CN101410691A - 执行角分辨傅立叶域光学相干断层成像的方法和系统 - Google Patents

执行角分辨傅立叶域光学相干断层成像的方法和系统 Download PDF

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CN101410691A
CN101410691A CNA2007800105177A CN200780010517A CN101410691A CN 101410691 A CN101410691 A CN 101410691A CN A2007800105177 A CNA2007800105177 A CN A2007800105177A CN 200780010517 A CN200780010517 A CN 200780010517A CN 101410691 A CN101410691 A CN 101410691A
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阿德里安·E·德雅尔丹斯
本杰明·J·瓦科奇
吉列尔莫·J·蒂尼
布雷特·E·鲍马
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47Scattering, i.e. diffuse reflection
    • G01N21/4795Scattering, i.e. diffuse reflection spatially resolved investigating of object in scattering medium
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0062Arrangements for scanning
    • A61B5/0066Optical coherence imaging
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01BMEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00Measuring instruments characterised by the use of optical techniques
    • G01B9/02Interferometers
    • G01B9/02041Interferometers characterised by particular imaging or detection techniques
    • G01B9/02043Imaging of the Fourier or pupil or back focal plane, i.e. angle resolved imaging
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01BMEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00Measuring instruments characterised by the use of optical techniques
    • G01B9/02Interferometers
    • G01B9/02083Interferometers characterised by particular signal processing and presentation
    • G01B9/02087Combining two or more images of the same region
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01BMEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00Measuring instruments characterised by the use of optical techniques
    • G01B9/02Interferometers
    • G01B9/0209Low-coherence interferometers
    • G01B9/02091Tomographic interferometers, e.g. based on optical coherence
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0073Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by tomography, i.e. reconstruction of 3D images from 2D projections
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01BMEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B2290/00Aspects of interferometers not specifically covered by any group under G01B9/02
    • G01B2290/70Using polarization in the interferometer
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47Scattering, i.e. diffuse reflection
    • G01N2021/4704Angular selective
    • G01N2021/4711Multiangle measurement
    • G01N2021/4714Continuous plural angles

Abstract

提供了用于从透明和混浊样本中测量空间分辨角后向散射分布的角分辨傅立叶域光学相干断层成像。示出了散斑减少和产生图像对比度。使用波长扫频激光源和行扫描照相机。对要测量的样本上的输入光束进行准直,在空间上扩展基准光束。来自样本的后向散射光与空间扩展的基准光束发生干涉。

Description

执行角分辨傅立叶域光学相干断层成像的方法和系统
相关申请的交叉引用
本申请基于并要求2006年2月24日提交的美国专利申请序列号第60/776,544号的优先权,其全部内容通过引用包含于此。
关于联邦资助研究的声明
本发明是按照美国国立卫生研究院(National Institute of Health)资助的第R01CA103769号合同在美国政府的支持下做出的。因此,美国政府在本发明中具有特定的权利。
技术领域
本发明涉及用于执行角分辨傅立叶域光学相干断层成像的方法和系统,尤其涉及使用傅立叶域光学相干断层成像技术从透明和混浊样本中测量空间分辨(spatially-resolved)的角后向散射分布。
背景技术
光学相干断层成像(“OCT”,optical coherence tomography)使得能够以从几微米到几十微米级别的分辨率获得生物样本的截面图像,从而允许对组织的显微结构的细节进行成像。已经证明傅立叶域OCT(“FD-OCT”,Fourier-domain OCT)可以提供相对于时域OCT显著改善的灵敏度,这使得能够进行高速成像。例如,已经以两种配置实现了FD-OCT,例如在2004年9月8日提交的国际专利申请PCT/US2004/029148、2005年11月2日提交的美国专利申请第11/266,779号和2004年7月9日提交的美国专利申请第10/501,276号中的至少一个中描述的谱域OCT(“SD-OCT”,spectral-domain OCT)和光学频域成像(“OFDI”,optical frequency domain imaging)。作为在许多临床环境中,包括心血管、肠胃和视网膜成像,用于识别形态变化的工具,FD-OCT已经显示具有巨大的潜力。
传统的OCT系统和方法的一个限制是仅收集了来自以180度为中心的一个角度范围的后向散射光。这在阵列检测可以用来在不进行光束扫描的情况下产生共面(en-face)二维图像的光学相干显微测量(“OCM”,optical coherence microscopy)系统的情况下也是一样的。图1示出了一个这种OCM系统的示例,如在E.Beaurepaire等,“Full-field opticalcoherence microscopy,”Optics Letters 23(4):244-246,1998中所描述的。可以使用角组合(angular compounding)技术来实现从不同角后向散射的光的获取,这可以减少散斑(speckle)。散斑通常在图像的散射区域内作为明暗图案而出现,使得更难以在组织反射中辨别微小的反射差。
用于在能够进行角组合的OCT的环境下在不同入射角处获取后向散射光的方法和系统使用路径长度编码。图2示出了这种系统的示例,如在N.Iftimia等,“Speckle reduction in optical coherence tomography by‘path length encoded’angular compounding,”Journal Of BiomedicalOptics 8(2):260-263,2003中所描述的。例如,可以在成像光束路径中放置光学玻璃,将入射场划分为两个或更多个小光束(beamlet)。该光学玻璃使入射光束的一部分(小光束2)比小光束1经历更大的路径长度延迟。另外,小光束2在与小光束1不同的角度处照亮样本。其结果是,在OCT显示器上同时出现样本的多个OCT图像(每一个在不同的角度获取)。在进行高速成像时,这些方法和系统通常不能依比例适当地确定多个角度,而可能涉及在空间分辨率和获取的角度的数量之间的折衷。
另一种方法和系统平移直角棱镜,将来自样本臂的光导向聚焦透镜的不同位置。图3示出这种系统的示例,如在M.Bashkansky等,“Statisticsand reduction of speckle in optical coherence tomography,”Optics Letters25(8):545-547,2000中所描述的。在这些方法和系统中,通常收集以180度为中心的窄角范围处的后向散射光,但是入射光束针对样本法线的入射角随着棱镜的位置而变化。这种方法和系统不可能提供(甚至允许)对角后向散射分布的测量。可以获取图像的速度可能被限制为棱镜以振荡的方式平移的速度。在又一种方法和系统中,可以使用4个检测器同时对OCT角度进行检测,这使得能够针对散斑减少进行角组合。图4示出这种系统的示例,如在J.M.Schmitt,“Array detection for speckle reduction inoptical coherence microscopy,”Physics In Medicine And Biology 42(7):1427-1439,1997中所描述的。具体地,该系统中的基准光束通常不大于入射光束。因此,该系统不适于测量角后向散射分布。此外,在每一个检测器元件接收在不同角度处后向散射的光时,针对给定检测器元件所收集的光所对着的立体角(solid angle)完全包含在入射光束所对着的立体角内。该系统在时域中进行检测。
在光散射谱研究领域中,已知后向散射光的角分布通常包含关于组织内的散射微粒的大小分布的信息。给定OCT的光学分辨率限制,则通过反射性质微小的差别得出组织之间鲁棒的对比的能力(在某些情况下)可以使用后向散射光的角分布的测量。如图5(a)和5(b)的配置所示,如在A.Wax等,“Measurement of angular distributions by use oflow-coherence interferometry for light-scattering spectroscopy,”OpticsLetters 26(6):322-324,2004中所描述的,以及如图6(a)和6(b)所示,如在J.W.Pyhtila等,“Determining nuclear morphology using an improvedangle-resolved low coherence interferometry system,”Optics Express15(25):3474-3484,2003中所描述的,已经设计了使用低相干干涉测量的深度分辨角后向散射测量用于以高角分辨率进行光散射测量。
例如,将来自低相干源的光分割到修正的迈克逊(Michelson)干涉仪的两个臂,一个光束入射到样本(或者样本臂)上,另一个光束入射到反射镜(或者基准臂)上。放置在基准臂中的透镜可以沿着与镜面平行的方向平移,以在样本臂中针对不同的散射角度提供选择性。通常在时域(使用图5(a)和5(b)所示的配置)或者在频域(使用图6(a)和6(b)所示的配置)中进行干涉光的测量。这些技术通常不允许同时测量角后向散射分布,并且测量速度会受到可以精确平移透镜的速度的限制。在针对角度点采样的本地测量进行优化时,其当前应用中的角分辨LCI可能不适合活体临床成像。
因此,存在克服上面描述的不足的需要。实际上,在光学相干断层成像的成像环境中同时测量从多个角度后向散射的光可以允许高水平的散斑减少以及附加形式的图像对比(contrast)。
因此,存在克服上面描述的不足的需要。
发明内容
为了解决和/或克服上述问题和/或不足,提供根据本发明的系统、设备和方法的示例性实施例,用来利用傅立叶域光学相干断层成像原理从透明和混浊样本中测量空间分辨角后向散射分布。另外,根据本发明的其它示例性实施例,提供利用后向散射分布的系统和方法来进行散斑减少并用来产生图像对比。
因此,根据本发明的一个示例性实施例,提供了设备和方法。具体地,可以接收至少一个第一电磁辐射,并且可以将立体角内的至少一个第二电磁辐射传送到样本。第二电磁辐射可以与第一电磁辐射相关联。从与第二电磁辐射相关联的样本接收多个第三电磁辐射,在立体角的外围外部提供第三电磁辐射的至少一部分。可以同时检测与第三电磁辐射中的每一个相关联的信号,其中这些信号与至少一个样本的多个深度处的信息相关联。可以使用第三电磁辐射中的至少一个来确定深度,而不需要利用第三电磁辐射中的另一个。
另外,可以检测第三辐射中的两个和至少一个与第一辐射相关联的第四辐射之间的干涉,可以基于干涉作为样本内的深度的函数获得与样本相关联的信息。可以作为信号的函数提供与样本的至少一部分的双折射性质、分光性质、运动、角后向散射性质或者弹性性质中的至少一个相关联的数据。可以作为信号的函数产生样本的至少一部分的至少一个图像。还可以作为信号的函数提供与样本的至少一部分的双折射性质、分光性质、运动、角后向散射性质或者弹性性质中的至少一个相关联的数据。数据可以是与至少一个图像相关联的对比度数据。还可以作为信号的组合的函数提供与样本的至少一部分的散射特性相关联的数据。此外,可以使用第三电磁辐射中的一个来确定深度。
根据本发明的另一个示例性实施例,可以提供便于产生与至少一个样本相关联的数据的设备和方法。例如,可以接收与从至少一个样本提供的多个电磁辐射的信号相关联的第一信息。可以沿着第一轴提供电磁辐射中的至少第一个,可以沿着与第一轴不同的第二轴提供电磁辐射中的至少第二个。第一信息的至少一部分内的信号中的每一个的数据可以包括至少一个样本内的多个深度的数据。可以作为第一信息的函数产生与至少一个样本的图像的至少一部分的对比度数据相关联的第二信息。
在本发明的又一示例性实施例中,可以进一步提供设备和方法。例如,可以接收至少一个第一电磁辐射,并且可以将立体角内的至少一个第二电磁辐射传送到样本。第二电磁辐射可以与第一电磁辐射相关联。可以从与至少一个第二电磁辐射相关联的样本同时接收多个第三电磁辐射中的至少两个,可以在立体角的外围外部提供第三电磁辐射的至少一部分。可以检测第三辐射中的至少两个和与第一辐射相关联的至少一个第四辐射之间的干涉。可以基于干涉作为样本内的至少一个深度的函数获得与样本相关联的信息。
在结合所附权利要求阅读下面对本发明的实施例的详细说明时,本发明的这些和其它目的、特征和优点将变得明显。
附图说明
从以下结合示出本发明的说明性实施例的附图进行的详细说明,本发明的其它目的、特征和优点将变得明显,在附图中:
图1是执行光学相干显微测量(“OCM”)的传统设备的框图;
图2是在光学相干断层成像(“OCT”)中执行用于减少散斑的路径长度编码的角组合的传统设备的框图;
图3是用于执行散斑减少的传统OCT设备的框图;
图4是针对散斑减少执行阵列检测的传统OCT设备的框图;
图5(a)和5(b)是用于执行角分辨低相干干涉测量的传统设备的框图;
图6(a)和6(b)是用于执行角分辨低相干干涉测量的其它传统设备的框图;
图7是根据本发明的利用一维检测器阵列的角分辨FD-OCT系统的示例性实施例的示意图,其中矩形灰色虚线区域被定向为垂直于干涉仪平面;
图8是图7所示的系统利用的波长扫频激光源的示例性实施例的示意图;
图9是根据本发明的使用同时检测波长和角度的二维检测器阵列的角分辨FD-OCT系统的另一个示例性实施例的干涉检测的示意操作图;
图10是根据本发明的设置在可以与内窥镜探头兼容的角分辨FD-OCT系统的又一个示例性实施例内的成像光学装置的示意操作图;
图11(a)是根据本发明的角分辨FD-OCT系统的示例性实施例针对一个示例性角样本上的平均值所获得的组织假体的二维图像;
图11(b)是根据本发明的角分辨FD-OCT系统的示例性实施例针对400个示例性角样本上的平均值所获得的组织假体的另一个二维图像;
图12(a)是根据本发明的示例性实施例在组织假体内从一个分辨元件获得的角分布的曲线图;
图12(b)是根据本发明的示例性实施例使用相应的归一化交叉相关函数从一个分辨元件获得的角分布的曲线图;
图13A是通过组合一个角样本而获得的示例性食道组织的图像,其中箭头指向上皮内的薄散射层;
图13B是通过组合三个角样本而获得的示例性食道组织的图像,其中箭头指向上皮内的薄散射层;
图13C是通过组合30个角样本而获得的示例性食道组织的图像,其中箭头指向上皮内的薄散射层;以及
图13D是通过组合400个角样本而获得的示例性食道组织的图像,其中箭头指向上皮内的薄散射层;
在所有附图中,除非特别说明,相同的附图标记和字母用于表示所说明的实施例的相似的特征、要素、部件或者部分。此外,在现在参考附图详细描述本发明时,将结合说明性实施例进行描述。可以对所描述的实施例进行变化和变形,而不脱离所附权利要求所限定的本发明的范围和精神。
具体实施方式
角分辨FD-OCT的示例性原理
下面,在傅立叶域OCT的环境下描述角分辨FD-OCT。例如,在FD-OCT中,可以在频域中测量基准光和从成像样本后向散射的光之间的干涉,以获得混浊、半混浊或者透明介质的深度分辨反射。可以将输入光源的电磁辐射(例如光、激光束等)划分为基准光束和样本光束。可以将样本光束的光导向要成像的样本,来自样本的后向散射光与基准光束发生干涉。在角分辨FD-OCT的情况下,可以在空间上扩展基准光束,从而可以使其截面面积大于样本光束的截面面积,以允许在超过入射样本光束所对着的后向散射角的后向散射角范围内发生干涉。例如可以使用检测阵列来测量基准光束和后向散射光之间的干涉,该检测器阵列可以包括(i)集成到单集成电路元件上的检测器,和/或(ii)在空间中设置在一起的各个检测器。可以在空间域中将所检测的后向散射光相对于入射光束的角依赖性编码为沿着检测器阵列的至少一个维度的光强度分布。可以测量干涉光的波长依赖性,并且可以获得与不同范围的后向散射角度相对应的傅立叶分析轴向反射分布图(profile)。
例如,可以由下面的比例表达式作为激光vn的频率的函数给出检测器阵列的第i像素检测的干涉信号Si
S i ( v n ) ∝ P ( v n ) γ r , i ( v n ) γ s , i ( v n ) ∫ 0 ∞ R ( z ) cos ( 4 πv n z / c + φ ( z ) ) dz - - - ( 1 )
其中P(vn)是源的总功率。R(z)和φ(z)分别是反射分布图的幅值和相位项。轴向距离z可以表示为相对距离,其中z=0对应于样本臂和基准臂之间的零光路差。表示为P(vn)的百分率的到达像素i的样本臂和基准臂电磁辐射(例如光)的量分别可以表示为γs,i和γr,i。可以通过沿着维度i对采样的干涉信号进行离散傅立叶变换来得到反射分布图R(z):
R ( z ) ∝ DFT ( S i ) - - - ( 2 )
利用角分辨FD-OCT减少散斑的示例性原理
散斑由于后向散射波前的畸变而产生,其可能由低角度多重前向散射引起,并且可能由于相邻很近(closely separated)的折射率不均匀而使多重后向散射扩散。通常根据作为这种干涉的结果对源自不同后向散射角的场进行去相关的观察来获得角组合技术。通过对来自不同散射角的信号不一致地求平均,例如对重构的反射分布图的幅值求平均,可以获得散斑减少的反射信号。
作为具有均匀散射性质的介质内的像素强度的方差的平均值与平方根的比,散斑信噪比(“SNR”,signal-to-noise ratio)可以是散斑减少的量度:
SNR = < S k > < ( S k - < S k > ) 2 > , - - - ( 3 )
其中,角括号表示用k作为索引的像素的集合的平均。散斑SNR可以是根据均匀样本获得的信号方差的归一化量度。这样,散斑SNR可以与系统灵敏度不同,在不存在散斑的情况下系统灵敏度可以被定义为最小可检测反射比(reflectance)。对于示例性角组合方法,SNR可以与不相关的不一致平均值的数目N的平方根成比例地增大:
SNR ( N ) = SNR ( 1 ) N . - - - ( 4 )
因此,SNR通过角组合可以增大的程度依赖于角去相关的水平。通常,对于包含大量散射体的OCT样本量以及在大光学深度处的OCT样本量,可以获得更高水平的去相关。相比而言,具有与样本量的维度类似的维度的明显的界面和散射体很可能表示来自角组合的少量对比度增强。
针对图像对比度根据角后向散射分布提取参数的原理
可以通过角分辨FD-OCT方法和系统测量的光的角后向散射图案可以包含关于成像样本的散射体大小和密度的信息。该信息在例如临床成像的情况下可能是相关的,以便区分具有非常类似的散射性质的组织的不同区域,这些散射性质可以在测量在单角度范围内后向散射的光的反射比的光学方法中使用。可以根据每一个像素处的角后向散射分布产生图像对比度测量值,可以在空间上使这些测量值平滑,和/或可以根据在空间上平滑的角后向散射分布产生图像对比度测量值。
角分辨傅立叶域OCT
SD-OCT和OFDI系统和方法的FD-OCT技术可以测量离散的谱干涉,并且在实现该测量时可以是不同的。OFDI系统和方法可以使用波长扫频源记录作为时间的函数的干涉,而SD-OCT系统和方法通常使用分光仪在检测器阵列或者阵列的一部分上对干涉谱进行成像。
图7示出根据本发明的角分辨FD-OCT成像系统的示例性实施例的示意图。该示例性系统可以包括下列模块:波长扫频源705、干涉仪707、以及具有相应电子设备785的获取照相机765。例如,可以将激光输出导向光耦合器710,其将光分离到干涉仪707的两个臂。从基准臂准直器725提供的准直光可以通过元件735、740、745入射到柱面透镜测微器(telescope),该测微器可以在行扫描照相机765的维度内扩展光束。可以将可变长度的自由空间耦合器712放置在准直器725之前的基准臂内,以便于进行基准臂长度调节。可以通过线性起偏器755和光束分离器750引导来自样本臂准直器730的准直光,该光可以入射到成像光学装置770、775上,成像光学装置770、775将该光聚焦到样本780上。
分别设置在准直器725、730前面的偏振控制器715、720可以被定位以使波长扫频源705的频率范围上的条纹(fringe)调制最大化。成像光学装置770和775包括检流计反射镜770,其轴平行于干涉仪707的平面并且垂直于从光束分离器750入射到其上的光束和放置在距离样本780一个焦距处的聚焦透镜775。入射光束接触检流计反射镜770的水平和垂直中心。从样本780后向反射的光可以经由反射镜770和聚焦透镜775向后通过,随后在光束分离器750处与基准光束产生干涉。干涉光可以入射到柱面透镜760上,柱面透镜760将光聚焦到行扫描照相机765上。来自He-Ne激光器700的光可以被注入到光纤耦合器710中,并且在成像过程中可以作为引导光束。
来自行扫描照相机765的信号可以被导向数据获取(“DAQ”,dataacquisition)板785的模拟数字(A-D)输入端口。例如,在对应于一行(one a-line)的时间段中,DAQ板785可以从n次曝光获得m个数据点,其中m是行扫描照相机765中的检测器的数量,n可以是在每一行上采样的频率的数量。一行获取速率可以确定为行扫描照相机读出速率和n的商。在每一个读出阶段开始时,行扫描照相机765可以使用例如TTL触发信号将从DAQ板785的读出与频率扫频激光源705同步。
如图8所示,波长扫频源的示例性实施例可以构成为环形腔激光器,包括:作为增益元件的半导体光学放大器(“SOA”,semiconductor opticalamplifier)845;以及检流计反射镜滤波器800,可以包括检流计反射镜802、测微器805、810、衍射光栅815和光纤准直器820。可以设置两个偏振控制器825、840以使激光偏振最优化以及输出耦合器835以提供激光输出。输出耦合器835可以在标称上(nominally)近似相等地在输出端口836和激光端口837之间分离光。光学循环器830可以将光从激光端口837经由偏振控制器840导向检流计反射镜滤波器800,并且可以引导光从检流计反射镜滤波器800经由偏振控制器825返回SOA 845。随着检流计反射镜802的旋转,从检流计反射镜滤波器800反射的波长通常发生变化。光学隔离器850可以用来将激光与示例性系统的其余部分分离。
用于分辨方位角和极角的2D检测
根据本发明的第二示例性实施例,可以使用二维的检测器阵列来进行干涉光的检测,两个维度对应于后向散射光的角分布。可以由波长可调谐的窄行宽源(narrow line-width source)提供入射到样本上的光。从成像样本后向散射的光与沿着两个空间维度扩展了的基准光束发生干涉。每一个检测器阵列元件可以对应于后向散射光的极角和方位角的唯一范围。在获取检测器阵列的读出值时,通过激光在其调谐范围上进行扫频,可以获得每一个离散方位-极(azimuth-polar)角对的矢量。傅立叶域光学相干断层成像重构技术可以应用这些矢量,其可以产生深度分辨反射分布图。在获取阵列的读出值时,通过光束在样本上进行扫描或者相对于光束移动样本,可以获得组织上不同位置的角分辨反射分布图。可以组合这些分布图以形成二维或者三维的截面反射图像。
用于同时分辨角度和波长的2D检测
根据本发明的第三示例性实施例,如图9的操作框图所示,可以使用例如二维检测器阵列来进行干涉光的检测,其中一维对应于波长,另一维对应于后向散射光的角度。可以由宽带源提供入射到样本上的光。从样本后向散射的光可以与已经沿着一个空间维度进行了扩展的基准光产生干涉,该维度可以对应于后向散射光的角度。干涉光900入射到衍射光栅905上,衍射光栅905将光沿着对应于波长的另一个维度分离。随后,该分离的光910入射到二维检测器阵列915上。沿着对应于特定后向散射角范围的检测器阵列读出值的每一个一维部分,傅立叶域光学相干断层成像重构技术可以应用于干涉谱,从而提供深度分辨反射分布图。在获取阵列的读出值时,通过光束在样本上进行扫描或者相对于光束移动样本,可以获得组织上不同点的角分辨反射分布图。可以组合这些分布图以形成二维或者三维的截面反射图像。
光纤丛光学探头
如图10的操作框图所示,可以与光纤丛一起使用适合利用根据本发明的小探头几何结构的应用的第四示例性实施例。根据该示例性实施例,可以使用光纤阵列1025将光传输到成像样本1000和从成像样本1000接收光。阵列1025中的一个或更多个光纤可以被称为“传送光纤”,通过其可以将光1010传输到样本1000和从样本1000接收光1010。阵列1025中的每一个光纤可以对应于角后向散射角度的唯一的窄范围。放置在光纤之前的透镜1020可以用来增强每一个光纤收集的光量。放置在透镜1020前面的透镜1015用来将光聚焦到样本1000上并且在透镜1020收集之前对从样本1000后向散射的光进行准直。
偏振敏感的角分辨FD-OCT
在光学相干断层成像情况下的偏振测量有利于在空间上分辨生物组织中的双折射。按照根据本发明的第五示例性实施例,可以通过下列中的一个或更多个来进行偏振测量:
a)在干涉仪接收光之前改变光的偏振,并且固定基准臂和/或样本臂的偏振状态;
b)作为时间的函数仅改变样本光束的偏振;
c)作为时间的函数仅改变基准光束的偏振;
d)作为空间的函数改变基准光束的一个或更多个部分的偏振状态,
使得存在偏振状态不同的基准光束的至少两个不同的部分;
e)在与基准光束发生干涉之前作为空间的函数改变后向散射光的一个或更多个部分的偏振状态,使得存在偏振状态不同的样本光束的至少两个不同的部分;
f)作为空间的函数改变干涉光的一个或更多个部分的偏振状态,使得存在偏振状态不同的至少两个不同的部分。
使用示例性技术(a)、(b)和/或(c),通过比较在不同时间接收的使得其源自的偏振状态可能不同的行,可以获得样本的双折射图。使用示例性技术(d)、(e)和/或(f),通过比较从不同后向散射角范围获得的使得其源自的偏振状态可能不同的行,可以获得样本的双反射图。
微粒大小测定
假设在分析中可以考虑来自平面波的光束偏移,可以使用米氏(Mie)散射的计算架构来分析从角分辨FD-OCT系统和/或方法获得的角频率含量(content)。具体地,因为可以使用米氏理论来确定源自球面介质(dielectric)散射体的角散射分布,所以可以执行根据角散射分布确定散射体的大小分布的逆问题。角后向散射分布的米氏散射分析使得可以在上皮组织内进行散射体分布的测量,这可以与癌变之前的畸形转变相关联。
角去相关
处理从角分辨FD-OCT获取的角后向散射分布的另一种方法涉及对其角频率含量的分析。图像对比度测量包括具有最大功率的角频率库(bin)和具有最高功率的峰宽度。对角后向散射分布的功率谱密度的分析等同于Wiener-Kinchine定理的自动相关函数分析。可以通过下式提供归一化的自动相关函数C:
C i = &Sigma; j ( S j - < S j > ) ( S j - i - < S j > ) &Sigma; j ( S j - < S j > ) 2 . - - - ( 5 )
其中j和i可以是角索引(angular index)。例如,相对于第一最小值测量的自动相关函数的中瓣(central lobe)的宽度可以表示连续角样本之间的相关程度。可以针对使用角分辨FD-OCT系统和方法获得的截面图像的每一个像素确定该示例性宽度,从而提供具有针对角后向散射分布的去相关水平的对比度的图像。
示例
通过下列试验证明了可以用来减少散斑的根据本发明的系统和方法的示例性实施例。由含水琼脂凝胶(按重量计算含0.5%的琼脂)和直径0.3mm的聚合微滴(microsphere)(Duke Scientific)构成两层组织假体。这些假体包含在硅隔离体(Sigma)中。形成具有大约2mm的深度的初始散射层。在第一散射层的顶部上形成被设计为具有比第一散射层低的散射系数的第二散射层,第二散射层具有大约450mm的深度。通过分析关于深度的幂信号衰减,对于第一和第二层,总散射系数估计分别为24cm-1和12cm-1。
如图11(a)所示,从单个角样本生成的二维图像显示明显的散斑,其中两个层之间的边界不是清晰可见的。如图11(b)所示,在角组合图像中散斑大大减少,并且两个层之间的边界清晰可见。通过定性检查,图11(b)中的图像的分辨率不可能显著低于图11(a)的图像的分辨率。图12(a)和图12(b)示出从假体表面下方500mm的点获得的示例性代表角分布的曲线图和相应的自动相关函数。
如图13A-13D的图像所示,当应用于食道组织时,角组合的效果是显著的。这些图像是从猪活体外获得的,通过盖玻片(coverslip)对成像样本稍微进行了压缩以增强上皮下方的层的可视性。具体地,如图13A所示,例如,在分辨出的特征和散斑产生的颗粒度(graininess)方面,从单个角样本生成的图像在质上与传统技术的OFDI系统获得的图像类似。在该示例性图像中,上皮内的散射层仅模糊可见(参见箭头)。如图13B的图像所示,利用三个组合角度,散斑减少的水平使得仅可以在图像的某些部分中分辨出该层。如图13C和13D的图像所示,利用30或更多角平均值,可以在图像的长度上清晰地分辨出散射层。在上皮下方的黏膜中层(1amina propria)和黏膜下层区域内可以看到通过角组合详细提供的类似的改善。
前面仅仅说明了本发明的原理。根据这里的启示,对所描述的实施例的各种变形和变化对于本领域技术人员将变得明显。实际上,可以与任何OCT系统、OFDI系统、谱域OCT(SD-OCT)系统或者其它成像系统,例如与在2004年9月8日提交的国际专利申请PCT/US2004/029148、2005年11月2日提交的美国专利申请第11/266,779号、以及2004年7月9日提交的美国专利申请第10/501,276号中描述的系统,一起使用根据本发明的示例性实施例的装置、系统和方法,这些申请的全部内容通过引用包含于此。因此,本领域技术人员应当理解,虽然这里没有明确示出或者描述,但是可以设计大量系统、装置和方法来实施本发明的原理,因此这些系统、装置和方法在本发明的精神和范围内。另外,对于以上没有通过引用明确包含的现有技术,其全部明确包含于此。上面引用的所有出版物的全部内容通过引用包含于此。

Claims (28)

1.一种设备,包括:
至少一个第一装置,被配置为接收至少一个第一电磁辐射,并且将立体角内的至少一个第二电磁辐射传送到样本,其中至少一个第二电磁辐射与至少一个第一电磁辐射相关联,其中至少一个第一装置被配置为从与至少一个第二电磁辐射相关联的样本接收多个第三电磁辐射,以及其中在立体角的外围外部提供第三电磁辐射的至少一部分;以及
至少一个第二装置,被配置为同时检测与第三电磁辐射中的每一个相关联的信号,其中这些信号与至少一个样本的多个深度处的信息相关联,以及其中至少一个第二装置能够使用第三电磁辐射中的至少一个来确定深度,而不需要利用其它第三电磁辐射。
2.根据权利要求1所述的设备,还包括至少一个第三装置,被配置为检测第三辐射中的至少两个和与至少一个第一辐射相关联的至少一个第四辐射之间的干涉,所述设备基于干涉作为样本内的深度的函数获得与样本相关联的信息。
3.根据权利要求1所述的设备,还包括至少一个第三装置,被配置为作为信号的函数提供与样本的至少一部分的双折射性质、分光性质、运动、角后向散射性质或者弹性性质中的至少一个相关联的数据。
4.根据权利要求1所述的设备,还包括至少一个第三装置,能够作为信号的函数产生样本的至少一部分的至少一个图像。
5.根据权利要求4所述的设备,其中至少一个第三装置还被配置为作为信号的函数提供与样本的至少一部分的双折射性质、分光性质、运动、角后向散射性质或者弹性性质中的至少一个相关联的数据。
6.根据权利要求5所述的设备,其中数据是与至少一个图像相关联的对比度数据。
7.根据权利要求1所述的设备,还包括至少一个第三装置,被配置为作为信号的组合的函数提供与样本的至少一部分的散射特性相关联的数据。
8.根据权利要求1所述的设备,其中至少一个第二装置能够使用第三电磁辐射中的单独一个来确定深度。
9.一种用于检测信号的方法,包括:
接收至少一个第一电磁辐射;
将立体角内的至少一个第二电磁辐射传送到样本,其中至少一个第二电磁辐射与至少一个第一电磁辐射相关联;
从与至少一个第二电磁辐射相关联的样本接收多个第三电磁辐射,其中在立体角的外围外部提供第三电磁辐射的至少一部分;
同时检测与第三电磁辐射中的每一个相关联的信号,其中这些信号与至少一个样本的多个深度处的信息相关联;以及
使用第三电磁辐射中的至少一个来确定深度,而不需要利用其它第三电磁辐射。
10.一种用于提供与至少一个样本相关联的数据的设备,包括:
至少一个第一装置,被配置为接收与从至少一个样本提供的多个电磁辐射的信号相关联的第一信息,其中电磁辐射中的至少第一个沿着第一轴提供,电磁辐射中的至少第二个沿着与第一轴不同的第二轴提供,其中第一信息的至少一部分内的信号中的每一个的数据包括至少一个样本内的多个深度的数据;以及
至少一个第二装置,被配置为作为第一信息的函数产生与至少一个样本的图像的至少一部分的对比度数据相关联的第二信息。
11.根据权利要求10所述的设备,其中在立体角的外围外部提供信号的至少一部分。
12.根据权利要求10所述的设备,其中至少一个第二装置能够使用第一信息确定样本内的至少一个深度的参数。
13.根据权利要求10所述的设备,其中至少一个第二装置能够使用与信号中的单独一个相关联的数据来确定至少一个深度。
14.根据权利要求10所述的设备,还包括至少一个第三装置,能够作为第二信息的函数产生样本的至少一部分的至少一个图像。
15.根据权利要求14所述的设备,其中至少一个第三装置还被配置为作为第二信息的函数提供与样本的至少一部分的双折射性质、分光性质、运动、角后向散射性质或者弹性性质中的至少一个相关联的数据。
16.根据权利要求15所述的设备,其中数据是与至少一个图像相关联的对比度数据。
17.根据权利要求10所述的设备,还包括至少一个第三装置,被配置为作为信号的组合的函数提供与样本的至少一部分的散射特性相关联的数据。
18.一种提供与至少一个样本相关联的数据的方法,包括:
接收与从至少一个样本提供的多个电磁辐射的信号相关联的第一信息,其中电磁辐射中的至少第一个沿着第一轴提供,电磁辐射中的至少第二个沿着与第一轴不同的第二轴提供,其中第一信息的至少一部分内的信号中的每一个的数据包括至少一个样本内的多个深度的数据;以及
作为第一信息的函数产生与至少一个样本的图像的至少一部分的对比度数据相关联的第二信息。
19.一种设备,包括:
至少一个第一装置,被配置为接收至少一个第一电磁辐射,并且将立体角内的至少一个第二电磁辐射传送到样本,其中至少一个第二电磁辐射与至少一个第一电磁辐射相关联,其中至少一个第一装置被配置为从与至少一个第二电磁辐射相关联的样本同时接收多个第三电磁辐射中的至少两个,以及其中在立体角的外围外部提供第三电磁辐射的至少一部分;以及
至少一个第二装置,被配置为检测第三辐射中的至少两个和与至少一个第一辐射相关联的至少一个第四辐射之间的干涉,以及被配置为基于干涉作为样本内的至少一个深度的函数获得与样本相关联的信息。
20.根据权利要求19所述的设备,其中至少一个第二装置能够基于干涉确定至少一个深度,而不需要利用其它第三电磁辐射。
21.根据权利要求20所述的设备,其中至少一个第二装置被配置为同时检测与第三电磁辐射中的每一个相关联的信号。
22.根据权利要求21所述的设备,还包括至少一个第三装置,被配置为作为信号的函数提供与样本的至少一部分的双折射性质、分光性质、运动、角后向散射性质或者弹性性质中的至少一个相关联的数据。
23.根据权利要求21所述的设备,还包括至少一个第三装置,能够作为信号的函数产生样本的至少一部分的至少一个图像。
24.根据权利要求23所述的设备,其中至少一个第三装置还被配置为作为信号的函数提供与样本的至少一部分的双折射性质、分光性质、运动、角后向散射性质或者弹性性质中的至少一个相关联的数据。
25.根据权利要求24所述的设备,其中数据是与至少一个图像相关联的对比度数据。
26.根据权利要求21所述的设备,还包括至少一个第三装置,被配置为作为信号的组合的函数提供与样本的至少一部分的散射特性相关联的数据。
27.根据权利要求20所述的设备,其中至少一个第二装置能够使用第三电磁辐射中的单独一个来确定深度。
28.一种用于检测信号的方法,包括:
接收至少一个第一电磁辐射;
将立体角内的至少一个第二电磁辐射传送到样本,其中至少一个第二电磁辐射与至少一个第一电磁辐射相关联;
从与至少一个第二电磁辐射相关联的样本同时接收多个第三电磁辐射中的至少两个,其中在立体角的外围外部提供第三电磁辐射的至少一部分;
检测第三辐射中的至少两个和与至少一个第一辐射相关联的至少一个第四辐射之间的干涉;以及
基于干涉作为样本内的至少一个深度的函数获得与样本相关联的信息。
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