CN101927065B - 用于癌症治疗和研究的紧凑型微束放疗***及方法 - Google Patents
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- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
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Abstract
当前主旨涉及基于碳纳米管分布式X射线源阵列技术的用于癌症研究和治疗的紧凑型非同步微束放疗(MPT)***和方法。所述***和方法能够以每秒10Gy或更高的峰值剂量率传输显微离散型X射线辐射。所述X射线辐射可以由空间分布式X射线源阵列提供。举例而非限制性的,所述技术可用于人类癌症治疗、术中放疗以及动物癌症模型上的潜伏期癌症研究。
Description
相关申请
当前公开的主旨要求2009年1月16日提交的61/205,240的优先权,其公开的内容在此全部引入作为参考。
政府利益
当前公开的主旨按照国家癌症中心授予的合同U54CA119343和1R21CA118351-01,由美国政府资助完成。因此,美国政府对当前公开的主旨具有一定的权利。
技术领域
在此公开的主旨一般涉及放疗***和方法。更特别地,在此公开的主旨涉及癌症治疗和研究的微束放疗***及方法。微束放疗(MRT)辐射可以由它的显微离散空间辐射分布(束宽小于1毫米且束间距为几毫米)以及超高剂量率(10Gy/s或更高)来表征。
背景技术
放疗的根本挑战是有效且安全地治疗癌症患者。当前的放疗***和方法为具有早期癌症且对放射敏感的癌症的患者提供了极好的益处,但对于具有抗辐射肿瘤(例如,脑或胰腺癌)的患者以及具有晚期肿瘤的患者,这些益处就减少了。对于这些患者,消除肿瘤所需的辐射会引起无法忍受的或致命的放射损伤。特别是对于儿科患者,其快速生长的正常组织经常比他们的肿瘤对放射更敏感,并且因此其不能忍受对患有同样疾病的成人来说是有效的放疗。因此,在当前的放疗中,正常组织附带的损伤是个主要的局限,妨碍了对年轻癌症患者、具有中枢神经***癌症、抗辐射癌症以及具有巨大肿瘤的晚期癌症的患者的有效放疗。这些癌症患者目前有不良的预后。
微束放疗(MRT)是一种单一形式的放射线,其在众多的动物研究中显示了消除肿瘤同时不伤害正常组织的非凡能力。MRT利用多重窄的但充分分散的X射线平面光束(即“微束”)并以非常高的剂量率传输放射线。MRT放射线在两个方面不同于传统的放疗射线:剂量空间离散性和剂量时间率。在传统治疗中,剂量率为大约低100倍且剂量分布在空间上是显微连续的。当前的解决方案,并非经常有效,以2Gy每次治疗地进行多次治疗。相反的,动物研究已经显示数百Gy(例如,大约102Gy或更高)的剂量水平的单次治疗可消除肿瘤同时不伤害正常组织,包括中枢神经***中生长中的组织。
目前存在关于MRT可用来提供消除肿瘤同时不伤害正常组织的两种假设机理。首先,认为肿瘤微脉管***不会自我修复而正常组织会。其次,显现出旁观者效应,其中,未经照射的肿瘤细胞通过细胞-细胞间发送信号随经照射的肿瘤细胞一同死亡(例如,参见D.Slatkin et al.,Proc.Natl.Acac.Sci.USA,Vol 92,pp8783-8787,1995)。然而,MRT的基础机理仍然难以理解。虽然如此,MRT对人类应用来说非常有吸引力,因为放疗的关键挑战已经变成如何消除肿瘤并将对宿主正常组织的相关损伤减到最小。
然而,不幸地是,MRT要求在瞬间用具有非常高剂量率(例如,类似于100Gy/s或更高等级)的X射线照射组织以确保由于靶移动引起的显微磨片的最小宽展。这个剂量率比通常用来做传统放疗的高几个数量等级。
如今现有的X射线管工艺不能提供MRT剂量分布和剂量率,因为MRT剂量率可以是当前放疗机器(~5Gy/分)的数千倍。高剂量率被认为对将在照射活性对象期间所需的十几微米宽的微束的宽展(由对象运动引起)最小化是重要的。传统的X射线管包括金属丝(阴极),其在电阻加热到超过1000℃时发射电子,以及金属靶(阳极),其在被加速电子轰击时发射X射线。X射线源的空间分辨率由焦点的大小决定,所述焦斑为X射线阳极上接收电子束的区域。由于高运行温度和能量消耗,基本上当前所有商业的X射线管为单象元装置,其中,从阳极上的单个焦点发射X射线射线。阳极的热负荷限制了X射线管的最大X射线通量。为了使用当前的X射线技术以超高剂量率产生小的MRT光束大小,要求超越实际可能性的超高电子束密度和热负荷。例如,当前的高能X射线管在~100kW下只能传输大约1~10cGy/s到源对象的距离为~0.6m的患者。
结果,由于这个高剂量率的要求,因而使用同步加速辐射专门地研究MRT,例如在美国的国家同步加速器光源(NSLS)以及在法国格勒诺布尔的欧洲同步加速器放射设备(ESRF)。因此,为了加速可能推进有前途的癌症治疗研究用于潜在的人类应用,需要紧凑型的、非同步辐射源MRT***及其相关的方法,其能够广泛适用于癌症中心用于潜伏期的研究和临床应用。
发明内容
依照本公开文本,提供一种用于微束放疗的紧凑型、非同步加速器放射源的MRT***及方法。一方面,提供一种微束放疗的方法。所述方法可包括围绕要照射的靶放置分布式X射线源阵列,所述X射线源阵列包括多个碳纳米管场发射X射线源;以及同时从多个带微束准直器的碳纳米管场发射X射线源产生多个X射线微束。
另一方面,提供一种微束放疗***。该***可包括分布式的X射线源阵列,其包括多个碳纳米管场发射X射线源,将每个X射线源放置为引导X射线辐射朝向共同的焦点;微束阵列准直;用于将靶靶与多个X射线微束对准的定位装置;以及控制***,其与分布式的X射线源阵列中的多个X射线源的每一个通信用于同时从多个X射线源产生多个X射线微束。
尽管在上文已经说明了本公开主旨的一些方面,并且通过当前公开的主旨全部或部分地实现了这些方面,但随着结合下文作最佳描述的附图所继续进行的描述,其它的方面将变得明显。
附图说明
从以下的应当结合附图阅读的详细描述,将很容易理解当前主旨的特性和优点,这些附图只是作为示范性的和非限制性的例子给出,其中:
图1A是对象内靶的微束放疗的侧视图;
图1B是横切图1A的X射线微束的剂量率分布的图示;
图2是采用微束放疗的方法照射的大白鼠后脑的水平组织切片的图像;
图3是根据当前公开主旨的实施例的与微束放疗***一同使用的场发射X射线源的示意图;
图4是根据当前公开主旨的另一实施例的与微束放疗***一同使用的场发射X射线源的示意图;
图5是根据当前公开主旨的实施例的微束放疗***的俯视图;
图6是根据当前公开主旨的实施例的布置在环形阵列中的微束放疗***的俯视图;
图7是根据当前公开主旨的实施例的布置在多边形阵列中的微束放疗***的俯视图;
图8是根据当前公开主旨的实施例的对象内靶的微束放疗的侧视图;以及
图9是根据当前公开主旨的实施例的微束放疗方法的流程图。
具体实施方式
传统的X射线源从接收电子的X射线阳极(“焦斑”)上的一小块区域产生X射线辐射。在它被高能电子轰击时阳极上的局部温度可达到超过1500℃。最大的X射线剂量可由阳极所能承受的热负荷限定,其还与焦斑的尺寸相关。例如,临床的线性加速器(LINAC)只能传输大约5Gy/分的剂量。相反的,当前主旨提供的紧凑型、非同步辐射源MRT装置、***以及方法能够利用多个分离的、狭窄的X射线平面或线束以相当高的剂量率传输辐射。例如,MRT装置、***以及方法可用来为具有脑瘤的人治疗癌症以及术中放疗。还可以想象在此公开的MRT装置、***和方法可用作动物模型的癌症研究。
如上所述,MRT在剂量空间离散性和剂量时间率上区别于传统的放疗技术。特别地,参考图1A和1B,而非在整个束宽上提供单一束宽的基本连续的剂量分布,MRT装置、***和方法产生多个X射线微束MB,其每一个都具有类似于大约1mm或更小级别的束宽。如图2所能看到的,用MRT方法辐射的样品可以被多个明显的X射线束路径所识别。这多个微束MB能够被引导朝向包含在对象O中的靶T(例如,肿瘤)。
MRT区别于传统放疗的第二个特性是相当高的时间剂量率。先前公开的MRT***和方法使用高能同步加速器或传统X射线管源产生X射线,但如上所述这些选择的每一个都具有重大的缺陷。相反的,当前公开的主旨提供相当高的足够用于MRT的空间剂量率,其可采用由多个围绕对象O放置的单独X射线源组成的空间分布式X射线源阵列实现。
在当前公开主旨的一个方面,空间分布式X射线源阵列能够基于碳纳米管(CNT)分布式X射线源阵列技术。例如,在名为“Large-Area Individually AddressableMulti-Beam X-Ray System and Method of Forming Same”的美国专利6,876,724;名为“X-Ray Generating Mechanism Usmg Electron Field Emission Cathode”的美国专利6,850,595以及名为“X-Ray Generating Mechanism Using Electron Field EmissionCathode”的美国专利6,553,096中公开的CNT场发射器,其内容在此全部引入作为参考。
图3和4中示出场发射X射线源的示范性结构。在显示的示范性结构中,场发射X射线源100可包括场发射阴极结构110,诸如象在导电底层上的纳米结构或碳纳米管薄膜。阳极110上可放置门电极120(例如,高熔化温度的金属栅格)从而在阳极110和门电极120之间施加电压能够引起从阴极110场发射的电子,例如作为电子束EB引导朝向用于产生X射线束的阳极130。X射线源100还可包括用于在其到达阳极130之前聚焦电子束EB的聚焦电极140,从而减少了在阳极130上焦斑的尺寸。
如图3所示,该***还可包括微束准直器150,其可放置在发射的X射线束路径中以只允许选定的具有固定束厚d的X射线微束MB传输,从而定义辐射区域。例如,在图5所示的一个实施例中,准直器150能够产生具有狭窄束宽(例如,具有大约在0.01mm和1mm之间的束宽)的扇束X射线辐射。结果,靶T的薄片能够被X射线微束MB照射。为了将对正常组织的损伤最小化,还可以校准该扇束的角度θ(即该扇束的伸展生)从而X射线辐射基本覆盖靶T占领的区域。此外,该***还可包括放置在每个X射线源100和靶T之间的放射性铬薄膜(例如,Gafchromic XR-QA)。在这个结构中,可以产生具有比在临床治疗使用的剂量率明显高的剂量率的X射线微束MB。如图4所示,在另一配置中,该***可包括多缝微束准直器或多个准直器150,其同样地可放置在所发射的X射线束路径中。这个配置能造成从每个X射线源100发射出多个不重叠(例如,平行)的X射线微束MB。
为获得MRT所需的高剂量率,如图5所示,多个X射线源100可装配成分布式X射线阵列200。每个X射线源100可以是带独立阴极110和阳极130的独特元件,其可以是独立地运行或与其它多个X射线源100联合起来运行。可选地,X射线源阵列200可包括在真空容器中的阳极环和相对的阴极环。在这个可选的配置中,阴极环和阳极环可共同地运行以从阳极环产生X射线辐射并照射到对象O中的靶T。
在任一个配置中,X射线源阵列200具有分布式X射线源的功能。代替使用从一个方向传输辐射的一个平行的X射线束或两个互相垂直的光束阵列(即,如在同步加速器源运行的试验所作的那样),X射线源阵列200围绕要被照射的靶T。这样,可以将X射线辐射从多个方向传输到共同焦点以增加在靶T接收的辐射量而不增加对象O的除靶T之外的任何居间部分接收的辐射量。此外,该多个X射线源100的每一个能够被布置使得从一个X射线源100发出的X射线微束MB照射靶T的第一部分,从第二个X射线源100发出的X射线束MB照射靶T的不同于第一部分的第二部分,以此类推。例如,参考图8,X射线微束MB的第一集合能够沿着多个平行的辐射平面照射靶T,而在图8中以MB’标出的不同的X射线微束集合能够沿着正交于X射线微束MB第一集合辐射平面的辐射平面照射靶T。这样,尽管每个单独的X射线微束没有具有基本连续的剂量分布,但在靶T的X射线辐射具有。
结果,通过跨越围绕靶T的大区域分配X射线能量,X射线源阵列200可产生微平面X射线束,其所具有的剂量率在靶T对MRT来说是足够的。例如,X射线源阵列200可产生类似于大约0.1到100Gy/秒级别的剂量率,或其能够产生更高的类似于500Gy/秒的剂量率。同时,对象O的靶T外的部分只从单一的X射线微束MB(或微束组)接收X射线辐射而不是在共同焦点接收组合辐射,从而可以大大降低这些居间部分的剂量率。
X射线源阵列200可配置为多种几何图形的任意一种,诸如环形、弓形、多边形或线性阵列。例如,在图6所示的一个配置中,X射线源阵列200可具有环形结构。对象O可放置在该环形结构中,靶T位于多个X射线源100的焦点,且因此多个X射线微束能够从多个位置沿着该环形的圆周朝着靶T发射。在图7所示的另一配置中,X射线源阵列200可具有带多个分段的多边形结构,每个分段本质上作为线性X射线源阵列运行。尽管图中显示的环形阵列和多边形阵列结构只在X射线源阵列200的一部分上具有X射线源100,本领域技术人员应当理解X射线源100可在X射线源阵列200的整个范围放置以更充分地分配发射的X射线微束MB到靶T。
因此,相比于传统的X射线管通常从X射线阳极上的一小块区域产生X射线,X射线源阵列200在较大的区域和/或到X射线阳极上的多个焦点分配能量,从而能够获得高剂量率。主要因为X射线阳极热负荷的限制,目前商业的热离子X射线管能够在大约100kW、有效焦斑尺寸为1×1mm(反射后)下运行。这对MRT所需的剂量率来说是不足的。特别地,先前的MRT研究表明大约100Gy/秒的剂量率是有效的,但先前只有使用同步加速器源才有可能达到这样的剂量率。然而,在本***和方法中,X射线微束MB可以围绕环形或多边形阳极结构的周边产生并被引导朝向靶T。通过在大的区域上分配能量,可以获得更高的X射线剂量而不会在任何一个X射线阳极产生过量的热负荷。此外,通过使用基于碳纳米管的场发射X射线源100,相比于先前技术的装置X射线焦斑的尺寸可以减小(即小于1×1mm)。
此外,微束放疗***可包括能够设置治疗参数的控制器210,该治疗参数包括传输的剂量、驻留时间、X射线辐射平面的宽度以及相邻辐射平面间的间距。另外,该***还可包括用于支持进行放疗的患者(即对象O)的病床和能够将靶T对准辐射场的定位装置220。例如,X射线源阵列200的对准可以使用与定位装置220连接的X射线计算机断层摄影(CT)扫描仪222(例如,动态微型CT)来执行。CT扫描仪222可识别靶T的位置,以及对象O的任何***结构(例如,围绕肿瘤的正常组织),并且然后定位装置220可用来将靶T对准微束MB的焦点。
在本公开主旨的另一方面,提供一种微束放疗的方法。该方法包括围绕要被照射的靶T(例如,医疗患者体内的肿瘤)放置分布式X射线源阵列200,X射线源阵列200包括多个碳纳米管场发射X射线源100,以及同时从多个碳纳米管场发射X射线源100产生多个X射线微束MB。X射线源阵列200可构造为使得能够从位于X射线源阵列200不同位置上的多个场发射X射线源100产生X射线微束MB。X射线源100可以切换以在短时间内向靶T上的一个或几个平行辐射平面传输X射线微束。可以用治疗计划程序来确定辐射剂量、X射线束的宽度、X射线辐射平面间的间隔、以及曝光时间,这些的每一个能够由与X射线源阵列200通信的控制器220控制。
为了产生多重且平行的照射平面,包含靶T的对象O或X射线源阵列200可以在每次曝光后在很小的时间间隔内平移到顺序位置,且在每次平移之后可以运行X射线源阵列200以照射靶T。可重复该过程直到整个靶T的区域被照射。这样,X射线源阵列200能够以在交替的高低剂量平面中分配剂量的形式将X射线辐射传输给靶T。
图9示出依照这个方法的示范性过程的步骤。特别地,微束放疗的方法可包括识别照射的感兴趣区域(ROI)(例如,靶T),以及将该ROI与辐射场对准。例如,对准该ROI可包括在病床上定位对象O以及将要被照射的对象O的感兴趣区域,诸如肿瘤(即靶T)与X射线微束MB的焦点对准。例如,上述的定位装置220可用来将靶T与辐射场对准。这个对准可以通过首先定位对象O内的靶T来促进。如上所述,这个定位可使用诸如X射线计算机断层摄影扫描仪222的成像装置来完成。该扫描仪还能够在治疗期间有利于监测靶T的位置。例如,通常能监测对象O或特别是对象T的生理运动,并且X射线源阵列200的运行能够与这种运动同步,其能够将运动引起的辐射场的模糊最小化。一旦已经对准ROI,该方法还可包括确定由X射线源阵列200产生的辐射平面的剂量、宽度以及间隔,以及照射该ROI。如上所述,对象O或X射线源阵列200可平移一预定的距离,并且能重复该照射过程直到整个ROI被照射。
概括来说,公开的紧凑型***和方法能够产生空间离散性的X射线微束用于微束治疗,所述X射线微束具有含高剂量率的平面或其它几何结构。这种微束放疗***和方法可提供用于诸如人类外部光速放疗、术中放疗、短距离放疗的癌症治疗以及在动物癌症模型上的潜伏期癌症研究。
当前的主旨能够表现为其它的形式而不脱离它的精神和本质特征。因此描述的各实施例被认为是在所有方面为示意性的而非限制性的。尽管已经在某些优选实施例方面对当前的主旨作了描述,对本领域技术人员来说是显然的其它实施例同样在当前主旨的范围内。
Claims (15)
1.一种紧凑型微束放疗***,包括:
包括多个碳纳米管场发射X射线源的分布式X射线源阵列,所述X射线源定位在要被照射的对象周围并产生引导为朝向靶的X射线辐射;
定位在每个X射线源和要被照射的所述对象之间的准直***,其中,所述准直***将来自所述分布式X射线源阵列的所述X射线辐射准直为多个平行的平面束,其中,每个平面束具有小于1毫米的宽度,并且其中,所述多个平行的平面束的相邻的平面束之间的间距小于1毫米;
用于将所述靶与所述多个平行的平面束对准的精确定位装置;以及
控制***,其与所述多个X射线源中的每个通信,用于同时从所述多个X射线源以预定的X射线剂量和剂量率产生所述多个平行的平面束。
2.根据权利要求1所述的***,其中,所述X射线源包括环形阵列,其中,所述X射线源被定位在沿着所述环形阵列的周界的多个位置上。
3.根据权利要求1所述的***,其中,所述X射线源包括多边形阵列,其中,所述X射线源被定位在沿着所述多边形阵列的周界的多个位置上。
4.根据权利要求1所述的***,其中,递送到所述靶的剂量率高于10Gy/秒且所述多个平行的平面束中的每个的宽度小于1mm。
5.根据权利要求1所述的***,其中,所述分布式X射线源阵列包括发射电子的基于碳纳米管的场发射阴极,所述电子通过聚焦电极被聚集到X射线阳极的狭窄聚焦轨迹上以产生引导为朝向所述靶的X射线辐射。
6.根据权利要求1所述的***,其中,所述分布式X射线源阵列包括多个沿着所述源阵列的周界定位的基于碳纳米管的场发射阴极,其中,每个场发射阴极发射电子到X射线阳极上的线聚焦轨迹的相应部分以产生引导为朝向所述靶的X射线辐射。
7.根据权利要求1所述的***,其中,所述X射线源阵列还包括将场发射电子聚焦到X射线阳极上的狭窄聚焦轨迹的电子聚焦元件,其中,所述聚焦轨迹的有效宽度相当于或小于来自所述准直***的所述多个平行的平面束之一的宽度。
8.根据权利要求1所述的***,其中,所述X射线源阵列包括多个平行的碳纳米管场发射阴极阵列,其中,来自每个阴极阵列的场发射电子束被聚焦到X射线阳极上的狭窄线聚焦轨迹,其中,每个线聚焦轨迹的有效宽度小于1毫米,且相邻聚焦轨迹间的有效间隔小于1毫米。
9.根据权利要求8所述的***,其中,每个聚焦轨迹的有效宽度在10微米到1mm的范围内。
10.根据权利要求1所述的***,还包括能够在垂直于微束平面的方向上平移所述X射线源阵列或所述要被照射的对象的平移***,从而使得所述靶能够被多重曝光照射,其中,在每次曝光中所述微束覆盖所述靶的部分。
11.根据权利要求1所述的***,其中,所述场发射X射线源每个均包括具有小于1×1mm的有效X射线焦斑尺寸的微聚焦X射线源。
12.根据权利要求1所述的***,其中,所述准直***包括定位在所述多个场发射X射线源中的每个和共同焦点之间的一个或多个准直器。
13.根据权利要求1所述的***,还包括定位来用于识别所述靶的位置的X射线断层成像***。
14.根据权利要求13所述的***,其中,所述X射线断层成像***包括计算机断层扫描器。
15.根据权利要求13所述的***,其中,所述X射线断层成像***包括层析X射线摄影合成***。
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US20140119496A1 (en) | 2014-05-01 |
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US8600003B2 (en) | 2013-12-03 |
US8995608B2 (en) | 2015-03-31 |
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