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1.发明授权Spectroscopic detection of cervical pre-cancer using radial basis function networks 失效使用径向基函数网络进行子宫颈癌的光谱检测
公开(公告)号：US6135965A
公开(公告)日：2000-10-24
申请号：US757116
申请日：1996-12-02
CPC分类号： A61B5/0084 , A61B5/0071 , A61B5/7267 , A61B5/0075 , G01J2003/2866 , Y10S128/925
摘要： An apparatus and methods for spectroscopic detection of tissue abnormality, particularly precancerous cervical tissue, using neural networks to analyze in vivo measurements of fluorescence spectra. The invention excites fluorescence intensity spectra in both normal and abnormal tissue. This fluorescence spectroscopy data is used to train a group (ensemble) of neural networks, preferably radial basis function (RBF) neural networks. Once trained, fluorescence spectroscopy data from unknown tissue samples is classified by the trained neural networks. This process is used to differentiate pre-cancers from normal tissues, and can also be used to differentiate high grade pre-cancers from low grade pre-cancers. One embodiment of the invention is able to distinguish pre-cancerous tissue from both normal squamous tissue (NS) and normal columnar (NC) tissue in a single-stage of analysis. The invention demonstrates significantly smaller variability in classification accuracy, resulting in more reliable classification, with superior sensitivity. Moreover, the single-stage embodiment of the invention simplifies the decision-making process as compared to a two-stage embodiment.
摘要翻译： 用于分光检测组织异常的装置和方法，特别是癌前宫颈组织，使用神经网络分析荧光光谱的体内测量。 本发明激发正常组织和异常组织中的荧光强度谱。 该荧光光谱数据用于训练神经网络的组（集合），优选径向基函数（RBF）神经网络。 一旦训练，来自未知组织样本的荧光光谱数据被训练的神经网络分类。 该过程用于区分癌前病变与正常组织，也可用于区分高级别前期癌症与低级别前期癌症。 本发明的一个实施方案能够在单阶段分析中区分癌前组织与正常鳞状组织（NS）和正常柱状（NC）组织。 本发明在分类精度方面显示出较小的可变性，导致更可靠的分类，具有优异的灵敏度。 此外，与两级实施例相比，本发明的单级实施例简化了决策过程。
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2.发明授权Method for probabilistically classifying tissue in vitro and in vivo using fluorescence spectroscopy 有权使用荧光光谱法在体外和体内概率分类组织的方法公开(公告)号：US07236815B2
公开(公告)日：2007-06-26
申请号：US10688152
申请日：2003-10-17
申请人： Rebecca Richards-Kortum , Nirmala Ramanujam , Anita Mahadevan-Jansen , Michele Follen , Urs Utzinger
发明人： Rebecca Richards-Kortum , Nirmala Ramanujam , Anita Mahadevan-Jansen , Michele Follen , Urs Utzinger
IPC分类号： A61B6/00
CPC分类号： G01N21/274 , A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/4331 , A61B5/7264 , G01N21/6486 , G01N2021/6417 , G01N2021/6419 , G01N2021/6484 , G06F19/00 , Y10S436/813
摘要： Fluorescence spectral data acquired from tissues in vivo or in vitro is processed in accordance with a multivariate statistical method to achieve the ability to probabilistically classify tissue in a diagnostically useful manner, such as by histopathological classification. The apparatus includes a controllable illumination device for emitting electromagnetic radiation selected to cause tissue to produce a fluorescence intensity spectrum. Also included are an optical system for applying the plurality of radiation wavelengths to a tissue sample, and a fluorescence intensity spectrum detecting device for detecting an intensity of fluorescence spectra emitted by the sample as a result of illumination by the controllable illumination device. The system also include a data processor, connected to the detecting device, for analyzing detected fluorescence spectra to calculate a probability that the sample belongs in a particular classification. The data processor analyzes the detected fluorescence spectra using a multivariate statistical method. The five primary steps involved in the multivariate statistical method are (i) preprocessing of spectral data from each patient to account for inter-patient variation, (ii) partitioning of the preprocessed spectral data from all patients into calibration and prediction sets, (iii) dimension reduction of the preprocessed spectra in the calibration set using principal component analysis, (iv) selection of the diagnostically most useful principal components using a two-sided unpaired student's t-test and (v) development of an optimal classification scheme based on logistic discrimination using the diagnostically useful principal component scores of the calibration set as inputs.
摘要翻译： 根据多变量统计学方法处理从体内或体外组织获得的荧光光谱数据，以实现以诊断有用的方式（例如通过组织病理学分类）对组织进行概率分类的能力。 该装置包括用于发射被选择使得组织产生荧光强度光谱的电磁辐射的可控照明装置。 还包括用于将多个辐射波长施加到组织样本的光学系统和用于通过可控照明装置的照明来检测由样品发射的荧光光谱的强度的荧光强度光谱检测装置。 该系统还包括连接到检测装置的数据处理器，用于分析检测到的荧光光谱以计算样品属于特定分类的概率。 数据处理器使用多变量统计方法分析检测到的荧光光谱。 多变量统计方法涉及的五个主要步骤是（i）从每个患者预处理光谱数据以考虑患者间变异，（ii）将预处理的光谱数据从所有患者划分为校准和预测组，（iii） 使用主成分分析对校准集中的预处理光谱进行维数减少，（iv）使用双侧不配对的学生的t检验来选择诊断上最有用的主成分，以及（v）基于物流歧视开发最优分类方案 使用校准集的诊断上有用的主成分分数作为输入。
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3.发明授权Diagnostic method and apparatus for cervical squamous intraepithelial lesions in vitro and in vivo using fluorescence spectroscopy 失效使用荧光光谱法在体外和体内宫颈鳞状上皮内病变的诊断方法和装置公开(公告)号：US06258576B1
公开(公告)日：2001-07-10
申请号：US08666021
申请日：1996-06-19
IPC分类号： G01N2164
CPC分类号： G01N21/6486 , A61B5/0059 , A61B5/7264 , G01N21/645 , G01N2021/6419 , G01N2021/6484
摘要： The present invention involves the use of fluorescence spectroscopy in the diagnosis of cervical cancer and precancer. Using multiple illumination wavelengths, it is possible to (i) differentiate normal or inflamed tissue from squamous intraepithelial lesions (SILs) and (ii) to differentiate high grade SILs from non-high grade SILs. The detection may be performed in vitro or in vivo. Multivariate statistical analysis was employed to reduce the number of fluorescence excitation-emission wavelength pairs needed to re-develop algorithms that demonstrate a minimum decrease in classification accuracy. Fluorescence at excitation-emission wavelength pairs was used to redevelop and test screening and diagnostic algorithms that have a similar classification accuracy to those that employ fluorescence emission spectra at three excitation wavelengths. Both the full-parameter and reduced-parameter screening algorithms discriminate between SILs and non-SILs with a similar specificity and a substantially improved sensitivity relative to Pap smear screening and differentiate high grade SILs from non-high grade SILs.
摘要翻译： 本发明涉及在宫颈癌和癌前期诊断中使用荧光光谱。 使用多个照明波长，可以（i）区分正常或发炎的组织与鳞状上皮内病变（SIL）和（ii）区分高等级SIL和非高等级SILs。 检测可以在体外或体内进行。 采用多元统计分析方法，减少重新开发算法所需的荧光激发 - 发射波长对数，证明其分类精度最小。 激发 - 发射波长对的荧光被用来重建和测试筛选和诊断算法，它们具有与在三个激发波长下采用荧光发射光谱相似的分类精度。 全参数和简化参数筛选算法都区分SILs和非SILs，具有相似的特异性，并且相对于Pap涂片筛选具有显着提高的敏感性，并区分高等级SIL和非高级SILs。
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4.发明授权Optical method and apparatus for the diagnosis of cervical precancers using raman and fluorescence spectroscopies 失效用于使用拉曼和荧光光谱诊断子宫颈预处理的光学方法和装置
公开(公告)号：US5697373A
公开(公告)日：1997-12-16
申请号：US403446
申请日：1995-03-14
CPC分类号： G01N21/6486 , A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/4331 , A61B5/7264 , G01N21/65 , A61B5/0086 , G01N2021/656
摘要： A method and apparatus for detecting tissue abnormality, particularly precancerous cervical tissue, through fluorescence or Raman spectroscopy, or a combination of fluorescence and Raman spectroscopy. In vivo fluorescence measurements were followed by in vitro NIR Raman measurements on human cervical biopsies. Fluorescence spectra collected at 337, 380 and 460 nm excitation were used to develop a diagnostic method to differentiate between normal and dysplastic tissues. Using a fluorescence diagnostic method, a sensitivity and specificity of 80% and 67% were observed for differentiating squamous intraepithelial lesions (SILs) from all other tissues. In accordance with another aspect of the invention, using Raman scattering peaks observed at selected wavenumbers, SILs were separated from other tissues with a sensitivity and specificity of 88% and 100%. In addition, inflammation and metaplasia samples are correctly separated from the SILs.
摘要翻译： 一种用于通过荧光或拉曼光谱法或荧光和拉曼光谱的组合检测组织异常，特别是癌前期宫颈组织的方法和装置。 体内荧光测量之后是人体宫颈活检的体外NIR拉曼测量。 使用在337,380和460nm激发下收集的荧光光谱来开发用于区分正常组织和发育不良组织的诊断方法。 使用荧光诊断方法，从所有其他组织中鉴别出鳞状上皮内病变（SILs）的灵敏度和特异度为80％和67％。 根据本发明的另一方面，使用在选定波数处观察到的拉曼散射峰，将SIL与其他组织分离，灵敏度和特异性为88％和100％。 此外，炎症和化生样本正确地从SILs分离。
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5.发明授权Near-infrared raman spectroscopy for in vitro and in vivo detection of cervical precancers 失效近红外拉曼光谱法用于宫颈预处理的体外和体内检测
公开(公告)号：US5991653A
公开(公告)日：1999-11-23
申请号：US667993
申请日：1996-06-19
CPC分类号： G01N21/6486 , A61B5/0059 , A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/4331 , G01N21/65 , A61B5/0086 , A61B5/7264 , G01N2021/656
摘要： Early diagnosis of cervical precancer is an important clinical goal. Optical spectroscopy has been suggested as a new technique to overcome limitations of current clinical practice. Herein, NIR Raman spectroscopy is applied to the diagnosis of cervical precancers. Using algorithms based on empirically selected peak intensities, ratios of peak intensities and a combination of Principal Component Analysis (PCA) for data reduction and Fisher Discriminant Analysis (FDA), normal tissues, inflammation and metaplasia were distinguishable from low grade and high grade precancers. The primary contributors to the tissue spectra appear to be collagen, nucleic acids, phospholipids and glucose 1-phosphate. These results suggest that near infrared Raman spectroscopy can be used effectively for cervical precancer diagnosis.
摘要翻译： 子宫颈癌的早期诊断是一个重要的临床目标。 光谱学被认为是克服当前临床实践的局限性的新技术。 在这里，NIR拉曼光谱法被应用于子宫颈预处理的诊断。 使用基于经验选择的峰值强度的算法，峰值强度的比率和用于数据降低的主成分分析（PCA）和Fisher判别分析（FDA），正常组织，炎症和化生的组合与低等级和高级别的预处理可以区分开。 组织光谱的主要贡献者似乎是胶原，核酸，磷脂和葡萄糖1-磷酸。 这些结果表明，近红外拉曼光谱可以有效地用于子宫颈癌前期诊断。
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6.发明授权Spectroscopic method and apparatus for optically detecting abnormal mammalian epithelial tissue 失效用于光学检测异常哺乳动物上皮组织的光谱法和装置
公开(公告)号：US6095982A
公开(公告)日：2000-08-01
申请号：US988840
申请日：1997-12-11
CPC分类号： G01N21/6486 , A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/4331 , A61B5/7264 , G01N21/65 , A61B5/0086 , G01N2021/656
摘要： A method and apparatus for detecting tissue abnormality, particularly precancerous cervical tissue, through fluorescence or Raman spectroscopy, or a combination of fluorescence and Raman spectroscopy. In vivo fluorescence measurements were followed by in vitro NIR Raman measurements on human cervical biopsies. Fluorescence spectra collected at 337, 380 and 460 nm excitation were used to develop a diagnostic method to differentiate between normal and dysplastic tissues. Using a fluorescence diagnostic method, a sensitivity and specificity of 80% and 67% were observed for differentiating squamous intraepithelial lesions (SILs) from all other tissues. In accordance with another aspect of the invention, using Raman scattering peaks observed at selected wavenumbers, SILs were separated from other tissues with a sensitivity and specificity of 88% and 100%. In addition, inflammation and metaplasia samples are correctly separated from the SILs.
摘要翻译： 一种用于通过荧光或拉曼光谱法或荧光和拉曼光谱的组合检测组织异常，特别是癌前期宫颈组织的方法和装置。 体内荧光测量之后是人体宫颈活检的体外NIR拉曼测量。 使用在337,380和460nm激发下收集的荧光光谱来开发用于区分正常组织和发育不良组织的诊断方法。 使用荧光诊断方法，从所有其他组织中鉴别出鳞状上皮内病变（SILs）的灵敏度和特异度为80％和67％。 根据本发明的另一方面，使用在选定波数处观察到的拉曼散射峰，将SIL与其他组织分离，灵敏度和特异性为88％和100％。 此外，炎症和化生样本正确地从SILs分离。
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7.发明申请SYSTEMS AND METHODS FOR SPECTRAL ANALYSIS OF A TISSUE MASS USING AN INSTRUMENT, AN OPTICAL PROBE, AND A MONTE CARLO OR A DIFFUSION ALGORITHM 有权使用仪器，光学探头和蒙特卡罗或扩散算法对组织质量进行光谱分析的系统和方法公开(公告)号：US20110112435A1
公开(公告)日：2011-05-12
申请号：US12680305
申请日：2008-09-29
IPC分类号： A61B10/02
CPC分类号： A61B5/0091 , A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/0086 , A61B5/413 , A61B5/4312
摘要： Systems and methods for spectral analysis of a tissue mass using an instrument, an optical probe, and a Monte Carlo algorithm or a diffusion algorithm are provided. According to one method, an instrument is inserted into a tissue mass. A fiber optic probe is applied via the instrument into the tissue mass. Turbid spectral data of the tissue mass is measured using the fiber probe. The turbid spectral data is converted to absorption, scattering, and/or intrinsic fluorescence spectral data via a Monte Carlo algorithm or diffusion algorithm. Biomarker concentrations in the tissue mass are quantified using the absorption, scattering, and/or intrinsic fluorescence spectral data.
摘要翻译： 提供了使用仪器，光学探针和蒙特卡洛算法或扩散算法对组织块进行光谱分析的系统和方法。 根据一种方法，将器械插入组织块中。 通过仪器将光纤探头施加到组织块中。 使用光纤探针测量组织块的浊度光谱数据。 通过蒙特卡罗算法或扩散算法将浊度光谱数据转换为吸收，散射和/或固有荧光光谱数据。 使用吸收，散射和/或固有的荧光光谱数据来量化组织块中的生物标志物浓度。
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公开(公告)号：US20100301229A1
公开(公告)日：2010-12-02
申请号：US12830078
申请日：2010-07-02
申请人： Nirmala Ramanujam , Lee G. Wilke
发明人： Nirmala Ramanujam , Lee G. Wilke
CPC分类号： G01N21/4738
摘要： The subject matter described herein includes an optical assay system for intraoperative assessment of tumor margins. According to one aspect, the subject matter described herein includes a biological sample containment and illumination apparatus for holding a biological sample for illumination by a plurality of electromagnetic radiation probes. The biological sample containment and illumination apparatus includes a plurality of frame members positioned with respect to each other to form an interior space for receiving a biological sample. At least one of the plurality of frame members includes a plurality of probe receiving locations for receiving a plurality of electromagnetic radiation probes. The probe receiving locations position the probes with respect to the biological sample to allow illumination of plural locations of the biological sample by the probes.
摘要翻译： 本文所述的主题包括用于术中评估肿瘤边缘的光学测定系统。 根据一个方面，本文所述的主题包括用于通过多个电磁辐射探针保持用于照明的生物样品的生物样品容纳物和照明装置。 生物样品容纳和照明装置包括相对于彼此定位的多个框架构件，以形成用于接收生物样品的内部空间。 多个框架构件中的至少一个包括用于接收多个电磁辐射探针的多个探针接收位置。 探针接收位置使探针相对于生物样品定位，以允许通过探针照射生物样品的多个位置。
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公开(公告)号：US07751039B2
公开(公告)日：2010-07-06
申请号：US11729967
申请日：2007-03-29
申请人： Nirmala Ramanujam , Lee G. Wilke
发明人： Nirmala Ramanujam , Lee G. Wilke
IPC分类号： G01N21/01
CPC分类号： G01N21/4738
摘要： The subject matter described herein includes an optical assay system for intraoperative assessment of tumor margins. According to one aspect, the subject matter described herein includes a biological sample containment and illumination apparatus for holding a biological sample for illumination by a plurality of electromagnetic radiation probes. The biological sample containment and illumination apparatus includes a plurality of frame members positioned with respect to each other to form an interior space for receiving a biological sample. At least one of the plurality of frame members includes a plurality of probe receiving locations for receiving a plurality of electromagnetic radiation probes. The probe receiving locations position the probes with respect to the biological sample to allow illumination of plural locations of the biological sample by the probes.
摘要翻译： 本文所述的主题包括用于术中评估肿瘤边缘的光学测定系统。 根据一个方面，本文所述的主题包括用于通过多个电磁辐射探针保持用于照明的生物样品的生物样品容纳物和照明装置。 生物样品容纳和照明装置包括相对于彼此定位的多个框架构件，以形成用于接收生物样品的内部空间。 多个框架构件中的至少一个包括用于接收多个电磁辐射探针的多个探针接收位置。 探针接收位置使探针相对于生物样品定位，以允许通过探针照射生物样品的多个位置。
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10.发明申请Side-firing probe for performing optical spectroscopy during core needle biopsy 审中-公开核心针活检期间进行光学光谱的侧火探针公开(公告)号：US20050203419A1
公开(公告)日：2005-09-15
申请号：US11063273
申请日：2005-02-22
CPC分类号： A61B5/0075 , A61B5/0071 , A61B5/0084 , A61B5/0086 , A61B5/0091 , A61B5/4312 , A61B5/6848 , A61B10/0275 , A61B90/36 , A61B2017/00061 , A61B2090/3614
摘要： A needle biopsy includes the step of inserting an optical spectroscopy probe in the needle and gathering optical information through a window formed in the side of the needle at its distal end. The optical probe includes an illumination optical fiber which conveys light to the tissues adjacent the side window and a detection optical fiber which collects light from the same tissues and conveys it to an optical spectroscopy instrument. Based on the results of the optical spectroscopy measurement, the optical probe may be withdrawn from the needle and a cutter advanced to acquire a sample of the tissues adjacent the side window.
摘要翻译： 针活组织检查包括将光学光谱探针插入针中并通过在其侧端形成的窗口收集光学信息的步骤。 光学探针包括向邻近侧窗的组织传送光的照明光纤和从相同组织收集光并将其传送到光谱仪器的检测光纤。 基于光谱测量的结果，光学探针可以从针中取出，并且切割器前进以获取邻近侧窗的组织样品。
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