Mosaic surface brachytherapy device and system

Abstract

A device for surface brachytherapy includes a base configured for positioning a source with respect to a target area, an aperture defined in the base, and a shield body configured for coupling with the base, so that the source is secured within the base proximate or adjacent the aperture. The aperture is configured to transmit radiation emitted by the source, where the radiation is directed toward the target area. The base and shield body are configured to absorb at least a portion of the radiation emitted by the source, where the radiation is not directed toward the target area.

Description

PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01MOSAIC SURFACE BRACHYTHERAPY DEVICE AND SYSTEMCROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] This application claims priority to U.S. Provisional Application No. 63 / 689,544, filed August, 30, 2024, entitled “Tessellated Surface Brachytherapy Device and System,” which is5 incorporated by reference herein, in the entirety and for all purposes.GOVERNMENT LICENSE RIGHTS

[0002] This invention was made with United States government support under contract 5U01HL152405-02 awarded by the National Institutes of Health. The U.S. government has certain rights in the invention.10 FIELD

[0003] This disclosure relates to radiation therapy, including brachytherapy treatment. More generally, the disclosure relates to surface brachytherapy and related radiology techniques for treatment of cancerous and noncancerous tumors and lesions, and related conditions.BACKGROUND

[0004] Tumors are a form of lesion defined by an abnormal growth or mass of tissue. Lesions are a broader class of abnormal or damaged tissue caused by injury, infection, or disease, including both tumors and other forms of damage such as wounds, scar tissue, warts, nevi, ulcers and sores. While tumors and other lesions may be either benign or malignant, even benign conditions can have adverse or deleterious effects, depending on type, size, growth rate and20 location. Lesions also include precancerous conditions that may cause pain or discomfort, or which can develop into cancer at a later time.

[0005] Skin cancers are a subclass of cancerous lesions affecting millions of Americans each year, and many times that number worldwide. Skin cancers are divided into melanoma skin cancer (MSC) and non-melanoma skin cancer (NMSC), the latter including both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).

[0006] Age and cumulative ultraviolet exposure are primary drivers of skin cancer and related conditions. Increased exposure can also lead to the formation of precancerous lesions such as actinic keratoses (or “solar” keratoses), which may develop into squamous cell carcinoma over time. Ultraviolet radiation can also affect the appearance and healing rate of other, non¬30 cancerous conditions such as keloids, an abnormal growth of scar tissue at the site of a cutaneous (skin) injury.PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01

[0007] Early detection and proper treatment are critical to managing these conditions. Fortunately, a range of successful techniques have been developed, including surgical, cryogenic, chemical, and radiological methods (radiotherapy).

[0008] Radiotherapy techniques include both external beam radiation and brachytherapy, in5 which a radioactive source is used to treat the tumor or lesion. An advantage to brachytherapy is that the source can be adapted to treat a particular tumor, lesion or other condition by selecting a suitable x-ray, gamma ray or low-energy electron emitter, based on the tumor or lesion type, size and location.

[0009] In surface brachytherapy an external source is used, placed adjacent the skin surface to be10 treated. When used intraoperatively, the source may be placed adjacent to tissues in a surgical bed. The source can also be shielded to reduce exposure to adjacent, healthy tissues, providing a more effective treatment modality for a wide range of surface lesions, with potentially fewer side effects than other, more invasive techniques. Surface brachytherapy can also be used to treat non-cancerous (benign) conditions such as keloids, and to improve outcomes for patients with15 contraindications to surgery such as immunodeficiency or infection, or in combination with other treatment options.

[0010] Radioactive materials have been rendered for the treatment of skin lesions since the first half of the twentieth century. Klinghoffer, U.S. Patent No. 2,269,027. The use of brachytherapy “skin patches” to treat cancerous tumors and lesions goes back to the provision of a radioactive20 material sealed in a flexible, flat (substantially two-dimensional) film or envelope that can be applied to provide radiation treatment for diseased tissues. Suthanthiran et al., U.S. Patent No. 4,946,435. Flat patches or films containing stable nuclides can also be irradiated with neutrons to convert them into radioactive sources, effective to treat various kinds of cancers and dermal diseases. Park et. al., U.S. Patent No. 5,871,708 A.

[0011] Conformal skin patches can be adapted to the shape of the skin area to be treated, for example using a flexible substrate and radioisotope matrix. Cipriani et al., U.S. Patent No. 9,486,642 B2. Thicker encapsulations can also be provided, for example radioactive patches with a layer of (e.g., plastic) film that is coated with a nonreactive adhesive agent, in the form of an encapsulating tape. Brooks, U.S. Publication No. 2023 / 0124323 Al.30

[0012] Flat patches with dosage-designed or variable radiation fields can also be produced, with thickness selected to provide a suitable therapeutic treatment. Sarazin et al., U.S. Publication No. 2020 / 0188691 Al. Encapsulations with stable metal materials such as titanium foils or canisters are also known; e.g., ranging up to several mil in thickness (or up to 100 pm or more). Finger et al., U.S. Publication No. 2021 / 0016105 Al; U.S. Publication No. 2022 / 0266059 Al.PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01

[0013] All of these radiation therapy techniques require careful dose analysis to improve efficacy, while reducing exposure to healthy tissues and protecting medical providers during treatment. While the use of surface brachytherapy can help address these concerns, there is an ongoing need for more advanced techniques that can improve patient outcomes while reducing5 unnecessary exposure, with lower incidence of undesirable side effects such as erythema (redness or discoloration) and desquamation (peeling). There is also a need for techniques that are adaptable to treatment of cancerous, noncancerous and precancerous tumors and lesions of varying type, size and location, in a wider range of patient populations, and which can be applied to both early and later-stage diagnoses, either alone or in combination with other treatment options.

[0014] The information included in this background, including any references cited and any description or discussion thereof, is included for technical reference purposes only. The background information and subject matter is not intended to and should not be regarded as limiting the scope of the appended claims.15 SUMMARY

[0015] Surface brachytherapy is a temporary radiotherapy technique used to treat a range of skin conditions including melanoma, lymphoma, basal cell and squamous cell (non-melanoma) sarcoma, Bowen’s disease, actinic keratosis, keloids, and other malignant (cancerous) and non- malignant (precancerous or benign) disorders. In contrast to interstitial brachytherapy, where the20 source material is typically inserted into the body, surface brachytherapy uses an external source placed next to the skin or tissue surface to be treated.

[0016] The source material can be selected from beta-emitting radionuclides and other suitable emitters, based on tumor type, size, shape, location and depth. The material is placed within a housing that provides shielding and can be contoured according to the patient’s anatomy. The shielding can be adapted to the emission characteristics of the source material, in order to protect the caregiver and reduce exposure to adjacent healthy tissues.

[0017] The dosage applied to the skin or tissue surface depends on the source emission and geometry. While flat (substantially two-dimensional) sources may be appropriate for a range of tumor and lesion types and locations that are substantially flat or flattenable, such as a region of30 the body including the cheek, neck, shoulder, trunk, leg, etc., more complex presentations, such as where the disease to be treated is on the nose, ear, face, digits, or other body part that is substantially non-planar, can benefit from a different approach. Conformal source geometries have also been used, but this can limit source selection based on the material properties required to provide a given source in a flexible matrix or similar structure. Conforming sources may alsoPCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 complicate the requirements for uniformity, shielding and encapsulation, may require custom designed sources for each patient, and make it more difficult to reprocess the source materials for reuse.

[0018] A mosaic source geometry can address these limitations by forming the source from a5 range of two-dimensional (2D) or curved shapes or “tiles,” which can be combined to provide arbitrary source geometries, with increased flexibility in the gap distance between the source and the treatment surface. The tiles can also be formed from a broad range of suitable source materials, individually encapsulated to reduce sluffing of radioactive material, oxidization and other effects, and more easily reprocessed after therapy is completed.10 BRIEF DESCRIPTION OF THE DRAWINGS

[0019] FIG. 1 A is an isometric view of a surface brachytherapy device with a mosaic source.

[0020] FIG. IB is an isometric view of the device, applied to a treatment surface on a patient.

[0021] FIG. 2A illustrates a mosaic geometric model for surface brachytherapy designed to be conformal to an anatomical feature of a patient.

[0022] FIG. 2B is an isometric view of a surface brachytherapy device with a mosaic source geometry based on the model.

[0023] FIG. 2C is an isometric view of the device in FIG. 2B, disposed on the anatomical feature in FIG. 2A.

[0024] FIG. 3A is a front elevation view of an anatomical feature with a skin surface selected for20 surface brachytherapy.

[0025] FIG. 3B is a section view of a surface brachytherapy device designed to be non- conformal to the patient for treatment of the skin surface, taken along line A-A of FIG. 3 A.

[0026] FIG. 3C is a section view illustrating dosage (energy) delivered by the device to the skin surface, along line A-A.

[0027] FIG. 4A is an isometric top view of a mosaic source for a surface brachytherapy device.

[0028] FIG. 4B is an isometric bottom view of a base for the source of FIG. 4A.

[0029] FIG. 4C is an isometric top view of a base shield or collimator for the source, with an aperture.

[0030] FIG. 4D is a top isometric view of a housing for the source.30

[0031] FIG. 4E is a perspective, disassembled view of the device with the source disposed in the housing and the base shield or collimator disposed in the base.

[0032] FIG. 5 is a cumulative histogram of the dose rate per unit activity for the source of FIGS. 4A-4E, for the planning target volume (PTV), an expansion volume surrounding the PTV (PTV expansion), and the remainder of the patient volume (patient).PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01

[0033] FIG. 6A illustrates calculated dosage delivered by the device along a first section of an anatomical feature.

[0034] FIG. 6B illustrates calculated dosage delivered by the device along a second section of the anatomical feature.5

[0035] FIGS. 7A-7D are top plan views of flat mosaic or tile geometries for a substantially two- dimensional mosaic source.

[0036] FIGS. 8A-8C are isometric views illustrating basic Johnson solid geometries suitable for forming non-planar mosaic brachytherapy sources.

[0037] FIGS. 9A and 9B are isometric views illustrating elongated Johnson Solid geometries10 suitable for forming non-planar mosaic brachytherapy sources.

[0038] FIGS. 10A-10D are isometric views illustrating modified Johnson Solid geometries with non-regular polyhedral tiles suitable for forming non-planar mosaic brachytherapy sources.

[0039] FIGS. 11 A and 1 IB are isometric views illustrating class solutions suitable for forming non-planar mosaic brachytherapy sources.15

[0040] FIGS. 12A and 12B are isometric views illustrating mosaic sources with finite seam width or gaps between tiles suitable for additional non-planar mosaic brachytherapy sources.

[0041] FIG. 13 A is a schematic illustration of the air gap (spacing) surrounding a cylindrical phantom inside a mosaic brachytherapy source with a square cross-section.

[0042] FIGS. 13B and 13C are circumferential dose profiles at different depths calculated for the20 cylindrical phantom in FIG. 13 A, for two different minimum air gap values.

[0043] FIG. 14A is a plot of circumferential dose profiles at different depths for a source with a conformal shape disposed about a cylindrical phantom.

[0044] FIG. 14B is a plot of circumferential dose profiles at different depths for a mosaic source with a portion of an octagonal cross section disposed about a cylindrical phantom.

[0045] FIG. 14C is a plot of circumferential dose profiles at different depths for a mosaic source with a portion of a first hexagonal cross section disposed about a cylindrical phantom.

[0046] FIG. 14D is a plot of circumferential dose profiles at different depths for a mosaic source with a portion of a second hexagonal cross section disposed about a cylindrical phantom.

[0047] FIG. 14E is a plot of circumferential dose profiles at different depths for a mosaic source30 with a portion of a pentagonal cross section disposed about a cylindrical phantom.

[0048] FIG. 14F is a plot of circumferential dose profiles at different depths for a mosaic source with a portion of a square cross section disposed about a cylindrical phantom.

[0049] FIG. 14G is a plot of circumferential dose profiles at different depths for a mosaic source with a portion of a diamond-shaped cross section disposed about a cylindrical phantom.PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01

[0050] FIGS. 15A-15F are dose plots for two-dimensional mosaic sources with different tile spacings, at different tissue depths.

[0051] FIGS. 16A-16F are dose plots for two-dimensional mosaic sources with different air gaps and tissue depths.5

[0052] FIG. 17A is a dose plot for a two-dimensional mosaic source with different air gaps, at different tissue depths.

[0053] FIG. 17B is a is a cumulative histogram of the dose rate per unit activity for a mosaic brachytherapy device, as compared to a conformal device.

[0054] FIG. 18A illustrates calculated dosage delivered by the mosaic brachytherapy device along a section of an anatomical feature.

[0055] FIG. 18B illustrates the calculated dosage delivered by the conformal device, along the same section.

[0056] FIG. 19 is a flow diagram illustrating a method for surface brachytherapy, using a mosaic source.15 DETAILED DESCRIPTION

[0057] FIG. 1A is an isometric view of a surface brachytherapy device 100 with a mosaic source 110 formed from a number of individual sectors or piece-of-pie-shaped tiles 120. FIG. IB is an isometric view of the device 100 as configured for radiotherapy treatment of a patient 180, for example on a skin surface (treatment surface) 185 defined on the patient’s face or other20 anatomical feature 190.

[0058] As illustrated in FIGS. 1A and IB, source 110 is disposed within a housing 130, which is adapted for coupling to a base 140 attached to the skin surface of a patient 180 via an applicator 150; e.g., a flexible adhesive tape. Other adhesives and mechanical couplings such as straps can also be used, or a combination of adhesive and mechanical elements.

[0059] The source 110 can have a planar or non-planar (e.g., convex) geometry, defining a gap between the source tiles 120 and treatment surface 185. In this particular example, the source 110 is divided into six similarly shaped sectors or tiles 120, separated by seam width or inter-tile spacing 122, and disposed symmetrically about a central axis. Suitable tiles 120 can also be provided in triangular, square, rectangular, other polygonal forms, or irregular shapes, and30 arranged into sources 110 with a variety of convex, concave, symmetric and asymmetric geometries.

[0060] Base 140 can be mechanically attached to the applicator 150, in order to position the base 140 with respect to the anatomical feature 190 on patient 180. The base 140 can include a collimator 144 disposed adjacent the treatment surface 185, with an aperture 146 exposing thePCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 tumor, lesion or other condition selected for treatment. The housing 130 and source 110 can then be coupled to base 140 with a number of coupling elements 132, for example magnetic elements 132 adapted for releasable engagement with a magnetic collimator element 144, or with one or more complementary engagement elements arranged elsewhere on the base 140 (see, e.g., Fig.5 4E).

[0061] The coupling elements 132 can be keyed to define a preselected or preferred rotational orientation for housing 130 on base 140, with source 110 positioned for irradiation of the treatment surface 185 through aperture 146. A biased, magnetic or mechanical engagement can also be used, and the applicator 150 can take other forms, for example as described in Sarazin et10 al., U.S. Publication No. 2024 / 0207640 Al, which is incorporated by reference herein, in the entirety and for all purposes.

[0062] FIG. 2A illustrates a computer-generated mesh model 200 for a surface brachytherapy treatment adapted to be substantially conformal to an anatomical feature 190 of a patient. As shown in FIG. 2A, for example, a three-dimensional (3D) model 200 can be defined as a mesh15 representation with any number of variously shaped sections or mesh tiles 220, adapted to the corresponding geometry of the treatment surface defined on feature 190.

[0063] In contrast to substantially conformal source configurations, model tiles 220 do not necessarily conform to the surface of feature 190; rather, model tiles 220 can be used to define a space between the radioactive element and the anatomical feature. In this particular20 implementation, the space would be filled with air and is referred to as an “air gap.” Suitable models 200 can also be defined using any number of substantially flat, curved or two- dimensional mesh tiles 220. Models 200 can also include geometric parameters for a collimator and shield elements adapted to the contours of the anatomical feature 190, and may accommodate additional conformal shielding, as described below. The mesh tiles 220 can also be25 spaced from the anatomical feature 190 to provide an air gap, and to accommodate the collimator and shielding. The mesh tiles 220 are thus not limited to simply modelling the geometry of feature 190, but can instead be used to generate a more complex tiling geometry suitable for a mosaic source to be used in surface brachytherapy, as further described below.

[0064] FIG. 2B is an isometric view of a brachytherapy device 100 with a mosaic source 110; e.g., based on the computer-generated mesh model 200 of FIG. 2A. As further illustrated in FIG. 2B, mosaic source 110 can be comprised of a number of source tiles 120 that are defined by or based on the mesh tiles 220.

[0065] Source tiles 120 are assembled into mosaic source 110, with individual tiles 120 separated by seam width (tile spacing) 122. The assembled source 110 is disposed in a shielded35 housing 130 that can be coupled to a base 140. The bottom surface of the base 140 can bePCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 contoured for attachment to the anatomical feature 190 of a patient; e.g., with the source 110 disposed adjacent the treatment surface, as further illustrated in FIG. 2C.

[0066] FIG. 2C is an isometric view of the device 100 disposed on an anatomical feature 190 for surface brachytherapy treatment. The base 140 of the device 100 can be adapted to the contours5 of the anatomical feature 190, in order to more precisely position the source with respect to the corresponding treatment surface.

[0067] FIGS. 2A-2C illustrate a mosaic approach to the development of a shaped source geometry, adapted to a particular patient geometry. The mosaic source 110 can be defined as a mosaic of smaller source tiles 120, with favorable implications for activation. The treatment10 surface can be mapped using a mesh representation or model 200 of the patient’s contoured anatomical feature, and the topology of the mesh tiles 220 represented in the model 200 can be processed to produce the source tiles 120. The base, applicator, collimator, shielding and housing components can also be specified in the model 200, and used for dose calculation. The effects of tile spacing (seams) and air gaps can also be considered, as further described below.15

[0068] FIG. 3 A is a front elevation view of an anatomical feature 190 on a patient 180, with a skin surface 185 selected for treatment by surface brachytherapy. For example, a tumor or lesion 195 may have formed on the nose of the patient 180, as shown in FIG. 3 A, in a location suitable for treatment by surface brachytherapy using a mosaic source configuration.

[0069] More generally, surface brachytherapy devices with mosaic source geometries can be20 suitable for treating various diseases of the skin including, melanoma, lymphoma, basal cell and squamous cell (non-melanoma) sarcoma, Bowen’s disease, actinic keratosis, keloids, and other disorders. The techniques described here are also adaptable to treat patients 180 with early or later-stage tumors, lesions or other conditions 195 on a wide range of different anatomical features 190, including the lips, cheeks, forehead, ears, eye regions, and other facial features, as25 well as the head, neck, shoulders, back, arms, legs, hands feet and other portions of the anatomy. Intraoperative treatments are also possible with a suitably adapted mosaic source geometry and applicator.

[0070] FIG. 3B is a section view of a surface brachytherapy device 100 with a substantially non- conformal mosaic source 110, taken along line A-A of FIG. 3B. The source 110 can be adapted for treatment of a skin surface (or treatment surface) 185, for example on the nose or other anatomical feature 190 according to FIG. 3 A.

[0071] As illustrated in FIG. 3B, source 110 can be formed of a number of generally flat (two- dimensional) or non-planar (curved) sections or tiles 120, in various polygonal forms. For example, source tiles 120 can be defined based on the corresponding mesh tiles 220 of a35 computer-generated mesh model 200, as described above. These tiles are not nominallyPCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 conformal, but instead form a three-dimensional (3D) mosaic dome or other 3D shape spaced over the targeted treatment area according to the air gap. The model can include a collimator 144 defining an aperture adjacent treatment surface 185, and additional shielding and housing components adapted for application of device 100 to the corresponding anatomical feature; e.g.,5 according to FIGS. 2A-2C.

[0072] Mosaic source 110 can be placed in a shielded housing, and coupled to a base with collimator 144 formed from a metal, ceramic, polymer or composite material adapted to the contour of the patient's anatomy, using the computer-generated mesh model. Additional conformal shielding can also be provided, made of similar materials. Alternatively, the geometry10 of the collimator 144 can be directly molded or shaped based on the geometry of the anatomical feature 190 itself, and included in the model. In some applications, additional shielding can also be provided when or after the base is positioned, for example using a flexible shielding material, or additional shield elements that can be attached adjacent the treatment surface 185.

[0073] FIG. 3C is a section view illustrating dosage 300 delivered by a surface brachytherapy15 device 100 to a treatment surface 185; e.g., a device 100 according to FIG. 3B, disposed with respect to the treatment surface 185 on an anatomical feature 190 of a patient 180 and taken along line A-A according to FIG. 3 A. In these examples, the section plane (A) of FIG. 3C corresponds to the section plane (A) of FIG. 3B. The dosage 300 is defined in terms of energy' equivalent, scaled in arbitrary units.20

[0074] A spacing or an air gap G can be defined between the treatment surface 185 and the adjacent tile section 120 of the mosaic source 110; e.g., perpendicular to treatment surface 185, as shown in FIG. 3C. The gap G can vary across the treatment surface 185, based on the geometry of source 110 and tiles 120, collimator 144, and any additional shielding or housing components. The gap G can also be selected to accommodate one or more layers of thin film or encapsulating material, as described herein. For example, one or more such layers can be disposed between the source material and the collimator, in order to seal the source material, to maintain source material integrity, to provide additional protection from flaking, sloughing, friation and other potential means of contamination, or any combination thereof.

[0075] FIG. 3C shows that the geometry of the source 110 and source tiles 120 can be adapted to30 the gap width G, in order to provide substantially uniform dosage across the treatment surface 185. The mesh model can also be modified according to the geometry of the source 110 and tiles 120 to provide a more modulated dosage; e.g., varying across a specified treatment surface 185 according to the depth or thickness of the targeted tumor, lesion or other condition. The mesh model may be adapted, for example, by including additional layers radioactive elements,PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 radioactive elements of varying thicknesses, seam widths of varying widths, or absorbing layers of varying thicknesses to modulate the dose to particular regions.

[0076] As further illustrated in FIGS. 3A-3C, suitable mosaic sources 110 may require a relatively higher or lower number of source tiles 120, depending on the characteristics of the5 tumor or lesion, and the adjacent patient anatomy . A standardized geometry for source 110 and / or tiles 120 can also be used; e.g., in combination with a range of customized collimators 144 adapted to various patient anatomies. The model can also employ both the positive and negative surfaces of convex solid sections for source riles 120, and define a combination of convex and concave section and tile geometries in the mosaic source 110.10

[0077] FIG. 4A is an isometric top view of a mosaic source 110 for a surface brachytherapydevice; e.g., a device 100 as described herein. As shown in FIG. 4A, source 110 can be formed of a number of polygonal tiles 120 defined by a mesh model or other computer-generated geometric model suitable to adapt the geometry- of source 110 for surface brachytherapy on particular anatomical features; e.g., where a tumor or lesion is present, as described above.15

[0078] FIG. 4B is an isometric bottom view of a base 140 for the device 100. The bottom surface 148 of base 140 can be contoured to conform to the anatomical features of a patient, for example using a computer-generated model, or by directly modelling the anatomical feature itself.

[0079] FIG. 4C is an isometric top view of a collimator 144; e.g., for assembly with a base 140 according to FIG. 4B. As illustrated in FIG. 4C, an aperture 146 is defined by the inner20 circumference of the collimator 144. Additional shielding can also be provided; e.g., before, after, or while the base is positioned on the patient.

[0080] FIG. 4D is a top isometric view of a housing 130 for the device 100. In this particular configuration, housing 130 has a tiled geometry corresponding to that of a mosaic source 110; e.g., according to FIG. 4A. Housing 130 can be formed of durable materials such as polymers,25 high-density polymers, ceramics, metals, and composite materials, and can be provided with shielding components to block stray radiation from the source, when installed in the housing 130. Elements of the housing 130 can be provided in modular form to facilitate rapid assembly of the source in different housing configurations; e.g., for the treatment of multiple lesions on a single patient, or multiple patients with different lesions.

[0081] FIG. 4E is a perspective, disassembled view of a brachytherapy device or system 100 with a mosaic source 110 disposed in the housing 130, and a collimator 144 disposed in the base 140. As illustrated in FIG. 4E, the housing 130 and base 140 can be formed of similar materials, with a similar perimeter geometry, and may be defined as complementary top and bottom (or top and base) housing components, respectively. Alternatively, the geometry and composition of35 housing 130 and base 140 may vary-.PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01

[0082] Coupling elements 132, 142 can be provided for releasably coupling the (top) housing 130 to the (bottom) base 140, for example using magnetic elements as shown, or with a biased engagement or other mechanical attachment. The attachment can be keyed, so that the source 110 disposed in housing 130 maintains a preselected orientation with respect to the collimator5 144, in order to produce the desired dosage via irradiation through aperture 146. Other suitable materials and configurations for the source 110, tiles 120, housing 130, base 140, collimator 144 and additional components of device 100 are described in the Applications section, below.

[0083] FIG. 5 is a cumulative histogram plot 500 of the dose rate per unit activity calculated for a surface brachytherapy device; e.g., a device 100 with a mosaic source 110, as described herein.10 Relative volume is indicated on the vertical axis with normalization being to the total volume of each structure for which a histogram is computed. Computed dose rates per unit activity are indicated on the horizontal axis in arbitrary units (e.g., Gray per hour per millicurie (Gy / hr / mCi) or other suitable units), for delineated structures including the planning target volume (PTV), an expansion volume surrounding the PTV (PTV expansion), and the rest of the patient volume15 (patient). Note that the curve representing the histogram for the patient volume lies close to the horizontal axis, except near the origin, indicating the patient volume beyond the PTV and PTV expansion receives practically zero (substantially no) dose.

[0084] FIG. 6A illustrates the calculated dosage 610 delivered by a surface brachytherapy device 100 to a treatment surface 185 defined along a first section of an anatomical feature 190; for20 example a device 100 as described herein, disposed with respect to the nose of a patient 180 (see inset, line B-B). FIG. 6B illustrates the calculated dosage 620 delivered by the device 100 to the treatment surface 185 defined along a second section of the anatomical feature; e.g., perpendicular to the section of FIG. 6A (inset, line C-C).

[0085] As shown in FIGS. 6 A and 6B, the air gap G between the treatment surface 185 and the25 individual tiles 120 of the mosaic source 110 may vary significantly, while the dosage 300 is maintained at a substantially uniform value laterally, but decreasing with tissue depth D (e.g., measured from the skin surface). The treatment device can also be modified to vary the dosage 300 across treatment surface 185 based on the size, shape, type and depth of the targeted tumor or lesion, or other target feature by varying, for example, the tile activity per unit area, seam width, air gap G, tile size and shape, tile thickness, and radiation absorbing layers. In other cases, the treatment device uses tiles of substantially similar thickness and activities per unit area creating a shape that can be used across various patient treatment geometries.

[0086] FIGS. 7A-7D, 8A-8C, 9A-9B, 10A-10D, 11A-11B and 12A-12B illustrate representative mosaic geometries defined by arrays of tiles 120 with shapes suitable for forming35 a mosaic brachytherapy source 110, and for computer-generated modelling of the sourcePCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 geometry. As shown in each of these figures, the array of tiles 120 can be configured to modulate the dose delivered by the source 110 to a treatment surface. For example, the source 110 can be disposed in a housing and coupled to a base, so that the dose is delivered to the treatment surface via an aperture defined in the base. In some examples, at least one element can be omitted from5 the array; e.g., where the omitted element is defined between two or more tiles 120 in the array, in order to further modulate the dose. In additional examples the tile spacing between adjacent tiles may be non-uniform, wherein the non-uniform spacing is configured to further modulate the dose.

[0087] Suitable geometries for the arrays of tiles 120 defining the source 110 can include flat10 mosaic geometries, portions of a regular polyhedron, Johnson solids, Platonic solids, Archimedean solids, Catalan solids, prisms, anti-prisms, Kepler-Poinsot polyhedra, irregular polyhedrals, and combinations and variations thereof. Additional examples of suitable mosaic geometries for the source 110 also include truncated icosohedrons, triangular prisms (diagonal cupolas or fastigia), triangular cupolas, square cupolas, pentagonal cupolas, and pentagonal15 rotundas, square pyramids, pentagonal pyramids, substantially flat arrangements; e.g., based on related polyhedra such as cubes, octahedrons, cuboctahedrons, rhombicuboctahedrons, dodecahedrons, rhombicosidodecahedrons, and icosidodecahedrons, formed of triangular, square and other polygonal tiles 120.

[0088] FIGS. 7A-7D are top plan views of flat mosaics or tiles 120 with geometries suitable for20 forming a substantially two-dimensional (planar) mosaic source 110. As shown in the figures, the tiles 120 for mosaic sources 110 can take on many forms including regular hexagons (FIG. 7 A), irregular hexagons (FIGS. 7B and 7C), or a surface with one or more curved edges, such as a circular source 110 formed from tile sectors 120 as shown in FIG. 7D. In these examples, the seam widths or tile spacings 122 can be uniform. Mosaics sources 110 can also be25 formed from combinations of regular or irregular tiles 120 with either regular or irregular spacings 122.

[0089] In addition to the planar shapes of FIGS. 7A-7D, a highly diverse range of non-planar solid surfaces can be used to create radiation emitting dome-shaped sources 110. The most symmetric shape would be a portion of a sphere, such as a hemisphere. The surface of the source 110 does not need to be completely symmetric or smooth, however, and could be replaced with a surface such as a sphere-hke shape 110 approximated by several substantially planar tiles 120. A common example of this is a truncated icosahedron (i. e. , a soccer ball-like shape) formed from a series of pentagons and hexagons. Other regular polyhedral tiles 120 include the pentagonal dodecahedron, rhombic dodecahedron, and approximately spherical shapes such as a volleyball.35 These examples can be further extended to one of many possible portions of a Johnson solid.PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01

[0090] FIGS. 8A-8C are isometric views illustrating basic Johnson solid geometries suitable for forming non-planar mosaic brachytherapy sources 110. Johnson solids are a broad class of convex 3D shapes created from regular polyhedral tiles 120. These polyhedral tiles 120 typically include equilateral triangles, squares, regular pentagons, regular hexagons, etc. To form a5 nonconforming source 110 that creates a 3D surface above the patch, one or more sections can be removed or omitted from the bottom portion of the shape. Some examples of suitably modified Johnson solids include a tetrahedron with one side omitted, a cube with one side omitted, and a square pyramid with the square base omitted. Additional examples include a pentagonal pyramid formed from triangular tiles 120, without the pentagonal base (FIG. 8 A),10 and a square cupola formed from square and triangular tiles 120, without the octagonal base (FIG. 8B). Additional, non-exhaustive examples include sources 110 based on various portions of pentagonal cupolas, square orthobicupola (e.g., formed of two squares and four triangles), and pentagonal rotundas formed of pentagonal and triangular tiles 120 (FIG. 8C). Many more geometries are also suitable for the mosaic source 110, as described herein, and as known in the15 art.

[0091] FIGS. 9A and 9B are isometric views illustrating elongated Johnson solid geometries suitable for forming non-planar mosaic brachytherapy sources 110. For example, the Johnson solid can be formed into various elongated versions using additional square tiles 120 as shown in FIG. 9A, or using triangular tiles 120 as shown in FIG. 9B. A few non-exhaustive examples are20 based on a cupola with added square or rectangular tiles 120 of various aspect ratios disposed around the perimeter of the base of the source 110, creating elongated square cupolas as shown. One example of a mosaic source 110 formed from tiles 120 arranged into an extended square cupola is shown in FIG. 9A, and a source 110 formed from tiles 120 arranged into a gyroelongated square cupola is shown in FIG. 9B.25

[0092] FIGS. 10A-10D are isometric views illustrating modified Johnson solid geometries with non-regular polyhedral tiles 120 suitable for forming non-planar mosaic brachytherapy sources 110. Elongated versions of the source 110 can be created by adding tiles 120 in the form of rectangles (e.g., instead of squares or triangles) around the base to create a taller or shorter version of the extended square cupola (FIG. 10A). In another implementation, tiles 120 in the form of squares, rectangles, or triangles can be appropriately added along the perimeter to create a non-standard extended cupola (FIG. 10B).

[0093] The idea of the modified Johnson solid can be extended to include sources 110 having other shapes and tiles 120 that are not regular polygons, including rectangles and triangles of various aspect ratios, such as those found in some geodesic dome shapes. These examples can35 include a square cupola that is modified such that the square at the center is replaced with aPCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 rectangular tile 120, which can have any suitable aspect ratio or be made from multiple, individual square tiles 120, as shown in FIGS. IOC and 10D.

[0094] FIGS. 11 A and 1 IB are isometric views illustrating class solutions suitable for forming non-planar mosaic brachytherapy sources 110. Johnson solids can also be extended to include5 mosaic sources 110 with shapes that are not convex, such as those seen in architectural spheres and similar shapes, and as encountered when creating triangular meshes of irregular shapes such as a face. Additional embodiments include a general class of solutions for mosaic sources 110 that can be fabricated from a smaller number of individual tiles or pieces 120, and adapted for treating a general area of the body, such as the ear, nose or other facial feature. Two examples of10 sources 110 with surfaces that can be created from a smaller number or set of tiles 120 are shown in FIG. 11 A and FIG. 1 IB; e.g., solutions which could generally be used to treat the tip of a nose.

[0095] FIGS. 12A and 12B are isometric views illustrating mosaic sources 110 with finite seam width or tile spacing (gaps) 122 between individual tiles 120, suitable for a range of additional15 non-planar mosaic brachytherapy sources 110. As shown in FIGS. 12A and 12B, assembly of tiles 120 into sources 110 with three-dimensional surfaces can, in some cases, include seams 122 defining various spaces between individual tiles 122. Non-inclusive examples of surfaces with finite width seams 122 are shown for a pentagonal pyramid (FIG. 18A) and a square cupola (FIG. 18B).20

[0096] More generally, the polygonal shapes of tiles 120 can be regular or irregular, and the corresponding polyhedral shape of mosaic source 110 can be uniform or nonuniform. A variety of cupola and rotunda forms can also be combined in a given source geometry. Additional suitable source and tile configurations are described in the Applications section, below.

[0097] FIG. 13 A is a schematic illustration of the air gap (or spacing) G surrounding a cylindrical phantom 700 with radius R, disposed inside a mosaic brachytherapy source 110 with a square cross-section. FIGS. 13B and 13C are circumferential dose profiles 750, 760 at different depths withing the cylindrical phantom of FIG. 13 A, calculated for two different minimum air gap values.

[0098] FIGS. 13A-13C show that the uniformity of dose delivered to a treatment area can be a30 function of the air gap. FIG. 13A shows the cylindrical water phantom 700 with radius R, disposed inside a mosaic source 110 formed from an assembly of tiles 120 defining a square cross section, taken perpendicularly to axis of the phantom 700. Doses in the water phantom 700 are calculated at a number of depths ranging from 0.5 mm to 2 mm, according to the different air gaps in FIG. 13B and FIG. 13C.PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01

[0099] FIG. 13B illustrates a dose calculation (vertical axis, in arbitrary units), where the source 110 is in contact with the water phantom at the tangents (i.e. a minimum gap spacing of G ~ 0). FIG. 13B shows that the magnitude of the dose varies with angle; e.g., the dose is at a minimum where a tile 120 is in contact with the water phantom 700 (at angles 0, 90, 180 and 270 degrees,5 defined along the horizontal axis), and at a maximum directly beneath the vertices or comers, formed at the intersection of two perpendicularly oriented tiles (at 45, 135, 225 and 315 degrees).

[0100] FIG. 13C shows the calculated dose for a source 110 with a minimum air gap of 5 mm to the water phantom at the tangents (that is, at 0, 90, 180 ad 270 degrees). In this case the nonuniformity is substantially reduced, as compared dose directly beneath the vertices (45, 135, 22510 and 315 degrees).

[0101] FIG. 14A is a plot 810 of circumferential dose profiles at different depths for a conformal Y-90 source 710 with a semi-circular cross section, taken perpendicular to the midsection of a right cylindrical phantom 700 designed to simulate radiation absorption into tissue. A cylindrical water phantom 700 with a diameter (= 2R) of 5 cm was selected. The geometry of the conformal15 source 710 was adapted to match the cylindrical water phantom 700; e.g., in a cylindrical configuration with a constant air gap of 2 mm.

[0102] A mesh simulation can be applied estimate the dose, indicated on the vertical axis in arbitrary units. The polar angle is indicated on the horizontal axis in degrees, with 180 degrees (180°) defined through the vertical. The plot 810 shows the dose delivered at depths into the20 water phantom 700 between 0.5 mm and 2.5 mm. This calculation shows that the conformal source 710 delivers a largely uniform dose at a given depth, and the dose decreases with depth into the water phantom 700, as expected.

[0103] FIG. 14B is a plot 820 of circumferential dose profiles at the same depths for a mosaic Y-90 source assembly 110 with a portion of an octagonal section; e.g., the perpendicular25 midsection of a right octagonal prism with a minimum air gap of 2 mm to the cylindrical water phantom 700 at the vertical, or 180°. Note that the vertical scale in FIG. 14B has been shifted with respect to FIG. 14A, placing zero dose on the horizontal axis (see also FIG. 14D, FIG. 14F, and FIG. 14E). The octagonal section exhibits very good dose uniformity for all depths into the water phantom 700; e.g., less than about five percent (< 5%) at the shallowest depth (0.5 mm) and improving with depth > 1.0 mm, as measured into the water phantom 700.

[0104] FIG. 14C is a similar dose plot 830 for a mosaic Y-90 source assembly 110 having a partial hexagonal section, with a vertex defined between sides at the vertical, or 180° (hexagonal-I). FIG. 14D is a dose plot 840 for a mosaic Y-90 source assembly 110 having an alternate partial hexagonal section, with the midpoint of a side at the vertical (hexagonal-II). The35 second hexagonal section (FIG. 14D, with an edge of the source 110 which is not tangent to thePCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 circular cross-section of the phantom 700), has similar uniformity to the first hexagonal section (FIG. 14C, with the edge of the source 110 tangent to the phantom 700), but may have a somewhat less uniform penumbra due to the increasing air gap at the edges of the mosaic source 110.5

[0105] Comparing FIG. 14A (conformal source) to FIG. 14C and FIG. 14D, the hexagonal-I and hexagonal -II mosaic Y-90 source assemblies 110 may have an increased circumferential dose non-uniformity, with the maximum dose occurring below the vertices of the polyhedral sources 110 and the minimum at the smallest air gap; however, these dose nonuniformities are within a 15 percent or less (< 15%, peak-to-trough) for varying air gaps across a broad angular range. At10 a depth of 0.5 mm, the uniformity of the hexagonal-I and hexagonal-II sections varies by about 10 percent or less (< 10%, peak-to-trough) between positions where the source is at a minimum and maximum air gaps. The dose uniformity further improves with depth into the water phantom 700.

[0106] FIG. 14E is a plot 850 of circumferential dose profiles at different depths for a mosaic Y-15 90 source assembly 110 with a portion of a pentagonal section; e.g., the perpendicular midsection of a right pentagonal prism with a minimum air gap of 2 mm at the vertical, or 180° to the cylindrical water phantom. FIG. 14F is a similar dose plot 860 for a mosaic source 110 with a square section; e.g., the perpendicular midsection of a right square prism, and FIG. 14G is a dose plot 870 for a mosaic source 110 with a diamond-shaped cross section.20

[0107] Comparing FIG. 14F to FIG. 14C and FIG. 14D, the mosaic source with a partial square section (FIG. 14F) exhibits a dose uniformity across a broad angular range that is substantially lower than that of the mosaic sources with partial hexagonal sections (FIG. 14C and FIG. 14D); e.g., within about 10 percent (< 10%) for depths of about 2.0 mm, increasing to between ten and fifteen percent (10-15%) at a depth of 0.5 mm, in the central angular region of 130 to 230 degrees.

[0108] The diamond-shaped section (FIG. 14G) may provide a less uniform dose that peaks toward the perpendicular (180°); e.g., falling off by up to ten to fifteen percent (10-15%) across the central angular region, for depths greater than 1.5 mm. At depths less than 1.5 mm the falloff may be more pronounced; e.g., up to about ten to twenty percent (10-20%) less than in the30 central region, for a gaps down to 0.5 mm. These uniformities may be more substantial for the diamond-shaped section (FIG. 14G) than for the square section (FIG. 14F) even though they are different portions of the same right-prism; e.g., the reduced uniformity of the diamond section may result from the edge of the source 110 occurring at a vertex of the square mosaic source 110, as opposed to a nearest approach or tangent to the water phantom 700.PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01

[0109] The observed uniformity is similar to what is seen in lighting applications that take advantage of Lambertian emission properties, such as an integrating sphere used in measuring light emission properties of samples, Lambertian reflecting projector screens or diffusing elements in a display such as a television to make projected images of similar intensity5 regardless of viewing angle. The emission of Beta particles from a surface of finite thickness are not precisely Lambertian, but we can use the general principle, so long as certain restrictions are imposed. Namely, the emitting surface should be relatively uniform in its emission properties (e.g. its activity per unit area), the emission from the surface should be at a range of solid angles, and a sufficient distance must exist between the emitting elements and the surface to be10 illuminated so that the dose originates from many parts of the mosaic surface.

[0110] The dose plots 810-870 in FIGS. 14A-14G investigate the effects of surface approximations on dose uniformity. Overall, FIGS. 14A to 14G show that substantial dose uniformity can be obtained using mosaic sources with a range of different geometrical sections, for minimum air gaps of 2.0 mm and depths into the water phantom between 0.5 and 2.5mm.15 The general trend is that the uniformity is largely uniform dose for a cylindrical (conformal) source, and decreases as the number of sides approximating the conformal source decreases and therefore the degree of conformality decreases. Mosaic sources based on hexagonal prisms have non-uniformities of less than 10%, peak to valley. Furthermore, it is seen that the dose is highest below vertices and that the uniformity increases with depth into the water phantom.20 Alternatively, the dose can also be selectively varied across the central angular range, by choosing a particular source geometry.

[0111] FIGS. 15A-15F are intensity plots for two-dimensional, mosaic sources with different seam widths, at different tissue depths. The sources are formed of nine individual tiles, each with a square geometry and each a size 10mm per side, arranged into a 3 x 3 grid.25

[0112] Intensity plots 910, 915, 920 are simulated for an air gap of 1 mm and at a tissue depth of 0,25 mm, for seam widths (tile spacings) of 0.1 mm (FIG. 15A), 0.2 mm (FIG. 15B) and 0.4 mm (FIG. 15C), respectively. Intensity plots 925, 930 and 935 are simulated for the same air gap and tile spacings, at a tissue depth of 2.0 mm (FIGS. 15D, 15E and 15F, respectively).

[0113] Intensity plots 910-935 investigate the effect of tile spacing (seams) on dose uniformity, including the impact of air gaps on the dose at or near the skin surface, and at depth. A mesh simulation can be used to determine the simulated energy deposition. The total activity is normalized to the same value for all of the tiled sources; e.g., by increasing the activity per area for tiles with larger spacing, to account for reduced tile size.

[0114] As shown in FIGS. 15A-15F, seam widths (tile spacings) of 0.1 mm and below appear to35 have relatively low effect on uniformity, at either depth. The effect increases with seam width,PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 for example on the order of about five to ten percent or less (< 5-10%), but decreases with tissue depth as the solid angle of the seam decreases and additional scattering withing the tissue averages out the dose distribution. Furthermore, additional simulations show that the uniformity increases with air gap distance.5

[0115] FIGS. 16A-16F are intensity plots for two-dimensional, mosaic sources with different air gaps and tissue depths. The sources are formed of nine individual tiles, each with a square geometry and a size of 10 mm per side, arranged into a 3 x 3 grid with a seam between tiles of 0.4 mm. For a depth of 0.25 mm into a skin equivalent water phantom, the dose uniformity is shown for various air gaps.10

[0116] FIG. 16A in an intensity plot 950 for an air gap of 0. 1 mm, FIG. 16B is an intensity plot 955 for an air gap of 1 mm, and FIG. 16C is an intensity plot 960 for an air gap of 2 mm. It is clear that increasing the air gap increases the dose uniformity, as the seam width becomes smaller in solid angle as seen from the skin surface. A similar geometric effect is seen at a depth of 2 mm into the water phantom for varying air gaps in the intensity plots 865, 970 and 975 for15 FIG. 16D (0.1 mm gap), FIG. 16E (1 mm gap), and FIG. 16F (2 mm gap). These effect may also be affected by electron scattering in the phantom, which tends to reduce non-uniformities in the dose distribution. Taking FIGS. 15A-15F and 16A-16F together, it is seen that both the air gap and depth into the tissue increase the uniformity of the absorbed dose.

[0117] FIG. 17A is a dose plot 1000 for two-dimensional mosaic sources with different air gaps20 of 0.1 mm, 1 mm and 2 mm, at different tissue depths. The simulated dose is indicated on the vertical axis, in arbitrary units, with tissue depth on the horizontal axis, also in arbitrary units (e.g., mm, or other suitable unit).

[0118] As shown in FIG. 17A, the depth-dose curve appears to be substantially independent of gap size for tissue depths of about 0.5 mm and greater. To the extent there is a variation25 approaching depths of 2 mm to 2.5 mm, the local percent difference may be about two percent or less (< 2%). To the extent there is a difference at tissue depths of 0.5 mm and below, it may range from about five to ten percent, or less (<5- 10%).

[0119] FIG. 17B is a cumulative histogram plot of the dose rate per unit activity calculated 1100 for a mosaic brachytherapy device; e.g., a device 100 with a mosaic source 110, as described herein, as compared to a conformal device. The mosaic device (see, e.g., FIG. 18A) that utilizes yttrium 90 (Y-90) source tiles (solid lines), and the conformal device (e.g., FIG. 18B) has a 1 mm layer of rhenium 188 (Re-188; dashed lines).

[0120] Relative volume is indicated on the vertical axis with normalization being to the total volume of each structure for which a histogram is computed. Computed dose rates per unit35 activity are indicated on the horizontal axis in arbitrary units (e.g., Gray per hour per millicuriePCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 (Gy / hr / mCi), or other suitable unit), for delineated structures including the planning target volume (PTV), an expansion volume surrounding the PTV (PTV expansion), and the rest of the patient volume (patient). Note that the curve representing the histogram for the patient volume lies close to the horizontal axis, except near the origin, indicating the patient volume beyond the5 PTV and PTV expansion receives practically zero (substantially no) dose. The mosaic source and conforming devices perform similarly with respect to PTV expansion, while the PTV curves appear to diverge as the relative volume decreases; e.g., by up to about fifteen percent (<15%) as the relative volume approaches zero. This indicates that the dose uniformity across the PTV is improved with the non-conformal Y-90 source compared to the conformal Re- 188 source.10

[0121] FIG. 18A illustrates calculated dose rates 1210 delivered by the mosaic Y-90 brachytherapy device along a section of an anatomical feature 190; for example a treatment surface 105 defined on the nose of a patient 180 (e.g., along line D-D, as shown in the inset). FIG. 18B illustrates the calculated dose rates 1220 delivered by the conformal Re-188 device, along the same section. The dose rates can be scaled in arbitrary units; e g., in Gy / hr / mCi.15

[0122] As illustrated in FIGS. 18A and 18B, the mosaic Y-90 source device ("Mosaic Source”) and the conformal Re-188 device (“Conformal Source”) deliver similar dosages below the outer layer of skin or tissue on treatment surface 105. The mosaic Y-90 source device may deliver a lower peak dosage to the outer layer.

[0123] Additional classes of solutions can be provided, for anatomical features and treatment20 locations applicable to a broad range of patients and conditions. The source, housing, collimator and shield components can have modular designs, for easy assembly and loading, or partial loading, depending on application. The base, housing, collimator, aperture and source geometry can also be contoured or otherwise adapted to treatment surfaces with more complex curvature, for example on the bridge of the nose, near the eyes, and on the edges of the ears.

[0124] FIG. 13 is a block diagram or flow diagram for a method 1300 of using a surface brachytherapy device, for example a device 100, as described herein. As shown in FIG. 13, method 1300 can include one or more steps of providing (or acquiring) the device (step 1310), providing a mosaic source in the device housing (step 1320), positioning the base of the device with respect to a treatment surface (step 1330), securing the base (step 1340), attaching the30 source and housing to the base (step 1350), treating the patient (step 1360), and removing the device (step 1370); e.g., when treatment is complete.

[0125] Depending on application, method 1300 may also include one or more steps of adapting or customizing the device (steps 1315, 1335 and 1445), activating the source in a radiation environment (step 1325), and refurbishing the device (step 1380). These steps can be performedPCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 in any order or combination, with or without additional techniques as described herein, and as known in the art.

[0126] In clinical environments, suitable brachytherapy devices can be provided (step 1310) to or by a doctor, radiation specialist, clinical technician, or other treatment provider. The device5 can be customized by configuring or adapting (step 1315) for treatment of a particular tumor, lesion or other condition, for example by selecting a radiation source material and activity according to the corresponding type, size, shape, thickness, location, desired dose, and other treatment considerations.

[0127] A mosaic source can be provided in the device housing (step 1320), for example as10 defined using a mesh model or other computer-generated geometrical model of the patient anatomy, taking the tile geometry, aperture, shielding and variable gap spacing into account to determine dosage, as described herein. The source can be assembled from any number of source tiles; e.g., provided in encapsulated form, optionally with one or more layers of thin film, a freestanding sheet, or other form of encapsulating material disposed between the source and15 collimator. Suitable encapsulating materials can thus be provided either in the form or a vapor- deposited thin film or other coating, or a free-standing thin film material (e.g., a sheet or foil of encapsulating material disposed over the source tiles, or positioned between the source tiles and the collimator). In some applications, additional shield components can also be disposed in the housing, including conformal shielding components adapted to the treatment surface and20 surrounding anatomy of the patient.

[0128] In some applications, the source can be activated (step 1325) in or near the clinical setting, for example to reduce storage time and allow for a wider range of radioisotopes to be used (e.g., with relatively shorter half-lives). The source can also be activated before the device is provided to the doctors, specialist, technician, or other treatment provider (step 1310).25

[0129] The base of the device can be positioned (step 1330) with respect to the treatment surface. The aperture can be aligned with respect to the treatment surface while positioning the base, for example by the doctor, specialist, technician, or other provider. The base can be customized or configured with a contoured bottom surface (step 1335), and the collimator and shielding can be adapted for application to a particular anatomical structure; e.g., on the face, head, neck, back, arm or leg of the patient, or on other parts of the body, in order to more effectively direct radiation toward the target area, while reducing unwanted exposure.

[0130] The base can be secured (step 1340) to the anatomical feature using a removable tape or adhesive material, or with a flexible band or other mechanical attachment, or a combination thereof. Securing the base maintains precise positioning and alignment of the collimator and35 aperture with respect to the treatment surface, improving treatment efficacy while reducing orPCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 minimizing unwanted exposure. Further adaptation (step 1345) can include providing additional (e.g., higher density) shielding materials adjacent the treatment surface, for example in the form of additional conformal shielding or other shielding elements, in order to reduce exposure levels in adjacent (healthy) tissues.5

[0131] The housing and source can be attached to the base (step 1350) using magnetic coupling elements, a biased engagement, or other mechanical coupling. Radiation emitted by the source propagates through the aperture in the collimator to the treatment surface, in order to treat the patient (step 1360). Radiation that is not directed to the target area is absorbed by collimator and shield components in the base and housing, reducing unwanted exposure.

[0132] The device can be removed (step 1370) following treatment. After removing the device (step 1370), the source can be refurbished (step 1380) for reuse. Refurbishment can be performed after a number of half-lives of the activated source radioisotope have elapsed, reducing emissions toward the background level. For example, if the source tiles can be removed from the housing, they can be reassembled into another mosaic source (step 1320), for use in15 another treatment cycle or method 1300, reducing waste and associated disposal costs.BRACHYTHERAPY DEVICE CONFIGURATIONS AND APPLICATIONS

[0133] The techniques described here can be applied to a set of source tiles with predetermined shapes to create larger mosaic sources or “patch” devices that can be used to provide radiation treatment to cancers of the skin or other intraoperative lesions or tumor beds, as well as other,20 non-cancerous conditions. The tile shapes can include one or more of triangles, squares, rectangles and other quadrilaterals, or pentagons or hexagons that can individually, or in conjunction, be used to completely tile a flat space, or other source geometry. One or more tiles may be irregularly shaped in order to provide a desired dose distribution.

[0134] The tile pieces may have minimal seam width or spacing between adjacent tiles, in order to reduce dose non-uniformity. As an example, consider tiling a bathroom; wall or floor tiles may cover most, but not all of a particular area, while there may be some grout between them, and in any case there is also a nominal gap even between “grout-less” tile installations. In other cases, an intentionally wider gap between tiles may be designed to reduce the dose below a vertex.30

[0135] There may also be an intentionally selected spacing between the mosaic source and the surface of the tissue to be treated. For example, an air gap can be provided, ranging from about 0.5 mm or less to about 25 mm or more.

[0136] The tile pieces can be substantially two-dimensional (flat) or have non-planar cur ature. In either case, the mosaic source assembly can be substantially three-dimensional (non-planar),PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 and need not simply mimic or conform to the shape of the treatment surface defined on a particular anatomical feature of the patient. Rather, the source geometry can be modified to vary the air gap, in order to improve dose uniformity, or to modulate the dose according to the characteristic of the target site (e.g., to modulate the dose across the treatment area according to5 tumor or lesion type, shape, size and thickness or depth).

[0137] Possible source and source tile geometries include, but are not limited to, sections or portions of a cylinder, sphere, ellipsoid, or other smooth, curved surface formed by molding or deforming the source material along one or two axes. For example, a cylinder geometry can be formed by deformation of the source material about a single axis, while a sphere, ellipsoid or10 mor complex geometry can be defined by deformation with respect to one, two, or more axes.

[0138] The mosaic source can have cylindrical, circular, elliptical or irregularly shaped sides, with a flat or curved cap structure at the apex. Three-dimensional (3D) shapes can be created from flat tile pieces, such as a geodesic dome, a portion or section of a soccer-ball geometry (e.g., a truncated icosahedron formed of pentagons and hexagons), and Johnson solid geometries15 (e.g., triangular, square, or pentagonal cupolas, pentagonal rotundas, and elongated or gyroelongated versions such as an elongated pentagonal pyramid, elongated square cupola, gyroelongated pentagonal pyramid, or any of the other Johnson solids).

[0139] Elongated mosaic source shapes such as an elongated square cupola can be lengthened in a particular direction by placing triangular or rectangular tiles of various aspect ratios along the20 sides to create a source shape with a larger or smaller height than if only square tiles were used. 3D source shapes can also be created from tile pieces that are curved along one axis; e.g., similar to a volleyball covered by six sets of three substantially rectangular curved tile pieces, or similar to a soccer ball, with somewhat more complex tile geometry.

[0140] Brachytherapy devices with non-planar, mosaic source assemblies can be generally25 applied, and used on different patients or different cancer, tumor, or lesion geometries. The source geometry can also be robust to patient-to-patient variations in the shape of their respective body parts, such as the anatomy of the nose, ears, face, or other features.

[0141] Various 3D mosaic source shapes can also be assembled from a smaller, defined set of tile shapes; e.g., from a set of regular triangles, squares, pentagons and rectangles. Suitable examples include a square cupola, a pentagonal cupola, and a rectangular cupola; e.g., with a rectangular base. Modified versions of these geometries are also contemplated; e.g., source geometries that are elongated with additional square, triangular or rectangular tiles disposed along the sides or edges of the mosaic source.

[0142] One particular example is a mosaic source with a square cupola geometry formed from35 five square tiles and four equilateral triangle tiles. An elongated version of this geometry canPCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 have an additional eight or more square, triangular or rectangular tiles disposed along the base, making the mosaic source taller; e.g., either to accommodate the geometry of the target, or to increase the air gap. Suitable gyroelongated forms for the mosaic source can have up to sixteen or more additional triangular tiles increasing their height. Similarly, a mosaic source in the form5 of a rectangular cupola can be assembled wi th two square tiles at the top or apex (cap). A pentagonal rotunda can be created from a pentagon, five equilateral triangles, and five squares.

[0143] One goal may be to minimize the number of different tile elements that need to be created in order to assemble mosaic sources with a broad number of Johnson solid-like shapes. For example, various mosaic source geometries can be assembled from a defined set of10 triangular, square or rectangular, and / or other regular polygonal tiles, in either flat (2D) or curved (3D) configurations.

[0144] Brachytherapy devices with mosaic sources can be used to treat cancer and other conditions on the nose, ear, or face of a patient, or on the digits (fingers or toes), or on other body parts and anatomical features with substantial curvature. For example, the tumor or lesion15 to be treated may be present on a substantially flat or flattenable region of the body, such as the cheek, neck, shoulder, trunk or leg, or on an anatomical feature with more curvature.

[0145] Suitable sources with 3D shapes can be formed by a combination of: a) stamping (pressing or deforming a flat part to define a tile), b) machining a tile out of a larger piece of material,20 c) forming particles into a selected shape and sintering or bonding the particles together to define a tile, and / or d) forming particles in a matrix into a desired or predesigned dome-like shape defining the source geometry.

[0146] The tiles forming a particular mosaic source can be substantially similar in thickness. The25 source can provide an activity per unit area that varies by less than 10%, less than 5%, or less than 2% across a particular treatment surface. Extra layers of tiles can be included to modulate (e.g., to increase) the delivered dose in particular regions of the treatment area, or across the treatment area.

[0147] A non-planar dome-shaped source geometry can also be fabricated from radioactive seeds. This differs from other examples in that the seeds are not necessarily planar, and can have substantial gaps between them.

[0148] An aperture can be used to define the area to be treated on a particular patient, for example as defined in a collimator or in the shield material of a base or housing in which the source is disposed. The shielding or collimator material may be selected from metal, ceramic,35 polymer, or polymer composites; e.g., a polymer loaded with tungsten (W) or another high-PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 density material with density greater than 7.5 g / cm3, or greater than 15 g / cm3. The aperture and collimator or shielding material can be contoured to a particular anatomical structure and treatment surface, and adapted to provide customization to the dose delivered to each patient.

[0149] The air gap defined between the treatment surface and the tiles or other structures5 defining the 3D source geometry can vary in a range of about 1 mm or less to about 25 mm or more, for example about 2 mm to about 10 mm. This gap distance can be measured normal to the treatment surface defined on the anatomical structure of the patient, to the surface of the source tile.

[0150] The source materials can be formed from an isotope that is stable but can be activated by10 exposure to neutron radiation. Examples include, but are not limited to, isotopes of barium (Ba), bismuth (Bi), cadmium (Cd), cesium (Cs), cerium (Ce), Chromium (Cr), cobalt (Co), copper (Cu), dysprosium (Dy), erbium (Er), europium (Eu), gadolinium (Gd), gold (Au), holmium (Ho), iodine (I), iridium (Ir), lanthanum (La), lithium (Li), lutetium (Lu), neodymium (Nd), nickel (Ni), palladium (Pd), platinum (Pt), praseodymium (Pr), phosphorous (P), promethium (Pm),15 rhenium (Re), ruthenium (Ru), samarium (Sm), scandium (Sc), silver (Ag), sodium (Na), strontium (Sr), terbium (Tb), thulium (Tm), ytterbium (Yb), yttrium (Y), zinc (Zn), and other isotopes. Suitable source materials and methods of activation are further described in Sarazin et al., U.S. Publication No. 2020 / 0188691A1, which is incorporated by reference herein, in the entirety and for all purposes.20

[0151] The source tiles can be encapsulated in a protective layer, for example using thin films of material selected to maintain source integrity and prevent the radioactive material from coming into contact with the patient’s skin, or to protect from or contain flaking, friation or sloughing off of the source material, and to reduce the risk of contamination and / or exposure to medical practitioners and other health care providers, and the surrounding environment.25

[0152] The film or encapsulant can be deposited onto the source material using chemical vapor deposition or a variant thereof, or using one or more techniques including, but not limited to, chemical vapor deposition, plasma-enhanced chemical vapor deposition, low-pressure chemical vapor deposition, metal-organic chemical vapor deposition, aerosol-assisted chemical vapor deposition, laser chemical vapor deposition, hot-wire chemical vapor deposition, pyrolysis, combustion chemical vapor deposition, and atomic layer deposition, as well as various variations thereof.

[0153] One or more layers of such a thin film or encapsulant can also be deposited using a physical vapor deposition or a variant thereof, or using one or more techniques including, but not limited to, thermal evaporation, electron-beam deposition, pulsed electron deposition, ion-beam35 assisted deposition, sputtering (DC, RF, magnetron, reactive, and variations thereof), pulsed laserPCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 deposition, arc vapor deposition, cathode arc deposition, or activated reactive evaporation, and variations thereof.

[0154] The film or encapsulant can also be deposited onto the source material by electroplating or electroless plating. For example, this technique may have applications to cadmium (Cd),5 chromium (Cr), copper (Cu), gold (Au), iridium (Ir), lead (Pb), nickel (Ni), palladium (Pd), platinum (Pt), rhodium (Rh), silver (Ag), tin (Sn), zinc (Zn), or carbon (C) containing polymer coatings.

[0155] In some examples, the source tiles can be encapsulated using thin films of a vapor- deposited polymer. Suitable examples include parylene-based materials and polymer materials10 including, but not limited to, polyacrylonitriles, polyaniline, polyimides, polymethyl methacrylate, substituted poly(p-xylylene) materials including, but no limited to, parylene-AF-4, parylene-HT, pary lene-C, parylene-D, parylene-F, and parylene-N, polytetrafluoroethylene, polyvinylidene fluoride, polysilanes, and silicones, and variations thereof, and other suitable polymer encapsulating materials.15

[0156] The encapsulating material can be coated onto the source tiles before or after neutron activation. In some examples, the coating or encapsulant can be selected from materials that are not subject to neutron activation, or which have a small cross section for neutron activation, with a suitably low activity level. Depending on application, suitable encapsulating materials can include aluminum (Al), rhodium (Rh), silicon (Si), titanium (Ti), vanadium (Va), and20 combinations or compounds or mixtures thereof, including nitrides, carbides, oxides, sulfides, complex compounds of such metals (e.g., oxynitrides, carbonitrides, oxy carbonitrides), as well as silicon dioxide (SiC>2), pyrolytic graphite, pyrolytic boron nitride, and diamond-like carbon.

[0157] The source material can also be coated after activation to avoid activation of the coating itself. For example, the source material could be encapsulated by electroplating or electroless plating of a metal such as gold (Au), nickel (Ni), copper (Cu), chromium (Cr), zinc (Zn), palladium (Pd), platinum (Pt), rhodium (Rh), iridium (Ir), or other suitable metal, or with a combination thereof.

[0158] A combination of thin film, sheet, foil and / or other encapsulating materials can also be used, for example either deposited or freestanding layers (sheets) of plastics, polymers, metal30 films or foils, or other encapsulating material selected to maintain integrity of the source material, and to prevent or contain flaking, friation or sloughing, as described above. Suitable thicknesses range from about 0.2 mil (about 5 pm) to about 1.0 mil (about 25 pm), for example about 0.4 mil (about 10 pm), or up to about 10 mil (about 250 pm). A suitable plastic or polymer layer could also be selected for a practically lower limit of thinness while maintain structuralPCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 integrity, for example about 0.5 mil to about 1.0 mil (about 12 pm to about 25 pm), depending on the selected material.

[0159] For example, a first layer of such a thin film, sheet, foil or encapsulating material can be applied to the source material according to any of the techniques above, and a second sheet or5 layer of thin film, foil, or other encapsulating material can be applied over the first layer. The first and second layers can be the same or different, and may be applied either or after neutron activation. The first layer could also be applied before activation, with the second layer applied either after activation or during assembly of the source material into a brachytherapy device. The layers can be selected to provide further protection against potential contamination, using materials with the same, different, or complimentary properties including mechanical strength and resistance to radiation, temperature, aging, and oxidation.

[0160] The activated source material can be chosen to emit a selected form of radiation with a selected energy range. For example, the activated source material may emit electrons (beta radiation) to be delivered to the treatment area, with an energy range, activity level and half-life15 selected for treatment of a particular tumor or lesion based on type, size, shape, thickness, and location. The activated source material may also emit gamma or x-ray radiation to be delivered to the treatment area, with a similarly selected energy range, activity level and half-life. The material and thickness of any thin film or encapsulating layers can be selected accordingly, in order to maintain integrity of the source material while transmitting the selected form of radiation.

[0161] The source tiles can be assembled into a desired or selected geometrical shape defining the mosaic source after neutron activation. The tiles can also be assembled into the desired or selected geometrical shape before neutron activation. Suitable activated source techniques are also described in U.S. Publications No. 2020 / 0188691A1 and No. 2024 / 0207640 Al,25 incorporated by reference herein.

[0162] This disclosure is made with reference to representative examples and embodiments. Changes can be made and equivalents can be substituted to adapt these teachings to other materials, problems and applications, as known to persons of skill in that art, while remaining within the scope of invention as defined by the appended claims.PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01Table 1. Figure referencesPCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01

Claims

1. PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01Claims1. A device comprising: a base configured to be disposed on or adjacent an anatomical feature of a patient; a collimator disposed in or on the base, wherein the collimator is configured to define an5 aperture adjacent a treatment surface on the anatomical structure, when the base is disposed thereon; a housing couplable to the base; and a radiation source disposed in the housing, wherein the radiation source comprises a plurality of tiles defining a source geometry of the source; wherein the source geometry is configured to deliver a dose from the source to the treatment surface via the aperture, when the housing is coupled to the base; wherein the source geometry is selected to modulate the dose based on a gap defined between the treatment surface and adjacent surfaces of the respective tiles, wherein the gap varies across the treatment surface.15 2. The device of claim 1, wherein one or more of the tiles comprises an isotopic source material with a substantial cross section for neutron absorption, whereby the isotopic source material is convertible to a radioisotope.

3. The device of claim 2 , wherein the radioisotope emits beta radiation, wherein the radioisotope emits x-ray radiation, or wherein the radioisotope emits gamma radiation.20 4. The device of claim 1, claim 2 or claim 3, wherein the source material is selected from an isotope of barium (Ba), bismuth (Bi), cadmium (Cd), cesium (Cs), cerium (Ce), Chromium (Cr), cobalt (Co), copper (Cu), dysprosium (Dy), erbium (Er), europium (Eu), gadolinium (Gd), gold (Au), holmium (Ho), iodine (I), iridium (Ir), lanthanum (La), lithium (Li), lutetium (Lu), neodymium (Nd), nickel (Ni), palladium (Pd), platinum (Pt), praseodymium (Pr), phosphorous (P), promethium (Pm), rhenium (Re), rhodium (Rh), ruthenium (Ru), samarium (Sm), scandium (Sc), silver (Ag), sodium (Na), strontium (Sr), terbium (Tb), thulium (Tm), ytterbium (Yb), yttrium (Y) or zinc (Zn).

5. The device of any of claims 1-4, wherein the source geometry comprises a mosaic geometry defined by an array of the plurality of tiles, wherein the array is configured to modulate30 the dose delivered by the source to the treatment surface via the aperture, when the housing is coupled to the base.PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.

016. The device of claim 5, where the mosaic geometry comprises at least one element omitted from the array, wherein the omitted element is defined between two or more of the plurality of tiles to further modulate the dose.

7. The device of claim 5 or claim 6, wherein the mosaic geometry comprises a tile spacing5 defined between adjacent tiles in the plurality of tiles.

8. The device of claim 7, where in the tile spacing is non-uniform between at least two of the adjacent tiles, wherein the non-uniform spacing is configured to further modulate the dose.

9. The device of claim 7 or claim 8, wherein the tile spacing is less than 5 mm, less than1 mm, or less than 0.2 mm.10 10. The device of any of claims 5-9, wherein the mosaic geometry comprises a section of a regular polyhedron, Johnson solid, Catalan Solid, Kepler-Poinsot polyhedron, irregular polyhedron or combinations and variations thereof defined by the plurality of tiles.

11. The device of any of claims 1-10, wherein each of tiles has a substantially planar geometry defined as a triangle, a square or a rectangle, or a regular or irregular polygon.15 12. The device of any of claims 1-11, wherein one or more of the tiles has a substantially nonplanar geometry define by curvature about or along one or more axes.

13. The device of any of claims 1-12, wherein the base and collimator are configured to maintain a minimum width of the gap across the treatment surface, wherein the minimum width is defined perpendicular from the treatment surface to a surface of a nearest tile of the plurality20 of tiles along the perpendicular, and wherein the minimum width is at least 0.2 mm, or at least2 mm.

14. The device of claim 13, wherein the minimum width of the gap varies from about 1 mm to about 50 mm over the treatment area, or between about 2 mm and about 10 mm.

15. The device of any of claims 1-14, wherein the source geometry is substantially25 nonplanar, and does not substantially conform to a geometry of the treatment surface, nor to a surface geometry of the anatomical feature.

16. The device of claim 15, wherein the geometry of the treatment surface or the surface geometry of the anatomical feature is substantially planar.PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.0117. The device of claim 15 or claim 16, wherein the geometry of the treatment surface or the surface geometry of the anatomical feature is substantially nonplanar.

18. The device of any of claims 1-17, wherein the collimator is configured to define the aperture adjacent a substantially nonplanar treatment surface on the anatomical structure, or5 wherein the treatment surface comprising at least a portion of a nose, ear, facial feature, finger, or digit of a patient.

19. The device of any of claims 1-18, wherein the tiles have a substantially uniform thickness or substantially uniform geometric shape, or wherein the tiles are selected from a set of four or fewer uniform geometric shapes.10 20. The device of any of claims 1-19, wherein the source geometry is selected to modulate the dose based on the gap varying between about 1 mm and about 4 mm, or between about 0.25 mm and about 50 mm.

21. The device of claim 20, wherein the dose is modulated to vary by less than 2% over the treatment area, or by less than 5%, or by less than 10%.15 22. The device of any of claims 1-21, wherein one or both of the housing and the collimator is formed of a metal, ceramic, polymer or composite material, or a combination thereof.

23. The device of claim 1, wherein one or more of the tiles comprises a source material, and further comprising one or more sheets or layers of a thin film, foil or encapsulating material deposited on or disposed over one or more surfaces of each of said one or more of the tiles,20 wherein the thin film or encapsulating material is selected to maintain integrity of the source material within the respective tile.

24. The device of claim 23, wherein one or more of the sheets or layers of thin film, foil or encapsulating material comprise a thin film deposited on the one or more tiles, or a freestanding film or foil disposed on the one or more tiles or between the source material and the collimator.25 25. The device of claim 23 or claim 24, wherein the one or more sheets or layers of thin film, foil or encapsulating material comprise at least one of aluminum (Al), carbon (C), rhodium (Rh), silicon (Si) titanium (Ti), vanadium (Va), or a combination or compound or mixture thereof, or a nitride, carbide, oxide, silicide, sulfide fluoride, chloride, or complex compound thereof, including oxynitrides, carbonitrides and oxy carbonitrides thereof; or silicon dioxide (SiO2),PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 pyrolytic graphite, pyrolytic boron nitride, or diamond-like carbon, amorphous carbon, pyrolytic carbon, carbon containing polymers, or a combination thereof.

26. The device of claim 23, claim 24 or claim 25, wherein the one or more sheets or layers of thin fdm, foil or encapsulating material comprise at least one of a vapor deposited polymer5 material, a polymer material selected from polyacrylonitrile, polyaniline, polyimide, polymethyl methacrylate, polyvinylidene fluoride, polysilanes, and silicone, or a combination thereof, or wherein the one or more shets or layers or thin film, foil or encapsulating material comprise a parylene or para-xylene material, a substituted poly(p-xylenes)z material, or a commercially available parylene-AF-4, parylene-HT, parylene-C, parylene-D, parylene-F, or parylene-N material, or a combination thereof.

27. The device of any of claims 1-26, wherein the aperture has a preselected geometry defined between the radiation source and the treatment surface, wherein the preselected geometry is configured for an anatomy of the treatment surface.

28. The device of claim 27, wherein the aperture is formed from or comprises a metal,15 ceramic, polymer, or composite material or metal-loaded polymer comprising steel, copper, or another metal with density higher than 7.5 gm / cm3, or tungsten, gold or another metal having a density greater than 15 g / cm3.

29. The device of any of claims 1-28, wherein at least some of the tiles have substantially different activities per unit area.

30. The device of any of claims 1-29, wherein the plurality of tiles define two or more layers of said tiles selected to increase or modulate the dose delivered to one or more areas of the treatment surface.

31. The device of any of claims 1-30, wherein the radiation source comprises one or more layers of non-radioactive material disposed on one or more of the tiles, wherein the non¬25 radioactive material is selected to spatially modulate the dose across the treatment surface.

32. The device of any of claims 1-31, wherein the base is formed of or comprises a metal, ceramic, polymer or composite material, or a combination thereof.

33. The device of any of claims 1-32, wherein the housing is formed of or comprises a metal, ceramic, polymer or composite material, or a combination thereof.PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.0134. The device of any of claims 1—33, wherein the housing is configured to maintain the source geometry of the radiation source, when disposed therein.

35. The device of any of claims 1-34, wherein the housing is configured to provide directional shielding of radiation emitted by the radiation source, when disposed therein.5 36. The device of any of claims 1-22 or 27-35, wherein at least one sheet or layer of thin film, foil or encapsulating layer is disposed on at least one of the tiles, or between the treatment surface and one or more of the tiles, or between the collimator and one or more of the tiles.

37. The device of claim 36, wherein the at least one sheet or layer of thin film, foil or encapsulating layer comprises an adhesive backed polymer sheet or polyimide tape, wherein one or more of the tiles are wrapped therein.

38. The device of claim 36 or claim 37, wherein the at least one sheet or layer of thin film, foil or encapsulating layer comprises a freestanding film or metal foil, a polymer sheet, or a shaped material.

39. The device of claim 36, claim 37 or claim 38, wherein the at least one sheet or layer of15 thin film, foil or encapsulating layer is selected to further modulate the dose.

40. A device comprising: a base configured to be disposed on or adjacent an anatomical feature of a patient; a collimator disposed in or on the base, wherein the collimator is configured to define an aperture adjacent a treatment surface on the anatomical structure, when the base is20 disposed thereon; a housing coupled to the base; and a radiation source disposed in the housing, the radiation source comprising a plurality of tiles defining a mosaic source geometry; wherein the mosaic source geometry is configured to modulate a dose delivered by the source to the treatment surface via the aperture based on a gap defined between the treatment surface and adjacent surfaces of the respective tiles defining the mosaic source geometry, wherein the gap varies across the treatment surface.

41. The device of claim 40, wherein one or more of the tiles comprises stamped or machined edge structures defined by stamping, punching, cutting or milling the tiles from a larger source30 material.PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.0142. The device of claim 40 or claim 41, wherein one or more of the tiles comprise a sintered, bonded, or composite matrix structure defined by forming the tiles from particles of source material.

43. The device of claim 40, claim 41 or claim 42, further comprising activating the source in5 an irradiation process, wherein one or more of the tiles comprise an isotopic source material convertible to a radioisotope in the irradiation process.

44. A method of making the device of claim 43, wherein one or more sheets or layers of thin film, foil or encapsulating material are disposed on one or more surfaces of at least one of the tiles, or between one or more such surfaces and the collimator.

45. The method of claim 44, wherein the one or more sheets or layers of thin film, foil or encapsulating material comprise one or more of gold (Au), nickel (Ni), copper (Cu), chromium (Cr), zinc (Zn), palladium (Pd), platinum (Pt) or iridium (Ir), or a combination thereof.

46. The method of claim 44 or claim 45, wherein the one or more sheets or lay ers of thin film, foil or encapsulating material are disposed on the one or more surfaces after activating the15 source material.

47. The method of claim 44, claim 45 or claim 46, wherein the one or more sheets or layers of thin film, foil or encapsulating material are disposed on the one or more surfaces by chemical vapor deposition, plasma-enhanced chemical vapor deposition, low-pressure chemical vapor deposition, metal-organic chemical vapor deposition, aerosol-assisted chemical vapor deposition,20 laser chemical vapor deposition, hot-wire chemical vapor deposition, pyrolysis, combustion chemical vapor deposition, atomic layer deposition, or a combination thereof.

48. The method of any of claims 44-47, wherein the one or more sheets or layers of thin film, foil or encapsulating material are disposed on the one or more surfaces by physical vapor deposition, thermal evaporation, electron-beam deposition, pulsed electron deposition, ion-beam assisted deposition, sputtering (DC, RF, magnetron, reactive, and variations thereof), pulsed laser deposition, arc vapor deposition, cathode arc deposition, or a combination thereof.

49. The method of any of claims 44-48, wherein the one or more sheets or layers of thin film, foil or encapsulating material are deposited on the one or more surfaces by electroplating, electroless plating, solution-based deposition, spin coating, spray coating, dip coating, brush or30 roller application, curtain coating, powder coat deposition, thin film deposition, vapor deposition, or a combination thereof, or wherein the one or more sheets or layers of thin film,PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 foil, or encapsulating material comprise a freestanding film or foil disposed on the one or more surfaces.

50. The device of claim of 40, wherein the mosaic source geometry is adapted to a selected anatomy of the treatment surface, or wherein the mosaic source geometry is adapted to two or5 more different treatment surfaces having different anatomies or disease geometries.

51. The device of claim 40 or claim 50, wherein the mosaic source geometry comprises a non-planar shape fabricated from one or more radioactive seeds, wherein the radioactive seeds are spaced along the non-planar shape.

52. The device of claim 40, claim 50 or claim 51, wherein the tiles have a substantially uniform thickness or substantially uniform geometric shape, or wherein the tiles are selected from a set of four or fewer uniform geometric shapes.

53. The device of claim 40 or any of claims 50-52, wherein the mosaic source geometry is defined by an array of the tiles, wherein at least one element is omitted from the array between two more of the tiles.15 54. A method of making the device of claim 40 or any of claims 50-53, wherein the mosaic source geometry defines a set of one or more three-dimensional shapes formed by the tiles.

55. The method of claim 54, wherein the set of three-dimensional shapes comprise one or more non-planar portions of a cylinder, sphere, ellipsoid, or other smooth curved surface.

56. The method of claim 54 or claim 55, wherein the set of three-dimensional shapes are20 formed by stamping, pressing or deforming one or more of the tiles, machining one or more of the tiles out of a larger working piece of material, or forming one or more assemblies of particles and sintering or bonding the one or more assemblies of particles together to form one or more of the tiles.

57. The method of claim 54, claim 55 or claim 56, wherein the set of three-dimensional shapes are formed by molding or deforming one or more of the tiles along one or two axes, or wherein the set of one or more three dimensional shapes comprise one or more portions of a cylinder curved along or about an axis, or one or more portions of a sphere or ellipsoid curved along or about two axes.

58. The method of any of claims 54-57, wherein the set of three-dimensional shapes30 comprise a partial tube geometry with a circular, elliptical or geometric cross section.PCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.0159. The method of claim 58, further comprising a flat or curved cap portion defined on the partial tube geometry.

60. A method comprising: providing a device comprising a base coupled to a housing,5 wherein a collimator is disposed in or on the base and a radiation source is disposed in the housing, and wherein the radiation source comprises a plurality of tiles defining a source geometry; disposing the base on or adjacent an anatomical structure of a patient, wherein the collimator is configured to define an aperture adjacent a treatment surface on the anatomical structure, wherein the source geometry is configured to modulate a dose delivered by the source to the treatment surface via the aperture based on a gap defined between the treatment surface and adjacent surfaces of the respective tiles,15 and wherein the gap varies across the treatment surface.

61. The method of claim 60, further comprising activating the source, wherein one or more of the tiles comprises an isotopic source convertible to a radioisotope having an activity substantially higher than background.20 62. The method of claim 61, wherein activating the source comprises exposing said one or more of the tiles to neutron radiation, wherein the isotopic source material is converted to the radioisotope thereby.

63. The method of claim 62, wherein exposing said one or more of the tiles to neutron radiation is performed before assembling said one or more tiles to define the source geometry of the radiation source.

64. The method of claim 61, claim 62 or claim 63, further comprising encapsulating with or disposing upon or adjacent said one or more of the tiles, one or more sheets or layers of a thin film, foil or encapsulating material selected for maintaining integrity of the isotopic source material and radioisotope within the respective tile, wherein the one or more sheets or layers comprise one or30 more deposited thin films or freestanding films or foils.

65. The method of claim 64, wherein encapsulating with or disposing upon said one or more of the tiles the one or more sheets or layers of thin film, foil or encapsulating material isPCT / US25 / 44073 28 August 2025 (28.08.2025)P319676.WO.01 performed before exposing said one or more of the tiles to neutron radiation, wherein the radiation source is activated thereby.

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