Diagnostic procedures using direct injection of gaseous hyperpolarized 129Xe and associated systems and products

• US 7,560,096 B2
• Filed: 07/10/2003
• Issued: 07/14/2009
• Est. Priority Date: 03/13/2000
• Status: Expired due to Fees

• Current Assignee: Polarean, Inc. (Polarean Imaging Plc)
• Original Assignee: Medi-Physics Incorporated (General Electric Company)
• Inventors: Hagspiel, Klaus D., Driehuys, Bastiaan
• Primary Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US10/617,326
• Publication Number:
  US 20040143179A1
• Time in Patent Office: 2,196 Days
• Field of Search: 424/1.11, 424/1.65, 424/9.1, 424/9.3, 424/9.36, 534/7, 600/410, 600/420, 436/173
• US Class Current: 424/9.3
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 5/416 the spleen
• CPC Class Codes: A61K 49/1815 compo-inhalant, e.g. breath tests
• CPC Class Codes: A61M 5/1483 using flexible bags externally pressurised by fluid pressure
• CPC Class Codes: G01R 33/5601 involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent

Abstract

A method of screening for pulmonary embolism uses gaseous phase polarized ¹²⁹Xe which is injected directly into the vasculature of a subject. The gaseous ¹²⁹Xe 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 polarized ¹²⁹Xe gas is presented in small quantities of (preferably isotopically enriched) hyperpolarized ¹²⁹Xe and can provide high-quality vasculature MRI images or NMR spectroscopic signals with clinically useful signal resolution or intensity. One method injects the polarized ¹²⁹Xe 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 the ¹²⁹Xe 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.

Claims

1. A method of evaluating the efficacy of targeted drug therapy, comprising the steps of:

delivering a quantity of predetermined gene treatment preparation or pharmaceutical drug in vivo into a mammalian subject having a target site and a treatment condition, wherein said treatment condition is one of a cardiac condition and a pulmonary condition;

injecting a predetermined quantity of gaseous phase hyperpolarized ¹²⁹Xe in vivo into a mammalian subject such that the hyperpolarized gas is delivered to the target site in gaseous or dissolved form;

generating a NMR image or spectroscopic signal of the target site associated with the injected hyperpolarized ¹²⁹Xe gas; and

evaluating the NMR image or spectroscopic signal to evaluate the efficacy of the gene treatment or drug on the treatment condition.

2. A method according to claim 1, further comprising the step of acquiring at least two sets of data, the data representing two temporally spaced apart points in time, to evaluate if the treatment condition is influenced by the drug or gene therapy introduced in said delivering step.

3. A method according to claim 1, further comprising the step of evaluating whether the drug is properly delivered to the target site.

4. A method according to claim 1, wherein said at least two data sets correspond with a hyperpolarized 129Xe gas NMR signal data acquisition obtained both before said delivering step and after said delivering step.

5. A method according to claim 2, further comprising at least one of adjusting the quantity or formulation of the drug and confirming the proper delivery to the target site.

6. A method according to claim 1, wherein the treatment condition is one of cardiac function and pulmonary function, and wherein the target site is selected so as to administer polarized ¹²⁹Xe gas to a region representative of that condition.