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

Abstract

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

1 - 63 . (canceled) 
     
     
         64 . 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;   injecting a predetermined quantity of gaseous phase hyperpolarized  129 Xe 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  129 Xe gas; and   evaluating the NMR image or spectroscopic signal to evaluate the efficacy of the gene treatment or drug on the treatment condition administered in said delivering step.   
     
     
         65 . A method according to  claim 64 , 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. 
     
     
         66 . A method according to  claim 64 , further comprising the step of evaluating whether the drug is properly delivered to the target site. 
     
     
         67 . A method according to  claim 64 , 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. 
     
     
         68 . A method according to  claim 65 , further comprising at least one of adjusting the quantity or formulation of the drug and confirming the proper delivery to the target site. 
     
     
         69 . A method according to  claim 64 , wherein the treatment condition is one of cancer, cardiac, renal, hepatic or pulmonary function, and cerebral function, and wherein the target site is selected so as to administer polarized  129 Xe gas to a region representative of that condition. 
     
     
         70 - 79 . (canceled) 
     
     
         80 . A method of preparing a gas container having a sealable gas holding chamber prior to the introduction of a polarized product therein, comprising the steps of:
 (a) evacuating the gas container;   (b) introducing a quantity of CO 2  gas therein; and   (c) repeating step (a) after step (b).   
     
     
         81 - 88 . (canceled)