Patent Publication Number: US-9849307-B2

Title: System and method for dose verification and gamma ray imaging in ion beam therapy

Description:
RELATED APPLICATIONS 
     This application claims priority to U.S. Provisional Patent Application No. 62/066,477, filed Oct. 21, 2014, which is herein incorporated by reference. 
    
    
     STATEMENT OF GOVERNMENT SUPPORT 
     This invention was made with government support under Contract No. DE-AC02-05CH11231 awarded by the U.S. Department of Energy. The government has certain rights in this invention. 
    
    
     TECHNICAL FIELD 
     This disclosure relates generally to ion beam therapy and more particularly to high-energy gamma ray imaging in ion beam therapy. 
     BACKGROUND 
     Radiation therapy using proton and ion beams is an effective method to treat various types of localized malignant tumors [1]. One of the main issues of using radiation for treatment is the lack of the capability to determine the dose deposited in organs in real time during the treatment. This is important to guide the treatment, to adjust the ion beam in real time so that minimal dose is delivered to sensitive organs and noncancerous tissue, to correct for the movement of the organs inside the body, and to act as a fail-safe mechanism. Over the past years, there have been several accidents with radiation treatment procedures which led to deliveries of much higher doses than planned, or radiation delivered to wrong areas, leading to fatalities. Mapping the radiation dose delivered during a treatment session is also important for the planning of future treatment sessions. 
     SUMMARY 
     One innovative aspect of the subject matter described in this disclosure can be implemented in a system including a position sensitive detector and a collimator. The position sensitive detector is configured to detect gamma rays generated by an ion beam interacting with a target. The collimator is positioned between the target and the position sensitive detector. The collimator includes a plurality of knife-edge slits, with a first knife-edge slit intersecting with a second knife-edge slit. 
     In some implementations, the collimator is about 1.5 centimeters to 12.7 centimeters thick. In some implementations, the collimator comprises tungsten. 
     Another innovative aspect of the subject matter described in this disclosure can be implemented in a system including a position sensitive detector and a collimator. The position sensitive detector is configured to detect gamma rays generated by an ion beam interacting with a target. The collimator includes a first plurality of knife-edge slits and a second plurality of knife-edge slits. The first plurality of knife-edge slits are substantially parallel to one another. The the second plurality of knife-edge slits are substantially parallel to one another. The first plurality of knife-edge slits are not parallel to the second plurality of knife-edge slits. 
     In some implementations, the collimator is about 1.5 centimeters to 12.7 centimeters thick. In some implementations, the collimator comprises tungsten. 
     Another innovative aspect of the subject matter described in this disclosure can be implemented in a method including providing a system. The system includes a position sensitive detector and a collimator. The position sensitive detector is configured to detect gamma rays generated by an ion beam interacting with a target. The collimator is positioned between the target and the position sensitive detector. The collimator includes a plurality of knife-edge slits, with a first knife-edge slit intersecting with a second knife-edge slit. Gamma rays are detected with the position sensitive detector to generate a data set. A two-dimensional image of emission of the gamma rays from the target is generated using the data set. The position of a Bragg peak of the ion beam is determined. 
     In some implementations, the collimator is about 1.5 centimeters to 12.7 centimeters thick. In some implementations, the collimator comprises tungsten. 
     Details of one or more embodiments of the subject matter described in this specification are set forth in the accompanying drawings and the description below. Other features, aspects, and advantages will become apparent from the description, the drawings, and the claims. Note that the relative dimensions of the following figures may not be drawn to scale. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows an example of a schematic illustration of an ion beam therapy dose verification system. 
         FIGS. 2A and 2B  show examples of a schematic illustrations of multi-slit knife-edge collimators having a pattern of knife-edge slits. 
         FIGS. 3A and 3B  show examples of schematic illustrations of a multi-slit knife-edge collimator having a pattern of knife-edge slits. 
         FIG. 4  shows an example of a flow diagram illustrating the use of an ion beam therapy dose verification system. 
         FIG. 5  shows an example of a schematic illustration of an ion beam therapy dose verification system. 
     
    
    
     DETAILED DESCRIPTION 
     Reference will now be made in detail to some specific examples of the invention including the best modes contemplated by the inventor for carrying out the invention. Examples of these specific embodiments are illustrated in the accompanying drawings. While the invention is described in conjunction with these specific embodiments, it will be understood that it is not intended to limit the invention to the described embodiments. On the contrary, it is intended to cover alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims. 
     In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. Particular example embodiments of the present invention may be implemented without some or all of these specific details. In other instances, well known process operations have not been described in detail in order not to unnecessarily obscure the present invention. 
     Various techniques and mechanisms of the present invention will sometimes be described in singular form for clarity. However, it should be noted that some embodiments include multiple iterations of a technique or multiple instantiations of a mechanism unless noted otherwise. 
     Systems configured to monitor a proton beam or an ion beam in real time are described herein. Monitoring the proton beam or ion beam may be performed by the imaging of gamma-radiation that is emitted from the nuclear reactions or by the scattering of the Bremsstrahlung radiation inside the body during proton beam or ion beam treatment. Previous attempts to monitor the dose delivered by ions have used PET imaging [ 2 ]. This technique, however, has limited use for real-time monitoring due to longer decay times of the beta+emitters and low counting statistics. Embodiments of ion beam therapy dose verification systems described herein may be able to image high-energy gamma rays with high position resolution and high sensitivity. Embodiments of ion beam therapy dose verification systems described herein may also be used to map the total radiation dose delivered during a treatment session; this information may be useful in planning future treatment sessions. 
       FIG. 1  shows an example of a schematic illustration of an ion beam therapy dose verification system. As shown in  FIG. 1 , the system  100  comprises a multi-slit knife-edge collimator  105  and a position sensitive detector  110 . In some embodiments, the system  100  includes a motor  125  (e.g., an electric motor) coupled to the multi-slit knife-edge collimator  105  and the position sensitive detector  110  and operable to adjust a position of the multi-slit knife-edge collimator  105  and a position of position sensitive detector  110 . In some embodiments, the motor  125  is only coupled to the multi-slit knife-edge collimator  105  and is operable to adjust a position of the multi-slit knife-edge collimator  105 . In these embodiments, the position sensitive detector  110  remains in place. 
     Also shown in  FIG. 1  are an ion beam  115  and a target  120 . The ion beam  115  may comprise, for example, protons or carbon atoms. The ion beam may be generated by an ion-accelerator system (not shown). The multi-slit knife-edge collimator  105  is positioned between the position sensitive detector  110  and the target  120 . In some embodiments, a distance between the multi-slit knife-edge collimator  105  and the position sensitive detector  110  is larger than a distance between the multi-slit knife-edge collimator  105  and the target  120 . In some embodiments, this may provide an image magnification that allows for better imaging resolution. In some embodiments, a distance between the multi-slit knife-edge collimator  105  and the position sensitive detector  110  is substantially the same as or similar to a distance between the multi-slit knife-edge collimator  105  and the target  120 . In some embodiments, a distance between the multi-slit knife-edge collimator  105  and the position sensitive detector  110  and a distance between the multi-slit knife-edge collimator  105  and the target  120  are configured to be adjustable or changeable. 
     A knife-edge slit in a collimator is distinguished from a parallel slit in a collimator in that a parallel slit has parallel walls in the collimator. In contrast, a knife-edge slit has a wide opening on a first side on the collimator, the slit narrows in the collimator, and then the slit has a wide opening on a second side of the collimator. For example, some knife-edge slits may have a cross-section of two isosceles triangles with the vertex angle (i.e., the angle formed by legs of an isosceles triangle) of one isosceles triangle being disposed on the vertex angle of the other isosceles triangle. In some embodiments, a knife-edge slit having a cross-section of two isosceles triangles with the vertex angle of one isosceles triangle being disposed on the vertex angle of the other isosceles triangle forms a symmetrical, bow-tie shaped cross-section for the knife-edge slit. A knife-edge slit allows for a larger field of view of radiation generated by the interaction of an ion beam with a target than a parallel slit. In some embodiments, knife-edge slits in a collimator all have the same cross-section in the collimator. 
     Due to the differences in the amount of material of a collimator that can block radiation in a collimator having a knife-edge slit, such a collimator may permit some attenuated radiation to pass though the collimator. For example, at the narrowest portion in a knife-edge slit, a collimator has the least amount of material that can serve to block radiation. In some embodiments, the narrowest portion of the knife-edge slit is half-way though the thickness of the collimator. At this portion of a knife-edge slit and at proximal portions of a knife-edge slit, attenuated radiation may pass though the collimator. 
     As shown in  FIG. 1 , a knife-edge slit can be defined by an angle  108  of knife-edge slit. In some embodiments, the angle of a knife-edge slit is about 5° to 35°, or about 10°. In some embodiments, a dimension of the smallest width  109  of a knife-edge slit is about 0.1 mm to 4 mm. 
     In some embodiments, knife-edge slits  107  of the multi-slit knife-edge collimator  105  are oriented at multiple angles with respect to the direction of the ion beam  115 . Each knife-edge slit  107  in the multi-slit knife-edge collimator  105  generates a one dimensional (1-D) projection of the source distribution on the position sensitive detector  110 . The projection produced by each knife-edge slit may partially overlap with the projections from other knife-edge slits, creating an inverse problem similar to a coded aperture [3, 4] or a compressive sensing [5, 6] imager. An image reconstruction algorithm can be used to reconstruct a two dimensional (2-D) image of the distribution of gamma ray emissions along the ion beam path. Note that a single knife-edge slit collimator [7, 8], with the single slit being perpendicular on the ion beam direction, would project a 1-D image of the ion beam. 
     In some embodiments, the material of the multi-slit knife-edge collimator  105  comprises a high density, high atomic number material. For example, the material of the multi-slit knife-edge collimator  105  may comprise tungsten, a tungsten alloy, or lead. In some embodiments, a thickness of the multi-slit knife-edge collimator  105  is about 5 centimeters (cm) or greater. In some embodiments, a thickness of the multi-slit knife-edge collimator  105  is about 1.5 cm to 12.7 cm, 2.5 cm to 12.7 cm, or about 7.6 cm. These thicknesses may allow for the attenuation of high-energy gamma ray photons. 
     Several factors can be considered in the design of the multi-slit knife-edge collimator  105 , particularly with respect to the positions and orientations of the slits:
         Photon penetration. In some embodiments, the separation of knife-edge slits is large enough to reduce or to minimize photon transmission through parts of the multi-slit knife-edge collimator that are meant to be opaque for gamma ray energies emitted along the path of an ion beam. In some embodiments, most of the gamma ray energies are above about 1.5 MeV. In some embodiments, a tungsten collimator thickness of about 7.5 cm attenuates the gamma ray beam flux by about 95%, which may be suitable for imaging.   Projection completeness. Each point along the beam path may be projected by multiple slits which cover a large range of angles. The angles of a slit can range from 0° to 90° with respect to the ion beam direction. A more uniform coverage of angles allows a better reconstruction of a 2-D image. Projection angles at or closer to 0° rather than 90° may be more important, as this allows for measurements of the distal position of the Bragg peak. A prototype was built using knife edge slits oriented at 0°, 30°, 45°, 60°, −60°, −45°, −30° with respect to the ion beam direction.   Projection overlap minimization. Because the opening angle of a knife-edge slit is limited, a small section of the image space will be in the field of view of each knife-edge edge slit. In some embodiments, the arrangement of the knife-edge slits reduces or minimizes the overlap of projections from points at different positions along the ion beam path. In some embodiments, the separation between consecutive parallel slits is chosen so that all the points along the beam path are in the full field of view of the same number of parallel knife edge slits. This helps to ensure a uniform imaging sensitivity along the whole beam path. In some embodiments, when the distance from the beam axis to the center of the collimator is equal to the distance from the center of the collimator to the position sensitive detectors, this spacing between slits may also help to reduce of to insure a minimum overlap of projections created by those slits. A prototype was built in which the parallel slits were spaced in such a manner. In this prototype, no point along the path of the beam was in the full field of view of two consecutive parallel slits. This condition was achieved for a pre-defined stand-off distance between the center of the collimator and the ion beam direction. If distances longer than such pre-defined distances are required by the application, the parallel knife-edge slits will still cover the beam path properly, although at reduced magnifications. However, for shorter distances, the parallel knife edge slits may not have all the beam path in their field of view.       

     In some embodiments, the position sensitive detector  110  comprises a high efficiency position sensitive detector. In some embodiments, the position sensitive detector  110  comprises a scintillator or a semiconductor detector that has a specific position resolution and a specific granularity. For example, the position sensitive detector  110  may comprise an array of bismuth germinate (BGO) crystals, an array of lutetium oxyorthosilicate (LSO) crystals, or an array of cadmium zinc telluride (CZT) detectors. 
     In some embodiments, the motor  125  is operable to change the position of the multi-slit knife-edge collimator  105  and the position sensitive detector  110  with respect to a surface of the target. For example, in some embodiments, the motor does not change the distance of the multi-slit knife-edge collimator  105  and the distance of the position sensitive detector  110  with respect to the surface of the target, but instead changes the position of the multi-slit knife-edge collimator  105  and the position of the position sensitive detector  110  with respect to the surface of the target  120 . For example, the position of a Bragg peak in the target  120  may be determined, and then the position of the multi-slit knife-edge collimator  105  and the position of the position sensitive detector  110  with respect to a surface of the surface of the target  120  may be adjusted with the motor  125  to center the position the Bragg peak on the position sensitive detector  110  or to other adjust the gamma rays being imaged. 
     In some embodiments, the system  100  (i.e., including the multi-slit knife-edge collimator  105  and the position sensitive detector  110 ) is configured to be moved and positioned at different angles around the target  120 . In some embodiments, two or more systems  100  are positioned at different angles around the target  120 . Such configurations may allow for the generation of multiple 2-D images, with the images being generated at different angles with respect to the sample  120 . The 2-D images may be combined into a 2-D distribution using analytical or iterative image reconstruction algorithms. 
     Image reconstruction algorithms can be used to generate a 2-D image of the distribution of gamma rays emitted along the ion beam path. The 2-D image generation can be performed using a computing device that acquires and processes data generated by the position sensitive detector  110 . For example, such image reconstruction algorithms include Expectation-Maximization Maximum Likelihood approaches, filtered back-projection approaches, and compressive sensing approaches. The relative geometric simplicity of the gamma ray source distribution along the ion beam path and the presence of a low image background (e.g., especially at gamma ray energies above 1.5 MeV) may allow for high fidelity image reconstruction. In some embodiments, a 2-D image of the distribution of gamma rays can be generated every about 17 milliseconds (ms). In some embodiments, two or more 2-D images are combined to generate a three dimensional (3-D) image. In some embodiments, a single 1-D image along the beam path is reconstructed. 
     In some embodiments, a system controller is employed to operate the ion beam therapy dose verification system. The controller will typically include one or more memory devices and one or more processors. The processor may include a CPU or computer, analog and/or digital input/output connections, controller boards, etc. The controller may control all of the activities of the ion beam therapy dose verification system. The system controller executes system control software including sets of instructions for controlling data collection. Other computer programs stored on memory devices associated with the controller may be employed in some embodiments. 
     In some embodiments, the system controller may be coupled to the system controller of the ion beam system used to generate the ion beam. In such a system, the dose of ions can be determined with the ion beam therapy dose verification system and this information can be used to control the ion beam system. For example, from an analysis of information generated by the ion beam therapy dose verification system, the controller of the ion beam system may modify or stop the ion beam when the measured distribution of the gamma ray sources does not correspond with the intended location for ion beam dose deposition. 
     Typically there will be a user interface associated with the controller. The user interface may include a display screen, graphical software displays of the system and/or operating parameters, and user input devices such as pointing devices, keyboards, touch screens, microphones, etc. 
     The computer program code for controlling the data collection and related processes in a process sequence can be written in any conventional computer readable programming language; for example, assembly language, C, C++, Pascal, Fortran or others. Compiled object code or script is executed by the processor to perform the tasks identified in the program. 
     In some embodiments, an ion beam therapy dose verification system is used with an imaging system that is used to determine the location of an organ or a feature in a human or animal body. For example, the imaging system may be an x-ray system or an ultrasound system. The imaging system can be used to direct the ion beam (and its associated Bragg peak) at a feature in the body and account for any shifts of the feature in the body. For example, an organ with a tumor that is to be radiated with the ion beam may shift in the human body. The imaging system can be used to help insure the Bragg peak of the ion beam is at the position of tumor. For example, an image of the gamma rays generated by the ion beam can be overlaid on an image generated with the imaging system and the dose to different portions of a body can be determined. 
       FIGS. 2A and 2B  show examples of schematic illustrations of multi-slit knife-edge collimators having a pattern of knife-edge slits. The multi-slit knife-edge collimator  105  shown in  FIG. 1  is a cross-sectional view of a collimator, and the multi-slit knife-edge collimator  205  shown in  FIG. 2A  is a top-down view of a collimator. The pattern of knife-edge slits in the multi-slit knife-edge collimator  205  shown in  FIG. 2A  may be specified to image the path of the ion beam  115  shown in  FIG. 1 . In some embodiments, dimensions of the multi-slit knife-edge collimator  205  as shown in  FIG. 2A  are about 4 inches by 4 inches to about 12 inches by 12 inches, or about 8 inches by 8 inches. While the multi-slit knife-edge collimator  205  is shown a having a square shape, a collimator may be rectangular or have another shape. 
     The multi-slit knife-edge collimator  205  includes a plurality of knife-edge slits. Knife-edge slits of the plurality of knife-edge slits may have different lengths and may be at disposed at different angles with respect to one another. For example, the multi-slit knife-edge collimator  205  includes a first plurality of knife-edge slits  214 ,  215 , and  216  that are substantially parallel to one another. In some embodiments, substantially parallel means that the slits are parallel to one another within 1°. The multi-slit knife-edge collimator  205  also includes a second plurality of knife-edge slits  210  and  211  that are substantially parallel to one another. In some embodiments, the first plurality knife-edge slits is not parallel to the second plurality of knife-edge slits. Stated in a different manner, in some embodiments there is an angle (i.e., an angle greater than 0°) between knife-edge slits of the first plurality of knife-edge slits and knife-edge slits of the second plurality of knife-edge slits. 
     In some embodiments, at least one of the slits of the first plurality of knife-edge slits intersects with at least one of the slits of the second plurality of knife-edge slits. As shown in  FIG. 2A , slit  211  intersects with slit  215 . 
     Turning to  FIG. 2B , the multi-slit knife-edge collimator  250  shown is a top-down view of a collimator. The pattern of knife-edge slits in the multi-slit knife-edge collimator  250  shown in  FIG. 2B  may be specified to image the path of the ion beam  115  shown in  FIG. 1 . In some embodiments, dimensions of the multi-slit knife-edge collimator  250  as shown in  FIG. 2B  are about 4 inches by 4 inches to about 12 inches by 12 inches, or about 8 inches by 8 inches. While the multi-slit knife-edge collimator  250  is shown a having a square shape, a collimator may be rectangular or have another shape. 
     The multi-slit knife-edge collimator  250  includes a plurality of knife-edge slits  254 ,  255 , and  256  that are substantially parallel to each other. In some embodiments, substantially parallel means that the slits are parallel to one another within 1°. In some embodiments, the multi-slit knife-edge collimator  250  includes 2, 3, 4, 5, 6 or more knife-edge slits that are substantially parallel to each other. In some embodiments, the multi-slit knife-edge collimator  250  only includes knife-edge slits that are substantially parallel to each other. 
       FIGS. 3A and 3B  show examples of schematic illustrations of a multi-slit knife-edge collimator having a pattern of knife-edge slits.  FIG. 3A  shows an example of a top-down view of a multi-slit knife-edge collimator  305 .  FIG. 3B  shows an example of an isometric illustration of the multi-slit knife-edge collimator  305 . As shown in  FIGS. 3A and 3B , the multi-slit knife-edge collimator  305  includes a plurality of knife-edge slits, including slit  310 . The multi-slit knife-edge collimator  305  includes a first knife-edge slit that intersects with a second knife-edge slit. The multi-slit knife-edge collimator  305  also include a first plurality of knife-edge slits that are substantially parallel to one another and a second plurality of knife-edge slits that are substantially parallel to one another, with the first plurality of knife-edge slits not being parallel to the second plurality of knife-edge slits. 
       FIG. 4  shows an example of a flow diagram illustrating the use of an ion beam therapy dose verification system. Starting at block  405  of the process  400 , an ion beam therapy dose verification system is provided. The system includes a position sensitive detector and a collimator. The position sensitive detector is configured to detect gamma rays generated by an ion beam interacting with a target. The collimator is positioned between the target and the position sensitive detector. The collimator may be any of the multi-slit knife-edge slits described herein. The system may be, for example, the system  100  shown in  FIG. 1  or any of the other systems described herein. 
     At block  410 , gamma rays are detected with the position sensitive detector to generate a data set. For example, when an ion beam impinges on a target, gamma rays are emitted from nuclear reactions of the ion beam with the target or by the scattering of the ion beam along the path of the ion beam. In some embodiments, the ion beam has an energy of 10 MeV to 260 MeV, about 60 to 180 MeV, or about 120 MeV. In some embodiments, the gamma rays generated by the interaction of the ion beam with the target have an energy of about 0.05 MeV to 10 MeV or about 2 MeV to 6 MeV. 
     At block  415 , a two-dimensional image of emission of gamma rays from the target is generated using the data set. For example, to generate a two-dimensional image of the emission of gamma rays from the target, matrix calculations involving the system response of the ion beam therapy dose verification system and the data set can be performed. Image reconstruction algorithms, known to one having ordinary skill in the art, can be used to generate the two-dimensional image of the gamma ray emissions. For example, iterative algorithms, such as Expectation Maximization-Maximum Likelihood, or analytical algorithms, such as filtered back-projection, can be used. 
     The system response of the ion beam therapy dose verification system depends on the pattern of knife-edge slits in the collimator. The system response includes information regarding how much a gamma ray emitted from each point in the target is attenuated by the collimator before impinging the position sensitive detector. The system response includes this information for each point on the target to be imaged and each point on the position sensitive detector. In some embodiments, the system response also includes information regarding the probability that a gamma ray will generate a signal at each point on the position sensitive detector. 
     In some embodiments, the data set is processed before generating the two-dimensional image to remove noise and other artifacts in the data. In some embodiments, the two-dimensional image is displayed on a computer screen or other display. 
     At block  420 , a position of the Bragg peak of the ion beam is determined. Using the two-dimensional image of emission of gamma rays from the target, a maximum position of gamma ray emission can be determined. This maximum position of gamma ray emission corresponds to the Bragg peak. 
     In some embodiments, different images of the emission of gamma rays can be generated. For example, in some embodiments, at block  415 , a one-dimensional (1-D) image of emission the gamma rays from the target is generated by constraining the solution of the image reconstruction problem to the direction of the ion beam. 
     In some embodiments, after determining a position of a Bragg peak of the ion beam at lock  420 , the positions of the position sensitive detector and the collimator are moved so that the Bragg peak is proximate a center of the position sensitive detector. In some embodiments, the positions of the position sensitive detector and the collimator are moved to otherwise adjust the position of the Bragg peak or the gamma rays being imaged on the position sensitive detector. In some embodiments, operations  405  through  420  are then performed again. 
     The embodiments described above of a system including a multi-slit knife-edge collimator having intersecting knife-edge slits may be used for imaging the majority of an extended beam path inside a target. In some instances, a multi-slit knife-edge collimator having substantially parallel slits perpendicular to the ion beam direction may be more suitable for imaging short beam paths inside a target. In some instances, a multi-slit knife-edge collimator having substantially parallel slits perpendicular to the ion beam direction may be more suitable for imaging longer paths inside a target when the collimator is used with a motorized system that is functionally connected to a beam delivery system. In such an embodiment, the collimator and the position sensitive detector are positioned so that the expected position of the Bragg peak is substantially in the middle of the field of view of the system. Because knife-edge slits perpendicular to the beam path provide projections that are the most suitable for determining the distal position of the Bragg peak, a plurality of knife-edge slits perpendicular to the beam path will increase the imaging sensitivity. 
       FIG. 5  shows an example of a schematic illustration of an ion beam therapy dose verification system. As shown in  FIG. 5 , the ion beam therapy dose verification system  500  comprises a collimator  504  and a position sensitive detector  505 . The collimator  504  includes a plurality of knife-edge slits  506 ,  507 ,  508 ,  509  and  510 . In some embodiments, the plurality of knife-edge slits are substantially parallel to one another. Also shown in  FIG. 5  are an ion beam path  501  and a target  502 . Most of the dose of the ion beam occurs at the end of the ion beam path  501  at a Bragg peak  503 . The collimator is disposed between the target  502  and the position sensitive detector  505 . The plurality of knife-edge slits  506 ,  507 ,  508 ,  509 , and  510  are defined in the collimator  504  in a manner so that an expected position of the Bragg peak  503  is contained in the field of view  512  of the plurality of knife-edge slits  506 ,  507 ,  508 ,  509 , and  510 . 
     In some embodiments, the plurality of knife-edge slits  506 ,  507 ,  508 ,  509 , and  510  cast projections on the position sensitive detector  505  that overlap, partially overlap, or be separated. In some embodiments, better imaging performance is expected when the projections are separated. The part of the ion beam path  501  in the field of view  512  of the plurality of knife-edge slits will be projected onto the position sensitive detector  505  at locations  513 ,  514 ,  515 ,  516 , and  517 . 
     The presence of multiple slits in the collimator  504  increases the imaging sensitivity of the system  505 . In some embodiment, the collimator  504  is designed so that no other part of the ion beam path  501  outside the field of view of the plurality of knife-edge slits  512  is un-collimated with respect to the detector  505 . 
     In some embodiments, the detector  505  is 1-D, 2-D, or 3-D position sensitive. In some embodiments, the detector  505  is a single detector or an array of detectors. For an array of detectors, individual detectors can be co-planar (as shown in  FIG. 5 ) or can be arranged at different angles. For example, the detectors can be arranged to face the openings of the plurality of knife-edge slits normally, so that projection  513  will be perpendicular to the line connecting the detector detecting projection  513  and slit opening  506 , projection  514  will be perpendicular to the line connecting the detector detecting projection  514  and slit opening  507 , and so on. 
     The field of view  512  of the plurality of knife-edge slits may include the expected position of the Bragg peak  503  and some area around the expected position of the Bragg peak. The area around the expected position of the Bragg peak may allow for the ion beam therapy dose verification system  500  to show an intensity decrease of gamma rays from the Bragg peak after the Bragg peak. This may help the system  500  provide the position of the Bragg peak with high accuracy. 
     Because the field of view  512  of the plurality of knife edge slits may be small to allow for improved imaging sensitivity in a region, in order to accommodate ion beams of various track lengths and positions, the collimator  504  can be moved along the distal direction of the ion beam (x-direction in coordinate system  519 ) in response to the expected movement of the Bragg peak  503  during the ion treatment. 
     Other patterns of knife-edge slits in the collimator  504  (i.e., the plurality of knife edge slits not being substantially parallel to one another) are also possible. For example, in some embodiments, knife-edge slits of the plurality of knife-edge slits are positioned on the surface of a virtual circle, with the center of the circle placed close to the field of view  512 . In such a configuration, the knife-edge slits may all have a geometry similar to knife-edge slit  508 . 
     Other approaches to imaging gamma rays emitted during proton beam treatment have been proposed or tested. These include: single knife-edge slit collimators (e.g., which generate a 1-D image of the beam) [7, 8], 1-0 parallel slit collimators [9], and Compton cameras [10, 11]. According to some estimates, single knife-edge collimators can provide a good combination of sensitivity and position resolution, with a 4*10 −4  detection sensitivity and 6 millimeter (mm) position resolution in the distal direction; the incident energy of the proton beam was 120 MeV. 
     According to Monte Carlo simulations, the systems described with respect to  FIGS. 1-3B  can provide a much more complete and accurate representation of the proton beam and the associated Bragg peak at comparable proton beam energies. The Bragg peak is a peak on the Bragg curve; a Bragg curve plots the energy loss of the ion beam as it travels though the target. 
     For example, for a 150 MeV proton beam, the detection sensitivity for the detection of gamma rays above 1.5 MeV was 3.5*10 −3 . The imaging position resolution was 2.7 mm FWHM for a gamma ray source situated on the normal direction above a multi-slit knife-edge collimator. An image resolution of around 1.8 mm FWHM was obtained when the source was positioned at 5 to 10 degrees off the normal direction above the multi-slit knife-edge collimator. These values represent a factor of 8.75 increase in sensitivity and a factor of 3 increase in resolution when compared to the single knife-edge slit collimator design described in Reference 7. 
     However, imaging resolution and detection sensitivity do not characterize the capability of the imaging system to accurately provide the distal position of the Bragg peak. A Linear Discriminant Analysis was used to determine how well the systems described with respect to  FIGS. 1-3B  were able to capture differences in the projected images when the Bragg peak of a proton beam is distally shifted by 1 mm. The linear discriminant for a single knife-edge slit collimator was calculated to be S=31 for 10 8  incident number of protons. For the multi-slit knife-edge collimators, the linear discriminant is S=750 for the same number of incident protons. This high discrimination may allow the system to provide the position of the Bragg peak with an integration time of a few seconds. This level of performance may allow for real-time dose distribution characterization and beam adjustment in close to real time. 
     While the embodiments described herein have been described as being implemented to generate dose distribution information for radiation therapy using ion beams, the proposed combination of a multi-slit knife-edge collimator and a position sensitive detector coupled to an image reconstruction algorithm can be used for many different applications involving imaging of sources of high-energy gamma rays. For example, the embodiments described herein could be used to characterize and diagnose materials by active interrogation using gamma rays, hard X-rays, neutrons, or other beams. 
     Conclusion 
     In the foregoing specification, the invention has been described with reference to specific embodiments. However, one of ordinary skill in the art appreciates that various modifications and changes can be made without departing from the scope of the invention as set forth in the claims below. Accordingly, the specification and figures are to be regarded in an illustrative rather than a restrictive sense, and all such modifications are intended to be included within the scope of invention. 
     REFERENCES 
     The following references are herein incorporated by reference:
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