Apparatus and method for dose delivery in radiotherapy or radiotherapy research

Abstract

The present disclosure provides Apparatus (100, 200, 300, 400) for dose delivery in radiotherapy or radiotherapy research, comprising: a moveable shutter assembly (110, 210, 310, 410) configured to provide one or more openings (112, 114; GP; 212b, 214b; 316; 418a, 418b); a drive mechanism (120) connected to the shutter assembly (110, 210, 310, 410) and configured to move at least a part of the shutter assembly (110, 210, 310, 410) to selectively open and close a radiation path (RP) between at least one radiation source (140) configured to provide a radiation beam (RB) and a radiation target (RT); and a controller (130) configured to control the drive mechanism (120) to selectively open and close the radiation path (RP) by a movement of the shutter assembly (110, 210, 310, 410), wherein the radiation path (RP) is open when the one or more openings (112, 114; GP; 212b, 214b; 316; 418a, 418b) of the shutter assembly (110, 210, 310, 410) are aligned with the radiation path (RP), so that the one or more openings (112, 114; GP; 212b, 214b; 316; 418a, 418b) expose essentially an entire area of the radiation target (RT), as projected on a plane perpendicular to the radiation path (RP), to the radiation beam (RB), and wherein the radiation path (RP) is closed when the radiation path (RP) is blocked by the shutter assembly (110, 210, 310, 410).

Description

APPARATUS AND METHOD FOR DOSE DELIVERY IN RADIOTHERAPY OR RADIOTHERAPY RESEARCHFIELD

[0001] Embodiments of the present disclosure relate to an apparatus for dose delivery in radiotherapy or radiotherapy research, a system for dose delivery in radiotherapy or radiotherapy research, a method of operating an apparatus for dose delivery in radiotherapy or radiotherapy research, and a computer-readable storage medium for executing the method. Embodiments of the present disclosure relate more particularly to FLASH radiotherapy in cancer treatment or cancer research.BACKGROUND

[0002] According to the World Health Organization, cancer is the second leading cause of death globally, right after cardiovascular diseases. As a result, substantial effort has been put into improving treatment options. Radiotherapy has been used as a tool for cancer treatment for more than one hundred years. Radiotherapy targets a tumor with ionizing radiation, which damages and eventually kills the tumor cells.

[0003] In general, two different types of radiotherapy can be distinguished: internal radiotherapy, in which the radiation source is a radioactive material located inside the body, and external radiotherapy, in which the radiation source is provided by a radiation system located outside the body.

[0004] Various radiation sources can be used in external radiotherapy. For example, X- rays can be used as a radiation source, but charged particles such as protons and electrons can also be considered for radiotherapy. Charged particles interact differently with tissue than photons and produce more localized dose deposition profiles in tissue depending on the incident energy. Thus, by modulating the energy of the charged particle beam, tumors in different positions can be targeted.

[0005] Even though the efficacy of external radiotherapy is based on the damaging effect on the cancer cells caused, for example, by charged particles, the damaging effect cannot be limited to the cancer cells. Thus, external radiotherapy can also have harmful effects on surrounding healthy cells, resulting in radiation toxicity. This results in a natural paradigm: on the one hand, a sufficient dose is needed to fight the tumor; on the other hand, too high a radiation dose can have serious toxic effects on the patient. Therefore, dose delivery must be precisely controlled.

[0006] In Cecchi et al, “Characterization of an x-ray tube-based ultrahigh dose-rate system for in vitro irradiations”, Med Phys. 2021; 48:7399-7409 a slit collimator method of irradiating cells with X-ray irradiation beams is presented. The slit collimator offers only a very narrow irradiation region and therefore is limited by the amount of cells it can irradiate at each moment in time. Irradiation of larger volumes may be achieved by rotation of the slit collimator. However, the rotation does not allow instantaneous irradiation of regions larger than 1 mm width, the width of slit used by Cecchi. Narrow irradiation regions are not suitable for X-ray irradiation of cellular regions that have larger size, such as, for example, 5 x 5 cm2, where all cells should be irradiated at the same time. In addition, the design in Checchi was not optimal for achieving sufficiently high irradiation doses.

[0007] At least some of the deficiencies of the prior art solutions are now addressed in the present invention.SUMMARY

[0008] In light of the above, an apparatus for dose delivery in radiotherapy or radiotherapy research, a system for dose delivery in radiotherapy or radiotherapy research, a method of operating an apparatus for dose delivery in radiotherapy or radiotherapy research, and a computer-readable storage medium for executing the method are provided.

[0009] It is an object of the present disclosure to precisely control dose delivery in radiotherapy or radiotherapy research. It is another object of the present disclosure to improve an efficiency of an apparatus and system for dose delivery in external radiotherapy or radiotherapy research, such as FLASH radiotherapy or FLASH radiotherapy research.

[0010] The objects are solved by the features of the independent claims. Preferred embodiments are defined in the dependent claims.

[0011] According to an independent aspect of the present disclosure, an apparatus for dose delivery in radiotherapy, such as FLASH radiotherapy, or radiotherapy research is provided. The apparatus includes a moveable shutter assembly configured to provide (e.g., having or defining) one or more openings; and a drive mechanism connected to the shutter assembly and configured to move at least a part of the shutter assembly to selectively open and close a radiation path.

[0012] The embodiments of the present disclosure relate to a shutter for a radiation beam and not to a collimator. While both devices may be used in systems involving radiation such as X-rays or particle beams, they serve fundamentally different purposes. A collimator is designed to shape and direct the radiation beam, typically by producing parallel or narrowly confined rays, thereby defining the spatial characteristics of the beam. In contrast, the shutter disclosed herein functions to control the timing of radiation exposure by selectively blocking or allowing the passage of the beam. That is, the shutter acts as a temporal gate, whereas a collimator acts as a spatial filter. The technical effect of the claimed shutter lies in its capacity to regulate when the beam is passing the opening, independent of its spatial distribution.

[0013] According to some embodiments, which can be combined with other embodiments described herein, the radiation path is provided between at least one radiation source configured to provide a radiation beam and a radiation target.

[0014] According to some embodiments, which can be combined with other embodiments described herein, the radiation target includes, or is, a biological material, such as a tumor or tumor tissue.

[0015] According to some embodiments, which can be combined with other embodiments described herein, the radiation target is a biological sample extracted from a living or dead body. The sample may be used to perform tests of the apparatus and / or medical studies. In further embodiments, the radiation target may be a target in a living body, such as a tumor or a target volume including the tumor.

[0016] According to some embodiments, which can be combined with other embodiments described herein, the apparatus further includes a controller configured to control the drive mechanism to selectively open and close the radiation path by a movement of the shutter assembly.

[0017] Preferably, the radiation path is open when the one or more openings of the shutter assembly are aligned with the radiation path. In particular, the radiation path is open when the radiation path passes through the one or more openings and thus the radiation beam coming from the at least one radiation source is not blocked by any part of the shutter assembly.

[0018] Preferably, the radiation path is open when the one or more openings of the shutter assembly are aligned with the radiation path so that the one or more openings expose essentially an entire area of the radiation target, as projected on a plane perpendicular to the radiation path, to the radiation beam. The radiation target is the whole sample or the whole organ or body part that needs to be irradiated, as opposed to only a part thereof. Accordingly, the term “essentially an entire area” refers to a comprehensive or near-complete portion of the whole sample or the whole organ or body part that needs to be irradiated. The term implies that most of this target region, or possibly all of it, is subjected to radiation. “Essentially an entire area” may be defined as at least 90% of the area, preferably at least 95%, preferably at least 97%, preferably at least 99%, and most preferably the entire area of the radiation target. The term “a plane perpendicular to the radiation path” refers to the plane that is perpendicular to the incident radiation beam extending directly from the at least one radiation source to the point where the radiation target is closest to the at least one radiation source.

[0019] Preferably, the radiation path is closed when the radiation path is blocked by the shutter assembly. In particular, the radiation path is closed when the radiation path and thus the radiation beam coming from the at least one radiation source is physically blocked by a portion of the shutter assembly.

[0020] According to some embodiments, which can be combined with other embodiments described herein, the area of the radiation target, as projected on a plane perpendicular to the radiation path, is equal to or more than 20 mm2, preferably 40mm2, most preferably 60 mm2.

[0021] According to some embodiments, which can be combined with other embodiments described herein, the shutter assembly includes, or is made of, a material selected from the group consisting of a metal, a synthetic material and combinations thereof.

[0022] Different materials may be used for reflection of radiation or radiation blocking, as known in the art. In a preferred embodiment, high-Z materials (i.e. materials with higher atomic numbers, e.g. tungsten) may be suitably used for blocking radiation. In a further preferred embodiment, medium-Z elements, such as copper or brass, may be used for radiation reflection.

[0023] Preferably, the shutter assembly includes, or is made of, a material selected from the group including or consisting of copper, a copper-based alloy, tungsten, and stainless steel. The copper-based alloy may be brass, i.e., an alloy of copper and zinc.

[0024] According to some embodiments, which can be combined with other embodiments described herein, the one or more openings have a circular, rectangular or other shape.

[0025] According to a first embodiment of the present disclosure, the shutter assembly includes, or is, at least one rotatable shutter body having the one or more openings.

[0026] According to some embodiments, which can be combined with other embodiments described herein, the drive mechanism is configured to rotate the at least one shutter body around a rotational axis to selectively open and close the radiation path between the at least one radiation source and the radiation target.

[0027] According to some embodiments, which can be combined with other embodiments described herein, the controller is configured to control the drive mechanism to selectively open and close the radiation path by rotation of the at least one shutter body, wherein the radiation path is open when the one or more openings of the at least one shutter body are aligned with the radiation path (e.g., so that the one or more openings expose essentially an entire area of the radiation target, as projected on a plane perpendicular to the radiation path, to the radiation beam), and wherein the radiation path is closed when the radiation path is blocked by the at least one shutter body.

[0028] Preferably, the radiation path is open when the at least one shutter body is in a first rotational position or orientation, and the radiation path is closed when the at least one shutter body is in a second rotational position or orientation different from the first rotational position or orientation. In the first rotational position or orientation of the at least one shutter body, the one or more openings are aligned with the radiation path, i.e., the one or more openings are located on the radiation path. In the second rotational position or orientation of the at least one shutter body, the one or more openings are not aligned with the radiation path, i.e., the one or more openings are not located on the radiation path.

[0029] The rotational angle between the first rotational position or orientation and the second rotational position or orientation is not particularly limited. For example, but without limitation, rotational angle may be about 30°, 45°, 60°, 90°, 120°, 135°, 150°, 180°, 210°, 225°, 240°, 270°, 300°, 315° or 330°.

[0030] Preferably, a rotational angle between the first rotational position or orientation and the second rotational position or orientation is about 90°.

[0031] According to some embodiments, which can be combined with other embodiments described herein, the controller is configured to control the drive mechanism to rotate the at least one shutter body between the first rotational position or orientation and the second rotational position or orientation to selectively open and close the radiation path.

[0032] Preferably, the controller is configured to control the drive mechanism to rotate the at least one shutter body between the first rotational position or orientation and the second rotational position or orientation to open and to close the radiation path, respectively.

[0033] Preferably, the controller is configured to control the drive mechanism to rotate the at least one shutter body in one rotational direction to open and / or close the radiation path.

[0034] Preferably, the rotational direction is a clockwise direction or a counterclockwise direction.

[0035] According to some embodiments, which can be combined with other embodiments described herein, the at least one shutter body is a cylindrical shutter body. The term “cylinder” can be understood as commonly accepted as having a circular bottom shape anda circular upper shape and a curved surface area or shell connecting the upper circle and the little lower circle.

[0036] Preferably, the rotational axis of the at least one shutter body corresponds to, or coincides with, a cylinder axis of the cylindrical shutter body.

[0037] According to some embodiments, which can be combined with other embodiments described herein, the at least one shutter body is a solid or full shutter body. In this case, the one or more openings can be openings of a through hole extending through the at least one shutter body. For example, the through hole can extend essentially perpendicular to the rotational axis of the at least one shutter body and / or through the rotational axis of the at least one shutter body.

[0038] According to further embodiments, which can be combined with other embodiments described herein, the at least one shutter body is a hollow shutter body. For example, the at least one shutter body can be a hollow cylinder.

[0039] Preferably, the one or more openings are provided in a shell of the hollow shutter body. For example, the one or more openings are provided in a cylinder shell of the hollow cylinder.

[0040] According to some embodiments, which can be combined with other embodiments described herein, the apparatus further includes a target support configured to support the radiation target.

[0041] According to some embodiments, which can be combined with other embodiments described herein, the target support is located inside the hollow shutter body. The target support may be located inside the hollow shutter body to perform tests of the apparatus and / or medical studies on a biological sample. By arranging the target support inside the hollow shutter body, the radiation target can be placed closer to the at least one radiation source.

[0042] In one embodiment, the target support and / or the radiation target are stationary inside the hollow shutter body. In particular, the target support and / or the radiation target canbe decoupled from the at least one shutter body so as not to rotate together with the at least one shutter body.

[0043] Preferably, the radiation path is open when an opening of the one or more openings is aligned with the radiation path so that the opening exposes an essentially entire area of the radiation target, as projected on a plane perpendicular to the radiation path, to the radiation beam provided by the at least one radiation source that enters the at least one shutter body through the one or more openings in a direction toward the radiation target located e.g. inside the hollow shutter body.

[0044] According to further embodiments, which can be combined with other embodiments described herein, the target support is located outside the at least one shutter body, such as the hollow shutter body or the solid / full shutter body. The target support may be located outside the shutter body to perform a treatment on a living body, such as a treatment of a tumor by radiotherapy.

[0045] Preferably, target support and / or the radiation target are stationary outside the hollow shutter body. In particular, the target support and / or the radiation target can be decoupled from the at least one shutter body so as not to rotate together with the at least one shutter body.

[0046] According to some embodiments, which can be combined with other embodiments described herein, the one or more openings, include, or are, at least two openings located on two sides of the at least one shutter body, such as the hollow shutter body, preferably two opposite sides of the at least one shutter body.

[0047] Preferably, a center axis of the at least two openings passes through the rotational axis of the at least one shutter body. In particular, the at least two openings can be arranged symmetrically with respect to the rotational axis of the at least one shutter body.

[0048] Preferably, the radiation path is open when the at least two openings are aligned with the radiation path so that the at least two openings expose essentially an entire area of the radiation target, as projected on a plane perpendicular to the radiation path, to a radiation beam that enters the at least one shutter body through at least one first opening and exits theat least one shutter body through at least one second opening in a direction toward the radiation target located outside the at least one shutter body.

[0049] According to a second embodiment of the present disclosure, the shutter assembly includes at least one first shutter element and at least one second shutter element.

[0050] Preferably, the at least one first shutter element and the at least one second shutter element include, or are, plates and / or blades.

[0051] Preferably, the at least one first shutter element is moveable with respect to (in particular, along) a first axis and the at least one second shutter element is moveable with respect to (in particular, along) a second axis.

[0052] Preferably, the first axis is a first linear axis, and the second axis is a second linear axis.

[0053] Preferably, the first axis (e.g., the first linear axis) and the second axis (e.g., the second linear axis) are essentially parallel to each other.

[0054] Preferably, the first axis and the second axis coincide or are offset with respect to each other. For example, the first axis and the second axis may be offset in a direction essentially parallel to the radiation path and / or essentially parallel to an axis of the one or more openings.

[0055] Preferably, the drive mechanism is configured to move the at least one first shutter element with respect to (in particular, along) the first axis and / or the at least one second shutter element with respect to (in particular, along) the second axis to selectively open and close the radiation path between the at least one radiation source and the radiation target.

[0056] Preferably, the drive mechanism includes a first motor configured to move the at least one first shutter element with respect to the first axis and / or a second motor configured to move the at least one second shutter element with respect to the second axis, e.g., in opposite directions.

[0057] Preferably, the first motor includes or is a first linear motor configured to move the at least one first shutter element along the first linear axis and / or the second motor includesor is a second linear motor configured to move the second shutter element along the second linear axis.

[0058] Preferably, the controller is configured to control the drive mechanism to selectively open and close the radiation path by a movement of the at least one first shutter element with respect to the first axis and / or a movement of the at least one second shutter element with respect to the second linear axis. For example, the controller can be configured to control the drive mechanism to selectively open and close the radiation path by a linear movement of the at least one first shutter element with respect to the first linear axis and / or a linear movement of the at least one second shutter element with respect to the second linear axis.

[0059] According to some embodiments, which can be combined with other embodiments described herein, the radiation path is open when the at least one first shutter element and the at least one second shutter element are spaced apart from each other such that at least one gap between the at least one first shutter element and the at least one second shutter element provides the one or more openings that expose essentially an entire area of the radiation target, as projected on a plane perpendicular to the radiation path, to the radiation beam, and the radiation path is closed when the at least one gap between the at least one first shutter element and the at least one second shutter element is closed. The term “gap” may refer to any space between the at least one first shutter element and the at least one second shutter element that can provide the one or more openings (e.g., a rectangular space, a circular space etc.).

[0060] Preferably, the at least one gap has a width in a direction essentially parallel to the first axis (e.g., the first linear axis) and / or the second axis (e.g., the second linear axis).

[0061] According to other embodiments, which can be combined with other embodiments described herein, the radiation path is open when at least one first opening of the one or more openings in the at least one first shutter element and at least one second opening of the one or more openings in the at least one second shutter element are aligned with each other and the radiation path so that the openings expose essentially an entire area of the radiation target, as projected on a plane perpendicular to the radiation path, to the radiation beam, and theradiation path is closed when the radiation path is blocked by the at least one first shutter element and / or the at least one second shutter element.

[0062] Preferably, the radiation path is open when the at least one first opening and the at least one second opening are aligned with the radiation path so that a radiation beam enters the shutter assembly through the at least one first opening and exits the shutter assembly through the at least one second opening in a direction toward the radiation target located outside the shutter assembly.

[0063] According to some embodiments, which can be combined with other embodiments described herein, the target support is located below or behind the at least one first shutter element and / or the at least one second shutter element.

[0064] Preferably, the target support and / or the radiation target are stationary outside the shutter assembly. In particular, the target support and / or the radiation target can be decoupled from the shutter assembly so as not to move together with the at least one first shutter element and / or the at least one second shutter element.

[0065] According to a third embodiment of the present disclosure, the shutter assembly includes at least two first shutter elements moveable along a first axis and at least two second shutter elements moveable along a second axis different from the first linear axis.

[0066] Preferably, the two first shutter elements and the two second shutter elements include, or are, plates and / or blades.

[0067] Preferably, the first axis is a first linear axis, and the second axis is a second linear axis.

[0068] Preferably, the at least two first shutter elements are offset with respect to the at least two second shutter elements in an offset direction.

[0069] Preferably, the offset direction is essentially perpendicular to the first axis (e.g., the first linear axis) and / or the second axis (e.g., the second linear axis).

[0070] Preferably, the first axis (e.g., the first linear axis) and the second axis (e.g., the second linear axis) are essentially perpendicular to each other.

[0071] Preferably, the drive mechanism is configured to move the at least two first shutter elements with respect to (in particular, along) the first axis in opposite directions and / or the at least two second shutter elements with respect to (in particular, along) the second axis in opposite directions to selectively open and close the radiation path between the at least one radiation source and the radiation target.

[0072] Preferably, the drive mechanism is configured to move the at least two first shutter elements with respect to the first axis in opposite directions away from each other and / or the at least two second shutter elements with respect to the second axis in opposite directions away from each other to open the radiation path between the at least one radiation source and the radiation target. Furthermore, the drive mechanism can be configured to move the at least two first shutter elements with respect the first axis in opposite directions towards each other and / or the at least two second shutter elements with respect to the second axis in opposite directions towards each other to close the radiation path between the at least one radiation source and the radiation target.

[0073] Preferably, the controller is configured to control the drive mechanism to selectively open and close the radiation path by a movement (e.g., a linear movement) of the at least two first shutter elements in the opposite directions and / or a movement (e.g., a linear movement) of the at least two second shutter elements in the opposite directions.

[0074] Preferably, the radiation path is open when at least one first gap exists between the at least two first shutter elements and at least one second gap exists between the at least two second shutter elements such that the gaps between the at least two first shutter elements and the at least two second shutter elements provide the one or more openings. Furthermore, the radiation path can be closed when the gap between the at least two first shutter elements and / or gap between the at least two second shutter elements are closed.

[0075] According to some embodiments, which can be combined with other embodiments described herein, the target support is located below or behind the at least two first shutter elements and / or the at least two second shutter elements.

[0076] Preferably, target support and / or the radiation target are stationary outside the shutter assembly. In particular, the target support and / or the radiation target can be decoupledfrom the shutter assembly so as not to move together with the at least two first shutter elements and / or the at least two second shutter elements.

[0077] According to a fourth embodiment of the present disclosure, the shutter assembly includes at least one first shutter element and at least one second shutter element, wherein a first end or end portion of the at least one first shutter element and a first end or end portion of the at least one second shutter element are moveably (e.g., rotatably) connected to each other at a joint.

[0078] Preferably, a second end or end portion of the at least one first shutter element includes at least one first opening and a second end or end portion of the at least one second shutter element includes at least one second opening.

[0079] Preferably, the at least one first shutter element includes a first portion extending in a first direction and a second portion extending in a second direction different from the first direction. The first direction and the second direction may be essentially perpendicular to each other. The first portion of the at least one first shutter element may have the first end or end portion connected to the joint and the second portion of the at least one first shutter element may have the second end or end portion having the at least one first opening.

[0080] Preferably, the at least one second shutter element includes a first portion extending in a first direction and a second portion extending in a second direction different from the first direction. The first direction and the second direction may be essentially perpendicular to each other. The first portion of the at least one second shutter element may have the first end or end portion connected to the joint and the second portion of the at least one second shutter element may have the second end or end portion having the at least one second opening.

[0081] Preferably, the at least one first shutter element and / or the at least one second shutter element are L-shaped.

[0082] Preferably, the drive mechanism is configured to move the at least one first shutter element and the at least one second shutter element with respect to each other in opposite directions to selectively open and close the radiation path between the at least one radiation source and the radiation target.

[0083] Preferably, the controller is configured to control the drive mechanism to selectively open and close the radiation path by a rotational movement of the at least one first shutter element and the at least one second shutter element around the joint.

[0084] According to some embodiments, which can be combined with other embodiments described herein, the radiation path is open when the at least one first opening of the at least one first shutter element and the at least one second opening of the at least one second shutter element are aligned with each other and the radiation path so that the at least one first opening and the at least one second opening expose essentially an entire area of the radiation target, as projected on a plane perpendicular to the radiation path, to the radiation beam, and the radiation path is closed when the radiation path is blocked by the at least one first shutter element and / or the at least one second shutter element.

[0085] Preferably, the radiation path is open when the at least one first opening and the at least one second opening are aligned with the radiation path so that a radiation beam enters the shutter assembly through the at least one first opening and exits the shutter assembly through the at least one second opening in a direction toward the radiation target located inside the shutter assembly.

[0086] According to some embodiments, which can be combined with other embodiments described herein, the target support is located below or behind the second end or end portion of the at least one first shutter element and / or the second end or end portion of the at least one second shutter element.

[0087] Preferably, target support and / or the radiation target are stationary inside the shutter assembly. In particular, the target support and / or the radiation target can be decoupled from the shutter assembly so as not to move together with the at least one first shutter element and / or the at least one second shutter element.

[0088] According to some embodiments, which can be combined with other embodiments described herein (particularly the first to fourth embodiments described above), the apparatus further includes at least one reflection element configured to at least partially reflect radiation provided by the at least one radiation source toward the radiation target. Inparticular, the at least one reflection element may be configured to scatter or deflect radiation provided by the at least one radiation source, such as X-rays or charged particles.

[0089] Preferably, a thickness of the at least one reflection element is in a range between 0.05cm and 2cm. For example, the thickness of the at least one reflection element can be between 0.1cm and 0.7cm, in particular about 0.4cm.

[0090] Preferably, the at least one reflection element includes, or is made of, a material selected from the group including or consisting of copper, a copper-based alloy. The copperbased alloy may be brass, i.e., an alloy of copper and zinc.

[0091] According to some embodiments, which can be combined with other embodiments described herein, the at least one reflection element includes one or more first reflection elements (e.g., a disc or a rectangular plate, such as a brass disc or a rectangular plate) located under the radiation target. For example, the first reflection element may be a backscatter plate. The one or more first reflection elements backscatter the radiation back to the radiation target to obtain a higher dose on the radiation target. In the context of the present application, backscatter refers to the phenomenon where X-rays or particles are scattered backward upon striking a material (e.g., copper or a copper-based material). When X-rays or particles interact with the first reflection element, they can be deflected in various directions due to scattering. Backscatter specifically denotes the X-rays or particles that are deflected back towards the direction from which they came, particularly towards the radiation target. The term “backscatter” is also understood to include the X-rays or particles that are deflected forward towards the direction of the irradiation target. Alternatively, the term “forward scatter” may also be used to specifically refer to such scattering in the forward direction. The effect of scattering or reflection effect can be caused by interactions such as Compton scattering, where the incident X-ray photon transfers some of its energy to an electron in the material, changing the photon’s direction while reducing its energy, while also simultaneously producing electrons that are ejected from the reflection surface. The scattering of radiation increases the number of electrons that can be used to deliver more dose to the target. In particular, by way of example, if the radiation reflects on a material that is located closer to the irradiation source than the target, this may be referred to as “forward scatter” or “forward reflection”. If the radiation reflects on a material that is located farther from the irradiation source than the target, this may be referred to as “backscatter” or “backreflection”. Alternatively, the term “backscatter” may be used in the context of the invention to cover both forward scatter and backscatter.

[0092] Preferably, the target support provides, or is, the at least one reflection element, particularly the first reflection element such as the backscatter plate. Alternatively, the at least one reflection element, particularly the first reflection element such as the backscatter plate, can be arranged between the target support and the radiation target.

[0093] Preferably, the first reflection element such as the backscatter plate includes, or is made of, a material selected from the group including or consisting of copper and a copperbased alloy. The copper-based alloy may be brass, i.e., an alloy of copper and zinc.

[0094] According to some embodiments, which can be combined with other embodiments described herein, the at least one reflection element includes one or more second reflection elements located at or inside the shutter assembly. For example, the one or more second reflection elements may be located inside the rotatable shutter body.

[0095] In one embodiment, the one or more second or third reflection elements include at least one first reflection plate and at least one second reflection plate.

[0096] Preferably, the at least one first reflection plate and the at least one second reflection plate are arranged inside or outside the shutter assembly so that the radiation path extends between the at least one first reflection plate and the at least one second reflection plate.

[0097] According to some embodiments, which can be combined with other embodiments described herein, the at least one reflection element includes one or more third reflection elements located outside the shutter assembly and / or located between the radiation source and the radiation target (or target support).

[0098] Preferably, the one or more third reflection elements are arranged so that the radiation path extends between sidewalls of the one or more third reflection elements.

[0099] Preferably, the one or more third reflection elements include a cone having a sidewall or outer wall which encloses the radiation path. In particular, the radiation path can extend from a top of the cone to a bottom of the cone. However, the present disclosure is notlimited thereto and other shapes of the one or more third reflection elements are feasible, such as one or more reflection plates.

[0100] According to some embodiments, which can be combined with other embodiments described herein, the controller is configured to control the drive mechanism to close the radiation path by a movement of the shutter assembly during an initial intensity increase of the radiation beam until the intensity has reached an essentially constant value. The controller may be further configured to control the drive mechanism to open the radiation path by a movement of the shutter assembly when the intensity has reached the essentially constant value to deliver a radiation dose to the radiation target.

[0101] According to some embodiments, which can be combined with other embodiments described herein, the controller is configured to control the drive mechanism to open the radiation path to deliver a predetermined radiation dose at a predetermined dose rate to the radiation target, such as a tumor or a target volume including the tumor.

[0102] According to some embodiments, which can be combined with other embodiments described herein, the controller is configured to control the drive mechanism (e.g., a moving speed of the shutter assembly) to open the radiation path to deliver the predetermined radiation dose during a single opening period of the radiation path. For example, the controller may be configured to control the drive mechanism to deliver the predetermined radiation dose in a single movement of the shutter assembly, such as a single rotation of the rotatable shutter body. In some embodiments, also the time or timing of the opening can be controlled.

[0103] According to some embodiments, which can be combined with other embodiments described herein, the controller is configured to control the drive mechanism to open the radiation path to deliver at least a minimum dose at a dose rate to one or more volumes of interest in and / or around the radiation target to provide the FLASH effect at the one or more volumes of interest.

[0104] Preferably, the minimum dose (e.g. the minimum dose for a FLASH effect) is in a range between 8 and 12Gy, and / or the dose rate is 30 Gy / s or more, 40 Gy / s or more, 50Gy / s or more, 60 Gy / s or more, 70 Gy / s or more, 80 Gy / s or more, 90 Gy / s or more, 100 Gy / s or more, 110 Gy / s or more, 120 Gy / s or more.

[0105] According to some embodiments, which can be combined with other embodiments described herein, the controller is configured to control the drive mechanism (e.g., a moving speed of the shutter assembly) to open the radiation path to deliver the dose rate during a single opening period of the radiation path. For example, the controller may be configured to control the drive mechanism to deliver the dose rate in a single movement of the shutter assembly, such as a single rotation of the rotatable shutter body.

[0106] According to some embodiments, which can be combined with other embodiments described herein, the controller is configured to control the drive mechanism (e.g., a moving speed of the shutter assembly) to open the radiation path for a predetermined time to deliver the predetermined radiation dose at the predetermined dose rate to the radiation target.

[0107] According to some embodiments, which can be combined with other embodiments described herein, the controller is configured to control the drive mechanism (e.g., a moving speed of the shutter assembly) to open the radiation path for the predetermined time to deliver at least the minimum dose at the dose rate to the radiation target.

[0108] Preferably, the predetermined time is in a range between 20ms and Is, such as between 30ms and 500ms, between 40ms and 100ms. Preferably, the predetermined time is in a range between 40 and 80ms. For example, the predetermined time can be about 40ms, 50ms, 60 ms, 70 ms or 80 ms.

[0109] According to another independent aspect of the present disclosure, a system for radiotherapy, particularly FLASH radiotherapy, or radiotherapy research is provided. The system includes the apparatus for dose delivery in radiotherapy or radiotherapy research according to the present disclosure; and at least one radiation source.

[0110] According to some embodiments, which can be combined with other embodiments described herein, the at least one radiation source includes, or is, an electromagnetic radiation source and / or a charged particle source.

[0111] According to some embodiments, which can be combined with other embodiments described herein, the radiation beam provided by the at least one radiation source is an electromagnetic beam, such as an X-ray beam.

[0112] According to some embodiments, which can be combined with other embodiments described herein, the radiation beam provided by the at least one radiation source is a charged particle beam.

[0113] Preferably, the charged particle beam is selected from the group including, or consisting of, proton beams, electron beams and ion beams.

[0114] According to some embodiments, which can be combined with other embodiments described herein, the radiation beam includes, or is, an ultra-high dose (rate) beam, such as an ultra-high dose (rate) charged particle beam.

[0115] According to some embodiments, which can be combined with other embodiments described herein, the radiation beam, such as the ultra-high dose (rate) beam, is a FLASH beam, i.e., a beam for FLASH radiotherapy (FLASH-RT).

[0116] According to some embodiments, which can be combined with other embodiments described herein, the system is configured to determine a configuration (e.g., fluence and / or intensity) of the radiation beam based on one or more dose constraints.

[0117] Preferably, the one or more dose constraints include one or more FLASH constraints.

[0118] Preferably, the one or more dose rate constraints include one or more FLASH dose rate constraints, such as a minimum dose rate to be provided in one or more volumes of interest. For example, the minimum dose rate can be 30 Gy / s or more, 40 Gy / s or more, or 50 Gy / s or more.

[0119] According to another independent aspect of the present disclosure, a method of operating an apparatus for dose delivery in radiotherapy or radiotherapy research is provided. The method includes moving, by controlling a driving mechanism, a moveable shutter assembly configured to provide (e.g., having or defining) one or more openings to open a radiation path between at least one radiation source and a radiation target to deliver aradiation dose to the radiation target, wherein the radiation path is open when the one or more openings of the shutter assembly are aligned with the radiation path so that the one or more openings expose essentially an entire area of the radiation target, as projected on a plane perpendicular to the radiation path, to the radiation beam; and further moving the movable shutter assembly to close the radiation path between the at least one radiation source and the radiation target, wherein the radiation path is closed when the radiation path is blocked by the shutter assembly.

[0120] Embodiments are also directed at apparatus aspects for carrying out the disclosed method and include method aspects for performing each described apparatus aspect. These method aspects can be performed by way of hardware components, a computer programmed by appropriate software, by any combination of the two or in any other manner. Furthermore, embodiments according to the disclosure are also directed at methods of operating the described apparatus. The disclosure includes method aspects for carrying out every function of the apparatus.

[0121] According to another independent aspect of the present disclosure, a machine- readable medium is provided. The machine-readable medium includes instructions executable by one or more processors to implement the method of operating an apparatus for dose delivery in radiotherapy or radiotherapy research of the embodiments of the present disclosure.

[0122] According to another independent aspect of the present disclosure, a controller for controlling an apparatus for dose delivery in radiotherapy or radiotherapy research is provided. The controller includes one or more processors; and a memory (e.g., the above machine-readable medium) coupled to the one or more processors and comprising instructions executable by the one or more processors to implement the method of operating an apparatus for dose delivery in radiotherapy or radiotherapy research of the embodiments of the present disclosure.BRIEF DESCRIPTION OF THE DRAWINGS

[0123] So that the manner in which the above recited features of the present disclosure can be understood in detail, a more particular description of the disclosure, briefly summarized above, can be had by reference to embodiments. The accompanying drawings relate to embodiments of the disclosure and are described in the following:FIG. 1 shows a spatial dose distribution of an X-ray beam generated by a conventional kV irradiation unit;FIGs. 2A and B show dose histograms of different regions of the spatial dose distribution of FIG. 1;FIG. 3 shows an intensity over time of an X-ray beam pulse generated by a conventional kV irradiation unit;FIG. 4 shows an apparatus for dose delivery in radiotherapy or radiotherapy research according to a first embodiment of the present disclosure;FIG. 5 shows a perspective view of the apparatus for dose delivery in radiotherapy or radiotherapy research according to the first embodiment of the present disclosure;FIG. 6 shows a shutter body in an open and a closed state according to the first embodiment of the present disclosure;FIG. 7 shows a shutter body in an open and a closed state according to the first embodiment of the present disclosure;FIG. 8 shows a shutter body in an open and a closed state according to the first further embodiment of the present disclosure;FIG. 9A shows a shutter assembly in an open state according to a second embodiment of the present disclosure;FIG. 9B shows a shutter assembly in a closed state according to the second embodiment of the present disclosure;FIG. 10 shows a shutter assembly according to variations of the second embodiment of the present disclosure;FIG. 11 A shows a shutter assembly in a closed state according to a third embodiment of the present disclosure;FIG. 1 IB shows a shutter assembly in an open state according to the third embodiment of the present disclosure;FIG. 12 shows a shutter assembly in a closed state according to a fourth embodiment of the present disclosure;FIG. 13 shows a perspective view of the apparatus for dose delivery in radiotherapy or radiotherapy research according to a further embodiment of the present disclosure;FIG. 14 shows experimental data related to backscattering by means of a disc underneath the radiation target;FIG. 15 shows a flowchart of a method of operating an apparatus for dose delivery in radiotherapy or radiotherapy research according to the embodiments of the present disclosure;FIG. 16 illustrates experimental data in the form of a dose-versus-time plot, demonstrating the performance of a FLASH X-ray shutter;FIG. 17 illustrates the attenuation of dose rate in water, measured as a function of varying liquid thickness; andFIG. 18 illustrates spatial uniformity of the dose rates in two orthogonal directions across the beam diameter.DETAILED DESCRIPTION OF EMBODIMENTS

[0124] Reference will now be made in detail to the various embodiments of the disclosure, one or more examples of which are illustrated in the figures. Within the following description of the drawings, the same reference numbers refer to same components. Generally, only the differences with respect to individual embodiments are described. Each example is provided by way of explanation of the disclosure and is not meant as a limitationof the disclosure. Further, features illustrated or described as part of one embodiment can be used on or in conjunction with other embodiments to yield yet a further embodiment. It is intended that the description includes such modifications and variations.

[0125] This document includes references to “one embodiment” or “an embodiment”. The appearances of the phrases “in one embodiment” or “in an embodiment” do not necessarily refer to the same embodiment. Particular features, structures, or characteristics may be combined in any suitable manner consistent with this disclosure.

[0126] The term “comprising” or “including” is open-ended. As used in the appended claims, this term does not foreclose additional structure or steps.

[0127] Various units, circuits, or other components may be described or claimed as “configured to” perform a task or tasks. In such contexts, “configured to” is used to connote structure by indicating that the units / circuits / components include structure (e.g., circuitry) that performs those task or tasks during operation. As such, the unit / circuit / component can be said to be configured to perform the task even when the specified unit / circuit / component is not currently operational (e.g., is not on). The units / circuits / components used with the “configured to” language include hardware for example, circuits, memory storing program instructions executable to implement the operation, etc. Additionally, “configured to” can include generic structure (e.g., generic circuitry) that is manipulated by software and / or firmware (e.g., an FPGA or a general-purpose processor executing software) to operate in manner that is capable of performing the task(s) at issue.

[0128] As used herein, the terms “first”, “second”, etc. are used as labels for nouns that they precede, and do not imply any type of ordering (e.g., spatial, temporal, logical, etc.).

[0129] As used herein, the term “based on” is used to describe one or more factors that affect a determination. This term does not foreclose additional factors that may affect a determination. That is, a determination may be solely based on those factors or based, at least in part, on those factors. Consider the phrase “determine Abased on B.” While in this case, B is a factor that affects the determination of A, such a phrase does not foreclose the determination of A from also being based on C. In other instances, A may be determined based solely on B.

[0130] The following description uses the concept of dose, which is defined as the energy (Joule) delivered per unit mass (kilogram) and is expressed in units of Gray (Gy). The Gray is used as a unit of the radiation quantity absorbed dose that measures the energy deposited by ionizing radiation in a unit mass of matter being irradiated, and is used for measuring the delivered dose of ionizing radiation radiotherapy. Often, treatments are based on a total dose that should be delivered to the tumor site, possibly specifying a maximum dose that can be delivered to surrounding healthy regions.

[0131] Radiotherapy has been used as a tool for cancer treatment for more than one hundred years. Radiotherapy targets a tumor with ionizing radiation, which damages and eventually kills the tumor cells. In general, two types of radiation can be used in external radiotherapy: electromagnetic radiation (e.g., X-rays) and charged particles (e.g., protons, ions, or electrons). Charged particles interact with tissue differently than electromagnetic radiation: while photons exhibit a dose deposition profile that changes quite slowly in tissue, the dose deposition profile of protons exhibits a sudden increase in dose deposition at a particular depth point or depth region, resulting in a maximum deposited dose at that depth point (single Bragg-Peak) or depth region (Spread-Out Bragg peak, SOBP). Consequently, the involvement of a different radiation directly leads to a different clinical outcome.

[0132] FLASH radiotherapy (FLASH-RT) is a sub-type of external radiotherapy that uses ultra-high dose rates for the electromagnetic radiation (e.g., X-rays) and / or charged particles (e.g., protons, ions, or electrons). FLASH radiotherapy has been associated with a reduction in radiation-induced toxicity effects while maintaining the same response for tumor tissue.

[0133] FLASH-RT uses ultrafast irradiation with dose rates that are several orders of magnitude higher than the dose rates used in conventional radiotherapy (e.g., 35-120 Gy / s compared to 1-4 Gy / min). Thus, with FLASH-RT, there are no longer any problems with organ motion because the tissue is irradiated for only short periods of time, usually less than 0.1 seconds. In addition, several studies have shown that the high dose rates allow for the reduction of toxicity directly induced by radiation to normal tissue while maintaining an equally effective response to tumor tissue. This is the so-called “FLASH effect”.

[0134] One of the best-known hypotheses to explain the FLASH effect is based on oxygen depletion. Oxygen is a molecule that is considered a radiation sensitizer: due to itslarge electron affinity, oxygen contributes to the conversion of radiation-induced damage, which can still be repaired by cellular mechanisms, into permanent damage to DNA. According to the oxygen depletion hypothesis, when tissue is irradiated with very high doses, as in FLASH-RT, oxygen is removed from the cell much faster than it is returned to the cell by diffusion processes in healthy tissue, creating a hypoxic situation in the cell. As a result, the radiation sensitizer effect of oxygen is absent. In addition, the lack of oxygen in the cell leads to a reduction in the formation of reactive oxygen species in the irradiation process and thus attenuates its potential toxic effect on the cell.

[0135] However, the oxygen depletion hypothesis might not be the only explanation for the FLASH effect, and further research is currently underway to determine the mechanisms responsible for, or contributing to, the FLASH effect.

[0136] FLASH-RT may use electromagnetic radiation (e.g., X-rays) and / or charged particles (e.g., protons, ions, or electrons) to irradiate tumors. The type of radiation can be selected based on various factors, such as the type of tumor, the location of the tumor in the patient’s body, the accessibility of the techniques, and the like. For example, the energy range of electron beams commonly used in radiotherapy only allows irradiation of superficial regions. Protons or ions, on the other hand, can be used to treat tumors that lie deeper in the patient’s body.

[0137] The electromagnetic radiation, such as X-rays, can be provided by kV irradiation units in which electrons are accelerated under a potential difference to generate the electromagnetic radiation.

[0138] The charged particles can be supplied by a particle accelerator that uses electromagnetic fields to bring the charged particles to desired energies and maintain the charged particles in well-defined charged particle beams. For example, linear accelerators, cyclotrons, or synchrotrons can be used to generate proton beams and / or ion beams for FLASH-RT. The particle accelerator may be configured to generate a Spread-Out Bragg peak, SOBP, FLASH dose. The SOBP FLASH dose can be created by varying the energy of the charged particle beam, using different energies with appropriate weighting to produce a flat, even SOBP.

[0139] A limiting factor for wide implementation of FLASH-RT is the need for high doses of at least 6Gy per pulse and very high dose rates of at least 30Gy / s to achieve the FLASH protection. In particular, it can be challenging to achieve these high doses and dose rates using conventional techniques for a variety of reasons, as explained below with reference to FIGs. 1, 2 A, 2B and 3.

[0140] FIG. 1 shows a spatial dose distribution of an X-ray beam, and FIGs. 2A and 2B show dose histograms of different regions of the spatial dose distribution of FIG. 1.

[0141] FIGs. 1 shows inhomogeneities in the spatial dose distribution of the X-ray beam generated by a conventional kV irradiation unit. FIG. 2A shows a dose histogram of the left circle in FIG. l, and FIG. 2B shows a dose histogram of the right circle in FIGI. Due to the inhomogeneities in the spatial dose distribution of the X-ray beam, the dose and dose rate delivered to a radiation target also vary.

[0142] FIGs. 3 shows an intensity over time of an X-ray beam pulse generated by a conventional kV irradiation unit.

[0143] The intensity increases from the beginning of the pulse until it reaches a constant value at time tl. As the intensity increases with time, the dose and dose rate delivered to a radiation target also vary.

[0144] In view of the above, the spatial and time variations in the intensity of the X-ray beam generated by a conventional kV irradiation unit make it difficult to precisely control dose delivery in radiotherapy. These and other disadvantages may be addressed using the present invention.

[0145] Various embodiments of the present disclosure are described in detail below. In particular, a first embodiment with a rotational shutter assembly is described with respect to FIGs. 4 to 8, a second embodiment with a linearly movable shutter assembly is described with respect to FIGs. 9 A, 9B and 10, a third embodiment with another linearly movable shutter assembly is described with respect to FIGs. 11 A and 1 IB, a fourth embodiment with a movable shutter assembly is described with respect to FIG. 12, and a fifth embodiment is described with respect to FIGs. 13 and 14.

[0146] FIG. 4 shows an apparatus 100 for dose delivery in radiotherapy according to a first embodiment of the present disclosure. FIG. 5 shows a perspective view of the apparatus 100. FIG. 6 shows a shutter body 110 of the apparatus 100 in an open state (left) and a closed state (right).

[0147] The apparatus 100 may be configured for dose delivery in FLASH radiotherapy, but the present disclosure is not limited thereto, and other radiotherapy techniques may benefit from the improved dose delivery achieved by the embodiments of the present disclosure.

[0148] The apparatus 100 includes at least one rotatable shutter body 110 having one or more openings 112, 114; and a drive mechanism 120 connected to the at least one shutter body 110 and configured to rotate the at least one shutter body 110 around a rotational axis RA to selectively open and close a radiation path RP through the at least one shutter body 110.

[0149] The drive mechanism 120 may be a motor, such as a solenoid motor. The drive mechanism 120 may be connected to the at least one shutter body 110 by at least one shaft 122 to drive the at least one shutter body 110, but the present disclosure is not limited thereto.

[0150] The radiation path RP may be provided between at least one radiation source 140 configured to provide a radiation beam RB and a radiation target RT.

[0151] The at least one radiation source 140 may include an electromagnetic radiation source configured to provide an electromagnetic beam, such as an X-ray beam, as the radiation beam RB. Additionally, or alternatively, the at least one radiation source 140 may include a charged particle source configured to provide a charged particle beam as the radiation beam RB. The charged particle beam may be a proton beam, an electron beam or an ion beam.

[0152] In some embodiments, the radiation beam RB includes, or is, an ultra-high dose (rate) beam, such as a FLASH beam, i.e., a beam for FLASH radiotherapy (FLASH-RT).

[0153] The radiation target RT may include, or be, a biological material, such as a tumor or tumor tissue. The radiation target may be a biological sample extracted from a living ordead body. The sample may be used to perform tests of the apparatus 100 and / or medical studies. In further embodiments, the radiation target RT may be a target in a living body, such as a tumor or a target volume including the tumor.

[0154] A target support TS can be provided to support the radiation target RT. The target support TS can be located outside the at least one shutter body 110, particularly below the shutter body 110, as it is shown in the example of FIG. 5. The target support TS may be located outside the at least one shutter body 110 to perform a treatment on a living body, such as a treatment of a tumor by radiotherapy, particularly FLASH radiotherapy.

[0155] Preferably, the target support TS and / or the radiation target RT are stationary outside the at least one shutter body 110. In particular, the target support TS and / or the radiation target RT can be decoupled from the at least one shutter body 110 so as not to rotate together with the at least one shutter body 110.

[0156] In some embodiments, the at least one shutter body 110 includes, or is made of, a metal, a synthetic material, or a combination thereof. For example, the shutter body may include, or be made of, copper, a copper-based alloy, tungsten, a plastic material, stainless steel, or a combination thereof. The copper-based alloy may be brass, i.e., an alloy of copper and zinc.

[0157] The apparatus 100 further includes a controller 130 configured to control the drive mechanism 120 to selectively open and close the radiation path RP by rotation of the at least one shutter body 110 around the rotational axis RA thereof. Optionally, the controller 130 can be configured to control the at least one radiation source 140 to provide the radiation beam RB in a specific manner.

[0158] The radiation path RP is open when the one or more openings 112, 114 of the shutter body 110 are aligned with the radiation path RP, as it is shown in the left part of FIG.6. In particular, the radiation path RP is open when the radiation path RP passes through the one or more openings 112, 114 and thus the radiation beam RB coming from the at least one radiation source 140 is not blocked by any part of the shutter body 110, so that the one or more openings 112, 114 expose essentially an entire area of the radiation target RT, as projected on a plane perpendicular to the radiation path RP, to the radiation beam RB. Thearea of the radiation target RT, as projected on a plane perpendicular to the radiation path RP, can be equal to or more than 20 mm2, preferably 40mm2, most preferably 60 mm2.

[0159] The radiation path RP is closed when the radiation path RP is blocked by the shutter body 110, as it is shown in the right part of FIG. 6. In particular, the radiation path RP is closed when the radiation path RP and thus the radiation beam RB coming from the at least one radiation source 140 is physically blocked by a portion of the at least one shutter body 110.

[0160] Preferably, the radiation path RP is open when the at least one shutter body 110 is in a first rotational position or orientation (left part of FIG. 6), and the radiation path RP is closed when the at least one shutter body 110 is in a second rotational position or orientation different from the first rotational position or orientation (right part of FIG. 6). In the first rotational position or orientation of the at least one shutter body 110, the one or more openings 112, 114 are aligned with the radiation path RP, i.e., the one or more openings 112, 114 are located on the radiation path RP. In the second rotational position or orientation of the at least one shutter body 110, the one or more openings 112, 114 are not aligned with the radiation path RP, i.e., the one or more openings 112, 114 are not located on the radiation path RP.

[0161] Arotational angle between the first rotational position or orientation (i.e., the open state of the shutter body 110) and the second rotational position or orientation (i.e., the closed state of the shutter body 110) may be about 90° as it is shown in FIG. 6, but the present disclosure is not limited thereto.

[0162] In some embodiments, the controller 130 can be configured to control the drive mechanism 120 to rotate the at least one shutter body 110 between the first rotational position or orientation and the second rotational position or orientation to selectively open and close the radiation path RP. For example, the controller 130 can be configured to control the drive mechanism 120 to continuously rotate the at least one shutter body 110 in one rotational direction RD to open and close the radiation path RP. The rotational direction RD may be a clockwise direction or a counterclockwise direction.

[0163] In a preferred embodiment, the at least one shutter body 110 can be a cylindrical shutter body. The rotational axis RA of the at least one shutter body 110 may correspond to, or coincide with, a cylinder axis of the cylindrical shutter body.

[0164] The at least one shutter body 110 may be a solid or full shutter body. In this case, the one or more openings 112, 114 can be openings of a through hole extending through the at least one shutter body 110. For example, the through hole can extend essentially perpendicular to the rotational axis RA of the at least one shutter body 110 and / or through the rotational axis RA of the at least one shutter body 110.

[0165] In alternative embodiments, the at least one shutter body 110 can be a hollow shutter body. For example, the at least one shutter body 110 can be a hollow cylinder. The one or more openings 112, 114 can be provided in a shell of the hollow shutter body 110. For example, the one or more openings 112, 114 can be provided in a cylinder shell of the hollow cylinder.

[0166] In some embodiments, the one or more openings 112, 114 are two openings located on opposite sides of the at least one shutter body 110, such as the hollow shutter body. The two openings 112, 114 can be arranged symmetrically with respect to the rotational axis RA of the at least one shutter body 110, as it is shown in FIGs. 4 to 6.

[0167] Preferably, the radiation path RP is open when the two openings 112, 114 are aligned with the radiation path RP so that the radiation beam RB enters the at least one shutter body 110 through a first opening 112 of the two openings and exits the at least one shutter body 110 through a second opening 114 of the two openings in a direction toward the radiation target RT located outside the at least one shutter body 110.

[0168] The one or more openings 112, 114 may have a circular shape. However, the present disclosure is not limited thereto, and the one or more openings 112, 114 may have other shapes suitable for the intended purpose of letting pass the radiation beam RB.

[0169] In some embodiments, the shape of the one or more openings 112, 114 may be configured to “cut out” a portion of a cross-section of the radiation beam RB. For example, as shown in FIG. 1, the one or more openings 112, 114 may shape or cut the radiation beam RB entering the opening 112, 114 such that the cross-sectional shape of the radiation beamRB exiting the opening 112, 114 corresponds to one of the circles shown in FIG. 1. This allows a portion of the cross-section of the radiation beam RB to be selected with an essentially uniform intensity distribution, whereby it is possible to more precisely control the radiation dose and radiation dose rate delivered to the radiation target RT.

[0170] In some embodiments, a diameter of the one or more openings 112, 114 is in a range between 5mm and 10cm, preferably between 1cm and 5cm, particularly in a range between 2cm and 4cm, and more particularly in a range between 3cm and 4cm. For example, the diameter of the one or more openings 112, 114 can be about 3.5cm.

[0171] In some embodiments, the controller 130 is further configured to control the drive mechanism 120 to close the radiation path RP by a rotation of the at least one shutter body 110 during an initial intensity increase of the radiation beam RB until the intensity has reached an essentially constant value. The controller 130 may be further configured to control the drive mechanism 120 to open the radiation path RP by a rotation of the at least one shutter body 110 when the intensity has reached the essentially constant value to deliver a radiation dose to the radiation target RT. Referring to FIG. 3, the radiation path RP can be closed until at least time point tl is reached. Thereafter, the radiation path RP can be opened when the intensity is essentially constant. Thereby, it is possible to more precisely control the radiation dose and radiation dose rate delivered to the radiation target RT.

[0172] In some embodiments, the controller 130 is configured to control the drive mechanism 120 to open the radiation path RP to deliver a predetermined radiation dose at a predetermined dose rate to the radiation target RT, such as a tumor or a target volume including the tumor. This can be done by adjusting a rotational speed of the at least one shutter body 110 to a suitable value. Preferably, the predetermined radiation dose is in a range between 8 and 20 Gy and / or the predetermined dose rate is in a range between 30 and 120 Gy / s.

[0173] Additionally, or alternatively, the controller 130 can be configured to control the drive mechanism 120 to open the radiation path RP to deliver at least a minimum dose at a dose rate to one or more volumes of interest, in and / or around the radiation target RT to provide the FLASH effect at the one or more volumes of interest. This can be done by adjusting a rotational speed of the at least one shutter body 110 to a suitable value. Preferably,the minimum dose is in a range between 8 and 12 Gy and / or the dose rate is in a range between 30 and 120 Gy / s.

[0174] In some embodiments, the controller 130 is configured to control the drive mechanism 120 to open the radiation path RP for a predetermined time to deliver the predetermined radiation dose at the predetermined dose rate to the radiation target RT. This can be done by adjusting a rotational speed of the at least one shutter body 110 to a suitable value.

[0175] Additionally, or alternatively, the controller 130 can be configured to control the drive mechanism 120 to open the radiation path RP for the predetermined time to deliver at least the minimum dose at a dose rate to the one or more volumes of interest, in and / or around the radiation target RT to provide the FLASH effect at the one or more volumes of interest. This can be done by adjusting a rotational speed of the at least one shutter body 110 to a suitable value.

[0176] Preferably, the predetermined time is in a range between 20 and Is, such as between 40ms and 80ms. For example, the predetermined time can be about 40ms, 50ms, 60 ms, 70 ms or 80 ms. The predetermined time can be adjusted by adjusting the rotational speed of the at least one shutter body 110: the lower the rotational speed, the longer the open state and the higher the radiation dose delivered to the radiation target RT.

[0177] FIG. 7 shows a shutter body 110 in an open state (left) and a closed state (right) according to further variations of the first embodiment of the present disclosure.

[0178] According to some embodiments, which can be combined with other embodiments described herein, the apparatus 100 further includes at least one reflection element 712, 714 configured to at least partially reflect radiation from the radiation beam RB, particularly in a direction toward the radiation target RT. In particular, the at least one reflection element 712, 714 may be configured to backscatter radiation provided by the at least one radiation source, such as X-rays and / or charged particles. The at least one reflection element 712, 714 can achieve a signal boost of e.g. 15%, 20% or even more.

[0179] Preferably, the at least one reflection element 712, 714 includes, or is made of, copper, a copper-based alloy, or a combination thereof. The copper-based alloy may be brass, i.e., an alloy of copper and zinc.

[0180] In some embodiments, the at least one reflection element includes one or more first reflection elements (not shown) located under the radiation target. For example, the first reflection element may be a backscatter plate. Preferably, the target support TS shown in FIG. 5 provides, or is, the at least one first reflection element. Examples of reflection elements located under the radiation target are described later with respect to FIG. 13.

[0181] Additionally, or alternatively, the at least one reflection element 712, 714 includes one or more second reflection elements 712, 714 located inside the shutter body 110. The one or more second reflection elements may include a first reflection plate 712 and a second reflection plate 714, such as backscatter plates.

[0182] Preferably, the first reflection plate 712 and the second reflection plate 714 are arranged inside the shutter body 110 so that the radiation path RP extends between the first reflection plate 712 and the second reflection plate 714.

[0183] In some embodiments, the at least one shutter body 110 is a hollow cylinder and the first reflection plate 712 and the second reflection plate 714 are cylindrical plates whose cylinder axes may or may not coincide with a cylinder axis of the at least one shutter body 110. A diameter of the cylindrical plates can be equal to or smaller than a diameter of the hollow cylinder.

[0184] Preferably, a thickness of the at least one reflection element, such as the one or more first reflection elements and / or the one or more second reflection elements, is in a range between 0.05cm and 2cm. For example, the thickness of the at least one reflection element can be between 0.1cm and 0.7cm, in particular about 0.4cm.

[0185] FIG. 8 shows a shutter body 110 in an open state (left) and a closed state (right) according to further variations of the first embodiment of the present disclosure.

[0186] In the examples of FIGs. 4 and 5, the target support TS with the radiation target RT is located outside the at least one shutter body 110. However, the present disclosure isnot limited thereto, and the target support TS with the radiation target RT can be located inside the at least one hollow shutter body 110, as it is shown in FIG. 8. The target support TS with the radiation target RT may be located inside the at least one hollow shutter body 110 to perform tests of the apparatus 100 and / or medical studies on a biological sample.

[0187] Preferably, target support TS and / or the radiation target RT are stationary inside the at least one hollow shutter body 110. In particular, the target support TS and / or the radiation target RT can be decoupled from the at least one shutter body 110 so as not to rotate together with the at least one shutter body 110.

[0188] In some embodiments, the radiation path RP is open when an opening 112 of the one or more openings is aligned with the radiation path RP so that the radiation beam RB provided by the at least one radiation source enters the at least one shutter body 110 through the opening 112 in a direction toward the radiation target RT located inside the at least one hollow shutter body 110, wherein the opening 112 exposes essentially an entire area of the radiation target RT, as projected on a plane perpendicular to the radiation path RP, to the radiation beam RB.

[0189] FIG. 9 A shows a shutter assembly 210 of an apparatus 200 for dose delivery in radiotherapy in an open state according to a second embodiment of the present disclosure. FIG. 9 A shows the shutter assembly 210 in an open state according to the second embodiment of the present disclosure.

[0190] The shutter assembly 210 includes a at least one first shutter element 212 and at least one second shutter element 214. In some embodiments, the at least one first shutter element 212 and the at least one second shutter element 214 can be plates or blades.

[0191] The first shutter element 212 is moveable with respect to a first axis LAI (e.g., a first linear axis) and the at least one second shutter element 214 is moveable with respect to a second axis LA2 (e.g., a second linear axis). In some embodiments, the first axis LAI and the second axis LA2 are essentially parallel to each other. Additionally, or alternatively, the first axis LAI and the second axis LA2 are offset with respect to each other. For example, the first axis LAI and the second axis LA2 may be offset in a direction essentially perpendicular to the radiation path RP.

[0192] The drive mechanism (not shown) of the apparatus 200 is configured to move the at least one first shutter element 212 with respect to the first axis LAI and / or the at least one second shutter element 214 with respect to the second axis LA2 to selectively open and close the radiation path RP between the at least one radiation source and the radiation target.

[0193] The radiation path RP may open when the at least one first shutter element 212 and the at least one second shutter element 214 are spaced apart from each other such that at least one gap GP between the at least one first shutter element 212 and the at least one second shutter element 214 provides the one or more openings that expose essentially an entire area of the radiation target RT, as projected on a plane perpendicular to the radiation path RP, to the radiation beam RB, as it is shown in FIG. 9A. Furthermore, the radiation path RP is closed when the at least one gap GP between the at least one first shutter element 212 and the at least one second shutter element 214 is closed, as it is shown in FIG. 9B. For example, the at least one gap GP between the at least one first shutter element 212 and the at least one second shutter element 214 can be closed when the at least one first shutter element 212 and the at least one second shutter element 214 overlap each other (FIG. 9B) or abut against each other (not shown).

[0194] Preferably, the at least one gap GP has a width WGP in a direction essentially parallel to the first axis LAI and / or the second axis LA2. The at least one gap GP, particularly the width WGP, can be defined between opposite edges 212a, 214a of the at least one first shutter element 212 and the at least one second shutter element 214.

[0195] FIG. 10 shows a shutter body 210 of the apparatus 200 for dose delivery according to further variations of the second embodiment of the present disclosure.

[0196] In the example of FIGs. 9 A and 9B, the one or more openings are provided by the at least one gap GP between the at least one first shutter element 212 and the at least one second shutter element 214. In the variation of FIG. 10, the one or more openings are provided by openings 212b, 214b in the at least one first shutter element 212 and the at least one second shutter element 214 rather than a gap between the first and the second shutter elements 212, 214.

[0197] The radiation path RP is open when at least one first opening 212b in the at least one first shutter element 212 and at least one second opening 214b in the at least one second shutter element 214 are aligned with each other and the radiation path RP, and the radiation path RP is closed when the radiation path RP is blocked by the at least one first shutter element 212 and / or the at least one second shutter element 214. In particular, the radiation path RP can be open when the at least one first opening 212b and the at least one second opening 214b are aligned with the radiation path RP so that the radiation beam RB enters the shutter assembly 210 through the at least one first opening 212b and exits the shutter assembly 210 through the at least one second opening 214b in a direction toward the radiation target RT located outside, e.g., below, the shutter assembly 210.

[0198] In some embodiments, the apparatus 200 may include the reflection element(s) described with respect to FIGs. 7 and 13.

[0199] FIG. 11 A shows a shutter assembly 310 of an apparatus 300 for dose delivery in a closed state according to a third embodiment of the present disclosure. FIG. 1 IB shows the shutter assembly 310 in an open state.

[0200] The shutter assembly 310 includes at least one two first shutter elements 312a, 312b moveable with respect to a first axis LAI (e.g., a first linear axis) and at least two second shutter elements 314a, 314b moveable with respect to a second axis LA2 (e.g., a second linear axis) different from the first axis LAI. The first axis LAI and the second axis LA2 can be essentially perpendicular to each other.

[0201] In some embodiments, the at least two first shutter elements 312a, 312b are offset with respect to the at least two second shutter elements 314a, 314b in an offset direction. This allows the shutter elements to move independently from each other. The offset direction may be essentially perpendicular to the first axis LAI and / or the second axis LA2.

[0202] The drive mechanism (not shown) can be configured to move the at least two first shutter elements 312a, 312b with respect to the first axis LAI in opposite directions Dla, Dlb and / or the at least two second shutter elements 314a, 314b with respect to the second axis LA2 in opposite directions D2a, D2b to selectively open and close the radiation path RP between the at least one radiation source and the radiation target. In particular, the drivemechanism can be configured to move the at least two first shutter elements 312a, 312b with respect to the first axis LAI in opposite directions DI a, Dlb away from each other and / or the at least two second shutter elements 314a, 314b with respect to the second axis LA2 in opposite directions D2a, D2b away from each other to open the radiation path RP between the at least one radiation source and the radiation target, as it is shown in FIG. 11 A. Furthermore, the drive mechanism can be configured to move the at least two first shutter elements 312a, 312b with respect to the first axis LAI in opposite directions towards each other and / or the at least two second shutter elements 314a, 314b with respect to the second axis LA2 in opposite directions towards each other to close the radiation path RP between the at least one radiation source and the radiation target, as it is shown in FIG. 1 IB.

[0203] In some embodiments, the radiation path RP is open when at least one first gap GP1 exists between the at least two first shutter elements 312a, 312b and at least one second gap GP2 exists between the at least two second shutter elements 314a, 314b such that the gaps GP1, GP2 between the at least two first shutter elements 312a, 312b and the at least two second shutter elements 314a, 314b provide the one or more openings 316. Furthermore, the radiation path RP can be closed when the gaps GP1, GP2 between the at least two first shutter elements 312a, 312b and the at least two second shutter elements 314a, 314b are closed. For example, the gaps GP1, GP2 can be closed when the respective shutter elements abut against each other.

[0204] In some embodiments, the apparatus 300 may include the reflection element(s) described with respect to FIGs. 7 and 13.

[0205] FIG. 12 shows a shutter assembly 410 of an apparatus 400 for dose delivery in a closed state according to a fourth embodiment of the present disclosure.

[0206] The shutter assembly 410 includes at least one first shutter element 412 and at least one second shutter element 414. A first end of the at least one first shutter element 412 and a first end of the at least one second shutter element 414 are moveably (e.g., rotatably) connected to each other at at least one joint 416. In some embodiments, this “spring” keeps the system in a closed position and when for example a solenoid magnet is on, the system opens the radiation path.

[0207] A second end of the at least one first shutter element 412 opposite the first end thereof includes at least one first opening 418a and a second end of the at least one second shutter element 414 opposite the first end thereof includes at least one second opening 418b.

[0208] In some embodiments, the at least one first shutter element 412 includes a first portion 412a extending in a first direction and a second portion 412b extending in a second direction different from the first direction. The first direction and the second direction may be essentially perpendicular to each other. The first portion 412a of the at least one first shutter element 412 may have the first end connected to the at least one joint 416 and the second portion 412b of the at least one first shutter element 412 may have the second end having the at least one first opening 418a.

[0209] Similarly, the at least one second shutter element 414 may include a first portion 414a extending in a first direction and a second portion 414b extending in a second direction different from the first direction. The first direction and the second direction may be essentially perpendicular to each other. The first portion 414a of the at least one second shutter element 414 may have the first end connected to the at least one joint 416 and the second portion 414b of the at least one second shutter element 414 may have the second end having the at least one second opening 418b.

[0210] In some embodiments, the at least one first shutter element 412 and / or the at least one second shutter element 414 are L-shaped.

[0211] The drive mechanism (not shown) may be configured to move the at least one first shutter element 412 and the at least one second shutter element 414 with respect to each other in opposite directions to selectively open and close the radiation path RP between the at least one radiation source and the radiation target. For example, the controller can be configured to control the drive mechanism, such as a solenoid drive (e.g., a solenoid electromagnet), to selectively open and close the radiation path RP by a rotational movement of the at least one first shutter element 412 and the at least one second shutter element 414 around the at least one joint 416.

[0212] The radiation path RP can be open when the at least one first opening 418a of the at least one first shutter element 412 and the at least one second opening 418b of the at leastone second shutter element 414 are aligned with each other and the radiation path RP, and the radiation path RP can be closed when the radiation path RP is blocked by the at least one first shutter element 412 and / or the at least one second shutter element 414. For example, the radiation path RP can be open when the at least one first opening 418a and the at least one second opening 418b overlap with each other so that the at least one first opening 418a and the at least one second opening 418b expose essentially an entire area of the radiation target RT, as projected on a plane perpendicular to the radiation path RP, to the radiation beam RB.

[0213] In some embodiments, the apparatus 400 may include the reflection element(s) described with respect to FIGs. 7 and 13.

[0214] FIG. 13 shows a perspective view of the apparatus 500 for dose delivery in radiotherapy or radiotherapy research according to a further embodiment of the present disclosure. FIG. 14 shows experimental data related to backscattering by means of a disc underneath the radiation target.

[0215] The apparatus 500 includes the moveable shutter assembly 510 configured to provide the one or more openings 512.

[0216] The apparatus 500 includes at least one reflection element 530, 540 configured to scatter or deflect radiation provided by the at least one radiation source 520, such as X-rays or charged particles, towards the radiation target RT.

[0217] The at least one reflection element 530, 540 includes one or more reflection elements 530 located under the radiation target, particularly between the target support TS and the radiation target RT. The one or more reflection elements 530 may be discs or rectangular plates, but the present disclosure is not limited thereto.

[0218] The one or more reflection elements 530 backscatter the radiation back to the radiation target RT to obtain a higher dose on the radiation target RT (see dashed arrows in FIG. 13). In the context of the present application, backscatter refers to the phenomenon where X-rays or particles are scattered backward upon striking a material (e.g., copper or a copper-based material). When X-rays or particles interact with the one or more reflection elements 530, they can be deflected in various directions due to scattering. Backscatterspecifically denotes the X-rays or particles that are deflected back towards the direction from which they came, particularly towards the radiation target RT.

[0219] Preferably, the first reflection element such as the backscatter plate includes, or is made of, a material selected from the group including or consisting of copper and a copperbased alloy. The copper-based alloy may be brass, i.e., an alloy of copper and zinc. FIG. 14 illustrates the beneficial effects of the one or more reflection elements 530 located beneath the radiation target RT, considering various materials, thicknesses, and currents.

[0220] The at least one reflection element 530, 540 can include one or more further reflection elements 540 located outside the shutter assembly 510 and / or located between the radiation source 520 and the radiation target RT, to scatter or deflect radiation provided by the at least one radiation source 520, such as X-rays or charged particles, towards the one or more openings 512 and thus the radiation target RT (see dashed arrows in FIG. 13). The one or more further reflection elements 540 can be arranged so that the radiation path RP extends between sidewalls of the one or more further reflection elements 540.

[0221] The one or more further reflection elements 540 may include a cone having a sidewall or outer wall which encloses the radiation path RP. In particular, the radiation path RP can extend from atop of the cone to a bottom of the cone. However, the present disclosure is not limited thereto and other shapes of the one or more further reflection elements are feasible, such as one or more reflection plates.

[0222] FIG. 15 shows a flowchart of a method 1500 of operating an apparatus for dose delivery in radiotherapy or radiotherapy research according to the embodiments of the present disclosure.

[0223] The method 1500 includes in block 1510 a moving (e.g., at time tl in FIG. 3), by controlling a driving mechanism, of a shutter assembly configured to provide one or more openings to open a radiation path between at least one radiation source and a radiation target to deliver a radiation dose to the radiation target, wherein the radiation path is open when the one or more openings of the shutter assembly are aligned with the radiation path so that the one or more openings expose essentially an entire area of the radiation target, as projected on a plane perpendicular to the radiation path, to the radiation beam; and in block 1520further moving the shutter assembly to close the radiation path between the at least one radiation source and the radiation target, wherein the radiation path is closed when the radiation path is blocked by the shutter assembly. In some embodiments, the “default” is a closed state (e.g., before block 510).

[0224] According to embodiments described herein, the method of operating an apparatus for dose delivery in radiotherapy or radiotherapy research can be conducted by means of computer programs, software, computer software products and the interrelated controllers, which can have a CPU, a memory, a user interface, and input and output means being in communication with the corresponding components of the apparatus for dose delivery in radiotherapy or radiotherapy research.

[0225] FIG. 16 illustrates experimental data in the form of a dose-versus-time plot, demonstrating the performance of a FLASH X-ray shutter. In particular, FIG. 16 shows a dose-versus-time plot illustrating the performance of the FLASH X-ray shutter operated at 133 kV and 30 mA. The data exhibit a stable and reproducible dose rate of 58.09 ± 0.61 Gy / s, as confirmed by the linear fit. Error bars indicate the uncertainty in the measured dose values. These results demonstrate the shutter’s capability to deliver high dose rates with high temporal precision, which is essential for radiation therapy applications employing FLASH.

[0226] In summary, the results of this study support the hypothesis that the shutter enables precise modulation of irradiation timing. The system is designed to deliver doses with minimal error margins, which is an essential aspect for both biological research and therapeutic applications. FIG. 16 provides experimental validation of the shutter’s performance, confirming its enhanced temporal resolution, synchronization, and beam control. Notably, the linear fit intersecting the origin highlights the absence of measurable delay or latency, underscoring the shutter’s capability for instantaneous opening and closing.

[0227] In further support of the above, the Table 1 below presents measurements of dose, dose rate, and associated uncertainties at different irradiation times using the FLASH X-ray shutter. The results demonstrate consistently high dose rate delivery with minimal variability across time points, thereby validating the system’s reliability and precision in delivering FLASH doses.Time Dose Error Dose Dose Rate Error Dose Rate Channel [ms] [Gy] [Gy] [Gy / s] [Gy / s]0 65 3.90 0.10 60.02 1.591 94 5.35 0.12 56.90 1.272 190 10.89 0.22 57.32 1.133 380 22.29 0.40 58.67 1.06Table 1

[0228] FIG. 17 illustrates the attenuation of dose rate in water, measured as a function of varying liquid thickness. In particular, FIG. 17 shows the attenuation of dose rate in water at a source-to-surface distance (SSD) of 50.2 centimeters, measured by varying the liquid thickness expressed as a function of a power-law relationship. The observed decrease in dose rate with increasing water thickness confirms the system’s ability to model and maintain FLASH dose rates at shallow depths in true aqueous environments.

[0229] In summary, the curve presented in FIG. 17 demonstrates the system’s capability to maintain a high initial dose rate (-38.6 Gy / s) while following a predictable attenuation profile with increasing depth. This behavior is essential for the accurate evaluation and planning of FLASH experiments, particularly in the context of depth-dependent dosimetry and studies of biological effects. Additionally, the smooth fit of the attenuation curve, along with minimal error bars, reflects the system’s high level of control and reproducibility. The ability to model attenuation with precision underscores the system’s reliability in delivering quantifiable radiation doses, which is an important requirement for both regulatory compliance and clinical translation.

[0230] FIG. 18 illustrates spatial uniformity of the dose rates in two different directions across the beam diameter.

[0231] In some embodiments, the shutter assembly of the present disclosure allows a portion of the cross-section of the radiation beam to be selected with an essentially uniform intensity distribution. This is illustrated in FIG. 18 for two different directions across the beam diameter, as indicated by the reference lines: the horizontal line across the beam diameter in the upper example and the vertical line across the beam diameter in the lower example. The ability to select a portion of the cross-section of the radiation beam with anessentially uniform intensity distribution underscores the system’s capability to more precisely control the radiation dose and radiation dose rate delivered to the radiation target.

[0232] While the foregoing is directed to embodiments of the disclosure, other and further embodiments of the disclosure can be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow.

Claims

CLAIMS1. Apparatus (100, 200, 300, 400) for dose delivery in radiotherapy or radiotherapy research, comprising: a moveable shutter assembly (110, 210, 310, 410) configured to provide one or more openings (112, 114; GP; 212b, 214b; 316; 418a, 418b); a drive mechanism (120) connected to the shutter assembly (110, 210, 310, 410) and configured to move at least a part of the shutter assembly (110, 210, 310, 410) to selectively open and close a radiation path (RP) between at least one radiation source (140) configured to provide a radiation beam (RB) and a radiation target (RT); and a controller (130) configured to control the drive mechanism (120) to selectively open and close the radiation path (RP) by a movement of the shutter assembly (110, 210, 310, 410), wherein the radiation path (RP) is open when the one or more openings (112, 114; GP; 212b, 214b; 316; 418a, 418b) of the shutter assembly (110, 210, 310, 410) are aligned with the radiation path (RP), so that the one or more openings (112, 114; GP; 212b, 214b; 316; 418a, 418b) expose essentially an entire area of the radiation target (RT), as projected on a plane perpendicular to the radiation path (RP), to the radiation beam (RB), and wherein the radiation path (RP) is closed when the radiation path (RP) is blocked by the shutter assembly (110, 210, 310, 410).

2. Apparatus (100, 200, 300, 400) of claim 1, wherein the area of the radiation target (RT), as projected on a plane perpendicular to the radiation path (RP), is equal to or more than 20 mm2, preferably 40mm2, most preferably 60 mm2.

3. Apparatus (100, 200, 300, 400) of claim 1 or 2, further including at least one reflection element (530, 540, 712, 714) configured to at least partially reflect radiation provided by the at least one radiation source (140) toward the radiation target (RT), in particular wherein the at least one reflection element (530, 540, 712, 714) includes, or is made of, copper or a copper-based alloy.

4. Apparatus (100, 200, 300, 400) of claim 3, wherein the at least one reflection element (530, 540, 712, 714) includes:one or more first reflection elements (530) located under the radiation target (RT); one or more second reflection elements (712, 714) located inside the shutter assembly, and / or one or more third reflection elements (540) located outside the shutter assembly (510) and / or located between the radiation source (140, 520) and the radiation target (RT).

5. Apparatus (100, 200, 300, 400) of claim 4, wherein the one or more second or third reflection elements (540, 712, 714) include at least one first reflection plate (540, 712) and at least one second reflection plate (540, 714), wherein the at least one first reflection plate (540, 712) and the at least one second reflection plate (540, 714) are arranged inside or outside the shutter assembly (110, 210), respectively, so that the radiation path (RP) extends between the at least one first reflection plate (540, 712) and the at least one second reflection plate (540, 714).

6. Apparatus (100) of any one of claims 1 to 5, wherein the shutter assembly (110) includes, or is, at least one rotatable shutter body (110) having the one or more openings (112, 114), wherein the drive mechanism (120) is configured to rotate the at least one shutter body (110) around a rotational axis (RA) to selectively open and close the radiation path (RP) between the at least one radiation source (140) and the radiation target (RT), and wherein the controller (130) is configured to control the drive mechanism (120) to selectively open and close the radiation path (RP) by rotation of the at least one shutter body (110), wherein the radiation path (RP) is open when the one or more openings (112, 114) of the at least one shutter body (110) are aligned with the radiation path (RP) so that the one or more openings (112, 114) expose essentially an entire area of the radiation target (RT), as projected on a plane perpendicular to the radiation path (RP), to the radiation beam (RB), and wherein the radiation path (RP) is closed when the radiation path (RP) is blocked by the at least one shutter body (110).

7. Apparatus (100) of claim 6, wherein:the at least one shutter body (110) is a cylindrical shutter body, and wherein the rotational axis (RA) of the at least one shutter body (110) corresponds to a cylinder axis of the cylindrical shutter body; and / or the at least one shutter body (110) is a hollow shutter body, and wherein the one or more openings (112, 114) are provided in a shell of the hollow shutter body, in particular wherein the radiation path (RP) is open when an opening (112) of the one or more openings (112, 114) is aligned with the radiation path (RP) so that the opening (112) exposes an essentially entire area of the radiation target (RT), as projected on a plane perpendicular to the radiation path (RP), to the radiation beam (RB) provided by the at least one radiation source (140) that enters the at least one shutter body (110) through the one or more openings (112) in a direction toward the radiation target (RT) located inside the hollow shutter body; and / or the one or more openings (112, 114) include, or are, at least two openings located on two sides of the at least one shutter body (110), in particular wherein the radiation path (RP) is open when the at least two openings (112, 114) are aligned with the radiation path (RP) so that the at least two openings (112, 114) expose essentially an entire area of the radiation target (RT), as projected on a plane perpendicular to the radiation path (RP), to the radiation beam (RB) that enters the at least one shutter body (110) through at least one first opening (112) and exits the at least one shutter body (110) through at least one second opening (114) in a direction toward the radiation target (RT) located outside the at least one shutter body (110).

8. Apparatus (200) of any one of claims 1 to 5: wherein the shutter assembly (210) includes at least one first shutter element (212) and at least one second shutter element (214), wherein the drive mechanism (120) is configured to move the at least one first shutter element (212) with respect to a first axis and / or the at least one second shutter element (214) with respect to a second axis to selectively open and close the radiation path (RP) between the at least one radiation source (140) and the radiation target (RT), preferably wherein the first axis is a first linear axis (LAI) and / or the second axis is a second linear axis (LA2), and wherein the controller (130) is configured to control the drive mechanism (120) to selectively open and close the radiation path (RP) at least by a movement of the at leastone first shutter element (212) with respect to the first axis and / or a movement of the at least one second shutter element (214) with respect to the second axis.

9. Apparatus (200) of claim 8, wherein the radiation path (RP) is open when the at least one first shutter element (212) and the at least one second shutter element (214) are spaced apart from each other such that at least one gap (GP) between the at least one first shutter element (212) and the at least one second shutter element (214) provides the one or more openings that expose essentially an entire area of the radiation target (RT), as projected on a plane perpendicular to the radiation path (RP), to the radiation beam (RB), and wherein the radiation path (RP) is closed when the at least one gap (GP) between the at least one first shutter element (212) and the at least one second shutter element (214) is closed, or wherein the radiation path (RP) is open when at least one first opening (212b) in the at least one first shutter element (212) and at least one second opening (214b) in the at least one second shutter element (214) are aligned with each other and the radiation path (RP) so that the openings (212b, 214b) expose essentially an entire area of the radiation target (RT), as projected on a plane perpendicular to the radiation path (RP), to the radiation beam (RB), and wherein the radiation path (RP) is closed when the radiation path (RP) is blocked at least by the at least one first shutter element (212) and / or the at least one second shutter element (214).

10. Apparatus (300) of any one of claims 1 to 5: wherein the shutter assembly (310) includes at least two first shutter elements (312a, 312b) moveable with respect to a first axis and at least two second shutter elements (314a, 314b) moveable with respect to a second axis different from the first axis, preferably wherein the first axis is a first linear axis (LAI) and / or the second axis is a second linear axis (LA2), wherein the drive mechanism (120) is configured to move the at least two first shutter elements (312a, 312b) with respect to the first axis in opposite directions and / or the at least two second shutter elements (314a, 314b) with respect to the second axis in opposite directions to selectively open and close the radiation path (RP) between the at least one radiation source (140) and the radiation target (RT), andwherein the controller (130) is configured to control the drive mechanism (120) to selectively open and close the radiation path (RP) by a movement of the at least two first shutter elements (312a, 312b) in the opposite directions and / or a movement of the at least two shutter elements (314a, 314b) in the opposite directions.

11. Apparatus (400) of any one of claims 1 to 5: wherein the shutter assembly (410) includes at least one first shutter element (412) and at least one second shutter element (414), wherein a first portion of the at least one first shutter element (412) and a first portion of the at least one second shutter element (414) are moveably connected to each other at at least one joint (416), wherein a second portion of the at least one first shutter element (412) includes at least one first opening (418a) and a second portion of the at least one second shutter element (414) includes at least one second opening (418b), wherein the drive mechanism (120) is configured to move the at least one first shutter element (412) and the at least one second shutter element (414) with respect to each other in opposite directions to selectively open and close the radiation path (RP) between the at least one radiation source (140) and the radiation target (RT), and wherein the controller (130) is configured to control the drive mechanism (120) to selectively open and close the radiation path (RP) by a rotational movement of the at least one first shutter element (412) and the at least one second shutter element (414) around the at least one joint (416).

12. Apparatus (400) of claim 11, wherein the radiation path (RP) is open when the at least one first opening (418a) in the at least one first shutter element (412) and the at least one second opening (418b) in the at least one second shutter element (414) are aligned with each other and the radiation path (RP) so that the at least one first opening (418a) and the at least one second opening (418b) expose essentially an entire area of the radiation target (RT), as projected on a plane perpendicular to the radiation path (RP), to the radiation beam (RB), and wherein the radiation path (RP) is closed when the radiation path (RP) is blocked by the at least one first shutter element (412) and / or the at least one second shutter element (414).

13. Apparatus (100, 200, 300, 400) of any one of claims 1 to 12, wherein the controller (130) is configured to control the drive mechanism (120) to: close the radiation path (RP) by a movement of the shutter assembly (110, 210, 310, 410) during an initial intensity increase of the radiation beam (RB) until the intensity has reached an essentially constant value; and open the radiation path (RP) by a movement of the shutter assembly (110, 210, 310, 410) when the intensity has reached the essentially constant value to deliver a radiation dose to the radiation target (RT).

14. Apparatus (100, 200, 300, 400) of any one of claims 1 to 13, wherein the controller (130) is configured to control the drive mechanism (120) to open the radiation path (RP) for a predetermined time to deliver a predetermined radiation dose at a predetermined dose rate to the radiation target (RT), in particular wherein the predetermined time is in a range between 40 and 60ms.

15. System for FLASH radiotherapy or FLASH radiotherapy research, comprising: an apparatus (100, 200, 300, 400) of any one of claims 1 to 14; and at least one radiation source (140), in particular wherein the at least one radiation source includes, or is, an electromagnetic radiation source and / or a charged particle source.

16. Method (1500) of operating an apparatus (100, 200, 300, 400) for dose delivery in radiotherapy or radiotherapy research, comprising: moving (1510), by controlling a driving mechanism (120), a shutter assembly (110, 210, 310, 410) configured to provide one or more openings (112, 114; GP; 212b, 214b; 316; 418a, 418b) to open a radiation path (RP) between at least one radiation source (140) and a radiation target (RT) to deliver a radiation dose to the radiation target (RT), wherein the radiation path (RP) is open when the one or more openings (112, 114; GP; 212b, 214b; 316; 418a, 418b) of the shutter assembly (110, 210, 310, 410) are aligned with the radiation path (RP) so that the one or more openings (112, 114; GP; 212b, 214b; 316; 418a, 418b) expose essentially an entire area of the radiation target (RT), as projected on a plane perpendicular to the radiation path (RP), to the radiation beam (RB); andfurther moving (1520) the shutter assembly (110, 210, 310, 410) to close the radiation path (RP) between the at least one radiation source (140) and the radiation target (RT), wherein the radiation path (RP) is closed when the radiation path (RP) is blocked by the shutter assembly (110, 210, 310, 410).

17. A machine-readable storage medium having computer-executable instructions stored, that, when executed, cause one or more processors to perform the method (1500) according to claim 15.

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