Tissue marker for multimodality radiographic imaging

• US 8,544,162 B2
• Filed: 04/19/2010
• Issued: 10/01/2013
• Est. Priority Date: 11/17/2005
• Status: Active Grant

• Current Assignee: Breast-Med, Inc.
• Original Assignee: Breast-Med, Inc.
• Inventors: Bolan, Patrick, Garwood, Michael G., Nelson, Michael T., Halpern, Daniel A.
• Primary Examiner(s): Bryant, David
• Assistant Examiner(s): KOEHLER, CHRISTOPHER M
• Application Number:
  US12/762,837
• Publication Number:
  US 20100287887A1
• Time in Patent Office: 1,261 Days
• Field of Search: 600/420, 600/431, 366/108, 294/60, 294/63, 295/272
• US Class Current: 29/460
• CPC Class Codes: A61B 17/3468 for implanting or removing devices, e.g. prostheses, implants, seeds, wires devices for implanting seeds A61M37/0069
• CPC Class Codes: A61B 2090/3908 Soft tissue, e.g. breast tissue
• CPC Class Codes: A61B 2090/3925 ultrasonic
• CPC Class Codes: A61B 2090/3954 magnetic, e.g. NMR or MRI
• CPC Class Codes: A61B 2090/3958 emitting a signal
• CPC Class Codes: A61B 2090/3966 Radiopaque markers visible in an X-ray image
• CPC Class Codes: A61B 2090/397 electromagnetic other than visible, e.g. microwave
• CPC Class Codes: A61B 2090/3995 Multi-modality markers
• CPC Class Codes: A61B 8/481 involving the use of contrast agent, e.g. microbubbles introduced into the bloodstream analysis of echo signal exploiting properties of a contrast enhancer in devices for short-range imaging with acoustic waves G01S7/52039
• CPC Class Codes: A61B 90/39 Markers, e.g. radio-opaque or breast lesions markers
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 49/0447 Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is a halogenated organic compound
• CPC Class Codes: A61K 49/18 characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: A61M 31/005 for contrast media
• CPC Class Codes: G01R 33/4812 MR combined with X-ray or computed tomography [CT]
• CPC Class Codes: G01R 33/4814 MR combined with ultrasound
• 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
• CPC Class Codes: H01F 41/02 for manufacturing cores, coils, or magnets H01F41/14 takes precedence; for dynamo-electric machines H02K15/00
• CPC Class Codes: H01F 41/0253 : for manufacturing permanent magnets
• CPC Class Codes: Y10T 29/49075 : including permanent magnet or core
• CPC Class Codes: Y10T 29/49888 : Subsequently coating
• CPC Class Codes: Y10T 29/4998 : Combined manufacture including applying or shaping of fluent material
• CPC Class Codes: Y10T 29/49982 : Coating

Abstract

An implantable tissue marker incorporates a contrast agent sealed within a chamber in a container formed from a solid material. The contrast agent is selected to produce a change, such as an increase, in signal intensity under magnetic resonance imaging (MRI). An additional contrast agent may also be sealed within the chamber to provide visibility under another imaging modality, such as computed tomographic (CT) imaging or ultrasound imaging.

Claims

1. A method of manufacturing a radiographic marker capable of being permanently implanted in a living human or animal subject, the method comprising:

forming a fully implantable, biocompatible container from a nonbiodegradable solid material and defining an internal chamber; and

sealing a contrast agent within the internal chamber, the contrast agent configured to produce a change in signal intensity in a magnetic resonance (MR) imaging modality with the marker fully implanted in the subject, wherein the solid material of the container includes a first magnetic susceptibility and the contrast agent includes a second magnetic susceptibility, wherein the solid material and the contrast agent are configured such that the first and second magnetic susceptibilities are matched so that the first magnetic susceptibility is substantially equivalent to the second magnetic susceptibility, wherein the permanently implantable radiographic marker is sized and shaped to fit within a lumen of a cannula configured to deliver the marker to a fully implanted location within the subject.

2. The method of claim 1, comprising mixing a first contrast agent configured to produce the change in signal intensity in the MR imaging modality and a second contrast agent configured to produce a signal in another imaging modality, wherein sealing the contrast agent within the internal chamber includes sealing the mixture of the first and second contrast agents within the internal chamber.

3. The method of claim 2, wherein the other imaging modality includes an X-ray based imaging modality.

4. The method of claim 1, comprising sealing a therapeutic agent within the internal chamber.

5. The method of claim 1, wherein forming the container includes forming the container from a solid material configured to produce a signal in an imaging modality other than MR.

6. The method of claim 1, wherein forming the container includes forming a tube defining first and second end portions, and wherein sealing the contrast agent within the internal chamber includes at least substantially sealing the first and second end portions using a biocompatible adhesive.

7. The method of claim 6, wherein forming the container includes forming the tube from a solid material including at least one of a glass material, a ceramic material, a polymer material, silicone, or carbon fiber.

8. The method of claim 1, wherein forming the container includes micromachining the container.

9. The method of claim 1, wherein forming the container includes injection molding the container.

10. The method of claim 1, wherein forming the container includes forming a vial-shaped portion of the container, the vial-shaped portion including an opening.

11. The method of claim 10, wherein forming the container includes forming a lid portion of the container.

12. The method of claim 11, wherein sealing the contrast agent within the internal chamber includes attaching the lid portion of the container at the opening of the vial-shaped portion of the container.

13. The method of claim 1, wherein forming the container includes:

forming a first portion including at least two openings; and

forming second and third portions configured to be attached to the first portion at the at least two openings.

14. The method of claim 13, wherein sealing the contrast agent within the internal chamber includes attaching the second and third portions at respective openings of the first portion.

15. The method of claim 1, comprising coating the container to encapsulate the container.

16. The method of claim 15, wherein coating the container includes hermetically sealing the container.

17. The method of claim 1, comprising at least partially filling the internal chamber with the contrast agent.

18. The method of claim 17, wherein at least partially filling the internal chamber includes immersing the container within the contrast agent to inhibit air from being sealed within the internal chamber.

19. The method of claim 17, wherein at least partially filling the internal chamber includes vibrating the container during filling to aid in removal of gas bubbles from within the internal chamber prior to sealing the container.

20. The method of claim 17, wherein at least partially filling the internal chamber includes filling the internal chamber with the container within a chamber filled with a gas other than ambient air to inhibit ambient air from being sealed within the internal chamber.

21. A method of manufacturing a radiographic marker capable of being permanently implanted in a living human or animal subject, the method comprising:

forming a fully implantable, biocompatible container from a nonbiodegradable solid material and defining an internal chamber, the container including first and second portions, the first portion including at least one opening configured to access the internal chamber;

at least partially filling the internal chamber with a contrast agent, the contrast agent configured to produce a change in signal intensity in a magnetic resonance (MR) imaging modality with the marker fully implanted in the subject, wherein the solid material of the container includes a first magnetic susceptibility and the contrast agent includes a second magnetic susceptibility, wherein the solid material and the contrast agent are configured such that the first and second magnetic susceptibilities are matched so that the first magnetic susceptibility is substantially equivalent to the second magnetic susceptibility, wherein the permanently implantable radiographic marker is sized and shaped to fit within a lumen of a cannula configured to deliver the marker to a fully implanted location within the subject; and

sealing the contrast agent within the internal chamber including attaching the second portion of the container at the opening of the first portion of the container.

22. The method of claim 21, comprising mixing a first contrast agent configured to produce the change in signal intensity in the MR imaging modality and a second contrast agent configured to produce a signal in another imaging modality, wherein sealing the contrast agent within the internal chamber includes sealing the mixture of the first and second contrast agents within the internal chamber.

23. The method of claim 21, wherein forming the container includes micromachining the container.

24. The method of claim 21, wherein forming the container includes injection molding the container.

25. The method of claim 21, wherein forming the container includes:

forming the first portion including at least two openings; and

forming the second portion and a third portion configured to be attached to the first portion at the at least two openings, wherein sealing the contrast agent within the internal chamber includes attaching the second and third portions at respective openings of the first portion.

26. The method of claim 21, comprising coating the container to encapsulate the container.

27. The method of claim 21, wherein at least partially filling the internal chamber includes immersing the container within the contrast agent to inhibit air from being sealed within the internal chamber.

28. The method of claim 21, wherein at least partially filling the internal chamber includes vibrating the container during filling to aid in removal of gas bubbles from within the internal chamber prior to sealing the container.

29. The method of claim 21, wherein at least partially filling the internal chamber includes filling the internal chamber with the container within a chamber filled with a gas other than ambient air to inhibit ambient air from being sealed within the internal chamber.

30. A method of manufacturing a radiographic marker capable of being permanently implanted in a living human or animal subject, the method comprising:

forming a fully implantable, biocompatible container from a nonbiodegradable solid material and defining an internal chamber;

at least partially filling the internal chamber with a contrast agent, the contrast agent configured to produce a change in signal intensity in a magnetic resonance (MR) imaging modality with the marker fully implanted in the subject, wherein the solid material of the container includes a first magnetic susceptibility and the contrast agent includes a second magnetic susceptibility, wherein the solid material and the contrast agent are configured such that the first and second magnetic susceptibilities are matched so that the first magnetic susceptibility is substantially equivalent to the second magnetic susceptibility, wherein the permanently implantable radiographic marker is sized and shaped to fit within a lumen of a cannula configured to deliver the marker to a fully implanted location within the subject, wherein at least partially filling the internal chamber includes;

immersing the container within the contrast agent; and

vibrating the container during filling to aid in removal of gas bubbles from within the internal chamber prior to sealing the container; and

sealing the contrast agent within the internal chamber.

31. The method of claim 30, wherein forming the container includes micromachining the container.

32. The method of claim 30, wherein forming the container includes injection molding the container.

33. The method of claim 30, comprising coating the container to encapsulate the container.

34. The method of claim 30, wherein forming the container includes forming first and second portions of the container, the first portion including the internal chamber and at least one opening configured to access the internal chamber;

wherein sealing the contrast agent within the internal chamber includes attaching the second portion of the container at the opening of the first portion of the container.

35. The method of claim 34, wherein forming the container includes:

forming the first portion including at least two openings; and

forming the second portion and a third portion configured to be attached to the first portion at the at least two openings, wherein sealing the contrast agent within the internal chamber includes attaching the second and third portions at respective openings of the first portion.