WO2022261085A1

WO2022261085A1 - Systems and methods for flexible beamline for accelerator-driven radiotherapy

Info

Publication number: WO2022261085A1
Application number: PCT/US2022/032490
Authority: WO
Inventors: Nathan MAJERNIK; James B. Rosenzweig; Salime M. Boucher
Original assignee: The Regents Of The University Of California; Radiabeam Technologies, Llc
Priority date: 2021-06-07
Filing date: 2022-06-07
Publication date: 2022-12-15

Abstract

A radiotherapy system is provided that can include a radiation generating system having a radiation source configured to emit a charged particle beam, and a radiation probe having a first end coupled to the radiotherapy system and a second end opposite the first end. The radiation probe can have an active plasma lens that includes a channel that is configured to receive plasma. The charged particle beam can be configured to be directed into the plasma channel so that the plasma located within the plasma channel focuses or steers the charged particle beam. The radiation probe can be configured to be articulated between a linear configuration and a curved configuration. In the linear configuration, the radiation probe can extend in a line from the first end and to the second end. In the curved configuration, the radiation probe can include at least one curve having a radius of curvature.

Description

SYSTEMS AND METHODS FOR FLEXIBLE BEAMLINE FOR ACCELERATOR-DRIVEN RADIOTHERAPY

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Patent Application No. 63/197,892 filed June 7, 2021, and entitled, “System or Method for Flexible Beamline for Accelerator-Driven Radiotherapy,” which is hereby incorporated by reference in its entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH [0002] Not applicable.

BACKGROUND

[0003] Cancer is a medical condition that accounts for almost 13% of all deaths worldwide and is one of the fastest growing diseases on earth. By 2020 there will be as many as 22 million cases worldwide. Radiation therapy alone or in conjunction with chemotherapy, surgery, or other modalities, is currently used to treat over 60% of cancer patients and used in nearly half of the curative cases. One type of radiation therapy, brachytherapy (also known as internal radiation therapy), typically involves implanting (or temporarily placing) radioactive materials inside the patient and proximate to the target region (e.g., a tumor). However, current brachytherapy techniques have downsides including undesirably radiating healthy tissues, inability to focus the radiation emitted, etc. Thus, it would be desirable to have improved systems and methods for internal radiation therapy.

SUMMARY OF THE DISCLOSURE

[0004] The present disclosure provides systems and methods for radiotherapy using a flexible beamline. In one non-limiting example, a plasma channel may be utilized to focus or steers charged particles with the probe being linear or non-linear (e.g., including curve(s)). The charged particles are injected into the plasma channel and then emitted out to the therapy site after being focused by the plasma channel. The energy of the particle beam may be varied by the radiation source, unlike other brachytherapy systems. In this way, systems and methods are provided that can adjust how much radiation can be delivered to a given location, at a time.

[0005] Some non-limiting examples of the disclosure provide a radiotherapy system. The radiotherapy system can include a radiation generating system having a radiation source configured to emit a charged particle beam, and a radiation probe having a first end coupled to the radiotherapy system and a second end opposite the first end. The radiation probe can have an active plasma lens that includes a channel that is configured to receive plasma. The charged particle beam can be configured to be directed into the plasma channel so that the plasma located within the plasma channel focuses or steers the charged particle beam. The radiation probe can be configured to be articulated between a linear configuration and a curved configuration. In the linear configuration, the radiation probe can extend in a line from the first end and to the second end. In the curved configuration, the radiation probe can include at least one curve having a radius of curvature.

[0006] Some non-limiting examples of the disclosure provide a radiation probe for brachy therapy. The radiation probe can include a first end configured to be coupled to a radiation generating system, a second end opposite the first end, and an active plasma lens having a channel that is configured to receive plasma. The plasma channel can have plasma therein that is configured to receive and focus a charged particle beam from a radiation source. The radiation probe can be configured to be articulated between a linear configuration and a curved configuration. In the linear configuration, the radiation probe can extend in a line from the first end and to the second end. In the curved configuration, the radiation probe can include at least one curve having a radius of curvature.

[0007] Some non-limiting examples of the disclosure provide a method of conducting a brachytherapy procedure using a radiation probe. The radiation probe can have a first end, a second end opposite the first end, and an active plasma lens. The method can include coupling the first end of the radiation probe to a radiation source, the radiation source configured to emit a charged particle beam, placing the second end of a radiation probe into a patient, curving the second end of the radiation probe relative to the radiation probe, emitting a charged particle beam through a channel of the active plasma lens that has plasma positioned therein, and focusing the charged particle beam to a center of the channel by movement of plasma electrons along the channel of the active plasma.

[0008] The foregoing and other aspects and advantages of the present disclosure will appear from the following description. In the description, reference is made to the accompanying drawings that form a part hereof, and in which there is shown by way of illustration one or more exemplary versions. These versions do not necessarily represent the full scope of the disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] The following drawings are provided to help illustrate various features of non- limiting examples of the disclosure, and are not intended to limit the scope of the disclosure or exclude alternative implementations.

[0010] FIG. 1 A shows a schematic illustration of a radiotherapy system.

[0011] FIG. IB shows one, non-limiting configuration for an electron accelerator with a flexible plasma channel.

[0012] FIG. 1C shows a perspective view of a electronic brachy therapy system in accordance with one, non-limiting aspect of the disclosure.

[0013] FIG. ID shows a the brachytherapy system of FIG. 1C with an electron source. [0014] FIG. IE shows model of a moderate voltage electronic brachytherapy x-ray source.

[0015] FIG. IF shows an insert showing a structure of the partitioned diamond-tungsten target of FIG. IE.

[0016] FIG. 2 shows a schematic illustration of an active plasma lens, including the physical principles of the active plasma lens (e.g., electron beam focusing).

[0017] FIG. 3 A shows a schematic illustration of a radiation probe.

[0018] FIG. 3B shows a cross-section of the triaxial version of an active plasma lens (“APL”).

[0019]

[0020] FIG. 4 shows a graph of the scattering relative to the length of the capillary of the active plasma lens.

[0021] FIG. 5 shows a compact X-band linear accelerator medical system.

[0022] FIG. 6 A shows a colorwash image of a high dose rate brachytherapy.

[0023] FIG. 6B shows a colorwash of a brachytherapy treatment with directional shielding.

[0024] FIG. 7 shows a graph of Measured pulser discharge profile.

[0025] FIG. 8 shows an initial temperature distribution for a FLASH simulation.

[0026] FIG. 9 shows a set of graphs of radial dependence of the azimuthal magnetic field, temperature, and ionization fraction at different time snapshots along the discharge curve for a 5 torr argon fill.

[0027] FIG. 10 shows a set of graphs of radial dependence of the azimuthal magnetic field, temperature, and ionization fraction at different time snapshots along the discharge curve for a 1 torr argon fill. [0028] FIG. 11 shows a set of graphs of Time dependence of the total deposited energy density, mean electron temperature, focusing gradient, and ionization fraction for alumina and PTFE channels.

[0029] FIG. 12A shows a first representation from Monte Carlo simulation of X-ray converters.

[0030] FIG. 12B shows a second representation from Monte Carlo simulation of X-ray converters.

[0031] FIG. 13 shows a set of graphs of Monte Carlo simulation results for the geometry.

[0032] FIG. 14 shows images of transverse (left), sagittal (middle), and coronal (left) isodose diagrams for the dual-source deterministic optimization (top) and clinical stochastic optimization (bottom) treatment plans for patient 25, as percentages of the CTV prescription dose.

[0033] FIG. 15 shows a diagram of an experimental apparatus.

[0034] FIG. 16 shows PTFE plates with machined channels and the plate assembled on to a flange for assembly in the vacuum chamber.

[0035] FIG. 17 shows alignment of the channel to the collimator using a laser.

[0036] FIG. 18 shows the pulser with the thyratron chassis and filament supply.

[0037] FIG. 19 shows an experimental apparatus installed on the FLEX linac beamline.

[0038] FIG. 20 shows images of the plasma plume emitted after a discharge.

[0039] FIG. 21 shows PTFE channel after 500 discharges.

[0040] FIG. 22 shows 3D height maps of a region near the center of the channel before (left) and after (right) 500 discharges.

[0041] FIG. 23 shows an example of a straight channel prototype concept.

[0042] FIG. 24 shows an example of a curved channel prototype concept.

[0043] FIG. 25 shows an example of a Triaxial channel concept.

DETAILED DESCRIPTION OF THE PRESENT DISCLOSURE

[0044] While current brachytherapy techniques promise superior dosimetry compared to external beam radiation therapy (“EBRT”), current brachytherapy techniques can have safety and handling issues that make it underutilized. For example, typical brachytherapy techniques utilize radioactive materials as the radiation source that are temporarily placed (or implanted) in the subject proximate to a target site (e.g., a tumor). However, because radioactive materials cannot be “turned off’ (e.g., in other words, radioactive materials continue emitting radiation), they pose difficulties to handling and safety. In some cases, placement of the radioactive materials require the radioactive material to be shielded from the patient (and the practitioners) before reaching the intended placement site. Otherwise, without shielding, the radioactive material can deliver undesirably radiation to healthy portions of the patient and the practitioner. Thus, handling of the radioactive materials can be difficult for the practitioner (e.g., ensuring that the material is shielded), with heavy consequences if handled improperly.

[0045] Current brachytherapy practices can also have undesirable radiation directionality. For example, because radioactive materials are isotropic and emit radiation in all directions (e.g., acting as a radioactive point source), radioactive materials deliver radiation to healthy tissue even when the radioactive material is coupled to a tumor site (or is implanted into a tumor site). Some conventional approaches have aimed to minimize this effect by shielding the radioactive material. However, the shield itself can be difficult to orient properly, and can be bulky, limiting the placement of the radioactive material to non ideal locations (e.g., not in contact with the tumor). In addition, even after radiation treatment with the radioactive material, additional safety issues result from the use of radioactive materials. For example, during removal of the radioactive material (or even placement of the radioactive material), the radioactive material can be lost in the patient (e.g., due to the small size of the radioactive material), which can continue delivering undesirable radiation to the patient.

[0046] Yet, current brachytherapy treatment sessions can be undesirably long. For example, because the radioactive materials continuously emit radiation in all directions at a generally constant radiation level (e.g., according to a half-life), the time can be used to augment the total radiation dosage for the patient. However, while adjusting the time can lead to relatively ideal dosimetry for the patient, the time typically lasts a long period of time (e.g., due to the relatively long half-life of the radioactive materials) - typically days, which requires the patient to be located in the hospital setting (e.g., and thus utilizing hospital resources) during treatment. In some cases, current brachytherapy treatments require replacing a radioactive material (e.g., due to a short half-life of the material), which can require additional hospital resources, and can lead to issues with handling, placement, and removal of radioactive sources.

[0047] Some non-limiting examples of the disclosure provide advantages to these issues (and others) by providing improved systems and methods for internal radiation therapy. For example, some non-limiting examples of the disclosure provide a radiation treatment system that can have a radiotherapy system and a radiation probe (e.g., which can define a brachytherapy system). The radiotherapy system can have a radiation source that is configured to emit a charged particle beam (e.g., an electron beam), while the radiation probe can be coupled to the radiotherapy system (e.g., a housing of the radiotherapy system) and can include an active plasma lens. The active plasma lens can include a channel that is configured to receive plasma, and in addition, the charged particle beam emitted from the radiotherapy system. Due to the plasma electrons flowing through and along the channel, the magnetic fields produced by the plasma electrons force the charged particle beam towards the center of the channel, as the charged particle beam travels along the channel. In some configurations, and advantageously, the radiation probe can be flexible (e.g., without deforming the shape of the channel), so that the electrons emitted from a second end of the radiation probe can be directed out at different positions and orientations relative to the radiation source, while still being focused by the plasma electrons. In other words, because the plasma electrons within the channel apply a radially inward force to the particle beam, the articulation of the radiation probe (e.g., curving of the probe) curves the channel (e.g., without changing the cross-section of the channel) thereby forcing the charged particle beam to traverse the adjusted path. In this way, by articulating the radiation probe, the emission position and path of the charged particle beam can be advantageously changed.

[0048] In addition to the adjustability in direction (and orientation) of the charged particle beam, the radiation dose can be tuned, unlike previous radioactive brachytherapy radiation sources. For example, the operational energy of the radiation source can be adjusted in energy level, which can adjust (e.g., increase or decrease) the penetration depth of the radiation in the patient. In other words, increasing the energy of the radiation source correspondingly increases the penetration depth (and vice versa). As a more specific example, the radiation source can be a linear accelerator (“LINAC”) and so by increasing the acceleration of the charged particle beam the radiation penetration can be increased, and by decreasing the acceleration of the charged particle beam the radiation penetration can be decreased. This selective adjustment in radiation penetration can be desirable as least because target regions of patients (e.g., tumors) are not uniformly sized, but rather can be amorphous, and thus the thickness of the target region can vary which can require different energies. In addition, different types of target regions (e.g., different cancers, different sized tumors, different tumor types, etc.) can require different energies, and thus the energy level of the radiation source can be adjusted to tailor the radiotherapy to the patient. In some cases, because the orientation and position of the radiation can be adjusted, the radiation energy can be increased to a higher level as compared to radioactive materials typically used in brachy therapy. In this way, the conformality of the dose to the tumor can be improved, and dose to the healthy tissues can be reduced.

[0049] FIG. 1A shows a schematic illustration of a radiotherapy system 100. The radiotherapy system 100 can include a radiation generating system 102 having a radiation source 104, a radiation probe 108 (e.g., which can be a brachytherapy system, and in particular, an electrical brachytherapy system), and a computing device 110. The radiation generating 102, including the radiation source 104, can be implemented in different ways. For example, the radiation source 104 can be a linear accelerator (“LINAC”) or other particle accelerator configured to accelerate particles (e.g., electrons, protons, etc.), such as, a cyclotron (e.g., a synchrotron). In this case, the radiation source 104 is configured to emit a charged particle beam 106. Although not shown, the radiation generating system 102 can include a gantry that supports the radiation source 104. The gantry can be moveable so that when the gantry moves, the radiation source 104 moves with the gantry. In some cases, the gantry can be a cylinder gantry, a ring gantry, a C-arm gantry, etc. In other configurations, the radiation generating system 102 can include a robotic arm, where the radiation source 104 is coupled to the robotic arm (e.g., a distal end of the robotic arm, so that the radiation source 104 can be the end effector of the robotic arm, with the radiation probe 108 coupled thereto). In some configurations, the radiation source 104 can be temporarily fixed, or fixed at all times. In this case, for example, the radiation probe 108 can be coupled to the robot arm (e.g., so that the radiation probe 108 is the end effector of the robot arm). In this way, the robot arm can control movements (e.g., orientation, position, etc.), of the radiation probe 108. This can be advantageous in that the robot arm can move the radiation probe 108 in ideal ways, including preventing the radiation probe from having a curve that exceeds a threshold (e.g., the length of the curvature vector of the curve being less than a threshold). [0050] As shown in FIG. 1A, the computing device 110 is in communication with the radiation generating system 102, and thus the computing device 110 can control aspects of the radiation generating system 102. For example, the computing device 110 can selectively control the radiation source (e.g., by turning on the radiation source 104 to emit a radiation beam or by turning the radiation source 104 off to stop the radiation source 104 from emihing the radiation beam). As another example, the computing device 110 can cause the radiation source to emit a particle beam having a different energy level as the particle beam 106. As yet another example, the computing device 110 can move the position of the radiation source 104, such as by rotating the gantry and thus the radiation source 104, rotating the radiation source 104 about the gantry, moving a robotic arm and thus the radiation source 104, etc. Thus, regardless of the configuration, the radiation generating system 102 (e.g., via instruction by the computing device 110), can cause the radiation source 104 to emit charged particle beams with different characteristics (e.g., energy level, duration, etc.). In some cases, while the radiation source 104 can move, the radiation source 104 can be stationary once the radiation source 104 moves to the desired position (e.g., just prior to coupling the radiation probe 108 to the radiation generating system 102). In this way, the radiation source 104 can move to different positions, but can remain stationary during radiation treatment.

[0051] The radiation probe 108 can include an active plasma lens 112 having a plasma channel 114, which is configured to receive plasma. For example, a gas (e.g., a non-reactive gas including helium, a gas admixture, etc.) can be loaded into the plasma channel 114 and energized to generate plasma within the plasma channel 114. With the plasma loaded into the plasma channel 114, the charged particle beam 106 can be emitted into the plasma channel 114, and focused by the plasma. For example, the plasma electrons flowing downstream though the plasma channel 114 subject the charged particle beam 106 to a radially inward force thereby forcing the charged particle beam 106 towards the center of the channel 114. In some cases, the plasma channel 114 can be aligned with an output of the radiation source 104 that emits the charged particle beam 106 (or other charged particle beam).

[0052] The radiation probe 108, and in particular the materials that define the channel 114 can be articulable to different orientations and curvatures. For example, the radiation probe 108 can define a first end that can be coupled to the radiation generating system 102 (e.g., the housing of the radiation generating system 102), and a second end (e.g., the free end of the radiation probe 108) that is opposite the first end. The second end of the radiation probe 108 can be manipulated to adjust its position and orientation relative to the first end of the radiation probe 108. For example, the second end of the radiation probe 108 can be manipulated from a linear configuration in which the first end and the second end of the radiation probe 108 extend in a line, to a curved configuration in which a section of the radiation probe 108 has a curve. For example, the second end can be curved relative to the first end along curve (and vice versa). As another example, in the curved configuration, the radiation probe 108 can have a plurality of curves, each of which can extend along a portion of the length of the radiation probe 108. In other words, in the curved configuration, the radiation probe 108 can have a serpentine shape that defines the plurality of curves. In some cases, each curve can have different or similar radii of curvatures, and each curve can have a curvature vector length that is less than a threshold (e.g., 2.4 cm). In other words, each curve can have a corresponding radius of curvature that is greater than a threshold. In this way, each curve can be small enough so that the plasma can still guide and focus the charged particle beam. As yet another example, the second end of the radiation probe 108 can be further manipulated to adjust the radius of curvature of each curve (e.g., a curve defined by the second end of the radiation probe 108 curving relative to the first end of the radiation probe 108). In some non-limiting examples, the cross-section of the plasma channel 114 is substantially (e.g., deviating be less than 10%) or exactly the same, regardless of the manipulated configuration of the radiation probe (e.g., the linear configuration, or any curved configuration). In this way, the plasma within the plasma channel 114 has the same charged particle focusing properties, regardless of the radius of curvature of the radiation probe 108, to ensure that the charged particles follow the desired trajectory.

[0053] In some non-limiting examples, the radiation probe 108 can include an X-ray generator 118 positioned downstream and outside of the plasma channel 114. For example, the X-ray generator 118 can be coupled to an end of the plasma channel 114 that is furthest downstream from the radiation source 104. The X-ray generator 118 is configured to generate X-rays from the bombardment of charged particles onto the X-ray generator 118. For example, the charged particle beam 106 is emitted from the radiation source 104, travels through and along the plasma channel 114 until the charged particles bombard the X-ray generator 118. As the charged particles bombard the X-ray generator 118, the X-ray generator 118 decelerates the charged particles thereby generating an X-ray beam 120 which is directed towards the patient. The X-ray generator 118 can be implemented in different ways. For example, the X-ray generator 118 can be a solid piece of material having various three-dimensional shapes (e.g., a cylinder), and can be formed out of radiation absorbing materials including tungsten, lead, etc.

[0054] In some non-limiting examples, a portion of the channel 114 is configured to be inserted into an inside region of the patient 122. In this way, the charged particle beam 106 (and the X-ray beam 120) can be guided all the way to the desired target region inside of the patient (e.g., a tumor), thus providing superior radiation directionality as opposed to radioactive brachytherapy radiation sources. In some non-limiting examples, the radiation probe 108 (e.g., the first end of the radiation probe 108) can be coupled to (or removably coupled to) the radiation generating system 102. In the removably coupled configuration, for example, the same radiation generating system 102 can be used for other conventional procedures (e.g., EBRT) with the radiation probe 108 decoupled from the radiation generating system 102. Then, when a brachytherapy radiation treatment is desired, the radiation probe 108 can be coupled to the radiation generating system 102.

[0055] As shown in FIG. 1A, the radiation generating system 102 can have a coupling feature 124 (e.g., the housing of the radiation generating system 102), and the radiation probe 108 can also have a coupling feature 126. Each of the coupling features 124, 126 can allow the radiation probe 108 (e.g., the first end of the radiation probe 108) to be removably coupled to the radiation generating system 102. For example, when the coupling features 124, 126 are engaged, the radiation probe 108 is coupled to the radiation generating system 102. The coupling features 124, 126 can be implemented in different ways. For example, one of the coupling features 124, 126 can be a slot, a hole, a threaded fastener, a clip, a magnet, a nut, etc., and the other coupling feature 124, 126 can be, respectively, a post, a protrusion, a nut, a protrusion, a magnet, a threaded fastener, etc.

[0056] The computing device 110 can be implemented in different ways. For example, the computing device 110 can include typical components used such as a processor, memory, a display, inputs (e.g., a keyboard, a mouse, a graphical user interface, a touch screen display, etc.), communication devices, etc. In some cases, the computing device 110 can simply be implemented as a processor. The computing device 110 can communicate with other computing devices and systems, such as the radiation generating system 102. In some non-limiting examples, the computing device 110 can implement some or all of the processes described below.

[0057] As explained above, brachytherapy, a crucial component of global radiation therapy and utilizes small radioactive sources. It is a cost-effective approach to therapy, with advantages in implementation in terms of dosimetry. In contrast to external beam radiotherapy that takes an outside-in approach, brachytherapy aims to place the radioactive source in or adjacent to the tumor. In many cases, this approach is able to achieve superior radiation dose distribution compared to external beams. Because brachytherapy applicators are implanted into the specific target organ, the brachytherapy dose distribution is more resilient to internal organ motion, making it well suited to treat tumors located at the cervix, breast, and prostate.

[0058] Despite the substantial benefits, brachytherapy, specifically high dose rate (HDR) brachytherapy, remains underutilized for several reasons. First, brachytherapy uses radioactive sources that cannot be “turned off,” posing a significant risk and cost in management. Second, there are few sources available that meet the requirements for specific activity and photon energy, and the only clinically-used HDR source, Ir-192, has a rather short half-life of 74.2 days, meaning it needs to be replaced several times a year. Finally, the achievable dose is often limited due to the physical limitations of the source. The average gamma-ray energy of Ir-192 is 380 keV, which is too low to cover a large target volume without densely placed catheters, yet too high for sparing of nearby critical organs. The dose profile of the source is nearly isotropic, making directional sparing generally impractical. [0059] Electronic brachytherapy has the potential to overcome these limitations and significantly improve the efficacy and utilization of brachytherapy. However, the only available internal electronic brachytherapy source is a miniaturized 50 kVp X-ray tube, which not only has short tissue penetration but also is too large in size to be compatible with standard brachytherapy applicators. For anew electronic brachytherapy source to overcome these limitations, the following features are necessary: the energy needs to be tunable to be in the range of 100 kVp-IMVp; the dose rate needs to be 1 Gy/min or higher at the effective treatment depth; and the radiation should be directional.

[0060] As illustrated in FIG. IB, the present disclosure provides an new systems for using such system for delivery of high-energy X-rays for brachytherapy to robustly replace the capabilities of currently employed radiation sources. The approach utilizes electron beam transport in current-carrying plasma channels, which can be adapted to allow implementation in high dose rate (HDR) applicators and bring such systems into ready clinical use, such as illustrated in FIG. 1C. That is, as illustrated in FIG. IB and 1C, the system includes, generally, an electron source, which is a compact linear accelerator system, and a plasma channel, which focuses the beam and transports it into the patient. The channel is attached to a specially designed applicator that guides the beam within the body, such as illustrated in FIG. ID.

[0061] The flexible plasma channels can achieve a bend radius of 2.4 cm for a 1 MeV beam. The electron source itself is to be obtained from an existing technical approach: a compact linear accelerator (linac). This path to brachytherapy yields a directional, tunable, radioactive source-free solution.

[0062] At present, brachytherapy, a crucial component of global radiation therapy, utilizes small radioactive sources. It is a cost-effective approach to therapy, with advantages in implementation in terms of dosimetry. However, the persistent long-term radioactivity of sources creates numerous safety and security issues and associated costs to manage such issues. Different from external beam radiotherapy that takes an outside-in approach, brachytherapy aims to place the radioactive source in or adjacent to the tumor target. In many cases, the inside-out approach is able to achieve superior radiation dose distribution compared to external beams. Because brachytherapy applicators are implanted into the specific target organ, the brachytherapy dose distribution is more resilient to internal organ motion, making it well suited to treat tumors located at the cervix, breast, and prostate. [0063] Despite the substantial benefits, brachytherapy, specifically high dose rate (HDR) brachytherapy, remains underutilized compared with the external beam due to reasons that are pertinent to the topic of the proposal. First, brachytherapy uses radioactive sources that pose a significant risk in management. Unlike external beam sources that can be turned off, misplaced or lost brachytherapy sources are a difficult-to-mitigate safety hazard. Complex and expensive protocols are currently in place for brachytherapy operations in the US. The cost to adopt such protocols unavoidably reduced the enthusiasm and feasibility for the technique. Second, despite a large number of existing radioactive isotopes, only a few can meet the requirements in energy, specific activity, half-life, and cost for brachytherapy. For instance, currently, the only clinically used HDR-source is Ir- 192, which is favored due to its high specific activity, acceptable energy, and half-life. However, Ir-192 is not without limitations. The half-life of 74.2 days means that the source needs to be replaced several times a year. The source replacement is costly and adds complications to radiation hazard management.

[0064] With modem HDR brachytherapy, after catheter placement, the radioactive source dwell times at various locations within the implanted catheters can be optimized to achieve target coverage and critical organ sparing. However, the achievable dose is often limited due to the physical limitations of the source. The average gamma-ray energy of Ir- 192 is 380 keV, which is too low to cover a large target volume without densely placed catheters, yet too high for sparing of nearby critical organs. The dose profile of the radioactive source is nearly isotropic, making directional sparing impossible. This limitation is exemplified in prostate brachytherapy, where the prostatic urethra receives a toxicity- inducing high dose to ensure sufficient prostate dose. In the past decade, significant effort has been made to remedy these limitations. For example, brachytherapy sources with lower energies, such as Yb-169 and Tm-170, are considered to be combined with Ir-192 for improved critical organ sparing. However, these lower energy sources have limitations in half-life, specific activities, and costs, making their clinical adoption extremely slow. Furthermore, rotational shields have been invented to make brachytherapy source dose profiles more directional for normal organ sparing. However, the thickness of material to achieve meaningful shielding for Ir-192 would be too large. The shielding material for lower energy sources such as Yb-169 would still make the entire source assembly incompatible with brachy therapy applicators.

[0065] To summarize, brachytherapy is an atractive modality for cancer treatment with many conceptual advantages. However, in practice, brachytherapy is severely underutilized. Electronic brachytherapy has the potential to overcome these limitations and significantly improve the efficacy and utilization of brachytherapy. Currently, other than surface applications, the only available internal electronic brachytherapy sources are a miniaturized X-ray tube that achieves 50 kVp, which has not only short tissue penetration but also is too large in size to be compatible with HDR applicators. A model of such a source is shown in further detail in FIG. IE and in FIG. IF, which shows an example structure of the partitioned diamond-tungsten target of the source of FIG. IE. For a new electronic brachytherapy source to overcome all aforementioned limitations, the following features are necessary besides its superior radiation safety: the energy needs to be tunable to be in the range of lOOkVp-IMVp; the dose rate needs to be 1 Gy/minute or higher at the effective treatment depth; the radiation is directional; the size of the fiber is sufficiently small; and all thermal heat loads are sufficiently small. The illustrated system delivers all these features.

[0066] The systems and methods provided herein address the challenges of taking an electron beam source, which is obtained from linac systems that, due to dimensional limitations of the system, must remain outside of the patient. Indeed, charged particle beams are often guided from the linac source to the application by “optical” systems of lenses and bends derived mainly from magnetic devices. These also, unfortunately, have footprints that exclude their use in solving the brachytherapy transport problem. Here we take a new approach to guiding (focusing and bending) electron beams by use of an emerging new technique based on active plasma lenses (APL).

[0067] An active plasma lens is an electron optic capable of simultaneously steering and focusing an electron beam. The basic operating principle utilizes a channel of gas which is ionized into a plasma and carries free current along its length; this current is approximately uniform, yielding a linear radial dependence in the azimuthal magnetic fields. These magnetic fields act to focus an electron beam moving paraxially along the nominal axis of the current. This scheme is illustrated in FIG. 2. As will be described, this focusing effect applies also to the restoration of the beam centroid; under its effect, the beam centroid tends to move toward the channel center. APLs have garnered increasing interest recently due to their achievable high focusing gradients (100’s of T/m) and their symmetric focusing action, which contrasts with conventional focusing by quadrupole magnets. [0068] FIG. 2 shows a schematic illustration of an active plasma lens 150, including the physical principles of the active plasma lens 150. For example, the active plasma lens 150 can include a channel 152, ports 156, 158, electrodes 160, 162, and a pulse forming network (“PFN”) 164. The channel 152 houses the plasma, including plasma electrons located within the channel 152 that flow downstream though the channel (e.g., in a direction from the electrode 160 to the electrode 162). The ports 156, 158 are positioned on opposing sides of the channel 152 and are each in fluid communication with the channel 152. Each port 156, 158 can both function as an input to emit fluid (e.g., a gas, such as a non-reactive gas) into the channel 152, and as an output to emit fluid out of the channel 152 (e.g., after the procedure has ended). With the fluid loaded into the channel 152 (e.g., at atmospheric pressure), the pulse forming network 164 excites the fluid until the fluid transforms into a plasma state. When this occurs, an electron bunch 166 directed into the channel 152 will be forced radially inward to the center of the channel 152 (e.g., by the inward radially force produced by the plasma electrons traveling along the channel 152).

[0069] To date, straight (i.e. having no curvature of the current-carrying axis) APLs have been experimentally demonstrated for the capture and focusing of high energy electron beams with a particular emphasis on laser-plasma accelerated beams. Curved-channel APLs have been considered theoretically and computationally with the basic principle of operation remaining the same, but with the added capability of redirecting the beam propagation direction. Here we propose to extend this concept to a flexible channel, capable of guiding an electron beam through an arbitrary trajectory, subject to bend radius constraints. The principle is similar to that of total internal reflection employed by fiber optic cables in guiding light pulses.

[0070] As an example, we consider a 1 mm inner diameter plasma capillary channel (fiber), pre-filled with ~5 Torr of argon or argon based gas admixture, pulsed at 1 kA, yielding 200 T/m focusing fields. These parameters are similar to those demonstrated by existing APLs. For a 1 MeV electron beam of interest to this proposal, this channel has a minimum bend radius of 2.4 cm. Preliminary calculations and Monte Carlo simulations indicate that the scattering from the gas produces a manageable heating of the electron beam that is well controlled by the strong focusing fields, allowing the beam to transit the meter- scale length of the channel intact.

[0071] The APL fiber can be formed of two sections, both operating on the same principle, but with different implementation details. For interstitial brachytherapy, where catheters for delivering the radiation source are surgically inserted into the patient, the overall fiber diameter is limited to 3 mm and is electrically coaxial. For intercavitary brachytherapy, the source is placed in a natural body cavity, such as the vagina, so outer diameter can be significantly larger. The plasma forms the center conductor while a metal sheath is the grounded current return path, thus protecting the patient. This small diameter section connects to a larger, electrically triaxial section which connects to the linac. The interface between these segments has an electrical grading ring to ensure controlled, uniform plasma breakdown. This concept is shown schematically in FIG. 3A.

[0072] FIG. 3A shows a schematic illustration of a radiation probe 200. The radiation probe 200 can include a body 202, an extension 204 coupled to the body 202, and an active plasma lens 206 having a channel 208 that extends through both the body 202 and the extension 204. In some cases, and as illustrated, the extension 204 is integrally formed with the body 202, however, in alternative configurations, the extension 204 can be coupled to the body 202. The body 202 and the extension 204 can each be formed of different layers of different materials, and the body 202 and the extension 204 can share some layers. For example, the body 202 can have an electrical insulating layer 214, an electrically conductive layer 216 positioned radially away from the electrical insulating layer 214 (e.g., relative to an axis 212 that extends along the length of the radiation probe 200), an electrical insulating layer 218 positioned radially away from the electrically conductive layer 216, an electrically conductive layer 220 positioned radially away from the electrical insulating layer 218, and an electrical insulating layer 222 positioned radially away from the electrically conductive layer 220. The electrical insulating layers 214, 218, 222 can be formed out of different materials than the electrically conductive layers 216, 220. For example, the electrical insulating layers 214, 218, 222 can be formed out of a dielectric material (e.g., polytetrafluoroethylene, polyamides (e.g., Kevlar^®), etc.), while the electrically conductive layers 216, 220 can be formed out of metals (e.g., copper). In some cases, and as illustrated in FIG. 3A, the layer 216 is coupled to the layer 214, the layer 218 is coupled to the layer 216, and the layer 220 is coupled to the layer 218, and the layer 222 is coupled to the layer 220.

[0073] As shown in FIG. 3A, the extension 204 can share the layers of the body 202. For example, the electrical insulating layer 218, the electrically conductive layer 220, and the electrically insulated layer 222 can extend from the body 202 and to the extension 204, with the same radial positioning as the body 202 (e.g., the layer 220 positioned radially away from the layer 218, and the layer 222 positioned radially away from the layer 222). In some cases, each layer 214, 216, 218, 220, 222 can extend entirely around the axis 212, while in other cases, the layers 216, 220 can extend partially around the axis 212. The radiation probe 200 can include a grading ring 224 that is positioned within the channel 208. The grading ring 224 is electrically connected to the electrically conductive layer 216, which can be electrically connected to a power source (e.g., a PFN, including another PFN, or the same PFN used to generate the plasma within the channel 208). The grading ring 224 can be formed out of various metals (e.g., copper), and can ensure that appropriate plasma breakdown occurs in the channel 208 (e.g., uniform breakdown). In some non-limiting examples, while a single grading ring 224 is illustrated in FIG. 3, in other configurations, the radiation probe 200 can have multiple grading rings 224 (e.g., two, three, four, etc.) each positioned within and separated from each other along the length of the channel 208. For example, the grading rings can be separated from each other by the same or different distances along the channel. In addition, each of the grading rings can be electrically connected to the electrically conductive layer 216 (and thus the power source). In other configurations, however, each grading ring can be electrically connected to a respective power source (e.g., a PFN), and thus each grading ring can operate at a different voltage, frequency, etc. Regardless of the configuration, although not shown, the grading ring(s) 224 can be positioned between the electrodes (not shown) of the radiation probe 200, which are electrically connected to a PFN and which drive plasma breakdown.

[0074] In some non-limiting examples, a portion 226 of the electrically conductive layer 220 can be positioned within the channel 208, or in some cases, an electrically conductive ring (e.g., a metal ring) can be positioned within the channel 208 and can be electrically connected to the electrically conductive layer 220. The electrically conductive layer 220 can be electrically connected to ground (e.g., or a different voltage). In this way, plasma electrons can flow through the channel 208 into the portion 226, and through the electrically conductive layer 220 to ground. In some cases, each electrically conductive layer 216, 220 can operate at a different voltage, with the electrically conductive layer 220 operating at a lower voltage (e.g., ground) than the electrically conductive layer 216.

[0075] In some non-limiting examples, the channel 208 can be defined in different ways, such as described above with regard to FIG. 1A. For example, a boundary of the channel 208 (e.g., a wall the defines the channel 208) can be defined by the electrical insulating layer 214 (e.g., at the body 202), and the electrical insulating layer 218 (e.g., at the extension 204). In some non-limiting examples, a window (not shown) can be positioned and coupled to the first end 232 of the radiation probe 200 (e.g., positioned upstream of the radiation probe 200). This window can be aligned with the channel 208 and an output of a radiation source (e.g., when the radiation probe 200 is coupled to the radiotherapy system). The window can be configured to more easily pass charged particles delivered by the radiation source (e.g., electrons), and thus can be formed out of materials including polymers (e.g., Kapton^®), and lower molecular weights (e.g., beryllium). In some configurations, differential pumping can be utilized to deliver the charged particle beam into the channel 208 without using the window. For example, the charged particle beam, from the radiation source, can pass through a series of apertures each separated from each other by small volumes that are vacuum pumped to preserve the quality of the charged particle beam.

[0076] In some non-limiting examples, the radiation probe 200 can include an X-ray generator 228 positioned outside and downstream of the channel 208. The X-ray generator 228 can be structured in a similar manner as the X-ray generator 118, and can be coupled to a second end 234 of the radiation probe 200 that is opposite a first end 232 of the radiation probe 200 (e.g., which is coupled to a radiation source). In addition, the X-ray generator 228 can be aligned with the channel 208 so that charged particles flowing through the channel 208 in a downstream direction (e.g., from the first end to the second end of the radiation probe 200) are emitted out of the channel 208 to bombard the X-ray generator 228 to generate X-rays (e.g., an X-ray beam). In some cases, the radiation probe 200 can include a collimator 230 positioned downstream of the X-ray generator 118. The collimator 230 can be coupled to the X-ray generator 228 and can shape the X-rays emitted from the X-ray generator 228. For example, the collimator 230 can be a passive collimator (e.g., a bowtie filter). The collimator 230 can be formed out of various radiation absorbing materials (e.g., tungsten, lead, etc.). In some non-limiting examples, if the radiation probe 200 is to deliver the charged particle beam (e.g., rather than X-rays), the X-ray generator 228 and the collimator 230 can be removed (e.g., so that the charged particle beam is emitted from the second end 234 of the radiation probe 200). In this way, for example, the radiation probe 200 can be manipulated to introduce additional (or changes) in curves to steer the charged particle beam emitted from the radiation probe 200 to different orientations and positions relative to the patient.

[0077] While the radiation probe 200 is illustrated in FIG. 3A as being linear in which the first end 232 and the second end 234 of the radiation probe 200 extend in a line, the radiation probe 200 can include a curve (or multiple curves) along a portion of or the entire length of the radiation probe 200. For example, as described above, the radiation probe 200 can have a serpentine shape defining multiple curves, or the radiation probe can have an arc shape. Regardless of the configuration, the radiation probe 200 can be manipulated to adjust the radii of curvature of each curve. In this way, the orientation and the position of the second end 234 relative to the first end 232 can be adjustable thereby adjusting the directionality of the radiation treatment. In some cases, the insulating layers 214, 218, 222 can be relatively flexible to allow for adjusting curvature of the radiation probe 200. In addition, as the radiation probe 200 is curved to different radii of curvature, the cross-section of the channel 208 is substantially uniform across each curve (or a range of curves) so that the focusing and directing ability of the plasma within the channel 208 is consistent (e.g., no kinks in the channel 208 form). In some cases, the radiation probe 200 can be curved between the linear configuration and a minimum radius of curvature of substantially (or exactly) 2.4 cm.

[0078] In some non-limiting examples, the body 202 is configured to be external to the patient during brachytherapy treatment, while the extension 204 is configured to be inside the patient during brachytherapy treatment. Thus, in some cases, the body 202 can be cooled (e.g., with water) thereby cooling the portions of the radiation probe 200 that have been heated by the plasma. For example, by cooling the body 202 the insulating layers (and electrically conductive layers) can remain at a desirable operating temperature. As shown in FIG. 3, the extension 204 has a smaller cross-section than the body 202, which can be desirable at least because there can be a smaller footprint for the extension 204. In addition, the relatively larger cross-section of the body 202 can accommodate the additional electrically conductive layer (e.g., the electrically conductive layer 216) that excites the fluid to generate plasma within the channel 208, while also providing a more structurally sound configuration (e.g., for cooling the body 202). In some non-limiting examples, such as when the body 202 includes additional grading rings, each electrically isolated from each other, the larger cross-section of the body 202 can accommodate the additional electrically conductive layers and insulating layers needed to electrically isolate the grading rings. [0079] In some non-limiting examples, a fluid (e.g., a gas) can be directed into the channel 208 and the power source that is electrically connected to the grading ring 224 can excite the fluid to create plasma within the channel 208. Plasma electrons flow through the channel 208 and generate a radially inward force on charged particles that are emitted into the channel 208 (e.g., at the first end 232 of the channel 208). For example, an output of a radiation source can be aligned with the channel 208, and can emit a charged particle beam at the first end 232 of the radiation probe 200 so that the charged particle beam is emitted into the channel 208. The radially inward force generated by the plasma electrons forces the charged particle beam within the channel 208 to be positioned at the center of the channel 208. As the charged particle beam is emitted from the channel 208, the charged particle beams bombards the X-ray generator 228 and an X-ray beam is generated and emitted out of the X-ray generator 228. This X-ray beam passes through the collimator 230, which attenuates the X-ray beam before being directed at the patient. In some cases, the charged particle beam can have an energy that is less than 10 MeV, less than 1 MeV, etc. In some configurations, the charged particle beam is an electron beam.

[0080] In some non-limiting examples, a radiation shield (not shown) can be positioned at various locations of the radiation probe 200 to prevent radially outward emission of radiation (e.g., X-rays). For example, a radiation shield can line an exterior surface of the radiation probe 200, including along a portion (or the entire) body 202, and including along a portion (or the entire) extension 204. In other cases, the radiation shield can be integrally formed into the body 202 (and the extension 204 of the radiation probe 200. For example, the radiation shield can be sandwiched within an insulating layer (e.g., the layer 214, 218, etc.). The radiation shield can be formed out of various radiation absorbing materials including metal foils (e.g., lead foil, tungsten foils, etc.).

[0081] In some non-limiting examples, the radiation probe 200 can include a jacket that is coaxially positioned around the radiation probe 200 and is configured to constrain the radiation probe 200 to curves with radii of curvatures greater than threshold.

[0082] In some non-limiting examples, while the plasma channel 114 and the channel 208 has been described as being channels with substantially uniform cross-sections along their respective lengths, in other configurations, the channels 114, 208 can have a cross- section that varies along the length of the channel. For example, the channels 114, 208 can have a frustoconical shape (e.g., with the cross-section decreasing along the length of the channel).

[0083] As illustrated in FIG. 3B, a triaxial segment (representing the longer, thicker tube that connects from the linac to the end effector) can be connected to a coaxial segment (representing the thin capillary that is inserted into the patient), of the style used in second prototype stage. For the triaxial design, shown in a closeup above, two added layers of PTFE tubing and one added layer of braided copper wire are included. In this design, the outer wall of PTFE is for biological compatibility. The triaxial and coaxial segments are driven by independent pulsers, permitting greater control of the heating in the portion of the beamline in contact with tissue, while ensuring maximum robustness of the transport to the end effector. EXAMPLES

[0084] The following examples have been presented in order to further illustrate aspects of the disclosure, and are not meant to limit the scope of the disclosure in any way. The examples below are intended to be examples of the present disclosure and these (and other aspects of the disclosure) are not to be bounded by theory.

[0085] Brachytherapy is a radiation therapy technique that utilizes small radioactive sources that are either implanted or positioned in temporary contact with an inside region of the patient. Generally, brachytherapy can be a cost-effective approach, with advantages in implementation in terms of dosimetry. However, the persistent long-term radioactivity of sources creates numerous safety and security issues, including the associated costs to manage such issues. Also, the lack of energy tunability and directionality restrict the potential efficacy of the treatment. This disclosure shows an innovative new system for delivery of energetic electron beams for brachytherapy to robustly replace the capabilities of currently employed radiation sources. This approach relies on electron beam transport in current-carrying plasma channels, which can be adapted to allow implementation using existing high dose rate (“HDR”) applicators. The electron source itself is to be obtained from an existing technical approach -a compact linear accelerator (“LINAC”). This path to brachytherapy yields a directional, tunable radioactive source-free solution.

[0086] At present, brachytherapy, a crucial component of global radiation therapy, utilizes small radioactive sources. It is a cost-effective approach to therapy, with advantages in implementation in terms of dosimetry. However, the persistent long-term radioactivity of sources creates numerous safety and security issues and associated costs to manage such issues. Different from external beam radiotherapy that takes an outside-in approach, brachytherapy aims to place the radioactive source in or adjacent to the tumor target. In many cases, the inside-out approach is able to achieve superior radiation dose distribution compared to external beams. Because brachytherapy applicators are implanted into the specific target organ, the brachytherapy dose distribution is more resilient to internal organ motion, making it well suited to treat tumors located at the cervix, breast, and prostate. [0087] Despite the substantial benefits, brachytherapy, specifically HDR brachytherapy, remains underutilized compared with the external beam due to reasons that are pertinent to the topic of this example. First, brachytherapy uses radioactive sources that pose a significant risk in management. Unlike external beam sources that can be turned off, misplaced or lost brachytherapy sources are a difficult-to-mitigate safety hazard. Complex and expensive protocols are currently in place for brachytherapy operations in the US. The cost to adopt such protocols unavoidably reduced the enthusiasm and feasibility for the technique. Second, despite a large number of existing radioactive isotopes, only a few can meet the requirements in energy, specific activity, half-life, and cost for brachy therapy. For instance, currently, the only clinically used HDR-source is Ir-192, which is favored due to its high specific activity, acceptable energy, and half- life. However, Ir-192 is not without limitations. The half-life of 74.2 days means that the source needs to be replaced several times a year. The source replacement is costly and adds complications to radiation hazard management. With modem HDR brachytherapy, after catheter placement, the radioactive source dwell times at various locations within the implanted catheters can be optimized to achieve target coverage and critical organ sparing. However, the achievable dose is often limited due to the physical limitations of the source. The average gamma-ray energy of Ir- 192 is 380 keV, which is too low to cover a large target volume without densely placed catheters, yet too high for sparing of nearby critical organs. The dose profile of the radioactive source is nearly isotropic, making directional sparing impossible. This limitation is exemplified in prostate brachytherapy, where the prostatic urethra receives a toxicity- inducing high dose to ensure sufficient prostate dose. In the past decade, significant effort has been made to remedy these limitations. For example, brachytherapy sources with lower energies, such as Yb-169 and Tm-170, are considered to be combined with Ir-192 for improved critical organ sparing. However, these lower energy sources have limitations in half-life, specific activities, and costs, making their clinical adoption extremely slow. Furthermore, rotational shields have been invented to make brachytherapy source dose profile more directional for normal organ sparing. However, the thickness of material to achieve meaningful shielding for Ir-192 would be too large. The shielding material for lower energy sources such as Yb-169 would still make the entire source assembly incompatible with existing brachytherapy applicators. To summarize, brachytherapy is an attractive modality for cancer treatment with many conceptual advantages. However, in practice, brachytherapy is severely underutilized.

[0088] Electronic brachytherapy has the potential to overcome these limitations and significantly improve the efficacy and utilization of brachytherapy. Currently, other than surface applications, the only available internal electronic brachytherapy source is a miniaturized X- ray tube that achieves 50 kVp, which has not only short tissue penetration but also is too large in size to be compatible with standard brachytherapy applicators. For a new electronic brachytherapy source to overcome all aforementioned limitations, the following features can be necessary besides its superior radiation safety: the energy needs to be tunable to be in the range of lOOkVp-IMVp; the dose rate needs to be lGy/ minute or higher at the effective treatment depth; and the radiation is directional. The proposed electronic brachytherapy source disclosed herein can deliver all of these features.

[0089] This example addresses the challenge of taking an electron beam source, which is obtained from LINAC systems that, due to dimensional limitations of the system, must remain outside of the patient. Indeed, charged particle beams are often guided from the LINAC source to the application by “optical” systems of lenses and bends derived mainly from magnetic devices. These also, unfortunately, have footprints that exclude their use in solving the brachytherapy transport problem. Here we take a new approach to guiding (focusing and bending) electron beams by use of an active plasma lens (“APL”).

[0090] An active plasma lens is an electron optic capable of simultaneously steering and focusing an electron beam. The basic operating principle utilizes a channel of gas which is ionized into a plasma and carries free current along its length; this current is approximately uniform, yielding a linear radial dependence in the azimuthal magnetic fields. These magnetic fields act to focus an electron beam moving paraxially along the nominal axis of the current. This focusing effect applies also to the restoration of the beam centroid; under its effect, the beam centroid tends to move toward the channel center. APLs have garnered increasing interest recently due to their achievable high focusing gradients (100’s of T/m)¹ and their symmetric focusing action, which contrasts with conventional focusing by quadrupole magnets.

[0091] Here we propose to extend this concept to a flexible channel, capable of guiding an electron beam through an arbitrary trajectory, subject to bend radius constraints.

[0092] A 1 mm inner diameter plasma capillary channel (fiber) can be used, which is pre-filled with ~5 Torr of helium or helium based gas admixture, pulsed at 1 kA, yielding 200 T/m focusing fields. These parameters are similar to those demonstrated by existing APLs. For a 1 MeV electron beam of interest to this example, this channel has a minimum bend radius of 2.4 cm. Preliminary calculations and Monte Carlo simulations indicate that the scattering from the gas produces a manageable heating of the electron beam that is well controlled by the strong focusing fields allowing the beam to transit the meter-scale length of the channel intact.

[0093] The APL fiber can be formed from two sections, both operating on the same principle, but with different implementation details. Inside the patient, the overall fiber diameter is limited to 3 mm and is electrically coaxial; the plasma forms the center conductor while a metal sheath is the grounded current return path, thus protecting the patient. This small diameter section connects to a larger, electrically triaxial section which connects to the LINAC. The interface between these segments has an electrical grading ring to ensure controlled, uniform plasma breakdown.

[0094] There are two major issues that one must address to implement the flexible fiber APL as a tool for brachy therapy. First, is the fundamental physics problem that the plasma is an ionized gas, with component particles that scatter the electron beam. This can present a problem for the stable transport without loss of the electron beam to a small target inside of a patient where X-rays are produced. The second is the practical engineering concern of how to cool the fiber, which is heated by the current flowing in the plasma. Preliminary work in both of these areas has been performed, with promising results that point to the research and development needed to bring the flexible fiber APL to mature application to brachy therapy. These initial studies are described below.

[0095] It is important to emphasize that this example seeks to provide a new path for beam delivery, a type of flexible electron gantry that should be an optimal solution for the brachytherapy transport problem. The electron beam to be transported can be obtained by a state-of-the-art miniaturized LINAC system.

[0096] Simulations of the plasma discharge must be undertaken to understand the implementation of long fiber systems. Some previous approaches have indicated that an APL plasma discharge produces a slightly non-uniform current distribution which has been observed experimentally in straight capillaries. This is a consideration for emittance- preserving transport of electron beams for high energy applications. In our case, the problem is less urgent, as the emittance (a measure of the electron beam transverse temperature) will go up due to gas scattering (see below). Existing plasma simulation codes can be employed to characterize the discharge specific to our scenario. Multiple factors can be considered in optimizing the plasma parameters via simulation, such as focusing strength, current uniformity/emittance preservation, shot-to-shot stability, and thermal load minimization. [0097] Due to the necessity of minimizing thermal load from the plasma discharges, the time dependent nature of the discharge, possibly including the initial breakdown dynamics, can be resolved to optimize the system parameters. This can be done using a kinetic code because magnetohydrodynamic (“MHD”) approximations do not capture this behavior. A particularly promising option is VSimPD which can simulate relevant features like collisions, field ionization, wall interactions, and external driving circuitry. It also supports relativistic particles which makes it suitable for use in the start-to-end beam dynamics simulations described below. [0098] Once a satisfactory set of plasma parameters has been identified by the plasma simulations, rigorous start-to-end simulations of the electron beam dynamics can be conducted. Such simulations can incorporate all relevant physical processes including non- uniform magnetic fields, scattering, and plasma wakefields. Analytical optimization of APL performance was sought in the context of the plasma wakefields and non-linear focusing but neglected scattering.

[0099] The preliminary simulations have shown that, due to the substantially lower electron beam energy (~1 MeV) scattering is not an ignorable effect. Without the strong focusing effect of the APL, the 5 Torr gas would scatter the beam to a greater size than the capillary diameter over a meter. However, with the 200 T/m fields, the spot size growth is only 10s of microns, leaving the beam intact (see, FIG. 4). These results were obtained using empirical approximations for scattering but were later validated using the Monte Carlo code

GEANT4.

[00100] At the end of the capillary, the electron beam interacts with a solid target converter to deliver radiation in a form and distribution suitable for brachytherapy. The composition and geometry of this target can be optimized using a Monte Carlo code (e.g., GEANT4). Tapering of the capillary tip can also be explored to change the magnetic field distribution and defocus the electron beam to improve the radiation isotropy. Based on the simulation, we create preliminary treatment plans by solving the following optimization problem of equation (1):

Where in equation (1) Do is the desired dose, AEB is the dose loading matrix for the electronic brachytherapy source, t is the dwell time, p = 1/2, and c is the channel number.

[00101] The preliminary dosimetric study focused on one of the most common applications for treating prostate cancer patients. Utilizing the energy modulation capability and the directional control over the beams, more effective critical organ sparing occurs without sacrificing prostate coverage. Each plan can be compared to a standard clinical plan using Ir-192. The electronic brachytherapy plans have lowered rectum and bladder dose, while having equivalent prostate target coverage and significantly reduced urethra dose (p<0.05). Specifically, the prostatic urethra dose can be reduced by >20% compared with using the Ir-192 source, as suggested by the plan using directional shielding (see, e.g., FIG. 5). FIGS. 6A and 6B show examples of dose colorwash comparison between high dose rate brachytherapy (FIG. 6A) and brachytherapy with directional shielding (FIG. 6B).

[00102] Based on the results of these simulations, a further experimental plans can validate the plasma simulation results and involve parametric sweeps to identify the optimal configuration. To this end, a high voltage, high current pulse forming network (“PFN”) can be designed and constructed. This PFN can have a Marx topology. The PFN circuit can be flexible, allowing control over the discharge voltage and duration. Tests can be conducted with this PFN on representative capillary samples, performing parametric sweeps on gas admixture fractions and pressure.

[00103] In parallel with these experiments on gas blend and PFN parameters, experiments can be conducted to optimize the fiber material. The inner fiber lining can be a dielectric material with a high breakdown field strength while also being mechanically flexible. Crucially, the liner must be able to survive the ablation from the plasma discharges for the duration of a course of therapy. Polytetrafluoroethylene (“PTFE”) is a promising candidate, with a high breakdown field (>170 kV/mm¹³), which is available commercially as small, flexible capillaries and frequently employed in medical devices.

[00104] In some non-limiting example studies, simulations of the plasma discharge, beam dynamics of the electron beam traveling through the channel, and X-ray production and dosimetry were performed. A prototype demonstration was planned, and an apparatus designed and built. Preliminary experiments were carried out.

[00105] Plasma simulations are a crucial means of understanding and optimizing the flexible plasma channel for beam transport, including aspects such as bending radius constraints, field linearity, emittance preservation, wall ablation/longevity, heat minimization, and gas pressure/admixture. To this end, we have undertaken simulations using the magnetohydrodynamics (MHD) code FLASH , a commonly employed tool for the simulation of active plasma lenses and capillary discharges more broadly [. In addition to FLASH’S baseline MHD capability, it includes the option to include equation-of-state information, enabling computationally efficient simulations of this scenario and parameter optimization. These efforts are supplemented with additional advanced codes, discussed in this section, which allow the accurate modeling of ablation of channels with custom chemistries. While some questions may be answered directly by FLASH (e.g. heating, wall effects) it is also crucial that the plasma simulation code can be readily interfaced with a beam dynamics code so the effects of the plasma, including its fields, can be accounted for during beam transport. This will be discussed in greater detail in the following section. [00106] A parameterized FLASH input deck has been created to simulate active plasma lens configurations. Arbitrary pulser current profiles can be defined, based on either experimental or simulated circuitry. For example, initial experiments (described in section B.4 below) use the thyratron based pulser described in which can deliver pulses over 300 A, with rise times on the order of tens of nanoseconds, and peak voltages up to 25 kV. A measured waveform (FIG. 7) from this pulser has been used as the basis of some FLASH simulations.

[00107] The initial conditions of the simulation are defined such that the gas within the channel is set to some initial temperature (e.g. Te = Ti = 0.5 eV) while the channel itself is at room temperature. Crucially, the channel is explicitly included within the simulation domain so effects like temperature gradients and wall ablation can be accurately simulated. A cross section of an initial temperature distribution is shown in FIG. 8. Naturally, the gas pressure and admixture is also readily variable. The resistivity is computed self-consistently throughout the simulation domain.

[00108] Efforts have been made to enhance the APL field linearity without compromising strength by appropriately tuning the gas density. For example, using argon as the fill gas and the discharge profile of FIG. 7, a 5 torr initial pressure (FIG. 9) yields a less linear azimuthal magnetic field while a 1 torr initial pressure (FIG. 10) is still able to achieve the same focusing gradient, at higher temperature and ionization fraction, with significantly improved linearity.

[00109] Simulating the ablation of different wall materials via equation-of-state definitions, including PTFE, a flexible, biocompatible insulator with a very high breakdown voltage (>170 kV/mm) yielded additional results. These simulations reveal which materials are best suited for use as channels by virtue of their longevity when subjected to plasma discharges and an acceptably low ablation rate, resulting in negligible effects on discharge dynamics. To model a baseline channel where ablative effects are minimal, we selected alumina, A1203, and modeled its ionization and excitation using detailed balance arguments via the code IONMIX. To model a complex material like PTFE, (C2F4)n, the radiative and collisional code FLYCHK was used to determine the species ionization states as a function of density and temperature. In FIG. 11, the effects on several key parameters (total deposited energy density, mean electron temperature, focusing gradient, and ionization fraction) are shown based on the discharge curves of FIG. 7 for channels composed of either alumina or PTFE. These simulations suggest that using PTFE negligibly affects the plasma discharge dynamics so, from that perspective, it is suitable for use as a channel material in a final, flexible brachytherapy device.

[00110] Beam dynamics simulations were performed in the particle-in-cell code, WARP [ ], using the time dependent electromagnetic fields as well as the plasma distribution from FLASH. Three-dimensional simulations were composed to enable propagation of the electron beam. The azimuthal magnetic fields focus and steer the electron beam, subject to nonlinearities arising during the discharge, while the plasma particles scatter the beam. Further, it is known that wakefield effects can be important in APLs, and space charge may play an important role, and these effects are modeled self-consistently by the PIC code. These simulations inform plasma channel design, beam parameters, and the beamline lattice by revealing the amount of beam lost from the channel (a quantity to be minimized) and also the phase space distribution of the beam at the exit of the channel, yielding information about the “kernel” required for designing a treatment plan, as described below.

[00111] An electron beam based on the FLEX beamline is imported and propagated through this plasma in WARP. The combination of electron beam length (100 ns duration at sub-MeV energies) and capillary length place significant constraints on the simulation domain, resolution, and capillary representation. Capturing the proper spatiotemporal- dependence of the fields has also proven to be computationally demanding, as loading and updating a large field map over many steps introduces additional expense. To address these issues, we generated a custom operator in WARP to apply an analytical approximation of the time-dependent magnetic fields generated by the lens as an external action on the simulation macroparticles at each step. Although a work in progress, this approach sufficiently captures the beam and lens dynamics, even for larger beams and lens structures. We are also exploring the use of slice-based models or cylindrically symmetric 2D R-Z simulations to permit rapid assessment of basic transverse beam dynamics for different lens configurations (e.g. discharge currents, gas densities, capillary radius, or wall material). [00112] Initial Monte-Carlo simulations were performed using GEANT4 in order to provide a dose distribution from the source, and can be used to develop treatment planning and optimization software. As an initial step, they evaluated both X-ray and electron therapy mode with a 1 MeV beam. For the X-ray mode, we tested two different types of X-ray converters, one transmission, and the other reflection. We varied the thickness of tungsten materials (in transmission mode, FIG. 12A) and heel angle (reflection mode, FIG. 12B) to search for optimal material dimensions in terms of conversion rate and X-ray beam angle. For the electron mode, we tested diffusers with varying low Z material and dimensions aiming to maximize the electron disperse for dose homogeneity.

[00113] FIG. 13 shows preliminary Monte Carlo simulation results using GEANT4. Each simulation uses 100,000,000 particles incident on a tungsten target. The beam is a circular plane beam with radius 0.32 mm and a Gaussian energy distribution centered at 0.823 MeV. The radius and energy were chosen to mimic a 1 MeV Ku-band linac. Each simulation is performed in a 15x15x15 cm3 water phantom with the center of the target face located at the origin. A 1 mm radius vacuum tube extends to the target face to mimic the plasma-filled catheters for beam transmission. The transmissive target is a 0.1 mm thickness tungsten cylinder. The face of the reflective target is oriented at 45 degrees and is 1.5 cm thick at the center of the target. Note that the reflection target results in asymmetric dose distribution with isodose lines tilting towards lower Y. The asymmetric dose distribution in combination with rotation creates the desired direction modulation that significantly improve normal organ sparing in brachy therapy.

[00114] With the optimal X-ray and electron emission kernels are determined, the kernels can be used for treatment planning, which determines the individual source dwell time for a given brachytherapy channel placement. Conventionally, stochastic methods such as simulated annealing have been used to solve the optimization problem. However, with the increasing degrees of freedom introduced by the electronic brachytherapy sources, the stochastic methods limited by computational efficiency are no longer viable in tractable time. Therefore, an analytical optimization framework is provided that is suited for ultra- large scale optimization problems.

[00115] In one non-limiting example, the following cost function can be used for dose optimization:

[00116] subject to t > 0, where t_c are the vectorized dwell times for each candidate channel, the As are dose loading matrices for each organ, the ds are the target doses for each organ, and a, b, y and w_c are optimization parameters. The first and second terms penalize CTV underdosing and overdosing, respectively. The third term penalizes OAR overdosing, and the final term is a group sparsity term, which is flexible to account for high degrees of optimization freedom, including energy and direction modulation. In the preliminary study, we exemplified automated channel selection from a large number of candidate channels. The candidate channel distribution was generated based on the clinical catheter distribution to more densely cover the CTV without intersecting the urethra. The channel selection step allows for optimal source positioning based on the source energy and patient anatomy. We then solve the optimization problem using a fast iterative shrinkage threshold algorithm (FISTA). Once the desired number of channels have been selected, this term is turned off to further optimize and smooth the dose distribution. FIG. 14 shows the preliminary planning results using our planning method. Our planning method reduced the urethra maximum dose by 8.3% with the same prostate PTV coverage.

[00117] An initial experiment was carried out to determine the feasibility of the proposed plasma channel approach. The goals of this experiment were to a) demonstrate that a PTFE channel could survive the high number of plasma exposures required for a treatment course and b) show that the beam current transported through the channel with the plasma present is higher than with no plasma.

[00118] As an electron source for injection into the plasma channel, we used RadiaBeam’s Flexible Linac for Electrons and X-rays (FLEX), an S-band traveling wave linac with a wide range of parameter control. The linac allows energy ramping from 2 to 9 MeV within a single RF pulse, and total peak beam power of up to 3.6 MW. The pulse width is variable between 100 ns and 16 ps. For X-ray output, an X-ray converter is configured after the linac exit. For electron beams, the converter is removed and the beam can be transported in vacuum to the downstream experiment.

[00119] FIG. 15 details the layout of the apparatus developed for this experiment. For simplicity, the channel was made from machining a 1 mm diameter groove into two halves of a PTFE plate. A raised surface surrounding the groove ensured that the groove was sealed when assembled and backfilled with argon. For alignment of each half of the channel with respect to each other, gage pins were placed in the channel during assembly and removed once the bolts were secured. The channel assembly is mounted onto a flange and installed in a 6” vacuum cube. Other ports of the vacuum cross hold the high-voltage feedthrough, gas injection feedthrough, and a faraday cup for measuring transmitted beam current. [00120] We had originally planned to include a differential pumping section in between the linac and the cube to protect against argon gas entering the linac, however due to limited time and budget, we decided to use a 0.003” aluminum window to separate the UHV of the linac from the vacuum in the apparatus.

[00121] FIG. 16, left shows the machined PTFE plates with groove and raised surrounding surface on one half, while the image on the right shows the assembly mounted on a vacuum flange with an XY stage for alignment. The geometry of the channel and gas injection was determined through a combination of spatial limitations, assembly considerations, availability of components, and gas flow simulations.

[00122] Not visible in the photograph is a 500 pm collimator inserted into the aperture of the flange immediately upstream of the channel. The purpose of the collimator is to aid alignment to the electron beam injected from the linac, and to filter out the portion of the electron beam that does not align to the channel.

[00123] Per the flow simulations, the argon needed to enter the channel as close to the entrance and exit points as possible. Due to spatial constraints inside a 6” vacuum cube and to allow for enough distance between conductive components to prevent electrical arcing, it was determined that we could only have a single gas injection point. With supply chain issues, we were unable to move up to a larger size chamber, thus this T-shaped PTFE design was created.

[00124] The channel assembly was then mounted to an XY stage so the channel could be aligned to the 500 pm collimator. Alignment was done on a benchtop using an alignment laser as shown in FIG. 17.

[00125] Once alignment was completed, the channel assembly was fitted inside a 6” CF cross and attached to a custom gas inlet feedthrough from below. The gas was then pulsed at 130 ml/s to maintain an intrachannel pressure of around 5 Torr.

[00126] The pulser for generating the plasma (shown in FIG. 18) was housed in a standard 19-inch server rack. It is composed of three separate units: a filament power supply, a thyratron trigger system, and the thyratron pulser chassis. The filament supply is a simple transformer that keeps the filament of the thyratron hot for proper operation. The trigger system is a unit made by e2v technologies that provides the 500V and 1000V trigger signals that the thyratron requires from a single external logic-level trigger pulse. The high voltage is provided by an external 0-30kV power supply, which was set to 25kV for the tests. Due to the fact that the thyratron acts as switch, connecting its cathode to its anode, the filament supply and trigger systems need to be held at the same 25kV, making the overall dimensions of each unit fairly large.

[00127] The channel electrodes were connected to the pulser through high voltage feedthroughs with the downstream end connected to an isolated ground rather than grounding to the chamber body to prevent arcing. A copper faraday cup with output to a BNC feedthrough was placed just downstream of the channel assembly. This assembly on the beamline is shown in FIG. 19. [00128] This channel was installed in a vacuum chamber and argon was fed through the bottom to achieve a pressure of approximately 1 torr in the channel. The pulser was charged to 25 kV and discharged through the channel, yielding a peak current in excess of 300 A. The discharge plasma and ejected plume were recorded using a high-speed camera, as shown in FIG. 20, confirming successful discharges through the channel.

[00129] These pulses were repeated 500 times (channel after 500 discharges show in FIG.

21), corresponding to a long course of brachy therapy treatment, to experimentally determine the resulting ablation of the PTFE. 3D scans were taken using a VHX microscope of a representative portion of the channel near the center before and after these discharges (FIG.

22). These scans revealed that approximately 30 microns had been ablated from the wall of the channel. This value is small relative to the expected wall thickness for the final brachytherapy device (-250 microns). This is crucial experimental evidence that the proposed flexible beamline can survive a course of treatment, as originally envisioned. [00130] Pre-clinical prototypes of the electronic brachytherapy system continue. As discussed in the previous section, the lessons learned will improve the experimental set up. Images of pre-clinical system components are shown in FIGS. 23 and 24. First, a straight, rigid coaxial channel will be tested. We still plan to use PTFE, but a coaxial geometry will be used, with the ground being provided by a copper sheath surrounding the PTFE cylinder. On the upstream end, a thin foil beam window will be brazed onto a gas fitting. The gas fitting will allow for the gas to be injected into the system via a flexible hose while the internal pressure can be monitored with a pressure gauge and adjusted using a mass flow control valve. The gas fitting will then be attached to the upstream end of the channel. The end will be capped with a thin aluminum foil electrically connected to the sleeve with conductive solder.

[00131] An in-air electron beam diagnostic system will be installed at the exit of the channel. A current transformer immediately after the window will provide a measure of current transported through the channel, and a dipole magnet and phosphor screen will provide a rough idea of the energy spectrum.

[00132] Second, a flexible, curved prototype, shown in FIG. 24, right, will be developed. It will mostly be the same as the rigid design, but it will use a much thinner walled tube of PTFE. We will start with testing it in a straight configuration, and then use an adjustable fixture to impose increasing amounts of curvature while measuring the output.

[00133] For the triaxial design, shown in a closeup in FIG. 25, we will build off the flexible design but with two added layers of PTFE tubing and one added layer of braided copper wire. In this design, the outer wall of PTFE is for biological compatibility. The triaxial portion (corresponding to the longer transport from the linac to end effector) and coaxial portion (corresponding to the thinner channel inserted into the patient) may be driven by independent pulser circuits to optimize performance. For example, it may be desirable to have a longer discharge profile in the triaxial section for optimal uniformity during beam transport, while the coaxial section could have a shorter discharge to minimize heating of patient tissue

[00134] The present disclosure has described one or more preferred non-limiting examples, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention.

[00135] It is to be understood that the disclosure is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The disclosure is capable of other non- limiting examples and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Unless specified or limited otherwise, the terms “mounted,” “connected,” “supported,” and “coupled” and variations thereof are used broadly and encompass both direct and indirect mountings, connections, supports, and couplings. Further, “connected” and “coupled” are not restricted to physical or mechanical connections or couplings.

[00136] As used herein, unless otherwise limited or defined, discussion of particular directions is provided by example only, with regard to particular non-limiting examples or relevant illustrations. For example, discussion of “top,” “front,” or “back” features is generally intended as a description only of the orientation of such features relative to a reference frame of a particular example or illustration. Correspondingly, for example, a “top” feature may sometimes be disposed below a “bottom” feature (and so on), in some arrangements or non-limiting examples. Further, references to particular rotational or other movements (e.g., counterclockwise rotation) is generally intended as a description only of movement relative a reference frame of a particular example of illustration.

[00137] In some non-limiting examples, aspects of the disclosure, including computerized implementations of methods according to the disclosure, can be implemented as a system, method, apparatus, or article of manufacture using standard programming or engineering techniques to produce software, firmware, hardware, or any combination thereof to control a processor device (e.g., a serial or parallel general purpose or specialized processor chip, a single- or multi-core chip, a microprocessor, a field programmable gate array, any variety of combinations of a control unit, arithmetic logic unit, and processor register, and so on), a computer (e.g., a processor device operatively coupled to a memory), or another electronically operated controller to implement aspects detailed herein. Accordingly, for example, non-limiting examples of the disclosure can be implemented as a set of instructions, tangibly embodied on a non-transitory computer-readable media, such that a processor device can implement the instructions based upon reading the instructions from the computer-readable media. Some non-limiting examples of the disclosure can include (or utilize) a control device such as an automation device, a special purpose or general purpose computer including various computer hardware, software, firmware, and so on, consistent with the discussion below. As specific examples, a control device can include a processor, a microcontroller, a field-programmable gate array, a programmable logic controller, logic gates etc., and other typical components that are known in the art for implementation of appropriate functionality (e.g., memory, communication systems, power sources, user interfaces and other inputs, etc.).

[00138] The term “article of manufacture” as used herein is intended to encompass a computer program accessible from any computer-readable device, carrier (e.g., non- transitory signals), or media (e.g., non-transitory media). For example, computer-readable media can include but are not limited to magnetic storage devices (e.g., hard disk, floppy disk, magnetic strips, and so on), optical disks (e.g., compact disk (CD), digital versatile disk (DVD), and so on), smart cards, and flash memory devices (e.g., card, stick, and so on). Additionally it should be appreciated that a carrier wave can be employed to carry computer- readable electronic data such as those used in transmitting and receiving electronic mail or in accessing a network such as the Internet or a local area network (LAN). Those skilled in the art will recognize that many modifications may be made to these configurations without departing from the scope or spirit of the claimed subject matter.

[00139] Certain operations of methods according to the disclosure, or of systems executing those methods, may be represented schematically in the FIGS or otherwise discussed herein. Unless otherwise specified or limited, representation in the FIGS of particular operations in particular spatial order may not necessarily require those operations to be executed in a particular sequence corresponding to the particular spatial order. Correspondingly, certain operations represented in the FIGS., or otherwise disclosed herein, can be executed in different orders than are expressly illustrated or described, as appropriate for particular non-limiting examples of the disclosure. Further, in some non-limiting examples, certain operations can be executed in parallel, including by dedicated parallel processing devices, or separate computing devices configured to interoperate as part of a large system.

[00140] As used herein in the context of computer implementation, unless otherwise specified or limited, the terms “component,” “system,” “module,” and the like are intended to encompass part or all of computer-related systems that include hardware, software, a combination of hardware and software, or software in execution. For example, a component may be, but is not limited to being, a processor device, a process being executed (or executable) by a processor device, an object, an executable, a thread of execution, a computer program, or a computer. By way of illustration, both an application running on a computer and the computer can be a component. One or more components (or system, module, and so on) may reside within a process or thread of execution, may be localized on one computer, may be distributed between two or more computers or other processor devices, or may be included within another component (or system, module, and so on). [00141] In some implementations, devices or systems disclosed herein can be utilized or installed using methods embodying aspects of the disclosure. Correspondingly, description herein of particular features, capabilities, or intended purposes of a device or system is generally intended to inherently include disclosure of a method of using such features for the intended purposes, a method of implementing such capabilities, and a method of installing disclosed (or otherwise known) components to support these purposes or capabilities. Similarly, unless otherwise indicated or limited, discussion herein of any method of manufacturing or using a particular device or system, including installing the device or system, is intended to inherently include disclosure, as non-limiting examples of the disclosure, of the utilized features and implemented capabilities of such device or system.

[00142] As used herein, unless otherwise defined or limited, ordinal numbers are used herein for convenience of reference based generally on the order in which particular components are presented for the relevant part of the disclosure. In this regard, for example, designations such as “first,” “second,” etc., generally indicate only the order in which the relevant component is introduced for discussion and generally do not indicate or require a particular spatial arrangement, functional or structural primacy or order. [00143] As used herein, unless otherwise defined or limited, directional terms are used for convenience of reference for discussion of particular figures or examples. For example, references to downward (or other) directions or top (or other) positions may be used to discuss aspects of a particular example or figure, but do not necessarily require similar orientation or geometry in all installations or configurations.

[00144] This discussion is presented to enable a person skilled in the art to make and use non-limiting examples of the disclosure. Various modifications to the illustrated examples will be readily apparent to those skilled in the art, and the generic principles herein can be applied to other examples and applications without departing from the principles disclosed herein. Thus, non-limiting examples of the disclosure are not intended to be limited to non- limiting examples shown, but are to be accorded the widest scope consistent with the principles and features disclosed herein and the claims below. The following detailed description is to be read with reference to the figures, in which like elements in different figures have like reference numerals. The figures, which are not necessarily to scale, depict selected examples and are not intended to limit the scope of the disclosure. Skilled artisans will recognize the examples provided herein have many useful alternatives and fall within the scope of the disclosure.

[00145] Also as used herein, unless otherwise limited or defined, “or” indicates a non exclusive list of components or operations that can be present in any variety of combinations, rather than an exclusive list of components that can be present only as alternatives to each other. For example, a list of “A, B, or C” indicates options of: A; B; C; A and B; A and C; B and C; and A, B, and C. Correspondingly, the term “or” as used herein is intended to indicate exclusive alternatives only when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” Further, a list preceded by “one or more” (and variations thereon) and including “or” to separate listed elements indicates options of one or more of any or all of the listed elements. For example, the phrases “one or more of A, B, or C” and “at least one of A, B, or C” indicate options of: one or more A; one or more B; one or more C; one or more A and one or more B; one or more B and one or more C; one or more A and one or more C; and one or more of each of A, B, and C. Similarly, a list preceded by “a plurality of’ (and variations thereon) and including “or” to separate listed elements indicates options of multiple instances of any or all of the listed elements. For example, the phrases “a plurality of A, B, or C” and “two or more of A, B, or C” indicate options of: A and B; B and C; A and C; and A, B, and C. In general, the term “or” as used herein only indicates exclusive alternatives (e.g. “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.”

[00146] Also as used herein, unless otherwise specified or limited, the terms “about” and “approximately,” as used herein with respect to a reference value, refer to variations from the reference value of ± 15% or less (e.g., ± 10%, ± 5%, etc.), inclusive of the endpoints of the range. Similarly, the term “substantially equal” (and the like) as used herein with respect to a reference value refers to variations from the reference value of less than ± 30% (e.g., ± 20%, ± 10%, ± 5%) inclusive. Where specified, “substantially” can indicate in particular a variation in one numerical direction relative to a reference value. For example, “substantially less” than a reference value (and the like) indicates a value that is reduced from the reference value by 30% or more, and “substantially more” than a reference value (and the like) indicates a value that is increased from the reference value by 30% or more. [00147] Various features and advantages of the disclosure are set forth in the following claims.

Claims

CLAIMS What is claimed is:

1. A radiotherapy system comprising: a radiation source configured to emit a charged particle beam; a radiation probe having a first end coupled to the radiation source and a second end opposite the first end, the radiation probe having an active plasma lens that includes a channel that is configured to receive plasma; wherein the charged particle beam is configured to be directed into the plasma channel so that the plasma located within the plasma channel focuses or steers the charged particle beam; wherein the radiation probe is configured to be in a linear configuration or articulated between the linear configuration and a curved configuration; wherein, in the linear configuration, the radiation probe extends in a line from the first end and to the second end; and wherein, in the curved configuration, the radiation probe includes at least one curve having a radius of curvature.

2. The radiotherapy system of claim 1, wherein the radiation probe is configured to be articulated between a plurality of curved configurations by adjusting the radius of curvature of the radiation probe.

3. The radiotherapy system of claim 1, includes a first cross-section proximate the first end, and a second cross-section proximate the second end, and wherein the first cross-section is larger than the second cross-section.

4. The radiotherapy system of claim 1, wherein the radiation probe is removably coupled to a housing of the radiation source.

5. The radiotherapy system of claim 1, wherein the radiation probe includes an X-ray generator aligned with the channel and positioned outside of the channel, and wherein the X-ray generator is configured to generate X-rays when particles of the charged particle beam interact with the X-ray generator.

6. The radiotherapy system of claim 5, wherein the radiation probe includes a collimator positioned downstream of the X-ray generator.

7. The radiotherapy system of claim 1, wherein the radiation source is a linear accelerator (LINAC).

8. The radiotherapy system of claim 7, wherein the charged particle beam is an electron beam.

9. The radiotherapy system of claim 1, wherein the second end of the radiation probe is configured to be inserted into a patient to deliver radiation internally to the patient.

10. A radiation probe for brachytherapy, the radiation probe comprising: a first end configured to be coupled to a radiation source; a second end opposite the first end, and configured to be adjusted relative to the first end to move between a linear configuration a curved configuration; and an active plasma lens having a channel that is configured to receive plasma, the plasma channel having plasma therein that is configured to receive and focus a charged particle beam from the radiation source.

11. The probe of claim 10, wherein the first end is configured to be removably coupled to a housing of the radiation source.

12. The probe of claim 10, further comprising an X-ray generator aligned with the channel and positioned outside of the channel and wherein the X-ray generator is configured to generate X-rays when particles of the charged particle beam interact with the X-ray generator.

13. The probe of claim 12, further comprising a collimator positioned downstream of the X-ray generator.

14. The probe of claim 10, wherein the radiation source is a linear accelerator (LINAC).

15. The probe of claim 10, wherein the charged particle beam is an electron beam.

16. The probe of claim 10, wherein the second end is configured to be inserted into a patient to deliver radiation internally to the patient.

17. A method of conducting a brachytherapy procedure using a radiation probe, the radiation probe having a first end, a second end opposite the first end, and an active plasma lens, the method comprising: coupling the first end of the radiation probe to a radiation source, the radiation source configured to emit a charged particle beam; placing the second end of a radiation probe into a patient; curving the second end of the radiation probe relative to the radiation probe; emitting a charged particle beam through a channel of the active plasma lens that has plasma positioned therein; and focusing the charged particle beam to a center of the channel by movement of plasma electrons along the channel of the active plasma to delivering radiation internally to the patient.

18. The method of claim 17, wherein placing the second end of a radiation probe into the patient includes inserting the second end of the radiation probe inside the patient to deliver radiation to a target region inside the patient that includes a tumor.

19. The method of claim 17 wherein placing the second end of a radiation probe into the patient inserting the second end of the radiation probe into a cavity of the patient or through an incision in the patient.

20. The method of claim 17 wherein curving the second end of the radiation probe includes moving the radiation probe to form at least one curve having a desired radius of curvature.