CN111317565A - 使用脉冲激光器进行组织消融的系统 - Google Patents
使用脉冲激光器进行组织消融的系统 Download PDFInfo
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Abstract
用于使极高峰值功率激光器脉冲能够通过光纤输送而优选以接触模式用于消融程序的系统。该激光器有利地以355nm波长发射。其它系统使能选择性去除血管内的非期望的组织,同时最小化损坏其血管的风险,基于320至400nm激光波长的短激光脉冲的消融性质的利用,利用导管施加到组织上的激光注量和力的、构成导管的管的机械壁的选定参数。另外地,公开了校准此类导管的新颖的方法,这也实现了对消融过程的实时监控。另外,公开了保护光纤出射面的新颖的方法。
Description
本申请是申请号为201580037816.4、申请日为2015年5月18日、发明名称为“使用脉冲激光器进行组织消融的系统”的申请的分案申请。
技术领域
本发明涉及脉冲高功率激光器领域以及通过光纤输送其输出的问题,尤其是利用通过那些光纤传输的能量用于组织消融。
背景技术
通过光纤输送高脉冲激光功率被广泛用于组织或其他目标的消融。对于这样的消融程序,紫外(UV)光具有许多优点,因为它被生物物质和有机化合物很好地吸收。UV激光不是灼烧或切割材料,而是添加足够的能量以破坏表面组织的分子键,其通过消融而不是灼烧以紧密控制的方式有效地分解成空气。激光能量也被强烈吸收,并且导致温度的急剧局部升高,并导致产生强的机械力,导致光声和光热消融。因此,在紫外线中发射的激光具有有用的性质,使得它们可以去除表面材料的异常精细的层,几乎不加热或改变保持完好的周围材料的剩余部分。通常使用在308nm发射的准分子激光器(XeCI)。然而,这种激光器体积大,需要仔细维护和频繁校准,并且光束质量差并且可能不稳定。三次谐波,以355nm发射的Q开关Nd:YAG激光器也已经用于这种UV消融程序。
为了获得有效的组织消融,需要高于某阈值的流度,并且通常期望在低至10nsec范围内的脉冲中的50mJ/mm2量级的高峰值功率脉冲。这种注量的输送对于光纤是非常具有挑战性的,并且会由于选择性加热、等离子体产生、自聚焦或在出射面处裂纹的产生而导致在光纤的入射面或出射面处或在光纤本体中的损坏。为了克服这种损坏的挑战,在现有技术中已经提出了采用由激光器发射的高质量光束并且在输入到光纤之前均匀化光束以消除“热点”的方法。已经提出的一些这样的方法包括:
(i)使用衍射光学元件(DOE)和耦合透镜将激光器耦合到光纤。DOE使波束空间能量密度均匀化并消除激光器的“热点”。DOE可以形成不同的形状,包括适合于光纤束的输入平面的不同形状的正方形、圆形、矩形。已经使用不同的耦合透镜和DOE与耦合透镜之间的不同距离,以便获得不同的光斑尺寸。
(ii)使用微透镜阵列来实现均匀光斑。还可以使用多于一个的阵列,以便实现更好的均匀性并避免由于子束干涉引起的热点。可以通过改变间距尺寸和耦合透镜焦距来操纵光斑的尺寸和形状。这种用于执行将高峰值功率激光脉冲耦合到光纤中的微透镜阵列均化器已经在T.Schmidt-Uhlig等人的、题为“NewSimplified Coupling Scheme for theDelivery of 20MW Nd:YAG Laser Pulses byLarge Core Optical Fibers”(发表于Applied Physics B,Lasers and Optics,卷72,第183-186页(2001年))的文章中进行了说明。
(iii)使用多模光纤以使光束能量密度均匀化。正透镜用于将激光束耦合到均化器光纤中,并且第二正透镜用于将均化器光纤输出成像到将光束传送到消融目标的光纤中。一个方便的选择是使用熔融石英纤维,其更适合于高功率传输。
(iv)使用脉冲对以实现从手术部位有效移除组织,其中第一脉冲“调节”组织,然后可以通过第二、通常更长的脉冲更容易地移除组织。与使用等效的单个脉冲相比,这种布置使得能够以更少的对光纤的损坏来完成消融。这种方法在M.S.Feld等人的美国专利No.5,312,396,“Pulsed Laser System for the SurgicalRemoval of Tissue”中进行了说明。
另外,在D.Albagli等人的、题为“Time dependence of laser-inducedsurfacebreakdown in fused silica at 355nm in the nanosecond regime”的文章中描述了使用多个脉冲的类似程序,该文章发表在SPIE卷1441,Laser induced DamageinOptical Materials(激光诱发的光学材料的损坏),1990年。也可以有利地使用在两个不同波长处的成对的第一脉冲和第二脉冲。
在可替代的方法中,激光的脉冲长度已经扩展至多于100nsec,以便提高光纤的损坏阈值,或者已经分裂成至少两个脉冲,在它们之间有100至200nsec的延时,但是这是以硬组织的消融效率为代价而发生的,例如Rod S.Taylor等人发表在“Lasers in Surgery andMedicine”(卷10,第5期,第414-419页,1990年)中的文章“Dependence of the XeCI lasercut rate of plaque on the degree ofcalcification,laser fluence,and opticalpulse duration”中所述的高度钙化病变。
然而,所有上述方法具有缺点,尤其是在对于所使用的光纤设置所能实现的能量密度携载容量、和/或系统能量吞吐量和/或当与组织接触时对光纤末端的损坏的有限的改善方面。
因此,对于克服现有技术的系统和方法的至少一些缺点的利用消融能量的光纤输送来执行消融手术方法的方法和装置存在需求。
除了对于实现消融过程的新系统的需求之外,由于例如引线断裂或绝缘磨损导致短路和感染的原因,对于在患者中去除起搏器和除颤器引线的具体程序的需求日益增长。全世界约有500万根引线植入,据估计,在患者的一生中,有时需要去除4-7%的引线。据估计,2010年在美国和欧洲取出了超过100,000根引线。
在引线取出程序(以下称为LE)中,当静脉中的弯曲处的引线必须被减积时,达到程序中的最关键点。当执行电极分离程序时,存在导管穿透静脉的危险,并且在严重的情况下,这甚至可能导致患者的死亡。使用主动扩张器报告1%的死亡病例或甚至更高的死亡率。
基于激光消融和机械的切割器是广泛使用的用于粥样斑块切除手术的解决方案,以便打开或部分打开血管内的堵塞物。减少血管壁穿孔危险的方法之一是使用具有优先切割或消融血管壁上的粥样组织的参数的系统。如果切割或消融效果在动脉粥样物质上比在动脉或静脉壁材料上显著地更有效,并且该程序在安全地落在对血管壁造成损害的阈值以下的条件下执行,则将存在在减积手术期间动脉或静脉壁将被切除的较小的可能性。在现有技术中,在M.R.Prince等人的题为“Preference Light Absorption in Atheromas inVitro-Implications ForLaser Angioplasty”的文章中(发表在Journal of ClinicalInvestigation,卷78(1):第295-302页,1986年7月),已经显示粉瘤实际上吸收比正常主动脉多,在420和530nm之间。然而,在UV中没有发现这一点,在广泛使用的308nm波长处,主动脉的吸收高于粉瘤的吸收。然而,由于使用420-530nm范围,具有其有利的消融选择性,在由有效消融和更深穿透所需的较大能量所引起的潜在热损伤中具有固有缺点,因此优选使用选择性消融的方法,该选择性消融的方法使用UV区域内的激光辐射。
然而,还发现,如R.O Esenaliev等人在IEEE Transactions onBiomedicalEngineering,卷36,第12期,第1188至1194页(1989年12月)中发表的题为“Laser Ablation of Atherosclerotic Blood Vessel Tissue Under VariousIrradiationConditions”的文章中所述,对于UV(355nm和266nm)中的波长,在动脉粥样硬化血管的正常壁和纤维斑块区域之间没有发现光衰减系数与短脉冲的差异。因此,其他现有技术方法,例如由D.Murphy-Chutorian等人在题为“SelectiveAbsorption ofUltraviolet Laser Energy by Human Atherosclerotic Plaque TreatedwithTetracycline”的文章中所公开的(发表在American Journal of Cardiology,卷55,第1293-1297页,1985年),建议使用敏化剂如四环素,以增加斑块中的吸收。四环素与斑块牢固结合,并且在UV中具有强吸收。用于临床治疗的此类方法的问题是四环素是抗生素,并且需要另外的调节和测试以确保没有副作用。
因此,还需要一种用于使用消融能量的纤维光学输送来安全地执行引线取出的方法和装置,其克服了现有技术的系统和方法的至少一些缺点。类似地,需要用于减灭血管中动脉粥样硬化的粥样斑块切除术工具,其降低血管穿孔或解剖以及良性前列腺增生(BPH)中扩大的腺体的减灭的风险,同时降低胶囊损伤的风险。
在操作之前应该校准激光导管,以便验证从导管发射的激光能量的注量和重复率。
现有技术涉及校准导管的方法,其中导管从其包装中拉出,耦合到激光器系统,远端末端由检测器前面的壳体保持,操作激光器并通过如授予TomDadisman的“Lasercatheter calibrator”的美国专利No.11/946,376中所述的检测器来测量能量。
因为导管在使用前灭菌,所以该方法会涉及到将导管的远侧末端移出手术室中的灭菌区域的风险。
因此,对于用于激光器系统的内部校准和用于检测系统和/或导管的故障的方法和装置也存在需求。
在说明书的该部分以及其它部分中所提到的各个出版物的公开内容均整体地通过引用方式合并于此。
发明内容
本公开描述了用于使得能够将具有非常短的脉冲宽度的极高能量脉冲(优选地来自发射UV的固态Q开关激光器)耦合和传输到用于在消融程序中使用的光纤的新的示例性系统,这实现了要传输的能量脉冲比在现有技术中描述的系统中实质上高。在现有技术的系统中,通常使用具有尽可能高的质量输出的激光器,与为了实现高耦合效率和更好的光束质量而没有“热点”的主旨一致,应使用具有最接近应使用单模输出(一般尽可能接近衍射极限高斯模式)的激光器。这是在使用激光束用于切割或点消融中可接受的逻辑,如例如在上述美国专利5,312,396中所指出的,其中在称赞它们针对该目的的适用性上阐明,所使用的Nd:YAG激光器“有良好的光束质量”。类似地,在上述T.Schmidt-Uhlig等人的参考文献中,声称在他们的系统中使用的Q开关倍频Nd:YAG激光器的脉冲具有“近高斯(sic)时间和空间分布”。相同的设计理念适用于大多数现有技术的高脉冲能量、纤维递送的外科消融系统。类似地,B.Richou等人的题目为“Delivery of 10-MW Nd:YAG laser pulses bylarge-core optical fibers:dependenceofthelaser-intensityprofileonbeampropagation”的文章发表在Applied Optics卷36,第7期(1997年),报道了与平帽形波束(130mJ)相比,脉冲Nd:YAG近高斯波束的更高(230mJ)的透射率。在本申请的系统的纤维束中使用的单根纤维通常具有小于200微米,优选小于100微米的纤芯直径,其中传输的能量为1-2mJ的量级,其中脉冲长度为10ns不会导致自聚焦。
然而,在本申请中所使用的系统设计利用了如下事实:即使当处置具有如100微米的小直径的纤芯的纤维时,由于这种激光器的光质量模态结构,确切地会发生通过光纤的耦合和传输的严重问题。
当前描述的系统与这些现有技术系统的不同之处在于,使用输出多个横向模态的源激光器,从而具有高度多模输出。空腔还应当有利地是稳定的谐振腔。这样的激光器先验地输出具有低空间相干性的光束,并且因此减少由于干涉现象而在光纤体内损坏的普遍性。这种激光器输出明显更接近具有均匀的光束分布的光束,称为顶帽配置,而不是现有技术中通常用于这种系统中的高质量激光器。为了更好地提高对纤维损伤的免疫力,现有技术的均匀化,束操纵方法也可以有利地应用于这种平顶束,从而具有相应改进的性能。与使用高质量激光脉冲时相比,这种脉冲沿着光纤的传输导致更高的损伤阈值,并且已经发现在光纤损坏启动之前,可以传输比现有技术系统具有更高能量密度的脉冲。认为该现象与在其分布上的波束的离散部分之间不存在有意义的相互作用相关,这可能产生热点或干涉。然而,应当理解,本发明独立于其物理操作的真实原因而要求保护。应当注意,由于本公开的导管使用一束光纤,并且单个激光脉冲的能量通过一束光纤而不是单个光纤传输,因此本公开中对单个光纤的提及通常旨在意味着光纤束中的单个光纤,并且不旨在表示仅通过单个光纤的传输。
激光输出光束的模态质量可以通过光束尺寸和光束发散来表征。给定尺寸和波长的光束的发散越小,光束质量越高。用于表征波束模态质量的一个参数是M2参数。在本申请中使用由激光器输出的光束模态的M2参数来表征光束性质,以实现纳秒范围内的这种脉冲的非常高的脉冲能量密度。然而,应当理解,M2参数的使用仅仅是表征光束质量的一种方式,并且本公开的发明不旨在受到该措施的使用的限制。
M2参数按以下关系与输出光束尺寸和光束发散的比率相关:
其中D=光束直径,
λ=激光束的波长,以及
θ=全角光束发散,单位为弧度。
纯衍射限制光束将具有1的M2参数,而用于外科手术或精密工业应用的实用的、高效率的商业激光器通常具有在低单数位范围内的M2参数。
通过在该点插入聚焦透镜且测量所获得的焦斑的尺寸,还可以对在沿其光路的任意点的光束定义M2参数。直观地,焦斑越密实,在该点光束的模态质量越好,M2参数越低。在该情况下M2参数由以下关系给出:
其中D现在是在透镜的插入点处的光束直径,
f是所使用的透镜的焦距,以及
d是所获得的焦斑的尺寸。
在本公开中应当理解的是,所使用的M2参数是根据这些公式中的适当的一个来计算的,取决于测量是涉及激光器输出光束,还是涉及光路下游的光束。
在本公开中所描述的系统和方法与现有技术中所描述的那些系统和方法的不同之处在于,用于沿着光纤传输并在治疗部位处进行消融的激光被选择为具有高度多模光束输出,优选地为三次谐波Nd:YAG激光器,使得输出光束的M2参数应该至少为几十的量级,通常至少30,和最佳地高达70或甚至更高,例如大于100。激光器的M2可以大于10,但是包括光学器件在内的系统的M2大于70,优选地大于200。该光束因此以非常不同于现有技术中所描述的那些光束的方式表现,并且允许传输具有至少如使用光光束质量激光器的现有技术消融系统可用的脉冲的至少两倍以及甚至更大的脉冲能量密度的脉冲。可以增加额外的光学装置,例如微透镜阵列,以进一步增加M2并增加通过典型地具有100微米纤芯或更小的纤维的、大量脉冲可靠地传输的脉冲能量密度。
该系统的典型性能的细节将见于下文的详细说明部分。
本公开还描述了用于能够基于使用320-400nm激光波长的短激光脉冲的消融特性来选择性地去除血管内不期望的组织同时使损伤血管本身的风险最小化的新的示例性系统,利用了构成导管的管的机械壁的选定参数、激光注量的选定参数和由导管施加在组织上的力的选定参数。如上所述,先前认为,不存在敏化剂的给定组织的选择性特征不能使用UV辐射来确定,因为正常主动脉和动脉粥样化组织共享许多常见分子,其吸收带全部在UV区域内,无论是在355nm或308nm。尽管许多有机分子键的解离能量通常高于355nm波长的光子能量(3.5eV),但这不适用于其光子能量较高(4eV)的308nm准分子激光器波长。因此,认为在355nm波长的主要消融机制是光机械的。相比之下,在准分子激光器的较短的308nm波长处,并且显然在甚至更短的波长处,其中化学键通过激光辐射解离的光化学过程更相关。由于与目标组织的相互作用机制的这种差异,波长的选择以及其它选择的参数被认为对目前描述的导管的成功具有中心影响。因此,通过使用正确选择的参数,血管壁的消融比动脉粥样化发生的可能性要小得多,因为血管壁比动脉粥样硬化具有更大的弹性,因此比动脉粥样硬化更好地承受操作于它们上的光机械机构,动脉粥样硬化更容易被这种光机械影响分解。
还可能的是,除了操作的波长方面之外,由于冲击波在光机械消融机制中起主要作用,因此脉冲持续时间(即较高的峰值功率)的减小可以导致过程的效率提高。
然而,应当强调的是,本申请涉及其中描述的导管,而不管其操作的成功所基于的物理机制,并且本申请不旨在受到关于导管实现其功能的可能机制的任何建议的限制。
根据本公开的一个示例性的导管系统,输出355nm的三次谐波Nd:YAG激光器耦合到混合导管,该混合导管包括接收激光照射的一束光纤,以及至少一个钝端管状结构,其远端边缘位于与光纤的输出面基本上是一个的表面上,以与血管内的动脉粥样化组织相互作用。不同的配置可用于LE使用和减灭或开放血管,其中发现动脉粥样硬化物质的大量沉积物,例如外周动脉疾病(PAD)中。在LE的情况下,需要薄的环形纤维束,其中圆柱形壁限定在环的内侧和外侧上。圆柱形壁构成钝端管状结构。另一方面,在PAD中,为了去除血管的整个横截面上的沉积物,纤维束基本上覆盖导管的整个横截面,通常在束的中央具有用于导丝的细的开口,但是同样在这种情况下,束区域的圆柱形壁构成钝端管状结构。在本公开中,这些钝端管状结构被称为“钝的机械刀片”。
使用LE壳体作为示例,导管一旦在血管内并且与血管内沉积物接触就通过使用激光脉冲来消融通常仅仅几十微米深的组织薄层来操作,从而形成薄的浅狭缝,以响应于远端施加在导管上的压力使得钝的机械刀片能够继续穿透。因此,一个或多个刀片被构造成太钝而不能开始解剖,但是具有足够的边缘以产生狭缝,以使得更深的导管穿透到组织中。具有瞬时区的被消融的组织的边界由于创伤而被机械地削弱,这便于被钝刀片切开。刀片的宽度以及发射消融能量的光纤束内的纤维的芯的总面积相对于导管的末端的、不包括空中心区域的总横截面积的比率是也表征本公开的导管的重要参数。
在导管上远端施加的力是附加参数,其水平被调节以确保导管以与激光消融速率和混合导管动作的机械剥离相称的速率前进通过动脉粥样化组织。导管的直径越大,需要施加的力就越大。
本公开还描述了新的示例性的系统,以使得能够以与组织接触的模式可靠地操作导管。
在一些实施方案中,在纤维的远端添加薄的蓝宝石窗口或类似物。在一些实施方案中,窗口涂覆有AR涂层。
在其它实施方案中,远侧末端处的纤维末端涂覆有硬涂层。涂覆导管末端可以提供额外的性能增强一种可能的材料是金刚石。类金刚石涂层(DLC)通常用于需要硬的、坚固和光滑的表面的工业应用中,例如以防止机械磨损。获得这种涂层的手段之一是通过化学气相沉积(CVD)。切削工具经常涂覆以提高耐久性。DLC具有优良的生物相容性,因为它通常用于关节置换和冠状动脉支架。
金刚石涂覆的导管可以具有以下优点。首先,涂层硬度可以保护纤维末端免受由于与硬生物介质接触和来自激光消融的合成冲击波的损害。第二,平滑度(低摩擦)和同时的纳米粗糙度可以有利于允许导管的进展和/或通过刮擦增强材料去除。第三,高热导率可以有助于分布来自组织中的激光脉冲的吸收的热量。
DLC因为它们的高吸收而通常不被认为适合于可见波长。然而,当考虑最大UV光(355nm)透射所需的最佳层厚度时,具有2.4的折射率的DLC涂层在应用于熔融石英时仅需要为约74nm厚,以获得3.7%的最小反射率。这种低厚度的材料的吸收应该是最小的。此外,可以使用透明金刚石涂层,如E.Pace等人的、题为“Fast stable visible-blind and highsensitive CVD diamond UVphotodetectors for laboratory and space applications”的文章(发表于“Diamond andRelated Materials”,卷9,第3-6期,第987-993页(2000年4月-5月))中所描述的。若干制造商已经将DLC涂层应用于玻璃,包括例如Jenoptik andReynardCorporation,其生产具有增强的可见光透射率的透明DLC。
使用CLD的另一个局限性是高的折射率,这导致非常高的“菲涅耳损失(FresnelLoses)”。处理这些损失的可能方式是添加AR涂层,但是在当前实施方案中这是有问题的,这是由于多个原因:
AR涂层不能在光纤末端承受非常高的功率。此外,其需要由生物相容性材料制成以允许与组织紧密接触。此外,AR涂层在与组织接触时经历机械磨损。
因此,根据本发明,金刚石层用作AR膜,其中其厚度被选为减少反射损失从而节约能量且避免反向反射到纤维中,这会损坏纤维。厚度可以根据防反射涂层中使用的规则,例如四分之一波长,5/4波长或根据发射光的角度(NA)的其它组合来确定。还可以以这样的方式确定厚度,使得355nn的波长将被透射,而可见光中的另一个波长将被反射。还可以以这样的方式来确定厚度:355nm的波长将被传输,而可见光中的另一波长将被反射。例如,在出射面的硬涂层可以使得利用9/4波长的厚度来将355nm传输离开导管,其中波长是355nm(并且根据折射率来校正),使得相同的层将在532nm波长的3/2(以及根据折射率校正)并且导致从纤维端面有效反向反射以校准系统所输送的能量,其中532nm和355nm是由相同的激光器产生的并且通过相同的耦合光学器件和导管来传输。这使得能够在手术之前进行有效的校准,并且在整个过程中用作导管的在线校准和质量控制。通过实施例的方式,如果折射率为2.4,则厚度为332.8nm的层等效于355nm(在真空中)的9/4波长和532nm(在真空中)的1.5波长。对于通过可以达到0.22的NA的光纤传输的激光光线的入射而言最优化的其他实施方案是可能的。
在其它实施方式中,激光脉冲被分成至少两个脉冲,其中脉冲之间的延迟小于15nsec延迟,以便保护光纤的远端面,而不显著影响消融效率。这种系统的细节可以在下面的详细描述部分中找到。
在替代实施方式中,描述了有助于在整个过程中用盐水冲洗末端的方法。这种系统的典型性能的细节在下面的详细描述部分中找到。
本公开还描述了新的示例性的系统,以使得能够实现有效且方便地用于校准通过纤维输送能量的激光系统的装置。这种系统的典型性能的细节在下面的详细描述部分中找到。
因此,根据在本公开中所描述的设备的示范性的实施方式提供一种消融腔血管内的区域的激光器设备,以及通过耦合光学器件与所述激光器耦合的至少一个光纤,其中激光器具有多模态输出而使得其M2参数大于30。M2参数可以大于70或者甚至100。
根据这些设备的另一实施方式,提供了用于消融腔血管或身体的其它管腔内的区域的激光器设备,包括在光谱的紫外线区域内发射的脉冲激光器,以及通过耦合光学器件与所述激光器耦合的至少一个光纤,其中激光束具有通过已知焦距的透镜聚焦的光束的光斑尺寸所测得的多模态分布,使得光束具有至少30的M2参数。M2参数可以大于70或者甚至大于100。
在这两个实施方式中的任一个中,至少一个光纤可以具有直径小于200微米的芯。另外,耦合光学器件可以包括微透镜阵列、衍射光学元件,全息漫射器、光管棒和大芯光纤中的任何一个或多个。在一些实施方式中,激光器的M2参数可以大于10或者大于30,但是激光器M2与上述元件一起的M2大于70,优选地大于200。
脉冲激光器可以有利地是Nd:YAG固态激光器,激光器波长可以是355nm,激光器脉冲宽度可以小于15nsec,并且脉冲激光器重复率可以大于10Hz。在后一种情况下,激光器使得至少60mJ/mm2的注量可以通过光纤输送超过一分钟。根据另外的实施方式,通过光纤输送多于一分钟的注量可以是至少200mJ/mm2或甚至300mJ/mm2。
因此,根据本公开中所描述的设备的示范性的实现方式提供了一种用于在血管内选择性切割的设备,其中所述设备包括:
(i)脉冲激光器,其以320至400nm的波长范围发射,并且与多根光纤耦合,使得从所述光纤发射能量通量,以及
(ii)管,其充当所述多根光纤的界限,每个所述管具有在与所述多根光纤的输出端相同的轴向平面中的钝性远侧边缘,使得当远侧力施加到所述设备上时,所述钝性远侧边缘推送通过从所述光纤发射所述能量通量的区域中所述血管中的动脉粥样物质,
其中从其中发射所述能量通量的总芯面积与所述设备的总远侧末端面积的比率是至少25%。
在该设备中,比率可以在30%至40%的范围内。另外,激光器可有利地是以355nm发射的三次谐波Nd:YAG激光器。
在上文所述的设备中的任意设备中,通量可以为至少50mJ/mm2或者可以在50至80mJ/mm2的范围内,或者甚至在在65至80mJ/mm2的范围内。
另外,上文所述的设备的多根光纤可以是一束光纤。在该情况下,各个管和纤维的总宽度应当小于400μm且大于200μm。
此外,根据该设备的另外的实现方式,可使用染料或衬底来增强期望波长下的吸收。染料可以是四环素,期望波长是355nm。
另一示例的实现方式可涉及用于消融组织的区域的系统,包括:
(i)激光器,其发射激光脉冲束,所述束由耦合光学器件耦合到至少一根光纤,使得从所述至少一根光纤发射能量通量,所述至少一根光纤具有输入面和输出面;
(ii)分束器,其布置在所述激光器与所述至少一根光纤之间,使得所述束能够非偏转地通过所述光束偏振器而到达所述至少一根光纤,用于传输到所述组织区域;以及
(iii)检测器,其布置在所述分束器处、与所述束非偏转地通过所述分束器的方向成法向的位置处;
其中所述检测器接收从至少一根光纤的所述输入面和所述输出面中的至少一个反射的所述束的预定部分,使得能够确定通过所述至少一根光纤的能量通量。
该系统还可以包括
(i)线性偏振器,其布置在光束的光路中,使得光束在撞到所述分束器上之前具有预定的线性偏振,以及
(ii)四分之一波片,其布置在分束器与至少一根光纤的输入面之间,使得从输入面和输出面中的至少一个反射的光束的预定部分具有与输入至少一根光纤的光束正交的线性偏振,使得分束器将预定部分朝向检测器导向。
在后者两种情况中的任一种中,输入面和输出面中的一个可以具有防反射涂层,使得反射光束的预定部分限于未涂层的该面。
附图说明
将从下面结合附图进行的详细描述中更全面地理解和领悟本发明,在附图中:
图1示意性地示出了使用多模态激光器的示范性的激光消融系统,其使能通过消融导管的光纤传输极高能量密度脉冲;
图2示意性地示出了图1所示的系统的另一示范性的实现方式,其中使用激光束的分裂从而实现通过光纤传输在时间上分离的双脉冲形式的脉冲串并且避免光纤的输出面处的损坏;
图3A和图3B分别是能够选择性地消融血管壁的组织上的动脉粥样硬化组织而使得能够更安全地执行引线取出或PAD程序的示范性的环状混合导管的示意性的端视图和剖面侧视图;
图4A和图4B分别是能够更安全地选择性地消融来自动脉粥样硬化血管的斑块的示范性的混合导管的示意性端视图和剖面侧视图;以及
图5A示意性地示出了在其操作期间校准图1至图4B所描述的混合导管以及实时检测系统的故障的布置。
图5B示意性地示出了用于图5A所描述的校准系统的示范性的空间滤波器的端视图。
图6A、图6B和图6C分别是具有用于冲刷导管的远侧末端的毛细管的示范性的导管的示意性的端视图和剖面侧视图。
具体实施方式
现在参考图1,图1示意性地示出了本公开中描述的类型的示例性激光消融系统,其包括以紫外线发射并具有多模态输出的固态激光源10,如由邻近输出光束的光束分布表示15所例示的。该表示仅用于说明的目的,以示出多模态输出与高斯光束非常远离,并且不旨在以任何方式限制应用。激光束输出应具有至少30,更有利地至少70的M2参数,但是具有超过100的M2参数的光束输出的激光器可以在图1的示例性的消融系统中提供甚至更好的性能。为了获得最佳性能,使用短脉冲宽度,优选小于10纳秒,并且激光器应当提供能够通过光纤提供至少50mJ/mm2的能量密度的脉冲。为了稳定性和紧凑性,使用固态激光器,例如工作在其三次谐波355nm的Nd:YAG。
尽管激光器10发射良好混合的多模态光束,但是激光光束被输入到光束均匀化和/或相干操纵单元14,以便更多地混合输出光束11的多个模态,使得光纤具有甚至比单独使用激光器的多模输出所获得的损伤阈值更高的损伤阈值。该单元14可以是均化板、衍射光学元件、全息元件、微透镜阵列或均化器光纤中的任何一个或多个,其弯曲以确保脉冲向下传播期间的附加模态混合。然后,使用耦合透镜12将激光束耦合到光纤束13中。虽然单个光纤可以具有小于200微米的芯尺寸,但是光纤束包括大量的这些单独光纤,因此实质上大于单根光纤的直径,使得将这种多模态光束耦合到这种小光纤中没有特殊的光学困难。虽然在图1中仅示出一个耦合透镜12,应当理解,系统可以结合两个耦合透镜——一个用于将原始激光束耦合到例如均匀器光纤中,另一个耦合透镜将经处理的光束的输出耦合到导管的纤维束中。在一些实施方案中,这种光学元件的组合使得能够通过100微米或更小的纤维输送高注量,还可以使用具有大于10的M2的激光束。
现在参考图2,该图示意性地示出了图1所示的系统的另一示例性的实现方式,其中使用激光束的偏振分裂,以便使脉冲串以时间上分开的双脉冲的形式沿着光纤传输,特别是当与组织接触时降低对每个光纤的输出面损坏的危险。这些输出面(其中纤维与被消融的组织接触)经受特别恶劣的条件。当图1中描述的系统被实施并且纤维与组织接触时,在输出面处的面损坏的可能性大于在光纤的输入面处的面损坏的可能性,因此这种实现方式将最有利于保护输出面免受损害,但是应当理解的是,它也可用于保护输入面和纤维本体本身。
来自高度多模态激光器10的光束传输通过半波片27然后到达偏振分束器28,以便将激光束分成S偏振和P偏振这两个分量部分。在图2所示的实施例中,S偏振被偏转90°,而P偏振通过立方分束器而没有偏转。S偏振在比P偏振更长的光路上传送,并且在通过两个全反射器反射镜实现的180°反射之后,S偏振光束和P偏振光束通过第二偏振分束器29再组合,准备通过耦合透镜12耦合到导管的纤维13中。通过调整P偏振和S偏振所行进的光程差,可以控制两个光束之间的时间延迟,使得输入由分开所选择的时间延迟的双脉冲组成,并且使用这样的双脉冲激光能量在与被消融材料接触的模式下,不仅能够在光纤的入射面处而且能够在光纤的有问题的输出面上避免光纤损伤。时间延迟必须被选择为使得双脉冲不被分开超过被处理的血管材料的弛豫时间,使得消融效率不会损失。对于10ns脉冲,10ns量级的脉冲之间的时间延迟被认为是可接受的。这种双脉冲模态的成功还取决于消融效率不是激光脉冲的峰值功率的线性函数的知识,使得将功率分成两个脉冲不会使消融效果降低相同的二分之一。另外,可以在较长的光路中设置透镜(图2中未示出),以便以这样的方式对束腰进行成像,使得穿过两个不同光路的两个光束的腰部都位于光纤输入面。这是必要的,以便补偿在较长光路中的光束经历的额外光束发散。作为图2所示的配置的替代,可以使用薄膜偏振器(TFP)来分裂和组合两个光束。
此外,激光束可以分裂成多于两个的通道,以甚至进一步降低纤维的潜在损伤水平。另外,由激光器发射的不同波长,例如Nd:YAG激光器的二次和三次谐波或基波和三次谐波,可以被分裂并再次组合。还可以使用在脉冲之间具有同步延迟的多个激光器。
现在参考图3A和图3B以及图4A和图4B,这些图示意性地示出了本公开的混合消融导管的进一步的实现方式,它们示出了导管如何能够用于选择性地消融来自血管的动脉粥样化物质,同时降低对血管壁穿孔的危险。在这些图中所示的混合导管的结构具有共同的特征,即,除了发射消融激光脉冲的纤维束之外,包围纤维束的管状元件的钝性远侧端也构造成使得它们有助于导管的操作。如在本公开的发明内容部分所说明的,管状结构的远侧端特别地构造为具有非尖锐端,下文称为钝性机械刀片,使得它们不会非有意地切开血管壁。
首先参考图3A和图3B,它们分别示出了示例性环形混合导管的示意性端视图和剖面侧视图,其可以比血管壁更容易地选择性地消融动脉粥样硬化组织,使得可以更安全地执行引线取出。激光能量通过嵌入在具有大中心透明区域33的环带形式的粘合剂基质内的光纤束30传输到导管的远端。光纤30的环带在其内侧由构成内钝性机械刀片的细管31定界,在其外侧由构成外钝性机械刀片的另一细管32定界。内管31的最内边缘和外管32的最外边缘之间的距离被称为导管或远侧末端的有效壁厚34。在使用中,将导管插入到血管中的待取出的引线上,使得引线位于中心环形区域33中。激光脉冲能量被施加到纤维束30,通常在320至400nm的紫外线区域内,并且具有50至80mJ/mm2的注量,伴随有向远侧施加到导管的力,使得导管能够在远侧方向上行进,从而从血管壁减少导线,而不损伤血管壁,如在上文的发明内容部分中所解释的。该过程成功的重要参数是基于在导管末端处的组织相互作用平面处发生的两个能量过程之间的权衡。一方面,发射激光脉冲的纤芯的总面积(称为有效发射面积)提供消融能量以便使动脉粥样硬化物质降解,同时机械地推动和剥离降解的物质的、向远侧施加到导管上的机械力操作通过所谓的远侧末端区域,远侧末端区域包括导管的远侧面的全部的机械部分,包括内钝性机械刀片区域和外钝性机械刀片区域,以及纤维粘合基质的机械区域,但是没有中空的中央区域。该导管的壁厚或远侧末端34典型地在200μm至400μm的范围内,使得纤芯面积与导管的远侧末端面积的比率在25%与50%之间。最有效的比率在30%至40%的范围内。施加到导管上的远侧力可以在0.5kg的区域内,甚至高达2kg的区域内。
图4A和4B现在以端视图和剖面侧视图示出了可以更安全地选择性地消融来自动脉粥样硬化血管的斑块,例如用于PAD治疗的示例性混合导管。这种类型的导管与图3A和图3B所示的不同之处在于,纤维束40填充导管的大部分中心区域,在内管41内仅留下小的中央开口43,通常留下使得导管可以骑在导丝上。该混合导管的有效壁厚44是外管42的外表面和内管41的内壁之间的距离,通常在400μm至1200μm的范围内。如在LE导管的情况下,纤芯面积与导管的远侧末端面积的比率在25%和50%之间。由于PAD治疗的本质,在推动导管通过例如弯曲血管时需要更多的注意,使得力可以更小,但是至少为100gm。
现在参考图5A,该图示意性地示出了用于校准在本公开中所描述的混合导管的布置。在操作之前校准是必要的,以便验证从导管发射的激光能量的注量和重复率。
在现有技术中,已经描述了导管的校准方法,其中导管与激光器系统耦合,而远侧末端由位于检测器前方的壳体来保持,并且在激光器工作的同时通过检测器来测量所传输的能量。因为导管在使用前灭菌,所以该方法会涉及到将导管的远侧末端移出手术室中的灭菌区域的风险。
图5A所示的系统与现有技术方法的不同之处在于,其在使用时能够进行导管的内部校准,并且还能够在系统操作时检测系统的故障。
来自激光器50的入射光束被引导通过光束偏振器51,该光束偏振器51将光束输出为P偏振,如图5A中标记的。在穿过耦合透镜52之后,P偏振光束被输入到偏振分束器53,P偏振光束从偏振分束器53无偏转地出射。P偏振光束然后通过四分之一波片54输入,四分之一波片54将其偏振转换成圆形。然后,该圆偏振光束进入光纤55,通过其全内反射(TIR)通过其中,并且大部分能量从光纤远端的输出面发射,用于消融程序59。然而,小百分比的能量由于来自输出面的菲涅耳反射而被反射回到光纤的入口。另外,来自前面的任何菲涅耳反射56也被反射回来。输入光束的这个小的反射部分现在返回通过四分之一波片54,在那里其从圆形转换成S偏振,使得当其进入偏振分束器53时,其沿着朝向检测器58大致垂直于其入射轴线的路径57偏转。由于来自前和后面的反射百分比是已知的,因此检测器能够根据该反射功率的测量来确定从光纤输出发射到消融应用的能量。因此,检测器输出的测量是在消融程序中使用的激光能量的实时监测。
如果入射面被涂覆有防反射涂层,则由检测器58测量的功率仅是由于来自输出面的反射,使得可以在来自这两个面的反射之间进行区分。
作为在入射面上使用防反射涂层以便区分前面和后面反射的替代,可以使用设置在前面和偏振分束器之间的空间滤波器,以便滤除来自输入面的反射,其具有比来自输出面的反射更小的发散角,因为输出反射的数值孔径明显更大。空间滤波器可以方便地是如图5B所示的薄膜偏振器(TFP),其中TFP60在其外围边缘61处被涂覆,使得那些边缘将反射光束从输出面发散到检测器58,而TFP60的中央区域62是未涂覆的,因此来自输入面的较小发散反射通过该中央未涂覆窗口,并且不到达检测器。
根据另一示例性实施方式,帽可以放置在导管的远侧末端上方,帽的内部涂覆有反射涂层,以便增强从纤维的远侧面反射的信号。
帽可以涂覆有改变输出反射光束的波长的荧光材料,并且通过使用光学滤波器,实现其与入射面反射的分离。帽可以与导管一起灭菌。
可替代地,帽还可以覆盖有当高于规定级别的能量撞到它时给出声音指示的材料,例如聚酰胺。可替代地,帽可以覆盖有当暴露于激光的辐射时改变其颜色的材料。
上述校准程序可以在光纤在其封装内卷起时执行,保持光纤的弯曲半径是已知的并且是恒定的,使得从输出面反射回来的能量的百分比不改变。
在一些其它的实施方案中,入射面未涂层,检测器将测量从输入面和输出面反射的能量。
在一些实施方案中,系统可以在内部校准,而不连接导管,其中存在当所述导管连接时移动到旁边的盖子,并且当所述导管移出时,所述盖子关闭。该盖子在指向激光器的一侧被镜面涂覆,并且从该镜面涂层反射的能量被偏振分束器折叠并且可以在检测器中测量。
通过在程序期间测量系统检测器中的反射能量并且通知用户由于纤维损伤引起的能量减少,所描述的校准这样的导管的方法还使得能够实时监测消融过程。
现在参考图6A至图6C。当UV激光导管用于减灭血管内的组织时,由于在血液和造影剂中的高吸收而产生的冲击波,纤维的远端尖端可能被损坏。为了保护导管的远侧末端,在正常程序中通过引导鞘注入盐水。或者,盐水可以通过导管的内腔注入,但是这限制了医生,因为需要选择比可能的更小的导丝。
现在参考图6A,其中示出了激光导管63的远端。空心毛细管65可以结合在光纤66之间,并且允许盐水流动到导管63的远侧末端和被消融组织的接触点。中空毛细管65可以从手柄延伸到导管63的远侧末端,并且盐水通过中空毛细管65的近侧注入。
现在参考图6B。为了允许盐水的自由流动而不受毛细管力的限制,大的中空毛细管67可以连接到放置在导管63的远侧末端处的小的且短的中空毛细管65。
图6C示出了另一个实施方案。在内管69和外管68之间注入光纤66位于其中的空间中的盐水。小毛细管65位于导管的远侧末端处,在胶72,内刀片71和外刀片70之间。因此,毛细管65能够通过导管的远侧末端滴注盐水。
虽然本发明使用来自血管的实例,但是该效用与需要组织的受控切除的其他医学指征例如巴雷特食管,在肠中或在泌尿学和妇科应用(例如BPH中的减积(debulking))中的扁平息肉的去除相关。
本领域技术人员应当理解,本发明不限于上文具体示出和描述的内容。相反,本发明的范围包括上述各种特征的组合和子组合以及本领域技术人员在阅读上述说明时将想到的并且不在现有技术中的变型和修改。
Claims (20)
1.一种用于激光消融系统的装置,包括:
激光源,其被配置为发射激光束,所述激光束包括多模式输出、紫外(UV)波长和大于或等于1纳秒(ns)且小于或等于10ns的脉冲宽度;
至少一个偏振器,其被配置为将所述激光束分离成第一偏振激光束和第二偏振激光束;
至少一个反射镜,其用于将时间延迟引入到所述第二偏振激光束中,所述时间延迟小于或等于15ns;
至少一个光学元件,其被配置成将所述第一偏振激光束和经时间延迟的第二偏振激光束组合成被光学耦合到导管的纤维束的经修改的激光束,所述经修改的激光束包括大于或等于2ns且小于或等于25ns的脉冲宽度,以及包括与所述第一偏振激光束相关联的第一峰值和与所述第二偏振激光束相关联的第二峰值的波形。
2.根据权利要求1所述的装置,其中,所述经修改的激光束具有50到80毫焦耳(mJ)每毫米(mm)平方(mJ/mm2)的注量;其中所述激光束的波长包括355nm;并且其中与相应于所述激光束相比,相应于所述经修改的激光束的待光学耦合到所述经修改的激光束的导管的纤维束具有更高的损伤阈值。
3.根据权利要求1所述的装置,其中,所述第一偏振激光束包括P偏振,并且所述第二偏振激光束包括S偏振。
4.根据权利要求1所述的装置,其中,所述经修改的激光束的脉冲宽度小于或等于20ns,且其中所述第一峰值和所述第二峰值在所述经修改的激光束的脉冲宽度内。
5.根据权利要求1所述的装置,其中,所述至少一个偏振器包括波片,并且所述至少一个光学元件包括薄膜偏振器(TFP)。
6.一种用于激光消融系统的装置,包括:
第一激光源,其被布置为发射第一脉冲激光束,所述第一脉冲激光束包括大于或等于1纳秒(ns)且小于或等于10ns的脉冲宽度;
光学系统,其与所述第一激光源光学通信,所述光学系统包括多个光学元件,所述多个光学元件被布置为:
接收所述第一脉冲激光束,以及
部分地基于所述第一脉冲激光束,形成包括多峰值波形和大于或等于2ns且小于或等于25ns的脉冲宽度的经修改的脉冲激光束,其中所述多峰值波形包括第一峰值和第二峰值,并且其中所述第二峰值在时间上与所述第一峰值分离小于或等于15ns。
7.根据权利要求6所述的装置,其中,所述光学系统进一步包括多个反射镜,以将时间延迟引入到所述第一脉冲激光束的至少一部分中以将所述经修改的脉冲激光束的所述第一峰值与所述经修改的脉冲激光束的所述第二峰值在时间上分离。
8.根据权利要求7所述的装置,其中,所述光学系统还包括:至少一个偏振器,用于将所述脉冲激光束分离成具有第一偏振的第一分量激光束和具有第二偏振的第二分量激光束;其中,所述第二偏振被配置为与所述第一偏振不同;其中所述多个反射镜被配置成将时间延迟引入到所述第二分量激光束中;并且其中所述经修改的脉冲激光束部分地基于所述第一分量激光束和经时间延迟的第二分量激光束。
9.根据权利要求6所述的装置,其进一步包括与所述光学系统光学通信的第二激光源,所述第二激光源布置成发射第二脉冲激光束,使得来自所述第二脉冲激光束的脉冲相对于所述第一脉冲激光束的脉冲在时间上分离,其中所述经修改的脉冲激光束部分地基于所述第一脉冲激光束和所述第二脉冲激光束。
10.根据权利要求6所述的装置,其中,所述时间间隔小于或等于15ns;其中所述经修改的脉冲激光束的波长包括355nm;其中所述经修改的脉冲激光束具有50至80毫焦耳(mJ)每毫米(mm)平方(mJ/mm2)的注量;并且其中纤维束具有比相应于所述激光束的相应于所述经修改的激光束的更低的干涉。
11.一种用于激光消融的激光束生成系统,包括:
固态激光源,其被布置为发射脉冲激光束,所述脉冲激光束包括大于或等于1纳秒(ns)且小于或等于10ns的脉冲宽度;
与所述固态激光源光学通信的薄膜偏振器(TFP),所述TFP被配置为传输所述脉冲激光束的P偏振分量并且偏转所述脉冲激光束的S偏振分量;
与所述TFP光学通信的反射镜阵列,所述反射镜阵列被配置为接收所述脉冲激光束的S偏振分量并将时间延迟引入到所述脉冲激光束的S偏振分量中,所述TFP被配置成将所述脉冲激光束的时间延迟S偏振分量与所述脉冲激光束的P偏振分量组合以形成经修改的脉冲激光束,所述经修改的脉冲激光束包括大于或等于2ns且小于或等于25ns的脉冲宽度,其中所述时间延迟小于或等于15ns;和
与所述TFP光学通信的至少一个透镜,所述至少一个透镜被配置为增加所述经修改的脉冲激光束与导管的纤维束的光学耦合。
12.根据权利要求11所述的激光束生成系统,其中,所述经修改的脉冲激光束包括具有与所述脉冲激光束的所述P偏振分量相关联的第一峰值和与所述脉冲激光束的所述S偏振分量相关联的第二峰值的波形。
13.根据权利要求11所述的激光束生成系统,还包括设置在所述固态激光源和所述TFP之间的光路中的半波片。
14.根据权利要求11所述的激光束生成系统,其中与相应于激光束相比,相应于所述经修改的激光束的待光学耦合到所述经修改的激光束的导管的纤维束的潜在损伤更低。
15.根据权利要求11所述的激光束生成系统,其中,所述反射镜阵列还包括至少一个四分之一波片。
16.根据权利要求15所述的激光束生成系统,其中,所述反射镜阵列包括多个反射镜和至少一个透镜。
17.根据权利要求11所述的激光束生成系统,其中,所述固态激光源还包括第三谐波Q开关Nd:YAG激光器。
18.根据权利要求11所述的激光束生成系统,其中,所述脉冲激光束的波长包括355nm。
19.根据权利要求11所述的激光束生成系统,其中所述经修改的脉冲激光束包括大于50毫焦耳(mJ)每毫米(mm)平方(MJ/mm2)的注量。
20.根据权利要求11所述的激光束生成系统,其中所述脉冲激光束具有大于或等于10的光束传播比(M2)。
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| CN201580037816.4A CN106794043B (zh) | 2014-05-18 | 2015-05-18 | 使用脉冲激光器进行组织消融的系统 |
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| CN113116516A (zh) * | 2021-04-01 | 2021-07-16 | 广州迪光医学科技有限公司 | 激光耦合装置 |
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| US20240407845A1 (en) | 2024-12-12 |
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