# Patent

## Title
Real-time dose reconstruction using dynamic simulation and image guided adaptive radiotherapy

## Abstract

A radiation therapy treatment method comprises imaging a subject and simulating four-dimensional aspects of radiotherapy. A treatment plan based on the simulation is generated to permit real-time, three-dimensional dose reconstruction at the time of treatment. The simulation and treatment plan are used during treatment fractions to achieve real-time image guidance.

## Background
FIELD OF THE INVENTION
The present invention relates generally to radiation therapy and in particular to real-time dose reconstruction using dynamic simulation and image guided adaptive radiotherapy.
BACKGROUND OF THE INVENTION
Radiation therapy can be given to treat proliferative tissue disorders including but not limited to cancer, arteriovenous malformations, dermatological legions etc. During radiation therapy, the tissue of the patient known to or suspected to contain the disease is exposed to radiation. Linear accelerators are commonly used to irradiate a target volume encompassing the tissue to be treated during radiation therapy. As is known, linear accelerators use microwave technology to accelerate electrons in a waveguide and then allow the electrons to collide with a heavy metal target. As a result of the collisions, high-energy x-rays are scattered from the target. A portion of the scattered x-rays is collected and shaped by a beam collimating device to form an output beam of radiation conforming to the shape of the target volume. The linear accelerator also includes a gantry that rotates around the patient allowing the output beam of radiation to be delivered to the desired target volume from any angle by rotating the gantry.
Prior to exposing a patient to radiation, a treatment plan is typically developed in order to determine accurately the location of the tissue to be treated and how best to treat the tissue with radiation. Many imaging techniques have been used in treatment planning such as for example, computed tomography (CT), magnetic resonance imaging (MRI), and nuclear scintigraphy including single photon emission tomography (SPECT) and positron emission tomography (PET). Acquired images of the tissue are used to define the target volume so that the actual tissue irradiated by the output beam of radiation conforms as much as possible to the target volume. In many instances, the images of the tissue used to define the target volume are acquired in a single simulation.
For dose delivery, techniques such as tumour immobilisation with IMRT and image guidance have commonly been utilized. The purpose of image guidance is to ensure that the target tissue is placed at the isocenter of the linear accelerator at the beginning of radiation treatment. In tissue sites where a large amount of tissue motion is expected (for instance lung cancer radiotherapy), image guided therapy also constitutes control of the output beam of radiation to ensure that the irradiation time is restricted to the moment when the tissue is localized at the linear accelerator isocenter.
Unfortunately, this method has a fundamental difficulty if the image used to define the target volume is acquired in a single simulation since it is not known if image guided reproduction of the target location in subsequent treatment fractions results in the planned dosimetry being accurately delivered to the target and non-target tissues. This is because it is not known, a priori, if the single simulation image is representative of the patient positioning and target volume configuration in subsequent radiotherapy treatment fractions.
To provide more accurate position information concerning the target tissue and ensure the beam of radiation is properly directed in subsequent radiotherapy treatment fractions, it has been considered to integrate a linear accelerator with a magnetic resonance imaging apparatus.
MRI is a well-known imaging technique. During MRI, a target, typically a human patient, is placed into an MRI machine and subjected to a uniform magnetic field produced by a polarizing magnet housed within the MRI machine. Radio frequency (RF) pulses, generated by an RF coil housed within the MRI machine in accordance with a particular localization method, are used to scan target tissue of the patient. MRI signals are radiated by excited nuclei in the target tissue in the intervals between consecutive RF pulses and are sensed by the RF coil. During MRI signal sensing, gradient magnetic fields are switched rapidly to alter the uniform magnetic field at localized areas thereby allowing spatial localization of MRI signals radiated by selected slices of the target tissue. The sensed MRI signals are in turn digitized and processed to reconstruct images of the target tissue slices using one of many known techniques.
Unfortunately, even in such systems which use inter-fraction image guidance, tissue motion during the treatment fraction results in the delivered dose of radiation differing from the planned dose, and necessitates the use of a planning target volume (PTV) to ensure tissue coverage. The consequence is that the normal tissue surrounding the target tissue also receives an additional radiation dose.
Further, real-time, three-dimensional (3D) imaging of the patient during the radiation therapy has not been incorporated into IMRT delivery devices, and so it does not allow for true radiation dose reconstruction post treatment. The current art only calculates a post-treatment radiation dose reconstruction based on a pre-treatment static image of the target volume.
In addition, while it is desirable to have real-time imaging during radiotherapy, the true quantity of interest is the real-time accumulation of radiation doses to all structures in the target volume. Real-time dose-accumulation data could be used to detect treatment errors at a very early time, and would allow intervention in the instance where the treatment fraction dose is outside of tolerance. This is not currently available since no method of radiation dose calculation is currently fast enough (unless prohibitively large numbers of parallel processing computers are used) to perform the necessary dose accumulation calculations in real-time. As well, the availability of real-time radiation dose calculation would allow safe dose escalation in those tissue sites where the optimal dose has not yet been defined.
As will be appreciated, improved radiation therapy techniques which obviate or mitigate one or more of the above-referenced problems are desired. It is therefore an object of the present invention to provide a novel real-time dose reconstruction using dynamic simulation and image guided adaptive radiotherapy.
SUMMARY OF THE INVENTION
According to one aspect there is provided a radiation therapy treatment method comprising:
imaging a subject and simulating four-dimensional aspects of radiotherapy;
generating a treatment plan based on the simulation thereby to permit real-time, three-dimensional dose reconstruction at the time of treatment; and
using the simulation and treatment plan during treatment fractions to achieve real-time image guidance.
In one embodiment, a high resolution, three-dimensional MRI apparatus is used to simulate the radiotherapy treatment by processing, in three-dimensions and in real-time, the target volume and the maximum possible extensions of the target volume that are likely to occur during the treatment. In certain clinical target tissue sites, this process is repeated several times on several days.
A four-dimensional treatment plan is calculated based on the mean trajectory of the target volume determined from the four-dimensional simulation. The range of likely deviations of the target volume from the mean trajectory of the target volume is also determined and a bank of three-dimensional dose distributions that cover the range of likely deviations of the target volume is calculated.
The target volume is tracked in three-dimensions and in real-time during radiotherapy treatment. Images generated using an MRI apparatus, which is interfaced to a linac, are used to track the target volume. Real-time dose distributions (i.e. four-dimensional dose distributions) are calculated at the time of treatment by drawing from information that is available from the treatment plan.
According to another aspect there is provided a computer-readable medium embodying a computer program for radiation therapy treatment, said computer program comprising:
computer program code for simulating four-dimensional aspects of radiotherapy based on subject images;
computer program code for generating a treatment plan based on the simulation thereby to permit three-dimensional dose reconstruction; and
computer program code for guiding irradiation during treatment fractions.



BRIEF DESCRIPTION OF THE DRAWINGS
Embodiments will now be described more fully with reference to the accompanying drawings in which:
FIG. 1 is a flowchart showing the steps performed during radiotherapy simulation and treatment plan generation;
FIG. 2 is a partial schematic, perspective view of an integrated linear accelerator and MRI system in one orientation;
FIG. 3 is a view in a transverse plane of the integrated linear accelerator and MRI system of FIG. 2 in another orientation;
FIG. 4 is a view in a saggital plane of the integrated linear accelerator and MRI system of FIG. 3; and
FIG. 5 is a flowchart showing the steps performed during radiation treatment to achieve real-time image guidance and three-dimensional dose reconstruction.



DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
A radiation therapy treatment method initially requires imaging of a subject and simulating four-dimensional aspects of radiotherapy. A treatment plan is generated based on the simulation such that real-time, three-dimensional radiation dose reconstruction is possible at the time of treatment. The simulation and treatment plan are used during treatment fractions to achieve real-time image guidance. Further specifics concerning the radiation therapy treatment method will now be described with reference to FIGS. 1 to 5.
As mentioned above, initially a four-dimensional (4D) radiotherapy simulation procedure is performed whereby the goal of the radiotherapy simulation is to determine the likely configuration and real-time three-dimensional motion (at the time of treatment) of a target volume, and other volumes that are critical for the success of the radiation therapy (“critical volumes”). This is accomplished by using an imaging modality that is capable of providing soft-tissue contrast and a three-dimensional, real-time imaging that can be registered to a subsequent treatment imaging device. In this particular embodiment, a high strength (for example 1.5 to 3 T) MRI apparatus is used to capture images of the target and critical volumes. Those of skill in the art will however appreciate that any suitable imaging modality may be used. The steps performed during the radiotherapy simulation procedure are shown in FIG. 1.
During the radiotherapy simulation procedure, acquired images are processed using computer software. In particular, during processing, the maximum possible target and critical volume movements that are likely to occur during radiotherapy treatment are determined (step 100). The imaged target and critical volumes are then examined to determine if the target and critical volumes are likely to change day-to-day (step 102). If not, a 4D treatment plan is generated based on the mean trajectory of the target and critical volumes (step 104) as will be described. At step 102, if the target and critical volumes are likely to change day-to-day, step 100 is repeated several times over a number of days.
The purpose of the radiotherapy simulation procedure is not to configure the patient such that a reproducible target volume position can be determined. Rather, the purpose of the radiotherapy simulation procedure is to define a patient configuration that can be reliably reproduced during subsequent radiotherapy treatment, and further to measure the target and critical volume motion that is likely to be present during the subsequent radiotherapy treatment. The result of the radiotherapy simulation procedure is the definition of a patient position (legs, torso, arms, head, any form of immobilisation, etc) that is reproduced at the time of treatment, as well as a measurement of the mean three-dimensional trajectory of internal tissue structures of the patient. Expected deviations from the average target and critical volume positions are also quantified such that the actual target and critical volume positions at the time of treatment can be estimated with a high degree of confidence.
By performing the radiotherapy simulation procedure, more accurate position data concerning the target and critical volumes within the patient is known at the time of treatment. This has the benefit that the selected treatment plan is based on a patient configuration that is more likely to be realized at the time of treatment unlike conventional radiotherapy that is based on the assumption that a static target volume position is reproduced at each treatment fraction.
As mentioned above, with the mean three-dimensional trajectory of internal tissue structures determined through the radiotherapy simulation procedure, the 4D treatment plan is created that specifically makes use of the mean three-dimensional trajectory of the target and critical volumes (step 104). The treatment plan is inherently four-dimensional, in that it explicitly accounts for target and critical volume motion (over a respiratory cycle, for example) at the time of treatment planning. The treatment plan therefore produces photon fluence distributions, and image guidance parameters to be used during radiation exposure at the time of treatment. This treatment planning is based on currently available three-dimensional treatment planning dosimetry. The range of expected deviations to the average target and critical volume positions that were measured during the four-dimensional radiotherapy simulation imaging are also calculated (step 106).
With the 4D treatment plan generated and the range of expected deviations to the average target and critical volume positions calculated, a bank of patient specific, three-dimensional radiation dose distributions that cover the range of expected deviations of the average target and critical volume positions are calculated and stored as data files (step 108). Thus, the data files include the treatment plan, as well as sufficient information that allows real-time dose reconstruction by correlation of observed variances to the treatment plan to pre-calculated perturbations of the treatment plan. The data files are then subsequently used by an integrated linear accelerator (“linac”) and MRI system during radiation dose delivery in order to compute 3D dose with sufficient speed so as to allow real-time radiation dose calculation with modest computing power as will be described.
Turning now to FIGS. 2 to 4, an integrated linac and MRI system is shown and is generally identified by reference numeral 110. As can be seen, the integrated linac and MRI system 110 includes a linac 112 and an MRI apparatus 114.
In this particular example, the MRI apparatus 114 has a 0.2 T magnetic field strength and is of the open bore type including a table 116 on which a patient P can lay. The poles 118 and 120 of a polarizing magnet are disposed above and below the table 116. The linac 112 and magnet poles 118 and 120 are mounted on a rotating gantry 122 that is supported by a frame 124.
The linac 112 includes a head 128 housing an electron beam generator 130 mounted on an arm 132 that is affixed to the gantry 122. In this manner, the linac 112 rotates in unison with the gantry 122 and thus, maintains its position relative to the magnet poles 118 and 120. Of course if desired, the linac 112 may have its own gantry. In this case, the gantry of the linac 112 and the gantry 122 are mechanically coupled so that the linac 112 rotates in unison with the magnet poles 118 and 120.
The electron beam generator 130 includes an electron gun 133, an RF generator 134, an accelerating waveguide 136, a heavy metal target 138 at one end of the accelerating waveguide 136 and a beam collimating device (not shown).
Interference reducing structure is also provided to inhibit the linac 112 and MRI apparatus 114 from interfering with one another during operation.
Alternatively, the linac 112 and MRI apparatus 114 may be mechanically coupled so that the electron beam is directed horizontally, and the magnet poles 118 and 120 are mounted vertically such that the magnetic field is horizontal, but perpendicular to the electron beam. These two components are fixed and non-movable. Variable angle electron or photon beam delivery is allowed by rotating the subject while in a sitting position. This integrated linac and MRI system configuration is particularly useful for lung cancer subjects who prefer standing/seating to laying supine, and for whom, conventional CT simulation does not allow simulation in the sitting position.
Further specifics of the integrated linac and MRI system 110 are described in Applicants' co-pending U.S. patent application Ser. No. 12/090,586 filed on even date herewith, published as U.S. Patent Application Publication No. 2009/0149735, and entitled “INTEGRATED EXTERNAL BEAM RADIOTHERAPY AND MRI SYSTEM”, the content of which is incorporated by reference. Accordingly further specifics of the integrated linac and MRI systems will not be described further herein.
In order to provide four-dimensional image guidance at the time of treatment for real-time dose reconstruction, the MRI apparatus 114 is used to image the patient in 3D real-time at the time of treatment. The MRI apparatus 114 provides exquisite soft-tissue delineation with open bore. Using standard and deformable image registration methods, the MRI images are registered to the radiotherapy simulation images (see step 200 in FIG. 5) taken previously by the very high resolution MRI apparatus. Identification of the target tissue, the surrounding critical tissue and contours of the target and critical volumes are then automatically defined from the registered images (step 202). This tissue delineation permits the intra-fraction three-dimensional motion of all important tissues to be quantified and recorded in real-time. From the contours of the target and critical volumes, the target and critical volumes can be tracked in real-time (step 204). This target and critical volume tracking information is used to control operation of the linac 112 so that the photon beam emitted by the linac 112 is properly positioned thereby to achieve real-time image guidance.
Real-time images are then correlated with the most representative situations for which there is a pre-calculated dosimetry (step 206) and real-time radiation dose information is obtained by analyzing the appropriate most representative situations (step 208). Thus, radiation doses delivered to the patient can be reconstructed in three-dimensions and in real-time. This permits the treatment to be modified if the real-time radiation dose calculation predicts a dose that is outside of a tolerance and allows the radiation therapy to be adapted if the projected total cumulative radiation dose is out of tolerance.
As will be appreciated, the image guidance allows dose escalation to be performed in a safe way, since real-time dosimetry is available. In certain tissue sites, it has been shown that dose escalation will benefit survival. In the past, dose escalation could not be done safely, since tissue motion caused too large a PTV to be used, resulting in an unacceptable toxicity to the patient. The image guidance provides for the elimination of the PTV margin, thus yielding low radiation doses to surrounding tissues. Further, real-time dosimetry calculation allows alerts to be set when normal tissue reaches a tolerance dose, thereby protecting these tissues.
As will be appreciated, three-dimensional MRI imaging is used to simulate the radiotherapy treatment by processing, in three-dimensions and in real-time, the target and critical volumes and the maximum possible extensions of the target and critical volumes that are likely to occur during the treatment.
Although illustrative embodiments have been described herein with reference to the accompanying drawings and examples, it is to be understood that the disclosure is not limited to these embodiments, and various other changes and modifications may be affected therein by one skilled in the art without departing from the scope and spirit of the disclosure. All such changes and modifications are intended to be included within the scope of the disclosure as defined by the appended claims.

## Claims

1. A radiation therapy treatment method comprising:
imaging a subject and determining a simulation of four-dimensional aspects of radiotherapy;
generating a treatment plan based on the simulation thereby to permit real-time, three-dimensional dose reconstruction at the time of treatment; and
during treatment fractions, further imaging the subject and also using the simulation and treatment plan to achieve real-time image guidance,
wherein determining a simulation comprises processing images to detect at least a target volume and movement of the target volume that is likely to occur during radiotherapy treatment,
wherein during said processing the target volume and a surrounding critical volume together with the likely target volume movement and a critical volume movement are detected, and
wherein said imaging and further imaging comprise capturing very high-resolution images of said target and critical volumes.

2. The method of claim 1 wherein during the detecting, the maximum possible target and critical volume movements are calculated and examined to determine if the target and critical volumes are likely to change over a selected period.

3. The method of claim 2 wherein if said target and critical volumes are determined likely to change, said imaging and determining are repeated over a specified period thereby to determine an averaged simulation.

4. The method of claim 3 wherein said imaging and determining are repeated over several days if the target and critical volumes are likely to change day-to-day.

5. The method of claim 2 wherein during the calculating the mean trajectory of the target and critical volumes are generated together with the range of likely deviations of the target and critical volumes from the mean trajectory.

6. The method of claim 5 wherein said treatment plan comprises photon fluence distributions and image guidance parameters to be used during treatment fractions.

7. The method of claim 5 wherein during said generating data files comprising three-dimensional radiation dose distributions that cover the range of expected deviations of the average target and critical volumes are generated.

8. A radiation therapy treatment method comprising:
imaging a subject and determining a simulation of four-dimensional aspects of radiotherapy;
generating a treatment plan based on the simulation thereby to permit real-time, three-dimensional dose reconstruction at the time of treatment; and
during treatment fractions, further imaging the subject and also using the simulation and treatment plan to achieve real-time image guidance,
wherein determining a simulation comprises processing images to detect at least a target volume and movement of the target volume that is likely to occur during radiotherapy treatment,
wherein during said processing the target volume and a surrounding critical volume together with the likely target volume movement and a critical volume movement are detected, and
wherein during the using, images of the target and critical volumes are captured and registered with images used to create the simulation allowing movement of the target and critical volumes to be tracked, the tracking information being used to control irradiation during treatment fractions.

9. The method of claim 8 wherein target tissue, surrounding critical tissue and contours of the target and critical volumes are determined from said image registration.

10. The method of claim 9 further comprising reconstructing radiation doses delivered during said treatment fractions in real time.

11. The method of claim 10 further comprising modifying said treatment fractions if delivered radiation doses are outside of tolerances.

12. A radiation therapy treatment method comprising:
imaging a subject and determining a simulation of four-dimensional aspects of radiotherapy;
generating a treatment plan based on the simulation thereby to permit real-time, three-dimensional dose reconstruction at the time of treatment; and
using the simulation and treatment plan during treatment fractions to achieve real-time image guidance,
wherein determining said simulation comprises processing said images to detect at least a target volume and movement of the target volume that is likely to occur during radiotherapy treatment,
wherein during said processing the target volume and a surrounding critical volume together with the likely target volume movement and a critical volume movement are detected, and
wherein said imaging comprises capturing very high-resolution images of said target and critical volumes.

13. The method of claim 12 wherein during the detecting, the maximum possible target and critical volume movements are calculated and examined to determine if the target and critical volumes are likely to change over a selected period.

14. The method of claim 13 wherein if said target and critical volumes are determined likely to change, said imaging and determining are repeated over a specified period thereby to determine an averaged simulation.

15. The method of claim 14 wherein said imaging and determining are repeated over several days if the target and critical volumes are likely to change day-to-day.

16. The method of claim 14 wherein during the calculating the mean trajectory of the target and critical volumes are generated together with the range of likely deviations of the target and critical volumes from the mean trajectory.

17. The method of claim 16 wherein said treatment plan comprises photon fluence distributions and image guidance parameters to be used during treatment fractions.

18. The method of claim 16 wherein during said generating data files comprising three-dimensional radiation dose distributions that cover the range of expected deviations of the average target and critical volumes are generated.

19. The method of claim 12 wherein during the using, images of the target and critical volumes are captured and registered with images used to create the simulation allowing movement of the target and critical volumes to be tracked, the tracking information being used to control irradiation during treatment fractions.

20. The method of claim 19 wherein target tissue, surrounding critical tissue and contours of the target and critical volumes are determined from said image registration.

21. The method of claim 20 further comprising reconstructing radiation doses delivered during said treatment fractions in real time.

22. The method of claim 21 further comprising modifying said treatment fractions if delivered radiation doses are outside of tolerances.