Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Magnetic imaging agent
Reexamination Certificate
1999-03-17
2002-02-12
Jones, Dameron (Department: 1616)
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Magnetic imaging agent
C424S009100, C424S009300
Reexamination Certificate
active
06346229
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to magnetic resonance imaging (“MRI”) and MR spectroscopy using hyperpolarized noble gases. More particularly, the present invention relates to imaging techniques using dissolved phase noble gases.
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. See U.S. Pat. No. 5,545,396 to Albert et al., entitled “Magnetic Resonance Imaging Using Hyperpolarized Noble Gases”, the disclosure of which is hereby incorporated by reference herein as if recited in full herein.
In order to obtain sufficient quantities of the polarized gases necessary for imaging, 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 Magnetic Resonance Imaging (“MRI”) signal intensity, thereby potentially allowing physicians to obtain better images of many tissues and organs in the body.
Generally stated, in order to produce the hyperpolarized gas, the hyperpolarizer is configured such that the noble gas is 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 described, 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”.
Conventionally, lasers have been used to optically pump the alkali metals. Various lasers emit light signals over various wavelength bands. In order to improve the optical pumping process for certain types of lasers (particularly those with broader bandwidth emissions), the absorption or resonance line width of the alkali metal can be broadened to more closely correspond with the particular laser emission bandwidth of the selected laser. This broadening can be achieved by pressure broadening, i.e., by using a buffer gas in the optical pumping chamber. Collisions of the alkali metal vapor with a buffer gas can lead to a broadening of the alkali's absorption bandwidth.
For example, it is known that the amount of polarized
129
Xe which can be produced per unit time is directly proportional to the light power absorbed by the Rb vapor. Thus, polarizing
129
Xe in large quantities generally takes a large amount of laser power. When using a diode laser array, the natural Rb absorption line bandwidth is typically many times narrower than the laser emission bandwidth. The Rb absorption range can be increased by using a buffer gas. Of course, the selection of a buffer gas can also undesirably impact the Rb-noble gas spin-exchange by potentially introducing an angular momentum loss of the alkali metal to the buffer gas rather than to the noble gas as desired. 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.
Conventionally, gas-phase imaging has been possible using both
3
He and
129
Xe, and has been particularly useful in producing ventilation-driven images of the lungs, a region where proton images have produced signal voids. However, in contrast to gas phase imaging, dissolved phase imaging has proven to be problematic. Dissolved phase imaging uses the solubility characteristic of
129
Xe in blood and lipid rich tissue. The gas phase is thus absorbed or “dissolved” into surrounding tissue or blood vessels and may allow perfusion imaging of the brain, lung, or other regions. Such images can potentially allow for the performance of non-invasive studies of the pulmonary vasculature to detect emboli and other circulatory system problems. Unfortunately, once the polarized gas has been dissolved (such as into the blood vessels), it has proven difficult to generate clinically useful images using the dissolved phase gas. Conventionally, dissolved phase imaging is attempted by performing a gas-based “regular” image and then looking for a spatially shifted dissolved phase image. However, the small flip angles typically associated with the “regular” image excitation pulses generally fail to produce sufficient detectable signal spectra in the dissolved phase, thus generating relatively inadequate dissolved phase images.
For example, MRI images using gas-space-imaging techniques have been generated using hyperpolarized
129
Xe gas. See Mugler III et al.,
MR Imaging and Spectroscopy Using Hyperpolarized
129
Xe gas:
Preliminary Human Results,
37 Magnetic Resonance in Medicine, pp. 809-815 (1997). While good correlation is seen between the gas-space signal in the xenon images and the gas-space signal void in the proton images, the spectra associated with the dissolved phase signal components were significantly lower than the gas-phase signal.
In addition, conventional imaging with MRI units generally requires relatively large magnetic fields. For example, 1.5 Tesla (“T”) units are common. The large magnetic fields can require special housing and shielding within the use site. Further, the MRI units must typically shim or control the magnetic field in order to produce magnet homogeneity which is suitable for imaging. As noted above, high field strength magnets generally require special handling and have relatively high operating costs. Unfortunately and disadvantageously, both the high field strength magnet and the relatively high homogeneity requirements can increase the unit's cost both to the medical facility and ultimately, the consumer.
OBJECTS AND SUMMARY OF THE INVENTION
In view of the foregoing, it is an object of the present invention to detect and/or manipulate dissolved-phase
129
Xe signals in a manner that yields clinically useful images.
It is another object of the present invention to provide an imaging method which can obtain useful images of dissolved
129
Xe in the pulmonary and/or cardiac vasculature.
It is an additional object of the present invention to provide an imaging method which yields useful images of the heart and major cardiac vessels using dissolved polarized
129
Xe.
It is yet another object of the present invention to provide an imaging method which can obtain useful information and/or images of dissolved
129
Xe which does not require high magnetic field strength and/or high magnetic field homogeneity.
It is a further object of the present invention to be able to obtain real-time blood flow path information such as local perfusion variation or blood flow abnormality using MR spectroscopy.
It is yet a further object of the present invention to provide an imaging method which can be used to determine quantitative measures of perfusion using dissolved polarized
129
Xe.
These and other objects are satisfied by the present invention, which
Bogorad Paul Lev
Driehuys Bastiaan
Hasson Kenton Christopher
Jones Dameron
Medi--Physics, Inc.
Myers Bigel Sibley & Sajovec P.A.
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