Method and material to acquire magnetic resonance imaging data
Provided are MR images of a subject gastrointestinal tract structure in which the lumen of the structure is usefully darkened on both T1-weighted and T2-weighted images when the structure is imaged following administration to the subject of an enteric contrast agent formulation with particles containing encapsulated gas or partial vacuum. The present invention provides an encapsulated gas or partial vacuum particle contrast medium of use in acquiring such MR images. 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.
1 . An enteric contrast medium formulation which is formulated for oral delivery to a subject contemporaneous with a medical magnetic resonance (MR) imaging procedure performed on the gastrointestinal tract of said subject, said enteric contrast medium formulation comprising:
a stable aqueous suspension of the enteric contrast medium, the enteric contrast medium comprising encapsulated partial vacuum or gas microspheres, wherein the enteric contrast medium is stably suspended in an aqueous pharmaceutically acceptable vehicle;
the enteric contrast medium formulation comprising from 10% (wt/wt) to 50% (wt/wt) of the enteric contrast medium; and
the aqueous pharmaceutically acceptable vehicle comprising 0.2 to 0.5% xanthan gum as a suspending agent maintaining the microspheres in suspension, the formulation having a viscosity of from 50 g/cm-sec to 2400 g/cm-sec; and
wherein each hollow microsphere comprises a glass microparticle comprising a central void defined by a solid silicon dioxide shell, comprising silicon dioxide and maintaining within the central void an encapsulated gas or partial vacuum.
2 . The enteric contrast medium formulation of claim 1 , wherein said enteric contrast medium formulation is a unit dosage formulation comprising a diagnostically effective amount of said enteric contrast medium.
3 . The enteric contrast medium formulation of claim 1 , wherein said enteric contrast medium 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.
4 . The enteric contrast medium formulation of claim 1 , wherein said enteric contrast medium formulation is a unit dosage formulation of from about 50 to about 100 mL in volume.
5 . The enteric contrast medium formulation of claim 1 , wherein enteric contrast medium formulation is a unit dosage formulation of from about 100 mL to about 800 mL in volume.
6 . The enteric contrast medium formulation of claim 1 , further comprising a suspension agent selected from guar gum, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, alginates, polyethylene glycol chains, and sodium carboxylmethylcellulose.
7 . The enteric contrast medium formulation of claim 1 , wherein said enteric contrast medium formulation is a unit dosage formulation and it contains more than about 20 g of said encapsulated gas or partial vacuum microsphere.
8 . The enteric contrast medium formulation of claim 1 , wherein said aqueous 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, or a combination thereof.
9 . The enteric contrast medium formulation of claim 1 , wherein said enteric contrast medium formulation produces low T1 signal similar to or lower than that of water.
10 . The enteric contrast medium formulation of claim 1 , wherein said enteric contrast medium formulation produces low T2 signal similar to or lower than that of skeletal muscle.
11 . The enteric contrast medium formulation of claim 1 , wherein the encapsulated gas or partial vacuum microsphere has a true density from about 0.15 to about 0.6.
12 . The enteric contrast medium formulation of claim 1 , wherein the encapsulated gas or partial vacuum microsphere has a mean diameter of from about 5 to about 60 micrometers.
13 . The enteric contrast medium formulation of claim 1 , wherein the encapsulated gas or partial vacuum microsphere has a mean diameter of from about 60 to about 200 micrometers.
14 . The enteric contrast medium formulation of claim 1 , 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 MR imaging, 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.
15 . The enteric contrast medium formulation of claim 1 , wherein the encapsulated gas or partial vacuum microsphere makes up 5% or more of the weight of the formulation.
16 . A kit comprising:
(a) a first vial or set of vials containing the enteric contrast medium of claim 1 ;
(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.
17 . An enteric contrast medium formulation which is formulated for oral delivery to a subject contemporaneous with a MR imaging procedure performed on the abdomen or pelvis of said subject, said enteric contrast medium formulation comprising:
a stable aqueous suspension of the enteric contrast medium, the enteric contrast medium comprising encapsulated partial vacuum or gas microspheres, wherein the enteric contrast medium is stably suspended in an aqueous pharmaceutically acceptable vehicle;
the enteric contrast medium formulation comprising from 10% (wt/wt) to 50% (wt/wt) of the enteric contrast medium; and
the aqueous pharmaceutically acceptable vehicle comprising 0.2 to 0.5% xanthan gum as a suspending agent maintaining the microspheres in suspension, the formulation having a viscosity of from 50 g/cm-sec to 2400 g/cm-sec; and
wherein each hollow microsphere comprises a glass microparticle comprising a central void defined by a solid silicon dioxide shell, comprising silicon dioxide and maintaining within the central void an encapsulated gas or partial, suspended in an aqueous pharmaceutically acceptable vehicle component partial vacuum.
18 . A method of acquiring a contrast enhanced MR image of a subject, said method comprising:
contemporaneously with performing a medical MR imaging procedure on said subject, administering to said subject a diagnostically effective amount of an enteric contrast medium formulation contemporaneous with a medical MR imaging procedure performed on said subject, wherein said enteric contrast medium formulation comprises:
a stable aqueous suspension of the enteric contrast medium, the enteric contrast medium comprising encapsulated partial vacuum or gas microspheres, wherein the enteric contrast medium is stably suspended in an aqueous pharmaceutically acceptable vehicle;
the enteric contrast medium formulation comprising from 10% (wt/wt) to 50% (wt/wt) of the enteric contrast medium; and
the aqueous pharmaceutically acceptable vehicle comprising 0.2 to 0.5% xanthan gum as a suspending agent maintaining the microspheres in suspension, the formulation having a viscosity of from 50 g/cm-sec to 2400 g/cm-sec; and
wherein each hollow microsphere comprises a glass microparticle comprising a central void defined by a solid silicon dioxide shell comprising, silicon dioxide and maintaining within the central void an encapsulated gas or partial vacuum; and
performing a medical MR imaging procedure on said subject, thereby acquiring the contrast enhanced MR image of the subject.
19 . The method according to claim 18 , wherein MR k-space data are used to reconstruct said contrast enhanced MR image.
20 . The method according to claim 18 , wherein said contrast enhanced MR image is used to distinguish said enteric contrast medium formulation from other materials in the abdomen or the pelvis.
21 . The method according to claim 18 , wherein said contrast enhanced MR image is an image of a region selected from the abdomen and the pelvis of said subject.
22 . The method of any of claim 18 wherein said enteric contrast medium formulation 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.
23 . The method of claim 18 , further comprising interpreting the contrast enhanced MR image of the subject and diagnosing said subject during image interpretation.
24 . The method of claim 23 , wherein said subject is evaluated for possible or known injury selected from a malignancy, inflammation, infection, and ischemia, and a combination thereof.
25 . The method of claim 23 , wherein said subject is evaluated for anatomical detail that involves the bowel or tissues adjacent to bowel.
26 . An MRI image acquired by the method according to claim 18 .
27 . Two or more MR images according to claim 26 , wherein said MR images are acquired during the same MR imaging procedure and at least one of said images is a T1-weighted image and at least one of said MR images is a T2-weighted image.
28 . The MR image of claim 27 , wherein the MR image is a T1-weighted image in which the signal in the lumen is darkened to below that of a member selected from soft tissue, bowel wall, or intravenous contrast enhanced tissue, on T1-weighted images, and the MR image is essentially free of T1-weighted image artifacts on the bowel wall or other gastrointestinal tract structures adjacent to the darkened bowel lumen.
29 . The MR image of claim 27 wherein the T2-weighted image shows the signal in the gastrointestinal tract lumen is darkened to below that of a member selected from soft tissue, bowel wall, or edematous bowel wall, on T2-weighted images, and the MR image is essentially free of T2-weighted image artifacts on the bowel wall or other gastrointestinal tract structures adjacent to the darkened bowel lumen, and wherein the T1-weighted image shows the signal in the gastrointestinal tract lumen is darkened to below that of a member selected from soft tissue, bowel wall, or intravenous contrast enhanced tissue, on T1-weighted images, and the MR image is essentially free of T1-weighted image artifacts on the bowel wall or other gastrointestinal tract structures adjacent to the darkened bowel lumen.
30 . The MR image of claim 26 , wherein the MR image is a T2-weighted image in which the signal in the lumen is darkened to below that of a member selected from soft tissue, bowel wall, or edematous bowel wall, on T2-weighted images, and the MR image is essentially free of T2-weighted image artifacts on the bowel wall or other gastrointestinal tract structures adjacent to the darkened bowel lumen.
31 . A MR image of at least a portion of the gastrointestinal tract of a subject, the MR image containing a first region of interest, which includes a lumen of a gastrointestinal tract structure and an interior void of said subject gastrointestinal tract structure defined by said lumen, the interior void having distributed therein suspended particles,
wherein each particle comprises a hollow microsphere encapsulating gas or partial vacuum suspended in water containing 0.2 to 0.5% xanthan gum as a suspending agent maintaining the microspheres in suspension, the suspension having a viscosity of from 50 g/cm-sec to 2400 g/cm-sec;
the suspension comprising from 10% (wt/wt) to 50% (wt/wt) of the particles; and
wherein each hollow microsphere comprises a glass microparticle comprising a central void defined by a solid silicon dioxide shell, comprising silicon dioxide and maintaining within the central void an encapsulated gas or partial, suspended in an aqueous pharmaceutically acceptable vehicle component partial vacuum.