Patent Publication Number: US-2020286601-A1

Title: Graphical display of dose rate information for radiation treatment planning

Description:
RELATED APPLICATIONS 
     This application is related to the application with Docket No. VAR-19001 (2019-009US01) entitled “Radiation Treatment Planning Based on Dose Rate” by D. Khuntia et al., filed concurrently herewith, and to the application with Docket No. VAR-19003 (2019-011US01) entitled “Radiation Treatment Based on Dose Rate” by D. Khuntia et al., also filed concurrently herewith, both of which are incorporated by reference in their entirety. 
     BACKGROUND 
     The use of radiation therapy to treat cancer is well known. Typically, radiation therapy involves directing a beam of high energy proton, photon, ion, or electron radiation (“therapeutic radiation”) into a target or target volume (e.g., a volume that includes a tumor or lesion). 
     Before a patient is treated with radiation, a treatment plan specific to that patient is developed. The plan defines various aspects of the therapy using simulations and optimizations based on past experiences. In general, the purpose of the treatment plan is to deliver sufficient radiation to the unhealthy tissue while minimizing exposure of surrounding healthy tissue to the radiation. 
     The planner&#39;s goal is to find a solution that is optimal with respect to multiple clinical goals that may be contradictory in the sense that an improvement toward one goal may have a detrimental effect on reaching another goal. For example, a treatment plan that spares the liver from receiving a dose of radiation may result in the stomach receiving too much radiation. These types of tradeoffs lead to an iterative process in which the planner creates different plans to find the one plan that is best suited to achieving the desired outcome. 
     A recent radiobiology study has demonstrated the effectiveness of delivering an entire, relatively high therapeutic radiation dose to a target within a single, short period of time. For example, each beam can deliver at least four grays (Gy) in less than one second, and may deliver as much as 20 Gy to 50 Gy or as much as 100 Gy or more in less than one second. This type of treatment is referred to generally herein as FLASH radiation therapy (FLASH RT). 
     Evidence to date suggests that FLASH RT advantageously spares normal, healthy tissue from damage when that tissue is exposed to a high radiation dose for only a very short period of time. FLASH RT thus introduces important constraints that are not considered in or achieved with conventional radiation treatment planning. 
     SUMMARY 
     In radiation therapy techniques in which the intensity of the particle beam is either constant or modulated across the field of delivery, such as in intensity modulated radiation therapy (IMRT) and intensity modulated particle therapy (IMPT), beam intensity is varied across each treatment region (target volume) in a patient. Depending on the treatment modality, the degrees of freedom available for intensity modulation include beam shaping (collimation), beam weighting (spot scanning), and angle of incidence (which may be referred to as beam geometry). These degrees of freedom lead to an effectively infinite number of potential treatment plans, and therefore consistently and efficiently generating and evaluating high-quality treatment plans is beyond the capability of a human and relies on the use of a computer system, particularly considering the time constraints associated with the use of radiation therapy to treat ailments like cancer, as well as the large number of patients that are undergoing or need to undergo radiation therapy during any given time period. 
     Embodiments according to the present invention provide an improved method of radiation treatment planning, and improved radiation treatment based on such planning, for FLASH radiation therapy (FLASH RT). 
     In embodiments, a dose rate-volume histogram (different from a dose-volume histogram) is generated for a target volume. The dose rate-volume histogram indicates dose rates and percentages of the target volume that receive the dose rates. The dose rate-volume histogram can be stored in computer system memory and used to generate a radiation treatment plan. Values of parameters that can have an effect on dose rate can be adjusted until the dose rate-volume histogram satisfies objectives associated with the radiation treatment plan. 
     In embodiments, the parameters include a number of irradiations of the target volume, a duration of each of the irradiations, and a dose deposited in each of the irradiations. In an embodiment, the parameters also include directions of beams to be directed into the target volume, and beam energies for each of the beams. In an embodiment, the parameters also include a period of time during which the irradiations are applied (e.g., the irradiations are intermittently applied over a period of time, such as an hour), and an interval of time between each of the periods of irradiations (e.g., each hour-long period is separated by a day). 
     In embodiments, an irradiation time-volume histogram (also different from a dose-volume histogram) is generated for the target volume. The irradiation time-volume histogram indicates irradiation times (durations) and percentages of the target volume that are irradiated for those amounts of time. The irradiation time-volume histogram can be stored in computer system memory and used to generate a radiation treatment plan. Values of parameters that can have an effect on irradiation time can be adjusted until the irradiation time-volume histogram satisfies objectives associated with the radiation treatment plan. 
     Both a dose rate-volume histogram and an irradiation time-volume histogram, or only a dose rate-volume histogram, or only an irradiation time-volume histogram, can be generated, evaluated, and used to generate a radiation treatment plan, with or without a dose-volume histogram. 
     In embodiments, a graphical user interface (GUI) that includes a representation of a target volume and sub-volumes of the target volume is rendered and displayed. In those embodiments, information in computer system memory that includes a dose rate received by each sub-volume is accessed. A value of an attribute is associated with each sub-volume, where the value corresponds to an amount of the dose rate received by that sub-volume. Each sub-volume is then rendered according to that value. 
     The rendering of the target volume can be a two-dimensional cross-section of the target volume or a virtual three-dimensional representation of the target volume. 
     In an embodiment, the GUI includes a dose rate-volume histogram. In an embodiment, the GUI includes isolines of dose rates relative to the target volume based on the dose rate-volume histogram. In an embodiment, the GUI includes an irradiation time-volume histogram for the target volume. 
     Embodiments according to the invention improve radiation treatment planning and the treatment itself by expanding FLASH RT to a wider variety of treatment platforms and target sites (e.g., tumors). Treatment plans generated as described herein are superior for sparing healthy tissue from radiation in comparison to conventional techniques for FLASH dose rates by optimizing the balance between the dose rate delivered to unhealthy tissue (e.g., a tumor) in a target volume and the dose rate delivered to surrounding healthy tissue. When used with FLASH dose rates, management of patient motion is simplified because the doses are applied in a short period of time (e.g., less than a second). Treatment planning, while still a complex task, is improved relative to conventional treatment planning. In addition to these benefits, a GUI facilitates treatment planning by allowing a planner to readily visualize key elements of a proposed treatment plan (e.g., the dose rate per sub-volume), to readily visualize the effects on those elements of changes to the proposed plan, and to readily visualize a comparison between different plans. 
     In summary, embodiments according to this disclosure pertain to generating and implementing a treatment plan that is the most effective (relative to other plans) and with the least (or most acceptable) side effects (e.g., a lower dose rate outside of the region being treated). Thus, embodiments according to the invention improve the field of radiation treatment planning specifically and the field of radiation therapy in general. Embodiments according to the invention allow more effective treatment plans to be generated quickly. Also, embodiments according to the invention help improve the functioning of computers because, for example, by reducing the complexity of generating treatment plans, fewer computational resources are needed and consumed, meaning also that computer resources are freed up to perform other tasks. 
     In addition to radiation therapy techniques such as IMRT and IMPT, embodiments according to the invention can be used in spatially fractionated radiation therapy including high-dose spatially fractionated grid radiation therapy and microbeam radiation therapy. 
     These and other objects and advantages of embodiments according to the present invention will be recognized by one skilled in the art after having read the following detailed description, which are illustrated in the various drawing figures. 
     This summary is provided to introduce a selection of concepts that are further described below in the detailed description that follows. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
       The accompanying drawings, which are incorporated in and form a part of this specification and in which like numerals depict like elements, illustrate embodiments of the present disclosure and, together with the detailed description, serve to explain the principles of the disclosure. 
         FIG. 1  is a block diagram of an example of a computer system upon which the embodiments described herein may be implemented. 
         FIG. 2  is a block diagram illustrating an example of an automated radiation therapy treatment planning system in embodiments according to the present invention. 
         FIG. 3  illustrates a knowledge-based planning system in embodiments according to the present invention. 
         FIG. 4  is a block diagram showing selected components of a radiation therapy system upon which embodiments according to the present invention can be implemented. 
         FIG. 5  illustrates a beam&#39;s eye view of a beam in embodiments according to the invention. 
         FIG. 6A  illustrates a perspective view of an example of a beam geometry in embodiments according to the invention. 
         FIG. 6B  illustrates a cross-sectional view of an example of a beam geometry in embodiments according to the invention. 
         FIG. 6C  illustrates a perspective view of an example of a beam geometry in embodiments according to the invention. 
         FIG. 6D  illustrates a cross-sectional view of an example of a beam geometry in embodiments according to the invention. 
         FIGS. 7A and 7B  illustrate examples of dose rate-volume histograms in an embodiment according to the present invention. 
         FIG. 7C  illustrates sub-volumes in a target volume in an embodiment according to the present invention. 
         FIG. 7D  illustrates an example of an irradiation time-volume histogram in an embodiment according to the present invention. 
         FIG. 8  is a flowchart of an example of computer-implemented operations for radiation treatment planning in embodiments according to the present invention. 
         FIG. 9  illustrates an example of dose rate isolines relative to a target volume in embodiments according to the present invention. 
         FIG. 10  is a flowchart of an example of computer-implemented operations for radiation treatment planning in embodiments according to the present invention. 
         FIG. 11  illustrates an example of a graphical user interface (GUI) that can be used to display information associated with a radiation treatment plan in embodiments according to the present invention. 
         FIGS. 12 and 13  are flowcharts of examples of computer-implemented operations for generating GUIs in embodiments according to the present invention. 
     
    
    
     DETAILED DESCRIPTION 
     Reference will now be made in detail to the various embodiments of the present disclosure, examples of which are illustrated in the accompanying drawings. While described in conjunction with these embodiments, it will be understood that they are not intended to limit the disclosure to these embodiments. On the contrary, the disclosure is intended to cover alternatives, modifications and equivalents, which may be included within the spirit and scope of the disclosure as defined by the appended claims. Furthermore, in the following detailed description of the present disclosure, numerous specific details are set forth in order to provide a thorough understanding of the present disclosure. However, it will be understood that the present disclosure may be practiced without these specific details. In other instances, well-known methods, procedures, components, and circuits have not been described in detail so as not to unnecessarily obscure aspects of the present disclosure. 
     Some portions of the detailed descriptions that follow are presented in terms of procedures, logic blocks, processing, and other symbolic representations of operations on data bits within a computer memory. These descriptions and representations are the means used by those skilled in the data processing arts to most effectively convey the substance of their work to others skilled in the art. In the present application, a procedure, logic block, process, or the like, is conceived to be a self-consistent sequence of steps or instructions leading to a desired result. The steps are those utilizing physical manipulations of physical quantities. Usually, although not necessarily, these quantities take the form of electrical or magnetic signals capable of being stored, transferred, combined, compared, and otherwise manipulated in a computer system. It has proven convenient at times, principally for reasons of common usage, to refer to these signals as transactions, bits, values, elements, symbols, characters, samples, pixels, or the like. 
     It should be borne in mind, however, that all of these and similar terms are to be associated with the appropriate physical quantities and are merely convenient labels applied to these quantities. Unless specifically stated otherwise as apparent from the following discussions, it is appreciated that throughout the present disclosure, discussions utilizing terms such as “determining,” “accessing,” “generating,” “representing,” “applying,” “indicating,” “storing,” “using,” “adjusting,” “including,” “computing,” “displaying,” “associating,” “rendering,” “determining,” or the like, refer to actions and processes (e.g., the flowcharts of  FIGS. 8, 10, 12, and 13 ) of a computer system or similar electronic computing device or processor (e.g., the computer system  100  of  FIG. 1 ). The computer system or similar electronic computing device manipulates and transforms data represented as physical (electronic) quantities within the computer system memories, registers or other such information storage, transmission or display devices. Terms such as “dose” or “dose rate” or “fluence” generally refer to a dose value or dose rate value or fluence value, respectively; the use of such terms will be clear from the context of the surrounding discussion. 
     Portions of the detailed description that follows are presented and discussed in terms of methods. Although steps and sequencing thereof are disclosed in figures herein (e.g.,  FIGS. 8, 10, 12, and 13 ) describing the operations of those methods, such steps and sequencing are examples only. Embodiments are well suited to performing various other steps or variations of the steps recited in the flowcharts of the figures herein, and in a sequence other than that depicted and described herein. 
     Embodiments described herein may be discussed in the general context of computer-executable instructions residing on some form of computer-readable storage medium, such as program modules, executed by one or more computers or other devices. By way of example, and not limitation, computer-readable storage media may comprise non-transitory computer storage media and communication media. Generally, program modules include routines, programs, objects, components, data structures, etc., that perform particular tasks or implement particular abstract data types. The functionality of the program modules may be combined or distributed as desired in various embodiments. 
     Computer storage media includes volatile and nonvolatile, removable and non-removable media implemented in any method or technology for storage of information such as computer-readable instructions, data structures, program modules or other data. Computer storage media includes, but is not limited to, random access memory (RAM), read only memory (ROM), electrically erasable programmable ROM (EEPROM), flash memory or other memory technology, compact disk ROM (CD-ROM), digital versatile disks (DVDs) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store the desired information and that can accessed to retrieve that information. 
     Communication media can embody computer-executable instructions, data structures, and program modules, and includes any information delivery media. By way of example, and not limitation, communication media includes wired media such as a wired network or direct-wired connection, and wireless media such as acoustic, radio frequency (RF), infrared and other wireless media. Combinations of any of the above can also be included within the scope of computer-readable media. 
     Radiation Treatment Planning Using Different Types of Histograms 
       FIG. 1  shows a block diagram of an example of a computer system  100  upon which the embodiments described herein may be implemented. In its most basic configuration, the system  100  includes at least one processing unit  102  and memory  104 . This most basic configuration is illustrated in  FIG. 1  by dashed line  106 . The system  100  may also have additional features and/or functionality. For example, the system  100  may also include additional storage (removable and/or non-removable) including, but not limited to, magnetic or optical disks or tape. Such additional storage is illustrated in  FIG. 1  by removable storage  108  and non-removable storage  120 . The system  100  may also contain communications connection(s)  122  that allow the device to communicate with other devices, e.g., in a networked environment using logical connections to one or more remote computers. 
     The system  100  also includes input device(s)  124  such as keyboard, mouse, pen, voice input device, touch input device, etc. Output device(s)  126  such as a display device, speakers, printer, etc., are also included. A display device may be, for example, a cathode ray tube display, a light-emitting diode display, or a liquid crystal display. 
     In the example of  FIG. 1 , the memory  104  includes computer-readable instructions, data structures, program modules, and the like associated with an “optimizer” model  150 . However, the optimizer model  150  may instead reside in any one of the computer storage media used by the system  100 , or may be distributed over some combination of the computer storage media, or may be distributed over some combination of networked computers. The functionality of the optimizer model  150  is described below. 
       FIG. 2  is a block diagram illustrating an example of an automated radiation therapy treatment planning system  200  in embodiments according to the present invention. The system  200  includes an input interface  210  to receive patient-specific information (data)  201 , a data processing component  220  that implements the optimizer model  150 , and an output interface  230 . The system  200  in whole or in part may be implemented as a software program, hardware logic, or a combination thereof on/using the computer system  100  ( FIG. 1 ). 
     In the example of  FIG. 2 , the patient-specific information is provided to and processed by the optimizer model  150 . The optimizer model  150  yields a prediction result. A treatment plan based on the prediction result can then be generated. 
       FIG. 3  illustrates a knowledge-based planning system  300  in embodiments according to the present invention. In the example of  FIG. 3 , the system  300  includes a knowledge base  302  and a treatment planning tool set  310 . The knowledge base  302  includes patient records  304  (e.g., radiation treatment plans), treatment types  306 , and statistical models  308 . The treatment planning tool set  310  in the example of  FIG. 3  includes a current patient record  312 , a treatment type  314 , a medical image processing module  316 , the optimizer model (module)  150 , a dose distribution module  320 , and a final radiation treatment plan  322 . 
     The treatment planning tool set  310  searches through the knowledge base  302  (through the patient records  304 ) for prior patient records that are similar to the current patient record  312 . The statistical models  308  can be used to compare the predicted results for the current patient record  312  to a statistical patient. Using the current patient record  312 , a selected treatment type  306 , and selected statistical models  308 , the tool set  310  generates a radiation treatment plan  322 . 
     More specifically, based on past clinical experience, when a patient presents with a particular diagnosis, stage, age, weight, sex, co-morbidities, etc., there can be a treatment type that is used most often. By selecting the treatment type that the planner has used in the past for similar patients, a first-step treatment type  314  can be chosen. Patient outcomes, which can include normal tissue complication probability as a function of dose rate and patient-specific treatment-type outcomes (e.g., local recurrent failure, and overall survival as a function of a dose rate-volume histogram ( FIG. 7A ) and/or an irradiation time-volume histogram ( FIG. 7D )), can be included in the treatment planning process. The medical image processing module  316  provides automatic contouring and automatic segmentation of two-dimensional cross-sectional slides (e.g., from any imaging modality such as, but not limited to, computed tomography (CT), positron emission tomography-CT, magnetic resonance imaging, and ultrasound) to form a three-dimensional (3D) image using the medical images in the current patient record  312 . Dose distribution maps and dose rate distribution maps are calculated by the dose and dose rate distribution module  320 , which may utilize the optimizer model  150 . 
     In embodiments according to the present invention, the optimizer model  150  uses a dose prediction model to provide, for example, a 3D dose distribution, fluences, and dose rates, and associated dose-volume histograms and dose rate-volume histograms. 
     The discussion to follow refers to beams, target volumes, doses, dose rates, and other elements or values. The discussion below is in the context of modeled elements and calculated values in the treatment planning tool set  310  and the optimizer model  150  ( FIG. 3 ), unless otherwise noted or made clear in the discussion. 
       FIG. 4  is a block diagram showing selected components of a radiation therapy system  400  upon which embodiments according to the present invention can be implemented. In the example of  FIG. 4 , the system  400  includes a beam system  404  and a nozzle  406 . 
     The beam system  404  generates and transports a beam  401 . The beam  401  can be a proton beam, electron beam, photon beam, ion beam, or atom nuclei beam (e.g., carbon, helium, and lithium). In embodiments, depending on the type of beam, the beam system  404  includes components that direct (e.g., bend, steer, or guide) the beam system in a direction toward and into a nozzle  406 . In embodiments, the radiation therapy system may include one or more multileaf collimators (MLCs); each MLC leaf can be independently moved back-and-forth by the control system  410  to dynamically shape an aperture through which the beam can pass, to block or not block portions of the beam and thereby control beam shape and exposure time. The beam system  404  may also include components that are used to adjust (e.g., reduce) the beam energy entering the nozzle  406 . 
     The nozzle  406  is used to aim the beam toward various locations (a target volume) within an object (e.g., a patient) supported on the patient support device  408  (e.g., a chair or table) in a treatment room. A target volume may be an organ, a portion of an organ (e.g., a volume or region within the organ), a tumor, diseased tissue, or a patient outline. A target volume may include both unhealthy tissue (e.g., a tumor) and healthy tissue. 
     The nozzle  406  may be mounted on or a part of a gantry that can be moved relative to the patient support device  408 , which may also be moveable. In embodiments, the beam system  404  is also mounted on or is a part of the gantry. In another embodiment, the beam system is separate from (but in communication with) the gantry. 
     The control system  410  of  FIG. 4  receives and implements a prescribed radiation treatment plan. In embodiments, the control system  410  includes a computer system having a processor, memory, an input device (e.g., a keyboard), and perhaps a display in well-known fashion. The control system  410  can receive data regarding operation of the system  400 . The control system  410  can control parameters of the beam system  404 , nozzle  406 , and patient support device  408 , including parameters such as the energy, intensity, direction, size, and/or shape of the beam, according to data it receives and according to the prescribed radiation treatment plan. 
     As noted above, the beam entering the nozzle  406  has a specified energy. Thus, in embodiments according to the present disclosure, the nozzle  406  includes one or more components that affect (e.g., decrease, modulate) the energy of the beam. The term “beam energy adjuster” is used herein as a general term for a component or components that affect the energy of the beam, in order to control the range of the beam (e.g., the extent that the beam penetrates into a target), to control the dose delivered by the beam, and/or to control the depth dose curve of the beam, depending on the type of beam. For example, for a proton beam or an ion beam that has a Bragg peak, the beam energy adjuster can control the location of the Bragg peak in the target volume. In various embodiments, the beam energy adjuster  407  includes a range modulator, a range shifter, or both a range modulator and a range shifter. 
     In radiation therapy techniques in which the intensity of the particle beam is either constant or modulated across the field of delivery, such as in intensity modulated radiation therapy (IMRT) and intensity modulated particle therapy (IMPT), beam intensity is varied across each treatment region (target volume) in a patient. Depending on the treatment modality, the degrees of freedom available for intensity modulation include beam shaping (collimation), beam weighting (spot scanning), and angle of incidence (which may be referred to as beam geometry). These degrees of freedom lead to an effectively infinite number of potential treatment plans, and therefore consistently and efficiently generating and evaluating high-quality treatment plans is beyond the capability of a human and relies on the use of a computer system, particularly considering the time constraints associated with the use of radiation therapy to treat ailments like cancer, as well as the large number of patients that are undergoing or need to undergo radiation therapy during any given time period. 
       FIG. 5  illustrates a beam&#39;s eye view (BEV) of a beam  502  in embodiments according to the invention. That is,  FIG. 5  illustrates a cross-section of a beam. The beam  502  is illustrated as being rectangular in shape having a height H and width W. However, the invention is not so limited, and the beam  502  can have virtually any regular or irregular cross-sectional (e.g., BEV) shape. For example, the shape of the beam  502  can be defined using an MLC that blocks a portion or portions of the beam. Different beams can have different shapes. 
     In the  FIG. 5  embodiment, the beam  502  includes a number of beam segments or beam lets (that also may be referred to as spots) exemplified by beam segments  504 ,  506 , and  508 . A maximum energy (e.g., 80 MeV) is specified for the beam  502 , and an energy level is defined for each of the beam segments as a percentage or fraction of the maximum energy. In essence, each of the beam segments is weighted in terms of its energy level; some beam segments are weighted to have a higher energy level than other beam segments. By weighting the energy per beam segment, in effect the intensity of each beam segment is also weighted. The defined energy level or intensity can be realized for each beam segment using the beam energy adjuster  407  of  FIG. 4 . 
     Each beam segment can deliver a relatively high dose rate (a relatively high dose in a relatively short period of time). For example, each beam segment can deliver at least four grays (Gy) in less than one second, and may deliver as much as 20 Gy to 50 Gy or 100 Gy or more in less than one second. 
     In operation, in embodiments, the beam segments are delivered sequentially. For example, the beam segment  504  is delivered to the target volume (turned on) and then turned off, then the beam segment  506  is turned on then off, then the beam segment  508  is turned on then off, and so on. Each beam segment may be turned on for only a fraction of a second (e.g., on the order of milliseconds). 
       FIG. 6A  illustrates a perspective view of an example of a beam geometry in embodiments according to the invention. In the example of  FIG. 6A , the beams (exemplified by beam  602 ) are in the same plane. The beams can be proton beams, electron beams, photon beams, ion beams, or atom nuclei beams. Each beam can deliver a relatively high dose rate (a relatively high dose in a relatively short period of time). For example, in embodiments, each beam can deliver doses sufficient for FLASH RT (e.g., at least 4 Gy in less than one second, and as much as 20 Gy to 50 Gy or 100 Gy or more in less than one second). Each beam can include one or more beam segments or beamlets. In this example, the beams&#39; paths overlap only within the target volume  604 , and do not overlap outside the target volume in the surrounding tissue  606 . 
     In the example of  FIG. 6A , the beam  602  (for example) is illustrated as passing completely through the target volume  604 . For beams that have a Bragg peak (e.g., proton beams and ion beams), the ranges of the beams can be controlled so that the beam does not pass completely through the target volume. 
     Although multiple beams are shown in  FIG. 6A , this does not mean that all beams are necessarily delivered at the same time or in overlapping time periods, although they can be. The number of beams delivered at any one time depends on the number of gantries or nozzles in the radiation treatment system (e.g., the radiation treatment system  400  of  FIG. 4 ) and on the treatment plan. 
       FIG. 6B  illustrates a cross-sectional view of an example of a beam geometry in embodiments according to the invention. In this example, the beams (exemplified by beams  605  and  607 ) overlap only within the target volume and are in the same plane. The figure depicts the beams in overlapping fashion to demonstrate that each portion of the target volume  604  receives a dose of radiation. The beams can be proton beams, electron beams, photon beams, ion beams, or atom nuclei beams. In the example of  FIG. 6B , the beams are illustrated as not extending beyond the distal edge of the target volume  604  (as would be the case for proton or ion beams, for example); however, the invention is not so limited. Each beam can deliver a relatively high dose in a relatively short period of time. For example, each beam can deliver dose rates sufficient for FLASH RT. 
       FIG. 6C  illustrates a perspective view of an example of a beam geometry in embodiments according to the invention. In the example of  FIG. 6C , the beams (exemplified by beam  612 ) are in different planes. Each beam can include one or more beam segments or beamlets. In this example, the beams&#39; paths overlap only within the target volume  604 , and do not overlap outside the target volume in the surrounding tissue  606 . Although multiple beams are shown in the figure, all beams are not necessarily delivered at the same time or in overlapping time periods as mentioned above. The beams can be proton beams, electron beams, photon beams, ion beams, or atom nuclei beams. Each beam can deliver a relatively high dose in a relatively short period of time. For example, each beam can deliver dose rates sufficient for FLASH RT. 
       FIG. 6D  illustrates a cross-sectional view of an example of a beam geometry in embodiments according to the invention. In this example, the beams (exemplified by beams  621 ,  622 , and  623 ) overlap only within the target volume and are in the same plane. While three beams are illustrated, the invention is not so limited. As described herein, each beam can include one or more beam segments or beamlets. In this example, the beams&#39; paths overlap only within the target volume  604 , and do not overlap outside the target in the surrounding tissue  606 . Although multiple beams are shown in the figure, all beams are not necessarily delivered at the same time or in overlapping time periods as mentioned above. The beams can be proton beams, electron beams, photon beams, ion beams, or atom nuclei beams. Each beam can deliver a relatively high dose in a relatively short period of time. For example, each beam can deliver dose rates sufficient for FLASH RT. 
     In the example of  FIG. 6D , the beams  621 ,  622 , and  623  intersect at the sub-volume  630 , other sub-volumes in the target volume  604  receive doses from two of the beams, other sub-volumes in the target volume receive doses from only one of the beams, and yet other sub-volumes do not receive a dose. The directions and/or numbers of beam can be varied over a number of treatment sessions (that is, fractionated in time) so that a uniform dose is delivered across the target. 
     In embodiments according to the present invention, a dose rate-volume histogram (which is different from, but may be used with, a dose-volume histogram) is generated for a target volume. The dose rate-volume histogram can be generated based on a proposed radiation treatment plan. The dose rate-volume histogram can be stored in computer system memory and used to generate a final radiation treatment plan that will be used to treat a patient. Values of parameters that can have an effect on dose rate can be adjusted until the dose rate-volume histogram satisfies objectives of or associated with treatment of the patient. 
       FIG. 7A  illustrates an example of a dose rate-volume histogram  700  in an embodiment according to the present invention. The dose rate-volume histogram plots a cumulative dose rate-to-target volume frequency distribution that summarizes the simulated dose rate distribution within a target volume of interest (e.g., the target volume  604  of  FIGS. 6A-6D ) that would result from a proposed radiation treatment plan. The simulated dose rate distribution can be determined using the optimizer model  150  of  FIG. 1 . The dose rate-volume histogram indicates dose rates and percentages of the target volume that receive the dose rates. For example, as shown in  FIG. 7A , 100 percent of the target volume receives a dose rate of X, 50 percent of the target volume receives a dose rate of Y, and so on. The dose rate-volume histogram  700  can be displayed as or as part of a graphical user interface (GUI) (see the discussion of  FIGS. 11, 12, and 13 , below). 
     The target volume  604  may include different organs, for example, or it may include both healthy tissue and unhealthy tissue (e.g., a tumor). Accordingly, with reference to  FIGS. 7B and 7C , the dose rate-volume histogram  710  includes multiple curves  712  and  714 , showing the simulated dose rate distribution for a first sub-volume  722  of the target volume (e.g., for one organ, or for the healthy tissue) and the simulated dose rate distribution for a second sub-volume  724  (e.g., for a second organ, or for the unhealthy tissue), respectively. More than two simulated dose rate distributions can be included in a dose rate-volume histogram. The dose rate-volume histogram  710  can be displayed as or as part of a GUI (see the discussion of  FIGS. 11, 12, and 13 , below). 
     The target volume  604  may be divided (virtually) into a number of voxels. A sub-volume can include a single voxel or multiple voxels. 
     In embodiments according to the present invention, an irradiation time-volume histogram (which is different from, but may be used with, a dose-volume histogram and/or a dose rate-volume histogram) is generated for the target volume. The irradiation time-volume histogram can be stored in computer system memory and used to generate a radiation treatment plan, in combination with or in lieu of a dose-volume histogram and/or a dose rate-volume histogram. 
       FIG. 7D  illustrates an example of an irradiation time-volume histogram  750  in an embodiment according to the present invention. The irradiation time-volume histogram plots a cumulative irradiation time-to-target volume frequency distribution that summarizes the simulated irradiation time distribution within a target volume of interest (e.g., the target volume  604  of  FIGS. 6A-6D ) that would result from a proposed radiation treatment plan. The simulated irradiation time distribution can be determined using the optimizer model  150  of  FIG. 1 . The irradiation time-volume histogram indicates irradiation times (lengths of times) and percentages of the target volume that are irradiated for those lengths of time. The dose rate-volume histogram  750  can be displayed as or as part of a GUI (see the discussion of  FIGS. 11, 12, and 13 , below). 
       FIG. 8  is a flowchart  800  of an example of computer-implemented operations for radiation treatment planning including generating a dose rate-volume histogram or an irradiation time-volume histogram in embodiments according to the present invention. The flowchart  800  can be implemented as computer-executable instructions (e.g., the optimizer model  150  of  FIG. 1 ) residing on some form of computer-readable storage medium (e.g., in memory of the computer system  100  of  FIG. 1 ). 
     In block  802  of  FIG. 8 , a proposed radiation treatment plan is defined (e.g., using the optimizer model  150  of  FIGS. 1 and 2 ), stored in a computer system memory, and accessed. The proposed radiation treatment plan includes values of parameters that can affect dose rate, as well as other parameters. The parameters that can affect dose rate include, but are not limited to, a number of irradiations of the target volume, a duration of each of the irradiations (irradiation times), and a dose deposited in each of the irradiations. The parameters may also include directions of beams to be directed into the target volume, and beam energies for each of the beams. The parameters may also include a period of time during which the irradiations are applied (e.g., a number of irradiations are applied over a period of time such as an hour, with each irradiation in the period of time separated from the next by another period of time) and an interval of time between each period of irradiations (e.g., each hour-long period is separated from the next by a day). If the target volume is divided into sub-volumes or voxels, then the values of the parameters can be on a per-sub-volume or per-voxel basis (e.g., a value per sub-volume or voxel). 
     Appropriate dose threshold curve(s) (e.g., normal tissue sparing dose versus dose rate or irradiation time) can be utilized in the optimization model  150  ( FIG. 3 ) to establish dose limits for radiation treatment planning. For example, the appropriate (e.g., tissue-dependent) dose threshold curve can be used to determine beam directions (gantry angles) and beam segment weights ( FIG. 7A ). That is, parameters that affect dose can be adjusted during radiation treatment planning so that the limits in the dose threshold curve are satisfied. The dose threshold curves can be tissue-dependent. For instance, the dose threshold curve for the lungs may be different from that for the brain. 
     Dose limits can include, but are not limited to: a maximum limit on irradiation time for each sub-volume (voxel) in the target (e.g., for each voxel of target tissue, treatment time less than x1 seconds); a maximum limit on irradiation time for each sub-volume (voxel) outside the target (e.g., for each voxel of normal tissue, treatment time less than x2 seconds; x1 and x2 may be the same or different); a minimum limit on dose rate for each sub-volume (voxel) in the target (e.g., for each voxel of target tissue, dose rate greater than y1 Gy/sec); and a minimum limit on dose rate for each sub-volume (voxel) outside the target (e.g., f or each voxel of normal tissue, dose rate greater than y2 Gy/sec; y1 and y2 may be the same or different). In general, the limits are intended to minimize the amount of time that normal tissue is irradiated. 
     In block  804 , in an embodiment, a dose rate-volume histogram is generated based on the values of the parameters in the proposed radiation treatment plan. A dose rate can be determined per sub-volume or voxel. The dose rate is the dose deposited in each irradiation divided by the sum of the durations of the irradiation, times the number of irradiations (e.g., number of fractions). The dose rate can be determined and recorded using a fine time index (e.g., time increments on the order of a millisecond); that is, for example, the dose to each sub-volume or voxel can be recorded for time increments on the order of per-millisecond per beam and per fraction. The dose rate is cumulative. The cumulative dose rate for some portions (e.g., sub-volumes or voxels) of the target volume may be higher than other portions, depending on the beam directions and energies, for example. The dose rate per sub-volume or voxel can be calculated to include ray tracing (and Monte Carlo-like simulations), where each beam particle is tracked to determine the primary, secondary, etc., scatters for each particle to get a realistic voxel-based or sub-volume-based dose rate over the course of each irradiation. 
     In an embodiment, an irradiation time-volume histogram is generated. An irradiation time-volume histogram can be generated essentially in the same manner as that just described for generating a dose rate-volume histogram. Both a dose rate-volume histogram and an irradiation time-volume histogram, or only a dose rate-volume histogram, or only an irradiation time-volume histogram, can be generated, in addition to or in lieu of a dose-volume histogram. 
     In block  806 , the dose rate-volume histogram and/or the irradiation time-volume histogram can be evaluated by determining whether or not objectives (e.g., clinical goals) that are specified for treatment of a patient are satisfied by the proposed radiation treatment plan. The clinical goals or objectives may be expressed in terms of a set of quality metrics, such as target homogeneity, critical organ sparing, and the like, with respective target values for the metrics. Another way to evaluate the dose rate-volume histogram and/or the irradiation time-volume histogram is a knowledge-based approach that incorporates and reflects present best practices gathered from multiple previous, similar treatments of other patients. Yet another way to assist the planner is to use a multi-criteria optimization (MCO) approach for treatment planning. Pareto surface navigation is an MCO technique that facilitates exploration of the tradeoffs between clinical goals. For a given set of clinical goals, a treatment plan is considered to be Pareto optimal if it satisfies the goals and none of the metrics can be improved without worsening at least one of the other metrics. 
     As mentioned above, for FLASH RT, dose rates of at least 4 Gy in less than one second, and as much as 20 Gy to 50 Gy or 100 Gy or more in less than one second, may be used. Thus, another way to evaluate a dose rate-volume histogram is to define a dose rate threshold value (e.g., a minimum dose rate) based on the FLASH RT dose rates, and to also specify a target volume percentage threshold value for dose rate. A dose rate-volume histogram can be evaluated by determining whether the percentage of the target volume that receives a dose rate above the dose rate threshold value satisfies the percentage threshold value. For example, a dose-rate volume histogram may be considered to be satisfactory if 80 percent of the target volume (specifically, the portion of the target volume that includes the unhealthy tissue) receives a dose rate of at least 50 Gy per second. 
     Another way to evaluate an irradiation time-volume histogram is to define an irradiation time threshold value or values (e.g., a maximum limit on irradiation time for each sub-volume or voxel inside the target volume and/or a maximum limit on irradiation time for each sub-volume or voxel outside the target volume), and to also specify a target volume percentage threshold value or values for irradiation time inside and/or outside the target volume. An irradiation time-volume histogram can be evaluated by determining whether the percentage of the tissue inside the target volume that is irradiated for less than the corresponding irradiation time threshold value satisfies the corresponding percentage threshold value, and/or by similarly determining whether the percentage of the tissue outside the target volume that is irradiated for less than the corresponding irradiation time threshold value satisfies the corresponding percentage threshold value. 
     In block  808 , in an embodiment, the information in the dose rate-volume histogram is used to determine and represent isolines of dose rate relative to a target volume  904  (e.g., a tumor) that includes or is surrounded by other (e.g., healthy) tissue, as shown in the example of  FIG. 9 . In that example, the 100 percent, 90 percent, and five percent dose rate isolines are shown.  FIG. 9  is illustrated in two dimensions, showing either a top down view of the target volume or one cross-sectional slice of the target volume, and can be displayed as or as part of a GUI (see the discussion of  FIGS. 11, 12, and 13 , below). The target volume and isolines can also be represented in three dimensions and displayed as or as part of the GUI. 
     Isolines of irradiation time relative to a target volume can be similarly determined and represented. 
     In block  810  of  FIG. 8 , some or all of the parameter values for the proposed radiation treatment plan can be iteratively adjusted to generate different dose rate-volume histograms and/or the irradiation time-volume histograms, to determine a final set of parameter values that produce a histogram (or histograms) that results in a prescribed (final) radiation treatment plan that best satisfies the objectives (clinical goals) for treatment of the patient or that satisfies the threshold values described above. 
     In block  812 , the final set of parameter values is then included in the prescribed radiation treatment plan used to treat the patient. 
     Generally speaking, embodiments according to the invention optimize a radiation treatment plan based on dose rate and/or irradiation time. This is not to say that treatment plan optimization is based solely on dose rate and/or irradiation time. For example, a dose-volume histogram can be used in conjunction with a dose rate-volume histogram and/or irradiation time-volume histogram when developing a radiation treatment plan. 
       FIG. 10  is a flowchart  1000  of an example of computer-implemented operations for generating a dose rate-volume histogram in embodiments according to the present invention. The flowchart  1000  can be implemented as computer-executable instructions (e.g., the optimizer model  150  of  FIG. 1 ) residing on some form of computer-readable storage medium (e.g., memory of the computer system  100  of  FIG. 1 ). 
     In block  1002  of  FIG. 10 , information in computer system memory is accessed. The information includes a dose rate received by a target volume per sub-volume or voxel, determined using a dose prediction model implemented with the optimizer model  150  ( FIG. 1 ). The information also can include irradiation time (duration) per sub-volume or voxel. 
     In block  1004  of  FIG. 10 , a dose rate-volume histogram and/or an irradiation time-volume histogram are/is generated for the target volume, as previously described herein (e.g., with reference to  FIG. 8 ). 
     In block  1006  of  FIG. 10 , histograms that are generated are stored in computer system memory. 
     In block  1008 , the dose rate-volume histogram and/or the irradiation time-volume histogram are/is used to generate a radiation treatment plan for treating the target volume. 
     Graphical User Interface for Radiation Treatment Planning 
       FIG. 11  illustrates an example of a GUI  1100  that can be used to display information associated with a radiation treatment plan in embodiments according to the present invention. The GUI  1100  can be implemented using computer-executable instructions (e.g., the optimizer model  150  of  FIG. 1 ) residing on some form of computer-readable storage medium (e.g., memory of the computer system  100  of  FIG. 1 ), and can be displayed on the output device  126  of the computer system. 
     In the example of  FIG. 11 , the GUI includes four windows  1104 ,  1105 ,  1106 , and  1107 , but the invention is not so limited. In this example, the window  1104  includes a menu or listing of different proposed radiation treatment plans (e.g., plan 1 and plan 2). If, for example, plan 2 is selected, then information associated with that plan is displayed in the windows  1106  and  1107 . 
     In the  FIG. 11  example, the window  1105  includes a menu or listing of types of information that can be presented in the GUI  1100 . The types of information may include, but are not limited to, dose, dose rate, and irradiation time. 
     In this example, the window  1106  displays a representation of a target volume  1108 . The representation can be two-dimensional, representing a cross-sectional slice of the target volume  1108 , or it can be a virtual three-dimensional representation of the target volume. 
     In the  FIG. 11  example, the target volume  1108  includes four sub-volumes  1110 ,  1111 ,  1112 , and  1113  ( 1110 - 1113 ). In an embodiment, the sub-volumes  1110 - 1113  may represent different regions (e.g., healthy tissue and non-healthy tissue or tumor) within a patient, different organs within a patient, or different regions within tissue or an organ, for example. The sub-volumes  1110 - 1113  can be any shape. In an embodiment, a sub-volume may be a single voxel or a set of voxels within a region or organ. 
     In embodiments, a value of an attribute is associated with each of the sub-volumes  1110 - 1113 . The attribute can be, but is not limited to, color, pattern, gray-scale, alphanumeric text, and brightness, or a combination of one or more of these. The value can be, for example, a particular color, a particular pattern, a level of gray-scale, a character or combination of characters, or a level of brightness. The value of the attribute for a sub-volume corresponds to, for example, the amount of the dose rate, the amount of dose, or the irradiation time received by or associated with the sub-volume according to the selected radiation plan (e.g., plan 2). For example, one color value (e.g., blue) may correspond to a dose rate between zero and a first threshold, a second color value (e.g., green) may correspond to a dose rate between the first threshold and a second threshold, and so on. 
     As discussed above, the dose rate received by a sub-volume can be determined using parameters including the number of irradiations of the sub-volume, a duration of each of the irradiations, a dose deposited in each of the irradiations, the dose rate accumulated over the number of irradiations of the sub-volume, and the dose rate accumulated over the number of irradiations of the sub-volume divided by the number of irradiations of the sub-volume. This type of information can also be presented in the GUI  1100 . For example, the value of the attribute for a sub-volume can correspond to one of the parameters. Thus, for example, a first color value may correspond to a first number of irradiations, a second color value may correspond to a second number of irradiations, and so on. 
     The GUI  1100  can also be used to present information such as the directions of beams to be directed into each sub-volume, and beam energies for each of the beams. 
     In the example of  FIG. 11 , the window  1107  displays a selected histogram or a selected set of isolines. For example, if dose rate is of interest, then the window  1107  can include a dose rate-volume histogram (e.g., the histograms  700  and  710  of  FIGS. 7A and 7B ). Alternatively, an irradiation time-volume histogram (e.g., the histogram  750  of  FIG. 7D ), dose rate isolines (e.g.,  FIG. 9 ), or irradiation time isolines can be displayed. 
     In embodiments, drop-down menus or other types of GUI elements (not shown) can be used to select and establish settings (e.g., attributes, thresholds, etc.) for the GUI  1100  and the type(s) of information to be displayed at any one time. 
     The GUI  1100  is not necessarily a static display. For example, the information presented in the GUI  1100  can be programmed to change over time to illustrate accumulated dose or dose rate versus time. Also, for example, the GUI  1100  can be programmed to present different cross-sectional slices of the target volume  1108  in sequence to provide a depth dimension to the two-dimensional representation, or to manipulate (e.g., rotate) the virtual three-dimensional representation so that it can be viewed from different perspectives. 
       FIGS. 12 and 13  are flowcharts  1200  and  1300 , respectively, of examples of computer-implemented operations for generating a GUI (e.g., the GUI  1100  of  FIG. 11 ) in embodiments according to the present invention. The flowcharts  1200  and  1300  can be implemented as computer-executable instructions (e.g., the optimizer model  150  of  FIG. 1 ) residing on some form of computer-readable storage medium (e.g., in memory of the computer system  100  of  FIG. 1 ). 
     In block  1202  of  FIG. 12 , information in the computer system memory is accessed. In an embodiment, the information includes a dose rate received by each sub-volume of a target volume. The dose rate received by each sub-volume is determined as previously described herein. In an embodiment, the information includes an irradiation time per sub-volume. 
     In block  1204 , a value of an attribute is associated with each sub-volume. In an embodiment, the value corresponds to an amount of the dose rate received by a respective sub-volume. The attribute can be, for example, color, pattern, gray-scale, alphanumeric text, brightness, or a combination of these attributes. The value can be, for example, a particular color, a particular pattern, a level of gray-scale, a character or combination of characters, or a level of brightness. 
     In block  1206 , each sub-volume is rendered and displayed according to the value that corresponds to the sub-volume as described above. 
     In block  1302  of  FIG. 13 , in an embodiment, information that includes a dose rate received by a target volume is accessed from the memory of the computer system. 
     In block  1304 , a histogram is generated for the target volume. The histogram may be a dose rate-volume histogram and/or an irradiation time-volume histogram as previously described herein. 
     In block  1306 , the histogram is displayed in a GUI as described above. 
     While the operations in  FIGS. 8, 10, 12, and 13  are presented as occurring in series and in a certain order, the present invention is not so limited. The operations may be performed in a different order and/or in parallel, and they may also be performed in an iterative manner. As noted above, because of the different parameters that need to be considered, the range of values for those parameters, the interrelationship of those parameters, the need for treatment plans to be effective yet minimize risk to the patient, and the need to generate high-quality treatment plans quickly, the use of the optimizer model  150  executing consistently on the computer system  100  ( FIG. 1 ) for radiation treatment planning as disclosed herein is important. 
     In summary, embodiments according to the invention improve radiation treatment planning and the treatment itself by expanding FLASH RT to a wider variety of treatment platforms and target sites. Treatment plans generated as described herein are superior for sparing normal tissue from radiation in comparison to conventional techniques even for non-FLASH dose rates by reducing, if not minimizing, the magnitude (and the integral in some cases) of the dose to normal tissue (outside the target) by design. When used with FLASH dose rates, management of patient motion is simplified because the doses are applied in a short period of time (e.g., less than a second). Treatment planning, while still a complex task of finding a balance between competing and related parameters, is simplified relative to conventional planning. The techniques described herein may be useful for stereotactic radiosurgery as well as stereotactic body radiotherapy with single or multiple metastases. 
     In addition to those benefits, a GUI facilitates treatment planning by allowing a planner to readily visualize key elements of a proposed treatment plan (e.g., the dose rate per sub-volume), to readily visualize the effects on those elements of changes to the proposed plan, and to readily visualize a comparison between different plans. 
     In addition to radiation therapy techniques in which the intensity of the particle beam is either constant or modulated across the field of delivery, such a IMRT and IMPT, embodiments according to the invention can be used in spatially fractionated radiation therapy including high-dose spatially fractionated grid radiation therapy and microbeam radiation therapy. 
     Although the subject matter has been described in language specific to structural features and/or methodological acts, it is to be understood that the subject matter defined in the appended claims is not necessarily limited to the specific features or acts described above. Rather, the specific features and acts described above are disclosed as example forms of implementing the claims.