Hyperpolarized helium-3 microbubble gas entrapment methods
AssigneeMedi-Physics, Inc.
InventorBastiaan Driehuys
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Abstract
Methods for increasing the T1 of injectable microbubble formulations of hyperpolarized 3He include the step of introducing the hyperpolarized 3He to a quantity of microbubbles held in a chamber and increasing the pressure therein to facilitate the movement or loading of the 3He into the microbubbles. Subsequently, a limited quantity of carrier liquid or a carrier liquid solution alone, or pre-mixed with 3He, can be introduced to the microbubble/3He in the chamber to inhibit the tendency of the 3He to leach out of the bubble. Related pharmaceutical products and associated containers as well as an evacuation based method for rapid mixing and delivery of the bubbles and the 3He is also disclosed. An additional method for dissolving 129Xe gas by using bubbles as an accelerant is also described.
Claims46
A method of producing an injectable in vivo formulation of hyperpolarized 3He, comprising the steps of:
- introducing a plurality of microbubbles into a chamber;
- directing a quantity of hyperpolarized 3He into the chamber with the plurality of microbubbles;
- directing a quantity of liquid into the chamber after the quantity of hyperpolarized 3He gas and the microbubbles are located therein such that microbubbles are formed and introduced into the chamber independent of the liquid being directed into the chamber, wherein the liquid has a low solubility for 3He;
- increasing the pressure in the container to above one atmosphere;
- and
- contacting the microbubbles and the hyperpolarized 3He with the liquid thereby producing an injectable formulation of hyperpolarized 3He microbubbles.
A method of acquiring clinically useful NMR data, comprising the steps of:
- (a) preparing an injectable in vivo microbubble hyperpolarized gas formulation;
- (b) injecting said formulation into a biological subject;
- and
- (c) using NMR to obtain spectroscopic or image data signals associated with said formulation in said subject;
- wherein said preparing step comprises the steps of:
- introducing a plurality of microbubbles into a chamber;
- directing a quantity of hyperpolarized 3He into the chamber with the plurality of microbubbles such that the microbubbles are formed independent of the liquid being directed into the chamber;
- directing a quantity of liquid into the chamber after the quantity of hyperpolarized 3He gas and the microbubbles are located therein;
- increasing the pressure in the container to above one atmosphere;
- and
- contacting the microbubbles and the hyperpolarized 3He with the liquid thereby producing an injectable formulation of hyperpolarized 3He microbubbles,
- wherein said preparing step is substantially carried out temporally proximate to said injecting step.
A method of MRI imaging, comprising the steps of:
- (a) preparing an injectable in vivo microbubble hyperpolarized gas formulation, wherein said preparing step comprises the steps of:
- introducing a plurality of microbubbles into a chamber;
- directing a quantity of hypcrpolarized 3He into the chamber with the plurality of microbubbles;
- directing a quantity of liquid into the chamber after the quantity of hyperpolarized 3He gas and the microbubbles are located therein such that the microbubbles are formed independent of the liquid being directed into the chamber, wherein the liquid has a low solubility for 3He;
- increasing the pressure in the container to above one atmosphere;
- and
- contacting the microbubbles and the hyperpolarized 3He with the liquid thereby producing an injectable formulation of hyperpolarized 3He microbubbles;
- (b) injecting said formulation into a biological subject;
- and
- (c) using MRI techniques to obtain an MR image associated with said formulation in the subject.
Dependencies are inferred from the claim text.