Obturator and introducer set for MRI-guided biopsy procedures

Abstract

An introducer set for a magnetic resonance imaging ("MRI")-guided biopsy procedure can include a cannula, an awl configured for insertion into the cannula, and an obturator also configured for insertion into the cannula. The cannula can include a depth-limiting collar around an elongate cannula body. The obturator can include an elongate obturator body having a distal end portion with an MRI-visible composition disposed therein. The MRI-visible composition can include a coordination complex of iron and oxalate. Configured as such, a distal end of the obturator body can indicate a middle of a biopsy sample upon insertion of the medical device into a tissue from which the biopsy sample is to be taken.

Description

OBTURATOR AND INTRODUCER SET FORMRI-GUIDED BIOPSY PROCEDURESPRIORITY

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 657,024, filed lune 6, 2024, which is incorporated by reference in its entirety into this application.BACKGROUND

[0002] While imaging in a magnetic resonance imaging (“MRI”)-guided biopsy procedure, an obturator is used to mark the location within a patient’ s body from which a biopsy sample is to be taken. Subsequent to taking the biopsy sample at the foregoing location, a cavity remains in the tissue. Upon placing a tissue marker into the tissue by way of the cavity, the obturator is again used while imaging to confirm placement of the tissue marker in the tissue from which the biopsy sample was taken.

[0003] The Encor Espire™ Breast Biopsy System utilizes an obturator including an aqueous solution of ferrous gluconate. Such an aqueous solution is suitable for clinical use, providing MRI visibility and differentiation of the obturator from surrounding tissues. However, the obturator has a shelf life of about 6 months due to oxidation of the ferrous gluconate in the aqueous solution, which leads to the formation of bubbles larger than about 5 pm as well as precipitation of particles in the obturator, both of which affect imaging under MRI. There is, therefore, a need to reduce such bubbles and precipitates in order to reduce MRI-image artifacts and increase the shelf life of the obturator.

[0004] Disclosed herein is an obturator and an introducer set including the obturator for MRI-guided biopsy procedures that address the foregoing need.SUMMARY

[0005] Disclosed herein is a medical device for an MRI-guided biopsy procedure. The medical device includes, in some embodiments, an elongate obturator body and a handle over a proximal end portion of the obturator body. The obturator body includes a distal end portion having an MRI-visible composition disposed therein. The MRI-visible composition includes a coordination complex of iron and oxalate. Configured as such, a distal end of the obturatorbody can indicate a middle of a biopsy sample upon insertion of the medical device into a tissue from which the biopsy sample is to be taken.

[0006] In some embodiments, the distal end of the medical device is also configured to confirm placement of a tissue marker in the tissue from which the biopsy sample is taken.

[0007] In some embodiments, the coordination complex is a water-soluble coordination complex dissolved in high-purity water or a buffer thereof, the MRI-visible composition thereby being an aqueous composition. When the buffer is used, the buffer includes at least citrate buffer, phosphate buffer, or bicarbonate buffer.

[0008] In some embodiments, the MRI-visible composition includes ferric oxalate, potassium ferric oxalate, ferric ammonium oxalate, or sodium ferric oxalate as the coordination complex.

[0009] In some embodiments, the MRI-visible composition includes one or more stabilizers configured to retard redox reactions of the iron of the coordination complex, precipitation of the iron of the coordination complex, or some combination thereof.

[0010] In some embodiments, the one or more stabilizers are selected from organic acids and their salts, optionally, with a capability of chelating the iron of the coordination complex, simple carbohydrates including monosaccharides and disaccharides, complex carbohydrates including polysaccharides, and hydrogels including those derived from at least plant cellulose, bacterial cellulose, derivatives of cellulose, polyvinylpyrrolidone, polyethylene oxide, polyacrylate, or polyacrylamide.

[0011] In some embodiments, the MRI-visible composition is optimized with respect to contrast-to-noise ratio (“CNR”) and shelf life. The CNR ratio is at least about 3-5 for a routine MRI image acquisition time, and the shelf life is at least about 12 months.

[0012] In some embodiments, the obturator body includes a tube and a rod. A proximal end portion of the tube fits over a distal end portion of the rod in a leak-free joint, and the tube includes a closed distal end. Thus, the tube seals the MRI-visible composition therein between the joint and the closed distal end.

[0013] In some embodiments, the handle is over a proximal end portion of the rod. A proximal end portion of the handle includes a handling knob, and a distal end portion of the handle includes a stop configured to abut a proximal end of a mouthpiece of a cannula.

[0014] In some embodiments, the medical device is an obturator.

[0015] Also disclosed herein is an introducer set for an MRI-guided biopsy procedure.The introducer set includes, in some embodiments, a cannula, an awl configured for insertion into the cannula, and an obturator also configured for insertion into the cannula. The cannula includes a depth-limiting collar around an elongate cannula body. The obturator includes an elongate obturator body having a distal end portion with an MRI-visible composition disposed therein. The MRI-visible composition includes a coordination complex of iron and oxalate. Configured as such, a distal end of the obturator body can indicate a middle of a biopsy sample upon insertion of the medical device into a tissue from which the biopsy sample is to be taken.

[0016] In some embodiments, the distal end of the medical device is also configured to confirm placement of a tissue marker in the tissue from which the biopsy sample is taken.

[0017] In some embodiments, the coordination complex is a water-soluble coordination complex dissolved in high-purity water or a buffer thereof, the MRI-visible composition thereby being an aqueous composition. When the buffer is used, the buffer includes at least citrate buffer, phosphate buffer, or bicarbonate buffer.

[0018] In some embodiments, the MRI-visible composition includes ferric oxalate, potassium ferric oxalate, ferric ammonium oxalate, or sodium ferric oxalate as the coordination complex.

[0019] In some embodiments, the MRI-visible composition includes one or more stabilizers configured to retard redox reactions of the iron of the coordination complex, precipitation of the iron of the coordination complex, or some combination thereof.

[0020] In some embodiments, the one or more stabilizers are selected from organic acids and their salts, optionally, with a capability of chelating the iron of the coordination complex, simple carbohydrates including monosaccharides and disaccharides, complex carbohydrates including polysaccharides, and hydrogels including those derived from at leastplant cellulose, bacterial cellulose, derivatives of cellulose, polyvinylpyrrolidone, polyethylene oxide, polyacrylate, or polyacrylamide.

[0021] In some embodiments, the MRI-visible composition is optimized with respect to CNR and shelflife. The CNR ratio is at least about 3-5 for a routine MRI image acquisition time, and the shelf life is at least about 12 months.

[0022] In some embodiments, the obturator body includes a tube and a rod. A proximal end portion of the tube fits over a distal end portion of the rod in a leak-free joint, and the tube includes a closed distal end. Thus, the tube seals the MRI-visible composition therein between the joint and the closed distal end.

[0023] In some embodiments, the handle is over a proximal end portion of the rod. A proximal end portion of the handle includes a handling knob, and a distal end portion of the handle includes a stop configured to abut a proximal end of a mouthpiece of the cannula.

[0024] In some embodiments, the introducer set further includes a needle-guide block configured to insert into a biopsy grid and guide the cannula into the tissue from which the biopsy sample is to be taken.

[0025] These and other features of the concepts provided herein will become more apparent to those of skill in the art in view of the accompanying drawings and following description, which describe particular embodiments of such concepts in greater detail.BRIEF DESCRIPTION OF DRAWINGS

[0026] FIG. 1 illustrates an obturator for MRI-guided biopsy procedures in accordance with some embodiments.

[0027] FIG. 2 illustrates a longitudinal cross section of the obturator in accordance with some embodiments.

[0028] FIG. 3 illustrates an introducer set including the obturator for MRI-guided biopsy procedures in accordance with some embodiments.

[0029] FIG. 4 illustrates a packaged introducer set in accordance with some embodiments.

[0030] FIG. 5 illustrates use of the obturator in MRI-guided biopsy procedures in accordance with some embodiments.DESCRIPTION

[0031] Before some particular embodiments are disclosed in greater detail, it should be understood that the particular embodiments disclosed herein do not limit the scope of the concepts provided herein. It should also be understood that a particular embodiment disclosed herein can have features that can be readily separated from the particular embodiment and optionally combined with or substituted for features of any of a number of other embodiments disclosed herein.

[0032] Regarding terms used herein, it should also be understood the terms are for the purpose of describing some particular embodiments, and the terms do not limit the scope of the concepts provided herein. Ordinal numbers (e.g., first, second, third, etc.) are generally used to distinguish or identify different features or steps in a group of features or steps, and do not supply a serial or numerical limitation. For example, “first,” “second,” and “third” features or steps need not necessarily appear in that order, and the particular embodiments including such features or steps need not necessarily be limited to the three features or steps. In addition, any of the foregoing features or steps can, in turn, further include one or more features or steps unless indicated otherwise. Labels such as “left,” “right,” “top,” “bottom,” “front,” “back,” and the like are used for convenience and are not intended to imply, for example, any particular fixed location, orientation, or direction. Instead, such labels are used to reflect, for example, relative location, orientation, or directions. Singular forms of “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise.

[0033] “Proximal” is used to indicate a portion, section, piece, element, or the like of a medical device intended to be near or relatively nearer to a clinician when the medical device is used on a patient. For example, a “proximal portion” or “proximal section” of the medical device includes a portion or section of the medical device intended to be near the clinician when the medical device is used on the patient. Likewise, a “proximal length” of the medical device includes a length of the medical device intended to be near the clinician when the medical device is used on the patient. A “proximal end” of the medical device is an end of the medical device intended to be near the clinician when the medical device is used on the patient. The proximal portion, the proximal section, or the proximal length of the medical device need not include the proximal end of the medical device. Indeed, the proximal portion, the proximalsection, or the proximal length of the medical device can be short of the proximal end of the medical device. However, the proximal portion, the proximal section, or the proximal length of the medical device can include the proximal end of the medical device. Should context not suggest the proximal portion, the proximal section, or the proximal length of the medical device includes the proximal end of the medical device, or if it is deemed expedient in the following description, “proximal portion,” “proximal section,” or “proximal length” can be modified to indicate such a portion, section, or length includes an end portion, an end section, or an end length of the medical device for a “proximal end portion,” a “proximal end section,” or a “proximal end length” of the medical device, respectively.

[0034] “Distal” is used to indicate a portion, section, piece, element, or the like of a medical device intended to be near, relatively nearer, or even in a patient when the medical device is used on the patient. For example, a “distal portion” or “distal section” of the medical device includes a portion or section of the medical device intended to be near, relatively nearer, or even in the patient when the medical device is used on the patient. Likewise, a “distal length” of the medical device includes a length of the medical device intended to be near, relatively nearer, or even in the patient when the medical device is used on the patient. A “distal end” of the medical device is an end of the medical device intended to be near, relatively nearer, or even in the patient when the medical device is used on the patient. The distal portion, the distal section, or the distal length of the medical device need not include the distal end of the medical device. Indeed, the distal portion, the distal section, or the distal length of the medical device can be short of the distal end of the medical device. However, the distal portion, the distal section, or the distal length of the medical device can include the distal end of the medical device. Should context not suggest the distal portion, the distal section, or the distal length of the medical device includes the distal end of the medical device, or if it is deemed expedient in the following description, “distal portion,” “distal section,” or “distal length” can be modified to indicate such a portion, section, or length includes an end portion, an end section, or an end length of the medical device for a “distal end portion,” a “distal end section,” or a “distal end length” of the medical device, respectively.

[0035] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art.

[0036] As set forth above, the Encor Espire™ Breast Biopsy System utilizes an obturator including an aqueous solution of ferrous gluconate. Such an aqueous solution issuitable for clinical use, providing MRI visibility and differentiation of the obturator from surrounding tissues. However, the obturator has a shelflife of about 6 months due to oxidation of the ferrous gluconate in the aqueous solution, which leads to the formation of bubbles larger than about 5 pm and precipitation of particles in the obturator, both of which affect imaging under MRI. There is, therefore, a need to reduce such bubbles and precipitates in order to reduce MRI-image artifacts and increase the shelf life of the obturator.

[0037] Disclosed herein is an obturator and an introducer set including the obturator for MRI-guided biopsy procedures that address the foregoing need. However, it should be understood that that the obturator is but one example of a medical device that can be configured as set forth below for MRI-guided biopsy procedures.Obturator

[0038] FIGS. 1 and 2 illustrate an obturator 100 for MRI-guided biopsy procedures in accordance with some embodiments.

[0039] As shown, the obturator 100 can include an elongate obturator body 102 and a handle 104 over a proximal end portion of the obturator body 102.

[0040] The obturator body 102 can include a tube 106 and a rod 108 with at least a distal end portion of the obturator body 102 having an MRI-visible composition 110 disposed therein. Indeed, a proximal end portion of the tube 106 can fit over a distal end portion of the rod 108 such as a reduced-diameter portion of the rod 108, thereby forming a leak-free joint 112. In addition, the tube 106 can include a closed distal end 114 such that the tube 106 seals the MRI-visible composition 110 therein between the joint 112 and the closed distal end 114.

[0041] The handle 104 can be over a proximal end portion of the rod 108. A proximal end portion of the handle 104 can include a handling knob 116, and a distal end portion of the handle 104 can include a stop 118 configured to abut a proximal end of the mouthpiece 132 of the cannula 122 set forth below.

[0042] Configured as such, a distal end of the obturator body 102 (or the closed distal end 114 of the tube 106) can indicate a portion of a biopsy sample (e.g., a middle of the biopsy sample) under MRI upon insertion of the obturator 100 through the cannula 122 and into a tissue from which the biopsy sample is to be taken. Notably, the distal end of the obturatorbody 102 can also be configured to subsequently confirm placement of a tissue marker in the tissue from which the biopsy sample is taken under MRI.MRI-visible composition

[0043] The MRI-visible composition 110 can include a coordination complex such as a water-soluble coordination complex dissolved in high-purity water or a buffer thereof, the MRI-visible composition 110 thereby being an aqueous composition. The coordination complex can include iron and oxalate. Indeed, the coordination complex can include, but is not limited to, ferric oxalate, potassium ferric oxalate, ferric ammonium oxalate, sodium ferric oxalate, or some combination thereof. Each of the foregoing coordination complexes are known to be water soluble while other ferric (or ferrous) oxalates are, at best, only slightly soluble in water. Further, as to ferric (Fe3+) or ferrous (Fe2+) ion, ferric ion is advantageously more chemically stable then ferrous ion.

[0044] The coordination complex can be dissolved in high-purity water such as any grade of water selected from Grades 1-3, as such water is defined by International Organization for Standardization. Alternatively, the coordination complex can be dissolved in a buffer of such high-purity water. When such a buffer is used, the buffer can include at least citrate buffer, phosphate buffer, or bicarbonate buffer.

[0045] Being that the formula weight of the coordination complex can vary in accordance with at least the foregoing species thereof, which species can further be anhydrous or hydrated before dissolution, a concentration of the coordination complex in the MRI-visible composition 110 can vary. Focusing instead on the concentration of Fe3+in the MRI-visible composition 110, the concentration of Fe3+can be at least 1.0 mg / mL, 2.0 mg / mL, 3.0 mg / mL, 4.0 mg / mL, 5.0 mg / mL, 6.0 mg / mL, 7.0 mg / mL, 8.0 mg / mL, 9.0 mg / mL, or 10.0 mg / mL inclusive of any intervening concentration defined by the so-called tenths place. For example, the concentration of Fe3+in the MRI-visible composition 110 can be at least 5.0 mg / mL, 5.1 mg / mL, 5.2 mg / mL, 5.3 mg / mL, 5.4 mg / mL, 5.5 mg / mL, 5.6 mg / mL, 5.7 mg / mL, 5.8 mg / mL, or 5.9 mg / mL. Alternatively, the concentration of Fe3+in the MRI-visible composition 110 can be no more than 10.0 mg / mL, 9.0 mg / mL, 8.0 mg / mL, 7.0 mg / mL, 6.0 mg / mL, 5.0 mg / mL, 4.0 mg / mL, 3.0 mg / mL, 2.0 mg / mL, or 1.0 mg / mL inclusive of any intervening concentration defined by the so-called tenths place. For example, the concentration of Fe3+in the MRI-visible composition 110 can be no more than 5.9 mg / mL, 5.8 mg / mL, 5.7 mg / mL, 5.6 mg / mL, 5.5 mg / mL, 5.4 mg / mL, 5.3 mg / mL, 5.2 mg / mL, 5.1 mg / mL, or 5.0 mg / mL. As such theconcentration of Fe3+in the MRI-visible composition 110 can be at least 1.0 mg / mL and no more than 10.0 mg / mL, including at least 2.0 mg / mL and no more than 8.0 mg / mL, such as at least 3.0 mg / mL and no more than 6.0 mg / mL, for example, at least 5.0 mg / mL and no more than 5.9 mg / mL. It should be appreciated that an optimum concentration of Fe3+in the MRI- visible composition 110 for both CNR and shelflife of the obturator 100 can vary in accordance with the species of the coordination complex in the MRI-visible composition 110, which species, at a minimum, can include different cations, the pH of the MRI-visible composition 110, the one-or-more stabilizers of the MRI-visible composition 110 set forth below, or some combination thereof.

[0046] As to pH of the MRI-visible composition 110, the pH can be at least pH 1.0, pH 2.0, pH 3.0, pH 4.0, pH 5.0, pH 6.0, pH 7.0, pH 8.0, pH 9.0, pH 10.0, pH 11.0, pH 12.0, pH 13.0, or pH 14.0 inclusive of any intervening pH defined by the so-called tenths place. For example, the pH of the MRI-visible composition 110 can be at least pH 4.0, pH 4.1, pH 4.2, pH 4.3, pH 4.4, pH 4.5, pH 4.6, pH 4.7, pH 4.8, pH 4.9, or pH 5.0, wherein for pH 4.3 or greater dianionic oxalate should predominate, the equilibrium constant (Kf) for loss of the first proton being 5.37 / 102(p / L = 1.27) and the Kafor loss of the second proton being 5.25 / 105(p A = 4.28). (See Riemenschneider, Wilhelm, and Minoru Tanifuji. “Oxalic acid.” Ullmann's encyclopedia of industrial chemistry

[2000] .) Alternatively, the pH of the MRI-visible composition 110 can be no more than pH 14.0, pH 13.0, pH 12.0, pH 11.0, pH 10.0, pH 9.0, pH 8.0, pH 7.0, pH 6.0, pH 5.0, pH 4.0, pH 3.0, pH 2.0, or pH 1.0 inclusive of any intervening pH defined by the so-called tenths place. For example, the pH of the MRI-visible composition 110 can be no more than pH 5.0, pH 4.9, pH 4.8, pH 4.7, pH 4.6, pH 4.5, pH 4.4, pH 4.3, pH 4.2, pH 4.1, or pH 4.0. As such the pH of the MRI-visible composition 110 can be at least pH 1.0 and no more than pH 14.0, including at least pH 2.0 and no more than pH 9.0, such as at least pH 3.0 and no more than pH 8.0, for example, at least pH 4.0 and no more than pH 7.0. It should be appreciated that an optimum pH of the MRI-visible composition 110 for both CNR and shelf life of the obturator 100 can vary in accordance with the species of the coordination complex in the MRI-visible composition 110, which species, as above, can include different cations, the one-or-more stabilizers of the MRI-visible composition 110 set forth below, or some combination thereof.

[0047] The MRI-visible composition 110 can also include one or more stabilizers configured to retard redox reactions of the iron of the coordination complex, precipitation ofthe iron of the coordination complex, or some combination thereof. For example, the one-or- more stabilizers can retard any oxalate-to-iron electron-transfer reactions, which otherwise lead to homolytic cleavage of Fe3+-0 coordination bonds and, thereby, species of ferrous ion (Fe2+), oxalate anion, and oxalate radical. Notwithstanding the one-or-more stabilizers, it can be beneficial to also degas the MRI-visible composition 110 to remove dissolved oxygen, which can otherwise participate in a redox cycle with at least the foregoing Fe2+to produce a precipitate of rust such as Fe20s, FeO(OH), Fe(OH)s, or some combination thereof.

[0048] As to the one-or-more stabilizers, they can be selected from organic acids and their salts, optionally, with a capability of chelating the iron of the coordination complex, such as citric acid, isocitric acid, and propane-1, 2, 3 -tricarboxylic acid; simple carbohydrates including monosaccharides such as glucose and disaccharides such as sucrose; complex carbohydrates including polysaccharides such as agar and chitosan; and hydrogels such as those derived from at least plant cellulose, bacterial cellulose, derivatives of cellulose, polyvinylpyrrolidone, chitosan, polyethylene oxide, polyacrylate, and polyacrylamide. Advantageously, a hydrogel selected from the foregoing hydrogels can prevent movement of any bubbles the might form in the MRI-visible composition 110, thereby minimizing any effect on imaging under MRI.

[0049] Notably, a hydrogel derived from a derivative of cellulose can include a hydrogel derived from methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, or the like. A hydrogel derived from chitosan can include a hydrogel resulting from physical crosslinking such as that effectuated by the so-called freeze-thaw technique. A hydrogel derived from polyvinylpyrrolidone can include a hydrogel resulting from chemical crosslinking such as that effectuated by the aldol reaction. That is, pyrrolidone units of such a hydrogel can be crosslinked by the aldol reaction. Alternatively, a hydrogel derived from polyvinylpyrrolidone can include a hydrogel resulting from physical crosslinking such as that effectuated by the freeze-thaw technique. Lastly, a hydrogel derived from polyethylene oxide can include a hydrogel resulting from chemical crosslinking such as that effectuated by peroxide-generated radicals. That is, polymer chains of such a hydrogel can be crosslinked by radicals generated by dicumyl peroxide.

[0050] Being that the formula weight of the foregoing stabilizers can vary in accordance with at least the foregoing species thereof, a concentration of any of the one-or- more stabilizers in the MRI-visible composition 110 can vary. However, to provide an exampleby way of glucose the concentration of glucose can be at least 1 mg / mL, 50 mg / mL, 100 mg / mL, 150 mg / mL, 200 mg / mL, 250 mg / mL, 300 mg / mL, 350 mg / mL, or 400 mg / mL inclusive of any intervening concentration defined by the so-called tens place, ones place, or some combination thereof. For example, the concentration of glucose in the MRI-visible composition 110 can be at least 100 mg / mL, 110 mg / mL, 120 mg / mL, 130 mg / mL, 140 mg / mL, or 150 mg / mL. Alternatively, the concentration of glucose in the MRI-visible composition 110 can be no more than 150 mg / mL, 140 mg / mL, 130 mg / mL, 120 mg / mL, 110 mg / mL, or 100 mg / mL inclusive of any intervening concentration defined by the so-called tens place, ones place, or some combination thereof. For example, the concentration of glucose in the MRI-visible composition 110 can be no more than 150 mg / mL, 140 mg / mL, 130 mg / mL, 120 mg / mL, 110 mg / mL, or 100 mg / mL. As such the concentration of glucose in the MRI- visible composition 110 can be at least 1.0 mg / mL and no more than 400 mg / mL, including at least 50 mg / mL and no more than 300 mg / mL, such as at least 50 mg / mL and no more than 200 mg / mL, for example, at least 100 mg / mL and no more than 200 mg / mL. It should be appreciated that an optimum concentration of glucose in the MRI-visible composition 110 for both CNR and shelf life of the obturator 100 can vary in accordance with the species of the coordination complex in the MRI-visible composition 110, which species, at a minimum, can include different cations, the pH of the MRI-visible composition 110, or some combination thereof.

[0051] Notwithstanding the given example being for concentrations of glucose as a stabilizer, it should be understood the foregoing concentrations can be extended to any stabilizer of the one-or-more stabilizers, particularly small-molecule stabilizers, thereby reducing burden on this disclosure.

[0052] The MRI-visible composition 110 can be optimized with respect to both CNR and shelf life of the obturator 100. While higher concentrations of the coordination complex can lead to higher CNRs for the obturator 100, such higher concentrations can also increase the number of redox reactions of the iron of the coordination complex as well as increase the amount of precipitation of the iron of the coordination complex, thereby decreasing the shelf life of the obturator 100. Thus, the CNR ratio of the obturator 100 can be at least about 3-5 for a routine MRI image acquisition time, and the shelf life of the obturator 100 can be at least about 12 months on account of the MRI-visible composition 110.

[0053] Particular embodiments of the MRI-visible composition 110 are set forth below as examples.Introducer set

[0054] FIGS. 3 and 4 illustrate an introducer set 120 including the obturator 100 for MRI-guided biopsy procedures in accordance with some embodiments. FIG. 5 illustrates use of a portion of the introducer set 120 in accordance with some embodiments.

[0055] As shown, the introducer set 120 can include a cannula 122, an awl 124 configured for insertion into the cannula 122, and the obturator 100 also configured for insertion into the cannula 122. Notably, when the awl 124 is disposed in the cannula 122 for penetrating tissue (e.g., breast tissue), such a combination of the awl 124 and the cannula 122 can be referred to herein as a trocar. Optionally, the introducer set 120 can further include a needle-guide block 126 configured to insert into a biopsy grid 128 and guide the cannula 122, the awl 124, the obturator 100, or some combination thereof into the tissue from which the biopsy sample is to be taken.

[0056] The cannula 122 can include an elongate cannula body 130, an integral mouthpiece 132 about a proximal end portion of the cannula body 130, and a terminal distal end of the cannula body 130. The cannula 122 can also include a slidable depth-limiting collar 134 around the cannula body 130. Such a depth-limiting collar 134 limits a depth to which at least a distal end of the cannula 122 (or the distal end of the cannula body 130) is disposed in tissue (e.g., breast tissue) when the needle-guide block 126 is inserted into the biopsy grid 128 and the cannula 122 is, in turn, inserted into the needle-guide block 126.

[0057] The awl 124 can include an elongate awl body 135, an elongate handle 136 about a proximal end portion of the awl body 135, and a tissue-penetrating distal tip 138 of the awl body 135. Such a tissue-penetrating distal tip 138 can be pyramidal with 3 or 4 cutting lateral edges for penetrating tissue (e.g., breast tissue) when the needle-guide block 126 is inserted into the biopsy grid 128 and the trocar including the awl 124 disposed in the cannula 122 is, in turn, inserted into the needle-guide block 126.

[0058] The obturator 100 of the introducer set 120 is that set forth above.

[0059] The needle-guide block 126 includes a patient-facing end portion configured to insert into the biopsy grid 128, a clinician-facing end portion configured to remain external ofthe biopsy grid 128, and a lever lock 140 configured to secure the needle-guide block 126 in the biopsy grid 128. The needle-guide block 126 also includes a plurality of through holes 142 configured to guide the cannula 122, the awl 124, the obturator 100, or some combination thereof into tissue (e.g., breast tissue) from which a biopsy sample is to be taken or has been taken. Notably, the four through holes 142 shown in FIG. 5 are arranged such that rotation of the square-shaped needle-guide block 126 through each 90° rotation available to the needleguide block 126 in the biopsy grid 128 effectively provides an array of 13 through holes 142, thereby providing fine control compared to the coarse control provided by the biopsy grid 128 for penetrating the tissue with the trocar.

[0060] As shown, the introducer set 120 can be packaged as a packaged introducer set 144, wherein packaging of the packaged introducer set 144 includes a tray 146 and a cover 148 thereover. However, it should be understood the packaged introducer set 144 shown in FIG. 4 is oriented bottom-side up for illustration, the cover 148 over the tray 146 appearing under the tray 146. Such a tray 146 can be a molded plastic tray including a compartment for each component of the introducer set 120, wherein each compartment has opposing finger scoops for withdrawing a corresponding component from the compartment upon removal of the cover 148. Notably, the introducer set 120 can be sterilized in the packaged introducer set 144 by a sterilization method such as ethylene oxide (“ETO”) sterilization; however, a chosen sterilization method should not degrade any component of the introducer set 120, particularly the MRI- visible composition 110 of the obturator 100.Methods

[0061] Methods of the obturator 100 or the introducer set 120 including the obturator 100 include those for making or using the obturator 100 or the introducer set 120, which can be gleaned from description set forth above. For example, methods can include a method of making the obturator 100 and a method of using the obturator 100.

[0062] The method of making the obturator 100 can include a molding operation of molding each component of the obturator body 102 and the handle 104, which obturator body 102 includes, as set forth above, the tube 106 and the rod 108. The method of making the obturator 100 can also include a composition-preparing operation of preparing the MRI- visible composition 110, which includes at least dissolving the coordination complex in water or a buffer thereof along with any of the one-or-more stabilizers. The method of making the obturator 100 can also include a tube-filling operation of filing the tube 106 with the MRI-visible composition 110. Lastly, the method of making the obturator 100 can also include an assembly operation of assembling the obturator 100. The assembly operation can include inserting the proximal end portion of the rod 108 into the handle 104, inserting the reduced- diameter portion of the rod 108 in the tube 106 to complete the obturator body 102, and, thus, completing the obturator 100.

[0063] FIG. 5 illustrates use of the obturator 100 in MRI-guided biopsy procedures in accordance with some embodiments.

[0064] As shown, the method of using the obturator 100 can include inserting the obturator 100 into the cannula 122. Provided the needle-guide block 126 is inserted into the biopsy grid 128 and the cannula 122 is, in turn, inserted into both the needle-guide block 126 and a trocar-created tract through tissue such as breast tissue of breast B, inserting the obturator 100 into the cannula 122 can indicate the tissue from which a biopsy sample is to be taken. Notably, such tissue is indicated as lesion L in FIG. 5. Provided the needle-guide block 126 remains inserted in the biopsy grid 128 and the cannula 122 remains, in turn, inserted in both the needle-guide block 126 and the foregoing trocar-created tract, inserting the obturator 100 into the cannula 122 can confirm placement of a tissue marker in the tissue from which the biopsy sample is taken under MRI.Advantages

[0065] Advantageously, the obturator 100 set forth herein with the MRLvisible composition 110 reduces bubbles and precipitates that are seen in existing obturators that include aqueous ferrous gluconate, thereby improving obturator shelf life. Notably, the safety profile of the obturator 100 improves upon that of existing obturators as well. Taking a coordination compound of the MRI-visible composition 110 such as ferric oxalate hexahydrate, the LD50 of ferric oxalate hexahydrate is a higher 500.01 mg / kg while the LD50 of ferrous gluconate is a lower 2.237 mg / kg, the acute toxicity of the ferrous gluconate in existing obturators thereby being almost 223 times greater than that of the obturator 100 set forth herein.Examples

[0066] Example 1: Ferric oxalate hexahydrate was dissolved in deionized water at about 50 °C to a concentration of 24 mg / mL for an Fe3+concentration of 5.54 mg / mL. The resulting MRI-visible composition 110 was subsequently dispensed in the obturator 100 as set forth herein.

[0067] Example 2: Ferric oxalate hexahydrate was dissolved in citrate buffer (pH 3.5- 4.0) at about 50 °C to a concentration of 12 mg / mL for an Fe3+concentration of 2.76 mg / mL. Like that set forth in Example 1, the resulting MRI- visible composition 110 was subsequently dispensed in the obturator 100 as set forth herein.

[0068] Example 3: Ferric oxalate hexahydrate was dissolved in deionized water at about 50 °C to a concentration of 24 mg / mL for an Fe3+concentration of 5.54 mg / mL in accordance with Example 1. In addition, glucose was added to a concentration of 50-200 mg / mL, thereby resulting in the MRI- visible composition 110. Like that set forth in Example 1, the resulting MRI-visible composition 110 is subsequently dispensed in the obturator 100 as set forth herein. Glucose was notably added to retard redox reactions of the iron, precipitation of the iron, or some combination thereof as set forth above.

[0069] Example 4: Ferric oxalate hexahydrate was dissolved in citrate buffer (pH 3.5- 4.0) at about 50 °C to a concentration of 12 mg / mL for an Fe3+concentration of 2.76 mg / mL in accordance with Example 2. In addition, glucose was added to a concentration of 50-200 mg / mL, thereby resulting in the MRI-visible composition 110. Like that set forth in Example 1, the resulting MRI-visible composition 110 was subsequently dispensed in the obturator 100 as set forth herein. Glucose and citrate buffer were notably added to retard redox reactions of the iron, precipitation of the iron, or some combination thereof as set forth above.

[0070] Example 5: Ferric oxalate hexahydrate was dissolved in an aqueous solution including a hydrogel to a concentration given in Example 1 or 2. Like that set forth in Example 1, the resulting MRI-visible composition 110 was subsequently dispensed in the obturator 100 as set forth herein. Notably, the hydrogel does not interfere with imaging under MRI, and the hydrogel can prevent movement of any bubbles that might form in the MRI-visible composition 110, thereby minimizing any effect on imaging under MRI. Further, the hydrogel can minimize any inadvertent leakage of the MRI-visible composition 110 through the leak-free joint 112 in the obturator body 102.

[0071] Example 6: The obturator 100 of each example of Examples 1-5 was characterized for both total iron concentration and MRI visibility. Further, the obturator 100 of each example of Examples 1-5 was observed for any bubbles or precipitates at various timepoints.

[0072] While some particular embodiments have been disclosed herein, and while the particular embodiments have been disclosed in some detail, it is not the intention for the particular embodiments to limit the scope of the concepts provided herein. Additional adaptations or modifications can appear to those of ordinary skill in the art, and, in broader aspects, these adaptations or modifications are encompassed as well. Accordingly, departures may be made from the particular embodiments disclosed herein without departing from the scope of the concepts provided herein.

Claims

CLAIMSWhat is claimed is:

1. A medical device for a magnetic resonance imaging (“MRI”)-guided biopsy procedure, comprising: an elongate obturator body including a distal end portion having an MRI-visible composition disposed therein, the MRI-visible composition including a coordination complex of iron and oxalate; a handle over a proximal end portion of the obturator body, wherein a distal end of the obturator body is configured to indicate a middle of a biopsy sample upon insertion of the medical device into a tissue from which the biopsy sample is to be taken.

2. The medical device of claim 1, wherein the distal end of the medical device is also configured to confirm placement of a tissue marker in the tissue from which the biopsy sample is taken.

3. The medical device of either claim 1 or 2, wherein the coordination complex is a water-soluble coordination complex dissolved in high-purity water or a buffer thereof including at least citrate buffer, phosphate buffer, or bicarbonate buffer, the MRI-visible composition thereby being an aqueous composition.

4. The medical device of any of the preceding claims, wherein the MRI-visible composition includes ferric oxalate, potassium ferric oxalate, ferric ammonium oxalate, or sodium ferric oxalate as the coordination complex.

5. The medical device of any of the preceding claims, wherein the MRI-visible composition includes one or more stabilizers configured to retard redox reactions of the iron of the coordination complex, precipitation of the iron of the coordination complex, or some combination thereof.

6. The medical device of any of the preceding claims, wherein the one or more stabilizers are selected from organic acids and their salts, optionally, with a capability of chelating the iron of the coordination complex, simple carbohydrates including monosaccharides and disaccharides, complex carbohydrates including polysaccharides, andhydrogels including those derived from at least plant cellulose, bacterial cellulose, derivatives of cellulose, polyvinylpyrrolidone, polyethylene oxide, polyacrylate, or polyacrylamide.

7. The medical device of any of the preceding claims, wherein the MRI-visible composition is optimized with respect to contrast-to-noise ratio (“CNR”) and shelf life, the CNR ratio being at least about 3-5 for a routine MRI image acquisition time, and the shelf life being at least about 12 months.

8. The medical device of any of the preceding claims, wherein the obturator body includes a tube and a rod, a proximal end portion of the tube fits over a distal end portion of the rod in a leak-free joint, and the tube includes a closed distal end, the tube thereby sealing the MRI-visible composition therein between the joint and the closed distal end.

9. The medical device of claim 8, wherein the handle is over a proximal end portion of the rod, a proximal end portion of the handle includes a handling knob, and a distal end portion of the handle includes a stop configured to abut a proximal end of a mouthpiece of a cannula.

10. The medical device of any of the preceding claims, wherein the medical device is an obturator.

11. An introducer set for a magnetic resonance imaging (“MRI”)-guided biopsy procedure, comprising: a cannula including a depth-limiting collar around an elongate cannula body; an awl configured for insertion into the cannula; and an obturator configured for insertion into the cannula, the obturator including: an elongate obturator body including a distal end portion having an MRI- visible composition disposed therein, the MRI-visible composition including a coordination complex of iron and oxalate; a handle over a proximal end portion of the obturator body, wherein a distal end of the obturator body is configured to indicate a middle of a biopsy sample upon insertion of the medical device into a tissue from which the biopsy sample is to be taken.

12. The introducer set of claim 11, wherein the distal end of the medical device is also configured to confirm placement of a tissue marker in the tissue from which the biopsy sample is taken.

13. The introducer set of either claim 11 or 12, wherein the coordination complex is a water-soluble coordination complex dissolved in high-purity water or a buffer thereof including at least citrate buffer, phosphate buffer, or bicarbonate buffer, the MRI-visible composition thereby being an aqueous composition.

14. The introducer set of any of claims 11-13, wherein the MRI-visible composition includes ferric oxalate, potassium ferric oxalate, ferric ammonium oxalate, or sodium ferric oxalate as the coordination complex.

15. The introducer set of any of claims 11-14, wherein the MRI-visible composition includes one or more stabilizers configured to retard redox reactions of the iron of the coordination complex, precipitation of the iron of the coordination complex, or some combination thereof.

16. The introducer set of any of claims 11-15, wherein the one or more stabilizers are selected from organic acids and their salts, optionally, with a capability of chelating the iron of the coordination complex, simple carbohydrates including monosaccharides and disaccharides, complex carbohydrates including polysaccharides, and hydrogels including those derived from at least plant cellulose, bacterial cellulose, derivatives of cellulose, polyvinylpyrrolidone, polyethylene oxide, polyacrylate, or polyacrylamide.

17. The introducer set of any of claims 11-16, wherein the MRI-visible composition is optimized with respect to contrast-to-noise ratio (“CNR”) and shelflife, the CNR ratio being at least about 3-5 for a routine MRI image acquisition time, and the shelf life being at least about 12 months.

18. The introducer set of any of claims 11-17, wherein the obturator body includes a tube and a rod, a proximal end portion of the tube fits over a distal end portion of the rod in a leak-free joint, and the tube includes a closed distal end, the tube thereby sealing the MRI- visible composition therein between the joint and the closed distal end.

19. The introducer set of claim 18, wherein the handle is over a proximal end portion of the rod, a proximal end portion of the handle includes a handling knob, and a distal end portion of the handle includes a stop configured to abut a proximal end of a mouthpiece of the cannula.

20. The introducer set of any of claims 11-19, further comprising a needle-guide block configured to insert into a biopsy grid and guide the cannula into the tissue from which the biopsy sample is to be taken.

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