Encapsulated gas or partial vacuum contrast material

Abstract

The present invention provides an encapsulated gas or partial vacuum particle contrast media for use in CT imaging. In an exemplary embodiment, the invention provides an enteric contrast medium formulation. An exemplary formulation comprises, (a) an enteric contrast medium comprising a encapsulated gas or partial vacuum particle suspended in water. Exemplary encapsulated gas or partial vacuum particle has a specific gravity between 0.2 and 1.5. In various embodiments, the encapsulated gas or partial vacuum particle is suspended in aqueous media by an agent compatible with enteric administration of the formulation to a subject in need of such administration. In an exemplary embodiment, the contrast material is incorporated into a pharmaceutically acceptable carrier in which the material is suspended homogeneously. In an exemplary embodiment, the encapsulated gas or partial vacuum particle comprises 5% or more of the weight of the contrast material formulation.

What is claimed is: 
     
         1 . An enteric contrast medium formulation which is formulated for oral delivery to a subject contemporaneous with a medical imaging procedure performed on the abdomen of said subject, said formulation comprising:
 an enteric contrast medium comprising a suspension of one encapsulated gas or partial vacuum particle (e.g., hollow borosilicate microsphere) and an aqueous vehicle component, with said aqueous component which is a pharmaceutically acceptable aqueous vehicle,   wherein said particle comprises a shell defining an interior void, said shell formed of a material contributing at least about 30 Hounsfield Units (HU) to the CT number of said contrast medium formulation or of a body cavity in which said contrast medium is distributed during said medical imaging procedure.   
     
     
         2 . An enteric contrast medium formulation which is formulated for oral delivery to a subject contemporaneous with a medical imaging procedure performed on the abdomen of said subject, said formulation comprising an encapsulated gas or partial vacuum particle. 
     
     
         3 . The enteric contrast medium formulation of any preceding claim, wherein said formulation is a unit dosage formulation comprising a diagnostically effective amount of said enteric contrast medium. 
     
     
         4 . The enteric contrast medium formulation of any preceding claim, wherein said formulation is a unit dosage formulation of from about 800 mL to about 1500 mL per adult human dose, which may be divided into smaller containers such as 400 mL to 500 mL in volume. 
     
     
         5 . The enteric contrast medium formulation of any preceding claim wherein said formulation is a unit dosage formulation of from about 50 to about 100 mL in volume. 
     
     
         6 . The enteric contrast medium formulation of any preceding claim wherein formulation is a unit dosage formulation of from about 100 mL to about 800 mL in volume. 
     
     
         7 . The enteric contrast medium formulation of any preceding claim, wherein said encapsulated gas or partial vacuum particle is stable at room or body temperature (e.g., hollow borosilicate microspheres, gas impregnated silicone rubber, coated silica gel particles, heat-sealed silica gel particles, barium impregnated heat sealed silica gel particles, gas and barium impregnated silicone rubber, ceramic hollow microparticles). 
     
     
         8 . The enteric contrast medium formulation of any preceding claim, wherein said formulation comprises at least about 5% weight/weight percentage of said encapsulated gas or partial vacuum particle (from about 5% to about 95% in terms of weight/weight percentage). 
     
     
         9 . The enteric contrast medium formulation of any preceding claim, wherein said formulation comprises at least about 10% weight/weight percentage of said encapsulated gas or partial vacuum particle (from about 10% to about 95% in terms of weight/weight percentage). 
     
     
         10 . The enteric contrast medium formulation of any preceding claim, wherein said suspension agent is selected from xanthan gum, guar gum, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, alginates, polyethylene glycol chains, and sodium carboxylmethylcellulose. 
     
     
         11 . The enteric contrast medium formulation of any preceding claim, wherein said formulation is a unit dosage formulation and it contains more than about  20  g of said encapsulated gas or partial vacuum particle. 
     
     
         12 . The enteric contrast medium formulation of any preceding claim, wherein said suspension agent comprises xanthan gum. 
     
     
         13 . The enteric contrast medium formulation of any preceding claim, wherein said pharmaceutically acceptable vehicle further comprises an additive to retard dehydration of said formulation in the bowel, a flavoring agent, a thickening agent, a flow agent, a pH buffer, a laxative, an osmolality-adjusting agent, and a combination thereof. 
     
     
         14 . The enteric contrast medium formulation of any preceding claim, wherein said enteric contrast medium has an 80:140 kVp CT number ratio of greater than about 2.1. 
     
     
         15 . The enteric contrast medium formulation of any preceding claim, wherein said enteric contrast medium has an 80:140 kVp CT number ratio of from about 0.6 to about 0.8. 
     
     
         16 . The enteric contrast medium formulation of any preceding claim, wherein said enteric contrast medium has an 80:140 kVp CT number ratio of from about 0.3 to about 0.5. 
     
     
         17 . The enteric contrast medium formulation of any preceding claim, wherein said enteric contrast medium has an 80:140 kVp CT number ratio below 0.3, including ratios below zero. 
     
     
         18 . The enteric contrast medium formulation of any preceding claim wherein the encapsulated gas or partial vacuum particle has a specific gravity similar to that of water (e.g., from about 0.7 to about 1.2 g/cc). 
     
     
         19 . The enteric contrast medium formulation of any preceding claim wherein the encapsulated gas or partial vacuum particle a specific gravity from about 0.2 to about 0.8. 
     
     
         20 . The enteric contrast medium formulation of any preceding claim wherein the encapsulated gas or partial vacuum particle has a mean diameter of from about 5 to about 60 micrometers. 
     
     
         21 . The enteric contrast medium formulation of any preceding claim wherein the encapsulated gas or partial vacuum particle has a mean diameter of from about 60 to about 200 micrometers. 
     
     
         22 . The enteric contrast medium formulation of any preceding claim wherein the encapsulated gas or partial vacuum particle has a mean diameter of from about 0.5 to about 5 micrometers. 
     
     
         23 . The enteric contrast medium formulation of any preceding claim wherein said enteric contrast medium is provided in powdered or other concentrated form to be mixed with water or other said acceptable pharmaceutical aqueous vehicle near the time of administration for CT scanning, together with instructions for preparing an administrable enteric contrast medium and, optionally, one or more device for administering said administrable enteric contrast medium to a subject. 
     
     
         24 . The enteric contrast medium formulation of any preceding claim, wherein the encapsulated gas or partial vacuum particle makes up 5% or more of the weight of the formulation. 
     
     
         25 . A method of acquiring contrast enhanced X-ray or computed tomography or dual energy computed tomography or spectral computed tomography projection data of a subject, said method comprising: administering to said subject a diagnostically effective amount of said enteric contrast medium formulation of any preceding claim; and
 acquiring said projection data of said subject.   
     
     
         26 . The method according to  claim 25 , wherein said X-ray or computed tomography or dual energy computed tomography or spectral computed tomography projection data is reconstructed into a computed tomography image. 
     
     
         27 . The method of any of  claims 25 - 26 , wherein said contrast agent is imaged using a dual energy or spectral CT scanner with X-ray filters of different material or thickness (including zero) that modify the energy spectra of the X-ray beams. Example materials to filter the energy spectra of the X-ray beams include but are not limited to aluminum, copper, gold, or tin 
     
     
         28 . The method according to  claims 25 - 27 , wherein said X-ray or computed tomography or dual energy computed tomography or spectral computed tomography projection data are used for 2-material, 3-material, or multi-material decomposition and reconstructed into CT images. 
     
     
         29 . The method according to  claims 25 - 28 , wherein said computed tomography images are used for 2-material, 3-material, or multi-material decomposition to reconstruct additional CT images. 
     
     
         30 . The method according to  claims 25 - 29 , wherein said computed tomography images are used to distinguish said enteric contrast medium formulation from other materials in the abdomen. 
     
     
         31 . The method according to any of  claims 25 - 30 , wherein said image is an image of a region selected from the abdomen and pelvis of said subject. 
     
     
         32 . The method according to any of  claims 25 - 31 , wherein said method further comprises administering to said subject a second contrast medium different from said enteric contrast medium, and said second contrast medium is administered through a route selected from oral administration, intrathecal administration, intravesicular administration, enteric administration, anal administration, intracatheter administration, intra-device administration, intravascular administration, administration into a fistula, and administration into a surgically created pouch. 
     
     
         33 . The method according to  claim 32 , wherein said second contrast medium is a member selected from an iodinated contrast medium, a Ba-, Gd- W-, Bi-, Mg-, Yb- and a Ta-based contrast medium and a silicon based contrast medium. 
     
     
         34 . The method according to any of  claims 32 - 33 , wherein said enteric contrast medium and said second contrast medium are distinguishable from each other in said image based on x-ray attenuation (CT number) at single energy spectrum CT. 
     
     
         35 . The method according to any of  claims 32 - 34  wherein said enteric contrast medium has CT number of less than about 50 Hounsfield Units in said image. 
     
     
         36 . The method according to any of  claims 32 - 35  wherein said enteric contrast medium has a CT number less than about −50 Hounsfield Units in said image. 
     
     
         37 . The method according to any of  claims 32 - 36  wherein said enteric contrast medium has a CT number greater than about 100 Hounsfield Units in said image. 
     
     
         38 . The method according to any of  claims 32 - 37 , wherein said enteric contrast medium and said second contrast medium are distinguishable from each other in said image based on their CT number, relative X-ray attenuation at different X-ray spectra, or both. 
     
     
         39 . The method according to any of  claims 32 - 38  wherein said enteric contrast medium has an 80:140 kVp CT number ratio of greater than about 2.1 in said image. 
     
     
         40 . The method according to any of  claims 32 - 38  wherein said enteric contrast medium has an 80:140 kVp CT number ratio of less than about 0.8 or less than zero in said image. 
     
     
         41 . The method of dual energy or spectral CT, wherein the formulations of the invention are imaged on dual energy or spectral CT scanners which use different filters for the low and high kVp imaging, such as aluminum or copper filters for the low kVp images and tin filters for the high kVp imaging. 
     
     
         42 . The method of any of  claims 25 - 41  wherein said enteric contrast agent is administered to said subject by delivery through:
 (a) a natural cavity selected from the mouth, vagina, bladder, rectum and urethra; 
 (b) a surgically created space selected from an ileal pouch, and a neobladder; 
 (c) a space created by injury selected from a fistula, sinus tract, and abscess; or 
 (d) a medical device selected from a catheter, a tube, a reservoir, a pouch and a pump. 
 
     
     
         43 . A kit comprising:
 (a) a first vial or set of vials containing the enteric contrast medium of any of  claims 1 - 24 ;   (b) a second vial containing a second contrast medium; and   (c) directions for formulating said enteric contrast medium with or without said second contrast medium.   
     
     
         44 . The method of  claim 25 - 42 , comprising diagnosing said subject. 
     
     
         45 . The method of  claim 44 , wherein said subject is diagnosed as having injury selected from a malignancy, inflammation, infection, and ischemia, and a combination thereof. 
     
     
         46 . The method of  claim 44 , wherein said subject is evaluated for anatomical detail that involves the bowel or tissues adjacent to bowel.