System for monitoring a hadron beam during hadron therapy treatment of a subject

Abstract

The invention relates to a method for monitoring a hadron beam during hadron therapy treatment of a subject, the subject comprising tumor cells labeled with a radiopharmaceutical product, wherein the hadron beam comprises a plurality of discrete hadron bursts, the method comprising the following steps: when a burst strikes the subject, detecting (111) prompt gamma rays generated by the interaction of the hadrons of the burst with the tissue of the subject by means of a Compton telescope, and reconstructing (112) an image of the interaction volume; when no burst strikes the subject, extracting (121) the positions of the tumor cells labeled with the radiopharmaceutical product by means of the Compton telescope, and reconstructing (122) an image of the total tumor volume; and comparing (131) the image of the interaction volume with the image of the total tumor volume, so as to locate the measured interaction volume relative to the measured total tumor volume.

Description

Technical Field

[0001] The present invention relates to a system and method for monitoring a hadron beam during hadron therapy treatment of a subject suffering from cancer. In particular, the present invention relates to a system and method for monitoring the interaction zone between the hadron beam and the tissue of the subject and thus indirectly monitoring the delivered dose relative to a tumor mass to be treated, the tumor mass having been labeled with a radiopharmaceutical product having a radioisotope that emits positrons and de-excites gamma rays in a quasi-coincidence manner. Background Art

[0002] Hadron therapy is a highly effective cancer treatment using beams of proton particles or carbon ions. This innovative technology has been shown to be effective against tumors that are difficult to treat using conventional radiotherapy because they are radiation resistant or are located deep or close to vital organs. The use of hadron beams enables very precise dose deposition both longitudinally and transversely. In fact, unlike photon beams, where the energy deposition is maximum from the first centimeters of entry into the patient and decreases with depth, the charged ions deposit their energy maximum (Bragg peak) at the end of their path, while maintaining a minimum input deposited dose. In addition, the lateral penumbra of protons is weaker than that obtained with photon beams. However, the high precision of the hadron emission makes this technique sensitive to any source of deviation related to the treatment plan: poor patient positioning, organ motion or anatomical changes between sites or tumor regression, weight loss, filling of anatomical cavities between treatment sessions.

[0003] In order to take advantage of the high accuracy of the emission, the location of the dose delivered by the radiation needs to be thoroughly checked.When the primary beam stops in the patient, the path of the hadrons can be monitored in real time by secondary radiation, especially gamma rays, from their nuclear reactions in the body.

[0004] Some imaging schemes seem promising to obtain information related to the profile of the hadron beam, such as ion-induced ultrasound, secondary electron bremsstrahlung measurement or magnetic resonance imaging (MRI), which have specific problems associated with hadron beam deflection in the magnetic field in the case of real-time MRI. However, these techniques may be difficult to implement. At present, an "in-beam" positron emission tomography (PET) system has been proposed, which uses 511keV coincident gamma rays from the annihilation of positrons emitted during the beta decay of radioactive isotopes produced by hadron interactions in tissues. However, due to the small number of isotopes undergoing beta decay, and considering that the observation of beta decay is delayed by the lifetime duration of the radioactive isotope relative to decay, a relatively long data acquisition time is required. Therefore, real-time beam imaging using in-beam PET only provides information related to the position of the dose delivered after treatment. In addition, unlike conventional PET systems, in-beam PET systems have a reduced coverage angle to be able to position the "gantry" isocentric rotating head, which reduces the sensitive volume of the system.

[0005] In this context, Frandes et al. (Frandes, Mirela et al. "A tracking Compton-scattering imaging system for hadron therapy monitoring." IEEE Transactions on Nuclear Science 57.1 (2010): 144-150.) demonstrated the feasibility of a medical imaging system based on a combination of a Compton telescope and a paired camera by digital simulation. The simulation of the system for different beam energies typical of hadron therapy enabled Frandes et al. to demonstrate the ability of this imaging system to detect gamma rays in the energy range characteristic of Compton interactions, thereby reconstructing the location of the delivered dose. However, this system, which aims to detect gamma rays from annihilation, has the same disadvantages as intra-beam PET.

[0006] Furthermore, the patient's internal anatomy can vary from one treatment session to the next or during the same treatment session. Therefore, being able to monitor in real time the location and amount of dose deposited within the patient is not sufficient to ensure that the target tumor volume is fully irradiated while minimizing the dose delivered to surrounding healthy tissue as much as possible. Indeed, deviations of the tumor volume relative to the external anatomical landmarks used to align the patient relative to the beam can have serious consequences, as the dose will not be delivered according to the treatment plan and therefore healthy tissue will be irradiated.

[0007] The present invention notably aims to remedy these drawbacks by proposing a system capable of monitoring in real time during hadron therapy treatment the position in the patient's body and of the tumor mass and of the dose delivered by the beam, thus enabling dose deposition according to the treatment plan. Summary of the invention

[0008] The invention relates to a method for monitoring a hadron beam during a hadron therapy treatment of a subject comprising tumor cells labeled with a radiopharmaceutical product having a radioisotope emitting positrons and de-excited gamma rays in a quasi-coincidence manner, wherein the hadron therapy treatment is carried out according to a treatment plan comprising predetermined parameters as a function of time so as to define at least one characteristic of the hadron beam over time during the hadron therapy treatment, wherein the hadron beam comprises a plurality of discrete hadron "bursts" emitted by an acceleration device at a predetermined frequency, the method comprising the following steps:

[0009] -When the "burst" hits the subject:

[0010] Detection of "prompt gamma rays" produced by the interaction of "burst" hadrons with the subject's tissues via a liquid xenon Compton telescope;

[0011] Use the detected “prompt gamma rays” to reconstruct an image of the interaction volume, within which the “burst” of hadrons interacts with the subject’s tissue.

[0012] -When no "burst" hits the subject:

[0013] The simultaneous detection of de-excitation gamma rays and two annihilation gamma rays produced by positrons by a liquid xenon Compton telescope to extract the location of tumor cells labeled with radiopharmaceutical products;

[0014] Reconstructing an image of the total tumor volume to be treated by the hadron beam during hadron therapy treatment;

[0015] - comparing the image of the interaction volume with the image of the total tumor volume in order to locate the measured interaction volume relative to the measured total tumor volume;

[0016] - Whenever the measured interaction volume is at least partially included in the measured total tumor volume, calculating a deviation between, on the one hand, the position of the measured interaction volume in the measured total tumor volume and, on the other hand, a predetermined position of the interaction volume in the total tumor volume defined in the treatment plan.

[0017] According to the present invention, due to the reconstruction and comparison of the image of the interaction volume and the image of the total tumor volume, it is possible to monitor the hadron therapy treatment process in real time and effectively evaluate whether the treatment has been implemented according to the treatment plan.

[0018] In one embodiment, an image of the interaction volume is acquired for each "burst" that impinges on the subject. This enables real-time monitoring of the position of the beam in the subject.

[0019] In one embodiment, the method further comprises the step of comparing the deviation between the predetermined position of the interaction volume and the measured position of the interaction volume relative to the measured total tumor volume with a predetermined threshold value. Advantageously, this embodiment enables real-time checking whether the dose distribution delivered by the beam in the subject is consistent with the treatment plan within an acceptable error range from a clinical perspective.

[0020] In one embodiment, whenever the deviation is greater than a predetermined threshold, the method includes the step of calculating at least one new parameter of the hadron beam in order to correct at least one characteristic of the hadron beam. Radiotherapy plans are usually defined based on a three-dimensional image of a subject obtained by "CT scan" computer axial tomography, which converts Hounsfield units (HUs) into proton stopping power to enable the calculation of dose distribution. However, a CT scan is only a static image of a subject at a given position and a given time before treatment. However, in hadron therapy, organ movement, such as defecation, breathing, heartbeat, or changes in internal anatomical structures due to bladder filling or weight changes, can also cause changes in density and thus change the length of the radiation path along the beam trajectory. Its impact in proton therapy can result in severe underdose of the target clinical volume and overdose of organs at risk and normal tissues away from the target. This embodiment makes it possible to take into account any geometric changes and correct the parameters of the hadron beam in real time, thereby enabling the delivery of doses in the target tumor volume in the treatment plan.

[0021] In one embodiment, the subject is positioned on a motorized mechanical support configured to move the subject relative to the beam during hadron therapy treatment. In this embodiment, at least one of the predetermined parameters of the treatment plan corresponds to a spatial position of the motorized mechanical support.

[0022] In one embodiment, whenever the deviation is greater than a predetermined threshold, the method comprises the step of calculating the parameters of the treatment plan corresponding to the new spatial position of the motorized mechanical support so as to correct at least one characteristic of the hadron beam. This makes it possible to place the beam source in a fixed position and avoid the use of a "Gantry".

[0023] In one embodiment, the new parameters of the hadron beam are sent to an acceleration device which modifies at least one characteristic of the hadron beam in order to modify the position of the interaction volume relative to the measured total tumor volume. This creates a feedback loop enabling real-time adjustment of the beam according to the treatment plan.

[0024] In one embodiment, the method comprises stopping the hadron beam whenever the deviation is greater than a predetermined threshold. Advantageously, this embodiment makes it possible to stop the treatment to prevent overdosing of the organ at risk.

[0025] In one embodiment, the method further comprises the step of reconstructing a three-dimensional image sequence by fusing the three-dimensional image of the interaction volume with a three-dimensional image of the total tumor volume in a reference having the same Compton camera.

[0026] The invention also relates to a system for monitoring a hadron beam during a hadron therapy treatment of a subject comprising tumor cells labeled with a radiopharmaceutical product having a radioisotope emitting positrons and de-excited gamma rays in a quasi-coincident manner, wherein the hadron therapy treatment is carried out according to a treatment plan comprising predetermined parameters as a function of time so as to define at least one characteristic of the hadron beam over time during the hadron therapy treatment, wherein the hadron beam comprises a plurality of discrete hadron "bursts" emitted by an acceleration device at a predetermined frequency, the system comprising:

[0027] a beam imaging module configured to receive data acquired from a liquid xenon Compton telescope when the "burst" impinges on the subject and to analyze these data to determine the emission points of the "prompt gamma rays" generated by the interaction of the "burst" with the tissue of the subject, from which to reconstruct an image of the interaction volume within which the hadrons of the "burst" interact with the tissue;

[0028] - a tumor imaging module configured to receive data acquired by the liquid xenon Compton telescope when no "burst" impinges on the subject, and configured to analyze these data to extract the location of tumor cells labeled with the radiopharmaceutical product by simultaneously detecting the de-excitation gamma rays and the two annihilation gamma rays produced by the positrons, and to use the location of the tumor cells to reconstruct an image of the total tumor volume to be treated by the hadron beam during hadron therapy treatment;

[0029] an evaluation module configured to compare an image of the interaction volume with an image of the total tumor volume in order to position the measured interaction volume relative to the measured total tumor volume and, whenever the measured interaction volume is at least partially included in the measured total tumor volume, to calculate a deviation between, on the one hand, a position of the measured interaction volume relative to the measured total tumor volume and, on the other hand, a predetermined position of the interaction volume in the total tumor volume defined in the treatment plan.

[0030] A system implementing the method according to the invention advantageously makes it possible to monitor in real time the dose delivered in the subject based on the reconstruction of the image of the interaction volume and the image of the total tumor volume and to check whether it complies with the dose distribution provided in the treatment plan.

[0031] In one embodiment, in the evaluation module, an image of the interaction volume is obtained for each burst impinging on the subject.

[0032] In one embodiment, the evaluation module is further configured to compare a deviation between a predetermined position of the interaction volume and a measured position of the interaction volume relative to the measured total tumor volume with a predetermined threshold.

[0033] In one embodiment, the subject is positioned on a motorized mechanical support configured to move the subject relative to the beam during hadron therapy treatment, and wherein at least one of the predetermined parameters of the treatment plan corresponds to a spatial position of the motorized mechanical support.

[0034] According to one embodiment, the system further comprises a correction module configured to calculate at least one new parameter of the hadron beam each time the deviation is greater than a predetermined threshold in order to correct at least one characteristic of the hadron beam.

[0035] According to an advantageous feature, the correction module is further configured to send new parameters of the hadron beam to an acceleration device which modifies at least one characteristic of the hadron beam in order to modify the position of the interaction volume relative to the measured total tumor volume.

[0036] According to one embodiment, the system further comprises a safety module configured to send an instruction to the acceleration device to stop the hadron beam whenever the deviation is greater than a predetermined threshold.

[0037] According to one embodiment, the system further comprises an image reconstruction module configured to reconstruct a three-dimensional image sequence obtained by fusing the three-dimensional image of the interaction volume with the three-dimensional image of the total tumor volume according to the same Compton camera reference.

[0038] According to one embodiment, the system includes a Compton telescope, the Compton telescope being a liquid xenon Compton telescope.

[0039] According to one embodiment, the system comprises an acceleration device and / or a motorized mechanical support.

[0040] According to one embodiment, the method for monitoring a hadron beam is a computer implemented method.

[0041] The invention also relates to a computer program comprising instructions which, when the program is run by a computer, cause the computer to implement the method for monitoring a hadron beam as described above.

[0042] The present invention also relates to a computer-readable recording medium comprising instructions, which, when executed by a computer, causes the computer to implement the above-mentioned method for monitoring a hadron beam.

[0043] definition

[0044] In the present invention, the following terms are defined as follows:

[0045] - A "burst" is a beam of hadrons with the same acceleration phase.

[0046] - "Prompt gamma rays" are high-speed and high-energy gamma rays emitted naturally following a nuclear reaction between hadrons and the tissues of a subject.

[0047] - "Organs at risk (OARs)" are organs that doctors set dose limits not to exceed in order to minimize radiation-related side effects

[0048] - "PTV (or Planning Target Volume)" refers to a volume that includes the tumor visible on imaging studies (GTV or "Gross Tumor Volume"), extended by adding margins defined by the imprecision of the treatment process (uncertainties regarding the path, positioning, inherent uncertainties of the treatment machine, etc.), and a treatment margin defined by the physician according to the type of disease being treated (CTV or "Clinical Target Volume").

[0049] - "Subject" refers to a mammal, preferably a human. According to the present invention, a subject can be a patient, ie a human being who is under medical supervision, undergoing or has undergone medical treatment, or undergoing follow-up of the progression of a disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] The characteristics and advantages of the invention will emerge from the following description of several embodiments of the system and method according to the invention, which description is given by way of non-limiting example only and with reference to the accompanying drawings, in which:

[0051] Figure 1 is a schematic perspective view of a treatment table and a Compton telescope in an open configuration according to a first embodiment of the present invention;

[0052] Figure 2 is a flow chart showing the steps of a method according to a first embodiment of the present invention;

[0053] Figure 3 is a schematic perspective view of a treatment table and a Compton telescope in an open configuration according to a second embodiment of the present invention;

[0054] Figure 4 is a schematic perspective view of a treatment table and a Compton telescope in a closed configuration according to a third embodiment of the present invention. DETAILED DESCRIPTION

[0055] The present invention relates to a method of monitoring a hadron beam during hadron therapy treatment of a subject suffering from a tumor.

[0056] Typically, in a hadron therapy center, hadrons are accelerated at a treatment energy between 70 and 250 MeV, usually using a cyclotron or synchrotron, and are transported to a treatment room where they enter a treatment nozzle. The thin initial hadron beam is distributed laterally and longitudinally and is appropriately formatted to achieve treatment. The hadrons used are usually protons or carbon ions. Electromechanical devices can be used to scatter and format the beam for treating patients with passive scattering hadron therapy (PSHT). This technique is particularly suitable for protons. The second mode is called uniform scanning and consists of scanning a coarse beam over a wide field of view, which is then collimated and depth compensated by an accessory customized for the patient's anatomy. This makes it possible to treat a wider area with a deeper path. Another method consists of magnetically scanning a microbeam of hadrons with an initial energy sequence. The hadrons scan the tumor very finely and accurately in three directions (x, y, z) so that the tumor is irradiated without the use of customized accessories. This technology can be used to treat patients with intensity modulated hadron therapy.

[0057] The hadron therapy is performed according to a treatment plan comprising predetermined parameters as a function of time in order to define at least one characteristic of the hadron beam over time during the hadron therapy treatment.

[0058] According to one embodiment, the predetermined parameter defining at least one characteristic of the beam varies depending on the hadron therapy technique used.

[0059] For the passive scattering method, lateral and longitudinal scattering of the beam is obtained thanks to the use of a path modulation wheel and one or two scatterers made of high-Z material to produce a flat, wide beam in the area of ​​interest. The modulation wheel is configured to insert blades of material of different thicknesses on the path of the hadrons during their rotation in order to spread the Bragg peak and adjust it to the depth of the target volume. The modulation of the Bragg peak is therefore discrete. The blade thickness and width are designed so that the sum of the resulting individual Bragg peaks gives a uniform and homogeneous depth dose distribution, SOBP or "spread Bragg peak". In order to adapt the dose distribution laterally to the shape of the target volume (plus an appropriate margin), an aperture is used, usually consisting of a brass block of sufficient thickness (2 cm to 8 cm) to absorb the highest energy incident hadrons. Finally, in order to create a dose distribution according to the distal shape of the target, a distance compensator is used to spread the Bragg peak of the passively scattered beam further.

[0060] According to one embodiment, hadron therapy uses a passive scattering technique. In this embodiment, the predetermined parameters include at least beam energy and hadron path modulation (ie, SOBP). In practice, the absorber and compensator are custom-made accessories for the patient, and their positions do not change during treatment.

[0061] For uniform scanning, an active scanning system is used, which builds up a Bragg peak modulation in the tumor by multiple microirradiations. The target volume is irradiated by lateral scanning layer by layer. A dedicated modulation wheel is used to translate the Bragg peak step by step. To better define the modulated Bragg peak, intermediate depth layers are irradiated due to the association of the absorption plates of the scatterers and the blades of the modulation wheel. Once modulated, the proton beam is extensively scanned in the Y and X directions, respectively, by the vertical magnets in the first position and then by the subsequent horizontal magnets.

[0062] According to one embodiment, hadron therapy uses a uniform scanning technique. In this embodiment, the predetermined parameters include at least beam energy, hadron path modulation, and X and Y positions of the beam.

[0063] Active microbeam scanning consists of using magnets to precisely scan the elementary ion beam in horizontal and vertical dimensions while varying the initial energy of the protons in order to scan the entire tumor volume layer by layer without the use of patient-customized accessories. The depth (Z) is managed by proton beam energy modulation thanks to the energy selection system. The position of the beamlets in the plane (X, Y) is controlled by the same scanning magnets as described below. A set of spots is thus generated and distributed over the entire target volume. The spot size at the isocenter is appropriate thanks to the quadrupole located before the scanning magnet. Its main advantage is the reduction in the number of neutrons produced and the output losses, both of which are due to passive beam formatting accessories.

[0064] According to one embodiment, hadron therapy uses active microbeam scanning technology. In this embodiment, the predetermined parameters include at least the X, Y and Z coordinates (ie, the beam energy) and the intensity of each light spot.

[0065] The technology implementing magnetic beam scanning can be configured to enable beam deflection to cover a treatment area of ​​up to 30 cm x 40 cm.

[0066] In a hadron therapy treatment room, the subject typically sits in a chair or reclines on a treatment table in a predetermined position relative to a treatment nozzle from which the beam is emitted to impinge on the subject.

[0067] In one embodiment, the treatment nozzle is located at a fixed position at a predetermined distance from the subject. The treatment nozzle can be positioned relative to the subject so that the direction of incidence of the beam F enters the subject perpendicular to the sagittal plane of the subject. In a preferred embodiment, the treatment nozzle is positioned facing the subject so that the entry point of the beam is in the front of the subject. This enables the beam to penetrate the subject up to the target volume by passing through the smallest possible thickness of healthy tissue and / or organs at risk, thereby reducing the dose they receive.

[0068] With the treatment nozzle in a fixed position, the direction of incidence of the beam F and therefore also its entry point in the tissue can be changed using magnetic scanning alone, which enables small deviations of the beam.

[0069] In order to be able to change the angle of incidence of the beam over an arc of more than 180 degrees, in one embodiment the treatment table T is configured to move the subject relative to the point of incidence of the beam, in particular during hadron therapy treatment. Figure 1 In the first embodiment shown, the treatment table T is rotatable in two rotational directions about three axes A1 , A2 and A3 and is translatable in two opposite directions along each of the axes A1 , A2 and A3 .

[0070] In this first embodiment, the Compton telescope TC comprises two Compton half-detectors in the form of two hollow half-cylinders, symmetrical with respect to the axis A1 and separated from each other along the direction A2 so as to allow the beam F arriving above the subject to pass. The two half-cylinders are complementary and, if connected together, are able to form a complete hollow cylinder. In particular, each half-detector forms an arc of an angle of 180°. In this embodiment, each Compton half-detector is capable of translation in two directions along the axes A1, A2 and A3 and of rotation about the axis A3.

[0071] exist Figure 3In the second embodiment shown, the treatment table T is also rotatable in two rotational directions about three axes A1, A2 and A3 and is also translatable in two opposite directions along each of the axes A1, A2 and A3. The Compton telescope TC comprises two Compton half-detectors in the form of two hollow semi-cylinders, which are symmetrical with respect to the axis A1 and separated from each other along the direction A3 so as to allow the beam F to pass to the side of the subject.

[0072] The configuration of the Compton telescope in the first and second embodiments is referred to in this specification as an "open configuration Compton telescope". In the first and second embodiments, each Compton half-detector can be moved independently of the other to better adapt to the position and direction of incidence of the beam F on the subject, while keeping the Compton telescope TC as closed as possible on the subject. In fact, when the two half-detectors are closest to the subject, the Compton telescope has a higher spatial resolution, making it possible to detect a greater number of events (i.e. prompt gamma rays, de-excited gamma rays or annihilation gamma rays).

[0073] exist Figure 4 In the third embodiment shown, the Compton telescope comprises a single detection volume in the form of a hollow cylinder and comprising a transverse slit of a size capable of allowing the passage of a beam F arriving to the side of the subject. This configuration of the Compton telescope is referred to in the present description as a "Compton telescope in closed configuration". The treatment table T is aligned along an axis A1 which is also the longitudinal axis of the hollow cylinder. The treatment table T is movable inside the Compton telescope in closed configuration, in particular capable of rotating in two directions of rotation about three axes A1, A2 and A3 and capable of translating in two opposite directions along each of the axes A1, A2 and A3. In this embodiment, the Compton telescope is mounted on a mechanical support which is motorized so as to be capable of translating along the axes A1, A2 and A3 and of pivoting about the axis A3.

[0074] In the first, second and third embodiments, the treatment table T on which the subject is located is firmly mounted on a motorized mechanical support (not shown) that enables the treatment table to move with the degrees of freedom described below. The motorized mechanical support specifically enables the treatment table T to perform rotational movements at intervals of 2 to 15 degrees and translational movements at intervals of 0.5 cm to 5 cm.

[0075] In one embodiment, the motorized support is a robotic positioning arm configured to have a sensitivity of 0.1 cm to 1 cm.

[0076] In an embodiment comprising a treatment table T on a motorized mechanical support, at least one of the predetermined parameters of the treatment plan corresponds to the spatial position of the treatment table T and, therefore, to the spatial position of the motorized mechanical support. This particularly advantageous embodiment makes it possible to avoid the use of a huge isocentric rotating head ("gantry") configured to deliver the beam at a variable angle of more than 180°. The "gantry" equipped with the treatment nozzles has extremely high production costs compared to a motorized treatment couch. Therefore, avoiding the use of a "gantry" can reduce the construction costs of the hadron therapy infrastructure, making this technology more accessible.

[0077] In embodiments where the Compton telescope is movable, at least one of the predetermined parameters of the treatment plan corresponds to a spatial position of the Compton telescope in a closed configuration, or to a spatial position of each Compton half-detector of the Compton telescope in an open configuration.

[0078] The accelerator device used in the method according to the invention produces a hadron beam comprising a plurality of discrete "bursts" of hadrons emitted by the accelerator device at a predetermined frequency.

[0079] In one embodiment, the acceleration device that produces the used hadron beam is a synchrotron or a linear accelerator. The synchrotron accelerates hadrons in the form of beams (pulses) at the required energy. Once the beam reaches the required energy, it is extracted and sent to the treatment room via a "beamline". However, regardless of the type of accelerator, the extracted narrow monoenergetic beam is magnetically guided to the treatment nozzle via the beamline.

[0080] In one embodiment, the accelerating device is a "digital" synchrotron comprising an induction unit, where the magnet is exposed to rapid changes in its operation due to external beam steering means and an on-board computer (switches and FPGA) capable of controlling them.

[0081] In addition to the self-activation and emission of charged particles, the "burst" interaction also produces rapid emission of high-energy gamma rays in the material, known as "prompt gamma rays". The prompt gamma ray production profile is well correlated with the hadron path. Therefore, the detection of prompt gamma rays can be effectively used to monitor the interaction point of the beam and dose deposition in the subject.

[0082] Figure 2 An embodiment of a method comprising several data acquisition and calculation steps is shown.

[0083] The method according to the invention is configured to enable real-time monitoring of hadron therapy treatment by obtaining a sequence of images of the interaction volume, within which the "burst" of hadrons interacts with the tissue of the subject, and of the total tumor volume. An image of the interaction volume is obtained only when the "burst" hits the subject.

[0084] Thus, the method comprises a first phase, when the "burst" hits the subject 10, which first phase comprises the following steps:

[0085] - Detection of 111 "prompt gamma rays" produced by the interaction of the "burst" of hadrons with the tissues of the subject through the Compton telescope;

[0086] - Use the detected "prompt gamma rays" to reconstruct an image of the 112 interaction volume, within which the "burst" of hadrons interacts with the subject's tissue.

[0087] In a preferred embodiment, the Compton telescope is a liquid xenon Compton telescope. The basic physical properties of liquid xenon, such as its high density and high atomic number, give a high stopping power to ionizing radiation, which makes liquid xenon an ideal material for gamma-ray detectors in the energy range of tens of keV to tens of MeV. Liquid xenon is both an excellent active medium for detecting ionizing radiation and an excellent scintillator, with the advantage that large detectors can be constructed with a uniform sensitive medium. The Compton telescope utilizes the continuous interaction (two or more than two) of incident photons in the interaction volume. Based on the interaction point and the energy deposited in each interaction, the direction of the incident photon can be reduced to a cone through the application of Compton kinematics. The position of the photon source can be determined by the intersection of different Compton cones, which is inferred from the subsequent interaction of photons from the same source. Therefore, this type of detector is very suitable for detecting "prompt gamma rays" in the corresponding energy range of several MeV, where Compton scattering is the main process.

[0088] The measured image of the interaction volume can be a three-dimensional image.

[0089] In one embodiment, for each "burst" that strikes the subject, an image of the interaction volume is acquired. In this embodiment, the image acquisition frequency depends on the "burst" generation frequency in the acceleration device. Therefore, the number of images acquired per second can vary from 5 to 30.

[0090] In one embodiment, the Compton telescope is configured to have a spatial resolution of about 1 mm for each image of a "burst".

[0091] In the present invention, the tumor cells of the subject are labeled with a radiopharmaceutical product containing a radioisotope that emits positrons and de-excites gamma rays in a quasi-coincidence manner. This enables the identification of the location of the radio marker due to the use of the three-photon imaging principle. In fact, the positron travels along a short path (about 1 mm) in the tissue and then annihilates into two photons of 511 keV moving in opposite directions ("back-to-back gamma rays").

[0092] Three-photon imaging is based on the combined use of a Compton telescope and a radiopharmaceutical having a radioisotope that emits positrons and de-excited gamma rays in a quasi-coincidence manner.

[0093] The simultaneous detection of the two annihilation photons makes it possible to draw a line of response (LOR), i.e. a line connecting the two interaction points of the annihilation photons in the Compton telescope and passing through the point of positron annihilation in the tissue. The position of the radioisotope is thus obtained by the intersection between the LOR and the Compton cone, which is defined based on the interaction of the de-excitation gamma ray with the Compton telescope. The surface of the Compton cone includes the direction of incidence of the de-excitation gamma ray and can be directly inferred from the Compton kinematics. The aperture angle θ of the Compton cone is defined by the Compton scattering formula, where the axis of the Compton cone is determined using the first of the two interaction points of the de-excitation gamma ray entering the telescope.

[0094] This technique advantageously reduces the number of decays required to acquire an image, thereby reducing acquisition time and / or the amount of material inoculated per patient.

[0095] When no "burst" hits the subject 11, the first stage of the method comprises the following steps:

[0096] - extracting the location of tumor cells labeled with a radiopharmaceutical product by simultaneously detecting the de-excitation gamma ray and the two annihilation gamma rays produced by the positrons using a Compton telescope as described above;

[0097] - Based on the location of the tumor cells, reconstructing 122 an image of the total tumor volume to be treated by the hadron beam during the hadron therapy treatment.

[0098] In a preferred embodiment, the radioisotope used in the radiopharmaceutical is 44 Sc, which emits positrons and photons with an energy of 1.157 MeV in accord with space and time.

[0099] Images of the total tumor volume were acquired between two consecutive “bursts” to prevent the images from being contaminated by signals generated by “prompt gamma rays.”

[0100] In one example, the Compton telescope is configured such that for a 10 s acquisition, the total tumor volume is imaged with a spatial resolution of approximately 1 mm. The resolution achieved is due to the physical limitations of the detectors and the activity of the isotope injected into the subject.

[0101] In one embodiment, the image of the total tumor volume is a three-dimensional image.

[0102] The method also includes a second phase, which includes the following stages:

[0103] - comparing 131 the image of the interaction volume and the image of the total tumor volume in order to locate the measured interaction volume relative to the measured total tumor volume;

[0104] - Whenever the measured interaction volume is at least partially included in the measured total tumor volume, calculating 132 a deviation between, on the one hand, a position of the measured interaction volume in the measured total tumor volume and, on the other hand, a predetermined position of the interaction volume in the total tumor volume defined in the treatment plan.

[0105] The deviation can be calculated by superimposing the images. This is easily obtained once the images of the measured interaction volume and the images of the measured total tumor volume are acquired by the same detector and are therefore reconstructed relative to the same reference.

[0106] The comparison phase makes it possible to compare the actual position of the Bragg peak with respect to the position calculated in the calculation software used to generate the treatment plan.

[0107] In one embodiment, the method further comprises step 133, wherein the deviation between the predetermined position of the interaction volume and the measured position of the interaction volume relative to the measured total tumor volume is compared with a predetermined threshold. The predetermined threshold can correspond to a margin of 1 mm to 5 mm around the target volume (PTV). The threshold can also be defined based on the radiosensitivity of the organs at risk around the target volume. For example, the predetermined threshold corresponds to a margin of 0.5 mm for highly radiosensitive lymph nodes and a margin of 1 mm in the direction of the less radiosensitive lungs.

[0108] In one embodiment, each time the deviation is greater than a predetermined threshold, the method comprises the step of calculating 134 at least one new parameter of the hadron beam in order to correct at least one characteristic of the hadron beam.

[0109] In one embodiment, each time the deviation is greater than a predetermined threshold, the method comprises the step of calculating parameters of the treatment plan corresponding to the new spatial position of the motorized support in order to correct at least one characteristic of the hadron beam.

[0110] In one embodiment, new parameters of the hadron beam are sent to an acceleration device which modifies at least one characteristic of the hadron beam in order to modify the position of the interaction volume relative to the measured total tumor volume.

[0111] In one embodiment, the method comprises stopping the hadron beam whenever the deviation is greater than a predetermined threshold. This makes it possible to take safety measures to avoid any irradiation that is inconsistent with the treatment plan.

[0112] In one embodiment, the method further comprises the step of reconstructing a three-dimensional image sequence obtained by fusing the three-dimensional image of the interaction volume with a three-dimensional image of the total tumor volume in the same Compton camera reference. Such an image sequence can be viewed in real time as the screen provides visual information to the medical professional.

[0113] The invention also relates to a system for monitoring a hadron beam during hadron therapy treatment of a subject. The system is configured to monitor a hadron beam comprising a plurality of discrete hadron "bursts" emitted by an acceleration device at a predetermined frequency during hadron therapy treatment performed according to a treatment plan comprising predetermined parameters as a function of time, so as to define at least one characteristic of the hadron beam over time during the hadron therapy treatment.

[0114] The system for monitoring hadron beams will now be described in detail. Hereinafter, modules should be understood as functional entities rather than physically separated hardware components. Therefore, they can be combined in the same specific hardware component, and can also be distributed in several such components. In addition, each of these modules is optionally shared between at least two physical components. In addition, modules are implemented in hardware, software, microprograms or any other combination thereof.

[0115] The system includes a beam imaging module configured to receive data acquired from the Compton telescope when the "burst" hits the subject. In one embodiment, data acquisition is performed online and continuously. Data acquired during a time window corresponding to the "burst" being emitted to the subject is sent to the beam imaging module. The module is also configured to analyze these data in order to determine the emission points of the "prompt gamma rays" generated by the interaction of the "burst" with the subject's tissue. Therefore, the module uses the emission points of the "prompt gamma rays" to reconstruct an image of the interaction volume within which the hadrons of the "burst" interact with the tissue.

[0116] In one embodiment, the beam imaging module is further configured to identify and reject any data corresponding to events that are not based on "prompt gamma ray" interactions in the sensitive volume of the Compton telescope.

[0117] The system also includes a tumor imaging module configured to receive data acquired by the Compton telescope when no "burst" hits the subject. In one embodiment, data acquisition is performed online and continuously, and only data acquired between two consecutive subject "bursts" are sent to the tumor imaging module. This makes it possible to select data only from beta decays of radioisotopes captured by tumor cells. In addition, the module is configured to analyze these data in order to extract the location of tumor cells labeled with radiopharmaceutical products by simultaneously detecting de-excitation gamma rays and two annihilation gamma rays produced by positrons, and use the location of tumor cells to reconstruct an image of the total tumor volume that will be treated by the hadron beam during hadron therapy treatment.

[0118] In one embodiment, the Compton telescope is a liquid xenon Compton telescope.

[0119] The system also includes an evaluation module that is configured to compare the image of the interaction volume and the image of the total tumor volume in order to position the measured interaction volume relative to the measured total tumor volume and, whenever the measured interaction volume is at least partially included in the measured total tumor volume, calculate a deviation between, on the one hand, the position of the measured interaction volume relative to the measured total tumor volume and, on the other hand, a predetermined position of the interaction volume in the total tumor volume defined in the treatment plan.

[0120] In one embodiment, the evaluation module is further configured to compare a deviation between a predetermined position of the interaction volume and a measured position of the interaction volume relative to the measured total tumor volume with a predetermined threshold.

[0121] In one embodiment, the system further comprises a correction module configured to calculate at least one new parameter of the hadron beam each time the deviation is greater than a predetermined threshold in order to correct at least one characteristic of the hadron beam.

[0122] As explained in the first part of the specification, the predetermined parameters defining the hadron beam characteristics vary depending on the type of hadron therapy treatment. Based on the type of treatment that can be delivered by the treatment nozzle, the predetermined parameters that can be dynamically affected during a treatment session include beam energy, hadron path modulation (i.e., SOBP), hadron path modulation, and / or X and Y positions of the beam.

[0123] In one embodiment, the correction module is further configured to send new parameters of the hadron beam to an acceleration device which modifies at least one characteristic of the hadron beam in order to modify the position of the interaction volume relative to the measured total tumor volume.

[0124] In one embodiment, the acceleration device comprises a treatment nozzle disposed in a fixed position relative to a treatment table in the treatment room.

[0125] In one embodiment, the treatment table T is configured to move the subject relative to the point of incidence of the beam, particularly during hadron therapy treatment. Figure 1 In the first embodiment shown, the treatment table T is rotatable in two rotational directions about three axes A1 , A2 and A3 and is translatable in two opposite directions along each of the axes A1 , A2 and A3 .

[0126] In this first embodiment, the Compton telescope TC comprises two Compton half-detectors in the form of two hollow half-cylinders, symmetrical with respect to the axis A1 and separated from each other along the direction A2 so as to allow the beam F arriving above the subject to pass. The two half-cylinders are complementary and, if connected together, are able to form a complete hollow cylinder. In particular, each half-detector forms an arc of an angle of 180°. In this embodiment, each Compton half-detector is capable of translation in two directions along the axes A1, A2 and A3 and of rotation about the axis A3.

[0127] exist Figure 3 In the second embodiment shown, the treatment table T is also rotatable in two rotational directions about three axes A1, A2 and A3 and is also translatable in two opposite directions along each of the axes A1, A2 and A3. The Compton telescope TC comprises two Compton half-detectors in the form of two hollow semi-cylinders, which are symmetrical with respect to the axis A1 and separated from each other along the direction A3 so as to allow the beam F to pass to the side of the subject.

[0128] The configuration of the Compton telescope in the first and second embodiments is referred to in this specification as an "open configuration Compton telescope". In the first and second embodiments, each Compton half-detector can be moved independently of the other to better adapt to the position and direction of incidence of the beam F on the subject, while keeping the Compton telescope TC as closed as possible on the subject. In fact, when the two half-detectors are closest to the subject, the Compton telescope has a higher spatial resolution, making it possible to detect a greater number of events (i.e. prompt gamma rays, de-excited gamma rays or annihilation gamma rays).

[0129] exist Figure 4In the third embodiment shown, the Compton telescope comprises a single detection volume in the form of a hollow cylinder and comprising a transverse slit of a size capable of allowing the passage of a beam F arriving to the side of the subject. This configuration of the Compton telescope is referred to in the present description as a "Compton telescope in closed configuration". The treatment table T is aligned along an axis A1 which is also the longitudinal axis of the hollow cylinder. The treatment table T is movable inside the Compton telescope in closed configuration, in particular capable of rotating in two directions of rotation about three axes A1, A2 and A3 and capable of translating in two opposite directions along each of the axes A1, A2 and A3. In this embodiment, the Compton telescope is mounted on a mechanical support which is motorized so as to be capable of translating along the axes A1, A2 and A3 and of pivoting about the axis A3.

[0130] In the first, second and third embodiments, the treatment table T on which the subject is located is firmly mounted on a motorized mechanical support (not shown) that enables the treatment table to move with the degrees of freedom described below. The motorized mechanical support specifically enables the treatment table T to perform rotational movements at intervals of 2 to 15 degrees and translational movements at intervals of 0.5 cm to 5 cm.

[0131] In one embodiment, the motorized support is a robotic positioning arm configured to have a sensitivity of 0.1 cm to 1 cm.

[0132] In an embodiment comprising a treatment table T on a motorized mechanical support, at least one of the predetermined parameters of the treatment plan corresponds to a spatial position of the motorized mechanical support, in particular to the spatial position of the treatment table T. The correction module is further configured to calculate new parameters of the treatment plan corresponding to the new spatial position of the motorized mechanical support so as to correct at least one characteristic of the hadron beam, in particular to the direction of incidence and the point of incidence of the beam.

[0133] In an embodiment where the Compton telescope is capable of being moved, at least one of the predetermined parameters of the treatment plan corresponds to a spatial position of the Compton telescope in a closed configuration, or to a spatial position of each Compton half-detector of a Compton telescope in an open configuration. The correction module is further configured to calculate a new parameter of the treatment plan corresponding to a new spatial position of the Compton telescope in a closed configuration or each Compton half-detector of a Compton telescope in an open configuration.

[0134] In one embodiment, the correction module is further configured to send new parameters of the hadron beam associated with the new position of the motorized mechanical support to the motorized mechanical support itself in order to modify the direction and / or point of incidence of the beam and, therefore, the position of the interaction volume relative to the measured total tumor volume.

[0135] In one embodiment, the system comprises an image reconstruction module configured to reconstruct a three-dimensional image sequence obtained by fusing a three-dimensional image of the interaction volume with a three-dimensional image of the total tumor volume having a reference according to the same Compton camera. This makes it possible to obtain images of the treatment course.

[0136] In one embodiment, the modules of the system include at least one processor and at least one processor-readable recording medium.

[0137] The term "processor" should not be interpreted as limited to "hardware" capable of running software, but rather refers generally to a processing device, which can include, for example, a computer, a microprocessor, an integrated circuit, or a programmable logic controller (PLD). The processor can also include one or more graphics processing units (GPUs), whether they are used for information graphics and image processing or for other functions. In addition, instructions and / or data for performing associated and / or resulting functions can be stored on any medium readable by the processor, such as an integrated circuit, a hard drive, a CD (compact disk), an optical disk such as a DVD (digital versatile disk), a RAM (random access memory), or a ROM (read-only memory). Instructions can be stored in hardware, software, a microprogram, or any combination thereof.

[0138] The invention also relates to a computer program comprising instructions which, when executed by a computer, cause the computer to implement the above-described method for monitoring a hadron beam.

[0139] The present invention also relates to a computer-readable recording medium comprising instructions, which, when executed by a computer, causes the computer to implement the above-mentioned method for monitoring a hadron beam.

[0140] In one embodiment, the computer readable recording medium is non-transitory.

Claims

1. A system for monitoring a hadron beam during hadron therapy treatment of a subject, the subject comprising tumor cells labeled with a radiopharmaceutical product having a radioisotope that emits positrons and de-excited gamma rays in a quasi-coincident manner, wherein: The hadron therapy treatment is performed according to a treatment plan including predetermined parameters as a function of time so as to define at least one characteristic of a hadron beam over time during the hadron therapy treatment, wherein the hadron beam comprises a plurality of discrete hadron bursts emitted by an acceleration device at a predetermined frequency, the system comprising: - a beam imaging module configured to receive data acquired from the Compton telescope when the burst hits the subject and to analyze these data to determine emission points of prompt gamma rays generated by the interaction of the burst with the tissue of the subject, from which to reconstruct an image of the interaction volume within which the hadrons of the burst interact with the tissue; - a tumor imaging module configured to receive data acquired by the Compton telescope when no bursts impinge on the subject, and to analyze these data to extract the location of tumor cells labeled with the radiopharmaceutical product by simultaneously detecting the de-excitation gamma rays and the two annihilation gamma rays produced by the positrons, and to use the location of the tumor cells to reconstruct an image of the total tumor volume to be treated by the hadron beam during hadron therapy treatment; - an evaluation module configured to compare the image of the interaction volume and the image of the total tumor volume in order to position the measured interaction volume relative to the measured total tumor volume and, whenever the measured interaction volume is at least partially included in the measured total tumor volume, to calculate a deviation between, on the one hand, the position of the measured interaction volume relative to the measured total tumor volume and, on the other hand, a predetermined position of the interaction volume in the total tumor volume defined in the treatment plan.

2. The system according to claim 1, wherein: The evaluation module is further configured to compare a deviation between a predetermined position of the interaction volume and a measured position of the interaction volume relative to the measured total tumor volume to a predetermined threshold.

3. The system according to claim 2, further comprising a correction module configured to calculate at least one new parameter of the hadron beam whenever a deviation between a predetermined position of the interaction volume and a measured position of the interaction volume relative to the measured total tumor volume is greater than a predetermined threshold so as to correct at least one characteristic of the hadron beam.

4. The system according to claim 3, wherein: The correction module is further configured to send new parameters of the hadron beam to an acceleration device which modifies at least one characteristic of the hadron beam in order to modify the position of the interaction volume relative to the measured total tumor volume.

5. The system of claim 2, further comprising a safety module configured to send an instruction to the acceleration device to stop the hadron beam whenever a deviation between a predetermined position of the interaction volume and a measured position of the interaction volume relative to the measured total tumor volume is greater than a predetermined threshold.

6. The system according to claim 1, wherein: The Compton telescope is a liquid xenon Compton telescope.

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