Particle beam monitoring device for flash radiotherapy based on the cherenkov effect

Abstract

The present invention relates to a particle beam monitoring device for FLASH radiotherapy based on the Cherenkov Effect, comprising a Cherenkov light radiator (1), which is transparent in the wavelength range of 350–600 nm, formed of a material having an atomic number less than or equal to 40, configured to receive a beam of charged particles having an energy in the range of 1 MeV to 250 MeV; and a light detection system comprising a photodetector (2) when the Cherenkov angle is less than the total internal reflection angle, or a photodetector (2) and an optical coupling material (3) when the Cherenkov angle is greater than the total internal reflection angle, in which the photodetector (2) is configured to detect wavelengths in the range of 350–600 nm and has a temporal resolution in the range of 10 to 99 ns.

Description

[0001] DESCRIPTION

[0002] "PARTICLE BEAM MONITORING DEVICE FOR FLASH RADIOTHERAPY BASED ON THE CHERENKOV EFFECT"

[0003] TECHNICAL FIELD

[0004] The present invention relates to a particle beam monitoring device for FLASH Radiotherapy based on the Cherenkov ef fect . This device enables real-time monitoring of high-intensity beams .

[0005] BACKGROUND OF THE INVENTION

[0006] Currently, cancer is the third leading cause of death worldwide , with over 19 million new cases and nearly 10 million deaths reported in 2020 . Based on this scenario , it is estimated that the number of new cases and deaths will continue to rise in the coming years . As such, one of the challenges of modern medicine is to reverse this trend .

[0007] Various treatment options are known, such as surgery, chemotherapy, and radiotherapy . Radiotherapy is currently one of the most widely used worldwide , accounting for approximately 50% of prescribed therapies . Radiation therapy is based on the use of ioni zing radiation that deposits its energy in tissues and consequently induces the death of cancer cells . Thi s radiation can be delivered to the body as either external beam radiation or internal radiation . In external radiation, high-energy beams are directed at the tumour site , whereas in internal radiation, radioactive sources are implanted to deliver the dose within the body, near the tumour.

[0008] Although there have been several advances in radiation therapy over the past decades, side effects remain a significant issue for patients in both the short and long term, and consequently, they affect their quality of life.

[0009] Ashraf, M. R., et al. "Dosimetry for FLASH Radiotherapy: A Review of Tools and the Role of Radioluminescence and Cherenkov Emission." Frontiers in Physics 8:328. (2020) (doi: 10.3389 / fphy.2020.00328 ) discuss the growing importance of FLASH Radiotherapy techniques over recent years. FLASH therapies are based on the delivery of radiation at ultra-high dose rates (> 40 Gy / s) , in contrast to conventional radiotherapy, which typically delivers at approximately 0.03 Gy / s. In 2014, Favaudon et al. demonstrated in mice that high dose-rate radiation achieves similar tumour control as conventional radiation therapy while significantly sparing healthy tissues — an effect known as the FLASH effect.

[0010] Due to these unique characteristics, FLASH therapy requires real-time beam monitoring for dose control. Many of the standard detectors used in radiotherapy for dosimetry exhibit saturation effects at the dose rates involved in FLASH therapy and are therefore not suitable.

[0011] Patent application US2021275833 (Al) , entitled "Dosimetry systems for radiation treatment using radiation- detector-triggered cameras to image Cherenkov emissions or thin-sheet scintillators," refers to an imaging system based on Cherenkov radiation or a thin-sheet scintillator . It uses a radio-optical triggering unit (RTU) that detects scattered radiation in a fast-response scintillator to detect radiation pulses and background images , allowing the capture of Cherenkov or scintillation light images during radiation pulses and background images during periods when no radiation pulses are present , without requiring an electrical interface with the accelerator delivering the radiation pulses . The Cherenkov images are background-corrected by subtraction and used for purposes that include treatment optimi zation .

[0012] Patent application JP2019015626 , entitled "Radiation monitoring device and radiation treatment device, and method for monitoring radiation, " refers to a device for measuring radiation ( dose ) within the body . This appears to be a scintillation-based device, and the application also describes a method for reducing Cherenkov light , which is considered a source of noise . As it is a scintillation-based device , it is expected to experience saturation when exposed to high dose rates such as those used in FLASH radiation therapy .

[0013] Patent CN116052839 , entitled "Dose veri fication method and device based on Cherenkov radiation, " describes a technique for measuring the dose delivered to a patient using the patient ' s body as the irradiated medium . The method is based on an arti ficial intelligence tool that performs calibration between detected photons and the delivered dose , which is necessary due to inter-patient and temporal tissue variability . The radiation measurement is performed after the dose has been applied to the patient . Sheppard, J. C., et al. "Picosecond resolution of a

[0014] Cherenkov cell-streak camera arrangement for monitoring charged particle bunches." Review of Scientific Instruments 51.12 (1980) : 1634-1637, describes an experiment in which the picosecond time structure of a Cherenkov radiation source was measured using an optical camera. The beam particles used were an electron beam. This experiment employed a gaseous compound as the radiator, which is prone to leakage and therefore unsuitable for clinical environments. Furthermore, since film was used, the system does not provide real-time data and requires post-acquisition analysis.

[0015] Accordingly, there is a need to provide a device capable of real-time monitoring of dose rate (dose per unit time) and per-pulse dose of radiotherapy beams, without exhibiting saturation effects and with minimal impact on the irradiation beam.

[0016] SUMMARY OF INVENTION

[0017] The present invention relates to a particle beam monitoring device for FLASH Radiotherapy based on the Cherenkov effect, comprising:

[0018] - a Cherenkov light radiator (1) , transparent in the wavelength range of 350-600 nm, formed of a material with an atomic number less than or equal to 40, configured to receive a beam of charged particles with energy in the range of 1 MeV to 250 MeV; and

[0019] - a light detection system comprising a photodetector (2) when the Cherenkov angle is less than the total internal reflection angle, the photodetector (2) being positioned after the radiator (1) in the direction of propagation of Particle beam; or a photodetector (2) and an optical coupling material (3) when the Cherenkov angle is greater than the total internal reflection angle, the photodetector (2) and the optical coupling material (3) being positioned on the surface of the radiator (1) ; wherein the photodetector (2) is configured to detect wavelengths in the range of 350-600 nm and has a temporal resolution in the range of 10 to 99 ns.

[0020] In one embodiment of the invention, the material of the radiator (1) has an atomic number less than or equal to 20, and in a more preferred embodiment, less than or equal to 10.

[0021] In another embodiment of the invention, the charged particle beam is selected from electrons and protons.

[0022] In a further embodiment of the invention, the charged particle beam comprises electrons having an energy in the range of 1-250 MeV. In this embodiment, the material of the radiator is aerogel or glass.

[0023] In yet another embodiment of the invention, the charged particle beam comprises protons having an energy in the range of 70-230 MeV. In this embodiment, the material of the radiator is diamond or zirconia.

[0024] In one aspect of the invention, the thickness of the radiator (1) is in the range of 1 to 10 mm.

[0025] In another aspect of the invention, the photodetector (2) comprises a silicon photomultiplier.

[0026] In yet another aspect, the optical coupling material (3) is selected from the group consisting of epoxy resins, optical adhesives, and equivalents thereof. In a preferred embodiment, the optical coupling material (3) is an epoxy resin .

[0027] BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 illustrates the device of the invention in use within a radiotherapy machine. The radiator (1) is positioned so as to be traversed by an electron beam, and the light detection system comprises a photodetector (2) placed at a distance from the radiator (1) such that it does not interact with the beam, but still ensures the detection of photons.

[0029] Figure 2 illustrates the device of the invention in use within a radiotherapy machine. The radiator (1) is positioned so as to be traversed by a proton beam, and the light detection system comprises a photodetector (2) and an optical coupling material (3) arranged on the face of the radiator (1) through which the radiation beam enters. Figure 3 illustrates an embodiment of the device of the invention in which the radiator ( 1 ) has a conical configuration .

[0030] Figure 4 illustrates the energy (K) of a primary proton beam with Cherenkov Ef fect as a function of the refractive index (n) . The figure shows the minimum energy required for a proton beam to produce the Cherenkov ef fect, as a function of the refractive index of the medium through which the particle travels .

[0031] Figure 5 illustrates the energy (K) of a primary electron beam with Cherenkov ef fect as a function of the refractive index (n) . The figure shows the minimum energy required for an electron beam to produce the Cherenkov ef fect , as a function of the refractive index of the medium through which the particle travels .

[0032] DETAILED DESCRIPTION OF THE INVENTION

[0033] The present invention relates to a particle beam monitoring device for FLASH Radiotherapy based on the Cherenkov ef fect , comprising :

[0034] - a Cherenkov light radiator ( 1 ) , transparent in the wavelength range of 350- 600 nm, formed of a material with an atomic number less than or equal to 40 , configured to receive a beam of charged particles with energy in the range of 1 MeV to 250 MeV; and

[0035] - a light detection system comprising a photodetector (2) when the Cherenkov angle is less than the total internal reflection angle, the photodetector (2) being positioned after the radiator (1) in the direction of propagation of Particle beam; or a photodetector (2) and an optical coupling material (3) when the Cherenkov angle is greater than the total internal reflection angle, the photodetector (2) and the optical coupling material (3) being positioned on the surface of the radiator (1) ; wherein the photodetector (2) is configured to detect wavelengths in the range of 350-600 nm and has a temporal resolution in the range of 10 to 99 ns.

[0036] The device of the invention can be used for the monitoring and calibration of charged particle beams in radiotherapy, particularly in FLASH Radiotherapy.

[0037] The term "Cherenkov angle" refers to the angle (0) at which Cherenkov photons are emitted relative to the direction of motion of the charged particle, given by the following relation: cos (0)= l / (pn) , where n is the refractive index of the medium and p= v / c (v is the speed of the charged particle and c is the speed of light in vacuum) .

[0038] The term "total internal reflection angle" refers to the angle associated with the phenomenon of total internal reflection, which occurs when photons, at the interface between two different media, are not refracted but instead entirely reflected (it can only occur when the refractive index of the incident medium (n±) is greater than that of the refractive medium (nr) , i.e., n± > nr) . The critical angle (the smallest angle of incidence at which total internal reflection occurs) , Qcrit, is given by the condition: 0Crit = arcsin (nr / n±) . Snell's law relates the angles of incidence (a±) and refraction (ar) with respect to the normal at the interface between the media, to their respective refractive indices (n) as follows: sin(ai)ni = sin(ar)nr.

[0039] The term "charged particle beam" refers to a beam of electrons or protons.

[0040] In the context of the present invention, the term "Cherenkov effect" refers to the phenomenon that occurs when charged particles travel through a medium in which the speed of light is lower than the speed of the particles, resulting in the emission of light (optical photons) with a wavelength spectrum ranging from 100 to 1000 nm.

[0041] The device of the invention comprises a Cherenkov light radiator (1) , transparent in the wavelength range of 350-600 nm, formed of a material having an atomic number less than or equal to 40, and configured to receive a charged particle beam (electrons or protons) with an energy in the range of 1 MeV to 250 MeV. Accordingly, as the charged particle beam passes through the radiator, Cherenkov light is generated.

[0042] The radiator (1) of the device of the invention is made of a material having an atomic number less than or equal to 40, preferably less than or equal to 20, and more preferably less than or equal to 10. For example, when the radiator (1) is made of zirconia, the element with the highest atomic number (Z) in the composition is zirconium, with Z = 40. This atomic number is considered the classifying factor, i.e., the highest atomic number among all the elements constituting the material. For proton beams, the radiator (1) material is selected from diamond (carbon, Z = 6) , zirconium dioxide (Z = 40) , and similar materials. For electron beams, the radiator (1) material is selected from aerogel (silicon, Z = 14) , glass (silicon, Z = 14) , and similar materials. Preferably, glasses are used whose refractive index is such that the total internal reflection angle is smaller than the Cherenkov angle.

[0043] The material of the radiator (1) also influences its thickness and, inherently, will have an impact on the particle beam.

[0044] One of the potential impacts on the beam due to the presence of the radiator is that, after passing through it, the particles in the beam may experience an angular deviation from their initial direction as a result of a phenomenon known as multiple scattering. This scattering can be modeled, considering only Coulomb interactions, by a Gaussian distribution centered approximately at zero, with a standard deviation given by the following expression:

[0045] 13.6 MeV x (x\ e =^^^(i + o-o38inU)where p denotes the momentum of the particle, q its charge number, and Xo is known as the radiation length, which depends on the properties of the material. This last quantity inversely proportional to Z (Z+1) , where Z is the atomic number of the element. In the case of materials composed of multiple elements, Xo can be calculated using the following formula, where w± e X± are, respectively, the weight fraction in the material and the radiation length of element i:

[0046] Accordingly, since the goal is to minimize the impact of the radiator on the beam, the value of 0 must be minimized, which justifies the use of materials composed of elements with an atomic number less than or equal to 40.

[0047] Preferably, the thickness of the radiator (1) is in the range of 1 to 10 mm, more preferably in the range of 1 to 5 mm, and most preferably, the thickness of the radiator (1) is 1 mm.

[0048] The radiator (1) may have a parallelepiped, conical, or other suitable geometry. The choice of the radiator (1) configuration should always aim to ensure optimal alignment of the particle beam within the radiator (1) to facilitate the emission and subsequent detection of photons, while minimizing particle scattering and the resulting loss of monitoring effectiveness.

[0049] It is important to ensure that, regardless of the material or geometry of the radiator (1) , the radiator (1) always allows the transmission of light and maximizes the amount of light produced, while simultaneously minimizing the impact on the particle beam. The device of the invention comprises a light detection system operating in the wavelength range of 350-600 nm, which has a temporal resolution in the range of 10 to 99 ns, allowing real-time detection of the Cherenkov light produced by the passage of the particle beam through the radiator

[0050] (1) . Accordingly, when the system detects light, it generates an electrical signal that provides real-time information on the number of particles composing the particle beam.

[0051] The light detection system comprises: a photodetector

[0052] (2) when the Cherenkov angle is less than the total internal reflection angle, the photodetector (2) being positioned after the radiator (1) in the direction of propagation of the particle beam; or a photodetector (2) and an optical coupling material (3) when the Cherenkov angle is greater than the total internal reflection angle, the photodetector (2) and the optical coupling material (3) being positioned on the entry surface of the radiator (1) , through which the particle beam enters.

[0053] Preferably, the photodetector (2) of the light detection system of the device of the invention is a silicon photomultiplier. Silicon photomultipliers are capable of detecting photons with energies corresponding to wavelengths ranging from the infrared to the ultraviolet, with a peak detection efficiency of approximately 30-40% in the visible range (400-500 nm) . Silicon photomultipliers typically have active areas ranging from 1 to 9 mm2, and therefore, at least one silicon photomultiplier ensures optimal detection of the generated light.

[0054] Thus, the photodetector (2) of the device of the invention exhibits high temporal resolution, on the order of tens of nanoseconds (10-99 ns) , enabling real-time detection of the light produced by the Cherenkov effect as the particles of the beam pass through the radiator (1) .

[0055] As previously described, the light detection system includes a photodetector (2) and an optical coupling material (3) when the Cherenkov angle exceeds the total internal reflection angle. In such cases, total internal reflection of the generated photons may occur at the interface between the radiator (1) and the photodetector (2) , which would prevent efficient light transmission — particularly if an air interface is present. To address this, the optical coupling material (3) , having a high refractive index, is placed between the radiator (1) and the photodetector (2) . This coupler eliminates the air interface and replaces it with a medium that lowers the total internal reflection angle, thereby allowing more light to pass through to the photodetector (2) . This configuration enhances the overall transmission and detection efficiency of the Cherenkov light .

[0056] The need for an optical coupling material (3) depends on the type of particle beam used and the material of the radiator (1) . For example, in the case of electron beams where the radiator (1) is made of aerogel or glass, the Cherenkov angle is less than the total internal reflection angle. In such configurations, photon detection is performed solely with a photodetector (2) positioned after the radiator (1) in the direction of propagation of the particle beam, such that it does not interact with the beam but ensures photon detection. In this case, the photons exit the radiator (1) and are immediately detected. In contrast, for proton beams where the radiator (1) is, for example, made of diamond or zirconia, the Cherenkov angle is greater than the total internal reflection angle. In this case, the photons are not detected by a photodetector (2) positioned after the radiator (1) in the direction of beam propagation. Therefore, the light detection system further comprises an optical coupling material (3) with a high refractive index (n > 1.5) , which ensures the transmission of Cherenkov photons from the radiator (1) to the photodetector (2) . Preferably, the optical coupling material (3) is selected from the group consisting of epoxy resins (n = 1.5-1.6) , optical adhesives (n = 1.6-1.9) , and equivalents thereof. More preferably, the optical coupling material (3) is an epoxy resin. In the case of proton beams, photon detection is preferably performed on the entry surface of the radiator (1) , i.e., the surface through which the particle beam enters (Figure 3) .

[0057] The device of the invention may also be used with gamma radiation beams. Gamma beams are generated from electron beams; therefore, placing the device in the primary electron beam path enables the monitoring of gamma radiation beams.

[0058] When in use, the device of the invention is coupled to a radiotherapy machine. In practice, the radiator (1) is positioned such that it is traversed by the beamline, and each particle passing through it emits a certain amount of light by the Cherenkov effect. This light is detected by the light detection system. The detection process must not interfere with the beam; that is, no component may be placed directly in the beam path. Accordingly, several configurations are possible, depending on the type of beam used (including its energy, particle type, and beam characteristics such as Gaussian spread or standard deviation) . As illustrated in Figures 1, 2, and 3, different implementation configurations are possible, all designed solely to ensure the detection of the generated light without affecting the particle beam.

[0059] The Cherenkov effect depends on the velocity of the particles (and, consequently, their energy) and the refractive index of the medium, defined as the ratio between the speed of light in vacuum and the speed of light in the medium, which is greater than 1. Due to this dual dependence, there is a minimum energy threshold for the effect to occur in a given medium. Specifically, for a medium with refractive index n, a particle must have a minimum kinetic energy K to generate Cherenkov radiation. As shown in Figure 4, electron beam treatments typically involve energies from 1 to 250 MeV, making aerogel (n = 1.08) a suitable radiator material. The photons emitted must then be detected by a light detection system. However, one must account for total internal reflection: a photon cannot transition into a second medium if that medium has a lower refractive index and the incident angle exceeds the critical angle. In the case of aerogel, the Cherenkov angle is smaller than the critical angle at the aerogel-air interface, allowing photon detection to be performed with a photodetector (2) positioned after the radiator (1) in the direction of propagation of the particle beam. In contrast, for proton beams, suitable radiator materials such as diamond or zirconia typically have refractive indices greater than 2, and at certain energies, the Cherenkov angle exceeds the critical angle for the radiator-air interface. In such cases, photons cannot be detected by a photodetector (2) positioned after the radiator (1) , because the photons undergo multiple total internal reflections and are not transmitted into air. To address this, an optical coupling material (3) with a high refractive index (e.g., n > 1.5) is placed between the radiator (1) and the photodetector (2) , eliminating the air gap and ensuring that the Cherenkov photons are transmitted to and detected by the photodetector (2) .

[0060] The positioning of the light detection system, when it comprises a photodetector (2) and an optical coupling material (3) , depends solely on enabling the fastest possible detection with the least possible photon loss. The system is placed on a surface of the radiator (1) , which may be either a lateral surface or the surface through which the particle beam enters the radiator. For example, detection of photons emitted via Cherenkov radiation by the passage of a proton beam is preferably performed on the beam entry surface; however, it could also be positioned on the lateral surfaces. It should be noted that the emission angle relative to the normal on the entry face is equal to the Cherenkov angle ( Qcherenkov) , whereas on the lateral faces, it corresponds to the complementary angle ( 90 ° -Qcherenkov) . In the case of protons, when the radiator (1) is made of diamond or zirconia, the Cherenkov angle is less than 45° . Photon detection in this case requires the use of an optical coupling material (3) to prevent total internal reflection. This occurs when the incidence angle exceeds the critical angle; therefore, it is desirable to minimize the angle with respect to the normal of the surface where photon detection occurs, which is why the beam entry face is selected. For example, in Figure 3, the light detection system is positioned on the surface of the radiator (1) through which the particle beam enters. In Figure 5, three different materials are indicated along with the minimum energy required for the beam to produce the Cherenkov effect. For example, diamond, which has a refractive index of 2.42 at a wavelength of 500 nm, can be used as a radiator material for proton beams with energies above 92 MeV. Typically, the energies used in proton therapy range from 70 to 230 MeV. The figure also shows a test with aerogel, which has a selected refractive index of 1.08 at 500 nm, and which can be used as a radiator (1) material for electron beams with energies above 0.84 MeV. The electron beam energies commonly used range from 1 to 250 MeV. The selected materials meet the required transparency condition necessary for the detection of optical photons.

[0061] Surprisingly, it has been found that, unlike known devices in the background art, which do not allow beam control under high-intensity conditions due to saturation effects, the device of the present invention enables realtime monitoring of high-intensity beams based on the Cherenkov effect, without exhibiting any saturation.

[0062] Moreover, the device enables temporal resolution on the order of nanoseconds, which was not previously achievable due to the saturation of state-of-the-art devices when exposed to high-intensity beams.

[0063] Real-time beam monitoring is essential in the administration of radiotherapy treatment. Depending on the measured values, it may be necessary to adjust the delivered dose. Therefore, it is crucial that the measurement is accurate in order to ensure the highest possible efficiency and effectiveness of the treatment. In the specific case of FLASH Radiotherapy, the dose rate exceeds 40 Gy / s, which is significantly higher than that of conventional radiotherapy (approximately 0.01 Gy / s) . Although both methods deliver the same total dose, FLASH Radiotherapy treatments are completed in approximately 500 milliseconds, whereas conventional radiotherapy treatments may take several days or even weeks.

[0064] Considering the significant temporal advantage of FLASH Radiotherapy over conventional radiotherapy, real-time monitoring is essential to ensure that the radiotherapy machine delivers the precise number of particles per unit time (particle flux) required for the patient, thereby avoiding any unwanted or harmful effects caused by excess radiation. This is achieved with the device of the present invention, which can also be applied to any type of radiotherapy .

[0065] Reference numbers in the description and figures:

[0066] (1) - Radiator

[0067] (2) - Photodetector

[0068] (3) - Optical coupling material

[0069] The description presented herein should be understood as illustrative and not limiting of the scope of the present invention, which is defined in the appended independent claims. The dependent claims serve to specify particular embodiments of the invention.

Claims

CLAIMS1. Particle beam monitoring device for FLASH radiotherapy based on the Cherenkov Effect, characterized by comprising :- a Cherenkov light radiator (1) , transparent in the wavelength range of 350-600 nm, formed of a material with an atomic number less than or equal to 40, configured to receive a beam of charged particles with energy in the range of 1 MeV to 250 MeV; and- a light detection system comprising a photodetector (2) when the Cherenkov angle is less than the total internal reflection angle, the photodetector (2) being positioned after the radiator (1) in the direction of propagation of the particle beam; or a photodetector (2) and an optical coupling material (3) when the Cherenkov angle is greater than the total internal reflection angle, the photodetector (2) and the optical coupling material (3) being positioned on the surface of the radiator (1) ; wherein the photodetector (2) is configured to detect wavelengths in the range of 350-600 nm and has a temporal resolution in the range of 10 to 99 ns.

2. Particle beam monitoring device for radiotherapy according to claim 1, characterized in that the material of the radiator (1) has an atomic number less than or equal to 20.

3. Particle beam monitoring device for radiotherapy according to claim 2, characterized in that the material of the radiator (1) has an atomic number less than or equal to 10.

4. Particle beam monitoring device for radiotherapy according to claim 1, characterized in that the charged particle beam comprises electrons or protons.

5. Particle beam monitoring device for radiotherapy according to claim 4, characterized in that the charged particle beam are electrons having an energy in the range of 1-250 MeV.

6. Particle beam monitoring device for radiotherapy according to claim 5, characterized in that the material of the radiator is aerogel or glass.

7. Particle beam monitoring device for radiotherapy according to claim 4, characterized in that the chargedparticle beam are protons having an energy in the range of 70-230 MeV.

8. Particle beam monitoring device for radiotherapy according to claim 7, characterized in that the material of the radiator (1) is diamond or zirconia.

9. Particle beam monitoring device according to claim 1, characterized in that the radiator (1) has a thickness in the range of 1 to 10 mm.

10. Particle beam monitoring device according to claim 1, characterized in that the photodetector (2) is a silicon photomultiplier .

11. Particle beam monitoring device according to claim 1, characterized in that the optical coupling material (3) is selected from the group consisting of epoxy resins, optical adhesives, and equivalents thereof.

12. Particle beam monitoring device according to claim 11, characterized in that the optical coupling material (3) is an epoxy resin.

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