Electricity: measuring and testing – Particle precession resonance – Using a nuclear resonance spectrometer system
Reexamination Certificate
1999-06-16
2003-05-20
Lefkowitz, Edward (Department: 2862)
Electricity: measuring and testing
Particle precession resonance
Using a nuclear resonance spectrometer system
C062S003100, C062S045100, C062S914000, C062S049100, C600S420000, C604S020000, C604S181000
Reexamination Certificate
active
06566875
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates generally to systems of determining or monitoring the condition of hyperpolarized gas, such as monitoring the polarization level of the hyperpolarized gas during transport. The hyperpolarized gases are particularly suitable for MR imaging and spectroscopy applications.
BACKGROUND OF THE INVENTION
Inert gas imaging (“IGI”) using hyperpolarized noble gases is a promising recent advance in Magnetic Resonance Imaging (MRI) and MR spectroscopic technologies. 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 are sensitive to handling and environmental conditions and can, undesirably, decay from the polarized state relatively quickly.
Various methods may be used to 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.
A “T
1
” decay constant associated with the hyperpolarized gas's longitudinal relaxation time is often used to characterize 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 thus the potential for undesirable decay of the gas from its hyperpolarized state prior to the planned end use, e.g., delivery to a patient for imaging. Processing, transporting, and storing the hyperpolarized gases—as well as delivering the gas to the patient or end user—can expose the hyperpolarized gases to various relaxation mechanisms such as magnetic field gradients, surface-induced relaxation, hyperpolarized gas atom interactions with other nuclei, paramagnetic impurities, and the like.
Multiple relaxation mechanisms can arise during production and transport of the hyperpolarized gas. These problems can be particularly troublesome when transporting the hyperpolarized gas from a production site to a (remote) use site. In transit, the hyperpolarized gas can be exposed to many potentially depolarizing influences. Indeed, the polarized state of the gas can be unknowingly destroyed and undesirably transported to a use site in a clinically ineffective polarized state.
There is, therefore, a need to be able to monitor the status of the hyperpolarized gas and/or its environment during transport or storage so as to minimize exposure to depolarizing effects during transport. Improved monitoring methods and systems are desired so that more accurate measurements can be achieved and/or so that the hyperpolarized product can retain sufficient polarization to allow effective imaging at delivery when transported over longer transport distances in various (potentially depolarizing) environmental conditions and for longer time periods from the initial polarization than has been viable previously.
OBJECTS AND SUMMARY OF THE INVENTION
It is therefore an object of the present invention to provide a portable monitoring system which can determine the polarization level of the hyperpolarized gas (and/or hyperpolarized gas products) during transport.
It is another object of the present invention to provide a monitoring system that can automatically adjust a magnetic holding field to a predetermined or optimal value. By so doing, the resonant frequency of the gas can be shifted above that of potentially substantially depolarizing environmental conditions during movement of the hyperpolarized gas products from a production site to a remote use site, thus increasing the usable lifespan of the hyperpolarized gas products.
It is also an object of the present invention to provide a portable monitoring system that is configured to engage with a portable transport unit or shipping container for transporting a quantity of hyperpolarized gas therein.
It is a further object of the present invention to provide a portable system which can provide information to a user and which allows user input to react to the information about gas-related parameters, thereby allowing a user to be alerted to and thus take action to reduce the likelihood of any introduction of substantially depolarizing factors onto the hyperpolarized gases (such as unprotected exposure to stray magnetic gradients).
It is another object of the present invention to provide a method for determining the polarization level of a quantity of hyperpolarized gas at successive intervals in time to determine the effectiveness of the hyperpolarized product and to determine the overall polarization decay rate.
It is yet another object of the present invention to provide a method of reliably identifying gas polarization values corresponding to a quantity of hyperpolarized gas during transport and/or at a destination site, particularly in the presence of stray magnetic fields.
It is an additional object of the present invention to provide a method for determining the polarization of the gas in a manner which accounts for NMR coil resonance to more accurately measure the polarization level of the gas.
These and other objects of the present invention are provided by a portable monitoring system for determining the polarization of hyperpolarized gas in transit. The method includes transporting a quantity of hyperpolarized gas from a first site to a second site and intermittently transmitting a predetermined excitation pulse to the quantity of hyperpolarized gas during the transporting step. An NMR signal corresponding to the response of the hyperpolarized gas to the excitation pulse is received. The magnitude of this signal is then multiplied by a calibration factor and the level of polarization of the hyperpolarized gas is determined. The method also preferably includes the step of selecting the excitation pulse such that a plurality of transmitted pulses are substantially non-depolarizing to the quantity of hyperpolarized gas. In a preferred embodiment, the received signal is analyzed and a frequency-dependent correction factor is applied to adjust the signal polarization value to compensate for any externally-induced frequency shift that may appear in the measured signal value.
Another aspect of the present invention is directed toward a portable monitoring system for determining the polarization level of a quantity of hyperpolarized gas product. The system includes positioning a NMR coil proximate to a quantity of hyperpolarized gas product packaged for transport from a first site to a second site and transmitting an excitation pulse to the NMR coil to, in turn, excite the hyperpolarized gas product. A signal corresponding to the response of the hyperpolarized gas product to the excitation pulse is received by the NMR coil and the response signal is analyzed to determine the polarization level of the hyperpolarized gas product during transport. The system also includes an adjustment means for compensating the magnetic field strength associated with a magnetic holding field that is positioned such that it is operably associated with the quantity of hyperpolarized gas during transport. In a preferred embodiment, the adjustment means can be used to alter the magnetic field so that a transmit and receive frequency used for monitoring the gas corresponds to an optimal value associated with the NMR coil resonance.
In a preferred embodiment, the hy
Hasson Kenton C.
Wheeler Bradley A.
Fetzner Tiffany A.
Lefkowitz Edward
Medi--Physics, Inc.
Myers Bigel & Sibley Sajovec, PA
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