CN1070714C - 针对血管目标的近红外选择性光热解 - Google Patents
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Abstract
本发明涉及利用近红外选择性光热解治疗扩张性血管,例如红色胎记的血管、腿部血管、或引起牛皮癣的血管等。由于近红外光的穿透力较强,所以本技术更为适合用于对较深层血管的处理。因此,在表皮/上皮以下的血管可以被处理。近红外的定义是波长为700~1200nm。对大多数人来讲,优选的光为接近760nm处、或在980~990nm之间。
Description
本发明的背景技术
血管创伤,包括放大或膨胀的血管、色素沉积的创伤、以及文身等都已经被用激光成功地治疗多年了。在称作选择性光热解的方法中,目标组织、创伤组织、文身的色素颗粒、以及周围的组织都一起被激光辐射。然而,所选择的激光的波长是要使激光的能量被目标组织所吸收。这种由倾向性的吸收所造成局部的加热,会导致对组织的破坏。
在血管创伤,例如,红色胎记中,在膨胀的血管中,红血细胞的血红蛋白就是激光的吸收剂,也就是色素团。这些细胞吸收激光的能量,并以热的形式将该能量向周围血管传递。如果具有足够的能量并且传递发生的很快,则周围血管的温度就会升高到使其蛋白质变性的温度。血管变性的温度的热通量,即每平方厘米的焦耳量,是在所吸收的能量的大部分被扩散到血管以外之前,使血管内的目标物的温度升高到约70℃的焦耳量。因此,必须对该热通量进行限制,防止周围组织的变性。
然而,仅仅对热通量的简单选择是不够的。同时还要对激光的强度和脉冲进行控制,使得在处理的期间内,向周围组织的扩散达到最小,防止局部蒸发。最好防止沸腾和蒸发的发生,因为它们会导致创伤周围组织的机械性而非化学性的损伤,从而提高创伤周围组织的受伤和出血。这些限制就要求在较低强度时,脉冲的周期应该长一些,以防止蒸发。但是,如果色素团是创伤血管中的血细胞血红蛋白时,情况就更为复杂了,因为血管比血细胞大一个数量级。辐射必须以较低的强度进行才可以不使较小的细胞被蒸发,并能够以足够长的时间对血管加热,使其热扩散达到其变性点,而又对周围组织造成的损伤为最小。
激发染料激光的脉冲比较长的闪灯已经被用来作为光源。这些激光具有选择性光热解所需要的高光谱亮度,而且可以被变为血红蛋白的α吸收带。色素团以及血管中的红血细胞对在577~585nm之间的有色光的吸收,比周围组织中的黑素的吸收更好。
本发明概述
以常规闪灯激发的染料激光进行的选择性光热解得到的不是最理想的结果。测量结构的保持热的能力的是热缓解常数。对血管而言,该常数是毫秒级的,血红细胞的热缓解常数是微秒级的。比血红细胞的热缓解常数更长的脉冲期间,会使热量被扩散到周围血管;与血管的热缓解常数相等或更小的脉冲期间,可以使热被局限在血管中,防止对周围组织的损害。事实上,根据理论计算,最佳光的脉冲应该等于血管的热缓解常数。比较大的血管,即大于30微米的血管,应该用脉冲期为0.5毫秒或更长的光来处理。然而,商业上可获得的染料激光的脉冲期为约0.5毫秒或更短。由于血管的热缓解常数随着其直径的增加而加大,这些染料激光对较大血管的实用性就迅速消失。其结果是,在选择性光热解的处理中,很多情况下都要使用比最佳热通量更高的热通量来弥补脉冲期的不足。这样,就造成临时的过量色素沉积,而不是出血。
另外,常规光的频率进一步限制了光热解的效率。化学物质的最佳吸收特性的描述参数是克分子消光系数,该系数对黑素和血红蛋白来讲,在577~585nm之间都是0.2。这就限制了光的有效穿透深度,例如,限制了可以被处理的血管的深度在白种人的皮肤下不能超过0.5mm。而这个深度是在表皮/上皮层以上的。
总之,常规的染料激光处理技术对处理位于表皮/上皮层交界以上的且直径在30微米以下的血管的创伤是十分有效的。但是,它的缺点是无法合适地对较大血管进行加热,无法到达较深层的血管,由于对光的吸收,使其穿透性被限制。这些都是十分重大的缺陷,因为深层较大血管的严重损伤是随时可见的严重情况的皮肤特征。
电磁波的近红外部分,即在本文中所指定的大约700~1400nm部分,提供了在黑素和血红蛋白吸收之间的有利吸收比区间。但是,使用这些波长对血管进行的治疗却被极大地忽视了,没有把其作为577~585nm的的替代方法,其原因是在此区间内的血红蛋白吸收特性不佳。这种结论没有认识到获得选择性的主要因素是血红蛋白及黑素的吸收比率,而不是净吸收量。此外,在处理深度血管时,较差的吸收特性对于激光整体的穿透性是有利的。
根据以上所述,本发明的一个方面是涉及利用近红外辐射对血管目标进行选择性光热解处理。
在本发明的具体实施例中,这一技术被用于处理非膨胀性和膨胀性血管,例如,红色胎记的血管。但是,本发明还包括处理腿部血管及牛皮癣的血管。根据近红外光的较强穿透力,本技术更为适合用于较深层的血管。因此,可以对表皮/上皮交接层以下的血管进行处理。
在具体实施例中,可以使用不同的一些波长范围。一般而言,近红外光的范围是700~1400nm,其上限是被水的吸收所限定的。更具体而言,其波长范围可以被限制在750~780nm。最佳颜色在760nm。此外,980~990nm的范围也是有效的。
激光优选翠绿宝石、钛蓝宝石、镀铬氟化物、或半导体二极管产生的激光,通过向患者传送激光光导纤维系统送达到患者。
根据本发明的另一方面,本发明涉及治疗血管目标的近红外选择性光热解设备。该设备包括激光系统,产生脉冲期大于0.2毫秒的近红外激光,以及将激光传送给患者的传递系统。
在具体实施例中,激光系统包括翠绿宝石、钛蓝宝石、镀铬氟化物、或半导体二极管类型的激光。如果所选择的激光装置无法单个产生合适的激光,则可以结合数个二极管激光的脉冲。当单个的激光装置的脉冲具有局限性时,则多倍的激光产生有效的长脉冲激光。因此,当单个二极管激光装置仅产生0.5毫秒的脉冲时,利用多倍效应,可以获得1~10毫秒的脉冲。将同时产生的光束结合起来可以获得提高了的有效能量。
根据本发明的另一方面,本发明涉及对血管目标的治疗方法。该方法包括用近红外激光照射该目标。该激光的脉冲被控制在与该目标的热缓解常数基本相等的范围内。该近红外激光的波长的范围为700~1400nm。
本发明的上述和其它特征,包括各种机构的细节、部件的结合以及其它优点等,将根据附图和权利要求书给予更为详细的描述。应该理解的是,本发明的方法和设备都是通过举例说明的,而不是对本发明的限制。本发明的原则和特点可以在不离开本发明的范围之内有很多种不同的变型。
附图的简要说明
在附图中,各个编号代表同一部件。各个附图不一定完全符合比例,重点是为了说明本发明的原则。
图1是使用单一激光的近红外选择性光热解装置的图示说明。
图2是氧合血红蛋白HbO2(实线)、脱氧血红蛋白Hb(虚线)、胆红素(断开线)、以及DOPA-黑素(明显的指数降低实线)的克分子消光系数对波长的纳米图。
图3是使用多个激光二极管或二极管阵列的本发明的近红外选择性光热解装置的图示说明。
图4是各个闪灯激发水平的TiS激光输出对时间的曲线,表示缓解震荡不是长脉冲期的因素。
本发明的详细描述
参见附图,图1是根据本发明的原则所构建的近红外选择性光热解装置100。该装置100的基本形式与现有技术相似,不同之处是该装置包括产生电磁波的近红外区光波的发射源。更为完全的是,激光系统110产生近红外光束B,即700~1400nm的范围的激光。该光束B被整合到传递系统120,例如,单一光导纤维,传递到患者的皮肤50。由于该光束B是在近红外区的光束,所以它可以基本穿过上皮/表皮交界55来治疗其下面的血管目标60。该目标可以是红色胎记、血管瘤、毛细血管扩张、自发性vulvodynia,腿部静脉,以及对牛皮癣的供血等中的任何一种。另外,还可以是年龄或日晒造成的血管扭曲、或伤疤组织的血管。
光束B的脉冲期与目标血管的热缓解常数相对应。一般,该脉冲期应该大于0.2毫秒。对于直径为30微米或更大的血管,例如在成年患者的红色胎记中,脉冲期应该最好大于0.2毫秒,通常为0.5毫秒,如果血管的直径大于100微米,则应该选择1毫秒~10毫秒之间的脉冲期。
参见图2,在近红外区内,有几个特定范围对于治疗血管损伤非常有效(由于黑素的分子量的确定不准确,所表示的光波是对1.5mg%的DOPA-黑素的在0~1.5标尺上的光密度值)。图2是克分子消光系数对波长的纳米图。
对于女性白人的皮肤而言,可以接受程度的选择性,是血红蛋白与黑素的克分子消光系数比率至少为0.05。脱氧血红蛋白(Hb)与氧合血红蛋白(HbO2)的吸收对黑素的吸收(DOPA-黑素)的比率在700~1200nm之间以0.05或更大为好。如果脱氧血红蛋白Hb是特定的目标,则激光光束B的波长可以在700~1000nm之间。脱氧血红蛋白的吸收峰在750~780nm之间,最佳的比率在大约760nm。
在近红外区的总吸收比在常规区577~585nm时为少。因此,治疗扩张性血管所需要的光束B的通量比常规较短波长的通量要大。因此,通常光束B的通量为2~20 J/cm2。
激光系统110可以包括数个可以产生约760nm的近红外激光的装置。例如,翠绿宝石在720~790nm内是可调节的。可调节的钛蓝宝石(TiS)产生720~950nm的激光。由于这两种激光的产生技术比较成熟,所以他们是最为优选的候选激光。另外,除了半导体二极管激光之外,其他的可调节镀铬氟化物激光,例如LiCaAlF6、LiCaGaF6、LiSrAlF6、和LiSrGaF6等都是潜在的候选激光。
翠绿宝石激光特别适合选择性光热解,因为其可以产生3~10毫秒脉冲的激光。该脉冲期特别适宜治疗100微米或更大直径的血管,而这些血管是现有技术无法治疗的。然而,这些激光表现出了在称作正常操作方式中的非常难以处理的行为。其原因是缓解震荡。
半导体二极管激光不把能量储存在亚稳定上激光水平,所以不表现非常难以处理的行为。然而,单个激光源的输出太低,无法达到治疗大部分血管所需要的通量。实际使用二极管激光时,需要将多个激光源的光束结合起来才能产生所需要的大于100瓦的输出。图3给出了这样的一个实施方案,其中,从激光系统205产生的3个二极管激光210、212、214的光束被合并为一束,并被导入传递系统220。二极管激光210、212、214,或者TiS激光由同步器230来协调控制它们各自的产生时间。此外,如果需要更多的能量,则可以将二极管210、212、214分别用另外的二极管阵列来替换。无论是哪种情况,传递系统220优选液体核心柔性光导,而不是单一玻璃光导纤维。液体核心光导具有较大的开孔,一般为5mm,并且还保持着柔韧性。因此,从几个二极管激光或几个阵列来的光束被导向并聚焦于液体光导,极大地简化了从激光二极管到含有目标血管的皮肤之间的传递光学装置。
将许多二极管激光结合起来的另一种装置揭示于题为“FaultTolerant Optical System Using Diode Laser Array”的美国专利申请第08/163,160号,本发明的发明人是该专利申请的共同发明人,该申请在此引述而合并于本申请。该装置使用校正微光学配合以使二维二极管阵列带有掩蔽的产生的二维阵列准直管微透镜和质量产生的转变装置。
TiS激光是另一种可用的激光。在测试过程中,这些激光产生1~5毫秒的脉冲,并且没有表现出闪灯激发固态激光系统所特有的难以处理的行为。大多数固态激光的上态寿命为约100μ秒。而对TiS激光来讲,该寿命仅为3μ秒。其结果是,如果TiS激光介质被过分激励,就如染料激光被激励的情况一样,则上态成为饱和,在经过大约2~3μ秒后就无法储存任何更多的能量。这就会中和大多数张弛振荡脉冲。例如,图4所示,闪灯激发的4种不同能级为2000、1800、1600、和1400 V.D.C.。所得到的脉冲宽度为2~3毫秒,没有显示出很强的张弛振荡脉冲特征。然而,由于热透镜效应,该脉冲会被限制为约3毫秒的脉冲期。
如果单个的TiS激光不能够产生所需要的脉冲期,则图3中的激光系统110就可以按照1994年1O月26日申请的题为“UltraLong Pulse Dye Laser for Treatment of Ectatic Vessels and MethodTherefor”的美国专利申请第08/329,195号所述将数个激光的输出总和起来,本发明人是该申请的共同发明人,该专利申请通过在此引述而合并于本文。具体而言,图3中的同步器230按次序启动二极管激光或TiS激光210-214,从而产生有效的脉冲期。另外,为了获得有效的输出,同步器230可以同时启动激光210-214的全体或其中的一部分。
脱氧血红蛋白HbO2可以为具体的目标,它的有效吸收范围在800~1200nm。最佳的吸收在980~990nm。在此,氧合血红蛋白HbO2的克分子消光系数达到峰值,并且氧合血红蛋白对黑素的系数比率实际上超过0.1。这是二极管激光治疗的理想区域。50瓦的光导纤维偶连的连续波二极管激光已经被充分发展出来并商业化了。这些当前的二极管激光阵列可以产生100瓦的半连续形式的激光波。这些形式的激光的脉冲期一般为400μ秒。因此,在治疗较大的血管时,使用上述的多倍二极管激光阵列就是必要的。
本发明已经被用最佳实施方案的形式进行了描述,但是,本领域的技术人员应该理解的是,在不离开本发明的实质精神和权利要求书的范围的条件下,本发明还可以有多种的变型。
Claims (17)
1.一种用于治疗血管目标的近红外选择性光热解装置,该装置包括:
产生脉冲期大于0.2毫秒的近红外激光脉冲的激光系统;以及
将该激光脉冲传递到患者的血管目标的传递系统。
2.根据权利要求1所述的装置,其中所述的血管目标包括膨胀的血管。
3.根据权利要求1或2所述的装置,其中所述的激光脉冲的波长为约700~1400nm。
4.根据权利要求1或2所述的装置,其中所述的激光脉冲的波长为约700~1000nm。
5.根据权利要求1或2所述的装置,其中所述的激光脉冲的波长为约750~780nm。
6.根据权利要求1或2所述的装置,其中所述的激光脉冲的波长为约760nm。
7.根据权利要求1或2所述的装置,其中所述的激光脉冲的波长为约800~1200nm。
8.根据权利要求1或2所述的装置,其中所述的激光脉冲的波长为约980~990nm。
9.根据权利要求1或2所述的装置,其中所述的激光系统包括翠绿宝石激光。
10.根据权利要求1或2所述的装置,其中所述的激光系统包括钛蓝宝石激光。
11.根据权利要求1或2所述的装置,其中所述的激光系统包括镀铬氟化物激光。
12.根据权利要求1或2所述的装置,其中所述的激光系统包括半导体二极管激光。
13.根据权利要求1~2中任何一项所述的装置,其中所述的激光系统包括多个激光。
14.根据权利要求1~13中任何一项所述的装置,其中所述的传递系统包括将激光合并与传递的光导纤维。
15.根据权利要求1~14中任何一项所述的装置,其中所述的激光系统将激光多倍化。
16.根据权利要求1~15中任何一项所述的装置,其中所述的多倍化的激光的脉冲期为1~10微妙。
17.根据权利要求1~16中任何一项所述的装置,其中所述的激光系统同时启动多个激光以提高有效输出水平。
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