U.S. patent application number 13/792997 was filed with the patent office on 2013-07-25 for multiple imaging mode tissue marker.
This patent application is currently assigned to C. R. BARD, INC.. The applicant listed for this patent is C. R. BARD, INC.. Invention is credited to R. Michael Casanova, Chandrashekhar P. Pathak, Dnyanesh A. Talpade.
Application Number | 20130190616 13/792997 |
Document ID | / |
Family ID | 39512460 |
Filed Date | 2013-07-25 |
United States Patent
Application |
20130190616 |
Kind Code |
A1 |
Casanova; R. Michael ; et
al. |
July 25, 2013 |
MULTIPLE IMAGING MODE TISSUE MARKER
Abstract
An intracorporeal marker for marking a site within living tissue
of a host having a body of porous hydroxyapatite whose physical
properties permit the body to be distinguished from human soft
tissue under visualization using ultrasonic and radiation imaging
modalities.
Inventors: |
Casanova; R. Michael;
(Scottsdale, AZ) ; Talpade; Dnyanesh A.;
(Kinnelon, NJ) ; Pathak; Chandrashekhar P.;
(Phoenix, AZ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
C. R. BARD, INC.; |
Murray Hill |
NJ |
US |
|
|
Assignee: |
C. R. BARD, INC.
Murray Hill
NJ
|
Family ID: |
39512460 |
Appl. No.: |
13/792997 |
Filed: |
March 11, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12518695 |
Jun 11, 2009 |
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PCT/US2007/087211 |
Dec 12, 2007 |
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13792997 |
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60869636 |
Dec 12, 2006 |
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Current U.S.
Class: |
600/431 |
Current CPC
Class: |
A61B 6/481 20130101;
A61B 2090/3908 20160201; A61B 2090/376 20160201; A61B 90/39
20160201; A61B 2090/3995 20160201; A61B 8/481 20130101; A61B
2090/3966 20160201; A61B 2090/3925 20160201; A61B 2090/3954
20160201 |
Class at
Publication: |
600/431 |
International
Class: |
A61B 6/00 20060101
A61B006/00; A61B 8/08 20060101 A61B008/08 |
Claims
1-15. (canceled)
16. A method of in vivo identification of a position in soft
tissue, comprising: inserting a marker containing hydroxyapatite at
a position in soft tissue of a living host; passing ultrasonic
energy through the living host to form an ultrasound image of the
marker; and using the image to locate a site for a medical
treatment.
17. The method of claim 16, wherein the hydroxyapatite is
porous.
18. The method of claim 16, wherein the marker consists
substantially of hydroxyapatite.
19. The method of claim 16, wherein the marker consists
substantially of porous hydroxyapatite.
20. A method of in vivo identification of a position in soft
tissue, comprising: inserting a unitary hydroxyapatite marker
containing a first hydroxyapatite portion and a second
hydroxyapatite portion having differing porosities at a position in
soft tissue of a living host; passing energy through the living
host to form one of an ultrasound image and an X-ray image of the
unitary hydroxyapatite marker; and using the image of the unitary
hydroxyapatite marker to locate a site for a medical treatment.
21-23. (canceled)
24. A method of in vivo identification of a position in soft
tissue, comprising: inserting a marker containing a porous ceramic
at a position in soft tissue of a living host; passing ultrasonic
energy through the living host to form an ultrasound image of the
marker; passing radiant energy through the living host to form an
X-ray image of the marker; and using the image to locate a site for
a medical treatment.
25. The method of claim 24, wherein the porous ceramic includes
hydroxyapatite.
26. The method of claim 24, wherein the porous ceramic is
substantially all hydroxyapatite.
27-29. (canceled)
30. The method of claim 16, wherein the marker containing
hydroxyapatite includes: a core region made of porous
hydroxyapatite; and an outer region comprised of a second
hydroxyapatite, the core region being completely contained with the
outer region, wherein the porous hydroxyapatite of the core region
has a first porosity and the second hydroxyapatite of the outer
region has a second porosity, wherein the first porosity of the
porous hydroxyapatite of the core region is higher than the second
porosity of the second hydroxyapatite of the outer region.
31. The method of claim 16, wherein the marker containing
hydroxyapatite includes a first hydroxyapatite portion having a
first porosity and a second hydroxyapatite portion having a second
porosity, wherein the first porosity of the first hydroxyapatite
portion is different from the second porosity of the second
hydroxyapatite portion.
32. The method of claim 16, wherein the marker containing
hydroxyapatite includes a porous body that has a central region and
a surface that surrounds the central region, the porous body having
pores filled with gas, the sizes of the pores and the gas being
such that the porous body is configured to be visualized under
ultrasound, wherein the porous body comprises a first dense
hydroxyapatite at the central region, a second dense hydroxyapatite
at the surface, and a porous hydroxyapatite between the central
region and the surface, and wherein the porous hydroxyapatite has
porosity levels in a range of 30 percent to 80 percent.
33. The method of claim 20, wherein the first hydroxyapatite
portion forms a core hydroxyapatite region having a first porosity
and the second hydroxyapatite portion forms an outer hydroxyapatite
region having a second porosity, wherein the first porosity of the
core hydroxyapatite region is higher than the second porosity of
the outer hydroxyapatite region.
34. The method of claim 24, wherein the marker includes: a core
region made of porous hydroxyapatite; and an outer region comprised
of a second hydroxyapatite, the core region being completely
contained with the outer region, wherein the porous hydroxyapatite
of the core region has a first porosity and the second
hydroxyapatite of the outer region has a second porosity, wherein
the first porosity of the porous hydroxyapatite of the core region
is higher than the second porosity of the second hydroxyapatite of
the outer region.
35. The method of claim 24, wherein the marker includes a first
hydroxyapatite portion having a first porosity and a second
hydroxyapatite portion having a second porosity, wherein the first
porosity of the first hydroxyapatite portion is different from the
second porosity of the second hydroxyapatite portion.
36. The method of claim 24, wherein the marker includes a porous
body that has a central region and a surface that surrounds the
central region, the porous body having pores filled with gas, the
sizes of the pores and the gas being such that the porous body is
configured to be visualized under ultrasound, wherein the porous
body comprises a first dense hydroxyapatite at the central region,
a second dense hydroxyapatite at the surface, and a porous
hydroxyapatite between the central region and the surface, and
wherein the porous hydroxyapatite has porosity levels in a range of
30 percent to 80 percent.
Description
PRIORITY DATA AND INCORPORATION BY REFERENCE
[0001] This application is a U.S. nation phase of International
Application No. PCT/US2007/087211, filed Dec. 12, 2007, which
claims priority to U.S. Provisional Patent Application No.
60/869,636, filed Dec. 12, 2006, which are incorporated herein by
reference in their entirety.
TECHNICAL FIELD
[0002] The invention relates generally to a biopsy tissue markers.
More specifically, the invention further relates to a biocompatible
tissue site marker that is visible under various modes of
imaging.
BACKGROUND ART
[0003] Advances in modern medical imaging technologies such as
X-ray, ultrasound, or magnetic resonance imaging make it possible
to identify and to biopsy tumors while they are still small. When
dealing with a small tumor, especially after a portion of the tumor
has been removed for biopsy, it is sometimes difficult to locate
the tumor at a later time for treatment. This is particularly true
in the case of tumors in the breast, where the ability to visualize
a small growth may depend upon the manner in which the breast is
positioned or compressed during the procedure. In addition, prior
to surgically removing a tumor, it is often advantageous to try to
shrink the tumor by chemotherapy or irradiation. This is especially
true in the case of breast cancer, where conservation of breast
tissue is a concern. Shrinkage of the tumor can sometimes make it
difficult for the surgeon to locate the tumor.
[0004] A solution to this problem is to place a marker within the
target tissues at the time of biopsy which can be visualized under
a variety of imaging modalities to facilitate finding the tumor at
a later time. When a suspicious mass is detected, a sample is taken
by biopsy, often, but not necessarily, using a specialized
instrument such as a biopsy needle. The needle is inserted in the
breast while the position of the needle is monitored using
fluoroscopy, ultrasonic imaging, X-rays, MRI or other suitable
imaging modalities.
[0005] In a new procedure, called stereotactic needle biopsy, the
breast is compressed between the plates of a mammography apparatus
and two separate X-rays are taken from different points of
reference. The exact position of the mass or lesion is calculated
within the breast. The coordinates of the lesion are then
programmed into a mechanical stereotactic apparatus which guides
the biopsy needle to the lesion.
[0006] Irrespective of the biopsy technique, the surgical site may
need to be examined or accessed for surgical treatment of a
cancerous lesion. Treatment requires the surgeon or radiologist
locate the lesion precisely and this may need to be done repeatedly
over a period of time. Since treatment may alter the host tissue,
the function of a marker even more important.
[0007] U.S. Pat. No. 6,725,083 for "Tissue site markers for in vivo
imaging" describes biopsy site markers and methods that permit
conventional imaging techniques to be used, such as ultrasonic
imaging. The biopsy site markers have high ultrasound reflectivity
due to high contrast of acoustic impedance resulting from
gas-filled internal pores. The markers may have a non-uniform
surface. The patent discloses the use of materials such as metal,
ceramic materials, metal oxides, polymer, and composites and
mixtures thereof.
[0008] U.S. Pat. No. 6,350,244 for "Bioabsorbable markers for use
in biopsy procedure" discloses a breast tissue marker that allows
the marker to be left in place avoiding the need for surgical
removal. One type of marker takes the form of hollow spheres made
of polylactite acid filled with iodine or other radiopaque material
to make them visible under X-rays and/or ultrasound. The radiopaque
materials are also bioabsorbable. Another type of marker disclosed
is a solid marker of pre-mixed radiopaque material and a
bioabsorbable material. The solid markers may also include dyes and
radioactive materials.
[0009] U.S. Pat. No. 6,347,241 for "Ultrasonic and x-ray detectable
biopsy site marker and apparatus for applying it" shows a biopsy
site marker of small bodies or pellets of gelatin which enclose
substantially a radioopaque object. The pellets are deposited at
the biopsy site by an applicator device inserted in the biopsy
site. Several gelatin pellets are deposited through the tube. The
radio opaque core in the gelatin bodies are of a non-biological
material and structure which are readily identified during X-ray
observations.
[0010] U.S. Pat. No. 6,161,034 for "Methods and chemical
preparations for time-limited marking of biopsy sites" describes
markers that remain present to permit detection and location of the
biopsy site. The markers are later absorbed by the host. The patent
discloses gelatin, collagen, balloons and detectability provided by
AgCl; Agl; BaCO.sub.3; BaSO.sub.4; K; CaCO.sub.3; ZnO;
Al.sub.2O.sub.3; and combinations of these.
[0011] US Patent Publication No. 2006/0079805 for "Site marker
visible under multiple modalities" describes site markers that
include balls or particles which are bonded together to form a
marker body. The balls or particles are made from biocompatible
materials such as titanium, stainless steel or platinum. The balls
or particles are described as being bonded together by sintering or
by adhesive such as epoxy. An alternative embodiment has at least
one continuous strand of wire of biocompatible material such as
titanium, stainless steel, platinum, or other suitable material,
compressed to form a mass that resembles a ball of yarn. Another
alternative is a resonating capsule, or a rod with drilled
holes.
[0012] US Patent Publication No. 2006/0036165 for "Tissue site
markers for in vivo imaging" shows ultrasound-detectable markers
whose shapes are distinct in an image from biological shapes.
Various shapes are disclosed including cylinders, coils, and other
more complex shapes.
[0013] It is believed that most known tissue markers have a
disadvantage in that they are not visible under all available
imaging modalities. The features of a marker that make it stand out
under X-rays do not necessarily make them stand out under MRI or
ultrasound imaging. One prior art mechanism for addressing the need
for multiple-imaging-mode markers is to employ a combination of
metal structure and biodegradable foam to provide ultrasonic
imaging visibility, MRI visibility and x-ray visibility. In this
case, the metal structure provides x-ray visibility and
biodegradable foam provides visibility in ultrasonic imaging.
[0014] There is a need for site markers made from biocompatible
materials that are visible under various modes of imaging to reduce
the number of procedures that patients must undergo in detection
and treatment of cancer or any disease requiring the user of tissue
markers. It will be a valuable contribution to the art for a marker
with a simple design and superior biocompatibility can be provided.
Also, selectable bioabsorbability by the host may be an advantage
as well.
SUMMARY OF THE INVENTION
[0015] A hydroxyapatite or porous metal or non-metal-based biopsy
marker is visible in multiple imaging modalities. In a preferred
embodiment, hydroxyapatite, a component of natural bone, is used.
This material is highly visible when viewed using X-ray imaging.
The ultrasonic visibility may be provided by creating one or more
voids within the hydroxyapatite marker and entrapping a
biocompatible gas within the void or voids. The biocompatible gas
provides a low density structure within the marker body which
provides high contrast when viewed using ultrasonic imaging
equipment. Also, hydroxyapatite has the advantage of being very
biocompatible. In addition, if biodegradability is desired,
hydroxyl apatite is capable of being rendered in a form that makes
it long-lasting, but ultimately biodegradable as well.
[0016] The manufacture of porous hydroxyapatite performs or molded
forms is well known. The hydroxyapatite can be made porous by many
methods known in ceramic manufacturing art. These methods include
but not limited to: molding the hydroxyapatite particles to a
desired geometry and then sintering the green mass. The preferred
porosity levels in porous Hydroxyapatite could range from 30% to
80%, and more preferably, from 60 to 80%. One exemplary method is
to mix powdered hydroxyapatite with a removable material to form a
slurry which when hardened can be removed and then to sinter the
hydroxyapatite to form a porous structure. Examples of removable
material include various soluble polymers, naphthalene, and others.
Purified hydroxyapatite powder can be made from known processes or
obtained from natural sources such as coral.
[0017] In an embodiment, a porous hydroxyapatite article may be
obtained, for example from commercial sources such as Berkeley
Advanced Biomaterials, Inc and incubated in carbon dioxide
atmosphere to fill the pores. The disk is visible under X-ray and
ultrasonic imaging.
[0018] Material other than hydroxyapatite can be used to make a
marker visible under multiple imaging modalities. For example, a
biocompatible porous ceramic may be used alone or in combination
with a biocompatible impermeable jacket, such as a coating of PTFE.
The porous ceramic material can be produced by sintering particles
with a sufficient void fraction to make the resulting article
distinct under ultrasound. Ceramics containing mixtures of
materials may be employed to enhance radio-opacity. For example,
ceramics can contain metallic inclusions. Ceramic particles (or
metal-ceramic particle mixtures) having a packing density of a
desired fraction, for example 70%, may be sintered to create a
mass. The result may have no, or limited, connections between the
void spaces so that the result needs no impermeable jacket to avoid
the voids filling with fluids. Alternatively, a coating may be
provided to prevent ingress of fluids. The coating need not be
mechanically continuous over the article if it is sufficient to
retard ingress of moisture. For example, the coating material may
be hydrophobic. In a variation, techniques used for making
refractory foams may be employed to create a marker.
[0019] In another embodiment, a biocompatible porous metal is used
in place of hydroxyapatite. The porous metal can be produced by
mechanical methods known in the art such as sand blasting. Other
methods such as laser etching, chemical etching or powder
metallurgical methods including sintering could also be used. In
one preferred approach, porous metals are obtained by compacting a
metal powder to a desired shape in presence of a polymeric and
non-polymeric binder and then sintering the metal powder particles
to form a homogenous metal mass with predetermined
porosity/density. Many metals and alloys suitable for long term
implant could be used and these include but not limited to:
Nitinol, gold, silver, stainless steel, cobalt-chromium alloy,
titanium, tantalum, and tungsten or combination thereof.
[0020] The shape and geometry of the porous biopsy marker can
depend on the clinical application. In general cylindrical,
spherical, disk like shapes are preferred. Irregular shapes may
also be used.
[0021] According to an embodiment, an intracorporeal marker marks a
site within living tissue of a host. The marker has a body of
porous hydroxyapatite whose size and shape permit visualization
under ultrasonic and radiation imaging modalities. Preferably, the
shape is generally cylindrical. In one embodiment, the marker has a
lower density core region and a higher density surface region.
[0022] According to an embodiment, an intracorporeal marker marks a
site within living tissue of a host. The marker has an
ultrasound-detectable portion defined by boundaries that are
distinctly different from normal tissue features. The
ultrasound-detectable portion is of a material that exhibits high
contrast in acoustical impedance compared to the host tissue. The
same portion, or a different portion, of a material exhibits high
contrast in at least one type of radiation imaging. The portion or
the same or different portion includes at least one of porous
ceramic, a porous metal, and a porous hydroxyapatite.
[0023] In a variation, the shape is generally cylindrical. In
another variation, the marker has a lower density core region and a
higher density surface region. A water-impermeable coating layer
may be provided to seal the marker against penetration by fluid,
particularly where the voids within are channeling voids. In a
particular embodiment the marker is of hydroxyapatite and in a
further, more specific variation, the surface region of the marker
has a higher density.
[0024] According to an embodiment, an intracorporeal marker for
marking a site within living tissue of a host has a porous body of
hydroxyapatite. The pores of the porous body are of such a size as
to maximize the visibility of the body under ultrasonic imaging. In
a variant, the body has a surface of higher density than a major
fraction beneath the surface.
[0025] According to an embodiment, an intracorporeal marker marks a
site within living tissue of a host. The marker includes a body of
porous hydroxyapatite whose physical properties permit the body to
be distinguished from human soft tissue under visualization using
ultrasonic and radiation imaging modalities. The body can have
various shapes, a preferred shape is a cylindrical shape. In a
preferred embodiment, the body has gas-filled pores. In another
preferred embodiment, the body has a core and a surface region, the
core region having a lower density than the surface region.
[0026] Note that, as used in this specification, the term soft
tissue is intended to characterize non-skeletal tissue which
relatively transparent to X-rays such that tissue such as bone and
some ligaments, cartilage, and fibrous tissue can be distinguished
from it. Thus, a hydroxyapatite marker may be substantially visible
under X-rays when placed in soft-tissue but might be hard to
distinguish from non-soft-tissue.
[0027] According to another embodiment, an intracorporeal marker
marks a site within living tissue of a host. The body includes at
least one material that exhibits detectable difference in
acoustical impedance relative to human soft tissue. The at least
one material also exhibits detectable difference in radiation
impedance relative to human soft tissue. The at least one material
includes at least one of porous ceramic and a porous metal.
Preferably, the body has a shape that is generally cylindrical. In
a variation of the embodiment, the body has a core and a surface
region, the core region having a lower density than the surface
region. In another variation of the embodiment, the body has a
surface and the surface has a water-impermeable coating layer. The
at least one material preferably includes hydroxyapatite and
preferably the material is solely hydroxyapatite.
[0028] According to another embodiment, an intracorporeal marker
marks a site within living tissue of a host. The marker has a
porous body of hydroxyapatite, the body having pores filled with
gas. The sizes of the pores and the gas are such that the body can
be visualized under ultrasound. In a variation, the body has a core
and a surface region, the core region having a lower density than
the surface region.
[0029] According to another embodiment, a method of in vivo
identification of a position in soft tissue includes inserting a
marker containing hydroxyapatite at a position in soft tissue of a
living host; passing ultrasonic energy through the soft tissue to
form an ultrasound image of the marker; and passing radiant energy
through the soft tissue to form an X-ray image of the marker.
Preferably, the hydroxyapatite defines a porous structure and more
preferably, the body consists substantially of hydroxyapatite.
[0030] According to another method of in vivo identification of a
position in soft tissue, a marker containing hydroxyapatite is
inserted at a position in soft tissue of a living host. Ultrasonic
energy is then passed through the living host to form an ultrasound
image of the marker. The image is then used to locate a site for a
medical treatment. Preferably, the hydroxyapatite is porous. The
marker may consist substantially of hydroxyapatite.
[0031] According to another embodiment, a method of in vivo
identification of a position in soft tissue, includes: inserting a
marker containing hydroxyapatite at a position in soft tissue of a
living host; passing radiant energy through the living host to form
an X-ray image of the marker using the image to locate a site for a
medical treatment. Preferably, the hydroxyapatite is porous. The
marker may consist substantially of hydroxyapatite.
[0032] According to another embodiment, a method of in vivo
identification of a position in soft tissue, includes: inserting a
marker containing a porous ceramic at a position in soft tissue of
a living host; passing ultrasonic energy through the living host to
form an ultrasound image of the marker; passing radiant energy
through the living host to form an X-ray image of the marker; using
the image to locate a site for a medical treatment. Preferably, the
porous ceramic includes hydroxyapatite and more preferably, the
porous ceramic is substantially made of hydroxyapatite.
[0033] According to another embodiment, a method of in vivo
identification of a position in soft tissue, includes: inserting a
marker containing a porous ceramic at a position in soft tissue of
a living host; passing ultrasonic energy through the living host to
form an ultrasound image of the marker; passing energy through the
living host to form an image of the marker based on a
non-ultrasound imaging modality; using the image to locate a site
for a medical treatment. Preferably, the porous ceramic includes
hydroxyapatite and more preferably, the porous ceramic is
substantially made of hydroxyapatite.
BRIEF DESCRIPTION OF THE DRAWINGS
[0034] The accompanying drawings, which are incorporated herein and
constitute part of this specification, illustrate exemplary
embodiments of the invention, and, together with the general
description given above and the detailed description given below,
serve to explain the features of the invention.
[0035] FIG. 1 is a cross-sectional view of a tissue marker with a
gas-impermeable (or resistant) casing.
[0036] FIG. 2 shows a tissue marker from the side which is
cylindrical shape according to exemplary embodiments.
[0037] FIG. 3 is a cross-sectional view of a tissue marker with a
gas-impermeable or liquid impermeable coating and a porous metal,
ceramic, or hydroxyapatite core.
[0038] FIG. 4 is a cross-sectional view of a tissue marker with a
porous outer layer of metal, ceramic, or hydroxyapatite and a
relatively solid metal, ceramic, or hydroxyapatite core.
[0039] FIG. 5 illustrates a monolithic porous marker, such as of
hydroxyapatite.
[0040] FIG. 6 illustrates the marker of FIG. 5 with a relatively
solid outer layer, such as a porous material of the core that has
been treated to densify the outer surface region to make it
relatively less susceptible to having the gas in the porous
gas-filled voids from being displaced by body fluids.
[0041] FIG. 7 illustrates a porous core with a relatively solid
outer layer which may be of the same or a different material from
the core.
DISCLOSURE OF THE INVENTION
[0042] Ceramics with voids in them, such as ceramic foams, are
often used as filtering materials. Some are used for filtering
molten metal, for example. Such materials may be manufactured in a
variety of different ways. Ceramic foam filters are generally made
by impregnating a polymeric foam with an aqueous slurry of ceramic
material containing a binder. The impregnated foam is dried to
remove water, and the dried impregnated foam is fired to eliminate
the polymer material. This leaves the ceramic foam. This process is
often used to create a channelized product but recipe variations,
such as a lower quantity of foaming agent, can produce
non-channelized product.
[0043] Foamed glass methods of manufacture and articles of
manufacture are disclosed in U.S. Pat. No. 5,972,817, "Foamed Glass
Article for Preparing Surfaces, Use Therefor, and Method of Making
Same" to Haines et al.; U.S. Pat. No. 5,821,184, "Foamed Glass
Article for Preparing Surfaces, Use Therefore and Method of Making
Same" to Haines et al.; U.S. Pat. No. 5,928,773, "Foamed Glass
Articles and Methods of Making Same and Methods of Controlling the
PH of Same Within Specific Limits" to James C. Andersen; and
published US Pat. Appl. No. 20040016195 for "Foamed glass article
for use as thermal energy control media;" each of which is hereby
incorporated by reference and attached hereto as if fully set forth
herein.
[0044] The voids may channel; i.e., they may generally intersect or
communicate with each other and the external surface.
Alternatively, they may be of a so-called closed cell type where
the voids do not communicate with each other or the external
surface. In void channeling materials or materials which are
naturally rough or porous, it is preferred for the matrix to be
hydrophobic or that the surface of the marker be sealed by an
impermeable, preferably hydrophobic, coating. This helps to resist
filling of the voids or surface pits with aqueous fluid. FIG. 1
illustrates, in section, a marker 100 having a core 105 with a
coating 110 overlying its surface. The coating also may promote the
biocompatibility of the surface as well as ensure against filling
of voids. FIG. 2 illustrates a side view of a marker 99 which is
consistent with the embodiment of FIG. 1 as well as with other
embodiments disclosed herein. FIG. 3 illustrates a marker with a
porous non-ceramic material, such as sintered metal alloy. A
coating 160, as described in the embodiment of FIG. 1, may be
provided in this particular marker 150.
[0045] FIG. 4 illustrates a two-component marker 200 of porous
hydroxyapatite 210 on an external layer over a core 107 which may
be of a different material, such as one which is predominantly
visible under X-ray imaging. The external layer 210 is
biocompatible owing to the use of hydroxyapatite. The porosity of
the outer layer 210 enhances the marker's visibility under
ultrasonic imaging. The outer layer 210 also provides the
biocompatibility of hydroxyapatite on the entire outer surface of
the marker 200. The core 107 may be metallic, ceramic composite
(with metallic material to enhance X-ray absorption), or it may be
a non-porous, or a less porous form of the outer layer 210, for
example, hydroxyapatite. In an alternative embodiment, the outer
layer 210 and core 107 materials discussed with reference to the
FIG. 4 embodiment may be reversed. For example, the core 107 may be
porous and the outer layer 210 could be solid or relatively more
solid than the core.
[0046] FIG. 5 illustrates a preferred embodiment of a
single-component porous hydroxyapatite marker 250 which is of
porous hydroxyapatite 109 throughout. A marker 255 which is a
variation on the embodiment 250 is shown in FIG. 6 in which a core
109 of porous hydroxyapatite is treated on its surface to close any
channeling and/or smooth its surface to create a denser outer layer
260 of hydroxyapatite. Another variation of a hydroxyapatite marker
is shown in FIG. 7 in which the marker 300 has a porous
hydroxyapatite core 111 and a more solid, or completely solid,
outer layer 310. Variations of these hydroxyapatite embodiments are
also considered useful, for example, a porous outer layer with a
non-porous or low porosity core and a dense core with a porous
outer layer that has been treated to form a thin dense outer layer
as in the embodiment of FIG. 6. In the latter embodiment, the
porosity would change from dense at the center, to porous toward
the surface and then back to dense at the surface. Table 1
illustrates various embodiments with H referring to hydroxyapatite,
M referring to metal, C referring to ceramic, and J referring to an
impermeable coating and the subscripts P and S referring to porous
and solid (or relatively low porosity). Note that other
combinations may be employed, the table providing merely a summary
of some preferred options.
TABLE-US-00001 TABLE 1 Structural embodiments of biopsy markers 1 2
3 4 5 6 7 8 9 10 11 12 13 14 15 Core H.sub.P M.sub.P C.sub.P
H.sub.S M.sub.S C.sub.S H.sub.P M.sub.P C.sub.P H.sub.S M.sub.S
C.sub.S M.sub.P C.sub.P M.sub.S Outer layer H.sub.S M.sub.S C.sub.S
H.sub.P M.sub.P C.sub.P -- -- -- H.sub.P -- -- M.sub.S C.sub.S --
Surface layer -- -- -- H.sub.S M.sub.S C.sub.S -- J J -- -- -- J J
J
[0047] Although referred to as porous, the materials above may
include one or more discrete voids formed non-randomly. For
example, the voids may be formed by binding filaments of the marker
material together, for example ultrasonic welding of thin wires to
form voids in a metal marker or component of a marker. Voids may be
also be formed by other processes such as machining, chemical
etching, laser etching, etc. In general, where the embodiments are
described as being porous, such alternative types of voids,
including a single void chamber, are also contemplated. The voids
may be formed by entrapping a biocompatible gas within the void or
voids.
[0048] The markers may be incubated in carbon dioxide atmosphere to
fill the voids with the gas. As discussed above, various methods
may be used to create the hydroxyapatite bodies. These methods
include but not limited to: molding the hydroxyapatite particles to
a desired geometry and then sintering the green mass. The preferred
porosity levels in porous Hydroxyapatite could range from 30% to
80%, and more preferably, from 60 to 80%.
[0049] Preferably porous portions are have a sufficient void
fraction and a size chosen to ensure the marker is distinct under
ultrasonic imaging. Porous ceramic material can be produced by
sintering particles with a sufficient void fraction to make the
resulting article distinct under ultrasound. As indicated above,
ceramics containing mixtures of materials may be employed to
enhance radio-opacity. For example, ceramics can contain metallic
inclusions. Ceramic particles (or metal-ceramic particle mixtures)
having a packing density of a desired fraction, for example 70%,
may be sintered to create a mass. The result may have no or limited
connections between the void spaces so that the result needs no
impermeable jacket to avoid the voids filling with fluids.
Alternatively, a coating may be provided to prevent ingress of
moisture. The coating need not be mechanically continuous over the
article if it is sufficient to retard ingress of moisture. For
example, the coating material may be hydrophobic. In a variation,
techniques used for making refractory foams may be employed to
create a marker.
[0050] In embodiments where a biocompatible porous metal is used
the metal porosity may be obtained by compacting a metal powder to
a desired shape in presence of a polymeric and non-polymeric binder
and then sintering the metal powder particles to form a homogenous
metal mass with predetermined porosity/density. Many metals and
alloys suitable for long term implant could be used and these
include but not limited to: Nitinol, gold, silver, stainless steel,
cobalt-chromium alloy, titanium, tantalum, and tungsten or
combination thereof.
[0051] The shape of the marker can depend on the clinical
application. In general cylindrical, spherical, disk like shapes
are preferred. Irregular shapes may also be used.
[0052] According to a feature of the above embodiments, a marker of
the any of the above described structures and compositions may be
used according to the following method which may include steps 1
and 2, steps 1 through 3, or steps 1 through 4, according to
different embodiments.
[0053] Step 1. Insert a marker at a location. The location can be
marked at a time and location of biopsy or otherwise positioned in
a tissue mass.
[0054] Step 2. Identify a location of the marker using a first
imaging modality. The modality may be X-ray-based imaging or
ultrasound-based imaging. This step may include passing a
corresponding form of energy through a soft tissue mass of a living
host.
[0055] Step 3. Identify a location of the marker using a second
imaging modality that is different from the first imaging modality
in step 2. The second imaging modality may be X-ray-based imaging
or ultrasound-based imaging. This step may also include passing a
corresponding form of energy through a soft tissue mass of a living
host.
[0056] Step 4. Surgically remove the marker.
[0057] Note that while the principal embodiments described above
had a generally symmetrical configuration, it is also possible to
form asymmetrical embodiments. For example, bodies having different
materials that can be imaged using different modalities can be
located adjacent each other on respective sides of the body. Also,
for example, cylindrical embodiments with a low density portion and
high density portion, each on a respective side of the axis in a
first embodiment, or each on a respective end of (displaced along
the axis) could be provided. Thus, the manner in which material is
distributed is not necessarily confined to the particular examples
shown. Such embodiments could be imaged using multiple imaging
modalities.
[0058] While the present invention has been disclosed with
reference to certain embodiments, numerous modifications,
alterations, and changes to the described embodiments are possible
without departing from the sphere and scope of the present
invention, as defined in the appended claims Accordingly, it is
intended that the present invention not be limited to the described
embodiments, but that it has the full scope defined by the language
of the following claims, and equivalents thereof.
* * * * *