阅读说明：本技术 用于在发射引导的放射治疗中使用的系统和方法 (System and method for use in emission guided radiation therapy ) 是由 S·马赞 A·南杜里 于 2012-03-30 设计创作，主要内容包括：本发明所描述的是在坐标系统中用于定位关于一个或多个兴趣区域的放射源的系统和方法。这样的系统和方法可用在用于将放射局部传送到一个或多个患者肿瘤区域的发射引导的放射治疗(EGRT)中。这些系统包括在患者区域周围可移动的机架,其中多个正电子发射检测器、放射源被可移动地布置在该机架上,和控制器。控制器被配置为识别重合正电子湮没发射路径并且被配置为定位放射源以便沿着所识别的发射路径应用放射波束。本发明所描述的系统和方法可单独使用或与用于肿瘤治疗的外科手术、化学疗法、和/或短程疗法结合一起使用。(Described herein are systems and methods for positioning a radiation source relative to one or more regions of interest in a coordinate system. Such systems and methods may be used in Emission Guided Radiation Therapy (EGRT) for localized delivery of radiation to one or more patient tumor regions. These systems include a gantry movable about a patient area, wherein a plurality of positron emission detectors, a radiation source are movably disposed on the gantry, and a controller. A controller is configured to identify coincident positron annihilation emission paths and to position a radiation source to apply radiation beams along the identified emission paths. The systems and methods described herein can be used alone or in combination with surgery, chemotherapy, and/or brachytherapy for tumor treatment.)

1. A system for hybrid radiation therapy, the system comprising:

a frame;

a radioactive source mounted on the gantry;

a positron emission detector mounted on the gantry, wherein the positron emission detector is configured to detect one or more positron annihilation emission paths; and

a controller in communication with the radiation source and the positron emission detector, the controller configured to deliver radiation to a target region of a patient according to an Intensity Modulated Radiation Therapy (IMRT) treatment plan or an Emission Guided Radiation Therapy (EGRT) treatment plan.

2. The system of claim 1, wherein the controller is further configured to determine whether to deliver radiation using the radiation source according to an IMRT treatment plan or an EGRT treatment plan.

3. The system of claim 1, wherein the controller is configured to deliver radiation according to the EGRT treatment plan by:

determining whether the detected positron annihilation emission path intersects the patient target volume, an

The radiation source is positioned with respect to the detected positron annihilation emission path if the detected positron annihilation emission path intersects the patient target portion.

4. The system of claim 2 wherein determining whether to deliver radiation according to the IMRT treatment plan or the EGRT treatment plan includes determining whether the one or more detected positron annihilation emission paths provide sufficient positron annihilation emission path data for delivering radiation according to the EGRT treatment plan.

5. The system of claim 4 wherein determining whether sufficient positron annihilation emission paths data exists comprises determining a signal strength of the one or more detected positron annihilation emission paths.

6. The system of claim 4 wherein the positron annihilation emission path data includes location data.

7. The system of claim 6, wherein the location data comprises positron annihilation event location data.

8. The system of claim 2, wherein determining whether to deliver radiation according to the IMRT treatment plan or the EGRT treatment plan uses a predetermined model stored in the controller.

9. The system of claim 2, wherein the controller is configured to deliver radiation according to the IMRT treatment plan by instructing the radiation source to generate a conformal radiation dose to the patient target portion.

10. The system of claim 9, wherein delivering radiation according to the IMRT treatment plan includes delivering radiation throughout a patient target portion.

11. The system of claim 3, wherein positioning the radiation source with respect to the detected positron annihilation emission path comprises aligning the radiation source along the detected positron annihilation emission path.

12. The system of claim 3, wherein the detected positron annihilation emission path is determined by a pair of photons emitted by a positron annihilation event, and wherein determining whether the detected positron annihilation emission path intersects the patient target volume comprises:

computing a time difference between detection of each photon of the pair of photons;

calculating a position of the positron annihilation event based on the computed time difference, wherein the position calculation has an estimation error;

extending the boundary of the target region of the patient according to the estimation error; and

determining whether the location of the positron annihilation event is located within the extended boundary of the patient target portion.

13. The system of claim 1, wherein the controller is further configured to deliver radiation according to an IMRT treatment plan for a first portion of a radiation treatment session and deliver radiation according to an EGRT treatment plan for a second portion of the radiation treatment session.

14. The system of claim 1, wherein the gantry is configured to position the radiation source at different gantry angles, and the controller is further configured to instruct the radiation source to deliver radiation according to the IMRT treatment plan and deliver radiation according to an EGRT treatment plan at each gantry angle.

15. The system of claim 1, wherein the gantry is configured to position the radiation source at a first gantry angle and a second gantry angle, and the controller is further configured to deliver radiation according to the IMRT treatment plan when the radiation source is positioned at the first gantry angle and deliver radiation according to the EGRT treatment plan at the second gantry angle.

16. A system for positioning a radiation source, comprising:

a frame;

a radioactive source mounted on the gantry;

a positron emission detector mounted on the gantry, wherein the positron emission detector is configured to detect a positron annihilation emission path; and

a controller in communication with the radiation source and the positron emission detector, the controller configured to determine whether the detected emission path intersects a first PET-avid region of interest and a second PET-avid region of interest within a coordinate system;

if it is determined that the detected emission path intersects a first PET-avid region of interest and a second PET-avid region of interest, positioning the radiation source at a location with respect to the emission path, wherein the radiation source is configured to generate radiation that is modulated according to a modulation factor calculated based on a projection of the first PET-avid region of interest onto the location of the radiation source.

17. The system of claim 16, wherein the radiation source is configured to generate a radiation beam having a temporal duration adjusted by the modulation factor.

18. The system of claim 16, wherein the radiation source is configured to produce radiation having an intensity adjusted by the modulation factor.

19. The system of claim 16, wherein the second PET-avid region of interest intersects a third region of interest, and the first region of interest does not intersect the third region of interest.

20. The system of claim 16, wherein the gantry is a circular gantry.

21. The system of claim 16, wherein the modulation factor is inversely proportional to a projection of the first PET-avid region of interest onto the location of the radiation source.

22. The system of claim 16, wherein the second aspirational PET region of interest is positioned within the planned target volume and the first aspirational PET region of interest is positioned outside the planned target volume.

23. The system of claim 16, wherein the modulation factor is inversely proportional to a projection of the first PET-avid region of interest onto the location of the radiation source.

24. The system of claim 16, wherein positioning the radiation source comprises aligning the radiation source along the emission path.

25. The system of claim 16, wherein the detected positron annihilation emission path is determined by a pair of photons emitted by a positron annihilation event, and the controller is further configured to compute a time difference between detection of each photon of the pair of photons,

computing a position of the positron annihilation event from the computed time difference, wherein the position computation has an estimation error,

determining whether the location of the positron annihilation event is within the estimation error from the boundary of the first PET-avid region of interest, an

If the position of the positron annihilation event is within the estimated error from the boundary of the first PET-avid region of interest, sending instructions to the radiation source to produce radiation to the first PET-avid region of interest adjusted according to the modulation factor.

26. The system of claim 16, wherein the radiation source is configured to generate radiation having a plurality of radiation emissions, wherein a number of the radiation emissions is adjusted by the modulation factor.

27. The system of claim 16, wherein the radiation source is configured to produce radiation having a radiation beam with a duty cycle adjusted by the modulation factor.

28. A system for positioning a radiation source, comprising:

a frame;

a radioactive source mounted on the gantry;

a positron emission detector mounted on the gantry, wherein the positron emission detector is configured to detect a positron emission path within a coordinate system that originates from a first region of interest; and

a controller in communication with the radiation source and the positron emission detector, wherein the controller is configured to position the radiation source with respect to the emission path, and wherein the radiation source is configured to produce radiation according to a selected probability coefficient.

29. The system of claim 28, wherein the controller is configured to determine within the coordinate system whether the emission path intersects a second region of interest, and wherein the radiation source is configured to generate radiation about the emission path according to the selected probability coefficient if the emission path intersects the second region of interest.

30. The system of claim 29, wherein the radiation source is configured to generate radiation about the transmit path if the transmit path intersects a second region of interest and the selected probability coefficient is below a pre-programmed probability threshold.

31. The system of claim 28, wherein the radiation source is configured to produce radiation intensity modulated according to the selected probability coefficients.

32. The system of claim 28, wherein the radiation source is configured to produce radiation scaled by the probability coefficients.

33. The system of claim 28, wherein the gantry is a circular gantry.

34. The system of claim 28, wherein the first region of interest is determined based on an imaging modality selected from the group consisting of CT imaging, PET imaging, MRI imaging, and X-ray imaging.

35. The system of claim 28, wherein

The controller is further configured to calculate an attenuation factor of the transmit path using the image of the first region of interest acquired by the selected imaging mode, and

wherein the radiation source is further configured to produce radiation modulated by the attenuation factor.

36. The system of claim 35 wherein the radiation source is configured to produce radiation that is adjusted to compensate for radiation attenuation along the positron annihilation emission path.

37. The system of claim 35, wherein the selected imaging modality is computed tomography.

38. The system of claim 35 wherein the radiation source is configured to produce radiation proportional to the attenuation of the detected positron annihilation emission path.

39. The system of claim 35, wherein the radiation source is configured to produce radiation having an intensity modulated in proportion to the attenuation factor or radiation having a temporal duration modulated in proportion to the attenuation factor.

40. The system of claim 28, wherein

The positron emission detector is further configured to detect a single positron annihilation emission path intersecting the first PET-avid region of interest and the second PET-avid region of interest; and

wherein the radiation source is configured to apply radiation adjusted according to a modulation factor inversely proportional to a projection of the first PET-avid region of interest on the location of the radiation source.

41. The system of claim 40, wherein the radiation source is configured to produce radiation having an intensity modified by the modulation factor.

42. The system of claim 28, wherein the radiation source is configured to produce radiation frequency modulated according to the probability coefficients.

43. The system of claim 28, wherein the probability coefficient is selected from a randomly generated number between 0 and 1 and is below a predetermined threshold.

44. The system of claim 43, wherein the predetermined threshold is about 0.2 or about 0.5.

45. The system of claim 28, wherein the detected positron annihilation emission path is determined by a pair of photons emitted by a positron annihilation event, and the controller is further configured to compute a time difference between detection of each photon of the pair of photons,

calculating a position of the positron annihilation event from the computed time difference, wherein the position calculation has an estimation error,

determining whether the location of the positron annihilation event is within the estimated error from the boundary of the first region of interest, an

If the position of the positron annihilation event is within an estimation error from a boundary of the first region of interest, instructions are sent to the radiation source to generate radiation to the first region of interest in accordance with the probability coefficients.

46. The system of claim 28, wherein the controller is configured to position the radiation source along the emission path.

47. A radiation delivery method, comprising:

detecting a positron annihilation emission path intersecting the first region of interest;

determining whether the detected positron annihilation emission path intersects the second region of interest;

if the positron annihilation emission path intersects the second region of interest, radiation is generated with respect to the detected positron annihilation emission path according to the selected probability coefficients.

48. The method of claim 47, wherein the selected probability coefficient is a randomly generated number between 0 and 1 below a predetermined probability threshold.

49. The method of claim 48, wherein the predetermined probability threshold is about 0.2 or about 0.5.

50. The method of claim 47, wherein generating radiation comprises modulating radiation intensity according to a selected probability coefficient.

51. The method of claim 47, wherein generating radiation comprises scaling radiation by the selected probability coefficients.

52. The method of claim 47 further comprising calculating an attenuation factor for the positron annihilation emission path using an image of the first region of interest obtained by the selected imaging modality, and wherein producing radiation comprises modulating radiation by the attenuation factor.

53. The method of claim 52 wherein generating radiation includes adjusting radiation to compensate for attenuation of radiation along the positron annihilation emission path.

54. The method of claim 52, wherein the selected imaging modality is computed tomography.

55. The method of claim 52 wherein generating radiation includes generating radiation proportional to the attenuation of the detected positron annihilation emission path.

56. A method as set forth in claim 52 wherein generating radiation includes generating radiation having an intensity modulated proportional to the attenuation factor or radiation having a time duration modulated proportional to the attenuation factor.

57. The method of claim 47, wherein:

detecting a positron annihilation event includes detecting a positron annihilation event that intersects the first PET-avid region of interest and the second PET-avid region of interest; and

generating radiation includes generating radiation with a radiation source at a location, wherein the generated radiation is adjusted according to a modulation factor that is inversely proportional to a projection of the first PET-avid region of interest on the location of the radiation source.

58. A method as set forth in claim 57 wherein generating radiation includes generating radiation having an intensity modified by the modulation factor.

59. The method of claim 47, wherein generating radiation comprises generating radiation that is frequency modulated according to selected probability coefficients.

60. The method of claim 47, wherein the detected positron annihilation emission path is determined by a pair of photons emitted by the positron annihilation event, and wherein the method further comprises:

computing a time difference between detection of each photon of the pair of photons;

calculating a position of the positron annihilation event from the computed time difference, wherein the position calculation has an estimation error;

determining whether the location of the positron annihilation event is within the estimated error from a boundary of the first region of interest; and

generating radiation to the first region of interest according to the probability coefficients if the location of the positron annihilation event is within the estimation error from the boundary of the first region of interest.

61. A system for positioning a radiation source, comprising:

a frame;

a radioactive source mounted on the gantry;

a positron emission detector mounted on the gantry, wherein the positron emission detector is configured to detect a positron emission path intersecting the region of interest within a coordinate system; and

a controller in communication with the radiation source and the positron emission detector, the controller configured to:

determining whether the detected transmit path intersects the region of varying density using an image of the region of interest acquired by the selected imaging modality;

if the detected transmission path intersects a region of varying density, an attenuation factor is calculated based on the density of the intersected region of varying density, and

positioning a radiation source with respect to the emission path, wherein the radiation source is configured to produce radiation modulated by the attenuation factor.

62. The system of claim 61, wherein the gantry is a circular gantry.

63. The system of claim 61, wherein the radiation source is configured to produce radiation that is adjusted to compensate for radiation attenuation along a positron emission path.

64. The system of claim 61, wherein the selected imaging modality is computed tomography.

65. The system of claim 64, wherein the radiation source is configured to produce radiation proportional to the attenuation of the detected positron emission path.

66. The system of claim 64, wherein the radiation source is configured to produce radiation that is inversely proportional to the attenuation of the detected positron emission path.

67. The system of claim 61, wherein the radiation source is configured to produce radiation having an intensity that is modulated in proportion to an attenuation factor.

68. The system of claim 61, wherein the radiation source is configured to produce radiation having a temporal duration that is modulated in proportion to an attenuation factor.

69. The system of claim 61, wherein the radiation source is configured to produce radiation having an intensity modulated inversely proportional to an attenuation factor.

70. The system of claim 61, wherein the radiation source is configured to produce radiation having a frequency tuned inversely proportional to an attenuation factor.

71. The system of claim 61, wherein the region of varying density has a higher density than the region of interest.

72. A system for emission guided radiation therapy, comprising:

a gantry movable about a patient area, wherein the gantry includes a rotatable inner gantry and a rotatable outer gantry;

a plurality of positron emission detectors disposed along the internal gantry and configured to detect a plurality of positron emission paths within the patient region; and

a radiation source disposed along the external gantry, wherein the radiation source is configured to apply radiation with respect to a plurality of positron emission paths within the patient region, wherein the internal gantry is rotatable at a higher rate than the external gantry.

73. The system of claim 72 further comprising a single photon emission detector disposed along said internal gantry.

74. The system of claim 73, wherein the radiation source comprises a collimator.

75. The system of claim 72, wherein the system comprises a sensing mode in which the plurality of positron emission detectors block the radiation source, and an emission mode in which the radiation source is unblocked and capable of applying radiation to a patient area.

76. The system of claim 72, wherein the gantry is a circular gantry.

77. A system for positioning a radiation source, comprising:

a frame;

a radioactive source mounted on the gantry;

a positron emission detector mounted on the gantry, wherein the positron emission detector is configured to detect positron emission paths intersecting the region of interest within a coordinate system; and

a controller in communication with the radiation source and the positron emission detector, the controller configured to

Extending the region of interest in the selected direction with an extended edge;

determining whether the detected transmit path is substantially perpendicular to the selected direction; and

positioning a radiation source with respect to an emission path if the emission path is substantially perpendicular to the selected direction, wherein the radiation source is configured to generate a radiation beam having a width corresponding to the extended rim width.

78. The system of claim 77, wherein a width of the radiation beam is the same as a width of the extended edge.

79. A system for positioning a radiation source, comprising:

a frame;

a radioactive source mounted on the gantry;

a positron emission detector mounted on the gantry, wherein the positron emission detector is configured to detect a boundary of a PET-avid region of interest within a coordinate system; and

a controller in communication with the radiation source and the positron emission detector, the controller configured to:

defining an extended region, the extended region exceeding the border of the PET-avid region of interest,

determining whether the detected transmission path is substantially perpendicular to an axis of the extended area, and

positioning a radiation source with respect to the emission path if the detected emission path is substantially perpendicular to an axis of the extended area, wherein the radiation source is configured to generate a radiation beam having a width corresponding to a width of the extended area.

80. The system of claim 79, wherein a width of the radiation beam is the same as a width of the extended edge.

81. The system of claim 77, wherein the region of interest is PET-avid, and wherein the extended edge includes a region adjacent the PET-avid region of interest.

82. The system of claim 77, wherein the selected direction is predetermined.

83. The system of claim 77, wherein the extended border is determined from patient data.

84. The system of claim 77, wherein the extended edge is determined by a computer-implemented image processing algorithm.

85. A system as in claim 77, wherein the extended edge is determined by a practitioner input.

86. The system of claim 81, wherein the extended edge comprises PET-avid tissue.

87. The system of claim 81, wherein the extended edge does not include PET-avid tissue.

88. The system of claim 77, wherein the extended edge comprises an edge for patient movement.

89. The system of claim 77, wherein the extended edge comprises an edge for organ motion.

90. The system of claim 77, wherein the extended edge corresponds to a change in organ shape and size.

91. The system of claim 77, wherein the extended edge corresponds to an uncertainty in radiation beam alignment.

92. The system of claim 77, wherein a width of the radiation beam is the same as a width of the extended edge.

93. The system of claim 82, wherein the extension zone is determined during a treatment planning stage.

94. The system of claim 79, wherein the controller is configured to determine an extension region by using images obtained by computed tomography.

95. The system of claim 79, wherein the controller is configured to determine the extension region by using an image obtained by magnetic resonance imaging.

96. The system of claim 79, wherein the direction of the axis of the extended region is predetermined.

97. The system of claim 79, wherein the extension region is determined from patient data.

98. The system of claim 79, wherein the extended region is determined by a computer-implemented image processing algorithm.

99. The system according to claim 79 wherein the extended region is determined by a practitioner input.

100. The system of claim 79, wherein the extended region comprises PET-avid tissue.

101. The system of claim 79, wherein the extended region does not include PET-avid tissue.

102. The system of claim 79, wherein the extended region includes edges for patient movement.

103. The system of claim 79, wherein the extended region comprises an edge for organ motion.

104. The system of claim 79, wherein the extended region corresponds to a change in organ shape and size.

105. The system of claim 79, wherein the extended region corresponds to uncertainty in radiation beam alignment.

106. The system of claim 79, wherein positioning the radiation source with respect to the emission path comprises positioning the radiation source along the emission path.

107. The system of claim 106 wherein the extension zone is determined during a treatment planning stage.

108. A system for positioning a radiation source, comprising:

a frame;

a radioactive source mounted on the gantry;

a positron emission detector mounted on the gantry, wherein the positron emission detector is configured to detect a positron emission path intersecting a planned target Portion (PTV), wherein the positron emission path is determined by a pair of photons emitted by a positron annihilation event; and

a controller in communication with the radiation source and the positron emission detector, the controller configured to

Computing a time difference between detection of each photon of the pair of photons,

calculating a position of the positron annihilation event based on the computed time difference, wherein the position calculation has an estimation error,

extending the boundary of the PTV according to the estimation error,

determining whether the position of the positron annihilation event is within an extended PTV boundary, an

The radiation source is positioned with respect to the detected positron emission path if the position of the positron annihilation event lies within the extended PTV boundary.

109. The system of claim 108, further comprising storing data from the detected positron emission paths in a memory of the controller.

110. The system of claim 109 wherein if the position of the positron annihilation event is not within the extended PTV boundary, storing data from the detected positron emission paths in the memory without positioning the radiation source with respect to the detected positron emission paths.

111. The system of claim 108, wherein the estimation error is about 5 cm.

112. The system of claim 108, wherein the radiation source is configured to direct radiation according to selected probability coefficients after positioning the radiation source with respect to the detected positron emission paths.

113. The system of claim 108, wherein extending a boundary of the PTV with the estimation error comprises extending the boundary along an extension axis, and wherein the controller is further configured to determine whether the detected positron emission path is substantially perpendicular to the extension axis.

114. The system of claim 108, wherein the controller is further configured to determine whether the detected positron emission path intersects a region of varying density using an image of the PTV obtained by the selected imaging modality,

based on the density of the intersecting regions of varying density, an attenuation factor is calculated,

wherein the radiation source is configured to produce radiation modulated by the attenuation factor.

115. The system of claim 108, wherein the extended PTV boundary is a first extended PTV boundary, the detected positron emission path intersects a second PTV, and wherein the controller is configured to

Extending the boundary of the second PTV according to the estimation error,

if the location of the positron annihilation event is not within the first extended PTV boundary, determining whether the location of the positron annihilation event is within the second extended PTV boundary, an

If the position of the positron annihilation event is located within the second extended PTV boundary, positioning the radiation source with respect to the detected positron emission path.

116. The system of claim 108, wherein positioning the radiation source with respect to the detected positron emission path includes aligning the radiation source along the detected positron emission path.

117. The system of claim 108 wherein the controller is configured to position the radiation source with respect to the detected positron emission path if the location of the annihilation event is within a PTV boundary that is not extended.

118. A method for positioning a radiation source, comprising:

(a) detecting a positron emission path, wherein the positron emission path is defined by a pair of photons emitted by a positron annihilation event;

(b) computing a time difference between detection of each photon of the pair of photons,

(c) calculating a position of the positron annihilation event based on the computed time difference, wherein the position calculation has an estimation error,

(d) extending a boundary of a planned target Portion (PTV) based on the estimation error,

(e) determining whether the calculated position of the positron annihilation event is within an extended PTV boundary, an

(f) If the calculated position of the positron annihilation event is within the extended PTV boundary, the radiation source is positioned with respect to the detected positron emission path.

119. The method of claim 118, wherein positioning the radiation source includes aiming the radiation source along the detected positron emission path.

120. The method of claim 118, further comprising:

(g) determining whether the detected positron emission path intersects the PTV; and

(h) if the detected positron emission path intersects the PTV and the calculated position of the positron annihilation event is not within the extended PTV boundary, storing data of the detected positron emission path in controller memory without positioning the radiation source with respect to the detected positron emission path.

121. The method of claim 118, wherein the estimation error is about 5 cm.

122. The method of claim 118, wherein step (f) further comprises generating radiation using a radiation source based on the selected probability coefficients.

123. The method of claim 118 wherein step (d) further comprises extending a boundary of the PTV along an extension axis, step (e) further comprises determining whether the detected positron emission path is substantially perpendicular to the extension axis, and step (f) comprises positioning the radiation source with respect to the detected positron emission path if the detected positron emission path is substantially perpendicular to the extension axis and the location of the positron annihilation event is within the extended boundary of the PTV.

124. The method of claim 118, further comprising:

(g) determining whether the detected positron emission path intersects a region of varying density using an image of the PTV obtained by the selected imaging modality,

(h) based on the density of the intersecting regions of varying density, an attenuation factor is calculated,

step (f) further comprises generating radiation modulated by the attenuation factor.

125. The method of claim 118, wherein the extended PTV boundary is a first extended PTV boundary, the method further comprising:

(g) determining whether the detected positron emission path intersects a second PTV,

(h) extending a boundary of a second PTV in accordance with the estimation error if the detected positron emission path intersects the second PTV,

(i) positioning the radiation source with respect to the detected positron emission path if the position of the positron annihilation event is within the first extended PTV boundary or within the second extended PTV boundary.

Background

The radiation therapy includes: delivering a tumoricidal radiation dose to a localized region of the body. Stereotactic radiotherapy, also known as radiosurgery, can be used to treat tumors (tumors) in the brain, chest, head, neck, lung, liver, pancreas, spine, and prostate. Various tumor localization techniques can be used to accurately determine the location of the tumor(s) to help ensure that a high dose of radiation is delivered to the tumor(s) and that healthy, cancer-free tissue is preserved. For example, on-board imaging techniques such as single and stereo x-ray imaging, kilovolt and megavolt CT imaging, implantable fiducial markers and transponders, ultrasound imaging, MRI, etc. may help improve the efficacy of radiation therapy by collecting tumor location information so that the radiation beam may be specifically directed to the tumor region. Various radiation beam shaping techniques can also be used to help precisely direct radiation at the tumor(s) to be treated and reduce radiation exposure to surrounding tissue.

Disclosure of Invention

Described herein are systems and methods for positioning a radiation source with respect to one or more regions of interest in a coordinate system. In some variations, such systems and methods may be used for Emission Guided Radiation Therapy (EGRT) for localized delivery of radiation to one or more patient tumor regions. The EGRT system may include: a gantry (gantry) movable around a patient area, wherein one or more positron emission detectors and a radiation source are movably arranged on the gantry. The EGRT system may include: a controller configured to identify coincident positron annihilation (annihilation) emission paths and direct the radiation source to apply radiation beams along the identified emission paths. Various methods may be used with the EGRT system in order to adjust the radiation beam applied to the target region(s) such that radiation is delivered to the target region(s) and radiation delivery to other tissue regions is reduced or avoided. The EGRT systems and methods described herein can be used alone or in combination with surgery, chemotherapy, and/or brachytherapy for tumor treatment.

One example of an ERGT system described herein may include: a gantry movable about a patient area, one or more positron emission detectors, one or more therapeutic radiation sources, a motion system, and a microprocessor. Some variations of the EGRT system may include: one or more single photon emission detectors. The therapeutic radiation source may be one or more radioactive materials, x-ray source(s), or particle beam source(s). Positron emission detectors and therapeutic radiation sources may be mounted at various positions around the gantry for the purpose of detecting coincident positron annihilation emission paths intersecting the target region and applying radiation beams to deliver prescribed radiation doses to the target region. The radiation beam may be applied along a transmission path and/or at a target location determined based on the detected transmissions. The movable gantry may adjust the position of the positron emission detectors and the therapeutic radiation source so that various regions of tissue may be treated within the patient area.

The methods described herein may be used with an EGRT system to adjust a radiation beam applied to a target region(s) in order to deliver radiation to the target region(s) and reduce or avoid delivery of radiation to other tissue regions. For example, the EGRT method may be used to deliver a prescribed dose of radiation to the target portion and avoid delivering radiation to radiation sensitive structures, compensate for PET signal and/or radiation beam attenuation, collect real-time tumor location data, and perform other functions in order to help ensure that tumoricidal levels of radiation are delivered to the target portion and protect surrounding tissue. The EGRT systems and methods described herein can be used alone or with surgery, chemotherapy, radiosensitizers, and/or brachytherapy for tumor treatment. For example, the EGRT systems and methods may be used before and/or after chemotherapy. The EGRT may also be used before and/or after surgery and/or brachytherapy. Some variations of tumor treatment plans may include: surgically removing a portion of the tumor, and treating any remaining tumor mass with chemotherapy and/or EGRT. The various therapies in a tumor treatment plan can be determined, in part, by the size, type, location, development, and etiology of the tumor(s), as well as a variety of patient variables (e.g., sex, age, allergies, tolerance to particular pharmacological agents, etc.).

One example of a method for emission guided radiation therapy of a target region of tissue may include: detecting, using a positron emission detector, a single coincident positron annihilation emission path intersecting both the target tissue and the radiation-sensitive tissue to be retained; and selectively applying radiation along the emission path such that the radiation applied to the target tissue is substantially greater than the radiation applied to the retained tissue. In certain variations, applying radiation along the emission path may comprise: the radiation is emitted probabilistically or the radiation that has been intensity modulated is emitted probabilistically.

Another example of an EGRT method for applying radiation to a target region of tissue may include: detecting a single coincident positron annihilation emission path intersecting the target tissue region using a positron emission detector; determining whether the transmit path intersects an organic structure; positioning a radiation source to apply radiation along the emission path; and applying radiation along the emission path, wherein the radiation source is modified by probability coefficients. In some variations, applying radiation may include: the application of such radiation: wherein the intensity of the radiation has been adjusted by the probability coefficient.

Another method for EGRT of a tissue target region may include: detecting a single coincident positron annihilation emission path intersecting a target region of tissue, wherein the emission path is substantially perpendicular to a predetermined extended edge from the target tissue; and applying a radiation beam to the target tissue along the emission path using a radiation source, wherein a width of the radiation beam may correspond to a width of the extended edge. In certain variations, the target tissue is a craving PET (PET-avid) tissue, and the extended edge may include tissue adjacent to the craving PET tissue.

Another method for EGRT of a target region of tissue may include: detecting a boundary of a PET-avid region of tissue using a positron emission detector; defining an extended region beyond the border of the PET-avid region; detecting a single coincident positron annihilation emission path intersecting a selected region of tissue, wherein the detected emission path may be substantially perpendicular to an axis of the extended region; and applying radiation along an emission path detected having a width corresponding to the width of the extended region. In certain variations, the positron emission detector may be configured to determine a boundary of the PET-avid region of the tissue region based on the detected positron annihilation emission paths.

Another method for EGRT of a target region of tissue may include: detecting a boundary of a PET-avid region of tissue using a positron emission detector configured to determine the boundary of the PET-avid region of tissue; defining an extended region beyond the border of the PET-avid region; detecting a single coincident positron annihilation emission path intersecting a selected region of tissue, wherein the detected emission path may be substantially perpendicular to an axis of the extended region, and applying radiation along the detected emission path may have a width that may correspond to a width of the extended region. In some embodiments, defining the extension region may include: images obtained from one or more of computed tomography, magnetic resonance imaging, PET, or any other suitable imaging modality are used.

Another method for EGRT of a target region of tissue may include: detecting a single coincident positron annihilation emission path using a positron emission detector, wherein the emission path intersects a first PET-avid region of the retained tissue and a second PET-avid region of the treated tissue, positioning a radiation source at a position that: the radiation source is capable of applying radiation from the location along the emission path and applying radiation along the emission path, wherein the radiation is adjustable according to a modulation factor that is inversely proportional to a projection of the first PET-avid region of tissue onto the location of the radiation source. In some variations, applying radiation may include: a radiation beam is applied having a time duration that is modifiable by the modulation factor. Alternatively or additionally, applying radiation may include: radiation is applied with an intensity that is modifiable by the modulation factor. In other variations, the second PET-avid region of tissue may intersect the target region of tissue, and the first region of tissue may not intersect the target region of tissue.

Yet another method for EGRT of a target region of tissue may comprise: detecting a single coincident positron annihilation emission path using a positron emission detector, wherein the emission path can intersect a target region of tissue; and applying radiation along the emission path using a radiation source, wherein the applied radiation is adjustable based on the overall attenuation of the detected positron annihilation emission along the complete emission path, as determined by alternative imaging modalities. In certain variations, the application of radiation may be adjusted based on the attenuation of the therapeutic radiation along the positron annihilation emission path. For example, the radiation applied may be directly or inversely proportional to the attenuation of the detected positron annihilation emission. Examples of alternative imaging modalities may include: computed tomography (computed tomography), magnetic resonance imaging, x-ray, and/or any suitable imaging modality.

Another example of a method for EGRT may include: detecting a single positron annihilation emission path using a positron emission detector, wherein the emission paths intersect a target region of tissue; calculating an attenuation factor for the transmit path using an image of a target region of tissue acquired by the selected imaging modality; and applying radiation along the emission path, wherein the radiation is modulated by the attenuation factor. In certain variations, the emission may be adjusted to compensate for attenuation of the emission along the positron annihilation emission path. The radiation applied may be directly or inversely proportional to the attenuation of the detected positron annihilation emission. In some variations, the selected imaging modality may be computed tomography. In some variations, the intensity of the radiation may be adjusted in direct proportion or inverse proportion to the attenuation coefficient. Additionally or alternatively, the applied radiation may have a duration that is adjusted either directly or inversely proportional to the attenuation coefficient. For example, the radiation applied along the emission path may have a frequency that is adjusted either directly or inversely proportional to the attenuation coefficient.

A variation of the system for EGRT may include: a gantry movable about a patient area, wherein the gantry includes a rotatable inner gantry and a rotatable outer gantry; a plurality of positron emission detectors movably disposed along an internal gantry configured to detect a plurality of positron annihilation emission paths within the patient region; and a radiation source movably disposed along the external gantry, wherein the radiation source is configured to apply radiation along each of a plurality of positron annihilation emission paths within the patient region. In some EGRT systems, the inner gantry can rotate at a higher rate than the outer gantry. In some variations, a system may comprise: a sensing mode in which a plurality of positron emission detectors block the radiation source; and an emission mode in which the radiation source is unobstructed and capable of applying radiation to the patient area. Alternatively or additionally, the EGRT system may comprise one or more single photon emission detectors movably arranged along the internal gantry. In some variations, the radiation source may also include a collimator (collimator).

One example of a method for emission guided radiation therapy may include: detecting positron annihilation emission paths intersecting a plurality of target tissue regions using a plurality of positron emission detectors; positioning a radiation source to apply radiation along each of the plurality of emission paths; and applying radiation along each of the radiation paths to deliver radiation to the plurality of target tissue regions.

Another example of a system for EGRT may include: a gantry moveable about a patient area, wherein the gantry includes a rotatable inner gantry and a rotatable outer gantry, a plurality of positron emission detectors movably disposed along the inner gantry configured to detect a plurality of positron annihilation emission paths within the patient area from a plurality of moving PET-desirous regions, and a radiation source movably disposed on the outer gantry, wherein the radiation source is configurable to apply radiation to the plurality of PET-desirous regions within the patient area. In some EGRT systems, the inner gantry is capable of rotating at a higher rate than the outer gantry. In certain variations, the EGRT system may comprise: a sensing mode in which a plurality of positron emission detectors block the radiation source; and an emission mode in which the radiation source is unobstructed and capable of applying radiation to the patient area. Alternatively or additionally, the EGRT system may comprise one or more single photon emission detectors movably arranged along the internal gantry. In some variations, the radiation source may also include a collimator.

One example of a method for EGRT may include: detecting positron annihilation emission paths intersecting a plurality of moving target tissue regions using a plurality of positron emission detectors; positioning a radiation source to apply radiation along the emission path; and applying radiation to a plurality of moving target tissue regions along a path derived from moving the detected emission path in accordance with the movement of the target tissue regions.

Described herein are systems that may be used to position a radiation source (e.g., a radiation source that may be used in an EGRT system). One variation of a system for positioning a radiation source may include: a circular gantry, a radiation source mounted on the gantry, a positron emission detector mounted on the gantry, and a controller in communication with the radiation source and the positron emission detector. The positron emission detector may be configured to detect a positron emission path originating from the first region of interest within the coordinate system, and the controller may be configured to position (e.g., by programming an algorithm stored in memory) the radiation source along the emission path. The radiation source may be configured (e.g., via a program stored in memory and/or one or more signals from the controller) to generate radiation according to the selected probability coefficients. In certain variations, the controller may be configured to determine whether the transmit path intersects a second region of interest within the coordinate system; if the emission path intersects the second region of interest, the radiation source may be configured to generate radiation along the emission path according to the selected probability coefficients. Alternatively or additionally, the radiation source may be configured to generate radiation along the transmit path if the transmit path intersects the second region of interest and the selected probability coefficient is below a pre-programmed probability threshold. In certain variations, the radiation source may be configured to produce radiation along the emission path that is probabilistically intensity-adjusted and/or may be configured to produce radiation that is expanded by the probability coefficients.

Another variation of a system for positioning a radiation source may include: a circular gantry, a radiation source mounted on the gantry, a positron emission detector mounted on the gantry, and a controller in communication with the radiation source and the positron emission detector. The positron emission detector may be configured to detect a plurality of positron emission paths originating from a plurality of regions of interest within a coordinate system, and the controller may be configured to position (e.g., by programming an algorithm stored in memory) the radiation source along the plurality of emission paths.

Another variation of a system for positioning a radiation source may include: a circular gantry, a radiation source mounted on the gantry, a positron emission detector mounted on the gantry, and a controller in communication with the radiation source and the positron emission detector. The positron emission detector may be configured to detect positron emission paths within a coordinate system that intersect a plurality of moving regions of interest, and the controller may be configured (e.g., by programming an algorithm stored in memory) to position the radiation source along an emission path derived from moving the detected emission paths in accordance with movement of the regions of interest.

One variation of a system for positioning a radiation source may include: a circular gantry, a radiation source mounted on the gantry, a positron emission detector mounted on the gantry, and a controller in communication with the radiation source and the positron emission detector. The positron emission detector may be configured to detect a positron emission path within a coordinate system that intersects the region of interest, wherein the emission path may be substantially perpendicular to a predetermined direction from an extended edge of the region of interest. The controller may be configured (e.g., by programming an algorithm stored in memory) to position the radiation source along the emission path, and the radiation source may be configured (e.g., by a program stored in memory and/or one or more signals from the controller) to generate a radiation beam having a width corresponding to the width of the extended edge. In certain variations, the region of interest may be PET-avid and the extended border may include a region adjacent to the PET-avid region of interest.

One variation of a system for positioning a radiation source may include: a circular gantry, a radiation source mounted on the gantry, a positron emission detector mounted on the gantry, and a controller in communication with the radiation source and the positron emission detector. The positron emission detector can be configured to detect a boundary of the PET-avid region of interest within a coordinate system and detect a single coincident positron annihilation emission path within the coordinate system that intersects the second region of interest. The controller may be configured (e.g., by programming an algorithm stored in memory) to define an extended region beyond the boundaries of the PET-avid region of interest and determine whether the detected emission path is substantially perpendicular to an axis of the extended region. The radiation source may be configured (e.g., via a program stored in memory and/or one or more signals from the controller) to generate a radiation beam having a width corresponding to the extended edge width. In some examples, the controller may be configured to define the extension region by using images obtained by computed tomography and/or magnetic resonance imaging.

Another variation of a system for positioning a radiation source may include a circular gantry, a radiation source mounted on the gantry, a positron emission detector mounted on the gantry, and a controller in communication with the radiation source and the positron emission detector. The positron emission detector can be configured to detect a single positron annihilation emission path intersecting the region of interest within a coordinate system. The controller may be configured (e.g., by programming an algorithm stored in memory) to calculate an attenuation factor for the emission path using images of the region of interest acquired by the selected imaging modality and to position a radiation source along the emission path. The radiation source may be configured (e.g., via a program stored in memory and/or one or more signals from the controller) to produce radiation that is adjusted by the attenuation factor. The selected imaging modality may be computed tomography and/or magnetic resonance imaging. In some examples, a radiation source may be configured to produce radiation that may be adjusted to compensate for attenuation of the radiation along the positron annihilation emission path. Alternatively or additionally, the radiation source may be configured to produce radiation that is directly proportional to the attenuation of the detected positron annihilation emission path. In other examples, the radiation source may be configured to produce radiation that is inversely proportional to the attenuation of the detected positron annihilation emission path. Alternatively or additionally, the radiation source may be configured to produce radiation having an intensity that is adjusted proportionally to the attenuation factor, and/or having a duration that is adjusted proportionally to the attenuation factor, and/or having an intensity that is adjusted inversely proportionally to the attenuation factor, and/or having a frequency that is adjusted inversely proportionally to the attenuation factor.

Another variation of a system for positioning a radiation source may include a circular gantry, a radiation source mounted on the gantry, a positron emission detector mounted on the gantry, and a controller in communication with the radiation source and the positron emission detector. The positron emission detector can be configured to detect a single positron annihilation emission path within the coordinate system that intersects the first PET-avid region of interest and the second PET-avid region of interest. The controller may be configured (e.g., by programming an algorithm stored in memory) to position the radiation source to a position along the emission path. The radiation source may be configured (e.g., via a program stored in memory and/or one or more signals from the controller) to generate radiation that is modulated according to a modulation factor that is inversely proportional to the projection of the first PET-avid region of interest onto the location of the radiation source. In certain variations, the radiation source may be configured to generate a radiation beam having a duration that is modified by the modulation factor. Alternatively or additionally, the radiation source may be configured to produce radiation having an intensity that is modified by the modulation factor. In some examples, the second PET-avid region of interest may intersect a third region of interest, and the first region of interest may not intersect the third region of interest.

A variation of the system for emission guided radiation therapy may include: a gantry movable about a patient region, a plurality of positron emission detectors movably disposed along an inner gantry configured to detect a plurality of positron annihilation emission paths within the patient region, and a radiation source movably disposed along the outer gantry. The gantry may comprise a rotatable inner gantry and a rotatable outer gantry, along which the radiation source may be movably arranged. A radiation source may be configured to apply radiation along the plurality of positron annihilation emission paths within the patient region, an inner gantry being rotatable at a higher rate than the outer gantry. Optionally, the system may further comprise a single photon emission detector movably arranged along the internal housing. In certain variations, the radiation source may include a collimator. Such a system may optionally include: a sensing mode in which the plurality of positron emission detectors block the radiation source, and an emission mode in which the radiation source is unblocked and capable of applying radiation to the patient area.

Drawings

Figure 1 is a variation of an emission guided radiation therapy system for calibrating radiation along a positron annihilation emission path.

FIG. 1A is a conceptual depiction of an example of an EGRT method for probabilistically applying radiation along lines of response (LORs) that intersect both a planning target Portion (PTV) and a radiation sensitive structure; FIG. 1B is a flow chart of one example of an EGRT method operating in accordance with the description in FIG. 1A; fig. 1C through 1E show contour plots (with uniform contour spacing) derived from computer simulations using the method of fig. 1B.

Fig. 2A is a conceptual depiction of another variation of the EGRT method for applying a radiation beam having a width corresponding to the width of an extended region substantially perpendicular to the PTV; FIG. 2B is a flow diagram of one method that may be used to define an extended region of a PTV; FIG. 2C is a flow chart of an example embodiment of the method shown in FIG. 2A.

FIG. 3A is a conceptual depiction of another EGRT method for applying radiation beams that distinguish PET-avid regions within a PTV from PET-avid regions outside the PTV; FIG. 3B is a flow chart of an example embodiment of the method shown in FIG. 3A.

FIG. 4A is a conceptual depiction of another EGRT method for applying a collimated attenuated radiation beam along coincident positron emission paths; fig. 4B is a flow chart of an example embodiment of the method shown in fig. 4A.

FIG. 5A is a conceptual depiction of another EGRT method for accurately applying radiation beams along coincident positron emission paths; fig. 5B is a flow chart of an example embodiment of the method shown in fig. 5A.

Fig. 6A to 6C are conceptual depictions of an example of the ERGT method applying multiple radiation beams along a single LOR; fig. 6D is a flow chart of an example embodiment of the method shown in fig. 6A through 6C.

Fig. 7 is a flow chart of one example of a method of using both EGRT technology and intensity modulated emission therapy (IMRT) technology.

FIGS. 8A and 8B are conceptual depictions of an EGRT method for updating location information for tumors and/or PTVs during EGRT; fig. 8C is a flow chart of an example embodiment of the method shown in fig. 8A and 8B.

FIG. 9A is a conceptual depiction of another example of an EGRT method for modulating radiation applied to a PTV for uniform dose distribution; fig. 9B is a flow chart of an example embodiment of the method shown in fig. 9A.

FIGS. 10A and 10B are conceptual depictions of an EGRT method for calculating the starting point of a LOR; FIG. 10C is a flow chart of an example embodiment of the method shown in FIG. 10A.

FIG. 11A is a conceptual depiction of a variation of the EGRT method for delivering radiation to a region of hypoxic tissue; FIG. 11B is a flow chart of an example embodiment of the method shown in FIG. 11A.

FIG. 12A is a conceptual depiction of a variation of the EGRT method for delivering radiation along LORs that intersect a PTV having reduced positron emission activity; fig. 12B is a flow chart of an example embodiment of the method shown in fig. 12A.

Fig. 13 is a flow chart of an example of an EGRT method using more than one PET tracer.

FIG. 14A is a conceptual depiction of an example of an EGRT method applying radiation along LORs intersecting multiple PTVs; FIG. 14B is a flow chart of an example embodiment of the method shown in FIG. 14A.

Fig. 15A through 15B are exemplary schematic diagrams of an EGRT system having a movable internal gantry and a separate movable external gantry; fig. 15C is a flow chart of one example of how the system shown in fig. 15A and 15B may be used.

Detailed Description

Described herein are methods and systems for positioning a radiation source with respect to one or more regions of interest in a coordinate system. In certain variations, such systems and methods may be used to guide radiation therapy for emission of radiation delivery along an emission path from a photon in a positron annihilation event. The methods and systems described herein may be used to deliver a high dose of radiation to a first region of interest (e.g., a tumor) and a small amount of radiation (if any) to a second region of interest (e.g., surrounding tissue). The systems and methods described below are capable of accurately locating a target tumor region so that high levels of radiation can be applied to the tumor(s) and protect the tissue surrounding the tumor(s). These systems and methods can help provide accurate tumor location and can be used to deliver radiation beams to the target tumor region in real time (e.g., within seconds after the positron annihilation emission path has been detected). To provide useful radiation therapy, these systems and methods can address and manage uncertainties derived from multiple processes (e.g., tumor volume delineation, patient positioning, and physiological motion). The systems and methods described herein may help improve radiation treatment efficacy, patient comfort, and/or cost efficiency. Although variations and examples are described below with reference to an EGRT system, it should be understood that these are merely examples of a system that may be used to position a radiation source with respect to one or more regions of interest in a coordinate system. The region of interest within the coordinate system may include, but is not limited to, tumor tissue, non-tumor regions, radiosensitive organs or structures, any anatomical structure, any positron-emitting (e.g., PET-avid regions) region or body, any positron-non-emitting (e.g., non-PET-avid regions) region or body, a defined region or body with respect to PET-avid regions, a fixed region or body, a moving region or body, any region or body identified by a user or practitioner (e.g., planning a target body) or a machine algorithm (e.g., an image processing algorithm), and so forth.

EGRT may be used alone or with other types of emission therapy. For example, EGRT may be used with intensity modulated emission therapy (IMRT) and/or image guided emission therapy (IGRT). IMRT is capable of producing a highly conformal dose distribution for delivering radiation to a targeted tumor region while retaining healthy tissue. Prior to treatment planning, IGRT may use an imaging modality such as MRI or CT to locate the tumor within the patient. For real-time location tracking of the target tumor region, it may be beneficial to combine one or both of these imaging techniques with EGRT in order to help ensure that the therapeutic radiation is directed at the tissue region of interest.

Disclosed herein are systems and methods of EGRT using PET tracers, wherein radiation may be applied along a line of response (LOR) that is calibrated to the coincident positron annihilation emission path of detection. A system that may be used for EGRT may include: a gantry movable about a patient area, one or more positron emission detectors movable along the gantry, and one or more therapeutic radiation sources also movable along the gantry. One or more positron emission detectors are capable of detecting and tracking emission paths corresponding to multiple regions of interest (e.g., tumor (s)). The one or more radiation sources may be configured to compensate for motion of individual ones of the plurality of tumors so that radiation may be accurately applied to the tumor(s) and not to healthy tissue. A variation of a system (130) for positioning a radiation source that may be used to emit guided radiation treatments is shown in fig. 1. The system 130 may include a circular moveable gantry (not shown), a radiation source (131) mounted on the gantry, one or more positron annihilation emission sensors (133) positioned at various locations on or around the gantry, one or more x-ray detectors (132), a motion system (134), and a controller or microprocessor (135). An x-ray detector (132) and positron annihilation emission sensor (133) may also be mounted on the moveable gantry. In certain variations, the positron emission detector (133) and the x-ray detector (132) may be disposed around a substantial portion of a perimeter of the gantry. A positron emission detector (133) can be configured to detect a positron annihilation event by sensing the emission path (136) of the photon caused by the annihilation event. A motion system (134) may be configured to move the gantry and the accessory device with respect to a region of interest or target volume (138) so that the radiation source (131) is aligned with the detected emission path (136). A microprocessor (135) is connectable to the radiation source (131), the positron emission detector (133), the x-ray detector (132) and the motion system (134) for adjusting the movement of the components relative to each other and for activating the components in a desired sequence. For example, the microprocessor (135) may identify the coincident positron emission paths (136) intersecting the target portion (138), and may coordinate the calibration, configuration, and triggering of the radiation source to direct radiation to the target portion (138) along the detected emission paths (136).

A microprocessor (135) may control rotation of the gantry to adjust an orientation of the radiation source (131) in response to a plurality of detected emission paths during an EGRT procedure. The microprocessor of the EGRT system may include a computer-readable storage medium and may be capable of performing various functions in accordance with software or firmware stored in the computer-readable storage medium. Examples of the computer-readable storage medium may include: but are not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus or device, a portable computer diskette (magnetic), a Random Access Memory (RAM) (magnetic), a read-only memory (ROM) (magnetic), a programmable erasable read-only memory (EPROM) (magnetic), a portable optical disk such as a CD, CD-R, CD-RW, DVD-R, or DVD-RW, or a flash memory such as a compact flash card, a secure digital card, a USB memory device, a memory stick, or the like. The software or firmware can also be propagated within any transport medium for use by or in connection with an instruction execution system, apparatus, or device, such as a computer-based system, processor-containing system, or other system that can fetch the instructions from the instruction execution system, apparatus, or device and execute the instructions. Examples of transmission media may include: but are not limited to, an electrical, magnetic, optical, electromagnetic, or infrared, or wired or wireless propagation medium.

Although the systems and methods of EGRT described herein may be configured to detect and respond to emission paths from coincident positron annihilation emission events resulting from PET tracers, other types of radiotracers may also be used for EGRT. For example, the EGRT systems and methods may additionally or alternatively be configured to detect and respond to single photon emissions resulting from SPECT tracers. Other radiotracers that are often used in nuclear medicine may also be used with the EGRT systems and methods described herein. The emission lines from such radiotracers may be used as a guide for accurate and near real-time tumor tracking. Depending on the type of radiotracer used, the EGRT system may include a variety of detectors, such as positron emission detectors, single photon emission detectors, and the like. The EGRT system may also include a variety of therapeutic radiation sources including linear accelerators, emissive materials, x-ray sources, particle beam sources, and the like. In certain variations, the radiation source may include a collimator capable of delivering radiation in response to single photon events. One example of a system that may be used for EGRT is described in U.S. patent No. 7,265,365, registered on 29.11.2004. Additional descriptions and examples of EGRT systems are provided below, and in U.S. patent application publication No. 2009/0256078, filed 2/9/2009, the entire contents of which are incorporated herein by reference.

The method for EGRT may be used to track the location of a tumor in real time, and/or may be used to deliver a desired dose of radiation to the tumor(s) in a Planning Target Volume (PTV) while protecting surrounding tissue. The PTV may be determined by a physician and/or technician (e.g., a radiation oncologist, medical physicist, radiation radiologist, radiation therapist, etc.) using a variety of imaging modalities (e.g., CT, PET, MRI, x-ray, etc., either alone or in combination) before treatment and/or during a planned procedure. The PTV may also be determined during a transmit therapy session. For example, the PTV may be periodically determined during a transmit therapy session using one or more types of on-board imaging modalities (e.g., CT, PET, MRI, x-ray, etc., either alone or in combination). Data about the PTV may be stored in the microprocessor of the EGRT system for use by a medical physicist and/or a radiation therapist during a radiation therapy session. The PTV may include the tumor region and surrounding non-tumor tissue in the tumor region, or the PTV may include only a tumor region without the surrounding non-tumor tissue. Alternatively or additionally, the PTV may include the visible region and growth of the tumor as determined by the selected imaging modality (e.g., CT, PET, MRI, x-ray, SPECT, etc.). In some cases, a PTV may include a PET-avid tissue region (e.g., a body of tissue that has been occupied by a PET tracer and emits photons resulting from positron annihilations), and in other cases, a PTV may include both a PET-avid region and a contiguous non-PET-avid tissue region. In certain variations, the PTV may include regions described above with one or more additional edges, such as edges of patient and/or organ motion, organ shape and size variations, and uncertainty in radiation beam calibration.

Certain methods may help compensate for tumor and/or PTV movement due to breathing or other patient movement, and/or provide for more accurate or precise tumor margin detection, and/or help ensure that the radiation applied to the PTV is homogenous by reducing "hot" or "cold" spots in the PTV (e.g., so that the radiation dose is delivered evenly throughout the entire PTV). While the various methods for EGRT are described separately below, it should be understood that one or more of the methods described herein may be combined before or during an EGRT procedure. Optionally, one or more of these methods of EGRT may be used in conjunction with surgery, chemotherapy, brachytherapy, and/or other cancer therapies during the treatment of cancer in a patient.

One variation of the method of EGRT may deliver a reduced dose of radiation to a radiation sensitive structure while delivering a prescribed dose of radiation to a tumor located in a PTV. Certain variations of such methods may avoid delivering any dose of radiation to a selected tissue region or any radiation-sensitive structure. The radiation-sensitive structure may be, for example, an organ that is particularly vulnerable to radiation. Radiation sensitive structures may include the heart, esophagus, rectum, stomach, large and small intestine, chest, salivary gland organs contained in gametes, spine and other neural tissue, and so forth. In certain variations of EGRT, the radiation-sensitive structures may optionally be treated with a radioprotective drug (e.g., amifostine), which helps these radiation-sensitive structures self-repair any radiation damage. One variation of the method of delivering a reduced dose of radiation to a radiation-sensitive structure may include delivering radiation infrequently along coincident positron annihilation emission paths or LORs that intersect the radiation-sensitive structure. Fig. 1A conceptually illustrates a patient region (100) having a planned target portion (102) and a radiation sensitive structure (104). At least a portion of the PTV, which may have occupied a PET tracer (e.g., FDG, FLT, F-MISO) and may be emitting photons due to positron annihilation events, for example, may be PET-avid. Transmit paths or lines of response (e.g., line of response (106)) originating within the PTV may intersect the radiation sensitive structure (104) while other ones of the transmit paths or lines of response (e.g., line of response (108)) do not intersect the radiation sensitive structure (104). A radiation source (not shown) may apply radiation at a particular frequency and intensity along the LOR (108) to deliver a prescribed dose to the PTV (102). A radiation source may apply radiation that has been attenuated or modulated (e.g., in frequency and/or intensity) along the LOR (106) in order to reduce exposure of the radiation to the radiation-sensitive structure (104). For example, the frequency with which radiation is transmitted along the LOR can be reduced in a probabilistic manner. Alternatively or additionally, the radiation transmitted along the LOR (106) may be attenuated (e.g., reduced in intensity or power) as compared to the radiation transmitted along the LOR (108).

An example of a method (110) of delivering a reduced amount of radiation to a radiation sensitive structure while delivering a prescribed dose of radiation to a PTV is schematically presented in fig. 1B. The method (110) may, for example, reduce the frequency at which radiation is applied along a LOR intersecting the radiation-sensitive structure. Such a method may be implemented using an EGRT system that includes a movable gantry, one or more positron emission detectors along the gantry, one or more radiation sources mounted on the gantry, a motion system, and a microprocessor. Processing the LOR (112) can include detecting a single coincident positron annihilation emission path using a positron emission detector, and optionally can include storing data (e.g., position data, signal intensity data, etc.) about the LOR in a memory of the microprocessor. The microprocessor may then evaluate whether the LOR intersects a PTV by comparing the position data of the LOR to position data of a PTV stored in memory of the microprocessor (114). If not, the EGRT system may return to the initial state (112) to detect another LOR. If so, the microprocessor may compare the position data of the LOR with the position data of the radiation sensitive structure to assess whether the LOR intersects a radiation sensitive structure (116). If not, the microprocessor may send instructions to the radiation source of the EGRT system to apply radiation along the LOR (122). If so, the microprocessor may randomly generate a number X between 0 and 118 (118). The microprocessor then determines whether the number X is below a pre-programmed probability threshold T (120). If not, the EGRT may return to the initial state (112) to detect another LOR. If the adjustment number X is below a pre-programmed threshold T, the microprocessor may send instructions to the radiation source to apply radiation along the LOR (122). Once radiation has been delivered along the detected LOR, the method (110) may be repeated if desired, for example, until a prescribed dose of radiation has been applied to the PTV and/or the radiation-sensitive structure. As an example, it may be desirable to prescribe a dose to the radiation sensitive structure that is no more than 20% of the dose level of the surrounding tissue and/or PTV. In this example, the probability threshold T may be selected to be 0.2 so that radiation is delivered to one fifth of the line of response that intersects both the radiation-sensitive structure and the PTV. Alternatively, the probability threshold T may also represent an attenuation or expansion coefficient by which the radiation is modulated. For example, the radiation applied along an LOR that intersects both the PTV and the radiation sensitive structure may be adjusted by the probability threshold of T ═ 0.2 such that the radiation application is at 20% of normal intensity level. Alternatively, the nominal leaf-open (leaf-open) time of the radiation source may be 20% of the nominal leaf-open time. The probability threshold T may be any suitable value, e.g., 0, 0.005, 0.01, 0.05, 0.10, 0.5, 0.75, 0.9, 1.0, etc. In other variations, the intensity or power of the radiation applied along the LOR is attenuated or spread by a probability coefficient. The probability coefficient may be derived from a randomly generated number between 0 and 1 that is less than the threshold T.

Fig. 1C through 1E are contour plots representing a computer simulated radiation dose map when the method (110) is implemented to apply radiation to a PTV (140). The different contours in fig. 1C to 1E have uniform contour spacing and reflect the effect of varying the probability threshold T on the amount of radiation applied to the radiation sensitive structure (142). Fig. 1C shows a dose profile plot when the probability threshold T is 1.0 (e.g., no penalty is given to delivering dose to the radiation sensitive structure). In this example, the radiation dose to the radiation sensitive structure (142) is similar to the radiation dose of surrounding tissue. Fig. 1D shows the dose profile when the probability threshold T is 0.2, and fig. 1E shows the dose profile when the probability threshold T is 0.0. When the probability threshold T is decreased towards 0, the total dose to the radiation sensitive structure (142) may be decreased as shown in the contour plot.

In other variations of the EGRT method, the radiation source may adjust characteristics of the radiation beam delivered to the PTV in order to deliver radiation to non-aspirational PET tissue within the PTV. For example, the width of the radiation beam may be expanded to deliver radiation to non-aspirational PET tissue within the PTV, and/or multiple radiation beams may be applied to non-aspirational PET tissue within the PTV over a period of time. One example of such a method is conceptually illustrated in fig. 2A. Such a method may include acquiring images (e.g., one or more of CT, MRI, PET, etc., including PET-CT images) during a treatment planning phase to define the planned target portion or portions to be treated during EGRT. The edge of the expanded PTV (202) may be expanded from the edge of the crave PET target portion (204) by a width (W1). During an EGRT procedure, when LORs (206) intersecting the PTV (202) are detected by positron emission detectors (not shown), a radiation beam (208) applied by the radiation source (210) may be adjusted such that the radiation beam width (W2) is wider in a direction that increases an edge between the eager PET body (204) and the PTV (202). In certain variations, the width (W2) of the radiation beam may be expanded in the direction of the edge if the radiation beam (208) is substantially perpendicular to the direction of expansion of the edge.

An example of a method of applying radiation to tissue within a PTV adjacent to a PET-avid body boundary is shown in fig. 2B and 2C. Fig. 2B illustrates a method (220) that may be used during a treatment plan, which may be performed prior to the EGRT procedure, or may be performed during the EGRT procedure. The method (220) may include acquiring (220) one or more images, such as CT, MRI, PET, and/or including PET-CT images. Based on the acquired image(s), PTV(s) may be defined by locating the PET-avid region. Optionally, any extended edge beyond the aspirational PET body may also be defined, e.g., the PTV(s) may include aspirational PET tissue and non-aspirational PET tissue adjacent to the aspirational PET tissue. In certain variations, the extended edge of the treatment body(s) and/or the PET-avid body may be defined by additional patient data, computer-implemented image processing algorithms, and/or physician input, and may have a length and width that exceeds the edge of the PET-avid body(s). Information about the aspirational PET body and/or an extended edge (e.g., length, width, body, direction of the extended edge about the target body, etc.) that defines a boundary of a PTV may be stored in a memory of a microprocessor of an EGRT system for use during a treatment session.

Fig. 2C shows an example of an EGRT method (230) that may use information from the method (220) to provide radiation therapy to a patient. Such a method may be implemented using the EGRT system described above and further described below. The imaged craving PET body, as well as extended edge data (e.g., length, width, body, direction of the extended edge with respect to the target body, etc.) from the method (220) may be stored in a memory of a microprocessor of the EGRT system prior to the EGRT procedure. Alternatively or additionally, an extended margin may be determined or calculated by the EGRT system at any point during the therapy session by acquiring one or more images (e.g., CT, MRI, PET, and/or PET-CT images including a composite) during therapy. Processing a LOR (232) can include detecting a single coincident positron annihilation emission path using a positron emission detector, and optionally can include storing data (e.g., position data, signal intensity data, etc.) about the LOR in a memory of the microprocessor. The microprocessor may then evaluate whether the LOR intersects a PTV by comparing the position data of the LOR with the position data of the PTV (234). If not, the EGRT system may return to the initial state (232) to detect another LOR. If so, the microprocessor may use data from the method (220) to calculate (236) whether the LOR is substantially perpendicular to the extended edge direction. If not, the microprocessor may send instructions to a radiation source of the EGRT system to apply radiation along the LOR (268). If the LOR is calculated to be substantially perpendicular to the extended edge direction, the microprocessor can send instructions to a radiation source to transmit (240) a radiation beam along the LOR, wherein the radiation beam has a width corresponding to the extended edge width. In certain variations, the extended edges may be calculated by a microprocessor of the EGRT system during the therapy session, and may be used alone or with any extended edges that may be determined during a treatment planning phase. Once radiation has been delivered along the LOR, the method (230) may be repeated if desired, for example, until a prescribed dose of radiation has been applied to the PTV.

Certain variations of the EGRT method can distinguish coincident positron annihilation emission paths originating from a planned target volume from emission paths originating outside the planned target volume. Positron annihilation events can occur outside of the PTV and enhanced uptake of certain PET tracers (e.g., FDG) can occur, for example, in the heart, brain, areas of inflammation, infected areas of the lung, or other structures. For example, the PET tracer may be occupied by tissue in multiple locations, and EGRTs may be planned for only a subset of those locations (e.g., some PET-avid tissues may be suitable targets for radiation while others may be unsuitable). Fig. 3A shows a patient area (300) having a first PET-avid body (302) and a second PET-avid body (304). In this example, the first crave PET body (302) may not be part of a PTV. A second crave PET body (304) may be located within the PTV. Methods that do not distinguish between EGRTs originating from coincident positron annihilation emission paths within a PTV and emission paths originating outside the PTV may apply an enhanced radiation dose in the direction connecting the PTV with the PET-avid region outside the PTV. One way in which the EGRT method may avoid creating localized regions of relatively higher radiation may include computing a mathematical projection of a PET-avid body outside the PTV for each orientation that a therapeutic radiation source may occupy. For example, a first crave PET body (302) may have a projection (306) of a radiation source at location 307. Similar projections of a PET-avid body outside the PTV may be calculated for the position of one or more radiation sources on the gantry of the EGRT system. In some variations, the calculated projections may be used to adjust the emission time or intensity or number of the radiation transmitted along the respective paths, which is inversely proportional to the projection values at a particular location. For example, a craving PET region outside the PTV may result in a higher relative projection value along the path through the PTV when compared to a different path through the PTV. The radiation source may deliver radiation in accordance with the calculated projection values. For example, an enhanced projection value at a particular position of the gantry may indicate that the therapeutic radiation source is from that position, and a lower projection value may indicate that the therapeutic radiation source is delivering a lesser proportion of radiation from that position. Radiation delivery may be adjusted in different ways, for example, to time, intensity, or number of shots taken along the emission path.

An example of a method (310) of avoiding the establishment of localized areas of high radiation is schematically given in fig. 3B. The method (310) adjusts the radiation applied along the LOR according to a projection of a "hot spot" at the location of the radiation source. Such a method may be implemented using an EGRT system that includes a moveable gantry, one or more positron emission detectors along the gantry, one or more radiation sources along the gantry, a motion system, and a microprocessor. Processing the LOR (312) can include detecting a single coincident positron annihilation emission path using a positron emission detector, and optionally can include storing data (e.g., position data, signal intensity data, etc.) about the LOR in a memory of the microprocessor. The microprocessor may then evaluate whether the LOR intersects a PTV by comparing the location data of the LOR to the location data of the PTV, which may be stored in the memory of the microprocessor (314). If not, the EGRT system may return to the initial state (312) to detect another LOR. If so, the microprocessor may calculate a modulation factor that is inversely proportional to the projection of one or more PET-avid regions that are not within the PTV (316). The calculated modulation factor may be used to adjust the frequency, duty cycle, intensity, number of transmissions, and/or other characteristics of the radiation beam. The microprocessor may then provide instructions to the radiation source to adjust the radiation beam according to the modulation factor. A radiation source may then deliver (318) the conditioned radiation along the LOR. Once radiation has been delivered along the detected LOR, the method (310) may be repeated if desired, for example, until a prescribed dose of radiation has been applied to the PTV.

Some methods of EGRT may compensate for any attenuation in LOR signal intensity that may occur due to density variations within the patient region. Fig. 4A conceptually illustrates a patient region (400) with a PET-avid body (401) and a higher density region. The high density areas may be due to the presence of an implanted prosthesis, an organ with a higher tissue density, such as bone (404), and the like. For example, LORs (402) that intersect the bone structure (404) may be attenuated more than LORs (406) that do not intersect any bone or high density regions. Various imaging modalities can be used to approximate the attenuation of the signal intensity of a LOR. In certain variations of EGRT, kilovoltage CT images may be used to estimate and compensate for the attenuation of the LOR signal. The LOR attenuation may also be calculated based on other imaging modalities, such as cone beam CT, MRI, X-ray, and the like. The estimation of said attenuation of LOR signals can be performed before a planning phase or session or during a radiation therapy session. In certain variations, the attenuation of LOR signals may be dynamically calculated during the radiation therapy session using PET or x-ray imaging techniques. The radiation beam can then be adjusted to compensate for LOR signal attenuation in accordance with the attenuation of the LOR signal so that a calibrated amount of radiation is delivered to the PTV while limited radiation is delivered to healthy tissue. In some cases, it may be desirable to apply an enhanced level of radiation along an attenuated LOR to compensate for the attenuation effects and help ensure that the PTV receives a therapeutically effective level of radiation. In other cases, where a high density region of the LOR is attenuated by a radiation sensitive structure, it may also be desirable to apply a reduced level of radiation along that LOR to reduce or limit the radiation delivered to the high density region. For example, a bone structure may attenuate a LOR signal, and the radiation applied along the attenuated LOR may be reduced to limit the radiation delivered to the bone structure. The radiation beam can be adjusted, for example, to compensate for the attenuation in amplitude or frequency of the detected LOR signal by increasing or decreasing in amplitude or frequency. Alternatively or additionally, the radiation beam may be adjusted in time (e.g., duty cycle) and/or intensity. Such adjustments can be made by estimating an intensity projection of a LOR along its entire path through the patient, converting that projection estimate to LOR positron energy (e.g., 511 kev), and adjusting the time or intensity of the radiation response so that the amount of radiation delivered compensates for the overall attenuation along the LOR path.

An example of a method to calibrate or compensate for LOR signal attenuation so that a sufficient amount of radiation is applied to the PTV is schematically given in fig. 4B. The method (410) adjusts the radiation applied along the LOR that compensates for the attenuation measured in the LOR signal. Such a method may be implemented using an EGRT system that includes a moveable gantry, one or more positron emission detectors along the gantry, one or more radiation sources along the gantry, a motion system, and a microprocessor. Processing the LOR (412) can include detecting a single coincident positron annihilation emission path using a positron emission detector, and optionally can include storing data (e.g., position data, signal intensity data, etc.) about the LOR in a memory of the microprocessor. The microprocessor may then evaluate whether the LOR intersects the PTV by comparing the location data of the LOR to location data of a PTV, which may be stored in memory of the microprocessor (414). If not, the EGRT system may return to the initial state (412) to detect another LOR. If so, the microprocessor may calculate (416) the attenuation of the LOR based on kilovolt or megavolt CT images that may have been previously input and/or stored in the microprocessor's memory. The attenuation of the LOR signal can be used to calculate an attenuation value (418), and the attenuation value (418) can be used to adjust the radiation beam. In certain variations, the calculated attenuation value may adjust the average energy of the radiation treatment by decreasing or increasing the amount of radiation in proportion to the amount of LOR signal attenuation, such that the calibrated amount of radiation is delivered along the attenuated LOR. The microprocessor may then provide instructions to the radiation source to adjust the radiation beam according to the calculated attenuation values. For example, the radiation beam may be adjusted proportionally or inversely proportionally to the attenuation coefficient. The radiation source may then deliver (420) the conditioned radiation along the LOR. Once radiation has been delivered along the detected LOR, the method (410) may be repeated if desired, for example, until a prescribed dose of radiation has been applied to the PTV.

One variation of the method that may be used with an EGRT system may be used to deliver radiation to multiple planned target portions. The method can include detecting positron emission events from a plurality of planned target portions and then applying one or more radiation beams along each detected LOR intersecting at least one of the planned target portions. The EGRT system and such method are capable of compensating for any movement of individual ones of the planned target portions by responding to the LOR in near real-time (e.g., within a few seconds after the LOR has been detected), regardless of their movement interrelationship. For example, after the LOR has been detected, a radiation beam may be applied along the detected LOR for less than 5 seconds, 4 seconds, 3 seconds, 2 seconds, 1 second, or 0.5 seconds. Fig. 14A shows an example in which the patient region (1400) has a first PET-avid region (1402) within a first PTV that moves along arrow (1404) and a second PET-avid region (1406) within a second PTV that moves along arrow (1408). The movement of the first and said second PET-avid bodies may be associated or not. LORs (1410), (1412), and (1414) represent LORs that intersect at least one of the planned target portions. An EGRT system may apply one or more radiation beams to the first PET-avid region (1402) along a LOR (1410) and/or one or more radiation beams to the second PET-avid region (1406) along a LOR (1412) and/or radiation beams to both the first PET-avid region and the second PET-avid region along a LOR (1414) to deliver a prescribed dose of radiation to the first and second PET-avid regions.

One example of a method (1420) of delivering radiation to multiple planned target portions is schematically presented in FIG. 14B. Such a method may be implemented using an EGRT system that includes a moveable gantry, one or more positron emission detectors along the gantry, one or more radiation sources along the gantry, a motion system, and a microprocessor. Processing the LOR (1422) can include detecting a single coincident positron annihilation emission path using a positron emission detector, and optionally can include storing data (e.g., position data, signal intensity data, etc.) about the LOR in a memory of the microprocessor. The microprocessor may then evaluate whether the LOR intersects the first PTV (1424) by comparing the position data of the LOR with the position data of the first PTV (1424). If so, then the microprocessor can provide instructions to the radiation source to apply radiation along the LOR (1428). If a LOR does not intersect a first PTV, the microprocessor may evaluate whether the LOR intersects the second PTV by comparing the location data of the LOR to the location data of the second PTV (1426). If so, the microprocessor can provide instructions to the radiation source to apply radiation along the LOR (1428). If not, the EGRT system may return to the initial state (1422) to detect another LOR. Once radiation has been delivered along the detected LORs, the method (1420) can be repeated if desired, for example, until a prescribed dose of radiation has been applied to the first and/or second planned target portions.

Certain variations of the EGRT method may be used to help the radiation therapy source accurately direct the radiation beam at the PTV. One example of such a method is conceptually illustrated in fig. 5A, where a patient represented by a patient area (500) is located within a central portion of a gantry (502) of an EGRT system. An LOR (503) detected by a positron emission detector may first be evaluated to determine whether the LOR (503) intersects the PTV (504). In some cases, the radiation source (506) may emit a radiation beam (508) when the radiation source (506) is placed a finite distance away from the detected LOR. At a particular point (507) in the PTV (504), the radiation beam (508) may be directed, which may help to calibrate the LOR (504) and the radiation beam (508). The point (507) may be the midpoint of a line segment made up of the intersection of the PTV and the LOR. For example, point (507) may be calculated by identifying a first point where the LOR crosses the boundary of the PTV, identifying a second point where the LOR crosses the PTV at a second location of the boundary, and connecting the first and second points to determine a line segment. The point (507) may be a midpoint of the defined line segment. Alternatively, the point (507) may be any other location within the PTV.

An example of a method (510) of accurately directing a radiation beam at a particular location in a PTV is schematically given in fig. 5B. A method (510) directs the radiation source to apply a radiation beam at a midpoint of a line segment formed by the intersection of the LOR and the PTV. Such a method may be implemented using an EGRT system that includes a moveable gantry, one or more positron emission detectors along the gantry, one or more radiation sources along the gantry, a motion system, and a microprocessor. Processing the LOR (512) can include detecting a single coincident positron annihilation emission path using a positron emission detector, and optionally can include storing data (e.g., position data, signal intensity data, etc.) about the LOR in a memory of the microprocessor. The microprocessor may then evaluate whether the LOR intersects the PTV (514) by comparing the position data of the LOR to the position data of the PTV (514). If not, the EGRT system may return to the initial state (512) to detect another LOR. If so, the microprocessor can calculate (516) the midpoint of the line segment made up of the intersection of the LOR and the PTV. The microprocessor may then provide instructions to the radiation source to direct and apply (518) a radiation beam to the midpoint calculated in the preceding steps. Once radiation has been delivered along the detected LOR, the method (510) may be repeated if desired, for example, until a prescribed dose of radiation has been applied to the PTV.

Other variations of the EGRT system may include delivering radiation from multiple locations and/or multiple points in time in response to a single LOR. By way of example, radiation beams may be transmitted along the LOR from either end of the LOR, or at different times from the same LOR end point. Fig. 6A and 6B conceptually illustrate one example of how multiple radiation beams may be applied along a LOR. Fig. 6A shows a patient (600) located in a gantry (602) with a craving PTV region of a PTV (604). LORs (606) originating within the PTV (604) are detectable at a first location (608) and a second location (610) along the gantry (602). A radiation source (612) is movable in various orientations along the gantry to apply a radiation beam to the PTV (604) along the LOR (606). For example, as shown in fig. 6B, the radiation source (612) may be moved to the first position (608) to apply a first radiation beam (614) to the PTV (604) along the LOR (606). Additionally or alternatively, as shown in fig. 6C, the radiation source (612) may be moved to the second position (608) to apply a second radiation beam (616) to the PTV (604) along the LOR (606). In certain variations, multiple radiation beams may be applied from the radiation source (612) along the LOR (606) at a single location.

An example of a method (620) of accurately directing a radiation beam at a particular location in a PTV is diagrammatically shown in fig. 6D. The method (620) directs the radiation source to apply a radiation beam from one or more endpoints of the detected LOR. Such a method may be implemented using an EGRT system that includes a moveable gantry, one or more positron emission detectors along the gantry, one or more radiation sources along the gantry, a motion system, and a microprocessor. Processing the LOR (622) can include detecting a single coincident positron annihilation emission path using a positron emission detector, and optionally can include storing data (e.g., position data, signal intensity data, etc.) about the LOR in a memory of the microprocessor. The microprocessor may then evaluate whether the LOR intersects the PTV (624) by comparing the position data of the LOR with the position data of the PTV (624). If not, the EGRT system may return to the initial state (622) to detect another LOR. If so, the microprocessor can provide instructions to the radiation source to transmit (626) a first radiation beam from a first location along the LOR. The microprocessor may then provide instructions to the radiation source to apply (628) a second radiation beam from a second location along the LOR. Alternatively, multiple radiation beams may be transmitted from the same location along the LOR. Once radiation has been delivered along the detected LOR, the method (620) may be repeated if desired, for example, until a prescribed dose of radiation has been applied to the PTV.

Another variation of the method may combine intensity modulated emission therapy (IMRT) and EGRT to deliver radiation therapy to a planned target portion. The hybrid IMRT-EGRT approach may be useful if the coincident positron annihilation emission signal is low, or if a short treatment time is desired. In certain variations, IMRT and EGRT may have separate pre-treatment plans, and during the radiation treatment, IMRT may be used to deliver radiation beams for one fraction of the treatment session, and EGRT may be used to deliver radiation beams for another fraction of the treatment session. For example, the radiation beams may be applied using IMRT first and then EGRT (or EGRT first and then IMRT) for various orientations of the radiation source along the gantry. During the emission therapy session, certain methods alternate between IMRT and EGRT for one or more radiation source orientations.

An example of a hybrid IMRT-EGRT method (700) is schematically presented in fig. 7. The method (700) may apply radiation to the PTV using both IMRT and EGRT techniques. The method (700) may be implemented using an EGRT system including a moveable gantry, one or more positron emission detectors along the gantry, one or more radiation sources along the gantry, a motion system, and a microprocessor. The radiation source can be moved to a first position along the gantry and at a particular gantry angle (702). In some variations, the arrangement of gantry angles may be evenly spaced around the circular gantry, while in other variations the spacing of the gantry angles may not be uniform. At various gantry angular positions, the microprocessor may receive data (e.g., position data, signal strength data, etc.) about the plurality of LORs from the positron emission detector(s), and based on a preprogrammed or predetermined model stored in the microprocessor, may calculate (704) or estimate whether IMRT or EGRT should be used to deliver radiation to the PTV (706). Using EGRT, this decision can be based on whether there is sufficient LOR data to respond. If IMRT is selected, the microprocessor may provide instructions to the radiation source to deliver (708) radiation to the entire PTV. If EGRT is selected, the microprocessor may evaluate whether the LOR intersects the PTV (710). If not, the EGRT system may return to the initial state (702) to process the next gantry angle. If so, the microprocessor can provide instructions to the radiation source to transmit a radiation beam along the LOR (712). Using IMRT or EGRT, once radiation has been delivered, the radiation source may be moved to another location and the method (700) may be repeated if desired, for example, until a prescribed dose of radiation has been applied to the PTV.

In another variation of the EGRT method, the method may include the step of updating the position and/or orientation of the PTV during the therapy session. For example, the center of mass of the PTV may be redefined to account for any tumor movement that may occur during the treatment (e.g., due to changes in patient breathing patterns, organ deformation, peristalsis, or changes in patient position, etc.). Fig. 8A and 8B conceptually illustrate a patient region (800) having a PTV (802) at an initial position and a tumor (804) at an initial position in the PTV (802). The initial position of the PTV and tumor may be measured during a pre-treatment session or at an earlier point in time during the radiation treatment session. During radiation treatment, the position of the PTV may need to be moved, for example, to the position shown in FIG. 8B. As shown in fig. 8B, the PTV may be redefined as a second orientation (806) to reflect the new range of motion of the tumor (808). In certain examples, the centroid of the PTV may be redefined according to the average range of motion of the tumor. Additionally or alternatively, a PET image may be reconstructed based on the PET signal data in a previous time interval (e.g., last 0.5 seconds, 1 second, 2 seconds, 10 seconds, 20 seconds, 50 seconds, 60 seconds, 90 seconds, etc.) and used to transform (translate, rotate, reorient, stretch or shrink, etc.) the PTV. Certain EGRT methods may include the step of redefining the PTV centroid based on a change in the centroid of the reconstructed PET image that is temporally blurred relative to the scan baseline or relative to the last reconstructed PET image.

An example of an EGRT method (810) that periodically updates the position of the PTV is shown in fig. 8C. The method (810) may update the position of the PTV every 30 seconds, but it should be understood that any update period may be selected as desired (e.g., 0.5 seconds, 1 second, 2 seconds, 10 seconds, 20 seconds, 50 seconds, 60 seconds, 90 seconds, etc.). The method (810) may be implemented using an EGRT system including a moveable gantry, one or more positron emission detectors along the gantry, one or more radiation sources along the gantry, a motion system, and a microprocessor. After the start of the EGRT treatment (812), the microprocessor can reconstruct (814) an initial or new PET image based on pre-treatment data or the most recent positron emission annihilation emission data from the last 30 seconds. The PET data and/or images may be stored in the memory of the microprocessor. The microprocessor may then determine (816) whether the current position of the PTV has changed from the previous position of the PTV by comparing the position data of the current position of the PTV with the position data of the previous position of the PTV. If there is no change, the microprocessor may provide instructions to the radiation source to apply a radiation beam along the detected LOR as previously described, and then the EGRT may continue to operate (818). If so, the position of the PTV may be updated (820) in the memory of the microprocessor. The microprocessor may then use the updated PTV position information to determine whether the LOR detected is located within the updated PTV. The EGRT may continue to operate 818. Once radiation has been delivered along the LOR, the method (810) can be repeated if desired, for example, until a prescribed dose of radiation has been applied to the PTV.

Certain variations of the EGRT method may be used to reduce or avoid the peak radiation dose that may occur in the center of other uniform back projection effects (e.g.) of a PET-avid body. This effect may occur because LORs that intersect a body near the center of the aspirational PET body may be detected more frequently than those that intersect the boundary of the aspirational PET body. The EGRT method may use a filtered-backprojection (filtered-backprojection) technique to reduce or eliminate emission peaks in PET-avid regions. Figure 9A conceptually illustrates a method that may be used to calculate a one-dimensional mathematical projection (902) of a PET-avid volume (900) that may emit photons at a generally uniform density, where the projection (902) is calculated by counting the number of coincident positron annihilation emissions that intersect a particular orientation of the radiation source. The computed mathematical projections (902) may be mathematically filtered with a filter (904) suitable for use in a filtered back-projection algorithm (e.g., a Ram-Lak filter, Shepp-Logan filter, or other filter that may be used for image reconstruction). The result of the filtered projection may result in a negative value that may be calibrated (e.g., set to zero) to obtain a post-filtered projection (906). Post-filtered projection (906) may then be used to adjust the radiation beam so that a more uniform radiation energy applied to the PET-avid body is delivered. For example, the intensity of the delivered radiation, and/or the time domain of the delivered radiation, may be proportional to the post-filtered projection (906).

An example of an EGRT method (910) that may be used to apply radiation that reduces or eliminates radiation peaks in PET-avid regions is shown in fig. 9B. The method may be implemented using an EGRT system including a moveable gantry, one or more positron emission detectors along the gantry, one or more radiation sources along the gantry, a motion system, and a microprocessor. Processing the LOR (912) can include detecting a single coincident positron annihilation emission path using a positron emission detector, and optionally can include storing data (e.g., position data, signal intensity data, etc.) about the LOR in a memory of the microprocessor. The microprocessor then evaluates whether the LOR intersects the PTV (914). If not, the EGRT system may return to the initial state (912) to detect another LOR. If so, the microprocessor estimates (916) the angle to which the radiation in response to the LOR should be adjusted. As shown in fig. 9A, the microprocessor can calculate the dose distribution and adjust the radiation response based on Ram-Lak filtered PTV projections, negative values being calibrated to zero. The microprocessor may then provide instructions to the radiation source to adjust the radiation beam according to the post-filtered projections. A radiation source may then deliver (918) the conditioned radiation along the LOR. Once radiation has been delivered along the detected LOR, the method (910) may be repeated if desired, for example, until a prescribed dose of radiation has been applied to the PTV.

Another method that may be used in EGRT may deliver a radiation dose proportional to the measured intensity of a positron emission profile or a photon emission profile in real time or near real time across the patient's body being treated. This method can be used with positron emission and/or single photon emission detectors having a detection emission path, and an EGRT system having a collimator to shape the radiation source of the radiation beam applied to the PTV. The distribution of coincident positron annihilation emissions and/or SPECT signals may be associated with hypoxic regions, enhanced cellular proliferation, or other physiological or functional aspects of the patient's body being treated. For example, as shown in fig. 11A, at a particular time (T1), a tumor (1100) may have a subregion (1102) at a first location that may exhibit an increased rate of radiotracer uptake. The tumor and/or the sub-region may be moved such that at time (T2) the sub-region (1104) may be at a second location in the tumor (1100). In some cases, it may be desirable to escalate the radiation dose to the sub-regions of the patient's body, which may include tracking the activity of the sub-regions. Certain variations of this method may use one or more PET tracers (e.g., FDG, F-MISO, FLT, F-ACBC, Cu-ATSM, etc.), as well as one or more SPECT tracers (e.g., Tc-99m-tagged compounds, 99mTc-HL91, 111 In-Carrocumab pentapeptide (Capromab pendentide), etc.), which may provide additional information about the physiological or functional composition throughout the PTV.

An example of an EGRT method (1110) that delivers radiation proportional to coincident positron annihilation emission signals from the PTV and/or the SPECT to the PTV is shown in figure 11B. The method may be implemented using an EGRT system including a moveable gantry, one or more positron emission detectors along the gantry, one or more radiation sources along the gantry, a motion system, and a microprocessor. A SPECT or PET tracer may be injected 1112 into the patient. Examples of PET tracers that may be injected include F-MISO, FLT, FDG, and the like. Examples of SPECT tracers that can be injected include Tc-99m-tagged compounds, 99mTc-HL91, 111 In-Carrocumab pentapeptide (Capromab pendide) (ProstaScint). After a sufficient period of time has elapsed (1114), the EGRT may begin to operate (1116), as described above, depending on the pharmacodynamics of the SPECT or PET tracer.

The method shown in fig. 11B may also be performed using a SPECT tracer. The EGRT system may include a single photon emission detector that captures single photons emitted from the target portion. A radiation source is then instructed by the microprocessor to apply radiation along the linear path of the single photon emission. The microprocessor may also distinguish between the energy levels of the detected photons and adjust the level of radiation applied along the linear path of the detected photons in accordance with the energy of the photons. In the case of PET tracers, one example of EGRT may use a positron emission detector to detect LOR emissions resulting from multiple PET tracers within the target portion. The microprocessor will instruct the radiation source to apply radiation along the detected LOR intersecting the planned target portion.

In some cases, a PTV may have a lower LOR signal than the tissue immediately surrounding the PTV. In this case, the radiation beam may instead be directed to a "cold spot," which may be a region of tissue having a smaller number of detected LORs than the average number of detected LORs of the surrounding tissue. The region detection "cold spot" (cold spot) of the "cold spot" can be determined from a previous PET scan or by reconstructing an image using PET data accumulated over a certain time interval (e.g., 0.5 seconds, 1 second, 5 seconds, 20 seconds, 30 seconds, 90 seconds before the application of the radiation beam) and using the reconstructed image. Figure 12A diagrammatically shows a planned target volume (1200) with a "cold spot" (1202), e.g., a region of tissue in a PTV with reduced coincident positron annihilation emission events. Examples of "cold spot" tissue may include regions in the brain with low-intensity FDG uptake or regions using PET tracers that detect apoptosis (e.g., 18F-ML-10). Low density LORs are detectable along the direction (1204), while high density LORs are detectable along the direction (1206). The EGRT system may be programmed to deliver more radiation in the direction (1204) to treat tissue within the "cold spot" (1202).

An example of a method of applying radiation to a tissue region with low LOR activity that can be used with an EGRT system is shown in fig. 12B. The method may be implemented using an EGRT system including a moveable gantry, one or more positron emission detectors along the gantry, one or more radiation sources along the gantry, a motion system, and a microprocessor. A radiation source may be disposed in a central position on the gantry (1212). The microprocessor may use data collected from the one or more positron emission detectors to calculate (1214) a PET volume LOR projection at the location of the radiation source. The microprocessor then compares (1216) the LOR count to a predetermined threshold, and the LOR count can be determined from a previously stored image, such as a previous PET scan image, or by reconstructing the image using PET data accumulated over a previous time interval. If the LOR count exceeds the predetermined threshold, the microprocessor sends no instructions to transmit a radiation beam, and the EGRT system may return to the initial state (1212) to process the LOR projection at another gantry position. If the LOR count is below the predetermined threshold, the microprocessor may evaluate whether the direction(s) of the LOR intersect the PTV (1218). If the direction(s) of the LOR do not intersect the PTV, then the microprocessor sends no instructions to transmit a radiation beam and the EGRT system can return to the initial state (1212) to process the LOR projection at another gantry position. If the direction(s) of the LOR intersect the PTV, the microprocessor may provide instructions to the radiation source such that the radiation source delivers (1220) radiation in the direction(s) in which the LOR count is below the predetermined threshold. The method shown in figure 12B can also be performed using a SPECT tracer and an EGRT system including a single photon emission detector.

Alternatively, any of the above methods may use multiple emissive tracers, such as PET or SPECT tracers, simultaneously. For example, the patient may be injected with a mixture of FDG and FLT, or any other desired combination of emissive tracers. The EGRT system may be configured to apply a radiation beam along any detected LOR that intersects the PTV, regardless of which type of tracer originated from the decay event.

One method (1300) in which multiple PET tracers may be used with any of the EGRT methods described herein is shown in fig. 13. The method may be implemented using an EGRT system including a moveable gantry, one or more positron emission detectors along the gantry, one or more radiation sources along the gantry, a motion system, and a microprocessor. A first tracer (e.g., FDG) can be injected (1302) into a patient. Subsequently or concurrently, a second tracer (e.g., FLT) may be injected (1304) into the patient. After a sufficient period of time has elapsed (1306) depending on the pharmacodynamics of the first and second tracers, the EGRT may begin operation (1308), as described above.

Additionally, any of the methods described above may be used with fiducial markers (medical markers), radio opaque x-ray markers (radiopaque markers), or any other marker used in transmission therapy that allows the PTV to be tracked. In certain variations, the methods described herein may be used in combination with surgery and/or chemotherapy, as the case may be.

Alternatively, any of the methods described above may use a time-of-flight (TOF) method to assess whether the origin of the positron annihilation emission is within, or sufficiently close to, the planned target volume. TOF methods can be used with PET systems to help promote diagnostic PET images by estimating the time difference between the directions of the various end points of a single LOR (e.g., the time difference between the directions of the various end points of coincident positron annihilation emission photons). Using information obtained from the TOF method, a microprocessor can estimate or calculate the origin of the positron emission along the LOR path. For example, a method with an estimated error of the start point on the order of 5 centimeters may trigger the system to exclude LOR events that have positron emission start points estimated from the PTV boundary greater than this error (e.g., 5 centimeters). Fig. 10A and 10B conceptually illustrate how the TOF method can be used with any of the EGRT systems and methods described above. A patient (1002) positioned within the gantry (1000) may have a PTV (1004). An EGRT system may detect an LOR (1006), and a microprocessor of the EGRT may use the TOF method to assess whether the origin of the LOR is within the PTV, or sufficiently close to the PTV. For example, in fig. 10A, the starting point (1008) of the estimation of LOR (1006) is shown. Because the starting point (1008) is not co-located with the PTV (1004) and is not close enough to the PTV (1004), the microprocessor may be programmed to discard the LOR (1006) and return to a state to process a new LOR. Another example shown in fig. 10B illustrates an example where the estimated starting point (1009) of the LOR (1007) is sufficiently close to the PTV and the microprocessor can be programmed to provide instructions to the radiation source so that the radiation source applies radiation along the LOR (1007). The inclusion of TOF methods in combination with any of the EGRT systems described above may help improve EGRT performance by excluding events that do not originate within, or are sufficiently close to, the PTV.

An example of the TOF method (1010) that can be used with any of the EGRT methods described above is shown in fig. 10C. The method may be implemented using an EGRT system including a moveable gantry, one or more positron emission detectors along the gantry, one or more radiation sources along the gantry, a motion system, and a microprocessor. Processing the LOR (1012) can include detecting a single coincident positron annihilation emission path using a positron emission detector, and optionally can include storing data (e.g., position data, signal intensity data, etc.) about the LOR in a memory of the microprocessor. The microprocessor may then evaluate whether the LOR intersects the PTV (1014) by comparing the position data of the LOR to the position data of the PTV (1014). If not, the EGRT system may return to the initial state (1012) to detect another LOR. If so, the microprocessor calculates the origin of the positron emission using the TOF method (1016). Based on the location of the starting point for the PTV, the microprocessor may then evaluate whether the starting point is sufficiently close to the PTV (1018). If not, then the microprocessor may return to the initial state (1012) to detect another LOR. If so, the microprocessor may then provide instructions to the radiation source to deliver (1020) radiation along the LOR. Once radiation has been delivered along the detected LOR, the method (1010) can be repeated if desired, e.g., until a prescribed dose of radiation has been applied to the PTV.

As previously noted, any of the above methods may be performed using any suitable EGRT system, for example, the EGRT system described in U.S. patent application publication No. 2009/0256078 filed 2, 9, 2009, which was previously incorporated by reference in its entirety as if set forth herein. Another variation of the EGRT system in conjunction with emission therapy PET may include: a housing having an inner housing and an outer housing, each of the inner and outer housings being independently rotatable. One or more positron emission detectors may be located on the inner gantry and one or more radiation sources may be located on the outer gantry. The inner gantry may rotate at a higher rate than the outer gantry. In certain variations, the inner gantry having the positron emission detector may rotate at a higher rate than the outer gantry having the radiation source. Additionally or alternatively, the internal or external racks may each be supported by power systems having different power outputs, wherein each of the power systems may be independently controlled. Fig. 15A and 15B show an example of an EGRT system (1500). The internal gantry (1502) has two positron emission detectors (1505) located 180 degrees from each other. The outer gantry (1504) has a radiation source (1506) configured to respond to a LOR (1508) that intersects a PTV (1510). An EGRT system may have a first mode (e.g., a "sense" mode) in which the EGRT system detects one or more LORs, and a second mode (e.g., an "transmit" mode) in which the EGRT applies radiation along the detected LORs that intersect the PTV (1510). In the perception mode, as shown in fig. 15A, the positron emission detector may occlude the patient from the radiation source (1506). In the perception mode, lines of response may be detected, but no radiation is delivered. In the emission mode shown in fig. 15B, the positron emission detector may no longer obstruct the patient from the radiation source (1506), and the radiation source (1506) may apply radiation along the detected LOR. The inner gantry (1502) supporting the inner gantry may rotate much faster than the outer gantry (1504) supporting the radiation source, which may allow for little lag time between LOR detection and radiation response.

One example of a method that may be used with an EGRT system is shown in fig. 15C, the EGRT system comprising: a gantry having separate rotatable inner and outer gantries, one or more positron emission detectors along the gantry, one or more radiation sources mounted on the gantry, a motion system, and a microprocessor. The microprocessor first determines whether the system is operating in a sensing mode based on user input and/or preprogrammed conditions (1522). If the system is operating in a sensing mode, LORs measured by the positron emission detector (1530) may be collected and optionally stored in memory of the positron emission detector and/or microprocessor. The microprocessor may compare the location and orientation of the LOR to the position of the PTV and determine whether the LOR intersects the PTV (1532). If the LOR does not intersect the PTV, the microprocessor may return to the initial state (1522). If the LOR does intersect the PTV, the LOR is added to a memory queue of the microprocessor (1534). When the EGRT system is operating in a sense mode, a plurality of LORs may be stored in the memory queue. In certain variations, the EGRT system may be initialized to a sensing mode at the beginning of a radiation therapy session.

However, if in the initial state (1522), the microprocessor determines that the EGRT system is not operating in a sense mode, or if the microprocessor can process a response line from a queue of valid response lines (1524). Processing the LOR can include detecting a single coincident positron annihilation emission path using a positron emission detector and optionally can include storing data about the LOR in a memory queue of the microprocessor. The microprocessor then compares the position of the LOR to the position of the radiation source to determine if the radiation source is substantially aligned with the LOR (1526), for example by interrogating the radiation source. If not, the microprocessor may provide no instructions to the radiation source to apply radiation along the LOR and return to the home state (1522). If so, the microprocessor can provide instructions to the radiation source to emit a beam of radiation along the LOR (1528). This may be repeated until the system is returned to sense mode, or until radiation has been transmitted along all of the LORs stored in the memory queue.

Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity and understanding, it will be apparent that certain changes and modifications may be practiced within the scope of the appended claims.

Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range is also expressly disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated value or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the stated limits, ranges excluding either or both of those included limits are also included in the invention.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, certain potential and preferred methods and materials are now described.

It must be noted that as used herein and in the appended claims, the terms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a knife" includes a plurality of such knives, reference to "an energy source" includes one or more energy sources and equivalents thereof known to those skilled in the art, and so forth.

The disclosures of the present discussion are provided solely for their disclosure and should not be construed as an admission that the present invention is not entitled to antedate such disclosure by virtue of prior invention. Further, the dates of publication provided, if any, may be different from their actual publication dates, which may need to be independently confirmed.

The preceding merely illustrates the principles of the invention. It will thus be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the invention and are included within its spirit and scope. Furthermore, all examples and conditional language recited herein are principally intended expressly to be only for pedagogical purposes to aid the reader in understanding the present invention and the concepts contributed by the inventor(s) to furthering the art, and are to be construed as being without limitation to such specifically recited examples and conditions. Moreover, all principles, aspects, and embodiments of the present invention and specific embodiments thereof described herein are intended to encompass both structural and functional equivalents thereof. Additionally, it is intended that such equivalents include both currently known equivalents as well as equivalents developed in the future, e.g., any elements developed that perform the same function, regardless of structure. Accordingly, the scope of the present invention is not limited to the example embodiments shown and described herein. Rather, the scope and spirit of the invention is embodied by the appended claims. For all embodiments described herein, the steps of the method need not be performed in order.