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Production of laser-polarized 3 He gas via metastability exchange optical pumping for magnetic resonance imaging

Production of laser-polarized 3 He gas via metastability exchange optical pumping for magnetic... The state-of-the-art in the production of hyperpolarized 3He gas for magnetic resonance imaging (MRI) of the human lungs is reviewed. The paper is focused on the metastability exchange optical pumping (MEOP) method, which is preferable in medical applications, because the polarized 3He gas is free of any contaminants. Two strategies, namely, "centralized" and "onsite" production, are compared from the point of view of efficiency, level of achievable polarization, and the cost. A novel design of the polarizer that is based on MEOP operating in nonstandard conditions is also presented. It is the most promising solution for the implementation of the technique in medical clinics, as it uses the magnetic field of the MRI scanner and operates at elevated 3He gas pressure. Keywords: atomic optics; hyperpolarization; magnetic resonance imaging; medical imaging; physics. DOI 10.1515/bams-2014-0004 Received February 17, 2014; accepted July 3, 2014; previously published online August 12, 2014 Bartosz Glowacz*, Mateusz Suchanek and Zbigniew Olejniczak Introduction Very often, advanced physical methods that were initially developed for fundamental research find new applications in other fields of science or technology that have not been considered before. A case in point was the *Corresponding author: Bartosz Glowacz, Institute of Physics, Jagiellonian University, Kraków 30-059, Poland, E-mail: b.glowacz@uj.edu.pl Mateusz Suchanek: Department of Chemistry and Physics, Agricultural University, Kraków, Poland Zbigniew Olejniczak: Institute of Physics, Jagiellonian University, Kraków, Poland; and Institute of Nuclear Physics, Polish Academy of Sciences, Kraków, Poland development of optical polarization techniques of 3He and 129 Xe noble gases, which was motivated by nuclear scattering experiments [1, 2]. Although the application of 3He in magnetometry was already suggested at that time [3], a real explosion of interest occurred when it was realized that hyperpolarized noble gases could be used as contrast agents in magnetic resonance imaging (MRI). The standard proton-based MRI is a well-established noninvasive medical diagnostic method. It provides highresolution images of the interior of the human body, without causing any side effects as in the case of computed tomography (CT), which uses ionizing radiation. MRI exploits high water density in living tissues, measuring the nuclear magnetization of water protons produced by the high magnetic field of the MRI scanner. However, this technique fails for lungs or sinuses that are filled with air of very low water density, which gives insufficient proton signal for a successful image generation. It should be stressed that similar difficulties occur in CT and ultrasonography (USG) due to the lack of proper absorber in the anatomical airspaces. Although important technological advances have been made in recent years to overcome the problem of low proton density in the lungs and short T2* value [4], it is still a field of active research that has not found its way to the clinics. Therefore, finding an alternative method of anatomical and functional characterization of ventilated airspaces was of critical importance for successful medical diagnostics and treatment. The solution was proposed and implemented in 1994 by Albert et al. [5], who used the optically polarized 129Xe gas as a contrast agent. When introduced into the lungs of a mouse, the spin ½ 129Xe nuclei of about 10% polarization produced a strong enough signal for MRI in spite of the low density of the gas and a much lower resonance frequency. One year later, an analogous experiment was performed using hyperpolarized 3He [6]. In both cases, the high nuclear polarization that is achieved by optical pumping (OP) is independent of magnetic field, in contrast to thermal equilibrium polarization. Therefore, 130Glowacz et al.: 3He MEOP polarizers for lung magnetic resonance imaging sufficiently strong signals for high-quality MRIs can be measured even in low magnetic field, low-cost medical scanners [7, 8]. The first image of the human lungs using the hyperpolarized 3He gas was obtained in 1996 [9, 10]. In the last 20 years, there has been great progress in the structural and functional imaging of the lungs. Apart from producing high-resolution anatomical images, novel techniques have been developed to monitor the dynamics of ventilation [11] and to determine diffusion maps [12] and the distribution of oxygen partial pressure [13]. In human studies, 3He is preferred over 129Xe, which gives a stronger signal due to the larger gyromagnetic ratio and higher level of nuclear polarization. Moreover, 3He does not cause any side effects, compared to 129Xe, which is anesthetic and requires a careful monitoring of the gas dose and the physiological conditions of the patient. In this paper, after a brief comparison of two optical polarization methods for noble gases, the 3He optical polarizers based on the metastability exchange optical pumping (MEOP) process are reviewed. Two main strategies of the gas production, namely, "centralized" and "on-site" are discussed, the latter being preferable when the MEOP in nonstandard conditions is implemented, utilizing the magnetic field of the medical MRI scanner. Due to the recent difficulties in purchasing 3He, a special section is dedicated to the problem of gas administration, recovery, and recycling. Finally, the prospects for the further development of the method are presented, including the idea of combining 3 He MRI with the positron emission tomography (PET) technique. the electron polarization of rubidium atoms is transferred to nuclear spins of noble gas atoms by atomic collisions [15]. The SEOP method requires high laser power, and it takes a few hours to achieve the required nuclear polarization at the pressure of several atmospheres. Finally, the gas is cooled down at the exit of the OP cell in order to remove the rubidium vapor. The last step is important if the polarized gas is to be used in a medical examination in vivo. The MEOP is another polarization method, which so far works for 3He only. The OP cell is filled with a pure 3 He gas [16] or an isotopic mixture of 3He and 4He [17] at the pressure of few mbar, and is located in a small magnetic field, of the order of few mT. The OP is performed on the 2 3S1 metastable state. Since the transition from the ground state to the 2 3S1 state is forbidden, it is populated indirectly using the radiofrequency (RF) discharge. A few MHz of RF is delivered to the electrodes that are wound on the surface of the cell or placed inside. Alternatively, an electron beam can be used for that purpose, depending on the technical feasibility and requirement. The metastable state is optically pumped by a circularly polarized light of 1083 nm wavelength, so that the electronic hyperfine sublevels corresponding to desired nuclear spin orientation are populated. The nuclear polarization of 3He atoms in the ground state is achieved in the process of binary collisions with spinpolarized 3He atoms in the metastable state. Compared to SEOP, the MEOP process is more efficient, does not require high laser power, and takes place at room temperature, but a subsequent compression of the polarized gas is needed. The absence of potentially harmful alkali elements is its important advantage in medical applications. Although the development of both optical polarization methods has begun approximately at the same time, the MEOP has obtained a strong support in Europe within the two European framework programs: Polarized Helium Imaging for Lungs (PHIL, 2000­2004) and Polarized Helium for Lung Imaging Network (PHeLINet, 2007­2011). A comprehensive theoretical model that fully describes the dynamics of MEOP was developed, including the magnetic field and 3He pressure dependence of the polarization process efficiency [18­20]. In parallel, the experimental data in the whole parameter range were accumulated, fully supporting the model and allowing to optimize the technique [21]. On the basis of these results, the MRI of the human lungs using hyperpolarized 3He gas was introduced to the clinics, and special examination protocols were established for both anatomical and functional lung studies [13, 22­27]. Brief description of optical polarization methods Historically, the first MRI experiments with polarized noble gases were performed using the spin exchange optical pumping (SEOP) method, which was invented in 1960 and 1982 for 3He and 129Xe, respectively [1, 14]. In SEOP, a small amount of rubidium is placed in the OP cell, which is filled with the noble gas to be polarized and a buffer gas (N2 or 4He). The cell is located in a small magnetic field, of the order of few mT, in order to establish the quantization axis for electron and nuclear spins. After heating the cell to cause the evaporation of rubidium, its vapor is illuminated by a circularly polarized laser light of 795 nm wavelength. Almost 100% polarization of rubidium electron spins is achieved in the OP process. Then, Glowacz et al.: 3He MEOP polarizers for lung magnetic resonance imaging131 Polarized 3He gas production and delivery strategies using MEOP Two main ideas on how to supply the medical MRI unit with polarized 3He gas for human lung imaging have been pursued within the European community: the centralized and on-site production. Taking advantage of the long relaxation time of polarized gas when it is kept at the 1 bar pressure in a homogeneous magnetic field, a high-efficiency centralized facility was built by the group of Werner Heil at the Johannes Gutenberg Universität in Mainz, Germany [28]. Since the gas polarization could be preserved for several tens of hours, it could be distributed all over Europe. It should be noted that such strategy would be hard to realize for 129Xe, which has a relaxation time of a few hours only. On the contrary, portable on-site devices that could be easily transported to hospitals were built by the group of Pierre-Jean Nacher, Laboratoire Kastler Brossel, Ecole Normale Supérieure, Paris, France [29], and later by the group of Tomasz Dohnalik, Jagiellonian University, Kraków, Poland [30]. A similar system was also built by the T.R. Gentile group, National Institute of Standards and Technology (NIST), Gaithersburg, MD, USA [31]. Recently, the Kraków group developed yet another on-site polarizer that works at nonstandard MEOP conditions, using high magnetic field of the MRI scanner and polarizing the gas at the elevated pressure [18]. The principal technical details of these systems are given in the following sections. Centralized production of polarized 3 He gas In analogy to PET, where the radioactive contrast agent is produced in a place that is equipped with an accelerator and then distributed over the regional diagnostic centers, the idea of a centralized polarized 3He gas production system was already tested in the early 1990s in Mainz [32, 33]. Since a large amount of 3He gas was required for both nuclear physics and MRI applications, the system comprised five OP cells of 2.4 m length that were connected in a series for a total volume of 35 L, and up to 30 W of 1083 nm laser power was used. The whole polarizer was located in a highly homogeneous magnetic field provided by a set of solenoids, with the relative field gradients not exceeding 10­4. In standard MEOP conditions, a highly polarized 3He gas was obtained at about 1 mbar pressure, so a significant gas compression was necessary. The mercury Toepler pump that was used initially to obtain about 1 bar of 3He gas at 30% polarization was later replaced by a mechanical titanium piston compressor, which reduced the polarization losses during the compression process and allowed for a better control. Further losses occurring during the gas passage from the compressor to the storage cell were minimized by a careful choice of the storage cell material and the cell preparation procedure [34, 35]. The longitudinal relaxation time of the order 100 h was achieved by using the aluminosilicate glass. The system was able to deliver from 2.5 to 4.2 bar L of gas/h, with polarization reaching 75% for the lowest rate, at the final pressure of 5­6 bar [36, 37]. Thus, the potential demand of the order of 80­100 bar L/day could be easily satisfied [38, 39]. The storage and transportation of the polarized 3He gas to the final destination was a critical issue if the centralized production system was to be successful. In order to preserve the gas polarization, it has to be kept in a constant homogeneous magnetic field and shielded from external stray fields. Otherwise, the relaxation time drops to a few minutes. A special transport box made of a soft ferromagnetic material was built for that purpose, providing the guiding field of about 1 mT, with the relative field gradients smaller than 10­3. The enclosed volume was sufficient to contain three storage cells, each containing 1.1 L of gas at 2.7 bar pressure, which could be transported for tens of hours without a significant loss of polarization [40]. The centralized production system in Mainz was successfully tested and exploited during the already mentioned PHIL program. The polarized gas was transported by air to several clinics in Europe [37, 38] and to Australia [41]. A single overnight delivery was sufficient to perform from 10 to 20 MRI experiments on three to five patients [28]. Thus, such strategy turned out to be optimal for fulfilling the polarized 3He gas demand in scientific research. However, if the MRI of the human lungs becomes a widely used diagnostic procedure in medical clinics, more production facilities spread over the world will be needed. On-site 3He gas polarizers The main advantage of the on-site 3He polarizer is that it can provide the required amount of contrast agent on demand independently of the external supplier. This is crucial in everyday activities of a medical clinic, where the proper synchronization of patients' examination schedule with the gas delivery may be difficult. Moreover, in the case of a large demand of polarized 3He that would require 132Glowacz et al.: 3He MEOP polarizers for lung magnetic resonance imaging frequent deliveries, the on-site production can be less expensive. These are the reasons for designing a portable, low-cost, and easy to operate MEOP polarizer that could work on-site in a medical diagnostic center performing the MRI of the human lungs. Although the commercial SEOP polarizers for both 129Xe and 3He are available, the MEOP technique offers much higher efficiency in the case of 3He, and it produces clean gas that can be directly applied to human patients. The first portable 3He MEOP polarizer was developed by the Pierre-Jean Nacher group in LKB, with the ultimate goal of using it both in the laboratory and at the hospital MRI unit [29]. The polarizer consists of two main parts: a high vacuum system equipped with the gas administration system and an optical setup located in a homogeneous magnetic field. The low-pressure part includes turbomolecular pump, bottles of 3He and 4He, gas filters, and pressure sensors, complemented by appropriate connections and valves for precise 3He dosing. When the polarizer is not used, the high vacuum pump works continuously in order to keep the OP system clean, which is critical for the successful MEOP operation. The OP system can be described by a simplified diagram shown in Figure 1. It consists of the OP cell, the peristaltic compressor, and the storage cell. The whole setup is located in a homogeneous magnetic field of about 1 mT, which is generated by a set of six square coils with 40 cm long sides. The OP cell is a 50 cm long, 6 cm diameter cylinder made of pure quartz or of glass with low magnetic impurities. The RF is applied to electrodes that are wound around the OP cell, generating the discharge and populating the 23S1 metastable state of 3He gas in the plasma. A 5 W fiber laser delivers a light beam that is circularly polarized by a quarter wavelength plate, passes through the OP cell, and is back reflected by a dielectric mirror to increase its absorption and improve the efficiency of the OP process. The resulting nuclear polarization of the 3He gas inside the OP cell can be monitored using either the polarimetry technique based on the emitted fluorescent light [42] or a probe laser absorption method [43]. A throttle needle valve is installed at the input to the OP cell in order to precisely control the continuous flow of Op cell Laser He-3 gas Compressor Storage cell Figure 1Simplified diagram of the OP system in the LKB polarizer. He gas into the OP cell. The polarized 3He gas at the output of the OP cell is fed to a specially designed, nonmagnetic peristaltic compressor [44, 45] and accumulated in the storage cell. The compressor increases the 3He gas pressure from about 1 to almost 200 mbar without a significant loss of polarization. The magnetization in the storage cell is monitored by the nuclear magnetic resonance (NMR) method using a low (5°) tilting angle pulse. It is sufficient to detect the NMR signal from the hyperpolarized 3He gas, conserving at the same time most of the nonequilibrium magnetization for further use. For medical applications, the pressure in the storage cell is increased to about 1 bar by adding a buffer gas (typically N2 or 4He). The same compressor is also used to transfer the gas from the storage cell into a plastic bag that is delivered to a patient already waiting in the MRI scanner. In the continuous flow mode, the polarizer can produce 0.2­0.3 bar L/h with a polarization of 40%­50%. The relaxation time in the storage cell is longer than 10 h, and it takes .5 h to produce the amount of polarized gas <0 that is sufficient for the MRI human lung examination in a single patient [7, 46, 47]. A similar table-top 3He MEOP polarizer was built in Kraków by the group of Tomasz Dohnalik, who has been actively cooperating with the Paris group for many years [30, 48]. It is shown schematically in Figure 2. The gas administration system together with the turbomolecular pump for cleaning the OP cell is mounted on a separate aluminum plate. The optical setup is placed in a magnetic field produced by six quadratic coils, generating 1.4 mT field with about 10­3 relative inhomogeneity in the OP cell region. The 48 cm long, 5 cm diameter OP cell is equipped with capillaries at its input and output to prevent the polarized gas backflow. The 3.5 MHz RF is applied to electrodes that are wound on the surface of the OP cell to generate discharge in the 3He gas at about 3 mbar. The OP is achieved by using the Keopsys 10 W, 1083 nm, 2.1 GHz full width at half maximum (FWHM) fiber laser, with the beam spatial profile adapted to the internal diameter of the OP cell (Gaussian FWHM equal to 4.9 mm). An improved version of the peristaltic compressor is used to transfer the polarized 3He gas to the storage cell. Separate NMR transmitting and receiving coils allowed for a direct measurement of nuclear polarization in the storage cell. The NMR data were calibrated against the absolute measurement of 1083 nm weak probe laser absorption (intensity of 20 W/ cm2) [43]. Owing to the close cooperation within the PHIL European Program, it was possible to obtain certified storage cells from the Mainz group, which had a relaxation time of the order of 150 h, as well as the transport box described earlier. Glowacz et al.: 3He MEOP polarizers for lung magnetic resonance imaging133 B0 Syringe Peristaltic compressor Pick-up coils Gas handling system He G F PI He Storage cell Vacuum membrane pump Optical pumping cell M /4 Turbomolecular pump BS Telescope*7 Transmitter coils Figure 2Scheme of the table-top polarizer in Kraków [48] (/4, quarter-wave plate; BS, beam splitter; F, 50 m filter; G, getter; M, mirror; PI, pressure sensor; V, one-way valve). The production rate of the polarizer reached 0.25 bar L/h with the nuclear polarization of 40% in the 300 cc storage cell at the 1 bar pressure. First experiments with the polarized 3He gas were performed on a homemade low-field MRI system (0.09 T), where the images of the rat lungs were obtained [49]. Subsequently, the 1.5 T Siemens Sonata medical MRI scanner located at the John Paul II Hospital in Kraków was adopted to allow for the 3He experiments, and the human lung MRIs were obtained for the first time in Poland [18, 48]. A compact 3He MEOP polarizer was also built by the group of T.R. Gentile at the NIST [31]. Two 20 cm long, 5 cm diameter OP cells located in the 2.6 mT homogeneous field were irradiated by the 3 W, 1083 nm Nd:LMA laser, characterized by a 2 GHz bandwidth. A commercial, low-cost, two-stage diaphragm pump was modified for the polarized gas compression. Although much cheaper than the titanium piston compressor that was used by the Mainz group, it caused from 20% to 40% polarization losses when used at moderate gas flow of 0.3­0.7 bar L/h. Faster gas flow was not feasible, because sufficient residence time of the 3He gas in the OP cells was necessary for the polarization buildup. The reported production rate of the NIST polarizer was equal to 0.3 bar L/h at the nuclear polarization of 3He gas reaching about 50%. A newer version of the system consisted of four 70 cm long, 5 cm diameter OP cells made of Pyrex glass, located in the 1 mT magnetic field and illuminated by a 4 W laser [50]. The compression of the polarized 3He gas was achieved by using two pneumatically driven aluminum pistons. This way, the production rate was increased to about 0.26 bar L/h at 55% polarization level in the storage cell. On-site 3He gas polarizer operating in nonstandard MEOP method The major factor that limits the production rate of the polarized 3He gas by the MEOP method operating in standard conditions is the low gas pressure in the OP cell. The achievable nuclear polarization dramatically drops when the gas pressure higher than a few mbar is attempted. This is due to increased frequencies of collision processes such as Penning ionization and dipole-dipole collisions, which lead to faster relaxation. Since about 1 bar of 3He gas is required for a complete examination of a single patient, this seriously restricts the application of this technique in medical diagnostics. One can overcome this limitation by increasing the volume of the OP cell or by using multiple cells. This is rather difficult to implement in a compact device equipped with an inexpensive compressor, which is to operate in the medical clinic environment. It turned out, however, somewhat unexpectedly, that the MEOP can be successfully performed at a high magnetic field and at much higher 3He gas pressure. Extensive experimental [51­53] and theoretical [21, 54] investigations of the whole range of operating parameters were carried out, with the magnetic field reaching 4.7 T and the gas 134Glowacz et al.: 3He MEOP polarizers for lung magnetic resonance imaging pressure up to 267 mbar [55], and the optimal conditions were determined. The successful operation of the MEOP in these socalled nonstandard conditions can be briefly explained by the interplay of several physical effects. First of all, although the hyperfine coupling is truncated in high field, reducing the efficiency of the polarization transfer from electronic to nuclear spins of the metastable atoms, the nuclear relaxation rate in the ground state is reduced as well, improving the dynamics of the polarization process. Moreover, the atomic collision frequency increases with pressure, enhancing the metastability exchange rate. From the technical point of view, the operation at high magnetic field relaxes the strict requirements for the circularly polarized pumping laser light that was necessary in the standard MEOP, because the transition lines in the metastable state excited by light of opposite polarizations are well separated. Altogether, the application of high magnetic field makes it possible to operate at about 100 mbar pressure in the OP cell, so that further compression is not difficult. Based on these theoretical and experimental studies, a novel MEOP polarizer operating in nonstandard conditions was built by the Kraków group [18]. It works at 1.5 T field that is provided by the magnet of the MRI medical scanner. An elevated gas pressure inside the OP cells allows for a substantial increase of the polarized gas production rate, at the same time keeping the construction compact, light, and easy to use. The main part of the polarizer that fits inside the magnet of MRI scanner during the optical polarization process is shown in Figure 3. The gas administration unit, which is similar to the one shown in Figure 2, is kept away from the magnet and connects to the main part by a flexible, nonmagnetic tube (black dashed curve on Figure 3). Three 80 cm long, 5 cm diameter OP cells are connected in series, forming a total volume of 1.1 L. A 10 W, 1083 nm fiber laser (Keopsys, France) is used for OP. A set of polarizing beam splitters and half- and quarter-wave plates circularly polarize the laser beam and distribute it to OP cells. The storage cell together with the pneumatically driven peristaltic compressor is mounted on a detachable plate, which can remain in the magnet after the polarizer is removed to accommodate the patient. When the 3He gas pressure in the OP cell exceeds about 30 mbar, the distribution of plasma inside the OP cell becomes strongly nonuniform. The metastable 3He atoms concentrate near the cell walls, close to the electrodes that produce the RF discharge. In order to optimize the absorption of the pumping laser light, the standard Gaussian spatial profile of the laser beam was transformed to a doughnut shape [56], using a pair of axicones [57], and the telescope to adjust the beam diameter. After these modifications, the production rate of polarized 3He gas reached about 1 bar L/h at the nuclear polarization of 33%. This is much higher than for the low-field, on-site systems. The time required to obtain a sufficient amount of gas for a single-patient MRI lung examination is of the order of few minutes. Moreover, since the storage cell stays in the magnet all the time, the losses of polarization that normally occur during transportation from the polarizer to medical scanner are eliminated. The Tedlar bag from which the patient inhales the Capillary PBS Getter /2 Telescope + Axicons Lens /2 /4 M /4 Vacuum Storage cell M He P. engine M PBS 3 Figure 3Main part of the high-field MEOP polarizer [18] (/2 and /4, half- and quarter-wave plate. M, mirror; P. Engine, pneumatic engine; PBS, polarizing beam splitter; PD, photodiode). Glowacz et al.: 3He MEOP polarizers for lung magnetic resonance imaging135 polarized gas is filled either naturally from the storage cell, when the pressure inside exceeds the atmospheric, or by using the compressor in a reverse mode. The quality of MRI images of the human lungs that were obtained at the John Paul II Hospital in Kraków confirmed the advantages of the high-field MEOP polarizer operating with the commercial medical scanner [18]. A permit was obtained from the Ethics Commission to carry out routine MRI lung examinations on patients using this technique. He gas administration and recycling system developed by the Mainz group [60]. It consists of a series of antibacterial filters, liquid nitrogen traps, and the cold head, in which contaminants such as bacteria and the air components are consecutively removed from the recovered mixture. Close to 95% of 3He gas is recovered in the cleaning process, but taking into account some losses that occur during the exhaled gas collection, the overall recycling efficiency is 76%­79%. When the recovered 3He gas is reused in the MEOP polarizer, any deterioration of its performance is not observed, and it obtained the necessary certificate to allow for medical applications. The introduction of the MRI human lung imaging using the polarized 3He gas into the medical diagnostics practice requires the gas administration procedure to be standardized. In order to assure the reproducibility of examinations, the whole process has to be carefully controlled, which includes the quantitative determination of the gas flow rate as well as the stage and depth of inhalation. Such administration unit was proposed by the Mainz group [58]. It is equipped with computer-controlled pneumatic valves and nonmagnetic spirometers and put inside the magnet bore of the medical scanner, next to the patient. The polarized 3He gas is transferred to the unit from the polarizer or transport box by a thin tube, which is placed along the lines of stray field of the magnet, to avoid the polarization losses caused by strong magnetic field gradients. Then, the gas can be delivered to the patient through the mask in an arbitrary stage of the breathing cycle. The timing can be synchronized with the MRI experiment, which is important in dynamic ventilation studies. Finally, the gas exhaled by the patient, which is a mixture of ambient air and 3He, is collected in a leak-tight bag for later compression, cleaning, and reuse. The last step became critical in the view of 3He gas shortage that has occurred during the last few years, which caused its price increase by almost an order of magnitude [59]. A complete 3He gas recovery system was Table 1Summary of the output parameters of four different polarizers. 1.Mainz University, Germany 2.LKB, Paris, France 3.NIST, USA 4.Jagiellonian University, Kraków, Poland Pressure in OP cell, mbar 1 1 1 100 Summary and outlook The principal technical parameters of the MEOP polarizers described above and their production efficiencies are compared in Table 1. Both centralized and on-site strategies led to the successful implementation of the MEOP method and the delivery of sufficient amount of polarized 3He gas for a given application. In practice, the overall cost of delivered gas will be a crucial factor in choosing whether it should be ordered from a centralized facility or made locally. In everyday activities of the medical clinic, the local access to polarized 3He gas may be preferable, making it easier to plan the patients' examination schedule. For these reasons, the high-field MEOP polarizer operating in nonstandard conditions and using the magnetic field of the medical MRI scanner looks most promising. It is a compact and rather inexpensive unit, producing sufficient amount of clean, polarized 3He gas. Naturally, there is still much room for its improvement in terms of optical setup and the optimum number of OP cells. Both the polarization and gas administration processes should be computer controlled to make it easier to operate. Another interesting development path that looks worth pursuing is the combination of MRI and PET techniques in a single, compact unit. It would make it possible to observe both anatomical and functional changes in Magnetic field, mT 1 1 1 1000 Polarization Up to 70% 40­50% 55% 33% Production rate, bar L/h Up to 4.2 0.2­0.3 0.26 1 1, the biggest device with a mechanical titanium piston compressor; 2, table-top polarizer with a small nonmagnetic peristaltic compressor; 3, table-top polarizer with pneumatically driven aluminum pistons; 4, high-field polarizer with a nonmagnetic peristaltic compressor. 136Glowacz et al.: 3He MEOP polarizers for lung magnetic resonance imaging the human lungs caused by a tumor, which is important especially in the early stage of the disease. Recent progress in constructing whole-body PET scanners by using a new scintillating material of extended length [61] allows for such design, in contrast to standard PET ring versions in which photomultipliers are incompatible with magnetic field. Therefore, the time-of-flight (TOF)-PET/MRI concept [62] has a good chance of being developed in the near future. As the first step, a low-cost, "two in one" unit based on a low-field MRI scanner can be designed. Since the optically generated high nuclear polarization of 3He gas is independent of magnetic field, the quality of the obtained human lung images is not compromised. Such project is under way at the Institute of Physics of the Jagiellonian University in Kraków, Poland. Conflict of interest statement Authors' conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding: None declared. Employment or leadership: None declared. Honorarium: None declared. 10. Ebert M, Grossmann T, Heil W, Otten EW. Nuclear magnetic resonance imaging with hyperpolarised helium-3. Lancet 1996;347:1297­9. 11. Kauczor HU, Hofmann D, Kreitner KF, Nilgens H, Surkau R, Heil W, et al. 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Production of laser-polarized 3 He gas via metastability exchange optical pumping for magnetic resonance imaging

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Abstract

The state-of-the-art in the production of hyperpolarized 3He gas for magnetic resonance imaging (MRI) of the human lungs is reviewed. The paper is focused on the metastability exchange optical pumping (MEOP) method, which is preferable in medical applications, because the polarized 3He gas is free of any contaminants. Two strategies, namely, "centralized" and "onsite" production, are compared from the point of view of efficiency, level of achievable polarization, and the cost. A novel design of the polarizer that is based on MEOP operating in nonstandard conditions is also presented. It is the most promising solution for the implementation of the technique in medical clinics, as it uses the magnetic field of the MRI scanner and operates at elevated 3He gas pressure. Keywords: atomic optics; hyperpolarization; magnetic resonance imaging; medical imaging; physics. DOI 10.1515/bams-2014-0004 Received February 17, 2014; accepted July 3, 2014; previously published online August 12, 2014 Bartosz Glowacz*, Mateusz Suchanek and Zbigniew Olejniczak Introduction Very often, advanced physical methods that were initially developed for fundamental research find new applications in other fields of science or technology that have not been considered before. A case in point was the *Corresponding author: Bartosz Glowacz, Institute of Physics, Jagiellonian University, Kraków 30-059, Poland, E-mail: b.glowacz@uj.edu.pl Mateusz Suchanek: Department of Chemistry and Physics, Agricultural University, Kraków, Poland Zbigniew Olejniczak: Institute of Physics, Jagiellonian University, Kraków, Poland; and Institute of Nuclear Physics, Polish Academy of Sciences, Kraków, Poland development of optical polarization techniques of 3He and 129 Xe noble gases, which was motivated by nuclear scattering experiments [1, 2]. Although the application of 3He in magnetometry was already suggested at that time [3], a real explosion of interest occurred when it was realized that hyperpolarized noble gases could be used as contrast agents in magnetic resonance imaging (MRI). The standard proton-based MRI is a well-established noninvasive medical diagnostic method. It provides highresolution images of the interior of the human body, without causing any side effects as in the case of computed tomography (CT), which uses ionizing radiation. MRI exploits high water density in living tissues, measuring the nuclear magnetization of water protons produced by the high magnetic field of the MRI scanner. However, this technique fails for lungs or sinuses that are filled with air of very low water density, which gives insufficient proton signal for a successful image generation. It should be stressed that similar difficulties occur in CT and ultrasonography (USG) due to the lack of proper absorber in the anatomical airspaces. Although important technological advances have been made in recent years to overcome the problem of low proton density in the lungs and short T2* value [4], it is still a field of active research that has not found its way to the clinics. Therefore, finding an alternative method of anatomical and functional characterization of ventilated airspaces was of critical importance for successful medical diagnostics and treatment. The solution was proposed and implemented in 1994 by Albert et al. [5], who used the optically polarized 129Xe gas as a contrast agent. When introduced into the lungs of a mouse, the spin ½ 129Xe nuclei of about 10% polarization produced a strong enough signal for MRI in spite of the low density of the gas and a much lower resonance frequency. One year later, an analogous experiment was performed using hyperpolarized 3He [6]. In both cases, the high nuclear polarization that is achieved by optical pumping (OP) is independent of magnetic field, in contrast to thermal equilibrium polarization. Therefore, 130Glowacz et al.: 3He MEOP polarizers for lung magnetic resonance imaging sufficiently strong signals for high-quality MRIs can be measured even in low magnetic field, low-cost medical scanners [7, 8]. The first image of the human lungs using the hyperpolarized 3He gas was obtained in 1996 [9, 10]. In the last 20 years, there has been great progress in the structural and functional imaging of the lungs. Apart from producing high-resolution anatomical images, novel techniques have been developed to monitor the dynamics of ventilation [11] and to determine diffusion maps [12] and the distribution of oxygen partial pressure [13]. In human studies, 3He is preferred over 129Xe, which gives a stronger signal due to the larger gyromagnetic ratio and higher level of nuclear polarization. Moreover, 3He does not cause any side effects, compared to 129Xe, which is anesthetic and requires a careful monitoring of the gas dose and the physiological conditions of the patient. In this paper, after a brief comparison of two optical polarization methods for noble gases, the 3He optical polarizers based on the metastability exchange optical pumping (MEOP) process are reviewed. Two main strategies of the gas production, namely, "centralized" and "on-site" are discussed, the latter being preferable when the MEOP in nonstandard conditions is implemented, utilizing the magnetic field of the medical MRI scanner. Due to the recent difficulties in purchasing 3He, a special section is dedicated to the problem of gas administration, recovery, and recycling. Finally, the prospects for the further development of the method are presented, including the idea of combining 3 He MRI with the positron emission tomography (PET) technique. the electron polarization of rubidium atoms is transferred to nuclear spins of noble gas atoms by atomic collisions [15]. The SEOP method requires high laser power, and it takes a few hours to achieve the required nuclear polarization at the pressure of several atmospheres. Finally, the gas is cooled down at the exit of the OP cell in order to remove the rubidium vapor. The last step is important if the polarized gas is to be used in a medical examination in vivo. The MEOP is another polarization method, which so far works for 3He only. The OP cell is filled with a pure 3 He gas [16] or an isotopic mixture of 3He and 4He [17] at the pressure of few mbar, and is located in a small magnetic field, of the order of few mT. The OP is performed on the 2 3S1 metastable state. Since the transition from the ground state to the 2 3S1 state is forbidden, it is populated indirectly using the radiofrequency (RF) discharge. A few MHz of RF is delivered to the electrodes that are wound on the surface of the cell or placed inside. Alternatively, an electron beam can be used for that purpose, depending on the technical feasibility and requirement. The metastable state is optically pumped by a circularly polarized light of 1083 nm wavelength, so that the electronic hyperfine sublevels corresponding to desired nuclear spin orientation are populated. The nuclear polarization of 3He atoms in the ground state is achieved in the process of binary collisions with spinpolarized 3He atoms in the metastable state. Compared to SEOP, the MEOP process is more efficient, does not require high laser power, and takes place at room temperature, but a subsequent compression of the polarized gas is needed. The absence of potentially harmful alkali elements is its important advantage in medical applications. Although the development of both optical polarization methods has begun approximately at the same time, the MEOP has obtained a strong support in Europe within the two European framework programs: Polarized Helium Imaging for Lungs (PHIL, 2000­2004) and Polarized Helium for Lung Imaging Network (PHeLINet, 2007­2011). A comprehensive theoretical model that fully describes the dynamics of MEOP was developed, including the magnetic field and 3He pressure dependence of the polarization process efficiency [18­20]. In parallel, the experimental data in the whole parameter range were accumulated, fully supporting the model and allowing to optimize the technique [21]. On the basis of these results, the MRI of the human lungs using hyperpolarized 3He gas was introduced to the clinics, and special examination protocols were established for both anatomical and functional lung studies [13, 22­27]. Brief description of optical polarization methods Historically, the first MRI experiments with polarized noble gases were performed using the spin exchange optical pumping (SEOP) method, which was invented in 1960 and 1982 for 3He and 129Xe, respectively [1, 14]. In SEOP, a small amount of rubidium is placed in the OP cell, which is filled with the noble gas to be polarized and a buffer gas (N2 or 4He). The cell is located in a small magnetic field, of the order of few mT, in order to establish the quantization axis for electron and nuclear spins. After heating the cell to cause the evaporation of rubidium, its vapor is illuminated by a circularly polarized laser light of 795 nm wavelength. Almost 100% polarization of rubidium electron spins is achieved in the OP process. Then, Glowacz et al.: 3He MEOP polarizers for lung magnetic resonance imaging131 Polarized 3He gas production and delivery strategies using MEOP Two main ideas on how to supply the medical MRI unit with polarized 3He gas for human lung imaging have been pursued within the European community: the centralized and on-site production. Taking advantage of the long relaxation time of polarized gas when it is kept at the 1 bar pressure in a homogeneous magnetic field, a high-efficiency centralized facility was built by the group of Werner Heil at the Johannes Gutenberg Universität in Mainz, Germany [28]. Since the gas polarization could be preserved for several tens of hours, it could be distributed all over Europe. It should be noted that such strategy would be hard to realize for 129Xe, which has a relaxation time of a few hours only. On the contrary, portable on-site devices that could be easily transported to hospitals were built by the group of Pierre-Jean Nacher, Laboratoire Kastler Brossel, Ecole Normale Supérieure, Paris, France [29], and later by the group of Tomasz Dohnalik, Jagiellonian University, Kraków, Poland [30]. A similar system was also built by the T.R. Gentile group, National Institute of Standards and Technology (NIST), Gaithersburg, MD, USA [31]. Recently, the Kraków group developed yet another on-site polarizer that works at nonstandard MEOP conditions, using high magnetic field of the MRI scanner and polarizing the gas at the elevated pressure [18]. The principal technical details of these systems are given in the following sections. Centralized production of polarized 3 He gas In analogy to PET, where the radioactive contrast agent is produced in a place that is equipped with an accelerator and then distributed over the regional diagnostic centers, the idea of a centralized polarized 3He gas production system was already tested in the early 1990s in Mainz [32, 33]. Since a large amount of 3He gas was required for both nuclear physics and MRI applications, the system comprised five OP cells of 2.4 m length that were connected in a series for a total volume of 35 L, and up to 30 W of 1083 nm laser power was used. The whole polarizer was located in a highly homogeneous magnetic field provided by a set of solenoids, with the relative field gradients not exceeding 10­4. In standard MEOP conditions, a highly polarized 3He gas was obtained at about 1 mbar pressure, so a significant gas compression was necessary. The mercury Toepler pump that was used initially to obtain about 1 bar of 3He gas at 30% polarization was later replaced by a mechanical titanium piston compressor, which reduced the polarization losses during the compression process and allowed for a better control. Further losses occurring during the gas passage from the compressor to the storage cell were minimized by a careful choice of the storage cell material and the cell preparation procedure [34, 35]. The longitudinal relaxation time of the order 100 h was achieved by using the aluminosilicate glass. The system was able to deliver from 2.5 to 4.2 bar L of gas/h, with polarization reaching 75% for the lowest rate, at the final pressure of 5­6 bar [36, 37]. Thus, the potential demand of the order of 80­100 bar L/day could be easily satisfied [38, 39]. The storage and transportation of the polarized 3He gas to the final destination was a critical issue if the centralized production system was to be successful. In order to preserve the gas polarization, it has to be kept in a constant homogeneous magnetic field and shielded from external stray fields. Otherwise, the relaxation time drops to a few minutes. A special transport box made of a soft ferromagnetic material was built for that purpose, providing the guiding field of about 1 mT, with the relative field gradients smaller than 10­3. The enclosed volume was sufficient to contain three storage cells, each containing 1.1 L of gas at 2.7 bar pressure, which could be transported for tens of hours without a significant loss of polarization [40]. The centralized production system in Mainz was successfully tested and exploited during the already mentioned PHIL program. The polarized gas was transported by air to several clinics in Europe [37, 38] and to Australia [41]. A single overnight delivery was sufficient to perform from 10 to 20 MRI experiments on three to five patients [28]. Thus, such strategy turned out to be optimal for fulfilling the polarized 3He gas demand in scientific research. However, if the MRI of the human lungs becomes a widely used diagnostic procedure in medical clinics, more production facilities spread over the world will be needed. On-site 3He gas polarizers The main advantage of the on-site 3He polarizer is that it can provide the required amount of contrast agent on demand independently of the external supplier. This is crucial in everyday activities of a medical clinic, where the proper synchronization of patients' examination schedule with the gas delivery may be difficult. Moreover, in the case of a large demand of polarized 3He that would require 132Glowacz et al.: 3He MEOP polarizers for lung magnetic resonance imaging frequent deliveries, the on-site production can be less expensive. These are the reasons for designing a portable, low-cost, and easy to operate MEOP polarizer that could work on-site in a medical diagnostic center performing the MRI of the human lungs. Although the commercial SEOP polarizers for both 129Xe and 3He are available, the MEOP technique offers much higher efficiency in the case of 3He, and it produces clean gas that can be directly applied to human patients. The first portable 3He MEOP polarizer was developed by the Pierre-Jean Nacher group in LKB, with the ultimate goal of using it both in the laboratory and at the hospital MRI unit [29]. The polarizer consists of two main parts: a high vacuum system equipped with the gas administration system and an optical setup located in a homogeneous magnetic field. The low-pressure part includes turbomolecular pump, bottles of 3He and 4He, gas filters, and pressure sensors, complemented by appropriate connections and valves for precise 3He dosing. When the polarizer is not used, the high vacuum pump works continuously in order to keep the OP system clean, which is critical for the successful MEOP operation. The OP system can be described by a simplified diagram shown in Figure 1. It consists of the OP cell, the peristaltic compressor, and the storage cell. The whole setup is located in a homogeneous magnetic field of about 1 mT, which is generated by a set of six square coils with 40 cm long sides. The OP cell is a 50 cm long, 6 cm diameter cylinder made of pure quartz or of glass with low magnetic impurities. The RF is applied to electrodes that are wound around the OP cell, generating the discharge and populating the 23S1 metastable state of 3He gas in the plasma. A 5 W fiber laser delivers a light beam that is circularly polarized by a quarter wavelength plate, passes through the OP cell, and is back reflected by a dielectric mirror to increase its absorption and improve the efficiency of the OP process. The resulting nuclear polarization of the 3He gas inside the OP cell can be monitored using either the polarimetry technique based on the emitted fluorescent light [42] or a probe laser absorption method [43]. A throttle needle valve is installed at the input to the OP cell in order to precisely control the continuous flow of Op cell Laser He-3 gas Compressor Storage cell Figure 1Simplified diagram of the OP system in the LKB polarizer. He gas into the OP cell. The polarized 3He gas at the output of the OP cell is fed to a specially designed, nonmagnetic peristaltic compressor [44, 45] and accumulated in the storage cell. The compressor increases the 3He gas pressure from about 1 to almost 200 mbar without a significant loss of polarization. The magnetization in the storage cell is monitored by the nuclear magnetic resonance (NMR) method using a low (5°) tilting angle pulse. It is sufficient to detect the NMR signal from the hyperpolarized 3He gas, conserving at the same time most of the nonequilibrium magnetization for further use. For medical applications, the pressure in the storage cell is increased to about 1 bar by adding a buffer gas (typically N2 or 4He). The same compressor is also used to transfer the gas from the storage cell into a plastic bag that is delivered to a patient already waiting in the MRI scanner. In the continuous flow mode, the polarizer can produce 0.2­0.3 bar L/h with a polarization of 40%­50%. The relaxation time in the storage cell is longer than 10 h, and it takes .5 h to produce the amount of polarized gas <0 that is sufficient for the MRI human lung examination in a single patient [7, 46, 47]. A similar table-top 3He MEOP polarizer was built in Kraków by the group of Tomasz Dohnalik, who has been actively cooperating with the Paris group for many years [30, 48]. It is shown schematically in Figure 2. The gas administration system together with the turbomolecular pump for cleaning the OP cell is mounted on a separate aluminum plate. The optical setup is placed in a magnetic field produced by six quadratic coils, generating 1.4 mT field with about 10­3 relative inhomogeneity in the OP cell region. The 48 cm long, 5 cm diameter OP cell is equipped with capillaries at its input and output to prevent the polarized gas backflow. The 3.5 MHz RF is applied to electrodes that are wound on the surface of the OP cell to generate discharge in the 3He gas at about 3 mbar. The OP is achieved by using the Keopsys 10 W, 1083 nm, 2.1 GHz full width at half maximum (FWHM) fiber laser, with the beam spatial profile adapted to the internal diameter of the OP cell (Gaussian FWHM equal to 4.9 mm). An improved version of the peristaltic compressor is used to transfer the polarized 3He gas to the storage cell. Separate NMR transmitting and receiving coils allowed for a direct measurement of nuclear polarization in the storage cell. The NMR data were calibrated against the absolute measurement of 1083 nm weak probe laser absorption (intensity of 20 W/ cm2) [43]. Owing to the close cooperation within the PHIL European Program, it was possible to obtain certified storage cells from the Mainz group, which had a relaxation time of the order of 150 h, as well as the transport box described earlier. Glowacz et al.: 3He MEOP polarizers for lung magnetic resonance imaging133 B0 Syringe Peristaltic compressor Pick-up coils Gas handling system He G F PI He Storage cell Vacuum membrane pump Optical pumping cell M /4 Turbomolecular pump BS Telescope*7 Transmitter coils Figure 2Scheme of the table-top polarizer in Kraków [48] (/4, quarter-wave plate; BS, beam splitter; F, 50 m filter; G, getter; M, mirror; PI, pressure sensor; V, one-way valve). The production rate of the polarizer reached 0.25 bar L/h with the nuclear polarization of 40% in the 300 cc storage cell at the 1 bar pressure. First experiments with the polarized 3He gas were performed on a homemade low-field MRI system (0.09 T), where the images of the rat lungs were obtained [49]. Subsequently, the 1.5 T Siemens Sonata medical MRI scanner located at the John Paul II Hospital in Kraków was adopted to allow for the 3He experiments, and the human lung MRIs were obtained for the first time in Poland [18, 48]. A compact 3He MEOP polarizer was also built by the group of T.R. Gentile at the NIST [31]. Two 20 cm long, 5 cm diameter OP cells located in the 2.6 mT homogeneous field were irradiated by the 3 W, 1083 nm Nd:LMA laser, characterized by a 2 GHz bandwidth. A commercial, low-cost, two-stage diaphragm pump was modified for the polarized gas compression. Although much cheaper than the titanium piston compressor that was used by the Mainz group, it caused from 20% to 40% polarization losses when used at moderate gas flow of 0.3­0.7 bar L/h. Faster gas flow was not feasible, because sufficient residence time of the 3He gas in the OP cells was necessary for the polarization buildup. The reported production rate of the NIST polarizer was equal to 0.3 bar L/h at the nuclear polarization of 3He gas reaching about 50%. A newer version of the system consisted of four 70 cm long, 5 cm diameter OP cells made of Pyrex glass, located in the 1 mT magnetic field and illuminated by a 4 W laser [50]. The compression of the polarized 3He gas was achieved by using two pneumatically driven aluminum pistons. This way, the production rate was increased to about 0.26 bar L/h at 55% polarization level in the storage cell. On-site 3He gas polarizer operating in nonstandard MEOP method The major factor that limits the production rate of the polarized 3He gas by the MEOP method operating in standard conditions is the low gas pressure in the OP cell. The achievable nuclear polarization dramatically drops when the gas pressure higher than a few mbar is attempted. This is due to increased frequencies of collision processes such as Penning ionization and dipole-dipole collisions, which lead to faster relaxation. Since about 1 bar of 3He gas is required for a complete examination of a single patient, this seriously restricts the application of this technique in medical diagnostics. One can overcome this limitation by increasing the volume of the OP cell or by using multiple cells. This is rather difficult to implement in a compact device equipped with an inexpensive compressor, which is to operate in the medical clinic environment. It turned out, however, somewhat unexpectedly, that the MEOP can be successfully performed at a high magnetic field and at much higher 3He gas pressure. Extensive experimental [51­53] and theoretical [21, 54] investigations of the whole range of operating parameters were carried out, with the magnetic field reaching 4.7 T and the gas 134Glowacz et al.: 3He MEOP polarizers for lung magnetic resonance imaging pressure up to 267 mbar [55], and the optimal conditions were determined. The successful operation of the MEOP in these socalled nonstandard conditions can be briefly explained by the interplay of several physical effects. First of all, although the hyperfine coupling is truncated in high field, reducing the efficiency of the polarization transfer from electronic to nuclear spins of the metastable atoms, the nuclear relaxation rate in the ground state is reduced as well, improving the dynamics of the polarization process. Moreover, the atomic collision frequency increases with pressure, enhancing the metastability exchange rate. From the technical point of view, the operation at high magnetic field relaxes the strict requirements for the circularly polarized pumping laser light that was necessary in the standard MEOP, because the transition lines in the metastable state excited by light of opposite polarizations are well separated. Altogether, the application of high magnetic field makes it possible to operate at about 100 mbar pressure in the OP cell, so that further compression is not difficult. Based on these theoretical and experimental studies, a novel MEOP polarizer operating in nonstandard conditions was built by the Kraków group [18]. It works at 1.5 T field that is provided by the magnet of the MRI medical scanner. An elevated gas pressure inside the OP cells allows for a substantial increase of the polarized gas production rate, at the same time keeping the construction compact, light, and easy to use. The main part of the polarizer that fits inside the magnet of MRI scanner during the optical polarization process is shown in Figure 3. The gas administration unit, which is similar to the one shown in Figure 2, is kept away from the magnet and connects to the main part by a flexible, nonmagnetic tube (black dashed curve on Figure 3). Three 80 cm long, 5 cm diameter OP cells are connected in series, forming a total volume of 1.1 L. A 10 W, 1083 nm fiber laser (Keopsys, France) is used for OP. A set of polarizing beam splitters and half- and quarter-wave plates circularly polarize the laser beam and distribute it to OP cells. The storage cell together with the pneumatically driven peristaltic compressor is mounted on a detachable plate, which can remain in the magnet after the polarizer is removed to accommodate the patient. When the 3He gas pressure in the OP cell exceeds about 30 mbar, the distribution of plasma inside the OP cell becomes strongly nonuniform. The metastable 3He atoms concentrate near the cell walls, close to the electrodes that produce the RF discharge. In order to optimize the absorption of the pumping laser light, the standard Gaussian spatial profile of the laser beam was transformed to a doughnut shape [56], using a pair of axicones [57], and the telescope to adjust the beam diameter. After these modifications, the production rate of polarized 3He gas reached about 1 bar L/h at the nuclear polarization of 33%. This is much higher than for the low-field, on-site systems. The time required to obtain a sufficient amount of gas for a single-patient MRI lung examination is of the order of few minutes. Moreover, since the storage cell stays in the magnet all the time, the losses of polarization that normally occur during transportation from the polarizer to medical scanner are eliminated. The Tedlar bag from which the patient inhales the Capillary PBS Getter /2 Telescope + Axicons Lens /2 /4 M /4 Vacuum Storage cell M He P. engine M PBS 3 Figure 3Main part of the high-field MEOP polarizer [18] (/2 and /4, half- and quarter-wave plate. M, mirror; P. Engine, pneumatic engine; PBS, polarizing beam splitter; PD, photodiode). Glowacz et al.: 3He MEOP polarizers for lung magnetic resonance imaging135 polarized gas is filled either naturally from the storage cell, when the pressure inside exceeds the atmospheric, or by using the compressor in a reverse mode. The quality of MRI images of the human lungs that were obtained at the John Paul II Hospital in Kraków confirmed the advantages of the high-field MEOP polarizer operating with the commercial medical scanner [18]. A permit was obtained from the Ethics Commission to carry out routine MRI lung examinations on patients using this technique. He gas administration and recycling system developed by the Mainz group [60]. It consists of a series of antibacterial filters, liquid nitrogen traps, and the cold head, in which contaminants such as bacteria and the air components are consecutively removed from the recovered mixture. Close to 95% of 3He gas is recovered in the cleaning process, but taking into account some losses that occur during the exhaled gas collection, the overall recycling efficiency is 76%­79%. When the recovered 3He gas is reused in the MEOP polarizer, any deterioration of its performance is not observed, and it obtained the necessary certificate to allow for medical applications. The introduction of the MRI human lung imaging using the polarized 3He gas into the medical diagnostics practice requires the gas administration procedure to be standardized. In order to assure the reproducibility of examinations, the whole process has to be carefully controlled, which includes the quantitative determination of the gas flow rate as well as the stage and depth of inhalation. Such administration unit was proposed by the Mainz group [58]. It is equipped with computer-controlled pneumatic valves and nonmagnetic spirometers and put inside the magnet bore of the medical scanner, next to the patient. The polarized 3He gas is transferred to the unit from the polarizer or transport box by a thin tube, which is placed along the lines of stray field of the magnet, to avoid the polarization losses caused by strong magnetic field gradients. Then, the gas can be delivered to the patient through the mask in an arbitrary stage of the breathing cycle. The timing can be synchronized with the MRI experiment, which is important in dynamic ventilation studies. Finally, the gas exhaled by the patient, which is a mixture of ambient air and 3He, is collected in a leak-tight bag for later compression, cleaning, and reuse. The last step became critical in the view of 3He gas shortage that has occurred during the last few years, which caused its price increase by almost an order of magnitude [59]. A complete 3He gas recovery system was Table 1Summary of the output parameters of four different polarizers. 1.Mainz University, Germany 2.LKB, Paris, France 3.NIST, USA 4.Jagiellonian University, Kraków, Poland Pressure in OP cell, mbar 1 1 1 100 Summary and outlook The principal technical parameters of the MEOP polarizers described above and their production efficiencies are compared in Table 1. Both centralized and on-site strategies led to the successful implementation of the MEOP method and the delivery of sufficient amount of polarized 3He gas for a given application. In practice, the overall cost of delivered gas will be a crucial factor in choosing whether it should be ordered from a centralized facility or made locally. In everyday activities of the medical clinic, the local access to polarized 3He gas may be preferable, making it easier to plan the patients' examination schedule. For these reasons, the high-field MEOP polarizer operating in nonstandard conditions and using the magnetic field of the medical MRI scanner looks most promising. It is a compact and rather inexpensive unit, producing sufficient amount of clean, polarized 3He gas. Naturally, there is still much room for its improvement in terms of optical setup and the optimum number of OP cells. Both the polarization and gas administration processes should be computer controlled to make it easier to operate. Another interesting development path that looks worth pursuing is the combination of MRI and PET techniques in a single, compact unit. It would make it possible to observe both anatomical and functional changes in Magnetic field, mT 1 1 1 1000 Polarization Up to 70% 40­50% 55% 33% Production rate, bar L/h Up to 4.2 0.2­0.3 0.26 1 1, the biggest device with a mechanical titanium piston compressor; 2, table-top polarizer with a small nonmagnetic peristaltic compressor; 3, table-top polarizer with pneumatically driven aluminum pistons; 4, high-field polarizer with a nonmagnetic peristaltic compressor. 136Glowacz et al.: 3He MEOP polarizers for lung magnetic resonance imaging the human lungs caused by a tumor, which is important especially in the early stage of the disease. Recent progress in constructing whole-body PET scanners by using a new scintillating material of extended length [61] allows for such design, in contrast to standard PET ring versions in which photomultipliers are incompatible with magnetic field. Therefore, the time-of-flight (TOF)-PET/MRI concept [62] has a good chance of being developed in the near future. As the first step, a low-cost, "two in one" unit based on a low-field MRI scanner can be designed. Since the optically generated high nuclear polarization of 3He gas is independent of magnetic field, the quality of the obtained human lung images is not compromised. Such project is under way at the Institute of Physics of the Jagiellonian University in Kraków, Poland. Conflict of interest statement Authors' conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding: None declared. Employment or leadership: None declared. Honorarium: None declared. 10. Ebert M, Grossmann T, Heil W, Otten EW. Nuclear magnetic resonance imaging with hyperpolarised helium-3. Lancet 1996;347:1297­9. 11. Kauczor HU, Hofmann D, Kreitner KF, Nilgens H, Surkau R, Heil W, et al. 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Bio-Algorithms and Med-Systems – de Gruyter

Published: Sep 30, 2014

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