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Publication numberUS20040236213 A1
Publication typeApplication
Application numberUS 10/753,694
Publication date25 Nov 2004
Filing date7 Jan 2004
Priority date23 May 2003
Also published asCA2526592A1, CA2526592C, EP1626667A2, EP1626667B1, EP2550927A1, US7970454, US7983734, US8626269, US8880154, US9801688, US20040236212, US20090018439, US20110237943, US20130310686, US20150051477, WO2004105626A2, WO2004105626A3
Publication number10753694, 753694, US 2004/0236213 A1, US 2004/236213 A1, US 20040236213 A1, US 20040236213A1, US 2004236213 A1, US 2004236213A1, US-A1-20040236213, US-A1-2004236213, US2004/0236213A1, US2004/236213A1, US20040236213 A1, US20040236213A1, US2004236213 A1, US2004236213A1
InventorsMichael Jones, Paul Lubock, John Merritt
Original AssigneeSenorx, Inc.
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Marker delivery device with releasable plug
US 20040236213 A1
Abstract
The invention is directed to marker delivery devices and methods of using such devices. The delivery devices embodying features of the invention include a delivery cannula with a discharge opening and a releasable plug disposed in the inner lumen of the delivery cannula so as to at least partially occlude the discharge opening. The releasable plug prevents ingress of tissue, body fluids and the like into the bore of the tube, and prevents the premature discharge of any markers proximal to the releasable plug from passing through the discharge opening before the distal end of the cannula is properly positioned at a desired location within a patient's body. The releasable plug preferably has an MRI detectable element. Preferably, at least one remotely detectable marker mass is provided in the inner lumen of the cannula proximal to the releasable plug.
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Claims(106)
What is claimed is:
1. A marker delivery device for an intracorporeal tissue site, comprising:
a) an elongated delivery cannula which has a distal end, an inner lumen and a discharge opening in the distal end in communication with the inner lumen;
b) at least one remotely detectable marker mass which is disposed within the inner lumen of the delivery cannula; and
c) a releasable plug which has a remotely detectable element incorporated therein and which is disposed at least in part within a distal portion of the inner lumen distal to the remotely detectable marker mass so as to occlude the discharge opening in the distal end.
2. The marker delivery device of claim 1 wherein the releasable plug is formed at least in part of oxidized cellulose.
3. The marker delivery device of claim 1 wherein the releasable plug is formed at least in part of a material which expands in the presence of body fluids.
4. The marker delivery device of claim 1 wherein the releasable plug is formed at least in part of polyethylene glycol.
5. The marker delivery device of claim 4 wherein the polyethylene glycol of which the releasable plug is at least partially formed has a molecular weight of about 5000 to about 120,000 Daltons.
6. The marker delivery device of claim 4 wherein the polyethylene glycol of which the releasable plug is at least partially formed has a molecular weight of about 5000 to about 20,000 Daltons.
7. The marker delivery device of claim 4 wherein the polyethylene glycol of which the releasable plug is at least partially formed has a molecular weight of about 8000 to about 10,000 Daltons.
8. The marker delivery device of claim 1 wherein the releasable plug has a non-magnetic marker element which is remotely detectable by magnetic resonance.
9. The marker delivery device of claim 1 wherein the marker element is formed of a material selected from the group consisting of titanium, platinum, gold, iridium, tantalum, tungsten, silver, rhodium.
10. The marker delivery device of claim 1 wherein the at least one remotely detectable marker body is formed at least in part of fibrous material.
11. The marker delivery device of claim 10 wherein the at least one fibrous marker body has a radiographic detectable element
12. The marker delivery device of claim 10 wherein the at least one fibrous marker body is formed at least in part of a bioabsorbable fibrous material.
13. The marker delivery device of claim 10 wherein the at least one fibrous marker body is formed of oxidized cellulose.
14. The marker delivery device of claim 10 wherein at least one fibrous marker body is formed of oxidized regenerated cellulose.
15. The marker delivery device of claim 11 wherein the radiographically detectable element surrounds an exterior portion of the fibrous marker body.
16. The marker delivery device of claim 1 wherein at least one remotely detectable marker mass is formed of polymeric material selected from the group consisting of polylactic acids, polyglycolic acids, copolymers and blends thereof and is disposed in the inner lumen proximal to the releasable plug.
17. The marker delivery device of claim 15 wherein at least one remotely detectable fibrous marker body formed at least in part of bioabsorbable fibrous material selected from the group consisting of oxidized cellulose and oxidized regenerated cellulose is disposed proximal to the remotely detectable marker bodies formed of polymeric material.
18. The marker delivery device of claim 1 wherein the releasable plug tip is formed at least in part of fibrous material.
19. The marker delivery device of claim 18 wherein the fibrous releasable plug tip has a radiographic detectable element.
20. The marker delivery device of claim 18 wherein the releasable plug tip is formed at least in part of a bioabsorbable fibrous material.
21. The marker delivery device of claim 18 wherein the fibrous releasable plug tip is formed of oxidized cellulose.
22. The marker delivery device of claim 18 wherein the fibrous releasable plug tip is formed of oxidized regenerated cellulose.
23. The marker delivery device of claim 19 wherein the radiographically detectable element surrounds an exterior portion of the fibrous releasable plug tip.
24. The marker delivery device of claim 18 wherein at least one remotely detectable marker mass is formed of polymeric material selected from the group consisting of polylactic acids, polyglycolic acids, copolymers and blends thereof and is disposed in the inner lumen proximal to the fibrous releasable plug.
25. The marker delivery device of claim 21 wherein the fibrous releasable plug tip is formed at least in part of bioabsorbable fibrous material selected from the group consisting of oxidized cellulose and oxidized regenerated cellulose is disposed proximal to the remotely detectable marker bodies formed of polymeric material.
26. The marker delivery device of claim 1 including a plunger which is slidably disposed within the inner lumen of the cannula and which has a distal end proximal to marker bodies in the inner lumen.
27. A marker delivery device for an intracorporeal tissue site, comprising:
a) an elongated delivery cannula which has a distal end, a discharge opening in the distal end and an inner lumen extending to and in communication with the discharge opening; and
b) a releasable plug which has an MRI detectable marker element incorporated therein and which is disposed at least in part within a distal portion of the inner lumen so as to occlude the discharge opening in the distal end.
28. The marker delivery device of claim 27 wherein the releasable plug is formed at least in part of a material selected from the group consisting of oxidized cellulose or oxidized regenerated cellulose.
29. The marker delivery device of claim 27 wherein the releasable plug is formed at least in part of a material which expands in the presence of body fluids.
30. The marker delivery device of claim 29 wherein the releasable plug is formed at least in part of polyethylene glycol.
31. The marker delivery device of claim 27 wherein at least one remotely detectable marker body is slidably disposed within the inner lumen of the delivery cannula proximal to the releasable plug.
32. The marker delivery device of claim 31 wherein the at least one remotely detectable marker body disposed proximal to the releasable plug is formed at least in part of fibrous material.
33. The marker delivery device of claim 32 wherein the fibrous marker body is expandable upon contact with body fluid or other water based fluid.
34. The marker delivery device of claim 32 wherein the fibrous material is bioabsorbable.
35. The marker delivery device of claim 34 wherein the fibrous material is oxidized cellulose.
36. The marker delivery device of claim 34 wherein the fibrous material is oxidized regenerated cellulose.
37. The marker delivery device of claim 32 wherein the at least one marker body formed of fibrous material has a radiographic imageable element.
38. The marker delivery device of claim 37 wherein the radiographically detectable element surrounds a portion of the fibrous marker body.
39. The marker delivery device of claim 27 wherein a plunger is slidably disposed within the inner lumen of the cannula with a pusher end proximal to the marker bodies in the inner lumen.
40. The marker delivery device of claim 27 wherein the MRI detectable marker element is about 0.5 to about 5 mm in maximum dimension.
41. The marker delivery device of claim 27 wherein the MRI detectable marker element is about 1 to about 3 mm in maximum dimension.
42. A marker delivery device system for an intracorporeal site within a patient, comprising:
a. an elongated delivery cannula which has a distal end, a discharge opening in the distal end and an inner lumen extending to and in communication with the discharge opening;
b. a releasable plug disposed within the inner lumen so as to at least partially occlude the discharge opening; and
c. at least one remotely detectable, short term marker disposed within the inner bore proximal to the releasable plug; and
d. at least one fibrous marker disposed within the inner lumen proximal to the at least one short term marker.
43. The marker delivery device of claim 42 wherein the releasable plug is formed at least in part of a material which expands in the presence of body fluids.
44. The marker delivery device of claim 42 wherein the releasable plug is formed at least in part of polyethylene glycol.
45. The marker delivery device of claim 42 wherein the releasable plug is covered with polyethylene glycol.
46. The marker delivery device of claim 42 wherein at least one remotely detectable marker body is slidably disposed within the inner lumen of the delivery cannula distal to the releasable plug.
47. The marker delivery device of claim 42 wherein the at least one remotely detectable marker body disposed distal to the releasable plug is formed at least in part of fibrous material.
48. The marker delivery device of claim 47 wherein the fibrous material is bioabsorbable.
49. The marker delivery device of claim 46 wherein the fibrous material is oxidized cellulose.
50. The marker delivery device of claim 46 wherein the fibrous material is oxidized regenerated cellulose.
51. The marker delivery device of claim 46 wherein the at least one marker body formed of fibrous material has a radiographic imageable element
52. The marker delivery device of claim 51 wherein the radiographically detectable element surrounds a portion of the fibrous marker body.
53. The marker delivery device of claim 42 wherein a plunger is slidably disposed within the inner lumen of the cannula with a pusher end proximal to the marker bodies in the inner lumen.
54. The marker delivery device of claim 42 wherein the releasable plug has a non-magnetic, MRI detectable marker element incorporated therein.
55. The marker delivery device of claim 54 wherein the non-magnetic, MRI detectable marker element is formed of a material selected from the group consisting of titanium, platinum, gold, iridium, tantalum, tungsten, silver and rhodium.
56. The marker delivery device of claim 54 wherein the non-magnetic, MRI detectable marker element is about 0.5 to about 5 mm in maximum dimension.
57. The marker delivery device of claim 54 wherein the non-magnetic, MRI detectable marker element is about 1 to about 3 mm in maximum dimension.
58. A marker delivery device for an intracorporeal tissue site, comprising:
a) an elongated delivery cannula which has a distal end, an inner lumen and a discharge opening in the distal end in communication with the inner lumen;
b) at least one remotely detectable marker mass which is formed at least in part of particulate and which is disposed within the inner lumen of the delivery cannula; and
c) a releasable plug which has a remotely detectable element incorporated therein and which is disposed at least in part within a distal portion of the inner lumen distal to the remotely detectable marker mass so as to occlude the discharge opening in the distal end.
59. The marker delivery device of claim 58 wherein the marker mass is remotely detectable by ultrasound.
60. The marker delivery device of claim 58 wherein the particulate of the marker mass is formed of bio-resorbable material.
61. The marker delivery device of claim 58 wherein the particulate has a particle size of about 20 to about 2000 microns.
62. The marker delivery device of claim 58 wherein the particulate has a particle size of about 100 microns to about 1500 microns.
63. The marker delivery device of claim 58 wherein the particulate has a particle size of about 500 microns to about 900 microns.
64. The marker delivery device of claim 58 wherein the particulate has bubble cavities.
65. The marker delivery device of claim 64 wherein the bubble cavities of the particulate is about 10 microns to about 500 microns in maximum dimension.
66. The marker delivery device of claim 64 wherein the bubble cavities of the particulate are about 50 microns to about 200 microns.
67. The marker delivery device of claim 60 wherein the particulate is formed at least in part of bio-resorbable polymeric material selected from the group consisting of poly(esters), poly(hydroxy acids), poly(lactones), poly(amides), poly(ester-amides), poly(amino acids), poly(anhydrides), poly(ortho-esters), poly(carbonates), poly(phosphazines), poly(thioesters), poly(urethanes), poly(ester urethanes), polysaccharides, polylactic acids, polyglycolic acids, polycaproic acids, polybutyric acids, polyvaleric acids, and copolymers, polymer alloys, polymer mixtures, and combinations thereof.
68. The marker delivery device of claim 60 wherein the particulate is formed at least in part of bio-resorbable polymeric material selected from the group consisting of polylactic acids, polyglycolic acids, polycaproic acids, and copolymers, polymer alloys, polymer mixtures, and combinations thereof.
69. The marker delivery device of claim 52 wherein the bio-resorbable material comprises about 65% by weight polylactic acid and about 35% by weight polyglycolic acid.
70. The ultrasound-detectable biopsy marker mass of claim 58, wherein said bio-resorbable polymeric material comprises a polymeric material having an average molecular weight of less than about 60 kD selected from the group consisting of polylactic acid and polycaproic acid polymers, copolymers, polymer alloys, polymer mixtures, and combinations thereof.
71. The marker delivery device of claim 60 wherein the particulate has a bulk density of about 0.8 g/ml to about 1.1 g/ml.
72. The marker delivery device of claim 60 wherein the particulate is held together by a binding agent.
73. The marker delivery device of claim 72 wherein the binding agent is selected from the group consisting of gelatin, polyethylene glycol, polyvinyl alcohol, glycerin, acrylic hydrogels, organic hydrogels, polysaccharides and combinations thereof.
74. The marker delivery device of claim 60 wherein the marker mass comprises gelatin and bio-resorbable polymeric particulate material having bubble cavities.
75. The marker delivery device of claim 74 wherein the gelatin binding agent is selected from the group consisting of bovine collagen, porcine collagen, ovine collagen, equine collagen, synthetic collagen, agar, synthetic gelatin, and combinations thereof.
76. An intracorporeal marker comprising an expandable bioabsorbable fibrous body with a radiopaque marker element secured to the fibrous body.
77. The intracorporeal marker of claim 76 wherein the radiopaque marker element is incorporated into the fibrous body.
78. The intracorporeal marker of claim 76 wherein the radiopaque marker is disposed about the fibrous body.
79. The intracorporeal marker of claim 76 wherein the radiopaque marker is incorporated into the fibrous body.
80. The intracorporeal marker of claim 76 wherein the fibrous body is formed at least in part of a bioabsorbable material selected from the group consisting of oxidized cellulose, oxidized regenerated cellulose, polylactic acid, a copolymer of polylactic acid and glycolic acid, and polycaprolactone.
81. The intracorporeal marker of claim 80 wherein the cellulose is oxidized, regenerated cellulose.
82. The intracorporeal marker of claim 76 wherein the fibrous body is formed of material which swells in the presence of body fluids or other water based fluids.
83. The intracorporeal marker of claim 76 wherein the fibrous body is formed at least in part of woven fabric.
84. The intracorporeal marker of claim 76 wherein the fibrous body is formed at least in part of felt fabric.
85. The intracorporeal marker of claim 76 wherein the fibrous body is compressed.
86. The intracorporeal marker of claim 85 wherein the compressed fibrous body has incorporated therein a binding agent to hold the fibrous body in the compressed condition.
87. The intracorporeal marker of claim 86 wherein the binding agent is selected from the group consisting of water soluble polymers selected from the group consisting of polyvinyl alcohol, polyethylene glycol and polyvinyl pyrollidone.
88. The intracorporeal marker of claim 76 wherein the fibrous body includes at least one bioactive component selected from the group consisting of therapeutic and diagnostic agents incorporated therein.
89. The intracorporeal expandable marker of claim 88 wherein the incorporated therapeutic or diagnostic agent is selected from the group consisting of a hemostatic agent, an anesthetic agent, a coloring agent, an antibiotic agent, an antifungal agent, an antiviral agent, a chemotherapeutic agent and a radioactive agent.
90. The intracorporeal expandable marker of claim 78 wherein the fibrous body contains a bioabsorbable material selected from the group consisting of polylactic acid, a co-polymer of polylactic acid and glycolic acid, polycaprolactone, collagen and mixtures thereof, including mixtures with the oxidized cellulose.
91. The intracorporeal expandable marker of claim 78 wherein the fibrous body includes a binding agent.
92. The intracorporeal expandable marker of claim 76 wherein the radiographically detectable marker element is disposed at a central portion of the fibrous body.
93. The intracorporeal expandable marker of claim 76 wherein a constricting member holds a portion of the fibrous body to prevent its expansion.
94. The intracorporeal expandable marker of claim 93 wherein the constricting member holds a central portion of the fibrous body to prevent its expansion.
95. The intracorporeal expandable marker of claim 76 wherein the radiographically detectable marker element is a constricting member which holds a portion of the fibrous body to prevent its expansion.
96. The intracorporeal expandable marker of claim 95 wherein the radiographically detectable constricting member holds a central portion of the fibrous body to prevent its expansion.
97. The intracorporeal expandable marker of claim 96 wherein the constricted fibrous body is configured to expand into a bow-tie shape when exposed to body fluid or other water based fluid.
98. The intracorporeal expandable marker of claim 76 wherein the fibrous body has a core formed of bioabsorbable felt surrounded by a bioabsorbable fabric jacket.
99. The intracorporeal expandable marker of claim 95 wherein the radiographically detectable marker element is a radiopaque wire element clamped about a central exterior portion of the fibrous body.
100. The expandable intracorporeal marker of claim 95 wherein the fibrous mass has been compressed at least 25%.
101. An intracorporeal marker comprising a compressed expandable bioabsorbable fibrous body which has been compressed and bound in the compressed condition.
102. The intracorporeal marker of claim 101 wherein the fibrous body is bound by a binding agent selected from the group consisting of water soluble polymers selected from the group consisting of polyvinyl alcohol, polyethylene glycol and polyvinyl pyrollidone.
103. The intracorporeal marker of claim 101 wherein the fibrous body is about 0.5 mm to about 12 mm in diameter.
104. The intracorporeal marker of claim 101 wherein the fibrous body is, about 1 to about 8 mm in diameter.
105. The intracorporeal marker of claim 101 wherein the fibrous body is about 5 to about 30 mm in length.
106. The intracorporeal marker of claim 101 wherein the fibrous body is about 10 to about 25 mm in length.
Description
    RELATED APPLICATIONS
  • [0001]
    This application is a continuation-in-part of application Ser. No. 10/444,770, filed on May 23, 2003 which is incorporated herein by reference in its entirety and from which priority is claimed.
  • FIELD OF THE INVENTION
  • [0002]
    The invention is generally directed to devices and methods for the delivery of remotely detectable markers to a desired location within a patient's body. In particular, the invention is directed to devices, and methods configured to retain a remotely detectable marker within a delivery device before delivery to a desired intracorporeal location.
  • BACKGROUND OF THE INVENTION
  • [0003]
    In diagnosing and treating certain medical conditions, it is often desirable to mark a suspicious body site for the subsequent taking of a biopsy specimen, for delivery of medicine, radiation, or other treatment, for the relocation of a site from which a biopsy specimen was taken, or at which some other procedure was performed. As is known, obtaining a tissue sample by biopsy and the subsequent examination are typically employed in the diagnosis of cancers and other malignant tumors, or to confirm that a suspected lesion or tumor is not malignant. The information obtained from these diagnostic tests and/or examinations is frequently used to devise a therapeutic plan for the appropriate surgical procedure or other course of treatment.
  • [0004]
    In many instances, the suspicious tissue to be sampled is located in a subcutaneous site, such as inside a human breast. To minimize surgical intrusion into a patient's body, it is often desirable to insert a small instrument, such as a biopsy needle, into the body for extracting the biopsy specimen while imaging the procedure using fluoroscopy, ultrasonic imaging, x-rays, magnetic resonance imaging (MRI) or any other suitable form of imaging technique. Examination of tissue samples taken by biopsy is of particular significance in the diagnosis and treatment of breast cancer. In the ensuing discussion, the biopsy and treatment site described will generally be the human breast, although the invention is suitable for marking biopsy sites in other parts of the human and other mammalian body as well.
  • [0005]
    Periodic physical examination of the breasts and mammography are important for early detection of potentially cancerous lesions. In mammography, the breast is compressed between two plates while specialized x-ray images are taken. If an abnormal mass in the breast is found by physical examination or mammography, ultrasound may be used to determine whether the mass is a solid tumor or a fluid-filled cyst. Solid masses are usually subjected to some type of tissue biopsy to determine if the mass is cancerous.
  • [0006]
    If a solid mass or lesion is large enough to be palpable, a tissue specimen can be removed from the mass by a variety of techniques, including but not limited to open surgical biopsy, a technique known as Fine Needle Aspiration Biopsy (FNAB) and instruments characterized as “vacuum assisted large core biopsy devices”.
  • [0007]
    If a solid mass of the breast is small and non-palpable (e.g., the type typically discovered through mammography), a vacuum assisted large core biopsy procedure is usually used. In performing a stereotactic biopsy of a breast, the patient lies on a special biopsy table with her breast compressed between the plates of a mammography apparatus and two separate x-rays or digital video views are taken from two different points of view. A computer calculates the exact position of the lesion as well as depth of the lesion within the breast. Thereafter, a mechanical stereotactic apparatus is programmed with the coordinates and depth information calculated by the computer, and such apparatus is used to precisely advance the biopsy needle into the small lesion. The stereotactic technique may be used to obtain histologic specimens. Usually at least five separate biopsy specimens are obtained from locations around the small lesion as well as one from the center of the lesion.
  • [0008]
    The available treatment options for cancerous lesions of the breast include various degrees of mastectomy or lumpectomy, radiation therapy, chemotherapy and combinations of these treatments. However, radiographically visible tissue features, originally observed in a mammogram, may be removed, altered or obscured by the biopsy procedure, and may heal or otherwise become altered following the biopsy. In order for the surgeon or radiation oncologist to direct surgical or radiation treatment to the precise location of the breast lesion several days or weeks after the biopsy procedure was performed, it is desirable that a biopsy site marker be placed in the patient's body to serve as a landmark for subsequent location of the lesion site. A biopsy site marker may be a permanent marker (e.g., a metal marker visible under x-ray examination), or a temporary marker (e.g., a bioresorbable marker detectable with ultrasound). While current radiographic type markers may persist at the biopsy site, an additional mammography generally must be performed at the time of follow up treatment or surgery in order to locate the site of the previous surgery or biopsy. In addition, once the site of the previous procedure is located using mammography, the site must usually be marked with a location wire which has a hook on the end which is advanced into site of the previous procedure. The hook is meant to fix the tip of the location wire with respect to the site of the previous procedure so that the patient can then be removed from the confinement of the mammography apparatus and the follow-up procedure performed. However, as the patient is removed from the mammography apparatus, or otherwise transported the position of the location wire can change or shift in relation to the site of the previous procedure. This, in turn, can result in follow-up treatments being misdirected to an undesired portion of the patient's tissue.
  • [0009]
    As an alternative or adjunct to radiographic imaging, ultrasonic imaging (herein abbreviated as “USI”) or visualization techniques can be used to image the tissue of interest at the site of interest during a surgical or biopsy procedure or follow-up procedure. USI is capable of providing precise location and imaging of suspicious tissue, surrounding tissue and biopsy instruments within the patient's body during a procedure. Such imaging facilitates accurate and controllable removal or sampling of the suspicious tissue so as to minimize trauma to surrounding healthy tissue.
  • [0010]
    For example, during a breast biopsy procedure, the biopsy device is often imaged with USI while the device is being inserted into the patient's breast and activated to remove a sample of suspicious breast tissue. As USI is often used to image tissue during follow-up treatment, it may be desirable to have a marker, similar to the radiographic markers discussed above, which can be placed in a patient's body at the site of a surgical procedure and which are visible using USI. Such a marker enables a follow-up procedure to be performed without the need for traditional radiographic mammography imaging which, as discussed above, can be subject to inaccuracies as a result of shifting of the location wire as well as being tedious and uncomfortable for the patient.
  • [0011]
    Placement of a marker or multiple markers at a location within a patient's body requires delivery devices capable of holding markers within the device until the device is properly situated within a breast or other body location. Accordingly, devices and methods for retaining markers within a marker delivery device while allowing their expulsion from the devices at desired intracorporeal locations are desired.
  • SUMMARY OF THE INVENTION
  • [0012]
    The invention is generally directed to the delivery of one or more markers to an intracorporeal site within a patient's body. A marker delivery device embodying features of the invention include a delivery tube or cannula having an inner lumen leading to a discharge opening and having a releasable plug which is disposed at least in part within the inner lumen and which at least partially occludes the discharge opening in the distal end of the delivery tube.
  • [0013]
    The releasable plug is configured to occlude or block off the discharge opening of the delivery cannula or the inner lumen leading thereto to prevent tissue and fluid from entering the inner lumen through the discharge opening during delivery and to hold in any other markers within the inner lumen proximal to the releasable plug during handling and delivery. In one embodiment having features of the invention, the delivery device has a releasable plug with a remotely detectable marker element incorporated therein. Preferably, the marker element incorporated into the releasable plug is non-magnetic and remotely detectable by magnetic resonance imaging.
  • [0014]
    In yet another embodiment having features of the invention, the delivery device has a releasable plug and has at least one short term, remotely detectable marker mass in the inner lumen or at least one fibrous marker in the inner lumen proximal to the releasable plug. Preferably, at least one short term marker and at least one fibrous marker are disposed within the inner lumen of the delivery cannula.
  • [0015]
    The releasable plug may be secured within the inner lumen by a variety of means, but It is preferred to press fit the plug into the distal portion of the inner lumen so as to occlude the discharge opening. However, the plug may alternatively be mechanically or adhesively secured within the distal portion of the inner lumen. For further plug details see co-pending application Ser. No. 10/174,401, filed on Jun. 17, 2002, entitled Plugged Tip Delivery Tube For Marker Placement which is incorporated herein in its entirety by reference. However, the releasable plug should be configured to be easily pushed out of the discharge opening of the delivery cannula, even if the releasable plug has swollen due to contact with a water based fluid. As described above, the releasable plug preferably has a non-magnetic, MRI detectable element which does not interfere with the subsequent imaging of adjacent tissue. The MRI detectable element is about 0.5 to about 5 mm in maximum dimension, preferably about 1 to about 3 mm. Suitable non-magnetic, MRI detectable materials include titanium, platinum, gold, iridium, tantalum, tungsten, silver, rhodium and the like.
  • [0016]
    The releasable plug is formed of a biocompatible, preferably bioabsorbable material such as oxidized regenerated cellulose, polyethylene glycol, polylactic acid, polyglycolic acid, polycaproic acid, and copolymers, polymer alloys, polymer blends, and combinations thereof. Preferable materials are oxidized regenerated cellulose and polymers of polyethylene glycol with molecular weights of about 5000 to about 120,000 Daltons. The releasable plug should be formed of a water swellable material, so that it swells upon contact with water based fluids (e.g. body fluids) to further occlude or otherwise seal the discharge opening of the delivery cannula and thereby prevent premature contact of body fluids with any markers within the inner lumen proximal to the releasable plug. The plug may also be formed of fibrous materials and be in the form of a fibrous marker described below.
  • [0017]
    The short term markers disposed within the inner lumen of the delivery cannula proximal to the releasable plug should be remotely detectable for at least two weeks, preferably at least up to six weeks, but not longer than about one year, preferably not more than about six months, so as to not interfere with subsequent imaging of the target site. The short term markers are preferably formed of bioabsorbable polymeric materials such as polymers of lactic acid, glycolic acid and caprolactones and copolymers and blends thereof. Other suitable materials include those described in co-pending application Ser. No. 09/717,909, filed Nov. 20, 2000 and co-pending application Ser. No. 10/124,757, filed on Jun. 17, 2002, both of which are incorporated by reference in their entireties. The plug and the short term markers may be formed of the same or similar material. The releasable plug may also be formed of fibrous material and be in the form of the fibrous markers described below.
  • [0018]
    The fibrous marker should be slidably disposed within the inner lumen of the delivery cannula, preferably proximal to at least one short term marker so that upon discharge from the cannula into a target site, the fibrous marker will block the accessing passageway and prevent loss of marker material therethrough. A suitable material for forming the fibrous marker is a felt and/or fiber material formed of oxidized regenerated cellulose which has an in vivo lifetime of a few hours up to about 6 weeks, typically about 3 days to about 4 weeks. However, the fibrous marker may be formed of a bioabsorbable polymer such as polylactic acid or polyglycolic acid, a co-polymer of polylactic acid and polyglycolic acid, polycaprolactone, collagen and mixtures thereof, including mixtures with oxidized regenerated cellulose. Suitable oxidized, regenerated cellulose includes SURGICEL™ from the Ethicon Division of Johnson & Johnson or other suitable oxidized regenerated cellulose which are naturally hemostatic. Alternatively, a hemostatic agent such as collagen, gelatin or polysaccharides may be incorporated into the fibrous material to provide the hemostasis upon contact with blood. A wide variety of other hemostatic agents may be incorporated into the marker. The thrombus formed by the hemostasis is formed very quickly to fill the cavity at the biopsy site and at least temporarily hold the plug and any other markers in position within the cavity. Anesthetic agents to control post procedure pain, chemotherapeutic agents to kill any residual neoplastic tissue and coloring agents (e.g. carbon black and methylene blue) for visual location of the biopsy site, may also be incorporated into the fibrous marker.
  • [0019]
    The fibrous material is formed into an elongated member, e.g. by rolling or folding, and bound in a compressed condition to provide sufficient column strength to facilitate introduction into and discharge from a tubular delivery device. Suitable binding agents for holding the fibrous marker in a compressed condition are water soluble polymers such as polyvinyl alcohol, polyethylene glycol, polyvinyl pyrollidone. One or more radiographically detectable marker elements are provided with at least one of the fibrous markers, preferably centrally located on the elongated marker to ensure that the radiographically detectable element is disposed at a more or less central location within the target site rather than at a site margin.
  • [0020]
    The releasable plug, the short term markers and the fibrous markers may include a variety of therapeutic or diagnostic materials such as hemostatic agents, anesthetic agents, coloring agents, antibiotics, antifungal agents, antiviral agents, chemotherapeutic agents, radioactive agents and the like.
  • [0021]
    The delivery device preferably has a plunger slidably disposed within the inner lumen of the delivery cannula which is movable from an initial position accommodating the releasable plug and any markers proximal to the plug within the tube, to a delivery position to push the plug and any desired number of markers out of the discharge opening in the distal end of the cannula into the target tissue site.
  • [0022]
    Upon being discharged into the intracorporeal target site, the markers at least partially fill the site to enable short term detection by remote imaging and preferably long term detection by remote imaging without interfering with imaging of tissue adjacent to the site. The markers may swell on contact with body fluid, e.g. blood so as to further fill the biopsy cavity. The fibrous marker partially fills the cavity at the target site, positioning the radiopaque marker element within the interior of the target cavity.
  • [0023]
    The marker mass proximal to the releasable plug may be in the form of ultrasound-detectable, bio-resorbable finely-divided particulate material (such as a powder or granulated material), in which many of the particles have internal cavities. Such particulate materials preferably have particle sizes less than about 2000 microns, and typically between about 20 microns and about 2000 microns. For optimum delivery and marker resolution, the particulate should have a particulate size of about 20 microns to about 1500 microns, preferably about 500 microns to about 800 microns. The ultrasound-detectable, bio-resorbable particulate materials may be formed of polymeric materials such as polylactic acid, polyglycolic acid, polycaprolactone, and combinations of these polymers and the particulate may be bound by suitable binding agents such as gelatin, polyethylene glycol, polyvinyl alcohol, glycerin, polysaccharides, other hydrophilic materials, and combinations of these. Suitable gelatins include bovine collagen, porcine collagen, ovine collagen, equine collagen, synthetic collagen, agar, synthetic gelatin, and combinations of these. Further details of the particulate marker material and the delivery thereof can be found in co-pending application Ser. No. 10/124,757, which has been incorporated herein. Polysaccharide particulate or powder may be included with the other particulate materials as a hemostatic agent.
  • [0024]
    The delivery tube of the device may be configured to fit within a guide cannula, such as a Mammotome® or SenoCor 360™ biopsy cannula or a coaxial needle guide.
  • [0025]
    The ultrasound-detectable biopsy site markers of the present invention provide several advantages. A biopsy cavity with marker material having features of the present invention provides a large USI-bright mass, making it much easier, for example, to distinguish the ultrasound signal of the marker from signals arising naturally from within a breast. The marker materials produce bright ultrasound echo signals from one portion of the filled region, which contrasts with the dark ultrasound shadow region immediately behind the bright ultrasound echo region. The strength of the reflected signal, and the contrast with the shadow region, make the marked site readily detectable. Such ready detectability allows, for example, less-experienced physicians to perform the identification by USI and the subsequent surgical resection without the need for an interventional radiologist to identify and mark the biopsy cavity. When a MRI marker element is incorporated into the releasable plug or the short term markers, the target site in which the markers are deployed may be subsequently detected by ultrasound, magnetic resonance and X-ray without interfering with imaging adjacent tissue at a later date.
  • [0026]
    The invention provides the advantages of securely retaining markers within a marker delivery device, improving accuracy and avoiding errors in placement of markers at desired locations within a patient's body, preventing ingress of tissue into the distal tip of the device when it is advanced through tissue, and guiding the device by use of an imaging device including ultrasound, X-ray and magnetic resonance based devices. These and other advantages of the invention will become more apparent from the following description when taken in conjunction with the accompanying drawings.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • [0027]
    [0027]FIG. 1A is a partly cut-away perspective view of a marker delivery assembly embodying features of the invention.
  • [0028]
    [0028]FIG. 1B is a transverse cross-sectional view of the marker delivery assembly of FIG. 1A taken at line 1B-1B.
  • [0029]
    [0029]FIG. 1C is a transverse cross-sectional view of the marker delivery assembly of FIG. 1A taken at line 1C-1C.
  • [0030]
    [0030]FIG. 2 is an end perspective view of a fibrous marker with a core member suitable for use with a marker delivery system embodying features of the invention.
  • [0031]
    [0031]FIG. 3 is an end perspective view of an alternative fibrous marker without a core member suitable for use with a marker delivery system embodying features of the invention.
  • [0032]
    [0032]FIG. 4A-4F illustrates forming a fibrous marker with a core member as depicted in FIG. 4.
  • [0033]
    [0033]FIG. 5 is a partially cut away, perspective view of a human breast from which a biopsy specimen has been removed, showing a markers being delivered to the biopsy site with the marker delivery assembly shown in FIG. 1A.
  • [0034]
    [0034]FIG. 6 is a partial cut-away view of a human breast shown in FIG. 2 with the markers delivered into the biopsy site and the delivery device removed.
  • [0035]
    [0035]FIG. 7 is a longitudinal cross-sectional view of the distal portion of an alternative marker delivery device embodying features of the invention with a sharp, tissue penetrating distal tip.
  • [0036]
    FIGS. 8 is a longitudinal cross-sectional view of the distal portion of a marker delivery device embodying features of the invention having particulate marker mass proximal to the releasable plug.
  • DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION
  • [0037]
    [0037]FIGS. 1A-1C illustrate a marker delivery device 10 embodying features of the invention which includes a delivery tube or cannula 11 with a bore 12, a distal portion 13, and a proximal portion 14 with a handle 15. A releasable distal plug 16, several (five) short term markers 17, a pair of fibrous markers 18 and 19 and a proximal plug 20 are shown disposed within the bore 12. A plunger 21 is slidably disposed within the tube bore 12, and is provided with a proximal end 22 configured to allow an operator to press the plunger further into the bore 12 and push the releasable plug 16 and one or more of the other markers out of the discharge port or opening 23 in the distal end 24 of delivery tube 11. Cannula handle 15 allows an operator to hold the cannula steady while pressing plunger 21 to discharge the releasable plug 16 and markers 17 and 18.
  • [0038]
    Releasable plug 16 may substantially fill the discharge opening 23, as shown in FIG. 1, or may occupy or block only a portion of the discharge opening 23. The exposed face of plug 16 is preferably provided with an inclined configuration to conform with the inclination of the discharge opening 23.
  • [0039]
    Markers 17, 18 and 19 and proximal plug 20 are preferably configured to slide readily within tube bore 12. Releasable plug 16 is configured to be tight enough, e.g. press fit, in the bore 12 to prevent its inadvertent release which would allow premature discharge of markers 17 and 18 from delivery tube 11 and undesirable contact with body fluid. But the plug 16 must be easily released when the plunger 21 is pressed deeper into the bore 12 of the delivery tube 11. An adhesive or mechanical element(s) may be used to hold the releasable plug 16 in a position within the bore 12 to occlude the discharge opening 23. Suitable adhesives include polyurethane or polyacrylic based adhesives, polyhydroxymethacrylate base adhesives, fibrin glue (e.g., Tisseal™), collagen adhesive, or mixtures thereof. Suitable mechanical means for securing the releasable plug 16 are described in co-pending application Ser. No. 10/174,401 which has been incorporated herein. The distal end 24 of the delivery cannula 11 is provided with a ramp 25 which guides the discharged plug 16 and markers 17, 18 and 19 out of the side port 26 into the target site. The distal tip 27 may be tapered for delivery through a guide tube as shown.
  • [0040]
    The delivery tube 11 may be provided with markings 28 which serve as visual landmarks to aid an operator in accurately placing the distal end 24 of the cannula 11 in a desired location within a patient“s body for discharging the markers. The markings 24 also be radiopaque, ultrasound-reflective, or otherwise configured to be detectable by remote imaging devices and imaging methods.
  • [0041]
    Short term markers 17 are made at least in part with detectable, biocompatible materials. Suitable marker materials include bioresorbable polymeric materials such as poly(esters), poly(hydroxy acids), poly(lactones), poly(amides), poly(ester-amides), poly(amino acids), poly(anhydrides), poly(ortho-esters), poly(carbonates), poly(phosphazines), poly(thioesters), poly(urethanes), poly(ester urethanes), polysaccharides, polylactic acid, polyglycolic acid, polycaproic acid, polybutyric acid, polyvaleric acid, and copolymers, polymer alloys, polymer blends, and combinations thereof. Preferable polymeric materials are polymers of lactic acid, glycolic acid and caprolactones. The short term markers 17 may also be formed at least in part of gelatin. One or more of the short term markers 17 may include a remotely detectable preferably radiopaque element 28.
  • [0042]
    Releasable plug 16 is preferably formed at least in part of oxidized regenerated cellulose or polyethylene glycol, but may be made from the same or similar bioabsorbable materials as marker 17. The polyethylene glycol quickly expands when contacting a water based fluid such as blood, which ensures that the releasable plug seals off the discharge opening to prevent premature contact between body fluid (or other water based fluid) and the markers 17 and 18 within the bore 12. The polyethylene glycol should have a molecular weight of about 5000 to about 20000 Daltons, preferably about 8000 to about 10000 Daltons in the final plug form. The releasable plug 16 preferably has a non-magnetic element 29 incorporated within the body of the releasable plug that is remotely detectable by magnetic resonance imaging (MRI). It may be formed of titanium, platinum, gold, iridium, tantalum, tungsten, silver, rhodium and the like. The MRI detectable element 29 should have a maximum dimension of about 0.5 to about 5 mm, preferably about 1 to about 3 mm to be MRI detectable. Elements with dimensions greater than about 5 mm tend to interfere with the imaging of adjacent tissue.
  • [0043]
    Releasable plug 16 and markers 17 and 18 are configured for a slidable fit within the bore 15 of the delivery tube 11. The exterior of the delivery tube 11 is preferably configured to fit within a guide cannula sized to accept a Mammotome®, Tru-Cut®, or SenoCor® biopsy device. Typically, plug 16 and markers 17 and 18 will have diameters determined by the size of a bore 15 and typically will be about 0.02 inch (0.5 mm) to about 0.5 inch (12 mm), preferably about 0.04 inch (1 mm) to about 0.3 inch (8 mm). Plug 16 may have slightly larger transverse dimensions to provide a tight fit. In addition, plugs 16 and 19 and short term marker 17 will have a length of about 0.04 inch (1 mm) to about 0.8 inch (20 mm), preferably about 0.1 inch (2.5 mm) to about 0.6 inch (15 mm).
  • [0044]
    Releasable plug 16, markers 17, 18 and 19 and plug 20 are configured for a slidable fit within the bore 15 of the delivery tube 11. The exterior of the delivery tube 11 is preferably configured to fit within a guide cannula sized to accept a Mammotome®, Tru-Cut®, or SenoCor® biopsy device. Typically, plug 16 and markers 17 and 18 will have diameters determined by the size of a bore 15 and typically will be about 0.02 inch (0.5 mm) to about 0.5 inch (12 mm), preferably about 0.04 inch (1 mm) to about 0.3 inch (8 mm). Plug 16 may have slightly larger transverse dimensions to provide a tight fit. In addition, plugs 16 and 20 and short term markers 17 will have a length of about 0.04 inch (1 mm) to about 0.8 inch (20 mm), preferably about 0.1 inch (2.5 mm) to about 0.6 inch (15 mm).
  • [0045]
    The fibrous markers 18 and 19 are preferably rolled or folded pieces of fibrous material such as oxidized cellulose or oxidized, regenerated cellulose which has been compressed and impregnated with a binding agent such as polyethylene glycol and freeze dried in the compressed condition. The fibrous material may be rolled up by itself, as shown in FIG. 5, or wrapped about a matt-like core 30 as shown in FIG. 4. The fibrous marker is generally configured to be slidably disposed within the inner lumen of the delivery cannula 11, and before delivery is about 0.5 mm to about 12 mm, preferably about 1 to about 8 mm in diameter and about 5 to about 30 mm, preferably about 10 to about 25 mm in length. Upon contact with a body fluid or other water based fluid, the length of the fibrous marker remains about the same but the wrapped structure unfolds upon swelling to a width of about 5 to about 25 mm, usually about 10 to about 20 mm. With a radiopaque marker element clamped about a center portion of the wrapped fibrous marker, the fibrous marker expands into a generally bow-tie shape when exposed to body fluids. However, even though secured to the fibrous marker, the radiopaque marker element need not restrict the expansion of the fibrous marker.
  • [0046]
    The manufacture and use of fibrous marker 18 with a core 30 is schematically illustrated in FIGS. 4A-4F. A felt pad or mat 31 of oxidized, regenerated cellulose about 0.125 to about 0.375 inch (3.2-9.3 mm), preferably about 0.25 inch (6.4 mm) thick is impregnated with a 10% (Wt.) polyethylene glycol in a 70% isopropyl alcohol solution and then compressed to a mat about 0.03 to about 0.05 inch (0.76-1.3 mm) thick. A reduction in thickness of 80% or more is suitable. The compressed mat 31 is cut up into elongated strips 32 with square or near square transverse cross-sectional shapes which form the core 30. The core 30 is wrapped in a fabric 33 of oxidized regenerated cellulose about 5 to about 10 mm in width and about 20 mm in length, compressed and impregnated with the 10% PEG dispersion and then freeze dried to a diameter of about 0.065 inch (1.65 mm). Elevated temperatures may be employed to dry the material. The fabric 33 should make at least one, preferably two or more complete wraps about the core 30. The wrapped and compressed product may then be cut to a desired length to form the fibrous marker 18. Alternatively, the uncompressed mat 31, the strip 32 and fiber wrap 33 may be provided at the desired length for the fibrous marker 18, wrapped and then compressed. A radiographically detectable marker element 34 may be formed of a radiopaque wire about 0.005 to about 0.01 inch, (0.13-0.25 mm) may then be crimped about or embedded in a central portion (or other desired portion) of the marker 13. The fibrous marker 18 is then ready for deployment. As shown in FIG. 1A, only fibrous marker 18 is provided with marker element 34. Marker 19 may be formed in the same or similar manner but without the radiopaque element 34.
  • [0047]
    Fibrous markers without the core member 30 may be formed by rolling or folding into the desired configuration. The fibrous material, oxidized rayon felt is first impregnated with a 10% PEG dispersion, compressed and then freeze dried. The dried felt material is rolled again compressed in the rolled state, impregnated with a 10-30% PEG solution, and freeze dried in the rolled compressed condition. The rayon felt material can be initially oxidized by treating in a solution of 80% (by vol.) Nitric Acid, 20% (by vol.) Sulfuric Acid and 1% (by weight) Sodium Nitrite. The felt is treated in the oxidizing, acidic solution at room temperature for about 4.5 hours and then rinsed with deionized water.
  • [0048]
    Radiopaque elements 28 and 34 may be made with suitable radiopaque material, including stainless steel, platinum, gold, iridium, titanium, tantalum, tungsten, silver, rhodium, nickel, bismuth, other radiopaque metals, alloys and oxides of these metals, barium salts, iodine salts, iodinated materials, and combinations of these. The radiopaque elements 28 and 34 may also be configured for detection by MRI. Radiopaque materials and markers may be permanent, or may be temporary and not detectable after a period of time subsequent to their placement within a patient. Colorants, such as dyes (e.g., methylene blue and carbon black) and pigments (e.g., barium sulfate), may also be included in markers 17 and 18 and plugs 16 and 19 embodying features of the invention.
  • [0049]
    [0049]FIG. 5 schematically illustrates the use of a marker delivery system 10 to deliver markers to a desired location 35 within a patient's body. The desired location 35 is typically a cavity from which a biopsy sample has been, or is to be, taken, or a lesion that has been or will be removed or otherwise treated. In FIG. 4, the marker delivery system 10 is shown inserted into a breast 40 through a guide cannula 41 until the distal end 24 is disposed at the delivery site, cavity 35 where a tissue specimen has been removed. While an operator holds the system 10 by the handle 15 of the delivery tube 11, the plunger 20 is pressed further into the bore 12 of delivery cannula 11 to discharge the releasable plug 16 and markers 17 and 18 into the cavity 35. FIG. 6 schematically illustrates the plug 16 and markers 17, 18 and 19 within the cavity 35 after deployment. When the markers contact body fluid within the cavity 35, they tend to swell and thereby further fill the cavity. The fibrous markers 18 and 19 generally block the accessing track 36 to the cavity 35 so that none of the smaller markers 17 will be lost through the track 36. Marks 37 are provided on the proximal end of cannula 11 to provide end location information to the operator.
  • [0050]
    [0050]FIG. 7 illustrates the distal portion 50 of cannula 51 of an alternative delivery system that is essentially the same as that shown in FIGS. 1A-1C except that the distal tip 52 of cannula 51 is configured in a needle-like shape. The delivery system cannula 51 may be used in conjunction with a guide cannula (not shown) or the cannula 51 can be inserted directly through tissue to reach the target site without the need for a guide cannula. The releasable plug 53 is secured in the discharge opening 54 as in the previously discussed embodiment. The exposed face 55 of the plug 53 is preferably flush with the discharge opening 54 of the distal tip 52.
  • [0051]
    Insertion of marker delivery devices embodying features of the invention may be performed with or without the aid of an imaging device, such as an ultrasound imaging device, an X-ray imaging device, a MRI device, or other imaging device. Alternatively, or additionally, insertion may be visually guided, or may be guided by palpation or by other means.
  • [0052]
    The size and composition of the short term markers 17 are selected so as to remain in place within the patient and be detectable by ultrasound for at least 2 weeks, preferably at least 6 weeks to have practical clinical value. However, the short term markers should not be detectable by ultrasound after about one year, preferably not after about six months, so as to avoid interfering with subsequent site examination. For most clinical purposes, a suitable in-situ lifespan when the short term marker is ultrasonically detectable is about six to about twenty weeks. The radiopaque and MRI detectable marker elements generally will have much longer lifespans.
  • [0053]
    [0053]FIG. 8 illustrates the distal shaft section 60 of an alternative delivery cannula 61 which has a fibrous releasable plug 62 in the inner lumen 63 of the distal shaft section which at least partially occludes the discharge opening 64 in the distal end of the shaft. The fibrous releasable plug 62 may be formed as shown in FIGS. 2, 3 and 4A-F.
  • [0054]
    The inner lumen proximal to the fibrous releasable plug 62 is filled with a particulate marker material 65. The corresponding parts of the system are the same as that shown in FIGS. 1A-1C. Plunger 66 is slidably disposed within the inner lumen 63 to eject the powdered mass 65. The particulate marker material 65 may be discharged dry or mixed with a suitable fluid and discharged as a slurry.
  • [0055]
    The particulate may be formed of a biocompatible and bio-resorbable polymeric material such as polylactic acid, polyglycolic acid, polycaprolactones, poly(esters), poly(hydroxy acids), poly(lactones), poly(amides), poly(ester-amides), poly(amino acids), poly(anhydrides), poly(ortho-esters), poly(carbonates), poly(phosphazines), poly(thioesters), poly(urethanes), poly(ester urethanes), polysaccharides, polybutyric acid, polyvaleric acid, and copolymers, polymer alloys, polymer mixtures, and combinations thereof. Of those, polylactic acid, polyglycolic acid, and polycaproic acid are preferred. The polymeric material in particulate form should have cavities or entrap bubbles which facilitate remote detection.
  • [0056]
    Suitable particulate materials have particle sizes typically about 20 microns to about 2000 microns, preferably about 20 microns to about 800 microns and more preferably about 300 microns to about 500 microns. The particulate should have cavities for USI with maximum dimensions of about 10 microns to about 500 microns, preferably about 20 microns to about 200 microns. The polymeric particulate materials suitable for use in making ultrasound-detectable biopsy marker materials typically have a bulk density of about 0.8 g/ml to about 1.5 g/ml, preferably about 0.8 g/ml to about 1 g/ml. The particulate may also contain or be mixed with binding agents such as polyethylene glycol, polyvinyl alcohol and the like. Polysaccharide particulate or powder may be incorporated into the particulate mass in amounts up to about 50% (by weight) of the total particulate mass for purposes of hemostasis.
  • [0057]
    While particular forms of the invention have been illustrated and described herein in the context of a breast biopsy site, it will be apparent that the device and methods having features of the invention may find use in a variety of locations and in a variety of applications, in addition to the human breast. Moreover, various modifications can be made without departing from the spirit and scope of the invention. Accordingly, it is not intended that the invention be limited to the specific embodiments illustrated. It is therefore intended that this invention to be defined by the scope of the appended claims as broadly as the prior art will permit, and in view of the specification if need be. Moreover, those skilled in the art will recognize that features shown in one embodiment may be utilized in other embodiments. Terms such as “element”, “member”, “device”, “section”, “portion”, “step”, “means” and words of similar import when used in the following claims shall not be construed as invoking the provisions of 35 U.S.C. §112(6) unless the following claims expressly use the terms “means” followed by a particular function without specific structure or “step” followed by a particular function without specific action. All patents and patent applications referred to above are hereby incorporated by reference in their entirety.
Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US2192270 *25 May 19385 Mar 1940American Brake CoBrake rigging
US3341417 *14 Jul 196512 Sep 1967Sinaiko Edwin SMethod of and means for diagnosis of ingested drugs with radio-opaque and other indicators
US3818894 *3 Jan 197225 Jun 1974Ceskoslovenska Akademie VedLaryngeal implant
US3823212 *28 May 19719 Jul 1974Freudenberg C FaProcess for the production of collagen fiber fabrics in the form of felt-like membranes or sponge-like layers
US4007732 *2 Sep 197515 Feb 1977Robert Carl KvavleMethod for location and removal of soft tissue in human biopsy operations
US4172449 *1 May 197830 Oct 1979New Research And Development Laboratories, Inc.Body fluid pressure monitor
US4197846 *25 Jun 197515 Apr 1980Louis BucaloMethod for structure for situating in a living body agents for treating the body
US4276885 *4 May 19797 Jul 1981Rasor Associates, IncUltrasonic image enhancement
US4294241 *19 Oct 197913 Oct 1981Teruo MiyataCollagen skin dressing
US4331654 *13 Jun 198025 May 1982Eli Lilly And CompanyMagnetically-localizable, biodegradable lipid microspheres
US4390018 *17 May 198228 Jun 1983Zukowski Henry JMethod for preventing loss of spinal fluid after spinal tap
US4545367 *18 Nov 19838 Oct 1985Cordis CorporationDetachable balloon catheter and method of use
US4647480 *1 Aug 19853 Mar 1987Amchem Products, Inc.Use of additive in aqueous cure of autodeposited coatings
US4693237 *21 Jan 198615 Sep 1987Hoffman Richard BRadiopaque coded ring markers for use in identifying surgical grafts
US4813062 *13 Aug 198614 Mar 1989Milliken Research CorporationRadio-opaque marker and method
US4832686 *24 Jun 198623 May 1989Anderson Mark EMethod for administering interleukin-2
US4847049 *20 Mar 198711 Jul 1989Vitaphore CorporationMethod of forming chelated collagen having bactericidal properties
US4863470 *24 Sep 19875 Sep 1989Medical Engineering CorporationIdentification marker for a breast prosthesis
US4889707 *29 Jan 198826 Dec 1989The Curators Of The University Of MissouriComposition and method for radiation synovectomy of arthritic joints
US4909250 *14 Nov 198820 Mar 1990Smith Joseph RImplant system for animal identification
US5081997 *20 Jul 198921 Jan 1992Vance Products IncorporatedEchogenic devices, material and method
US5137928 *24 Apr 199111 Aug 1992Hoechst AktiengesellschaftUltrasonic contrast agents, processes for their preparation and the use thereof as diagnostic and therapeutic agents
US5147307 *17 Jun 199115 Sep 1992Gluck Seymour MAnatomical marker device and method
US5221269 *15 Oct 199022 Jun 1993Cook IncorporatedGuide for localizing a nonpalpable breast lesion
US5236410 *11 Mar 199117 Aug 1993Ferrotherm International, Inc.Tumor treatment method
US5281197 *27 Jul 199225 Jan 1994Symbiosis CorporationEndoscopic hemostatic agent delivery system
US5281408 *19 Jan 199325 Jan 1994Unger Evan CLow density microspheres and their use as contrast agents for computed tomography
US5282781 *25 Oct 19901 Feb 1994Omnitron International Inc.Source wire for localized radiation treatment of tumors
US5289831 *21 Apr 19921 Mar 1994Vance Products IncorporatedSurface-treated stent, catheter, cannula, and the like
US5334381 *30 Jun 19932 Aug 1994Unger Evan CLiposomes as contrast agents for ultrasonic imaging and methods for preparing the same
US5368030 *9 Sep 199229 Nov 1994Izi CorporationNon-invasive multi-modality radiographic surface markers
US5394875 *21 Oct 19937 Mar 1995Lewis; Judith T.Automatic ultrasonic localization of targets implanted in a portion of the anatomy
US5395319 *29 Feb 19927 Mar 1995Suddeutsche Feinmechanik GmbhNeedle for inserting an object into the body
US5422730 *25 Mar 19946 Jun 1995Barlow; Clyde H.Automated optical detection of tissue perfusion by microspheres
US5433204 *16 Nov 199318 Jul 1995Camilla OlsonMethod of assessing placentation
US5451408 *23 Mar 199419 Sep 1995Liposome Pain Management, Ltd.Pain management with liposome-encapsulated analgesic drugs
US5469847 *28 Feb 199428 Nov 1995Izi CorporationRadiographic multi-modality skin markers
US5494030 *12 Aug 199327 Feb 1996Trustees Of Dartmouth CollegeApparatus and methodology for determining oxygen in biological systems
US5538726 *19 Jan 199423 Jul 1996Order; Stanley E.Method and compositions for delivering cytotoxic agents to cancer
US5549560 *13 May 199327 Aug 1996Wijdeven Gijsbertus G P Van DeApparatus and method for injecting a pharmaceutical preparation in solid form
US5580568 *27 Jul 19953 Dec 1996Micro Therapeutics, Inc.Cellulose diacetate compositions for use in embolizing blood vessels
US5629008 *7 Jun 199413 May 1997C.R. Bard, Inc.Method and device for long-term delivery of drugs
US5636255 *5 Mar 19963 Jun 1997Queen's University At KingstonMethod and apparatus for CT image registration
US5643246 *24 Feb 19951 Jul 1997Gel Sciences, Inc.Electromagnetically triggered, responsive gel based drug delivery device
US5646146 *25 May 19958 Jul 1997Novo Nordisk A/SHeterocyclic compounds and their preparation and use
US5667767 *27 Jul 199516 Sep 1997Micro Therapeutics, Inc.Compositions for use in embolizing blood vessels
US5676146 *13 Sep 199614 Oct 1997Osteotech, Inc.Surgical implant containing a resorbable radiopaque marker and method of locating such within a body
US5676925 *7 Jun 199514 Oct 1997Nycomed Imaging AsContrast agents comprising gas-containing or gas-generating polymer microparticles or microballoons
US5688490 *7 Feb 199618 Nov 1997Bracco International B.V.Mucoadhesive compositions for increasing the ultrasonic image contrast of the digestive tract
US5695480 *29 Jul 19969 Dec 1997Micro Therapeutics, Inc.Embolizing compositions
US5762903 *8 Mar 19969 Jun 1998Korea Atomic Energy Research InstituteRadioactive chitosan complex for radiation therapy
US5782775 *14 Jun 199621 Jul 1998United States Surgical CorporationApparatus and method for localizing and removing tissue
US5823198 *31 Jul 199620 Oct 1998Micro Therapeutics, Inc.Method and apparatus for intravasculer embolization
US5851508 *14 Feb 199722 Dec 1998Microtherapeutics, Inc.Compositions for use in embolizing blood vessels
US5853366 *8 Jul 199629 Dec 1998Kelsey, Inc.Marker element for interstitial treatment and localizing device and method using same
US5902310 *21 Feb 199711 May 1999Ethicon Endo-Surgery, Inc.Apparatus and method for marking tissue
US5942209 *3 Nov 199724 Aug 1999Focal, Inc.Method of local radiotherapy by polymerizing a material in vivo to form a hydrogel
US6015541 *3 Nov 199718 Jan 2000Micro Therapeutics, Inc.Radioactive embolizing compositions
US6056700 *13 Oct 19982 May 2000Emx, Inc.Biopsy marker assembly and method of use
US6071301 *1 May 19986 Jun 2000Sub Q., Inc.Device and method for facilitating hemostasis of a biopsy tract
US6183497 *17 Jun 19996 Feb 2001Sub-Q, Inc.Absorbable sponge with contrasting agent
US6214315 *10 Sep 199910 Apr 2001Micro Therapeutics IncRadioactive embolizing compositions
US6228055 *19 May 19978 May 2001Ethicon Endo-Surgery, Inc.Devices for marking and defining particular locations in body tissue
US6231615 *18 Oct 199915 May 2001Parallax Medical, Inc.Enhanced visibility materials for implantation in hard tissue
US6234177 *12 Aug 199922 May 2001Thomas BarschApparatus and method for deploying an expandable biopsy marker
US6251418 *18 Dec 199726 Jun 2001C.R. Bard, Inc.Systems and methods for local delivery of an agent
US6270464 *18 Jun 19997 Aug 2001Artemis Medical, Inc.Biopsy localization method and device
US6316522 *14 Sep 199913 Nov 2001Scimed Life Systems, Inc.Bioresorbable hydrogel compositions for implantable prostheses
US6336904 *6 Apr 19998 Jan 2002Pro Duct Health, Inc.Methods and devices for the localization of lesions in solid tissue
US6347241 *30 Jun 199912 Feb 2002Senorx, Inc.Ultrasonic and x-ray detectable biopsy site marker and apparatus for applying it
US6356782 *2 Apr 199912 Mar 2002Vivant Medical, Inc.Subcutaneous cavity marking device and method
US6371904 *2 Jul 199916 Apr 2002Vivant Medical, Inc.Subcutaneous cavity marking device and method
US6394965 *15 Aug 200028 May 2002Carbon Medical Technologies, Inc.Tissue marking using biocompatible microparticles
US6427081 *5 Sep 200030 Jul 2002Senorx, Inc.Methods and chemical preparations for time-limited marking of biopsy sites
US6450937 *17 Dec 199917 Sep 2002C. R. Bard, Inc.Needle for implanting brachytherapy seeds
US6537193 *30 Oct 200025 Mar 2003Scimed Life Systems, Inc.Method and device for delivery of therapeutic agents in conjunction with isotope seed placement
US6540981 *11 Dec 20001 Apr 2003Amersham Health AsLight imaging contrast agents
US6562317 *20 Feb 200113 May 2003Micro Therapeutics, Inc.Radioactive embolizing compositions
US6567689 *27 Feb 200220 May 2003Senorx, Inc.Methods and chemical preparations for time-limited marking of biopsy sites
US6766186 *16 Jun 199920 Jul 2004C. R. Bard, Inc.Post biospy tissue marker and method of use
US6862470 *16 Apr 20021 Mar 2005Senorx, Inc.Cavity-filling biopsy site markers
US20010003791 *30 Jun 199914 Jun 2001Heller Ehrman White & McauliffeUltrasonic and x-ray detectable biopsy site marker and apparatus for applying it
US20010006616 *2 Oct 19975 Jul 2001D Leavitt RichardPolymeric delivery of radionuclides and radiopharmaceuticals
US20010033867 *25 Jun 200125 Oct 2001Ahern John E.Systems and methods for local delivery of an agent
US20020038087 *31 Oct 200128 Mar 2002Senorx, Inc.Imageable biopsy site marker
US20020052572 *25 Sep 20012 May 2002Kenneth FrancoResorbable anastomosis stents and plugs and their use in patients
US20030116806 *20 Dec 200226 Jun 2003Oki Electric Industry Co., Ltd.Input protection circuit connected to protection circuit power source potential line
US20040101479 *10 Oct 200327 May 2004Senorx, Inc.Biopsy site marker and process and apparatus for applying it
US20040193044 *12 Apr 200430 Sep 2004Senorx, Inc.Tissue site markers for in vivo imaging
US20040233101 *30 Dec 200325 Nov 2004Kim Jin-WoongMethod for providing location information in mobile communication system
US20040236211 *23 May 200325 Nov 2004Senorx, Inc.Marker or filler forming fluid
US20040236212 *23 May 200325 Nov 2004Senorx, Inc.Fibrous marker and intracorporeal delivery thereof
US20050045192 *16 Sep 20043 Mar 2005Artemis Medical, Inc.Biopsy localization method and device
US20050063908 *10 Sep 200324 Mar 2005Senorx, Inc.Tissue site markers for in vivo imaging
US20050065453 *3 Aug 200424 Mar 2005Senorx, Inc.Biopsy device with selectable tissue receiving aperture orientation and site illumination
US20050119562 *27 Oct 20042 Jun 2005Senorx, Inc.Fibrous marker formed of synthetic polymer strands
US20050143656 *16 Nov 200430 Jun 2005Senorx, Inc.Cavity-filling biopsy site markers
US20060036159 *30 Sep 200516 Feb 2006Sirimanne D LBiopsy cavity marking device
US20060036165 *29 Sep 200516 Feb 2006Senorx, Inc.Tissue site markers for in vivo imaging
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US756519129 Sep 200521 Jul 2009Senorx, Inc.Tissue site markers for in vivo imaging
US765150517 Jun 200226 Jan 2010Senorx, Inc.Plugged tip delivery for marker placement
US770237817 Nov 200520 Apr 2010Breast-Med, Inc.Tissue marker for multimodality radiographic imaging
US779256916 Nov 20047 Sep 2010Senorx, Inc.Cavity-filling biopsy site markers
US787713323 May 200325 Jan 2011Senorx, Inc.Marker or filler forming fluid
US794284316 Jul 200917 May 2011Navotek Medical Ltd.Implantation device for soft tissue markers and other implants
US795207910 Aug 200631 May 2011Navotek Medical Ltd.Localization of a radioactive source
US798373423 May 200319 Jul 2011Senorx, Inc.Fibrous marker and intracorporeal delivery thereof
US806889525 Feb 200829 Nov 2011Devicor Medical Products, Inc.Biopsy site marker deployment instrument
US807556810 Jun 200513 Dec 2011Selis James EBiopsy devices and methods
US80755699 Feb 201013 Dec 2011Selis James EBiopsy devices and methods
US807996425 Feb 200820 Dec 2011Devicor Medical Products, Inc.Method and apparatus for inserting biopsy site marker in marker body
US816406418 Nov 201024 Apr 2012Navotek Medical Ltd.Localization of a radioactive source within a body of a subject
US817779218 Nov 200915 May 2012Senorx, Inc.Plugged tip delivery tube for marker placement
US81985881 Nov 201012 Jun 2012Navotek Medical Ltd.Localization of a radioactive source within a body of a subject
US819860021 Apr 201112 Jun 2012Navotek Medical Ltd.Localization of a radioactive source
US82191826 Aug 201010 Jul 2012Senorx, Inc.Cavity-filling biopsy site markers
US822442413 Jul 200917 Jul 2012Senorx, Inc.Tissue site markers for in vivo imaging
US823900210 Aug 20067 Aug 2012Novatek Medical Ltd.Guiding a tool for medical treatment by detecting a source of radioactivity
US831161022 Jan 200913 Nov 2012C. R. Bard, Inc.Biopsy tissue marker
US8371443 *22 Sep 200912 Feb 2013Devicor Medical Products, Inc.Biopsy marker delivery device
US840162217 Dec 200719 Mar 2013C. R. Bard, Inc.Biopsy marker with in situ-generated imaging properties
US841460227 Jan 20109 Apr 2013James E. SelisBiopsy devices and methods
US843783428 Sep 20117 May 2013C. R. Bard, Inc.Breast marker
US844738614 Dec 201021 May 2013Senorx, Inc.Marker or filler forming fluid
US845462928 Nov 20114 Jun 2013James E. SelisBiopsy devices and methods
US848602830 Sep 201116 Jul 2013Bard Peripheral Vascular, Inc.Tissue marking apparatus having drug-eluting tissue marker
US854416219 Apr 20101 Oct 2013Breast-Med, Inc.Tissue marker for multimodality radiographic imaging
US857993129 Sep 201112 Nov 2013Bard Peripheral Vascular, Inc.Apparatus for the percutaneous marking of a lesion
US86262698 Jun 20117 Jan 2014Senorx, Inc.Fibrous marker and intracorporeal delivery thereof
US862627013 Jun 20127 Jan 2014Senorx, Inc.Cavity-filling biopsy site markers
US86348993 Feb 200621 Jan 2014Bard Peripheral Vascular, Inc.Multi mode imaging marker
US863931516 May 201328 Jan 2014Senorx, Inc.Marker or filler forming fluid
US866873721 Mar 201211 Mar 2014Senorx, Inc.Tissue marking implant
US867081830 Dec 200811 Mar 2014C. R. Bard, Inc.Marker delivery device for tissue marker placement
US871874525 May 20106 May 2014Senorx, Inc.Tissue site markers for in vivo imaging
US87583696 Jan 201024 Jun 2014James E. SelisBiopsy devices and methods
US878443327 Apr 201222 Jul 2014Senorx, Inc.Plugged tip delivery tube for marker placement
US888015419 Jul 20134 Nov 2014Senorx, Inc.Fibrous marker and intracorporeal delivery thereof
US89654866 Dec 201324 Feb 2015Senorx, Inc.Cavity filling biopsy site markers
US896673510 Sep 20133 Mar 2015Breast-Med, Inc.Tissue marker for multimodality radiographic imaging
US903976328 Jan 201426 May 2015Senorx, Inc.Tissue marking implant
US904296421 Apr 201026 May 2015Cook Medical Technologies LlcSystem and method for fiducial deployment via slotted needle
US90429656 Mar 201326 May 2015C. R. Bard, Inc.Biopsy marker with in situ-generated imaging properties
US904416225 Jan 20132 Jun 2015Senorx, Inc.Marker delivery device with releasable plug
US9149341 *21 Nov 20116 Oct 2015Senorx, IncDeployment of polysaccharide markers for treating a site within a patient
US923487713 Mar 201312 Jan 2016Endomagnetics Ltd.Magnetic detector
US923793720 Feb 201519 Jan 2016Senorx, Inc.Cavity-filling biopsy site markers
US923931413 Mar 201319 Jan 2016Endomagnetics Ltd.Magnetic detector
US92417732 Mar 201526 Jan 2016Breast-Med, Inc.Imaging fiducial markers and methods
US932706121 Sep 20093 May 2016Senorx, Inc.Porous bioabsorbable implant
US94271866 Dec 201030 Aug 2016Endomagnetics Ltd.Magnetic probe apparatus
US948055418 May 20151 Nov 2016Senorx, Inc.Tissue marking implant
US952226413 Feb 201420 Dec 2016Cook Medical Technologies LlcRatchet-slide handle and system for fiducial deployment
US952374811 Jan 201620 Dec 2016Endomagnetics LtdMagnetic detector
US957907712 Dec 200728 Feb 2017C.R. Bard, Inc.Multiple imaging mode tissue marker
US95791595 Nov 201328 Feb 2017Bard Peripheral Vascular, Inc.Apparatus for the percutaneous marking of a lesion
US96228222 Oct 201318 Apr 2017Suros Surgical Systems, Inc.Securement for a surgical site marker and deployment device for same
US964909314 Jan 201616 May 2017Senorx, Inc.Cavity-filling biopsy site markers
US977026214 May 201526 Sep 2017Cook Medical Technologies LlcScrew-driven handles and systems for fiducial deployment
US979545522 Aug 201424 Oct 2017Breast-Med, Inc.Tissue marker for multimodality radiographic imaging
US980168821 Oct 201431 Oct 2017Senorx, Inc.Fibrous marker and intracorporeal delivery thereof
US980853910 Mar 20147 Nov 2017Endomagnetics Ltd.Hypoosmotic solutions for lymph node detection
US20030233101 *17 Jun 200218 Dec 2003Senorx, Inc.Plugged tip delivery tube for marker placement
US20040236212 *23 May 200325 Nov 2004Senorx, Inc.Fibrous marker and intracorporeal delivery thereof
US20050119562 *27 Oct 20042 Jun 2005Senorx, Inc.Fibrous marker formed of synthetic polymer strands
US20050277871 *10 Jun 200515 Dec 2005Selis James EBiopsy devices and methods
US20060036165 *29 Sep 200516 Feb 2006Senorx, Inc.Tissue site markers for in vivo imaging
US20060084865 *25 Oct 200520 Apr 2006Burbank Fred HImageable biopsy site marker
US20070055090 *10 Aug 20068 Mar 2007Navotek Medical Ltd.Medical Treatment System and Method
US20070110665 *17 Nov 200517 May 2007Bolan Patrick JTissue marker for multimodality radiographic imaging
US20080234532 *18 Apr 200825 Sep 2008Invibio LimitedFiducial marker
US20080262473 *19 Oct 200523 Oct 2008Navotek Medical Ltd.Locating a Catheter Tip Using a Tracked Guide
US20080287729 *16 May 200720 Nov 2008Anthony BiscottiInterstitial marker and method for creation thereof
US20090127459 *10 Aug 200621 May 2009Navotek Medical Ltd.Localization of a Radioactive Source
US20090131734 *15 Feb 200721 May 2009Navotek Medical Ltd.Implantable medical marker and methods of preparation thereof
US20090131825 *18 Dec 200821 May 2009Senorx, Inc.Imageable biopsy site marker
US20090171198 *19 Dec 20082 Jul 2009Jones Michael LPowdered marker
US20090171199 *31 Jan 20072 Jul 2009Anders WidmarkMethod and instrument as well as use of instrument for permanent application of reference marker for precision aiming of treatment beam
US20090216150 *25 Feb 200827 Aug 2009Lee ReichelMethod and Apparatus For Inserting Biopsy Site Marker In Marker Body
US20090216181 *25 Feb 200827 Aug 2009Speeg Trevor W VBiopsy Site Marker Deployment Instrument
US20100010342 *13 Jul 200914 Jan 2010Senorx, Inc.Tissue site markers for in vivo imaging
US20100042041 *16 Jul 200918 Feb 2010Navotek Medical Ltd.Implantation device for soft tissue markers and other implants
US20100106168 *6 Jan 201029 Apr 2010Selis James EBiopsy devices and methods
US20100130887 *27 Jan 201027 May 2010Selis James EBiopsy devices and methods
US20100145363 *9 Feb 201010 Jun 2010Selis James EBiopsy devices and methods
US20100280367 *21 Apr 20104 Nov 2010Ducharme Richard WSystem and method for fiducial deployment
US20100292711 *9 Feb 201018 Nov 2010James SelisBiopsy devices and methods
US20110071424 *22 Sep 200924 Mar 2011Nock Andrew PBiopsy marker delivery device
US20110184449 *5 Apr 201128 Jul 2011Senorx, Inc.Marker delivery device with obturator
US20120116215 *21 Nov 201110 May 2012Jones Michael LDeployment of polysaccharide markers for treating a site within a patient
US20130123829 *30 Nov 201216 May 2013Senorx, Inc.Mri detectable obturator
USD71544224 Sep 201314 Oct 2014C. R. Bard, Inc.Tissue marker for intracorporeal site identification
USD71594224 Sep 201321 Oct 2014C. R. Bard, Inc.Tissue marker for intracorporeal site identification
USD71645024 Sep 201328 Oct 2014C. R. Bard, Inc.Tissue marker for intracorporeal site identification
USD71645124 Sep 201328 Oct 2014C. R. Bard, Inc.Tissue marker for intracorporeal site identification
EP2156806A116 Jul 200924 Feb 2010Navotek Medical Ltd.Implantation device for soft tissue markers and other implants
WO2006049911A1 *21 Oct 200511 May 2006Senorx, Inc.Fibrous marker formed of synthetic polymer strands
Classifications
U.S. Classification600/431, 600/432
International ClassificationA61B19/00, A61B17/00
Cooperative ClassificationA61B90/39, A61B19/54, A61B2090/3987, A61B2090/3954, A61B2090/3925, A61B2090/392, A61B2090/3908, A61B17/0057, A61B2017/00637, A61B2017/00898
European ClassificationA61B19/54, A61B17/00P
Legal Events
DateCodeEventDescription
24 Jun 2004ASAssignment
Owner name: SENORX, INC., CALIFORNIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:JONES, MICHAEL L.;LUBOCK, PAUL;MERRITT, JOHN;REEL/FRAME:015502/0497
Effective date: 20040304