Medi-physics, Inc.

Duke University

Other

Magnetic Imaging Technologies Incorporated

Bastiaan Driehuys

Kenton Christopher Hasson

David L Zollinger

Daniel M Deaton

Paul Lev Bogorad

Matthew S Freeman

Gary Price Cofer

Ian Nelson

John Nouls

Claudio Marelli

Margaret Hall

Zivko Djukic

Steve Kadlecek

Alan Langhorn

K C Hasson

Jan Wolber

Klaus D Hagspiel

James R Brookeman

Geri T K Zollinger

Sven Mansson

Ziyi Wang

Patrick A Cella

Sudarshan Rajagopal

Dennis Fujii

Sven Mansoon

Elianna Bier

Daniel Denton

Patrick Cella

Methods and systems withXe dynamic spectroscopy with a fitting function that includes one or more non-Lorentzians, optionally with a barrier Voigt, and signal processing for identifying cardiogenic oscillations for evaluating disease states, use in drug discovery or monitoring disease status.

Dynamic 129Xe gas exchange spectroscopy

Systems, methods and related devices used to produce and collect polarized noble gas to inhibit, suppress, detect or filter alkali metal nanoclusters to preserve or increase a polarization level thereof. The systems can include a pre-sat chamber that has an Area Ratio between 20 and 500.

Hyperpolarized noble gas production systems with nanocluster suppression, detection and/or filtering and related methods and devices

Methods and systems for assessing pulmonary gas exchange and/or alveolar-capillary barrier status include obtaining at least one MRI image and/or image data ofXe dissolved in the red blood cells (RBC) in the gas exchange regions of the lungs of a patient. The image is sufficiently sensitive to allow a clinician or image recognition program to assess at least one of pulmonary gas exchange, barrier thickness or barrier function based on theXe MRI RBC image.

Systems and methods for assessing pulmonary gas transfer using hyperpolarized 129XE MRI

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Methods and systems for assessing pulmonary gas exchange and/or alveolar-capillary barrier status include obtaining at least one MRI image and/or image data of hyperpolarizedXe dissolved in the red blood cells (RBC) in the gas exchange region of the lungs of a patient. The image is sufficiently sensitive to allow a clinician or image recognition program to assess at least one of pulmonary gas exchange, barrier thickness or barrier function based on theXe MRI image.

In certain embodiments, methods of the present invention obtain dynamic data sets of an NMR spectroscopy signal of polarizedXe in a selected structure, environment, or system. The signal data can be used to evaluate: (a) the physiology of a membrane or tissue; (b) the operational condition or function of a body system or portion thereof (when at rest or under stimulation); and/or (c) the efficacy of a therapeutic treatment used to treat a diagnosed disorder, disease, or condition. Thus, the present invention provides methods for screening and/or diagnosing a respiratory, cardiopulmonary disorder or disease such as chronic heart failure, and/or methods for monitoring the efficacy of therapeutics administered to subject to treat the disorder or disease.

A circuit for determining a polarization of a gas. The circuit includes a polarimetry circuit having an NMR coil that is configured to excite a polarized gas and that is responsive to an electromagnetic signal generated by the excited, polarized gas. The polarimetry circuit has a reproducible polarization measurement variability of less than about 2% when the NMR coil is exposed to a temperature in a range of about 0&#xb0; C. to about 200&#xb0; C.

Methods, systems, circuits and computer program products for determining polarization of a gas

A method of screening for pulmonary embolism uses gaseous phase polarizedXe which is injected directly into the vasculature of a subject. The gaseousXe can be delivered in a controlled manner such that the gas substantially dissolves into the vasculature proximate to the injection site. Alternatively, the gas can be injected such that it remains as a gas in the bloodstream for a period of time (such as about 8-29 seconds). The injectable formulation of polarizedXe gas is presented in small quantities of (preferably isotopically enriched) hyperpolarizedXe and can provide high-quality vasculature MRI images or NMR spectroscopic signals with clinically useful signal resolution or intensity. One method injects the polarizedXe as a gas into a vein and also directs another quantity of polarized gas into the subject via inhalation. In this embodiment, the perfusion uptake allows arterial signal information and the injection (venous side) allows venous signal information. The dual delivery is used to generate a combined introduction path with a more complete image signal of both the arterial and venous side of the pulmonary vasculature. In this NMR imaging method, the pulmonary embolism screening method can use the same NMR chest coil for the excitation and detection of theXe signals. The direct injection of small quantities of gas at particular sites along the vasculature targets specific target regions to provide increased signal intensity NMR images. The disclosure also includes related methods directed to other diagnostic vasculature regions physiological and conditions. Associated delivery and dispensing systems and methods, containers, and quantitative formulations of the polarized gas are also described.

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

An in vivo non-invasive method for detecting and/or diagnosing a pathological condition using hyperpolarizedXe spectroscopy is disclosed. Generally stated, the method includes determining the magnitude of spectral peaks which represent particular chemical shifts and comparing the observed magnitudes to those of healthy individuals. Preferably, the method includes subtracting substantial backgrounds and accounting for secondary conditions such as the polarization of hyperpolarized gas administered. Additionally, a quantitative analysis of hyperpolarizedXe spectra advantageously allows, a physician to establish the extent of disease progression. Advantageously, this method can be used regardless of the method of hyperpolarizedXe administration.

A system for determining polarization of a gas comprises a container that contains the polarized gas. An oscillator circuit comprises an Nuclear Magnetic Resonance (NMR) coil that is positioned adjacent to the container. A pulse generator circuit is configured to generate an electrical pulse that may be transmitted to an optical cell through the NMR coil to excite the polarized gas responsive to a control processor. A Q-reduction circuit that is independent of the pulse generator circuit is configured to reduce oscillations in the oscillator circuit from the transmitted electrical pulse responsive to the control processor. A receive circuit is responsive to an electrical signal that is induced in the oscillator circuit due to the electromagnetic excitation of the polarized gas. The control processor is configured to determine the polarization of the gas based on the output signal of the receive circuit. A polarimetry circuit for determining polarization of a gas includes an NMR coil that may be configured to excite a polarized gas and be responsive to an electromagnetic signal generated by the excited, polarized gas. The polarimetry circuit has a reproducible polarization measurement variability of less than 2% when the NMR coil is exposed to a temperature in a range of about 0&#xb0; C. to about 200&#xb0; C. Moreover, circuit-to-circuit polarization measurement variability may be less than about 3%.

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Chapel Hill, NC, United States of America

Bastiaan Driehuys