Patent ID: 12186583

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

Referring now toFIG.1D, the inventive method and/or system may form a therapeutic agent referenced in commonly assigned U.S. patent application Ser. No. 14/243,623 filed on Apr. 2, 2014, where the entire contents of which are hereby incorporated by reference. The inventive therapeutic agent may have a cylindrical container25ofFIG.1Aand it may be placed in a cavity4of a wand3having a handle2ofFIG.1Dof an ophthalmic treatment device1. However, the inventive therapeutic agent is not limited to ophthalmic treatment devices1and may be used in other medical devices as understood by one of ordinary skill in the art and as described in further detail below.

The inventive therapeutic agent may be included in other treatment devices for treating other organs in the human body besides the human eye, eye lids or orbit. Other organs besides the human eye may include, but are not limited to the following organs and organ systems: organs of digestion including, but not limited to, the stomach, liver, small intestine, large intestine, rectum, and anus; organs of respiration, including, but not limited to, the lungs, nose, trachea, and bronchi; organs of excretion, including, but not limited to, the kidneys, urinary bladder, and urethra; organs of circulation, including, but not limited to, the heart, blood vessels, and spleen; organs of the nervous system, including, but not limited to, the brain and spinal cord; organs of reproduction, including, but not limited to, the testis and penis in male, the uterus, ovaries & mammary glands in the female; organs of the endocrine system, including, but not limited to, the pituitary gland, adrenal, thyroid, pancreas, parathyroid, and prostate glands; organs of senses, including, but not limited to, the skin, tongue, nose, and ears; organs of the immune system, including, but not limited to, the spleen, thymus, and bone marrow; organs of metabolism, including, but not limited to, the liver, just to name a few.

Referring back toFIG.1A, this figure illustrates a cross-sectional view of a therapeutic agent comprising a radioactive source20enclosed by a cylindrical container25. The exemplary container25and radioactive source20illustrated inFIG.1Aeach are shown with a cylindrical shape. However, other geometries for the source20and container25are possible and are within the scope of this disclosure as understood by one of ordinary skill in the art. The container25may be placed within a cavity4as illustrated inFIG.1D. The inventive method and system has thus been devised to allow the radioactive source20to be manufactured in such a manner as to control and spatially modulate the delivery of radiation doses30to the treatment area.

From the container25, radiation doses30and/or a radiation field35is produced by the radiation source20. The geometry and size of the radiation doses30are controlled by the geometry of the container25and the geometry of the radiation source20as well as the type, number, and geometry of holes/slots [not shown in thisFIG.1A] in a top wall of the container25.

As understood by one of ordinary skill in the art, the radiation field35illustrated inFIG.1Ais an over-simplification. Radiation, almost by definition is not linear. There usually exists at least Compton Scatter and photo-electric effects associated with radiation from a source and the source's resultant radiation field. The illustration of the radiation field35inFIG.1does not show penumbra, backscatter, and/or absorption which are generally present in all radiation fields.

A generally/substantially linear radiation distribution profile35is illustrated inFIGS.1A and1s, but at least one, object/goal of the combination of the container25and source20compared to conventional radiation distribution profiles of conventional sources [not shown] which do not have substantially linear profiles and/or are un-even.

Exemplary materials for the source20may include, but are not limited to,9Sr,16Yb,90Y,192Ir,103Pd,177Lu,149Pm,140La,153Sm,186Re,188Re,166Ho,166Dy,137Cs,57Co,169Er,165Dy,97Ru,193mPt,195mPt,105Rh,68Ni,67C,64Cu,109Cd,111Ag,198Au,199Au,201Tl,175Yb,47Sc,159Gd, and212Bi, just to name a few. The source20may include any combination of these materials as understood by one of ordinary skill in the art.

The source20may have a width dimension W1 between about 1.9 mm and about 21.9 mm. Meanwhile, the container25may have a width dimension W2 between about 2.0 mm and about 22.0 mm if the side wall of the container25is about 0.1 mil wide.

The cavity4may have a width dimension W3 which may be generally equal to the width dimension W2 of the container25plus a few mils, and thus, the width dimension W3 should range from between about 2.1 mm to about 22.1 mm, depending upon the size of the container25. However, as understood by one of ordinary skill in the art, each of the structures20,25may be tightly fitted within cavity4, and thus, the width dimensions can closely approach each corresponding structure which may contain another structure.

The container25may also have a thickness dimension T2 between about 0.25 mm and about 1.00 mm. The cavity4may also have a thickness dimension T3 between about 0.75 mm and about 3.00 mm. The thickness of the source20will be described in further detail below in connection withFIG.1C.

A variety of ways/methods/systems to control and spatially modulate the delivery of radiation doses30to a treatment area are outlined below. Briefly, modifications to the source20itself may be employed, its construction or production, along with modifications to its encapsulation/container25to both control and vary the spatial intensity and characteristics of delivered radiation dosages30. For clarity, these approaches are presented below in three subsections with the attached Figures:

(1) Methods/Systems for Manufacturing and Processing of Radionuclide Materials for Source20to Shape Sources20in Ways that Will Control their Output.

These approaches to controlling the distribution of the mass of the radionuclide source20afford the ability to vary the specific output across the face of a source20. This can have several results, the first being able to achieve greater uniformity of the isodose35despite source geometries that would normally result in non-uniform activity levels based solely on the perimeter profile of the source20. Another result could be the deliberate variation of the isodose35across the face of the source20to reflect the variable therapeutic dose requirements of a particular condition, patient or both.

(2) Methods/Systems for Shaping Radionuclide Materials for Sources20in an Additive or Molded Manufacturing Process.

Another way of controlling dose profiles for the purposes mentioned above would be to use manufacturing methods that would allow the selective deposition of variable amounts of a radionuclide-containing compound (including but not limited to such compounding agents as a polymer, adhesive, paint or ceramic) onto a uniform or shaped substrate material to form source20. Current methods of so-called additive manufacturing techniques could be adapted to use radioactive compounds as the deposited medium.

(3) Methods of Creating and Configuring Spatially Variable Dose-Rate Brachytherapy Sources20.

Sources20are often encapsulated in a secondary material, such as a container25, to give greater protection from damage to the source20, prevention of unwanted leaching or leakage of source material, or to provide shield of the body from nonbiocompatible materials. The invention, according to several different exemplary embodiments described below, may use this encapsulation/container25to control radiation effects by the following approaches:a. Variation of encapsulation/container25thickness to partially, and/or selectively shield the source to control emissions through variable attenuation.b. Vary the materials making up the encapsulation/container25to selectively deliver differing emissions around the source20.c. Vary the contours of the encapsulation/container25to control the internal position of the source20within the capsule/container25and thus the proximity of the source20and dose rate delivered to the tissue treatment volume.d. Shaping the encapsulation/container25to control, focus or distribute radiation35in a desired direction and/or intensity for therapeutic purposes.
(1) Ways to Process Radionuclide Source Material20to Control the Activity Profile Across the Source20

FIG.1Bshows a cylindrically shaped radionuclide source20with a variable concentric thickness/width denoted by dimensions TS1 and TS2 (inFIG.1C) which affects the dose profile35ofFIG.1A. As illustrated inFIG.1C, which is a cross-sectional view of source20, the edges having dimensions TS1 of the source disc20are thicker relative to the center which is thinner and has the dimension TS2 resulting in a concave shape on the large, facial surface of the source disc20. Exemplary edge dimensions TS1 may be between about 0.25 mm and about 2.00 mm. Exemplary center dimensions TS2 may be between about 0.05 mm and about 1.00 mm. However, other ranges are possible and are included with thin the scope of this disclosure. Such an exemplary geometry would result in a largely uniform dose distribution35across the source20compared to a conventional source20[not shown] which may have a uniform thickness across its cross-section.

Referring now toFIG.1E, this figure illustrates a disc-like geometry for a radioactive source20having a uniform mass across its area that may produce a centrally biased radiation/dose distribution profile35. Meanwhile,FIG.1Fillustrates a disc-like geometry for a radioactive source20having a non-uniform mass across its area that may produce a more uniform radiation/dose distribution profile35. In a general case, by varying the distribution of mass in selectively non-uniform patterns across the area of the source20, one can create a dose distribution profile35that is tailored to the specific, desired dosage pattern in a treatment situation that requires greater dose delivery in one portion of the treatment volume versus that in others.

FIGS.2A-2Eshow radionuclide source20with various perforation sizes and patterns which affects the dose profile35. Other patterns and perimeter shapes, beyond those illustrated, may be used as well as understood by one of ordinary skill in the art.

Specifically,FIG.2Ashows the radionuclide source20A with a series of holes/perforations35A that may range in diameter from between about 0.05 mm and about 1.00 mm. The holes35A are laid out in a diamond grid pattern according to this exemplary embodiment. While the holes35A are shown to have a circular shape, other geometries for the holes35A are possible and are within the scope of this disclosure. This holds true for the remaining embodiments illustrated in all the figures: while circular geometries25are shown, other geometries, like square, triangular, pentagonal, hexagonal, octagonal, etc. are possible without departing from the scope of this disclosure.

In the exemplary embodiment ofFIG.2A, holes35A having a larger diameter may be positioned in a geometric center of the pattern while holes35A having a smaller diameter maybe positioned at a periphery relative to the diamond grid pattern, or graduated in diameter from central to peripheral placement.

FIG.2Bshows the radionuclide source20B with a series of holes that may range in diameter from between about 0.05 mm and about 1.00 mm. The holes35B are laid out in a square grid pattern in which each rows and columns of the holes35B are in parallel alignments. Similar toFIG.2A, the larger diameter holes35B of this exemplary embodiment ofFIG.2Bmay be positioned in a geometric center or central region of the square grid pattern. Meanwhile, smaller diameter holes35B may be positioned at a periphery of the square grid pattern, or graduated in diameter from central to peripheral placement.

FIG.2Cshows the radionuclide source20C with a series of holes35C that range in diameter from between about 0.05 mm and about 1.00 mm. The holes35C of this exemplary embodiment and are laid out in a radiating grid pattern. For this radiating grid pattern ofFIG.2C, the holes35C may be aligned such that the holes35C are positioned along imaginary/geometric rays that emanate/originate from a single point in the geometric center of the disc source20C.

Similar toFIG.2AandFIG.2B, the larger diameter holes35C of this exemplary embodiment ofFIG.2Cmay be positioned in a geometric center or central region of the radiating grid pattern. Meanwhile, smaller diameter holes35C may be positioned at a periphery of the radiating grid pattern, or graduated in diameter from central to peripheral placement.

FIG.2Dillustrates a series of slots35D that may range in length and may have variable width over their length and are laid out in a parallel pattern in which a length of each slot is in parallel alignment with a neighboring slot35D. Exemplary length dimensions may range from between about 0.5 mm and about 10.0 mm. Exemplary width dimensions may range from between about 0.05 mm and about 0.50 mm.

In the exemplary embodiment illustrated inFIG.2D, a shortest length slot35D may be positioned at the top and bottom portion of the disc source20D and relative to the pattern. And a few longest length slots35D may populate a middle portion of the parallel pattern. The slots may have a taper such that their ends are narrow while their middle is broad.

FIG.2Eillustrates a custom shaped source20E with a series of variable perforations35D in a custom/unique arrangement. The custom shaped source20E ofFIG.2Eis shown to have an irregular, curved geometry which may have some geometrical symmetry. Other irregular geometries are possible including those which may not have any lines of symmetry as understood by one of ordinary skill in the art. According to this exemplary embodiment ofFIG.2E, the perforations35D are shown to be circular in shape. The diameters of the perforations may have ranges similar to those described in connection withFIG.2A.

According to this exemplary embodiment ofFIG.2E, and like the embodiment ofFIG.2A, the larger diameter holes35D may be positioned in a geometric center or central region of the custom pattern. Meanwhile, smaller diameter holes35D may be positioned at a periphery of the custom grid pattern. As understood by one of ordinary skill in the art, any of the perforation approaches shown inFIG.2AthroughFIG.2Dcould be utilized in this asymmetric variable design.

FIG.3shows a radionuclide source20F that has a uniform skin thickness TS3 but has surface deformations/folds40that may affect/impact an amount of material per unit volume. These deformations/folds40may affect the dose profile35. The deformations40may form channels47which may have a cross-sectional sinusoidal or v-shape. The channels47may have a depth that ranges from about 0.1 mm to about 1.5 mm.

The depth of the deformations may increase at a periphery of the source20F while they decrease towards the geometric center of the source20F. Stated differently, in this exemplary embodiment ofFIG.3, the disc20F has a pattern of concentric folds40that increase (or decrease) in height from the center towards the edge of the disc20F.

(2) Ways for Shaping Radionuclide Source Materials in an Additive or Molded Manufacturing Process (Shown Encapsulated within a Container25)

FIG.4Ashows a shape regulated matrix core material20G with radionudide particles uniformly distributed in matrix.FIG.4Aalso shows a simple capsule25A having a cylindrical shape that encapsulates the shaped core20G. The shaped core20G may have edge thicknesses TS1 and a central thickness TS2 which may be similar to those described above in connection withFIG.1C. Each capsule/container25ofFIGS.4A-4Dmay have a thickness between about 0.5 mm and about 2.0 mm.

FIG.4Bshows a shaped capsule25B with a matching core20H (matching geometry) which could result from being formed by using the capsule25B as a mold for the matrix core material. The central thickness dimension TS4 of this exemplary embodiment may have a magnitude between about 0.5 mm and about 2.0 mm.

FIG.4Cshows a capsule25C with a perforated matrix core20I. In this exemplary embodiment, the perforations may have a cylindrical shape with various diameters D1, D2. The smallest diameter D1 may have a magnitude of about 0.05 mm, while the largest diameter D2 may have a magnitude of about 1.00 mm.

FIG.4Dshows a shaped capsule25D with a non-matching core20J where the capsule shape maintains the source position within the capsule25D. The shaped core20J may have edge thicknesses TS1 and a central thickness TS2 which may be similar to those described above in connection withFIG.1C.

FIG.4Eillustrates a configuration of a radionudide source where layers of radionudide source material having either the same or differing perimeter profiles relative to each other. In this exemplary embodiment, four different layers20EE1,20EE2,20EE3, and20EE4are provided. The first layer20EE1has a sector shape/geometry while the second layer20EE2may comprise a thin ring geometry. The third layer20EE3and fourth layer20EE4may comprise a disc geometry similar to the other disc geometries previously described. The arrows indicate a sequence in which each layer20EE is coupled to the next.

Referring now toFIG.4F, this figure illustrates the four layers ofFIG.4Ethat are assembled and housed in an encapsulation/container25(shown partially cut away) or atop a substrate to effect a specific radiation output profile or level. As illustrated inFIG.4F, the first layer20EE1is positioned within the second layer20EE2since the second layer20EE2has a ring-shape. Both the first layer20EE1and second layer20EE2rest upon the third layer20EE3which has a disc shape/geometry.

The container25may further comprise an orientation marker35FF1having a triangular shape in this exemplary embodiment. The orientation marker35FF1provides the medical practitioner with guidance as to the placement of the variable output pattern of the radionuclide source20. Other marker types and configurations for orientation marker35FF1are possible and are included within the scope of this disclosure. These markers35FF1may be applied by one or more known methods including, but not limited to, painting, etching, laser marking, debossing, and/or embossing, etc.

The three layers20EE1,20EE2,20EE3may each have uniquely sized perimeters as well as geometries. Thus, each layer20EE may have a different surface topography which may change each layer's respective mass pattern to effect asymmetric absorption of energy when activated in a reactor. Geometry of each layer20EE and the distance of each layer20EE to the anterior surface of the container25FF1may create unique and customized radiation patterns.

Referring now toFIG.4G, this figure illustrates a cross-sectional view of how the layers of the radionuclide source material20EE ofFIGS.4E-4Fmay be coupled together with an adhesive425, such as glue. As shown inFIG.4E, the fourth, bottom layer20EE4may be placed down on a surface. Next, the third layer20EE3may be coupled to the fourth layer20EE4by the adhesive425. Subsequently, the second layer20EE2having the ring-shape/geometry may be placed on top of the third layer20EE3and coupled to the third layer20EE3with the adhesive425. The first layer20EE1having the sector-shape/geometry may then be positioned on top of the third layer20EE3and within the second layer20EE2and coupled to the third layer20EE3with the adhesive425. The coupled layers20EE of the radionuclide source material may then be positioned within the container25FF1. Container25FF1may take the form of an of the container25described in this disclosure.

Referring now toFIG.4H, this figure illustrates a cross-sectional view of how the layers of the radionuclide source material20EE ofFIGS.4E-4Fmay be coupled together with welds403via spot welding or laser welding. As shown inFIG.4E, the fourth, bottom layer20EE4may be placed down on a surface. Next, the third layer20EE3may be coupled to the fourth layer20EE4by a weld430. Subsequently, the second layer20EE2having the ring-shape/geometry may be placed on top of the third layer20EE3and secured to the third layer20EE3by a weld430.

The first layer20EE1having the sector-shape/geometry may then be positioned on top of the third layer20EE3and within the second layer20EE2and coupled to the third layer20EE3with a weld430. The coupled layers20EE of the radionuclide source material may then be positioned within the container25FF1. Container25FF1may take the form of any of the containers25described in this disclosure.

Referring now toFIG.4I, this figure illustrates a cross-sectional view of how the layers of the radionuclide source material20EE ofFIGS.4E-4Fmay be coupled together with a potting material435. The potting material may comprise thermosetting plastics and silicone rubber gels, which may include, but are not limited to, polyurethane, silicone, and epoxy. In the potting process, the potting material435is applied as an insulating liquid compound that hardens, permanently protecting the layers20EE.

As shown inFIG.4E, the fourth, bottom layer20EE4may be placed down on a surface. Next, the third layer20EE3may be positioned on the fourth layer20EE4. Subsequently, the second layer20EE2having the ring-shape/geometry may be placed on top of the third layer20EE3. The first layer20EE1having the sector-shape/geometry may then be positioned on top of the third layer20EE3and within the second layer20EE2. Next, the layers20EE are all coupled together by the potting material435which may be applied as an insulating liquid which later hardens. The coupled layers20EE of the radionuclide source material may then be positioned within the container25FF1. Container25FF1may take the form of any of the containers25described in this disclosure.

Referring now toFIG.4J, this figure shows a configuration where layers20JJ of radionuclide source material may have either the same or differing perimeter profiles and features relative to each other. Specifically, each layer20JJ may have options of the previously described features such as, but not limited to perforations/holes35, selective sectional thickness variations, and/or variable surface contours to affect each layer's local output of radiation. In the exemplary embodiment illustrated inFIG.4J, three layers20JJ1,20JJ2,20JJ3are depicted. Each layer20JJ may have holes35where each layer20JJ has holes35having varying diameters, similar to those described above and illustrated in connection withFIG.2E.

Referring now toFIG.4K, this figure illustrates the layers20JJ ofFIG.4Jassembled together and contained within a housing25FF1. The housing25FF1is shown partially cut away. Container25FF1may take the form of any of the containers25described in this disclosure. The container25FF1may further comprise an orientation marker35FF1, which has been previously described in connection with FIG.FIG.4Fabove.

The three layers20JJ1,20JJ2,20JJ3may each have uniquely sized perimeters and geometries, as well as thicknesses. Further the patterns for the aperture35in each layer20JJ may be unique or similar relative to another layer20JJ. Thus, each layer20JJ may have a different surface topography, and/or pattern of apertures35which may change each layer's respective mass pattern to effect asymmetric absorption of energy when activated in a reactor. Geometry of each layer20JJ and the distance of each layer20JJ to the anterior surface of the container25may create unique and customized radiation patterns.

FIGS.5A-5Dshow composite sources20, both with and without a substrate material50, with various methods of formation. Specifically,FIG.5Ashows a shaped substrate50A with molded or poured source material20K. The shaped source material20K may have edge thicknesses TS1 and a central thickness TS2 which may be similar to those described above in connection withFIG.1C. The areas/regions of the substrate50A [and for the other embodiments ofFIGS.5B-5D] which do not have the source material may be made of a polymeric material, a ceramic or other moldable compound material as understood by one of ordinary skill in the art.

Polymeric materials, as understood by one of ordinary skill in the art, can be grouped into three general categories: 1) thermoplastics; 2) thermosets; and 3) elastomers. Thermoplastics can be softened and re-hardened indefinitely, as often as they are reheated providing the temperature is not high enough as to cause decomposition. Thermoplastics have linear or branched molecular chain structures with few links, if any between chains. Typical examples include nylon, polyethylene, polycarbonate, and polyvinyl chloride (PVC).

Meanwhile, thermoset polymers are rigid and not softened by the application of heat. Such polymers have molecular structures which are extensively cross-linked. Because of this, when heat causes the bonds to break, the effect is not reversible on cooling. Typical examples of thermoset polymers include, but are not limited to, phenolics, epoxies and resins.

Elastomers are polymers which as a result of their molecular structure allow considerable elastic behavior. Such materials are lightly cross-linked polymers. Between the cross-links the molecular chains are fairly free to move. Elastomers may include, but are not limited to, rubber, silicone, and polyurethane.

FIG.5Bshows a custom shaped substrate50B with molded or poured source material20L. According to this exemplary embodiment, the source material20K may have an irregular geometry which is not symmetrical. However, irregular geometries which have one or more lines of symmetry are possible and are within the scope of this disclosure.

FIG.5Cshows an additive application of source material20M on a substrate50C as indicated by the sequence of curved lines55A,55B forming the source material20M.

FIG.5Dshows a selectively built-up coating of source material20N on a substrate50D. Either generic regular/symmetrical or custom/irregular profiles/cross-sections are possible, where encapsulation is also shown by either a molded or poured encapsulating material such as a polymer, ceramic or other moldable compound60A, or by an outer encapsulating container.

FIG.5Eshows a 3D printed source material20-O on substrate50E with encapsulation shown by either a molded or poured encapsulating material such as a polymer, ceramic or other moldable compound60B, or by an outer encapsulating container251.

FIG.5Fshows a 3D printed source material20P with no substrate and in encapsulation (potted) by either a molded or poured encapsulating material such as a polymer, ceramic or other moldable compound60C, or by being placed within an outer encapsulating container25J. The source material20P may be centrally placed in potting material or adhered if in a capsule.

FIGS.6A-6Dshow other carrier methods used in conjunction with beads, seeds, and microspheres to form the desired dose profile35. Specifically,FIG.6Ashows controlled spacing of radioactive seeds20Q in a molded carrier65. Each seed20Q may have length dimension L1 which has a magnitude that ranges between about 1.0 mm to about 20.0 mm. Each seed20Q may have width dimension W1 which has a magnitude that ranges between about 0.8 mm to about 4.0 mm. The seeds20Q may be secured to a carrier/encapsulation65. The carrier/encapsulation65may be the same as inFIG.5Fdiscussed above.

FIG.6Bshows radioactive beads20R on a wire or string70, spaced and coiled to derive the desired dosage profile. Each bead20R may have length dimension L2 which has a magnitude that ranges between about 0.02 mm to about 5.0 mm. Each bead20R may have width dimension W2 which has a magnitude that ranges between about 0.02 mm to about 5.0 mm. The beads20R may be secured to a carrier/encapsulation75. Carrier/encapsulation75may be formed as similarly described and as illustrated inFIG.5Fdiscussed above.

FIG.6Cshows radioactive microspheres S in a polymer matrix75with activity/dose35controlled by a molded thickness as illustrated inFIG.6D. As illustrated inFIG.6D, the polymer matrix20K may have edge thicknesses TS1 and a central thickness TS2 which may be similar to those described above in connection withFIG.1C. The microspheres S may have diameters which range from between about 0.2 mm and about 2.0 mm. The biocompatible resin microspheres S containing yttrium-90 have a median diameter of about 32.5 microns (a range between about 20.0 and 60.0 microns). Yttrium-90 is a high-energy beta-emitting isotope with no primary gamma emission. The maximum energy of the beta particles is usually about 2.27 MeV with a mean of about 0.93 MeV. Materials could include epoxies, PMMA, polyesters and copolyesters and other materials of suitable structural strength, biocompatibility and radiation resistance.

FIG.7shows a capsule25used for encapsulating radionuclide source materials (not shown). The capsule25may have dimensions described above in connection withFIGS.4-5. This thin-walled encapsulation25could be made from metals, polymers, ceramics or glass. In another exemplary embodiment the encapsulation25may comprise a material which is poured or molded so as to wholly or partially surround or pot the source20(not shown) with encapsulating material25. Exemplary materials for capsule25may include, but are not limited to, any one or a combination of titanium, gold, silver, steel, copper, and acrylic.

FIGS.8A-8Eillustrate manufacturing methods for source encapsulation housings25. Bonding between the components illustrated inFIGS.8A-8Emay accomplished by welding, sealing, crimping, or any combination thereof. The housings/capsules25ofFIGS.8A-8Emay have dimensions as previously described for the earlier exemplary embodiments.

Specifically,FIG.8Ashows a three-piece assembly capsule25which includes a lid800, perimeter wall804and substantially flat bottom802. Once assembled, this three-piece capsule25may hold any one of the radioactive sources20described previously and illustrated in the Figures of this disclosure.

FIG.8Billustrates a two-piece capsule25that comprises a lid800which is attached to a bottom806with an integral wall that is either a stamped formed element or a machined element. Once assembled, this two-piece capsule25may hold any one of the radioactive sources20described previously and illustrated in the Figures of this disclosure.

FIGS.8C-8Dshow configurations with two nested capsule halves800-806, welded, sealed, or crimped together to form a capsule25. Specifically,FIG.8Cillustrates a lid800which has its own integral side wall808A which is positioned within a bottom806A. The bottom806A ofFIG.8Chas its own integral side wall808B which encapsulates/surrounds the integral side wall of the lid800. The integral side wall808B of the bottom806may have a height which completely surrounds/encapsulates [is greater than] a height dimension for the integral side wall808A of the lid800.

FIG.8Dillustrates an exemplary embodiment similar toFIG.8Cexcept that the integral side wall808B of the bottom806may have a height which does not completely surround/encapsulate [is less than or equal to] a height dimension for the integral side wall808A of the lid800.

FIG.8Eillustrates a clamshell configuration having a lid800and bottom806C suitable for welding. According to this exemplary embodiment, the lid800and bottom806C may have symmetrical geometries relative to one another. That is, the lid800may have a geometry which is a mirror image of the bottom806C. However, other exemplary embodiments are possible in which the geometries of the lid800and bottom806are not identical, similar toFIGS.8A-8D, and which may be suitable for welding.

FIGS.9A-9Eshow examples of various assembly methods for encapsulation to form a capsule/housing25using non-metallic materials. Other material combinations are also possible, such as metal/glass, metals/polymers combinations, etc. The housings/capsules25ofFIGS.9A-9Emay have dimensions as previously described for the earlier exemplary embodiments. The capsule25may encapsulate any of the radioactive sources20previously described and illustrated.

Specifically,FIG.9Aillustrates a glass lid800and glass bottom806bonded to a polymer wall804. Exemplary polymers for polymer wall804include, but are not limited to epoxies, Polymethyl methacrylate (PMMA), Polyesters and copolyesters and other materials of suitable structural strength, biocompatibility and radiation resistance.

FIG.9Bshows a glass lid800bonded to a glass bottom806with an integral sidewall808.FIG.9Cillustrates a poured or molded encapsulation900surrounding any source core type described here. The encapsulation900may include one or more of the following materials: epoxies, PMMA, Polyesters and copolyesters and other materials of suitable structural strength, biocompatibility and radiation resistance.

FIGS.9D-9Eshows encapsulations900A-B,900C-D with variable thickness or protruding inner features. Such shaping could serve simply to hold the source or to act as a defacto mold for poured or injected radionuclide source materials, thus inducing a desired shape variation to the source20. This would provide a positionally controllable activity level resulting from the source thickness profile.

Specifically,FIG.9Dillustrates encapsulations900A-B forming a capsule25which has an irregular, non-repeating, non-geometrical protrusions. Meanwhile,FIG.9Eillustrates encapsulations900C-D forming a capsule25which has regular, repeating, and simple geometry type protrusions.

FIGS.10A-10Cshow several configurations of metallic enclosures25wherein control of radiation emissions are implemented. The housings/capsules25ofFIGS.10A-10Cmay have dimensions as previously described for the earlier exemplary embodiments. The capsules25ofFIGS.10A-10Cmay encapsulate any of the radioactive sources20[not shown in these figures] but were previously described above and illustrated.

FIG.10Aillustrates a metal encapsulation25where a secondary metal section1000B having a different shielding capability relative to a primary metal section1000A has been added to the capsule25and affixed in a sealed manner thereto, usually by welding and/or by crimping with a chemical adhesive as understood by one of ordinary skill in the art.

FIG.10Bshows a metal encapsulation25where a section1000C has been made thinner to allow greater radiation levels to be allowed through the wall of the capsule25relative to the remaining section1000A of the wall. As understood by one of ordinary skill in the art, shielding radiation and a corresponding radiation attenuation amount are based on material, initial thickness, reduced thickness, shielding material, the type of radionuclide in the source, and the source activity level.

FIG.10Cillustrates a metal encapsulation25where a section1000D has been shaped to focus radiation in a particular direction, or at a specific focal area that is projected through a thin section1000C of the capsule25. The thicknesses of this exemplary embodiment ofFIG.10Cmay be similar to those described above in connection withFIG.10B.

FIGS.11A-11Cshow several configurations for capsules25where several layers of a material, such as a polymer, glass or a ceramic is produced using additive/layered manufacturing methods to form the encapsulation25. If metal-containing materials are used such as lead or tungsten, such materials may provide shielding properties relative to the radioactive source20contained within each capsule25. The housings/capsules25ofFIGS.11A-11Emay have dimensions as previously described for the earlier exemplary embodiments. The capsules25ofFIGS.11A-11Cmay encapsulate any of the radioactive sources20that were previously described above and illustrated.

Some of the exemplary embodiments ofFIGS.11A-11Ehave variable shielding features to provide further control over the type and distribution35[SeeFIG.1A] of radiation emissions from the source20. Compounds capable of being printed by additive means/by layers can have metal constituents added to them, allowing uniquely suited and shaped shielding for the radiation source material to be produced or “printed”/3-D printed as understood by one of ordinary skill in the art.

Exemplary compounds include, but are not limited to, finely granulated, dense metal such as tungsten, stainless steel or lead mixed into a carrier matrix such as a thermoplastic polymer such as a copolyester, Poly Cyclohexylenedimethylene Terephthalate glycol (PCTG) for example, or a catalyzing reaction polymer such as an ultra-violet (UV) light initiated reaction epoxy or polyester compound.

Specifically,FIG.11Ashows a 3D printed encapsulation25optionally with a metal, such as stainless steel, titanium or gold, or a metal impregnated compound1100. The compound1100may include, but is not limited to, finely granulated tungsten, stainless steel or lead mixed into a carrier matrix such as a thermoplastic polymer such as a copolyester, PCTG for example, or a catalyzing reaction polymer such as a UV light-initiated-reaction epoxy or polyester compound, or a ceramic or a glass.

The printed encapsulation25embodiment ofFIGS.11A-11Emay be formed in layers using 3D printing techniques, build-up manufacturing, or other layering methods. Other layering or additive manufacturing methods that one of ordinary skill in the art can utilize, include, but are not limited to at least seven technologies listed in the ISO standards which may comprise any one and/or a combination of the following methods: binder jetting, directed energy deposition, material extrusion, material jetting, powder bed fusion, sheet lamination, and vat photopolymerization.

FIG.11Bshows a composite shield type of capsule25where the inside of the capsule25is given a contour1105to allow variable dose rate emissions across the face of the source20within.FIG.11Cshows a composite shield type of capsule where the inside of the capsule25is given a contour1105with a secondary layer1110of different shielding density to allow variable shielding across the face of the source20within. A first shielding material may comprise a low density shielding material that may include, but is not limited to, a polymer such as PMMA or a glass, while a second material may comprise a high density shielding material. The high density shielding material may include, but is not limited to, metal, (as mentioned above in reference toFIG.11A,) infused into a polymer, glass or polymer/ceramic slurry.

FIG.11Dillustrates a composite shield type of capsule25where the outer surface1115is given a contour to vary the shielding across the face of the source20and/or to fit against an anatomical feature. This embodiment ofFIG.11Dmay be formed from 3D printing techniques, in a layered fashion as understood by one of ordinary skill in the art.

FIG.11Eshows a multi-material composite shield type of capsule25to allow variable shielding across the face of the source20within. In this exemplary embodiment, the first material1115enveloping the entire source20may comprise a high density shielding material while the second material1120that is deposited on the first material1115may comprise a low density shielding material.

The low density shielding material1120may comprise a polymer such as PMMA or a glass while the high density material1115may comprise a metal, (as mentioned above in reference toFIG.11A,) a metal infused into a polymer, glass or polymer/ceramic slurry to be molded or built up through 3D printing techniques.

Referring now toFIGS.12and13, an organ of the body, such as an eye1205A, can grow a tumor1210A which usually needs treatment. Placement of a radionuclide, such as the radioactive sources20illustrated inFIGS.1-11described above, in close contact with the tumor1210A, often referred to as brachytherapy, is a widely used cancer treatment.

Here two treatment situations are illustrated: one shown inFIG.12A-12B, where the tumor1210A does not present a distortion of the geometry of an outer wall of the organ1205A. The other situation illustrated inFIGS.13A-13Bis where the tumor1210B grows outward from the surface of the organ12058, creating a new contour1315which distorts a geometry of an outer wall of the organ1205B. As noted previously, the inventive radioactive sources20ofFIGS.1-13may be included in other treatment devices for treating other organs1205in the human body besides the human eye.

Other organs1205besides the human eye, eye lids and orbit which may be treated by the inventive radioactive sources20, may include, but are not limited to the following organs and organ systems: organs of digestion including, but not limited to, the stomach, liver, small intestine, large intestine, rectum, and anus; organs of respiration, including, but not limited to, the lungs, nose, trachea, and bronchi; organs of excretion, including, but not limited to, the kidneys, urinary bladder, and urethra; organs of circulation, including, but not limited to, the heart, blood vessels, and spleen; organs of the nervous system, including, but not limited to, the brain and spinal cord; organs of reproduction, including, but not limited to, the testis and penis in male, the uterus, ovaries & mammary glands in the female; organs of the endocrine system, including, but not limited to, the pituitary gland, adrenal, thyroid, pancreas, parathyroid, and prostate glands; organs of senses, including, but not limited to, the skin, tongue, nose, and ears; organs of the immune system, including, but not limited to, the spleen, thymus, and bone marrow; organs of metabolism, including, but not limited to, the liver, just to name a few.

Referring back toFIG.12B, the variable strength source20has its outer surface geometry contoured to match the normally contoured surface1215of the organ1205A while the cross sectional geometry1230of the source20may be variable in its thickness dimension and is so shaped as to provide, through its cross sectional thickness variations, a unique radiation output/emission corresponding to the treatment demands of non-uniformities present in a typical tumor1210A. The substrate or container shell1225A is formed to hold the radiation source material20and provide any necessary features for placement and/or anchoring.

Also illustrated inFIG.12Bis a medical device1shown with dashed lines which may comprise the cavity4described above in connection withFIG.1D. The medical device1ofFIG.13Bis a mere representation [oversimplification] of the ophthalmic treatment device1illustrated inFIG.1D. However, other medical devices1that are used to treat other cancers and other organs as discussed above are included within the scope of this disclosure.

FIG.12Cshows a sample cross sectional view through the radiation source1225. ThisFIG.12Cshows the source material20the substrate or container shell1225A, and the variable thickness source material20, is custom made to match to the patient's tumor characteristics, and specifically the unique external and internal geometry of the tumor1210A. The source material20may be formed by any one of the methods described previously and illustrated inFIGS.1-11.

FIG.12Dillustrates an external, perspective view of the container shell1225A. The external view ofFIG.12Dshows how the external shell1225A may have a regular geometry having one or more lines of symmetry. Meanwhile, as illustrated inFIG.12Cdescribed above, the internal source or source material20may comprise an irregular geometry which may or may not have any lines of geometrical symmetry.

Referring now toFIG.13A, this figure illustrates a tumor1210B which creates a protruding, convex contour or surface geometry1315, (or in other instances not illustrated—a depressed or concave contour). As illustrated inFIG.13B, a face or surface geometry1320of the radioactive source material20is contoured in its manufacture to conform to the irregularities present in the external geometry and internal geometry of the tumor1210B. This data for the external geometry and internal geometry of the tumor1210B may be derived from a variety of sources including photography, but most advantageously from three-dimensional (3D) datasets from magnetic resonance imaging (MRI), computed tomography (CT) scan data, or other medical imaging techniques capable of producing such 3D data.

InFIG.13A, an organ12056having an internal tumor12106creating an irregular protruding geometry1315of the organ1205B that would otherwise make brachytherapy difficult is illustrated. InFIG.13B, a source20that has been manufactured to have its mating surface1320conform to the irregularities in the surface geometry1315of the organ1205B so as to make close contact across the mating surface1320between the source20and the irregular surface geometry1315. As noted above, the container1225B may be placed in the cavity4of wand3as illustrated inFIGS.1A and1D.

Also illustrated inFIG.13Bis a medical device1shown with dashed lines which may comprise the cavity4described above in connection withFIG.1D. The medical device1ofFIG.13Bis a mere representation [oversimplification] of the ophthalmic treatment device1illustrated inFIG.1D. Other medical devices1besides the ophthalmic treatment device1are possible for treating other types of cancer as described above and are included within the scope of this disclosure as understood by one of ordinary skill in the art.

InFIG.13C, the source20has variations in its thickness at different locations1325A,13256across the width dimension of the source20. These correspond with the therapeutic requirements for the internal tumor1210B as relates to the variable tumor geometries (both internal and external) needing radioactive irradiation treatment. In other words, both the contact/mating surface1320and the thickness of the source20, as shown by locations1325A,13256ofFIG.136, are manufactured as controlled contours based on contour conformity and dose conformity corresponding to the unique geometry of the internal tumor1210B. As noted above, the substrate or container shell12256is formed to hold the radiation source material20and provide any necessary geometrical features/contours for placement and/or anchoring to the organ1205so as to be in very close proximity to the internal tumor1210B.

FIG.13Dillustrates an external, perspective view of the container shell1225B. The external view ofFIG.13D, likeFIG.12D, shows how the external shell1225B may have a regular geometry having one or more lines of symmetry—opposite to the source material20contained therein. Specifically, as illustrated inFIG.13Cdescribed above, the internal source or source material20may comprise an irregular geometry which may or may not have any lines of geometrical symmetry.

Referring now toFIG.13E, this figure illustrates a source20that has been manufactured to have its mating surface1320conform to the irregularities in the surface geometry of a tumor1210C growing external relative to the organ1205C of the eye. This conforming shape of the mating surface1320of the source20facilitates dose contact between the source20and the irregular surface geometry of the external tumor1210C. LikeFIG.13E, the irregularly shape source20may have a regularly shaped container/shell1225C that may have one or more lines of geometrical symmetry while the source20may not have any lines of symmetry or far less relative to the container1225C. As noted above, the container1225C may be placed in the cavity4of wand3as illustrated inFIGS.1A and1D. The container1225C may have contoured geometries/geometrical features that mirror an organ1205and/or a tumor1210to facilitate closer coupling of the container1225C to human tissue.

InFIG.13F, the source20has variations in its thickness at different locations across the width dimension of the source20. These correspond with the therapeutic requirements for the external tumor1210C ofFIG.13Eas relates to the variable tumor geometries (both internal and external) needing radioactive irradiation treatment. In other words, both the contact/mating surface1320and the thickness of the source20are manufactured as controlled contours based on contour conformity and dose conformity corresponding to the unique geometry of the external tumor1210C. As noted above, the substrate or container shell1225C is formed to hold the radiation source material20and may provide any necessary geometrical features/contours for placement and/or anchoring directly to the external tumor1210C (ofFIG.13E).

FIG.13Gillustrates an external, perspective view of the container shell1225C ofFIGS.13E and13F. The external view ofFIG.13G, likeFIG.12D, shows how the external shell1225C for the source20may have a regular geometry having one or more lines of symmetry—opposite to the irregular shaped source material20contained therein. Specifically, as illustrated inFIG.13Gdescribed above, the internal source or source material20may comprise an irregular geometry which may or may not have any lines of geometrical symmetry or far fewer relative to the several geometrical lines of symmetry present in the shell/container1225C.

The shell container1225C is not limited to its regular/normal geometry. Each source container1225may have a shape related to both its shielding requirements and the use requirements. For example, like the source material20, the container may be designed/shaped to fit around anatomical features such as shown in13E where it may fit around the eyelid, and clears the nose, plus other features arising from use requirements, such as mounting, grasping or suturing eyelets for example.

Referring now toFIG.14, this figure illustrates an exemplary method1400for providing a customized radiation source for producing a unique therapeutic radiation dose. Block1405is the first step of the exemplary method1400in which a unique geometry of a tumor1210and/or organ1205may be determined/calculated. According to one exemplary embodiment, data for the external geometry and internal geometry of a tumor1210and/or organ may be derived from a variety of sources including photography, but most advantageously from three-dimensional (3D) datasets from magnetic resonance imaging (MRI), computed tomography (CT) scan data, or other medical imaging techniques capable of producing such 3D data.

Next, in step1410the therapeutic radiation dose requirements for the tumor1210and/or organ1205may be determined. A general purpose computer running a specific application program and/or a medical practitioner may assess what levels of therapeutic radiation should be applied to the tumor1210and/or organ1205based on the data collected in Step1405.

Subsequently, in step1415, a unique radioactive source20may be prepared by controlling a distribution of mass across the geometry of the radionuclide source material20in accordance with the unique geometry found in step14015. Generally, the unique radioactive source20may be prepared according to any one and/or combination of structures illustrated inFIGS.1B-1C,1E-1F, and2A-6Ddescribed above.

In step1420, elements of the container25for the radionuclide source20may be optionally adjusted in order to further control the therapeutic radiation emitted by the radioactive source20. Generally, the container25may be prepared according to any one and/or combination of structures illustrated inFIGS.7-11Edescribed above.

Next, in step1425, the radioactive source20is placed into the container25. In optional step1430, the container25is then placed in a cavity4of a medical device1, such as illustrated inFIG.1D, in step1430. Step1430is optional since a medical device may not be needed to position the container25adjacent to or in proximity to the tumor1210and/or organ. Other structures besides medical devices1could be deployed without departing from this disclosure. For example, a bandage, an adhesive, or some other physical structure may be used to position the container25adjacent to or in proximity to the tumor1210and/or organ1205. Further, the container25may be manufactured to have a structure for fastening itself adjacent or in proximity to the tumor1210or organ1205.

In step1435, the radioactive source20within the container25is then placed against and/or in proximity of the tumor1210and/or organ1205. See for example the exemplary embodiments illustrated inFIGS.12B,13B, and13E. The process1400then returns where the steps may be repeated.

The exemplary embodiments of the inventive method and system described above are interchangeable as understood by one of ordinary skill in the art. Various embodiments may be combined with other embodiments without departing from the scope of this disclosure. That is, one or more embodiments illustrated in the several figures may be combined together. As but one non-limiting example, the exemplary embodiments illustrated inFIG.2CandFIG.2Dcould be combined. Thus, a source20may be produced that includes a combination of holes35C [fromFIG.2C] and slots35D [fromFIG.2D]. Other combinations of the exemplary embodiments are possible and are included within the scope of this disclosure.

Certain steps in the exemplary methods described herein naturally precede others for the invention to function as described. However, the invention is not limited to the order of the steps described if such order or sequence does not alter the functionality of the system and methods of the present disclosure. That is, it is recognized that some steps may performed before, after, or parallel (substantially simultaneously with) other steps without departing from the scope and spirit of the invention. In some instances, certain steps may be omitted or not performed without departing from the invention. Further, words such as “thereafter”, “then”, “next”, etc. are not intended to limit the order of the steps. These words are simply used to guide the reader through the description of the exemplary methods.

Alternative embodiments for the system and method of the present disclosure will become apparent to one of ordinary skill in the art to which the invention pertains without departing from the scope of this disclosure.

In the claims, means-plus-function clauses are intended to cover the structures described herein as performing the recited function and not only structural equivalents, but also equivalent structures. Thus, although a nail and a screw may not be structural equivalents in that a nail employs a cylindrical surface to secure wooden parts together, whereas a screw employs a helical surface, in the environment of fastening wooden parts, a nail and a screw may be equivalent structures. It is the express intention of the applicant not to invoke 35 U.S.C. § 112, sixth paragraph for any limitations of any of the claims herein, except for those in which the claim expressly uses the words ‘means for’ together with an associated function.

Therefore, although selected aspects have been illustrated and described in detail, it will be understood that various substitutions and alterations may be made therein without departing from the spirit and scope of the present invention, as defined by the following claims.