# Patent

## Title
Real-time, on-line and offline treatment dose tracking and feedback process for volumetric image guided adaptive radiotherapy

## Abstract

A method of treating an object with radiation that includes generating volumetric image data of an area of interest of an object and emitting a therapeutic radiation beam towards the area of interest of the object in accordance with a reference plan. The method further includes evaluating the volumetric image data and at least one parameter of the therapeutic radiation beam to provide a real-time, on-line or off-line evaluation and on-line or off-line modification of the reference plan.

## Background
Applicants claim, under 35 U.S.C. §119(e), the benefit of priority of 1) the filing date of May 25, 2006, of U.S. Provisional Patent Application Ser. No. 60/808,343, filed on the aforementioned date and 2) the filing date of Jan. 18, 2007, of U.S. Provisional Patent Application Ser. No. 60/881,092, filed on the aforementioned date, the entire contents of each of which are incorporated herein by reference.


BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to image guided radiotherapy, and in particular, the invention relates to volumetric image guided adaptive radiotherapy.
2. Discussion of the Related Art
Presently, online treatment dose construction and estimation include portal ex-dose reconstruction to reconstruct treatment dose on a conventional linear accelerator. Specifically, the exit dose is measured using an MV portal imager to estimate treatment dose in the patient. However, this method has not been employed for patient treatment dose construction, since the dose reconstruction method lacks patient anatomic information during the treatment, and the scattered exit dose is difficult to calibrate properly.
In the past, a single pre-treatment computed tomography scan has been used to design a patient treatment plan for radiotherapy. Use of such a single pre-treatment scan can lead to a large planning target margin and uncertainty in normal tissue dose due to patient variations, such as organ movement, shrinkage and deformation, that can occur from the start of a treatment session to the end of the treatment session.
BRIEF SUMMARY OF THE INVENTION
One aspect of the present invention regards a system for radiotherapy that includes an imaging system that generates volumetric image data of an area of interest of an object and a radiation source that emits a therapeutic radiation beam towards the area of interest of the object in accordance with a reference plan. The system for radiotherapy further includes a processing system that receives and evaluates the volumetric image data and at least one parameter of the therapeutic radiation beam to provide a real-time, on-line or off-line evaluation and on-line or off-line modification of the reference plan.
A second aspect of the present invention regards a method of treating an object with radiation that includes generating volumetric image data of an area of interest of an object and emitting a therapeutic radiation beam towards the area of interest of the object in accordance with a reference plan. The method further includes evaluating the volumetric image data and at least one parameter of the therapeutic radiation beam to provide a real-time, on-line or off-line evaluation and on-line or off-line modification of the reference plan.
A third aspect of the present invention regards a planning and control system for radiotherapy that includes a system that captures and evaluates parameters of a volumetric image of an area of interest of an object and a therapeutic radiation beam directed towards the area of interest of the object in accordance with a reference plan so as to provide a real-time, on-line or off-line evaluation and on-line or off-line modification of the reference plan. The system further includes a monitor that displays information based on one or more of the captured parameters of the volumetric image and the therapeutic radiation beam.
A fourth aspect of the present invention regards a method of planning and controlling a radiation therapy session, the method including capturing and evaluating parameters of a volumetric image of an area of interest of an object and a therapeutic radiation beam directed towards the area of interest of the object in accordance with a reference plan so as to provide a real-time, on-line or off-line evaluation and on-line or off-line modification of the reference plan. The method further including displaying information based on one or more of the captured parameters of the volumetric image and the therapeutic radiation beam.
A fifth aspect of the present invention regards a system for radiotherapy that includes a radiation source that is programmed to emit a therapeutic radiation beam towards an area of interest of an object in accordance with a reference plan during a real-time time period when the object is on-line. The system further includes an imaging system that generates on-line volumetric image data of the area of interest of the object during the real-time time period when the object is on-line, and off-line volumetric image data of the area of interest of the object during a non-real time off-line time period. The system further includes a processing system that receives and processes one or more of the on-line and off-line volumetric image data to alter the reference plan.
A sixth aspect of the present invention regards a method of treating an object with radiation that includes planning on emitting a therapeutic radiation beam towards an area of interest of an object in accordance with a reference plan during a real-time time period when the object is on-line. The method includes generating on-line volumetric image data of the area of interest of the object during the real-time time period when the object is on-line, and off-line volumetric image data of the area of interest of the object during a non-real time off-line time period. The method further includes altering the reference plan based on one or more of the on-line and off-line volumetric image data.
A seventh aspect of the present invention regards a method of forming a portal image, the method including forming a two-dimensional image of an object of interest and superimposing an image of a collimator element on the two-dimensional image. The image represents the position of the collimator element when a radiation therapy beam is to be directed towards the object of interest.
One or more aspects of the present invention provide the advantage of providing online and offline treatment dose reconstruction, and a treatment decision tool that provides real-time, on-line and off-line treatment evaluation and on-line or off-line modification of a reference plan.
Additional objects, advantages and features of the present invention will become apparent from the following description and the appended claims when taken in conjunction with the accompanying drawings.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 schematically shows an embodiment of a radiation therapy system that employs a dose tracking and feedback process and a possible workflow for auto-construction, estimation and evaluation of cumulative treatment dose, and patient anatomy and dose feedback for adaptive planning optimization in accordance with the present invention;
FIGS. 2a-c show various embodiments of onboard imaging systems and/or radiation therapy systems to be used with the radiation therapy system of FIG. 1 for performing dose tracking and feedback;
FIGS. 3a-b provides a visual representation of a possible process to form a kV portal image;
FIGS. 4a-b show a reference image and a kV portal image with a beam eye view of organs of interest:
FIG. 5 shows a possible image on a quality assurance workstation that shows kV portal images with a position/volume tracking chart for a daily kV portal image;
FIG. 6 is a flow diagram of a sequence of steps for forming either of the kV portal images of FIGS. 3-5; and
FIG. 7 shows an embodiment of a radiotherapy process to be used with the systems of FIGS. 1-2.



PREFERRED EMBODIMENTS OF THE INVENTION
In accordance with the present invention, a volumetric image guided adaptive radiotherapy system, such as cone-beam computerized tomography (CBCT) image guided adaptive radiotherapy (IGART) system 100, and a corresponding workflow sequence for auto-construction and evaluation of daily cumulative treatment dose are shown in FIGS. 1-7, wherein like elements are denoted by like numerals. As shown in FIG. 1, the CBCT IGART system 100 includes a number of major systems: 1) a three-dimensional volumetric imaging system, such as an x-ray cone-beam computed tomography system 200, 2) a megavoltage imaging system 300 that includes a radiation therapy source, such as a linear accelerator 302, and an imager 304, 3) a kV portal imager processor/software system 400 and 4) a treatment dose tracking and feedback system 600, each of which are discussed below.
Three-Dimensional Volumetric Imaging System
Mechanical operation of a cone-beam computed tomography system 200 is similar to that of a conventional computed tomography system, with the exception that an entire volumetric image is acquired through less than two rotations (preferably one rotation) of the source and detector. This is made possible by the use of a two-dimensional (2-D) detector, as opposed to the one-dimensional (1-D) detectors used in conventional computed tomography.
An example of a known cone-beam computed tomography imaging system is described in U.S. Pat. No. 6,842,502, the entire contents of which are incorporated herein by reference. The patent describes an embodiment of a cone-beam computed tomography imaging system that includes a kilovoltage x-ray tube and a flat panel imager having an array of amorphous silicon detectors. As a patient lies upon a treatment table, the x-ray tube and flat panel image rotate about the patient in unison so as to take a plurality of images as described previously.
As shown in FIGS. 2a-c, various volumetric imaging systems to be used with the present invention are illustrated. While the discussion to follow will describe the cone-beam computed tomography system 200 and megavoltage portal imaging system 300 of FIG. 2a, the discussion will be equally applicable to the scanning slot cone-beam computed tomography and megavoltage portal imaging systems of FIGS. 2b-c. FIG. 2a shows an embodiment of a wall-mounted cone-beam computed tomography system 200 and megavoltage portal imaging system 300 that can be adapted to be used with the cone-beam computed tomography and megavoltage portal imaging system sold under the trade name Synergy by Elekta of Crawley, the United Kingdom. Such systems 200 and 300 are described in pending U.S. patent application Ser. No. 11/786,781, entitled “Scanning Slot Cone-Beam Computed Tomography and Scanning Focus Spot Cone-Beam Computed Tomography” and filed on Apr. 12, 2007, the entire contents of which are incorporated herein by reference.
The cone-beam computed tomography system 200 includes an x-ray source, such as x-ray tube 202, a rotary collimator 204 and a flat-panel imager/detector 206 mounted on a gantry 208. As shown in FIG. 2a, the flat-panel imager 206 can be mounted to the face of a flat, circular, rotatable drum 210 of the gantry 208 of a medical linear accelerator 302, where the x-ray beam produced by the x-ray tube 202 is approximately orthogonal to the treatment beam produced by the radiation therapy source 302. Note that an example of mounting an x-ray tube and an imager to a rotatable drum is described in U.S. Pat. No. 6,842,502, the entire contents of which are incorporated herein by reference.
Note that the detector 206 can be composed of a two-dimensional array of semiconductor sensors that may be each made of amorphous silicon (α-Si:H) and thin-film transistors. The analog signal from each sensor is integrated and digitized. The digital values are transferred to the data storage server 102.
After the fan beams from collimator 204 traverse the width of a patient and impinge on the entire detector 206 in the manner described above, computer 234 of FIG. 1 instructs the drum 210 to rotate causing the x-ray source 202, the collimator 204 and the detector 206 rotate about the patient to another position so that the scanning process described above can be repeated and another two-dimensional projection is generated. The above rotation of the x-ray source 202, collimator 204 and detector 206 is continued until a sufficient number of two-dimensional images are acquired for forming a cone-beam computed tomography image. Less than two rotations should be needed for this purpose (it is envisioned that images formed from a rotation of less than 360° can be formed as well). The two-dimensional projections from each position are combined in the computer 234 to generate a three-dimensional image to be shown on display 236 of FIG. 1 in a manner similar to that of the cone-beam computed tomography systems described previously.
While the above described embodiment for the collimator 208 is rotary, a linear moving collimator can be used instead as described in pending U.S. patent application Ser. No. 11/786,781, entitled “Scanning Slot Cone-Beam Computed Tomography and Scanning Focus Spot Cone-Beam Computed Tomography” and filed on Apr. 12, 2007, the entire contents of which are incorporated herein by reference.
Radiation Therapy Source and Imager
As shown in FIG. 2a, (original) The system 300 includes a separate radiation therapy x-ray source, such as a linear source 302, and a detector/imager 304 that are separately mounted to the rotating drum 210. The source 302 operates at a power level higher than that of x-ray tube 202 so as to allow for treatment of a target volume in a patient lying on movable table 306 (movable in x, y and z-direction via computer 234 of FIG. 1). The linear source 302 generates a beam of x-rays or particles, such as photons, protons or electrons, which have an energy ranging from 4 MeV to 25 MeV.
As mentioned above, the particles are used to treat a specific area of interest of a patient, such as a tumor. Prior to arriving at the area of interest, the beam of particles is shaped to have a particular cross-sectional area via a multi-leaf collimator 308. The cross-sectional area is chosen so that the beam of particles interacts with the area of interest to be treated and not areas of the patient that are healthy. The radiation penetrating through the area of interest can be imaged via imager 304 in a well known manner.
Alternative Embodiments for Volumetric Imaging System and Radiation Source and Imager
Another embodiment of a cone-beam computed tomography system 200a and megavoltage portal imaging system 300a is shown in FIG. 2b. In this embodiment, the systems 200a and 300a can be adapted to be used with the cone-beam computed tomography and megavoltage portal imaging system sold under the trade name Trilogy by Varian Medical Systems of Palo Alto, Calif. The system 200a includes an x-ray tube 202, a rotary collimator 204 and a flat-panel imager/detector 206 similar to those used in the embodiment of FIG. 2a. Unlike the system 200 of FIG. 2a mounted on a drum, the x-ray tube 202 and collimator 204 are mounted on an arm 214 pivotably mounted to a support 309 of the system 300a. Similarly, the flat panel imager 206 is mounted on an arm 216 mounted to the support 309.
As with the embodiment of FIG. 2a, the x-ray beam 212 produced by the x-ray tube 202 of FIG. 2b is approximately orthogonal to the treatment beam produced by the radiation therapy source 302. As shown in FIG. 2b, the system 300a includes a linear source 302 and detector 304 similar to those described previously with respect to FIG. 2a. Accordingly, the linear source 302 generates a beam of x-rays or particles, such as photons or electrons, which have an energy ranging from 4 MeV to 25 MeV so as to allow for treatment of a target volume in a patient lying on movable table 306 (movable in x, y and z-direction via computer 234 of FIG. 1). Unlike the system 300 of FIG. 2a mounted on a drum, the linear source 302 and the detector 304 are connected with support 309.
Another embodiment of a scanning slot cone-beam computed tomography system 200b is shown in FIG. 2c. In this embodiment, system 200b includes a kilo-voltage x-ray tube 202, a rotary collimator 204 and a flat-panel imager/detector 206 similar to those used in the embodiment of FIG. 2a. Unlike the system 200 of FIG. 2a mounted on a drum, the x-ray tube 202 and collimator 204 are mounted at one end of a C-arm 218 while the flat panel imager 206 is mounted at the other end of the C-arm 218. The C-arm 218 is mounted to a movable base 220 so that it can pivot about axes A and B shown in FIG. 2c. 
Treatment Dose Tracking and Feedback System
As shown in FIG. 1, the treatment dose tracking and feedback system 600 includes a workstation or data server 110 that includes processors dedicated to perform a segmentation/registration process on a three-dimensional, volumetric image of a patient received from server 102 that was generated by cone-beam computed tomography system 200. The workstation 110 is able to identify and register each volume of image data within each volumetric image. Such identification and registration allows for the same volume of image data to be tracked in position from one therapy session to another therapy session.
The treatment dose tracking and feedback system 600 further includes a workstation or data server 112 that includes processors dedicated to perform a treatment dose construction process based on 1) the segmentation/registration process performed by workstation 110 and 2) parameters of the beam of radiation emitted from the source 302 as it impinges on the patient that are measured and stored in server 102, such as angular position, beam energy and cross-sectional shape of the beam, in accordance with the reference plan 502. Such parameters can be in the form of the angular position of the gantry 208, the angular orientation of the collimator 308, the positions of the leaves of the multi-leaf collimator 308, position of the table 306 and energy of the radiation beam. Once the position and shape of a subvolume of image data is known, the treatment dosage received by that very same subvolume can be determined/constructed based on the above mentioned parameters of the beam of radiation emitted from the source 302 as it impinges on the patient. Such a determination is made for each of the subvolumes of image data for each of the volumetric images generated by system 200.
The treatment dose tracking and feedback system 600 further includes a workstation or data server 114 that includes processors dedicated to perform a an adaptive planning process that can either 1) adjust the radiation therapy treatment for the particular day in a real-time manner based on off-line and on-line information or 2) adjust a radiation therapy treatment plan in a non-real-time manner based on off-line information. The adjustment is based on how the dose calculated by the workstation 112 differs from dose preferred by the treatment plan. Note that the term “real-time” refers to the time period when the radiation therapy source is activated and treating the patient. The term “on-line” regards when a patient is on the treatment table and “off-line” refers to when the patient is off the treatment table.
In summary, the treatment dose tracking and feedback system 600 can perform real time treatment dose construction and 4D adaptive planning based on volumetric image information and therapy beam parameters that are measured in a real time manner during a therapy session. The system 600 can also perform adaptive planning in a non-real-time manner as well. Such real time and non-real time processes will be discussed in more detail with respect to the process schematically shown in FIG. 7. Note that in an alternative embodiment, the workstations 110, 112 and 114 can be combined into a single workstation wherein the processes associated with workstations 110, 112 and 114 are performed by one or more processors. Note that the real time treatment dose construction determined by workstation 112 and the 4D adaptive planning determined by workstation 114 can be displayed on a monitor 117 of Quality Assurance (QA) evaluation station 116. Based on the information displayed on monitor 117, medical personnel can alter, if required, the calculated 4D adaptive plan so as to be within acceptable parameters. Thus, the QA evaluation station 116 acts as a way to ensure confidence in future real time changes made to the therapy session. In this scenario, the QA evaluation station 116 and the treatment dose tracking and feedback system 600 can be collectively thought of as a 4D planning and control system.
With the above description of the onboard cone-beam computed tomography system 200, megavoltage imaging and radiation therapy system 300, QA evaluation station 116 and the treatment dose tracking and feedback system 600 in mind, the operation of the CBCT IGART system 100 of FIG. 1 can be understood. In particular, the previously described online volumetric imaging information and real time therapy beam parameters are captured from systems 200, 300 and 400 and stored in data storage server 102. The volumetric imaging information and therapy beam parameters are then sent to data monitor job controller 104 that automatically assigns tasks, based on pre-designed treatment schedule and protocol, to each of the work stations 110, 112 and 114 and controls the accomplishment of such tasks. The tasks are stored in temporal job queues 118 for dispatching, based on clinical priorities, to each of the workstations 110, 112 and 114. The clinical priority can be reassigned from a clinical user's request 120 based on the treatment review and evaluation on the physician evaluation/decision making station 122. In addition, the station 122 also provides commands for treatment/plan modification decisions. The modification server 124 receives commands from the station 122 and modifies the ongoing treatment plan, beam or patient position on the system 300 based on the optimized adaptive plan created from the adaptive planning workstation 114.
As shown in FIG. 1, the raw data from server 102 is also sent to a workstation 110. The workstation 110 is dedicated to perform an autosegmentation/registration process on a three-dimensional, volumetric image of a patient generated by cone-beam computed tomography system 200. The raw data from server 102 is also sent to workstation 112 and workstation 114. Workstation 112 performs daily and cumulative treatment dose construction/evaluation from the raw data. Workstation 114 performs adaptive planning from the raw data. These three workstations 110, 112 and 114 perform their tasks automatically with order of their job queues 126, 128 and 130, respectively. The above described segmentation/registration, treatment dose construction/evaluation and adaptive planning will be described later with respect to the process schematically shown in FIG. 7.
As shown in FIG. 1, the segmentation/registration, treatment dose construction and adaptive planning information generated from workstations 110, 112 and 114 is sent to the QA evaluation station 116 which interacts with a clinical user to verify and modify, if necessary, the results from the above workstations 110, 112 and 114. The output from QA evaluation station 116 is then stored in derived data server 102. The output from QA evaluation station 116 is then stored in derived data server 103.
The QA station 116 provides an update execution status to job execution log server 132 that supplies information whether processing of information is presently occurring, whether processing is completed or whether an error has occurred. Whenever a task of treatment dose construction or adaptive planning modification is completed by workstations 112 and 114, respectively, the evaluation station 116 provides treatment evaluation information which includes both the current treatment status and the completed treatment dose and outcome parameters estimated based on the patient and treatment data from previous treatments. The user at QA evaluation station 116 can then provide commands or a new clinical schedule to the high priority job request server 120 to either request new information or modify clinical treatment schedule. In addition, the user can also make decisions to execute a new adaptive plan or perform a treatment/patient position correction through the server 124.
The CBCT IGART system 100 performs a number of processes, including a kV portal imaging process via kV portal imaging processor/software 400 and a an image guided adapted radiation therapy process 500, both of which will be described below with respect to FIGS. 3-7.
Pre-Treatment Process
As an example of how the radiation therapy process proceeds, assume a patient who has undergone previous radiation therapy sessions at a clinic has another session scheduled for a particular day. The patient arrives at the clinic on the scheduled day and proceeds to the therapy room similar to that shown in FIG. 3a. The therapy room includes the cone-beam computed tomography system 200 and megavoltage portal imaging system 300 previously described with respect to FIG. 2a. The patient lies on the table 306 and is prepared for the on-line therapy session by the medical staff (“on-line” being defined as events and processes performed as the patient is positioned on the radiation therapy treatment table 306).
At this point of time, a reference treatment plan for applying therapeutic radiation to the patient has previously been determined for the patient based on the previous radiation therapy sessions. A reference treatment plan is designed before the treatment delivery based on the most likely planning volumetric image of the area of interest to be treated. The reference treatment plan contains patient setup position, therapy machine parameters and expected daily and cumulative doses to be applied to various areas of the patient. Such a reference plan specifies the area(s) of the patient to be exposed to radiation and the dosage the area(s) are to receive from the radiation source during a single session. Thus, the reference plan will include information regarding the beam angle/gantry position, beam energy and cross-sectional area of the beam formed by the multi-leaf collimator 308. Based on the reference plan, the patient is instructed per step 402 of a pre-treatment kV portal imaging process, to move to a particular position, such as on his or her side, that is optimal for applying radiation to the area of interest within the patient per the reference plan. While at the particular position, the previously mentioned pre-treatment kV portal imaging process employing kV processor/software 400 is performed prior to the radiation therapy session. The pre-treatment kV portal imaging process is schematically shown in FIGS. 3-6. In particular, the process includes forming a two-dimensional projection/radiographic image from the cone-beam computed tomographic image 404 of the patient prior to treatment, wherein the image 404 contains the area of interest while the patient is at the particular position on the table 306 per step 406 of the process. According to the reference plan, the radiation source 302 is to be moved to one or more positions to apply radiation at each position while the patient is at the particular position. At each position of the radiation source 302, the leaves of the multi-leaf collimator 308 are to be moved to form a desired outline for forming the radiation beam to a particular cross-sectional shape. The positions of the leaves at each position of the radiation source are determined, per step 408, as schematically represented by the multi-leaf outlines 410 of FIGS. 3a-b.
The cone-beam computed tomographic image 404 of the area of interest while the patient is at the particular position and the positions of the leaves/outlines 410 are then stored and processed in a processor of workstation 110 as shown in FIGS. 3b and 4-6. Such processing involves, per step 412, superimposing each outline 410 on a two-dimensional projection/radiographic image based on the cone-beam image 404 to form a treatment beam eye (BEV) view kV portal image such as shown in FIGS. 3b and 4b. Note that the kV portal image can be formed as a kV digital reconstructed radiographic (DRR) image for static patient anatomy verification or as a digital reconstructed fluoroscopic (DRF) image for verification of dynamic patient anatomy motion, such as respiratory motion. In either case, each kV portal image with corresponding outline 410 (FIG. 4b, for example) is compared with a treatment reference radiographic image (FIG. 4a, for example) that is generated according to the real-time radiation therapy plan to be executed. Should one or more areas of interest, such as a tumor or organ, of the kV portal image be displaced by at least a predetermined amount relative to the position of the corresponding area of interest of the reference image, then steps are taken to adjust the real-time radiation therapy plan for the day's treatment session. If the displacement is below the predetermined amount, then the real-time radiation plan is not adjusted.
In addition to the treatment dose, kV portal image can also be constructed for treatment recordation and verification as shown in FIGS. 3a-b. Further, organs of interest manifested on the CBCT image are auto-segmented and registered to the pre-treatment CT image. Therefore, daily and cumulative dose-volume relationships of each organ of interest can be created. In some implementations, a numerical filter is employed to estimate the final treatment dose in each organ of interest by performing parameter estimation for both stationary and non-stationary random processes of patient anatomical variation. Methods for sample estimation, such as the least square estimation, the principal component analysis (PCA) based estimation and singular value decomposition (SVD) estimation, may be implemented.
The estimation is then used to provide information for the treatment evaluation and plan modification decision to determine when to switch on the adaptive planning modification engine.
On-Line, Off-Line Image Guided Adaptive Radiation Therapy Planning
After the kV imaging process is completed, resulting in the initial radiation therapy plan being modified or retained, the patient is repositioned to receive radiation therapy per the modified/original reference plan and image guided adapted radiation therapy process 500 is performed as schematically shown in FIG. 7. In particular, the reference plan 502 is applied to the linear source 302 per process 504 so as to move the source 302 to a position designated in the reference plan 502 and to format parameters of the beam of radiation emitted from the source 302 as it impinges on the patient, such as angular position, beam energy and cross-sectional shape of the beam, in accordance with the reference plan 502. Such on-line and real-time parameters can be in the form of the angular position of the gantry 208, the angular orientation of the collimator 308, the positions of the leaves of the multi-leaf collimator 308, position of the table 306 and energy of the radiation beam. Process 504 can also involve moving individual leaves of a multi-leaf collimator 308 to desired positions per reference plan 502 so that that the radiation therapy beam generated by the linear source 302 is collimated so as to radiate a particular shaped area of the patient per the reference plan 502.
Once the reference plan 502 is implemented per process 504, the reference plan 502 can be altered to account for various factors that occur during the radiation therapy session. For example, the process 500 can entail having the system 100 monitor real-time, on-line machine treatment parameters of the linear source 302 and its radiation output online per process 506. The process 506 entails monitoring treatment parameters, such as beam angle, beam energy and cross-sectional shape of the beam. Such parameters can entail the position of the gantry, the angular position of the collimator 308, position of the leaves of the multi-leaf collimator 308, position of the table 306, the energy of the beam.
The real-time, on-line information obtained by the above mentioned monitoring process 506 is fed to workstation 112 of FIG. 1 so that it can be used during either the online and offline daily and cumulative dose construction process 508.
While a radiation therapy beam is applied to the patient per process 504, the area of interest to be treated is imaged via the cone-beam computed tomography system 200. The three-dimensional volumetric image is used to register and track various individual volumes of interest in a real-time and on-line manner. Prior to registration and tracking, a correction parameter must be determined by server 102 per process 510 so as to be applied to the volumetric image. The correction parameter is associated with the fact that rigid body components of the volumetric image are often not oriented in a preferred manner due to a number of factors, such as the position of the patient on the table 306 and the angular position of the collimator. Based on the measurement of those factors, a correction parameter is determined per process 510 that when applied to the three-dimensional image the image is re-oriented to a preferred position. The re-oriented three-dimensional image is stored at workstation 102 of FIG. 1. The workstation 102 contains a library of stored three-dimensional images of one or more areas of interest of the patient.
Once the correction parameter is determined, the segmentation-deformable organ registration workstation 110 receives the volumetric image generated by system 200 and correction parameter from server 102 via process 512. The workstation 110 executes process 512 so as to match the patient anatomical elements manifested on the volumetric image to those on the reference planning volumetric image associated with the reference plan. The image registration results are used to map the pre-treatment organ contours on the planning volumetric image commonly delineated by clinicians, to the corresponding points on the treatment volumetric image automatically. The registration methods applied for this process are quite standard such as the finite element method and the method of image similarity maximization. However, there have been number of modifications performed to optimize these methods for the specific applications of the CBCT image and organs of interest in radiotherapy, such as described in the publications: 1) Liang J., et al., “Reducing Uncertainties in Volumetric Image Based Deformable Organ Registration,” Med Phys, 30(8), 2003, pp. 2116-2122, 2) Chi Y., et al., “Sensitivity Study on the Accuracy of Deformable Organ Registration Using Linear Biomechical Models,” Med Phys, 33: (2006), pp. 421-33, 3) Zhang T., et al., “Automatic Delineation of Online Head and Neck CT Images: Towards Online Adaptive Radiotherapy,” International Journal of Radiation Oncology Biology Physics, 68(2), (2007) pp. 522-30 and 4) Yan D., et al., “A Model to Accumulate Fractionated Dose in a Deforming Organ,” International Journal of radiation Oncology, Biology Physics, 44(3): (1999), pp. 665-675, the entire contents of each of which is incorporated herein by reference.
Once each point in the volumetric image is tracked, that information is sent to workstation 112, which also receives the parameters per process 506. At workstation 112, an online daily and cumulative dose construction process 508 is performed. The daily dose construction process entails calculating/constructing for a real-time treatment the dose received for each volume of image data within the volumetric image tracked per process 512. After the treatment session for the day is completed, the daily dose for each volume of image data is stored in server 102. The daily dose for each volume of image data can be combined with daily doses for the same volumes of image data calculated/constructed from previous therapy sessions so that an accumulated dosage over time for each volume of image data is determined per process 508 and stored in server 102. Further details of the construction of the daily and cumulative treatment doses are discussed in the publications: 1) Yan D., et al., “A Model to Accumulate Fractionated Dose in a Deforming Organ,” International Journal of radiation Oncology, Biology Physics, 44(3): (1999), pp. 665-675, 2) Yan D. et al. “Organ/Patient Geometric Variation in External Beam Radiotherapy and Its Effect,” Medical Physics, 28(4), (2001), pp. 593-602 and 3) Lockman D., et al., “Estimating the Dose Variation in a Volume of Interest with Explicit Consideration of Patient Geometric Variation,” Medical Physics, 27: (2000) pp. 2100-2108, the entire contents of each of which is incorporated herein by reference.
As shown in FIG. 7, treatment evaluation 514 is performed by workstation 114 following the patient organ registration and treatment dose construction processes 512 and 508, respectively. There are two purposes for treatment evaluation, (a) to determine if the current treatment delivery is the same as the one previously planned for the treatment quality assurance; and (b) to modify the ongoing treatment plan by including the patient anatomy/dose variations observed and quantified so far to optimize the treatment outcome. Such treatment evaluation 514 can be performed real-time, on-line and off-line.
Final treatment dose and outcome estimation are used to provide information for the treatment evaluation and plan modification decision to determine when to switch on the adaptive planning modification engine per process 514 of FIG. 7. A numerical filter is employed to estimate the final treatment dose in each organ of interest by performing parameter estimation for both stationary and non-stationary random processes of patient anatomical variation. Methods for sample estimation, such as the least-square estimation (LSE), the principal component analysis (PCA) based estimation and singular value decomposition (SVD) estimation, are implemented. The detail discussions of using these filters for organ geometry and dose estimation of different treatment sites have been discussed in the following documents: 1) Yan D. et al. “Organ/Patient Geometric Variation in External Beam Radiotherapy and Its Effect,” Medical Physics, 28(4), (2001), pp. 593-602, 2) Lockman D., et al., “Estimating the Dose Variation in a Volume of Interest with Explicit Consideration of Patient Geometric Variation,” Medical Physics, 27: (2000) pp. 2100-2108, 3) Sohn M. et al., “Modeling Individual Geometric Variation Based on Dominant Eigenmodes of Organ Deformation: Implementation and Evaluation,” Phys Med Biol, 50: (2005) pp. 5893-908 and 4) Yan D., “Image-Guided/Adaptive Radiotherapy,” Medical Radiology-Radiation Oncology, Volume: New Technologies in Radiation Oncology, Edited by W. Schlegel, T. Bortfeld and A L Grosu, Springer-Verlag Berlin Heidelberg New York Hong Kong, (2005) ISBN 3-540-00321-5, the entire contents of each of which is incorporated herein by reference.
The first task of treatment evaluation is related to treatment delivery and plan comparison performed by workstation 112 per process 514. If the comparison shows that the daily or cumulative treatment dosage for a particular subvolume of the image and the corresponding daily or cumulative planned dosages for the corresponding subvolume are outside a certain tolerance (see, Yan D., et al., “A New Model for ‘Accept Or Reject’ Strategies in On-Line and Off-Line Treatment Evaluation,” International Journal of Radiation Oncology, Biology Physics, 31(4): (1995) pp. 943-952, the entire contents of which are incorporated herein by reference.), then this means that the reference plan currently being implemented needs to be revised during the present therapy session. Note that the above described daily and cumulative dosages of a subvolume of interest can be tracked/displayed in time, such as on monitor 117 of FIG. 7 in a manner similar to the chart shown at the bottom of FIG. 5.
Besides comparing the dosages, the positioning of areas to be treated with respect to the therapeutic beam is tested by forming a kV portal image per the previously described process of FIG. 6. If the real-time kV portal image is compared with a reference portal image and a subvolume of interest of the real-time kV portal image is found to be displaced in position or deformed in shape outside a certain tolerance with respect to a corresponding subvolume position in the reference portal image, then the reference plan, such as adjusting the leaves of the multi-leaf collimator, needs to be changed in this instance as well Note that the above described position of a subvolume of interest can be tracked/displayed in time as shown by the bottom chart of FIG. 5, wherein x, y and z positions of a particular subvolume is tracked from one daily treatment session to another daily treatment session.
If either of the comparisons described above are outside the corresponding tolerance, then a revision of the reference therapy treatment plan is performed in the on-line or off-line adaptive planning optimization process 516. Adaptive planning optimization is different than conventional radiotherapy planning where only pre-treatment computed tomographic image data is used. Instead, adaptive planning intends to utilize individual treatment history from patient anatomy/dose tracking as feedback to optimize treatment control parameters. Examples of techniques of adaptive planning optimization are described in the following publications: 1) Yan D., et al., “An Off-Line Strategy for Constructing a Patient-Specific Planning Target Volume for Image Guided Adaptive Radiotherapy of Prostate Cancer,” International Journal of radiation Oncology, Biology Physics, 48(1), (2000) pp. 289-302, 2) Birkner M., et al., “Adapting Inverse Planning to Patient and Organ Geometrical Variation: Algorithm and Implementation,” Med Phys, 30(10): (2003), pp. 2822-2831, 3) Yan D., “On-Line Adaptive Strategy for Dose Per Fraction Design,” Proceeding, XIIIth International Conference on The Use of Computers in Radiotherapy, Heidelberg, Germany (2000), pp. 518-520 and 4) Yan D., et al., “Strategies for Off-Line and On-Line Image Feedback Adaptive Radiotherapy,” Editors: B K Paliwal, D E Herbert, J F Fowler, M P Mehta, Biological & Physical Basis of IMRT & Tomotherapy, AAPM Symposium Proceeding No. 12, 2002, pp. 139-50.
Note that the above-described process regarding FIG. 7 can include real-time data/information by capturing data volumetric image data from system 200 and therapy beam parameter information during the time the therapy beam is generated. Such real-time information can be processed per processes 506, 508, 510, 512 and used in process 514 to determine if the therapy plan should be revised in “real-time.” If it is so determined that revision is recommended, then the real-time data/information can be used in conjunction with prior dose information and position/shape information of the volume of interest determined from previous therapy sessions (off-line information) to reformulate the therapy plan.
While the above description demonstrates how “real-time” data/information can be used to revise a therapy plan via the process of FIG. 7, the description is equally applicable to non-real-time adaptive therapy. In this case, processes 506, 508, 510 and 512 use off-line information from previous treatment sessions and process 514 determines if a therapy plan to be used in the future should be revised. in “real-time.”
In summary, the system 100 and process 500 provide volumetric image guided adaptive radiotherapy, which can be performed in real time, online and offline for treatment dose construction and feedback. Therefore, they provide all possible feedback information for image guided real time, online and offline radiotherapy. Thus, the system 100 and process 500 are able to fully utilize individual treatment information, which primarily includes the patient dose delivered in the previous treatment, patient anatomy in the present treatment and patient anatomy estimated for remaining treatment deliveries.
The foregoing discussion discloses and describes merely exemplary embodiments of the present invention. One skilled in the art will readily recognize from such discussion, and from the accompanying drawings and claims, that various changes, modifications and variations can be made therein without departing from the spirit and scope of the invention as defined in the following claims.

## Claims

1. A system for radiotherapy comprising:
an imaging system that generates volumetric image data of an area of interest of an object, wherein said imaging system comprises a cone-beam computed tomography system comprising:
an x-ray source that emits x-rays towards said object;
a first detector for receiving x-rays penetrating through said area of interest of said object and generating signals to generate said volumetric image data of said area of interest of said object, wherein said first detector receives fan-shaped x-rays after they pass through said area of interest of said object, said first detector generating a first imaging signal for each of said received fan-shaped x-rays; and
a computer connected to said detector so as to receive said first imaging signals for each of said received fan-shaped x-rays, wherein said x-ray source and said first detector rotate about said object so that multiple imaging signals are reconstructed by said computer to generate a three-dimensional cone-beam computed tomography image therefrom;
a radiation source that emits a therapeutic radiation beam towards said area of interest of said object in accordance with a reference plan;
a second detector that receives radiation from said therapeutic radiation beam that passes through said area of interest, said second detector generating second imaging signals from said radiation; and
a processing system (a) that receives and evaluates said volumetric image data, said second imaging signals and at least one parameter of said therapeutic radiation beam to provide 1) a real-time evaluation of said reference plan and 2) a real-time modification of said reference plan, wherein real-time is defined to be a time period when said therapeutic radiation beam is emitted towards said area of interest of said object, (b) that constructs a treatment dose received in said area of interest, and c) that estimates a final treatment dose in said area of interest by performing parameter estimation for random processes of patient anatomical variation.

2. The system of claim 1, wherein said x-ray source comprises a kV x-ray source.

3. The system of claim 1, wherein said therapeutic radiation has an energy ranging from 4 MeV to 25 MeV.

4. The system of claim 1, wherein said reference plan specifies said area of said object to be exposed to said therapeutic radiation beam and a dosage said area of said object to be exposed to said therapeutic radiation beam is to receive from said radiation source during a single treatment session.

5. The system of claim 1, wherein said at least one parameter of said therapeutic radiation beam is selected from the group consisting of angle of said therapeutic radiation beam, energy of said therapeutic radiation beam and cross-sectional shape of said therapeutic radiation beam.

6. The system of claim 1, wherein said processing system comprises a workstation that performs a segmentation/registration process on said volumetric image data.

7. The system of claim 1, further comprising a workstation that compares said volumetric image data with a stored volumetric image taken from a previous volumetric image so that changes in movement and shape of each subvolume of said volumetric image data is tracked with respect to a corresponding subvolume of said stored volumetric image.

8. The system of claim 7, further comprising a second workstation that constructs a treatment dose received for each subvolume tracked by said workstation that compares said volumetric image data with said stored volumetric image.

9. The system of claim 8, further comprising a third workstation that compares said constructed treatment dose with a preferred treatment dose specified by said reference plan.

10. The system of claim 9, wherein if said constructed treatment dose and said preferred treatment dose are within a certain tolerance, then said reference plan is retained.

11. The system of claim 9, wherein if said constructed treatment dose and said preferred treatment dose are outside a certain tolerance, then said reference plan is altered.

12. The system of claim 11, wherein said reference plan is altered based on said real-time evaluation of said reference plan.

13. The system of claim 12, wherein said real-time modification of said reference plan is based on off-line information.

14. The system of claim 11, wherein said real-time modification of said reference plan is based on off-line information.

15. The system of claim 1, further comprising a workstation that constructs a treatment dose received for each subvolume in said area of interest.

16. The system of claim 15, further comprising a second workstation that compares said constructed treatment dose with a preferred treatment dose specified by said reference plan.

17. The system of claim 16, wherein if said constructed treatment dose and said preferred treatment dose are within a certain tolerance, then said reference plan is retained.

18. The system of claim 16, wherein if said constructed treatment dose and said preferred treatment dose are outside a certain tolerance, then said reference plan is altered.

19. The system of claim 18, wherein said reference plan is altered based on said real-time evaluation of said reference plan.

20. The system of claim 19, wherein said real-time modification of said reference plan is based on off-line information.

21. The system of claim 18, wherein said real-time modification of said reference plan is based on off-line information.

22. The system of claim 1, wherein said real-time evaluation and said real-time modification are performed in an on-line manner.

23. The system of claim 1, wherein said real-time evaluation and said real-time modification are performed in an off-line manner.

24. The system of claim 1, wherein the random processes of patient anatomical variation are stationary or non-stationary processes, or a combination thereof.

25. The system of claim 1, wherein the random processes of patient anatomical variation are non-stationary processes.

26. The system of claim 1, wherein the parameter estimation is based on the least square estimation, principal component analysis estimation, or singular value decomposition estimation, or any combination thereof.

27. A method of treating an object with radiation, comprising:
generating volumetric image data of an area of interest of an object, wherein said generating volumetric image data comprises:
emitting x-rays towards said object; and
detecting x-rays penetrating through said area of interest of said object and generating signals to generate said volumetric image data of said area of interest of said object;

emitting a therapeutic radiation beam towards said area of interest of said object in accordance with a reference plan;
generating an image based on said therapeutic radiation beam;
evaluating said volumetric image data, said image based on said therapeutic beam, and at least one parameter of said therapeutic radiation beam to provide 1) a real-time evaluation of said reference plan and 2) a real-time modification of said reference plan, wherein real-time is defined to be a time period when said therapeutic radiation beam is emitted towards said area of interest of said object;
constructing a treatment dose received in said area of interest; and
estimating a final treatment dose in said area of interest by performing parameter estimation for random processes of patient anatomical variation.

28. The method of claim 27, wherein said reference plan specifies said area of said object to be exposed to said therapeutic radiation beam and a dosage said area of said object to be exposed to said therapeutic radiation beam is to receive from said radiation source during a single treatment session.

29. The method of claim 27, wherein said at least one parameter of said therapeutic radiation beam is selected from the group consisting of angle of said therapeutic radiation beam, energy of said therapeutic radiation beam and cross-sectional shape of said therapeutic radiation beam.

30. The method of claim 27, wherein said evaluating comprises performing a segmentation/registration process on said volumetric image data.

31. The method of claim 27, further comprising comparing said volumetric image data with a stored volumetric image taken from a previous volumetric image so that changes in movement and shape of each subvolume of said volumetric image data is tracked with respect to a corresponding subvolume of said stored volumetric image.

32. The method of claim 31, further comprising constructing a treatment dose received for each subvolume tracked.

33. The method of claim 32, further comprising comparing said constructed treatment dose with a preferred treatment dose specified by said reference plan.

34. The method of claim 33, wherein if said constructed treatment dose and said preferred treatment dose are within a certain tolerance, then said reference plan is retained.

35. The method of claim 33, wherein if said constructed treatment dose and said preferred treatment dose are outside a certain tolerance, then said reference plan is altered.

36. The method of claim 35, wherein said reference plan is altered based on said real-time evaluation of said reference plan.

37. The method of claim 36, wherein said real-time modification of said reference plan is based on off-line information.

38. The method of claim 35, wherein said real-time modification of said reference plan is based on off-line information.

39. The method of claim 27, wherein said real-time evaluation and said real-time modification are performed in an on-line manner.

40. The method of claim 27, wherein said real-time evaluation and said real-time modification are performed in an off-line manner.

41. The method of claim 27, wherein the random processes of patient anatomical variation are stationary or non-stationary processes, or a combination thereof.

42. The method of claim 27, wherein the random processes of patient anatomical variation are non-stationary processes.

43. The method of claim 27, wherein the parameter estimation is based on the least square estimation, principal component analysis estimation, or singular value decomposition estimation, or any combination thereof.

44. A planning and control system for radiotherapy comprising:
a system that captures and evaluates parameters of a volumetric image of an area of interest of an object, a therapeutic radiation beam directed towards said area of interest of said object in accordance with a reference plan, and an image of said area of interest formed from said therapeutic radiation beam so as to provide 1) a real-time evaluation of said reference plan and 2) a real-time modification of said reference plan, wherein real-time is defined to be a time period when said therapeutic radiation beam is emitted towards said area of interest of said object, wherein said system constructs a treatment dose based on said captured parameters of said volumetric image and said therapeutic radiation beam and estimates a final treatment dose in said area of interest by performing parameter estimation for random processes of patient anatomical variation; and
a monitor that displays information based on one or more of the captured parameters of said volumetric image and said therapeutic radiation beam.

45. The planning and control system of claim 44, further comprising a processor that identifies and registers each subvolume of image data within said volumetric image.

46. The planning and control system of claim 45, further comprising a second processor that constructs a treatment dose for each of said volume of image data based on said captured parameters of said volumetric image and said therapeutic radiation beam.

47. The planning and control system of claim 46, wherein said treatment dose is a daily treatment dose.

48. The planning and control system of claim 46, wherein said treatment dose is a cumulative treatment dose.

49. The planning and control system of claim 46, further comprising a third processor that performs a 4D adaptive planning process that adjusts radiation therapy treatment of said area of interest for a particular day in a real-time manner based on said real-time evaluation.

50. The planning and control system of claim 49, wherein said third processor adjusts said radiation therapy treatment of said area of interest based on a comparison of a real-time position or shape of said subvolume of image data and a planned position or shape of a corresponding subvolume of image data.

51. The planning and control system of claim 49, wherein said third processor adjusts said radiation therapy treatment of said area of interest based on a comparison of said treatment dose and a planned treatment dose.

52. The planning and control system of claim 44, wherein said treatment dose is a daily treatment dose.

53. The planning and control system of claim 44, wherein said treatment dose is a cumulative treatment dose.

54. The planning and control system of claim 44, further comprising a processor that performs a 4D adaptive planning process that adjusts radiation therapy treatment of said area of interest for a particular day in a real-time manner based on said real-time evaluation.

55. The planning and control system of claim 45, wherein said processor adjusts therapy treatment of said area of interest based on a comparison of a real-time position or shape of said object within said area of interest and a planned position or shape of said object.

56. The planning and control system of claim 44, wherein said processor adjusts therapy treatment of said area of interest based on a comparison of a real-time treatment dose of said object within said area of interest and a planned treatment dose of said object.

57. The planning and control system of claim 44, wherein said real-time evaluation and said real-time modification are performed in an on-line manner.

58. The planning and control system of claim 44, wherein said real-time evaluation and said real-time modification are performed in an off-line manner.

59. The system of claim 44, wherein the random processes of patient anatomical variation are stationary or non-stationary processes, or a combination thereof.

60. The system of claim 44, wherein the random processes of patient anatomical variation are non-stationary processes.

61. The system of claim 44, wherein the parameter estimation is based on the least square estimation, principal component analysis estimation, or singular value decomposition estimation, or any combination thereof.

62. A method of planning and controlling a radiation therapy session, the method comprising:
capturing and evaluating parameters of a volumetric image of an area of interest of an object, a therapeutic radiation beam directed towards said area of interest of said object in accordance with a reference plan, and an image of said area of interest formed from said therapeutic radiation beam so as to provide 1) a real-time evaluation and 2) a real-time modification of said reference plan, wherein real-time is defined to be a time period when said therapeutic radiation beam is emitted towards said area of interest of said object;
planning and controlling a radiation therapy session based on said real-time evaluation;
displaying information based on one or more of said captured parameters of said volumetric image and said therapeutic radiation beam;
constructing a treatment dose based on said captured parameters of said volumetric image and said therapeutic radiation beam; and
estimating a final treatment dose in said area of interest by performing parameter estimation for random processes of patient anatomical variation.

63. The method of claim 62, further comprising identifying and registering each subvolume of image data within said volumetric image.

64. The method of claim 63, further comprising constructing a treatment dose for each of said identified and registered subvolumes of image data based on said captured parameters of said volumetric image and said therapeutic radiation beam.

65. The method of claim 62, further comprising performing a 4D adaptive planning process that adjusts radiation therapy treatment of said area of interest for a particular day in a real-time manner based on said real-time evaluation.

66. The method of claim 65, wherein said performing comprises adjusting said radiation therapy treatment based on a comparison of a real-time position or shape of said object within said area of interest and a planned position or shape of said object.

67. The method of claim 65, wherein said performing comprises adjusting said radiation therapy treatment based on a comparison of a real-time treatment dose of said object within said area of interest and a planned treatment dose of said object.

68. The method of claim 65, wherein said real-time modification of said reference plan is based on off-line information.

69. The method of claim 62, wherein said real-time modification of said reference plan is based on off-line information.

70. The method of claim 62, wherein said real-time evaluation and said real-time modification are performed in an on-line manner.

71. The method of claim 62, wherein said real-time evaluation and said real-time modification are performed in an off-line manner.

72. The method of claim 62, wherein the random processes of patient anatomical variation are stationary or non-stationary processes, or a combination thereof.

73. The method of claim 62, wherein the random processes of patient anatomical variation are non-stationary processes.

74. The method of claim 62, wherein the parameter estimation is based on the least square estimation, principal component analysis estimation, or singular value decomposition estimation, or any combination thereof.

75. A system for radiotherapy comprising:
a radiation source that is programmed to emit a therapeutic radiation beam towards an area of interest of an object in accordance with a reference plan during a real-time time period when said object is on-line;
a first imaging system that generates on-line volumetric image data of said area of interest of said object during said real-time time period when said object is on-line, and off-line volumetric image data of said area of interest of said object during a non-real time off-line time period, wherein real-time is defined to be a time period when said therapeutic radiation beam is emitted towards said area of interest of said object;
a second imaging system that generates an image based on said therapeutic radiation beam; and
a processing system (a) that receives and processes said image based on said therapeutic radiation beam and one or more of said on-line and off-line volumetric image data to alter said reference plan, (b) that constructs a treatment dose received in said area of interest, and (c) that estimates a final treatment dose in said area of interest by performing parameter estimation for random processes of patient anatomical variation.

76. The system of claim 75, wherein said processing system processes said on-line volumetric image data to alter said reference plan.

77. The system of claim 76, wherein said processing system processes said off-line volumetric image data to alter said reference plan.

78. The system of claim 75, wherein said processing system processes said off-line volumetric image data to alter said reference plan.

79. The system of claim 75, wherein the random processes of patient anatomical variation are stationary or non-stationary processes, or a combination thereof.

80. The system of claim 75, wherein the random processes of patient anatomical variation are non-stationary processes.

81. The system of claim 75, wherein the parameter estimation is based on the least square estimation, principal component analysis estimation, or singular value decomposition estimation, or any combination thereof.

82. A method of treating an object with radiation, comprising:
planning on emitting a therapeutic radiation beam towards an area of interest of an object in accordance with a reference plan during a real-time time period when said object is on-line;
generating on-line volumetric image data of said area of interest of said object during said real-time time period when said object is on-line, and off-line volumetric image data of said area of interest of said object during a non-real time off-line time period, wherein real-time period is defined to be a time period when said therapeutic radiation beam is emitted towards said area of interest of said object;
generating an image based on said therapeutic radiation beam;
altering said reference plan based on said image based on said therapeutic radiation beam and one or more of said on-line and off-line volumetric image data;
constructing a treatment dose received in said area of interest; and
estimating a final treatment dose in said area of interest by performing parameter estimation for random processes of patient anatomical variation.

83. The method of claim 82, wherein said altering is based on said on-line volumetric image data.

84. The method of claim 83, wherein said altering is based on said off-line volumetric image data.

85. The method of claim 82, wherein said altering is based on said off-line volumetric image data.

86. The method of claim 82, wherein the random processes of patient anatomical variation are stationary or non-stationary processes, or a combination thereof.

87. The method of claim 82, wherein the random processes of patient anatomical variation are non-stationary processes.

88. The method of claim 82, wherein the parameter estimation is based on the least square estimation, principal component analysis estimation, or singular value decomposition estimation, or any combination thereof.