Method and system for monitoring a hadron beam during a hadron therapy treatment of a subject - Patents.com

Abstract

The present invention relates to a method for monitoring a hadron beam during hadron therapy treatment of a subject containing radiopharmaceutical-labeled tumor cells, the hadron beam comprising a plurality of discrete hadron bursts, the method comprising: detecting (111) by a Compton telescope prompt gammas produced by the interaction of the hadrons of the burst with the tissue of the subject, if the burst affects the subject, and reconstructing (112) an image of the interaction volume; extracting (121) by a Compton telescope the location of the radiopharmaceutical-labeled tumor cells, if the burst does not affect the subject, and reconstructing (122) an image of the total tumor volume; and comparing (131) the image of the interaction volume with an image of the total tumor volume to position the measured interaction volume relative to the measured total tumor volume.

Description

[Technical field]

[0001] FIELD OF THEINVENTION The present invention relates to a method and system for monitoring a hadron beam during hadron therapy treatment of a subject suffering from cancer, and in particular to a system and method for indirectly monitoring the interaction zone between the hadron beam and the tissue of the subject, and thus the delivered dose to a tumor mass to be treated, labeled with a radiopharmaceutical comprising a radioisotope that emits positrons and de-excitation gamma rays almost simultaneously. [Background technology]

[0002] Background technology Hadron therapy is a highly effective cancer treatment that uses proton or carbon ion beams. This innovative technology has proven effective in cases of tumors that are difficult to treat using conventional radiotherapy, either because of their radioresistance or because of their deep location or closeness to vital organs. The use of hadron beams allows high precision in the dose deposition, both longitudinal and transverse. Indeed, unlike photon beams, whose energy deposition is maximum from the first centimeters upon penetration into the patient and weakens with depth, charged ions deposit their maximum energy (Bragg peak) at the end of their range, while maintaining a minimum input dose deposition. Moreover, the lateral penumbra of proton beams is weaker than that obtained with photon beams. However, the high ballistic precision of hadron therapy makes this technology sensitive to any source of deviation to the treatment plan (poor patient positioning, organ movements or anatomical changes or tumor regression between fractions, weight loss, anatomical cavity filling between treatment sessions).

[0003] To take advantage of the high ballistic accuracy, thorough inspection of the location of the radiation delivered dose is necessary. When the primary beam stops inside the patient's body, secondary radiation, especially gamma rays from nuclear reactions of hadrons inside the body, allows real-time monitoring of the hadron range.

[0004] Some imaging regimes, such as ion-induced ultrasound, secondary electron bremsstrahlung measurements, or magnetic resonance imaging (MRI), which in the case of real-time MRI has specific problems related to hadron beam deflection in magnetic fields, appear promising for obtaining information about the profile of the hadron beam. However, these techniques can be difficult to implement. Currently, "in-beam" positron emission tomography (PET) systems have been proposed, which use coincident gamma rays of 511 keV due to the annihilation of positrons emitted during beta decay of radioisotopes produced by hadronic interactions in tissue. However, relatively long data acquisition times are required due to the small number of isotopes that beta decay, and considering that beta decay is recognized to be delayed relative to its decay due to the duration of the radioisotope's lifetime. As a result, real-time beam imaging with in-beam PET only provides information related to the position of the delivered dose after treatment. Furthermore, unlike conventional PET systems, in-beam PET systems have a reduced coverage of angles allowing the positioning of the "gantry" isocentric rotary head, which reduces the effective volume of the system.

[0005] In this regard, 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 digital simulation the feasibility of a medical imaging system based on a combination of a Compton telescope and a pair-production camera. Simulations of the system for different beam energies specific to hadron therapy allowed Frandes et al. to demonstrate the gamma-ray detection capability of this imaging system in the energy region characteristic of Compton interactions in order to reconstruct the location of the delivered dose. However, this system, which targets the detection of gamma rays from annihilation, has the same drawbacks as in-beam PET.

[0006] Furthermore, the internal anatomy of the patient may change from one session to the next, or even during the same session. Thus, the ability to monitor in real time the location and amount of radiation delivered relative to the patient volume is insufficient to ensure that the entire target tumor volume is irradiated while delivering the minimum possible dose to the surrounding normal tissue. In fact, changes in the tumor volume relative to the external anatomical markers used to align the beam to the patient may have serious consequences in that the dose will not be delivered according to the treatment plan, and therefore normal tissue will be irradiated.

[0007] The present invention aims in particular to remedy these shortcomings by proposing a system capable of monitoring in real time, during hadron therapy treatment, both the position of the tumor mass and the position of the dose delivered to the patient by the beam, thus allowing the dose to be administered according to the treatment plan. Summary of the Invention

[0008] The present invention relates to a method for monitoring a hadron beam during a hadron therapy treatment of a subject containing tumor cells labeled with a radiopharmaceutical having a radioisotope that emits positrons and de-excitation gamma rays at approximately the same time, the hadron therapy treatment being carried out according to a treatment plan comprising predefined parameters as a function of time to define over time at least one characteristic of the hadron beam during the hadron therapy treatment, the hadron beam comprising a plurality of discrete hadron "bursts" emitted at predefined frequencies by an accelerator, the method comprising the steps of: - When "Burst" affects a target: detecting the "prompt gammas" produced by the interaction of the hadrons in the "burst" with tissue of interest using a liquid xenon Compton telescope; Using the detected "prompt gammas" to reconstruct an image of the interaction volume inside which the "burst" hadrons interact with the tissue of interest; - If "Burst" does not affect the target: extracting the location of the radiopharmaceutical-labeled tumor cells by simultaneous detection of the de-excitation gamma rays and the two annihilation gamma rays generated by the positrons with a liquid xenon Compton telescope; reconstructing an image of the total volume of the tumor treated by the hadron beam during the hadron therapy treatment; - comparing 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; - calculating, each time the measured interaction volume is at least partially contained in the measured total volume of the tumor, the deviation between, on the one hand, the position of the measured interaction volume in the measured total volume of the tumor and, on the other hand, the predefined position of the interaction volume in the total volume of the tumor defined in the treatment plan.

[0009] The present invention makes it possible to monitor hadron therapy treatment sessions in real time and, by reconstructing and comparing images of the interaction volume and images of the total tumor volume, effectively evaluate whether the treatment has been carried out according to the treatment plan.

[0010] In one embodiment, an image of the interaction volume is obtained after each "burst" that impacts the target, allowing real-time monitoring of the beam position in the target.

[0011] In one embodiment, the method further comprises a step in which the deviation between the predefined position of the interaction volume and the position of the measured interaction volume relative to the total volume of the measured tumor is compared to a predefined threshold. Advantageously, this embodiment allows to verify in real time that the distribution of the dose delivered by the beam in the object matches the treatment plan, within an acceptable error from a clinical point of view.

[0012] In one embodiment, each time the deviation becomes larger than a predefined threshold, the method includes a step of calculating at least one new parameter of the hadron beam to modify at least one characteristic of the hadron beam. Radiotherapy treatment plans are usually defined with reference to a three-dimensional image of the object obtained by "CT scan" computed transverse tomography by converting Hounsfield units (HU) into proton stopping power from which the dose distribution can be calculated. However, a CT scan is only a static image of the object at a given position and at a given time before treatment. However, in hadron therapy, organ movements such as bowel movements, breathing, heartbeat, or changes in internal structures due to bladder filling or weight fluctuations also cause density changes and therefore changes in the length of the radiation range along the beam trajectory. The effect in proton therapy can result in significant underdosing of the target clinical volume and overdosing of risk organs and normal tissues distal to the target. This embodiment allows for real-time modification of the parameters of the hadron beam to take into account any geometric changes and deliver the dose within the target tumor volume of 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 a hadron therapy treatment, in which at least one of the predefined parameters of the treatment plan corresponds to a spatial position of the motorized mechanical support.

[0014] In one embodiment, each time the deviation becomes larger than a predefined threshold, the method includes calculating parameters of the treatment plan corresponding to a new spatial position of the motorized mechanical support in order to modify at least one characteristic of the hadron beam, thereby allowing the beam source to be placed in a fixed position and avoiding the use of a "gantry."

[0015] In one embodiment, new parameters of the hadron beam are sent to the accelerator which modifies at least one property of the hadron beam to modify the location of the interaction volume relative to the measured total tumor volume, creating a feedback loop that allows real-time adjustments to the beam treatment plan.

[0016] In one embodiment, the method stops the hadron beam whenever the deviation becomes larger than a predefined threshold. Advantageously, this embodiment makes it possible to stop the treatment to prevent overdosing of organs at risk.

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

[0018] The present invention also relates to a system for monitoring a hadron beam during a hadron therapy treatment of a subject containing tumor cells labeled with a radiopharmaceutical having a radioisotope that emits positrons and de-excitation gamma rays at approximately the same time, the hadron therapy treatment being carried out according to a treatment plan including predefined parameters as a function of time to define at least one characteristic of the hadron beam over time during the hadron therapy treatment, the hadron beam including a plurality of discrete hadron "bursts" emitted at predefined frequencies by an accelerator, the system comprising: - a beam imaging module configured to receive data obtained from the liquid xenon Compton telescope and to analyze these data in order to determine, in case of a "burst" impacting the subject, the emission points of "prompt gamma" generated by the interaction of the "burst" with the subject's tissue (from which an image of the interaction volume, inside which the hadrons of the "burst" interact with the tissue, is reconstructed); - a tumor imaging module configured to receive data acquired by the liquid xenon Compton telescope when the "burst" does not affect the subject, extract the locations of tumor cells labeled with a radiopharmaceutical by coincident detection of the de-excitation gamma ray and the two annihilation gamma rays generated by the positron, and to analyze these data in order to reconstruct, using the locations of the tumor cells, an image of the total tumor volume treated by the hadron beam during the hadron therapy treatment; 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 with respect 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 with respect to the measured total tumor volume and, on the other hand, a predefined position of the interaction volume in the total tumor volume defined in the treatment plan; Includes.

[0019] The system implementing the method according to the invention advantageously allows, as a result of the reconstruction of an image of the interaction volume and an image of the total volume of the tumor, to monitor in real time the dose delivered to the subject and to verify that it complies with the dose distribution provided in the treatment plan.

[0020] In one embodiment, in the evaluation module, an image of the interaction volume is obtained for each burst that impacts the object.

[0021] 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 volume of the measured tumor against a predefined threshold.

[0022] In one embodiment, the subject is positioned on a motorized mechanical support configured to move the subject relative to the beam during the hadron therapy treatment, and at least one of the predefined parameters of the treatment plan corresponds to a spatial position of the motorized mechanical support.

[0023] In one embodiment, whenever the deviation becomes larger than a predefined threshold, the system further includes a correction module configured to calculate at least one new parameter of the hadron beam to correct at least one property of the hadron beam.

[0024] In one advantageous feature, the correction module is further configured to transmit new parameters of the hadron beam to the accelerator device which modifies at least one characteristic of the hadron beam in order to correct the position of the interaction volume relative to the measured total volume of the tumor.

[0025] In one embodiment, the system further comprises a safety module configured to send an instruction to the accelerator to stop the hadron beam whenever the deviation becomes greater than a predefined threshold.

[0026] In one embodiment, the system further includes an image reconstruction module configured to reconstruct a three-dimensional image sequence resulting from merging 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 criterion.

[0027] In one embodiment, the system includes a Compton telescope that is a liquid xenon Compton telescope.

[0028] In one embodiment, the system includes an accelerator and / or a motorized mechanical support.

[0029] In one embodiment, the method for monitoring a hadron beam is a computer-implemented method.

[0030] The invention also relates to a computer program comprising instructions which, when executed by a computer, cause the computer to carry out the method for monitoring a hadron beam as described above.

[0031] The present invention also relates to a computer-readable recording medium comprising instructions which, when executed by a computer, cause the computer to carry out the above-described method for monitoring a hadron beam.

[0032] The features and advantages of the invention will become apparent from the following description of some embodiments of the system and method according to the invention, given purely as non-limiting examples, with reference to the accompanying drawings, in which: [Brief description of the drawings]

[0033] [Figure 1] FIG. 1 is a schematic perspective view of a treatment table and an open-configuration Compton telescope according to a first embodiment of the present invention. [Diagram 2] FIG. 2 is a flow chart illustrating the steps of a method according to a first embodiment of the invention. [Diagram 3] FIG. 3 is a schematic perspective view of a treatment table and an open magnetic configuration Compton telescope according to a second embodiment of the present invention. [Figure 4] FIG. 4 is a schematic perspective view of a treatment table and a closed-configuration Compton telescope according to a third embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0034] definition For purposes of the present invention, the following terms are defined as follows: - "Burst" means a bunch of hadrons with the same acceleration phase. - "Prompt Gamma" means fast and high-energy gamma rays that are emitted spontaneously following nuclear reactions of hadrons with the tissue of a target. - "Organs At Risk (OAR)" means organs for which physicians set dose constraints that must not be exceeded in order to prevent radiation-related side effects as far as possible. - "PTV (or Planning Target Volume)" means the volume of the tumor visible on imaging (GTV or "Gross Tumor Volume"), extended by a treatment margin defined by the physician according to the type of disease being treated (CTV or "Clinical Target Volume"), plus a margin defined by the inaccuracies due to the treatment process (uncertainties related to range, positioning, inherent uncertainties of the treatment machine, etc.). - "Subject" means a mammal, preferably a human. In the present invention, a subject may be a patient, i.e. a person under the care of a physician, undergoing or having undergone treatment, or being followed for the progression of a disease.

[0035] Detailed Description The present invention relates to a method for monitoring a hadron beam during a hadron therapy treatment of a subject suffering from a tumor.

[0036] Typically, in hadron therapy centers, hadrons are accelerated, usually in a cyclotron or synchrotron, to therapeutic energies of 70-250 MeV and delivered to the treatment room, where they enter the treatment nozzle. The thin initial hadron beam is distributed transversely and longitudinally and appropriately formatted to be therapeutic. The hadrons used are usually proton or carbon ion beams. Beam scattering and formatting can be performed using electromechanical means for the treatment of patients with passively-scattered hadron-therapy (PSHT). In this technique, in particular, proton beams are used. The second mode, also called uniform scanning, consists of scanning the coarse beam over a wide field, followed by collimation and depth compensation by accessories customized to the patient's anatomy. This makes it possible to treat a wider radiation field with a deeper range. Another technique consists of magnetic field scanning of mini-beams of hadrons in an initial energy sequence. Hadrons are precisely and accurately scanned in three directions (x,y,z) through the tumor to irradiate the tumor without the use of customized accessories. This technique can be used to treat patients with intensity modulated hadron therapy.

[0037] The hadron therapy is performed according to a treatment plan that includes predefined parameters as a function of time to define at least one characteristic of the hadron beam over time during the hadron therapy treatment.

[0038] In certain embodiments, the predefined parameters defining at least one characteristic of the beam vary depending on the hadron therapy technique used.

[0039] In the case of passive scattering, the transverse and longitudinal scattering of the beam is obtained by the use of a path modulation wheel and one or two scatterers made of high-Z material, producing a flat and wide beam in the region of interest. The modulation wheel is configured to insert blades of different material thicknesses on the range of the hadrons during its rotation to spread the Bragg peak and adapt it to the depth of the target volume. The modulation of the Bragg peak is therefore discrete. The thickness and width of the blades are designed such that the sum of the resulting individual Bragg peaks results in a uniform and homogenous depth dose distribution, SOBP or "spread-out Bragg peak". To adapt the dose distribution laterally to the target volume (plus a suitable margin), an aperture made of a brass block of sufficient thickness (2 cm to 8 cm) is usually used to absorb the highest energy incident hadrons. Finally, the Bragg peak of the passively scattered beam is further spread using a distance compensator to produce a dose distribution according to the distal shape of the target.

[0040] In one embodiment, the hadron therapy treatment uses passive scattering technology. In this embodiment, the predefined parameters include at least the beam energy and the hadron range modulation (i.e., SOBP). In fact, the absorber and the compensator are accessories customized for the patient, and their positions do not change during the treatment.

[0041] For uniform scanning, an active scanning system is used, which uses multiple mini-irradiations to build up a modulated Bragg peak in the tumor. The target volume is irradiated by lateral scanning of successive layers. A dedicated modulation wheel is used to translate the Bragg peak step by step. To obtain a better definition of the modulated Bragg peak, layers of intermediate depth are irradiated by a combination of scatterer absorber plates and modulation wheel blades. Once modulated, the proton beam is scanned extensively in the Y and X directions, respectively, by the vertical magnet in the first position and then by the horizontal magnet.

[0042] In one embodiment, the hadron therapy treatment uses a uniform scanning technique, in which the predefined parameters include at least the beam energy and hadron range modulation as well as the Y and X positions of the beam.

[0043] Active mini-beam scanning consists of scanning an elemental ion beam precisely horizontally and vertically with a magnet while varying the initial energy of the proton beam 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 by an energy selection system. The position in the plane (X,Y) of the microbeam is controlled by the same scanning magnet as described below. A series of spots is thus generated and distributed throughout the target volume. The size of the spot at the isocenter is adapted by a quadrupole placed in front of the scanning magnet. Its main advantage is the reduction of both the amount of neutrons generated and the power losses due to passive beam-forming accessories.

[0044] In one embodiment, the hadron therapy treatment uses active mini-beam scanning technology. In this embodiment, the predefined parameters include at least the X, Y and Z coordinates (i.e., beam energy) and intensity of each spot.

[0045] The technology of implementing magnetic beam scanning allows beam deflection to cover a treatment field that can reach 30cmx40cm.

[0046] In a hadron therapy treatment room, the subject typically sits in a chair or lies in a predefined position on a treatment table relative to the treatment nozzle, from which emerges the beams that impinge on the subject.

[0047] In one embodiment, the treatment nozzle is placed at a fixed position at a predefined distance from the object. The treatment nozzle can be positioned relative to the object such that the incidence direction of the beam F enters the object perpendicular to the sagittal plane of the object. In a preferred embodiment, the treatment nozzle is positioned facing the object such that the beam has its point of incidence in front of the object. This allows the beam to penetrate to a target volume within the object with as little penetration as possible into normal tissues and / or organs at risk, reducing the dose received by the normal tissues and / or organs at risk.

[0048] By using the treatment nozzle in a fixed position, the direction of incidence of the beam F, and therefore also the point of incidence in the tissue, can be changed simply by using magnetic field scanning, which allows the beam to be shifted by small amounts.

[0049] In order to be able to change the incidence angle of the beam over an arc of more than 180°, in one embodiment, the treatment table T is configured to move the subject relative to the incidence point of the beam, in particular during a hadron therapy treatment. In this first embodiment shown in Fig. 1, the treatment table T can rotate around three axes A1, A2 and A3 in both rotational directions, and can translate along the axes A1, A2 and A3 in both opposite directions of each axis.

[0050] In this first embodiment, the Compton telescope TC comprises two Compton half-detectors in the form of two hollow half-cylinders symmetrical to axis A1 and separated from each other along the direction A2 so as to allow the passage of the beam F that has reached the top of the object. The two half-cylinders are complementary and, when joined, can form a complete hollow cylinder. In particular, each half-detector forms an arc with an angle of 180°. In this embodiment, the Compton half-detectors can be translated in both directions along the axes A1, A2 and A3, and can be rotated around axis A3.

[0051] In a second embodiment shown in Fig. 3, the treatment table T can likewise rotate about three axes A1, A2 and A3 in both rotational directions and translate along the axes A1, A2 and A3 in opposite directions of each axis. The Compton telescope TC comprises two Compton half-detectors in the form of two hollow semi-cylinders symmetrical to the axis A1 and separated from each other along the direction of A3 so as to allow the passage of the beam F arriving at the sides of the subject.

[0052] The Compton telescope arrangements of the first and second embodiments are referred to in this description as "open magnetic configuration Compton telescopes". In the first and second embodiments, each Compton half detector can be moved independently of the other to better match the incident position and direction of the beam F on the target, while at the same time maintaining the closest possible arrangement of the Compton telescope TC relative to the target. In fact, the Compton telescope has a higher spatial resolution and allows the detection of a larger number of events (i.e. prompt gammas, de-excitation gamma rays or annihilation gammas) when the two half detectors are closest to the target.

[0053] In a third embodiment shown in FIG. 4, the Compton telescope has the form of a hollow cylinder and includes a single detection volume with a side slit whose dimensions allow the passage of the beam F that reaches the side of the object. A Compton telescope in this configuration is referred to in the present description as a "closed magnetically-configured Compton telescope". The treatment table T is aligned along the axis A1, as is the longitudinal axis of the hollow cylinder. The treatment table T can move within the closed magnetically-configured Compton telescope, in particular it can rotate around three axes A1, A2 and A3 in both rotational directions, and it can translate along the axes A1, A2 and A3 in both opposite directions of each axis. In this embodiment, the Compton telescope is mounted on a mechanical support and is motorized so that it can translate along the axes A1, A2 and A3 and swivel around the axis A3.

[0054] In the first, second and third embodiments, the treatment table T on which the subject is placed is rigidly mounted on a motorized mechanical support (not shown) movable with degrees of freedom as described hereinafter. The motorized mechanical support is in particular capable of allowing a rotational movement of the treatment table T with intervals varying between 2 and 15° and a translational movement with intervals varying between 0.5 cm and 5 cm.

[0055] In one embodiment, the motorized support is a robotic positioning arm configured to have a sensitivity of 0.1 cm to 1 cm.

[0056] In some embodiments including the treatment couch T on a motorized mechanical support, at least one of the predefined parameters of the treatment plan corresponds to the spatial position of the treatment couch T and thus the motorized mechanical support. This particularly advantageous embodiment allows to avoid the use of huge isocentric rotary heads ("gantry") configured to deliver beams with variable angles of more than 180°. "Gantries" incorporating treatment nozzles are extremely expensive to manufacture compared to motorized treatment beds. As a result, avoiding the use of "gantry" allows to reduce the construction costs of hadron therapy infrastructure, making this technology more accessible.

[0057] In some embodiments in which the Compton telescope is movable, at least one of the predefined parameters of the treatment plan corresponds to a spatial position of the closed magnetically-configured Compton telescope or a spatial position of each Compton half detector of the open magnetically-configured Compton telescope.

[0058] The accelerator used in the method according to the invention produces a hadron beam comprising a plurality of discrete hadron "bursts" emitted by the accelerator at predefined frequencies.

[0059] In one embodiment, the accelerator that produces the hadron beam used is a synchrotron or linear accelerator. A synchrotron accelerates hadrons as bunches (pulses) at the desired energy. Once the bunch reaches the required energy, it is extracted and sent via a "beamline" to the treatment chamber. However, regardless of the type of accelerator, the extracted narrow monochromatic beam is magnetically guided via the beamline to the treatment nozzle.

[0060] In one embodiment, the accelerator is a "digital" synchrotron that includes an induction cell and magnets that undergo rapid changes in their operation via external beam control means and an on-board computer that can control them (switches and FPGAs).

[0061] The interaction of the "burst" produces in the material a rapid emission of high-energy gamma rays, called "prompt gammas", in addition to self-activation and emission of charged particles. The "prompt gamma" production profile correlates well with the hadron range. Thus, detection of the "prompt gammas" can be used to effectively monitor the interaction point of the beam and the dose deposition in the target.

[0062] FIG. 2 illustrates an embodiment of the method, which includes several data acquisition and calculation steps.

[0063] The method according to the invention is adapted to allow real-time monitoring of a hadron therapy treatment by obtaining a series of images of the interaction volume within which the hadrons of a "burst" interact with the target tissue and of the total volume of the tumor. Images of the interaction volume can be obtained only while the "burst" is affecting the target.

[0064] Thus, the method includes a first phase when a "burst" affects the subject 10, which first phase includes the following steps: - Step 111, detecting with the Compton telescope the "prompt gammas" produced by the interaction of hadrons from the "burst" with the tissue of interest; - Step 112: using the detected "prompt gammas" to reconstruct an image of the interaction volume within which the hadrons of the "burst" interact with the tissue of interest.

[0065] 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 atomic number, impart high stopping power to ionizing radiation, making it an ideal material for gamma ray detectors with energies ranging from tens of KeV to tens of MeV. Liquid xenon is both an excellent active medium and an excellent scintillator for detecting ionizing radiation, allowing the construction of large-dimension detectors containing homogeneous sensitive media. Compton telescopes use successive interactions (two or more) of incident photons in an interaction volume. Based on the interaction points and the energy deposited in each interaction, the direction of the incident photon can be converted into a cone by application of Compton dynamics. The location of the photon source can be determined by the intersection of different Compton cones inferred from subsequent interactions from photons of the same source. This type of detector is therefore well adapted for the detection of "prompt gammas" in the corresponding range of energies of several MeV, where Compton scattering is the dominant process.

[0066] The image of the measured interaction volume may be a three-dimensional image.

[0067] In one embodiment, an image of the interaction volume is obtained for each "burst" that impacts the object. In this embodiment, the image acquisition frequency depends on the "burst" generation frequency in the accelerator. The number of images acquired per second can therefore vary between 5 and 30.

[0068] In one embodiment, the Compton telescope is configured to have a spatial resolution of approximately 1 mm for each image of a "burst."

[0069] In the present invention, the tumor cells of the subject are labeled with a radiopharmaceutical containing a radioisotope that emits positrons and de-excitation gamma rays almost simultaneously. This allows the location of the radioactive marker to be determined by using the three-photon imaging principle. In fact, the positron travels along a short range (on the order of 1 mm) in tissue before annihilation into two 511 keV photons moving in opposite directions ("back-to-back gamma").

[0070] Three-photon imaging is based on the combined use of a Compton telescope and a radiopharmaceutical having a radioisotope that emits positrons and de-excitation gamma rays nearly simultaneously.

[0071] The coincident detection of the two annihilation photons makes it possible to plot the line of response (LOR), i.e. the line connecting the two interaction points of the annihilation photon in the Compton telescope and passing through the annihilation point of the positron in the tissue. The position of the radioisotope can therefore be obtained as the intersection point between the LOR and the Compton cone, which is defined based on the interaction of the de-excited gamma with the Compton telescope. The surface of the Compton cone contains the direction of incidence of the de-excited gamma and can be directly deduced from the Compton kinetics. The aperture angle of the Compton cone, θ, is defined by the Compton scattering formula and the axis of the Compton cone is determined using the first of the two interaction points of the de-excited gamma entering the telescope.

[0072] This technique can advantageously reduce the number of disruptions required to obtain an image, thus reducing acquisition time and / or the amount of material inoculated per patient.

[0073] The first phase of the method, in the case where the "burst" does not affect subject 11, includes the following steps: - extracting the location of the radiopharmaceutical labeled tumor cells by coincidence detection of the de-excitation gamma rays and the two annihilation gamma rays generated by the positrons using a Compton telescope as described above 121; - Reconstructing 122 an image of the total volume of the tumor treated by the hadron beam during the hadron therapy treatment based on the location of the tumor cells.

[0074] In a preferred embodiment, the radioisotope used in the radiopharmaceutical is 44 Sc, which emits positrons and photons of energy 1.157 MeV nearly simultaneously in space and time.

[0075] Images of the total tumor volume are acquired between two successive "bursts" to prevent contamination of the image by signals generated by "prompt gamma"

[0076] In one example, the construction of the Compton telescope is such that for a 10 second acquisition, the spatial resolution of the image of the total volume of the tumor is about 1 mm. The resolution obtained depends on the physical limitations of the detector and the activity of the isotope injected into the subject.

[0077] In one embodiment, the image of the total tumor volume is a three-dimensional image.

[0078] The method further includes a second phase comprising the steps of: - comparing 131 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; - step 132, each time the measured interaction volume is at least partially contained in the measured total tumor volume, calculating the deviation between, on the one hand, the position of the measured interaction volume in the measured total tumor volume and, on the other hand, the predefined position of the interaction volume in the total tumor volume defined in the treatment plan.

[0079] The offset can be calculated by superimposing the images. If the image of the measured interaction volume and the image of the measured total tumor volume are acquired by the same detector and therefore reconstructed to the same reference, it is easy to obtain the offset.

[0080] The comparison phase makes it possible to compare the actual positions of the Bragg peaks against the positions calculated by the calculation software to generate the treatment plan.

[0081] 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 volume of the measured tumor is compared to a predefined threshold. The predefined threshold may correspond to a margin of 1 mm to 5 mm around the target volume (PTV). The threshold may also be defined with reference to the radiosensitivity of the risk organs surrounding the target volume. For example, the predefined threshold corresponds to a margin of 0.5 mm towards the more radiosensitive lymph nodes and a margin of 1 mm towards the less radiosensitive lungs.

[0082] In one embodiment, each time the deviation becomes larger than a predefined threshold, the method includes a step 134 of calculating at least one new parameter of the hadron beam to modify at least one property of the hadron beam.

[0083] In one embodiment, each time the deviation becomes greater than a predefined threshold, the method includes calculating parameters of the treatment plan corresponding to a new spatial position of the motorized mechanical support to modify at least one characteristic of the hadron beam.

[0084] In one embodiment, new parameters of the hadron beam are transmitted to an accelerator that modifies at least one property of the hadron beam to modify the position of the interaction volume relative to the measured total tumor volume.

[0085] In one embodiment, the method comprises stopping the hadron beam whenever the deviation becomes larger than a predefined threshold, which makes it possible to have a safety measure to avoid any irradiation that does not comply with the treatment plan.

[0086] In one embodiment, the method further comprises a step of reconstruction of a three-dimensional image sequence resulting from merging a three-dimensional image of the interaction volume with a three-dimensional image of the total volume of the tumor at the same Compton camera reference, such an image sequence being viewable in real time on a screen providing visual information to the medical professional.

[0087] The present invention also relates to a system for monitoring a hadron beam during a hadron therapy treatment of a subject, the system being configured to monitor a hadron beam comprising a plurality of discrete hadron "bursts" emitted at a predefined frequency by an accelerator during a hadron therapy treatment performed according to a treatment plan comprising predefined parameters as a function of time to define at least one characteristic of the hadron beam over time during the hadron therapy treatment.

[0088] A system for monitoring hadron beams will now be detailed. In the following, the modules are to be understood as functional entities, and not as physically separate hardware components. They can therefore be grouped in the same concrete hardware component or divided into several of these components. Furthermore, each of these modules is optionally shared in turn between at least two physical components. Furthermore, the modules are implemented in other forms of hardware, software, microprograms or any combination thereof.

[0089] The system includes a beam imaging module configured to receive data acquired from the Compton telescope when the "burst" impacts the subject. In an embodiment, the data acquisition is performed online and continuously. The data acquired during the time frame corresponding to the delivery of the "burst" to the subject is transmitted to the beam imaging module. This module is further configured to analyze these data in order to determine the emission points of the "prompt gammas" generated by the interaction of the "burst" with the tissue of the subject. This module thus uses the emission points of the "prompt gammas" to reconstruct an image of the interaction volume within which the hadrons of the "burst" interact with the tissue.

[0090] In one embodiment, the beam imaging module is further configured to identify and reject all data corresponding to events that are not based on "prompt gamma" interactions within the active volume of the Compton telescope.

[0091] The system also includes a tumor imaging module configured to receive data acquired by the Compton telescope when the "burst" does not affect the subject. In an embodiment, the data acquisition is performed online and continuously, and only data acquired between two subsequent "bursts" of the subject are transmitted to the tumor imaging module. This allows to select only data from the beta decay of radioisotopes captured by the tumor cells. This module is further configured to extract the location of tumor cells labeled with radiopharmaceuticals by coincident detection of the de-excitation gamma rays and the two annihilation gamma rays generated by the positrons, and to analyze these data in order to reconstruct an image of the total tumor volume treated by the hadron beam during the hadron therapy treatment using the tumor cell locations.

[0092] In one embodiment, the Compton telescope is a liquid xenon Compton telescope.

[0093] The system further includes an evaluation module configured to compare an image of the interaction volume with an image of the total tumor volume to position the measured interaction volume relative to the measured total tumor volume and, whenever the measured interaction volume is at least partially contained within 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 predefined position of the interaction volume in the total tumor volume defined in the treatment plan.

[0094] In one embodiment, the evaluation module of the method 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 measured total volume of the tumor against a predefined threshold.

[0095] In one embodiment, whenever the deviation becomes larger than a predefined threshold, the system further includes a correction module configured to calculate at least one new parameter of the hadron beam to correct at least one property of the hadron beam.

[0096] As explained in the first part of this description, the predefined parameters that define the characteristics of the hadron beam vary depending on the type of hadron therapy treatment. Based on the type of treatment that can be performed with the treatment nozzle, the predefined parameters that can be dynamically affected during a session include the beam energy, hadron range modulation (i.e., SOBP), hadron range modulation and / or the X and Y position of the beam.

[0097] In one embodiment, the correction module is further configured to transmit new parameters of the hadron beam to the accelerator device that modifies at least one characteristic of the hadron beam to correct a position of the interaction volume relative to the measured total volume of the tumor.

[0098] In some embodiments, the accelerator includes a treatment nozzle located in a fixed position relative to the treatment couch within the treatment room.

[0099] In an embodiment, the treatment table T is configured to move the subject relative to the point of incidence of the beam, in particular during a hadron therapy treatment. In this first embodiment shown in Fig. 1, the treatment table T can rotate around three axes A1, A2 and A3 in both rotational directions and can translate along the axes A1, A2 and A3 in both opposite directions of each axis.

[0100] In this first embodiment, the Compton telescope TC comprises two Compton half-detectors in the form of two hollow half-cylinders symmetrical to axis A1 and separated from each other along the direction A2 so as to allow the passage of the beam F that has reached the top of the object. The two half-cylinders are complementary and, when joined, can form a complete hollow cylinder. In particular, each half-detector forms an arc with an angle of 180°. In this embodiment, the Compton half-detectors can be translated in both directions along the axes A1, A2 and A3, and can be rotated around axis A3.

[0101] In a second embodiment shown in Fig. 3, the treatment table T can likewise rotate about three axes A1, A2 and A3 in both rotational directions and translate along the axes A1, A2 and A3 in opposite directions of each axis. The Compton telescope TC comprises two Compton half-detectors in the form of two hollow semi-cylinders symmetrical to the axis A1 and separated from each other along the direction of A3 so as to allow the passage of the beam F arriving at the sides of the subject.

[0102] The Compton telescope arrangements of the first and second embodiments are referred to in this description as "open magnetic configuration Compton telescopes". In the first and second embodiments, each Compton half detector can be moved independently of the other to better match the incident position and direction of the beam F on the target, while at the same time maintaining the closest possible arrangement of the Compton telescope TC relative to the target. In fact, the Compton telescope has a higher spatial resolution and allows the detection of a larger number of events (i.e. prompt gammas, de-excitation gamma rays or annihilation gammas) when the two half detectors are closest to the target.

[0103] In a third embodiment shown in FIG. 4, the Compton telescope has the form of a hollow cylinder and includes a single detection volume with a side slit whose dimensions allow the passage of the beam F that reaches the side of the object. A Compton telescope in this configuration is referred to in the present description as a "closed magnetically-configured Compton telescope". The treatment table T is aligned along the axis A1, as is the longitudinal axis of the hollow cylinder. The treatment table T can move within the closed magnetically-configured Compton telescope, in particular it can rotate around three axes A1, A2 and A3 in both rotational directions, and it can translate along the axes A1, A2 and A3 in both opposite directions of each axis. In this embodiment, the Compton telescope is mounted on a mechanical support and is motorized so that it can translate along the axes A1, A2 and A3 and swivel around the axis A3.

[0104] In the first, second and third embodiments, the treatment table T on which the subject is placed is rigidly mounted on a motorized mechanical support (not shown) movable with degrees of freedom as described hereinafter. The motorized mechanical support is in particular capable of allowing a rotational movement of the treatment table T with intervals varying from 2 to 15° and a translational movement with intervals varying from 0.5 cm to 5 cm.

[0105] In one embodiment, the motorized support is a robotic positioning arm configured to have a sensitivity of 0.1 cm to 1 cm.

[0106] In some embodiments including the treatment couch T on a motorized mechanical support, at least one of the predefined parameters of the treatment plan corresponds to a spatial position of the motorized mechanical support, in particular the treatment couch T. The modification module is further configured to calculate new parameters of the treatment plan corresponding to a new spatial position of the motorized mechanical support in order to modify at least one property of the hadron beam, in particular the properties corresponding to the beam direction and point of incidence.

[0107] In some embodiments in which the Compton telescope is movable, at least one of the predefined parameters of the treatment plan corresponds to a spatial position of the closed magnetically-configured Compton telescope or a spatial position of each Compton half-detector of the open magnetically-configured Compton telescope, and the correction module is further configured to calculate new parameters of the treatment plan that correspond to the new spatial positions of the closed magnetically-configured Compton telescope or each Compton half-detector of the open magnetically-configured Compton telescope.

[0108] In one embodiment, the correction module is further configured to transmit new parameters of the hadron beam associated with a new position of the motorized mechanical support to the motorized mechanical support in order to correct the direction and / or point of incidence of the beam and thus the position of the interaction volume relative to the measured total volume of the tumor.

[0109] In one embodiment, the system includes an image reconstruction module configured to reconstruct a three-dimensional image sequence resulting from the merging 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, which makes it possible to obtain a film of the treatment session.

[0110] In one embodiment, a module of the system includes at least one processor and at least one processor-readable storage medium.

[0111] The term "processor" should not be construed as being limited to "hardware" capable of executing software, but generally refers to a processing device, which may include, for example, a computer, a microprocessor, an integrated circuit, or a programmable logic controller (PLD). The processor may also include one or more graphics processing units (GPUs), whether used for infographic and image processing or other functions. Furthermore, instructions and / or data for performing related and / or resulting functions may be stored on any medium readable by the processor, such as an integrated circuit, a hard drive, an optical disk such as a CD (compact disk), a DVD (digital versatile disk), a RAM (random access memory) or a ROM (read only memory), etc. The instructions may be stored in hardware, software, a microprogram, or any combination thereof, among others.

[0112] The invention also relates to a computer program comprising instructions which, when executed by a computer, cause the computer to carry out the method for monitoring a hadron beam as described above.

[0113] The present invention also relates to a computer-readable recording medium comprising instructions which, when executed by a computer, cause the computer to carry out the above-described method for monitoring a hadron beam.

[0114] In some embodiments, the computer readable storage medium is non-transitory.

Claims

1. A method for monitoring a hadron beam during a hadron therapy treatment of a subject (1) containing tumor cells labeled with a radiopharmaceutical having a radioisotope that emits positrons and de-excitation gamma rays at approximately the same time, the hadron therapy treatment being performed according to a treatment plan including predefined parameters as a function of time to define at least one characteristic of the hadron beam over time during the hadron therapy treatment, the hadron beam including a plurality of discrete hadron bursts emitted at a predefined frequency by an accelerator; The method comprises: - If a "burst" affects said object (10): - detecting (111) prompt gammas produced by the interaction of hadrons of the "burst" with tissue of the subject by a liquid xenon Compton telescope (TC); Using the detected prompt gammas to reconstruct (112) an image of an interaction volume within which hadrons of the burst interact with tissue of the subject; - If the "burst" does not affect the subject (11): - extracting the location of the tumor cells labeled with the radiopharmaceutical by coincidence detection of the de-excitation gamma rays and two annihilation gamma rays generated by the positrons using the Compton telescope (121); - reconstructing (122) an image of the total volume of the tumor treated by the hadron beam during the hadron therapy treatment; - comparing (131) an image of the interaction volume with an image of the total volume of the tumor in order to position the measured interaction volume with respect to the measured total volume of the tumor; - calculating (132) each time the measured interaction volume is at least partially included in the measured total tumor volume, 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 predefined position of an interaction volume in the total tumor volume defined in the treatment plan; Including, method.

2. The method of claim 1 , wherein an image of the interaction volume is obtained for each burst that impacts the object.

3. The method of claim 1 or claim 2, further comprising a step (133) of comparing the deviation between the predefined position of the interaction volume and the position of the measured interaction volume relative to the total volume of the measured tumor with a predefined threshold.

4. The method according to any one of claims 1 to 3, further comprising the step of calculating (134) at least one new parameter of the hadron beam to modify at least one characteristic of the hadron beam whenever the deviation becomes larger than the predefined threshold.

5. 5. The method according to claim 1, wherein the subject is positioned on a motorized mechanical support configured to move the subject relative to the beam during the hadron therapy treatment, and at least one predefined parameter of the treatment plan corresponds to a spatial position of the motorized mechanical support.

6. 6. The method of claim 5, further comprising the step of calculating parameters of the treatment plan corresponding to a new spatial position of the motorized mechanical support to modify at least one characteristic of the hadron beam whenever the deviation becomes greater than the predefined threshold.

7. The method according to any one of claims 1 to 6, characterized in that new parameters of the hadron beam are transmitted to the accelerator 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.

8. A monitoring method according to any one of claims 1 to 3, characterized in that it comprises shutting off the hadron beam whenever the deviation becomes larger than the predefined threshold.

9. The monitoring method according to any one of claims 1 to 8, further comprising a reconstruction step of a three-dimensional image sequence resulting from merging a three-dimensional image of the interaction volume with a three-dimensional image of the total volume of the tumor at the same Compton camera reference.

10. 1. A system for monitoring a hadron beam during a hadron therapy treatment of a subject including tumor cells labeled with a radiopharmaceutical having a radioisotope that emits positrons and de-excitation gamma rays substantially simultaneously, the hadron therapy treatment being performed according to a treatment plan including predefined parameters as a function of time to define at least one characteristic of the hadron beam over time during the hadron therapy treatment, the hadron beam including a plurality of discrete hadron bursts emitted at a predefined frequency by an accelerator; The system comprises: a beam imaging module configured to receive data acquired from a liquid xenon Compton telescope and to analyze these data in order to determine the emission point of the prompt gammas produced by the interaction of the burst with the tissue of the subject, in case the burst impacts the subject, within which an image of the interaction volume is reconstructed, in which the hadrons of the burst interact with the tissue; a tumor imaging module configured to receive the data acquired by the Compton telescope, in particular a liquid xenon Compton telescope, when the burst does not affect the subject, and to extract the positions of tumor cells labeled with a radiopharmaceutical by coincident detection of de-excitation gamma rays and two annihilation gamma rays generated by positrons, and to analyze these data in order to reconstruct, using the positions of the tumor cells, an image of the total volume of the tumor treated by the hadron beam during the hadron therapy treatment; 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 with respect 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 the deviation between, on the one hand, the position of the measured interaction volume with respect to the measured total tumor volume and, on the other hand, a predefined position of the interaction volume in the total tumor volume defined in the treatment plan; Including, system.

11. The system of claim 10 , wherein the evaluation module is further configured to compare the deviation between a predefined position of the interaction volume and a position of the measured interaction volume relative to the measured total tumor volume against a predefined threshold.

12. 12. The system of claim 10 or claim 11, further comprising a modification module configured to calculate at least one new parameter of the hadron beam to modify at least one characteristic of the hadron beam whenever the deviation becomes larger than the predefined threshold.

13. 13. The system of claim 12, wherein the modification module is further configured to transmit new parameters of the hadron beam to the accelerator device that modifies at least one characteristic of the hadron beam to modify a position of the interaction volume relative to the measured total tumor volume.

14. The system of any one of claims 10 to 13, further comprising a safety module configured to send an instruction to the accelerator to stop the hadron beam whenever the deviation becomes greater than the predefined threshold.

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