Low energy - high intensity proton or deuteron beam accelerating system

Abstract

The invention relates to a cyclotron comprising first and second internal ion sources configured to form first and second beams of the same charged particles, wherein the cyclotron is also configured to create a local asymmetry of the accelerating electric field and / or of the magnetic field so as to combine the first and second beams to form a combined beam and to drive te combined beam through a single extraction outlet. The invention also concerns an accelerating system comprising N cyclotrons, of which M > 0 are according to the present invention. The invention also concerns an apparatus for treating a patient by BNCT comprising an accelerating system according to the present invention, a target configured to emit an epithermal beam of neutrons upon bombarding with a multi-combined beam of protons or deuterons, and a treatment area configured to hold a patient to be treated within a treatment zone.

Description

FIELD OF THE INVENTION

[0001] The invention relates to the field of cyclotrons for accelerating charged particles. In particular, it concerns cyclotrons configured to extract beams of charged particles of a given energy with intensity values approximately twice as high as in conventional cyclotrons. The invention also concerns a charged particles accelerating system combining two or more cyclotrons arranged in parallel to combine their respective beams, at least one the cyclotrons preferably all of the cyclotrons being according to the present invention. For example, accelerated beams of protons or deuterons having low energy and high intensity are required for producing epithermal neutron beams, which can be used e.g., in boron neutron capture therapy (BNCT).BACKGROUND OF THE INVENTION

[0002] Charged particles accelerators can be used in a number of applications. For example, beams of charged particles can be used to treat cancers by killing tumoural cells or to produce isotopes for medical imaging applications. For example, boron neutron capture therapy (BNCT) is a neutron-based technique that allows selective cancer treatment at the tumour cellular level. It combines the biological targeting precision of a benign boron-10 ( 10< B) target drug with a neutron source to deliver a therapeutic treatment dose only in cells that contain 10< B. The neutrons captured by 10< B then generate short-range alpha and lithium particles in the cancer cells that directly create a double DNA strand break in the cancer cells, outperforming other conventional cancer treatments. Indeed, as the particles have a limited path length of approximately 10 µm, which corresponds to the diameter of a cell, the destructive effects of the therapy are limited to the cells containing boron.

[0003] Neutron sources for boron neutron capture therapy may be nuclear reactors or charged particle accelerators. Accelerators have the potential to produce a neutron beam with an energy distribution that is better than that of a reactor, i.e. lower and less widely distributed neutron energies. Accelerators are also more compact than reactors and better suited to be hosted in hospitals.

[0004] An accelerator produces a beam of charged particles, such as proton or deuteron, accelerated to a specified energy. The proton or deuteron beam can be directed towards a target material causing a nuclear reaction to yield a neutron beam with specified energy and energy distribution useful for BNCT. Figure 7 gives some examples of target materials and charged particle types and energy required to produce neutrons. The first symbol in parentheses, d or p, indicates the charged particles and the second symbol, n, in parentheses indicates the beam formed by the nuclear reaction, with p = proton, d = deuteron, and n = neutron. For example, "Li(d, n)" indicates bombardment of a lithium target by a deuteron beam to form neutrons. It can be seen that, for forming neutron beams, beams of relatively low energy (< 5.0 MeV) are generally sufficient and preferred for forming epithermal neutron beams, which are preferred for BNCT to high energy neutron beams.

[0005] For example, two major types of targets are usually used to generate neutrons with a proton beam, lithium ( 7< Li) and beryllium ( 9< Be). Lithium: p + 7< Li → n + 7< Be - requiring a proton beam of energy comprised between 1,9 and 5 MeV for the formation of epithermal neutrons and of intensity comprised between 10 mA and 30 mA, to yield acceptable treatment duration. Beryllium: p + 9< Be → n + 9< B - requiring a proton beam of energy < 40 MeV and of intensity >1 0mA if the energy is low, and < 2mA if the energy is > 30MeV. Similar reactions can be achieved with beams of deuterons starting at slightly lower energy as shown in Figure 7 with the dashed lines representing the reactions with deuteron. 13C can also be a target for deuterons beams.

[0006] Systems developed so far have an important footprint, driven in a large extent by the size / length of the accelerator itself. Even cyclotrons, generally known as a more compact solution than e.g., linear accelerators, must be quite large, because existing cyclotrons generating proton beams of even 30 MeV yield a maximum current generally comprised between 1 to about 3 mA which is insufficient for producing enough epithermal neutrons without considerably prolonging patient irradiation.

[0007] In order to reduce footprint and costs of an installation, it would be interesting to develop a 2.5 to 5 MeV cyclotron to be used in BNCT instead of a 30 MeV cyclotron as the latter promotes the formation of higher energy neutron beams, which is not desired for BNCT. The challenge at these low energy values is to provide an intensity of 6-20 mA when standard cyclotrons perform at about 1 to 2 mA and when cyclotrons alternatives are much larger and more expensive.

[0008] EP3024306 proposes to use two sources of ion particles which can be used alternatively, in case of failure of one of the sources, or simultaneously. When used simultaneously, the beam current produced may be twice as high, but it is directed through two different extraction outlets to reach two distinct targets. It follows that each target is bombarded by a beam of same energy and intensity regardless of whether the two sources are used alternatively or simultaneously.

[0009] Similarly, EP2196073 describes a cyclotron comprising two internal ion sources, which can be used alternatively or simultaneously. Unlike EP3024306 discussed supra, EP2196073 does not explicitly describe whether one or two targets are bombarded when both internal ion sources are used simultaneously. The cyclotron is, however, described as having a two-fold rotational symmetry with respect to the central vertical axis, thus requiring two diametrically opposed extraction outlets, and hence two different targets. This is also clear since the first and second internal ion sources are so designed and located such as to prevent the beam extracted from one internal ion source to hit the other internal ion source. The two beams therefore follow two distinct and parallel paths, without ever merging into a single beam. It follows again, that each target is bombarded by a beam of same energy and intensity regardless of whether the two sources are used alternatively or simultaneously.

[0010] KR20200095277 describes a cyclotron comprising two internal ion sources positioned side by side, which are oriented differently such as to emit ions along different directions. The resulting extraction outlets of the two beams are offset.

[0011] WO03092339 describes a particle accelerator comprising at least one first cyclotron, a second cyclotron enclosing the first cyclotron and configured to accelerate particles derived from the first cyclotron. Proton beams of energy higher than 10 MeV and intensity of 10 mA can be obtained.

[0012] US6130926 describes a cyclotron and a target system inside the cyclotron. The accelerated particles hit a first time the target, transferring part of their energy to the target to drive nuclear reactions. As the particles are accelerated in the next orbit, they hit the target again and again. This process of continuing strikes results in accumulation of the beam current striking the target and proportionally increases the rate of nuclear reactions. Since the beam after hitting the target is recirculated and regains the energy lost to the target, the integrated unit was called by the author, "Recyclotron."

[0013] KR102178632 describes a system for accelerating charged particles for the production of a neutron beam for neutron capture therapy (NCT). In order to produce a beam of low energy and high intensity the beams of N cyclotrons are combined. If all N cyclotrons are identical, the combined beam thus obtained has the same energy as each individual beam, but the intensity is N times higher than each individual beam.

[0014] WO2022040219 describes a system comprising 2 electron accelerators of the type Rhodotron ®< that engage two different electron beamlines to irradiate a target from two different directions simultaneously.

[0015] The present invention proposes a simple and compact cyclotron configured to generate a combined beam of charged particles of low energy (about 1 to 5 MeV) or medium energy (e.g., about 75 MeV) and high intensity (about 2 to 10 mA). By combining the combined beam of the cyclotron of the present invention with the beams of other cyclotrons, preferably with combined beams of other cyclotrons according to the present invention, a low energy beam can be obtained having high intensity. These and other advantages are described in continuation.SUMMARY OF THE INVENTION

[0016] The present invention concerns a cyclotron centred on a Z1-axis for generating a combined beam of charged particles, comprising, a first internal ion source configured to produce charged particles selected among protons, deuterons, molecular hydrogen ion (H 2 +< ), and He ions (He 2+< or He +< ) and to introduce the charged particles into the cyclotron through a first slit to form a first beam of the charged particles, wherein the charged particles are preferably selected among protons, deuterons, a second internal ion source configured to produce the same charged particles as the first internal ion source and, at a same time as the first internal ion source to introduce the charged particles into the cyclotron through a second slit to form a second beam of the charged particles, wherein the second internal ion source is positioned at an opposite side from the first internal ion source relative to the Z1-axis, a dee electrode assembly and a counter dee electrode assembly separated from each other by a gap, a generator configured to apply an alternating high voltage to the dee electrode assembly for producing an accelerating electric field in the gap, for accelerating the first and second beams of charged particles, a magnetic field system configured to produce a magnetic field parallel to the Z1-axis, to guide the first and second beams of charged particles along first and second spiralling trajectories, respectively, passing through the accelerating electric field in the gap to accelerate the first and second beams of charged particles at each passage therethrough,

[0017] The cyclotron of the present invention is configured to create a local asymmetry of the accelerating electric field and / or of the magnetic field configured to deviate the first and / or second trajectories such as to drive through a single extraction outlet the combined beam formed by the first and second beams along their first and second trajectories. The directions at a level of the extraction outlet of the first and second beams forming the combined beam form an angle (2α) on a plane normal to the Z1-axis, lower than 15°, preferably lower than 10°, more preferably lower than 5, more preferably the two directions are substantially parallel with an angle of 2° ± 1°. The angle (2α) must allow the two beams to intersect a given target plane within a combined spot of a given diameter, wherein the target plane is located at a given distance from the extraction outlet along the Z-axis.

[0018] In an embodiment, the magnetic field system comprises a pair of coils powered by a generator and surrounding a volume of a ferromagnetic material having a thickness measured along the Z1-axis. The local asymmetry of the magnetic field to deviate the first and / or second trajectories is created by a local variation of the thickness and / or of the shape of the ferromagnetic material. Alternatively, or additionally, the local asymmetry of the magnetic field can be created by one or more local magnetic sources selected among coils and permanent magnets.

[0019] In an alternative or concomitant embodiment, the local asymmetry of the accelerating electric field can be created by a local difference of a gap geometry between the dee and counter dee electrode assemblies, and / or by a non-symmetrical geometry and / or location of the first and second internal ion sources relative to the Z1-axis. For example, the non-symmetrical location of the first and second sources relative to the Z1-axis can be created at least partly by an offset of a position of the second internal ion source from axial symmetry with a position of the first internal ion source relative to the Z1-axis. The offset can either be in a circumferential direction relative to the Z1-axis, or in a radial direction relative to the Z1-axis, or a combination of radial and circumferential directions relative to the Z1-axis.

[0020] The cyclotron of the present invention can be configured to emit the combined beam having at the single extraction outlet an energy (E1) lower than 75 MeV per nucleon (i.e., E1 ≤ 75 MeV / A), preferably lower than 5 MeV per nucleon (i.e., E1 ≤ 5 MeV / A). The electrical current intensity (i) can be at least 1 mA (i.e., i ≥ 1 mA), preferably at least 2 mA (i.e., i ≥ 2 mA), preferably at least 5 mA (i.e., i ≥ 5 mA), more preferably at least 10 mA (i.e., i ≥ 10 mA).

[0021] The present invention also concerns an accelerating system for producing a low energy, high intensity beam of charged particles, preferably selected among protons, deuterons, molecular hydrogen ion (H 2 +< ), and He ions (He 2+< or He +< ). The accelerating system comprises N cyclotrons, wherein N ≥ 2 and i = 1 to N. Each of the N cyclotrons is configured to emit an individual beam of same charged particles and of given energy (Eij) along a trajectory comprised in a plane normal to a corresponding Zi-axis, wherein the accelerating system is configured to combine the N individual beams accelerated from the N cyclotrons. A number M of the N cyclotrons, with M = 1 to N, preferably M = N, are according to the present invention as described supra. The individual beams of the M cyclotrons according to the present invention are the combined beams formed by the combination of the corresponding first and second beams.

[0022] The N individual beams (i.e., the M combined beams of the M cyclotrons of the present invention and the (N - M) first beams of the (N - M) conventional cyclotrons) form a multi-combined beam and are contained within a cone of aperture 2θ of not more than 70° (i.e., 2θ ≤ 70°), preferably not more than 50° (i.e., 2θ ≤ 50°), more preferably of not more than 25° (i.e., 2θ ≤ 25°). The N individual beams form N individual spots of given diameter on the target plane contiguous to a target, perpendicular to an axis (X) of the cone and located at a predefined position. The N individual spots are inscribed in an ellipse of area (A) lower than a predefined maximum area (Am) which defines a multi-combined spot. The area (A) is defined as the area where 90% of incoming beam particles hit the target plane and the maximum area (Am) is preferably, at least 10 cm 2< , more preferably at least 50 cm 2< .

[0023] The multi-combined beam has at the multi-combined spot an energy (Ec) lower than 75 MeV per nucleon (i.e., Ec ≤ 75 MeV / A), preferably lower than 5 MeV per nucleon (i.e., Ec ≤ 5 MeV / A). The multi-combined beam has an electrical current intensity (Ic) of at least 2 mA (i.e., Ic ≥ 2 mA), preferably at least 4 mA (i.e., Ic ≥ 4 mA), preferably at least 10 mA (i.e., i ≥ 10 mA), more preferably at least 20 mA (i.e., i ≥ 20 mA).

[0024] In an embodiment, the accelerating system comprises M1 cyclotrons among the N cyclotrons with 2 ≤ M1 ≤ N, preferably M1 = N. The M1 cyclotrons can be positioned side by side on a same plane normal to the Zi-axes which are parallel to one another. Alternatively, the M1 cyclotrons can be positioned on top of one another preferably tilted relative to one another, the Zi-axes of 2 adjacent cyclotrons forming an angle preferably lower than 30°. The M1 cyclotrons are preferably positioned and configured to generate magnetic fields having a rotational symmetry of order M1 between one another.

[0025] In an embodiment, the accelerating system comprises M2 cyclotrons among the N cyclotrons, with 2 ≤ M2 ≤ N, preferably M2 = N. The M2 cyclotrons share components in common in one or more of the following manners. In one embodiment, each of the M2 cyclotrons comprises a dee electrode assembly and a counter dee electrode assembly and the accelerating system comprises a single RF-generator configured to apply an alternating high voltage to the dee electrode assemblies of the M2 cyclotrons to produce the accelerating electric field. Alternatively, or concomitantly, each of the M2 cyclotrons comprises coils configured to produce a magnetic field (B) passing normal to the plane (X, Y), and the accelerating system comprises a single magnetic field generator configured to apply a current to the coils of the M2 cyclotrons to produce the magnetic field (B). Alternatively, or concomitantly, the M2 cyclotrons share a yoke in common to define a single magnetic flux circuit spanning over all of the M2 cyclotrons.

[0026] The accelerating system preferably comprises a scanner configured to scan the multi-combined spot over a predefined area of the target plane. The predefined area can be at least 30 cm 2< , preferably at least 100 cm 2< .

[0027] Contiguous to the target plane, the accelerating system can comprise a target made of a material configured to emit upon being traversed through the multi-combined spot by the low energy, high intensity beam of protons or deuterons, either neutrons, or specific isotopes. In an alternative embodiment, the target plane can be upstream of and contiguous to an inlet of a second accelerating system comprising at least one accelerating device to increase the energy of the multi-combined beam.

[0028] The invention also concerns an apparatus for applying a treatment by boron neutron capture therapy (BNCT). The apparatus comprises a target, a cyclotron or an accelerating system according to the present invention as defined supra, a beam shaping assembly, and a treatment area. The target is made of a material configured to emit neutrons upon being traversed through by a beam of accelerated protons or deuterons. The material can be selected among beryllium (Be) and Lithium (Li), The cyclotron or accelerating system is configured to emit a (multi-) combined beam of protons or deuterons. The beam shaping assembly is configured to form an epithermal neutron beam and to guide the epithermal neutron beam thus formed towards a treatment zone. The treatment area is configured to receive and support a portion of a patient to be treated by the epithermal neutron beam within the treatment zone.

[0029] The beam shaping assembly preferatbly comprises a collimator comprising an outlet of the shaping assembly, which is located at a distance (L23) from the treatment zone preferably less than 400 mm, preferably less than 200 mm, more preferably, less than 125 mm.

[0030] The apparatus of the present invention is configured to move the epithermal beam relative to the treatment zone. This can be achieved in different ways, which can be combined with one another. For example, the epithermal beam can be moved relative to the treatment zone by moving the treatment zone and the patient relative to the epithermal beam whose position remains fixed. This can also be achieved by moving the epithermal beam relative to the treatment zone whose position remains fixed. In this case the apparatus comprises a rotating mechanism configured to rotate and guide both combined beam and epithermal beam. Of course, the epithermal beam and the treatment zone can be moved relative to one another by moving both the treatment zone and the epithermal beam relative to one another as defined supra.SHORT DESCRIPTION OF THE DRAWINGS

[0031] These and further aspects of the invention will be explained in greater detail by way of example and with reference to the accompanying drawings in which, Figures 1a to 1e show, (1a) a combined beam formed by two parallel individual beams, (1b) a combined beam formed by two coincident individual beams, (1c) a combined beam formed by two converging individual beams intersecting the target plane upstream of the focal point, (1d) a combined beam formed by two converging individual beams intersecting the target plane downstream of the focal point, and (1e) a combined beam formed by two diverging individual beams, Figure 1f shows a multi-combined beam formed by several combined beams and first beams from corresponding cyclotrons. Figures 2 shows a top view of a cyclotron according to the present invention with the first and last turns of the paths of the beams issued from the first and second internal ion sources to combine to form a combined beam extracted through a single extraction outlet. Figure 3a shows a top view of a cyclotron according to the present invention showing the positions of the first and second internal sources relative to one another and relative to the dees and counter dees. Figures 3b and 3c show a system formed by two or three cyclotrons of the type illustrated in Figure 3a, arranged in parallel to combine their respective combined beams to form a multi-combined beam of the type illustrated in Figure 1c. Figures 4a to 4d show different local asymmetries of the accelerating electric field created by non-symmetrical geometry and / or location of the first and second internal ion sources relative to the Z1-axis. Figure 5a shows two cyclotrons arranged side-by-side and where magnetic flux circulates from one cyclotron to another via their top and bottom yokes. Figure 5b shows two cyclotrons arranged side-by-side and with independent magnetic flux circuits. Figure 6a shows two cyclotrons arranged on top of one another and where magnetic flux circulates from one cyclotron to another via their shared internal poles. Figure 6b shows two cyclotrons arranged on top of one another with a tilting angle and with independent magnetic flux circuits. Figure 7 shows a graph of neutron yield as a function of the energy of the beam striking a target material (Li, C, Be), the type of particles forming the beam is defined by the first letter in parentheses with d = deuteron and p = proton; the letter n in second position indicates that neutrons are formed. Figure 8 shows an apparatus for applying a treatment by boron neutron capture therapy (BNCT) according to the present invention. Figure 9a to 9c show three embodiments for moving the target orientation relative to the neutron beam, (9a) the treatment area is configured to move relative to the neutron beam by rotation about the Z- and Y-axes and by translation along the X- and Y-axes, (9b) the accelerating system and beam shaping assembly are configured to rotate about the Y-axis relative to the treatment area, and (9c) the accelerating system and beam shaping assembly are configured to rotate about the X-axis relative to the treatment area DETAILED DESCRIPTION OF THE INVENTION

[0032] As shown in Figures 2 and 3a, the present invention concerns a cyclotron (10.1) centred on a Z1-axis for generating a combined beam (1c1) of charged particles. The cyclotron comprises first and second internal ion sources (12.11, 12.12), a dee electrode assembly (5D) and a counter dee electrode assembly (5C), a generator (7RF) configured to apply an alternating high voltage between the dee electrode assembly (5D) and the counter dee (5C), and a magnetic field generator (7B, 7C) configured to produce a magnetic field parallel to the Z1-axis.

[0033] The first internal ion source (12.11) is configured to produce charged particles and to introduce charged particles into the cyclotron through a first slit to form a first beam (1.11) of the charged particles. The second internal ion source (12.12) is configured to produce the same charged particles as the first internal ion source (12.11) and, at a same time as the first internal ion source (12.11), to introduce the charged particles into the cyclotron through a second slit to form a second beam (1.12) of the charged particles. The second internal ion source (12.12) is positioned at an opposite side from the first internal ion source (12.11) relative to the Z1-axis (i.e., an angle formed at the Z1-axis between the first and second internal ion sources is at least 90°, is preferably 180° ± 20°, more preferably 180° ± 10°, most preferably 180° ± 5°.

[0034] The dee electrode assembly (5D) and the counter dee electrode assembly (5C) are separated from each other by a gap (5G). The generator (7RF) is configured to apply an alternating high voltage to the dee electrode assembly (5D) for producing an accelerating electric field in the gap (5G), for accelerating the first and second beams (1.11, 1.12) of charged particles. The dee electrode assembly (5D) and the counter dee electrode assembly (5C) can have different geometries known in the art. In Figure 3a the dee electrode assembly (5D) and the counter dee electrode assembly (5C) comprises two dee electrodes positioned symmetrically relative to the Z1-axis. Each dee electrode is coupled to two counter-dee electrodes separated therefrom by the gap (5G). The counter dee electrodes as well as the first and second internal ion sources (12.11, 12.12) are grounded to ground potential. Other geometries known in the art can be used instead in the present invention.

[0035] The magnetic field system (7B, 7C) is configured to produce a magnetic field parallel to the Z1-axis, through the dee and counter-dee electrode assemblies (5D, 5C) to guide the first and second beams (1.11, 1.12) of charged particles along first and second spiralling trajectories, respectively, passing through the accelerating electric field in the gap (5G) to accelerate the first and second beams of charged particles at each passage therethrough.

[0036] Absent any specific measure to prevent it, the first and second beams (1.11, 1.12) would follow first and second trajectories without ever merging and would exit the cyclotron through separated extraction outlets (13). The gist of the present invention is that the cyclotron (10.1) is configured to create a local asymmetry of the accelerating electric field and / or of the magnetic field configured to converge the first and second beams (1.11, 1.12) towards one another to form the combined beam (1c1) and drive it through a single extraction outlet (13). The combined beam (1c1) is formed by converging the first and second trajectories of the first and second beams (1.11, 1.12), such that the respective directions of the first and second trajectories at the level of the extraction outlet (13) are either substantially parallel (cf. Figure 1a), even coincident (cf. Figure 1b), or convergent towards a given point located outside the cyclotron with an angle lower than 15°, preferably lower than 10°, more preferably lower than 5° (cf. Figure 1c).

[0037] The cyclotron (10.1) of the present invention can be configured to accelerate charged particles selected among protons, deuterons, molecular hydrogen ion (H 2 +< ), and He ions (He 2+< or He +< ). For production of a neutron beam for use e.g., in boron neutron capture therapy (BNCT), the charged particles are preferably protons or deuterons.ASYMMETRY OF THE ELECTRIC FIELD AND / OR OF THE MAGNETIC FIELD

[0038] As discussed in the Background Art section, two beams of the same charged particles, introduced into the cyclotron (10.1) through two separate internal ion sources (12.11, 12.12) and exposed to identical electric and magnetic fields must follow two separate trajectories bound to remain separate and substantially parallel throughout their progressions in the cyclotron (10.1) until they reach their corresponding extraction outlets (13).

[0039] The challenge of the present invention is to form a single combined beam (1c1) by modifying independently the two separate trajectories to extract the combined beam (1 c1) through a single extraction outlet (13). This is achieved in the present invention by creating a local asymmetry of the accelerating electric field and / or of the magnetic field configured to modify the first and / or second trajectory.

[0040] Some examples of asymmetries are discussed in continuation, depending on whether they affect mostly the magnetic field or the electric field.. The following embodiments can be implemented as alternatives or concomitantly.Asymmetry (7L) of the magnetic field

[0041] In an embodiment of the present invention, the combination of the two trajectories to form the combined beam (1c1) can be driven by an asymmetry (7L) of the magnetic field. For example, the magnetic field system (7B, 7C) can comprise a pair of coils (7C) powered by a generator (7B) and surrounding a volume of a ferromagnetic material having a thickness measured along the Z1-axis The local asymmetry (7L) of the magnetic field can be created by a local variation of the thickness and / or of the shape of the ferromagnetic material located at a specific segment of the first and / or second beams (1.11, 1.12). Alternatively, or concomitantly and as shown in Figure 3a, the asymmetry (7L) of the magnetic field can be created by one or more local magnetic sources (7M) selected among coils and permanent magnets positioned at adequate locations creating a local asymmetry (7L) of the magnetic field which deviates the first and / or second trajectory from its "non-deviated" trajectory absent the local magnetic sources (7M). The local magnetic field asymmetry (7L) created by coils can be controlled by designing them appropriately but can also be varied by controlling the electrical power fed thereto. The local magnetic field asymmetry created by permanent magnets, on the other hand, is controlled solely by the design thereof and cannot be varied at will.Asymmetry (7L) of the electric field

[0042] In an embodiment of the present invention, the combination of the two trajectories to form the combined beam (1c1) can be driven by an asymmetry (7L) of the electric field. For example, the asymmetry (7L) of the electric field can be created by a local difference of a gap geometry between the dee and counter dee electrode assemblies (5D, 5C). Alternatively, or concomitantly, the asymmetry (7L) of the electric field can be created by a non-symmetrical geometry and / or location of the first and second internal ion sources (12.11, 12.12) relative to the Z1 axis and to the gaps (5G).

[0043] As illustrated in Figures 4a to 4d, the non-symmetrical geometry and / or location of the first and second internal ion sources (12.11, 12.12) relative to the Z1 axis can be created at least partly by an offset of a position of the second internal ion source (12.12) from axial symmetry with a position of the first internal ion source (12.11) relative to the Z1-axis. The offset can be obtained in different ways.

[0044] In an embodiment illustrated in Figure 4b, the offset can be in a circumferential direction relative to the Z1-axis, by having the first and second internal ion sources (12.11, 12.12) located at a same distance to the Z1-axis, but not aligned with the Z1-axis.

[0045] In an embodiment illustrated in Figure 4c, the offset can be in a radial direction relative to the Z1-axis, by having the first internal ion source (12.11) at a distance to the Z1-axis different from the distance to the Z1-axis of the second internal ion source (12.12), the two internal ion sources (12.11, 12.12) being aligned with the Z1-axis. In an embodiment illustrated in Figure 4b,

[0046] As shown in Figure 4d, the offset can be a combination of offsets in both radial and circumferential directions relative to the Z1-axis. Figure 4a illustrates an embodiment wherein the first and second internal ion sources (12.11, 12.12) are located symmetrically relative to the Z1-axis but have different geometries, which perturbs locally the electric field. First and second internal ion sources can of course combine different geometries and positions offsets relative to the Z1-axis.

[0047] Contrary to cyclotrons comprising two internal sources to extract two beams of exactly same properties through two separate extraction outlets, it is not essential in the present invention that the first and second beams be exactly identical in terms of energy and current intensity, since they combine to form the combined beam (1c1). This means that the second beam (1.12) can cross the gaps (5G) less times than the first beam (1.11) to allow them to combine to form the combined beam (1c1). In such case, if emitted separately from their corresponding first and second internal ion sources, the second beam (1.12) would have a lower energy than the first beam (1.11). In general, the two beams will differ from one another by half a complete revolution, so that they can be approximated as having substantially same energy at the extraction outlet (13).COMBINED BEAM (1c1)

[0048] The combined beam (1c1) is formed by combining the first and second trajectories of the first and second beams (1.11, 1.12). Ideally, when combining, the first and second trajectories are parallel to one another as illustrated in Figure 1a, preferably coincident (i.e., superimposed) as shown in Figure 1b. It is, however, not essential to control the first and second trajectories to become perfectly parallel or even coincident. As illustrated in Figures 1c and 1d, the first and second beams (1.11, 1.12) forming the combined beam (1c1) can propagate by converging towards a focal point and intersecting the target plane (6p) within the combined spot (1s1) of predefined dimensions either upstream or downstream of the focal point. As illustrated in Figure 1e, the first and second beams could also be divergent, with the condition that they intersect the combined spot (1s1) of given diameter. The angle (2α) between first and second beams has an absolute value lower than 15° (i.e., 2α ≤ 15°), and can be lower than 10° (i.e., 2α ≤ 10°), preferably lower than 5° (i.e., 2α ≤ 5°) or even 2α = 2° ± 1°. The first and second beams are configured to hit the given target plane (6p) within a predefined combined spot (1si) as shown in Figures 1a to 1c. At the single extraction outlet (13), the first and second beams are close to one another, preferably separated by a distance of less than 30 mm, more preferably of less than 20 mm, or less than 10 mm. At the extraction outlet, the first and second beams (1.11, 1.12) can be parallel or coincident (cf. Figure 1a and 1b), convergent with the target plane (6p) located upstream or downstream of the focal point as shown in Figures 1c and 1d, respectively, or even be slightly divergent as shown in Figure 1e, as long as they both intersect the target plane (6p) within the combined spot (1s1).

[0049] At the single extraction outlet (13), the combined beam (1c1) of a cyclotron of the present invention (comprising first and second internal ion sources (12.11, 12.12)) has approximately same energy (E1) and approximately double intensity as an individual beam of a state-of-the-art cyclotron comprising a single internal ion source. For example, the combined beam (1c1) can have an energy (E1) lower than 75 MeV per nucleon (i.e., E1 ≤ 75 MeV / A), preferably lower than 10 MeV per nucleon (i.e., E1 ≤ 5 MeV / A), more preferably lower than 5 MeV per nucleon (i.e., E1 ≤ 5 MeV / A), more preferably lower than 3.5 MeV per nucleon (i.e., E1 ≤ 3.5 MeV / A). The combined beam (1c1) can have a maximum electrical current intensity (i) of at least 1 mA (i.e., i ≥ 1 mA), preferably at least 2 mA (i.e., i ≥ 2 mA), more preferably at least 3 mA (i.e., i ≥ 3 mA), more preferably at least 4 mA (i.e., i ≥ 4 mA), more preferably at least 5 mA (i.e., i ≥ 5 mA), more preferably at least 7 mA (i.e., i ≥ 7 mA), more preferably at least 10 mA (i.e., i ≥ 10 mA). For protons, the combined beam (1c1) can have at the single extraction outlet (13) a power, E1 x i, higher than 10 MeV.mA, preferably higher than 20 MeV.mA.ACCELERATING SYSTEM

[0050] The present application also concerns an accelerating system for producing a low energy, high intensity beam of charged particles, preferably selected among protons, deuterons, molecular hydrogen ion (H 2 +< ), and He ions (He 2+< or He +< ). The system comprises N cyclotrons (10.i), wherein N ≥ 2 and i = 1 to N. Each of the N cyclotrons is configured to accelerate one or two beams (1.ij, with j = 1 or 2) along a trajectory comprised in a plane normal to a corresponding Zi-axis, wherein the accelerating system is configured to combine (N + 1) or more individual beams (1.ij) accelerated from corresponding (N + 1) or more slits of internal ion sources (12.ij) by the one or more cyclotrons (10.i). All beams of the accelerating system of the present invention are preferably formed of the same charged particles.

[0051] According to the present invention, a number M of cyclotrons (10.i), with M comprised between 1 and N, are according to the present invention as discussed supra, comprising first and second internal ion sources (12.i1, 12.i2) and configured to extract a combined beam (1ci), with i = 1 to M. In total, the accelerating system can extract a number N of individual beams composed of M combined beams (1ci = 1c1 to 1cM) extracted from the M cyclotrons according to the present invention and (N - M) first beams (1.i1) extracted from the (N - M) conventional cyclotrons comprising a single internal ion source (12.i1).).

[0052] The N individual beams (1ci, 1.i) are combined to form a single multi-combined beam (1c). As shown in Figure 1d, the N individual beams (1ci, 1.i) forming the multi-combined beam (1c) are contained within a cone of aperture (2θ) of not more than 70° (i.e., 2θ ≤ 70°), preferably not more than 50° (i.e., 2θ ≤ 50°), more preferably of not more than 25°(i.e., 2θ ≤ 25°). The N individual beams are formed by a number n = ni1 + ni2 of first and second beams (1.ij) accelerated by the N cyclotrons (10.i), wherein the number of first beams (1i.1) is, ni1 = N, because all cyclotrons emit a first beam (1.i1)) and the number of second beams (1i.2) is, ni2 = M because only the cyclotrons according to the present invention emit a second beam (1.i2). The number, n , of first and second beams (1i1, 1i2) involved in the formation of the multi-combined beam (1c) is therefore n = N + M, and is comprised between (N + 1) when ni2 = M = 1 cyclotron according to the present invention, and 2N when ni2 = M = N, wherein all cyclotrons of the accelerating system are according to the present invention i.e., comprising first and second internal ion sources (12.i1, 12.i2).

[0053] The N individual beams (1ci, 1.i) form N corresponding individual spots (1si) of given diameter on the target plane (6p) contiguous to a target (6), perpendicular to an axis (X) of the cone and located at a predefined position. The N individual spots (1si) are inscribed in an ellipse defining a multi-combined spot (1s). The multi-combined spot (1s) has an area (A) lower than a predefined maximum area (Am). The area (A) is defined as the area where 90% of incoming beam particles hit the target plane (6p). The maximum area (Am) is preferably, at least 10 cm 2< , more preferably at least 50 cm 2< .

[0054] For example, as shown in Figures 3b and 3c, the system comprises respectively N = M = 2 and 3 cyclotrons and corresponding combined beams (1c1 to 1cN) formed by n = 2N = 4 and 6 first and second beams (1.i1, 1.i2, with I = 1 to N), respectively. The N combined beams (1c1 to 1cN) are combined to form a single multi-combined beam (1c), converging to the multi-combined spot (1s) at the level of the target plane (6p).

[0055] If all n first and second beams (1.1j to 1.Nj, with j = 1 or 2) have identical energy, Eij, and identical intensity, lij, then the multi-combined beam (1c) has a combined energy Ec ≅ Eij, and a combined intensity, Ic ≅ n × lij. The multi-combined beam (1c) emitted by the accelerating system of the present invention forms at the multi-combined spot (1s) a multi-combined beam (1c) of combined energy (Ec) lower than 75 MeV per nucleon (i.e., Ec ≤ 75 MeV / A), preferably lower than 10 MeV per nucleon (i.e., Ec ≤ 10 MeV / A), more preferably lower than 5 MeV per nucleon (i.e., Ec ≤ 5 MeV / A), and has a maximum combined electrical current intensity (Ic) of at least 2 mA (i.e., Ic ≥ 2 mA), preferably at least 4 mA (i.e., Ic ≥ 4 mA), preferably at least 10 mA (i.e., Ic ≥ 10 mA), more preferably at least 20 mA (i.e., Ic ≥ 20 mA) or at least 30 mA (i.e., Ic ≥ 30 mA).

[0056] In a preferred embodiment illustrated in Figures 3b, 3c, and 5b a number M1 of the N cyclotrons (10.1-10.M1) with 2 ≤ M1 ≤ N and with preferably M1 = N, are positioned side by side on a same plane normal to the Zi-axes which are parallel to one another. Alternatively, as illustrated in Figure 6b, the M1 cyclotrons are positioned on top of one another preferably albeit not necessarily tilted relative to one another, the Zi-axes of 2 adjacent cyclotrons forming an angle preferably lower than 30°. If the Zi-axes of two adjacent cyclotrons form too small an angle or are parallel, or even coincident, one or both cyclotrons are preferably equipped with a steering magnet unit (15) (e.g., formed by a dipole) located downstream of the extraction outlets to steer the two individual beams (1ci or 1.i) within the cone of aperture 2θ. As shown in Figure 3b, it is preferred to position and configure the M1 cyclotrons to generate magnetic fields having a rotational symmetry of order M1 between one another. It is preferred that the M1 cyclotrons -and even the N cyclotrons- be according to the present invention.

[0057] In a preferred embodiment allowing reduction of the cost of production and use, as well as reduction of the footprint, a number M2 of cyclotrons (10.1-10.M2) among the N cyclotrons, with 2 ≤ M2 ≤ N share one or more components. Preferably, M2 = N. For example, as shown in Figure 3b, each of the M2 cyclotrons (10.1-10.M2) comprises a dee electrode assembly (5D) and a counter dee electrode assembly (5D), wherein the accelerating system comprises a single RF-generator (7RF) configured to apply an alternating high voltage to the dee electrode assemblies of the M2 cyclotrons (10.i) to produce the accelerating electric field. Alternatively or concomitantly, as also illustrated in Figures 3c, 5a, and 5b, each of the M2 cyclotrons (10.1-10.M2) comprises coils (7C) configured to produce a magnetic field (B) passing normal to the plane (X, Y), and wherein the accelerating system comprises a single magnetic field generator (7B) configured to apply a current to the coils (7C) of the M2 cyclotrons (10.1-10.M) to produce the magnetic field (B). In an alternative embodiment illustrated in Figure 5a, that can be combined with any one or two of the foregoing embodiments, the M2 cyclotrons (10.1-10.M2) can share a yoke (14) in common to define a single magnetic flux circuit spanning over all of the M2 cyclotrons (10.1-10.M2). In yet an alternative embodiment that can be combined with any one of the foregoing embodiments, shown in Figure 6a, the M2 cyclotrons can share a pole in common.

[0058] The accelerating system of the present invention can comprise a scanner configured to scan the multi-combined spot (1s) over a predefined area of the target plane (6p). The predefined area is preferably at least 30 cm 2< , more preferably at least 100 cm 2< . For the production of epithermal neutron beams or of specific isotopes, it can be advantageous to scan the multi-combined beam over a larger area to reduce local overheating of the target (6).

[0059] Downstream of and contiguous to the target plane (6p) the accelerating system of the present invention can comprise a target (6) made of a material configured to emit upon being traversed through the multi-combined spot (1s) by the low energy, high intensity beam of protons or deuterons, either neutrons, or configured to produce specific isotopes. Alternatively, instead of a target (6), an inlet of a second accelerating system comprising at least one accelerating device can be positioned downstream and contiguous to the target plan (6p). This way, the multi-combined beam (1c) of energy, Ec, and intensity, Ic, exiting the accelerating system of the present invention can be further accelerated to reach a second energy, Ec2 > Ec, with approximately the same intensity Ic2 ≅ Ic.APPARATUS FOR APPLYING A TREATMENT BY BNCT

[0060] The present invention also concerns an apparatus illustrated in Figures 8 and 9a to 9c. for applying a treatment by boron neutron capture therapy (BNCT), comprising an accelerating system according to the present invention, a beam shaping assembly (21s), and a treatment area. The accelerating system used in the apparatus comprises a target (6) positioned downstream or upstream of and contiguous to the target plane (6p) as discussed supra. The target (6) comprise a material configured to emit neutrons upon being traversed through the multi-combined spot (1s) by the low energy, high intensity multi-combined beam (1c) of protons or deuterons. The material is preferably selected among beryllium (Be) and Lithium (Li).

[0061] The beam shaping assembly (21s) is configured to form an epithermal neutron beam (22en) and to guide the epithermal neutron beam (22en) thus formed towards a treatment zone (23). The treatment area is configured to receive and support a portion of a patient (23p) to be treated by the epithermal neutron beam within the treatment zone (23). Figures 8, 9a to 9c show a treatment area supporting the patient in a supine position with the head located within the treatment zone (23). Other configurations are of course possible, such as supporting the patient is a sitting position, or kneeling position, and the like, as long as the tumoural cells to be treated by BNCT is stably maintained within the treatment zone (23) during the treatment.

[0062] The beam shaping assembly (21s) can comprise a collimator (21c) comprising an outlet (21o) of the shaping assembly (21s). The outlet (21o) is located at a distance (L23) from the treatment zone (23) preferably less than 400 mm, more preferably less than 200 mm, most preferably less than 125 mm.

[0063] Referring to Figure 7 plotting the neutron yield as a function of the energy of the beam of protons (p) or deuterons (d) used to bombard different targets (6), it can be seen that relatively low values of the energy, Ec, of the combined or multi-combined beam (1ci, 1c) are required to get a maximum yield. The irradiation time decreases with increasing current intensity of the (multi-) combined beam (1c1, 1c). The current intensity, Ic, of the beam is preferably at least 5 mA, more preferably at least 6 mA, more preferably at least 7 mA, preferably at least 10 mA, or at least 20 mA and more. The combined beam (1c1) of the cyclotron of the present invention and the multi-combined beams (1c) produced by the accelerating system of the present invention can produce beams of such low energy values and high current intensity values.

[0064] To control the orientation of the epithermal beam (22en) relative to the treatment zone (23), the apparatus of the present invention can be configured to move the epithermal beam (22en) and / or to move the treatment zone (23) relative to one another. For example, as illustrated in Figure 9a, the treatment area can be moved together with the patient (23p) relative to the epithermal beam (22en), by translation along the X-axis and / or rotation about the Y-axis and / or about the Z-axis (cf. Figures 9a to 9c for the orientation of the axes (X, Y, Z)).

[0065] As shown in Figures 9b and 9c, the apparatus can be configured to move the epithermal beam (22en) relative to the treatment zone (23). This can be achieved by rotating the accelerating system together with the beam shaping assembly (21s) about the Y-axis, as shown in Figure 9b and / or about the X-axis, as shown in Figure 9c. Of course, the apparatus can be configured to move both epithermal beam (22en) and treatment area, so that multiple degrees of freedom are available to best bombard the pateint's tumoural cells maintained within the treatment zone.

[0066] The accelerating system of the apparatus is preferably equipped with a scanner configured to scan the multi-combined spot (1s) over a predefined area of the target plane (6p) of preferably at least 30 cm 2< , more preferably at least 100 cm 2< . This allows spreading and homogenising the power density of the beam over a larger area of the target plane (6p) and over a larger volume of the target (6). # Feature 1Combined beam1.iIndividual beam from a conventional cyclotron of the accelerating system1.ijj th< Individual beam of a i th< cyclotron, with i = 1 to N and j = 1 or 21ciCombined beam exiting a i th< cyclotron formed by beams 1.i1 and 1.i21cMulti-combined beam combined from several cyclotrons1siCombined spot of a combined beam 1ci1sijIndividual spot of an individual beam 1.ij1DDee electrode system5CCounter dee electrode assembly5DDee electrode assembly5GGap6Target or following beam line entry point6pTarget plane7BGenerator for the coils7LLocal asymmetry7MLocal magnetic source7RFGenerator for the dee electrode system10.ii th< cyclotron with i = 1 to N12.ij...12.ij th< Internal ion source of the i th< cyclotron, with i = 1 to N and j = 1 or 213Single extraction outlet of a cyclotron14Yoke15Beam bending unit21cCollimator of the beam shaping assembly21mNeutron moderator of the beam shaping assembly21oOutlet of the beam shaping assembly21sBeam shaping assembly22fnFast neutron beam22enEpithermal neturon beam23Treatment zone23pPatient30Rotating mechanismEij, Ei, EcEnergy of the 1 st< / 2 nd< beam 1.ij, of the combined beam 1ci and of the multi-combined beam (1c)lij, li, IcCurrent intensity of the 1 st< / 2 nd< beam 1.ij, of the combined beam 1ci and of the multi-combined beam (1c)L23Distance between outlet of the beam shaping assembly and the treatment zoneMNumber of cyclotrons according to the invention in the accelerating systemM1Number of cyclotrons having a specified relative positioningM2Number of cyclotrons sharing a componentNNumber of cyclotrons in the accelerating systemnNumber of first and second beams forming the multi-combined beam, n = ni1 + ni2ni1, ni2Number of first and second beams forming the multi-combined beamiRefers to the i th< cyclotron with i = 1 to NjRefers to the j th< internal ion source and corresponding individual beam, with j = 1 or 2XCone axisZiCentral axis of the i th< cyclotronαHalf aperture of the cone of the combined beam (1ci)θHalf aperture of the cone of the multi-combined beam (1c)

Examples

Embodiment Construction

[0032]As shown in Figures 2 and 3a, the present invention concerns a cyclotron (10.1) centred on a Z1-axis for generating a combined beam (1c1) of charged particles. The cyclotron comprises first and second internal ion sources (12.11, 12.12), a dee electrode assembly (5D) and a counter dee electrode assembly (5C), a generator (7RF) configured to apply an alternating high voltage between the dee electrode assembly (5D) and the counter dee (5C), and a magnetic field generator (7B, 7C) configured to produce a magnetic field parallel to the Z1-axis.

[0033]The first internal ion source (12.11) is configured to produce charged particles and to introduce charged particles into the cyclotron through a first slit to form a first beam (1.11) of the charged particles. The second internal ion source (12.12) is configured to produce the same charged particles as the first internal ion source (12.11) and, at a same time as the first internal ion source (12.11), to introduce the charged particles ...

FIELD OF THE INVENTION

[0001] The invention relates to the field of cyclotrons for accelerating charged particles. In particular, it concerns cyclotrons configured to extract beams of charged particles of a given energy with intensity values approximately twice as high as in conventional cyclotrons. The invention also concerns a charged particles accelerating system combining two or more cyclotrons arranged in parallel to combine their respective beams, at least one the cyclotrons preferably all of the cyclotrons being according to the present invention. For example, accelerated beams of protons or deuterons having low energy and high intensity are required for producing epithermal neutron beams, which can be used e.g., in boron neutron capture therapy (BNCT).BACKGROUND OF THE INVENTION

[0002] Charged particles accelerators can be used in a number of applications. For example, beams of charged particles can be used to treat cancers by killing tumoural cells or to produce isotopes for medical imaging applications. For example, boron neutron capture therapy (BNCT) is a neutron-based technique that allows selective cancer treatment at the tumour cellular level. It combines the biological targeting precision of a benign boron-10 ( 10< B) target drug with a neutron source to deliver a therapeutic treatment dose only in cells that contain 10< B. The neutrons captured by 10< B then generate short-range alpha and lithium particles in the cancer cells that directly create a double DNA strand break in the cancer cells, outperforming other conventional cancer treatments. Indeed, as the particles have a limited path length of approximately 10 µm, which corresponds to the diameter of a cell, the destructive effects of the therapy are limited to the cells containing boron.

[0003] Neutron sources for boron neutron capture therapy may be nuclear reactors or charged particle accelerators. Accelerators have the potential to produce a neutron beam with an energy distribution that is better than that of a reactor, i.e. lower and less widely distributed neutron energies. Accelerators are also more compact than reactors and better suited to be hosted in hospitals.

[0004] An accelerator produces a beam of charged particles, such as proton or deuteron, accelerated to a specified energy. The proton or deuteron beam can be directed towards a target material causing a nuclear reaction to yield a neutron beam with specified energy and energy distribution useful for BNCT. Figure 7 gives some examples of target materials and charged particle types and energy required to produce neutrons. The first symbol in parentheses, d or p, indicates the charged particles and the second symbol, n, in parentheses indicates the beam formed by the nuclear reaction, with p = proton, d = deuteron, and n = neutron. For example, "Li(d, n)" indicates bombardment of a lithium target by a deuteron beam to form neutrons. It can be seen that, for forming neutron beams, beams of relatively low energy (< 5.0 MeV) are generally sufficient and preferred for forming epithermal neutron beams, which are preferred for BNCT to high energy neutron beams.

[0005] For example, two major types of targets are usually used to generate neutrons with a proton beam, lithium ( 7< Li) and beryllium ( 9< Be). Lithium: p + 7< Li → n + 7< Be - requiring a proton beam of energy comprised between 1,9 and 5 MeV for the formation of epithermal neutrons and of intensity comprised between 10 mA and 30 mA, to yield acceptable treatment duration. Beryllium: p + 9< Be → n + 9< B - requiring a proton beam of energy < 40 MeV and of intensity >1 0mA if the energy is low, and < 2mA if the energy is > 30MeV. Similar reactions can be achieved with beams of deuterons starting at slightly lower energy as shown in Figure 7 with the dashed lines representing the reactions with deuteron. 13C can also be a target for deuterons beams.

[0006] Systems developed so far have an important footprint, driven in a large extent by the size / length of the accelerator itself. Even cyclotrons, generally known as a more compact solution than e.g., linear accelerators, must be quite large, because existing cyclotrons generating proton beams of even 30 MeV yield a maximum current generally comprised between 1 to about 3 mA which is insufficient for producing enough epithermal neutrons without considerably prolonging patient irradiation.

[0007] In order to reduce footprint and costs of an installation, it would be interesting to develop a 2.5 to 5 MeV cyclotron to be used in BNCT instead of a 30 MeV cyclotron as the latter promotes the formation of higher energy neutron beams, which is not desired for BNCT. The challenge at these low energy values is to provide an intensity of 6-20 mA when standard cyclotrons perform at about 1 to 2 mA and when cyclotrons alternatives are much larger and more expensive.

[0008] EP3024306 proposes to use two sources of ion particles which can be used alternatively, in case of failure of one of the sources, or simultaneously. When used simultaneously, the beam current produced may be twice as high, but it is directed through two different extraction outlets to reach two distinct targets. It follows that each target is bombarded by a beam of same energy and intensity regardless of whether the two sources are used alternatively or simultaneously.

[0009] Similarly, EP2196073 describes a cyclotron comprising two internal ion sources, which can be used alternatively or simultaneously. Unlike EP3024306 discussed supra, EP2196073 does not explicitly describe whether one or two targets are bombarded when both internal ion sources are used simultaneously. The cyclotron is, however, described as having a two-fold rotational symmetry with respect to the central vertical axis, thus requiring two diametrically opposed extraction outlets, and hence two different targets. This is also clear since the first and second internal ion sources are so designed and located such as to prevent the beam extracted from one internal ion source to hit the other internal ion source. The two beams therefore follow two distinct and parallel paths, without ever merging into a single beam. It follows again, that each target is bombarded by a beam of same energy and intensity regardless of whether the two sources are used alternatively or simultaneously.

[0010] KR20200095277 describes a cyclotron comprising two internal ion sources positioned side by side, which are oriented differently such as to emit ions along different directions. The resulting extraction outlets of the two beams are offset.

[0011] WO03092339 describes a particle accelerator comprising at least one first cyclotron, a second cyclotron enclosing the first cyclotron and configured to accelerate particles derived from the first cyclotron. Proton beams of energy higher than 10 MeV and intensity of 10 mA can be obtained.

[0012] US6130926 describes a cyclotron and a target system inside the cyclotron. The accelerated particles hit a first time the target, transferring part of their energy to the target to drive nuclear reactions. As the particles are accelerated in the next orbit, they hit the target again and again. This process of continuing strikes results in accumulation of the beam current striking the target and proportionally increases the rate of nuclear reactions. Since the beam after hitting the target is recirculated and regains the energy lost to the target, the integrated unit was called by the author, "Recyclotron."

[0013] KR102178632 describes a system for accelerating charged particles for the production of a neutron beam for neutron capture therapy (NCT). In order to produce a beam of low energy and high intensity the beams of N cyclotrons are combined. If all N cyclotrons are identical, the combined beam thus obtained has the same energy as each individual beam, but the intensity is N times higher than each individual beam.

[0014] WO2022040219 describes a system comprising 2 electron accelerators of the type Rhodotron ®< that engage two different electron beamlines to irradiate a target from two different directions simultaneously.

[0015] The present invention proposes a simple and compact cyclotron configured to generate a combined beam of charged particles of low energy (about 1 to 5 MeV) or medium energy (e.g., about 75 MeV) and high intensity (about 2 to 10 mA). By combining the combined beam of the cyclotron of the present invention with the beams of other cyclotrons, preferably with combined beams of other cyclotrons according to the present invention, a low energy beam can be obtained having high intensity. These and other advantages are described in continuation.SUMMARY OF THE INVENTION

[0016] The present invention concerns a cyclotron centred on a Z1-axis for generating a combined beam of charged particles, comprising, a first internal ion source configured to produce charged particles selected among protons, deuterons, molecular hydrogen ion (H 2 +< ), and He ions (He 2+< or He +< ) and to introduce the charged particles into the cyclotron through a first slit to form a first beam of the charged particles, wherein the charged particles are preferably selected among protons, deuterons, a second internal ion source configured to produce the same charged particles as the first internal ion source and, at a same time as the first internal ion source to introduce the charged particles into the cyclotron through a second slit to form a second beam of the charged particles, wherein the second internal ion source is positioned at an opposite side from the first internal ion source relative to the Z1-axis, a dee electrode assembly and a counter dee electrode assembly separated from each other by a gap, a generator configured to apply an alternating high voltage to the dee electrode assembly for producing an accelerating electric field in the gap, for accelerating the first and second beams of charged particles, a magnetic field system configured to produce a magnetic field parallel to the Z1-axis, to guide the first and second beams of charged particles along first and second spiralling trajectories, respectively, passing through the accelerating electric field in the gap to accelerate the first and second beams of charged particles at each passage therethrough,

[0017] The cyclotron of the present invention is configured to create a local asymmetry of the accelerating electric field and / or of the magnetic field configured to deviate the first and / or second trajectories such as to drive through a single extraction outlet the combined beam formed by the first and second beams along their first and second trajectories. The directions at a level of the extraction outlet of the first and second beams forming the combined beam form an angle (2α) on a plane normal to the Z1-axis, lower than 15°, preferably lower than 10°, more preferably lower than 5, more preferably the two directions are substantially parallel with an angle of 2° ± 1°. The angle (2α) must allow the two beams to intersect a given target plane within a combined spot of a given diameter, wherein the target plane is located at a given distance from the extraction outlet along the Z-axis.

[0018] In an embodiment, the magnetic field system comprises a pair of coils powered by a generator and surrounding a volume of a ferromagnetic material having a thickness measured along the Z1-axis. The local asymmetry of the magnetic field to deviate the first and / or second trajectories is created by a local variation of the thickness and / or of the shape of the ferromagnetic material. Alternatively, or additionally, the local asymmetry of the magnetic field can be created by one or more local magnetic sources selected among coils and permanent magnets.

[0019] In an alternative or concomitant embodiment, the local asymmetry of the accelerating electric field can be created by a local difference of a gap geometry between the dee and counter dee electrode assemblies, and / or by a non-symmetrical geometry and / or location of the first and second internal ion sources relative to the Z1-axis. For example, the non-symmetrical location of the first and second sources relative to the Z1-axis can be created at least partly by an offset of a position of the second internal ion source from axial symmetry with a position of the first internal ion source relative to the Z1-axis. The offset can either be in a circumferential direction relative to the Z1-axis, or in a radial direction relative to the Z1-axis, or a combination of radial and circumferential directions relative to the Z1-axis.

[0020] The cyclotron of the present invention can be configured to emit the combined beam having at the single extraction outlet an energy (E1) lower than 75 MeV per nucleon (i.e., E1 ≤ 75 MeV / A), preferably lower than 5 MeV per nucleon (i.e., E1 ≤ 5 MeV / A). The electrical current intensity (i) can be at least 1 mA (i.e., i ≥ 1 mA), preferably at least 2 mA (i.e., i ≥ 2 mA), preferably at least 5 mA (i.e., i ≥ 5 mA), more preferably at least 10 mA (i.e., i ≥ 10 mA).

[0021] The present invention also concerns an accelerating system for producing a low energy, high intensity beam of charged particles, preferably selected among protons, deuterons, molecular hydrogen ion (H 2 +< ), and He ions (He 2+< or He +< ). The accelerating system comprises N cyclotrons, wherein N ≥ 2 and i = 1 to N. Each of the N cyclotrons is configured to emit an individual beam of same charged particles and of given energy (Eij) along a trajectory comprised in a plane normal to a corresponding Zi-axis, wherein the accelerating system is configured to combine the N individual beams accelerated from the N cyclotrons. A number M of the N cyclotrons, with M = 1 to N, preferably M = N, are according to the present invention as described supra. The individual beams of the M cyclotrons according to the present invention are the combined beams formed by the combination of the corresponding first and second beams.

[0022] The N individual beams (i.e., the M combined beams of the M cyclotrons of the present invention and the (N - M) first beams of the (N - M) conventional cyclotrons) form a multi-combined beam and are contained within a cone of aperture 2θ of not more than 70° (i.e., 2θ ≤ 70°), preferably not more than 50° (i.e., 2θ ≤ 50°), more preferably of not more than 25° (i.e., 2θ ≤ 25°). The N individual beams form N individual spots of given diameter on the target plane contiguous to a target, perpendicular to an axis (X) of the cone and located at a predefined position. The N individual spots are inscribed in an ellipse of area (A) lower than a predefined maximum area (Am) which defines a multi-combined spot. The area (A) is defined as the area where 90% of incoming beam particles hit the target plane and the maximum area (Am) is preferably, at least 10 cm 2< , more preferably at least 50 cm 2< .

[0023] The multi-combined beam has at the multi-combined spot an energy (Ec) lower than 75 MeV per nucleon (i.e., Ec ≤ 75 MeV / A), preferably lower than 5 MeV per nucleon (i.e., Ec ≤ 5 MeV / A). The multi-combined beam has an electrical current intensity (Ic) of at least 2 mA (i.e., Ic ≥ 2 mA), preferably at least 4 mA (i.e., Ic ≥ 4 mA), preferably at least 10 mA (i.e., i ≥ 10 mA), more preferably at least 20 mA (i.e., i ≥ 20 mA).

[0024] In an embodiment, the accelerating system comprises M1 cyclotrons among the N cyclotrons with 2 ≤ M1 ≤ N, preferably M1 = N. The M1 cyclotrons can be positioned side by side on a same plane normal to the Zi-axes which are parallel to one another. Alternatively, the M1 cyclotrons can be positioned on top of one another preferably tilted relative to one another, the Zi-axes of 2 adjacent cyclotrons forming an angle preferably lower than 30°. The M1 cyclotrons are preferably positioned and configured to generate magnetic fields having a rotational symmetry of order M1 between one another.

[0025] In an embodiment, the accelerating system comprises M2 cyclotrons among the N cyclotrons, with 2 ≤ M2 ≤ N, preferably M2 = N. The M2 cyclotrons share components in common in one or more of the following manners. In one embodiment, each of the M2 cyclotrons comprises a dee electrode assembly and a counter dee electrode assembly and the accelerating system comprises a single RF-generator configured to apply an alternating high voltage to the dee electrode assemblies of the M2 cyclotrons to produce the accelerating electric field. Alternatively, or concomitantly, each of the M2 cyclotrons comprises coils configured to produce a magnetic field (B) passing normal to the plane (X, Y), and the accelerating system comprises a single magnetic field generator configured to apply a current to the coils of the M2 cyclotrons to produce the magnetic field (B). Alternatively, or concomitantly, the M2 cyclotrons share a yoke in common to define a single magnetic flux circuit spanning over all of the M2 cyclotrons.

[0026] The accelerating system preferably comprises a scanner configured to scan the multi-combined spot over a predefined area of the target plane. The predefined area can be at least 30 cm 2< , preferably at least 100 cm 2< .

[0027] Contiguous to the target plane, the accelerating system can comprise a target made of a material configured to emit upon being traversed through the multi-combined spot by the low energy, high intensity beam of protons or deuterons, either neutrons, or specific isotopes. In an alternative embodiment, the target plane can be upstream of and contiguous to an inlet of a second accelerating system comprising at least one accelerating device to increase the energy of the multi-combined beam.

[0028] The invention also concerns an apparatus for applying a treatment by boron neutron capture therapy (BNCT). The apparatus comprises a target, a cyclotron or an accelerating system according to the present invention as defined supra, a beam shaping assembly, and a treatment area. The target is made of a material configured to emit neutrons upon being traversed through by a beam of accelerated protons or deuterons. The material can be selected among beryllium (Be) and Lithium (Li), The cyclotron or accelerating system is configured to emit a (multi-) combined beam of protons or deuterons. The beam shaping assembly is configured to form an epithermal neutron beam and to guide the epithermal neutron beam thus formed towards a treatment zone. The treatment area is configured to receive and support a portion of a patient to be treated by the epithermal neutron beam within the treatment zone.

[0029] The beam shaping assembly preferatbly comprises a collimator comprising an outlet of the shaping assembly, which is located at a distance (L23) from the treatment zone preferably less than 400 mm, preferably less than 200 mm, more preferably, less than 125 mm.

[0030] The apparatus of the present invention is configured to move the epithermal beam relative to the treatment zone. This can be achieved in different ways, which can be combined with one another. For example, the epithermal beam can be moved relative to the treatment zone by moving the treatment zone and the patient relative to the epithermal beam whose position remains fixed. This can also be achieved by moving the epithermal beam relative to the treatment zone whose position remains fixed. In this case the apparatus comprises a rotating mechanism configured to rotate and guide both combined beam and epithermal beam. Of course, the epithermal beam and the treatment zone can be moved relative to one another by moving both the treatment zone and the epithermal beam relative to one another as defined supra.SHORT DESCRIPTION OF THE DRAWINGS

[0031] These and further aspects of the invention will be explained in greater detail by way of example and with reference to the accompanying drawings in which, Figures 1a to 1e show, (1a) a combined beam formed by two parallel individual beams, (1b) a combined beam formed by two coincident individual beams, (1c) a combined beam formed by two converging individual beams intersecting the target plane upstream of the focal point, (1d) a combined beam formed by two converging individual beams intersecting the target plane downstream of the focal point, and (1e) a combined beam formed by two diverging individual beams, Figure 1f shows a multi-combined beam formed by several combined beams and first beams from corresponding cyclotrons. Figures 2 shows a top view of a cyclotron according to the present invention with the first and last turns of the paths of the beams issued from the first and second internal ion sources to combine to form a combined beam extracted through a single extraction outlet. Figure 3a shows a top view of a cyclotron according to the present invention showing the positions of the first and second internal sources relative to one another and relative to the dees and counter dees. Figures 3b and 3c show a system formed by two or three cyclotrons of the type illustrated in Figure 3a, arranged in parallel to combine their respective combined beams to form a multi-combined beam of the type illustrated in Figure 1c. Figures 4a to 4d show different local asymmetries of the accelerating electric field created by non-symmetrical geometry and / or location of the first and second internal ion sources relative to the Z1-axis. Figure 5a shows two cyclotrons arranged side-by-side and where magnetic flux circulates from one cyclotron to another via their top and bottom yokes. Figure 5b shows two cyclotrons arranged side-by-side and with independent magnetic flux circuits. Figure 6a shows two cyclotrons arranged on top of one another and where magnetic flux circulates from one cyclotron to another via their shared internal poles. Figure 6b shows two cyclotrons arranged on top of one another with a tilting angle and with independent magnetic flux circuits. Figure 7 shows a graph of neutron yield as a function of the energy of the beam striking a target material (Li, C, Be), the type of particles forming the beam is defined by the first letter in parentheses with d = deuteron and p = proton; the letter n in second position indicates that neutrons are formed. Figure 8 shows an apparatus for applying a treatment by boron neutron capture therapy (BNCT) according to the present invention. Figure 9a to 9c show three embodiments for moving the target orientation relative to the neutron beam, (9a) the treatment area is configured to move relative to the neutron beam by rotation about the Z- and Y-axes and by translation along the X- and Y-axes, (9b) the accelerating system and beam shaping assembly are configured to rotate about the Y-axis relative to the treatment area, and (9c) the accelerating system and beam shaping assembly are configured to rotate about the X-axis relative to the treatment area DETAILED DESCRIPTION OF THE INVENTION

[0032] As shown in Figures 2 and 3a, the present invention concerns a cyclotron (10.1) centred on a Z1-axis for generating a combined beam (1c1) of charged particles. The cyclotron comprises first and second internal ion sources (12.11, 12.12), a dee electrode assembly (5D) and a counter dee electrode assembly (5C), a generator (7RF) configured to apply an alternating high voltage between the dee electrode assembly (5D) and the counter dee (5C), and a magnetic field generator (7B, 7C) configured to produce a magnetic field parallel to the Z1-axis.

[0033] The first internal ion source (12.11) is configured to produce charged particles and to introduce charged particles into the cyclotron through a first slit to form a first beam (1.11) of the charged particles. The second internal ion source (12.12) is configured to produce the same charged particles as the first internal ion source (12.11) and, at a same time as the first internal ion source (12.11), to introduce the charged particles into the cyclotron through a second slit to form a second beam (1.12) of the charged particles. The second internal ion source (12.12) is positioned at an opposite side from the first internal ion source (12.11) relative to the Z1-axis (i.e., an angle formed at the Z1-axis between the first and second internal ion sources is at least 90°, is preferably 180° ± 20°, more preferably 180° ± 10°, most preferably 180° ± 5°.

[0034] The dee electrode assembly (5D) and the counter dee electrode assembly (5C) are separated from each other by a gap (5G). The generator (7RF) is configured to apply an alternating high voltage to the dee electrode assembly (5D) for producing an accelerating electric field in the gap (5G), for accelerating the first and second beams (1.11, 1.12) of charged particles. The dee electrode assembly (5D) and the counter dee electrode assembly (5C) can have different geometries known in the art. In Figure 3a the dee electrode assembly (5D) and the counter dee electrode assembly (5C) comprises two dee electrodes positioned symmetrically relative to the Z1-axis. Each dee electrode is coupled to two counter-dee electrodes separated therefrom by the gap (5G). The counter dee electrodes as well as the first and second internal ion sources (12.11, 12.12) are grounded to ground potential. Other geometries known in the art can be used instead in the present invention.

[0035] The magnetic field system (7B, 7C) is configured to produce a magnetic field parallel to the Z1-axis, through the dee and counter-dee electrode assemblies (5D, 5C) to guide the first and second beams (1.11, 1.12) of charged particles along first and second spiralling trajectories, respectively, passing through the accelerating electric field in the gap (5G) to accelerate the first and second beams of charged particles at each passage therethrough.

[0036] Absent any specific measure to prevent it, the first and second beams (1.11, 1.12) would follow first and second trajectories without ever merging and would exit the cyclotron through separated extraction outlets (13). The gist of the present invention is that the cyclotron (10.1) is configured to create a local asymmetry of the accelerating electric field and / or of the magnetic field configured to converge the first and second beams (1.11, 1.12) towards one another to form the combined beam (1c1) and drive it through a single extraction outlet (13). The combined beam (1c1) is formed by converging the first and second trajectories of the first and second beams (1.11, 1.12), such that the respective directions of the first and second trajectories at the level of the extraction outlet (13) are either substantially parallel (cf. Figure 1a), even coincident (cf. Figure 1b), or convergent towards a given point located outside the cyclotron with an angle lower than 15°, preferably lower than 10°, more preferably lower than 5° (cf. Figure 1c).

[0037] The cyclotron (10.1) of the present invention can be configured to accelerate charged particles selected among protons, deuterons, molecular hydrogen ion (H 2 +< ), and He ions (He 2+< or He +< ). For production of a neutron beam for use e.g., in boron neutron capture therapy (BNCT), the charged particles are preferably protons or deuterons.ASYMMETRY OF THE ELECTRIC FIELD AND / OR OF THE MAGNETIC FIELD

[0038] As discussed in the Background Art section, two beams of the same charged particles, introduced into the cyclotron (10.1) through two separate internal ion sources (12.11, 12.12) and exposed to identical electric and magnetic fields must follow two separate trajectories bound to remain separate and substantially parallel throughout their progressions in the cyclotron (10.1) until they reach their corresponding extraction outlets (13).

[0039] The challenge of the present invention is to form a single combined beam (1c1) by modifying independently the two separate trajectories to extract the combined beam (1 c1) through a single extraction outlet (13). This is achieved in the present invention by creating a local asymmetry of the accelerating electric field and / or of the magnetic field configured to modify the first and / or second trajectory.

[0040] Some examples of asymmetries are discussed in continuation, depending on whether they affect mostly the magnetic field or the electric field.. The following embodiments can be implemented as alternatives or concomitantly.Asymmetry (7L) of the magnetic field

[0041] In an embodiment of the present invention, the combination of the two trajectories to form the combined beam (1c1) can be driven by an asymmetry (7L) of the magnetic field. For example, the magnetic field system (7B, 7C) can comprise a pair of coils (7C) powered by a generator (7B) and surrounding a volume of a ferromagnetic material having a thickness measured along the Z1-axis The local asymmetry (7L) of the magnetic field can be created by a local variation of the thickness and / or of the shape of the ferromagnetic material located at a specific segment of the first and / or second beams (1.11, 1.12). Alternatively, or concomitantly and as shown in Figure 3a, the asymmetry (7L) of the magnetic field can be created by one or more local magnetic sources (7M) selected among coils and permanent magnets positioned at adequate locations creating a local asymmetry (7L) of the magnetic field which deviates the first and / or second trajectory from its "non-deviated" trajectory absent the local magnetic sources (7M). The local magnetic field asymmetry (7L) created by coils can be controlled by designing them appropriately but can also be varied by controlling the electrical power fed thereto. The local magnetic field asymmetry created by permanent magnets, on the other hand, is controlled solely by the design thereof and cannot be varied at will.Asymmetry (7L) of the electric field

[0042] In an embodiment of the present invention, the combination of the two trajectories to form the combined beam (1c1) can be driven by an asymmetry (7L) of the electric field. For example, the asymmetry (7L) of the electric field can be created by a local difference of a gap geometry between the dee and counter dee electrode assemblies (5D, 5C). Alternatively, or concomitantly, the asymmetry (7L) of the electric field can be created by a non-symmetrical geometry and / or location of the first and second internal ion sources (12.11, 12.12) relative to the Z1 axis and to the gaps (5G).

[0043] As illustrated in Figures 4a to 4d, the non-symmetrical geometry and / or location of the first and second internal ion sources (12.11, 12.12) relative to the Z1 axis can be created at least partly by an offset of a position of the second internal ion source (12.12) from axial symmetry with a position of the first internal ion source (12.11) relative to the Z1-axis. The offset can be obtained in different ways.

[0044] In an embodiment illustrated in Figure 4b, the offset can be in a circumferential direction relative to the Z1-axis, by having the first and second internal ion sources (12.11, 12.12) located at a same distance to the Z1-axis, but not aligned with the Z1-axis.

[0045] In an embodiment illustrated in Figure 4c, the offset can be in a radial direction relative to the Z1-axis, by having the first internal ion source (12.11) at a distance to the Z1-axis different from the distance to the Z1-axis of the second internal ion source (12.12), the two internal ion sources (12.11, 12.12) being aligned with the Z1-axis. In an embodiment illustrated in Figure 4b,

[0046] As shown in Figure 4d, the offset can be a combination of offsets in both radial and circumferential directions relative to the Z1-axis. Figure 4a illustrates an embodiment wherein the first and second internal ion sources (12.11, 12.12) are located symmetrically relative to the Z1-axis but have different geometries, which perturbs locally the electric field. First and second internal ion sources can of course combine different geometries and positions offsets relative to the Z1-axis.

[0047] Contrary to cyclotrons comprising two internal sources to extract two beams of exactly same properties through two separate extraction outlets, it is not essential in the present invention that the first and second beams be exactly identical in terms of energy and current intensity, since they combine to form the combined beam (1c1). This means that the second beam (1.12) can cross the gaps (5G) less times than the first beam (1.11) to allow them to combine to form the combined beam (1c1). In such case, if emitted separately from their corresponding first and second internal ion sources, the second beam (1.12) would have a lower energy than the first beam (1.11). In general, the two beams will differ from one another by half a complete revolution, so that they can be approximated as having substantially same energy at the extraction outlet (13).COMBINED BEAM (1c1)

[0048] The combined beam (1c1) is formed by combining the first and second trajectories of the first and second beams (1.11, 1.12). Ideally, when combining, the first and second trajectories are parallel to one another as illustrated in Figure 1a, preferably coincident (i.e., superimposed) as shown in Figure 1b. It is, however, not essential to control the first and second trajectories to become perfectly parallel or even coincident. As illustrated in Figures 1c and 1d, the first and second beams (1.11, 1.12) forming the combined beam (1c1) can propagate by converging towards a focal point and intersecting the target plane (6p) within the combined spot (1s1) of predefined dimensions either upstream or downstream of the focal point. As illustrated in Figure 1e, the first and second beams could also be divergent, with the condition that they intersect the combined spot (1s1) of given diameter. The angle (2α) between first and second beams has an absolute value lower than 15° (i.e., 2α ≤ 15°), and can be lower than 10° (i.e., 2α ≤ 10°), preferably lower than 5° (i.e., 2α ≤ 5°) or even 2α = 2° ± 1°. The first and second beams are configured to hit the given target plane (6p) within a predefined combined spot (1si) as shown in Figures 1a to 1c. At the single extraction outlet (13), the first and second beams are close to one another, preferably separated by a distance of less than 30 mm, more preferably of less than 20 mm, or less than 10 mm. At the extraction outlet, the first and second beams (1.11, 1.12) can be parallel or coincident (cf. Figure 1a and 1b), convergent with the target plane (6p) located upstream or downstream of the focal point as shown in Figures 1c and 1d, respectively, or even be slightly divergent as shown in Figure 1e, as long as they both intersect the target plane (6p) within the combined spot (1s1).

[0049] At the single extraction outlet (13), the combined beam (1c1) of a cyclotron of the present invention (comprising first and second internal ion sources (12.11, 12.12)) has approximately same energy (E1) and approximately double intensity as an individual beam of a state-of-the-art cyclotron comprising a single internal ion source. For example, the combined beam (1c1) can have an energy (E1) lower than 75 MeV per nucleon (i.e., E1 ≤ 75 MeV / A), preferably lower than 10 MeV per nucleon (i.e., E1 ≤ 5 MeV / A), more preferably lower than 5 MeV per nucleon (i.e., E1 ≤ 5 MeV / A), more preferably lower than 3.5 MeV per nucleon (i.e., E1 ≤ 3.5 MeV / A). The combined beam (1c1) can have a maximum electrical current intensity (i) of at least 1 mA (i.e., i ≥ 1 mA), preferably at least 2 mA (i.e., i ≥ 2 mA), more preferably at least 3 mA (i.e., i ≥ 3 mA), more preferably at least 4 mA (i.e., i ≥ 4 mA), more preferably at least 5 mA (i.e., i ≥ 5 mA), more preferably at least 7 mA (i.e., i ≥ 7 mA), more preferably at least 10 mA (i.e., i ≥ 10 mA). For protons, the combined beam (1c1) can have at the single extraction outlet (13) a power, E1 x i, higher than 10 MeV.mA, preferably higher than 20 MeV.mA.ACCELERATING SYSTEM

[0050] The present application also concerns an accelerating system for producing a low energy, high intensity beam of charged particles, preferably selected among protons, deuterons, molecular hydrogen ion (H 2 +< ), and He ions (He 2+< or He +< ). The system comprises N cyclotrons (10.i), wherein N ≥ 2 and i = 1 to N. Each of the N cyclotrons is configured to accelerate one or two beams (1.ij, with j = 1 or 2) along a trajectory comprised in a plane normal to a corresponding Zi-axis, wherein the accelerating system is configured to combine (N + 1) or more individual beams (1.ij) accelerated from corresponding (N + 1) or more slits of internal ion sources (12.ij) by the one or more cyclotrons (10.i). All beams of the accelerating system of the present invention are preferably formed of the same charged particles.

[0051] According to the present invention, a number M of cyclotrons (10.i), with M comprised between 1 and N, are according to the present invention as discussed supra, comprising first and second internal ion sources (12.i1, 12.i2) and configured to extract a combined beam (1ci), with i = 1 to M. In total, the accelerating system can extract a number N of individual beams composed of M combined beams (1ci = 1c1 to 1cM) extracted from the M cyclotrons according to the present invention and (N - M) first beams (1.i1) extracted from the (N - M) conventional cyclotrons comprising a single internal ion source (12.i1).).

[0052] The N individual beams (1ci, 1.i) are combined to form a single multi-combined beam (1c). As shown in Figure 1d, the N individual beams (1ci, 1.i) forming the multi-combined beam (1c) are contained within a cone of aperture (2θ) of not more than 70° (i.e., 2θ ≤ 70°), preferably not more than 50° (i.e., 2θ ≤ 50°), more preferably of not more than 25°(i.e., 2θ ≤ 25°). The N individual beams are formed by a number n = ni1 + ni2 of first and second beams (1.ij) accelerated by the N cyclotrons (10.i), wherein the number of first beams (1i.1) is, ni1 = N, because all cyclotrons emit a first beam (1.i1)) and the number of second beams (1i.2) is, ni2 = M because only the cyclotrons according to the present invention emit a second beam (1.i2). The number, n , of first and second beams (1i1, 1i2) involved in the formation of the multi-combined beam (1c) is therefore n = N + M, and is comprised between (N + 1) when ni2 = M = 1 cyclotron according to the present invention, and 2N when ni2 = M = N, wherein all cyclotrons of the accelerating system are according to the present invention i.e., comprising first and second internal ion sources (12.i1, 12.i2).

[0053] The N individual beams (1ci, 1.i) form N corresponding individual spots (1si) of given diameter on the target plane (6p) contiguous to a target (6), perpendicular to an axis (X) of the cone and located at a predefined position. The N individual spots (1si) are inscribed in an ellipse defining a multi-combined spot (1s). The multi-combined spot (1s) has an area (A) lower than a predefined maximum area (Am). The area (A) is defined as the area where 90% of incoming beam particles hit the target plane (6p). The maximum area (Am) is preferably, at least 10 cm 2< , more preferably at least 50 cm 2< .

[0054] For example, as shown in Figures 3b and 3c, the system comprises respectively N = M = 2 and 3 cyclotrons and corresponding combined beams (1c1 to 1cN) formed by n = 2N = 4 and 6 first and second beams (1.i1, 1.i2, with I = 1 to N), respectively. The N combined beams (1c1 to 1cN) are combined to form a single multi-combined beam (1c), converging to the multi-combined spot (1s) at the level of the target plane (6p).

[0055] If all n first and second beams (1.1j to 1.Nj, with j = 1 or 2) have identical energy, Eij, and identical intensity, lij, then the multi-combined beam (1c) has a combined energy Ec ≅ Eij, and a combined intensity, Ic ≅ n × lij. The multi-combined beam (1c) emitted by the accelerating system of the present invention forms at the multi-combined spot (1s) a multi-combined beam (1c) of combined energy (Ec) lower than 75 MeV per nucleon (i.e., Ec ≤ 75 MeV / A), preferably lower than 10 MeV per nucleon (i.e., Ec ≤ 10 MeV / A), more preferably lower than 5 MeV per nucleon (i.e., Ec ≤ 5 MeV / A), and has a maximum combined electrical current intensity (Ic) of at least 2 mA (i.e., Ic ≥ 2 mA), preferably at least 4 mA (i.e., Ic ≥ 4 mA), preferably at least 10 mA (i.e., Ic ≥ 10 mA), more preferably at least 20 mA (i.e., Ic ≥ 20 mA) or at least 30 mA (i.e., Ic ≥ 30 mA).

[0056] In a preferred embodiment illustrated in Figures 3b, 3c, and 5b a number M1 of the N cyclotrons (10.1-10.M1) with 2 ≤ M1 ≤ N and with preferably M1 = N, are positioned side by side on a same plane normal to the Zi-axes which are parallel to one another. Alternatively, as illustrated in Figure 6b, the M1 cyclotrons are positioned on top of one another preferably albeit not necessarily tilted relative to one another, the Zi-axes of 2 adjacent cyclotrons forming an angle preferably lower than 30°. If the Zi-axes of two adjacent cyclotrons form too small an angle or are parallel, or even coincident, one or both cyclotrons are preferably equipped with a steering magnet unit (15) (e.g., formed by a dipole) located downstream of the extraction outlets to steer the two individual beams (1ci or 1.i) within the cone of aperture 2θ. As shown in Figure 3b, it is preferred to position and configure the M1 cyclotrons to generate magnetic fields having a rotational symmetry of order M1 between one another. It is preferred that the M1 cyclotrons -and even the N cyclotrons- be according to the present invention.

[0057] In a preferred embodiment allowing reduction of the cost of production and use, as well as reduction of the footprint, a number M2 of cyclotrons (10.1-10.M2) among the N cyclotrons, with 2 ≤ M2 ≤ N share one or more components. Preferably, M2 = N. For example, as shown in Figure 3b, each of the M2 cyclotrons (10.1-10.M2) comprises a dee electrode assembly (5D) and a counter dee electrode assembly (5D), wherein the accelerating system comprises a single RF-generator (7RF) configured to apply an alternating high voltage to the dee electrode assemblies of the M2 cyclotrons (10.i) to produce the accelerating electric field. Alternatively or concomitantly, as also illustrated in Figures 3c, 5a, and 5b, each of the M2 cyclotrons (10.1-10.M2) comprises coils (7C) configured to produce a magnetic field (B) passing normal to the plane (X, Y), and wherein the accelerating system comprises a single magnetic field generator (7B) configured to apply a current to the coils (7C) of the M2 cyclotrons (10.1-10.M) to produce the magnetic field (B). In an alternative embodiment illustrated in Figure 5a, that can be combined with any one or two of the foregoing embodiments, the M2 cyclotrons (10.1-10.M2) can share a yoke (14) in common to define a single magnetic flux circuit spanning over all of the M2 cyclotrons (10.1-10.M2). In yet an alternative embodiment that can be combined with any one of the foregoing embodiments, shown in Figure 6a, the M2 cyclotrons can share a pole in common.

[0058] The accelerating system of the present invention can comprise a scanner configured to scan the multi-combined spot (1s) over a predefined area of the target plane (6p). The predefined area is preferably at least 30 cm 2< , more preferably at least 100 cm 2< . For the production of epithermal neutron beams or of specific isotopes, it can be advantageous to scan the multi-combined beam over a larger area to reduce local overheating of the target (6).

[0059] Downstream of and contiguous to the target plane (6p) the accelerating system of the present invention can comprise a target (6) made of a material configured to emit upon being traversed through the multi-combined spot (1s) by the low energy, high intensity beam of protons or deuterons, either neutrons, or configured to produce specific isotopes. Alternatively, instead of a target (6), an inlet of a second accelerating system comprising at least one accelerating device can be positioned downstream and contiguous to the target plan (6p). This way, the multi-combined beam (1c) of energy, Ec, and intensity, Ic, exiting the accelerating system of the present invention can be further accelerated to reach a second energy, Ec2 > Ec, with approximately the same intensity Ic2 ≅ Ic.APPARATUS FOR APPLYING A TREATMENT BY BNCT

[0060] The present invention also concerns an apparatus illustrated in Figures 8 and 9a to 9c. for applying a treatment by boron neutron capture therapy (BNCT), comprising an accelerating system according to the present invention, a beam shaping assembly (21s), and a treatment area. The accelerating system used in the apparatus comprises a target (6) positioned downstream or upstream of and contiguous to the target plane (6p) as discussed supra. The target (6) comprise a material configured to emit neutrons upon being traversed through the multi-combined spot (1s) by the low energy, high intensity multi-combined beam (1c) of protons or deuterons. The material is preferably selected among beryllium (Be) and Lithium (Li).

[0061] The beam shaping assembly (21s) is configured to form an epithermal neutron beam (22en) and to guide the epithermal neutron beam (22en) thus formed towards a treatment zone (23). The treatment area is configured to receive and support a portion of a patient (23p) to be treated by the epithermal neutron beam within the treatment zone (23). Figures 8, 9a to 9c show a treatment area supporting the patient in a supine position with the head located within the treatment zone (23). Other configurations are of course possible, such as supporting the patient is a sitting position, or kneeling position, and the like, as long as the tumoural cells to be treated by BNCT is stably maintained within the treatment zone (23) during the treatment.

[0062] The beam shaping assembly (21s) can comprise a collimator (21c) comprising an outlet (21o) of the shaping assembly (21s). The outlet (21o) is located at a distance (L23) from the treatment zone (23) preferably less than 400 mm, more preferably less than 200 mm, most preferably less than 125 mm.

[0063] Referring to Figure 7 plotting the neutron yield as a function of the energy of the beam of protons (p) or deuterons (d) used to bombard different targets (6), it can be seen that relatively low values of the energy, Ec, of the combined or multi-combined beam (1ci, 1c) are required to get a maximum yield. The irradiation time decreases with increasing current intensity of the (multi-) combined beam (1c1, 1c). The current intensity, Ic, of the beam is preferably at least 5 mA, more preferably at least 6 mA, more preferably at least 7 mA, preferably at least 10 mA, or at least 20 mA and more. The combined beam (1c1) of the cyclotron of the present invention and the multi-combined beams (1c) produced by the accelerating system of the present invention can produce beams of such low energy values and high current intensity values.

[0064] To control the orientation of the epithermal beam (22en) relative to the treatment zone (23), the apparatus of the present invention can be configured to move the epithermal beam (22en) and / or to move the treatment zone (23) relative to one another. For example, as illustrated in Figure 9a, the treatment area can be moved together with the patient (23p) relative to the epithermal beam (22en), by translation along the X-axis and / or rotation about the Y-axis and / or about the Z-axis (cf. Figures 9a to 9c for the orientation of the axes (X, Y, Z)).

[0065] As shown in Figures 9b and 9c, the apparatus can be configured to move the epithermal beam (22en) relative to the treatment zone (23). This can be achieved by rotating the accelerating system together with the beam shaping assembly (21s) about the Y-axis, as shown in Figure 9b and / or about the X-axis, as shown in Figure 9c. Of course, the apparatus can be configured to move both epithermal beam (22en) and treatment area, so that multiple degrees of freedom are available to best bombard the pateint's tumoural cells maintained within the treatment zone.

[0066] The accelerating system of the apparatus is preferably equipped with a scanner configured to scan the multi-combined spot (1s) over a predefined area of the target plane (6p) of preferably at least 30 cm 2< , more preferably at least 100 cm 2< . This allows spreading and homogenising the power density of the beam over a larger area of the target plane (6p) and over a larger volume of the target (6). # Feature 1Combined beam1.iIndividual beam from a conventional cyclotron of the accelerating system1.ijj th< Individual beam of a i th< cyclotron, with i = 1 to N and j = 1 or 21ciCombined beam exiting a i th< cyclotron formed by beams 1.i1 and 1.i21cMulti-combined beam combined from several cyclotrons1siCombined spot of a combined beam 1ci1sijIndividual spot of an individual beam 1.ij1DDee electrode system5CCounter dee electrode assembly5DDee electrode assembly5GGap6Target or following beam line entry point6pTarget plane7BGenerator for the coils7LLocal asymmetry7MLocal magnetic source7RFGenerator for the dee electrode system10.ii th< cyclotron with i = 1 to N12.ij...12.ij th< Internal ion source of the i th< cyclotron, with i = 1 to N and j = 1 or 213Single extraction outlet of a cyclotron14Yoke15Beam bending unit21cCollimator of the beam shaping assembly21mNeutron moderator of the beam shaping assembly21oOutlet of the beam shaping assembly21sBeam shaping assembly22fnFast neutron beam22enEpithermal neturon beam23Treatment zone23pPatient30Rotating mechanismEij, Ei, EcEnergy of the 1 st< / 2 nd< beam 1.ij, of the combined beam 1ci and of the multi-combined beam (1c)lij, li, IcCurrent intensity of the 1 st< / 2 nd< beam 1.ij, of the combined beam 1ci and of the multi-combined beam (1c)L23Distance between outlet of the beam shaping assembly and the treatment zoneMNumber of cyclotrons according to the invention in the accelerating systemM1Number of cyclotrons having a specified relative positioningM2Number of cyclotrons sharing a componentNNumber of cyclotrons in the accelerating systemnNumber of first and second beams forming the multi-combined beam, n = ni1 + ni2ni1, ni2Number of first and second beams forming the multi-combined beamiRefers to the i th< cyclotron with i = 1 to NjRefers to the j th< internal ion source and corresponding individual beam, with j = 1 or 2XCone axisZiCentral axis of the i th< cyclotronαHalf aperture of the cone of the combined beam (1ci)θHalf aperture of the cone of the multi-combined beam (1c)

Examples

Embodiment Construction

[0032]As shown in Figures 2 and 3a, the present invention concerns a cyclotron (10.1) centred on a Z1-axis for generating a combined beam (1c1) of charged particles. The cyclotron comprises first and second internal ion sources (12.11, 12.12), a dee electrode assembly (5D) and a counter dee electrode assembly (5C), a generator (7RF) configured to apply an alternating high voltage between the dee electrode assembly (5D) and the counter dee (5C), and a magnetic field generator (7B, 7C) configured to produce a magnetic field parallel to the Z1-axis.

[0033]The first internal ion source (12.11) is configured to produce charged particles and to introduce charged particles into the cyclotron through a first slit to form a first beam (1.11) of the charged particles. The second internal ion source (12.12) is configured to produce the same charged particles as the first internal ion source (12.11) and, at a same time as the first internal ion source (12.11), to introduce the charged particles ...

Claims

1. A cyclotron (10.1) centred on a Z1-axis for generating a combined beam (1c1) of charged particles, comprising, • a first internal ion source (12.11) configured to produce charged particles selected among protons, deuterons, molecular hydrogen ion (H2+), and He ions (He2+ or He+) and to introduce the charged particles into the cyclotron through a first slit to form a first beam (1.11) of the charged particles, • a second internal ion source (12.12) configured to produce the same charged particles as the first internal ion source (12.11) and, at a same time as the first internal ion source (12.11), to introduce the charged particles into the cyclotron through a second slit to form a second beam (1.12) of the charged particles, wherein the second internal ion source (12.12) is positioned at an opposite side from the first internal ion source (12.11) relative to the Z1-axis, • a dee electrode assembly (5D) and a counter dee electrode assembly (5C) separated from each other by a gap (5G), • a generator (7RF) configured to apply an alternating high voltage to the dee electrode assembly (5D) for producing an accelerating electric field in the gap (5G), for accelerating the first and second beams (1.11, 1.12) of charged particles, • a magnetic field system (7B, 7C) configured to produce a magnetic field parallel to the Z1-axis, to guide the first and second beams (1.11, 1.12) of charged particles along first and second spiralling trajectories, respectively, passing through the accelerating electric field in the gap (5G) to accelerate the first and second beams of charged particles at each passage therethrough, characterized in that, the cyclotron (10.1) is configured to create a local asymmetry (7L) of the accelerating electric field and / or of the magnetic field configured to drive through a single extraction outlet (13) the combined beam (1c1) formed by the first and second beams (1.11, 1.12) along their first and second trajectories, wherein the directions at a level of the extraction outlet (13) of the first and second beams (1.11, 1.12) forming the combined beam (1c1) form an angle (2 α) on a plane normal to the Z1-axis, lower than 15°, preferably lower than 10°, more preferably lower than 5°, more preferably the two directions are substantially parallel with an angle of 2° ± 1°, and allowing the two beams to intersect a given target plane (6p) wjthin a combined spot (1s1) of a given diameter.

2. Cyclotron according to claim 1, wherein the magnetic field system (7B, 7C) comprises a pair of coils (7C) powered by a generator (7B) and surrounding a volume of a ferromagnetic material having a thickness measured along the Z1-axis and wherein the local asymmetry (7L) of the magnetic field is created by a local variation of the thickness and / or of the shape of the ferromagnetic material and / or by one or more local magnetic sources (7M) selected among coils and permanent magnets.

3. Cyclotron according to claim 1 or 2, wherein the local asymmetry of the accelerating electric field is created by, • a local difference of a gap geometry between the dee and counter dee electrode assemblies (5D, 5C), and / or • a non-symmetrical geometry and / or location of the first and second internal ion sources (12.11, 12.12) relative to the Z1-axis.

4. Cyclotron according to claim 3, wherein the non-symmetrical location of the first and second sources (12.11, 12.12) relative to the Z1-axis is created at least partly by an offset of a position of the second internal ion source (12.12) from axial symmetry with a position of the first internal ion source (12.11) relative to the Z1-axis, wherein the offset is either, • in a circumferential direction relative to the Z1-axis, or • in a radial direction relative to the Z1-axis, or • a combination of radial and circumferential directions relative to the Z1-axis.

5. Cyclotron according to anyone of the preceding claims, wherein the charged particles are selected among protons, deuterons.

6. Cyclotron according to anyone of the preceding claims, wherein the combined beam (1c1) has at the single extraction outlet (13) an energy (E1) lower than 75 MeV per nucleon (i.e., E1 ≤ 75 MeV / A), preferably lower than 5 MeV per nucleon (i.e., E1 ≤ 5 MeV / A), and has an electrical current intensity (i) of at least 1 mA (i.e., i ≥ 1 mA), preferably at least 2 mA (i.e., i ≥ 2 mA), preferably at least 5 mA (i.e., i ≥ 5 mA), more preferably at least 10 mA (i.e., i ≥ 10 mA).

7. Accelerating system for producing a low energy, high intensity beam of charged particles, preferably selected among protons, deuterons, molecular hydrogen ion (H2+), and He ions (He2+ or He+)., using N cyclotrons (10.i), wherein N ≥ 2 and i = 1 to N, wherein each of the N cyclotrons is configured to emit an individual beam of same charged particles and of given energy (Eij) along a trajectory comprised in a plane normal to a corresponding Zi-axis, wherein the accelerating system is configured to combine the N individual beams (1ci, 1i) accelerated from the N cyclotrons (10.i), characterized in that, a number M of the N cyclotrons (10.i), with M = 1 to N, are according to any one of the preceding claims whose individual beam is the combined beam (1ci), and in that, the N individual beams form a multi-combined beam (1c) and, • are contained within a cone of aperture (2θ) of not more than 70° (i.e., 2θ ≤ 70°), preferably not more than 50° (i.e., 2θ ≤ 50°), more preferably of not more than 25° (i.e., 2θ ≤ 25°), and • form N individual spots (1sij) of given diameter on the target plane (6p) contiguous to a target (6), perpendicular to an axis (X) of the cone and located at a predefined position, wherein the N individual spots are inscribed in an ellipse of area (A) lower than a predefined maximum area (Am) which defines a multi-combined spot (1s), wherein the area (A) is defined as the area where 90% of incoming beam particles hit the target plane (6p) and wherein the maximum area (Am) is preferably, at least 10 cm2, more preferably at least 50 cm2. and in that, the multi-combined beam (1c) has at the multi-combined spot (1s) an energy (Ec) lower than 75 MeV per nucleon (i.e., Ec ≤ 75 MeV / A), preferably lower than 5 MeV per nucleon (i.e., Ec ≤ 5 MeV / A), and has an electrical current intensity (Ic) of at least 2 mA (i.e., Ic ≥ 2 mA), preferably at least 4 mA (i.e., Ic ≥ 4 mA), preferably at least 10 mA (i.e., i ≥ 10 mA), more preferably at least 20 mA (i.e., i ≥ 20 mA).

8. Accelerating system according to claim 7, comprising M1 cyclotrons (10.1-10.M1) among the N cyclotrons with 2 ≤ M1 ≤ N, • are positioned side by side on a same plane normal to the Zi-axes which are parallel to one another, or • are positioned on top of one another preferably tilted relative to one another, the Zi-axes of 2 adjacent cyclotrons forming an angle preferably lower than 30°, and / or • wherein the M1 cyclotrons are preferably positioned and configured to generate magnetic fields having a rotational symmetry of order M1 between one another.

9. Accelerating system according to claim 7 or 8, wherein M2 cyclotrons (10.1-10.M2) among the N cyclotrons, with 2 ≤ M2 ≤ N share components in common as follows, • each of the M2 cyclotrons (10.1-10.M2) comprises a dee electrode assembly (5D) and a counter dee electrode assembly (5D), wherein the accelerating system comprises a single RF-generator (7RF) configured to apply an alternating high voltage to the dee electrode assemblies of the M2 cyclotrons (10.i) to produce the accelerating electric field, and / or • each of the M2 cyclotrons (10.1-10.M2) comprises coils (7C) configured to produce a magnetic field (B) passing normal to the plane (X, Y), and wherein the accelerating system comprises a single magnetic field generator (7B) configured to apply a current to the coils (7C) of the M2 cyclotrons (10.1-10.M) to produce the magnetic field (B), and / or • the M2 cyclotrons (10.1-10.M2) share a yoke (14) in common to define a single magnetic flux circuit spanning over all of the M2 cyclotrons (10.1-10.M2).

10. Accelerating system according to any one of claim 7 to 9, comprising a scanner configured to scan the multi-combined spot (1s) over a predefined area of the target plane (6p), wherein the predefined area is preferably at least 30 cm2, more preferably at least 100 cm2.

11. Accelerating system according to any one of claim 7 to 10, comprising a target (6) contiguous to the target plane (6p) and made of a material configured to emit upon being traversed through the multi-combined spot (1s) by the low or medium energy, high intensity beam of protons or deuterons, either neutrons, or specific isotopes.

12. Accelerating system according to any one of claim 7 to 9, wherein the target plane (6p) is upstream of and contiguous to an inlet of a second accelerating system comprising at least one accelerating device.

13. Apparatus for applying a treatment by boron neutron capture therapy (BNCT), comprising, • a target (6) made of a material configured to emit neutrons upon being traversed through by a beam of accelerated protons or deuterons, wherein the material is preferably selected among beryllium (Be) and Lithium (Li), • either, ∘ the cyclotron (10.1) according to any one of claims 1 to 6, configured to emit a combined beam (1c1) of protons or deuterons; or ∘ the accelerating system according to any one of claims 7 to 11, configured to emit a multi-combined beam (1c) of protons or deuterons, • a beam shaping assembly (21s) configured to form an epithermal neutron beam (22en) and to guide the epithermal neutron beam (22en) thus formed towards a treatment zone (23), and • a treatment area (23) configured to receive and support a portion of a patient (23p) to be treated by the epithermal neutron beam within the treatment zone (23).

14. Apparatus according to claim 13, wherein the beam shaping assembly (21s) comprises a collimator (21c) comprising an outlet (21o) of the shaping assembly (21s) and wherein the outlet (21o) is located at a distance (L23) from the treatment zone (23) preferably less than 400 mm, preferably less than 200 mm, more preferably, less than 125 mm.

15. Apparatus according to claim 13 or 14, configured to move the epithermal beam (22en) relative to the treatment zone (23), • by moving the treatment zone (23) and the patient (23p) relative to the epithermal beam (22en) whose position remains fixed, and / or • by moving the epithermal beam (22en) relative to the treatment zone (23) whose position remains fixed, wherein the apparatus comprises a rotating mechanism (30), configured to rotate and guide the combined beam (1c) and epithermal beam (22eb), or • by moving both the treatment zone (23) and the epithermal beam (22en) relative to one another as defined supra.

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