WO2017097035A1 - 射束的照射角度评价方法 - Google Patents

射束的照射角度评价方法 Download PDF

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WO2017097035A1
WO2017097035A1 PCT/CN2016/102312 CN2016102312W WO2017097035A1 WO 2017097035 A1 WO2017097035 A1 WO 2017097035A1 CN 2016102312 W CN2016102312 W CN 2016102312W WO 2017097035 A1 WO2017097035 A1 WO 2017097035A1
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angle
tumor
evaluating
organ
irradiation angle
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PCT/CN2016/102312
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English (en)
French (fr)
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刘渊豪
陈韦霖
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南京中硼联康医疗科技有限公司
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Priority to EP16872229.6A priority Critical patent/EP3369458B1/en
Priority to JP2018529629A priority patent/JP6695981B2/ja
Publication of WO2017097035A1 publication Critical patent/WO2017097035A1/zh
Priority to US15/991,290 priority patent/US10643761B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1048—Monitoring, verifying, controlling systems and methods
    • A61N5/1071—Monitoring, verifying, controlling systems and methods for verifying the dose delivered by the treatment plan
    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21K—TECHNIQUES FOR HANDLING PARTICLES OR IONISING RADIATION NOT OTHERWISE PROVIDED FOR; IRRADIATION DEVICES; GAMMA RAY OR X-RAY MICROSCOPES
    • G21K5/00—Irradiation devices
    • G21K5/04—Irradiation devices with beam-forming means
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
    • A61N5/1007—Arrangements or means for the introduction of sources into the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
    • A61N5/1028—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy using radiation sources applied onto the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/103—Treatment planning systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/103—Treatment planning systems
    • A61N5/1031—Treatment planning systems using a specific method of dose optimization
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1048—Monitoring, verifying, controlling systems and methods
    • A61N5/1064—Monitoring, verifying, controlling systems and methods for adjusting radiation treatment in response to monitoring
    • A61N5/1065—Beam adjustment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1077—Beam delivery systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N2005/1085—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy characterised by the type of particles applied to the patient
    • A61N2005/109—Neutrons
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T2207/00—Indexing scheme for image analysis or image enhancement
    • G06T2207/10—Image acquisition modality
    • G06T2207/10072—Tomographic images
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T2207/00—Indexing scheme for image analysis or image enhancement
    • G06T2207/30—Subject of image; Context of image processing
    • G06T2207/30004—Biomedical image processing
    • G06T2207/30096—Tumor; Lesion

Definitions

  • the invention relates to a method for evaluating an illumination angle, and in particular to a method for evaluating an illumination angle of a beam.
  • neutron capture therapy combines the above two concepts, such as Boron Neutron Capture Therapy (BNCT), through the specific agglomeration of boron-containing drugs in tumor cells, coupled with precise beam regulation, A better cancer treatment option than traditional radiation.
  • BNCT Boron Neutron Capture Therapy
  • Boron neutron capture therapy is a high-capture cross-section of thermal neutrons using boron-containing ( 10 B) drugs, and 4 He and 7 Li are produced by 10 B(n, ⁇ ) 7 Li neutron capture and nuclear splitting reactions.
  • Heavy-charged particles the total range of the two particles is about the same as a cell size, so the radiation damage caused by the organism can be limited to the cell level, when the boron-containing drugs are selectively aggregated in the tumor cells, with appropriate neutron source It can achieve the purpose of locally killing tumor cells without causing too much damage to normal tissues.
  • the illumination geometry is manually judged and defined based on experience. Due to the complexity of the human body structure, the sensitivity of various tissues or organs to radiation is also very different. Therefore, it is possible to ignore the better illumination angle by manual judgment alone, and the treatment effect is greatly reduced. In order to optimize the therapeutic effect, the angle of illumination of the beam is an essential part to consider.
  • the inventors have developed an executable illumination angle optimization method which can be used as an advantageous reference and, together with the experience of a doctor, finds the best illumination angle as much as possible.
  • Optimize the implementation of calculus It is divided into multiple tracks from the tumor to the surface of the body, and considering the proportion of organs in the track and the evaluation factors for determining individual tracks for radiation-sensitive factors, you can use positive calculation (from body surface to tumor) or inverse calculation. (from tumor to body surface) method, you can take points in order or take random points.
  • the evaluation score of the tumor incident on each point of the body surface can be calculated, and can be fused with the 2D or 3D image to help the user find the optimal incident point.
  • an aspect of the invention provides a method for evaluating an illumination angle of a beam, comprising:
  • the illumination angle of the beam is defined as a vector direction of the irradiation point of the beam to a tumor preset point
  • the illumination angle of the beam is defined as a vector direction of the irradiation point of the beam to the tumor preset point
  • step of giving the worst evaluation factor is entered and the step of sampling the angle of illumination of the beam is returned.
  • the performance of the beam at a certain position and at a certain angle can be clearly recognized, thereby providing powerful data support for the doctor or the physicist to determine the illumination mode.
  • the “tumor preset point” can be set to the tumor centroid or the deepest part of the tumor, and the specific tumor preset point position can be adjusted according to user needs.
  • the illumination angle of the beam is defined as the vector direction of the beam's illumination point to the tumor centroid or the deepest point of the tumor.
  • the angle of illumination of the beam can also be customized depending on the needs of use.
  • the vector direction described above includes the positive vector direction and the negative vector direction of the irradiation point of the beam to the tumor preset point.
  • the beam is one or more of a neutron beam, a charged particle beam, or a gamma ray, wherein the charged particle beam may be an electron beam, a proton beam, a heavy particle beam, or the like.
  • the evaluation factor is calculated based on beam characteristics, radiation sensitivity factor, and organ boron concentration.
  • the weighting factor (W(i)) of the organ (i) is calculated using Equation 1:
  • I(i), S(i) and C(i) are the beam intensity, the radiation sensitivity factor of the organ (i) and the boron concentration of the organ (i), respectively.
  • Equation 2 which simulates the depth strength of the human body or the dose curve integral according to the beam used:
  • i(x) is the depth intensity or dose curve function of the therapeutic beam in the approximate human body
  • x 0 -x is the depth range of the organ (i) in the beam track.
  • Equation 3 The evaluation factor is calculated using Equation 3:
  • W tumor is the weighting factor of the tumor.
  • the “medical image data” may be Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) or Positron Emission Computed Tomography (PET-CT).
  • MRI Magnetic Resonance Imaging
  • CT Computed Tomography
  • PET-CT Positron Emission Computed Tomography
  • the step of reading the medical image data is the step of reading at least one of the CT image data or the MRI image data or the PET-CT image data.
  • Organ track refers to a beam path through the skin, bones, tissues, and tumors when irradiated with a beam at a specific location and at a specific angle.
  • organ tracks are sequentially sequenced through the skin and bones. Tracks of tissues, tissues, tumors, tissues, bones, and skin. In some calculations, such as the weighting factors of the organs in the organ track, the weighting factors of the tumor may not be included.
  • the organ track is a track of the skin sequentially through the skin, the skull, the brain tissue, the tumor, the brain tissue, the skull, and the skin. This will give you a clear idea of the path through which the beam passes through the brain.
  • the organ track may be sequentially ordered by the beam to pass through other parts of the human brain, such as the liver.
  • the irradiation angle evaluation method of the beam further includes the step of displaying each evaluation factor in a 3D image.
  • each evaluation factor in a 3D image.
  • those skilled in the art can also display various evaluation factors by other means, as long as the doctor or physicist can recognize the individual evaluation factors displayed.
  • the so-called “beam” may be one or more types of radioactive beams, as a preferred, the beam is a neutron beam and gamma
  • the mixed beam of the beam may also be a separate neutron beam, a separate proton beam or a separate heavy particle beam.
  • the beam angle evaluation method further includes the steps of: reading medical image data; defining or reading a contour range of organs, tissues, and tumors; and defining steps of materials, tissues, and tumor materials and densities.
  • Figure 1 is a schematic diagram of a boron neutron capture reaction.
  • Figure 2 is a 10 B(n, ⁇ ) 7 Li neutron capture nuclear reaction equation.
  • Fig. 3 is a logic block diagram of a method of evaluating an irradiation angle of a beam in an embodiment of the present invention.
  • Fig. 4 is a schematic view showing the organ track at the time of beam irradiation in the embodiment of the present invention.
  • the irradiation angle evaluation method of the beam for neutron capture treatment is an embodiment of the present invention.
  • the following is a brief introduction to neutron capture therapy, especially boron neutron capture therapy.
  • Neutron capture therapy has been increasingly used as an effective means of treating cancer in recent years, with boron neutron capture therapy being the most common, and neutrons supplying boron neutron capture therapy can be supplied by nuclear reactors or accelerators.
  • Embodiments of the invention take the accelerator boron neutron capture treatment as an example.
  • the basic components of the accelerator boron neutron capture treatment typically include an accelerator, target and heat removal for accelerating charged particles (eg, protons, deuterons, etc.).
  • Systems and beam shaping bodies in which accelerated charged particles interact with metal targets to produce neutrons, depending on the desired neutron yield and energy, the energy and current of the accelerated charged particles, and the physicochemical properties of the metal target.
  • the nuclear reactions that are often discussed are 7 Li(p,n) 7 Be and 9 Be(p,n) 9 B, both of which are endothermic.
  • the energy thresholds of the two nuclear reactions are 1.881 MeV and 2.055 MeV, respectively. Since the ideal neutron source for boron neutron capture therapy is the superheated neutron of the keV energy level, theoretically, if proton bombardment with energy only slightly higher than the threshold is used.
  • a metallic lithium target that produces relatively low-energy neutrons that can be used clinically without too much slow processing.
  • proton interaction cross sections for lithium metal (Li) and base metal (Be) targets and threshold energy Not high, in order to generate a sufficiently large neutron flux, a higher energy proton is usually used to initiate the nuclear reaction.
  • BNCT Boron Neutron Capture Therapy
  • boron-containing ( 10 B) drugs with 10 B(n, ⁇ ) 7 Li neutron capture and nuclear splitting reactions.
  • Two heavy charged particles of 4 He and 7 Li are produced. 1 and 2, which respectively show a schematic diagram of a boron neutron capture reaction and a 10 B(n, ⁇ ) 7 Li neutron capture nuclear reaction equation, the average energy of the two charged particles is about 2.33 MeV, which has high linearity.
  • Linear Energy Transfer (LET) short-range characteristics, the linear energy transfer and range of ⁇ particles are 150 keV/ ⁇ m and 8 ⁇ m, respectively, while the 7 Li heavy particles are 175 keV/ ⁇ m and 5 ⁇ m.
  • the total range of the two particles is approximately equivalent.
  • a cell size so the radiation damage caused by the organism can be limited to the cell level.
  • the boron-containing drug is selectively accumulated in the tumor cells, with appropriate neutron source, it can cause too much damage to normal tissues. Under the premise, the purpose of locally killing tumor cells is achieved.
  • the nuclear reaction of the charged particles from the nuclear reactor or the accelerator produces a mixed radiation field, that is, the beam contains low-energy to high-energy neutrons and photons; for deep tumors in boron
  • Sub-capture treatment in addition to super-thermal neutrons, the more radiation content, the greater the proportion of non-selective dose deposition in normal tissue, so these will cause unnecessary doses of radiation should be minimized.
  • the human head tissue prosthesis is used for dose calculation in the embodiment of the present invention, and the prosthetic beam quality factor is used as the beam. Design references are described in detail below.
  • the International Atomic Energy Agency has given five air beam quality factor recommendations for clinical neutron sources for clinical boron neutron capture therapy. These five recommendations can be used to compare the pros and cons of different neutron sources and provide The reference basis for selecting the neutron generation route and designing the beam shaping body.
  • the five recommendations are as follows:
  • the superheated neutron energy region is between 0.5eV and 40keV, the thermal neutron energy region is less than 0.5eV, and the fast neutron energy region is greater than 40keV.
  • the beam flux and the concentration of boron-containing drug in the tumor together determine the clinical treatment time. If the concentration of boron-containing drug in the tumor is high enough, the requirement for beam flux can be reduced; conversely, if the concentration of boron-containing drug in the tumor is low, high-throughput superheated neutrons are required to give the tumor a sufficient dose.
  • the IAEA requires a superheated beam flux of more than 10 9 per square centimeter of epithermal neutrons. This flux beam can roughly control treatment time for one hour for current boron-containing drugs. In addition, short treatment time has advantages in patient positioning and comfort, and it can also effectively utilize the limited residence time of boron-containing drugs in tumors.
  • Fast neutron contamination is defined as the fast neutron dose accompanying the unit's superheated neutron flux.
  • the IAEA's recommendation for fast neutron contamination is less than 2x 10 -13 Gy-cm 2 /n.
  • ⁇ -rays are strong radiation, which will non-selectively cause dose deposition of all tissues in the beam path. Therefore, reducing ⁇ -ray content is also a necessary requirement for neutron beam design.
  • ⁇ -ray pollution is defined as the unit of superheated neutron flux.
  • the gamma dose is recommended by IAEA for gamma ray contamination to be less than 2 x 10 -13 Gy-cm 2 /n.
  • thermal neutrons Due to the fast decay rate and poor penetrability of thermal neutrons, most of the energy is deposited on the skin tissue after entering the human body. In addition to melanoma and other epidermal tumors, thermal neutrons are needed as the neutron source for boron neutron capture therapy. Deep tumors such as tumors should reduce the thermal neutron content.
  • the IAEA's ratio of thermal neutron to superheated neutron flux is recommended to be less than 0.05.
  • the ratio of neutron current to flux represents the directionality of the beam. The larger the ratio, the better the beam forwardness.
  • the high forward neutron beam can reduce the surrounding normal tissue dose caused by neutron divergence. It can treat the depth and elasticity of the posture.
  • the IAEA's ratio of neutron current to flux is recommended to be greater than 0.7.
  • the prosthesis was used to obtain the dose distribution in the tissue, and the prosthetic beam quality factor was derived according to the dose-depth curve of normal tissues and tumors. The following three parameters can be used to compare the benefits of different beam treatments.
  • the tumor dose is equal to the depth of the maximum dose of normal tissue. At this post-depth, the tumor cells receive a dose that is less than the maximum dose of normal tissue, ie, the advantage of boron neutron capture is lost. This parameter represents the penetration ability of the beam. The greater the effective treatment depth, the deeper the tumor depth that can be treated, in cm.
  • the effective dose rate of the tumor is also equal to the maximum dose rate of normal tissues. Because the total dose received by normal tissues is a factor that affects the total dose of tumor, the parameters affect the length of treatment. The greater the effective dose rate, the shorter the irradiation time required to give a tumor dose, the unit is cGy/mA. -min.
  • the effective therapeutic dose ratio received by the tumor and normal tissue is called the effective therapeutic dose ratio; the calculation of the average dose can be obtained by integrating the dose-depth curve.
  • Irradiation time ⁇ 30min (the proton current used by the accelerator is 10mA)
  • RBE Relative Biological Effectiveness
  • the following various random illumination angles are calculated randomly or one by one, and the evaluation factors are calculated by Formula 1 and Formula 2, and each evaluation is performed.
  • the factor appears as a 3D image, which is convenient for the doctor or physicist to judge the angle of treatment of the treatment.
  • the steps of establishing the 3D evaluation factor image will be detailed below, which is a preferred implementation step, which is well known to those skilled in the art and does not necessarily follow the preferred implementation steps.
  • the step is specifically: reading a patient with a clear human anatomy such as CT/MRI/PET-CT, defining the contours of each organ, tissue, and tumor one by one, and setting the material type and density. After completing the definition of the geometric material and density, it is decided to calculate the starting position of the beam and the beam angle.
  • the decision of the starting position and angle in the calculation can be a forward algorithm or a reverse algorithm, which will start in the forward algorithm.
  • the starting position is determined by the external position and can be sampled and calculated according to the fixed angle or distance interval. It can also be performed by random sampling.
  • the part of the beam angle can be set as the irradiation point to the tumor centroid or the deepest part of the tumor.
  • the specific tumor endpoint position can be adjusted according to the user's needs; in the reverse algorithm, the starting position is determined within the tumor range, and the starting position may be the tumor centroid, the deepest point, or a random point within the tumor range.
  • the beam angle can be measured by random sampling or by sampling at specified intervals.
  • the tumor range falls within the maximum therapeutic depth range. If yes, based on the track information, the boron concentration, organ radiation sensitivity factor and beam characteristic information of the organ set by the user are calculated, and the evaluation factor of the track is calculated; if not, the worst evaluation factor is given, Sampling of the beam position and the illumination angle is performed. After the calculation of the evaluation factor is completed, a record of the irradiation position, angle, and evaluation factor is performed. After repeating the above calculations for a certain amount, the report can be output and provided to the doctor or physicist as a reference to determine the illumination mode. The data can be expressed in the form of a 3D image to more conveniently determine the evaluation factor around the beam axis. Judging the pros and cons.
  • the evaluation factor is calculated based on beam characteristics, organ radiation sensitivity factor, and organ boron concentration.
  • the weight factor (W(i)) of organ i is calculated as shown in Equation 1.
  • I(i), S(i) and C(i) are the neutron intensity, the radiation sensitivity factor of organ i and the boron concentration of organ i, respectively.
  • I(i) is obtained by integrating the depth intensity or dose curve of the beam used in the simulated human body, as shown in Equation 2, where i(x) is the depth of penetration of the therapeutic beam into the approximate human body or The dose curve function, x 0 -x, is the depth range of organ i in the beam track.
  • the weighting factors of the organs in the organ track are calculated in sequence, and the sum is taken to obtain the evaluation factor corresponding to the beam, as shown in the formula 3.
  • the tumor is The weighting factor should not be included in the calculation.
  • the evaluation ratio factor can also be used for evaluation, which is defined as the ratio of the evaluation factor to the tumor weighting factor, as shown in Equation 4, so that the irradiation position can be more fully revealed.
  • the expected therapeutic effect of the angle is defined as the ratio of the evaluation factor to the tumor weighting factor, as shown in Equation 4, so that the irradiation position can be more fully revealed.

Abstract

一种射束的照射角度评价方法，包括：对射束的照射角度进行取样的步骤，其中，所述射束的照射角度定义为射束的照射点至肿瘤预设点的向量方向；计算射束通过器官径迹的步骤；判断肿瘤是否充分涵盖于有效治疗深度内：如果是，则进入计算评价因数、记录照射条件及计算结果的步骤并返回对射束的照射角度进行取样的步骤；如果否，则进入给予最差评价因数的步骤并返回对射束的照射角度进行取样的步骤。根据此射束的照射角度评价方法，可以清楚地认识到射束在某一特定位置和某一特定角度照射时的优劣表现，从而为医生或物理师决定照射模式提供强有力的数据支持。

Description

射束的照射角度评价方法 技术领域
本发明涉及一种照射角度评价方法，尤其涉及一种射束的照射角度评价方法。
背景技术
随着原子科学的发展，例如钴六十、直线加速器、电子射束等放射线治疗已成为癌症治疗的主要手段之一。然而传统光子或电子治疗受到放射线本身物理条件的限制，在杀死肿瘤细胞的同时，也会对射束途径上大量的正常组织造成伤害；另外由于肿瘤细胞对放射线敏感程度的不同，传统放射治疗对于较具抗辐射性的恶性肿瘤(如：多行性胶质母细胞瘤(glioblastoma multiforme)、黑色素细胞瘤(melanoma))的治疗成效往往不佳。
为了减少肿瘤周边正常组织的辐射伤害，化学治疗(chemotherapy)中的标靶治疗概念便被应用于放射线治疗中；而针对高抗辐射性的肿瘤细胞，目前也积极发展具有高相对生物效应(relative biological effectiveness,RBE)的辐射源，如质子治疗、重粒子治疗、中子捕获治疗等。其中，中子捕获治疗便是结合上述两种概念，如硼中子捕获治疗(Boron Neutron Capture Therapy,BNCT)，借由含硼药物在肿瘤细胞的特异性集聚，配合精准的射束调控，提供比传统放射线更好的癌症治疗选择。
硼中子捕获治疗是利用含硼(10B)药物对热中子具有高捕获截面的特性，借由10B(n,α)7Li中子捕获及核分裂反应产生4He和7Li两个重荷电粒子，两粒子的总射程约相当于一个细胞大小，因此对于生物体造成的辐射伤害能局限在细胞层级，当含硼药物选择性地聚集在肿瘤细胞中，搭配适当的中子射源，便能在不对正常组织造成太大伤害的前提下，达到局部杀死肿瘤细胞的目的。
现有中子捕获治疗计划系统中，其照射几何角度皆为人工根据经验判断及定义。由于人体结构相当复杂，各种组织或器官对辐射的敏感度也大不相同，因此单单靠人工判断很可能忽略更好的照射角度，而导致治疗效果大打折扣。为了达到治疗效果的优化，射束的照射角度是需要考虑的必要环节。
因此，有必要提出一种射束的照射角度评价方法。
发明内容
为了克服现有技术的缺陷，本发明人发展一种可执行的照射角度优化的方法，可以做为一个有利的参考依据，并搭配医生的经验，尽可能地找出最佳照射角度。优化演算的实施， 是分为多直线由肿瘤至体表的径迹，并考虑径迹中的器官比例及其对辐射敏感因素求出个别径迹的评价因素，可以采用正算(由体表至肿瘤)或逆算(由肿瘤至体表)法，可以依序取点或是随机取点计算。通过上述方法，可以算出由体表各点入射肿瘤的评价分数，可以与2D或3D影像进行融合，帮助用户找出最佳入射点。
具体地，本发明的一个方面提供一种射束的照射角度评价方法，包括：
对射束的照射角度进行取样的步骤，其中，所述射束的照射角度定义为射束的照射点至肿瘤预设点的向量方向；
计算射束通过器官径迹的步骤，其中，所述射束的照射角度定义为射束的照射点至肿瘤预设点的向量方向；
判断肿瘤是否充分涵盖于有效治疗深度内：
如果是，则进入计算评价因数、记录照射条件及计算结果的步骤并返回对射束的照射角度进行取样的步骤；
如果否，则进入给予最差评价因数的步骤并返回对射束的照射角度进行取样的步骤。
根据此射束的照射角度评价方法，可以清楚地认识到射束在某一特定位置和某一特定角度照射时的优劣表现，从而为医生或物理师决定照射模式提供强有力的数据支持。
“肿瘤预设点”可设定为肿瘤质心或肿瘤最深处，具体的肿瘤预设点位置可视用户需求而调整。作为一种优选地，所述射束的照射角度定义为射束的照射点至肿瘤质心或肿瘤最深处的向量方向。当然，本领域技术人员熟知地，也可以根据使用需要自定义射束的照射角度。
当然，本领域技术人员熟知的，上述的向量方向包括射束的照射点至肿瘤预设点的正向量方向和负向量方向。
所述射束为中子射束、带电粒子射束或γ射线中的一种或多种，其中带电粒子射束可以为电子射束、质子射束及重粒子射束等。
为了更加精准的计算出所述评价因数，所述评价因数基于射束特性、辐射敏感因数及器官含硼浓度进行计算。
取样的照射角度及照射径迹中，器官(i)的权重因数(W(i))采用公式一进行计算：
W(i)＝I(i)×S(i)×C(i)    (公式一)
其中，I(i)、S(i)及C(i)分别为射束强度、器官(i)的辐射敏感因数及器官(i)的含硼浓度。
进一步地，所述I(i)采用根据所用的射束模拟人体的深度强度或剂量曲线积分的公式二进行计算：
Figure PCTCN2016102312-appb-000001
其中，i(x)为治疗用射束在近似人体中的深度强度或剂量曲线函数，x0-x为器官(i)在射束径迹中的深度范围。
所述评价因数采用公式三进行计算：
Figure PCTCN2016102312-appb-000002
其中，Q(x,y,z,Φ,θ)作为评价因数等于器官径迹中各器官的权重因数总和。
当然，也可以采用另一种评价因数的呈现方式，即器官评价因数与肿瘤评价因数的比值。所述评价因数与肿瘤评价因数之比(QR(x,y,z,Φ,θ))采用公式四进行计算：
Figure PCTCN2016102312-appb-000003
其中，W(tumor)为肿瘤的权重因数。
“医学影像数据”可以为核磁共振成像(Magnetic Resonance Imaging,MRI)或电子计算机断层扫描(Computed Tomography,CT)或正电子发射计算机断层显像(Positron Emission computed Tomography,PET-CT)。但本领域技术人员熟知地，还可以使用其他的医学影像数据，只要该医学影像数据能够定义出器官、组织及肿瘤的材料及密度，就能够应用于本发明揭示的射束的照射角度评价方法中。作为一种优选地，所述读取医学影像数据的步骤为读取CT影像数据或MRI影像数据或PET-CT影像数据中的至少一种医学影像数据的步骤。
“器官径迹”是指在某一特定位置和某一特定角度采用射束照射时通过皮肤、骨头、组织及肿瘤的一条射束径迹，如器官径迹为射束依次序经由皮肤、骨头、组织、肿瘤、组织、骨头、皮肤的径迹。在某一些计算中，如器官径迹中各器官的权重因数加总时，可以不包括肿瘤的权重因数。作为一种优选地，所述器官径迹为射束依次序经由皮肤、头骨、脑组织、肿瘤、脑组织、头骨、皮肤的径迹。这样便可以清晰的了解到射束通过脑部的径迹。当然，本领域技术人员熟知地，器官径迹可以为射束依次序经由人体脑部以外的其他部位，如肝部等。
作为一种优选地，所述射束的照射角度评价方法进一步包括将各个评价因数以3D图像显示的步骤。当然，本领域技术人员也可以通过其他方式显示各个评价因数，只要医生或物理师能够识别显示出的各个评价因数即可。
所谓“射束”可以为一种或多种放射性射束，作为一种优选地，所述射束为中子束及γ 射束的混合射束，也可以是单独的中子束、单独的质子束或单独的重粒子束。
所述射束的照射角度评价方法进一步包括：读取医学影像数据的步骤；定义或读取器官、组织及肿瘤的轮廓范围的步骤；定义器官、组织及肿瘤的材料及密度的步骤。
附图说明
图1是硼中子捕获反应示意图。
图2是10B(n,α)7Li中子捕获核反应方程式。
图3是本发明实施例中的射束的照射角度评价方法的逻辑框图。
图4是本发明实施例中的射束照射时的器官径迹示意图。
具体实施方式
下面结合附图对本发明的实施例做进一步的详细说明，以令本领域技术人员参照说明书文字能够据以实施。
作为一种优选地，以用于中子捕获治疗的射束的照射角度评价方法为本发明的实施例。下面将简单介绍一下中子捕获治疗，尤其是硼中子捕获治疗。
中子捕获治疗作为一种有效的治疗癌症的手段近年来的应用逐渐增加，其中以硼中子捕获治疗最为常见，供应硼中子捕获治疗的中子可以由核反应堆或加速器供应。本发明的实施例以加速器硼中子捕获治疗为例，加速器硼中子捕获治疗的基本组件通常包括用于对带电粒子(如质子、氘核等)进行加速的加速器、靶材与热移除系统和射束整形体，其中加速带电粒子与金属靶材作用产生中子，依据所需的中子产率与能量、可提供的加速带电粒子能量与电流大小、金属靶材的物化性等特性来挑选合适的核反应，常被讨论的核反应有7Li(p,n)7Be及9Be(p,n)9B，这两种反应皆为吸热反应。两种核反应的能量阀值分别为1.881MeV和2.055MeV，由于硼中子捕获治疗的理想中子源为keV能量等级的超热中子，理论上若使用能量仅稍高于阀值的质子轰击金属锂靶材，可产生相对低能的中子，不须太多的缓速处理便可用于临床，然而锂金属(Li)和铍金属(Be)两种靶材与阀值能量的质子作用截面不高，为产生足够大的中子通量，通常选用较高能量的质子来引发核反应。
硼中子捕获治疗(Boron Neutron Capture Therapy,BNCT)是利用含硼(10B)药物对热中子具有高捕获截面的特性，借由10B(n,α)7Li中子捕获及核分裂反应产生4He和7Li两个重荷电粒子。参照图1和图2，其分别示出了硼中子捕获反应的示意图和10B(n,α)7Li中子捕获核反应方程式，两荷电粒子的平均能量约为2.33MeV，具有高线性转移(Linear Energy Transfer,LET)、短射程特征，α粒子的线性能量转移与射程分别为150keV/μm、8μm，而7Li重荷粒子则为175keV/μm、5μm，两粒子的总射程约相当于一个细胞大小，因此对于 生物体造成的辐射伤害能局限在细胞层级，当含硼药物选择性地聚集在肿瘤细胞中，搭配适当的中子射源，便能在不对正常组织造成太大伤害的前提下，达到局部杀死肿瘤细胞的目的。
无论硼中子捕获治疗的中子源来自核反应堆或加速器带电粒子与靶材的核反应，产生的皆为混合辐射场，即射束包含了低能至高能的中子、光子；对于深部肿瘤的硼中子捕获治疗，除了超热中子外，其余的辐射线含量越多，造成正常组织非选择性剂量沉积的比例越大，因此这些会造成不必要剂量的辐射应尽量降低。除了空气射束品质因素，为更了解中子在人体中造成的剂量分布，本发明的实施例中使用人体头部组织假体进行剂量计算，并以假体射束品质因素来作为射束的设计参考，将在下文详细描述。
国际原子能机构(IAEA)针对临床硼中子捕获治疗用的中子源，给定了五项空气射束品质因素建议，此五项建议可用于比较不同中子源的优劣，并供以作为挑选中子产生途径、设计射束整形体时的参考依据。这五项建议分别如下：
超热射束通量Epithermal neutron flux>1x 109n/cm2s
快中子污染Fast neutron contamination<2x 10-13Gy-cm2/n
光子污染Photon contamination<2x 10-13Gy-cm2/n
热中子与超热中子通量比值thermal to epithermal neutron flux ratio<0.05
中子电流与通量比值epithermal neutron current to flux ratio>0.7
注：超热中子能区在0.5eV到40keV之间，热中子能区小于0.5eV，快中子能区大于40keV。
1、超热射束通量：
射束通量和肿瘤中含硼药物浓度共同决定了临床治疗时间。若肿瘤含硼药物浓度够高，对于射束通量的要求便可降低；反之，若肿瘤中含硼药物浓度低，则需高通量超热中子来给予肿瘤足够的剂量。IAEA对于超热射束通量的要求为每秒每平方厘米的超热中子个数大于109，此通量下的射束对于目前的含硼药物而言可大致控制治疗时间在一小时内，短治疗时间除了对病人定位和舒适度有优势外，也可较有效利用含硼药物在肿瘤内有限的滞留时间。
2、快中子污染：
由于快中子会造成不必要的正常组织剂量，因此视之为污染，此剂量大小和中子能量呈正相关，因此在射束设计上应尽量减少快中子的含量。快中子污染定义为单位超热中子通量伴随的快中子剂量，IAEA对快中子污染的建议为小于2x 10-13Gy-cm2/n。
3、光子污染(γ射线污染)：
γ射线属于强穿辐射，会非选择性地造成射束路径上所有组织的剂量沉积，因此降低γ射线含量也是中子束设计的必要要求，γ射线污染定义为单位超热中子通量伴随的γ射线剂量，IAEA对γ射线污染的建议为小于2x 10-13Gy-cm2/n。
4、热中子与超热中子通量比值：
由于热中子衰减速度快、穿透能力差，进入人体后大部分能量沉积在皮肤组织，除黑色素细胞瘤等表皮肿瘤需用热中子作为硼中子捕获治疗的中子源外，针对脑瘤等深层肿瘤应降低热中子含量。IAEA对热中子与超热中子通量比值建议为小于0.05。
5、中子电流与通量比值：
中子电流与通量比值代表了射束的方向性，比值越大表示射束前向性佳，高前向性的中子束可减少因中子发散造成的周围正常组织剂量，另外也提高了可治疗深度及摆位姿势弹性。IAEA对中子电流与通量比值建议为大于0.7。
利用假体得到组织内的剂量分布，根据正常组织及肿瘤的剂量-深度曲线，推得假体射束品质因素。如下三个参数可用于进行不同射束治疗效益的比较。
1、有效治疗深度：
肿瘤剂量等于正常组织最大剂量的深度，在此深度之后的位置，肿瘤细胞得到的剂量小于正常组织最大剂量，即失去了硼中子捕获的优势。此参数代表射束的穿透能力，有效治疗深度越大表示可治疗的肿瘤深度越深，单位为cm。
2、有效治疗深度剂量率：
即有效治疗深度的肿瘤剂量率，亦等于正常组织的最大剂量率。因正常组织接收总剂量为影响可给予肿瘤总剂量大小的因素，因此参数影响治疗时间的长短，有效治疗深度剂量率越大表示给予肿瘤一定剂量所需的照射时间越短，单位为cGy/mA-min。
3、有效治疗剂量比：
从大脑表面到有效治疗深度，肿瘤和正常组织接收的平均剂量比值，称之为有效治疗剂量比；平均剂量的计算，可由剂量-深度曲线积分得到。有效治疗剂量比值越大，代表该射束的治疗效益越好。
为了使射束整形体在设计上有比较依据，除了五项IAEA建议的空气中射束品质因素和上述的三个参数，本发明实施例中也利用如下的用于评估射束剂量表现优劣的参数：
1、照射时间≤30min(加速器使用的质子电流为10mA)
2、30.0RBE-Gy可治疗深度≥7cm
3、肿瘤最大剂量≥60.0RBE-Gy
4、正常脑组织最大剂量≤12.5RBE-Gy
5、皮肤最大剂量≤11.0RBE-Gy
注：RBE(Relative Biological Effectiveness)为相对生物效应，由于光子、中子会造成的生物效应不同，所以如上的剂量项均分别乘上不同组织的相对生物效应以求得等效剂量。
请参照图3和图4，为提供中子捕获治疗时射束照射角度的参考依据，下面利用随机或逐一计算各个可能的照射角度，并通过公式一和公式二计算出评价因数，将各个评价因数以3D图像的方式显现，即方便医生或物理师判断治疗的照射角度。
下面将详述3D评价因数图像的建立步骤，该步骤为一种优选实施步骤，本领域技术人员熟知地，并不一定要按照优选实施步骤。该步骤具体为：读取患者CT/MRI/PET-CT等具有明确人体解剖的影像，逐一定义各个器官、组织及肿瘤的轮廓，并给设定材料种类及密度。在完成几何材料及密度的定义后，便决定计算射束的起始位置及射束角度，计算中起始位置与角度的决定，可以是顺向算法或逆向算法，顺向算法中是将起始位置决定于体外位置并可依固定角度或距离间隔依序取样计算，也可以透过随机取样的方式进行；射束角度的部分，则可设定为照射点至肿瘤质心或肿瘤最深处的向量方向，具体的肿瘤端点位置可视用户需求而调整；逆向算法中，则是将起始位置决定于肿瘤范围内，其起始位置可以是肿瘤质心、最深处或肿瘤范围内随机取点，而射束角度则可以利用随机取样或依指定间隔取样的方式进行。在决定完射束的照射位置与角度后，则计算射束轴所通过的器官径迹，即计算出射束进入人体后所经过的器官种类及其厚度。在取得射束轴通过人体的径迹信息后，则判断肿瘤范围是否落于最大可治疗深度范围内。若是，则以此径迹信息为依据配合用户设定的器官含硼浓度、器官辐射敏感因数及射束特性信息，计算该径迹的评价因数；若否，则给予最差的评价因数，重新进行射束位置与照射角度的取样。完成评价因数的计算后，则进行照射位置、角度及评价因数的纪录。重复进行上述演算达一定数量后，即可输出报表，提供给医生或物理师作为参考从而决定照射模式，更可以将数据以3D图像的形式表示，以更便利地根据射束轴周围的评价因数判断优劣。
评价因数是基于射束特性、器官辐射敏感因数及器官含硼浓度所进行计算的，对应某位置及某照射径迹中，器官i的权重因数(W(i))计算如公式一所示，式中I(i)、S(i)及C(i)分别为中子强度、器官i的辐射敏感因数及器官i的含硼浓度。
W(i)＝I(i)×S(i)×C(i)   (公式一)
其中，I(i)乃根据所用射束于模拟人体的深度强度或剂量曲线积分而得，如公式二所示，式中，i(x)为治疗用射束于近似人体中的深度强度或剂量曲线函数，x0-x为器官i于射束径迹中的深度范围。
Figure PCTCN2016102312-appb-000004
通过上述算法，依序完成器官径迹中各器官的权重因数计算后，并取其加总，即可求得该射束对应的评价因数，如公式三所示，于此计算中，肿瘤的权重因数应不列入计算。
Figure PCTCN2016102312-appb-000005
根据上述的评价因数高低，可以更直观地判断治疗时对正常组织所受到的危害程度。除了利用评价因数进行照射位置及角度的评价外，也可利用评价比因数来进行评价，其定义为评价因数对肿瘤权重因数的比值，如公式四所示，如此可以更充分地显现照射位置与角度的预期治疗效果。
Figure PCTCN2016102312-appb-000006
以上实施例中涉及到这些步骤——“读取患者CT/MRI/PET-CT等具有明确人体解剖的影像，逐一定义各个器官、组织及肿瘤的轮廓，并给设定材料种类及密度。”可以参照本申请人于2015年11月17日递交到国家知识产权局、申请号为201510790248.7、发明名称为“基于医学影像数据的几何模型建立方法”的专利申请，在此全文引入。
本领域技术人员熟知的，上述公式一至公式四中的一些简单变换，仍然在本发明要求保护的范围之内，如I(i)、S(i)及C(i)由相乘变换为相加；I(i)、S(i)及C(i)分别乘以n次方，n根据情况而定，可以为1的整数倍也可以是其他倍数；i(x)可以是x0-x间的平均数或中间数乘上(x0-x)，或任何可以达到与强度积分计算结果相符的计算方法。
尽管上面对本发明说明性的具体实施方式进行了描述，以便于本技术领域的技术人员理解本发明，但应该清楚，本发明不限于具体实施方式的范围，对本技术领域的普通技术人员来讲，只要各种变化在所附的权利要求限定和确定的本发明的精神和范围内，这些变化是显而易见的，都在本发明要求保护的范围之内。

Claims (10)

  1. 一种射束的照射角度评价方法，包括：
    对射束的照射角度进行取样的步骤，其中，所述射束的照射角度定义为射束的照射点至肿瘤预设点的向量方向；
    计算射束通过器官径迹的步骤；
    判断肿瘤是否充分涵盖于有效治疗深度内：
    如果是，则进入计算评价因数、记录照射条件及计算结果的步骤并返回对射束的照射角度进行取样的步骤；
    如果否，则进入给予最差评价因数的步骤并返回对射束的照射角度进行取样的步骤。
  2. 根据权利要求1所述的射束的照射角度评价方法，其特征在于：所述射束为中子射束、带电粒子射束或γ射线中的一种或多种。
  3. 根据权利要求1所述的射束的照射角度评价方法，其特征在于：所述评价因数基于射束特性、辐射敏感因数及器官含硼浓度进行计算。
  4. 根据权利要求3所述的射束的照射角度评价方法，其特征在于：取样的照射角度及照射径迹中，器官(i)的权重因数(W(i))采用公式一进行计算：
    W(i)＝I(i)×S(i)×C(i)  (公式一)
    其中，I(i)、S(i)及C(i)分别为射束强度、器官(i)的辐射敏感因数及器官(i)的含硼浓度。
  5. 根据权利要求4所述的射束的照射角度评价方法，其特征在于：所述I(i)采用根据所用的射束模拟人体的深度强度或剂量曲线积分的公式二进行计算：
    Figure PCTCN2016102312-appb-100001
    其中，i(x)为治疗用射束在近似人体中的深度强度或剂量曲线函数，x0-x为器官(i)在射束径迹中的深度范围。
  6. 根据权利要求4或5中任一项所述的射束的照射角度评价方法，其特征在于：所述评价因数采用公式三进行计算：
    Figure PCTCN2016102312-appb-100002
    其中，Q(x,y,z,Φ,θ)作为评价因数等于器官径迹中各器官的权重因数总和。
  7. 根据权利要求6所述的射束的照射角度评价方法，其特征在于：所述评价因数与肿瘤评价因数之比(QR(x,y,z,Φ,θ))采用公式四进行计算：
    Figure PCTCN2016102312-appb-100003
    其中，W(tumor)为肿瘤的权重因数。
  8. 根据权利要求1-5中任一项所述的射束的照射角度评价方法，其特征在于：所述读取医学影像数据的步骤为读取CT影像数据或MRI影像数据或PET-CT影像数据中的至少一种医学影像数据的步骤。
  9. 根据权利要求1-5中任一项所述的射束的照射角度评价方法，其特征在于：所述射束的照射角度评价方法进一步包括将各个评价因数以3D图像显示的步骤。
  10. 根据权利要求1-5中任一项所述的射束的照射角度评价方法，其特征在于：所述射束的照射角度评价方法进一步包括：读取医学影像数据的步骤；定义或读取器官、组织及肿瘤的轮廓范围的步骤；定义器官、组织及肿瘤的材料及密度的步骤。
PCT/CN2016/102312 2015-12-08 2016-10-18 射束的照射角度评价方法 WO2017097035A1 (zh)

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