CA2478709A1 - Metal structure compatible with mri imaging, and method of manufacturing such a structure - Google Patents

Metal structure compatible with mri imaging, and method of manufacturing such a structure Download PDF

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Publication number
CA2478709A1
CA2478709A1 CA002478709A CA2478709A CA2478709A1 CA 2478709 A1 CA2478709 A1 CA 2478709A1 CA 002478709 A CA002478709 A CA 002478709A CA 2478709 A CA2478709 A CA 2478709A CA 2478709 A1 CA2478709 A1 CA 2478709A1
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Canada
Prior art keywords
bridge
rings
adjacent
structure according
tubular
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002478709A
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French (fr)
Other versions
CA2478709C (en
Inventor
Thiemo Arnim Blank
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Angiomed GmbH and Co Medizentechnik KG
Original Assignee
Angiomed Gmbh & Co. Medizintechnik Kg
Thiemo Arnim Blank
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Application filed by Angiomed Gmbh & Co. Medizintechnik Kg, Thiemo Arnim Blank filed Critical Angiomed Gmbh & Co. Medizintechnik Kg
Publication of CA2478709A1 publication Critical patent/CA2478709A1/en
Application granted granted Critical
Publication of CA2478709C publication Critical patent/CA2478709C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/89Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure the wire-like elements comprising two or more adjacent rings flexibly connected by separate members
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2002/828Means for connecting a plurality of stents allowing flexibility of the whole structure
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A61F2002/91525Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other within the whole structure different bands showing different meander characteristics, e.g. frequency or amplitude
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A61F2002/91533Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other characterised by the phase between adjacent bands
    • A61F2002/91541Adjacent bands are arranged out of phase
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A61F2002/9155Adjacent bands being connected to each other
    • A61F2002/91558Adjacent bands being connected to each other connected peak to peak
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A61F2002/9155Adjacent bands being connected to each other
    • A61F2002/91591Locking connectors, e.g. using male-female connections
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2230/00Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2230/0002Two-dimensional shapes, e.g. cross-sections
    • A61F2230/0028Shapes in the form of latin or greek characters
    • A61F2230/0054V-shaped
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0014Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
    • A61F2250/0039Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis differing in diameter

Abstract

8he present invention relates to expandable metal stents (2) having an abluminal wall, a luminal wall and a radial wall thic therebetween, with struts (3) defining through-apertures in the wall, the stent further having a longitudinal axis and defining a plurality of expansible rings (4) arranged adjacent one another along the longitudinal axis of the stent, each of the rings defining at least one bridge strut (14A, 14B), and adjacent rings bein g linked by a bridge (12) extending between adjacent bridge struts on adjacent rings, the stent being characterised in that the bridges (12) exhibit reduce d electrical conductivity throughout the wall thickness, and there are a plurality of said bridges, distributed throughout the length of the stent an d configured and arranged to divide the tubular structure into axially spaced and electrically insulated sections. The present invention relates furthermo re to a method of manufacturing such a stent.

Claims (24)

1. A tubular radially expansible metal structure (2) having an abluminal major wall surface, a luminal major wall surface and a radial wall thickness therebetween, with struts (3) defining through-apertures in the wall, the structure further having a longitudinal axis and defining a plurality of expansible rings (4) arranged adjacent one another along the longitudinal axis of the structure, each of the rings (4) defining at least one bridge strut (14A, 14B) and adjacent rings being linked by at least one bridge (12) formed by co-operation between adjacent bridge struts (14A, 14B) on adjacent rings (4), characterised in that said bridge (12) exhibits reduced electrical conductivity throughout the wall thickness, and there are a plurality of said bridges, distributed throughout the length of the tubular structure and configured and arranged to divide the tubular structure into axially spaced and electrically insulated sections.
2. The structure according to claim 1, wherein the bridge (12) comprises inter-engaged joint portions.
3. The structure according to claims 1 or 2, wherein the bridge (12) comprises complementary mating portions (16A, 16B).
4. The structure according to claim 3, wherein the mating portions (16A, 16B) are male-female form-fitting portions.
5. The structure according to claim 4, wherein the form-fitting portions have a frusto-conical shape.
6. The structure according to claims 4 or 5, wherein the male form-fitting portion comprises a mating head portion (16A) having an arcuate end surface, and the female form-fitting portion comprises a mating arcuate . end portion (16B) with a rebated internal abutment surface to receive the arcuate head portion.
7. The structure according to any one of claims 3 to 6, wherein at least one of the mating portions carries a biocompatible adhesive for enhancing the rigidity of the bridge.
8. The structure according to any one of the preceding claims, wherein the portion of reduced electrical conductivity comprises a portion, in which the chemical composition of said metal structure is modified.
9. The structure according to one of claims 3 to 8, wherein the portion of reduced electrical conductivity comprises a conductivity reducing layer on an abutment surface of at least one of the complementary mating portions.
10. The structure according to any one of the preceding claims, wherein the conductivity reducing portion comprises an oxide layer.
11. The structure according to claim 1, wherein said bridges comprise a sleeve (50) connected to adjacent bridge struts (42, 44), and wherein said bridge structs are spaced apart within said sleeve.
12. The structure according to any one of the preceding claims, wherein the length axis of the bridge is not parallel to the longitudinal axis of the structure.
13. The structure according to any one of the preceding claims, wherein the bridge has the shape of a meander.
14. The structure according to any one of the preceding claims, wherein the rings have the shape of a meander.
15. The structure according to claim 14, wherein the number of bridges connecting one ring with an adjacent ring is less than the number of meanders in one ring.
16. The structure according to any one of the preceding claims, wherein the shape of the bridge resembles that of an "S".
17. The structure according to any one of the preceding claims, wherein the structure is made of a nickel titanium shape-memory alloy.
18. The structure according to any one of claims 1 to 16, wherein the structure is made of stainless steel.
19. The structure according to any one of the preceding claims, wherein the structure is a medical stent.
20. A method of manufacturing a tubular radially expansible metal structure (2) having an abluminal major wall surface, a luminal major wall surface and a radial wall thickness therebetween, the method comprising the steps of:
forming a plurality of expansible rings (4) so that the rings are arranged adjacent one another along the longitudinal axis of the structure, and that each of the rings define at least one bridge strut (14A, 14B);

forming bridges (12) between adjacent rings by approximating respective bridge struts (14A, 14B) of adjacent rings;
characterised by the step of furnishing said bridges (12) between each ring and its adjacent ring with reduced electrical conductivity throughout the wall thickness, such that there are a plurality of bridges distributed throughout the length of the tubular structure, and arranged and configured to divide the tubular structure into axially spaced and electrically insulated sections.
21. The method according to claim 20, wherein the step of forming the expansible rings includes the steps of:
providing a tubular workpiece;
mounting the tubular workpiece on a support; and laser-cutting the workpiece to form meanders in the rings arranged longitudinally adjacent one another, each having a first end and a second end, and at least one complementary mating portion (16A) arranged on said first end of each of said rings to mate with a complementary mating portion (16B) on the second end of the adjacent ring.
22. The method according to claim 20 or 21, wherein the step of linking each of the rings with an adjacent ring by at least one bridge includes the steps of:
oxidising abutment surfaces on said bridge struts, whereby each bridge includes a conductivity reducing layer which constitutes said portion of reduced conductivity.
23. The method according to claim 20 or 21, wherein the step of linking each of the rings with an adjacent ring by at least one bridge includes the steps of:
providing an insulating sleeve (50); and mounting said sleeve to adjacent bridge struts (42, 44) on adjacent rings, such that the bridge struts are spaced apart within said sleeve.
24. A method of visualising a lumen supported by a tubular metal structure (2) deployed in a bodily lumen, the method including the step of:
subjecting said bodily lumen to an MRI imaging technique, said tubular structure (2) comprising a plurality of rings (4) arranged adjacent one another along the longitudinal axis of the structure, each ring being linked with an adjacent ring by at least one bridge (12) exhibiting reduced conductivity .throughout the wall thickness of the structure, the plurality of bridges being configured and arranged to divide the tubular structure into axially spaced and electrically insulated sections, whereby artefacts in the MRI-image arising from said tubular structure are reduced.
CA2478709A 2002-03-14 2003-03-14 Metal structure compatible with mri imaging, and method of manufacturing such a structure Expired - Fee Related CA2478709C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB0206061.4 2002-03-14
GBGB0206061.4A GB0206061D0 (en) 2002-03-14 2002-03-14 Metal structure compatible with MRI imaging, and method of manufacturing such a structure
PCT/EP2003/002708 WO2003075797A2 (en) 2002-03-14 2003-03-14 Mri compatible stent and method of manufacturing the same_______

Publications (2)

Publication Number Publication Date
CA2478709A1 true CA2478709A1 (en) 2003-09-18
CA2478709C CA2478709C (en) 2010-06-01

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
CA2478709A Expired - Fee Related CA2478709C (en) 2002-03-14 2003-03-14 Metal structure compatible with mri imaging, and method of manufacturing such a structure

Country Status (9)

Country Link
US (1) US7789906B2 (en)
EP (1) EP1485044B1 (en)
JP (1) JP4416514B2 (en)
AT (1) ATE380003T1 (en)
AU (1) AU2003209736A1 (en)
CA (1) CA2478709C (en)
DE (1) DE60317883T2 (en)
GB (1) GB0206061D0 (en)
WO (1) WO2003075797A2 (en)

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