CN115887943A - Ion flash therapeutic device with continuous variable energy scanning - Google Patents

Abstract

The invention relates to an ion flash therapy device with continuous variable energy scanning, which is used for releasing particle beams of specific ions to a volume of a target area to be treated, and comprises: an injector; a synchrotron, wherein the synchrotron continuously stimulates particles to overflow from the transverse phase space stable region into the electrostatic deflector through the radio frequency stimulation device in the whole process that the particle energy passes through a preset variable energy range, and the particles are separated from the synchrotron under the action of the electrostatic deflector, wherein the energy time interval and the energy numerical value interval of the particles overflowing from the transverse phase space stable region are narrow enough to be considered as meeting the requirement of continuous energy extraction; and a beam delivery system that receives particles extracted from the synchrotron and expands the beam transverse scan range, and then provides it to the treatment target volume; the synchrotron also comprises a beam intensity measuring device for measuring the beam intensity in the synchrotron in real time without cutoff.

Description

Ion flash therapeutic device with continuous variable energy scanning

Technical Field

The invention relates to an ion flash therapy device, in particular to an ion flash therapy device with continuous variable energy scanning.

Background

Flash therapy (flash radiotherapy) is a non-invasive treatment that delivers beam current to a cancer site in the human body at extremely high dose rates (typically >40 Gy/s) in an extremely short time (on the order of hundreds of ms, within 500 ms). The protective capability to normal tissues is greatly improved while the tumor treatment effect is ensured. Fig. 1A and 1B show a comparison of conventional radiotherapy (light arrows in the figure) and ion flash therapy (dark arrows in the figure) in terms of single treatment time and the number of treatments required for one treatment session, respectively. Compared with the conventional radiotherapy, the flash therapy has short treatment time, greatly reduces the treatment times required by one treatment course, and improves the treatment convenience of patients and the hospital benefit.

Flash therapy was first noted by researchers as early as 1959, when Dewey et al found that oxygen-enriched cells were less sensitive to radiation after increasing radiation dose rates. During the period between 1967 and 1978, researchers studied and analyzed the difference of cell survival curves of in vitro cells exposed to the radiation with the extremely high dose rate under the condition of different oxygen concentrations, and basically tried to explain the reason of the decrease of the cell sensitivity to the radiation caused by the increase of the radiation dose rate by using the oxygen consumption theory, and finally, the more breakthrough result cannot be found. In 2014, related studies have finally progressed from in vitro cell and tissue experiments to animal experiments, and the name of flash therapy was also generated at this time point. In 2014, favaudon et al revealed different responses of mouse normal and tumor tissues to high dose rates. In 2019, bourhis et al applied flash therapy to the first patients all over the world, one ulcer lesion with a diameter of 3.5cm was treated in a skin lymphoma patient 75 years old by applying total dose 15Gy radiotherapy within 90ms by using a 5.6MeV linear accelerator, the tumor was completely relieved after 36 days of treatment, and no other visible toxic reaction was caused after 5 months except for reduction of irradiated hair. From this, the presence of the flash effect was confirmed again by the results of experiments, clinical trials, etc.

Compared with photon or electron radiotherapy, the ion (proton, heavy ion, etc.) has better spatial dose distribution because the dose distribution has the characteristic of 'Bragg peak' in the radiotherapy, so that the ion radiotherapy can mainly deposit energy near the tumor, thereby avoiding the damage to normal tissue cells. Ion flash therapy can combine the advantages of more optimal spatial dose distribution of ions and the unique temporal effects of flash therapy, and thus is a hot research point for the current radiotherapy internationally.

It has been confirmed through experiments that electron beam flash therapy has a stronger protective effect on normal tissues than conventional radiotherapy, and has the same tumor treatment effect, the experimental progress of ion flash therapy is slower, mainly because flash therapy has a higher requirement on the dose rate, and the existing equipment is difficult to meet the requirement of ion flash therapy. On 25/10/2021, the first proton flash clinical trial FAST-01 (flash radiation therapy for bone metastasis cancer) worldwide was conducted in cooperation with the healthy proton therapy center at the university of California/Cincinnati and Wacinatiti, inc. Validan, cincinnati. The beam current meeting the requirement of the dose rate of the ion FLASH therapy (FLASH) in the experiment is provided by an adjusted Wairan ProBeam proton treatment system (superconducting cyclotron). In order to meet the dose rate requirement, a mode of fixed high-energy (250 MeV) irradiation is adopted for the beam distribution system of probe in the experiment, because the beam loss of the beam distribution system is serious during low-energy output, the dose rate requirement cannot be met. The high-energy projection type irradiation mode deposits more dose outside the volume of the target area to be treated (tumor target area), and cannot give full play to the advantage of spatial dose distribution of ions.

Unlike the superconducting cyclotron used in the clinical experiment of proton flash therapy, the synchrotron is a device which makes charged particles move along a fixed circular orbit under the control of magnetic field force in high vacuum and continuously accelerate (raise energy) under the action of the electric field force to reach high energy. In order to maintain the stable particle orbit in the energy increasing process, the synchrotron needs to keep the magnetic field amplitude and the electric field frequency to change synchronously with the particle energy, and finally the particle beam is led out to provide various particle beams and radiation rays for the fields of basic scientific research, clinical medicine and industrial production. The synchrotron can well regulate the energy of the extracted beam, the energy regulation of a rear end energy reducer is not needed, and the utilization rate of the beam is greatly improved.

With the increasing requirements and research on the application of the extracted particle beam at the terminal, especially in the aspect of three-dimensional point scanning of cancer treatment, the problem of multi-energy slow extraction by conformal irradiation of a shielding body is solved, people solve the problems of secondary particle generation and larger residual radiation, but the problem of long energy switching time still exists, if the characteristic that the synchronous accelerator can actively adjust the energy of the extracted beam can be fully utilized to realize 'extraction and energy change', particles with continuously changed energy can be extracted, so that the characteristic that the synchronous accelerator can actively adjust the energy and the time characteristic of rapid energy adjustment are combined, the average dose rate in the radioactive treatment process of the synchronous accelerator is improved, the application scene of the extracted beam of the synchronous accelerator is further enriched, and a possible solution is provided for the application of ultrahigh dose rate radiotherapy (flash therapy).

To this end, the applicant of the present application filed a patent application entitled "synchrotron continuous variable energy extraction method" at the same date as the present application at the university of qinghua, which proposes a synchrotron continuous variable energy extraction method in which particles are continuously excited by a radio frequency excitation device (RF-KO) to overflow from a transverse phase space stabilization zone into an electrostatic deflector and are separated from a circular orbit of a synchrotron under the action of the electrostatic deflector during the entire process in which the particle energy passes through a predetermined variable energy range, wherein the energy time interval and the energy value interval of the particles overflowing from the transverse phase space stabilization zone are sufficiently narrow to be able to be regarded as requirements for continuous energy extraction.

The applicant of the present application also filed a patent application entitled "ion flash therapy apparatus with discrete spot scanning" on the same day as the present application at the university of qinghua, which proposed an ion flash therapy apparatus with discrete spot scanning. A synchrotron of the ion flash therapy device with discrete point scanning separates a plurality of discrete beam clusters with particle energy at a preset extraction energy value from the particle beam clusters running in the circular orbit at intervals of time by manipulating a longitudinal phase space, and extracts the discrete beam clusters out of the circular orbit of the synchrotron. The beam delivery system of the ion flash apparatus receives the particles extracted from the synchrotron and expands the beam lateral scan range before providing it to the treatment target volume. A beam intensity measuring device of the synchrotron measures the longitudinal density distribution of the beam in the circular orbit in real time without truncation, and sets the number of particles in discrete beam groups to be separated according to the measured longitudinal density distribution of the beam, thereby setting the number of particles led out from each discrete scanning point in the volume of a target area to be treated according to the given ion flash treatment dose rate.

Therefore, it is desirable to provide a method and a corresponding apparatus for ion flash therapy with continuous variable energy extraction based on the above, which can have faster energy adjustment speed, lower beam loss and relatively acceptable cost, and can achieve the purpose of reducing energy switching time and increasing dose rate, and finally achieve that the dose rate at the treatment target volume meets the requirement of ion flash therapy.

Disclosure of Invention

In order to solve the above technical problem, the present invention provides a continuous variable energy scanning ion flash therapy device for releasing a particle beam of specific ions to a treatment target volume, the continuous variable energy scanning ion flash therapy device comprising: an injector for providing a particle beam of specific ions; a synchrotron, which receives the particle beam from the injector and enables the particles to stably run in a circular orbit of the synchrotron through the control of a high-frequency system and the strength of dipolar iron, quadrupole iron and hexapole ferromagnetic fields, wherein the synchrotron continuously stimulates the particles to overflow from a transverse phase space stable region into an electrostatic deflector and to be separated from the synchrotron under the action of the electrostatic deflector in the whole process that the particle energy passes through a preset energy change range through a radio frequency stimulation device (RF-KO), and the energy time interval and the energy numerical interval of the particles overflowing from the transverse phase space stable region are narrow enough to be considered as meeting the requirement of continuous energy extraction; and a beam delivery system that receives particles extracted from the synchrotron and expands the beam transverse scan range, and then provides it to the treatment target volume; the synchrotron also comprises a beam intensity measuring device for measuring the beam intensity in the synchrotron in real time without truncation, and a relation curve of extraction energy and extraction process time can be calculated and set according to the measured real-time beam intensity and the given ion flash treatment dose rate, so that the synchrotron can provide the extraction beam meeting the requirement of the ion flash treatment dose rate.

The ion flash therapy device adopting continuous variable energy scanning adopts the synchrotron, and the synchrotron realizes continuous and rapid change of the energy of the extracted particles by continuously exciting the particles to overflow from the stable region of the transverse phase space. Due to the bragg peak effect of the dose distribution, a specific energy of the extracted particles corresponds to a specific longitudinal position of the treatment target volume. On the basis, the beam distribution system is used for expanding the transverse beam scanning range, so that the specific transverse position of the volume of the target area to be treated can be covered, namely the whole volume of the target area to be treated can be accurately covered in a three-dimensional space.

The ion flash therapy device for continuous variable energy scanning realizes real-time measurement of the beam intensity in the synchrotron without truncation through the beam intensity measuring device. The real-time extraction particle dose rate can be calculated based on the measurement results, so that a curve of the extraction energy versus the extraction process time can be set, i.e. how long the extraction particles are irradiated at each three-dimensional spatial position of the treatment target volume at a high energy level.

Preferably, the injector is a linear injector or another synchrocyclotron. Linear implanters include, for example, ion sources, linear accelerators, and beam transport lines. Particles produced by the ion source are accelerated by the linac and then provided to the synchrotron via the beam transport line.

In a preferred embodiment of the ion flash therapy device with continuous variable energy scanning according to the present invention, the beam intensity measuring device is a dc power transformer. The beam intensity measuring device calculates the particle number reduction rate in the annular track, namely the particle number extraction rate, according to the measured beam intensity change, so that the dose rate of the extracted particles is converted. The extracted dose rate can be controlled by the synchrotron in real time under the real-time monitoring of the beam intensity measuring device.

In the whole process that the particle energy passes through a preset variable energy range, the synchrotron extracts particle beams with corresponding energy corresponding to different longitudinal positions of a treatment target area volume, and the beam distribution system expands the beam transverse scanning range through a scattering method and/or a point scanning method. The scattering method expands the beam transverse scanning range by using scattering objects to scatter or nonlinear magnets, and the point scanning method expands the beam transverse scanning range by using transverse scanning equipment, wherein the transverse scanning equipment comprises at least one of a scanning magnet, a resonant cavity and a scanning electric field.

Drawings

Embodiments of the present invention are explained below with reference to the drawings. In the drawings:

figure 1 schematically shows a schematic diagram of a continuously variable energy scanning ion flash therapy device according to the present invention;

fig. 1A and 1B show a comparison of conventional radiotherapy (light arrows in the figure) and ion flash therapy (dark arrows in the figure) in terms of single treatment time and the number of treatments required for one treatment session, respectively.

Detailed Description

The present invention is explained in detail below with reference to the accompanying drawings. Fig. 1 schematically shows a schematic diagram of a continuously variable energy scanning ion flash therapy device according to the present invention.

The ion flash therapy device for continuous variable energy scanning according to the invention realizes the continuous variable energy scanning based on the synchrotron 20, and comprises: the system comprises an injector 10, a synchrotron 20, a beam distribution system 50 and a beam intensity measuring device for measuring the beam intensity in the synchrotron 20 in real time without interruption. The synchrotron 20 receives the particle beam from the injector 10 and makes the particles stably run in the circular orbit of the synchrotron 20 through the control of the high frequency system and the strength of the dipolar, quadrupolar and hexapolar ferromagnetic fields, wherein the synchrotron 20 continuously excites the particles to overflow from the transverse phase space stable region to enter the electrostatic deflector 23 through the radio frequency excitation device 22 in the whole process of the particle energy passing through the preset variable energy range and separates from the circular orbit of the synchrotron 20 under the action of the electrostatic deflector 23, wherein the energy time interval and the energy numerical interval of the particles overflowing from the transverse phase space stable region are narrow enough to meet the requirement of continuous energy extraction.

The beam intensity measuring device 21 (not shown in the figure) is, for example, a direct current transformer (DCCT), and is configured to measure the beam intensity in the synchrotron 20 without interruption, further calculate the number of the particles in the ring according to the measured beam intensity change, obtain the rate of the number of the extracted particles according to the rate of reduction of the number of the particles in the ring track, and further obtain the dose rate of the extracted particles, so as to adjust the rate of the extracted particles by adjusting parameters such as the extraction process time, and obtain the extracted beam meeting the dose rate requirement of the ion flash therapy.

The implanter 10 is illustratively comprised of an ion source 11, a beam transport line 12, and a linear accelerator 13.

In the ion flash therapy device with continuous variable energy scanning, the radio frequency excitation device 22 continuously excites particles to overflow from the transverse phase space stable region to enter the electrostatic deflector 23 and to be separated from the circular track of the synchrotron 20 under the action of the electrostatic deflector 23 and the extraction cutting magnet 25, and compared with the mode that the excited particles overflow from the longitudinal phase space stable region, the active adjustment and continuous change of the energy of the particles extracted by the synchrotron 20 can be realized.

By means of the continuous energy-varying extraction method, the synchrotron 20 actively adjusts the energy of the extracted particles, and the extracted particles with different energies realize longitudinal layered scanning at the treatment target area in the treatment room 60. The beam delivery system 50 receives the particles extracted from the synchrotron 20 and extends the beam lateral scan range, which provides the particles to the entire treatment target volume in space.

The extension of the beam flow transverse scanning range can take the form of a scatter method or a point scan method. The scattering method is to use scatterer scattering or nonlinear magnet to transversely expand the beam (generally in mm level) from the synchrotron 20, so as to satisfy the irradiation of the treatment target area in a large volume range (generally in cm level). The spot scanning method is to use a scanning magnet, a resonant cavity, a scanning electric field, and other transverse scanning devices (here, the "transverse" refers to a plane perpendicular to the particle forward direction) to laterally expand the coverage area of the beam extracted from the synchrotron 20, so as to satisfy the irradiation of a large range (generally cm level) of the treatment target volume.

Flash therapy is to achieve very high dose rate (typically >40 Gy/s) irradiation at the treatment target volume for a short time (on the order of hundreds of ms, within 500 ms), which can be calculated according to the following equation:

where D is the total dose received within the treatment target volume and T is the total time of target irradiation.

For the beam distribution mode of point scanning, the total dose received in the target area can be divided into the sum of the dose values received by a plurality of different points, namely sigma _n D _n The dose rate can then be calculated according to:

wherein the total time T of target irradiation can be divided into beam timing T of different point scanning _n Interval time of scanning T _slew And energy switching time T for different scan depths _{energy switch,m} 。

For the scatter method, the illumination and scan interval time for different points can be omitted, so that the whole scanned target area can be covered with a shorter time T, but additional beam loss due to scatter may be introduced, resulting in a reduction of the total dose D received in the target area.

The time required by the energy change in the scanning process at the target station is shortened by continuously leading out ions by the energy change, the dose value D required in the irradiation time T and the corresponding particle number N are calculated according to the size of the target area by a scattering or point scanning method, the number of storage particles required to be led out from the annular track in the irradiation time is calculated according to the transmission efficiency and the particle leading-out efficiency of a beam distribution system, the change of the number of the storage particles in the ring is observed in real time by DCCT, relevant parameters (RF-KO strength, energy change leading-out time, quadrupole iron strength, hexapole iron strength and the like) led out by the continuous energy change are adjusted, and finally the dose rate at the treatment target area is ensured to meet the requirement of the flash therapy dose rate.

While embodiments of the present invention have been shown and described, it will be understood by those of ordinary skill in the art that: many changes, modifications, substitutions, variations and any combination of these embodiments may be made without departing from the principles and spirit of the invention, the scope of which is defined by the claims and their equivalents.

List of reference numerals

10. Injector

11. Ion source

12. Linear accelerator

13. Beam transportation line

20. Synchrotron

21. Beam intensity measuring device

22. Radio frequency excitation device

23. Electrostatic deflector

24. Leading-out cutting magnet

25. Magnetic alloy cavity

50. Beam flow distribution system

60. A treatment room.

Claims (11)

1. A continuous variable energy scanning ion flash therapy device for delivering a particle beam of specific ions to a treatment target volume, the continuous variable energy scanning ion flash therapy device comprising:

an injector (10) for providing a particle beam of specific ions;

a synchrotron (20) which receives the particle beam from the injector (10) and enables the particles to stably run in a circular orbit of the synchrotron (20) through the control of a high-frequency system and the strength of dipolar, quadrupolar and hexapolar ferromagnetic fields, wherein the synchrotron (20) continuously stimulates the particles to overflow from a transverse phase space stable region to enter an electrostatic deflector (23) through a radio frequency excitation device (22) in the whole process of the particle energy passing through a preset energy change range and separates from the synchrotron (20) under the action of the electrostatic deflector (23), wherein the energy time interval and the energy numerical interval of the particles overflowing from the transverse phase space stable region are narrow enough to be considered as meeting the requirement of continuous energy extraction; and

a beam delivery system (50) that receives particles extracted from the synchrotron (20) and expands the beam lateral scan range before providing it to the treatment target volume;

the synchrotron (20) also comprises a beam intensity measuring device (21) for measuring the beam intensity in the synchrotron (20) in real time without truncation, and a relation curve of extraction energy and extraction process time can be calculated and set according to the measured real-time beam intensity and the given ion flash treatment dose rate, so that the synchrotron (20) gives the extraction beam meeting the requirement of the ion flash treatment dose rate.

2. The ion flash therapy device of claim 1, wherein the injector (10) is a linear injector or another synchrocyclotron.

3. The apparatus of claim 2, wherein the linear implanter comprises an ion source (11), a linear accelerator (12) and a beam transport line (13).

4. The apparatus according to any of claims 1 to 3, wherein the beam intensity measuring device (21) is a DC intensity transformer.

5. The apparatus for ion flash therapy according to any one of claims 1 to 3, wherein the beam intensity measuring means (21) calculates a reduction rate of the number of particles in the circular orbit as an extracted particle number rate from the measured beam intensity variation, thereby obtaining the dose rate of the extracted particles.

6. The apparatus according to any of claims 1 to 3, wherein the synchrotron (20) extracts particle beams of respective energies corresponding to different longitudinal positions of the treatment target volume throughout the course of their energy passing through the predetermined range of energies.

7. The apparatus for ion flash therapy according to any one of claims 1 to 3, wherein said beam distribution system (50) extends the beam lateral scan range by a scattering method.

8. The apparatus for ion flash therapy according to any one of claims 1 to 3, wherein the beam distribution system (50) extends the beam lateral scan range by a point scan method.

9. The apparatus for ion flash therapy with continuous variable energy scanning according to any one of claims 1 to 3, wherein the beam distribution system (50) expands the beam lateral scan range by a scattering method and a point scan method.

10. The apparatus of claim 7, wherein the beam distribution system (50) extends the beam lateral scan range using scatterer scattering or a non-linear magnet.

11. The apparatus of claim 8, wherein the beam delivery system (50) extends the beam lateral scan range using a lateral scanning device comprising at least one of a scanning magnet, a resonant cavity, and a scanning electric field.

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