Refrigeration – Storage of solidified or liquified gas – With measuring
Reexamination Certificate
2001-09-07
2003-02-25
Doerrler, William C. (Department: 3744)
Refrigeration
Storage of solidified or liquified gas
With measuring
C604S181000, C604S026000, C424S009300
Reexamination Certificate
active
06523356
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to equipment and methods used to remove or dispense hyperpolarized gases from containers. The invention is particularly suitable for dispensing sterile or pharmaceutical hyperpolarized gases for Magnetic Resonance Imaging (“MRI”) applications.
BACKGROUND OF THE INVENTION
Conventionally, MRI has been used to produce images by exciting the nuclei of hydrogen molecules (present in water protons) in the human body. However, it has recently been discovered that polarized noble gases can produce improved images of certain areas and regions of the body which have heretofore produced less than satisfactory images in this modality. Polarized Helium-3 (“
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 is sensitive to handling and environmental conditions and can potentially rapidly decay from the polarized state.
Hyperpolarizers are used to produce and accumulate polarized noble gases. Hyperpolarizers 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 by reference as if recited in full herein.
The hyperpolarized gas is typically produced by spin-exchange with an optically pumped alkali metal. The alkali metal is removed from the hyperpolarized gas prior to introduction into a patient to form a non-toxic and/or sterile composition. Unfortunately, the hyperpolarized state of the gas can deteriorate or decay relatively quickly and therefore must be handled, collected, transported, and stored carefully.
The “T
1
” decay constant associated with the hyperpolarized gas' longitudinal relaxation time is often used to describe the length of time it takes a gas sample to depolarize in a given situation. The handling of the hyperpolarized gas is critical because of the sensitivity of the hyperpolarized state to environmental and handling factors and the potential for undesirable decay of the gas from its hyperpolarized state prior to the planned end use, i.e., delivery to a patient for imaging. Processing, transporting, and storing the hyperpolarized gases—as well as delivery of the gas to the patient or end user—can expose the hyperpolarized gases to various relaxation mechanisms such as magnetic gradients, contact-induced relaxation, paramagnetic impurities, and the like.
In the past, rigid containers have been used to transport the hyperpolarized gas from a polarization site to an imaging site such as a hospital. Unfortunately, these conventional transport containers can leave relatively large residual amounts of the gas in the container at the end use point. For example, absent active pumping (which generally introduces unacceptable depolarization to the hyperpolarized gas) an atmosphere of hyperpolarized gas typically remains in the transport vessel, in equilibrium with the ambient air pressure. As such, a larger volume of gas is typically transported to the imaging site to provide the volume desired for clinical use. Unfortunately, the hyperpolarized gas is relatively expensive to produce and this wasted residual gas can disadvantageously escalate the cost of the hyperpolarized product even further. Further, as noted above, conventional pump delivery systems which attempt to extract the gas from the transport container can cause the polarization of the hyperpolarized gas to rapidly decay, thereby limiting the life of the product and providing potentially severe time constraints in which successful clinical imaging can be performed.
Further, bag containers have also been used in the past to administer hyperpolarized gas to a subject via inhalation. Unfortunately, the quantity of gas actually dispensed into the bag can vary. Therefore, it can be problematic, especially when blending hyperpolarized gas with a buffer gas, to provide reliable repeatable concentrations and/or quantities of the inhalable hyperpolarized gas or gas mixtures over a plurality of doses. In addition it may be desirable to use different amounts of gas or gas mixtures as well as different sized dose containers, patient to patient.
For example, it may be beneficial to provide different known concentrations of hyperpolarized gases (25%, 50%, and the like) within a relatively constant overall volume of inhalable gas mixture such as a 1 or 1.5 liter volume (the remainder of the mixture being formed by suitable buffer gases). That is, it is often desirable to have a subject inhale a sufficient quantity of the hyperpolarized gas mixture to either partially or substantially “fully” inflate the lungs. For image calibration and/or regulatory agency guidelines of human or animal administered hyperpolarized gas, it can be desirable to provide reliable doses of predetermined inhalable volumes of the hyperpolarized gas mixture. Unreliable concentrations can, unfortunately, yield varying signal intensities, dose to dose. On the other hand, dispensing only hyperpolarized gas (no buffer gas) can be more costly, and unnecessary from an image viewpoint, as successful images can be obtained with lower concentrations of hyperpolarized gas.
Accordingly, there remains a need to provide improved extraction systems and containers to reduce the depolarizing effect of the extraction system, to relatively efficiently deliver the hyperpolarized gas to the desired subject, and provide more reliable concentrations and/or dosages of hyperpolarized gas.
OBJECTS AND SUMMARY OF THE INVENTION
In view of the foregoing, it is an object of the present invention to provide improved methods to extract hyperpolarized gases from polarization cells or vessels, collection, and transport vessels in a way which reduces the de-polarization of the gas attributed thereto.
It is another object of the invention to reduce the residual amounts of hyperpolarized gas in collection vessels or transport vessels at the end use site.
It is an additional object of the present invention to provide improved gas dispensing and metering methods and systems which allow more reliable dose equantities of hyperpolarized gases and/or concentrations of hyperpolarized gas mixtures to be dispensed.
It is yet another object of the invention to provide improved gas dispensing methods and associated containers and apparatus to reduce any degrading effect that the dispensing may have on the polarized life of a hyperpolarized product so that the hyperpolarized product retains sufficient polarization at the end use site to allow effective imaging at delivery.
It is still another object of the present invention to provide dual purpose transport containers which are configured to both collect and transport the hyperpolarized gas.
It is another object of the present invention to provide improved dose metering of the hyperpolarized gas into containers in a manner which reduces depolarizing activity associated with the dispensing and delivery of the hyperpolarized gas to a subject.
It is yet another object of the invention to provide methods and apparatus which can reduce the de-polarizing effects on the hyperpolarized state of the gas attributed to active dispensing of the gas from a polarization cell, collection, or transport vessel.
It is another object of the present invention to provide improved methods for inhibiting the introduction of oxygen into gas extraction systems or hyperpolarized gas flow paths.
It is an additional object of the present invention to provide a masking method, which inhibits the direct contact of hyperpolarized gas with a potentially de-polarizing material or surface.
It is another object of the present invention to provide a polarization verification method which can identify the expiration date of the hyperpolarized gas ex
Bogorad Paul L.
Hasson Kenton C.
Nouls John
Zollinger David L.
Zollinger Geri T. K.
Doerrler William C.
Medi--Physics, Inc.
Myers Bigel & Sibley Sajovec, PA
LandOfFree
Meted hyperpolarized noble gas dispensing methods and... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Meted hyperpolarized noble gas dispensing methods and..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Meted hyperpolarized noble gas dispensing methods and... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3121349