Polymeric microsphere for use as a scout before radioembolization procedure

Abstract

Compositions, delivery assemblies, and methods for use or of medical imaging of a composition of a plurality of particles and fluid within a subject include delivering the composition of the plurality of particles and fluid into a target area of a body of the subject, the plurality of particles comprising a plurality of non-radioactive polymeric microspheres comprising a biocompatible material; imaging the plurality of particles of the composition disposed within the body of the subject using a medical imaging source disposed external to the body of the subject; and estimating a lung shunt activity, tumor to normal (T:N) ratio, or both based off the imaging of the plurality of particles of the composition at the target area using the medical imaging source.

Description

POLYMERIC MICROSPHERE FOR USE AS A SCOUT BEFORE RADIOEMBOLIZATION PROCEDURETECHNICAL FIELD

[0001] The present disclosure generally relates to components of medical devices for treating cancer, and more particularly to a scouting system, delivery assembly, composition, and the methods of use and medical imaging for planning a delivery of radioactive compounds for the treatment of a designated area within a patient’s body in procedures such as transarterial radioembolization.BACKGROUND

[0002] In cancer treatments involving radiation therapy, inadvertent or excess exposure to radiation from radioactive therapeutic agents can be harmful and potentially lethal to patients or medical personnel. Accordingly, medical instruments for radiation therapies must be configured to localize the delivery of radioactive material to a particular area of the patient’s body while shielding others from unnecessarily being exposed to radiation.

[0003] Transarterial Radioembolization is a transcatheter intra-arterial procedure performed by interventional radiology and is commonly employed for the treatment of malignant tumors. During this medical procedure, a microcatheter is navigated into a patient’s liver where radioembolizing microspheres loaded with a radioactive compound, such as yttrium-90 (90Y), are delivered to the targeted tumors. The microspheres embolize blood vessels that supply the tumors while also delivering radiation to kill tumor cells.

[0004] Accordingly, a need exists for components of a medical device configured and operable to monitor radiation and optimize flow when delivering the radioactive compound to the patient’s body.SUMMARY

[0005] In accordance with an embodiment of the disclosure, a composition of a plurality of particles and fluid for use in a method of medical imaging of the composition of the plurality of particles and fluid within a subject are described herein. The method comprises: delivering the composition of the plurality of particles and fluid into a target area of a body of the subject, theplurality of particles comprising a plurality of non-radioactive polymeric microspheres comprising a biocompatible material; imaging the plurality of particles of the composition disposed within the body of the subject using a medical imaging source disposed external to the body of the subject; and estimating a lung shunt activity, tumor to normal (T:N) ratio, or both based off the imaging of the plurality of particles of the composition at the target area using the medical imaging source.

[0006] In another embodiment, a delivery assembly comprises: a console including a vial containment region; a vial engagement mechanism extending from the console within the vial containment region, and a medical imaging source. The vial assembly includes a vial body and a plunger. The vial body contains a plurality of particles comprising a plurality of non-radioactive polymeric microspheres comprising a biocompatible material. The plunger comprising a proximal end and a distal end, the proximal end disposed outside of the vial body, the distal end disposed within the vial body. The vial engagement mechanism is configured to engage the proximal end of the plunger, move the plunger in a proximal direction to pull a fluid into the vial body of the vial assembly to mix with the plurality of particles to form a composition of a plurality of particles and fluid, and move the plunger in a distal direction to push the composition of the plurality of particles and fluid out of the vial body of the vial assembly and through a catheter into a target site of a body of a subject. The medical imaging source is configured to image the composition of the plurality of particles and fluid at the target site to estimate a lung shunt activity, tumor to normal (T:N) ratio, or both.

[0007] In yet another embodiment, a method of use of a delivery assembly comprises: engaging a vial engagement mechanism extending from a vial containment region of a console with a proximal end of a plunger of a vial assembly. The vial assembly further comprises a vial body containing a plurality of particles comprising a plurality of non-radioactive polymeric microspheres comprising a biocompatible material, the proximal end of the plunger disposed outside the vial body, and a distal end of the plunger disposed within the vial body. The method further comprises: moving the plunger in a proximal direction to pull a fluid into the vial body of the vial assembly to mix with the plurality of particles to form a composition of a plurality of particles and fluid; moving the plunger in a distal direction to push the composition of the plurality of particles and fluid out of the vial body of the vial assembly and through a catheter into a target site of a body of a subject; imaging the plurality of particles of the composition at the target sitevia a medical imaging source; and estimating a lung shunt activity, tumor to normal (T :N) ratio, or both based on the imaging via the medical imaging source.

[0008] These and additional features provided by the embodiments described herein will be more fully understood in view of the following detailed description, in conjunction with the drawings.BRIEF DESCRIPTION OF THE DRAWINGS

[0009] FIG. l is a perspective view of a delivery device including a protective shield and a vial sled according to one or more embodiments shown and described herein;

[0010] FIG. 2 is a cross-sectional view of the vial sled of FIG. 1 according to one or more embodiments shown and described herein, the cross-section along line 2-2 of FIG. 1;

[0011] FIG. 3 is a perspective view of a vial assembly including an engagement head according to one or more embodiments shown and described herein;

[0012] FIG. 4 is a perspective view of the vial sled of FIG. 1 with the vial assembly of FIG. 3 received therein, with a series of delivery lines coupled to the vial sled, according to one or more embodiments shown and described herein;

[0013] FIG. 5 is a partial perspective view of the delivery device of FIG. 1 illustrating an onboard sensor, according to one or more embodiments shown and described herein;

[0014] FIG. 6 is a schematic view of an embodiment of a biocompatible material embedded polymeric microsphere with a single biocompatible material nanoparticle, according to one or more embodiments shown and described herein;

[0015] FIG. 7 is a schematic view of a biocompatible material encased polymeric microsphere, according to one or more embodiments shown and described herein;

[0016] FIG. 8 is a schematic view of a biocompatible material embedded polymeric microsphere including a plurality of biocompatible material nanoparticles, according to one or more embodiments shown and as described herein;

[0017] FIG. 9 is a schematic view of a biocompatible material embedded and encased polymeric microsphere, according to one or more embodiments shown and described herein;

[0018] FIG. 10 schematically illustrates a medical imaging environment, according to one or more embodiments shown and described herein;

[0019] FIG. 11 is a flowchart of a process for medical imaging of a component of a plurality of particles and fluid within a subject using any of the particles of FIGS. 6-9 or combinationsthereof with the medical imaging environment of FIG. 10, according to one or more embodiments shown and described herein; and

[0020] FIG. 12 is a flowchart of a process for use of a delivery device of FIGS. 1-5 with the process for medical imaging of FIG. 11, according to one or more embodiments shown and described herein.DETAILED DESCRIPTION

[0021] Reference will now be made in detail to various embodiments of delivery devices for administering radioactive compounds to a patient, examples of which are illustrated in the accompanying drawings. Whenever possible, the same reference numerals will be used throughout the drawings to refer to the same or like parts. Directional terms as used herein — for example up, down, right, left, front, back, top, bottom, distal, and proximal — are made only with reference to the figures as drawn and are not intended to imply absolute orientation.

[0022] Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint.

[0023] Unless otherwise expressly stated, it is in no way intended that any method set forth herein be construed as requiring that its steps be performed in a specific order, nor that with any apparatus specific orientations be required. Accordingly, where a method claim does not actually recite an order to be followed by its steps, or that any apparatus claim does not actually recite an order or orientation to individual components, or it is not otherwise specifically stated in the claims or description that the steps are to be limited to a specific order, or that a specific order or orientation to components of an apparatus is not recited, it is in no way intended that an order or orientation be inferred, in any respect. This holds for any possible non-express basis for interpretation, including: matters of logic with respect to arrangement of steps, operational flow, order of components, or orientation of components; plain meaning derived from grammatical organization or punctuation, and; the number or type of embodiments described in the specification.

[0024] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosure belongs. The terminology used in the description herein is for describing particular embodiments only and is not intended to be limiting. As used in the specification and appended claims, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise.

[0025] As used herein, the terms “horizontal,” “vertical,” “distal” and “proximal” are relative terms only, are indicative of a general relative orientation only, and do not necessarily indicate perpendicularity. These terms also may be used for convenience to refer to orientations used in the figures, which orientations are used as a matter of convention only and are not intended as characteristic of the devices shown. The present disclosure and the embodiments thereof to be described herein may be used in any desired orientation. Moreover, horizontal and vertical walls need generally only be intersecting walls, and need not be perpendicular. As used herein, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a” component includes aspects having two or more such components, unless the context clearly indicates otherwise.

[0026] In embodiments described herein, a particulate material delivery assembly may include a radioembolization delivery device. A radioembolization delivery device comprises a medical device configured to deliver radioactive compounds to a treatment area within a patient’s body in procedures such as transarterial radioembolization. The radioactive compounds may be a mixed solution of saline and radioactive microspheres (i.e., a mixed particulate) mixed in a vial of a vial assembly. The needle may include one or more ports as an outlet to inject fluid (i.e., saline), such as from a syringe or catheter line, into a vial including the radioactive microspheres to generate the mixed solution and as an inlet to deliver the mixed solution to the patient.I. Mechanical Delivery Device with Removable Sled Assembly

[0027] FIGS. 1-5 show an embodiment of a delivery device 500 that is configured and operable to deliver a radioactive material (e.g., radioembolizing beads via a mixed particulate, such as of beads in a saline solution) while reducing radioactive emissions during use of the delivery device 500. The delivery device 500 may operate as described in International PCT App. No. PCT / 2019 / 033001, filed May 17, 2019, the entirety of which is incorporated herein, except withrespect to components as described in greater detail below with respect to FIGS. 6-12 and in one or more embodiments herein.

[0028] Referring initially to FIG. 1, the delivery device 500 comprises a console assembly 510, which includes a console. The delivery device 500 may include a sled assembly 540 that is operable to transition between a coupled state and decoupled state relative to the console assembly 510. The console assembly 510 of the delivery device 500 comprises a base 512 defined by and extending between a proximal end 514 and a distal end 516. The proximal end 514 of the base 512 includes a handle (delivery handle) 528 movably coupled to the console assembly 510 and an interface display 530 positioned on the console assembly 510.

[0029] The proximal end 514 of the base 512 further includes an attachment device 538 that is configured to securely retain an external device to the base 512 of the console assembly 510. The attachment device 538 is operable to facilitate an attachment of a complimentary device to the console assembly 510 for use with the delivery device 500 during a procedure.

[0030] Still referring to FIG. 1, the distal end 516 of the console assembly 510 defines a vial containment region 518 that is sized and shaped to receive a vial assembly 580 therein, as will be described in greater detail herein. The console assembly 510 further includes a vial engagement mechanism 520 extending from the base 512 adjacent to the distal end 516. In particular, the vial engagement mechanism 520 extends laterally outward from the base 512 of the console assembly 510 toward the distal end 516. The vial engagement mechanism 520 is positioned within the vial containment region 518 of the console assembly 510 and is movably coupled to the handle 528. In particular, the handle 528 of the console assembly 510 is operable to move, and in particular translate, the vial engagement mechanism 520 within the vial containment region 518 in response to an actuation of the handle 528.

[0031] The console assembly 510 includes a mechanical assembly disposed within the base 512 that is configured and operable to convert a manual motion of the handle 528 to a corresponding linear displacement of the vial engagement mechanism 520. In the present example, the mechanical assembly is coupled to the handle 528 and the vial engagement mechanism 520 such that selective actuation of the handle 528 at the proximal end 514 causes a simultaneous actuation of the vial engagement mechanism 520 at the distal end 516.

[0032] The sled cavity 532 is sized and shaped to receive the sled assembly 540 therein. As will be described in greater detail herein, the sled assembly 540 is configured to store and administer therapeutic particles (e.g., radioactive beads, microspheres, medium) therethrough. Inparticular, the sled assembly 540 is configured to partially receive a vial assembly 580 therein for administering the therapeutic particles from the delivery device 500 and to a patient during a procedure.

[0033] In embodiments, and referring to FIG. 2, a flow sensor of the delivery device 500 may be positioned in-line with the tubing set of the delivery device 500, and in particular the needle 559, the manifolds 555A, 555B, and / or one or more of the ports 556, and may be configured to measure an amount of fluid (e.g., suspension liquid after the therapeutic particles have effectively mixed with the fluid medium) that passes thereby. Referring back to FIG. 1, the vial engagement mechanism 520 comprises a pair of lever arms 522 extending outwardly from a neck 524 of the vial engagement mechanism 520, with the neck 524 extending laterally outward from the base 512 of the console assembly 510. The neck 524 of the vial engagement mechanism 520 is disposed within a protective cover 525 such that only the pair of lever arms 522 of the vial engagement mechanism 520 extends through the protective cover 525. The protective cover 525 is operable to shield one or more internal components of the console assembly 510 from an exterior of the console assembly 510, and in particular from the vial containment region 518.

[0034] The pair of lever arms 522 is simultaneously movable with the neck 524 of the vial engagement mechanism 520 in response to an actuation of the handle 528 of the console assembly 510. Further, the pair of lever arms 522 are fixed relative to one another such that a spacing formed between the pair of lever arms 522 is relatively fixed. The pair of lever arms 522 of the vial engagement mechanism 520 is configured to securely engage the vial assembly 580 therebetween, and in particular within the spacing formed by the pair of lever arms 522. Accordingly, the vial engagement mechanism 520 is operable to securely attach the vial assembly 580 to the console assembly 510 at the vial containment region 518. Although the vial engagement mechanism 520 is shown and described herein as including a pair of lever arms 522, it should be understood that the vial engagement mechanism 520 may include various other structural configurations suitable for engaging the vial assembly 580. In a non-limiting example, the vial engagement mechanism 520 may include one or more magnets configured to engage with one or more corresponding magnets on the vial assembly.

[0035] Still referring to FIG. 1, the console assembly 510 further may include a safety shield 526 secured to the distal end 516 of the base 512 along the vial containment region 518. In particular, the safety shield 526 is a protective covering that is sized and shaped to enclose the vial containment region 518 of the console assembly 510 when secured thereon. The safety shield 526is selectively attachable to the distal end 516 of the base 512 and is formed of a material that is configured to inhibit radioactive emissions from one or more radioactive doses stored within the vial containment region 518.

[0036] The distal end 516 of the console assembly 510 further includes a sled cavity 532 that is sized and shaped to receive the sled assembly 540 therein. The sled cavity 532 includes one or more or a pair of alignment features 534 extending therein, with the alignment features 534 sized and shaped to correspond with complimentary alignment features of the sled assembly 540 (e.g., alignment ribs 554) to thereby facilitate a coupling of the sled assembly 540 with the base 512 of the console assembly 510 within the sled cavity 532.

[0037] Still referring to FIG. 1, the sled assembly 540 is configured to partially receive a vial assembly 580 therein for administering therapeutic particles (e.g., radioactive fluid medium) from the delivery device 500 and to a patient. In particular, the sled assembly 540 comprises a distal end 542 and a proximal end 544 with a pair of sidewalls 546 extending therebetween. The distal end 542 of the sled assembly 540 includes a handle 552 extending proximally therefrom. The handle 552 is configured to facilitate movement of the sled assembly 540, and in particular, an insertion of the sled assembly 540 into the sled cavity 532 of the console assembly 510. The distal end 542 further includes one or more ports 556 for coupling one or more delivery lines (i.e., tubing) to the sled assembly 540. With the one or more delivery lines further be coupled to one or more external devices at an end of the line opposite of the ports 556, the ports 556 effectively serve to fluidly couple the sled assembly 540 to the one or more external devices via the delivery lines connected thereto. The pair of sidewalls 546 of the sled assembly 540 includes at least one alignment rib 554 extending laterally outward therefrom, where the alignment ribs 554 are sized and shaped to correspond with and mate to the pair of alignment features 534 of the console assembly 510. Accordingly, the pair of alignment ribs 554 are configured to facilitate an alignment and engagement of the sled assembly 540 with the console assembly 510 when the proximal end 544 is slidably received within the sled cavity 532 of the base 512.

[0038] The sled assembly 540 further includes a top surface 548 extending from the distal end 542 and the proximal end 544 and positioned between the pair of sidewalls 546. The top surface 548 of the sled assembly includes a recessed region 549 and a locking system 550. The recessed region 549 is sized and shaped to form a recess and / or cavity along the top surface 548, where the recessed region 549 is capable of receiving and / or collecting various materials therein, including, for example, leaks of various fluid media during use of the delivery device 500. The lockingsystem 550 of the sled assembly 540 forms an opening along the top surface 548 that is sized and shaped to receive one or more devices therein, such as a priming assembly 560 and a vial assembly 580. In some embodiments, the sled assembly 540 comes preloaded with the priming assembly 560 disposed within the locking system 550. The priming assembly 560 includes a priming line 562 extending outwardly from the locking system 550 of the sled assembly 540. The priming assembly 560 connects the priming line 562 to needle 559 and manifolds 555A and 555B and serves to purge the delivery device 500, including the manifolds 555A and 555B, of air prior to utilizing the delivery device 500 in a procedure.

[0039] Referring now to FIG. 2, the locking system 550 includes an annular array of projections 551 extending outwardly therefrom, and in particular, extending laterally into the aperture formed by the locking system 550 along the top surface 548. The annular array of projections 551 are formed within an inner perimeter of the locking system 550 and extend along at least two sequentially-arranged rows. In embodiments, a single row may be used. The annular array of projections 551 included in the locking system 550 are configured to engage a corresponding locking feature 586 of the vial assembly 580 (See FIG. 3) to thereby securely fasten the vial assembly 580 to the sled assembly 540. It should be understood that the multiple rows of projections 551 of the locking system 550 serve to provide a double-locking system to ensure the sled assembly 540, and in particular a needle 559 of the sled assembly 540, is securely maintained through a septum 592 of the vial assembly 580 See FIG. 3) during use of the delivery device 500 in a procedure.

[0040] The sled assembly 540 further includes a vial chamber 558 that is sized and shaped to receive the priming assembly 560 and the vial assembly 580 therein, respectively. In other words, the vial chamber 558 is sized to individually receive both the priming assembly 560 and the vial assembly 580 separate from one another. The vial chamber 558 is encapsulated around a protective chamber or shield 557 disposed about the vial chamber 558. The protective shield 557 is formed of a material configured to inhibit radioactive emissions from extending outwardly from the vial chamber 558, such as, for example, a metal or plastic. Additionally, the sled assembly 540 includes a needle extending through the protective shield 557 and into the vial chamber 558 along a bottom end of the vial chamber 558. The needle 559 is fixedly secured relative to the vial chamber 558 such that any devices received through the aperture of the locking system 550 and into the vial chamber 558 are to encounter and interact with the needle 559 (e.g., the priming assembly 560, the vial assembly 580, and the like).

[0041] Still referring to FIG. 2, the needle 559 is coupled to a distal manifold 555A and a proximal manifold 555B disposed within the sled assembly 540, and in particular the manifold 555A, 555B is positioned beneath the vial chamber 558 and the protective shield 557. The proximal manifold 555B is fluidly coupled to the needle 559 and the distal manifold 555A is fluidly couplable to one or more delivery lines via the one or more ports 556 of the sled assembly 540. The proximal manifold 555B is in fluid communication with the distal manifold 555A through a one-way check valve 553 disposed therebetween.

[0042] Accordingly, the proximal manifold 555B is in fluid communication with the one or more ports 556 via the distal manifold 555A, however, the one or more ports 556 are not in fluid communication with the proximal manifold 555B due to a position of the one-way check valve 553 disposed between the manifolds 555A, 555B. Thus, the needle 559 is in fluid communication with the one or more delivery lines and / or devices coupled to the sled assembly 540 at the one or more ports 556 via the manifolds 555A, 555B secured therebetween. The one or more ports 556 of the sled assembly 540 may be coupled to a bag (e.g., saline bag), a syringe, a catheter, and / or the like via one or more delivery lines coupled thereto. In other embodiments, the needle 559 may be a cannula, catheter, or similar mechanism through which to inject and receive fluid and / or a solution as described herein.

[0043] Still referring to FIG. 2, the sled assembly 540 includes a removable battery pack 570 coupled to the sled assembly 540 along the proximal end 544. The removable battery pack 570 comprises a battery 572, electrical contacts 574, and a removable tab 576. The battery 572 of the delivery device 500 is isolated from one or more fluid paths and radiation sources due to a location of the battery 572 in the removable battery pack 570.

[0044] The electrical contacts 574 of the removable battery pack 570 extend outwardly from the removable battery pack 570 and are operable to contact against and interact with corresponding electrical contacts 511 of the console assembly 510 (See FIG. 1) when the sled assembly 540 is coupled to the base 512 at the sled cavity 532. Accordingly, the removable battery pack 570 is operable to provide electrical power to the delivery device 500, and in particular the console assembly 510, when the sled assembly 540 is coupled to the console assembly 510.

[0045] Additionally, as will be described in greater detail herein, in some embodiments the locking system 550 may include at least one planar wall relative to a remaining circular orientation of the locking system 550. In this instance, an aperture formed by the locking system 550 through the top surface 548 of the sled assembly 540 is irregularly-shaped, rather than circularly-shapedas shown and described above. In this instance, the vial assembly 580 includes a locking feature 586 that has a shape and size that corresponds to the locking system 550, and in particular the at least one planar wall such that the vial assembly 580 is received within the sled assembly 540 only when an orientation of the vial assembly 580 corresponds with an alignment of the locking feature 586 and the locking system 550. In other words, a corresponding planar wall 586A of the locking feature 586 (See FIG. 3) must be aligned with the planar wall of the locking system 550 for the vial assembly 580 to be receivable within an aperture formed by the locking system 550 of the sled assembly 540.

[0046] Referring now to FIG. 3, the vial assembly 580 of the delivery device 500 is depicted. The vial assembly 580 comprises an engagement head 582, a plunger 584, a locking feature 586, and a vial body 589. In particular, the engagement head 582 of the vial assembly 580 is positioned at a terminal end of the plunger 584 opposite of the locking feature 586 and the vial body 589. The engagement head 582 includes a pair of arms 581 extending laterally outward relative to a longitudinal length of the plunger 584 extending downwardly therefrom. In the present example, the engagement head 582 is integrally formed with the plunger 584, however, it should be understood that in other embodiments the engagement head 582 and the plunger 584 may be separate features fastened thereto. In either instance, the engagement head 582 and the plunger 584 is movable relative to the locking feature 586 and the vial body 589 such that the engagement head 582 and the plunger 584 are slidably translatable through the locking feature 586 and the vial body 589. In particular, as will be described in greater detail herein, the plunger 584 may translate into and out of an internal chamber 588 of the vial body 589 in response to a linear translation of the vial engagement mechanism 520 when the engagement head 582 is secured to the pair of lever arms 522.

[0047] The plunger 584 includes a plurality of indicia and / or markings 583 positioned along a longitudinal length of the plunger 584. The plurality of markings 583 is indicative of a relative extension of the engagement head 582 and the plunger 584 from the locking feature 586 and the vial body 589. As briefly noted above, the engagement head 582 is configured to attach the vial assembly 580 to the vial engagement mechanism 520. In particular, the pair of arms 581 of the engagement head 582 are sized and shaped to couple with the pair of lever arms 522 of the vial engagement mechanism 520 when the vial assembly 580 is received within the sled assembly 540 and the sled assembly is inserted into the sled cavity 532 of the console assembly 510. As will be described in greater detail herein, the pair of lever arms 522 are received between the pair of arms581 of the engagement head 582 and the plunger 584 in response to a predetermined translation force applied to the vial engagement mechanism 520. The engagement head 582 and the plunger584 may be formed of various materials, including, but not limited to, a metal, plastic, and / or the like.

[0048] Still referring to FIG. 3, the vial assembly 580 further includes a safety tab 585 coupled to the plunger 584 relatively above the locking feature 586 and below the engagement head 582 such that the safety tab 585 is positioned along the longitudinal length of the plunger 584. The safety tab 585 may be formed of various materials, such as, for example, a plastic, and is preassembled onto the vial assembly 580 prior to a use of the delivery device 500. The safety tab585 is removably fastened to the plunger 584 and inhibits the plunger 584 from translating relative to the vial body 589. In particular, the safety tab 585 abuts against the locking feature 586 in response to an application of linear force onto the plunger 584 to translate the plunger 584 relatively downward into the vial body 589. In this instance, the safety tab 585 is configured to inhibit an inadvertent movement of the plunger 584, and in response, an inadvertent delivery of a fluid media stored within the internal chamber 588 of the vial body 589 (e.g., therapeutic particles, radioembolizing beads). As will be described in greater detail herein, the safety tab 585 is selectively disengaged from the plunger 584 in response to a coupling of the vial assembly 580 with the vial engagement mechanism 520, and in particular an engagement of the pair of lever arms 522 with the engagement head 582.

[0049] Referring back to FIG. 3, the locking feature 586 extends about a top end of the vial body 589. In the present example, the locking feature 586 of the vial assembly 580 comprises a bushing that defines a lateral edge 587 extending laterally outward along an outer perimeter of the locking feature 586. The lateral edge 587 of the locking feature 586 is sized and shaped to engage the annular array of projections 551 of the locking system 550 when the vial assembly 580 is received within the vial chamber 558 of the sled assembly 540. As will be described in greater detail herein, the locking feature 586, and in particular the lateral edge 587 of the locking feature 586, is configured to securely fasten the vial assembly 580 to the locking system 550 to inhibit removal of the vial body 589 from the vial chamber 558 of the sled assembly 540 during use of the delivery device 500 in a procedure. In some embodiments, as briefly described above, the locking feature 586 includes at least one planar wall 586A such that the locking feature 586 comprises an irregular-profile. The at least one planar wall 586A is configured to correspond to the planar wall 550A of the locking system 550 such that an alignment of the planar walls 550A,586A is required for the vial assembly 580 to be received through an aperture formed by the locking system 550.

[0050] Still referring to FIG. 3, the vial body 589 extends downwardly relative from the locking feature 586 and has a longitudinal length that is sized to receive at least a portion of a longitudinal length of the plunger 584 therein. Accordingly, in some embodiments a longitudinal length of the plunger 584 exceed a longitudinal length of the vial body 589 such that a translation of the plunger 584 into the internal chamber 588 of the vial body 589 causes a fluid media stored therein to be transferred outward from the vial body 589. As will be described in greater detail herein, a translation of the plunger 584 through the internal chamber 588 of the vial body 589 provides for an administration of a fluid media stored within the vial body 589 outward from the vial assembly 580. The vial body 589 may be formed of various materials, including, for example, a thermoplastic polymer, copolyester, polycarbonate, a biocompatible plastic, polysulfone, ceramics, metals, and / or the like.

[0051] The vial body 589 is of the present example is formed of a material that is configured to inhibit radioactive emissions from a fluid media stored within the internal chamber 588 of the vial body 589. For example, the vial body 589 may be formed of a plastic, such as polycarbonate, and have a width. A density and material composition of the vial body 589 may collectively inhibit beta radiation emission from electron particles stored within the internal chamber 588. In the present example, a chemical composition of the plastic of the vial body 589, along with the 9 mm wall thickness, provides a plurality of atoms disposed within the vial body 589 that are capable of encountering the electron particles generating beta radiation and reducing an emission of said radiation from the vial assembly 580. Accordingly, the vial assembly 580 allows an operator to handle the radioactive material stored within the vial body 589 without being exposed to beta radiation. It should be understood that various other materials and / or wall sections may be incorporated in the vial body 589 of the vial assembly 580 in other embodiments without departing from the scope of the present disclosure.

[0052] Still referring to FIG. 3, the vial body 589 of the vial assembly 580 is sealed at a first terminal end 598 by the locking feature 586. The vial assembly 580 further includes a cap 590 positioned at an opposing, terminal end of the vial body 589 opposite of the locking feature 586, such that the cap 590 seals a second terminal end of the vial body 589 of the vial assembly 580. Additionally, the vial assembly 580 includes a septum 592 positioned adjacent to the cap 590 and in fluid communication with a terminal end of the vial body 589 opposite of the locking feature586. The septum 592 forms a seal against a terminal end of the vial body 589 and the cap 590 retains the septum 592 therein. The septum 592 may be formed of various materials, including, for example, an elastomer, silicon, bromobutyl elastomer, rubber, urethanes, and / or the like. The septum 592 is configured to provide an air-tight seal for the vial body 589 to thereby inhibit a release of a fluid media stored therein (e.g., radioembolizing beads). As will be described in greater detail herein, the septum 592 of the vial assembly 580 is configured to be punctured by the needle 559 of the sled assembly 540 when the vial assembly 580 is received within the vial chamber 558, thereby establishing fluid communication between the vial body 589 and the sled assembly 540. In other embodiments, the septum 592 may be omitted entirely for an alternative device, such as, for example, a valve system, needle injection port, and / or the like.

[0053] Referring now to FIG. 4, in response to determining that the battery 572 contains or other power source provides a sufficient amount of power, one or more delivery lines are coupled to the sled assembly 540 via the one or more ports 556. In particular, a dose delivery line 10A is coupled to the sled assembly 540 at a delivery port 556A, a contrast line 10B is coupled to the sled assembly 540 at a contrast port 556B, and a flushing line 10C is coupled to the sled assembly 540 at a flushing port 556C. An opposing end of the dose delivery line 10A is initially coupled to a fluid reservoir, such as, for example, a collection bowl. As will be described in greater detail herein, the dose delivery line 10A may be subsequently coupled to an external device, such as a catheter, once the sled assembly 540 has been effectively primed by a fluid medium via the contrast line 10B. An opposing end of the flushing line 10C is coupled to an external device, such as, for example, a syringe. With both the dose delivery line 10A and the flushing line 10C coupled to the sled assembly 540, the sled assembly 540 is flushed with a fluid medium (e.g., saline) from the syringe coupled to the flushing line 10C. In this instance, the fluid medium is injected through the flushing line 10C, into the distal manifold 555A of the sled assembly 540, and out of the sled assembly 540 through the dose delivery line 10A. Accordingly, the fluid medium is ultimately received at the collection bowl and disposed thereat by the dose delivery line 10A.

[0054] With the distal manifold 555A of the sled assembly 540 separated from the proximal manifold 555B by the one-way valve 553 disposed therebetween, the fluid medium flushed through the distal manifold 555A from the syringe (via the flushing port 556C) is prevented from passing through the proximal manifold 555B and the needle 559 coupled thereto. Rather, the fluid medium injected from the syringe and through the flushing line 10C is received at the flushing port 556C, passed through the distal manifold 555A in fluid communication with the flushing port556C, and redirected by the one-way valve 553 towards the dose delivery port 556 A that is coupled to the dose delivery line 10A. In this instance, the dose delivery line 10A receives and transfers the fluid medium to the collection bowl coupled thereto, such that the fluid medium is not directed beyond the one-way valve 553 and into the proximal manifold 555B that is in fluid communication with the needle 559.

[0055] The contrast line 10B is coupled to the sled assembly 540 at a contrast port 556B. An opposing end of the contrast line 10B is coupled to a fluid medium supply, such as, for example, a bag secured to the console assembly 510 via the attachment device 538. In the present example, the bag is a saline bag such that the fluid medium stored therein is saline. In this instance, with the sled assembly 540 including the priming assembly 560 positioned within the vial chamber 558 and the needle end 568 in fluid communication with the needle 559, a syringe is fluidly coupled to the priming line 562 of the priming assembly 560 and a plunger of the syringe is drawn back to pull saline through the contrast line 10B, the contrast port 556B, the sled assembly 540, the priming line 562 and into the syringe from the saline bag. The plunger of the syringe is thereafter pushed inwards to transfer the extracted saline back through the priming line 562, the central body 564, the elongated shaft 566, and the needle end of the priming assembly 560 such that the saline is received into the needle 559 of the sled assembly 540. Accordingly, the manifolds 555A, 555B of the sled assembly 540 are effectively primed with the saline from the syringe as the needle 559 that received the saline from the priming assembly 560 is in fluid communication with the manifolds 555A, 555B. With the manifolds 555A, 555B in further fluid communication with the dose delivery line 10A via the delivery port 556 A, the saline is effectively distributed to the collection bowl coupled thereto.

[0056] The sled assembly 540 is coupled to one or more external devices via the one or more ports 556. In particular, the sled assembly 540 is fluidly coupled to a catheter (e.g., microcatheter) via the dose delivery line 10A that is coupled to the delivery port 556A of the sled assembly 540. In this instance, the catheter is in fluid communication with the sled assembly 540 via the dose delivery line 10A. Further, the sled assembly 540 is fluidly coupled to a contrast source, such as, for example, a saline bag secured to the console assembly 510 via the attachment device 538 (See FIG. 1). The sled assembly 540 is in fluid communication with the saline bag via a contrast line 10B coupled to the contrast port 556B of the sled assembly 540. In this instance, the saline bag is in fluid communication with the sled assembly 540 via the contrast line 10B secured to the contrast port 556B.

[0057] The contrast port 556B is in fluid communication with the proximal manifold 555B while the delivery port 556A is in fluid communication with the distal manifold 555A. As will be described in greater detail herein, saline from the saline bag may be withdrawn through the needle 559 of the sled assembly 540 and into the vial body 589 of the vial assembly 580 as the contrast port 556B is coupled to the proximal manifold 555B, rather than the distal manifold 555A which is separated from the proximal manifold 555B by the one-way check valve 553 disposed therebetween.

[0058] Referring again to FIGS. 1 and 3, with the vial assembly 580 securely coupled to the sled assembly 540, the sled assembly 540 is coupled to the console assembly 510 by translating the distal end 542 of the sled assembly 540 toward and into the distal end 516 of the console assembly 510. In particular, the distal end 542 of the sled assembly 540 is directed into the sled cavity 532 of the console assembly 510 by aligning the alignment ribs 554 of the sled assembly 540 with the alignment features 534 of the console assembly 510. Once the proximal end 544 and the distal end 542 of the sled assembly 540 are fully seated within the sled cavity 532 of the console assembly 510, the electrical contacts 574 (FIG. 2) of the removable battery pack 570 interact with corresponding electrical contacts 511 (FIG. 1) of the console assembly 510. In this instance, power from the battery 572 is transmitted to the console assembly 510 via the electrical contacts 574, thereby activating the console assembly 510 of the delivery device 500. In this instance, the interface display 530 of the console assembly 510 is activated to display pertinent, real-time information relating to the delivery device 500 during a procedure.

[0059] Referring again to FIG. 4, as the vial engagement mechanism 520 and the plunger 584 are simultaneously translated within the vial containment region 518, a negative pressure is generated within the internal chamber 588 of the vial body 589 due to a retraction of the stopper 594. In this instance, with the saline bag coupled to the sled assembly 540 via the contrast line 10B and the contrast port 556B, saline from the saline bag is pulled into the internal chamber 588 of the vial body 589 through the proximal manifold 555B and the needle 559. Accordingly, with the vial body 589 being preloaded with a radioactive fluid media (e.g., radioembolizing microspheres), the saline is effectively mixed with the radioactive fluid media within the vial body 589 as the plunger 584 is retracted from the internal chamber 588 and the negative pressure is generated through the delivery device 500.

[0060] The sled assembly 540 further includes one-way check valves 553A in-line with the contrast line 10B and the flushing line 10C. In particular, the one-way check valves 553A areconfigured to permit fluid communication from the contrast port 556B and the flushing port 556C into the manifolds 555A, 555B, and further configured to prevent fluid communication from the manifolds 555A, 555B to the contrast port 556B and the flushing port 556C. Accordingly, it should be understood that the dose delivered from the vial body 589 to the manifold 555A, 555B is incapable of being directed into the contrast line 10B or the flushing line IOC due to the oneway check valves 553A positioned therein. Thus, the dose is directed to the dose delivery port 556A and received at the catheter fluidly coupled thereto by the dose delivery line 10A. In other words, the one-way check valves 553A prevent a backflow of fluid into the sled assembly 540 and / or the vial assembly 580 coupled thereto.

[0061] Referring to FIG. 5, an interface display communicatively coupled to the delivery device 500 may be operable to transmit information and / or data to an operator of the delivery device 500, and in particular data detected by an electrical system of the delivery device 500 which may comprise one or more sensors disposed within the delivery device 500, such as an onboard sensor (that may be, for example, radiation sensor 533 as described in greater detail further below). It should be understood that the delivery device 500 may include an electrical microprocessor that operates the interface display. In other embodiments, the interface display may comprise a remote smart device, a tablet, and / or the like.

[0062] The console assembly 510 includes a mechanical assembly 529 disposed within the base 512 that is configured and operable to convert a manual motion of the handle 528 to a corresponding linear displacement of the vial engagement mechanism 520. In the present example, the mechanical assembly 529 is coupled to the handle 528 and the vial engagement mechanism 520 such that selective actuation of the handle 528 at the proximal end 514 causes a simultaneous actuation of the vial engagement mechanism 520 at the distal end 516. As will be described in greater detail herein, the mechanical assembly 529 of the present example allows for fluid volume control and fluid flow volume control during a dose delivery with the delivery device 500. It should be understood that a mechanical configuration of the mechanical assembly 529 of the present example may comprise various linkages, gears, pullies, springs and / or the like that are specifically configured to amplify a force applied to the handle 528 with a corresponding displacement of the vial engagement mechanism 520. In some embodiments, the mechanical assembly 529 may comprise and / or be substituted by one or more electrically-driven systems, motors, and / or other devices operable to provide for a movement of the vial engagementmechanism 520 relative to the vial containment region 518 and / or provide a feedback to an operator as the handle 528 is actuated.

[0063] In other embodiments the mechanical assembly 529 may be configured such that the handle 528 may be actuated (i.e., moved) in various other arrangements or orientations than that shown and described herein to generate a corresponding linear displacement of the vial engagement mechanism 520. For example, the mechanical assembly 529 of the console assembly 510 may be configured to convert a linear, rotational, lateral and / or other various motions of the handle 528 to generate a disproportionate displacement of the vial engagement mechanism 520, with the displacement exceeding a force applied at the handle 528.

[0064] Still referring to FIG. 5, and as briefly described above, the console assembly 510 includes one or more sensors for monitoring and detecting certain conditions and / or materials stored in the console assembly 510 during use of the delivery device 500. In the present example, the console assembly 510 includes a linear displacement sensor 531 and a radiation sensor 533. The linear displacement sensor 531 is securely attached to the mechanical assembly 529 of the console assembly 510 such that the linear displacement sensor 531 is operable to move within the console assembly 510 in response to an actuation of the handle 528 and a corresponding movement of the vial engagement mechanism 520. The linear displacement sensor 531 is configured to detect and monitor a displacement distance, a velocity of displacement, and / or the like of the handle 528 and the vial engagement mechanism 520.

[0065] As will be described in greater detail herein, by measuring a displacement distance or velocity of the handle 528 and / or the vial engagement mechanism 520, computer readable and executable instructions of the delivery device 500, when executed by a processor of the delivery device 500, may determine a flow rate of a fluid media being delivered by the delivery device 500. Additionally or alternatively, the computer readable and executable instructions of the delivery device 500, when executed by a processor of the delivery device 500, may further determine a remaining volume of a fluid media stored within the delivery device 500. As briefly noted above, the data detected by the linear displacement sensor 531 and the information determined by the processor of the delivery device 500 may be displayed at the interface display 530 for operator review.

[0066] Still referring to FIG. 5, the radiation sensor 533 is securely attached to the base 512 of the console assembly 510 at a location adjacent to the vial containment region 518. In particular, the radiation sensor 533 is positioned proximate to the sled cavity 532 that is sized and shaped toreceive the sled assembly 540 therein. As will be described in greater detail herein, the sled assembly 540 is configured to store and administer therapeutic particles (e.g., radioactive beads, microspheres, medium) therethrough such that the radiation sensor 533 is operable to detect and monitor a radiation level of the therapeutic particles due to a proximate location of the radiation sensor 533 with the sled assembly 540. In particular, the sled assembly 540 is configured to partially receive a vial assembly 580 therein for administering the therapeutic particles from the delivery device 500 and to a patient.

[0067] As will further be described herein, by detecting a radiation level of the radioactive medium stored and transferred through the sled assembly 540, computer readable and executable instructions of the delivery device 500, when executed by a processor of the delivery device 500, may determine a radiation dosage delivered from the delivery device 500. Additionally or alternatively, the computer readable and executable instructions executed by a processor of the delivery device 500 may further determine a remaining radiation dosage contained within the delivery device 500 during a procedure. As briefly noted above, the data detected by the radiation sensor 533 and the information determined by the processor of the delivery device 500 may be displayed at the interface display for operator review. It should be understood that in other embodiments the delivery device 500 may include additional or fewer sensors than those shown and described herein (e.g., a dosimeter, a linear encoder, an optical sensor, a linear displacement sensor, a flow sensor, an ultrasonic sensor, a magnetic encoder, a laser distance sensor, an inductance sensor, a radial encoder, a volumetric sensor, mechanical transducers, etc.). A dosimeter and / or radiation sensor of the delivery device 500 may be configured to measure a remaining exposure to ionizing radiation stored within the delivery device 500, and in particularly the sled assembly 540 and / or the vial assembly 580.

[0068] By way of further examples, a flow sensor of the delivery device 500 may be positioned in-line with the tubing set of the delivery device 500, and in particular the needle 559, the manifolds 555A, 555B, and / or one or more of the ports 556, and may be configured to measure an amount of fluid (e.g., suspension liquid after the therapeutic particles have effectively mixed with the fluid medium) that passes thereby. An ultrasonic sensor of the delivery device 500 may comprise a transmitter, receiver, and / or transceiver configured to measure a distance to an object (e.g., remaining volume of dosage within the vial assembly 580) based on transmitting ultrasonic signals (i.e. sound waves) therein and measuring an elapsed time before receiving back the bounced sound waves. A radial encoder of the delivery device 500 may comprise an absoluteencoder and / or an incremental encoder configured to convert an angular position or motion of the handle 528, the plunger 584, the mechanical assembly 529, and / or other components of the delivery device 500 to analog or digital output signals corresponding to a remaining dosage within the vial assembly 580.II. Nonradioactive Biocompatible Polymeric Microspheres and Their Application for Pre-Radiation Scouting

[0069] In some aspects of the presenting description, it can be beneficial to pre-determine or pre-calculate the amount of radioactive material required for effective treatment. Tissue density can vary significantly between subjects and knowing an exact dosing need to effectively treat tissue can be paramount: too much radioactive material is extremely harmful and too little is extremely ineffective. Thus, a need exists to know what precise dose a subject requires.

[0070] One example includes intra-arterial hepatic radioembolization for hepatocellular carcinoma and / or liver metastasis. An arteriogram allows for assessment of the vascular anatomy of the liver and areas to exclude for liver-lung shunting for subsequent treatment with radioactive microparticles, such as90Y radioactive microparticles. The hepatic artery delivery requires calculation of the lung shunting fraction (LSF) to estimate deposition to the lungs and quantify risk of radiation pneumonitis. A further example includes tumor to normal (T :N) ratio calculations for tissue, as these can be utilized to estimate absorbed doses and / or predictive dosimetry.

[0071] One aspect of the present disclosure concerns a system and methods of use thereof that allows for the pre-determination of distribution radioactive material a subject requires. In some aspects, the system and methods provide an initial mimic of a radioactive dose to allow for the calculation and adjustment thereof of radioactive material to administer. In some aspects, the present disclosure is directed to composition, systems, and methods for delivering non-radiative particles at least partially including a biocompatible material to a target area of a subject, wherein the particles can then be imaged within and / or around the target area of the body of the subject to determine the distribution therein. Such can then provide material information such as lung shunt activity and / or tumor to normal tissue ratio(s) and thus allow for adjustment of the subsequent radiation treatment.

[0072] In some aspects, the biocompatible material is of sufficient density to be visualized through the application of medical imaging techniques as set forth herein. In some aspects, the biocompatible material is of a density of at least two grams per cubic centimeter (2 g / cc or 2 g / cm3)In aspects, the biocompatible material is a high density material. It is to be understood that as referenced herein, “high” with respect to density may be of a value equal or greater than four grams per cubic centimeter (4 g / cc or 4 g / cm3). Thus, in some aspects, the biocompatible material is a high density biocompatible material of at least 4 g / cc or 4 g / cm3.

[0073] In some aspects, the non-radioactive particles of the present disclosure include one or more non-radioactive biocompatible materials. Biocompatible materials are understood to be inert or non-reactive when in situ within a subject, such as a human subject. It is a further aspect of the biocompatible material that it be of sufficient density to be captured or tracked with the visualization techniques as set forth herein. In some aspects, the biocompatible material is of gold, titanium, steel, chromium, cobalt, yttrium, cerium, iodine, glass, platinum, or a combination thereof. In some aspects, the biocompatible material is a steel, such as a surgical steel or a medical grade steel or SAE 316, SAE 440, SAE 420, 17-4, SAE 316, or SAE316L steel. In some aspects, the biocompatible material is gold (Au). In further aspects, a biocompatible material maybe a composite of two or more materials. In aspects, the composite is of a high density such as of at least 4 g / cc or 4 g / cm3.

[0074] In some aspects, the system and the methods utilize a liquid suspension of particles that are configured to mimic a visualization under medical imaging as described herein of radioactive compounds, such as90Y, to simulate visually via the medical imaging similar dynamics of the radioactive compounds. Turning to FIGS 6-9, several embodiments of such particles 600 are shown. The particles 600 include a combination of biocompatible material 608 and a polymeric microsphere 604.

[0075] Turning to FIG. 6, a particle 600 is shown of biocompatible material 608 embedded in polymeric microsphere 602. The particle 600 of biocompatible material 608 embedded in polymeric microsphere 602 includes a biocompatible material nanoparticle 606 made of the biocompatible material 608 embedded within a polymeric microsphere 604. In embodiments, the biocompatible material nanoparticle 606 may be compacted with the biocompatible material 608 in one or more areas and / or the biocompatible material 608 may be spread out in one or more areas of the manufactured biocompatible material nanoparticle 606. In certain aspects, the biocompatible materials is a high density material of 4 g / cm3or higher, such as gold or similar as set forth herein Additionally or alternatively, the biocompatible material nanoparticle 606 may be manufactured to be microencapsulated for drug delivery based on, for example, desired flow characteristics (e.g., density, volume, and surface finish), final material selection, weight and / orsize to best imitate visually a radioactive microsphere to act as a surrogate during a scout dose. In particular, a plurality of biocompatible material nanoparticles 606 based on any of the embodiments described herein may be used to create a scout dose representative of plurality of radioactive microspheres to administer during a procedure to plan out an ideal amount of use of the plurality of radioactive microspheres during the procedure. In an aspect, the scout dose using the particle 600 will mimic the density of a radioactive dose sphere to be used during the procedure. If a weight of the biocompatible material nanoparticle 606 is lower than the radioactive dose sphere to mimic, the sphere material density of the biocompatible material nanoparticle 606 may need to be adjusted and increased to mimic and accommodate the targeted volume and higher weight of the radioactive dose sphere. Alternatively, if the weight of the biocompatible material nanoparticle 606 is greater than the radioactive dose sphere to mimic, the sphere material density of the biocompatible material nanoparticle 606 may need to be adjusted and decreased to mimic and accommodate the targeted volume and lower weight of the radioactive dose sphere.

[0076] In some aspects, the particle 600 shares similar flow characteristics as a radioactive microsphere counterpart, such as a Y-90 labelled microparticle as a radiolabeled particle. Administration of such can allow a user to pre-image or scout the distribution of the particle 600 in a subject to adjust and / or calculate the dose of radiolabeled particles to be administered. By using the particle 600 as a scout dose to mimic the radiolabeled counterpart and, in particular, the associated flow characteristics that may include density, volume, and surface finish, a user can, based on the results of the imaging and analysis of the particle 600 as described herein, plan out the ideal amount of the radioactive microspheres to use during a procedure. As a non-limiting embodiment, the amount of radioactive material to be administered may be adjusted via being increased or decreased from a planned pre-scout amount and based on the scout dose results of the particle 600 to maximize efficacy while also prevent overdosing and / or toxicity when the radioactive material is administered during the procedure. Characteristics of the particle 600 for consideration to mimic the radioactive particle include, but is not limited to, diameter / cross- sectional width, mass, density, volume, surface friction / finish, specific gravity, or one or more combinations thereof. The polymeric microsphere 604 is formed around the biocompatible material nanoparticle 606, such as by cross-linking of monomeric polymer units, such as with an initiator and / or a cross-linking reagent. In some aspects, the polymeric microspheres are of polystyrene.

[0077] Remaining with FIG. 6, the particles 600 can be milled or sized or selected for a particle width 610. In some aspects, the particle width 610 of the particles 600 can be of a size of about 10 to about 100 micrometers (pm), including about 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, and 95 pm (± 1-4 pm). In some aspects, the particles 600 have a width 610 of about 25 pm. In some aspects, the particles 600 have a width 610 of about 10-50 pm, 10-30 pm, 10-20 pm, 20-50 pm, 20-40 pm, 20-30 pm, 25-50 pm, 25-40 pm, 25-30 pm, 15-50 pm, 15-40 pm, 15- 30 pm, or 15-25 pm. In some aspects, the particles 600 have a density of about 1 to about 5 grams per milliliter (g / mL), 1 to 4.5 g / mL, 1- 4 g / mL, 1-3.5 g / mL, 1-3 g / mL, 1-2.5 g / mL, 1.5-5 g / mL 1.5-4.5 g / mL, 1.5-4 g / mL, 1.5-3.5 g / mL, 1.5-3 g / mL, 2-5 g / mL, 2-4.5 g / mL, 2-4 g / mL, 2-3.5 g / mL, 2.5-5 g / mL, 2.5-4.5 g / mL, 2.5-4 g / ml, 2.5-3.5 g / mL, 3-5 g / mL, 3-4.5 g / mL and 3-4 g / mL, or a combination thereof. In some aspects, the particles 600 have a coefficient of friction on a surface thereof of about 0.1-0.6, 0.1-0.5, 0.1-0.4, 0.1-0.3, 0.1-0.2, 0.2-0.6, 0.2-0.5, 0.2-0.4, 0.2- 0.3, 0.3-0.6, 0.3-0.4, 0.3-0.5, 0.3-0.4, 0.4-0.6, 0.4-0.5, 0.5-0.6, or a combination thereof. In some aspects, the particles 600 have a combination of properties of width, density, coefficient of friction and so forth so as to emulate the flow of a radioactive counterpart particle. In some aspects, the polymer of the particle 600 is a biodegradable polymer such that the subject’s body can naturally degrade the polymer without issue. Examples of suitable polymers include polyglycolic acid, polylactic acid, polylactic-co-glycolic acid, polycaprolactone (PCL), poly-DL-lactic acid (PDLLA), poly(trimethylene carbonate) (PTMC), poly (ester amine)s (PEA), poly(para- dioxanone) (PPDO), poly-2-hydroxy butyrate (PHB), resin, and co-polymers with various ratios thereof. It will be appreciate that the choice of polymer and / or the density thereof may be adjusted to reflect the mass of biocompatible material used in the particle 600. As set forth herein, the particles 600 are to possess the same or similar flow characteristics as a radioactive counterpart. In some aspects, the polymer is of about 10-90% by weight (wt) of the particle 600, including about 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, and 85% by wt (± 1-4%). Such can include about 10-80, 10-70, 10-60, 10-50, 10-40, 10-30, 10-20, 20-90, 20-80, 20-70, 20-60, 20- 50, 20-40, 20-30, 30-90, 30-80, 30-70, 30-60, 30-50, 30-40, 40-90, 40-80, 40-70, 40-60, 40-50, 50-90, 50-80, 50-70, 50-60, 60-90, 60-80, 60-70, 70-90, 70-80, and 80-90% by wt of the particle 600.

[0078] As shown in an embodiment in FIG. 7, in some aspects, the biocompatible material 608 can encase a polymeric microsphere 604. FIG. 7 depicts a particle 600 of such a biocompatible material encased polymeric microsphere 700. A biocompatible material coating 702 surrounds thecircumference of an interior encased polymeric microsphere 604. The biocompatible material encased polymeric microsphere 700 can be produced by encasing a polymeric microsphere 604 in the biocompatible material 608. In some aspects, the polymeric microspheres 604 for the biocompatible material encased polymeric microspheres 700 can be selected for a certain size, such as a preferred cross-sectional diameter or particle width as discussed herein (see, e.g., particle width 610 of FIG. 6).

[0079] As shown in an embodiment in FIG. 8, in some aspects, the particle 600 of the present disclosure includes a polymeric microsphere 604 embedded with at least two biocompatible material nanoparticles 606 such as a plurality of biocompatible material nanoparticles 606. FIG. 8 depicts a particle 600 with a plurality of biocompatible material nanoparticles 606 of the biocompatible material 608 embedded therein. In some aspects, a biocompatible material embedded polymeric microsphere 800 as shown in FIG. 8 includes a polymeric microsphere 604 with two or more biocompatible material nanoparticles 606 of the biocompatible material 608 embedded therein. In some aspects, the polymeric microspheres 604 can be selected for a certain size, such as a preferred cross-sectional diameter or particle width as discussed herein (see, e.g., particle width 610 of FIG. 6).

[0080] Turning to FIG. 9, in some aspects, a biocompatible material embedded and encased polymeric microsphere 900 including a particle 600 embedded with one or more biocompatible material(s)nanoparticle(s) 606 of the biocompatible material 608 and a biocompatible material coating 702 at least partially disposed about an exterior surface of the polymeric microsphere 604.

[0081] With reference to FIG. 10, in some aspects, the particles 600 are delivered to a subject as part of a composition 1002, such as through suspension in a fluid 1004. It will be appreciated that the fluid composition can be variable, but for administration to a human subject should be aqueous in nature. It will be appreciated that such fluid 1004 may include one or more salts, such as potassium chloride, sodium chloride, magnesium chloride, or similar, as is appreciated in the art (see, e.g. Remington: The Science and Practice of Pharmacy, Lippincott Williams & Wilkins, 21st Ed., 2005). In some aspects, the fluid 1004 includes saline such as a saline solution. It will also be appreciated that a composition 1002 as used herein may further include one or more therapeutic agents suspended and / or dissolved therein, as well as one or more surfactants, antioxidants, pharmaceutically acceptable carriers, excipients or similar as is understood in the art.

[0082] As shown in FIG. 10, a medical imaging environment 1000 includes the composition 1002 of the particles 600 suspended in a fluid 1004 in a vial assembly 580 as described herein. As described hereinabove, and referring to FIG. 3, the vial assembly 580 includes a plunger 584 and a vial body 589. As depicted in FIG. 9, a plurality of particles 1006 of the particles 600 is suspended in the fluid 1004. The composition 1002 can be housed in then vial assembly 580 as described above and administered to a target area 1008 of a body 1010 of a subject, such as by a delivery assembly, which may be a delivery device 500 as described herein. A medical imaging source 1012 may be directed at the target area 1008 and surrounding tissues of the subject to determine distribution and / or localization of the plurality of particles 1006 within the target area 1008 of the body 1010 , thereby generating material data such as an estimated lung shunt activity and an estimated tumor to normal ratio (T:N) of tissue. In embodiments, examples of medical imaging sources 1012 may include X-ray, computerized tomography (CT) scan, cone-beam CT (CBCT), magnetic resonance (MRI) imaging, positron emission tomography, ultrasound, or the like. The medical imaging sources 1012 may be configured to allow for three-dimensional (3D) scans and volumetric determinations for imaging and analysis of the scout doses as described herein.

[0083] Referring to FIGS. 10 and 11, a process 1100 is used in a method of medical imaging of medical imaging of a composition 1002 of a plurality of particles 1006 and fluid 1004 within a body 1010 of a subject. In block 1102, the composition 1002 of the plurality of particles 1006 and fluid 1004 is delivered into a target area 1008 of the body 1010 of the subject. The target area 1008 may be disposed in an area surrounding a tumor in the body 1010 of the subject. The plurality of particles 1006 may include a plurality of non-radioactive polymeric microspheres as particles 600 comprising the biocompatible material 608. In block 1104, the plurality of particles 1006 of the composition 1002 disposed within the body 1010 of the subject may be imaged using a medical imaging source 1012 disposed external to the body 1010 of the subject. In block 1106, a lung shunt activity, tumor to normal (T :N) ratio, or both may be estimated based off the imaging of the plurality of particles of the composition 1002 at the target area using the medical imaging source 1012. In an embodiment, heat may be to the plurality of particles 1006 of the composition 1002 disposed within the body 1010 of the subject such that the plurality of particles 1006 degrade as the biocompatible material 608 within the plurality of particles is heated. The plurality of particles 1006 may be heated via an electromagnetic field and may concurrently be used when heated to ablate tissue as well.

[0084] In embodiments, the imaging of block 1104 may include anterior and posterior planar imaging of the plurality of particles 1006 of the composition 1002 at the target area 1008. With respect to block 1106, based on the anterior and posterior planar imaging, (i) a count of the plurality of particles 1006 of the composition 1002 at a lung site as part of the target area 1008 and (ii) a total count of the plurality of particles 1006 of the composition 1002 at the lung site in combination with a liver site may be calculated. The lung shunt activity may be determined as a lung shunt fraction including (i) the count of the plurality of particles 1006 of the composition 1002 at a lung site divided by (ii) the total count of the plurality of particles 1006 of the composition 1002 at the lung site in combination with the liver site.

[0085] In additional or alternative embodiments, in block 1106, based on the imaging of block 1104, a calculation may include (i) a count the plurality of particles 1006 of the composition 1002 at a tumor site as part of the target site and (ii) a total count of the plurality of particles 1006 of the composition 1002 at a non-tumor site. The T:N ratio may be determined as a ratio of (i) the count of the plurality of particles 1006 of the composition 1002 at the tumor site to (ii) the count of the plurality of particles 1006 of the composition 1002 at the non-tumor site

[0086] In embodiments, the plurality of non-radioactive polymeric microspheres as the plurality of particles 1006 of particles 600 are coated with (e.g., encased by) the biocompatible material 608, such as described for the biocompatible material encased polymeric microsphere 700 of FIG. 7, the biocompatible material embedded and encased polymeric microsphere 900 of FIG. 9, or combinations thereof. Additionally or alternatively, the plurality of non-radioactive polymeric microspheres as particles 600 are embedded with the biocompatible material 608. Embodiments may include the biocompatible material embedded polymeric microsphere 608 with a single biocompatible material nanoparticle 606 of FIG. 6, the biocompatible material embedded polymeric microsphere 800 with a plurality of biocompatible material nanoparticles 606 of FIG. 8, the biocompatible material embedded and encased polymeric microsphere 900 of FIG. 9, or combinations thereof. In some aspects, the plurality of non-radioactive polymeric microspheres as particles 600 are coated and embedded with the biocompatible material 608, such as in the biocompatible material embedded and encased polymeric microsphere 900 of FIG. 9. The plurality of particles 1006 may be configured to mimic or imitate a specific shape, size, and gravity of a corresponding procedural dose of radioembolizing microspheres loaded with a radioactive compound, which radioactive compound may be yttrium-90 (90Y).

[0087] In embodiments, referring to FIGS. 1 and 10, a delivery assembly, such as the delivery device 500 described herein, may include a console (such as the console assembly 510) including a vial containment region 518, a vial assembly 580, a vial engagement mechanism 520 extending from the console within the vial containment region 518, and a medical imaging source 1012. The vial assembly 580 may include a vial body 589 and a plunger 584. The vial body 589 may contain a plurality of particles 1006 including a plurality of non-radioactive polymeric microspheres as particles 600 including the biocompatible material 608 as described herein. The plunger 584 may include a proximal end and a distal end, the proximal end disposed outside of the vial body 589, the distal end disposed within the vial body 589.

[0088] The vial engagement mechanism 520 is configured to (i) engage the proximal end of the plunger 584, (ii) move the plunger 584 in a proximal direction to pull a fluid 1004 into the vial body 589 of the vial assembly 580 to mix with the plurality of particles 1006 to form a composition 1002 of a plurality of particles 1006 and fluid 1004, and (iii) move the plunger 584 in a distal direction to push the composition 1002 of the plurality of particles 1006 and fluid 1004 out of the vial body 589 of the vial assembly 580 and through a catheter into a target site of a body 1010 of a subject. The medical imaging source 1012 is configured to image the composition 1002 of the plurality of particles 1006 and fluid 1004 at the target area to estimate a lung shunt activity, tumor to normal (T:N) ratio, or both as described herein.

[0089] In embodiments, the vial assembly 580 includes a septum 592 as described hereinabove disposed within a distal end of the vial body 589 that is configured to seal the vial body 589. The delivery assembly may further include a needle 559 (FIG. 2) as described herein above fluidly coupled to a fluid source (e.g., a bag such as a saline bag, a syringe, a catheter, and / or the like) housing the fluid 1004. The needle 559 may be configured to puncture the septum 592 of the vial body 589 to direct the fluid 1004 from the fluid source through the needle 559 into the vial body 589 upon movement of the plunger 584 in the proximal direction.

[0090] Referring to FIGS. 1 and 12, a process 1200 for a method of using a delivery assembly (e.g., delivery device 500) for delivery of the composition 1002 of a plurality of particles 1006 and fluid 1004 as described herein (e.g., for block 1102) is set forth. In block 1202, the vial engagement mechanism 520 extending from the vial containment region 518 of the console (e.g., the console assembly 510) is engaged with a proximal end of the plunger 584 of the vial assembly 580 The vial assembly 580 further includes the vial body 589 containing the plurality of particles 1006 including a plurality of non-radioactive polymeric microspheres as the plurality of particles1006 of particles 600 comprising a biocompatible material 608. The proximal end of the plunger 584 is disposed outside the vial body 589, and a distal end of the plunger 584 is disposed within the vial body 589.

[0091] In block 1204, the plunger 584 is moved in a proximal direction to pull a fluid into the vial body of the vial assembly to mix with the plurality of particles 1006 to form the composition 1002 of a plurality of particles 1006 and fluid 1004. In block 1206, the plunger 584 is moved in a distal direction to push the composition 1002 of the plurality of particles 1006 and fluid 1004 out of the vial body 589 of the vial assembly 580 and through a catheter as described herein into a target site (e.g., the target area 1008) of the body 1010 of a subject.

[0092] Referring back to FIG. 11, the plurality of particles of the composition at the target area is then imaged in block 1104 via a medical imaging source, and the lung shunt activity, tumor to normal (T :N) ratio, or both are estimated based on the imaging via the medical imaging source in block 1106.

[0093] In some aspects, administration of the composition 1002 (such as with a delivery assembly as described herein) serves as a scout dose or surrogate for radioactive microspheres to be later administered (via the delivery assembly). The “scout dose” that the composition 1002 serves as is imaged by the medical imaging source 1012 in block 1104 of process 1100 as described herein to provide imaging data concerning the tissue of the target area 1008 of the body 1010 of the subject to which the scout dose is administered. The particles 600, i.e. the plurality of particles 1006, should therefore be of a similar density and width as radioactive microparticles that are selected for treatment. For example, as set forth herein, yttrium 90 (90Y) microparticles can be utilized as radioactive microparticles for the treatment of tumorous tissues, such as hepatic carcinomas and / or metastasized hepatic cells, during the radioembolization procedures as set forth herein. It will therefore be appreciated that the particles 600 be of a similar mass and width as90Y radioactive microparticles to ensure that distribute and flow of the polymeric microparticles closely mimics what can be expected when the90Y radioactive microparticles are eventually administered. In some aspects, the particles 600 mimic at least one of the same sizing, same specific gravity, same surface structure, same density, or a combination thereof as a90Y radioactive microparticle. Accordingly, application of the medical imaging source 1012 effectively provides feedback for not only the location of the plurality of particles 1006, but also for what can be expected when the radioactive microparticles are administered.III. Aspects Listing

[0094] Aspect 1. A composition of a plurality of particles and fluid for use in a method of medical imaging of the composition of the plurality of particles and fluid within a subject, the method comprising: delivering the composition of the plurality of particles and fluid into a target area of a body of the subject, the plurality of particles comprising a plurality of non-radioactive polymeric microspheres comprising a biocompatible material; imaging the plurality of particles of the composition disposed within the body of the subject using a medical imaging source disposed external to the body of the subject; and estimating a lung shunt activity, tumor to normal (T:N) ratio, or both based off the imaging of the plurality of particles of the composition at the target area using the medical imaging source.

[0095] Aspect 2. The method of Aspect 1, wherein the biocompatible material is a high density material selected from a group consisting of gold, titanium, steel, chromium, cobalt, cerium, yttrium, iodine, glass, platinum, or a combination thereof.

[0096] Aspect 3. The method of any of Aspect 1 to Aspect 2, wherein the plurality of nonradioactive polymeric microspheres are coated with the biocompatible material.

[0097] Aspect 4. The method of any of Aspect 1 to Aspect 3, wherein the plurality of nonradioactive polymeric microspheres are embedded with the biocompatible material.

[0098] Aspect 5. The method of any of Aspect 1 to Aspect 4, wherein the plurality of nonradioactive polymeric microspheres are coated and embedded with the biocompatible material.

[0099] Aspect 6. The method of any of Aspect 1 to Aspect 5, wherein the target area is disposed in an area surrounding a tumor in the body of the subject.

[0100] Aspect 7. The method of any of Aspect 1 to Aspect 6, wherein the imaging comprises anterior and posterior planar imaging of the plurality of particles of the composition at the target area, the method further comprising: calculating, based on the anterior and posterior planar imaging, a count of the plurality of particles of the composition at a lung site as part of the target area; calculating, based on the anterior and posterior planar imaging, a total count of the plurality of particles of the composition at the lung site in combination with a liver site; and determining the lung shunt activity as a lung shunt fraction comprising the count of the plurality of particles of the composition at the lung site divided by the total count of the plurality of particles of the composition at the lung site in combination with the liver site.

[0101] Aspect 8. The method of any of Aspect 1 to Aspect 7, the method further comprising: calculating, based on the imaging, a count of the plurality of particles of the composition at a tumor site as part of the target area; calculating, based on the imaging, a total count of the plurality of particles of the composition at a non-tumor site; and determining the T :N ratio as a ratio of the count of the plurality of particles of the composition at the tumor site to the count of the plurality of particles of the composition at the non-tumor site.

[0102] Aspect 9. The method of any of Aspect 1 to Aspect 8, wherein the plurality of particles are configured to mimic a specific shape, size, and gravity of a corresponding procedural dose of radioembolizing microspheres loaded with a radioactive compound:

[0103] Aspect 10. The method of Aspect 9, wherein the radioactive compound is yttrium-90 (90Y).

[0104] Aspect 11. The method of any of Aspect 1 to Aspect 10, wherein the fluid comprises a saline solution.

[0105] Aspect 12. The method of any of Aspect 1 to Aspect 11, the method further comprising: applying heat to the plurality of particles of the composition disposed within the vial body such that the plurality of particles degrade as the biocompatible material within the plurality of particles is heated.

[0106] Aspect 13. A delivery assembly comprising: a console including a vial containment region; a vial assembly, comprising: a vial body containing a plurality of particles comprising a plurality of non-radioactive polymeric microspheres comprising a biocompatible material, and a plunger comprising a proximal end and a distal end, the proximal end disposed outside of the vial body, the distal end disposed within the vial body; a vial engagement mechanism extending from the console within the vial containment region, wherein the vial engagement mechanism is configured to engage the proximal end of the plunger, move the plunger in a proximal direction to pull a fluid into the vial body of the vial assembly to mix with the plurality of particles to form a composition of a plurality of particles and fluid, and move the plunger in a distal direction to push the composition of the plurality of particles and fluid out of the vial body of the vial assembly and through a catheter into a target site of a body of a subject; and a medical imaging source configured to image the composition of the plurality of particles and fluid at the target site to estimate a lung shunt activity, tumor to normal (T:N) ratio, or both.

[0107] Aspect 14. The method of Aspect 13, wherein the vial assembly comprises a septum disposed within a distal end of the vial body that is configured to seal the vial body.

[0108] Aspect 15. The method of Aspect 14, wherein the delivery assembly further comprises a needle fluidly coupled to a fluid source housing the fluid, the needle configured to puncture the septum of the vial body to direct the fluid from the fluid source through the needle into the vial body upon movement of the plunger in the proximal direction.

[0109] Aspect 16. The method of any of Aspect 13 to Aspect 15, wherein the plurality of nonradioactive polymeric microspheres are coated, embedded, or both with the biocompatible material, wherein the biocompatible material is selected from a group consisting of gold, titanium, steel, chromium, cobalt, cerium, yttrium, iodine, glass, platinum, or a combination thereof.

[0110] Aspect 17. The method of any of Aspect 13 to Aspect 16, wherein the plurality of particles are configured to mimic a specific shape, size, and gravity of a corresponding procedural dose of radioembolizing microspheres loaded with a radioactive compound, the radioactive compound comprising yttrium-90 (90Y):

[0111] Aspect 18. A method of use of a delivery assembly, comprising: engaging a vial engagement mechanism extending from a vial containment region of a console with a proximal end of a plunger of a vial assembly, the vial assembly further comprising a vial body containing a plurality of particles comprising a plurality of non-radioactive polymeric microspheres comprising a biocompatible material, the proximal end of the plunger disposed outside the vial body, and a distal end of the plunger disposed within the vial body; moving the plunger in a proximal direction to pull a fluid into the vial body of the vial assembly to mix with the plurality of particles to form a composition of a plurality of particles and fluid; moving the plunger in a distal direction to push the composition of the plurality of particles and fluid out of the vial body of the vial assembly and through a catheter into a target site of a body of a subject; imaging the plurality of particles of the composition at the target site via a medical imaging source; and estimating a lung shunt activity, tumor to normal (T:N) ratio, or both based on the imaging via the medical imaging source.

[0112] Aspect 19. The method of Aspect 18, wherein the vial assembly comprises a septum disposed within a distal end of the vial body that is configured to seal the vial body, and the delivery assembly further comprises a needle fluidly coupled to a fluid source housing the fluid, the needle configured to puncture the septum of the vial body, the method further comprising moving the plunger in the proximal direction to direct the fluid from the fluid source through the needle into the vial body.

[0113] Aspect 20. The method of any of Aspect 18 to Aspect 19, wherein the plurality of nonradioactive polymeric microspheres are coated, embedded, or both with the biocompatiblematerial, the biocompatible material is selected from a group consisting of gold, titanium, steel, chromium, cobalt, cerium, yttrium, iodine, glass, platinum, or a combination thereof, and the plurality of particles are configured to mimic a specific shape, size, and gravity of a corresponding procedural dose of radioembolizing microspheres loaded with a radioactive compound, the radioactive compound comprising yttrium-90 (90Y):

[0114] It is noted that the terms “substantially” and “about” may be utilized herein to represent the inherent degree of uncertainty that may be attributed to any quantitative comparison, value, measurement, or other representation. These terms are also utilized herein to represent the degree by which a quantitative representation may vary from a stated reference without resulting in a change in the basic function of the subject matter at issue.

[0115] For the purposes of describing and defining the present disclosure it is noted that the term “substantially” is used herein to represent the inherent degree of uncertainty that may be attributed to any quantitative comparison, value, measurement, or other representation. The term “substantially” is used herein also to represent the degree by which a quantitative representation may vary from a stated reference without resulting in a change in the basic function of the subject matter at issue. As such, it is used to represent the inherent degree of uncertainty that may be attributed to any quantitative comparison, value, measurement, or other representation, referring to an arrangement of elements or features that, while in theory would be expected to exhibit exact correspondence or behavior, may in practice embody something slightly less than exact.

[0116] While particular embodiments have been illustrated and described herein, it should be understood that various other changes and modifications may be made without departing from the spirit and scope of the claimed subject matter. Moreover, although various aspects of the claimed subject matter have been described herein, such aspects need not be utilized in combination. It is therefore intended that the appended claims cover all such changes and modifications that are within the scope of the claimed subject matter.

[0117] What is claimed is:

Claims

CLAIMS1. A composition of a plurality of particles and fluid for use in a method of medical imaging of the composition of the plurality of particles and fluid within a subject, the method comprising: delivering the composition of the plurality of particles and fluid into a target area of a body of the subject, the plurality of particles comprising a plurality of non-radioactive polymeric microspheres comprising a biocompatible material; imaging the plurality of particles of the composition disposed within the body of the subject using a medical imaging source disposed external to the body of the subject; and estimating a lung shunt activity, tumor to normal (T:N) ratio, or both based off the imaging of the plurality of particles of the composition at the target area using the medical imaging source.

2. The method of claim 1, wherein the biocompatible material is a high density material selected from a group consisting of gold, titanium, steel, chromium, cobalt, cerium, yttrium, iodine, glass, platinum, or a combination thereof.

3. The method of claim 1, wherein the plurality of non-radioactive polymeric microspheres are coated with the biocompatible material.

4. The method of claim 1, wherein the plurality of non-radioactive polymeric microspheres are embedded with the biocompatible material.

5. The method of claim 1, wherein the plurality of non-radioactive polymeric microspheres are coated and embedded with the biocompatible material.

6. The method of claim 1, wherein the target area is disposed in an area surrounding a tumor in the body of the subject.

7. The method of claim 1, wherein the imaging comprises anterior and posterior planar imaging of the plurality of particles of the composition at the target area, the method further comprising: calculating, based on the anterior and posterior planar imaging, a count of the plurality of particles of the composition at a lung site as part of the target area;calculating, based on the anterior and posterior planar imaging, a total count of the plurality of particles of the composition at the lung site in combination with a liver site; and determining the lung shunt activity as a lung shunt fraction comprising the count of the plurality of particles of the composition at the lung site divided by the total count of the plurality of particles of the composition at the lung site in combination with the liver site.

8. The method of claim 1, the method further comprising: calculating, based on the imaging, a count of the plurality of particles of the composition at a tumor site as part of the target area; calculating, based on the imaging, a total count of the plurality of particles of the composition at a non-tumor site; and determining the T:N ratio as a ratio of the count of the plurality of particles of the composition at the tumor site to the count of the plurality of particles of the composition at the non-tumor site.

9. The method of claim 1, wherein the plurality of particles are configured to mimic a specific shape, size, and gravity of a corresponding procedural dose of radioembolizing microspheres loaded with a radioactive compound.

10. The method of claim 9, wherein the radioactive compound is yttrium-90 (90Y).

11. The method of claim 1, wherein the fluid comprises a saline solution.

12. The method of claim 1, the method further comprising: applying heat to the plurality of particles of the composition disposed within the body such that the plurality of particles degrade as the biocompatible material within the plurality of particles is heated.

13. A delivery assembly comprising: a console including a vial containment region; a vial assembly, comprising:a vial body containing a plurality of particles comprising a plurality of nonradioactive polymeric microspheres comprising a biocompatible material, and a plunger comprising a proximal end and a distal end, the proximal end disposed outside of the vial body, the distal end disposed within the vial body; a vial engagement mechanism extending from the console within the vial containment region, wherein the vial engagement mechanism is configured to engage the proximal end of the plunger, move the plunger in a proximal direction to pull a fluid into the vial body of the vial assembly to mix with the plurality of particles to form a composition of a plurality of particles and fluid, and move the plunger in a distal direction to push the composition of the plurality of particles and fluid out of the vial body of the vial assembly and through a catheter into a target site of a body of a subject; and a medical imaging source configured to image the composition of the plurality of particles and fluid at the target site to estimate a lung shunt activity, tumor to normal (T:N) ratio, or both.

14. The delivery assembly of claim 13, wherein the vial assembly comprises a septum disposed within a distal end of the vial body that is configured to seal the vial body.

15. The delivery assembly of claim 14, wherein the delivery assembly further comprising a needle fluidly coupled to a fluid source housing the fluid, the needle configured to puncture the septum of the vial body to direct the fluid from the fluid source through the needle into the vial body upon movement of the plunger in the proximal direction.

16. The delivery assembly of claim 13, wherein the plurality of non-radioactive polymeric microspheres are coated, embedded, or both with the biocompatible material, wherein the biocompatible material is selected from a group consisting of gold, titanium, steel, chromium, cobalt, cerium, yttrium, iodine, glass, platinum, or a combination thereof.

17. The delivery assembly of claim 13, wherein the plurality of particles are configured to mimic a specific shape, size, and gravity of a corresponding procedural dose of radioembolizing microspheres loaded with a radioactive compound, the radioactive compound comprising yttrium-90 (90Y).

18. A method of use of a delivery assembly, comprising: engaging a vial engagement mechanism extending from a vial containment region of a console with a proximal end of a plunger of a vial assembly, the vial assembly further comprising a vial body containing a plurality of particles comprising a plurality of nonradioactive polymeric microspheres comprising a biocompatible material, the proximal end of the plunger disposed outside the vial body, and a distal end of the plunger disposed within the vial body; moving the plunger in a proximal direction to pull a fluid into the vial body of the vial assembly to mix with the plurality of particles to form a composition of a plurality of particles and fluid; moving the plunger in a distal direction to push the composition of the plurality of particles and fluid out of the vial body of the vial assembly and through a catheter into a target site of a body of a subject; imaging the plurality of particles of the composition at the target site via a medical imaging source; and estimating a lung shunt activity, tumor to normal (T:N) ratio, or both based on the imaging via the medical imaging source.

19. The method of claim 18, wherein the vial assembly comprises a septum disposed within a distal end of the vial body that is configured to seal the vial body, and the delivery assembly further comprises a needle fluidly coupled to a fluid source housing the fluid, the needle configured to puncture the septum of the vial body, the method further comprising moving the plunger in the proximal direction to direct the fluid from the fluid source through the needle into the vial body.

20. The method of claim 18, wherein: the plurality of non-radioactive polymeric microspheres are coated, embedded, or both with the biocompatible material; the biocompatible material is selected from a group consisting of gold, titanium, steel, chromium, cobalt, cerium, yttrium, iodine, glass, platinum, or a combination thereof; andthe plurality of particles are configured to mimic a specific shape, size, and gravity of a corresponding procedural dose of radioembolizing microspheres loaded with a radioactive compound, the radioactive compound comprising yttrium-90 (90Y).

Images