CN102264304B - 利用多功能声透镜的光声成像 - Google Patents
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Abstract
为了利用由多模光纤传输以产生光声脉冲的脉冲激光光激励来成像体内的各种软组织,然后以声检测器阵列使产生的光声脉冲成像,探针包括反射镜和声透镜或可在液体环境中操作的、可变焦距和放大率的特殊声透镜,该特殊声透镜像差校正到足以获得具有横向分辨率以及深度分辨率的高分辨率成像的程度。
Description
相关申请的参考
本申请要求2008年10月15日提交的美国临时专利申请No.61/105,590(确认号(Confirmation)No.6495)的权益。本申请中公开的发明与2009年7月17日提交的美国专利申请No.12/505,264(确认号No.1769)中公开的发明有关。这两个申请的公开内容在此全部以参引的方式并入本公开中。
技术领域
本发明涉及光声成像,更具体地,涉及利用多元件声透镜的这样的成像。
背景技术
前列腺癌是最常见的新诊断的男性恶性肿瘤,在引起癌症相关死亡方面仅次于肺癌。前列腺腺癌是西方世界中最常见的恶性肿瘤。2007年在美国确诊预计218,890名前列腺癌新病例,其中,估计27,050人死亡。随着男人年龄的增大,患前列腺癌的风险增大。已经在大约30%的六十岁的男人的尸检标本中偶然地发现前列腺癌。70%至80%的具有前列腺癌的病人在65岁以上。通常基于升高的前列腺特异抗原(PSA)测试或反常的直肠指检(DRE),或基于用于确诊的前列腺直肠超声(TRUS)活体检查,怀疑临床局部疾病。然而,TRUS不足够可靠以单独地用作用于活体检查的样板。有在TRUS上不可见的(等回声的)癌。此外,在PSA筛查人口中,TRUS的准确性由于遇到的假阳性结果而仅为52%。与良性前列腺组织相比,增加的肿瘤血管(血管新生)已显微显示在前列腺癌中。可能由于受限制的分辨率和较小的流速,已不显示彩色和能量多普勒超声的功效。具有许多变型的弹性成像是当前正在广泛研究的新的模型。显而易见的是,考虑到本诊断医疗方案的局限性,改进前列腺癌的可视化并提高活体检查量的新成像模型的开发是有利的。此外,通过使其更加经济,我们可将其置于主治医生的手中,在此,新成像模型将作为PSA、DRE以及TRUS的附属物而满足其主要目的。
对肿瘤可视化的需要在局部前列腺癌疾病的治疗中是同样重要的。现有的治疗策略,即,体外放疗、前列腺近距离治疗、冷冻手术以及观察等待,都将显著地受益于保证更好的肿瘤对比的新的模型的开发。因此,尽管最近有进展,但是前列腺癌继续是需要进步的领域。
除PSA水平和DRE之外,前列腺癌的适当成像是用于诊断前列腺癌和其分期的重要组成部分。用于诊断前列腺癌的前列腺成像的当前状态包括超声波、超声引导的前列腺活检、磁共振成像(MRI)以及核显像。这些模式是有用的,但是具有缺点和局限性。MRI是昂贵的并且是不可移动的。核闪烁是昂贵的,提供低分辨率的平面成像,并且存在通过肾的示踪剂排出的问题。这些模式并非一般用途均可使用。
超声波不足够可靠以单独地用作用于诊断前列腺癌的样板。其具有两个问题。首先,在许多情况下,前列腺癌看上去像是引起高缺失率的等回声病变(与周围组织的灰度值相似的灰度值)。其次,当其可见(高回声或低回声的)时,因为许多其它的非癌症状态,比如前列腺萎缩、前列腺炎症以及良性肿瘤,在超声检查时在外观上看起来也是相似的,因此,不能够确定地说其是否是癌或良性肿瘤。必须在怀疑的病变上执行活检用于确诊。活检是不舒服的,并且流血可能作为并发症。由于较差的病变检测,因此甚至当前前列腺活检技术漏掉大约30%的前列腺癌。已经探索与灰度超声结合的彩色血流和能量多普勒超声的使用,但是不成功。因此,迫切需要新成像方法,该新成像方法是可便携的,制造经济,并且将作为用于前列腺癌的主要筛查和诊断工具而具有广泛的应用。
发明内容
因此,本发明的目的是满足该需要。
为了实现以上和其它目的,本发明涉及声透镜/变焦声透镜或声透镜和声反射镜的组合的实施。本发明满足对提高医疗光声成像中的信噪比(S/N)的需要;但是,优选实施方式将针对前列腺成像。
为了利用由多模光纤传输以产生光声脉冲的脉冲激光光激励来成像体内的各种软组织,然后以声检测器阵列使产生的光声脉冲成像,本发明的至少一些实施方式实现一种可在液体环境中操作的、可变焦距和放大率的特殊声透镜,该特殊声透镜像差校正到足以获得具有横向分辨率以及深度分辨率的高分辨率成像的程度。
附图说明
以下参照附图阐明本发明的优选实施方式,在附图中:
图1A是示出利用声透镜和反射镜的、用于前列腺的光声成像的探针的示意图;
图1B是示出利用声透镜而没有反射镜的、用于前列腺的光声成像的探针的示意图;
图2示出单个双凹声聚焦透镜;
图3示出具有凸元件和凹元件的多元件声透镜;以及
图4示出具有连续变化的放大率的多元件声透镜。
具体实施方式
将参照附图详细地阐明本发明的优选实施方式,其中,相同的附图标记在全文中指的是相同的元件。
第一优选实施方式通过直肠探针提供前列腺成像。图1A示出以探针100A成像前列腺的实施例,探针100A的外壳102设计成放置到直肠中。探针100A包括几个元件。多模光纤104传输500至1500nm波长的波长范围内的、十纳秒持续时间范围内的一定能量的激光脉冲。光纤将激光能量传输到声光窗口106,激光能量通过声光窗口106传到直肠壁R,在此其照亮前列腺P的一部分。光纤具有一定的数值孔径并且以一定角度的光锥C照亮前列腺。通常,NA=0.25的光纤将照亮25度圆锥的范围。外壳102通常被密封并填充适当的流体。
激光波长选择为以便优选地吸收在病变L中,病变L可包含增强密度的血管。在这种情况下,光吸收主要通过血红蛋白/还原血红蛋白,并且优选800nm范围内的波长。关心的病变还可通过利用目标探针分子而具有增强的红外吸收,上述目标探针分子仅附着在关心的病变或区域上并提供增强的红外辐射吸收。病变中的增强的吸收产生增强生成的光声脉冲I,光声脉冲I向四面八方辐射出前列腺。该声辐射的一定部分穿透直肠壁R,穿过声光窗口106,在反射镜108上反射,并被引导到特别设计的声透镜110中。接着,声透镜110使光声信号直接成像到包含声检测器阵列112的图像平面上。声检测器阵列112包含N×M个元件(其中,在设计探针期间选择N和M以给出需要的成像分辨率),N×M个元件还提供时间分辨输出,以使时域信息可用于深度相关图像处理。
图1A中示出的声反射镜108可由某些金属制成,比如铜或钨,或者可由薄膜制成,比如安装成以便包括膜后面的较薄空隙的聚酯薄膜。原则上,该反射镜还可是曲面的,使其成为反折射成像系统的部分。
图1B示出了可选择的构造100B,其中,不使用声反射镜。在这种情况下,透镜114和检测器成像系统112的光轴垂直于探针的轴线,需要更加紧凑地实现透镜114。两种构造都包括窗口106,窗口106对于激光以及声信号需要是透射的。这在机械上也应当是坚固的。薄的蓝宝石板是这种窗口材料的实施例。
现在将描述透镜110或114的设计。
声透镜的功能在有些方面与光学透镜是相似的。在光学系统中,当透镜、光源以及图像分辨率元件的尺寸远大于光波长时,几何光学出于透镜和光学系统设计的目的而提供较好的近似。就声学而言,考虑范围内的对于突起的关心的波长在0.2至5mm范围内。可在射线模型中描述声能,与折射的斯涅尔定律相似的规则适用于在不相似材料之间的交界面处弯曲的射线。就声学而言,这种射线弯曲由对于各种材料可完全不同的材料特性的差异控制,比如声速、阻抗等等。
图2示出了单个元件200的简单例子。当透镜材料具有比周围介质的声速更高的声速时,双凹透镜提供聚焦作用以将来自声源S的声波聚焦到检测器202上。
就通过直肠通道的前列腺病变成像的本实施例而言,严重限制了成像条件。探针的外径必须不大于30mm,从前列腺壁到检测器阵列的总距离将在4-7cm范围内。本发明的优选实施方式将包括可变放大率“变焦透镜”功能,以便能够首先执行广角扫描,如果看到关心的更小的区域,可调节到更高的放大率,以便提供这些区域中的增强水平的细节。另外,就声透镜能够以最高分辨率成像所关心的小区域的声发射而言,该最高分辨率可能具有完美的成像,即,仅受辐射本身的衍射效应限制,希望获得声学衍射极限操作。这意味着这种声透镜将必须设计和构造成提供衍射极限声成像。
所有透镜系统均经受一定水平的像差,比如球面像差、色差、像散、彗形像差以及场曲,所有这些均需校正,以便提供衍射极限成像性能。此外,透镜元件应展示所关心波长范围内的高透射性,并应校正用于元件表面上的过度反射。在光学领域,高透明度不难实现,防反射涂层可应用于表面上。在声学领域,必须注意交界面的声学阻抗匹配,以避免过度损失,与光学领域相比,材料损耗更是问题。希望为高性能多功能声透镜的设计提供新的材料选择。
为了同时满足性能中的像差校正、光强透光率、成像质量以及柔性的要求,希望构造更复杂的声透镜。图3示出多元件透镜300的示意图。其包括各种折射装置302,一些折射装置具有正向(聚焦)能力,一些折射装置具有负向(散焦)能力。
执行这样一个复杂透镜系统的完整声学设计以便优化所有相关像差和优化性能是必要的。就前列腺成像而言,最大透镜孔径为大约25mm,从声源到检测器的总距离在4-7cm范围内;因此,透镜几乎在f/1构造处操作。能力的范围受可用的声学材料的限制。就多元件光透镜设计而言,使用显示一系列色散和折射特征的一系列玻璃以便优化透镜系统性能是标准技术。
建议使用水凝胶材料作为声透镜元件。该材料由不同的单体材料的集合组成,不同的单体材料以确定比例混合在一起并聚合以产生聚合物,当上述聚合物浸没在水中时吸收几个百分点到高达80%范围内的预定比例的水。相应地,这些材料的物理性质与水的比例相称。大范围的这种水凝胶是可用的,包括硅基材料和非硅基材料。硅树脂被广泛用作用于声透镜的材料,掺杂纳米晶体材料的硅树脂已示出展示了低声速和低声学衰减。对于声透镜设计的重要且相关的参数为声速、声阻抗、衰减以及品质因数。因为在一个极限(接近0%的水)中,这种材料将显示与熟悉的硅树脂材料相似的声学性质,而在相反的极限(80%的水)中,水凝胶将显示与水的声学性质更接近的声学性质,因此,水凝胶材料系统对多元件声透镜设计是有利的。因此,我们期望,在可用水凝胶的范围内几乎线性地缩放所有相关的声学材料参数,并期望这些能够用于制造在如图3所示的多元件声透镜中采用的一系列元件。测量各种配方的水凝胶的相关声学参数以便确定可用选择的范围是必要的。
如前所述,希望在医疗声学成像中获得与常规摄影中已知的“变焦透镜”相同的性能。这种透镜可在焦距或放大率的连续可变范围上提供成像。这种功能可通过结合可动元件的多元件声透镜的特定设计获得,如通常结合可动元件的光学变焦透镜。图4示出了这一概念。在图4的多元件声透镜400中,声透镜元件408的几个组402、404、406布置成在致动器410的控制下以规定的动作移动,以便连续地改变图像的放大率,而同时保持像差的优化控制。在这种透镜系统中,透镜的特定组,比如组402、组404和组406,布置成响应于外部控制而提供动作,使得总放大率连续地变化,同时保持优化的性能。这给予系统操作者看到宏观特征的能力以及“放大”以看到更多细节的能力。
这种复杂透镜的成功设计取决于适当的声透镜设计软件的可用性以及关于材料性质与相关控制参数相比的详细信息的可用性,就水凝胶而言,上述相比的详细信息是关键参数与水浓度相比的变化。我们注意到,在用于如图1A和1B所示的探针的设计中,探针100A或100B可能是完全密封的,因此,周围的溶液是附加自由度,该附加自由度可包括盐水或油或待定的其它容纳物。
虽然如上已阐明优选的实施方式,但是,已审核过本公开的本领域技术人员将理解,在本发明的范围内可实现其它的实施方式。例如,数值是说明性的而非限制性的,如同特定材料和特定透镜构造的列举。此外,本发明具有除前列腺之外的应用范围,可用于人类或非人类的动物体中的其它成像,或用于包括非生物成像的任何其它种类的光声成像。因此,本发明应当理解为仅由所附权利要求限制。
Claims (16)
1.一种用于使目标成像的方法,所述方法包括:
(a)用激光激励所述目标,以通过光声效应产生超声波;
(b)通过包括多元件声透镜的声学系统聚焦所述超声波;以及
(c)使聚焦的所述超声波成像为二维的,
其中,所述多元件声透镜包括可动元件或元件组,所述可动元件或元件组提供具有可变焦距和放大率的所述多元件声透镜。
2.如权利要求1所述的方法,其中,所述焦距和放大率变化以便提供深度分辨率。
3.如权利要求1所述的方法,其中,所述多元件声透镜构造为校正像差,以便提供近衍射极限声学成像。
4.如权利要求1所述的方法,其中,所述多元件声透镜包括由水凝胶材料制成的元件。
5.如权利要求1所述的方法,其中,所述目标是软组织。
6.如权利要求5所述的方法,其中,所述软组织在前列腺中。
7.如权利要求1所述的方法,其中,所述声学系统还包括声反射镜。
8.如权利要求7所述的方法,其中,所述声反射镜是曲面的。
9.一种用于使目标成像的探针,所述探针包括:
外壳;
在所述外壳中的声光窗口;
光纤,所述光纤用于将激光施加到所述目标上,以通过光声效应产生超声波;
用于聚焦所述超声波的声学系统,所述声学系统包括多元件声透镜;以及
检测器阵列,所述检测器阵列布置成使得所述声学系统将所述超声波聚焦到所述检测器陈列上,用于使聚焦的所述超声波成像为二维的,
其中,所述多元件声透镜包括可动元件或元件组,所述可动元件或元件组提供具有可变焦距和放大率的所述多元件声透镜。
10.如权利要求9所述的探针,其中,所述多元件声透镜构造为校正像差,以便提供近衍射极限声学成像。
11.如权利要求9所述的探针,其中,所述多元件声透镜包括由水凝胶材料制成的元件。
12.如权利要求9所述的探针,其中,所述声学系统还包括声反射镜。
13.如权利要求12所述的探针,其中,所述声反射镜是曲面的。
14.一种多元件声透镜,包括:
多个声透镜元件,所述多个声透镜元件包括:
具有正向能力的至少一个声透镜元件;以及
具有负向能力的至少一个声透镜元件;
所述多个透镜元件布置为同轴,
其中,所述多个声透镜元件中的至少一个构造为可动元件或元件组,所述可动元件或元件组提供具有可变焦距和放大率的所述多元件声透镜。
15.如权利要求14所述的多元件声透镜,其中,所述多元件声透镜构造为校正像差,以便提供近衍射极限声学成像。
16.如权利要求14所述的多元件声透镜,其中,所述多元件声透镜包括由水凝胶材料制成的元件。
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PCT/US2009/060774 WO2010045421A2 (en) | 2008-10-15 | 2009-10-15 | Photoacoustic imaging using a versatile acoustic lens |
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EP2337500A2 (en) | 2011-06-29 |
EP2337500A4 (en) | 2012-08-29 |
WO2010045421A3 (en) | 2010-07-29 |
WO2010045421A2 (en) | 2010-04-22 |
US20100298688A1 (en) | 2010-11-25 |
US20140303476A1 (en) | 2014-10-09 |
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