CN101598685B - 对样品的至少一部分成像的装置和方法 - Google Patents
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Abstract
一种用于执行样品的低相干性测距的设备,该样品具有高横向分辨率和大的焦深,该装置包括光学测距***,该***包括光源、用于将光从光源引导到样品的装置,将反射光从样品引导到检测器的装置,至少一个检测器,用于处理由检测器接收的光数据并产生图像的装置;并且光学元件具有小于或等于5μm的横向分辨率Δris,和至少约50μm的焦深Δz。
Description
本申请是申请号为03805597.X,国际申请号为PCT/US03/00699的发明专利申请的分案申请。
原案申请日:2003年1月10日。
原案发明名称:用于具有可提高分辨率和景深的轴线焦点的OCT成像的装置。
发明人:
GUILLERMO J.TEARNEY
BREET E.BOUMA
互相参考的相关申请
本申请要求2002年1月11日申请的共同未决的美国临时申请No.60/347582的优先权,在此结合本申请的全部内容作为参考。
发明领域
本发明涉及使用光学相干X线体层照相术用于成像组织样本,并结合光学元件来改善横向分辨率和焦深的装置。
目前,光学相干X线体层照相术(OCT)的使用只限于显现生物组织内部的体系形态结构。具有OCT的亚细胞特征的图像没有被很好的论证,因为相对差的横向分辨率需要保持焦深。执行高横向分辨率、大的景深截面OCT图像的能力将允许应用于上皮癌的较早诊断,以及其他需要亚细胞级分辨率的生物医学成像诊断。
到今天,还没有已知的光学相干X线体层照相术结构能在大的景深上执行高横向分辨率成像。人们将期待有一种简单的设备来执行高横向分辨率,大景深光学相干X线体层照相术。另外,由于允许通过单个光纤传送光,该设备也能容易的结合到导管或内诊镜中。这些特性将使得该设备能制造用于执行光学相干X线体层照相术的应用,该应用需要在生物***内的远地的亚细胞分辨率成像。
发明内容
本发明的一个方面,是提供一种用于对具有高横向分辨率和大焦深的样品执行低相干测距的装置,包括:
a.一个光学测距***,包括:
i)光源;
ii)用于将来自所述光源的光引导到所述样品的装置,
iii)至少一个检测器接收基于来自所述样品的反射光的另一光,
iv)用于处理由所述检测器接收的基于另一光的光数据并产生图像的装置;和
b.一个光学结构,其光学地连接到引导光的装置,并具有
i)小于或等于5μm的横向分辨率以引导光至所述样品,和
ii)至少50μm的焦深。
其中所述光源是宽谱光源。
其中所述光源是脉冲激光器。
其中所述光源是连续波激光器。
其中用于将光引导到所述样品的所述装置是干涉仪。
其中用于将光引导到所述样品的所述装置是光学波导透镜。
其中用于将光引导到所述样品的所述装置是光纤透镜。
其中所述检测器是单检测器。
其中所述检测器是检测器阵。
其中所述用于处理的装置能够分析干涉测量的数据。
其中所述用于处理的装置能够分析临时检测。
其中所述用于处理的装置能够分析光谱分析。
其中所述光学结构是锥透镜结构。
其中所述光学结构是能透射的。
其中所述光学结构是能反射的。
其中所述光学结构是能折射的。
其中所述光学结构是变迹透镜。
其中所述光学结构是全息图。
其中所述光学结构是衍射元件和透镜的组合体。
其中所述光学结构是变迹透镜、全息图和衍射元件的组合体。
本发明的另一方面,是提供一种用于对具有高横向分辨率和大焦深的样品执行低相干测距的装置,包括:
a.一个光学测距***,包括:
i)用于将来自一光源的光引导到所述样品的装置,和
ii)至少一个检测器,接收基于来自所述样品的反射光的另一光;
b.用于处理由所述检测器接收的基于另一光的光数据并产生图像的装置;和
c.产生在深度上分布的多个焦斑的锥透镜光学结构。
其中所述多个焦斑在直的垂直线中。
其中所述多个焦斑相对于一个垂直平面具有一个角度。
其中所述多个焦斑具有不同的纵向位置。
其中所述光学结构是能透射的。
其中所述光学结构是能反射的。
其中所述光学结构包括能折射的。
其中所述光学结构包括变迹透镜。
其中所述光学结构包括全息图。
其中所述光学结构包括衍射元件和透镜的组合体。
其中所述光学结构包括变迹透镜、全息图和衍射元件的组合体。
还包括用于产生多个物斑的装置,以便每个斑点从它的起点到光学结构具有唯一距离,以便每个斑点的图像具有唯一纵向位置。
其中所述用于产生多个物斑的装置包括多个光纤。
其中所述用于产生多个物斑的装置包括多孔障板。
其中所述用于产生多个物斑的装置包括衍射光栅。
其中所述用于产生多个物斑的装置包括微透镜阵列。
还包括扫描装置,该扫描装置引导光到样品上和引导来自样品的光。
还包括用于扫描所述光的装置。
其中所述扫描装置是扫描镜。
其中所述扫描装置是用于相对于所述光学元件移动光纤的装置。
其中所述扫描装置是用于移动所述光纤和光学元件的装置。
其中所述扫描装置是用于移动由所述光纤发出的光束的装置。
其中所述扫描装置是用于改变光束相对于光学元件的角度的装置。
还包括用于密封所述装置的外壳。
还包括用于扫描所述轴向焦点的装置。
本发明的另一方面,还提供一种获得高分辨率和高焦深的样品图像的方法,包括:
通过光引导装置将来自一光源的光通过光学结构引导到样品上;
接收来自样品通过所述光学结构的反射光;
将所述反射光引导到检测器;和
处理来自检测器的数据以产生所述图像,所述数据是基于由检测器接收的所述光,其中所述光学结构具有小于5μm的横向分辨率和 大于50μm的焦深。
附图概述
本发明如附图中所示,其中相同的参考符号指定所有附图中相同或相似的部分;
图1描述了使用折射旋转三棱镜聚焦。并行光束,从左入射,在具有窄的宽度和大的深度的轴线上聚焦。
图2描述了在样本支架中具有旋转三棱镜光学部件的OCT***视图。
图3描述了在轴向位置和照明环之间的关系的示意图。
图4A是图像形成的示意图。
图4B是在Y轴方向中整个光学***的变换示意图。
图4C是整个光学***的旋转示意图。
图4D是在X-Y平面内轴线焦点的角偏转示意图。
图5是用于在高景深下执行高横向分辨率测距的***示意图。
图6是偏移光纤阵列的示意图。
图7是光纤阵列、微透镜阵列和衍射光栅的示意图。
图8是变迹光瞳平面滤波器的实施例示意图。
图9是使用在成像透镜前面的变迹器的示意图。
优选实施例的详细描述
定义
“旋转三棱镜”应当指能够产生轴线焦点的任何光学元件(或其组合)。折射、衍射,和反射旋转三棱镜已经被演示,见J.H.McLeod,J.Opt.Soc.Am44,592(1954);J.H.McLeod,J.Opt.Soc.Am50,166(1960);和J.Opt.Soc.Am48,576(1958).
“焦深“应当指纵向距离,在该距离上光束直径增加系数ζ(典型的ζ=sqrt(2)或2)。对于高斯光束,该sqt(2)焦深是
对于d=5μm的典型高斯光点直径(1/e2直径),以及830nm的波长,该焦深大约是48μm。用于均匀光束的焦深(3dB半幅值全宽强度响应移动通过纵向平面的平面反射器)可定义为:
对于NA=0.2,其产生5μm的光点直径,在830nm时用于均匀光束的焦深大约是17μm。
“纵向”应当指实质上平行于光轴。
“纵向分辨率”应当指两个点可以分开的纵向上的最大距离Δz,并且仍然能被光学检测装置区分开。
“光点直径”应当指聚焦光点的横向直径。对于高斯光束,该光点直径被定义为光点的横向宽度,该焦点的亮度减去系数1/e2。对于平行高斯光束,该光点直径被定义为
其中D是透镜中的光束直径,f是透镜的焦点长度,以及λ是波长。对于平顶或均匀光束,该光点半径被定义为Airy磁盘的第一零点的横向长度,
其中
并且n是浸没媒质的折射指数。
“横向”应当指实质上垂直于光轴。
“横向分辨率”应当指两个点可以分开的横向上的最小距离Δr,并且仍然能被光学检测装置区别开。一种普遍使用的横向分辨率大约是Δr=d(用于高斯光束)或Δr=W(用于均匀光束)。
基本原理
产生具有窄的横向光束直径和大的长度(或焦深)的轴线焦点。结合OCT使用,该线状焦点的直径确定横向分辨率并且该长度确定景深。在标准OCT中,利用麦尔逊干涉仪来执行来自沿着轴向焦点的点上的光背射的检测。当光源具有有限的光谱宽度时,该结构可用于确定背射点的轴向位置。通过光源的相干长度来确定该轴向分辨率。
本领域技术人员将明白存在各种公知设备用于产生线焦点。对于本领域技术人员来说,对于此,旋转三棱镜(折射、透射,或衍射光学元件(“DOE”))是一种可接受模型,并该方法将用于本发明来论证使用具有轴线较点的OCT来实现在大景深上的高分辨率成像。应 当理解,该方法是示意性的并且不打算作为排除的模型。其他公知模型包括,但不限于,多焦点透镜,诸如Rayleigh-Wood透镜(OpticalProcesing and Computing,H.H Arsenault,T.Szoplik,andB.Macukow eds.,Academic Press Inc.,San Diego,CA,1989),使用色差以产生沿着纵向轴的依靠聚焦的波长阵列,等等。
分辨率
下面的部分讨论了如图1所示的使用折射的典型旋转三棱镜的物理原理。通过折射旋转三棱镜传输的光的强度分布(见R.Arioto,C.Saloma,T.Tanaka,and S.Kawata,APPL.Opt.31,6653(1992))由公式(1)给出:
其中E2(R)是入射在旋转三棱镜上的光的强度,并作为半径R,λ的函数,该半径是光的波长,并且β是通过旋转三棱镜的光的半角。与β有关的锥角α和焦深zD由公式(2a)和(2b)表示:
nSin(α)=Sin(α+β),(2a)
zD=R(Cot(β)-Tan(α)),(2b)
其中n是旋转三棱镜的折射系数。上述等式可用以确定轴线焦点的直径。对于平面波照明,该焦点直径由公式(3)给出:
在折射或衍射旋转三棱镜的情况下,等式(1)被修改,但在所 有情况中,轴向焦点的直径确定成像***的横向分辨率。本发明的主题是通过变化标准聚焦几何学来改善当前OCT***典型的较差横向分辨率,在该几何学中焦点量(功率分布)被限制在横向和轴向尺寸中,该焦量中的一个只限制在横向上。
通过组合具有OCT的旋转三棱镜的高的横向局部(和弱的轴向局部),可以实现在大的视野之上提供高的三维局部的成像***。通过光源的相干长度可独自确定关于该图像技术的轴向分辨率(OE.S.Swanson,D.Huang,M.R.Hee,J.G.Fujimoto,C.P.Lin,和C.A.Puliafito,Opt.Lett.17,151(1992))并通过公式(4)给出:
其中Δλ是光源的光谱宽度(半幅值全宽(“FWHM”))。
在优选实施例中,光学元件具有在大约0.5μm到10μm,尤其是小于或等于5μm范围内被定义为Δr=d0的横向分辨率。该光学元件最好在至少大约50μm具有Δz=zD。
成像
图4A描述了本发明一个实施例的完整OCT/旋转三棱镜***。除了旋转三棱镜探针,所有部件对于OCT是标准部件。使用OCT来确定背射,提供了空间光栅扫描,该背射作为沿着轴线焦点的距离的函数。这典型的通过扫描干涉仪基准臂的长度来实现。旋转三棱镜具有这样的属性,即每个焦点的轴向位置对应三棱镜入射孔上唯一的环(见图3)。这种关系将允许通过扫描三棱镜孔上的照明环来代替扫描基准臂长度。
不管如何扫描轴向尺寸,为获得图像,必须执行对其他轴的扫描。通常以缓慢速率执行第二扫描尺寸。实现副轴慢扫描的方法包括在y方向上移动光学样品支架,包括光纤、准直透镜和旋转三棱镜(见图4B),绕着光纤轴旋转整个探针(见图4C),或在x-y平面上有角度的偏转线焦点(见图4D)。见,(G,J.Tearney,S.A.Boppart,B.E.Bouma,M.E.Brezinski,Opt.Lett.22,1618(1997))。通过使用压电转换器或机械或气动传动器,沿着y或z轴的线性移动以及旋转很容易在小型探针中实现。
图5是用于执行具有高景深的高横向分辨率测距的替代装置的示意图。该***包括光源、光束重定向元件、检测器、和光学元件。该光学元件提供线焦点和样品上的焦斑阵列。
图6显示了偏移光纤阵列,该光纤阵列通过物镜被镜子定向,并用于取代样品上的纵向和横向尺寸中的焦(成像)斑。扫描该斑点(通过水平线和箭头指示该扫描方向)以产生多维图像。
图7示意了用于取代样品上的纵向和横向尺寸中的焦(成像)斑的光纤阵列、微透镜阵列和衍射光栅(镜子阵列)的示意图。来自光源(未示出)的光通过阵列中的光纤,并通过微透镜阵列到衍射光栅。通过光栅将光引导通过物镜并聚焦在样品上。扫描该斑点(由水平线和箭头指示该扫描方向)以产生多维图像。
一种用于在大的焦深上提供高横向分辨率的替换装置是在成像透镜的背面使用滤波器。该技术,通常称为变迹法,允许在旋转三棱镜中产生线焦点或产生沿着纵向尺寸定位的许多焦斑。使用环形变迹 法形成射束焦点,先前已经描述在文献中(M,.MARTINEZ-Corral,P.Andres,J.Ojeda-Castaneda,G.Saavedra,Opt.Comm.119,491(1955))。然而,使用变迹法以产生在大的焦距上的高横向分辨率,其中以前没有描述由OCT进一步分析纵向数据。
图8显示了变迹光瞳平面滤波器的实施例。
图9显示了在成像透镜前面使用变迹器,其输出被聚焦在轴线上的示意图。
成像方法
本发明也提供一种获得样品的高分辨率和高焦深的方法,包括:
a.提供光源;
b.通过光引导装置将来自所述光源的光通过光学元件引导到样品上,该光学元件具有小于约5μm的横向分辨率和大于50μm的焦深;
c.接收来自样品返回通过所述光学元件的反射光;
d.引导所述反射光到检测器;和
e.处理来自检测器的数据产生图像
本发明的优点是OCT成像装置能沿着样品的横向和纵向尺寸进行亚细胞分辨率成像,该样品在小型,基于光纤的组件中。其他优点包括潜在的小规模和低成本的轴线焦点光学元件,诸如组合旋转三棱镜的变迹透镜。
尽管上面只详细描述了本发明很少的典型实施例,但本领域技术人员明白在本质上不脱离本发明的新技术和优点的情况下,对典型实 施例的任何修改是可能的。因此,包含在本发明范围内的所有修改都被下面的权利要求所定义。而且应当注意,在此涉及的任何专利、申请和出版物,其全部内容被结合参考。
Claims (46)
1.一种用于对样品执行低相干测距的具有高横向分辨率和大焦深的装置,包括:
a.一个光学测距***,包括:
i)光源;
ii)用于将来自所述光源的光引导到所述样品和能产生轴线焦点的装置,
iii)至少一个检测器接收基于来自所述样品的反射光的另一光,
iv)用于处理由所述检测器接收的基于所述另一光的光数据并产生图像的装置;和
b.一个锥透镜光学结构,其光学地连接到引导光的装置,配置成沿着轴线焦点产生合成电磁强度分布,并具有
i)小于或等于5μm的横向分辨率以引导光至所述样品,和
ii)至少50μm的焦深。
2.如权利要求1的装置,其中所述光源是宽谱光源。
3.如权利要求1的装置,其中所述光源是脉冲激光器。
4.如权利要求1的装置,其中所述光源是连续波激光器。
5.如权利要求1的装置,其中用于将光引导到所述样品的所述装置是干涉仪。
6.如权利要求1的装置,其中用于将光引导到所述样品的所述装置是光学波导透镜。
7.如权利要求1的装置,其中用于将光引导到所述样品的所述装置是光纤透镜。
8.如权利要求1的装置,其中所述检测器是单检测器。
9.如权利要求1的装置,其中所述检测器是检测器阵。
10.如权利要求1的装置,其中所述用于处理的装置能够分析干涉测量的数据。
11.如权利要求1的装置,其中所述用于处理的装置能够分析临时检测。
12.如权利要求1的装置,其中所述用于处理的装置能够分析光谱分析。
13.如权利要求1的装置,其中所述光学结构是锥透镜结构。
14.如权利要求13的装置,其中所述光学结构是能透射的。
15.如权利要求13的装置,其中所述光学结构是能反射的。
16.如权利要求13的装置,其中所述光学结构是能折射的。
17.如权利要求13的装置,其中所述光学结构是变迹透镜。
18.如权利要求13的装置,其中所述光学结构是全息图。
19.如权利要求13的装置,其中所述光学结构是衍射元件和透镜的组合体。
20.如权利要求13的装置,其中所述光学结构是变迹透镜、全息图和衍射元件的组合体。
21.一种用于对样品执行低相干测距的具有高横向分辨率和大焦深的装置,包括:
a.一个光学测距***,包括:
i)用于将来自一光源的光引导到所述样品和能产生轴线焦点的装置,和
ii)至少一个检测器,接收基于来自所述样品的反射光的另一光;
b.用于处理由所述检测器接收的基于另一光的光数据并产生图像的装置;和
c.沿着轴线焦点产生在深度上分布的多个焦斑的锥透镜光学结构。
22.如权利要求21的装置,其中所述多个焦斑在直的垂直线中。
23.如权利要求21的装置,其中所述多个焦斑相对于一个垂直平面具有一个角度。
24.如权利要求21的装置,其中所述多个焦斑具有不同的纵向位置。
25.如权利要求21的装置,其中所述光学结构是能透射的。
26.如权利要求21的装置,其中所述光学结构是能反射的。
27.如权利要求21的装置,其中所述光学结构包括能折射的。
28.如权利要求21的装置,其中所述光学结构包括变迹透镜。
29.如权利要求21的装置,其中所述光学结构包括全息图。
30.如权利要求21的装置,其中所述光学结构包括衍射元件和透镜的组合体。
31.如权利要求21的装置,其中所述光学结构包括变迹透镜、全息图和衍射元件的组合体。
32.如权利要求21的装置,还包括用于产生多个物斑的装置,以便每个斑点从它的起点到光学结构具有唯一距离,以便每个斑点的图像具有唯一纵向位置。
33.如权利要求32的装置,其中所述用于产生多个物斑的装置包括多个光纤。
34.如权利要求32的装置,其中所述用于产生多个物斑的装置包括多孔障板。
35.如权利要求32的装置,其中所述用于产生多个物斑的装置包括衍射光栅。
36.如权利要求32的装置,其中所述用于产生多个物斑的装置包括微透镜阵列。
37.如权利要求21的装置,还包括扫描装置,该扫描装置引导光到样品上和引导来自样品的光。
38.如权利要求21的装置,还包括用于扫描所述光的装置。
39.如权利要求37的装置,其中所述扫描装置是扫描镜。
40.如权利要求37的装置,其中所述扫描装置是用于相对于所述光学结构移动光纤的装置。
41.如权利要求37的装置,其中所述扫描装置是用于移动光纤和所述光学结构的装置。
42.如权利要求37的装置,其中所述扫描装置是用于移动由光纤发出的光的装置。
43.如权利要求37的装置,其中所述扫描装置是用于改变光相对于所述光学结构的角度的装置。
44.如权利要求21的装置,还包括用于密封所述装置的外壳。
45.如权利要求21的装置,还包括用于扫描所述轴线焦点的装置。
46.一种获得高分辨率和高焦深的样品图像的方法,包括:
通过光引导装置将来自一光源的光通过光学结构引导到样品上;
接收来自样品通过所述光学结构的反射光;
将所述反射光引导到检测器;和
处理来自检测器的数据以产生所述图像,所述数据是基于由检测器接收的所述光,其中与上述光学结构光学连接的锥透镜光学结构具有小于5μm的横向分辨率和大于50μm的焦深,并配置成沿着轴线焦点产生合成电磁强度分布。
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EP1468245B1 (en) | 2011-03-30 |
CA2473465C (en) | 2011-04-05 |
EP2290319B1 (en) | 2015-08-26 |
DE60336534D1 (de) | 2011-05-12 |
AU2009202383B2 (en) | 2012-09-13 |
JP2005530128A (ja) | 2005-10-06 |
WO2003060423A8 (en) | 2005-05-19 |
CN101598685A (zh) | 2009-12-09 |
EP2290318B1 (en) | 2015-08-26 |
ATE503982T1 (de) | 2011-04-15 |
CN1639539A (zh) | 2005-07-13 |
AU2003207507A1 (en) | 2003-07-30 |
AU2009202383A1 (en) | 2009-07-09 |
AU2003207507A2 (en) | 2003-07-30 |
EP2327954A1 (en) | 2011-06-01 |
WO2003060423A2 (en) | 2003-07-24 |
EP2290318A1 (en) | 2011-03-02 |
CA2473465A1 (en) | 2003-07-24 |
US20050018200A1 (en) | 2005-01-27 |
US7310150B2 (en) | 2007-12-18 |
WO2003060423A3 (en) | 2003-12-11 |
EP2290319A1 (en) | 2011-03-02 |
EP1468245A2 (en) | 2004-10-20 |
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