Medi-physics, Inc.

Kenton Christopher Hasson

David L Zollinger

Bastiaan Driehuys

Paul Lev Bogorad

Geri T K Zollinger

Bradley A Wheeler

Daniel M Deaton

William Happer

John Nouls

Ian Nelson

Alan Langhorn

Patrick A Cella

Daniel Denton

Patrick Cella

A transport unit includes a plurality of permanent magnets arranged to provide a magnetic holding field for protecting hyperpolarized gas during storage and/or transport. The permanent magnets are configured in a relatively light weight manner to project a substantially cylindrical magnetic holding field or spherical holding field in space. The magnet arrangements can include primary magnets and field shaping secondary magnets which act to enlarge the region of homogeneity. The permanent magnet arrangement can also be provided with a cylindrical shaped flex sheet magnetically activated to provide the magnetic holding field. The permanent magnet arrangements do not require disassembly to insert or remove one or more containers of hyperpolarized gas in or out of the transport unit.

Hyperpolarized gas transport and storage devices and associated transport and storage methods using permanent magnets

Methods of collecting, thawing, and extending the useful polarized life of frozen polarized gases include heating a portion of the flow path and/or directly liquefying the frozen gas during thawing. A polarized noble gas product with an extended polarized life product is also included. Associated apparatus such as an accumulator and heating jacket for collecting, storing, and transporting polarized noble gases include a secondary flow channel which provides heat to a portion of the collection path during accumulation and during thawing.

Polarized gas accumulators and heating jackets and associated gas collection and thaw methods and polarized gas products

A compact portable transport unit for shipping hyperpolarized noble gases and shielding same from electromagnetic interference and/or external magnetic fields includes a means for shifting the resonance frequency of the hyperpolarized gas outside the bandwidth of typical frequencies associated with prevalent time-dependent fields produced by electrical sources. Preferably the transport unit includes a magnetic holding field which is generated from a solenoid in the transport unit. The solenoid includes a plurality of coil segments and is sized and configured to receive the gas chamber of a container. The gas container is configured with a valve, a spherical body, and an extending capillary stem between the valve and the body. The gas container or hyperpolarized product container can also be formed as a resilient bag. The distribution method includes positioning a multi-bolus container within the transport unit to shield it and transporting same to a second site remote from the first site and subsequently dispensing into smaller patient sized formulations which can be transported (shielded) in another transport unit to yet another site.

Hyperpolarized gas containers, solenoids, transport and storage devices and associated transport and storage methods

MR spectroscopy and imaging methods for imaging pulmonary and cardiac vasculature and the cardiac region and evaluating blood flow or circulatory deficits use dissolved phase polarized Xe gas and large flip angle excitation pulses. Pulmonary and cardiac vasculature MRI images are obtained by delivering gas to a patient via inhalation such as with a breath-hold delivery-procedure, exciting the dissolved phase gas with a large flip angle pulse, and generating a corresponding image. Preferably, the image is obtained using multi-echo imaging techniques. Blood flow is quantified using low field MR spectroscopy and an RF excitation pulse with a frequency which corresponds to the resonance of the dissolved phase Xe.

Methods for imaging pulmonary and cardiac vasculature and evaluating blood flow using dissolved polarized 129Xe

Methods of extracting and removing hyperpolarized gas from a container include introducing an extraction fluid into the container to force the hyperpolarized gas out of an exit port. The hyperpolarized gas is forced out of the container separate and apart from the extraction fluid. Alternatively, if the fluid is a gas, a portion of the gas is mixed with the hyperpolarized gas to form a sterile mixed fluid product suitable for introduction to a patient. An additional method includes engaging a gas transfer source such as a syringe to a transport container and pulling a quantity of the hyperpolarized gas out of the container in a controlled manner. Another method includes introducing a quantity of liquid into a container and covering at least one predetermined internal surface or component with the liquid to mask the surfaces and keep the hyperpolarized gas away from the predetermined internal surface, thereby inhibiting any depolarizing affect from same. Examples of surfaces or components suitable for masking include valves, seals, and the like. Yet another extraction method includes expanding a resilient member inside the container to force the hyperpolarized gas to exit therefrom. Containers include a resilient member positioned in fluid communication with the hyperpolarized gas in the container. An additional container includes inlet and outlet ports in fluid communication with the chamber and positioned on opposing sides or end portions of the container. Another container includes a port configured to receive a portion of a syringe therein. An additional aspect of the disclosure relates to calibration methods and apparatus for identifying the hyperpolarization status of the gas.

Hyperpolarized noble gas extraction methods, masking methods, and associated transport containers

A system, method, and computer program products and associated apparatus, to monitor and determine the polarization level of a quantity of hyperpolarized gas during transport. A portable device is configured to transmit an excitation pulse and analyze a response signal in transit to provide a polarization level corresponding to the hyperpolarized gas. Preferably, the monitoring system can provide magnetic field fluctuation feedback to the transport unit and adjust operating current to a solenoid. The system also can compensate for NMR frequency shifts that may appear in the measured response signal to provide a more accurate polarization level or &ldquo;real&rdquo; T for the hyperpolarized gas.

Portable hyperpolarized gas monitoring systems, computer program products, and related methods using NMR and/or MRI during transport

A resilient multi-layer container is configured to receive a quantity of hyperpolarized noble fluid such as gas and includes a wall with at least two layers, a first layer with a surface which minimizes contact-induced spin-relaxation and a first or second layer which is substantially impermeable to oxygen. The container is especially suitable for collecting and transporting He. The resilient container can be formed of material layers which are concurrently responsive to pressure such as polymers, deuterated polymers, or metallic films. The container can include a capillary stem and/or a port or valve isolation means to inhibit the flow of gas from the main volume of the container during transport. The resilient container can be configured to directly deliver the hyperpolarized noble gas to a target interface by deflating or collapsing the inflated resilient container. In addition, single layer resilient containers with T 's of above 4 hours for Xe and above 6 hours for He include materials with selected relaxivity values. In addition, a bag with a port fitting or valve member and one or more of a capillary stem and port isolation means is configured to minimize the depolarizing effect of the container valve or fitting(s). Also disclosed is a method for determining the gas solubility in an unknown polymer or liquid using the measured relaxation time of a hyperpolarized gas.

Resilient containers for hyperpolarized gases and associated methods

Methods of dispensing meted quantities of hyperpolarized gas to form a hyperpolarized gas mixture include pre-filling a gas syringe with a quantity of non-polarized gas, then introducing the hyperpolarized gas therein while the non-polarized gas is held therein, and expelling both the hyperpolarized gas and non-polarized gas from the syringe. Methods of inhibiting the presence of oxygen in gas flow paths and extraction systems are also described.

Meted hyperpolarized noble gas dispensing methods and associated devices

MR spectroscopy and imaging methods for imaging pulmonary and cardiac vasculature and the cardiac region and evaluating blood flow or circulatory deficits use dissolved phase polarized Xe gas and large flip angle excitation pulses. Pulmonary and cardiac vasculature MRI images are obtained by delivering gas to a patient via inhalation such as with a breath-hold delivery -procedure, exciting the dissolved phase gas with a large flip angle pulse, and generating a corresponding image. Preferably, the image is obtained using multi-echo imaging techniques. Blood flow is quantified using low field MR spectroscopy and an RF excitation pulse with a frequency which corresponds to the resonance of the dissolved phase Xe.

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Durham, NC, United States of America

Kenton Christopher Hasson