United States Patent: 6,364,823

( 15 of 68 )

United States Patent	6,364,823
Garibaldi , et al.	April 2, 2002

Methods of and compositions for treating vascular defects

Abstract

Embolic compositions for treating vascular defects such as aneurysms include a mixture of a biocompatible polymer material, a biocompatible solvent, and preferably also an adhesive. The compositions preferably further comprise magnetic particles for controlling the delivery of the embolic agent. These magnetic particles preferably lose magnet strength over time, so that they do not interfere with subsequent magnetic diagnostic and therapeutic procedures. The compositions preferably also include radiopaque particles, which may be the magnetic particles, to facilitate imaging the embolic material.

Inventors:	Garibaldi; Jeffrey M. (St. Louis, MO); Hogg; Bevil J. (Santa Cruz, CA); Hastings; Roger N. (Maple Grove, MN); Ren; Brooke (Champlin, MN)
Assignee:	Stereotaxis, Inc. (St. Louis, MO)
Appl. No.:	527108
Filed:	March 16, 2000

Current U.S. Class: 600/12

Intern'l Class: A61M 037/00; A61N 002/00

Field of Search: 600/12-15,433,435,139 604/264,523,19,48

References Cited

U.S. Patent Documents

5326410	Jul., 1994	Granov et al.	600/12.
5695480	Dec., 1997	Evans et al.	604/264.
5702361	Dec., 1997	Evans et al.	604/53.
5830178	Nov., 1998	Jones et al.	604/49.

Other References

Alksne et al., Iron-acrylic Compound for Stereotaxic Aneurysm Thrombosis, J. of Neurosurgery. 47:137-141 (1977).*
Gaston et al., External Magnetic Guidance of Endovascular Catheters with a Superconducting Magnet: Preliminary Trials, J. Neuroradiol. 15:137-147 (1988).

Primary Examiner: Nasser; Robert L.
Assistant Examiner: Szmal; Brian
Attorney, Agent or Firm: Harness, Dickey & Pierce, P.L.C.

Parent Case Text

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation-in-part of prior U.S. patent application Ser. No. 09/271,118, filed Mar. 17, 1999, entitled "Magnetic Vascular Defect Treatment System" incorporated herein by reference, and of prior U.S. patent application Ser. No. 09/430,200, filed Oct. 29, 1999, entitled Methods of and Compositions for Treating Vascular Defects, incorporated herein by reference.

Claims

What is claimed:

1. A magnetic embolic agent for magnetic placement in a vascular defect with increased X-ray opacification to form an embolus in the defect to occlude the defect, the agent comprising:

between about 4 and about 70 weight percent biocompatible polymer;

between about 10 and about 80 weight biocompatible solvent capable of solubilizing the biocompatible polymer;

between about 10 and about 50 weight percent magnetic particles responsive to a magnetic field; and

between about 10 and about 50 weight percent X-ray opaque magnetic particles responsive to a magnetic field.

2. A magnetic embolic agent for magnetic placement in a vascular defect using diluted solvents to form an embolus in the defect to occlude the defect, the agent comprising:

between about 4 and about 70 weight percent biocompatible reactive polymer;

between about 10 and about 80 weight biocompatible solvent diluted in water capable of solubilizing the biocompatible polymer;

between about 0 and about 50 weight percent biocompatible polymer; and

between about 10 and about 50 weight percent magnetic particles responsive to a magnetic field.

3. A magnetic embolic agent for magnetic placement in a vascular defect using diluted solvents with increased X-ray opacification to form an embolus in the defect to occlude the defect, the agent comprising:

between about 4 and about 70 weight percent biocompatible polymer;

between about 10 and about 80 weight biocompatible solvent diluted in water capable of solubilizing the biocompatible polymer;

between about 0 and about 50 weight percent adhesive; and

between about 10 and about 50 weight percent magnetic particles responsive to a magnetic field;

between about 10 and about 50 weight percent Xray opaque magnetic particles responsive to a magnetic field.

4. The magnetic embolic agent according to claim 3 wherein the dilute solvent contains acetone.

5. The magnetic embolic agent according to claim 3 wherein the dilute solvent contains ethanol.

6. The magnetic embolic agent according to claim 3 wherein the dilute solvent contains saline.

7. The magnetic embolic agent according to claim 3 wherein the biocompatible polymer comprises prolamine, and wherein the dilute solvent comprises ethanol.

8. An embolic agent for delivery into a vascular defect to form an embolus in the defect to occlude the defect, the agent comprising:

between about 4 and about 80 weight percent biocompatible polymer;

between about 30 and about 95 weight biocompatible solvent capable of solubilizing the biocompatible polymer;

between about 1 and about 70 weight percent adhesive; and

an X-ray opaque material is added to enhance the visibility of the under fluoroscopy.

9. The embolic agent according to claim 8 wherein the xray opaque material comprises a particulate material.

10. The embolic agent according to claim 8 wherein the x-ray opaque material comprises a liquid material.

11. An embolic agent for delivery into a vascular defect to form an embolus in the defect to occlude the defect, the agent comprising:

between about 4 and about 80 weight percent biocompatible reactive polymer;

between about 10 and about 90 weight biocompatible solvent diluted in water capable of solubilizing the biocompatible polymer;

between about 0 and about 80 weight percent biocompatible polymer; and

an X-ray opaque material to enhance visibility under fluoroscopy.

12. A magnetic embolic agent for magnetic placement in a vascular defect to form an embolus in the defect to occlude the defect, the agent comprising:

between about 10 and about 90 weight percent biocompatible reactive polymer;

between about 10 and about 80 weight percent magnetic particles responsive to a magnetic field; and

between about 10 and about 80 weight percent X-ray opaque magnetic particles responsive to a magnetic field.

13. A two-part magnetic embolic agent for magnetic placement in a vascular defect to form an embolus in the defect to occlude the defect, the agent comprising:

a first part comprising between about 10 and about 90 weight percent biocompatible reactive polymer; between about 10 and about 80 weight percent magnetic particles responsive to a magnetic field; and between about 10 and about 80 weight percent X-ray opaque magnetic particles responsive to a magnetic field; and

a second part comprising between about 10 and about 90 weight percent biocompatible polymer catalyst.

14. A method of treating a vascular defect, the method comprising the steps of:

introducing a flowable first magnetic composition into the vascular defect under the guidance of an externally applied magnetic field;

introducing a flowable second magnetic composition into the vascular defect under the guidance of an externally applied magnetic field, the second magnetic composition when mixed with the first magnetic composition forming a substantially non-flowable material; and

mixing the first and second magnetic compositions in the vascular defect by varying the externally applied magnetic field to form an occulsion in the vascular defect.

15. A method retarding the hardening of an embolic material injected into a vascular defect comprising injecting a biocompatible liquid with a high surface tension prior to injecting the embolic material to create a clean barrier between bodily fluid and embolic material.

16. A magnetic liquid embolic agent responsive to an externally applied magnetic field to flow into a vascular defect and harden to occlude the vascular defect, the embolic agent comprising a biocompatible polymeric material, a biocompatible solvent, between about 25 and about 40 weight percent percent magnetite, and about 15 and about 25 weight percent gold plated nickel.

17. A magnetic liquid embolic agent responsive to an externally applied magnetic field to flow into a vascular defect and harden to occlude the vascular defect, the embolic agent comprising about 8 weight percent cellulose acetate, about 42 weight percent acetone, about 30 weight percent magnetite, and about 20 weight percent gold plated nickel.

18. A magnetic liquid embolic agent responsive to an externally applied magnetic field to flow into a vascular defect and harden to occlude the vascular defect, the embolic agent comprising about 10 weight percent prolamine, about 2 weight percent poly vinyl acetate, about 33 weight percent diluted ethanol, about 35 weight percent magnetite, and about 20 weight percent gold plated nickel.

Description

FIELD OF THE INVENTION

This invention relates to methods of and compositions for treating vascular defects, such as aneurysms and atriovenous malformations, and in particular a method and related apparatus for treating such defects with magnetically manipulated objects and materials.

BACKGROUND OF THE INVENTION

There are many types of vascular defects that can be treated by blocking the defect. One example of such a defect is an aneurysm, which is a permanent, abnormal blood-filled dilatation or ballooning of a blood vessel that may be congenital or the result of disease. Aneurysms typically have thin walls vulnerable to rupture. If an aneurysm ruptures, the resulting hemorrhage that can put injurious pressure on surrounding tissue, impair downstream blood flow, and even cause death. Another example of a vascular defect is an atriovenous malformation--a typically congenital shunt formed between an artery and a vein that often carries a substantial blood flow. One of the principal complications in treating these and other vascular defects is the blood flow in the adjacent vessels which impairs treatment, but should be maintained for the health of the patient.

Current treatments for aneurysms include embolizing the aneurysm to remove the dilatation or balloon from the wall of the vessel. In the most mature technique, the surgeon accesses the region of the aneurysm under direct visualization and places one or more aneurysm clips on the opening or "neck" of the aneurysm. While this conventional surgical technique has a high rate of success, it is highly invasive and for that reason it is undesirable. More recently, less invasive techniques have been developed for the treatment of aneurysms. One such technique involves the introduction of small wire coils into the aneurysm. A catheter is navigated to the site of the aneurysm, and the coils are delivered through the lumen of the catheter into the aneurysm. The coils reduce the blood flow through the aneurysm, which results in clotting within the aneurysm. This coiling procedure can be time consuming both in navigating the catheter through the vasculature to the site of the aneurysm, and in introducing the coils into the aneurysm. In some cases, the shape of the aneurysm allows the coils to escape from the aneurysm, requiring the coil to be retrieved and replaced.

Another less invasive technique for treating vascular defects is the delivery of embolic materials to the site of the vascular defect to occlude the defect. In the case of an aneurysm a balloon is inflated over the neck of the aneurysm and a liquid embolic agent is introduced into the aneurysm. Attempts have been made to deliver embolic agents directly into the dilation or balloon of the aneurysm. Embolic agents have also been used to occlude atriovenous malformations, but it can be difficult to accurately deliver the embolic agents. In one of the more common procedures a catheter is navigated to the site of the atriovenous malformation and particles of polyvinyl alcohol with sizes selected for the particular application are introduced. This procedure requires guessing at the proper size of the particles and there is limited control over the placement of the particles, which upon release follow the path of greatest flow.

Alksne, "Iron-acrylic Compound for Stereotactic Aneurysm Thrombosis." J. Neurosurg. 47:137-141 (1977), incorporated herein by references, discloses injecting an iron-acrylic mixture into the dome of an aneurysm, and holding the mixture in place with a magnet inside the body. Gaston et al., "External Magnetic Guidance of Endovascular Catheters with Superconducting Magnet: Preliminary Trials" J. Neuroradiol. 15: 137-147 (1988), incorporated herein by reference, discloses delivering magnetic particles with an external source magnet. Evans, U.S. Pat. No. 5,702,361 "Method of Embolizing blood Vessels" incorporated herein by reference, discloses various embolizing agents including polymers and/or adhesives. Granov et al., U.S. Pat. No. 5,236,410, "Tumor Treatment Method," incorporated herein by reference, discloses the use of magnetic materials in tumor treatment.

Difficulties with prior embolic agents include complications from the delivery method, which sometimes employed balloons to temporarily block flow through the vessel and the difficulty in controlling and containing the embolic agents, which allows some material to escape and block downstream vessels.

In addition, some embolic agents did not adequately adhere to the vessel walls, allowing blood to seep between the embolic plug and the vessel wall. When biocompatible adhesives were used, the adhesives tended to adhere to the delivery equipment, resulting in a potentially fatal attachment of the delivery catheter to the embolic plug, or the pulling of a "string" of embolic material from the body of embolic material as the delivery catheter was retracted.

Another limitation on the use of embolic agents has been the limited ability to simultaneously view the ejection of the embolic agent under fluoroscopy of adequate quality. Conventional image intensifiers cannot operate in the presence of magnetic fields much larger than the relatively weak field of the earth (about 0.5 gauss). Fields of hundreds to thousands of gauss are required to control magnetic embolic agents, and these fields must be projected at distances large enough to reach aneurysms inside the body. External magnets which project such strong fields prohibit the use of conventional image intensifiers near the patient. One attempted solution is to use mirrors to project the X-ray image impinging on a phosphor plate to a remote camera, but this approach is not practical for human operating room procedures. First, the loss of light intensity due to the optical converter would require increased X-ray intensity which is unacceptable in clinical hospital settings. Second, the dim light being projected would require that the optical path to the distant camera be entirely black. This is difficult to implement with moving imaging systems.

Despite these and other possible difficulties, flowable embolic agents offer advantages over objects including the ability to uniformly fill the defect, and the relative ease of delivering a flowable embolic agent versus multiple discrete objects, such as coils.

SUMMARY OF THE INVENTION

The present invention provides improved methods and related devices for treating vascular defects. According to one aspect of this invention, various magnetic objects are provided that can be delivered intravascularly through a catheter and which can be guided into and/or held in place in the vascular defect with an applied magnetic field. One embodiment of these magnetic objects includes magnetic coils. These coils may either be magnetic, or include magnetic elements. Another embodiment of these magnetic objects includes a magnetic patch, adapted to cover the vascular defect. The magnetic patch may include a hoop for ensuring that the patch is fully deployed.

In another aspect of this invention, a catheter is provided for delivering the magnetic objects and materials of the present invention. The catheter has a proximal end and a distal end, and lumen therebetween. There is a coil at the distal end, and leads extending along the catheter by which a current can be selectively applied to the coil at the distal end 126 of the catheter. Current can be selectively applied to the coil on the distal end of the catheter to selectively enhance the magnetic responsiveness of the distal end of the catheter so that it can be navigated in the body with an externally applied magnetic field, but the coil can be disconnected from current so that the coil does not interfere with the delivery of magnetic objects or magnetic materials through the lumen. The magnetism created by the current in the coil is enhanced by the presence of the magnetic objects or the magnetic material in the lumen of the catheter. The coil can also be energized to help retain magnetic materials in the lumen of the catheter. A second coil may be provided on the catheter to enhance magnetic responsive and to enhance the ability to retain magnetic materials in the lumen. In another embodiment, lateral coils (as opposed to circumferential coils) are provided in the sidewall of the catheter. These coils facilitate movement of the distal end 126 of the catheter, for example when it is n the opening of an aneurysm.

Thus, the method and devices of the present invention allows a catheter to be brought to the procedure site through magnetically assisted navigation, but the catheter can remain at the site as a further magnetic procedure, such as the magnetic delivery of magnetic objects and magnetic materials, is conducted.

In accordance with one aspect of this invention a liquid embolic agent is provided with a magnetic constituent, which allows the magnetic embolic agent to be controlled by a magnetic field applied by an external source magnet. The applied magnetic field creates a force that draws the magnetic embolic agent into the defect completely filling the defect without voids. The force direction can be adjusted during the procedure by moving an external magnet or changing the direction of externally generated fields to optimize filling. The magnetic force obviates the need for an occluding balloon, allowing more distal sites to be treated with the catheter alone. Aneurysms of all shapes and at all locations can be treated equally by simply adjusting the magnetic force direction.

The magnetic embolic agent in accordance with another aspect of the present invention preferably combines a precipitating polymer and a glue. The precipitating polymer preferably comprises a biocompatible polymer chosen from the group comprising: cellulose acetate, polymethylmethacrylate, polyvinyl acetate, polyvinyl alcohol, hydrogel, polyurethane, polyethylene vinyl alcohol, or preferably cellulose acetate, and a biocompatible solvent chosen from the group comprising: dimethylsulfoxylate, ethyl alcohol, ethyl acetate, and preferably acetone. The solvent dissolves the polymer, and with the proper combination of viscosity and surface tension, the solution will then be able to homogeneously suspend paramagnetic particles. The solution is easy to deliver through a catheter to the vascular defect. The polymer precipitates at the vascular defect as the solvent dissipates into the blood. However, the polymer may not adhere to the walls of the vasculature, and may tend to internally fracture due to the lack of intra-polymer cohesion. Thus, an adhesive is preferably included to provide adhesion and cohesion. This adhesive is preferably either cyanoacrylate and fibrin glue. The adhesive stays inert in the polymer solution. However, once the magnetic material is ejected, the water activates the adhesive, the composition adheres to the vessel, and enhances the cohesiveness of the material as well. The weakened vessel wall is reinforced by the adhesive bond with the magnetic embolic material which fills the defect.

A metal powder such as barium or tantalum may be added to render the composition radiopaque and thus visible under fluoroscopy. Preferably the metal powder is paramagnetic material, i.e., one that is attracted by a magnetic field, but does not retain magnetism once the magnetic field is removed. The presence of the paramagnet particles allows the embolic composition to be directed, deposited, and held in place with a magnetic field. The paramagnetic particle is preferably a magnetic powder such as pure iron, carbonyl iron, coated iron and coated carbonyl iron (preferably pure iron) is used for both radiopacity and magnetic attraction.

The magnetic embolic material in accordance with the present invention allow magnetic control for superior placement. In some embodiments the settings of the material can be controlled buy the application of a curing agent. The embolic compositions have superior adhesion and cohesion. In one embodiment, the material becomes less magnetically responsive over time so that the embolic does not interfere with or restrict subsequent magnetic procedures such as magnetic surgical procedures or MRIs.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side elevation view of a first embodiment of a magnetic coil constructed according to the principles of this invention;

FIG. 2A is a side elevation view of the magnetic coil of the first embodiment shown as it is being inserted in an aneurysm without an externally applied magnetic field;

FIG. 2B is a side elevation view of the magnetic coil of the first embodiment shown as it is being inserted in an aneurysm with an externally applied magnetic field in accordance with the present invention;

FIG. 3 is a side elevation view of a second embodiment of a coil with a magnetic element constructed according to the principles of this invention;

FIG. 4A is a side elevation view of the coil of the second embodiment shown as it is being inserted into an aneurysm without an externally applied magnetic field;

FIG. 4B is a side elevation view of the coil of the second embodiment shown as it is being inserted into an aneurysm with an externally applied magnetic field;

FIG. 5 is a side elevation view of a third embodiment of a coil with two magnetic elements constructed according to the principles of this invention;

FIG. 6A is a side elevation view of the coil of the third embodiment shown as it is being inserted in an aneurysm without an externally applied magnetic field;

FIG. 6B is a side elevation view of the coil of the third embodiment shown as it is being inserted in an aneurysm with an externally applied magnetic field;

FIG. 7 is a longitudinal cross-sectional view of a catheter and push wire combination adapted for delivery coils in accordance with the principles of the present invention;

FIG. 8 is a perspective view of a fourth embodiment of a coil constructed according to the principles of this invention;

FIG. 9 A is a longitudinal cross-sectional view of a catheter adapted for delivering the coil fourth embodiment, prior to delivery of the coil;

FIG. 9B is a longitudinal cross-sectional view of a catheter adapted for delivering the coil fourth embodiment, subsequent to delivery of the coil;

FIG. 10 is a top plan view of a magnetic patch constructed according to the principles of this invention;

FIG. 11 is a cross-sectional view of the patch taken along the plane of line 8--8 in FIG. 7;

FIG. 12A is a side elevation view of the patch deployed in an aneurysm;

FIG. 12B is a perspective view of an alternate apparatus for deploying the patch;

FIG. 13 is a cross-sectional view of the aneurysm, showing the patch occluding the opening of the aneurysm;

FIG. 14 is a cross-sectional view of a magnetic pellet constructed according to the principles of this invention;

FIG. 15 is a side elevation view of a catheter incorporating a coil in the distal end in accordance with the principles of this invention;

FIG. 16 is a longitudinal cross-sectional view of the catheter shown in FIG. 15;

FIG. 17 is a side elevation view of a catheter incorporation two coils in the distal end 26 in accordance with a first alternate embodiment.

FIG. 18 is a transverse cross-sectional view of a catheter incorporating three coils in the distal end in accordance with a second alternative embodiment;

FIG. 19 is a side elevation view of the second alternative embodiment of a catheter;

FIG. 20 is a side elevation view of the second alternative embodiment of the catheter shown as it could be positioned in the neck of an aneurysm;

FIG. 21A is a perspective view of a catheter constructed according to the principles of this invention; and

FIG. 21B is a perspective view of the split rectangular coil incorporated into the catheter of FIG. 21A;

FIG. 22 is a perspective view of the delivery of a magnetic embolic agent under the influence of an axial magnetic field with a parallel gradient;

FIG. 23 is a perspective view of the delivery of a magnetic embolic agent under the influence of a side magnetic field with a perpendicular gradient.

Corresponding reference numerals indicate corresponding parts throughout the several views of the drawings.

DETAILED DESCRIPTION OF THE INVENTION

A first embodiment of a magnetic coil constructed according to the principles of this invention is indicated generally as 20 in FIG. 1. The magnetic coil 20 is preferably made from a permeable magnetic material, such as 400 series stainless steel or Hiperco.TM. wire, or some other suitable material. The magnetic coil 20 could also be made from a permanent magnetic material, such as combination of neodymium iron boron powder in a polymer binder. The magnetic coil 20 preferably has a length of between about 20 mm and about 200 mm, and a diameter of between about 0.010 inches and about 0.018 inches.

As shown in FIG. 2, the magnetic coil 20 is delivered to the site of the vascular defect in the patient, in this case an aneurysm, inside a catheter 22. The catheter 22 may be a conventional catheter having a proximal end, a distal end 26, and a lumen extending therebetween. The distal end 26 of the catheter 22 is navigated to the aneurysm, for example using a guide wire. Once at the site of the aneurysm, the coil 20 is then ejected from the distal end 26 of the catheter 22. A magnetic field, as indicated by arrows B, is applied at the site of the aneurysm to draw the coil 20 into the aneurysm. (The magnetic gradient is preferably parallel to the magnetic field). The coil 20 is advanced from the distal end 26 of the catheter 20, and in contrast to when no magnetic field is applied as shown in FIG. 2A, the application of the magnetic field helps keep the coil within the aneurysm as shown in FIG. 2B, so that the coil 20 coils upon itself in the aneurysm. Additional coils 20 may be inserted in the aneurysm until the aneurysm is substantially filled, and blood flow in the aneurysm is reduced. This allows clotting in the aneurysm. Eventually the aneurysm is completely occluded.

A second embodiment of a magnetic coil constructed according to the principles of this invention is indicated generally as 30 in FIG. 3. The magnetic coil is preferably made from a non-magnetic material, such as platinum or some other suitable material. The magnetic coil 30 preferably has a length of between about 20 mm and about 200 mm, and a diameter of between about 0.010 inches and about 0.018 inches. The magnetic coil 30 has first and second ends 32 and 34. A magnetic element 36 is secured at the first end 32 of the coil 30. The magnetic element 36 can be a magnetically permeable material such as Hiperco.TM. or cold rolled steel. The magnetic element 36 may also be a permanent magnetic material, such as Neodymium Iron Boron.

As shown in FIG. 4, the magnetic coil 30 is delivered to the site of the vascular defect in the patient, in this case an aneurysm, inside a catheter 22. Once at the site of the aneurysm, the first end 32 of the coil 30 is ejected from the distal end 26 of the catheter. A magnetic field, indicated by arrows B, is applied at the site of the aneurysm to draw the coil 30 into the aneurysm. (The magnetic gradient is preferably parallel to the magnetic field). The coil 30 is advanced from the distal end 26 of the catheter 22, and in contrast to when no magnetic field is applied as shown in FIG. 4A, the application of the magnetic field helps steer the end of the coil within the aneurysm as shown in FIG. 4B, so that the coil 30 coils upon itself in the aneurysm. Additional coils 30 may be inserted in the aneurysm until the aneurysm is substantially filled, and blood flow in the aneurysm is reduced.

A third embodiment of a magnetic coil constructed according to the principles of this invention is indicated generally as 40 in FIG. 5. The magnetic coil 40 is preferably made from a non-magnetic material, such as platinum or some other suitable material. The magnetic coil 40 preferably has a length of between about 20 mm and about 200 mm, and a diameter of between about 200 and about 0.018 inches. The magnetic coil 40 has first and second ends 42 and 44. A magnetic element 46 is secured to the first end 42, and a magnetic element 48 is secured to the second end 44. The magnetic elements 46 and 48 can be a permeable magnetic material such as Hiperco.TM. or cold rolled steel. The magnetic elements 46 and 48 may also be a permanent magnetic material, such as Neodymium Iron Boron. The magnetic elements 46 and 48 allow the coils 40 to be joined end to end in the lumen 28 of the catheter 22. This allows the coils to be delivered into the aneurysm in a continuous strand, if desired.

As shown in FIG. 6, a series of magnetic coils 40 is delivered to the site of the vascular defect in the patient, in this case an aneurysm, inside a catheter 22. Once at the site of the aneurysm, the first end 42 of the distal-most coil 40 is ejected from the distal end 26 of the catheter 22. A magnetic field indicated by arrows B, is applied at the site of the aneurysm to draw the coil 40 into the aneurysm. (The magnetic gradient is preferably parallel to the magnetic field). The coils 40 are advanced from the distal end 26 of the catheter 22, and in contrast to when no magnetic field is applied as shown in FIG. 6A, the application of the magnetic field helps steer the ends 42 and 49 of the coil 40 within the aneurysm as shown in FIG. 6B, so that the coil 40 coils upon itself in the aneurysm. Additional coils 40 may be inserted in the aneurysm, either as a continuous strand, or separately until the aneurysm is substantially filled, and blood flow in the aneurysm is reduced. Adjacent coils 40 can be separated by changing the direction of the magnetic field or gradient to separate the adjacent coils.

The distal end of a catheter 50 for delivering the coil 40 is shown in FIG. 7. The catheter 50 could also be used to deliver coils 20 or 30 or any of the other magnetic objects of the present invention. The catheter 50 has a proximal end, a distal end 52, and a central lumen 54 therein. A push wire 56 is disposed in the lumen 54. The push wire 56 has a magnet 58 on its distal end. The push wire 56 also has a coil 60 on its distal end, generally surrounding the magnet 58. Leads 62 and 64 extend proximally from the coil 60, allowing the coil to be selectively connected to a power supply. The magnet 58 on the distal end of the push wire 56 magnetically engages the magnet 48 on the second end 44 of the coil 40, allowing the push wire 56 to push the coil 40 out of the lumen 54 of the catheter 50. Once the coil 40 has been pushed out of the catheter 50, then the coil 60 can be energized, to neutralize the magnetic attraction between the magnet 58 and the magnet 48 on the second end 44 of the coil 40, to thereby release the coil 40.

A fourth embodiment of a coil constructed according to the principles of this invention is indicated generally as 70 in FIG. 8. Coil 70 comprises a coil section 72, and has a first end 74 and a second end 76. There is a magnet 78 at the first end 74, and a magnet 80 on the second end 76. The magnets 78 and 80 are preferably tube-shaped.

The distal end of a catheter 90 for delivering the coil 70 is shown in FIGS. 9A and 9B. The catheter 90 has a proximal end, a distal end 92. The catheter 90 has a central lumen 94 with a circular cross-section, surrounded by an annular lumen 96. The distal end of the annular lumen 96 is resiliently closed with a flap 98. A push wire 100 having a magnet 102 on its distal end 104, can slide in the central lumen 94. As show in FIG. 9A, the magnet 102 magnetically engages the magnet 80 on the second end 76 of the coil 70. The push wire 100 can be advanced distally in the lumen which pushes the coil 70 distally out of the distal end of the lumen 96. Once the coil 70 has been pushed out of the lumen 96, the flaps 98 close behind it. As shown in FIG. 9B, when the push wire 90 is drawn proximally back into the central lumen 94, the flaps 98 separate the coil 70 from the push wire 100.

A magnetic patch 120 constructed according to the principles of this invention is shown in FIGS. 10 and 11. The patch 120 is made from a highly flexible material such as silicone or polyurethane or some other suitable material. In some embodiments it may be desirable to make the patch from a bioadsorbable material. In the preferred embodiment the patch 120 includes a hoop 122 of nitinol "memory" wire, which allows the patch to be compressed to be delivered through the lumen of a catheter or by being wrapped around the distal end of the catheter. The hoop 122 causes the patch 120 to open to its normal (preferably round) shape. Of course some other structure or construction can be provided to cause the patch to assume its extended configuration. The patch 120 includes magnet material, for example particles of a magnetically responsive material or a magnetic wire mesh. The magnetically responsive material may be a permeable magnetic material or it may be a permanent magnetic material. For example food grade iron particles of between about 0.05 .mu.m and about 50 .mu.m.

As shown in FIG. 12A, the patch is delivered to the interior of the aneurysm. This is conveniently done by navigating the distal end 26 of the catheter 22 into the aneurysm. The patch 120 is then deployed from the lumen of the catheter 22, and the hoop 122 causes the patch 120 to open to its full shape. Alternatively, as shown in FIG. 12B, the patch could be delivered wrapped on the outside of the distal end portion of the catheter 22, and retained thereon by a retractable sheath 126. The catheter 22 is navigated to the site of the vascular defect and the sheath 126 retracted distally to release the patch 120 at the site of the defect. A magnetic field, indicated as arrows B, is then applied to the patch 120 to urge the patch against the interior of the neck of the aneurysm, as shown in FIG. 13. Preferably a transverse magnetic gradient (gradient perpendicular to the field direction) is applied, with the patch 120 being magnetized along a long axis (along its surface) and the transverse gradient pulling the patch parallel to its thickness. The edge margins 124 of the patch 120 preferably have a wettable adhesive thereon, such as a hydrogel, cellulose ether, collagen or even cyanoacrylate so that the edge margins of the patch adhere to the margins of the interior of the aneurysm surrounding the neck or opening of the aneurysm. Alternatively, the edge margins 124 of the patch 120 may have an adhesive activated by some other agent, such as a chemical agent, ultraviolet light, or laser. Thus the patch 120 covers the opening of the aneurysm. The patch can also have growth promoting substances on its surface, such as Vascular Endothelial Growth Factor (VEGF) to promote growth of epithelial cells over the patch to close covered aneurysm opening.

The patch 120 could also be used to cover injured sections on the inside walls of the patient's vasculature. In this use, the patch might contain agents which promote healing and/or tissue growth, such as VEGF and even cells. The patch 120 could be applied to sites of plaque rupture, or to sites of intra-vascular therapy such as angioplasty or atherectomy. A patch 120 can be applied to one side of a blood vessel, while being held in place by a transverse gradient field, or multiple patches could be applied sequentially around the inside circumference of a blood vessel by successive rotating the field gradient direction. In this latter case, the patches would collectively form a continuous interior wall reinforcement, like a stent. This stent could be adsorbable over time by the body, and contain agents which promote healing of the arterial wall.

As shown in FIG. 14 the magnetic object can also be a pellet 130 comprising magnetically responsive particle 132, with a coating 134 of a biocompatible material such as polyvinyl alcohol. The magnetically responsive particle 132 may be iron and preferably has a diameter of between about 1 .mu.m and about 500 .mu.m. With the coating 134, the pellet preferably has a diameter of between about 100 .mu.m and about 1000 .mu.m. The pellets 130 can be delivered from the lumen of a catheter navigated to the site of the vascular defect. A magnetic field can be applied from an external source magnet to guide the pellets 130 into a particular branch of an atriovenous malformation, and hold them in place to occlude the malformation.

In accordance with the methods of this invention, magnetic fields are used to deploy and place magnetic objects and magnet materials to treat vascular defects. However this means that magnetic navigation techniques generally cannot be used to navigate the delivery catheter, because magnetizing the distal end 26 of the catheter would interfere with the delivery of the magnetic objects. However, in accordance with another aspect of this invention, and as shown in FIGS. 15 and 16, a catheter 150, having a proximal end 152, a distal end 154, and a lumen 156 therebetween, is provided with a coil 158 formed in its distal end 154. Leads 160 and 162 extend along the wall 164 of the catheter to selectively apply an electric current to the distal end 154 of the catheter 150. The application of current to the coil 158 magnetizes the distal end 154 of the catheter 150, allowing it be navigated by the application of a magnetic field with an external source magnet. Thus with current applied to the coil 158 via leads 160 and 162, the distal end 154 of the catheter 150 can be conveniently navigated to the site of the vascular defect by the application of a magnetic field, or with the assistance from an applied magnetic field. While the magnetic objects in the lumen 156 are not sufficiently responsive to allow magnetic navigation of the catheter 150 containing them, magnetic objects or magnetic material in the lumen, together with the energized coil 158, render the catheter sufficiently magnetically responsive so that it can be magnetically navigated or at least navigated with magnetic assistance. The coil 158 may be 5 mm (0.200 inch) long, and comprises 5 layers, each layer having 200 turns of AWG 50 insulated copper or silver magnet wire. The magnetic material in the lumen will typically have a .mu. ranging from about 10 to about 100. For a magnetic material with a .mu.of 25, a current of 0.2 A will achieve a magnetization of IT, which is comparable to permanent magnets used in magnetic navigation. With a current of 0.5A, a magnetic material in the lumen having a .mu.of 10 will achieve a similar level of magnetization. Currents as high as 0.5A in this coil should not significantly raise the local temperature, provided there is adequate blood flow for cooling.

The coil 158 in catheter 150 also facilitates the delivery of magnetic materials, such as magnetic embolic agents. The coil 158 can be energized to help retain the magnetic embolic material in the catheter 150 as the catheter is navigated to and navigated from the site of the vascular defect, functioning as a valve.

An alternative construction of catheter 150 indicated as 150 ' is shown in FIG. 17. Catheter 150', in addition to having coil 158, also has coil 166, with leads 168 and 170 extending along wall 164. The coil 166 can be connected in series with coil 158 to enhance the magnetic effect at the distal tip of the catheter 150'. The coil 166 can also be connected oppositely from coil 158, so that together the coils cut off the flow of magnetic embolic material through the lumen 156 of the catheter 150', but the net magnetic effect distal to the catheter is negligible so that the catheter 150'does not disturb the magnetic embolic agent that has already been deposited.

As shown in FIGS. 18 and 19, a catheter 200, having a proximal end 202, a distal end 204, and a lumen 206 therebetween, is provided with three coils 208, 210, and 212 formed in its distal end 204. The sidewall 214 of the catheter 200 contains leads 216 and 218 extending to coil 208, leads 220 and 222 extending to coil 210, and leads 224 and 226 extending to coil 212. The leads allow the coils 208, 210 and 212 to be selectively energized. The coils 208, 210, and 212 can be energized to facilitate magnetic navigation of the distal end 204 of the catheter 200 to the vascular defect. The coils can also be selectively energized at the site of the vascular defect to manipulate the distal end 204 of the catheter 200 to control the delivery of a magnetic embolic agent. For example, as shown in FIG. 20, if the catheter 200 has been navigated to an aneurysm and is being used to deliver a magnetic embolic agent into the dilatation or balloon of the catheter, the tip of the catheter would be pointing into the neck of the aneurysm, and the applied magnetic field would preferably be oriented transversely to the neck of the aneurysm, with the gradient oriented toward the back wall of the aneurysm, to deposit the magnetic embolic agent in layers in the aneurysm. Selectively energizing one or more of the coils 208, 210, and 212 allows the position of the distal end 204 of the catheter 200 to be adjusted.

The catheters 150 and 150' of the present invention also permit ejected magnetic material to be drawn into the lumen of the catheter. By properly energizing the coil 158, magnetic material can be magnetically drawn into the lumen even when the viscosity of the magnetic material and small lumen size would make it difficult or impossible to suction the material back into the lumen. With the catheter 200' of the present invention, the coils 158 and 166 can be differentially energized to apply a force to draw in magnetic material immediately adjacent the distal end of the catheter, and to repel magnetic material more than a few millimeters away. This prevents the catheter from drawing a string of material from the mass of ejected material or otherwise disturbing the mass of ejected material.

A catheter 300 having a proximal end, a distal end 304, and a lumen 306 therebetween is shown in FIG. 21A. The wall 308 of the catheter 300 has a coil 310 embedded therein. As shown in FIG. 21B, the coil 310 is a split longitudinal coil. Leads 312 and 314 extend longitudinally in the wall 308 to the proximal end of the catheter 300 to permit the coil to be selectively connected to a power supply. Catheter 300, like catheter 200 can be manipulated within an applied magnetic field by selectively applying power to the coil 310.

An important aspect of this invention is the ability to visually monitor the treatment process. A preferred method is the use of bi-planar fluoroscopy to provide images of the treatment site in the patient. In bi-planar imaging two images of the treatment site are provided from different angles (preferably 90.degree. apart). Real time imaging has generally not been available in prior magnetic treatment procedures because the magnetic fields interfered with the operation of the imaging equipment. However, the inventors have discovered that by using shielded x-ray sources and digital imaging plates such as LAST plates, available from Varian Medical Systems, Inc., real time imaging can be provided in the presence of the relatively strong magnetic fields (which typically range from about 0.01T to 0.5T at the treatment site) for the magnetic treatment procedures of the present invention.

Bi-planar imaging also provides a convenient interface for physician control of the procedure. By computer processing and display of the images, the displays can be used by the physician to identify the current positions of the treatment devices and the desired future positions and orientations of the treatment devices. For example, the user can manipulate a cursor or other indicator on the display with a mouse, joystick, or other input device and "click" at the points to identify a particular point. By identifying a point on each of the two bi-planar displays the point is uniquely identified in three-dimensional space. The computer can then determine and implement the necessary movements of the external source magnet to achieve the desired future positions and orientations.

The physician can also identify desired field and/or gradient directions on the displays, and the computer can then determine and implement the necessary movements of the external source magnet or electrical current changes in an electromagnet to achieve the desired field and/or gradient directions.

Embolic Compositions

Generally, the embolic agent of the present invention is a flowable magnetic material that can be delivered through a microcatheter, but which hardens to form a solid embolic. The composition preferably comprises a biocompatible polymer chosen from the group comprising: cellulose acetate, polymethylmethacrylate, polyvinyl acetate, polyvinyl alcohol, hydrogel, polyurethane, polyvinyl alcohol, or preferably cellulose acetate, and a biocompatible solvent chosen from the group comprising: dimethylsulfoxylate, ethyl alcohol, ethyl alcohol diluted with water, ethyl acetate, and preferably acetone. The solvent should be somewhat water soluble to promote the dissipation in the blood, in the case of cellulose acetate, polymethylmethacrylate, and polyvinyl alcohols, acetone and ethyl acetate work effectively.

The preferred polymers are non-water soluble, but yet hydrophilic, so a desired surface tension can be achieved. A non-water-soluble polymer gives clean deposition, whereas water-soluble polymer tends to spread. The desired range of surface tension is in the range from 30 dynes/cm to 50 dynes/cm. For example, polyvinyl alcohol has a surface tension of about 37 dynes/cm, and polyethylene oxide has a surface tension of about 43 dynes/cm. The composition also has a surface tension which is high enough to suspend the metal powder homogeneously and to prevent it from separating from the fluid component in the presence of an attracting magnetic field. In the preferred composition of cellulose acetate and acetone, a composition of between about 5% and about 30% weight percent cellulose acetate, and more preferably about 17% cellulose acetate achieves an appropriate range of viscosity and surface tension, with a range of 5% to 30% solids, with 17% solids being the preferred composition.

In one preferred embodiment the biocompatible polymer is one or more materials selected from cellulose acetate, cellulose acetate butyrate, cellulose acetate propionate, ethyl cellulose ether, sodium carboxymethyl cellulose ether, cellulose, polymethyl methacrylate, epoxy, polyvinyl chloride, polyvinyl acetate, polystyrene, and the biocompatible solvent is acetone, with cellulose acetate being the preferred polymeric material. In another preferred embodiment the biocompatible polymer is one or more materials selected from prolamines, ethyl cellulose, polyvinyl acetate, polynivyl butyrate, polyvinyl alcohol, hydrogels, polyvinyl pyrrolidone, mussel adhesive protein, and the biocompatible is diluted ethanol (i.e., preferably not 100% ethanol.), with prolamine being the preferred biocompatable polymeric material.

The composition also includes a glue or adhesive selected from the group comprising: cyanoacrylate and fibrin glue. When adhesive is added to the composition, the solubility of the polymer is altered. Appropriate composition properties are maintained when the adhesive is no more than 50% of the total weight of adhesive and polymer. When the adhesive to polymer ratio is greater than 1:1, the cure time of the composition becomes too short to allow careful delivery of the composition to the aneurysm, allowing time to adjust the fill (for example by manipulation of the magnetic field). A minimum percentage of adhesive is required to insure enough cohesion of the embolic plug to prevent its breaking or flaking in the presence of high velocity blood flow, and to provide sufficient adhesion of the plug to the wall of the artery. In the case of cyanoacrylate combined with cellulose acetate and acetone, the preferred ratio of adhesive:polymer is between about 1:40 to about 1:1, and most preferably about 1:6.7.

The composition also includes a magnetic material dispersed in the embolic material so that the embolic material can be magnetically manipulated. The additive is preferably FDA grade iron, which is used as a food supplement. In the case of 2 .mu.m iron particles, the preferred polymer:iron weight ratio ranges from about 1:0.5 to about 1:10, and is most preferably 1:3. In this preferred composition, the iron itself provides sufficient radiopacity to render the magnetic embolic visible under fluoroscopy. Other acceptable magnetic materials include iron, iron oxide (Fe.sub.3 O.sub.4), nickel, cobalt, Alnico, tantalum, carbonyl iron, Hyperco, barium ferrite, silver-coated nickel microspheres and flakes, samarium-cobalt, and gold coated nickel microspheres and flakes. According to one aspect of this invention, the magnetic particles are preferably reactive so that they become less magnetically responsive over time. Thus, while at the time of delivery the magnetic embolic material is sufficiently magnetically responsive to be controlled by the application of a magnetic field from an external source magnet, the magnetic embolic material loses its magnetic responsiveness over time. Thus the plug of magnetic embolic material will not interfere with later magnetic diagnostic and therapeutic procedures, such as MRI. Fine particles (1 to 3 .mu.m) of essentially pure (99.97%) iron, that can be used in the magnetic embolic agents of this invention will rust or react to form iron oxide (FeO or Fe.sub.2 O.sub.3) when exposed to the oxygen content of blood. To facilitate oxidation, the iron particles may be coated with a hydrophilic, water-soluble agent such as PVA. When the coated particles solidify in the polymer matrix within the aneurysm, blood plasma will be attracted to the hydrophilic coating on the iron particles. The coating will eventually dissolve, exposing the small iron particles to blood oxygen. The iron will be converted to iron oxide over a period of hours (following solidification of the embolic plug). Alternatively, a magnetic iron oxide particle (Fe.sub.2 O.sub.4) could be used that can convert to non-magnetic iron-oxide particles (FeO and Fe.sub.2 O.sub.3).

To facilitate the chemical transition of the magnetic particles to state with significantly reduced magnetic properties, a transition agent, (e.g. water in the case of iron or iron oxide) can be associated with the magnetic particle, such as by encapsulation within the coating, to cause the magnetic material to react and become less magnetic.

Rather then relying on a chemical change to reduce the magnetic property of the embolic material, a magnetic material could be provided that naturally converts to a state with significantly reduced magnetic properties. For example, certain materials decay into non-magnetic materials, such as magnetic Fe-55 decaying over time to non-magnetic Mn-55. All or some of the iron in the embolic material would consist of Fe-55. After the embolic is placed within body, the natural decay of the isotope would slowly reduce the magnetic properties of the filled aneurysm. The half-life of this isotope is 2.7 years and it decays by electron capture emitting x-rays and neutrinos in the process. This half-life would have a limiting effect on the shelf-life of the embolic material. Other isotopes with electron capture decay modes, such as xenon and palladium, are presently implanted in the body and allowed to decay as part of existing medical procedures.

Another way of providing a magnetically controllable embolic material that does not remain strongly magnetic after the procedure so as to interfere with subsequent diagnostic and therapeutic procedures is to use a magnetic material in the embolic that has a sufficiently high Curie temperature, that the temperature of the patient can be reduced below the Curie temperature of the magnetic embolic material. Then, after the emoblic cures, the body temperature of the patient is restored, significantly reducing the magnetic properties of the embolic. The Curie Point of a ferromagnetic material is defined by the temperature above which it loses it's ferromagnetism. Magnetic material whose Curie temperature are below normal body temperature (98.6 F) can be used to make the embolic material magnetic. The surrounding tissue wold be sub-cooled to a temperature below this point while the aneurysm is filled and polymerization is occurring so that the material is highly susceptible to the magnetic field. When the procedure is completed the patient would be allowed to warm up to normal body temperature and the filled aneurysm would lose its ferromagnetic properties. Examples of materials with appropriate Curie temperatures are Gadolinium (15 C) and PdNi alloy (32 C). Gadolinium is presently used in MRI contrast agents, and PdNi alloy is used as passively-regulated implants that can be heated using magnetic fields.

Still another way of providing a magnetically controllable embolic material that does not remain strongly magnetic after the procedure is to use magnetic material that is naturally absorbed by the body. For example some of the iron in an embolic material will be naturally replaced by protein. Bioabsorbtion relies upon the natural processes within the body to remove the magnetic material over a period of time. For example, a protein called ferritin is produced within the body to store iron for latter use in the hemoglobin. The protein can be artificially manufactured and the iron molecules within the protein structure can be replaced with magnetite that is very magnetic. Once placed in the body, the natural process of the ferritin enzyme removes the iron from the magnetite-filled ferritin and replaces it with non-magnetic oxides of iron.

A metal powder such as barium or tantalum may be added to render the composition radiopaque and thus visible under fluoroscopy. Preferably, however, a magnetic powder such as pure iron, carbonyl iron, coated iron and coated carbonyl iron (preferably pure iron) is used to provide some radiopacity and magnetic responsiveness. However, a mixture of iron and heavy metal powders may optimize magnetic and opacity properties. The concentration of FDA iron or other magnetic material must be high enough to allow manipulation of the composition in the magnetic fields and field gradients available from the source system, yet the concentration must be low enough provide a homogenous suspension and prevent separation or clumping of the magnetic component in the applied field. The composition preferably has a force metric of about 0.006 to 0.010 tesla.sup.2 /meter. Too high a concentration of paramagnetic particles creates too strong an attraction that can cause particles separating from the suspension. Too low a concentration of paramagnetic particles does not generate enough attraction to the suspension.

Many of the particles that provide X-ray opacification have surface properties which are incompatible with liquid embolic compositions. These particles tend to separate from the embolic material causing an undesirable condition. In accordance with one embodiment of this invention, a homogeneous dispersion of X-ray opaque particles is achieved by providing a combination of magnetic particles that homogeneously disperse in the embolic material, with magnetic X-ray opague particles. For example, particles of Fe.sub.3 O.sub.4 are magnetic, and because of the oxygen bonds form chemical bonds with the embolic that help retain the particles in suspension. However, these particles are not as radiopaque as desired. Magnetic particles with x-ray opaque surfaces, such as gold or silver coated nickel, are very radiopaque, but because of the coating do not remain suspended in the embolic material. The inventors have determined that combining these two types of particles, the particles with the X-ray opaque surfaces will homogeneously disperse in the embolic materials. The inventors suspect that the magnetic particle with X-ray opaque surface attaches magnetically to the magnetic particle, which functions as a carrier to homogeneously distribute the combined particles. The magnetic particle chemically links to the solution while the magnetic particle with X-ray opaque surface magnetically links to the other magnetic particle. The inventors have also found that the mixture of particles dramatically increases X-ray opacification. The adjacent particles will significantly improve the visibility of the embolic in which they are dispersed. The inventors suspect that the particles' close proximity, causes a greater scattering of the X-rays. The inventors have identified several magnetic "scaffold" materials for maintaining magnetic radiopaque materials in suspension in an embolic material:

                    Magnetic Scaffold material
                           MnOFe.sub.2 O.sub.3
                           FeOFe.sub.2 O.sub.3
                           CoOFe.sub.2 O.sub.3
                           NiOFe.sub.2 O.sub.3
                           CuOFe.sub.2 O.sub.3
                           MgOFe.sub.2 O.sub.3
                           BaO6Fe.sub.2 O.sub.3
                    Magnetic Scaffold material
                           MnOFe.sub.2 O.sub.3
                           FeOFe.sub.2 O.sub.3
                           CoOFe.sub.2 O.sub.3
                           NiOFe.sub.2 O.sub.3
                           CuOFe.sub.2 O.sub.3
                           MgOFe.sub.2 O.sub.3
                           BaO6Fe.sub.2 O.sub.3

The composition of the magnetic embolic material is selected to have a range of properties which are most desirable for the filling of aneurysms. The preferred composition has a viscosity low enough to allow delivery through a standard neuro catheter (typical inner lumen size ranging from 0.014 inch to about 0.021 inches) from a puncture site in the groin area to cerebral aneurysms, but high enough to suspend metal particles used for radiopacity and/or magnetic attraction. The desired range of viscosity for the magnetic embolic agent is between about 30 and about 1500 centipoise. When the viscosity is lower than 30 centipoise, it generally is not capable of suspending the paramagnetic particles. When the viscosity is greater than about 1500 centipoise is too difficult to deliver through microcathter.

The magnetic embolic material can be provided as two components, Part A and Part B, that are mixed just prior to use. Part A comprises solvent, polymer, and cyanoacrylate. Part B comprises solvent, polymer, and magnetic particles. The mixture of solvent and polymer in Part B are used sparingly to wet the iron particles sufficiently to allow flow and good mixing with the Part A. In a preferred embodiment Part A comprises about 16 weight percent cellulose acetate; about 79 weight percent acetone, and about 5 weight percent cyanoacrylate, and Part B comprises about 91 weight percent cellulose acetate, about 44 weight percent acetone, and about 34 weight percent FDA iron. At the time of the procedure the two parts are mixed in the ratio of about 4:1, using a syringe mixing column.

Alternatively, the embolic material can provided in two parts that are mixed after delivery to the vascular defect. Such a two-part embolic agent would include first and second parts that are separately injected into the vascular defect. The two parts can comprise the two parts of a two-part polyurethane adhesive, the two parts of an epoxy adhesive, fibrin adhesives, long-chaing cyanoacrulates, prolamines, mussel protein adhesive, or any other biocompatible two part adhesive material.

Each of the components preferably non-reactive, and thus if one of the components escapes into the patient's system while the vascular defect is being filled it does not pose as great a hazard as a reactive embolic agent. When a two-part magnetic embolic agent is used, and once both parts have been delivered to the vascular defect, the components should be mixed to ensur e thorough reaction between the parts. This can be accomplished by changing (e.g., rotating or alternating) the magnetic field applied to the vascular defect to move the two parts within the vascular defect. Magnetic mixing after delivery of a two-part, and even after delivery of a one-part embolic mixture, helps reduce the net magnetic moment of the cured embolic material.

To provide greater control over the setting time, a material can be used that only cures upon, or whose curing is significantly accelerated by, exposure to a curing agent. This curing agent may be a chemical curing agent which causes the flowable magnetic material to harden, or the curing agent may be energy such as ultraviolet or laser light, which can be provided via a fiber optic line to cure the material once the physician is satisfied with its placement. Magnetic materials can be made with sufficient properties that can be "painted" on the surface of an internal body structure, such as a blood vessel, and magnetically held in place until the magnetic material sets. The magnetic material can include therapeutic agents, including growth factors and cells. Thus, for example, the endoluminal surface of a blood vessel can be painted with a substance that fills gaps, fortifies the wall, and applies therapeutic agents. Filling of grossly interrupted endolrninal surfaces such as abdominal aortic aneurysms can fill voids, and allow a smooth, continuous surface to be constructed. Stents and grafts used for these purposes often have rough ends and gaps between the graft and the interior surface of the blood vessel that pool with blood.

The shape of the magnetic embolic material is affected by the direction of the magnetic field. Thus, when the applied field and gradient are parallel, the magnetic material forms columns parallel to the field direction. Thus, as shown in FIG. 22, when the magnetic field and the magnetic gradient are parallel, for example when the magnetic field is an axial field of a permanent magnet or an electromagnet, the magnetic material forms columns or pillars. This is sometimes advantageous, depending upon the application, but these ends of the columns or pillars can sometimes project into the main blood vessel which is undesirable, particularly where there are still voids within the aneurysm. As shown in FIG. 23, when the magnetic field and the magnetic gradient are perpendicular, for example with the side field of a permanent magnet or electromagnet, the magnetic material forms layers. This is advantageous in some instances because it forms a mass with a smooth surface that completely fills the aneurysm, and does not project into the blood vessel. Particularly with the direct visualization available with the present invention, an aneurysm or other vascular defect can be filled, layer upon layer, to the appropriate level.

While a significant objective of the embolic agents of the present invention is to provide an embolic agent that can be effectively implanted using magnetic fields, it has been found that the embolic agents of the present invention are effective even when deployed conventionally, without the use of magnetic fields. In this case the embolic agent does not have to include magnetic particles, but it may include magnetic particles because of their radiopacity, which improves the visibility of the embolic materials under fluoroscopy.

An example of an embolic agent for non-magnetic delivery into a vascular defect to form an embolus in the defect to occlude the defect comprises between about 4 and about 80 weight percent biocompatible polymer, such as cellulose acetate; between about 30 and about 95 weight biocompatible solvent capable of solubilizing the biocompatible polymer such as acetone, and between about 1 and about 70 weight percent adhesive. An X-ray opaque material, in particle or liquid form, may be added to provide visibility under fluoroscopy. Another example of an embolic agent for delivery into a vascular defect to form an embolus in the defect to occlude the defect comprises between about 4 and about 80 weight percent biocompatible reactive polymer, such as prolamine; between about 10 and about 90 weight biocompatible solvent diluted in water capable of solubilizing the biocompatible polymer, such as ethyl alcohol; between about 0 and about 80 weight percent biocompatible polymer, such as polyvinyl acetate. An X-ray opaque material, in particle or liquid form, may be added to provide visibility under fluoroscopy. These non-magnetic embolics could be optimally delivered in some aneurysms (e.g., lateral aneurysms) using a standard balloon remodeling technique. These non-magnet embolic agents could also be delivered in other vascular defects using standard techniques.

A difficulty sometimes encountered with filling vascular defects with embolic materials, is that the leading surface of the embolic material being injected reacts and hardens. To eliminate the premature reaction and hardening of the embolic material, the embolic material can isolated from the body fluids with a biocompatible liquid with a high surface tension to create a clean barrier between bodily fluid and embolic. For example the catheter for delivering the embolic is first flushed with D5 (a solution of 5% dextrose and 95% saline), then injected with about 0.1 to about 1.0 cc of D50 (a solution of 50% dextrose and 50% saline) to form a barrier before injecting the embolic material.

According to still another embodiment of this invention, a specially constructed catheter can be provided for delivering an embolic into a vascular defect. The catheter is provided with a sheath on its distal end. The sheath is expanded by the attraction of the magnetic field on the sheath, which then conforms to the vascular defect (such as an aneurysm). Filling continues until the sheath-contained embolic conforms to the entire vascular defect. The filled sheath is released in the vascular defect to complete the treatment. The sheath can be provided with a small hole or plurality of small holes, to allow a small quantity of the embolic material to seep through the sheath, to secure the sheath to the vascular defect and hold the sheath in place.

Operation

In operation, a magnetic object for treating a vascular defect is delivered by navigating the distal end of a catheter to the site of the vascular defect. The magnetic object may or may not already be in the distal portion of the lumen of the catheter during this navigation. In the case of a coil 20, 30, or 40, the coil is preferably at least partly ejected from the distal end 204 of the catheter and a magnetic field applied from an external source magnet. The field is preferably aligned in the direction of the opening of the aneurysm, and the gradient is preferably toward the back wall of the aneurysm.

In accordance with this invention, the distal end of a delivery catheter is navigated to the site of the vascular defect. This could be done with a magnetic surgical system, such as that disclosed in pending U.S. patent application Ser. No. U.S. utility patent application Ser. No. 09/211,723, filed Dec. 14, 1998, entitled Open Field System for Magnetic Surgery, or U.S. patent application No. U.S. patent application Ser. No. 09/271,424, filed Mar. 17, 1999, entitled Gapped Toroid Magnet for Magnetic Surgery System, or U.S. Patent Application No. U.S. patent application Ser. No. 09/189,633, filed Nov. 10, 1998, entitled Articulated Magnetic Guidance System. Each of these magnetic surgery systems provides both bi-planar imaging and magnetic control that is useful not just in navigating the distal end of the catheter, but in controlling the ejection of a magnetic embolic material.

The magnetic surgery system preferably includes bi-planer fluoroscopic imaging that permits visualization of the magnetic manipulation of magnetic objects and magnetic embolic materials. The magnetic surgery system is preferably one that is not adversely affected by the presence of the strong magnetic fields used in the magnetic surgery, and thus one that is not affected by the use of magnetic fields in manipulating the magnetic objects and magnetic materials. The imaging system preferably includes LAST plates available from Varian Medical Systems, Inc., Palo Alto, Calif. Thus, the physician can guide the delivery of the magnetic embolic while visualizing the procedure under fluoroscopy without compromising the image quality expected in modern radiology suites.

In the case of the magnetic coil 20, as the coil is advanced, as shown in FIG. 28 the applied magnetic field compresses the coil, pulling it toward the back wall of the aneurysm, and away from the open neck of the aneurysm. As more of the coil 20 is advanced into the aneurysm. The applied magnetic field prevents the end of the coil from snaking out the open neck, and allows the coil to be wound inside the aneurysm to substantially occlude the aneurysm. Additional coils 20 can be delivered in this manner until the aneurysm is satisfactorily occluded.

In the case of the coil 30 with magnetic elements on at least one end, as the coil is advanced, as shown in FIG. 4B the applied magnetic field steers the magnetic element 36 on the first end 22 of the coil toward the back wall of the aneurysm, and away from the open neck of the aneurysm. The applied magnetic field prevents the first end 32 of the coil 30 from snaking out the open neck, and allows the coil to be wound inside the aneurysm to substantially occlude the aneurysm. Additional coils 30 can be delivered in this manner until the aneurysm is satisfactorily occluded.

In the case of the coil 40 with magnetic elements on each end, as the coil is advanced as shown in FIG. 6B, the applied magnetic field steers the magnetic elements 46 and 48 on the ends 42 and 44 of the coil toward the back wall of the aneurysm, and away from the open neck of the aneurysm. This prevents the ends of the coil from snaking out the open neck, and allows the coil to be wound inside the aneurysm to substantially occlude the aneurysm. The coils 40 can be inserted continuously end to end, or each coil can be separately introduced. The coils can be separated at the distal end of the catheter 22 by turning the magnetic field to torque the magnetic element 48 on the proximal end 44 of the distal most coil 40 from the magnetic element 46 on the distal end 42 of the adjacent coil. A continuous strand of several coils 40, or several separate coils 40, can be inserted until the aneurysm is satisfactorily occluded.

In the case of a magnetic patch 50, the catheter 22 is navigated to the neck of the aneurysm, and the patch is introduced into the aneurysm. The resilient hoop 52 causes the patch to expand to its normal flat configuration. The blood present in the aneurysm wets the adhesive on the edge margins 54 of the patch 50. A magnetic field is applied to the aneurysm to urge the patch 50 against the opening of the aneurysm. The magnetic field helps to hold the patch 50 in place until the patch is secured, occluding the opening of the aneurysm.

In the case of the magnetic pellets 60, the catheter 22 is navigated to the site of the vascular defect and the pellets are released from the distal end 26 of the catheter. A magnetic field is applied to the vascular defect, in a direction of the branch to be occluded. The pellets 60 align in the direction of the applied magnetic field and travel in the direction of the applied gradient to occlude the vascular defect.

In the case of a magnetic embolic agent, the catheter is navigated to the site of the vascular defect. A magnetic field is applied and the magnetic embolic agent is ejected from the distal end of the catheter. The magnetic field rigidifies the ejected magnetic embolic agent. Thus, the magnetic field can be applied to rigidify the magnetic embolic agent and hold its shape until the magnetic embolic agent hardens on its own. A long rigid plug can be extruded from the catheter for occluding an atriovenous malformation. The applied magnetic field rigidities and helps the plug retain its shape as the plug is advanced into the atriovenous malformation.

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Current U.S. Class:	600/12
Intern'l Class:	A61M 037/00; A61N 002/00
Field of Search:	600/12-15,433,435,139 604/264,523,19,48