Ultra compact particle therapy system

Abstract

Described herein are compact particle therapy systems comprising a superconducting cyclotron for proton therapy applications. In some aspects, an electromagnetic beamline incorporating energy selection systems and pencil beam scanning magnets directs particle beams from the cyclotron to a treatment isocenter. A patient positioning device comprising a robotic positioner with six degrees of freedom supports patient alignment, t. The particle system can be ultra compact and able to be installed in existing photon linear accelerator (e.g., radiation therapy) vaults.

Description

[0001] ULTRA COMPACT PARTICLE THERAPY SYSTEM

[0002] RELATED APPLICATION

[0003] This application claims the benefit of U.S. Provisional Application No. 63 / 701,430, filed on September 30, 2024, which is incorporated herein by reference in its entirety.

[0004] BACKGROUND OF INVENTION

[0005] Particle therapy is a type of radiation therapy used in cancer treatment that provides a better therapeutic ratio by reducing dose to healthy tissue and increasing the Relative Biological Effectiveness (RBE) in cancer cells. As the Linear Energy Transfer (LET) increases within the Bragg peak, the amount of cancer cells that are killed within a particle therapy beam for the same dose [J7kg] also increases, when compared to photon therapy. Certain cancer cells also have DNA repair mutations that further increase their sensitivity to LET relative to the healthy tissues surrounding them.

[0006] Particle therapy may be delivered using particle accelerators and gantries based on copper resistive conductor or Low Temperature Superconductors (LTS). Resistive or LTS based treatment machines are large and expensive, and they also require construction of new treatment rooms that are shielded by thick concrete walls.

[0007] There is a need for less expensive and smaller treatment machines that can readily be installed into existing radiation treatment vaults (e.g., Mega Electron Volt (MeV) electron linear accelerator (linac) photon radiation treatment vaults).

[0008] SUMMARY OF INVENTION

[0009] Provided herein are novel systems for delivering particle therapy wherein a small-scale particle source (e.g., small-scale particle accelerator) is combined with one or more scanning and / or imaging devices to control therapeutic particle delivery to a patient (e.g., a patient having cancer).

[0010] In some aspects, provided is a particle therapy system comprising: a particle accelerator structured to generate a particle beam; an electromagnetic beamline configured to direct the particle beam from the particle accelerator to a corresponding patient positioning device (e.g., to position the patient upright), the electromagnetic beamline comprising a plurality of electromagnets structured to bend and steer the particle beam; and a patient positioning device

[0011] #14454901 v1 being structured to support a patient within a location such that a target area of the patient is located at a center of the particle beam.

[0012] In some aspects, the electromagnetic beamline comprises a Pencil Beam Scanning (PBS) magnet. In some aspects, the electromagnetic beamline further comprises an energy selection system. In some aspects, the particle accelerator may be coupled to alternative beamline configurations including but not limited to passive scattering systems, rotating gantries, vertical beamlines, or compact beamline designs utilizing permanent magnets or combined function magnets.

[0013] In some aspects, the plurality of electromagnets are structured to selectively bend the particle beam on a substantially horizontal plane to selectively direct the particle beam to the target area of the patient.

[0014] In some aspects, the patient positioning device (e.g., upright patient positioning device) comprises: a selectively movable patient support platform, optionally with a seat, structured to support the patient and connected to a robotic positioner and a vertical carbon fiber couch; a robotic positioner; and a vertical carbon fiber couch mounted onto the patient support platform in a location behind a patient. In some aspects, the patient positioning device may comprise alternative configurations including horizontal treatment couches, seated treatment chairs, standing treatment frames, or any patient support system capable of maintaining patient position during particle therapy delivery. The particle accelerator described herein is compatible with and may be integrated with any such patient positioning configuration.

[0015] In some aspects, the robotic positioner comprises at least two members that are movably connected and can rotate the selectively movable patient support platform with six degrees of freedom. In some aspects, the robotic positioner comprises at least two members that are movably connected and can rotate the selectively movable patient support platform with 360 degrees in a horizontal plane.

[0016] In some aspects, the patient positioning device further comprises a scanner mounted at the bottom of the vertical carbon fiber couch.

[0017] In some aspects, the scanner is a CT scanner, CBCT scanner, or MRI scanner.

[0018] In some aspects, the patient positioning device further comprises a surface imaging system (e.g., a surface imager) mounted at the top of the vertical carbon fiber couch and structured to form a surface image and establish the position of the patient in the treatment room. In some aspects, a surface imager is mounted at the top of the vertical carbon fiber couch and structured to form a position image of the patient. In some aspects, patient positioning and alignment may be achieved through various imaging modalities including but not limited to CT,

[0019] #14454901 v1 CBCT, MRI, PET, stereoscopic X-ray, optical surface imaging, ultrasound imaging, infrared tracking, electromagnetic tracking, or combinations thereof. The compact superconducting cyclotron described herein, in some embodiments, is compatible with, and may operate independently of, the specific imaging modalities employed.

[0020] In some aspects, the surface imaging system (e.g., surface imager) is a surface machine vision array comprising an array of sensors arranged in a circle above the patient and structured to integrate with each other to form the position image of the patient. In some aspects, the surface imaging system (e.g., surface imager) is a surface machine vision array comprising an array of 3D cameras arranged in a horizontal circle above the patient and structured to integrate with each other to form the position image of the patient.

[0021] In some aspects, the particle accelerator comprises a superconducting cyclotron.

[0022] In some aspects, the superconducting cyclotron comprises an ion source selected from the group consisting of an electron cyclotron resonance (ECR) ion source, a Penning ion source, a multicusp ion source, a hot cathode ion source, a cold cathode ion source, a PIG (Penning Ionization Gauge) ion source, an H-minus (H ) ion source, combinations thereof, and dual ion source configurations comprising both internal and external ion sources.

[0023] In some aspects, the particle therapy system further comprises a computer system.

[0024] In some aspects, the particle therapy system is installed in a linear accelerator vault (e.g., a photon linear accelerator vault).

[0025] In some aspects, the particle is a proton, a helium ion, a lithium ion, a beryllium ion, a boron ion, a carbon ion, a nitrogen ion, an oxygen ion, or other light ion suitable for particle therapy.

[0026] In some aspects, the electromagnetic beamline comprises quadrupole focusing magnets, zero or more dipole bending magnets, and at least one pencil beam scanning magnet. In some aspects, the electromagnetic beamline comprises at least one quadrupole triplet, at least one quadrupole doublet, at least one dipole bending magnet, and at least one pencil beam scanning magnet.

[0027] In some aspects, the electromagnetic beamline comprises an electromagnetic beamline comprising an arrangement from the accelerator to the patient of three quadrupoles, one dipole, three quadrupoles, one dipole and two quadrupoles, and a pencil beam scanning magnet.

[0028] Further provided is a method of treating a subject with particle therapy, the method comprising: providing a particle therapy system described herein, positioning a patient on the selectively movable patient support platform; actuating surface imaging sensors to obtain surface position and the radiological imaging system to obtain tumor position coordinates;

[0029] #14454901 v1 actuating the robotic positioner to move the selectively movable patient support platform to position the tumor position coordinates in the isocenter of the particle beam; and actuating delivery of the particle beam to the tumor position. Further provided is a method of treating a subject with particle therapy, the method comprising: providing a particle therapy system described herein, positioning a patient on the selectively movable patient support platform; actuating the CT scanner and 3D cameras to obtain surface position and tumor position coordinates; actuating the robotic positioner to move the selectively movable patient support platform to position the tumor position coordinates in the isocenter of the particle beam; and actuating delivery of the particle beam to the tumor position.

[0030] In some aspects, the superconducting cyclotron comprises at least one high temperature superconductor (HTS). In some aspects, the HTS is selected from the group consisting of bismuth-based superconductors, Rare Earth Barium Copper Oxide (REBCO) superconductors, iron-based superconductors, advanced HTS tape conductors, and combinations thereof. In some aspects, the bismuth-based superconductor is selected from the group consisting of Bi-2212 (Bi2Sr2CaCu2Os+x), Bi-2223 (Bi2Sr2Ca2Cu30w+x), and BSCCO. In some aspects, the bismuth- based superconductor comprises Bi-2212 in round wire form. In some aspects, the Bi-2212 round wire has a current density of at least 300 A / mm2producing at least 11 Tesla along the central axis of the cyclotron.

[0031] In some aspects, the In some aspects, the REBCO superconductor is selected from the group consisting of YBCO (YBa2CusO7x, also referred to as Y123), GdBCO (GdBa2Cu3O?-x, also referred to as Gdl23), DyBCO (DyBa2Cu3O?-x, also referred to as Dy 123), SmBCO (SmBa2Cu3O?-x, also referred to as Sml23), EuBCO (EuBa2Cu3O?-x, also referred to as Eul23), NdBCO (NdBa2Cu3O?-x, also referred to as Ndl23), HoBCO (HoBa2Cu3O?-x, also referred to as Ho 123), ErBCO (ErBa2CusO7x, also referred to as Er 123), YbBCO (YbBa2Cu3O?x, also referred to as Ybl23), TmBCO (TmBa2Cu3O?-x, also referred to as Tml23), and LaBCO (LaBa2Cu3O7-x, also referred to as Lal23), wherein x ranges from 0 to 0.5. In some aspects, the REBCO superconductor comprises commercially available flat tape conductors having widths of 4mm, 6mm, 10mm, or 12mm and thicknesses of 50-150 micrometers, configured in stacked pancake coils similar to high-field fusion magnet designs. In some aspects, multiple REBCO tapes are stacked and co-wound in parallel to achieve the required operating current while maintaining individual tape current densities within optimal ranges. In some aspects, the REBCO tapes are alternatively processed into round wire configurations to achieve improved isotropic performance, including symmetric tape round (STAR) wires comprising multiple REBCO tapes arranged symmetrically around a central core, conductor on round core (CORC)

[0032] #14454901 v1 cables comprising REBCO tapes wound helically around a cylindrical former, and twisted stacked-tape cables (TSTC) comprising multiple REBCO tapes stacked and twisted into a round configuration. In some aspects, the flat tape configuration provides manufacturing simplicity and proven performance in high-field applications, while the round wire configurations offer advantages for specific coil geometries and mechanical support requirements in cyclotron applications.

[0033] In some aspects, the REBCO superconductor comprises commercially available tape conductors having widths of 4mm, 6mm, 10mm, or 12mm and thicknesses of 50-150 micrometers. In some aspects, the REBCO tape achieves engineering critical current densities of 400-1200 A / mm2while producing at least an 11 Tesla field in the central region of the cyclotron where the particles are accelerated .

[0034] In some aspects, the REBCO tape achieves engineering critical current densities of at least 600 A / mm2at 12 Tesla and 4.2 Kelvin. In some aspects, the REBCO tape achieves engineering critical current densities of at least 400 A / mm2and produces fields above 11 Tesla. In some aspects, single REBCO tapes carry critical currents of 200-800 amperes for 4mm width tapes or 1000-2000 amperes for 12mm width tapes producing fields above 11 Tesla.

[0035] In some aspects, the HTS inner coils are configured with conductor path lengths of less than 2000 meters per coil, enabling use of commercially available single-piece REBCO conductors without joints in the high-field region. In some aspects, the REBCO conductors are available in continuous lengths of 100-2000 meters. In some aspects, the REBCO conductors are available in continuous lengths of 500-1500 meters. In some aspects, multiple REBCO tapes are used in parallel to achieve the required total operating current while maintaining current density within the specified range for each individual tape.

[0036] In some aspects, the iron-based superconductor is selected from the group consisting of Ba(Fe,Co)2As2, (Ba,K)Fe2As2, and related pnictide compounds. In some aspects, the HTS has a current density of at least 500 A / mm2.In some aspects, the HTS has a current density of at least 300 A / mm2.

[0037] In some aspects, the superconducting cyclotron further comprises at least one low temperature superconductor (LTS). In some aspects, the LTS is selected from the group consisting of NbsSn, NbTi, NbsAl, VsGa, and combinations thereof.

[0038] In some aspects, the superconducting cyclotron comprises a multi-type superconductor configuration (e.g., a hybrid configuration) with HTS coils and LTS coils. In some aspects, the multi-type superconductor configuration comprises HTS inner coils and LTS outer coils. In some aspects, the multi-type superconductor configuration is selected from the group consisting

[0039] #14454901 v1 of: Bi-2212 inner coils with NbsSn outer coils; REBCO inner coils with NbsSn outer coils; Bi- 2223 inner coils with NbsSn outer coils; advanced HTS tape conductors with NbsSn outer coils; HTS inner coils with NbsSn outer coils; HTS inner coils with NbTi outer coils; HTS inner coils with NbsAl outer coils; and any combination thereof.

[0040] In some aspects, the superconducting cyclotron comprises only HTS superconductors. In some aspects, the superconducting cyclotron comprises only LTS superconductors. In some aspects, the superconducting cyclotron consists entirely of REBCO superconductors without any other superconducting materials. In some aspects, the superconducting cyclotron consists entirely of Bi-2212 superconductors without any other superconducting materials.

[0041] In some aspects, the superconducting cyclotron is configured in a Helmholtz configuration (FIG. 5A).

[0042] In some aspects, the superconducting cyclotron generates a magnetic field of approximately 12 Tesla. In some aspects, the superconducting cyclotron has an outside diameter of less than 1.2 meters. In some aspects, the superconducting cyclotron weighs less than 5,000 kg-

[0043] In some aspects, the particle is a proton and the superconducting cyclotron provides a final beam energy in the range of 160 MeV to 240 MeV with a corresponding range in water of 17.7 cm to 35.4 cm. In some aspects, the superconducting cyclotron provides a beam energy of 210 MeV with a range in water of 28.2 cm. In some aspects, the superconducting cyclotron provides a beam energy of 230 MeV with a range in water of 32.9 cm.

[0044] In some aspects, the particle is a helium ion and the superconducting cyclotron provides a final beam energy of 180 MeV per nucleon with a range in water of 22 cm. In some aspects, the superconducting cyclotron weighs between 20,000 kg and 30,000 kg.

[0045] In some aspects, the particle is a carbon ion and the superconducting cyclotron provides a final beam energy of 280 MeV per nucleon with a range in water of 15 cm. In some aspects, the superconducting cyclotron weighs between 50,000 kg and 120,000 kg.

[0046] In some aspects, the superconducting cyclotron comprises different superconductor configurations optimized for the specific particle type.

[0047] In some aspects, the particle therapy system further comprises a room-mounted stereoscopic X-ray imaging system for patient positioning. In some aspects, the room-mounted stereoscopic X-ray imaging system comprises at least two X-ray sources positioned at different angles relative to the patient. In some aspects, the room-mounted stereoscopic X-ray imaging system comprises corresponding X-ray detectors positioned to receive X-rays from the X-ray sources. In some aspects, the room-mounted stereoscopic X-ray imaging system is configured to

[0048] #14454901 v1 provide real-time patient positioning verification. In some aspects, the room-mounted stereoscopic X-ray imaging system is integrated with the computer system to automatically adjust patient position based on stereoscopic X-ray images. In some aspects, the room-mounted stereoscopic X-ray imaging system operates in conjunction with the surface imaging system (e.g., imager) and radiological imaging system (e.g., scanner) for enhanced patient positioning accuracy. In some aspects, the room-mounted stereoscopic X-ray imaging system is configured to track patient movement during particle beam delivery. In some aspects, the X-ray sources are mounted on ceiling-mounted or wall-mounted positioning systems. In some aspects, the stereoscopic X-ray imaging system provides sub-millimeter patient positioning accuracy.

[0049] In some aspects, the superconducting cyclotron comprises an ion source selected from the group consisting of an external electron cyclotron resonance (ECR) ion source, an internal ion source, and combinations thereof. In some aspects, the external ECR ion source is positioned outside the cyclotron magnetic field and injects ions into the cyclotron through an injection system. In some aspects, the internal ion source is positioned within the cyclotron and generates ions directly in the cyclotron's magnetic field. In some aspects, the internal ion source is selected from the group consisting of a Penning ion source, a multicusp ion source, a hot cathode ion source, a cold cathode ion source, and combinations thereof.

[0050] In some aspects, the cyclotron comprises both an external ECR ion source and an internal ion source for enhanced ion production and beam intensity. In some aspects, the ion source is configured to produce hydrogen ions for proton therapy. In some aspects, the ion source is configured to produce helium ions for helium ion therapy. In some aspects, the ion source is configured to produce carbon ions for carbon ion therapy.

[0051] In some aspects, the ion source is configured to switch between different ion types for multi-particle therapy capability.

[0052] In some aspects, the internal ion source is positioned at the center of the cyclotron to optimize ion injection efficiency.

[0053] In some aspects, the ion source system is integrated with the computer system for automated control of ion source parameters including gas flow, ionization voltage, and extraction voltage.

[0054] In some aspects, the ion source system includes automated gas switching capability to change between hydrogen, helium, and carbon-containing gases for different particle therapy applications. In some aspects, the carbon-containing gas is selected from the group consisting of methane (CH4), acetylene (C2H2), and carbon dioxide (CO2). In some aspects, the single superconducting cyclotron is configured to accelerate multiple ion types from the same

[0055] #14454901 v1 accelerator system. In some aspects, the cyclotron magnetic field and RF frequency are adjustable to optimize acceleration for different ion mass-to-charge ratios. In some aspects, the gas switching system includes automated purging and conditioning sequences when changing between different gas types. In some aspects, the multi-ion capability allows treatment of different cancer types with optimal particle therapy for each specific application from a single treatment system.

[0056] In some aspects, the superconducting cyclotron operates cryogen-free without liquid helium. In some aspects, the superconducting cyclotron operates at a temperature in the range of 4 Kelvin to 30 Kelvin. In some aspects, the superconducting cyclotron operates at a temperature below 15 Kelvin.

[0057] In some aspects, the superconducting cyclotron uses cryocoolers or liquid helium for cooling. In some aspects, the cryocoolers are selected from the group consisting of Gifford- McMahon cryocoolers, pulse tube cryocoolers, Stirling cryocoolers, and combinations thereof. In some aspects, the cryocoolers provide cooling capacity equivalent to liquid helium cooling without requiring liquid cryogens.

[0058] In some aspects, the cryogen-free operation eliminates the need for liquid helium supply infrastructure and reduces operational complexity.

[0059] BRIEF DESCRIPTION OF DRAWINGS

[0060] The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present disclosure, which can be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein. The drawings are not necessarily drawn to scale.

[0061] FIG. 1A illustrates a non-limiting embodiment of a system for delivering particle therapy to a patient. FIG. IB shows a particle therapy treatment machine from various angles. FIG. 1C illustrates a configuration of the beamline. FIG. ID illustrates a non-limiting embodiment of a computer system that can be used in a particle therapy system.

[0062] FIG. 2 shows a particle therapy system inside of an existing radiation therapy vault.

[0063] FIG. 3 shows a superconducting cyclotron 600 with electron cyclotron resonance (ECR) ion source 610 and a beam (accelerated particles) 620.

[0064] FIG. 4 shows a robotic patient setup with a robotic positioner, compact CT or CBCT radiological imaging system and machine vision array.

[0065] FIG. 5A shows a magnetic field cross-sectional view. This is from a COMSOL Multiphysics simulation that shows the magnetization of the steel of the cyclotron and the

[0066] #14454901 v1 magnetic field provided by the Helmholtz style pair of coils. The cyclotron is rotationally symmetric around the vertical axis, located where the horizontal axis is zero. The accelerating plane of the protons occurs when y=0 with x ranging from 0 to 300 mm which is the limit of the accelerating plane and extraction radius. The outer radius of the magnetized steel is near x=550mm. FIG. 5B shows a magnetic field along the central accelerating plane of the cyclotron. This is taken radially from x=0 mm to x=400 mm, the proton beam extraction occurs near radius x=180 to 300 mm. The magnetic field decreases from a maximum value of 12T to an extraction value of 1 IT. FIG. 5C shows the proton therapy treatment machine from various angles, including a high view (upper left), a front view (upper right), an overhead view (bottom right), and a side view (bottom left).

[0067] FIG. 6A shows a magnetic field cross-sectional view of a helium cyclotron. The accelerating plane of the helium ions occurs when y=0 with x ranging from 0 to 450 mm which is the limit of the accelerating plane and extraction radius. The outer radius of the magnetized steel is near x=900mm. FIG. 6B shows a magnetic field along the central accelerating plane of the helium cyclotron. This is taken radially from x=0 mm to x=500 mm, the helium beam extraction occurs near radius x=300 to 450 mm. The magnetic field decreases from a maximum value of 12T to an extraction value of 1 IT. FIG. 6C shows the helium therapy treatment machine from various angles, including a high view (upper right), a front view (lower left), an overhead view (top right), and a side view (bottom right).

[0068] FIG. 7A shows a magnetic field cross-sectional view of a carbon cyclotron. The accelerating plane of the carbon ions occurs when y=0 with x ranging from 0 to 600 mm which is the limit of the accelerating plane and extraction radius. The outer radius of the magnetized steel is near x=l 100mm. FIG. 7B shows a magnetic field along the central accelerating plane of the carbon cyclotron. This is taken radially from x=0 mm to x=500 mm, the carbon ion beam extraction occurs near radius x=300 to 450 mm. The magnetic field decreases from a maximum value of 12T to an extraction value of 1 IT. FIG. 7C shows the carbon therapy treatment machine from various angles, including a high view (upper right), a front view (lower left), an overhead view (top right), and a side view (bottom right).

[0069] DETAILED DESCRIPTION OF INVENTION

[0070] Provided herein are novel systems for delivering particle therapy wherein a small-scale particle source is combined with one or more scanning and / or imaging devices to control therapeutic particle delivery to a patient (e.g., a patient or subject having cancer).

[0071] #14454901 v1 In some aspects, the disclosure provides a particle therapy system comprising a superconducting cyclotron having an outside diameter less than 1.2 meters and weight less than 5,000 kilograms for proton applications (e.g., proton therapy). The cyclotron, in some embodiments, comprises superconducting coils utilizing high temperature superconductor (HTS) materials selected from REBCO and Bi-2212, achieving engineering critical current densities exceeding 400 A / mm2at operational magnetic fields above 11 Tesla. The high temperature superconductors are employed either exclusively or in combination with low temperature superconductors, such as NbsSn and / or NbTi. In some embodiments, the cyclotron operates below liquid nitrogen temperatures using closed-cycle cryocoolers without requiring liquid helium. In some embodiments, an electromagnetic beamline incorporating energy selection systems and pencil beam scanning magnets directs particle beams from the cyclotron to a treatment isocenter. A patient positioning device comprising a robotic positioner with six degrees of freedom supports patient alignment, in some embodiments. Radiological imaging and surface imaging systems may provide patient position verification. Different cyclotron configurations are provided for different therapeutic particles, with the proton cyclotron achieving 210 MeV at less than 5,000 kg, while helium and carbon cyclotrons require proportionally larger dimensions and weights for their respective applications. The compact proton configuration also enables installation within existing radiation therapy vaults (FIG. 2).

[0072] FIGs. 1A and IB illustrate non-limiting examples of particle therapy systems described herein. FIG. 1A illustrates a non-limiting system 100 that includes a particle source 110 connected to an electromagnet beamline 115, optionally comprising a pencil bean scanning magnet, that is configured to deliver particles (e.g., H, He, or C) to a subject (e.g., a patient, for example a human patient) positioned on a patient positioning device 120. The location of a target tumor tissue in a patient can be determined using a scanner 130 that can optionally be attached to the patient positioning device 120. The patient can be further monitored using a surface imaging system (e.g., imager) 140 that can obtain image information about the position and / or movement of the subject. As shown in FIG. ID, this information can be processed using a computer system 160 that can also be used to provide instructions (e.g., automatically or with user input) to the particle source, electromagnet beamline, and patient positioning device to adjust the intensity and / or targeting of the particle beam relative to the subject’s body. The computer system 160 can be connected to each of the particle source, an electromagnet beamline, patient positioning device, radiological imaging device (e.g., scanner), and / or surface imaging system (e.g., imager) wirelessly or via an optional wired connection 150. FIG. IB illustrates further details of a non-limiting embodiment of a particle therapy system.

[0073] #14454901 v1 In some aspects, an ultra-compact pencil beam scanning particle therapy system, also referred to herein as a “particle therapy system,” comprises an electron cyclotron resonance (ECR) ion source, a superconducting cyclotron, an electromagnetic beamline with energy selection system, and a pencil beam scanning magnet.

[0074] In some aspects, the disclosure provides a method of treating a subject with particle therapy, the method comprising: providing a particle therapy system; positioning a patient on the selectively movable patient support platform; actuating the radiological imaging system and surface imaging cameras to obtain surface position and tumor position coordinates; actuating the robotic positioner to move the selectively movable patient support platform to position the tumor position coordinates in the isocenter of the particle beam; and actuating delivery of the particle beam to the tumor position.

[0075] CYCLOTRON PARTICLE ACCELERATOR

[0076] The present disclosure provides a compact superconducting cyclotron that represents a fundamental advance in particle therapy technology. While specific embodiments described herein include particular beamline configurations, patient positioning systems, and imaging modalities, it should be understood that the compact HTS superconducting cyclotron is a modular, self-contained unit that can operate independently of these specific downstream components. Examples of particle therapy treatment machines are provided in FIGs. 5C (particle), 6C (helium), and 7C (carbon). The cyclotron may be integrated with any beamline design capable of transporting charged particles, including but not limited to the fixed horizontal beamlines described herein, rotating gantries commonly used in particle therapy, vertical beamlines for specialized applications, or future beamline technologies not yet developed. Similarly, the cyclotron output is compatible with any patient positioning system, whether the upright configurations described herein, traditional horizontal treatment couches, seated treatment chairs, or novel patient support systems. The cyclotron operates independently of specific imaging modalities and can function with or without integrated imaging systems.

[0077] In some aspects, a particle beam of a particle therapy system is generated in a cyclotron. In some aspects, a particle beam of a particle therapy system is generated in a synchrocyclotron. The synchrocyclotron, in some aspects, utilizes a radially decreasing magnetic field, e.g., from about 12T to about 11T to provide axial focusing and decreases the accelerating frequency as the particles are accelerated). In some aspects, the cyclotron is a superconducting cyclotron. In some aspects, the superconducting cyclotron comprises at least one high temperature superconductor (HTS). An HTS is a superconducting material that achieves a superconducting

[0078] #14454901 v1 state at temperatures above the boiling point of liquid nitrogen (about 77 K or 196.2 °C). Each application of the superconducting wire will be operated at 4.2K. In some aspects, the HTS has a current density of at least 500 A / mm2. In some aspects, the HTS has a current density of at least 500 A / mm2, at least 600 A / mm2, at least 700 A / mm2, at least 800 A / mm2, at least 900 A / mm2, at least 1000 A / mm2, at least 1100 A / mm2, at least 1200 A / mm2, at least 1300 A / mm2, at least 1400 A / mm2, at least 1500 A / mm2, at least 1600 A / mm2, at least 1700 A / mm2, at least 1800 A / mm2, at least 1900 A / mm2, or at least 2000 A / mm2. In some aspects, the HTS is selected from the group consisting of bismuth-based superconductors, REBCO superconductors, iron-based superconductors, advanced HTS tape conductors, and combinations thereof.

[0079] In some aspects, a particle therapy system comprises a bismuth-based superconductor. The bismuth-based superconductor, in some aspects, comprises a superconductor such as Bi- 2212-, Bi-2223-, or BSCCO-based superconductor. In some aspects, the bismuth-based superconductor is Bi-2212. In some aspects, the Bi-2212 is in round wire form. The term “BSCCO,” as used herein, refers to Strontium Calcium Copper Oxide having the generalized formula: Bi2Sr2Can-iCunO 2n+4+x. The term “Bi-2212,” as used herein, refers to the n = 2 compound Bi2Sr2CaCu20s+x. In some aspects, the superconductor is in round or rectangular wire form. In some aspects, the wire (e.g., a Bi-2212 round wire) has a current density of at least 400 A / mm2at 12 Tesla when operating at 4.2 Kelvin. In some aspects, the current density is at least 500 A / mm2, at least 600 A / mm2, at least 700 A / mm2, at least 800 A / mm2, at least 900 A / mm2, at least 1000 A / mm2, or at least 1500 A / mm2at 12 Tesla and 4.2 Kelvin. In some aspects, the current density is less than 3000 A / mm2, less than 2500 A / mm2, less than 2000 A / mm2, or less than 1500 800 A / mm2at 12 Tesla and 4.2 Kelvin. The term “Bi-2223,” as used herein, refers to the n = 3 compound Bi2Sr2Ca2Cu30io+x. In some aspects, the superconducting cyclotron comprises coils formed entirely from Bi-2212 round wire superconductor, wherein Bi-2212 is the sole superconducting material utilized in the cyclotron. In some aspects, the Bi-2212 round wire maintains critical current density exceeding 400 A / mm2at magnetic fields above 10 Tesla when operated at 4.2 Kelvin. In some aspects, the Bi-2212 round wire has a diameter between 0.8 mm and 1.2 mm (e.g., 0.8 mm, 0.9 mm, 1.0 mm, 1.1 mm, or 1.2 mm). In some aspects, the Bi-2212 round wire maintains a current density of at least 400 A / mm2, producing at least 11 Tesla in the particle accelerating plane.

[0080] In some aspects, the HTS is a REBCO superconductor. In some aspects, the REBCO superconductor is selected from the group consisting of YBCO (YBa2Cu3O7), GdBCO (GdBa2Cu3O7), DyBCO (DyBa2Cu3O7), SmBCO (SmBa2Cu3O7), EuBCO (EuBa2Cu3O7), and NdBCO (NdBa2Cu3O7), HoBCO (HoBa2Cu3O7x, also referred to as Ho 123), ErBCO

[0081] #14454901 v1 (ErBa2CusO7-x, also referred to as Er 123), YbBCO (YbBa2Cu3O?x, also referred to as Ybl23), TmBCO (TmBa2Cu3O7x, also referred to as Tml23), and LaBCO (LaBa2Cu3O7x, also referred to as Lal23), wherein x ranges from 0 to 0.5. In some aspects, the superconducting cyclotron comprises coils formed entirely from REBCO superconductor, wherein REBCO is the sole superconducting material utilized in the cyclotron. In some aspects, the REBCO superconductor maintains engineering critical current density of 400-1200 A / mm2at magnetic fields above 10 Tesla when operated at 4.2 Kelvin. In some aspects, the REBCO superconductor maintains engineering critical current density of 400-800 A / mm2at magnetic fields of 10-12 Tesla in the cyclotron accelerating plane.

[0082] In some aspects, the REBCO superconductor comprises tape conductors. In some aspects, the REBCO superconductor comprises tape conductors having a width selected from 4mm, 6mm, 10mm, and 12mm (e.g., 4 mm - 12 mm; 6 mm - 8 mm). In some aspects, the REBCO superconductor comprises tape conductors having a thickness of 50-150 micrometers (e.g., 50 pm, 60 pm, 70 pm, 80 pm, 90 pm, 100 pm, 110 pm, 120 pm, 130 pm, 140 pm, or 150 pm). In some aspects, the REBCO tape conductors achieve engineering critical current densities of 400-1200 A / mm2, producing a magnetic field of at least 1 IT in the particle acceleration plane. In some aspects, the REBCO tape conductors achieve engineering critical current densities of at least 600 A / mm2, producing a magnetic field of at least 1 IT in the particle acceleration plane. In some aspects, the REBCO tape conductors achieve engineering critical current densities of at least 800 A / mm2, producing a magnetic field of at least 1 IT in the particle acceleration plane. In some aspects, individual REBCO tape conductors carry critical currents of 200-800 A for 4mm width tapes or 1000-2000 A for 12mm width tapes, producing a magnetic field of at least 1 IT in the particle acceleration plane. In some aspects, multiple REBCO tapes are configured in parallel within each coil to achieve total operating currents of 1000-10,000 A while maintaining individual tape current densities within 400-1200 A / mm2.

[0083] In some aspects, the HTS is an iron-based superconductor. In some aspects, the ironbased superconductor is selected from the group consisting of Ba(Fe,Co)2As2, (Ba,K)Fe2As2, and related pnictide compounds including phosphorus-based compounds such as BaFe2P2 and (Ba,K)Fe2P2, and additional arsenic -based compounds such as LaFeAsO, LiFeAs, and NaFeAs.

[0084] In some aspects, the HTS comprises advanced HTS tape conductors comprising REBCO or BSCCO tapes that have been processed into round wire configurations. These configurations include symmetric tape round (STAR) wires, conductor on round core (CORC) cables, twisted stacked-tape cables (TSTC), and other methods for converting flat tape geometry into round or quasi-round conductors suitable for coil winding applications.

[0085] #14454901 v1 In some aspects, the REBCO tape conductors comprise REBCO tapes that have been processed into round wire configurations through techniques selected from the group consisting of symmetric tape round (STAR) wires, conductor on round core (CORC) cables, and twisted stacked- tape cables (TSTC). In some aspects, the round REBCO wire configurations achieve improved isotropic performance in magnetic fields compared to flat tape geometries while maintaining current densities of 400-1200 A / mm2. In some aspects, the STAR wires comprise multiple REBCO tapes arranged symmetrically around a central core to form a round conductor. In some aspects, the CORC cables comprise REBCO tapes wound helically around a round former. In some aspects, the twisted stacked-tape cables comprise multiple REBCO tapes stacked and twisted into a round configuration.

[0086] In some aspects, the superconducting cyclotron further comprises at least one low temperature superconductor (LTS). As used herein, the term “LTS” refers to a material that exhibits superconductivity below 30K (-243 °C) and requires cooling with liquid helium. In some aspects, the LTS is selected from the group consisting of NbsSn, NbTi, NbsAl, VsGa, and combinations thereof.

[0087] In some aspects, a particle therapy system comprises a niobium (NbaSn)- based superconductor. In some aspects, the LTS comprises a niobium (Nb3Sn)-based superconductor. In some aspects, the LTS comprises a NbTi-based superconductor. In some aspects, the LTS comprises a NbsAl-based superconductor. In some aspects, the LTS comprises a VsGa-based superconductor.

[0088] In some aspects, the superconducting cyclotron comprises inner coils and outer coils. In some aspects, the superconducting cyclotron comprises a multi-type superconductor configuration (e.g., a hybrid configuration). The multi-type superconductor configuration, in some aspects comprises HTS coils and LTS coils. In some aspects, the multi-type superconductor configuration comprises HTS inner coils and LTS outer coils. In some aspects, the multi-type superconductor configuration comprises LTS inner coils and HTS outer coils.

[0089] In some aspects, the multi-type superconductor configuration comprises Bi-2212 inner coils and NbsSn outer coils. In some aspects, the multi-type superconductor configuration comprises REBCO inner coils and NbsSn outer coils. In some aspects, the multi-type superconductor configuration comprises exclusively Bi-2212 inner coils (e.g., Bi-2212 high critical current superconducting round wire) and NbTi outer coils. In some aspects, the multitype superconductor configuration comprises exclusively REBCO inner coils (e.g., REBCO high critical current superconducting wire) and NbTi outer coils. In some aspects, the multi-type superconductor configuration comprises Bi-2223 inner coils and NbsSn outer coils. In some

[0090] #14454901 v1 aspects, the multi-type superconductor configuration comprises advanced HTS tape conductors and NbsSn outer coils. In some aspects, the multi-type superconductor configuration comprises HTS inner coils and NbsSn outer coils. In some aspects, the multi-type superconductor configuration comprises HTS inner coils with NbTi outer coils. In some aspects, the multi-type superconductor configuration comprises HTS inner coils with NbsAl outer coils. In some aspects, the multi-type superconductor configuration comprises a combination of at least two of the following: Bi-2212 inner coils with NbsSn outer coils; REBCO inner coils with NbsSn outer coils; Bi-2223 inner coils with NbsSn outer coils; advanced HTS tape conductors with NbsSn outer coils; HTS inner coils with NbsSn outer coils; HTS inner coils with NbTi outer coils; and HTS inner coils with NbsAl outer coils. In some aspects, the inner coils comprise high critical current superconducting wires selected from HTS materials including Bi-2212, Bi-2223, BSCCO, and REBCO; and the outer coils comprise NbsSn or NbTi superconducting wires. In some aspects, the high critical current HTS wires are positioned where magnetic fields exceed

[0091] 10 Tesla.

[0092] In some aspects, the HTS inner coils utilize REBCO conductors in continuous lengths of 100-2000 meters (e.g., 100 m, 200 m, 300 m, 400 m, 500 m, 600 m, 700 m, 800 m, 900 m, 1000 m, 1100 m, 1200 m, 1300 m, 1400 m, 1500 m, 1600 m, 1700 m, 1800 m, 1900 m, or 2000 ) without joints in the high-field region. In some aspects, the HTS inner coils are configured with conductor path lengths of less than 2000 meters per coil, enabling use of commercially available single-piece REBCO conductors.

[0093] In some aspects, the superconducting cyclotron comprises HTS superconductors only. In some aspects, the superconducting cyclotron consists entirely of REBCO superconducting coils without any Bi-2212, LTS, or other superconducting materials. In some aspects, the superconducting cyclotron consists entirely of REBCO superconducting coils without any Bi- 2212, LTS, or other superconducting materials and the REBCO coils alone generate magnetic fields exceeding 11 Tesla for particle acceleration. In some aspects, the superconducting cyclotron consists entirely of Bi-2212 round wire superconducting coils without any REBCO, LTS, or other superconducting materials. In some aspects, the superconducting cyclotron consists entirely of Bi-2212 round wire superconducting coils without any REBCO, LTS, or other superconducting materials and the Bi-2212 coils alone generate magnetic fields exceeding

[0094] 11 Tesla for particle acceleration. In some aspects, the superconducting cyclotron comprises LTS superconductors only.

[0095] In some aspects, the superconducting cyclotron is configured in a Helmholtz configuration. In some aspects, the Helmholtz configuration is an iron-dominated

[0096] #14454901 v1 superconducting system. In some aspects, the Helmholtz configuration is an iron-free superconducting system.

[0097] In some aspects, the superconducting cyclotron generates a magnetic field of approximately 12 Tesla (T). In some aspects, the superconducting cyclotron generates a magnetic field of approximately 2-20 T (e.g., 2-6 T, 3-7 T, 4-8 T, 5-9 T, 6-10 T, 7-11 T, 8-12 T, 9-13 T, 10-14 T, 11-13 T, 11-15 T, 12-16 T, 13-17 T, 14-18 T, 15-19 T, or 16-20 T). In some aspects, the superconducting cyclotron generates a magnetic field of approximately 2 T, 3 T, 4 T, 5 T, 6 T, 7 T, 8 T, 9 T, 10 T, 11 T, 12 T, 13 T, 14 T, 15 T, 16 T, 17 T, 18 T, 19 T, or 20 T. In some aspects, the superconducting cyclotron generates a magnetic field exceeding 11 T with a radially decreasing profile for weak focusing.

[0098] In some aspects, a superconducting cyclotron has an outside diameter of about 4 m, about 3.8 m, about 3.6 m, about 3.4 m, about 3.2 m, about 3 m, about 2.8 m, about 2.6 m, about 2.4 m, about 2.2 m, about 2 m, about 1.8 m, about 1.6 m, about 1.4 m, about 1.2 m, about 1 m, about 0.9 m, about 0.8 m, about 0.7 m, about 0.6 m, about 0.5 m, about 0.4 m, or about 0.3 m. In some aspects, the superconducting cyclotron has an outside diameter of about 0.3 m to about 2 m (e.g., about 0.4 m to about 1.9 m, about 0.5 m to about 1.8 m, about 0.6 m to about 1.7 m, about 0.7 m to about 1.6 m, about 0.8 m to about 1.5 m, about 0.9 m to about 1.4 m, about 1.0 m to about 1.3 m, or about 1.1 m to about 1.2 m). In some aspects, the superconducting cyclotron has an outside diameter of less than 1.2 m. In some aspects, the superconducting cyclotron has an outside diameter of less than 1.5 m. In some aspects, the superconducting cyclotron has an outside diameter of less than 2 m. In some aspects, the superconducting cyclotron has an outside diameter of less than 2.5 m. In some aspects, the superconducting cyclotron has an outside diameter of less than 1 m. In some aspects, the superconducting cyclotron has an outside diameter of less than 0.5 m.

[0099] In some aspects, a superconducting cyclotron operates cryogen-free. In some aspects, the superconducting cyclotron operates cryogen-free without liquid helium. In some aspects, the superconducting cyclotron operates at a temperature range of 4 K to 30 K (e.g., In some aspects, the superconducting cyclotron operates within a temperature range from about 4 K to about 30 K (e.g., about 4 K to about 7 K, about 7 K to about 10 K, about 10 K to about 13 K, about 13 K to about 16 K, about 16 K to about 19 K, about 19 K to about 22 K, about 22 K to about 25 K, about 25 K to about 28 K, or about 28 K to about 30 K). In some aspects, the superconducting cyclotron operates within a temperature of about 4 K, about 5 K, about 6 K, about 7 K, about 8 K, about 9 K, about 10 K, about 11 K, about 12 K, about 13 K, about 14 K, about 15 K, about 16 K, about 17 K, about 18 K, about 19 K, about 20 K, about 21 K, about 22 K, about 23 K, about

[0100] #14454901 v1 24 K, about 25 K, about 26 K, about 27 K, about 28 K, about 29 K, or about 30 K). In some aspects, the superconducting cyclotron operates at a temperature below 15 K (e.g., about 4 K, about 5 K, about 6 K, about 7 K, about 8 K, about 9 K, about 10 K, about 11 K, about 12 K, about 13 K, or about 14 K). In some aspects, a superconducting cyclotron operates at a temperature below 15 K (e.g., below 10 K, below 5 K). In some aspects, a superconducting cyclotron operates at a temperature range of about 4 K to about 80 K (e.g., 4 K, 8 K, 12 K, 16 K, 20 K, 24 K, 28 K, 32 K, 36 K, 40 K, 44 K, 48 K, 52 K, 56 K, 60 K, 64 K, 68 K, 72 K, 76 K, or 80 K).

[0101] In some aspects, a superconducting cyclotron uses cryocoolers for cooling. In some aspects, the cryocoolers are selected from the group consisting of Gifford-McMahon cryocoolers, pulse tube cryocoolers, Stirling cryocoolers, and combinations thereof. In some aspects, a superconducting cyclotron uses liquid helium for cooling. In some aspects, the cryocoolers provide cooling capacity equivalent to liquid helium cooling without requiring liquid cryogens. Without wishing to be bound by theory, it is thought that, by using a cryogen- free operation and eliminating the need for liquid helium supply infrastructure, operational complexity is reduced.

[0102] In some aspects, a particle beam of a particle therapy system is a pencil beam. In some aspects, a particle therapy system described herein comprises a pencil beam scanning magnet. The term “pencil beam scanning,” as used herein, refers to a process in which a particle beam is magnetically scanned across a target volume, e.g., a tumor area, using magnets to steer the particle beam. The process can achieve both distal and proximal dose conformality, thus improving the therapeutic ratio. The term “conformality,” as used herein refers to a particle therapy treatment that creates high-dose volume that is shaped to closely “conform” to the desired target volume. The term “therapeutic ratio,” or “therapeutic index,” as used herein, refers to a comparison of the amount of particle therapy that causes toxicity to the amount of particle therapy that causes the therapeutic effect.

[0103] In some aspects, a pencil beam has a size of about 0.5 mm x 5 mm to about 2 mm x 10; or about 0.5 mm x 5 mm, about 0.6 mm x 5 mm, about 0.7 mm x 5 mm, about 0.8 mm x 5 mm, about 0.9 mm x 5 mm, about 1 mm x 5 mm, about 1.2 mm x 5 mm, about 1.3 mm x 5 mm, about 1.4 mm x 5 mm, about 1.5 mm x 5 mm, about 1.6 mm x 5 mm, about 1.7 mm x 5 mm, about 1.8 mm x 5 mm, about 1.9 mm x 5 mm, about 2 mm x 5 mm; or about 0.5 mm x 7 mm, about 0.6 mm x 7 mm, about 0.7 mm x 7 mm, about 0.8 mm x 7 mm, about 0.9 mm x 7 mm, about 1 mm x 7 mm, about 1.2 mm x 7 mm, about 1.3 mm x 7 mm, about 1.4 mm x 7 mm, about 1.5 mm x 7 mm, about 1.6 mm x 7 mm, about 1.7 mm x 7 mm, about 1.8 mm x 7 mm, about 1.9

[0104] #14454901 v1 mm x 7 mm, about 2 mm x 7 mm; or about 0.5 mm x 10 mm, about 0.6 mm x 10 mm, about 0.7 mm x 10 mm, about 0.8 mm x 10 mm, about 0.9 mm x 10 mm, about 1 mm x 10 mm, about 1.2 mm x 10 mm, about 1.3 mm x 10 mm, about 1.4 mm x 10 mm, about 1.5 mm x 10 mm, about l.6 mm x 10 mm, about 1.7 mm x 10 mm, about 1.8 mm x 10 mm, about 1.9 mm x 10 mm, or about 2 mm x 10 mm. In some aspects, a pencil beam has a size of about 0.9 mm x 10 mm.

[0105] In some aspects, a pencil beam has a sigma spot size (e.g., a lateral sigma spot size in air) of about 2 mm, about 2.5 mm, about 3 mm, about 3.5 mm, about 4 mm, about 4.5 mm, about 5 mm, about 5.5 m, about 6 mm, about 6.5 mm, about 7 mm, about 7.5 mm, about 8 mm, about 8.5 mm, about 9 mm, about 9.5 mm, about 10 mm, about 10.5 m, about 11 mm, about 11.5 mm, about 12 mm, about 12.5 mm, about 13 mm, about 13.5 mm, about 14 mm, about 14.5 mm, about 15 mm, about 15.5 m, about 16 mm, about 16.5 mm, about 17 mm, about 17.5 mm, about 18 mm, about 18.5 mm, about 19 mm, about 19.5 mm, or about 20 mm or greater. In some aspects, a pencil beam has a sigma spot size ranging from about 2 mm to about 20 mm or greater (e.g., about 2 mm to about 6 mm, about 5 mm to about 10 mm, about 8 mm to about 12 mm, about 10 mm to about 15 mm, or about 14 mm to about 20 mm or greater).

[0106] In some aspects, pencil beam scanning magnets are part of an electromagnetic beamline further comprising an energy selection system, bending, focusing, and scanning magnets. In some aspects, the pencil beam scanning magnets (e.g., electromagnetic beamline) are attached to a solid support structure. In some aspects, the solid support structure is a housing. In some aspects, the pencil beam scanning magnets (e.g., electromagnetic beamline) are enclosed within a housing. The housing, in some aspects, is a fixed housing or a flexible housing or an articulated housing, configured such that the proximal end of the housing is in an appropriate position for particle therapy. As used herein, the ’’proximal end of the housing” refers to the end of the housing nearest to the patient / tumor. The length of the electromagnetic beamline depends on the number of magnets and the configuration of the room and can be any suitable length, e.g., about 1 m to about 10 m (e.g., about 1 m, about 2 m, about 3 m, about 4 m, about 5 m, about 6 m, about 7 m, about 8 m, about 9 m, or about 10 m). The housing, in some aspects, is connected to the cyclotron. The different components, the housing, support structure, can be made of any suitable material, including metallic material, polymeric material, plastic material, glass material, or any combination of thereof. In some aspects, the housing incorporates any suitable radiation- shielding materials (e.g., lead, concrete, and steal).

[0107] In some aspects, a particle therapy system comprises an electromagnetic beamline comprising a variety of bending, focusing, and scanning magnets. In some aspects, the electromagnetic beamline focuses and steers a particle beam toward a pencil beam scanning

[0108] #14454901 v1 magnet beam delivery system. In some aspects, an electromagnetic beamline comprises at least one quadrupole triplet (e.g., two, three, four, five, or more). In some aspects, an electromagnetic beamline comprises at least one quadrupole doublet (e.g., two, three, four, five, or more). In some aspects, an electromagnetic beamline comprises at least one dipole bending magnet (e.g., two, three, four, five, or more). In some aspects, an electromagnetic beamline comprises at least one pencil beam scanning magnet (e.g., two, three, four, five, or more).

[0109] In some aspects, an electromagnetic beamline comprises at least one pencil beam scanning magnet and at least one quadrupole triplet. In some aspects, an electromagnetic beamline comprises at least one pencil beam scanning magnet and at least one quadrupole doublet. In some aspects, an electromagnetic beamline comprises at least one pencil beam scanning magnet and at least one dipole bending magnet.

[0110] In some aspects, an electromagnetic beamline comprises at least one quadrupole triplet and at least one quadrupole doublet. In some aspects, an electromagnetic beamline comprises at least one quadrupole triplet and at least one dipole bending magnet. In some aspects, an electromagnetic beamline comprises at least one quadrupole triplet and at least one pencil beam scanning magnet.

[0111] In some aspects, an electromagnetic beamline comprises at least one pencil beam scanning magnet, at least one quadrupole triplet and at least one quadrupole doublet. In some aspects, an electromagnetic beamline comprises at least one pencil beam scanning magnet, at least one quadrupole triplet and at least one dipole bending magnet.

[0112] In some aspects, an electromagnetic beamline comprises at least one quadrupole doublet and at least one dipole bending magnet. In some aspects, an electromagnetic beamline comprises at least one quadrupole doublet and at least one pencil beam scanning magnet.

[0113] In some aspects, an electromagnetic beamline comprises at least one pencil beam scanning magnet, at least one quadrupole doublet and at least one dipole bending magnet.

[0114] In some aspects, a particle therapy system comprises an electromagnetic beamline comprising at least one quadrupole triplet, at least one quadrupole doublet, at least one dipole bending magnet, and at least one pencil beam scanning magnet.

[0115] In some aspects, a particle therapy system comprises an electromagnetic beamline comprising two quadrupole triplets, one quadrupole doublet, two dipole bending magnets, and one pencil beam scanning magnet.

[0116] In some aspects, a particle therapy system comprises an electromagnetic beamline comprising three quadrupoles, one dipole, three quadrupoles, one dipole and two quadrupoles before a pencil beam scanning magnet.

[0117] #14454901 v1 In some aspects, a particle therapy system comprises an electromagnetic beamline comprising an arrangement from the accelerator to the patient of three quadrupoles, one dipole, three quadrupoles, one dipole and two quadrupoles, and a pencil beam scanning magnet.

[0118] In some aspects, a particle therapy system comprises an electromagnetic beamline comprising at least two quadrupole focusing magnets, zero or more dipole bending magnets, and at least one pencil beam scanning magnet.

[0119] In some aspects, a particle therapy system comprises an electromagnetic beamline comprising an arrangement from the accelerator to the subject (e.g., patient) of multiple quadrupoles, multiple dipoles and a pencil beam scanning magnet.

[0120] In some aspects, a pencil beam scanning magnet comprises a plurality of electromagnets structured to bend and steer the pencil beam to a desired location in the patient, e.g., a tumor.

[0121] In some aspects, a plurality of electromagnets is structured to bend the pencil beam to target a target site, e.g., a tumor in a patient. In some aspects, a plurality of electromagnets is structured to bend the pencil beam around a curvature to target a target site, e.g., a tumor in a patient, wherein the particle source and the patient are located in a space that does not exceed the dimensions of a radiotherapy treatment room, e.g., the particle therapy system is ultra-compact. As used herein, an “ultra-compact” particle therapy system is a system located in a single radiotherapy treatment room. A radiotherapy treatment room, in some aspects is 20 x 20 feet. In some aspects, the radiotherapy treatment room is about 10 x 10 feet. In some aspects, the radiotherapy treatment room is about 12 x 12 feet. In some aspects, the radiotherapy treatment room is about 14 x 14 feet. In some aspects, the radiotherapy treatment room is about 16 x 16 feet. In some aspects, the radiotherapy treatment room is about 18 x 18 feet. In some aspects, the radiotherapy treatment room is about 20 x 22 feet. In some aspects, the radiotherapy treatment room is about 22 x 22 feet. In some aspects, the radiotherapy treatment room is about 24 x 24 feet. In some aspects, the radiotherapy treatment room is about 25 x 25 feet. In some aspects, the radiotherapy treatment room is about 26 x 28 feet. In some aspects, the radiotherapy treatment room is about 28 x 30 feet. In some aspects, the radiotherapy treatment room is about 30 x 30 feet.

[0122] In some aspects, a plurality of electromagnets is structured to bend the pencil beam around a curvature of about 0 degrees, about 5 degrees, about 10 degrees, about 15 degrees, about 20 degrees, about 25 degrees, about 30 degrees, about 35 degrees, about 40 degrees, about 45 degrees, about 50 degrees, about 55 degrees, about 60 degrees, about 65 degrees, about 70 degrees, about 75 degrees, about 80 degrees, about 85 degrees, about 90 degrees, about 95 degrees, about 100 degrees, about 105 degrees, about 110 degrees, about 115 degrees, about 120

[0123] #14454901 v1 degrees, about 125 degrees, about 130 degrees, about 135 degrees, about 140 degrees, about 145 degrees or about 150 degrees. In some aspects, the plurality of electromagnets is structured to bend the pencil beam around a curvature ranging from about 0 degrees to about 180 degrees (e.g., about 0 degrees to about 20 degrees, about 10 degrees to about 30 degrees, about 20 degrees to about 40 degrees, about 30 degrees to about 50 degrees, about 40 degrees to about 60 degrees, about 50 degrees to about 70 degrees, about 60 degrees to about 80 degrees, about 70 degrees to about 90 degrees, about 80 degrees to about 100 degrees, about 90 degrees to about 110 degrees, about 100 degrees to about 120 degrees, about 110 degrees to about 130 degrees, about 120 degrees to about 140 degrees, about 130 degrees to about 150 degrees, about 140 degrees to about 160 degrees, about 150 degrees to about 170 degrees, or about 160 degrees to about 180 degrees).

[0124] In some aspects, an ultra-compact particle therapy system comprises a cyclotron, e.g., a superconducting cyclotron. In some aspects, an ultra-compact particle therapy system comprises an ultra-compact cyclotron. In some aspects, the superconducting cyclotron weighs less than 5,000 kg. In some aspects, the superconducting cyclotron weighs less than 5,000 kg for proton acceleration. In some aspects, the weight of less than 5,000 kilograms represents at least an 80% (e.g., 85%, 90%, 95%, 96%, 97%, 98%, 99%) reduction compared to superconducting cyclotrons utilizing low temperature superconductors achieving equivalent beam energy. In some aspects, a particle therapy system comprises a superconducting cyclotron that weighs between about 1,000 kg and 100,000 kg. In some aspects, the superconducting cyclotron weighs less than 25,000 kg. In some aspects, the superconducting cyclotron weighs less than 20,000 kg. In some aspects, the superconducting cyclotron weighs less than 15,000 kg. In some aspects, the superconducting cyclotron weighs less than 10,000 kg.

[0125] In some aspects, an ultra-compact therapy system comprises a hydrogen superconducting cyclotron that weighs between about 3,300 kg and about 9,400 kg, between about 3400 kg and about 9,200 kg, between about 4,300 kg and about 9,000 kg, between about 3,600 kg and about 8,800 kg, between about 3,700 kg and about 8,600 kg, between about 3,800 kg and about 8,400 kg, between about 3,900 kg and about 8,200 kg, between about 4,000 kg and about 8,200 kg, between about 4,100 kg and about 8,000 kg, between about 4,200 kg and about 7,800 kg, between about 4,300 kg and about 7,600 kg, between about 4,400 kg and about 7,400 kg, between about 4,500 kg and about 7,200 kg, between about 4,600 kg and about 7,000 kg, between about 4,700 kg and about 6,800 kg, between about 4,800 kg and about 6,600 kg, between about 4,900 kg and about 6,200 kg, or between about 5,000 kg and about 6,000 kg. In some aspects, the superconducting cyclotron weighs about 4,000 kg, about 4,200 kg, about

[0126] #14454901 v1 4,400kg, about 4,600 kg, about 4,800 kg, about 5,000 kg, about 5,200 kg, about 5,400 kg, about 5,600 kg, about 5,800 kg, about 6,000 kg, about 6,200 kg, about 6,400 kg, about 6,600 kg, about 6,800 kg, or about 7,000 kg.

[0127] In some aspects, the particle of the particle therapy system is a proton (FIG. 5B). In some aspects, an ultra-compact particle system comprises a proton superconducting cyclotron that provides a final beam energy of 210 MeV with a range in water of 28 cm. In some aspects, an ultra-compact particle system comprises a proton superconducting cyclotron that provides a final beam energy of 210 MeV with a range in water of 28.2 cm. In some aspects, an ultra-compact particle system comprises a proton superconducting cyclotron that provides a final beam energy of 230 MeV with a range in water of 32.9 cm. In some aspects, an ultra-compact particle system comprises a proton superconducting cyclotron that provides a final beam energy of 160 MeV to 240 MeV with a range in water of 17.7 cm to 35.4 cm, respectively.

[0128] In some aspects, a proton cyclotron provides a final beam energy of about 100 MeV, about 120 MeV, about 140 MeV, about 160 MeV, about 180 MeV, about 200 MeV, about 210 MeV, 220MeV about 230 MeV, about 240 MeV, about 250 MeV, about 260 MeV, about 270 MeV, about 280 MeV, about 290 MeV, about 300 MeV, or more. Selected ranges in water and non-limiting clinical applications are shown in the Table 1 below.

[0129] Table 1.

[0130] In some aspects, the particle of the particle therapy system is a helium ion (an exemplary magnetic field cross-sectional view is shown in FIG. 6A). In some aspects, an ultra-compact particle system comprises a helium particle superconducting cyclotron that weighs between about 10,000 kg and 30,000 kg, or between about 15,000 kg and 25,000 kg, or between about 18,000 kg and 22,000 kg, or between about 20,000 kg and 25,000 kg (e.g., about 10,000 kg, about 11,000 kg, about 12,000 kg, about 13,000 kg, about 14,000 kg, about 15,000 kg, about 16,000 kg, about 17,000 kg, about 18,000 kg, about 19,000 kg, about 20,000 kg, about 21,000 kg, about 22,000 kg, about 23,000 kg, about 24,000 kg, about 25,000 kg, about 26,000 kg, about

[0131] #14454901 v1 27,000 kg, about 28,000 kg, about 29,000 kg, or about 30,000 kg). In some aspects, an ultracompact particle system comprises a helium particle superconducting cyclotron that weighs about 25,000 kg.

[0132] In some aspects, an ultra-compact particle system comprises a helium superconducting cyclotron that provides a final beam energy of 180 MeV per nucleon with a range in water of 22 cm. An example a magnetic field along the central accelerating plane of the helium cyclotron is demonstrated in FIG. 6B.

[0133] In some aspects, the particle of the particle therapy system is a lithium ion. In some aspects, an ultra-compact particle system comprises a lithium particle superconducting cyclotron that provides a final beam energy of 150-220 MeV per nucleon with a range in water of 15-25 cm. In some aspects, an ultra-compact particle system comprises a lithium particle superconducting cyclotron that provides a final beam energy of 260-400 MeV per nucleon with a range in water of 15-25 cm. In some aspects, the lithium particle superconducting cyclotron is optimized for intermediate LET therapy applications. Without wishing to be bound by theory, it is thought that lithium ions offer intermediate LET characteristics between helium and carbon, providing unique therapeutic advantages for certain tumor types.

[0134] In some aspects, the particle of the particle therapy system is a beryllium ion. In some aspects, a particle therapy system comprises a beryllium particle superconducting cyclotron that provides a final beam energy of 240-380 MeV per nucleon. Beryllium ions provide higher LET than lithium while maintaining reasonable range characteristics for deep-seated tumors (e.g., radioresistant tumors).

[0135] In some aspects, the particle of the particle therapy system is a boron ion. In some aspects, a particle therapy system comprises a boron particle superconducting cyclotron that provides a final beam energy of 220-360 MeV per nucleon. In some aspects, the boron particle super conducting cyclotron is optimized for high LET therapy applications (e.g., for hypoxic tumor treatment). Boron ions offer high LET suitable for radioresistant tumors while maintaining practical accelerator requirements.

[0136] In some aspects, the ion source comprises a laser ablation system configured to produce lithium, beryllium, and boron ions from solid targets for multi-ion therapy capability.

[0137] In some aspects, the ion source is configured for rapid switching between at least two different ion species within a treatment session, enabling mixed- ion therapy protocols.

[0138] In some aspects, a helium cyclotron provides a final beam energy of about 100 MeV, about 120 MeV, about 140 MeV, about 160 MeV, about 180 MeV, about 200 MeV, about 210 MeV, 220MeV about 230 MeV, about 240 MeV, about 250 MeV, about 260 MeV, about 270

[0139] #14454901 v1 MeV, about 280 MeV, about 290 MeV, about 300 MeV, about 310 MeV, about 320 MeV, about 330 MeV, about 340 MeV, about 350 MeV, about 360 MeV, about 370 MeV, about 380 MeV, about 390 MeV, or about 400 MeV per nucleon. In some aspects, a helium cyclotron provides a final beam energy ranging from about 100 MeV to about 400 MeV per nucleon (e.g., about 100 MeV to about 140 MeV per nucleon, about 120 MeV to about 160 MeV per nucleon, about 140 MeV to about 180 MeV per nucleon, about 160 MeV to about 200 MeV per nucleon, about 180 MeV to about 220 MeV per nucleon, about 200 MeV to about 230 MeV per nucleon, about 210 MeV to about 230 MeV, about 220 MeV to about 240 MeV, about 230 MeV to about 250 MeV, about 240 MeV to about 260 MeV, about 250 MeV to about 270 MeV, about 260 MeV to about 280 MeV, about 270 MeV to about 290 MeV, about 280 MeV to about 300 MeV, about 290 MeV to about 310 MeV, about 300 MeV to about 320 MeV, about 310 MeV to about 330 MeV, about 320 MeV to about 340 MeV, about 330 MeV to about 350 MeV, about 340 MeV to about 360 MeV, about 350 MeV to about 370 MeV, about 360 MeV to about 380 MeV, about 370 MeV to about 390 MeV, or about 380 MeV to about 400 MeV).

[0140] In some aspects, the particle of the particle therapy system is a carbon ion. A magnetic field cross-section view of a carbon cyclotron is provided in FIG. 7A. In some aspects, an ultracompact particle system comprises a carbon particle superconducting cyclotron that weighs between about 50,000 kg and 120,000 kg, or between about 55,000 kg and 115,000 kg, between about 70,000 kg and 110,000 kg, between or about 80,000 kg and about 100,000 kg. In some aspects, an ultra-compact particle system comprises a carbon particle superconducting cyclotron that weighs about 50,000 kg, about 60,000 kg, about 70,000 kg, about 80,000 kg, about 90,000 kg, about 100,000 kg, about 110,000 kg, or about 120,000 kg.

[0141] In some aspects, an ultra-compact particle system comprises a carbon particle superconducting synchrocyclotron that provides a final beam energy of 280 MeV per nucleon with a range in water of 15 cm.

[0142] In some aspects, a carbon superconducting cyclotron provides a final beam energy of about 150 MeV, about 180 MeV, about 200 MeV, about 220 MeV, about 240 MeV, about 260 MeV, about 280 MeV, or about 300 MeV per nucleon. In some aspects, a carbon superconducting cyclotron provides a final beam energy ranging from about 150 MeV to about 400 MeV per nucleon (e.g., about 150 MeV to about 200 MeV per nucleon, about 180 MeV to about 220 MeV per nucleon, about 200 MeV to about 240 MeV per nucleon, about 220 MeV to about 260 MeV per nucleon, about 240 MeV to about 280 MeV per nucleon, about 260 MeV to about 300 MeV per nucleon, about 280 MeV to about 320 MeV per nucleon, about 300 MeV to about 340 MeV per nucleon, about 320 MeV to about 360 MeV per nucleon, about 340 MeV to

[0143] #14454901 v1 about 380 MeV per nucleon, or about 360 MeV to about 400 MeV per nucleon). In some aspects, the superconducting cyclotron provides a final beam energy of 300-400 MeV per nucleon.

[0144] In some aspects, the superconducting cyclotron comprises superconductor configurations according to specific particle type (e.g., proton, helium ion, or carbon ion).

[0145] In some aspects, a superconducting cyclotron of an ultra-compact particle system has an outside diameter of less than 3 m, less than 2.5 m, less than 2 m, less than 1.8 m, less than 1.5 m, or less than 1.2 m.

[0146] In some aspects, a superconducting cyclotron of an ultra-compact particle system has an outside diameter of about 4 m, about 3.8 m, about 3.6 m, about 3.4 m, bout 3.2 m, about 3 m, about 2.8 m, about 2.6 m, about 2.4 m, about 2.2 m, about 2 m, about 1.8 m, about 1.6 m, about 1.4 m, about 1.2 m, about Im, about 0.9 m, about 0.8 m, about 0.7 m, about 0.6 m, about 0.5 m, about 0.4 m, or about 0.3 m.

[0147] In some aspects, a particle therapy system comprises a superconductor with current density of greater than 100 A / mm2.

[0148] In some aspects, a particle therapy system comprises a superconductor with current density of greater than 100 A / mm2, greater than 200 A / mm2, greater than 250 A / mm2, greater than 250 A / mm2, greater than 300 A / mm2, greater than 350 A / mm2, greater than 400 A / mm2. A / mm2, greater than 450 A / mm2, greater than 500 A / mm2, greater than 550 A / mm2, greater than 600 A / mm2, greater than 1500 A / mm2.

[0149] In some aspects, a particle therapy system comprises a superconductor with current density of about 100 A / mm2, about 110 A / mm2, about 120 A / mm2, about 130 A / mm2, about 140 A / mm2, about 150 A / mm2, about 160 A / mm2, about 170 A / mm2, about 180 A / mm2, about 190

[0150] A / mm2, about 200 A / mm2, about 205 A / mm2, about 210 A / mm2, about 215 A / mm2, about 220

[0151] A / mm2, about 225 A / mm2, about 230 A / mm2, about 235 A / mm2, about 240 A / mm2, about 245

[0152] A / mm2, about 250 A / mm2, about 255 A / mm2, about 260 A / mm2, about 265 A / mm2, about 270

[0153] A / mm2, about 275 A / mm2, about 280 A / mm2, about 285 A / mm2, about 290 A / mm2, about 295

[0154] A / mm2, about 300 A / mm2, about 305 A / mm2, about 310 A / mm2, about 315 A / mm2, about 320

[0155] A / mm2, about 325 A / mm2, about 330 A / mm2, about 335 A / mm2, about 340 A / mm2, about 345

[0156] A / mm2, about 350 A / mm2, about 355 A / mm2, about 360 A / mm2, about 365 A / mm2, about 370

[0157] A / mm2, about 375 A / mm2, about 380 A / mm2, about 385 A / mm2, about 390 A / mm2, about 395

[0158] A / mm2, or about 400 A / mm2, about 405 A / mm2, about 410 A / mm2, about 415 A / mm2, about 420 A / mm2, about 425 A / mm2, about 430 A / mm2, about 435 A / mm2, about 440 A / mm2, about 445 A / mm2, about 450 A / mm2, about 455 A / mm2, about 460 A / mm2, about 465 A / mm2, about

[0159] #14454901 v1 470 A / mm2, about 475 A / mm2, about 480 A / mm2, about 485 A / mm2, about 490 A / mm2, about 495 A / mm2, or about 500 A / mm2, about 505 A / mm2, about 510 A / mm2, about 515 A / mm2, about 520 A / mm2, about 525 A / mm2, about 530 A / mm2, about 535 A / mm2, about 540 A / mm2, about 545 A / mm2, about 550 A / mm2, about 555 A / mm2, about 560 A / mm2, about 565 A / mm2, about 570 A / mm2, about 575 A / mm2, about 580 A / mm2, about 585 A / mm2, about 590 A / mm2, about 595 A / mm2, or about 600 A / mm2. In some aspects, the superconductor is an HTW and has as current density of at least 500 A / mm2.

[0160] In some aspects, a superconducting cyclotron (e.g., a compact superconducting cyclotron) for particle therapy comprises superconducting coils comprising at least one high temperature superconductor (HTS) configured to generate a magnetic field exceeding 10 Tesla; an ion source configured to produce ions for acceleration; and a radiofrequency acceleration system. In some aspects, the cyclotron has an outside diameter of less than 1.5 meters and weighs less than 10,000 kg (e.g., for proton acceleration applications). In some aspects, the HTS comprises REBCO superconductor as the sole superconducting material, with current density exceeding 400 A / mm2at operational magnetic fields. In some aspects, the HTS comprises Bi- 2212 round wire superconductor as the sole superconducting material, with current density exceeding 400 A / mm2at operational magnetic fields. In some aspects, the superconducting coils comprise a combination of HTS and low temperature superconductor (LTS) materials, with HTS positioned in high-field regions exceeding 10 Tesla. In some aspects, the superconducting cyclotron achieves a weight-to-energy ratio of less than 30 kilograms per MeV of final proton energy, enabled by high temperature superconductors operating at engineering current densities exceeding 400 A / mm2at magnetic fields above 10 Tesla.

[0161] In some aspects, the superconducting cyclotron (e.g., compact superconducting cyclotron) is configured to operate cryogen-free using closed-cycle cryocoolers without liquid helium. In some aspects, the cyclotron is configurable for integration with various beamline configurations including but not limited to fixed horizontal beamlines, rotating gantries, and vertical beamlines. In some aspects, the cyclotron provides particle beam output compatible with various patient positioning systems including upright, horizontal, and pivoted configurations. In some aspects, the superconducting cyclotron (e.g., compact superconducting cyclotron) is configured to accelerate multiple ion species including protons, helium, lithium, beryllium, boron, carbon, nitrogen, and oxygen ions with automated switching capability. In some aspects, the superconducting cyclotron (e.g., compact superconducting cyclotron) is configured for integration with future particle therapy technologies including FLASH therapy delivery systems, mini-beam therapy systems, or spatially fractionated radiation therapy systems.

[0162] #14454901 v1 In some aspects, the HTS comprises REBCO tape conductors configured in pancake coils, layer-wound coils, or racetrack coils, adaptable to various cyclotron geometries and field requirements. In some aspects, the cyclotron operates autonomously from specific control systems, being compatible with various treatment planning systems, patient management systems, and facility integration protocols.

[0163] In some aspects, a particle therapy system comprises a compact superconducting cyclotron; any electromagnetic beamline configuration capable of directing the particle beam to a treatment location; and any patient support system capable of positioning a patient for particle therapy treatment. In some aspects, the system operates independently of specific imaging modalities, being compatible with CT, CBCT, MRI, PET, stereoscopic X-ray, optical surface imaging, ultrasound imaging, or combinations thereof.

[0164] In some aspects, the cyclotron is installable in existing radiation therapy vaults, newly constructed facilities, mobile treatment units, or research facilities without requiring specific vault configurations. In some aspects, the disclosure provides a method of retrofitting an existing radiation therapy facility comprising providing a compact superconducting cyclotron; installing the cyclotron in an existing vault without structural modification; connecting the cyclotron to any beamline configuration; and integrating the cyclotron with existing patient positioning and imaging systems.

[0165] In some aspects, the superconducting cyclotron (e.g., compact superconducting cyclotron) is configured for operation with various beam delivery methods including pencil beam scanning, passive scattering, uniform scanning, wobbling, or ridge filter-based delivery systems. In some aspects, the cyclotron output is compatible with beamlines utilizing superconducting magnets, resistive magnets, permanent magnets, combined function magnets, or combinations thereof.

[0166] In some aspects, a modular particle therapy system comprising a compact superconducting cyclotron as a self-contained unit, wherein the cyclotron includes standardized interfaces for connection to various beamline configurations, and wherein the cyclotron operates independently of specific downstream components, is provided.

[0167] In some aspects, the cyclotron further comprises, or is connected to, a power source, such as electricity, radioactive materials (e.g., radionuclides) or any other suitable power source.

[0168] ION SOURCE

[0169] In some aspects, the superconducting cyclotron comprises an ion source (FIG. 3). The ion source, in some aspects, is an external electron cyclotron resonance (ECR) ion source, an

[0170] #14454901 v1 internal ion source, or both an external ECR ion source and an internal ion source. In some aspects, the cyclotron comprises both an external ECR ion source and an internal ion source. Without wishing to be bound by theory, it is thought that the inclusion of both an external ECR ion source and an internal ion source leads to enhanced ion production and beam intensity.

[0171] The term “electron cyclotron resonance (ECR) ion source,” as used herein, refers to a device that produces ion beams with a variety of charge states.

[0172] In some aspects, the ion source is selected from the group consisting of a Penning ion source, a multicusp ion source, a hot cathode ion source, a cold cathode ion source, a PIG (Penning Ionization Gauge) ion source, an H-minus (H ) ion source, and combinations thereof.

[0173] In some aspects, the internal ion source is selected from the group consisting of a Penning ion source, a multicusp ion source, a hot cathode ion source, a cold cathode ion source, a PIG (Penning Ionization Gauge) ion source, an H-minus (H ) ion source, and combinations thereof. In some aspects, the internal ion source is a Penning ion source. In some aspects, the internal ion source is a Penning ion source configured for operation in high magnetic fields. In some aspects, the internal ion source is a multicusp ion source. In some aspects, the internal ion source is a hot cathode ion source. In some aspects, the internal ion source is a cold cathode ion source. In some aspects, the internal ion source is a cold cathode PIG ion source. In some aspects, the ion source (e.g., internal ion source) is an H-minus (H") ion source configured to produce negative hydrogen ions for acceleration and subsequent stripping to produce protons. In some aspects, the H-minus ion source is selected from the group consisting of a multicusp ion source, a surface plasma source, and a volume plasma source. In some aspects, the internal ion source comprises a combination of two or more of the foregoing.

[0174] In some aspects, the ion source is an external ion source. In some aspects, the external ion source is an ECR ion source. In some aspects, the external ECR ion source is positioned outside the cyclotron magnetic field and injects ions into the cyclotron through an injection system. In some aspects, the external ion source is positioned outside the cyclotron magnetic field. In some aspects, the external ion source is configured to inject ions through an axial or radial injection system.

[0175] In some aspects, the internal ion source is positioned within the cyclotron and generates ions directly in the cyclotron's magnetic field. In some aspects, the ion source is an internal ion source positioned within the cyclotron magnetic field. In some aspects, the internal ion source is positioned at the center of the cyclotron to optimize ion injection efficiency.

[0176] In some aspects, an ion source is hydrogen gas. In some aspects, the ion source is configured to produce hydrogen ions for proton therapy. In some aspects, an ion source is a

[0177] #14454901 v1 helium ion. In some aspects, the ion source is configured to produce helium ions for helium ion therapy. In some aspects, an ion source is a carbon ion. In some aspects, the ion source is configured to produce carbon ions for carbon ion therapy. In some aspects, an ion source is lithium ion. In some aspects, the ion source is configured to produce lithium ions for lithium ion therapy. In some aspects, an ion source is a beryllium ion. In some aspects, the ion source is configured to produce beryllium ions for beryllium ion therapy. In some aspects, an ion source is a boron ion. In some aspects, the ion source is configured to produce boron ions for boron ion therapy. In some aspects, an ion source is a nitrogen ion. In some aspects, the ion source is configured to produce nitrogen ions for nitrogen ion therapy. In some aspects, an ion source is an oxygen ion. In some aspects, the ion source is configured to produce oxygen ions for oxygen ion therapy. In some aspects, an ion source is another light ion having an atomic number less than or equal to 10. In some aspects, the ion source is configured to produce such light ions for ion therapy using ions having an atomic number less than or equal to 10.

[0178] In some aspects, the ion source is configured to switch between different ion types (e.g., for multi-particle therapy capability). In some aspects, the ion source system is configured to deliver sequential treatments with protons, helium ions, lithium ions, and carbon ions in a single patient session, with automated ion source switching and beamline energy adjustment completed in less than 60 seconds between ion types. In some aspects, the ion source system is integrated with the computer system for automated control of ion source parameters. Examples of ion source parameters include, but are not limited to, gas flow, ionization voltage, and extraction voltage.

[0179] In some aspects, the ion source system includes automated gas switching capability to change between hydrogen, helium, and carbon-containing gases for different particle therapy applications. In some aspects, the carbon-containing gas is selected from the group consisting of methane (CtE), acetylene (C2H2), and carbon dioxide (CO2). In some aspects, the carbon- containing gas is methane (CH4). In some aspects, the carbon-containing gas is acetylene (C2H2). In some aspects, the carbon-containing gas is carbon dioxide (CO2).

[0180] In some aspects, the single superconducting cyclotron is configured to accelerate multiple ion types from the same accelerator system. In some aspects, the cyclotron magnetic field and RF frequency are adjustable to optimize acceleration for different ion mass-to-charge ratios. In some aspects, the gas switching system includes automated purging and conditioning sequences when changing between different gas types.

[0181] In some aspects, the multi-ion capability allows treatment of different cancer types with optimal particle therapy for each specific application from a single treatment system.

[0182] #14454901 v1 RADIOLOGICAL IMAGING SYSTEM

[0183] In some aspects, a particle therapy system described herein comprises a radiological imaging system (e.g., a scanner) that locates a tumor inside a patient.

[0184] In some aspects, a particle therapy system comprises a compact scanner. In some aspects, a particle therapy system comprises a x-ray computer tomography (CT) scanner. In some aspects, a particle therapy system comprises a x-ray cone beam computer tomography (CBCT) scanner. In some aspects, a particle therapy system comprises a magnetic resonance imaging (MRI) scanner. In some aspects, a particle therapy system comprises a positron emission tomography (PET) scanner. In some aspects, a particle therapy system comprises radiological imaging acquired over the time span of multiple patient respiration cycles to provide 4D imaging in any of the radiological or surface imaging modalities.

[0185] In some aspects, the radiological imaging system of a particle therapy system described herein is mounted on a patient positioning device. In some aspects, a radiological imaging system is included with a particle therapy system described herein is mounted at a lower end (e.g., at a bottom) of a patient positioning device. In some aspects, a radiological imaging of a particle therapy system described herein is mounted at a lower end (e.g., at a bottom) of a vertical couch (e.g., a vertical carbon fiber couch) of a patient positioning device. In some aspects, a radiological imaging system of a particle therapy system described herein is mounted at a lower end (e.g., at a bottom) of a horizontal couch (e.g., a horizontal carbon fiber couch) of a patient positioning device.

[0186] In some aspects, a radiological imaging system of a particle therapy system described herein is mounted at a higher end (e.g., at a top) of a patient positioning device. In some aspects, a radiological imaging system of a particle therapy system described herein is mounted at a higher end (e.g., at a top) of a vertical couch (e.g., a vertical carbon fiber couch) of a patient positioning device. In some aspects, a radiological imaging system of a particle therapy system described herein is mounted at a higher end (e.g., at a top) of a horizontal couch (e.g., a horizontal carbon fiber couch) of a patient positioning device

[0187] SURFACE IMAGING DEVICES - MACHINE VISION

[0188] In some aspects, a particle therapy system described herein comprises a surface imaging system (e.g., a surface imager) that locates an outer edge of a patient body.

[0189] In some aspects, a surface imaging system (e.g., a surface imager) comprises a surface machine vision array. In some aspects, a surface machine vision array comprises multiple image

[0190] #14454901 v1 acquisition devices. In some aspects, a surface imaging system comprises a surface machine vision array comprising an array of sensors (e.g., 3D cameras). In some aspects, a surface imaging system comprises a surface machine vision array comprising an array of sensors mounted at a higher end (e.g., at a top) of a vertical couch (e.g., a vertical carbon fiber couch). In some aspects, a surface imaging system comprises a surface machine vision array comprising an array of sensors located above a horizontal couch (e.g., a horizontal carbon fiber couch). In some aspects, a surface imaging system comprises a surface machine vision array comprising an array of sensors mounted at a lower end (e.g., at a bottom) of a vertical couch (e.g., a vertical carbon fiber couch). In some aspects, a surface imaging system comprises a surface machine vision array comprising an array of sensors mounted at a lower end (e.g., at a bottom) of a horizontal couch (e.g., a horizontal carbon fiber couch).

[0191] In some aspects, a surface imaging system (e.g., a surface imager) comprises a surface machine vision array comprising an array of sensors (e.g., 3D cameras) arranged in a horizontal circle above a patient. In some aspects, the array of sensors is configured to cooperate with each other to form a position image of the subject (e.g., patient). In some aspects, a surface imaging system comprising a surface machine vision array of sensors is structured such that the sensors integrate with each other to form a position image of the patient. In some aspects, a surface imaging system comprising a surface machine vision array of sensors is structured to transmit a position image of the patient to a computer system. In some aspects, a surface imaging system tracks a patient’s respiratory movement during a respiratory cycle (e.g., a bi-cyclic respiratory cycle). In some aspects, a surface imaging system transmits a cyclic position image based on a respiratory cycle of the patient to a computer system. In some aspects, a computer system outputs reposition instructions to a robotic positioner such that the robotic positioner repositions the patient and, thereby, the tumor target area, e.g., during a respiratory cycle such that a pencil beam is delivered to the tumor target area during both phases of a respiratory cycle. In some aspects, a surface imaging system transmits a cyclic position image based on a respiratory cycle of the patient to a computer system and the computer system outputs reposition instructions to the robotic positioner such that the delivery of a pencil beam is timed to deliver the pencil beam when the tumor target area is located at a same predetermined position during one phase of the respiratory cycle. In some aspects, a surface imaging system comprising a surface machine vision array of sensors transmitting a cyclic position image of the patient to the computer system allows a pencil beam to target a predetermined position during pencil beam scanning.

[0192] PATIENT POSITIONING DEVICE

[0193] #14454901 v1 In some aspects, a particle therapy system described herein comprises a patient positioning device. In some aspects, the patient positioning device comprises a selectively movable patient support platform. In some aspects, the patient positioning device comprises a selectively movable patient support platform that supports a patient in an upright position. In some aspects, the patient positioning device is an upright patient positioning device. In some aspects, the upright patient positioning device comprises a seat.

[0194] In some aspects, the patient positioning device comprises a selectively movable patient support platform that supports a patient in a horizontal laying down position (e.g., a laying position). In some aspects, the patient positioning device is a horizontal patient positioning device.

[0195] In some aspects, the patient positioning device comprises a selectively movable patient support platform that supports a patient in a position that is between an upright and a laying position, e.g., a pivoted position. In some aspects, the patient positioning device is a pivotable patient positioning device.

[0196] In some aspects, the patient positioning device is structured to support the patient in an upright, horizontal, or pivoted position such that the pencil beam is targeted to a predetermined position in the patient, e.g., a tumor in a patient.

[0197] In some aspects, the patient positioning device is connected to a robotic positioner (FIG. 4). In some aspects, a robotic positioner comprises at least two members that are movably connected. In some aspects, the at least members can rotate the selectively movable patient support platform with six degrees of freedom. In some aspects, the robotic positioner can rotate the selectively movable patient support platform in a horizontal plane (e.g., up to 360 degrees in a horizontal plane). In some aspects, the robotic positioner is operably connected to a computer system. In some aspects, the robotic positioner rotates the selectively movable patient support platform according to patient position data received by the computer system from a surface imaging system and / or according to tumor position data received by the computer system from a radiological imaging system.

[0198] In some aspects, the patient positioning device is connected to a couch, e.g., a carbon fiber couch. In some aspects, the carbon fiber couch is a vertical carbon fiber couch. In some aspects, a radiological imaging system is mounted at the bottom of the vertical carbon fiber couch. In some aspects, a surface imaging system is mounted at the top of the vertical carbon couch. In aspects, the surface imaging system is configured to form a position image of the subject (e.g., patient). In some aspects, the carbon fiber couch is a horizontal carbon fiber couch. In some aspects, the carbon fiber couch is a pivoted carbon fiber couch.

[0199] #14454901 v1 In some aspects, the patient positioning device comprises a robotic arm connected to a patient support system (e.g., connected to an upright patient support system).

[0200] In some aspects, the patient positioning device is connected to a radiological imaging system (e.g., a compact CT or CBCT or other scanner) and an imaging system (e.g., a surface guidance camera array or any surface imaginer). In some aspects, the patient positioning device comprises a stereoscopic X-ray imaging device. In some aspects, the stereoscopic X-ray imaging device is a room-mounted stereoscopic X-ray imaging device (e.g., to position the patient). In some aspects, the room-mounted stereoscopic X-ray imaging system comprises at least two, three, four, five, six, seven, eight, nine, or ten X-ray sources positioned at different angles relative to the patient. In some aspects, the room-mounted stereoscopic X-ray imaging system comprises two X-ray sources positioned at different angles relative to the patient. In some aspects, the room-mounted stereoscopic X-ray imaging system comprises corresponding X-ray detectors positioned to receive X-rays from the X-ray sources.

[0201] In some aspects, the room-mounted stereoscopic X-ray imaging system is configured to provide real-time patient positioning verification. In some aspects, the room-mounted stereoscopic X- ray imaging system is integrated with the computer system. In some aspects, the room-mounted stereoscopic X-ray imaging system is integrated with the computer system to automatically e.g., without human intervention) adjust patient position based on stereoscopic X-ray images. In some aspects, the room-mounted stereoscopic X-ray imaging system operates in conjunction with the surface imaging system. In some aspects, the room-mounted stereoscopic X-ray imaging system operates in conjunction with the radiological imaging system (e.g., scanner). In some aspects, the room-mounted stereoscopic X-ray imaging system operates in conjunction with the surface imaging system (e.g., surface imager) and the radiological imaging system (e.g., scanner) for enhanced patient positioning accuracy. In some aspects, the stereoscopic X-ray imaging system provides submillimeter patient (e.g., subject) positioning accuracy.

[0202] In some aspects, the room-mounted stereoscopic X-ray imaging system is configured to track patient movement during particle beam delivery.

[0203] In some aspects, the X-ray sources are mounted on ceiling-mounted position systems, wall- mounted positioning systems, or both ceiling-mounted and wall-mounted positioning systems.

[0204] In some aspects, the stereoscopic X-ray imaging system provides sub-millimeter patient positioning accuracy.

[0205] In some aspects, the robotic positioner of a patient positioning device rotates the selectively movable patient support to locate an area, e.g., a tumor area in a patient into the center of the pencil beam.

[0206] #14454901 v1 INTEGRATION OF THE DIFFERENT COMPONENTS

[0207] A) RELATIVE LOCATIONS OF SCANNER, SURFACE IMAGING, AND PATIENT

[0208] SUPPORT DEVICES

[0209] In some aspects, the radiological imaging system (e.g., scanner), the surface imaging system (e.g., surface imager), and the selectively movable patient support platform are integrated within a single robotic apparatus or located on a same gantry.

[0210] In some aspects, the radiological imaging system (e.g., scanner), the surface imaging system (e.g., surface imager), and the selectively movable patient support platform are distributed among a plurality of independent robotic systems configured to operate in coordinated motion or located on different gantries.

[0211] For example, in some aspects, one or more of the scanning and / or imaging devices are attached to the same gantry. In some aspects, one or more of the scanning and / or imaging devices are attached to separate gantries.

[0212] In some aspects, at least one of the radiological imaging system and the surface imaging system is mounted to the same robotic positioner that controls the patient support platform. In other aspects, at least one of the radiological imaging system and the surface imaging system is mounted to a separate robotic system configured to operate independently of the robotic positioner controlling the patient support platform.

[0213] In some aspects, the radiological imaging system is mounted to a first robotic positioning system and the surface imaging system is mounted to a second robotic positioning system, wherein the first and second robotic positioning systems are configured to operate independently. In some aspects, the radiological imaging system is mounted to a first robotic manipulator coupled to the carbon fiber couch, and the surface imaging system is mounted to a second robotic manipulator configured for independent motion relative to the patient.

[0214] In some aspects, both the radiological imaging system and the surface imaging system are mounted to a common robotic positioning system that additionally controls the vertical carbon fiber couch. In other aspects, the radiological imaging system is mounted to a dedicated robotic gantry configured for independent rotation about the patient, while the surface imaging system is integrated with the patient positioning robotic system.

[0215] In some aspects, the particle therapy system comprises a plurality of coordinated robotic systems comprising: a primary robotic system configured to control the patient support platform and couch; a secondary robotic system configured to control the radiological imaging system; and a tertiary robotic system configured to control the surface imaging array, wherein said

[0216] #14454901 v1 plurality of robotic systems are synchronized through the computer control system to provide coordinated motion control during patient positioning and treatment delivery.

[0217] In some aspects, a scanner is mounted on a patient positioning device and an imager is mounted on a patient positioning device. In some aspects, a scanner is mounted on a couch e.g., a carbon fiber couch of a patient positioning device and an imager is mounted on the couch, e.g., the carbon fiber couch of a patient positioning device. In some aspects, a scanner and an imager are mounted on couch, e.g., a vertical carbon fiber couch of a patient positioning device. In some aspects, a scanner and an imager are mounted on a couch, e.g., a horizontal carbon fiber couch of a patient positioning device.

[0218] In some aspects, the particle therapy system is installed in a photon linear accelerator vault.

[0219] B) COMPUTER SYSTEM

[0220] In some aspects, the particle therapy system is controlled by a computer system that allows for user input to target and align the patient with the particle beam. For example, in some aspects the components of the particle therapy system are controlled via a computer system that allows a user to identify the location of a tumor, target the particle beam to the tumor, and adjust the targeting based on patient movement (e.g., breathing, etc.). In some aspects, a computer system receives inputs from a radiological imaging system (e.g., an scanner), a surface imaging system (e.g., a surface imager), and a cyclotron. In some aspects, information from the radiological imaging system and / or imager are displayed to help a user align a patient with a pencil beam. In some aspects, a computer system receives inputs from a radiological imaging system, a surface imaging system, and a cyclotron and automatically generates outputs to a robotic positioner and a cyclotron. In some aspects, a computer system receives inputs from a radiological imaging system and a surface image of the position of a patient surface and a patient tumor, respectively, and a cyclotron on the delivery of a pencil beam. In some aspects, based on the inputs, a computer system automatically generates outputs to a robotic positioner and a cyclotron to position the patient positioning device to a position in which the tumor is positioned in a predetermined area for optimal pencil beam scanning.

[0221] An illustrative implementation of a computer system 160 that may be used in connection with any of the aspects of the technology described herein is shown in FIG. 1C. The computer system 160 includes one or more processors 161 and one or more articles of manufacture that comprise non-transitory computer-readable storage media (e.g., memory 162 and one or more non-volatile storage media 163). In some aspects, a processor 161 receives inputs 166, e.g.,

[0222] #14454901 v1 connected to 150, from a radiological imaging system (e.g., a scanner), a surface imaging system (e.g., a surface imager), and a cyclotron. In some aspects, a processor 161 receives inputs from a radiological imaging system (e.g., a scanner), a surface imaging system (e.g. a surface imager), and a cyclotron through a network input / output (I / O) interface 164. The processor 161 may control writing data to and reading data from the memory 162 and the non-volatile storage device 163 in any suitable manner, as the aspects of the technology described herein are not limited in this respect. To perform any of the functionality described herein, the processor 161 may receive input data from the radiological imaging system, imager, and / or cyclotron and execute one or more processor-executable instructions stored in one or more non-transitory computer-readable storage media (e.g., the memory 162), which may serve as non-transitory computer-readable storage media storing processor-executable instructions for execution by the processor 161. Computing device 160 may also include a network input / output (I / O) interface 164 via which the computing device may communicate with other computing devices (e.g., over a network), e.g., the radiological imaging system, imager and / or cyclotron and may also include one or more user I / O interfaces 165, via which the computing device may provide output to and receive input from a user. The user I / O interfaces may include devices such as a keyboard, a mouse, a microphone, a display device (e.g., a monitor or touch screen), speakers, a camera, and / or various other types of I / O devices. The embodiments described herein, can be implemented in any of numerous ways. For example, the embodiments may be implemented using hardware, software or a combination thereof. When implemented in software, the software code can be executed on any suitable processor (e.g., a microprocessor) or collection of processors, whether provided in a single computing device or distributed among multiple computing devices. It should be appreciated that any component or collection of components that perform the functions described above can be generically considered as one or more controllers that control the above-described functions. The one or more controllers can be implemented in numerous ways, such as with dedicated hardware, or with general purpose hardware (e.g., one or more processors) that is programmed using microcode or software to perform the functions recited above. In this respect, it should be appreciated that one implementation of the embodiments described herein comprises at least one computer-readable storage medium (e.g., RAM, ROM, EEPROM, flash memory or other memory technology, CD- ROM, digital versatile disks (DVD) or other optical disk storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or other tangible, non-transitory computer-readable storage medium) encoded with a computer program (i.e., a plurality of executable instructions) that, when executed on one or more processors, performs the above-

[0223] #14454901 v1 described functions of one or more embodiments. The computer-readable medium may be transportable such that the program stored thereon can be loaded onto any computing device to implement aspects of the techniques described herein. In addition, it should be appreciated that the reference to a computer program which, when executed, performs any of the abovedescribed functions, is not limited to an application program running on a host computer. Rather, the terms computer program and software are used herein in a generic sense to reference any type of computer code (e.g., application software, firmware, microcode, or any other form of computer instruction) that can be employed to program one or more processors to implement aspects of the techniques described herein. Aspects of the technology described herein provide computer implemented methods for evaluating, generating, visualizing, and / or targeting a tumor in a patient. In some embodiments, a software program may provide a user with a visual representation of a subject’s tumor and / or other information related to a subject’s medical condition (e.g., cancer) using an interactive graphical user interface (GUI). Such a software program may execute in any suitable computing environment including, but not limited to, a cloud-computing environment, a device co-located with a user (e.g., the user’s laptop, desktop, smartphone, etc.), one or more devices remote from the user (e.g., one or more servers), etc. In some aspects, a software program also provides a user with options for selecting the appropriate intensity of a particle beam and positioning the subject using the patient positioning device. In some aspects, a software program also processes feedback from radiological imaging system 130 and / or imager 140 and sends instructions to patient positioning device 120 to adjust the position of the subject relative to the position of the particle beam.

[0224] Determining the location of the target tumor tissue, positioning the subject, controlling the particle beam, and optionally adjusting the subject’s position during treatment can be performed via user input and / or automatically using the computer system. In some aspects, the computer system also can generate a report of the therapeutic conditions for the subject’s medical record.

[0225] PATIENTS AND COMBINATION THERAPIES

[0226] In some aspects, a patient (e.g., a human patient or subject) is a subject having a cancer (e.g., a solid tumor). In some aspects, a patient (e.g., a subject) is a human patient. In some aspects, the solid tumor is prostate cancer, lung cancer, head and neck cancer, liver cancer, esophageal cancer, brain cancer, breast cancer, cervical cancer, or pancreatic cancer. In some aspects, a tumor is a lymphoma. In some aspects, a tumor is a Hodgkin lymphoma or a nonHodgkin lymphoma. In some aspects, the patient is under 5 years of age (e.g., less than a year, 1

[0227] #14454901 v1 year, 2 years, 3 years, or 4 years old). In some aspects, the patient is 5-12 years of age. In some aspects, the patient is 12-18 years of age. In some aspects, the patient is 18-30 years of age. In some aspects, the patient is 30-60 years of age. In some aspects, the patient is 50-70 years of age. In some aspects, the patient is 60-80 years of age. In some aspects, the patient is over the age of 80.

[0228] In some aspects, a particle therapy using the particle therapy system described herein can be used in conjunction with other therapies (e.g., immunotherapy, chemotherapy, etc.). In some aspects, the particle beam therapy provides a daily Radio Biological Effective (RBE) dose ranging from 1 to 20 Gray [Gy], totaling 30Gy to 70Gy RBE. In some aspects, the total particle therapy RBE dose is delivered before immunotherapy or chemotherapy is administered. In some aspects, the total particle therapy RBE dose is delivered following immunotherapy or chemotherapy. In some aspects, the temporal separation of particle therapy and immunotherapy and / or chemotherapy is one day, one week, or one month.

[0229] In some aspects, the temporal separation of particle therapy and immunotherapy and / or chemotherapy is 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 1 month, or longer. In some aspects, particle therapy and immunotherapy are delivered simultaneously or on alternating days.

[0230] In some aspects, immunotherapy is cytokine therapy, immune cell therapy, e.g., T cell or NK cell therapy, or antibody therapy. In some aspects, separate or simultaneous administration of immunotherapy with particle therapy provide more effective treatment of a condition, e.g., a cancer than administration of each therapy alone. In some aspects, provided are methods of administering combined particle therapy and immunotherapy. In some aspects, provided are methods of administering combined particle therapy and immunotherapy, wherein the dose of either the particle therapy or the immunotherapy, or both, is reduced compared to a therapy applying only a particle therapy or immunotherapy. For example, the combined particle therapy and immunotherapy allows a reduction of a dose of the immunotherapy, which dose reduction reduces immunotherapy toxicity to various organs, including the nervous system and hematopoietic stem cell compartment.

[0231] In some aspects, provided are methods of administering particle therapy before immunotherapy such as CAR-T, e.g., to avoid killing the immune cells with the particle therapy.

[0232] In some aspects, provided are methods of administering particle therapy before immunotherapy, e.g., to allow the immune cells to penetrate the tumor microenvironment more readily. Without wishing to be bound by theory, this approach may reduce the “immune desert”

[0233] #14454901 v1 common in many tumors, where no immune cells are able to penetrate the tumor microenvironment.

[0234] In some aspects, provided are methods of administering particle therapy after immunotherapy, e.g., to kill residual cancer cells that were not killed by the immunotherapy.

[0235] In some aspects, provided are methods of administering particle therapy and immunotherapy on alternate days or on the same day to reduce the daily dose of both particle therapy and immunotherapy, resulting in less patient toxicity.

[0236] In some aspects, provided are methods of administering particle therapy and chemotherapy. In some aspects, chemotherapy can be any chemotherapy administered to a patient for cancer treatment. Exemplary, non-limiting chemotherapies include alkylating agents, antimetabolites, antibiotics, plant alkaloids, topoisomerase inhibitors, anthracyclines, and vinca alkaloids. In some aspects, separate or simultaneous administration of chemotherapy with particle therapy provides more effective treatment of a condition, e.g., a cancer than administration of each therapy alone. In some aspects, provided are methods of administering combined particle therapy and chemotherapy. In some aspects, provided are methods of administering combined particle therapy and chemotherapy, wherein the dose of either the particle therapy or the chemotherapy, or both, is reduced compared to a therapy applying only a particle therapy or chemotherapy. For example, the combined particle therapy and chemotherapy allows a reduction of a dose of the chemotherapy, which dose reduction reduces chemotherapy toxicity to various organs.

[0237] In some aspects, provided are methods of administering particle therapy before chemotherapy. In some aspects, provided are methods of administering particle therapy before chemotherapy, e.g., to allow a patient’s immune cells to penetrate a tumor microenvironment more readily. Without wishing to be bound by theory, it is thought that approach may reduce the “immune desert” common in many tumors, where no immune cells are able to penetrate the tumor microenvironment.

[0238] In some aspects, provided are methods of administering particle therapy after chemotherapy, e.g., to kill residual cancer cells that were not killed by the chemotherapy.

[0239] In some aspects, provided are methods of administering particle therapy and chemotherapy on alternate days or on the same day to reduce the daily dose of both particle therapy and chemotherapy, resulting in less patient toxicity.

[0240] In some aspects, a hydrogen particle therapy system with a range in water of about 28 cm is used for particle therapy of a patient having prostate cancer, lung cancer, liver cancer,

[0241] #14454901 v1 esophageal cancer, brain cancer, breast cancer, cervical cancer, pancreatic cancer, Hodgkin lymphoma or non-Hodgkin lymphoma.

[0242] In some aspects, a helium or carbon particle therapy system with a range in water of less than about 20 cm is used particle therapy of a patient having a head and neck cancer or a patient having a skin cancer. See, e.g., Table 1.

[0243] EXAMPLES

[0244] Example 1: REBCO-Based Proton Synchrocyclotron for 210 MeV Operation

[0245] This embodiment demonstrates a 210 MeV proton synchrocyclotron utilizing exclusively REBCO (Rare Earth Barium Copper Oxide) high temperature superconductors with diameter of approximately 1.1m and a total system weight of approximately 4,500 kilograms. The synchrocyclotron design accommodates the relativistic mass increase of accelerating protons through frequency modulation of the radiofrequency system, enabling compact dimensions suitable for installation in existing radiation therapy facilities.

[0246] The magnet system employs REBCO coated conductor tapes manufactured through established vapor deposition processes on metallic substrates with appropriate stabilizer layers. The conductor operates at 4.2 Kelvin and achieves engineering current densities in the range of 400 to 600 A / mm2at the operational magnetic field levels required for 210 MeV proton acceleration. The magnetic field profile decreases radially from approximately 12 Tesla at the center to 11 Tesla at extraction radius, providing the necessary weak focusing for beam stability throughout the acceleration cycle (FIGs. 5B and 7B).

[0247] Example 2: Bi-2212-Based Proton Synchrocyclotron for 210 MeV Operation

[0248] This embodiment presents a 210 MeV proton synchrocyclotron employing exclusively Bi-2212 (Bi2Sr2CaCu2Os+x) round wire superconductors, achieving a diameter of approximately 1.1m and a total system weight of approximately 4,500 kilograms. The synchrocyclotron configuration utilizes the round wire geometry advantages in coil fabrication while implementing the frequency-modulated acceleration characteristic of synchrocyclotron operation.

[0249] The conductor comprises Bi-2212 round wires manufactured through the powder-in-tube process with subsequent heat treatment to form the superconducting phase. The round wire configuration facilitates conventional coil winding techniques while providing isotropic current- carrying capability essential for the complex field shaping required in synchrocyclotron magnets. Operating at 4.2 Kelvin, the conductor maintains engineering current densities between

[0250] #14454901 v1 400 and 600 A / mm2at the magnetic field levels necessary for 210 MeV synchrocyclotron operation. The radially decreasing magnetic field profile, fundamental to synchrocyclotron design, extends from the high central field to the lower extraction field while maintaining the weak focusing gradient.

[0251] The coil system employs winding configurations appropriate for generating the specific magnetic field topology required for synchrocyclotron operation. The conductor arrangement produces the radially decreasing field that provides vertical beam confinement through weak focusing while the frequency-modulated RF system maintains acceleration synchronism. The coil design accommodates the specific characteristics of Bi-2212 conductor including the necessary heat treatment process for superconducting phase formation.

[0252] Example 3: Multi-type Superconductor Combinations

[0253] An ultra-compact pencil beam scanning proton therapy system (FIG. 5C) that allows the treatment machine to fit inside of existing radiation shielded vaults at radiation oncology treatment centers already in operation is provided.

[0254] The patient's internal anatomy is determined by a compact CT (or CBCT) radiological imaging system (e.g., a CT scanner) mounted at the bottom of the vertical carbon fiber couch. After the patient’s tumor has been localized, the robotic positioner moves the tumor into alignment with the proton beam. During treatment the patient is monitored by the surface guidance camera array to ensure the tumor stays in alignment with the radiation beam.

[0255] The surface guidance camera array can also be used to track the patient's respiratory cycle and adjust the proton beam during delivery depending on the motion of the tumor. The proton beam can both be gated or the scanning pattern can be adjusted to follow the motion of the tumor.

[0256] This device makes use of a superconducting cyclotron weighing less than 5,000 kg with an outside diameter of less than 1.2 meters. The cyclotron may utilize High Temperature Superconductors (HTS) such as Bi-2212, Bi-2223, BSCCO, or REBCO as standalone materials, or in combination with Low Temperature Superconductors (LTS) such as NbsSn, NbTi, NbsAl, and VsGa. These superconductor configurations achieve current densities greater than 200 A / mm2and magnetic fields exceeding 10 Tesla for ultra-compact design. The proton cyclotron may be designed to provide a final beam energy between 160 MeV to 240 MeV with a corresponding range in water of 17.7 cm to 35.4 cm. The proton cyclotron provides a final beam energy of 210MeV with a range in water of 28 cm, example cyclotrons for helium and carbon are shown in the table below.

[0257] #14454901 v1 Features of the particle therapy system include:

[0258] • The use of any combination of HTS and LTS superconductor in a compact proton therapy system.

[0259] • Design target: Compact superconducting particle therapy cyclotron weighing less than 5,000 kg and diameter of less than 1.2m

[0260] • Maximum practical size: Less than 12,000 kg and diameter of less than 1.7m to fit existing vault infrastructure

[0261] • The project install time, from start to treating the first patient, of less than one year. Enabled by eliminating major construction and limiting building modification.

[0262] • Robotic mounted CBCT or CT radiological imaging system (e.g., CT scanner) and surface guidance system; allows for upright treatment and traditional horizontal treatment.

[0263] • 3mm sigma spot size for pencil beam scanning and LET optimization without a physical collimator.

[0264] • Helium and Carbon treatment machines with a range in water less than 20 cm, this still allows treatment of patients, such as head and neck cancer, that benefit the most from high LET (greater than lOKeV / um).

[0265] ADDITIONAL EMBODIMENTS

[0266] 1. A particle therapy system comprising: (a) a particle accelerator configured to generate a particle beam; (b) an electromagnetic beamline configured to direct the particle beam from the particle accelerator to a patient positioning device, the electromagnetic beamline comprising a plurality of electromagnets configured to bend and steer the particle beam; and (c) a patient positioning device being configured to support a subject (e.g., patient) within a location such that a target area of the subject (e.g., patient) is located at a center of the particle beam.

[0267] #14454901 v1 2. The particle therapy system of embodiment 1, wherein the electromagnetic beamline comprises a pencil beam scanning magnet.

[0268] 3. The particle therapy system of any one of embodiments 1-2, wherein the electromagnetic beamline further comprises an energy selection system.

[0269] 4. The particle therapy system of any one of embodiments 1-3, wherein the plurality of electromagnets are configured to selectively bend the particle beam on a substantially horizontal plane to selectively direct the particle beam to the target area of the subject (e.g., patient).

[0270] 5. The particle therapy system of any one of embodiments 1-4, wherein the patient positioning device comprises: (a) a selectively movable patient support platform, optionally with a seat, configured to support the subject (e.g., patient) and connected to a robotic positioner and a vertical carbon fiber couch; (b) a robotic positioner; and (c) a vertical carbon fiber couch mounted onto the patient support platform in a location behind the subject (e.g., patient).

[0271] 6. The particle therapy system of embodiment 5, wherein the robotic positioner comprises at least two members that are movably connected and can rotate the selectively movable patient support platform with six degrees of freedom.

[0272] 7. The particle therapy system of embodiment 5, wherein the robotic positioner comprises at least two members that are movably connected and can rotate the selectively movable patient support platform 360 degrees in a horizontal plane.

[0273] 9. The particle therapy system of any one of embodiments 5-7, further comprising a radiological imaging system (e.g., scanner) mounted at the bottom of the vertical carbon fiber couch.

[0274] 10. The particle therapy system of embodiment 9, wherein the radiological imaging system (e.g., scanner) is a CT, CBCT or MRI radiological imaging system.

[0275] 11. The particle therapy system of any one of embodiments 5-10, further comprising a surface imaging system (e.g., surface imager) mounted at the top of the vertical carbon fiber couch and configured to form a position image of the subject (e.g., patient).

[0276] #14454901 v1 12. The particle therapy system of embodiment 11, wherein the surface imaging system (e.g., surface imager) is a surface machine vision array comprising an array of sensors (e.g., 3D cameras) arranged in a horizontal circle above the subject (e.g., patient) and configured to cooperate with each other to form the position image of the subject (e.g., patient).

[0277] 13. The particle therapy system of any one of embodiments 1-12, wherein the particle accelerator comprises a superconducting cyclotron.

[0278] 14. The particle therapy system of embodiment 13, wherein the superconducting cyclotron comprises an electron cyclotron resonance (ECR) ion source.

[0279] 15. The particle therapy system of embodiment 13, wherein the superconducting cyclotron comprises an ion source selected from the group consisting of: (a) an electron cyclotron resonance (ECR) ion source; (b) a Penning ion source; (c) a multicusp ion source; (d) a hot cathode ion source; (e) a cold cathode ion source; (f) a PIG (Penning Ionization Gauge) ion source; (g) an H-minus (H") ion source; (h) combinations thereof; and (i) dual ion source configurations comprising both internal and external ion sources.

[0280] 16. The particle therapy system of any one of embodiments 1-15, further comprising a computer system.

[0281] 17. The particle therapy system of any one of embodiments 1-16, wherein the particle therapy system is installed in a photon linear accelerator vault.

[0282] 18. The particle therapy system of any one of embodiments 1-17, wherein the particle of the particle beam is a proton, a helium ion or a carbon ion.

[0283] 19. The particle therapy system of any one of embodiments 1-17, wherein the particle of the particle beam is selected from the group consisting of a proton, a helium ion, a lithium ion, a beryllium ion, a boron ion, a carbon ion, a nitrogen ion, an oxygen ion, and other light ions having an atomic number less than or equal to 10.

[0284] #14454901 v1 20. The particle therapy system of any one of embodiments 1-19, wherein the electromagnetic beamline comprises at least two quadrupole focusing magnets, zero or more dipole bending magnets, and at least one pencil beam scanning magnet.

[0285] 21. The particle therapy system of any one of embodiments 1-20, wherein the electromagnetic beamline focuses and steers the particle beam towards the pencil beam scanning magnet beam delivery system.

[0286] 22. The particle therapy system of any one of embodiments 1-21, wherein the electromagnetic beamline comprises at least one quadrupole triplet, at least one quadrupole doublet, at least one dipole bending magnet, and at least one pencil beam scanning magnet.

[0287] 23. The particle therapy system of any one of embodiments 1-22, wherein the electromagnetic beamline comprises an arrangement from the accelerator to the subject (e.g., patient) of three quadrupoles, one dipole, three quadrupoles, one dipole and two quadrupoles, and a pencil beam scanning magnet.

[0288] 24. The particle therapy system of any one of embodiments 1-23, wherein the electromagnetic beamline comprises an arrangement from the accelerator to the subject (e.g., patient) of multiple quadrupoles, multiple dipoles and a pencil beam scanning magnet.

[0289] 25. A method of treating a subject with particle therapy, the method comprising: (a) providing a particle therapy system of any one of embodiments 1-24; (b) positioning the subject (e.g., patient) on the selectively movable patient support platform; (c) actuating the radiological imaging system (e.g., CT scanner) and surface imaging cameras (e.g., 3D cameras) to obtain surface position and tumor position coordinates; (d) actuating the robotic positioner to move the selectively movable patient support platform to position the tumor position coordinates in the isocenter of the particle beam; and (e) actuating delivery of the particle beam to the tumor position.

[0290] 26. The particle therapy system of any one of embodiments 13-25, wherein the superconducting cyclotron comprises at least one high temperature superconductor (HTS).

[0291] #14454901 v1 27. The particle therapy system of embodiment 26, wherein the HTS is selected from the group consisting of bismuth-based superconductors, REBCO superconductors, iron-based superconductors, advanced HTS tape conductors, and combinations thereof.

[0292] 28. The particle therapy system of embodiment 27, wherein the bismuth-based superconductor is selected from the group consisting of Bi-2212 (Bi2Sr2CaCu2Os+x), Bi-2223 (Bi2Sr2Ca2Cu30w+x), and BSCCO.

[0293] 29. The particle therapy system of embodiment 28, wherein the bismuth-based superconductor comprises Bi-2212 in round wire form.

[0294] 30. The particle therapy system of embodiment 29, wherein the Bi-2212 round wire comprises a diameter between 0.8 mm and 1.2 mm.

[0295] 31. The particle therapy system of any one of embodiments 29-30, wherein the Bi-2212 round wire has a current density of at least 400 A / mm2at 12 Tesla in the cyclotron accelerating plane.

[0296] 32. The particle therapy system of any one of embodiments 29-30, wherein the Bi-2212 round wire has a current density of at least 400 A / mm2producing at least 11 Tesla in the particle accelerating plane.

[0297] 33. The particle therapy system of any one of embodiments 27-32, wherein the REBCO superconductor is selected from the group consisting of YBCO (YBa2CusO7x, also referred to as Y123), GdBCO (GdBa2CusO7x, also referred to as Gdl23), DyBCO (DyBa2Cu3O?x, also referred to as Dy 123), SmBCO (Snd^CmO?x, also referred to as Sml23), EuBCO (EuBa2Cu3O7-x, also referred to as Eul23), NdBCO (NdBa2Cu3O7-x, also referred to as Ndl23), HoBCO (HoBa2Cu3O7x, also referred to as Ho 123), ErBCO (ErBa2Cu3O?x, also referred to as Erl23), YbBCO (YbBa2Cu3O?x, also referred to as Ybl23), TmBCO (Tnd^CmO?x, also referred to as Tml23), and LaBCO (LaBa2Cu3O7x, also referred to as Lal23), wherein x ranges from 0 to 0.5.

[0298] 34. The particle therapy system of any one of embodiments 13-27, and 33, wherein the superconducting cyclotron comprises coils formed entirely from REBCO superconductor, wherein REBCO is the sole superconducting material utilized in the cyclotron.

[0299] #14454901 v1 35. The particle therapy system of embodiment 34, wherein the REBCO superconductor maintains engineering critical current density of 400-1200 A / mm2at magnetic fields above 10 Tesla when operated at 4.2 Kelvin.

[0300] 36. The particle therapy system of embodiment 34, wherein the REBCO superconductor maintains engineering critical current density of 400-800 A / mm2at magnetic fields of 10-12 Tesla in the cyclotron accelerating plane.

[0301] 37. The particle therapy system of any one of embodiments 13-32, wherein the superconducting cyclotron comprises coils formed entirely from Bi-2212 round wire superconductor, wherein Bi- 2212 is the sole superconducting material utilized in the cyclotron.

[0302] 38. The particle therapy system of embodiment 37, wherein the Bi-2212 round wire maintains critical current density exceeding 400 A / mm2at magnetic fields above 10 Tesla, optionally when operated at 4.2 Kelvin.

[0303] 39. The particle therapy system of any one of embodiments 27-38, wherein the advanced HTS tape conductors comprise REBCO or BSCCO tapes that have been processed into round wire configurations, including STAR (symmetric tape round) wires, CORC (conductor on round core) cables, or twisted stacked-tape cables.

[0304] 40. The particle therapy system of any one of embodiments 27-39, wherein the iron-based superconductor is selected from the group consisting of Ba(Fe,Co)2As2, (Ba,K)Fe2As2, and related pnictide compounds.

[0305] 41. The particle therapy system of any one of embodiments 26-34 and 39-40, wherein the HTS has a current density of at least 500 A / mm2.

[0306] 42. The particle therapy system of any one of embodiments 26-41, wherein the superconducting cyclotron further comprises at least one low temperature superconductor (LTS).

[0307] 43. The particle therapy system of embodiment 42, wherein the LTS is selected from the group consisting of NbsSn, NbTi, NbsAl, VsGa, and combinations thereof.

[0308] #14454901 v1 44. The particle therapy system of embodiment 42, wherein the superconducting cyclotron comprises a multi-type superconductor configuration with HTS coils (e.g., conductors) and / or LTS coils (e.g., conductors).

[0309] 45. The particle therapy system of embodiment 44, wherein: inner coils comprise high critical current superconducting wires (e.g., conductors) selected from HTS materials including Bi-2212, Bi-2223, BSCCO, and REBCO; and outer coils comprise NbsSn or NbTi superconducting wires (e.g., conductors); wherein the high critical current HTS wires (e.g., conductors) are positioned where magnetic fields exceed 10 Tesla.

[0310] 46. The particle therapy system of embodiment 44, wherein the multi-type superconductor configuration comprises: inner coils formed exclusively from REBCO high critical current superconducting wire; and outer coils formed from NbsSn or NbTi.

[0311] 47. The particle therapy system of embodiment 44, wherein the multi-type superconductor configuration comprises: inner coils formed exclusively from Bi-2212 high critical current superconducting round wire; and outer coils formed from NbsSn or NbTi.

[0312] 48. The particle therapy system of embodiment 44, wherein the multi-type superconductor configuration comprises HTS inner coils or LTS outer coils.

[0313] 49. The particle therapy system of embodiment 44, wherein the multi-type superconductor configuration is selected from the group consisting of: Bi-2212 inner coils with NbsSn outer coils; REBCO inner coils with NbsSn outer coils; Bi-2223 inner coils with NbsSn outer coils; Advanced HTS tape conductors with NbsSn outer coils; HTS inner coils with NbTi outer coils; HTS inner coils with NbsAl outer coils; and combinations thereof.

[0314] 50. The particle therapy system of any one of embodiments 25-43, wherein the superconducting cyclotron comprises only HTS superconductors.

[0315] 51. The particle therapy system of any one of embodiments 25-43, wherein the superconducting cyclotron comprises only LTS superconductors.

[0316] #14454901 v1 52. The particle therapy system of any one of embodiments 25-51, wherein the superconducting cyclotron is configured in a Helmholtz configuration.

[0317] 53. The particle therapy system of any one of embodiments 25-52, wherein the superconducting cyclotron generates a magnetic field of approximately 12 Tesla.

[0318] 54. The particle therapy system of any one of embodiments 25-52, wherein the superconducting cyclotron generates a magnetic field exceeding 11 Tesla with a radially decreasing profile for weak focusing.

[0319] 55. The particle therapy system of any one of embodiments 25-54, wherein the superconducting cyclotron has an outside diameter of less than 1.2 meters.

[0320] 56. The particle therapy system of any one of embodiments 25-55, wherein the superconducting cyclotron weighs less than 5,000 kg.

[0321] 57. The particle therapy system of any one of embodiments 26-55, wherein the superconducting cyclotron weighs less than 5,000 kilograms for proton acceleration applications.

[0322] 58. The particle therapy system of embodiment 57, wherein the weight of less than 5,000 kilograms represents at least an 80% reduction compared to superconducting cyclotrons utilizing low temperature superconductors achieving equivalent beam energy.

[0323] 59. The particle therapy system of any one of embodiments 53-54, wherein the particle is a proton and the superconducting cyclotron provides a final beam energy in the range of 160 MeV to 240 MeV with a corresponding range in water of 17.7 cm to 35.4 cm.

[0324] 60. The particle therapy system of embodiment 59, wherein the superconducting cyclotron provides a beam energy of 210 MeV with a range in water of 28.2 cm.

[0325] 61. The particle therapy system of embodiment 59, wherein the superconducting cyclotron provides a beam energy of 230 MeV with a range in water of 32.9 cm.

[0326] #14454901 v1 62. The particle therapy system of any one of embodiments 53-54, wherein the particle is a helium ion and the superconducting cyclotron provides a final beam energy of 180 MeV per nucleon with a range in water of 22 cm.

[0327] 63. The particle therapy system of embodiment 62, wherein the superconducting cyclotron weighs between 10,000 kg and 30,000 kg.

[0328] 64. The particle therapy system of any one of embodiments 53-54, wherein the particle is a carbon ion and the superconducting cyclotron provides a final beam energy of 300-400 MeV per nucleon.

[0329] 65. The particle therapy system of embodiment 64, wherein the superconducting cyclotron weighs between 50,000 kg and 120,000 kg.

[0330] 66. The particle therapy system of embodiment 59, wherein the superconducting cyclotron comprises different superconductor configurations optimized for the specific particle type.

[0331] 67. The particle therapy system of any one of embodiments 1-66, further comprising a roommounted stereoscopic X-ray imaging system for subject (e.g., patient) positioning.

[0332] 68. The particle therapy system of embodiment 67, wherein the room-mounted stereoscopic X- ray imaging system comprises at least two X-ray sources positioned at different angles relative to the subject (e.g., patient).

[0333] 69. The particle therapy system of embodiment 68, wherein the room-mounted stereoscopic X- ray imaging system comprises corresponding X-ray detectors positioned to receive X-rays from the X-ray sources.

[0334] 70. The particle therapy system of any one of embodiments 67-69, wherein the room-mounted stereoscopic X-ray imaging system is configured to provide real-time subject (e.g., patient) positioning verification.

[0335] #14454901 v1 71. The particle therapy system of any one of embodiments 67-70, wherein the room-mounted stereoscopic X-ray imaging system is integrated with the computer system to automatically adjust subject (e.g., patient) position based on stereoscopic X-ray images.

[0336] 72. The particle therapy system of any one of embodiments 67-71, wherein the room-mounted stereoscopic X-ray imaging system operates in conjunction with the surface imaging system and radiological imaging system for enhanced subject (e.g., patient) positioning accuracy.

[0337] 73. The particle therapy system of any one of embodiments 67-72, wherein the room-mounted stereoscopic X-ray imaging system is configured to track subject (e.g., patient) movement during particle beam delivery.

[0338] 74. The particle therapy system of any one of embodiments 67-73, wherein the X-ray sources are mounted on ceiling-mounted or wall-mounted positioning systems.

[0339] 75. The particle therapy system of any one of embodiments 67-74, wherein the stereoscopic X- ray imaging system provides sub-millimeter subject (e.g., patient) positioning accuracy.

[0340] 76. The particle therapy system of any one of embodiments 15-75, wherein the ion source is an internal ion source positioned within the cyclotron magnetic field.

[0341] 77. The particle therapy system of embodiment 76, wherein the internal ion source is a Penning ion source configured for operation in high magnetic fields.

[0342] 78. The particle therapy system of embodiment 76, wherein the internal ion source is a cold cathode PIG ion source.

[0343] 79. The particle therapy system of any one of embodiments 15-75, wherein the ion source is an external ion source positioned outside the cyclotron magnetic field and configured to inject ions through an axial or radial injection system.

[0344] 80. The particle therapy system of embodiment 79, wherein the external ion source is an ECR ion source.

[0345] #14454901 v1 81. The particle therapy system of any one of embodiments 15-80, wherein the ion source is an H-minus (H") ion source configured to produce negative hydrogen ions for acceleration and subsequent stripping to produce protons.

[0346] 82. The particle therapy system of embodiment 81, wherein the H-minus ion source is selected from the group consisting of a multicusp ion source, a surface plasma source, and a volume plasma source.

[0347] 83. The particle therapy system of any one of embodiments 15-82, wherein the cyclotron comprises both an internal ion source and an external ion source for enhanced ion production and beam intensity.

[0348] 84. The particle therapy system of any one of embodiments 15-83, wherein the ion source is configured to produce hydrogen ions for proton therapy.

[0349] 85. The particle therapy system of any one of embodiments 15-83, wherein the ion source is configured to produce helium ions for helium ion therapy.

[0350] 86. The particle therapy system of any one of embodiments 15-83, wherein the ion source is configured to produce carbon ions for carbon ion therapy.

[0351] 87. The particle therapy system of any one of embodiments 15-83, wherein the ion source is configured to produce lithium ions for lithium ion therapy.

[0352] 88. The particle therapy system of any one of embodiments 15-83, wherein the ion source is configured to produce beryllium ions for beryllium ion therapy.

[0353] 89. The particle therapy system of any one of embodiments 15-83, wherein the ion source is configured to produce boron ions for boron ion therapy.

[0354] 90. The particle therapy system of any one of embodiments 15-83, wherein the ion source is configured to produce nitrogen ions for nitrogen ion therapy.

[0355] #14454901 v1 91. The particle therapy system of any one of embodiments 15-83, wherein the ion source is configured to produce oxygen ions for oxygen ion therapy.

[0356] 92. The particle therapy system of any one of embodiments 15-91, wherein the ion source is configured to switch between different ion types for multi-particle therapy capability.

[0357] 93. The particle therapy system of any one of embodiments 76-78, wherein the internal ion source is positioned at the center of the cyclotron to optimize ion injection efficiency.

[0358] 94. The particle therapy system of any one of embodiments 15-93, wherein the ion source system is integrated with the computer system for automated control of ion source parameters including gas flow, ionization voltage, and extraction voltage.

[0359] 95. The particle therapy system of any one of embodiments 84-94, wherein the ion source system includes automated gas switching capability to change between hydrogen, helium, lithium- containing sources, bery Ilium-containing sources, boron-containing sources, carbon-containing gases, nitrogen-containing gases, and oxy gen-containing gases for different particle therapy applications.

[0360] 96. The particle therapy system of embodiment 95, wherein the carbon-containing gas is selected from the group consisting of methane (CFU), acetylene (C2H2), and carbon dioxide (CO2).

[0361] 97. The particle therapy system of any one of embodiments 95-96, wherein a single superconducting cyclotron is configured to accelerate multiple ion types from the same accelerator system.

[0362] 98. The particle therapy system of embodiment 97, wherein the single cyclotron magnetic field and RF frequency are adjustable to optimize acceleration for different ion mass-to-charge ratios.

[0363] 99. The particle therapy system of any one of embodiments 95-98, wherein the gas switching system includes automated purging and conditioning sequences when changing between different gas types.

[0364] #14454901 v1 100. The particle therapy system of any one of embodiments 95-99, wherein the multi-ion capability allows treatment of different cancer types with optimal particle therapy for each specific application from a single treatment system.

[0365] 101. The particle therapy system of any one of embodiments 33-100, wherein the REBCO superconductor comprises tape conductors having a width selected from 4mm, 6mm, 10mm, and 12mm, and a thickness of 50-150 micrometers.

[0366] 102. The particle therapy system of embodiment 101, wherein the REBCO tape conductors achieve engineering critical current densities of 400-1200 A / mm2, producing a magnetic field of at least 1 IT in the particle acceleration plane.

[0367] 103. The particle therapy system of embodiment 101 or 102, wherein the REBCO tape conductors achieve engineering critical current densities of at least 600 A / mm2, producing a magnetic field of at least 1 IT in the particle acceleration plane.

[0368] 104. The particle therapy system of embodiment 101 or 102, wherein the REBCO tape conductors achieve engineering critical current densities of at least 800 A / mm2, producing a magnetic field of at least 1 IT in the particle acceleration plane.

[0369] 105. The particle therapy system of any one of embodiments 101-104 , wherein individual REBCO tapes carry critical currents of 200-800 A for 4mm width tapes or 1000-2000 A for 12mm width tapes, producing a magnetic field of at least 1 IT in the particle acceleration plane.

[0370] 106. The particle therapy system of any one of embodiments 46-105, wherein the HTS inner coils utilize REBCO conductors in continuous lengths of 100-2000 meters without joints in the high-field region.

[0371] 107. The particle therapy system of embodiment 106, wherein the HTS inner coils are configured with conductor path lengths of less than 2000 meters per coil, enabling use of commercially available single-piece REBCO conductors.

[0372] #14454901 v1 108. The particle therapy system of any one of embodiments 46-108, wherein multiple REBCO tapes are configured in parallel within each coil to achieve total operating currents of 1000- 10,000 A while maintaining individual tape current densities within 400-1200 A / mm2.

[0373] 109. The particle therapy system of any one of embodiments 46-109, wherein the REBCO tape conductors comprise REBCO tapes that have been processed into round wire configurations through techniques selected from the group consisting of: symmetric tape round (STAR) wires, conductor on round core (CORC) cables, and twisted stacked-tape cables (TSTC).

[0374] 110. The particle therapy system of embodiment 109, wherein the round REBCO wire configurations achieve improved isotropic performance in magnetic fields compared to flat tape geometries while maintaining current densities of 400-1200 A / mm2.

[0375] 111. The particle therapy system of embodiment 109, wherein the STAR wires comprise multiple REBCO tapes arranged symmetrically around a central core to form a round conductor.

[0376] 112. The particle therapy system of embodiment 109, wherein the CORC cables comprise REBCO tapes wound helically around a round former.

[0377] 113. The particle therapy system of embodiment 109, wherein the twisted stacked-tape cables comprise multiple REBCO tapes stacked and twisted into a round configuration.

[0378] 114. The particle therapy system of any one of embodiments 26-113, wherein the superconducting cyclotron operates cryogen-free without liquid helium.

[0379] 115. The particle therapy system of embodiment 114, wherein the superconducting cyclotron operates at a temperature in the range of 4 Kelvin to 30 Kelvin, or 4 Kelvin to 80 Kelvin.

[0380] 116. The particle therapy system of any one of embodiments 114-115, wherein the superconducting cyclotron operates at a temperature below 15 Kelvin.

[0381] 117. The particle therapy system of embodiments 114-116, wherein the superconducting cyclotron uses cryocoolers for cooling.

[0382] #14454901 v1 118. The particle therapy system of embodiment 117, wherein the cryocoolers are selected from the group consisting of Gifford-McMahon cryocoolers, pulse tube cryocoolers, Stirling cryocoolers, and combinations thereof.

[0383] 119. The particle therapy system of any one of embodiments 117-118, wherein the cryocoolers provide cooling capacity equivalent to liquid helium cooling without requiring liquid cryogens.

[0384] 120. The particle therapy system of any one of embodiments 114-119, wherein the cryogen-free operation eliminates the need for liquid helium supply infrastructure and reduces operational complexity.

[0385] 121. The particle therapy system of any one of embodiments 13-120, wherein the superconducting cyclotron consists entirely of REBCO superconducting coils without any Bi- 2212, LTS, or other superconducting materials, wherein the REBCO coils alone generate magnetic fields exceeding 11 Tesla for particle acceleration.

[0386] 122. The particle therapy system of any one of embodiments 13-121, wherein the superconducting cyclotron consists entirely of Bi-2212 round wire superconducting coils without any REBCO, LTS, or other superconducting materials, wherein the Bi-2212 coils alone generate magnetic fields exceeding 11 Tesla for particle acceleration.

[0387] 123. The particle therapy system of any one of embodiments 53-122, wherein the particle is a lithium ion and the superconducting cyclotron provides a final beam energy of 260-400 MeV per nucleon with a corresponding range in water of 15-25 cm, optimized for intermediate LET therapy applications.

[0388] 124. The particle therapy system of any one of embodiments 53-123, wherein the particle is a beryllium ion and the superconducting cyclotron provides a final beam energy of 240-380 MeV per nucleon with enhanced LET characteristics for radioresistant tumors.

[0389] 125. The particle therapy system of any one of embodiments 53-124, wherein the particle is a boron ion and the superconducting cyclotron provides a final beam energy of 220-360 MeV per nucleon with high LET optimized for hypoxic tumor treatment.

[0390] #14454901 v1 126. The particle therapy system of any one of embodiments 15-125, wherein the ion source comprises a laser ablation system configured to produce lithium, beryllium, and boron ions from solid targets for multi-ion therapy capability.

[0391] 127. The particle therapy system of any one of embodiments 15-126, wherein the ion source is configured for rapid switching between at least two different ion species within a treatment session, enabling mixed-ion therapy protocols.

[0392] 128. The particle therapy system of any one of embodiments 1-127, wherein the system is configured to deliver sequential treatments with protons, helium ions, lithium ions, and carbon ions in a single subject (e.g., patient) session, with automated ion source switching and beamline energy adjustment completed in less than 60 seconds between ion types.

[0393] 129. A compact superconducting cyclotron for particle therapy comprising: superconducting coils comprising at least one high temperature superconductor (HTS) configured to generate a magnetic field exceeding 10 Tesla; an ion source configured to produce ions for acceleration; a radiofrequency acceleration system; wherein the cyclotron has an outside diameter of less than 1.5 meters and weighs less than 10,000 kg for proton acceleration applications.

[0394] 130. The compact superconducting cyclotron of embodiment 129, wherein the HTS comprises REBCO superconductor as the sole superconducting material, with current density exceeding 400 A / mm2at operational magnetic fields.

[0395] 131. The compact superconducting cyclotron of embodiment 129, wherein the HTS comprises Bi-2212 round wire superconductor as the sole superconducting material, with current density exceeding 400 A / mm2at operational magnetic fields.

[0396] 132. The compact superconducting cyclotron of embodiment 129, wherein the superconducting coils comprise a combination of HTS and low temperature superconductor (LTS) materials, with HTS positioned in high-field regions exceeding 10 Tesla.

[0397] 133. The compact superconducting cyclotron of any one of embodiments 129-132, configured to operate cryogen-free using closed-cycle cryocoolers without liquid helium.

[0398] #14454901 v1 134. The compact superconducting cyclotron of any one of embodiments 129-133, wherein the cyclotron is configurable for integration with various beamline configurations including but not limited to fixed horizontal beamlines, rotating gantries, and vertical beamlines.

[0399] 135. The compact superconducting cyclotron of any one of embodiments 129-134, wherein the cyclotron provides particle beam output compatible with various patient positioning systems including upright, horizontal, and pivoted configurations.

[0400] 136. The compact superconducting cyclotron of any one of embodiments 129-135, configured to accelerate multiple ion species including protons, helium, lithium, beryllium, boron, carbon, nitrogen, and oxygen ions with automated switching capability.

[0401] 137. The compact superconducting cyclotron of any one of embodiments 129-136, wherein the cyclotron is installable in existing radiation therapy vaults, newly constructed facilities, mobile treatment units, or research facilities without requiring specific vault configurations.

[0402] 138. The compact superconducting cyclotron of any one of embodiments 129-137, configured for operation with various beam delivery methods including pencil beam scanning, passive scattering, uniform scanning, wobbling, or ridge filter-based delivery systems.

[0403] 139. The compact superconducting cyclotron of any one of embodiments 129-138, wherein the cyclotron output is compatible with beamlines utilizing superconducting magnets, resistive magnets, permanent magnets, combined function magnets, or combinations thereof.

[0404] 140. The compact superconducting cyclotron of any one of embodiments 129-139, wherein the HTS comprises REBCO tape conductors configured in pancake coils, layer-wound coils, or racetrack coils, adaptable to various cyclotron geometries and field requirements.

[0405] 141. The compact superconducting cyclotron of any one of embodiments 129-140, wherein the cyclotron operates autonomously from specific control systems, being compatible with various treatment planning systems, patient management systems, and facility integration protocols.

[0406] #14454901 v1 142. The compact superconducting cyclotron of any one of embodiments 129-141, configured for integration with future particle therapy technologies including FLASH therapy delivery systems, mini-beam therapy systems, or spatially fractionated radiation therapy systems.

[0407] 143. A particle therapy system comprising: the compact superconducting cyclotron of any one of embodiments 129-142; any electromagnetic beamline configuration capable of directing the particle beam to a treatment location; and any patient support system capable of positioning a subject (e.g., patient) for particle therapy treatment.

[0408] 144. The particle therapy system of embodiment 143, wherein the system operates independently of specific imaging modalities, being compatible with CT, CBCT, MRI, PET, stereoscopic X- ray, optical surface imaging, ultrasound imaging, or combinations thereof.

[0409] 145. A method of retrofitting an existing radiation therapy facility comprising: providing the compact superconducting cyclotron of any one of embodiments 129-141; installing the cyclotron in an existing vault without structural modification; connecting the cyclotron to any beamline configuration; and integrating the cyclotron with existing patient positioning and imaging systems.

[0410] 146. A modular particle therapy system comprising: the compact superconducting cyclotron of any one of embodiments 129-141 as a self-contained unit; wherein the cyclotron includes standardized interfaces for connection to various beamline configurations; and wherein the cyclotron operates independently of specific downstream components.

[0411] #14454901 v1

Claims

CLAIMS1. A particle therapy system comprising: a particle accelerator configured to generate a particle beam; an electromagnetic beamline configured to direct the particle beam from the particle accelerator to a corresponding patient positioning device, the electromagnetic beamline comprising a plurality of electromagnets structured to bend and steer the particle beam; and a patient positioning device configured to support a subject within a location such that a target area of the subject is located at a center of the particle beam.

2. The particle therapy system of claim 1, wherein the particle accelerator comprises a superconducting cyclotron.

3. The particle therapy system of claim 2, wherein the superconducting cyclotron comprises a high temperature superconductor (HTS).

4. The particle therapy system of claim 3, wherein the HTS is selected from the group consisting of bismuth-based superconductors, REBCO superconductors, iron-based superconductors, advanced HTS tape conductors, and combinations thereof.

5. The particle therapy system of claim 4, wherein the bismuth-based superconductor is selected from the group consisting of Bi-2212 (Bi2Sr2CaCu2Os+x), Bi-2223 (Bi2Sr2Ca2Cu30w+x), and BSCCO.

6. The particle therapy system of claim 4, wherein the REBCO superconductor is selected from the group consisting of YBCO (YBa2Cu3O7),7-x, also referred to as Y 123), GdBCO (GdBa2Cu3O7),7-x, also referred to as Gdl23), DyBCO (DyBa2Cu3O7),7x, also referred to asDy 123), SmBCO (SmBa2Cu3O7),7-x, also referred to as Sml23), EuBCO (EuBa2Cu3O?), and 7-x, also referred to as Eul23), NdBCO (NdBa2Cu3O7).7-x, also referred to as Ndl23), HoBCO (HoBa2Cu3O7-x, also referred to as Ho 123), ErBCO (ErBa2Cu3O?x, also referred to as Er 123), YbBCO (YbBa2Cu3O?x, also referred to as Ybl23), TmBCO (Tnd^CmO?x, also referred to as Tml23), and LaBCO (LaBa2Cu3O7x, also referred to as Lal23), wherein x ranges from 0 to 0.5.#14454901 v17. The particle therapy system of any one of claims 3-6, wherein the superconductor has an outside diameter of less than 2 meters and weighs less than 20,000 kg.

8. The particle therapy system of any one of claims 3-7, wherein the superconductor further comprises a low temperature superconductor (LTS).

9. The particle therapy system of claim 8, wherein the superconductor comprises: inner coils comprising high critical current superconducting conductors selected from HTS materials including Bi-2212, Bi-2223, BSCCO, and REBCO; and outer coils comprising NbsSn or NbTi superconducting conductors; wherein the high critical current superconducting conductors are positioned where magnetic fields exceed 10 Tesla.

10. The particle therapy system of any one of claims 1-9, wherein the electromagnetic beamline comprises a pencil beam scanning magnet.

11. The particle therapy system of any one of claims 1-10, wherein the plurality of electromagnets are structured to selectively bend the particle beam on a substantially horizontal plane to selectively direct the particle beam to the target area of the subject.

12. The particle therapy system of any one of claims 1-11, wherein the patient positioning device comprises: a selectively movable patient support platform, optionally with a seat, structured to support the patient and connected to a robotic positioner and a vertical carbon fiber couch; a robotic positioner; and a vertical carbon fiber couch mounted onto the patient support platform in a location behind a patient.

13. The particle therapy system of claim 12, wherein the robotic positioner comprises at least two members that are movably connected and can rotate the selectively movable patient support platform with six degrees of freedom.

14. The particle therapy system of claim 12 or 13, wherein the patient positioning device further comprises a radiological imaging system mounted at the bottom of the vertical fiber couch.#14454901 v115. The particle therapy system of claim 14, wherein the radiological imaging system comprises a computed tomography (CT), a cone beam computed tomography (CBCT), or a magnetic resonance imaging (MRI) radiological imaging system.

16. The particle therapy system of any one of claims 1-15, wherein a particle of the particle therapy system is selected from the group consisting of a proton, a helium ion, a lithium ion, a beryllium ion, a boron ion, a carbon ion, a nitrogen ion, an oxygen ion, and other light ions having an atomic number less than or equal to 10.

17. The particle therapy system of any one of claims 1-16, wherein the electromagnetic beamline comprises an arrangement from the accelerator to the subject of three quadrupoles, one dipole, three quadrupoles, one dipole and two quadrupoles, and a pencil beam scanning magnet.

18. A method of treating a subject having a tumor using the particle therapy system of any one of claims 1-17, optionally wherein the method comprises:(a) positioning the subject on a selectively movable patient support platform;(b) configuring a radiological imaging system and surface imaging system to obtain surface position and tumor position coordinates;(c) obtaining the surface position and tumor position coordinates;(d) actuating a robotic positioner to move the selectively movable patient support platform to position the tumor position coordinates in the isocenter of the particle beam; and(e) delivering the particle beam to the tumor.

19. A compact superconducting cyclotron comprising: superconducting coils comprising at least one high temperature superconductor (HTS) configured to generate a magnetic field exceeding 10 Tesla; an ion source configured to produce ions for acceleration; and a radiofrequency acceleration system; wherein the cyclotron has an outside diameter of less than 1.5 meters and weighs less than 10,000 kg.

20. The compact superconducting cyclotron of claim 19, wherein:(a) the HTS comprises REBCO superconductor as the sole superconducting material, with current density exceeding 400 A / mm2at operational magnetic fields; or#14454901 v1(b) the HTS comprises Bi-2212 round wire superconductor as the sole superconducting material, with current density exceeding 400 A / mm2at operational magnetic fields.#14454901 v1

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