cooled to preferably 120°C. Within a couple of minutes, the rubidium vapour density is decreased and the laser begins to penetrate though the cell again. After optimising the cooling of the cell entrance, it is possible to recover almost the entire polarisation that was initially achieved due to increased laser power. With this setup it is possible to increase the Xe partial pressure and achieve a polarisation of 15.8 % at a gas flow rate of 0.5 SLM. Xe signal changes from ca. 0.2 a.u. at 100W output to ca. 0.85 at 150 W, i.e. ca. A 4-fold increase due to optimized temperature handling.

Reference signs:

1. Inner enclosure

2. Outer enclosure

3. Cooled compartment

4. Heated compartment

5. Rb vapor

6. Gas mix inlet

7. Gas mix outlet

8. Circularly polarised laser light

9. Window transparent to laser light

10. PID contorller

11. mass flow controller

12. Temperature regulator

13. Room temperature air

14. Temperature sensors

15. Xenon gas mix

16. Heating device

17. NMR control unit

18. Trigger signal

19. Sample flow controller

20. Bypass flow controller

21. Control computer

22. Gas vent

23. Gas outlet from polarizing cell

24. Sample

25. Gas bypass

26. Gas to sample Gas from sample Polarizer Flow setpoints

Claims

Claims What is claimed is:

1. A polarizing cell comprising an inner enclosure having a side wall defining an interior with at least one pair of openings including a gas entrance and exit to allow a gas mixture to pass through the interior, and at least one window transparent to laser light, wherein this polarizing cell is contained within an outer enclosure with at least one partitioning device to divide the volume outside the above mentioned inner enclosure into two or more compartments.

2. A cell of claim 1 , wherein the partitioning device of the outer enclosure is fitting

around the cross sectional shape of the inner enclosure, wherein

b. one compartment is for cooling another section of the inner enclosure,

preferably including a feed-through for the gas exit/entrace that leads out of the inner enclosure and at least one opening transparent to laser light;

c. these two compartment work to maintain a temperature differential across the polarizing ceil.

3. A cell of claim 2, wherein the inner enclosure contains at least one alkali metal

residing in that area of the inner enclosure that protrudes into the heated

compartment.

4. A cell of claim 2, wherein the part of the outer enclosure defining the cooled

compartment comprises a method for cooling the polarizing cell in this region.

5. A cell of claim 4, wherein the temperature of the cooled section of the polarizing cell is controlled by:

b. a method of adjusting the cooling apparatus to maintain a constant, desired temperature as measured by the device of a. The device can be any temperature sensor known to the skilled person.

6. A cell of claim 5, wherein the surface temperature of the inner enclosure in the heated compartment is more than 1 10°C.

7. A cell of claim 6, wherein the surface temperature of the inner enclosure in the cooled compartment is more than 100°C and at least 10°C colder than the surface temperature of the inner enclosure in the heated compartment.

8. A polarizing apparatus comprising:

a. a polarizing cell setup of claim 1 located in a sufficiently uniform magnetic field;

b. laser light, at the absorption wavelength of the alkali metal vapor, propagating through at least one transparent window into the outer and inner enclosure of the cell;

c. an optical arrangement to cause the laser light to be substantially circularly polarized.

9. A polarizing apparatus of claim 8 further comprising:

a. a gas mixture at least containing a polarizable nuclear species, at least one alkali metal vapor generated by at least one alkali metal and at least one gas for quenching optical transition of the alkali metal(s);

10. A polarizing apparatus of claim 8 wherein the apparatus comprises:

b. the window of the inner and outer enclosure allowing laser light to at least partially illuminate the interior of the inner enclosure.

11. A polarizing apparatus of claim 10, wherein the inner enclosure is more than two times greater in length than in diameter.

12. A gas flow control apparatus for hyperpolarized species generated with an apparatus of claim 8 comprising:

a. tubing connecting the outlet of the polarizing apparatus with the inlet of a test volume inside a setup capable of performing NMR and/or MRI experiments; b. tubing connecting the outlet of this very test volume to vent gas out of

NMR/MRI setup;

c. a flow control unit before or after the test volume.

13. A gas flow control apparatus of claim 12, wherein the gas flow through the pumping cell is stabilized and can be adjusted to a setpoint and the flow through the cell and the inlet tubing is maintained constant even if the flow through the test volume is temporarily stopped.

14. A gas flow control apparatus of claim 13, wherein the inlet tubing bifurcates closely to the test volume inlet into another tubing that directs gas out of the NMR/MRI setup while flow through the test volume is stopped.

15. A gas flow control apparatus of claim 14, wherein the gas flow through the venting tubes is controlled via mass flow controllers that can be triggered by signals from the NMR/MRI setup while executing a NMR/MRI pulse sequence.

16. A gas flow control apparatus of claim 15, wherein the mass flow controllers are

operated through a computer-controlled user interface or a manual interface.

17. A computer-controlled user interface to control an apparatus of claim 8 to select the set value for the cooling process and to monitor the process value of a controller circuit and the amount of gas flow through a device for adjusting the flow, especially a mass flow controller.