System for charged particle therapy verification

Abstract

A system for charged particle therapy verification, comprising: a first detector configured to detect secondary particles emitted from a target irradiated with a charged particle beam, wherein the detector is configured to cause at least two consecutive elastic scatterings of secondary particles of fast neutrons in the detector, and to cause two consecutive incoherent scatterings and a subsequent third scattering of secondary particles of the prompt gamma-ray type, the third scattering being one of: a photoelectric effect, an incoherent scattering or a pair production.

Description

Technical Field

[0001] This invention relates to the field of charged particle therapy (CPT), specifically cancer treatment using accelerated ion beams. More specifically, this invention relates to a detection system for real-time measurement of the extent of a charged particle beam in a target object, human body, or animal, and for measuring the dose distribution. The system comprises detector modules based on plastic scintillators arranged in a matrix shape. Background Technology

[0002] More than half of cancer patients receive radiation therapy as part of their treatment (Delaney, G. et al., The role of radiotherapy in cancer treatment, Cancer, 2005, Vol. 104, pp. 1129–1137). Curative radiation therapy (RT) aims to inactivate all cancer cells by delivering ionizing radiation to the tumor while minimizing radiation damage to surrounding healthy tissue. Charged particles, such as protons, helium ions, and carbon ions, interact with the target or tumor more attractively than conventional RT using megavolt (MV) photons. This is because the dose from charged particles is deposited more precisely within the target object at a specific range or depth of penetration and does not penetrate beyond that range. Furthermore, they deposit the maximum amount of energy in a narrow region known as the Bragg peak, thus providing a higher dose to the tumor while significantly less to surrounding healthy tissue. Charged particles are also more effective at killing cancer cells than photons, meaning the same physical dose produces a greater biological effect. Therefore, charged particle therapy (CPT) is the preferred radiotherapy for treating certain tumors at the skull base (chordoma, chondrosarcoma), childhood cancers (Patel, S. et al., Recommendations for thereferral of patients for proton-beam therapy, an Alberta Health Services report: a model for Canada? Curr. Oncol., 2014, Vol. 21, p. 251), and central nervous system tumors (Mishra, MV et al., Establishing Evidence-Based Indications for Proton Therapy: An Overview of Current Clinical Trials. Int. J. Radiat. Oncol., 2017, Vol. 97, pp. 228–235).

[0003] A significant challenge associated with CPT is the considerable uncertainty in the particle extent within tissue caused by tissue heterogeneity, anatomical changes during treatment, and organ motion between and within fractions. These uncertainties lead to increased distal treatment margins in clinical protocols and limit the available beam angles due to attempts to avoid treatment fields directed towards healthy organs distal to the tumor, caused by extent uncertainty. Therefore, it is impossible to fully utilize the potential of the limited range of particles within tissue, especially when the tumor is located near a dangerous organ and when organ motion may adversely affect the delivered dose. Consequently, the extent of the particle beam must be monitored with high precision of approximately 1 mm to 2 mm during treatment, with the ultimate goal of minimizing the dose to healthy tissue.

[0004] To date, the clinical solution for developing and adapting CPT to photon therapy to mitigate these uncertainties is to increase the safety margin around the tumor to define the so-called planned target volume and to monitor anatomical changes via image guidance to minimize these margins as much as possible (van Herk, M., Errors and margins in radiotherapy. Semin. Radiat. Oncol. 2004, Vol. 14, pp. 52–64). In CPT, a typical safety margin is approximately 3.5% + 1 mm of the nominal range or a fixed 5 mm, or even larger in areas with internal organ movement (Xie, Y. et al., Prompt Gamma Imaging for In Vivo Range Verification of Pencil Beam Scanning Proton Therapy. Int. J. Radiat. Oncol. 2017, Vol. 99, pp. 210–218).

[0005] WO2010 / 000857A1 discloses an apparatus and method for verifying the range of particle therapy. The apparatus is operated to detect transient gamma rays generated when an object or body is irradiated, and includes a pinhole camera and a shielding device for avoiding the detection of stray particles.

[0006] EP2977083 B1 discloses a device for verifying particle therapy by detecting and quantifying transient gamma rays, which uses a collimator in front of a scintillator to obtain a one-dimensional dose-related distribution of the transient gamma ray profile of the irradiated target. Summary of the Invention

[0007] The purpose of this invention is to overcome the problems of the prior art and to disclose a system for real-time range and dose verification in CPT. Specifically, the invention provides an online detector capable of providing real-time measurement of the penetration range of a charged particle beam in a target or body irradiated with charged particles such as protons, helium ions, or carbon ions. Furthermore, the objective of this invention is to provide verification of the delivered dose in a target or body irradiated by charged particles.

[0008] The present invention that solves the problems mentioned above is the system described in the independent claims.

[0009] An advantage of at least one embodiment of the present invention is that complete kinematic reconstruction of the angles and energies of the secondary transient gamma rays and fast neutrons is possible.

[0010] Compared to existing technologies, in some implementations, the present invention can improve the efficiency of a real-time range verification system by up to an order of magnitude.

[0011] According to one aspect of the invention, an improved system is provided for real-time range verification and dose delivery verification in charged particle therapy.

[0012] According to another aspect of the invention, verification of the penetration depth of charged particle beams is provided with high statistical accuracy.

[0013] In another aspect, the present invention enables time-resolved two-dimensional and three-dimensional reconstruction of the coordinates of neutron and transient gamma rays in a target or patient with high statistical accuracy at particle beam intensities lower than those disclosed.

[0014] Another aspect of the invention is a range verification and image-guided system for charged particle therapy, which has a reduced physical size and increased flexibility compared to existing systems, which is important in a clinical setting. Attached Figure Description

[0015] The accompanying drawings illustrate embodiments or partial embodiments of the present invention and should not be construed as limiting the scope of protection.

[0016] Figure 1 A conceptual design of a detector based on an optical segmented strip of an organic scintillator is shown: (10) scintillator strip, (20) reflective strip, (30) aluminum housing, and (40) photomultiplier for light readout.

[0017] Figure 2 A schematic representation shows the MCNP6.2 Monte Carlo simulation geometry used to determine the detection efficiency of secondary neutrons and transient gamma rays for detector design: (1) proton beam, (2) water model, (3) detector, and (4) an angle of approximately 30°.

[0018] Figure 2 B shows, in graphical form, the detected one-dimensional 1D profiles of the distribution of secondary neutron and prompt gamma-ray generation locations along the beam direction for the illustrated 200 MeV proton beam, and the “range marker” positions for the corresponding neutron and prompt gamma-ray profiles: (1) the range marker positions estimated based on the detected neutron profile, (2) the range marker positions estimated based on the detected prompt gamma-ray profile, (3) the detected neutron profile, and (4) the detected prompt gamma-ray profile.

[0019] Figure 2 C is graphically represented as a linear fit between the estimated linear fit of the "range marker" positions of neutrons (solid lines) and transient gamma rays (dashed lines) and the nominal proton range in water, where (1) is the range marker position for a proton energy of 100 MeV, (2) is the range marker position for a proton energy of 160 MeV, (3) is the range marker position for a proton energy of 200 MeV, and (4) is the range marker position for secondary neutrons and transient gamma rays with a proton energy of 230 MeV.

[0020] Figure 3 The principle of neutron and transient gamma ray detection and imaging in the detector is illustrated.

[0021] Figure 3 A illustrates neutron detection. The detection is based on the back projection of the event cone onto the detection of two consecutive (n, p) events in the detector's sensitive volume: (2)E n - Energy of the incident neutron, (3) First (n, p) collision, measurement of the energy of the recoil proton in the first collision, (5) Scattered neutron from the first event, (4) Second (n, p) collision, used only for time-of-flight measurement, tau and collision location. The sketch is given for a “strip” scintillator with a pixelated photodetector for light readout (1).

[0022] Figure 3 B shows the detection of transient gamma rays. (6)E y - The energy of the incident transient gamma ray, (7) ΔE1 – a measurement of the energy deposited by the incident transient gamma photon in the first incoherent scattering event, (8) ΔE2 – a measurement of the energy deposited by the scattered photon in the second incoherent scattering event, (9) a measurement of the collision location in the third scattering event, which can be of any type, such as incoherent, photoelectric, or diploidal. The sketch is given for a “strip” scintillator with a (1) pixelated photodetector.

[0023] Figure 3C illustrates ultra-high-energy neutron detection: based on the recoil protons tracking the (n, p) events in the detector's sensitive volume and the back projection of the resulting event line rather than the event cone, a complete kinematic reconstruction of the incident angle and energy of the incoming high-energy neutrons is performed. This situation will be encountered in the context of CPT due to the extremely high energies of secondary neutrons (up to the primary beam energy in proton therapy and up to 300 MeV to 400 MeV in carbon ion therapy). (10)E n - The energy of the incident neutron, (11) the energy of the recoil proton in each penetrating scintillator bar and its direction in the first collision, (12) the energy of the recoil proton in each penetrating scintillator column and its direction in the second collision. The sketch is given by using a pixelated photodetector for light readout for a "bar" shaped scintillator.

[0024] Figure 4 The distribution of the time when the transient gamma rays and neutrons arrive at the detector (the time of the first interaction in the detector) is shown in graphical form.

[0025] Figure 4 A shows the neutron arrival time as a function of the initial neutron kinetic energy at an initial proton beam energy of 160 MeV.

[0026] Figure 4 B shows the arrival time of the transient gamma ray as a function of the initial transient gamma ray energy at an initial proton beam energy of 160 MeV.

[0027] Figure 4 C shows the neutron (1) dominant region at arrival time (time of first interaction) and depth at an initial proton beam energy of 160 MeV, and the transient gamma-ray (2) dominant region at arrival time (time of first interaction) and depth at an initial proton beam energy of 160 MeV.

[0028] Figure 5 A block diagram illustrating an embodiment of the system for time-of-flight (ToF) measurement and differentiation according to the present invention is shown.

[0029] Figure 6 shows the pulse shape differentiation (PSD) graphically.

[0030] Figure 6A A quality factor method for separating neutron and transient gamma-ray events is shown. (1) The average value μ of the PSD signal distribution for transient gamma rays. γ (2) The average value μ of the PSD signal distribution for neutrons n (3) Full width at half maximum (FWHM) of the PSD signal distribution for transient gamma rays.γ (4) Full width at half maximum (FWHM) of the PSD signal distribution of neutrons n .

[0031] Figure 6B Charge integrals of neutron-induced and transient gamma-ray-induced waveforms are shown to distinguish between neutron-induced and transient gamma-ray-induced events. (1) Typical pulse shape (waveform) from a transient gamma-ray-induced event, (2) Typical pulse shape (waveform) from a neutron-induced event, (3) Short integral of the pulse, Q short (4) Long integral of the pulse, Q long The number of PSDs is used as the ratio (Q). long -Q short ) / Q long .

[0032] Figure 7A The uncertainties of the neutron range markers obtained from the detected neutron profiles are shown. (1) Standard deviation of the estimated neutron range markers as a function of primary proton intensity at 230 MeV, (2) Standard deviation of the estimated neutron range markers as a function of primary proton intensity at 200 MeV, (3) Standard deviation of the estimated neutron range markers as a function of primary proton intensity at 160 MeV, (4) Standard deviation of the estimated neutron range markers as a function of primary proton intensity at 100 MeV.

[0033] Figure 7B The uncertainties of the transient gamma-ray range markers obtained from the detected transient gamma-ray profiles are shown. (1) Standard deviation of the estimated transient gamma-ray range markers as a function of primary proton intensity at 230 MeV, (2) Standard deviation of the estimated transient gamma-ray range markers as a function of primary proton intensity at 200 MeV, (3) Standard deviation of the estimated transient gamma-ray range markers as a function of primary proton intensity at 160 MeV, (4) Standard deviation of the estimated transient gamma-ray range markers as a function of primary proton intensity at 100 MeV. Detailed Implementation

[0034] In the following description, various examples and embodiments of the invention are set forth in order to provide those skilled in the art with a more thorough understanding of the invention. The specific details described in the context of the various embodiments and with reference to the accompanying drawings are not intended to be construed as limiting. Rather, the scope of the invention is defined by the appended claims.

[0035] The embodiments described below are numbered. Additionally, related embodiments defined with respect to the numbered embodiments are described. Unless otherwise stated, any embodiment that can be combined with one or more numbered embodiments can also be directly combined with any related embodiment of the mentioned numbered embodiments.

[0036] In a first embodiment, the present invention is a system for verifying charged particle therapy, comprising:

[0037] A first detector is configured to detect secondary particles emitted from a target irradiated with a beam of charged particles, wherein, in order to detect secondary neutrons, the detector is configured to generate at least two consecutive elastic scatterings, i.e. (n, p) scatterings, on hydrogen-1 nuclei in the sensitive volume of the detector, and in order to detect secondary transient gamma rays, the detector is configured to generate at least two consecutive incoherent transient gamma scatterings and any subsequent third scattering of any type in the sensitive volume of the detector.

[0038] In a first relevant embodiment, the detector includes a scintillator comprising an optically segmented organic scintillator element array, wherein the scintillator is configured to induce at least two consecutive elastic (n, p) scatterings for detecting secondary neutrons; and to induce two consecutive incoherent scatterings and a subsequent third scattering of any type for detecting secondary transient gamma rays, wherein all the mentioned scattering events are detected in different scintillator elements.

[0039] In the second related embodiment, the scintillator element is columnar and arranged in an array in a cross section perpendicular to the length of the scintillator element.

[0040] Scintillators can be smaller than 30x30cm 2 The cross-section and a length / depth of 20cm or more.

[0041] Each scintillator element can be smaller than 2x2cm 2 The cross section.

[0042] Each scintillator element can be 2x2cm 2 With 0.5 x 0.5 cm 2 The cross section between them.

[0043] A scintillator may include a reflective liner between at least some of the scintillator elements.

[0044] The reflective liner can be titanium dioxide or a reflective film, such as an enhanced specular reflection (ESR) film.

[0045] Scintillator elements can be spaced apart.

[0046] Scintillator elements can be organic.

[0047] The organic element can be a fast plastic scintillator with PSD capability or stilbene.

[0048] Scintillators can include both organic and inorganic scintillator elements.

[0049] Inorganic components can be CeBr3 or lutetium-yttrium oxide silicate (LYSO) crystals.

[0050] A scintillator may include a metallic enclosure surrounding at least a portion of the scintillator element. The metallic enclosure provides mechanical support for the assembly and potentially provides shielding against scattering and secondary charged particles.

[0051] In a second embodiment, which can be combined with any related embodiment of the first embodiment, the system includes an array of photodetectors arranged at both ends of the scintillator element for reading out the scintillating light.

[0052] The photodetector array can include, for example, a SiPM (silicon photomultiplier) or an MCP-PM (microchannel plate photomultiplier).

[0053] Photodetectors can be placed at each end of the scintillator element.

[0054] In a third embodiment, which can be combined with any related embodiment of the second embodiment, the system includes a processing unit connected to a photodetector array, wherein the processing unit is configured to estimate the direction and energy of incoming fast neutrons and gamma rays.

[0055] The processing unit can be configured to estimate the location of the nuclear interaction between the charged particle beam and the target.

[0056] The processing unit can be configured to estimate the dose distribution at the target location.

[0057] The processing module can be configured to distinguish between fast neutrons and transient gamma rays.

[0058] The processing module can be configured to distinguish between secondary neutrons and transient gamma rays by pulse shape discrimination (PSD) or time-of-flight (ToF) measurements.

[0059] The processing module can be configured to distinguish between secondary neutrons and transient gamma rays by simultaneously applying pulse shape discrimination (PSD) and time-of-flight (ToF) measurements.

[0060] Systems, such as processing modules, can be configured to provide real-time two-dimensional or three-dimensional images of the distribution of neutron and transient gamma-ray production in a target.

[0061] In a fourth embodiment, which can be combined with any of the embodiments described above, the system includes a second detector that is spatially separated from the first detector and configured to detect secondary particles emitted from the target.

[0062] The second detector can include any combination of the same features as the first detector.

[0063] The processing unit can be connected to the photodetector array of the second detector.

[0064] In one implementation, the first detector and the second detector may each have a preprocessor for preprocessing the input from the respective photodetector before forwarding the preprocessed signal to the processing unit.

[0065] In some implementations, the system may include an optically segmented organic scintillator array and a segmented inorganic scintillator array.

[0066] In another embodiment, the detector includes optically segmented "strips" or pillars of a pixelated photodetector and an organic scintillator mounted at each end of the detector, enabling simultaneous acquisition of two waveforms for each event in each strip, see [link to relevant documentation]. Figures 6A to 6B .

[0067] Further details regarding specific embodiments of the system according to the present invention will be described below.

[0068] The system includes a scintillator-based detector module. A proton beam enters the target object, human body, or animal body, and generates secondary particles along its path until the proton beam stops inside the object or body. Secondary neutrons and transient gamma rays are present in the secondary particles. A significant portion of the secondary neutrons will leave the object or body, and some of them will reach the detector system. The same applies to the secondary transient gamma rays. The principles of the detection and imaging techniques using the detector are described below. Traditionally, imaging of fast neutrons relies on detecting two consecutive elastic scattering events of neutrons on the hydrogen-1 nucleus, i.e., (n, p) in an organic scintillator (Knoll, GFRadiation Detection and Measurement, John Wiley & Sons, 2010). In the first (n, p) scattering event, the energy Ep of the recoil proton is measured based on the detected scintillator intensity. The second (n, p) scattering event is used for... Figure 3 A gives the time of flight (TOF) as τ(tau) and Figure 3 A gives the measurement and distance between the first (n, p) scattering event and the second (n, p) scattering event, denoted as d.

[0069] Based on measurements of TOF and distance, the energy En′ of the scattered neutron was determined.

[0070]

[0071] Then, the energy of the incident neutron is estimated as En = Ep + En′, and the scattering angle of the incident neutron is given as... However, due to the ambiguity in determining the azimuth angle, it is impossible to reconstruct the accurate neutron incident direction. Conversely, even if the neutron incident is known to be located somewhere on the surface of the "event cone," it is still impossible to reconstruct the exact neutron incident direction. Figure 3 As described by A.

[0072] If a statistically sufficient number of such event cones are back-projected onto an image plane in 3D space, the resulting image obtained from the intersection of the bases of these cones will reveal the location of neutron emission.

[0073] In CPT, Figure 3 The scenario described in C also represents a possible detection mechanism that would allow for more precise determination of neutron emission locations. Extremely high-energy neutrons (up to the energy of a primary particle beam) will produce high-energy recoil protons upon elastic collision with a hydrogen-1 nucleus, with energy sufficient to penetrate several scintillator elements.

[0074] The cross-sectional area of ​​each strip or column is 0.25 cm². 2 In this case, recoil protons with kinetic energies exceeding 40 MeV can penetrate at least three elements. Tracking these protons and reconstructing their energies allows for a complete kinematic reconstruction of the angle and energy of the incident neutron. This allows for the backprojection of the event line rather than the cone, thus reducing the uncertainty at the secondary neutron origin and the uncertainty in the incident neutron energy.

[0075] The calculation of the event line involves identifying the trajectory of the recoil proton originating from the first (n, p) collision. In the non-relativistic kinematics of the (n, p) elastic scattering collision, the recoil momentum of the scattering neutron and proton is orthogonal to each other. The recoil proton momentum from both (n, p) collisions is reconstructed, and a straight line connecting the two collision sites is plotted, thus giving the momentum of the scattering neutron from the first (n, p) collision. The direction of the scattering neutron is then identified using the recoil proton momentum of the two recoil protons that is nearly perpendicular to this, and thus the first (n, p) collision is identified.

[0076] Reconstructing the energies and orientations of the two recoil protons from the two (n, p) interactions allows for the reconstruction of the incident neutron's energy and angle of incidence, reducing uncertainty compared to the situation described above for conventional detection of fast neutrons. Therefore, the reconstruction eliminates ambiguity in azimuth determination, and eliminating ambiguity in the incoming neutron angle of incidence allows for the reconstruction of the neutron's incident direction, now positioned along the "event line" rather than the cone surface.

[0077] In the described detector, a similar principle applies to incident transient gamma rays ( Figure 3 B) Reconstruction of the origin and energy. The transient gamma-ray photon arrives at the detector and undergoes an incoherent interaction, namely Compton scattering (first scattering), within the detector's sensitive volume. The energy of the Compton recoil electron and the location of the scattering interaction must be measured. In all cases, the interaction location is determined based on the position of the scintillator element in the (x, y) direction. In the z-direction, the location is reconstructed based on the waveform collected by the photodetector at both ends of the given scintillator element. The scattered transient gamma-ray photon interacts again within the detector's sensitive volume through another incoherent scattering event (second scattering).

[0078] Similarly, the energy of the second Compton recoil electron and the interaction position of the second scattering event must be measured. The double-scattered transient gamma rays interact a third time (third scattering) within the detector's sensitive volume via incoherent scattering, the photoelectric effect, or sporadic occurrence. Only the interaction position is needed. Information from the third and second scattering events is used to determine the scattering angle in the second incoherent scattering event.

[0079] The recoil energies of the electrons from the first and second scatterings are then combined with the scattering angle of the second scattering event to determine the energy and incident angle of the incoming transient gamma ray.

[0080] In the alternative case, a third scattering is not required. In this case, a correction factor needs to be derived and applied to the measured recoil electron energy from the second scattering to determine the energy of the scattered gamma rays after the first scattering.

[0081] Information from these two alternative scenarios then allows for the determination of the approximate incident angle and energy of the incident transient gamma ray. In this case, the "event cone" is reconstructed, and the emission point of the transient gamma ray is assumed to be located somewhere on the cone's surface.

[0082] As described above, incoherent scattering of gamma rays occurs in the depicted detector, and a useful double or triple scattering efficiency is achieved due to the compactness of the detector, enabling simultaneous imaging of neutrons and transient gamma rays. The double and triple transient gamma scattering efficiency can be further improved by increasing the overall size of the detector, i.e., by adding more detector elements.

[0083] An array of photodetectors is arranged at either end of the scintillator element. The detection steps for neutrons and transient gamma rays, as described above, generate optical photons in the scintillator, the intensity of which is proportional to the energy deposited in each scintillator. The optical photons undergo total internal reflection (TIR) ​​at the scintillator-air interface, or are reflected back to the scintillator using a reflector with high reflectivity. In this way, the optical photons propagate to either end of the scintillator strip, where an array of photodetectors is mounted. In the photodetectors, the arriving optical photons are then converted into electrical charges.

[0084] The processing unit is arranged to communicate with a photodetector array configured to read out waveforms and distinguish between those induced by photons and those induced by neutrons. The unit receives the waveform to be processed from the photodetector array. The pulse is then sensed by the readout circuitry. To simultaneously image neutrons and gamma rays, the pulses induced by both must be distinguished.

[0085] The difference between photon-induced and neutron-induced signals can be distinguished using pulse shape discrimination (PSD) or time-of-flight (TOF) measurements. These two methods will be explained below.

[0086] Figures 6A to 6B The pulse shape distinction is shown in the figure. PA et al., Digital pulse-shape discrimination of fast neutrons and rays. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 2008, Vol. 594, pp. 79–89. For certain types of organic scintillators (e.g., liquids and plastics), signals induced by incident photons and neutrons differ in their time-intensity profiles. In organic scintillators, fast neutron-induced events generate longer-lived scintillation pulses compared to gamma-ray-induced events. To distinguish between neutron-induced events and those induced by incident transient gamma rays, the integration of the recorded signal pulse is performed in two parts (long and short), see [reference needed]. Figure 6B In this approach, the PSD method relies on the long Q of these signals. long and short Q short Integrate, and derive the third signal based on the ratio of the short integration pulse to the long integration pulse, PSD = (Q long -Q short ) / Q long .

[0087] One quantitative method for PSD differentiation is to use a factor of quality (FoM) to quantify the PSD quality of organic scintillators deployed in the detector, such as... Figure 6A As shown. FoM is given below:

[0088]

[0089] Where, μ γ It is the average value of the PSD signal distribution for transient gamma rays, μ n It is the average value of the PSD signal distribution for neutrons, FWHM γ (Full width at half maximum) is the PSD signal distribution for transient gamma rays, and F FWHM n Yes (full width at half maximum) is the PSD signal distribution for neutrons.

[0090] The measurement of the arrival time of transient gamma rays and neutrons, i.e., time-of-flight (ToF) measurement. Figure 5 This can be an additional means of distinguishing between neutron-induced events and those induced by transient gamma rays in the detector's sensitive volume. The arrival times of transient gamma rays and neutrons show a significant difference. Compared to transient gamma rays, high-energy neutrons typically arrive at the detector with a delay of several nanoseconds. Depending on the initial distance between the origin and the detector surface, as well as the neutron slowing in the target itself, the arrival time of incident secondary neutrons will show variations—increasing with lower energy and greater distance.

[0091] Most transient gamma rays reach the detector within 2 to 3 ns—the time measured as the time between the proton pencil beam incident on the water model and the first incoherent scattering event registered in the detector's sensitive volume. Neutrons exhibit large variations depending on the energy produced and the depth within the water model. Most neutrons reach the detector within 5 to 6 ns, with long tails reaching approximately 30 to 40 ns.

[0092] The scintillator element, or "strip," provides containment of scintillation light from neutron and transient gamma-ray scattering events along the individual element via an air gap and a liner with reflective material. Compared to monolithic methods, this structure eliminates crosstalk between individual channels, thereby significantly reducing data throughput and the complexity of subsequent data analysis.

[0093] The collision location can then be reconstructed along a given strip (z-axis) height using the amplitude and relative timing of the two waveforms from the photodetector. Strip size, scintillation light production, scintillation decay time constant, light channel guidance efficiency through the strip, photodetector quantum efficiency, and photodetector transit time spread are parameters that ultimately affect the accuracy at which the scintillation light production location (i.e., the collision location along the length of a given scintillator strip) and the energy of the recoil particles (protons and electrons) can be estimated.

[0094] The physical thickness of each strip ultimately determines the accuracy of the estimates of the collision location along the x and y axes, while the statistical uncertainty of the estimate of the collision location along the z axis will dominate the overall uncertainty in estimating the collision locations of neutrons and transient gamma rays.

[0095] In implementations, means for distinguishing between neutrons and transient gamma rays include scintillators with pulse shape differentiation (PSD) capability, such as stilbene and PSD plastic scintillators.

[0096] These are scintillation crystals in which neutron-induced events typically produce scintillation pulses longer than those produced by transient gamma-ray-induced events (Pozzi, SA et al., Pulse shape discrimination in the plasticscintillator EJ-299-33. Nucl. Instrum. Methods Phys. Res. Secret. Accel. Spectrometers Detect. Assoc. Equip., 2013, Vol. 723, pp. 19–23).

[0097] Monte Carlo (MC) simulations have been conducted to reveal the expected detection efficiency of the depicted detector as a dual imaging device capable of detecting both neutrons and transient gamma rays produced by proton bombardment of a water model using MCNP6.2. MCNP6.2 (Goorley, T. et al., Initial MCNP6 Release Overview. NT, 2012, Vol. 180, pp. 298–315) is the MC code system used to simulate the interactions and paths of neutrons, photons, electrons, positrons, alphas, protons, and other heavier ions (a total of 37 different particle types) in arbitrary geometries and materials.

[0098] The relevant MC simulations included monoenergetic proton beams and water models with energies of 100 MeV, 160 MeV, 200 MeV, and 230 MeV; however, the depicted detector was modeled as a 10x10x20 cm integral hydrogen-rich liquid organic scintillator. 3 "Block" (density 0.959 g / cm³) 3(and the H / C ratio is 1.25). At each energy, the proton beam intensity is set to 1 x 10⁻⁶. 9 The protons were detected, and the detector was positioned directly above the expected nominal Bragg peak location.

[0099] Figure 2 A sample of the simulated geometry results is shown in Figure A. The number of secondary neutrons in the detector volume, having undergone their first two interactions as elastic scattering from the hydrogen-1 nucleus, is recorded. Additionally, the number of transient gamma rays having undergone their first two interactions as incoherent, i.e., Compton scattering events, is also recorded. The table below gives the double (n, p) scattering rate of incident neutrons per primary proton and the double incoherent scattering rate of incident transient gamma rays per primary proton, along with their corresponding statistical uncertainties (one standard deviation):

[0100]

[0101] The results reveal that the dual incoherent scattering rate for incident transient gamma rays is approximately 5 times lower than the dual (n, p) scattering rate for incident neutrons. The expected reduction in efficiency would be even greater when more stringent constraints are applied, i.e., when a third interaction is also required within the sensitive volume of the detector.

[0102] Although the detector incorporates organic scintillators with low density and low atomic number, its compactness and overall size compensate for this. Therefore, useful efficiencies can be achieved, which also applies to high-energy transient gamma rays. Existing technology-based real-time range verification systems for transient gamma ray imaging achieve efficiencies in the range of 10-1. -5 Up to 5.6x10 -5 The count of transient gamma rays / protons, or even lower for the Compton camera and collimating camera, is thus lower. Therefore, the detector design described here can achieve unprecedented detection efficiency, even for transient gamma rays alone. Since the detector is sensitive to both neutrons and transient gamma rays and will combine data from both particle species, the efficiency will be unparalleled.

[0103] Furthermore, the detected neutron profile is advantageous, such as... Figure 2 As shown in Figure B, there is a steep drop precisely near the Bragg peak. To obtain "range markers" that can be correlated with the range of the primary proton beam, a simple logistic function is fitted to the neutron profile, while a Savitsky-Gorye filter is applied to the transient gamma-ray profile to further smooth the resulting detection profile. For both the neutron and transient gamma-ray profiles, the inflection point locations are considered "range markers," see [reference needed]. Figure 2 C.

[0104] Then for 1x10 9The dataset collected from the primary proton beam intensity is divided into 1x10... 8 Ten equal data blocks are formed corresponding to the proton intensity of each proton. Then, the boundary values ​​of each repeated range in these data blocks are calculated for statistical analysis of the results.

[0105] Next, the original dataset will be divided into 5x10... 7 Twenty equal data blocks corresponding to the proton intensity of each proton. The range markers are then recalculated for ten trials. This process is repeated to obtain the statistical uncertainty of the range marker estimation at lower proton beam intensities.

[0106] The statistical precision of the range demarcation estimates obtained from both neutron and transient gamma-ray profiles reveals that submillimeter precision is achievable up to approximately 1 x 10⁻⁶. 7 The initial proton beam intensity for each proton is shown in the figure. Figure 7A and Figure 7B This is very encouraging for MC simulation of existing technology-based verification systems.

[0107] Repeated simulations at proton beam energies of 100 MeV, 160 MeV, 200 MeV, and 230 MeV also revealed a linear correlation between the range marker positions from both neutron and transient gamma-ray profiles and the Bragg peak positions, such as... Figure 2 As shown in C.

[0108] In summary, the described detector concept for real-time range verification and image-guided imaging in CPT is clearly demonstrated by superior detection efficiency, detected neutron and transient gamma-ray profiles, the possibility of performing 2D and 3D imaging in real time, and the possibility of unifying neutron and transient gamma-ray imaging in a single compact device.

[0109] This example is for illustrative purposes only and illustrates that the depicted detector system can be used to verify the detection of neutrons and transient gamma rays with superior detection efficiency relative to the existing technology range in CPT. The detection of both neutrons and transient gamma rays enables more accurate identification and verification of treatment by more precisely determining the location of the Bragg peak in the target.

[0110] In exemplary embodiments, various features and details are illustrated in combination. The fact that several features are described with respect to a particular example should not be construed as implying that these features must be included together in all embodiments of the invention. Rather, features described with reference to different embodiments should not be construed as mutually exclusive. As will be readily understood by those skilled in the art, the inventors have contemplated any subset of features incorporated herein that are not explicitly interdependent, and these embodiments are part of the intended disclosure. However, a clear description of all these embodiments will not contribute to understanding the principles of the invention, and therefore some substitutions of features have been omitted for simplicity or brevity.

Claims

1. A system for validating charged particle therapy, comprising: A detector comprising an array of optically segmented organic scintillator elements, wherein the scintillator elements are columnar and the array is arranged to have a cross-section perpendicular to the length of the scintillator elements, the system being characterized by further comprising: - A photodetector array, which is arranged at both ends of the scintillator element, and - A processing unit connected to the photodetector array, wherein the processing unit is configured to estimate the direction and energy of incoming fast neutrons and transient gamma rays. The system is configured to detect secondary particles of the fast neutron and transient gamma-ray types emitted from a target irradiated with a charged particle beam, wherein: The detector is configured to detect at least two consecutive elastic scattering collisions of incident fast neutrons and at least two incoherent scattering collisions of incident transient gamma rays in different scintillator elements, as well as any subsequent third events of any type, to achieve sufficient counting statistics for both particle types, and to reconstruct the momentum of the recoil protons from the two consecutive elastic scattering collisions to reconstruct the incident angle and incident fast neutron energy located along the event line, and to estimate the range markers obtained from the distributions of fast neutrons and transient gamma rays with sub-millimeter accuracy.

2. The system according to claim 1, wherein, The third event is one of the following: photoelectric effect, incoherent scattering, or sporadic generation of secondary transient gamma rays.

3. The system according to claim 1, wherein, The processing unit is configured to estimate the location of the nuclear interaction between the charged particle beam and the target.

4. The system according to any one of claims 1 to 3, wherein, The processing unit is configured to estimate the dose distribution at the target location from the detected and reconstructed distribution of secondary fast neutron and transient gamma ray production locations.

5. The system according to any one of claims 1 to 3, wherein, The processing unit is configured to distinguish between the fast neutrons and the transient gamma rays.

6. The system according to any one of claims 1 to 3, wherein, The processing unit is configured to distinguish between the fast neutrons and the transient gamma rays by pulse shape differentiation PSD or time-of-flight (ToF) measurements.

Images