METHOD AND SYSTEM FOR MONITORING A HADRON BEAM DURING HADRON THERAPY TREATMENT OF A SUBJECT

Abstract

METHOD AND SYSTEM FOR TRACKING A HADRON BEAM DURING HADRON THERAPY TREATMENT OF A SUBJECT The present invention relates to a method for tracking a hadron beam during hadron therapy treatment of a subject comprising tumor cells labeled with a radiopharmaceutical product, wherein the hadron beam comprises a plurality of discrete bursts of hadrons, the method comprising the following steps: when a burst impacts the subject, detect the gamma prompts (111) generated by the interaction of the burst's hadrons with the subject's tissues using a Compton telescope and reconstruct an image (112) of the interaction volume; when no burst impacts the subject, extract the position of the tumor cells (121) labeled with the radiopharmaceutical product using the Compton telescope and reconstruct an image of the total tumor volume (122);compare the interaction volume image and the total tumor volume image (131) so as to locate the measured interaction volume relative to the measured total tumor volume. Abbreviated figure: Figure 2;

Description

Title of the invention: METHOD AND SYSTEM FOR TRACKING A HADRON BEAM DURING A HADRONTHERAPY TREATMENT OF A SUBJECT FIELD OF THE INVENTION

[0001] The invention relates to a system and method for tracking a hadron beam during a hadrontherapy treatment of a subject suffering from cancer. In particular, the invention relates to a system and method for tracking the interaction zone between the hadrons of the beam and the tissues of the subject, and therefore indirectly the delivered dose, relative to the tumor mass to be treated which has been labeled with a radiopharmaceutical product comprising a radioisotope emitting a positron and a de-excitation gamma ray in quasi-coincidence. STATE OF THE ART

[0002] Hadron therapy is a highly effective cancer treatment that uses beams of proton or carbon ion particles. This innovative technique has proven its effectiveness in the case of tumors that are difficult to treat by conventional radiotherapy because they are either radio-resistant, located deep within or close to vital organs. The use of hadron beams allows for high precision in dose deposition, both longitudinally and transversely. Indeed, unlike photon beams, whose energy deposition is maximum in the first few centimeters upon entering the patient and attenuates with depth, charged ions deposit their maximum energy at the end of their paths (Bragg peak) while maintaining a minimum dose deposited at the entrance. In addition, the lateral penumbra of the protons is lower than that obtained with a photon beam.However, the high ballistic precision of hadrontherapy makes this technique sensitive to any source of deviation from the treatment plan: poor patient positioning, organ movements or anatomical changes between fractions or even tumor regression, weight loss, filling of anatomical cavity between treatment sessions.

[0003] In order to exploit the advantage of high ballistic precision, rigorous control of the location of the dose delivered by radiation is necessary. When the primary beam stops inside the patient, real-time tracking of the path of the hadrons can be achieved by means of secondary radiation, in particular gamma rays, resulting from nuclear reactions of the hadrons in the body.

[0004] Certain imaging modalities appear promising for obtaining information concerning the profile of the hadron beam, such as induced ultrasoundby ions, the measurement of secondary electrons of bremsstrahlung or magnetic resonance imaging (MRI) which presents specific problems associated with the deflection of the hadron beam in the magnetic field in case of real-time MRI. However, these techniques can be difficult to perform. Currently, "in-beam" positron emission tomography (PET) systems have been proposed which exploit the coincident gamma rays at 511 keV resulting from the annihilation of positions emitted during the beta decay of radioactive isotopes generated by the interactions of hadrons in tissues. However, because of the small number of isotopes undergoing beta decay, and the fact that the observation of beta decay is delayed, compared to decay, by the duration of the lifetime of the radioactive isotopes, a rather long data acquisition time is required.As a result, real-time beam imaging with in-beam PET only provides information regarding the position of the delivered dose after treatment. In addition, unlike the conventional PET system, the in-beam PET system has a reduced coverage angle to allow for isocentric “Gantry” rotating head positioning, 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, by numerical simulations, the feasibility of a system for medical imaging based on the combination of a Compton telescope and a pair creation camera. Simulations of the system for different beam energies, typical of hadron therapy, allowed Frandes et al. to demonstrate the ability of this imaging system to detect gamma rays in an energy regime characteristic of Compton interactions so as to reconstruct the position of the delivered dose. However, this system, aimed at detecting gamma rays resulting from annihilation, has the same drawback as in-beam PET.

[0006] In addition, the internal anatomy of the patient may vary between one session and the next or during the same session. Consequently, being able to monitor the position and the amount of dose deposited in the patient's volume in real time is not sufficient to guarantee that the target tumor volume is irradiated in its entirety while minimizing as much as possible the dose delivered to healthy tissues in the surrounding area. Indeed, a displacement of the tumor volume relative to the external anatomical landmarks that are used to align the patient relative to the beam can have serious consequences because the dose will not be delivered according to the treatment plan and therefore healthy tissues will be irradiated.

[0007] It is these drawbacks that the invention more particularly intends to remedy by proposing a system allowing real-time monitoring during treatment hadrontherapy, both the position of the tumor mass and the position of the dose delivered by the beam in the patient allowing a dose deposition in accordance with the treatment plan. SUMMARY

[0008] The subject of the invention is a method for tracking a hadron beam during a hadron therapy treatment of a subject comprising tumor cells labeled with a radiopharmaceutical product having a radioisotope emitting a positron and a de-excitation gamma ray in quasi-coincidence, in which the hadron therapy treatment is delivered according to a treatment plan comprising predefined 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, in which the hadron beam comprises a plurality of discrete hadron bursts emitted at a predefined frequency by an accelerator device, the method comprising the following steps: - when a “burst” impacts the subject: • detect the “prompt gamma rays” generated by the interaction of the burst hadrons with the subject’s tissues using a liquid xenon Compton telescope; • use the detected “prompt gammas” to reconstruct an image of the interaction volume within which the “burst” hadrons interact with the subject’s tissues; - when no “burst” impacts the subject: • extract the position of tumor cells labeled with the radiopharmaceutical by simultaneously detecting the de-excitation gamma ray and two annihilation gamma rays produced by the positron using the liquid xenon Compton telescope; • reconstruct an image of the total volume of the tumor to be treated by the hadron beam during the hadrontherapy treatment; - compare the image of the interaction volume and the image of the total volume of the tumor so as to locate the measured interaction volume in relation to the total measured volume of the tumor; - whenever the measured interaction volume is at least partially included in the total measured volume of the tumor, calculate the difference between, on the one hand, the position of the measured interaction volume in the total measured volume of the tumor and, on the other hand, a predefined position of the interaction volume in the total volume of the tumor defined in the treatment plan.

[0009] Thanks to the invention, it is possible to follow a hadrontherapy treatment session in real time and effectively evaluate whether the treatment has been administered in accordance with the treatment plan thanks to the reconstruction and comparison of the image of the interaction volume and the image of the total volume of the tumor.

[0010] In one embodiment, the image of the interaction volume is obtained for each burst impacting the subject. This makes it possible to monitor the position of the beam in the subject in real time.

[0011] In one embodiment, the method further comprising a step in which the deviation between the predefined position of the interaction volume and the position of the interaction volume measured relative to the total measured volume of the tumor is compared to a predefined threshold. Advantageously, this embodiment makes it possible to verify in real time that the distribution of the dose delivered by the beam in the subject is consistent, within a clinically acceptable margin of error, with the treatment plan.

[0012] In one embodiment, each time the deviation is greater than the predefined threshold, the method comprises a step of calculating at least one new parameter of the hadron beam so as to correct at least one characteristic of the hadron beam. A radiotherapy treatment plan is usually established on the basis of a three-dimensional image of the subject obtained by computed axial tomography "CT-scan" by converting the Hounsfield units (HUs) into proton stopping power in order to be able to calculate the dose distribution. But the CT-scan is only a static image of the subject in a given position and at a given time preceding the treatment.However, in hadron therapy, organ movements, such as bowel movements, breathing, heartbeats, or changes in internal anatomy due to bladder filling or weight variation, also cause density changes, and thus a change in the radiological path length, along the beam trajectory. Their influence in proton therapy can lead to severe underdosing of the clinical target volume and overdosing of organs at risk and normal tissues distal to the target. This embodiment allows for any geometry changes to be taken into account and for correcting the hadron beam parameters in real time to enable the dose to be delivered to the target tumor volume in the treatment plan.

[0013] In one embodiment, the subject is positioned on a motorized mechanical support configured to move the subject relative to the beam during the hadrontherapy treatment. In this embodiment, at least one of the predefined parameters of the treatment plan corresponds to the position in space of the motorized mechanical support.

[0014] In one embodiment, each time the deviation is greater than the predefined threshold, the method comprises a step of calculating the parameter of the treatment plan corresponding to a new position in the space of the motorized mechanical support so as to correct at least one characteristic of the hadron beam. This makes it possible to have the source of the beam in a fixed position and to avoid the use of a “Gantry”.

[0015] In one embodiment, the new parameter of the hadron beam is transmitted to the accelerator device, which modifies at least one characteristic of the hadron beam so as to modify the position of the interaction volume relative to the total measured volume of the tumor. This creates a feedback port allowing real-time adjustment of the beam to the treatment plan.

[0016] In one embodiment, each time the deviation is greater than the predefined threshold, the method comprises stopping the hadron beam. Advantageously, this embodiment makes it possible to stop the treatment to avoid an overdose of the organs at risk.

[0017] In one embodiment, the method further comprises a step of reconstructing a three-dimensional image sequence resulting from the fusion of a three-dimensional image of the interaction volume with a three-dimensional image of the total volume of the tumor in the same frame of reference of the Compton camera.

[0018] The invention also relates to a system for tracking a hadron beam during a hadron therapy treatment of a subject comprising tumor cells labeled with a radiopharmaceutical product having a radioisotope emitting a positron and a de-excitation gamma ray in quasi-coincidence, in which the hadron therapy treatment is delivered according to a treatment plan comprising predefined 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, in which the hadron beam comprises a plurality of discrete hadron bursts emitted at a predefined frequency by an accelerator device, the system comprising: - a beam imaging module configured to receive data acquired from a liquid xenon Compton telescope when a burst impacts the subject and to analyze this data so as to determine the emission point of the prompt gamma rays generated by the interaction of the burst with the tissues of the subject from which an image of the interaction volume within which the hadrons of the burst interact with the tissues is reconstructed; - a tumor imaging module configured to receive data acquired by the liquid xenon Compton telescope when no burst is impacting the subject and to analyze this data so as to extract the position of the tumor cells labeled with the radiopharmaceutical product by simultaneously detecting the de-excitation gamma ray and two annihilation gamma rays produced by the positron and using the position of the tumor cells to reconstruct an image of the total volume of the tumor to be treated by the hadron beam during the hadrontherapy treatment; - an evaluation module configured to compare the image of the interaction volume and the image of the total volume of the tumor so as to locate the measured interaction volume relative to the total measured volume of the tumor and, each time the measured interaction volume is included at least partially in the total measured volume of the tumor, to calculate the difference between, on the one hand, the position of the measured interaction volume relative to the total measured volume of the tumor and, on the other hand, a predefined position of the interaction volume within the total volume of the tumor defined in the treatment plan.

[0019] The system implementing the method of the invention advantageously makes it possible to monitor in real time the dose delivered to the subject thanks to the reconstruction of the image of the interaction volume and the image of the total volume of the tumor, and to verify that this is indeed in accordance with the dose distribution provided for in the treatment plan.

[0020] In one embodiment, the evaluation module is further configured to compare the deviation between the predefined position of the interaction volume and the position of the measured interaction volume relative to the total measured volume of the tumor, to a predefined threshold.

[0021] 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 the predefined threshold, in order to correct at least one characteristic of the hadron beam.

[0022] According to an advantageous characteristic, the correction module is further configured to transmit the new parameter of the hadron beam to the acceleration device, which modifies at least one characteristic of the hadron beam so as to modify the position of the interaction volume relative to the total measured volume of the tumor.

[0023] According to one embodiment, the system further comprises a safety module configured to transmit to the acceleration device the instruction to stop the hadron beam each time the deviation is greater than the predefined threshold. DEFINITIONS

[0024] In the present invention, the terms below are defined as follows: - “Burst” refers to a bunch of hadrons having the same phase acceleration. - "Gamma Prompts" refers to fast, high-energy gamma rays energy that is naturally emitted as a result of nuclear reactions of hadrons with the subject's tissues. - “Organs at Risk (OAR)” refers to the organs on which the The doctor imposes dose constraints that must not be exceeded in order to best avoid side effects linked to irradiation. - “PTV (or Planning Target Volume)”, refers to a volume, which includes the tumor visible on imaging examinations (GTV or "Gross Tumor Volume") extended by therapeutic margins defined by the doctor according to the type of pathology treated (CTV or "Clinical Target Volume"), adding a margin defined by the inaccuracies due to the treatment process (uncertainties of route, positioning, uncertainties intrinsic to the treatment machine, etc.). - "Subject" refers to a mammal, preferably a human being. For the purposes of the present invention, a subject may be a patient, i.e., a person under medical supervision, undergoing or having undergone medical treatment, or being monitored for the development of a disease. DETAILED DESCRIPTION

[0025] The characteristics and advantages of the invention will appear in the following description of several embodiments of a system and a method according to the invention, given solely by way of example and made with reference to the appended drawings in which:

[0026] [Fig-1] [Fig.l] is a schematic perspective view of a treatment table and of the Compton telescope in open configuration, in accordance with a first embodiment of the invention;

[0027] [Fig.2] [Fig.2] is a flowchart representing the steps of the process according to a first embodiment of the invention;

[0028] [Fig.3] [Fig.3] is a schematic perspective view of a treatment table and a Compton telescope in open configuration, in accordance with a second embodiment of the invention;

[0029] [Fig.4] [Fig.4] is a schematic view of a treatment table and a telescope Compton, in closed configuration, in accordance with a third embodiment of the invention.

[0030] The present invention relates to a method for tracking a hadron beam during a hadron therapy treatment of a subject suffering from a tumor.

[0031] Typically, in a hadron therapy center, hadrons are accelerated to therapeutic energies, between 70 and 250 MeV, generally with a cyclotron or a synchrotron, and are transported to the treatment room where they enter a treatment nose. The initial thin beams of hadrons are distributed laterally and longitudinally and shaped appropriately to allow treatments. The hadrons used are typically protons or carbon ions. The scattering and shaping of the beam can be carried out by electromechanical means to treat patients with passive scattering hadron therapy (PSHT or "passively-scattered hadron therapy"). This technique is notably used with the proton.A second mode, called uniform scanning, involves scanning a coarse beam over a wide field that is then collimated and depth-compensated by accessories customized for the patient's anatomy. This allows for the treatment of wider fields with deeper paths. Another approach involves magnetic scanning of mini-beams of hadrons at a sequence of initial energies. The hadrons are scanned very finely and precisely into the tumor in all three directions (x,y,z) to irradiate the tumor without the need for customized accessories. This latter technique can be used to treat patients with optimized intensity-modulated hadron therapy.

[0032] Said hadrontherapy treatment is delivered according to a treatment plan comprising predefined parameters as a function of time in order to define at least one characteristic of the hadron beam over time during the hadrontherapy treatment.

[0033] According to one embodiment, the predefined parameters that define at least one characteristic of the beam vary according to the hadrontherapy technique used.

[0034] For the passive scattering method, lateral and longitudinal beam scattering is achieved through the use of a path modulation wheel and one or two scatterers made of high-Z materials to produce a broad, flat beam in the region of interest. The modulation wheel is configured to interpose blades of different material thicknesses in the path of the hadrons as it rotates 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 thicknesses and widths are designed so that the sum of the resulting individual Bragg peaks gives a uniform and homogeneous depth dose distribution, the SOBP or "spread-out Bragg peak".To adapt the dose distribution laterally to the shape of the target volume (plus appropriate margins), an aperture, usually made of brass blocks of sufficient thickness (2 cm to 8 cm) to absorb the highest energy incident hadrons, is used. Finally, to create a dose distribution . conforming to the distal shape of the target, the Bragg peak of the passively scattered beam is spread further using a distance compensator.

[0035] According to one embodiment, the hadron therapy treatment uses the passive diffusion technique. In this embodiment, the predefined parameters include at least the beam energy and the modulation of the hadron path (i.e. SOBP). Indeed, the absorber and the compensator are accessories customized for the patient and their position does not change during the treatment.

[0036] For uniform scanning, an active scanning system is used which, with multiple mini-irradiations, builds a modulated Bragg peak in the tumor. The irradiation of the target volume is carried out by lateral scanning of one layer after another. A dedicated modulation wheel is used to translate the Bragg peaks step by step. For a better definition of the modulated Bragg peak, intermediate depth layers are irradiated thanks to the combination of absorber plates of a diffuser and blades of the modulation wheel. Once modulated, the proton beam is then widely scanned in the Y and X directions respectively by a vertical magnet in the first position and then by a horizontal magnet which follows.

[0037] According to one embodiment, the hadron therapy treatment uses the uniform scanning technique. In this embodiment, the predefined parameters include at least the beam energy, the modulation of the hadron path and the X and Y position of the beam.

[0038] Active mini-beam scanning consists of scanning an elementary beam of ions precisely with magnets horizontally and vertically while changing the initial energy of the protons in order to scan the entire tumor volume layer by layer without using the patient's personalized accessories. The depth (Z) is managed by the energy modulation of the proton beam thanks to the energy selection system. The position of the fine brush in the (X, Y) plane is controlled using the same scanning magnets as described below. A set of spots is thus created and distributed over the entire target volume. The spot size at the iso-center is adapted thanks to the quadrupoles located before the scanning magnets. Its main advantage is to reduce the quantity of neutrons produced and the loss of flow rate, both due to the passive beam shaping accessories.

[0039] According to one embodiment, the hadron therapy treatment uses the active scanning technique of mini-beams. In this embodiment, the predefined parameter comprises at least the X, Y and Z coordinates (i.e. the beam energy) and the intensity of each spot.

[0040] Techniques implementing magnetic beam scanning may be configured to allow beam deflection to cover a treatment field of up to 30 cm x 40 cm.

[0041] In a hadrontherapy treatment room, the subject is normally seated in a chair or lying on a treatment table in a predefined position relative to the treatment nose, from which the beam emerges to impact the subject.

[0042] In one embodiment, the treatment nose is in a fixed position at a predefined distance from the subject. The treatment nose 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 nose is positioned facing the subject so that the beam has its entry point on the anterior part of the subject. This allows the beam to penetrate the subject to the target volume by passing through a thickness of healthy tissues and / or organs at risk as small as possible, so as to reduce the dose they receive.

[0043] With a treatment nose in a fixed position, the direction of incidence of the beam F, and therefore also its point of entry into the tissues, can be varied only by using magnetic scanning, which allows for small beam deviations.

[0044] To enable the angle of incidence of the beam to be varied 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 the hadrontherapy treatment. In this first embodiment illustrated in [Fig.l], the treatment table T is capable of rotating around the three axes A1, A2 and A3 in both directions of rotation and of translating along the axes A1, A2 and A3 in the two opposite directions of each axis.

[0045] In this first embodiment, the Compton telescope TC comprises two Compton semi-detectors in the form of two hollow half-cylinders, symmetrical with respect to the axis A1 and separated from each other in the direction A2 so as to allow the passage of a beam F arriving above the subject. The two half-cylinders are complementary and capable of forming a complete hollow cylinder if joined. In particular, each semi-detector forms an arc of a circle with an angle of 180°. In this embodiment, each Compton semi-detector is capable of translating along the axes A1, A2 and A3 in both directions and rotating around the axis A3.

[0046] In the second embodiment illustrated in [Fig. 3], the treatment table T is also capable of rotating around the three axes A1, A2 and A3 in both directions of rotation and of translating along the axes A1, A2 and A3 in the two opposite directions of each axis. The Compton telescope comprises two Compton semi-detectors in the form of two hollow half-cylinders symmetrical with respect to the axis A1 and separated from each other along the direction A3 so as to allow the passage of a beam F arriving on the side of the subject.

[0047] The configuration of the Compton telescope in the first and second embodiments is referred to in the present description as a “Compton telescope in open configuration”. In the first and second embodiments, each Compton semi-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 configuration as closed as possible on the subject. Indeed, the Compton telescope has a higher spatial resolution when the two semi-detectors are closest to the subject, allowing the detection of a greater number of events (i.e. gamma prompts, de-excitation gamma rays or annihilation gamma rays).

[0048] In the third embodiment illustrated in [Fig.4], the Compton telescope comprises a single detection volume having the shape of a hollow cylinder and comprising a lateral slit having dimensions capable of allowing the passage of a beam F arriving on the side of the subject. This configuration of the Compton telescope is called in the present description "Compton telescope in closed configuration". The treatment table T aligned along the axis A1, also being the longitudinal axis of a hollow cylinder. The treatment table T is capable of being moved inside the Compton telescope in closed configuration and in particular of rotating around the three axes A1, A2 and A3 in both directions of rotation and of translating along the axes A1, A2 and A3 in the two opposite directions of each axis.In this embodiment, the Compton telescope is mounted on a mechanical support, motorized so as to be able to translate along the axes A1, A2 and A3 and to pivot around the axis A3.

[0049] In the first, second and third embodiments, the treatment table T on which the subject is positioned is securely mounted to a motorized mechanical support (not shown) which allows it to move with the degrees of freedom described above. The motorized mechanical support is in particular capable of allowing rotational movements of the treatment table T with a pitch which varies between 2 and 15 degrees and translational movements with a pitch which varies between 0.5 cm and 5 cm.

[0050] In one embodiment, the motorized support is a robotic positioning arm configured to have a sensitivity of between 0.1 cm and 1 cm.

[0051] In the embodiments comprising a treatment table T on a motorized mechanical support, at least one of the predefined parameters of the treatment plan corresponds to the position in space of the treatment table T and therefore of the motorized mechanical support. This particularly advantageous embodiment makes it possible to dispense with the use of gigantic isocentric rotating heads ("Gantry") configured to deliver the beam with a variable angle over more than 180°. The "Gantry", in which the treatment nose is incorporated, has an extremely high manufacturing cost compared to that of a motorized treatment bed. Consequently, dispensing with the "Gantry" makes it possible to reduce the cost of building hadrontherapy infrastructures, making this technique more accessible.

[0052] In the embodiments in which the Compton telescope is capable of being moved, at least one of the predefined parameters of the processing plan corresponds to the position in space of the Compton telescope in the closed configuration or of each Compton semi-detector of the Compton telescope in the open configuration.

[0053] The accelerating device used in the method of the present invention produces a hadron beam comprising a plurality of discrete hadron bursts emitted at a predefined frequency by an accelerating device.

[0054] In one embodiment, the accelerator device that generates the hadron beam used is a synchrotron or a linear accelerator. Synchrotrons accelerate hadrons to the desired energy in bunches (pulses). Once a bunch has reached the required energy, it is extracted and transmitted via the "beam line" to the treatment room. However, regardless of the type of accelerator, the extracted narrow mono-energetic beam is magnetically guided through the beam line to the treatment nose.

[0055] In one embodiment, the acceleration device is a “digital” synchrotron comprising induction cells in which the magnets are exposed to rapid variations in their operation thanks to external beam control means and to on-board computers capable of controlling them (switch and FPGA).

[0056] The interaction of a "burst" produces in matter, in addition to self-activation and the emission of charged particles, the rapid emission of high-energy gamma rays called "prompt gamma rays". The generation profile of "prompt gamma rays" is well correlated with the path of the hadrons. Consequently, the detection of "prompt gamma rays" can be effectively used to track the beam interaction point and the dose deposition in the subject.

[0057] In [Fig.2] an embodiment of the method is illustrated comprising several stages of data acquisition and calculations.

[0058] The method of the present invention is configured to enable real-time monitoring of a hadrontherapy treatment by obtaining image sequences of the interaction volume within which the hadrons of the burst interact with the tissues of the subject and of the total volume of the tumor. The image of the interaction volume can be obtained only while a burst impacts the subject.

[0059] The method therefore comprises a first phase, when a “burst” impacts the subject 10, this first phase comprising the following steps: - detect the “prompt gamma rays”111 generated by the interaction of the burst hadrons with the subject’s tissues using a Compton telescope; - use the detected “prompt gammas” to reconstruct an image 112 of the interaction volume within which the hadrons of the “burst” interact with the subject’s tissues.

[0060] In a preferred embodiment, the Compton telescope is a liquid xenon Compton telescope. The fundamental physical properties of liquid xenon, such as its high density and high atomic number, provide high stopping power to ionizing radiation, making liquid xenon an ideal material as a gamma ray detector in the energy range from a few tens of keV to several tens of MeV. Liquid xenon is both an excellent active medium for the detection of ionizing radiation and an excellent scintillator, with the advantage of making it possible to construct large detectors with a homogeneous sensitive medium. A Compton telescope uses the successive interactions (two or more) of an incident photon in the interaction volume.From the interaction points and the energy deposited at each interaction, the direction of the incident photon can be reduced to a cone, via the application of Compton kinematics. The position of the photon source can be determined by the intersection of different Compton cones, deduced from subsequent interactions of photons coming from the same source. This type of detector is therefore well suited to detect "prompt gamma rays" in the corresponding energy range of several MeV in which Compton scattering is the dominant process.

[0061] The image of the measured interaction volume may be a three-dimensional image.

[0062] In one embodiment, the image of the interaction volume is obtained for each burst impacting the subject. In this embodiment, the image acquisition frequency depends on the burst production frequency of the acceleration device. The number of images acquired per second can therefore vary from 5 to 30.

[0063] In one embodiment, the Compton telescope is configured to have a spatial resolution of approximately 1 mm for each image of a burst.

[0064] In the present invention, the tumor cells of the subject are labeled with a radiopharmaceutical product comprising a radioisotope emitting a positron and a de-excitation gamma ray in quasi-coincidence. This allows the identification of the position of the radiolabel thanks to the use of the three-photon imaging principle. Indeed, the positron travels a short path in the tissues (of the order of mm) before annihilating into two photons at 511 keV moving in opposite directions ("back-to-back gammas").

[0065] 3-photon imaging is based on the joint use of a Compton telescope and a radiopharmaceutical having a radioisotope emitting a positron and a de-excitation gamma ray in quasi-coincidence.

[0066] The simultaneous detection of these two annihilation photons makes it possible to draw the response line (LOR), that is to say 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 therefore obtained by the intersection between LOR and the Compton cone defined from the interaction of the de-excitation gamma with the Compton telescope. The surface of the Compton cone includes the incident direction of the de-excitation gamma and can be directly deduced from the Compton kinematics. The opening angle of the Compton cone, 0, is defined by the Compton scattering formula, in which the axis of the Compton cone is determined using the first of the two interaction points of the de-excitation gamma entering the telescope.

[0067] This technique advantageously allows a reduction in the number of disintegrations necessary to obtain the image and therefore a reduction in the acquisition time and / or the quantity of substance inoculated per patient.

[0068] The first phase of the method comprises, when no “burst” impacts the subject 11, the following steps: - extracting the position of the tumor cells 121 labeled with the radiopharmaceutical by simultaneously detecting the de-excitation gamma ray and two annihilation gamma rays produced by the positron using the Compton telescope, as described above; - reconstruct, on the basis of the positions of the tumor cells, an image of the total volume of the tumor 122 to be treated by the hadron beam during the hadrontherapy treatment.

[0069] In a preferred embodiment, the radioisotope used in the radiopharmaceutical is ^Sc, which emits a positron (or "positron" in English) and a photon of energy 1.157 MeV in quasi-coincidence in space and time.

[0070] The image of the total volume of the tumor is acquired between two successive "bursts" to avoid contamination of the image by the signal generated by the "gamma prompts" ".

[0071] In one example, the structure of the Compton telescope is such that for a 10 s acquisition the spatial resolution of the image of the total volume of the tumor is approximately 1 mm. The resolution achieved is due to the physical limits of the detector and the activity of the isotope injected into the subject.

[0072] In one embodiment, the image of the total tumor volume is a three-dimensional image.

[0073] The method further comprises a second phase comprising the following steps: - comparing the image of the interaction volume and the image of the total volume of the tumor 131 so as to locate the measured interaction volume relative to the total measured volume of the tumor; - whenever the measured interaction volume is included at least partially in the total measured volume of the tumor, calculate the difference 132 between, on the one hand, the position of the measured interaction volume in the total measured volume of the tumor and, on the other hand, a predefined position of the interaction volume in the total volume of the tumor defined in the treatment plan.

[0074] The difference can be calculated by superimposing the images. This is easy to obtain, as long as the images of the measured interaction volume and the total volume of the measured tumor are acquired by the same detector and are therefore reconstructed with respect to the same reference frame.

[0075] This comparison phase makes it possible to compare the actual position of the Bragg peak with the position which was calculated in a calculation software for the generation of the treatment plan.

[0076] In one embodiment, the method further comprises a step 133 in which the deviation between the predefined position of the interaction volume and the position of the measured interaction volume relative to the total measured volume of the tumor is compared to a predefined threshold. The only predefined threshold may correspond to a margin of 1 mm to 5 mm around the target volume (PTV). The threshold may also be defined on the basis of the radiosensitivity of the organs at risk which surround the targeted volume. For example, the predefined threshold corresponds to a margin of 0.5 mm in the direction of the lymph nodes which are highly radiosensitive and a margin of 1 mm in the direction of the lungs which are less so.

[0077] In one embodiment, each time the deviation is greater than the predefined threshold, the method comprises a step of calculating at least one new parameter of the hadron beam 134 so as to correct at least one characteristic of the hadron beam.

[0078] In one embodiment, each time the deviation is greater than the predefined threshold, the method comprises a step of calculating the parameter of the treatment plan corresponding to a new position in the space of the motorized mechanical support so as to correct at least one characteristic of the hadron beam.

[0079] In one embodiment, the new parameter of the hadron beam is transmitted to the accelerator device which modifies at least one characteristic of the hadron beam so as to modify the position of the interaction volume relative to the total measured volume of the tumor.

[0080] In one embodiment, each time the deviation is greater than the predefined threshold, the method comprises stopping the hadron beam. This provides a safety measure to avoid any irradiation that does not comply with the treatment plan.

[0081] In one embodiment, the method further comprises a step of reconstructing a three-dimensional image sequence resulting from the fusion of a three-dimensional image of the interaction volume with a three-dimensional image of the total volume of the tumor according to the same Compton camera reference. Such an image sequence can be viewed in real time using a screen to provide visual information to the medical staff.

[0082] The invention also relates to a system for tracking a hadron beam during a hadron therapy treatment of a subject. The system is configured to track a hadron beam, comprising a plurality of discrete hadron bursts emitted at a predefined frequency by an acceleration device, during a hadron therapy treatment delivered according to a treatment plan comprising predefined 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.

[0083] The system comprises a beam imaging module configured to receive data acquired from a Compton telescope when a burst impacts the subject. In one embodiment, the data acquisition is performed online and continuously. The data acquired during a time window, corresponding to the sending of a burst on the subject, are sent to the beam imaging module. This module is further configured to analyze this data so as to determine the emission point of the gamma prompts generated by the interaction of the burst with the tissues of the subject. This module therefore uses the emission point of the gamma prompts to reconstruct an image of the interaction volume within which the hadrons of the burst interact with the tissues.

[0084] In one embodiment, the beam imaging module is further configured to identify and re-eject any data corresponding to events that do not result from the interaction of a "gamma prompt" in the sensitive volume of the Compton telescope.

[0085] The system also comprises a tumor imaging module configured to receive the data acquired by the Compton telescope when no burst impacts the subject. In one embodiment, the data acquisition is performed online and continuously and only the data acquired between two successive bursts of the subject are sent to the tumor imaging module. This makes it possible to select only the data resulting from the beta decay of the radioisotope captured by the tumor cells. This module is further configured to analyze this data so as to extract the position of the tumor cells labeled with the radiopharmaceutical product by simultaneously detecting the de-excitation gamma ray and the two annihilation gamma rays produced by the positron and to use the position of the tumor cells to reconstruct an image of the total volume of the tumor to be treated by the hadron beam during the hadrontherapy treatment.

[0086] In one embodiment, the Compton telescope is a liquid xenon Compton telescope.

[0087] The system further comprises an evaluation module configured to compare the image of the interaction volume and the image of the total volume of the tumor so as to locate the measured interaction volume relative to the total measured volume of the tumor and, each time the measured interaction volume is included, at least partially, in the total measured volume of the tumor to calculate the difference between, on the one hand, the position of the measured interaction volume relative to the total measured volume of the tumor and, on the other hand, a predefined position of the interaction volume within the total volume of the tumor defined in the treatment plan.

[0088] In one embodiment, the evaluation module is further configured to compare the deviation between the predefined position of the interaction volume and the position of the measured interaction volume relative to the total measured volume of the tumor, to a predefined threshold.

[0089] 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 the predefined threshold, in order to correct at least one characteristic of the hadron beam.

[0090] As explained in the first part of the description, the predefined parameters defining the characteristics of the hadron beam vary depending on the type of hadrontherapy treatment. Based on the type of treatment that can be delivered by the treatment nose, the predefined parameters that can be dynamically influenced during a session include the beam energy, the modulation of the hadron path (i.e. SOBP), the modulation of the hadron path and / or the X and Y position of the beam.

[0091] In one embodiment, the correction module is further configured to transmit the new parameter of the hadron beam to the acceleration device which modifies at least one characteristic of the hadron beam so as to modify the position of the interaction volume relative to the total measured volume of the tumor.

[0092] In one embodiment, the acceleration device comprises a treatment nose disposed in the treatment room in a fixed position relative to the treatment table.

[0093] 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 the hadrontherapy treatment. In this first embodiment illustrated in [Fig.l], the treatment table T is capable of rotating around the three axes A1, A2 and A3 in both directions of rotation and of translating along the axes A1, A2 and A3 in the two opposite directions of each axis.

[0094] In this first embodiment, the Compton telescope TC comprises two Compton semi-detectors in the form of two hollow half-cylinders, symmetrical with respect to the axis Al and separated from each other in the direction A2 in such a way that to allow the passage of a beam F arriving above the subject. The two half-cylinders are complementary and capable of forming a complete hollow cylinder if joined. In particular, each semi-detector forms an arc of a circle with an angle of 180°. In this embodiment, each Compton semi-detector is capable of translating along the axes A1, A2 and A3 in both directions and rotating around the axis A3.

[0095] In the second embodiment illustrated in [Fig. 3], the treatment table T is also capable of rotating around the three axes A1, A2 and A3 in both directions of rotation and of translating along the axes A1, A2 and A3 in the two opposite directions of each axis. The Compton telescope comprises two Compton semi-detectors in the form of two hollow half-cylinders symmetrical with respect to the axis A1 and separated from each other along the direction A3 so as to allow the passage of a beam F arriving on the side of the subject.

[0096] The configuration of the Compton telescope in the first and second embodiments is referred to in the present description as a “Compton telescope in open configuration”. In the first and second embodiments, each Compton semi-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 configuration of the Compton telescope TC as closed as possible on the subject. Indeed, the Compton telescope has a higher spatial resolution when the two semi-detectors are closest to the subject, allowing the detection of a greater number of events (i.e. gamma prompts, de-excitation gamma rays or annihilation gamma rays).

[0097] In the third embodiment illustrated in [Fig.4], the Compton telescope comprises a single detection volume having the shape of a hollow cylinder and comprising a lateral slit having dimensions capable of allowing the passage of a beam F arriving on the side of the subject. This configuration of the Compton telescope is called in the present description "Compton telescope in closed configuration". The treatment table T aligned along the axis A1, also being the longitudinal axis of a hollow cylinder. The treatment table T is capable of being moved inside the Compton telescope in closed configuration and in particular of rotating around the three axes A1, A2 and A3 in both directions of rotation and of translating along the axes A1, A2 and A3 in the two opposite directions of each axis.In this embodiment, the Compton telescope is mounted on a mechanical support, motorized so as to be able to translate along the axes A1, A2 and A3 and to pivot around the axis A3.

[0098] In the first, second and third embodiments, the treatment table T on which the subject is positioned is securely mounted to a motorized mechanical support (not shown) which allows it to move with the degrees of freedom described above. The motorized mechanical support is in particular capable of allowing rotational movements of the treatment table T with a step varying between 2 and 15 degrees and translational movements with a step varying between 0.5 cm and 5 cm.

[0099] In one embodiment, the motorized support is a robotic positioning arm configured to have a sensitivity of between 0.1 cm and 1 cm.

[0100] In the embodiments comprising a treatment table T on a motorized mechanical support, at least one of the predefined parameters of the treatment plan corresponds to the position in space of the motorized mechanical support, in particular the treatment table T. The correction module is further configured to calculate a new parameter of the treatment plan corresponding to a new position in space of the motorized mechanical support so as to correct at least one characteristic of the hadron beam, corresponding in particular to the direction and the point of incidence of the beam.

[0101] In embodiments in which the Compton telescope is capable of being moved, at least one of the predefined parameters of the processing plan corresponds to the position in space of the Compton telescope in the closed configuration or of each Compton semi-detector of the Compton telescope in the open configuration. The correction module is further configured to calculate a new parameter of the processing plan corresponding to a new position in space of the Compton telescope in the closed configuration or of each Compton semi-detector of the Compton telescope in the open configuration.

[0102] In one embodiment, the correction module is further configured to transmit the new parameter of the hadron beam relating to a new position of the motorized mechanical support to the motorized mechanical support, itself so as to modify the direction and / or the point of incidence of the beam and therefore the position of the interaction volume relative to the total measured volume of the tumor.

[0103] In one embodiment, the system comprises an image reconstruction module configured to reconstruct a sequence of three-dimensional images resulting from the fusion of a three-dimensional image of the interaction volume with a three-dimensional image of the total volume of the tumor according to the same frame of reference of the Compton camera. This makes it possible to obtain a film of the treatment session.

Claims

1. Claims A system for tracking a hadron beam during a hadron therapy treatment of a subject comprising tumor cells labeled with a radiopharmaceutical having a positron-emitting radioisotope and a near-coincident de-excitation gamma ray, wherein the hadron therapy treatment is delivered according to a treatment plan comprising predefined time-dependent parameters 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 bursts of hadrons emitted at a predefined frequency by an accelerator device, the system comprising: - a beam imaging module configured to receive data acquired from a liquid xenon Compton telescope when a burst impacts the subject and to analyze this data so as to determine the emission point of the prompt gamma rays generated by the interaction of the burst with the tissues of the subject from which an image of the interaction volume within which the hadrons of the burst interact with the tissues is reconstructed; - a tumor imaging module configured to receive the data acquired by the Compton telescope, in particular a liquid xenon Compton telescope, when no burst impacts the subject and to analyze this data so as to extract the position of the tumor cells labeled with the radiopharmaceutical product by simultaneously detecting the de-excitation gamma ray and two annihilation gamma rays produced by the positron and using the position of the tumor cells to reconstruct an image of the total volume of the tumor to be treated by the hadron beam during the hadrontherapy treatment; - an evaluation module configured to compare the image of the interaction volume and the image of the total volume of the tumor so as to locate the measured interaction volume relative to the total measured volume of the tumor and, whenever the measured interaction volume is included at least partially within the total measured tumor volume, to calculate the deviation between, on the one hand, the position of the measured interaction volume relative to the total measured tumor volume and, on the other hand, a predefined position of the interaction volume within the total tumor volume defined in the treatment plan.

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

3. System according to any one of claims 1 or 2, the image of the interaction volume is obtained for each burst impacting the subject.

4. System according to any one of claims 1 to 3, further comprising a correction module configured to calculate at least one new parameter of the hadron beam, each time the deviation is greater than the predefined threshold, in order to correct at least one characteristic of the hadron beam.

5. The system of claim 4, wherein the correction module is further configured to transmit the new parameter of the hadron beam to the accelerator device, which modifies at least one characteristic of the hadron beam so as to modify the position of the interaction volume relative to the total measured volume of the tumor.

6. A system according to any one of claims 4 or 5, the subject is positioned on a treatment table comprising a motorized mechanical support configured to move the subject relative to the beam during the hadrontherapy treatment and wherein at least one of the predefined parameters of the treatment plan corresponds to the position in space of the motorized mechanical support.

7. System according to claim 6, in which the correction module is further configured to calculate a new parameter of the treatment plan corresponding to a new position in the space of the motorized mechanical support so as to correct at least one characteristic of the hadron beam, corresponding in particular to the direction and the point of incidence of the beam.

8. System according to any one of claims 1 to 7, further comprising a safety module configured to transmit to the acceleration device the instruction to stop the hadron beam each time the deviation is greater than the predefined threshold.

9. System according to any one of claims 1 to 8, further comprising an image reconstruction module configured to reconstruct a three-dimensional image sequence resulting from the fusion of a three-dimensional image of the interaction volume with a three-dimensional image of the total volume of the tumor according to the same Compton telescope reference frame.

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