Automated Modular Hyperpolarizers and Related Devices and Methods

Abstract

Modular expandable hyperpolarizers include a central control module and at least one optical pumping module that can be expandable to a plurality of optical pumping modules that can be separately operated depending on the capacity demands at the production site (hospital, clinic and the like). Methods for producing blended polarized gas products include introducing a pre-packaged pre-mixed amount of a polarizer-ready blend of unpolarized gas. Methods for producing the polarized gas can be carried out at the point of use site and the production run according to patient load. Other methods consider the patient load and automatically schedule the hyperpolarizer to yield the desired polarized gas doses to support the patient and/or MRI/NMR equipment schedule.

1 .- 15 . (canceled)  
   
   
       16 . A kit for producing polarized noble gas, comprising: 
 a sealed container comprising a predetermined quantity of a pharmaceutical grade unpolarized gas mixture comprising an inert noble gas to be polarized and a second high-purity carrier gas therein; and    a dispensing container configured to hold a quantity of polarized gas mixture therein.    
   
   
       17 . A kit according to  claim 16 , wherein the predetermined quantity of unpolarized gas mixture corresponds to a single patient batch quantity.  
   
   
       18 . A kit according to  claim 17 , wherein the unpolarized gas container has a collapsible structure, and wherein the single patient batch quantity is sufficient in amount to at least one bolus sized dose of polarized gas mixture formulated for human in vivo administration.  
   
   
       19 . A kit according to  claim 17 , wherein the unpolarized gas mixture comprises  3 He and N 2 , and wherein the single batch quantity is sufficient to form about 2-4 inhalation doses of polarized  3 He mixture suitable for in vivo administration to patient during a single MRI/NMR evaluation session.  
   
   
       20 . A kit according to  claim 16 , wherein the dispensing container may be sealed with a quantity of high purity inert filler gas therein.  
   
   
       21 . A kit according to  claim 21 , wherein the high-purity filler gas comprises N 2 .  
   
   
       22 . A kit according to  claim 16 , wherein the inert noble gas to be polarized is  129 Xe.  
   
   
       23 . A kit according to  claim 16 , wherein the inert noble gas to be polarized is  3 He.  
   
   
       24 . A kit according to  claim 26 , wherein the unpolarized gas mixture carrier gas comprises at least one of helium, nitrogen, or xenon.  
   
   
       25 . A method of providing polarized noble gas for NMR or MRI applications, comprising: 
 expelling the unpolarized gas mixture from a pre-packaged quantity of unpolarized gas mixture comprising a noble gas to be polarized into a hyperpolarizer located at a point of use site;    polarizing the noble gas via spin-exchange interactions with an alkali metal in the hyperpolarizer;    measuring the polarization level of the noble gas;    dispensing the polarized noble gas out of the hyperpolarizer into a patient dispensing device; and    blending in situ, at the point of use site, the polarized noble gas with a biocompatible fluid to provide a pharmaceutical grade polarized noble gas product suitable for in vivo administration to a subject.    
   
   
       26 . A method according to  claim 25 , further comprising connecting the pre-packaged quantity of unpolarized gas to an externally accessible gas inlet port on the hyperpolarizer so that the connection is air-tight before the expelling step.  
   
   
       27 . A method according to  claim 25 , wherein the prepackaged quantity is a partial volume quantity held in a collapsible container.  
   
   
       28 . A method according to  claim 25 , wherein the prepackaged quantity is formulated as a single batch size sufficient to supply a single patient during a single NMR/MRI session.  
   
   
       29 . A method according to  claim 25 , further comprising: 
 heating the gas during the polarizing step; and    cooling the polarized gas after the polarizing step;    wherein the measuring step is carried out so as to obtain a reading after the cooling step and wherein the blending step is a based on polarization level of the polarized gas after the cooling step, and wherein the biocompatible fluid is a medical grade high purity inert gas.    
   
   
       30 . A method for supplying meted amounts of unpolarized pharmaceutical grade inert noble gas mixtures, each formulated to be independently introduced to a hyperpolarizer to provide polarized noble gas, comprising: 
 introducing a meted single batch quantity of an unpolarized pharmaceutical grade noble gas mixture into an optical pumping cell in a hyperpolarizer at a production site, the meted batch quantity comprising a predetermined amount of carrier gas and a predetermined amount of inert noble gas, the single batch quantity being sufficient to yield polarized noble gas in a quantity sufficient for a single patient during a single MRI or NMR evaluation session; and    sealing the container so that the unpolarized pharmaceutical grade noble gas mixture has a shelf life of at least about 1-6 months.    
   
   
       31 . A method according to  claim 30 , further comprising shipping the unpolarized gas mixture to a point of use site.  
   
   
       32 . A method of polarizing unpolarized inert noble gas in a hyperpolarizer, comprising: 
 receiving a plurality of pre-packaged compressible containers of predetermined quantities of an unpolarized gas mixture, the unpolarized gas mixture comprising a noble inert gas and a carrier gas;    engaging one of the pre-packaged containers of the unpolarized gas mixture to a hyperpolarizer having an optical pumping cell and an unpolarized gas inlet path and a polarized gas exit path;    releasing the unpolarized gas mixture from the pre-packaged container;    directing the unpolarized gas mixture to travel to through the gas inlet path to the optical pumping cell;    polarizing the gas via spin-exchange interactions with an alkali metal held in the optical pumping cell;    heating the optical pumping cell during the polarizing step;    cooling the polarized gas;    measuring the polarization level of the polarized gas;    dispensing the polarized gas from the optical pumping cell and out of the gas exit path; and    blending N 2  with the dispensed polarized gas to provide a pharmaceutical grade polarized gas formulation.    
   
   
       33 . A method according to  claim 32 , wherein the method steps are carried out at a point of use site.  
   
   
       34 .- 38 . (canceled)