Refrigeration – Cryogenic treatment of gas or gas mixture – Separation of gas mixture
Reexamination Certificate
2001-08-23
2002-11-26
Capossela, Ronald (Department: 3744)
Refrigeration
Cryogenic treatment of gas or gas mixture
Separation of gas mixture
C062S055500
Reexamination Certificate
active
06484532
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to the collection and accumulation of polarized noble gases, and relates more particularly to the determination of the level of polarization of hyperpolarized gases used in NMR and magnetic resonance imaging (“MRI”) applications.
BACKGROUND OF THE INVENTION
It has recently been discovered that polarized inert noble gases can produce improved MRI images of certain areas and regions of the body which have heretofore produced less than satisfactory images in this modality. Polarized helium-3 (“
3
He”) and xenon-129 (“
129
Xe”) have been found to be particularly suited for this purpose. Unfortunately, as will be discussed further below, the polarized state of the gases are sensitive to handling and environmental conditions and can, undesirably, decay from the polarized state relatively quickly. Further, because of the sensitivity of the polarized gas, it is desirable to monitor the polarization level of the gas at various times during the product's life. For example, in-process monitoring can indicate the polarization achieved during the optical pumping process (described below) or the polarization lost at certain phases of the life cycle process (so as to determine the remaining useable life of the polarized gas or to help identify critical production path issues).
Hyperpolarizers are used to produce and accumulate polarized noble gases. Hyperpolarizes artificially enhance the polarization of certain noble gas nuclei (such as
129
Xe or
3
He) over the natural or equilibrium levels, i.e., the Boltzmann polarization. Such an increase is desirable because it enhances and increases the MRI signal intensity, allowing physicians to obtain better images of the substance in the body. See U.S. Pat. No. 5,545,396 to Albert et al., the disclosure of which is hereby incorporated herein by reference as if recited in fill herein.
In order to produce the hyperpolarized gas, the noble gas is typically blended with optically pumped alkali metal vapors such as rubidium (“Rb”). These optically pumped metal vapors collide with the nuclei of the noble gas and hyperpolarize the noble gas through a phenomenon known as “spin-exchange.” The “optical pumping” of the alkali metal vapor is produced by irradiating the alkali-metal vapor with circularly polarized light at the wavelength of the first principal resonance for the alkali metal (e.g., 795 nm for Rb). Generally stated, the ground state atoms become excited, then subsequently decay back to the ground state. Under a modest magnetic field (10 Gauss), the cycling of atoms between the ground and excited states can yield nearly 100% polarization of the atoms in a few microseconds. This polarization is generally carried by the lone valence electron characteristics of the alkali metal. In the presence of non-zero nuclear spin noble gases, the alkali-metal vapor atoms can collide with the noble gas atoms in a manner in which the polarization of the valence electrons is transferred to the noble-gas nuclei through a mutual spin flip “spin-exchange.”
In any event, after the spin-exchange has been completed, the hyperpolarized gas is separated from the alkali metal prior to introduction into a patient (to form a non-toxic pharmaceutically acceptable product). Unfortunately, both during and after collection, the hyperpolarized gas can deteriorate or decay relatively quickly (lose its hyperpolarized state) and therefore must be handled, collected, transported, and stored carefully. Thus, handling of the hyperpolarized gases is critical, because of the sensitivity of the hyperpolarized state to environmental and handling factors and the potential for undesirable decay of the gas from its hyperpolarized state.
Some accumulation systems employ cryogenic accumulators to separate the buffer gas from the polarized gas and to freeze the collected polarized gas. Co-pending and co-assigned U.S. patent application Ser. No. 08,989,604 to Driehuys et al. describes a suitable accumulator and method of cryogenically collecting, freezing, and then thawing frozen polarized xenon. The contents of this application are hereby incorporated by reference as if recited in full herein.
Conventionally, the level of polarization has been monitored at the polarization transfer process point (i.e., at the polarizer or optical cell) in a hyperpolarizer device or measured at a site remote from the hyperpolarizer after the polarized gas is dispensed from the hyperpolarizer. For example, for the latter, the polarized gas is directed to an exit or dispensing port on the hyperpolarizer and into two separate sealable containers, a gas delivery container, such as a bag, and a small (about 5 cubic centimeter) sealable glass bulb specimen container. This glass bulb specimen container is then sealed at the hyperpolarizer site and then carried away from the hyperpolarizer to a remotely located high-field NMR spectroscopy unit (4.7T) to determine the level of polarization achieved during the polarization process. See J. P. Mugler, B. Driehuys, J. R. Brookeman et al.,
MR Imaging and Spectroscopy Using Hyperpolarized
129
Xe Gas; Preliminary Human Results,
Mag. Reson. Med. 37, 809-815 (1997).
Generally stated, as noted above, conventional hyperpolarizers may also monitor the polarization level achieved at the polarization transfer process point, i.e., at the optical cell or optical pumping chamber. In order to do so, typically a small “surface” NMR coil is positioned adjacent the optical pumping chamber to excite and detect the gas therein and thus monitor the level of polarization of the gas during the polarization-transfer process. The small surface NMR coil will sample a smaller volume of the proximate polarized gas and thus have a longer transverse relaxation time (T
2
*) compared to larger NMR coil configurations. A relatively large tip angle pulse can be used to sample the local-spin polarization. The large angle pulse will generally destroy the local polarization, but because the sampled volume is small compared to the total size of the container, it will not substantially affect the overall polarization of the gas.
Typically, the surface NMR coil is operably associated with low-field NMR detection equipment which is used to operate the NMR coil and to analyze the detected signals. Examples of low-field NMR detection equipment used to monitor polarization at the optical cell and to record and analyze the NMR signals associated therewith include low-field spectrometers using frequency synthesizers, lock-in amplifiers, audio power amplifiers, and the like, as well as computers.
In any event, it is now known that on-board hyperpolarizer monitoring equipment no longer requires high-field NMR equipment, but instead can use low-field detection techniques to perform polarization monitoring for the optical cell at much lower field strengths (e.g., 1-100 G) than conventional high-field NMR techniques. This lower field strength allows correspondingly lower detection equipment operating frequencies, such as 1-400 kHz.
For applications where the entire hyperpolarized gas sample can be located inside the NMR coil, an adiabatic fast passage (“AFP”) technique has been used to monitor the polarization of the gas in this type of situation. Unfortunately, in most production-oriented situations, this technique is not desirable. For example, in order to measure the polarization in a one-liter patient dose bag, a relatively large NMR coil and spatially large magnetic field is needed.
More recently, Saam et al. has proposed a low-frequency NMR circuit expressly for the on-board detection of polarization levels for hyperpolarized
3
He at the optical cell inside the temperature-regulated oven which encloses the cell. See Saam et al.,
Low Frequency NMR Polarimeter for Hyperpolarized Gases,
Jnl. of Magnetic Resonance 134, 67-71 (1998). Magnetic Imaging Technologies, Inc. (“MITI”) and others have used low-field NMR apparatus for on-board polarization measurement.
However, there remains a need to be able to efficiently and reliably determine and/or monitor the l
Capossela Ronald
Medi--Physics, Inc.
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