WO2017066358A1

WO2017066358A1 - Methods and systems to perform proton computed tomography

Info

Publication number: WO2017066358A1
Application number: PCT/US2016/056693
Authority: WO
Inventors: Ramdas G. PAI; Jerry D. SLATER; Reinhard W. Schulte; Ying Nie; Sudha PAI
Original assignee: Loma Linda University
Priority date: 2015-10-12
Filing date: 2016-10-12
Publication date: 2017-04-20

Abstract

Embodiments include methods and systems to perform computed tomography. Respiratory signal data and imaging data associated with a heart can be received, and a target area of the heart can be determined responsive to the imaging data. An initial energy and a direction of a proton beam to deliver a Bragg peak of the proton beam to the target area can be determined. The initial energy and the direction of the proton beam then can be modified responsive to the respiratory signal data to generate a modified initial energy and a modified direction. A proton computed tomography controller can be instructed to deliver the proton beam to the heart at the modified initial energy and the modified direction.

Description

METHODS AND SYSTEMS TO PERFORM PROTON COMPUTED TOMOGRAPHY

FIELD OF INVENTION

[0001] Embodiments of the invention relate to perform proton computed tomography and, more specifically, to methods and systems to perform proton computed tomography in connection with cardiac arrhythmia.

BACKGROUND

[0002] Cardiac arrhythmia is a set of heart diseases characterized by an irregular or abnormal heart rhythm. Cardiac arrhythmia, including atrial fibrillation, is a disease of epidemic proportions. Atrial fibrillation is a leading cause of stroke morbidity and mortality in the United States. The societal burden from arrhythmia and atrial fibrillation is steadily increasing with an aging population because age is a risk factor. Atrial fibrillation currently affects 5 million Americans, about half of whom are symptomatic, and costs the U.S. healthcare system $12 billion annually. The number of adults with atrial fibrillation may exceed 16 million by 2050.

[0003] Cardiac ablation is the only curative form of treatment for cardiac arrhythmia and atrial fibrillation, but it is often only used as a last resort due to the risks and side effects associated with conventional methods of cardiac tissue ablation. The goal of cardiac ablation is to prevent the propagation of an arrhythmia in the heart, typically by forming lesions and scar tissue that electrically isolate the pulmonary veins. Methods of cardiac ablation include the use of a catheter to deliver ablative energy such as radiofrequency, ultrasound, laser, or cryothermic energy. However, these methods are highly invasive and carry serious risk of bleeding and infection.

SUMMARY

[0004] Systems and methods according to embodiments of the invention advantageously provide solutions to these problems the inventors have recognized in the treatment of cardiac arrhythmia. For example, the inventors have recognized that although catheter ablation can be used to treat cardiac arrhythmia, catheter ablation can be associated with certain negative side effects, including bleeding at the site when the catheter is removed, infection, blood clot formation within the blood vessel, and bleeding under the skin (including formation of a hematoma).

[0005] In view of these and other problems associated with the use of catheter ablation, methods and systems are provided to perform computed tomography (CT) to treat a patient that has experienced cardiac arrhythmia with particle Bragg peaks, for example. The sharp dose peak (Bragg peak) that occurs at the end of proton beams can be used to treat cardiac arrhythmias. A proton beam can be delivered by a proton computed tomography (pCT) machine, which can also be used to image the patient's heart to determine a target area of the heart for the proton beam. Further, to minimize the effect of respiratory motion and to establish a regular pattern of respiratory motion, the patient's lungs can be ventilated with small pulses of small tidal volumes delivered to the lungs rapidly, such as about 300 times per minute. Using such ventilation, such as high-frequency jet ventilation, can allow the delivery of Bragg peaks to be planned very accurately. Additionally, the correct position of the Bragg peak then can be verified with an imaging CT modality using penetrating proton beams. Immunohistochemical verification also can be used. For example, a combination of antibodies that are tagged with fluorescence dyes directed to conductive heart tissue and proteins formed in response to radiation damage to cells can be used to verify that the Bragg peak reached a target area of the heart.

[0006] Embodiments can include methods, systems, apparatuses, machines, and computer- readable media. For example, a method according to an embodiment can include instructing a first controller to begin high frequency jet ventilation and receiving respiratory signal data associated with the high frequency jet ventilation. A method also can include determining motion associated with respiration during the high frequency jet ventilation responsive to receipt of the respiratory signal data. Further, a method can include creating a model representing the motion associated with respiration and instructing a second controller to image, by a computed tomography scanner, a heart. Still further, a method can include receiving imaging data responsive to imaging the heart and determining a target area of the heart responsive to the imaging data. A method then can include determining an initial energy and a direction of a proton beam to deliver a Bragg peak of the proton beam to the target area. In addition, a method can include modifying the initial energy and the direction of the proton beam responsive to the model representing the motion associated with respiration to generate a modified initial energy and a modified direction. A method also can include instructing the second controller to deliver the proton beam to the heart at the modified initial energy and the modified direction during the high frequency jet ventilation.

[0007] In some instances, the computed tomography scanner can be a proton computed tomography scanner, and the proton beam can be delivered by the proton computed tomography scanner. Further, the target area can be associated with a pulmonary vein opening into the heart. Imaging the heart can be performed during the high frequency jet ventilation. Additionally, a method further can include, after delivering the proton beam to the heart, instructing the second controller to image the heart to determine whether the Bragg peak of the proton beam reached the target area. The high frequency jet ventilation can include high frequency bursts of oxygen to lungs through thin-jet catheters along with an outwardly open airway.

[0008] Another method can include receiving respiratory signal data and receiving imaging data associated with a heart. Further, a method can include determining a target area of the heart responsive to the imaging data and determining an initial energy and a direction of a proton beam to deliver a Bragg peak of the proton beam to the target area. A method also can include modifying the initial energy and the direction of the proton beam responsive to the respiratory signal data to generate a modified initial energy and a modified direction. A method further can include instructing a controller to deliver the proton beam to the heart at the modified initial energy and the modified direction.

[0009] In some circumstances, determining the initial energy and the direction of the proton beam to deliver the Bragg peak of the proton beam to the target area can include determining a penetration depth and associated beam energy to align the Bragg peak of the proton beam with the target area. Additionally, instructing the controller to deliver the proton beam to the heart can include instructing the controller to deliver one or more scanning proton beams from a plurality of angles.

[0010] Further, determining the target area of the heart can include obtaining, from the imaging data, measured data for one or more protons of a plurality of protons that pass through a body. The measured data can include information indicative of first and second tracks of the one or more protons, and the first and second tracks can correspond to the one or more protons' trajectories before and after its passage through the body, respectively. The measured data further can include information indicative of an interaction quantity of the one or more protons resulting from its passage through the body. Determining the target area of the heart also can include, for the one or more protons, estimating a path taken by the one or more protons within the body. The estimating can be based at least in part on the first and second tracks of the one or more protons. Additionally, determining the target area of the heart can include arranging the interaction quantity and the estimated path of the one or more protons such that the passage of the one or more protons through the body is represented as or is representable as a system of equations Ax=b, where x is a body parameter distribution of a parameter associated with the body, b represents the interaction quantity of the one or more protons resulting from interactions along a respective path of the one or more protons in the body, and A is an operator that operates on x to yield b. The operator A can have information indicative of the estimated path of the one or more protons in the body. Further, the system of equations can be configured so as to have a plurality of solutions. Determining the target area of the heart also can include estimating an initial solution for the system of equations. Further, determining the target area of the heart can include obtaining one or more feasible solutions among the plurality of solutions by perturbing an existing solution. The one or more feasible solutions can have a superior characteristic for a quantity associated with a reconstruction of the body parameter distribution than another solution obtained without the perturbation of the existing solution. In addition, determining the target area of the heart can include calculating the body parameter distribution based on a selected one of the one or more feasible solutions.

[0011] In some instances, receiving imaging data associated with a heart can include obtaining a representation of a body. The representation can include information about structures within or on the body. Further, determining the target area of the heart can include identifying a volume of interest in the representation of the body. In addition, determining the initial energy and the direction of the proton beam to deliver the Bragg peak of the proton beam to the target area can include dividing the volume of interest into a plurality of sub-volumes. Determining the initial energy and the direction of the proton beam to deliver the Bragg peak of the proton beam to the target area also can include, for each of the plurality of sub-volumes, setting a dose constraint, determining one or more proton treatment plans that satisfy the dose constraints for each of the plurality of sub-volumes, and from the one or more proton treatment plans, selecting a proton treatment plan that satisfies treatment criteria. Further, delivering the proton beam to the heart can include delivering protons to the body based on the selected proton treatment plan. Dividing the volume of interest into a plurality of sub- volumes can include dividing the volume of interest into a total number of voxels and identifying one or more features of interest. Further, dividing the volume of interest into a plurality of sub-volumes can include ordering the voxels according to increasing distance from a nearest feature of interest. Dividing the volume of interest into a plurality of sub-volumes also can include, for each of the plurality of sub-volumes, selecting a fractional value corresponding to a ratio of a size of the sub-volume to a size of the volume of interest. Dividing the volume of interest into a plurality of sub- volumes still further can include, for each of the plurality of sub-volumes, defining a sub-volume as a group of a number of consecutive voxels from the ordered voxels. A ratio of the number of consecutive voxels to the total number of voxels can be approximately equal to the fractional value for the sub- volume.

[0012] An exemplary system can include one or more processors and a non-transitory computer- readable medium in communication with the one or more processors. The non-transitory computer-readable medium can have one or more computer programs stored thereon that, when executed by the one or more processors, cause the system to perform certain steps. For example, the one or more computer programs stored can cause the system to receive respiratory signal data and receive imaging data associated with a heart and determine a target area of the heart responsive to the imaging data. Further, the one or more computer programs stored can cause the system to determine an initial energy and a direction of a proton beam to deliver a Bragg peak of the proton beam to the target area. The one or more computer programs stored also can cause the system to modify the initial energy and the direction of the proton beam responsive to the respiratory signal data to generate a modified initial energy and a modified direction and instruct a controller to deliver the proton beam to the heart at the modified initial energy and the modified direction.

[0013] A system also can include a proton computed tomography scanner in some instances. Further, receiving the imaging data associated with the heart can be by the proton computed tomography scanner, and delivering the proton beam to the heart can be by the proton computed tomography scanner. Additionally, the target area can be associated with a pulmonary vein opening into the heart. In some circumstances, the imaging data associated with the heart can be obtained during high frequency jet ventilation. The high frequency jet ventilation can include high frequency bursts of oxygen to lungs through thin-jet catheters along with an outwardly open airway. In addition, the one or more computer programs, when executed by the one or more processors, further can cause the system to, after instructing the controller to deliver the proton beam to the heart, image the heart to determine whether the Bragg peak of the proton beam reached the target area. Determining the initial energy and the direction of the proton beam to deliver the Bragg peak of the proton beam to the target area can include determining a penetration depth and associated beam energy to align the Bragg peak of the proton beam with the target area. Further, instructing the controller to deliver the proton beam to the heart can include instructing the controller to deliver one or more scanning proton beams from a plurality of angles.

[0014] Determining the target area of the heart can include obtaining, from the imaging data, measured data for one or more protons of a plurality of protons that pass through a body. The measured data can include information indicative of first and second tracks of the one or more protons, and the first and second tracks corresponding to the one or more protons' trajectories before and after its passage through the body, respectively. The measured data further can include information indicative of an interaction quantity of the one or more protons resulting from its passage through the body. Determining the target area of the heart also can include, for the one or more protons, estimating a path taken by the one or more protons within the body, and the estimating can be based at least in part on the first and second tracks of the one or more protons. Additionally, determining the target area of the heart can include arranging the interaction quantity and the estimated path of the one or more protons such that the passage of the one or more protons through the body is represented as or is representable as a system of equations Ax=b, where x is a body parameter distribution of a parameter associated with the body, b represents the interaction quantity of the one or more protons resulting from interactions along a respective path of the one or more protons in the body, and A is an operator that operates on x to yield b. The operator A can have information indicative of the estimated path of the one or more protons in the body. Further, the system of equations can be configured so as to have a plurality of solutions. Determining the target area of the heart also can include estimating an initial solution for the system of equations and obtaining one or more feasible solutions among the plurality of solutions by perturbing an existing solution. The one or more feasible solutions can have a superior characteristic for a quantity associated with a reconstruction of the body parameter distribution than another solution obtained without the perturbation of the existing solution. Determining the target area of the heart still further can include calculating the body parameter distribution based on a selected one of the one or more feasible solutions.

[0015] Yet another method can include initiating high frequency jet ventilation toward a target area and receiving respiratory signal data associated with the high frequency jet ventilation of the target area. Further, a method can include determining motion associated with respiration in the target area during the high frequency jet ventilation responsive the respiratory signal data. A method also can include generating a simulation model representing the motion associated with respiration and initiating a computed tomography scanner toward the target area. In addition, a method can include receiving computed tomography imaging data responsive to imaging the target area and determining a smaller subset of the target area responsive to the computed tomography imaging data. A method also can include determining an initial energy and a direction of a proton beam to deliver a Bragg peak of the proton beam to the smaller subset of the target area. Still further, a method can include modifying the initial energy and the direction of the proton beam responsive to the simulation model representing the motion associated with respiration to generate a modified initial energy and a modified direction. A method also can include delivering a proton beam to the smaller subset of the target area at the modified initial energy and the modified direction during the high frequency jet ventilation. In some instances, the step of delivering a proton beam can include operating a proton beam controller to apply the proton beam to the smaller subset of the target area with modified energy and modified direction when high frequency jet ventilation is occurring.

BRIEF DESCRIPTION OF DRAWINGS

[0016] These and other features, aspects, and advantages of the present invention will become better understood with regard to the following descriptions, claims, and accompanying drawings. It is to be noted, however, that the drawings illustrate only several embodiments of the invention and are therefore not to be considered limiting of the invention's scope as it can admit to other equally effective embodiments.

[0017] FIG. 1 is a schematic diagram of a computed tomography machine according to an embodiment of the invention.

[0018] FIG. 2 is a schematic diagram of a human heart. [0019] FIG. 3 is a schematic diagram of a human heart. [0020] FIG. 4 is a schematic diagram of a human heart.

[0021] FIG. 5 is a schematic diagram of a method according to an embodiment of the invention.

[0022] FIGS. 6A-B is a schematic diagram of a method according to an embodiment of the invention.

[0023] FIG. 7 is a schematic diagram of a system according to an embodiment of the invention.

[0024] FIG. 8 is a schematic diagram of a system according to an embodiment of the invention.

[0025] FIG. 9 is a schematic diagram of a system according to an embodiment of the invention.

[0026] FIG. 10 is a schematic diagram of a system according to an embodiment of the invention.

[0027] FIG. 11 is a schematic diagram of a system according to an embodiment of the invention.

[0028] FIG. 12 is a schematic diagram of a system according to an embodiment of the invention.

[0029] FIG. 13 is a schematic diagram of a method according to an embodiment of the invention.

DETAILED DESCRIPTION

[0030] So that the manner in which the features and advantages of the embodiments of systems, machines, media, apparatuses and methods of the present invention, as well as others, which will become apparent, may be understood in more detail, a more particular description of the embodiments of systems, machines, media, apparatuses and methods of the present invention briefly summarized above may be had by reference to the embodiments thereof, which are illustrated in the appended drawings, which form a part of this specification. It is to be noted, however, that the drawings illustrate only various embodiments of the embodiments of systems, machines, media, apparatuses and methods of the present invention and are therefore not to be considered limiting of the embodiments of systems, machines, media, apparatuses and methods of the present invention's scope as it may include other effective embodiments as well.

[0031] Cardiac arrhythmia is a set of heart diseases characterized by an irregular or abnormal heart rhythm. To treat prevent the propagation of arrhythmia, lesions and scar tissue can be formed in the heart near the pulmonary veins to thereby electrically isolate the pulmonary veins. For example, a normal electrical pattern 112 in a heart 110 is illustrated in FIG. 2. In contrast, abnormal electrical pathways 122 in a heart 120 are illustrated in FIG. 3, for example. The pulmonary veins— the left superior pulmonary vein 134, the left inferior pulmonary vein 136, the right inferior pulmonary vein 138, and the right superior pulmonary vein 140— of a heart 130 are illustrated in FIG. 4, for example, along with the superior vena cava 132. Cardiac ablation to form such lesions or scar tissue can be performed using a catheter to deliver ablative energy, but proton beams also can be used to perform cardiac ablation, such as by use of computed tomography (CT). An exemplary CT scanner 102 is illustrated in FIG. 1, for example. As illustrated, a CT scanner 102 can be associated and in communication with one or more computers 104, including one or more controllers to control its operations.

[0032] Proton therapy can be an efficacious way to selectively destroy targeted cells because protons have unique dosimetric characteristics compared to other radiation, such as electrons or photons. Protons deposit most of their energy near the end of their path through a tissue, in contrast to photons, for example, which deposit an exponentially decreasing amount of energy as a function of penetration depth. More specifically, protons have a sharp energy loss at the end of their travel in a given material. Such a sharp energy loss has a relatively sharp peak called a Bragg peak. Few protons having similar initial beam energy penetrate beyond depth of the Bragg peak. Thus, a proton therapy system can achieve greater targeted treatment compared to photon-based therapy, for example, by exposing targeted tissue to more radiation and/or healthy tissue to less radiation. Further, an operator can control a depth of penetration and a dose profile of protons by selecting an initial energy of the proton treatment beams. Generally, a deeper Bragg peak can be achieved by a higher energy proton beam.

[0033] For these and other reasons, the use of proton beams can be advantageous for treating atrial fibrillation or other cardiac arrhythmia without invasive insertion of a catheter. In view of these advantages, methods and systems disclosed herein can relate to treating a patient that has experienced cardiac arrhythmia or atrial fibrillation by delivering one or more proton treatment beams to the patient's heart. For example, one or more proton treatment beams can be delivered to create an annular scar at or near the entry to a patient's pulmonary vein.

[0034] Before the delivery of proton treatment beams, the patient can be imaged in order to locate the target cardiac area for treatment. Protons can also be used to develop a detailed image of a patient in a process known as proton computed tomography (pCT). The combined use of protons for imaging a patient and for ablating cardiac tissue provides unique synergy in the treatment of cardiac arrhythmia. Because the same or similar equipment or system can be used to image and to treat a patient with protons, both processes can be performed in a single, efficient session with minimal movement of the patient. In some embodiments, the patient can be kept ventilated and anesthetized during both treatments to provide maximum precision in delivery of the imaging protons and proton treatment beams.

[0035] When using imaging means other than pCT, uncertainty can arise in part from characterizing the medium with a probe or imaging radiation different from the therapy radiation that interacts differently with the medium. For example, calculating proton range in a sample using X-ray CT measurements can yield an uncertainty of about 3.5% of a proton's range. In different portions of a human body, this uncertainty equates to different distances, such as about 3-5 mm in brain and about 10-12 mm in pelvis. Additional uncertainties can be introduced due to the presence of materials with unknown densities, as well as streak artifacts in the X-ray CT images. Using pCT techniques can reduce the range uncertainty to about 1% or less of the proton's range.

[0036] Proton therapy and imaging can be improved by minimizing patient motion. In some embodiments, the present disclosure relates to combining methods for reducing motion of a patient due to respiration with methods of pCT imaging and proton treatment for cardiac arrhythmia. High frequency jet ventilation (HFJV) can be used to reduce or eliminate patient motion due to respiration. The combination of HFJV with proton therapy and pCT imaging can be particularly effective for treating cardiac arrhythmia. Reducing respiratory movement with HFJV can maximize the therapeutic advantages due to both the precise energy delivery from proton Bragg peaks and the fine resolution capable with pCT imaging. The precision achieved by these three tools working in concert can synergistically contribute to an accurate ablation of cardiac tissue sufficient to electrically isolate pulmonary veins with minimal damage to surrounding tissue.

[0037] An exemplary method according to an embodiment is illustrated in FIG. 5, for example. After the method starts at step 202, a method can include both receiving imaging data (such as pCT data) at step 204 and receiving respiratory signal data (such as data from an ECG) at step 212. After receiving imaging data at step 204, a method can include converting the imaging data into an image representing, for example, a heart within a body at step 206. Embodiments thus can include transforming imaging data into an image, for example. A method then can include determining a target area of the heart at step 208 to which the Bragg peak of a proton beam could be directed to form a lesion or scar tissue near the pulmonary veins. After determining the target area at step 208, a method can include determining a planned level of initial energy and a planned direction of the proton beam to deliver the Bragg peak of the beam to the target area at step 210. Before, after, or at the same time as analyzing this imaging data, a method can include determining respiratory motion at step 214 based on the received respiratory motion. A method then can include creating a model representing that respiratory motion at step 216 and further can include generating a simulation of the motion. Further, the model can be updated and modified as additional respiratory signal data is received at step 212. The planned initial energy level and planned direction of the proton beam determined at step 210 can be modified based on the respiratory model at step 218. Further, a method can include instructing a controller, such as a proton beam controller, to deliver a proton beam directed to the target area at step 220 before the method, as illustrated, ends at step 222.

[0038] Another method according to one or more embodiments is illustrated in FIGS. 6A-B, for example. After the method starts at step 230, a method can include both instructing a first controller (such as a controller associated with a CT scanner) to scan/image a heart at step 232 and instructing another controller (or the same controller, in some instances) to begin high- frequency jet ventilation (HFJV) operation at step 242. A method then can include receiving imaging data at step 234 and receiving HFJV respiratory signal data at step 244. After receiving imaging data at step 234, a method can include converting the imaging data into an image representing, for example, a heart within a body at step 236. A method then can include determining a target area of the heart at step 238 to which the Bragg peak of a proton beam could be directed to form a lesion or scar tissue near the pulmonary veins. After determining the target area at step 238, a method can include determining a planned level of initial energy and a planned direction of the proton beam to deliver the Bragg peak of the beam to the target area at step 240. Before, after, or at the same time as analyzing this imaging data, a method can include determining respiratory motion at step 246 based on the received respiratory motion. A method then can include creating a model representing that respiratory motion at step 248 and further can include generating a simulation of the motion. Further, the model can be updated and modified as additional respiratory signal data is received at step 242, in some instances. The planned initial energy level and planned direction of the proton beam determined at step 240 can be modified based on the respiratory model at step 250. Further, a method can include instructing a controller, such as a proton beam controller, to deliver a proton beam directed to the target area at step 252. In order to verify that the Bragg peak reached the target area, an additional image of the heart can be taken (such as contrast-enhanced CT scans using contrast injections, such as fluorescence dyes, which can be analyzed by color), and additional imaging data therefore can be received at step 254. The additional data can be analyzed at step 256 to determine whether the Bragg peak reached the target area at step 258 before the method, as illustrated, ends at step 222. In some instances, the outcome of step 258 can be used as feedback to improve the accuracy of the proton beam targeting process.

[0039] Systems according to one or more embodiments, such as system 300, can include one or more processors 302 and one or more computer memories 304, as illustrated in FIG. 7, for example. Further, the one or more computer memories 304 can have one or more computer programs 306 including instructions stored thereon. As illustrated in FIG. 7, a system 300 also can be in communication with other computers, controllers, and/or devices, such as a scanning/imaging device 308 (for example, a CT scanner or a pCT scanner), a radiation (such as pCT) delivery device 310, a respiratory controlling device 312 (such as a controller for a ventilator or ventilating machine), a respiratory monitoring device 314 (such as an ECG machine), and one or more input/output devices 316. In some instances, a scanning/image device 308 can be a separate device from a radiation delivery device 310, as illustrated in FIGS. 7 and 8, but they can be one device, such as scanning/imaging and radiation delivery device 318, as illustrated in FIGS. 9 and 10. A system 400 as illustrated in FIG. 8, for example, or a system 600 as illustrated in FIG. 10, for example, can be similar to system 300 as illustrated in FIG. 7 or a system 500 as illustrated in FIG. 9, respectively, for example, but can include additional components, such as one or more of scanning/imaging device 308, a radiation delivery device 310, a respiratory controlling device 312, a respiratory monitoring device 314, and one or more input/output devices 316. Alternatively or in addition to being in communication with other devices that can provide respiratory and imaging data as illustrated in FIGS. 7-10, a system 700 can be in communication with one or more databases 320 that include data such as respiratory data 322 and imaging data 324, as illustrated in FIG. 11, for example. Further, a system 800 can include such database(s) in some instances, as illustrated in FIG. 12, for example.

[0040] In addition to proton beams, carbon ion beams can be used in one or more embodiments. Imaging can be performed using a CT machine such as a pCT machine or scanner or an X-ray CT machine or scanner. Bragg peaks can include unmodulated pencil beam Bragg peaks.

[0041] Proton therapy can be an efficacious way to selectively destroy targeted cells because protons have unique dosimetric characteristics compared to other radiation, such as electrons or photons. Protons deposit most of their energy near the end of their path through a tissue, compared to photons, for example, which deposit an exponentially decreasing amount of energy as a function of penetration depth. Protons have a sharp energy loss at the end of their travel in a given material. Such a sharp energy loss has a relatively sharp peak called a Bragg peak and few of the protons having similar initial beam energy penetrate beyond depth of the Bragg peak. Thus, a proton therapy system can achieve greater targeted treatment compared to photon-based therapy (e.g., by exposing targeted tissue to more radiation and/or healthy tissue to less radiation) because an operator can control a depth of penetration and a dose profile of protons by selecting an initial energy of the proton treatment beams. Generally, a deeper Bragg peak can be achieved by a higher energy proton beam.

[0042] For these and other reasons, the use of proton beams can be advantageous for treating atrial fibrillation or other cardiac arrhythmia without invasive insertion of a catheter. In some embodiments, the present disclosure relates to treating a patient that has experienced cardiac arrhythmia or atrial fibrillation by delivering one or more proton treatment beams to create an annular scar at or near the entry to a patient's pulmonary vein. Some examples of proton therapy systems and techniques are described in U.S. Patent No. US 8,644,571 B l, titled "Intensity- Modulated Proton Therapy," filed on December 5, 2012.

[0043] Before the delivery of proton treatment beams, the patient can be imaged in order to locate the target cardiac area for treatment. Protons can also be used to develop a detailed image of a patient in a process known as proton computed tomography (pCT). Some examples of pCT systems and techniques are described in U.S. Patent Publication No. US 2011/0220794 Al, titled "Systems and Methodologies for Proton Computed Tomography," filed on February 11, 2011. The combined use of protons for imaging a patient and for ablating cardiac tissue provides unique synergy in the treatment of cardiac arrhythmia. Because the same or similar equipment or system can be used to image and to treat a patient with protons, both processes can be performed in a single, efficient session with minimal movement of the patient. In some embodiments, the patient can be kept ventilated and anesthetized during both treatments to provide maximum precision in delivery of the imaging protons and proton treatment beams.

[0044] When using imaging means other than pCT, uncertainty can arise in part from characterizing the medium with a probe or imaging radiation different from the therapy radiation that interacts differently with the medium. For example, calculating proton range in a sample using X-ray CT measurements can yield an uncertainty of about 3.5% of a proton's range. In different portions of a human body, this uncertainty equates to different distances, such as about 3-5 mm in brain and about 10-12 mm in pelvis. Additional uncertainties can be introduced due to the presence of materials with unknown densities, as well as streak artifacts in the X-ray CT images. Using pCT techniques can reduce the range uncertainty to about 1% or less of the proton's range.

[0045] Proton therapy and imaging can be improved by minimizing patient motion. In some embodiments, the present disclosure relates to combining methods for reducing motion of a patient due to respiration with methods of pCT imaging and proton treatment for cardiac arrhythmia. High frequency jet ventilation (HFJV) can be used to reduce or eliminate patient motion due to respiration. The combination of HFJV with proton therapy and pCT imaging can be particularly effective for treating cardiac arrhythmia. Reducing respiratory movement with HFJV can maximize the therapeutic advantages due to both the precise energy delivery from proton Bragg peaks and the fine resolution capable with pCT imaging. The precision achieved by these three tools working in concert can synergistically contribute to an accurate ablation of cardiac tissue sufficient to electrically isolate pulmonary veins with minimal damage to surrounding tissue.

[0046] Some examples of HFJV are described in Alina Santiago et al., Reproducibility Of Target Coverage In Stereotactic Spot Scanning Proton Lung Irradiation Under High Frequency Jet Ventilation, Radiotherapy and Oncology 109 (2013) 45-50. Further examples of HFJV are described in Peter Fritz et al., High- Frequency Jet Ventilation For Complete Target Immobilization And Reduction Of Planning Target Volume In Stereotactic High Single-Dose Irradiation Of Stage I Non-Small Cell Lung Cancer And Lung Metastases, Int. J. Radiation Oncology Biol. Phys., Vol. 78, No. 1, pp. 136-142, 2010, which is hereby incorporated by reference in its entirety and attached as an appendix. Further examples of HFJV are described in Fang-Fang Yin et al., Extracranial Radiosurgery: Immobilizing Liver Motion In Dogs Using High-Frequency Jet Ventilation And Total Intravenous Anesthesia, Int. J. Radiation Oncology Biol. Phys., Vol. 49, No. 1, pp. 211-216, 2001.

[0047] Energy from a proton beam can be precisely delivered at the Bragg peak of the proton beam. In some embodiments, the Bragg peaks of the proton treatment beams can be aimed at a target area of cardiac tissue (e.g., a target cardiac area) in a patient to ablate at least some of the cardiac tissue in the target area and thereby to treat atrial fibrillation or other cardiac arrhythmia. As used herein, the term "cardiac tissue" has its broadest reasonable interpretation, including but not limited to, any tissue in or around a patient's heart (e.g., tissue connected to a patient's heart and associated with a cardiac arrhythmia). In some embodiments, as shown in Figure 13, a method of treating a patient that has experienced cardiac arrhythmia can include: ventilating a patient with high frequency jet ventilation at step 270; performing proton computed tomography on the patient while ventilating the patient with high frequency jet ventilation at step 272; positioning the patient to receive one or more proton beams at least one target cardiac area at step 276; and delivering the one or more proton beams to the at least one target cardiac area while ventilating the patient with high frequency jet ventilation at step 278. In some embodiments, a method can include calculating the proton treatment beam associated with positioning Bragg peaks at the at least one target area at step 274. In some embodiments, a single proton delivery system configured to provide protons for both pCT and ablation therapy can be utilized for both the treatment and pCT imaging steps.

[0048] In some embodiments, a method of treating a patient that has experienced cardiac arrhythmia or atrial fibrillation can include one or more of the following: ventilating a patient under anesthesia with high frequency jet ventilation that provides at least about 150 breaths per minute at low tidal volumes; delivering one or more imaging protons to the patient or a portion of the patient; tracking trajectories of the one or more imaging protons both before and after interacting with the patient or portion of the patient; imaging the patient or portion of the patient based at least in part on the tracked trajectories of the one or more imaging protons while ventilating the patient with the high frequency jet ventilation; locating at least one target cardiac area associated with a cardiac arrhythmia in the patient based at least in part on an image of the patient or portion of the patient; determining a penetration depth and associated beam energy for Bragg peaks of one or more proton treatment beams to align with the at least one target cardiac area; positioning the patient to receive the Bragg peaks of the one or more proton treatment beams at the at least one target cardiac area; and delivering one or more proton treatment beams to the at least one target cardiac area while ventilating the patient with the high frequency jet ventilation; wherein the delivering of one or more imaging protons step and the delivering one or more proton treatment beams step utilize a common source of protons.

[0049] Methods of treating a patient that has experienced cardiac arrhythmia can include ventilating a patient with HFJV. Respiratory motion can create uncertainty in the delivery of protons to ablate cardiac tissue; it can be difficult to accurately aim proton beams at moving cardiac tissue. The motion of cardiac tissue due to the beating of the patient's heart can be one to two millimeters, which can be tolerable during delivery of proton beams. In contrast, the motion of cardiac tissue due to respiration can be one or more centimeters, which can exceed tolerable limits for ablation of cardiac tissue with proton beams. HFJV can greatly reduce or eliminate motion due to a patient's respiration and can establish a consistent, predictable pattern for the remaining motion. Examples of systems and techniques regarding HFJV are described in the: Reproducibility Of Target Coverage In Stereotactic Spot Scanning Proton Lung Irradiation Under High Frequency Jet Ventilation; High-Frequency Jet Ventilation For Complete Target Immobilization And Reduction Of Planning Target Volume In Stereotactic High Single-Dose Irradiation Of Stage I Non-Small Cell Lung Cancer And Lung Metastases; and Extracranial Radiosurgery: Immobilizing Liver Motion In Dogs Using High-Frequency Jet Ventilation And Total Intravenous Anesthesia.

[0050] HFJV can be the rapid continuous exchange of small tidal volumes of air in a patient's lungs. HFJV can in some embodiments include blowing oxygen under pressure into a patient's airways in high-frequency bursts through thin-jet catheters, pushing endotracheal air toward a patient's alveoli, and allowing breath to be passively released through an outwardly open airway. A patient can be transitioned onto HFJV from conventional ventilation. In some embodiments, a patient can be transitioned off of HFJV onto conventional ventilation. HFJV can provide about 150 breathes per minute to a patient. In some embodiments, HFJV can be pulsed at a frequency of about 300 to about 400 times per minute. In some embodiments, HFJV can provide tidal volumes of about 50 mL.

[0051] In some embodiments, one or more of the following parameters can be monitored during HFJV: end tidal C0₂, pulse oximetry, arterial blood gases, respiration rate, heart rate, and arterial blood pressure. Settings for HFJV including tidal volume and respiratory frequency can be based at least in part on end tidal C0₂ and blood gases. The inspiration to expiration ratio and fractional inspired 0₂ during HFJV can, in some embodiments, also be controlled to maintain pulse oximetry above a certain threshold, for example above 97%. In some embodiments, one or more of parameters such as frequency, driving pressure, fractional inspired 0₂, and inspiratory time percent for operating HFJV can be adjusted based on any one or more of pulse oximetry, transcutaneous C0₂, and arterial blood gases.

[0052] A method of treating a patient that has experienced cardiac arrhythmia can include imaging a patient with pCT. An image of subcutaneous tissue can be used in treating cardiac arrhythmia to locate and target an area for ablation. In some embodiments, a patient's internal cardiac tissue can be imaged using protons, such as through the use of pCT. pCT can include delivering one or more imaging protons to the patient, tracking trajectories of one or more of the imaging protons both before and after interacting with the patient, and imaging the patient based at least in part on the tracked trajectories of the one or more imaging protons. Imaging protons can be one or more protons directed at imaging a patient or portion of a patient. Imaging a patient with pCT can provide information regarding the proton penetration depth for the imaged medium, e.g., the imaged portion of the patient's body. In some embodiments, knowledge regarding the penetration depth of protons through a patient can be utilized in planning the delivery of proton treatment beams to a target cardiac area. In some embodiments, the same source of protons or proton beams can be used for imaging a patient with pCT as for ablating a target cardiac area. In some embodiments, the same system can be used for imaging a patient with pCT as for ablating a target cardiac area.

[0053] In some embodiments, pCT includes obtaining measured data for at least one proton of a plurality of protons that pass through an object, which can be a patient or a portion of a patient. The measured data can include information about first and second tracks for the at least one proton. The first and second tracks correspond to the at least one proton's trajectories before and after its passage through the object, respectively. The measured data can include information indicative of an interaction quantity of the at least one proton resulting from its passage through the object. In some embodiments, pCT can include estimating a path taken by at least one proton within the object based at least in part on the first and second tracks of the at least one proton. pCT can include arranging the interaction quantity and the estimated paths of the at least one proton such that the passages of the protons through the object is represented as or is representable as a system of equations Ax=b where x is a patient parameter distribution of a parameter associated with the object, b represents the interaction quantity of the at least one proton resulting from interactions along a respective path of the at least one proton in the object, and A is an operator that operates on x to yield b. The operator A can include information indicative of the estimated path of the at least one proton in the object. The system of equations Ax=b can be configured so as to have a plurality of solutions. In some embodiments, pCT can include estimating an initial solution for the system of equations. In some embodiments, pCT can include obtaining one or more feasible solutions among the plurality of solutions, by perturbing an existing solution, the one or more feasible solutions having a superior characteristic for a quantity associated with a reconstruction of the object parameter distribution than another solution obtained without the perturbation of the existing solution. pCT can include calculating the object parameter distribution based on a selected one of the one or more feasible solutions. Examples of systems, methods, and techniques regarding pCT are described in U.S. Patent Publication No. US 2011/0220794 Al, titled "Systems and Methodologies for Proton Computed Tomography," filed on February 11, 2011.

[0054] A method of treating a patient that has experienced cardiac arrhythmia can include locating a target cardiac area associated with a cardiac arrhythmia in the patient based at least in part on an image of the patient. The target cardiac area can be any tissue that if ablated could interrupt, prevent, or otherwise treat an arrhythmia in the patient's heart. In some embodiments, a physician or medical professional can identify the target cardiac area for ablating. The target cardiac area can be tissue that if ablated could electrically isolate the pulmonary veins. In some embodiments, the target cardiac area can be an annular portion at the entry of the patient's pulmonary vein.

[0055] The target cardiac area can be located by referencing a pCT image of the patient. In some embodiments, a physician or medical professional can determine the location of the target cardiac area by examining a pCT image of a patient. A pCT image of the patient can provide a location of the target cardiac area within the patient. The location can be described in terms of penetration depth for protons to reach the target cardiac area. In some embodiments, the location of the target cardiac area can be described in units of distance measured from the surface of a patient's skin in one or more directions. In some embodiments, the location of the target cardiac area can be described with reference to a point external to the patient.

[0056] A method of treating a patient that has experienced cardiac arrhythmia can include calculating a proton treatment for ablating the target cardiac area. In some embodiments, a method of treating a patient that has experienced cardiac arrhythmia can include: identifying at least one target cardiac area ablation of which can treat a patient's cardiac arrhythmia, locating the at least one target cardiac area with reference to a pCT image of the patient or portion of the patient, planning the dose of protons to be delivered to the target cardiac area, and calculating the parameters for one or more proton treatment beams to deliver the planned dose to the target cardiac area. Examples of systems and techniques for proton therapy are described in US Patent No. US 8,644,571 B l, titled "Intensity-Modulated Proton Therapy," filed on December 5, 2012.

[0057] Calculating a proton treatment can include determining a penetration depth and associated beam energy for the Bragg peaks of one or more proton treatment beams to align with the target cardiac area. The Bragg peaks of one or more proton treatment beams and the target cardiac area can be aligned when the proton beams deliver sufficient energy to ablate the target cardiac area. In some embodiments, the Bragg peaks of one or more proton treatment beams and the target cardiac area can be aligned when the spatial position of the one or more Bragg peaks overlap with at least a portion of the target cardiac area. In some embodiments, the position of the one or more Bragg peaks for the one or more proton treatment beams can change over time to align with different portions of the target cardiac area. In some embodiments, the parameters of one or more proton treatment beam can be adjusted over time to spatially move one or more of the Bragg peaks about the target cardiac area.

[0058] Calculating a proton treatment for ablating the target cardiac area can include planning a dose of protons to be delivered to the target cardiac area. Planning the dose of protons to be delivered can be done to insure formation of sufficient electrical isolation to treat a cardiac arrhythmia, while avoiding excessive damage to surrounding tissues. In some embodiments, the proton dose can be inversely planned. A dose plan for protons can include adjustments to the parameters for one or more proton treatment beams over time during treatment. Parameters for one or more proton treatment beams can include, in some embodiments, one or more of the following: proton energy, initial beam intensity, intensity modulations, angle of incidence on the patient, external distance from the patient, scanning patterns, duration, and movement. In some embodiments, one or more parameters calculated for one or more proton treatment beams can be adjusted over time during ablation of a target cardiac area. In some embodiments, proton treatment beams can be delivered from one or more nozzles, which can be configured to make calculated movements during the delivery of proton treatment beams.

[0059] Calculating of a proton treatment can be done while the patient is ventilated and anesthetized. A patient can be ventilated and anesthetized for pCT imaging, kept ventilated and anesthetized during the calculation and planning of a proton treatment, and kept ventilated and anesthetized until the proton treatment has been delivered. In some embodiments, the time a patient is ventilated and anesthetized can be reduced by reducing the duration required for calculating and planning a proton treatment. In some embodiments, the calculation and planning can be done in less than about sixty minutes. In some embodiments, the calculation and planning can be done in less than about twenty minutes. In some embodiments, the calculation and planning can be done in less than about ten minutes. In some embodiments the calculation and planning can be done in less than about five minutes. In some embodiments, the calculation and planning can be done in about two minutes or less.

[0060] A method of treating a patient that has experienced cardiac arrhythmia in some embodiments can include positioning the patient to receive the Bragg peaks of the one or more proton treatment beams at the target cardiac area. The patient can be turned or rotated in order to receive proton treatment beams. In some embodiments, the patient may remain in the same position for the ablation of the target cardiac area as for the pCT imaging. Positioning the patient can include confirming the patient is in position to receive the Bragg peaks. Positioning the patient can include moving systems or equipment relative to the patient. The pCT imaging and proton treatment of a patient can be performed with the same system and source or protons. In some embodiments, the patient gantry may be moved between a pCT imaging system and a proton treatment system. In some embodiments, the patient can be moved between more than one system for pCT imaging and proton treatment while still ventilated and under anesthesia. In some embodiments, a patient can be subjected to a single anesthesia and ventilation for the combined processes of pCT imaging and proton treatment of cardiac arrhythmia.

[0061] A method of treating a patient that has experienced cardiac arrhythmia can include delivering one or more proton treatment beams to the target cardiac area. A proton treatment beam can be one or more protons directed at ablating a target cardiac area. Proton treatment beams can deliver a dose of protons sufficient to ablate the cardiac tissue, forming lesions and scarring. The delivering of one or more proton treatment beams can include delivering proton treatment beams according to the calculated proton treatment. In some embodiments, delivering one or more proton treatment beams to the target cardiac area can include directing one or more proton treatment beams toward a target cardiac area with incident energy such that penetration depth of the Bragg peaks of the one or more proton treatment beams align with the target cardiac area. The angle of incidence, intensity, and energy of the one or more proton treatment beams can be modulated over time to ablate different portions of the target cardiac area. Delivering one or more proton treatment beams to the target cardiac area can include forming lesions on an annular portion at the entry of a patient's pulmonary vein sufficient to create scarring electrically isolating portions of the pulmonary vein.

[0062] Proton therapy and proton treatment beams can be delivered using several techniques, including passive scattering, pencil beam scanning, and intensity-modulated proton therapy. Proton treatment beams used for cardiac ablation can, in some embodiments, have energies in a range of about 70 MeV to about 250 MeV. In some embodiments, other ranges of proton energies can be selected. In some embodiments, more than one proton treatment beam can be delivered to a patient to ablate cardiac tissue. Proton beams can be delivered from a plurality of directions relative to the patient. Proton treatment beams can be scanning beams, which, in some embodiments, can be raster scanned over a target cardiac area. Proton treatment beams can be thin, pencil beams delivered from one or more nozzles. In some embodiments, the proton treatment beams can be intensity modulated. The dose to be delivered to a patient by proton treatment beams can be inversely planned. Examples of systems, methods, and techniques regarding proton therapy are described in U.S. Patent No. US 8,644,571 B l, titled "Intensity- Modulated Proton Therapy," filed on December 5, 2012. [0063] The delivering of one or more imaging protons and the delivering of one or more proton treatment beams can utilize a common source of protons. In some embodiments, the same or similar equipment or system can be used to deliver protons for imaging a patient and to deliver protons for ablating cardiac tissue.

[0064] Reference throughout this specification to "some embodiments" or "an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least some embodiments. Thus, appearances of the phrases "in some embodiments" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment and may refer to one or more of the same or different embodiments. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to one of ordinary skill in the art from this disclosure, in one or more embodiments.

[0065] As used in this application, the terms "comprising," "including," "having," and the like are synonymous and are used inclusively, in an open-ended fashion, and do not exclude additional elements, features, acts, operations, and so forth. Also, the term "or" is used in its inclusive sense (and not in its exclusive sense) so that when used, for example, to connect a list of elements, the term "or" means one, some, or all of the elements in the list. The term "about" when used herein to convey uncertainty or an approximation has its broadest reasonable interpretation. For example, in connection with any numerical value, the term "about" encompasses variations of the numerical value (e.g., less than 5% of the numerical value, less than 10% of the numerical value, less than 20% of the numerical value). In some cases, the term "about" can denote much larger variations where reasonable in context.

[0066] Similarly, it should be appreciated that in the above description of embodiments, various features are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that any claim require more features than are expressly recited in that claim. Rather, inventive aspects lie in a combination of fewer than all features of any single foregoing disclosed embodiment. Accordingly, no feature or group of features is necessary or indispensable to each embodiment. [0067] Embodiments of the disclosed systems and methods may be used and/or implemented with local and/or remote devices, components, and/or modules. The term "remote" may include devices, components, and/or modules not stored locally, for example, not accessible via a local bus. Thus, a remote device may include a device which is physically located in the same room and connected via a device such as a switch or a local area network. In other situations, a remote device may also be located in a separate geographic area, such as, for example, in a different location, building, city, country, and so forth.

[0068] Methods and processes described herein may be embodied in, and partially or fully automated via, hardware and/or software code modules executed by one or more general and/or special purpose computers. The word "module" refers to logic embodied in hardware and/or firmware, or to a collection of software instructions, possibly having entry and exit points, written in a programming language, such as, for example, C or C++. A software module may be compiled and linked into an executable program, installed in a dynamically linked library, or may be written in an interpreted programming language such as, for example, BASIC, Perl, or Python. It will be appreciated that software modules may be callable from other modules or from themselves, and/or may be invoked in response to detected events or interrupts. Software instructions may be embedded in firmware, such as an erasable programmable read-only memory (EPROM). It will be further appreciated that hardware modules may comprise connected logic units, such as gates and flip-flops, and/or may comprise programmable units, such as programmable gate arrays, application specific integrated circuits, and/or processors. The modules described herein may be implemented as software modules, or may be represented in hardware and/or firmware. Moreover, although in some embodiments a module may be separately compiled, in other embodiments a module may represent a subset of instructions of a separately compiled program, and may not have an interface available to other logical program units.

[0069] In certain embodiments, code modules may be implemented and/or stored in any type of non-transitory computer-readable medium or other non-transitory computer storage device. In some systems, data (and/or metadata) input to the system, data generated by the system, and/or data used by the system can be stored in any type of computer data repository, such as a relational database and/or flat file system. Any of the systems, methods, and processes described herein may include an interface configured to permit interaction with patients, health care practitioners, administrators, other systems, components, programs, and so forth.

[0070] A number of applications, publications, and external documents may be incorporated by reference herein. Any conflict or contradiction between a statement in the body text of this specification and a statement in any of the incorporated documents is to be resolved in favor of the statement in the body text.

[0071] Although described in the illustrative context of certain preferred embodiments and examples, it will be understood by those skilled in the art that the disclosure extends beyond the specifically described embodiments to other alternative embodiments and/or uses and obvious modifications and equivalents. Thus, it is intended that the scope of the claims which follow should not be limited by the particular embodiments described above.

[0072] In the various embodiments of the invention described herein, a person having ordinary skill in the art will recognize that various types of memory are readable by a computer, such as the memory described herein in reference to the various computers and servers, e.g., computer, computer server, web server, or other computers with embodiments of the present invention. Examples of computer-readable media can include but are not limited to: nonvolatile, hard-coded type media, such as read only memories (ROMs), CD-ROMs, and DVD-ROMs, or erasable, electrically programmable read only memories (EEPROMs); recordable type media, such as floppy disks, hard disk drives, CD-R/RWs, DVD-RAMs, DVD-R/RWs, DVD+R/RWs, flash drives, memory sticks, and other newer types of memories; and transmission type media such as digital and analog communication links. For example, such media can include operating instructions, as well as instructions related to the systems and the method steps described above and can operate on a computer. It will be understood by those skilled in the art that such media can be at other locations instead of, or in addition to, the locations described to store computer program products, e.g., including software thereon. It will be understood by those skilled in the art that the various software modules or electronic components described above can be implemented and maintained by electronic hardware, software, or a combination of the two, and that such embodiments are contemplated by embodiments of the present invention.

[0073] In the drawings and specification, there have been disclosed embodiments of systems, machines, media, apparatuses and methods of the present invention, and although specific terms are employed, the terms are used in a descriptive sense only and not for purposes of limitation. The embodiments of systems, machines, media, apparatuses and methods of the present invention have been described in considerable detail with specific reference to these illustrated embodiments. It will be apparent, however, that various modifications and changes can be made within the spirit and scope of the embodiments of systems, machines, media, apparatuses and methods of the present invention as described in the foregoing specification, and such modifications and changes are to be considered equivalents and part of this disclosure.

Claims

CLAIMS THAT CLAIMED IS:

1. A method to perform computed tomography, the method comprising: instructing a first controller to begin high frequency jet ventilation; receiving respiratory signal data associated with the high frequency jet ventilation; determining motion associated with respiration during the high frequency jet ventilation responsive to receipt of the respiratory signal data; creating a model representing the motion associated with respiration; instructing a second controller to image, by a computed tomography scanner, a heart; receiving imaging data responsive to imaging the heart; determining a target area of the heart responsive to the imaging data; determining an initial energy and a direction of a proton beam to deliver a Bragg peak of the proton beam to the target area; modifying the initial energy and the direction of the proton beam responsive to the model representing the motion associated with respiration to generate a modified initial energy and a modified direction; and instructing the second controller to deliver the proton beam to the heart at the modified initial energy and the modified direction during the high frequency jet ventilation.

2. A method as defined in Claim 1, wherein the computed tomography scanner is a proton computed tomography scanner, and wherein the proton beam is delivered by the proton computed tomography scanner.

3. A method as defined in one or more of Claims 1-2, wherein the target area is associated with a pulmonary vein opening into the heart.

4. A method as defined in one or more of Claims 1-3, wherein imaging the heart is performed during the high frequency jet ventilation.

5. A method as defined in one or more of Claims 1-4, wherein the method further comprises, after delivering the proton beam to the heart, instructing the second controller to image the heart to determine whether the Bragg peak of the proton beam reached the target area.

6. A method as defined in one or more of Claims 1-5, wherein the high frequency jet ventilation includes high frequency bursts of oxygen to lungs through thin-jet catheters along with an outwardly open airway.

7. A method to perform computed tomography, the method comprising: receiving respiratory signal data; receiving imaging data associated with a heart; determining a target area of the heart responsive to the imaging data; determining an initial energy and a direction of a proton beam to deliver a Bragg peak of the proton beam to the target area; modifying the initial energy and the direction of the proton beam responsive to the respiratory signal data to generate a modified initial energy and a modified direction; and instructing a controller to deliver the proton beam to the heart at the modified initial energy and the modified direction.

8. A method as defined in Claim 7, wherein determining the initial energy and the direction of the proton beam to deliver the Bragg peak of the proton beam to the target area includes determining a penetration depth and associated beam energy to align the Bragg peak of the proton beam with the target area.

9. A method as defined in one or more of Claims 7-8, wherein instructing the controller to deliver the proton beam to the heart includes instructing the controller to deliver one or more scanning proton beams from a plurality of angles.

10. A method as defined in one or more of Claims 7-9, wherein determining the target area of the heart includes: obtaining, from the imaging data, measured data for one or more protons of a plurality of protons that pass through a body, the measured data including information indicative of first and second tracks of the one or more protons, the first and second tracks corresponding to the one or more protons' trajectories before and after its passage through the body, respectively, the measured data further including information indicative of an interaction quantity of the one or more protons resulting from its passage through the body; for the one or more protons, estimating a path taken by the one or more protons within the body, the estimating based at least in part on the first and second tracks of the one or more protons; arranging the interaction quantity and the estimated path of the one or more protons such that the passage of the one or more protons through the body is represented as or is representable as a system of equations Ax=b, where x is a body parameter distribution of a parameter associated with the body, b represents the interaction quantity of the one or more protons resulting from interactions along a respective path of the one or more protons in the body, and A is an operator that operates on x to yield b, the operator A having information indicative of the estimated path of the one or more protons in the body, the system of equations configured so as to have a plurality of solutions; estimating an initial solution for the system of equations; obtaining one or more feasible solutions among the plurality of solutions by perturbing an existing solution, the one or more feasible solutions having a superior characteristic for a quantity associated with a reconstruction of the body parameter distribution than another solution obtained without the perturbation of the existing solution; and calculating the body parameter distribution based on a selected one of the one or more feasible solutions.

11. A method as defined in one or more of Claims 7-9, wherein receiving imaging data associated with a heart includes obtaining a representation of a body, the representation including information about structures within or on the body; wherein determining the target area of the heart includes identifying a volume of interest in the representation of the body; wherein determining the initial energy and the direction of the proton beam to deliver the Bragg peak of the proton beam to the target area includes: dividing the volume of interest into a plurality of sub- volumes, for each of the plurality of sub- volumes, setting a dose constraint, determining one or more proton treatment plans that satisfy the dose constraints for each of the plurality of sub- volumes, and from the one or more proton treatment plans, selecting a proton treatment plan that satisfies treatment criteria; and wherein delivering the proton beam to the heart includes delivering protons to the body based on the selected proton treatment plan,

12. A method as defined in Claim 11, wherein dividing the volume of interest into a plurality of sub-volumes includes: dividing the volume of interest into a total number of voxels; identifying one or more features of interest; ordering the voxels according to increasing distance from a nearest feature of interest; for each of the plurality of sub-volumes, selecting a fractional value corresponding to a ratio of a size of the sub- volume to a size of the volume of interest; and for each of the plurality of sub-volumes, defining a sub- volume as a group of a number of consecutive voxels from the ordered voxels, wherein a ratio of the number of consecutive voxels to the total number of voxels is approximately equal to the fractional value for the sub- volume.

13. A system to perform computed tomography, the system comprising: one or more processors; a non-transitory computer-readable medium in communication with the one or more processors and having one or more computer programs stored thereon that, when executed by the one or more processors, cause the system to: receive respiratory signal data; receive imaging data associated with a heart; determine a target area of the heart responsive to the imaging data; determine an initial energy and a direction of a proton beam to deliver a Bragg peak of the proton beam to the target area; modify the initial energy and the direction of the proton beam responsive to the respiratory signal data to generate a modified initial energy and a modified direction; and instruct a controller to deliver the proton beam to the heart at the modified initial energy and the modified direction.

14. A system as defined in Claim 13, wherein the system further comprises a proton computed tomography scanner, wherein receiving the imaging data associated with the heart is by the proton computed tomography scanner, and wherein delivering the proton beam to the heart is by the proton computed tomography scanner.

15. A system as defined in one or more of Claims 13-14, wherein the target area is associated with a pulmonary vein opening into the heart.

16. A system as defined in one or more of Claims 13-15, wherein the imaging data associated with the heart is obtained during high frequency jet ventilation, and wherein the high frequency jet ventilation includes high frequency bursts of oxygen to lungs through thin-jet catheters along with an outwardly open airway.

17. A system as defined in one or more of Claims 13-16, wherein the one or more computer programs, when executed by the one or more processors, further cause the system to, after instructing the controller to deliver the proton beam to the heart, image the heart to determine whether the Bragg peak of the proton beam reached the target area.

18. A system as defined in one or more of Claims 13-17, wherein determining the initial energy and the direction of the proton beam to deliver the Bragg peak of the proton beam to the target area includes determining a penetration depth and associated beam energy to align the Bragg peak of the proton beam with the target area.

19. A system as defined in one or more of Claims 13-18, wherein instructing the controller to deliver the proton beam to the heart includes instructing the controller to deliver one or more scanning proton beams from a plurality of angles.

20. A system as defined in one or more of Claims 13-19, wherein determining the target area of the heart includes: obtaining, from the imaging data, measured data for one or more protons of a plurality of protons that pass through a body, the measured data including information indicative of first and second tracks of the one or more protons, the first and second tracks corresponding to the one or more protons' trajectories before and after its passage through the body, respectively, the measured data further including information indicative of an interaction quantity of the one or more protons resulting from its passage through the body; for the one or more protons, estimating a path taken by the one or more protons within the body, the estimating based at least in part on the first and second tracks of the one or more protons; arranging the interaction quantity and the estimated path of the one or more protons such that the passage of the one or more protons through the body is represented as or is representable as a system of equations Ax=b, where x is a body parameter distribution of a parameter associated with the body, b represents the interaction quantity of the one or more protons resulting from interactions along a respective path of the one or more protons in the body, and A is an operator that operates on x to yield b, the operator A having information indicative of the estimated path of the one or more protons in the body, the system of equations configured so as to have a plurality of solutions; estimating an initial solution for the system of equations; obtaining one or more feasible solutions among the plurality of solutions by perturbing an existing solution, the one or more feasible solutions having a superior characteristic for a quantity associated with a reconstruction of the body parameter distribution than another solution obtained without the perturbation of the existing solution; and calculating the body parameter distribution based on a selected one of the one or more feasible solutions.

21. A method of enhanced computed tomography, the method comprising: initiating high frequency jet ventilation toward a target area; receiving respiratory signal data associated with the high frequency jet ventilation of the target area; determining motion associated with respiration in the target area during the high frequency jet ventilation responsive the respiratory signal data; generating a simulation model representing the motion associated with respiration; initiating a computed tomography scanner toward the target area; receiving computed tomography imaging data responsive to imaging the target area; determining a smaller subset of the target area responsive to the computed tomography imaging data; determining an initial energy and a direction of a proton beam to deliver a Bragg peak of the proton beam to the smaller subset of the target area; modifying the initial energy and the direction of the proton beam responsive to the simulation model representing the motion associated with respiration to generate a modified initial energy and a modified direction; and delivering a proton beam to the smaller subset of the target area at the modified initial energy and the modified direction during the high frequency jet ventilation.

22. A method as defined in Claim 21, wherein the step of delivering a proton beam includes operating a proton beam controller to apply the proton beam to the smaller subset of the target area with modified energy and modified direction when high frequency jet ventilation is occurring.