US-12622767-B2 - Tissue markers

US12622767B2US 12622767 B2US12622767 B2US 12622767B2US-12622767-B2

Abstract

The inventions provided herein relate to tissue markers and uses thereof, e.g., to mark a target tissue site (e.g., a biopsy site in a breast tissue) or to produce a cell scaffold. The tissue markers described herein are designed to be resistant to fast migration (e.g., immediate migration after implantation through a needle track) and slow migration (e.g., over an extended period of time) upon implantation at a target tissue site (e.g., a biopsy site in a breast tissue), without using an adhesive. Additionally or alternatively, the tissue markers described herein can be readily detectable by at least one imaging modality, e.g., but not limited to magnetic resonance imaging, X-ray imaging, ultrasound imaging, or a combination thereof.

Inventors

Mark W. Grinstaff
Boris Nicolas BLOCH
Jonah KAPLAN

Assignees

TRUSTEES OF BOSTON UNIVERSITY
BOSTON MEDICAL CENTER CORPORATION

Dates

Publication Date: 20260512
Application Date: 20180822

Claims (20)

1 . An implantable tissue marker comprising: a sheet having opposing first and second surfaces and comprising at least a first layer of low density polyethylene (LDPE) film and a second layer of LDPE film, and is expandable from a rolled configuration to at least a partially unrolled configuration; a single shape-memory alloy wire sandwiched between the first and second layers of LDPE film, and wherein the shape-memory alloy wire is expandable from a rolled configuration to an unrolled configuration, and wherein the shape-memory alloy wire is straight in the unrolled configuration; iron oxide nanoparticles either on the shape-memory alloy wire or embedded in the sheet; and wherein at least one of the sheet and the shape-memory alloy wire is imageable by a first imaging modality.
2 . The implantable tissue marker of claim 1 , wherein the sheet is configured as a membrane, film, mat or mesh, or wherein the sheet has a thickness of 0.05 mm to about 4 mm.
3 . The implantable tissue marker of claim 1 , wherein the shape-memory alloy wire is made of a nickel-titanium alloy.
4 . The implantable tissue marker of claim 1 , wherein the LDPE film has a density at least substantially the same as a target tissue defined to be a soft tissue.
5 . The implantable tissue marker of claim 1 , wherein the sheet is imageable by the first imaging modality, and the shape-memory alloy wire is imageable by a second imaging modality, which is different than the first imaging modality.
6 . The implantable tissue marker of claim 1 , wherein at least one of the first and second layers is elastic.
7 . The implantable tissue marker of claim 1 , comprises pores penetrating through the entire thickness of the sheet.
8 . The implantable tissue marker of claim 1 , wherein the material of the shape-memory alloy wire is selected from the group consisting of: a copper-aluminum-nickel alloy, nickel-titanium alloy or an alloy comprising at least two or more metals selected from: zinc, copper, gold, or iron.
9 . The implantable tissue marker of claim 1 , wherein the shape-memory alloy wire comprises a viscoelastic element.
10 . The implantable tissue marker of claim 1 , wherein the iron oxide nanoparticles are imageable by the first imaging modality.
11 . The implantable tissue marker of claim 1 , wherein the sheet has the same density in the rolled configuration and the partially unrolled configuration.
12 . The implantable tissue marker of claim 1 , wherein the sheet has the same electrostatic pressure in the rolled configuration and the partially unrolled configuration.
13 . The implantable tissue marker of claim 1 , wherein the sheet has a square shape.
14 . The implantable tissue marker of claim 1 , wherein the sheet comprises woven fibers or non-woven fibers.
15 . The implantable tissue marker of claim 1 , wherein the sheet is further comprises at least one of: penetrating pores, macropores, bubbles, microbubbles, or air pockets, to allow the sheet to be imageable by the first imaging modality.
16 . The implantable tissue marker of claim 1 , wherein the iron oxide nanoparticles are embedded in the sheet.
17 . The implantable tissue marker of claim 1 , wherein the LDPE film has the dimension or width of between 0.2 cm and 2 cm.
18 . The implantable tissue marker of claim 1 , wherein the implantable tissue marker is configured to be permanently implanted.
19 . The implantable tissue marker of claim 1 , wherein the shape-memory alloy wire extends from a first end to a second end of the sheet; wherein the first end, the second end, and the shape-memory alloy wire are located completely within the sheet between the first and second surfaces.
20 . The implantable tissue marker of claim 1 , wherein the implantable tissue marker is configured to migrate less than 10 mm from the target site over a period of at least one month from the target site upon the implantation of the implantable tissue marker at the target site.

Description

CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser. No. 14/646,502, filed May 21, 2015, which is a 35 U.S.C. § 371 National Phase Entry Application of international Application No. PCT/US2013/071256 filed Nov. 21, 2013, which designates the U.S., and which claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 61/728,971 filed Nov. 21, 2012, the contents of each of which are incorporated herein by reference in their entirety. TECHNICAL FIELD OF THE DISCLOSURE The inventions described herein generally relate to tissue markers and uses thereof. In some embodiments, the tissue markers described herein can be used to mark a target tissue site, e.g., a biopsy site in various tissues including, but are not limited to, a breast, colon, rectal, liver, ovarian, prostate, and/or lung tissue. In some embodiments, the tissue markers described herein can be used as cell scaffolds. BACKGROUND Many cancers such as breast and prostate cancers are typically diagnosed using minimally invasive biopsies of the suspicious tissue with a tissue-coring needle. During the biopsy, or immediately thereafter, a tissue marker is placed in the tissue void space, for example, for future reference/biopsy or examination, for surgical removal of tissue surrounding the biopsy area after confirmatory diagnosis, for avoiding sampling the same area in future biopsies, and/or for use as a fiducial marker in treatment, e.g., radiation treatment planning Imaging of a tissue with or without tissue markers can be performed using conventional imaging modalities. Examples of conventional imaging modalities include ionizing radiation imaging (e.g., x-ray imaging, computed tomography (CT), or mammography), magnetic imaging (e.g., magnetic resonance imaging (MRI)), and ultrasound imaging. Conventional tissue markers typically consist of one of more solid objects, such as a piece of metallic wire, ceramic beads, etc., which are implanted either by themselves or within a gelatinous matrix to increase visibility to imaging such as ultrasound, MRI, or x-ray imaging. The conventional markers have been shown to have a few significant problems associated with their use. For example, titanium-based clips or tissue markers typically produce small MRI and ultrasound signals and may distort the surrounding tissue, depending on the scan/sequence used. Other clips or tissue markers may not be seen on all three main imaging techniques used (MRI, x-ray, ultrasound). Some clips or tissue markers are bio-resorbable (e.g., collage-based plugs) and thus lose ultrasound visibility after about 6 months. In addition, the surface and shape of these clips or tissue markers are generally smooth and narrow, respectively; therefore, the clips or tissue markers can be drawn back immediately into a biopsy needle when the needle is withdrawn from the tissue, or dense metal markers can migrate through the less dense tissue over time, resulting in poor image registration and inaccurate biopsy site location in subsequent examinations and imaging. Accordingly, there is a need to develop tissue markers that can provide precise lesion or biopsy location over an extended period of time, e.g., for targeted treatments or follow-up monitoring. Further, there is a need for tissue markers that can be readily visible on MRI, ultrasound, and/or mammography so that a lesion can be detected in a minimally-invasive manner. SUMMARY Existing tissue markers (e.g., biopsy markers) generally have issues with securing the tissue markers in place at a target site after implantation. For example, a typical rigid, smooth tissue marker in its single defined form (e.g., a cylinder) can migrate through a implantation needle track due to the negative pressure caused by the simultaneous withdrawal of the delivery needle (fast migration), and/or it can migrate slowly over time through the void space and needle track due to normal physiological movements (slow migration), thus resulting in poor image registration and inaccurate marker site location in subsequent examinations and imaging. To this end, the inventors have developed, in some embodiments, flexible polymeric tissue markers and methods of using the same to overcome the aforementioned challenges associated with the existing tissue markers and to mark a tissue without using an adhesive. In some embodiments, a tissue marker described herein can comprise a flexible polymeric film with at least the density and electrostatic pressure substantially the same as (i.e., similar to) the target tissue, thus preventing the tissue marker, without using an adhesive, from slow migration over time. Further, the flexible polymeric film can be adapted to be visible by at least one or more imaging modalities. Additionally, the flexible polymeric film can adopt different configurations or forms as its surrounding volume or degree of confinement varies. For example, a flexible polymeric film can ado