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1.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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2.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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公开(公告)号：US5842995A
公开(公告)日：1998-12-01
申请号：US672623
申请日：1996-06-28
CPC分类号： A61B5/444 , A61B5/0071 , A61B5/0075 , A61B5/0086 , A61B5/4331 , A61B5/445 , G01N21/65
摘要： An optical probe is disclosed which is suitable for rapidly measuring Raman spectra in vivo. The probe is designed to minimize interfering Raman and fluorescence signals generated within the probe itself. In addition, the probe design is compact, making it particularly suited for use in confined spaces such as body cavities. In one embodiment, the probe is employed to detect tissue abnormalities such as cervical cancers and precancers.
摘要翻译： 公开了适用于在体内快速测量拉曼光谱的光学探针。 探头设计用于最小化探针本身内产生的干扰拉曼和荧光信号。 此外，探头设计紧凑，使其特别适用于诸如体腔的密闭空间。 在一个实施方案中，探针用于检测组织异常，例如宫颈癌和胃癌。
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4.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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公开(公告)号：US20170046586A1
公开(公告)日：2017-02-16
申请号：US14822447
申请日：2015-08-10
CPC分类号： G06K9/3233 , A61B5/0071 , A61B5/0075 , A61B90/30 , A61B2090/366 , A61B2090/373 , A61B2505/05 , G06K9/2027 , G06K9/2054 , G06T7/0014 , G06T2207/30004 , H04N9/3185 , H04N9/3194
摘要： Devices and methods for producing a highlighted overlay of a region, including an illumination source configured to illuminate the region at a bandwidth containing a first wavelength at a working distance, an imager at a working distance configured to image the illuminated region at a bandwidth containing a second wavelength, where the first and second bandwidths and wavelengths are not visible, a visible light projector configured to illuminate the region and registered to the imager to produce alignment of imaged feature with projected features at the same location on the region, and a controller executing a program configured to filter acquired images from the imager to identify areas of the region of a predetermined light intensity, and control the projector to visibly highlight those areas on the region.
摘要翻译： 用于产生区域的突出覆盖的装置和方法，包括被配置为在工作距离处以包含第一波长的带宽照亮区域的照明源，工作距离处的成像器被配置成以包含 第二波长，其中第一和第二带宽和波长不可见，可见光投影器被配置为照亮该区域并被注册到成像器以产生成像特征与区域上相同位置处的投影特征的对准，以及控制器执行 程序，被配置为从所述成像器过滤所获取的图像，以识别所述区域的预定光强度的区域，并且控制所述投影仪以可视地突出显示所述区域上的那些区域。
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6.发明授权公开(公告)号：US08498699B2
公开(公告)日：2013-07-30
申请号：US13013816
申请日：2011-01-26
申请人： Jonathon D. Wells , Mark P. Bendett , James S. Webb , Charles A. Lemaire , Austin R. Duke , E. Duco Jansen , Peter E. Konrad , Anita Mahadevan-Jansen
发明人： Jonathon D. Wells , Mark P. Bendett , James S. Webb , Charles A. Lemaire , Austin R. Duke , E. Duco Jansen , Peter E. Konrad , Anita Mahadevan-Jansen
IPC分类号： A61N1/00
CPC分类号： A61N1/36017 , A61B2018/2025 , A61N1/36082 , A61N1/378 , A61N5/0601 , A61N5/0613 , A61N5/0622 , A61N2005/063 , A61N2005/0659
摘要： An apparatus and method for stimulating animal tissue (for example to trigger a nerve action potential (NAP) signal in a human patient) by application of both electrical and optical signals for treatment and diagnosis purposes. The application of an electrical signal before or simultaneously to the application of a NAP-triggering optical signal allows the use of a lower amount of optical power or energy than would otherwise be needed if an optical signal alone was used for the same purpose and effectiveness. The application of the electrical signal may precondition the nerve tissue such that a lower-power optical signal can be used to trigger the desired NAP, which otherwise would take a higher-power optical signal were the electric signal not applied. Some embodiments include an implanted nerve interface having a plurality of closely spaced electrodes placed transversely and/or longitudinally to the nerve and a plurality of optical emitters.
摘要翻译： 一种用于刺激动物组织（例如在人类患者中触发神经动作电位（NAP）信号）的装置和方法）通过应用电信号和光信号用于治疗和诊断目的。 在应用NAP触发光信号之前或同时应用电信号允许使用比如果单独使用光信号用于相同目的和有效性时所需要的更少量的光功率或能量。 电信号的应用可以预处理神经组织，使得可以使用较低功率的光信号来触发所需的NAP，否则将在不施加电信号的情况下采取更高功率的光信号。 一些实施例包括植入的神经界面，其具有横向和/或纵向设置于神经的多个紧密间隔的电极以及多个光发射器。
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7.发明授权System and method for differentiation of normal and malignant in vivo liver tissues 有权正常和恶性体内肝组织分化的系统和方法公开(公告)号：US07979107B2
公开(公告)日：2011-07-12
申请号：US12537008
申请日：2009-08-06
IPC分类号： A61B5/05
CPC分类号： A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/4244
摘要： A method for differentiating malignant in vivo liver tissues from normal in vivo liver tissues of a living subject includes the steps of: (a) illuminating a first area and a second area of in vivo liver tissues of the living subject with a first excitation light, (b) measuring an intensity of fluorescent light emitted from each of the first area and the second area of in vivo liver tissues in response to the first excitation light as a function of wavelength so as to obtain a first and a second fluorescent spectra, respectively, (c) illuminating the first area and the second area of in vivo liver tissues with a second excitation light, (d) measuring an intensity of diffuse light reflected by each of the first area and the second area of in vivo liver tissues in response to the second excitation light as a function of wavelength so as to obtain a first and a second diffused reflectance spectra, respectively, and (e) identifying one of the first area and the second area of in vivo liver tissues as malignant liver tissues and the other one of the first area and the second area of in vivo liver tissues as normal liver tissues, by comparing the first fluorescence spectrum and the second florescence spectrum, and comparing the first diffused reflection spectrum and the second diffused reflection spectrum.
摘要翻译： 用于区分恶性体内肝组织与活体受试者的正常体内肝组织的方法包括以下步骤：（a）用第一激发光照射活体的肝脏组织的第一区域和第二区域， （b）响应于作为波长的函数的第一激发光，测量从体内肝组织的第一区域和第二区域发射的荧光的强度，以分别获得第一和第二荧光光谱 （c）用第二激发光照射体内肝组织的第一区域和第二区域，（d）响应于测量由体内肝组织的第一区域和第二区域反映的漫射光的强度 作为波长的函数的第二激发光，以分别获得第一和第二扩散反射光谱，（e）识别体内肝脏的第一区域和第二区域之一 通过比较第一荧光光谱和第二荧光光谱，比较第一扩散反射光谱和第二扩散反应谱图，将组织作为恶性肝组织，将体内肝组织的第一区域和第二区域作为正常肝组织 反射光谱。
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8.发明申请Methods and Apparatus for Optical Spectroscopic Detection of Cell and Tissue Death 有权光学检测细胞和组织死亡的方法和装置公开(公告)号：US20090292211A1
公开(公告)日：2009-11-26
申请号：US12537008
申请日：2009-08-06
IPC分类号： A61B6/00
CPC分类号： A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/4244
摘要： A method for detecting death process of a cell or tissue of a living subject. In one embodiment, the method includes the steps of illuminating the cell or tissue of the living subject with a coherent light, collecting fluorescent light returned from the illuminated cell or tissue of the living subject, identifying a NAD(P)H peak of a spectrum of the collected fluorescent light with a wavelength, λpeak, and obtaining the intensity of the NAD(P)H peak of the spectrum of the collected fluorescent light substantially corresponding to the wavelength λpeak. These steps are repeated at sequential stages until the intensity of the NAD(P)H peak of the spectrum at a current stage is less than the intensity of the NAD(P)H peak of the spectrum at an earlier stage immediately prior to the current stage so as to detect death process of the cell of the living subject at the current stage using the intensity of the NAD(P)H peak of the spectrum.
摘要翻译： 一种用于检测活体受试者的细胞或组织的死亡过程的方法。 在一个实施例中，该方法包括以相干光照射活体的细胞或组织的步骤，收集从活体受试者的照射细胞或组织返回的荧光，识别光谱的NAD（P）H峰 所收集的荧光的波长为lambdapeak，并且获得基本上对应于波长兰帕达克的所收集的荧光的光谱的NAD（P）H峰的强度。 这些步骤在连续阶段重复，直到当前阶段的光谱的NAD（P）H峰的强度小于在电流之前的较早阶段的光谱的NAD（P）H峰的强度 使用光谱的NAD（P）H峰的强度来检测当前阶段的活体的细胞的死亡过程。
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公开(公告)号：US06921413B2
公开(公告)日：2005-07-26
申请号：US10333700
申请日：2001-08-15
CPC分类号： A61N5/0622 , A61B5/0048 , A61N5/0601 , A61N5/0613 , A61N5/0619 , A61N2005/063 , A61N2005/0659 , A61N2005/0665 , A61N2005/067
摘要： The present invention provides methods of directly stimulating neural tissue with optical energy. By stimulating neural tissue at wavelengths, laser pulses, and spot sizes disclosed herein, nerve stimulation may be used to uniquely stimulate neural tissue in way not afforded by other means of stimulation. It can allow basic scientists to study the properties of individual neurons or populations of neurons without piercing tissue with fragile microelectrodes. Furthermore, responses of neural tissue can be studied in a pure fashion without contamination by electrical artifact commonly seen with electrical stimulation. With respect to clinical uses, optical stimulation can be used to map function in subsections of peripheral nerves as an aid to operative repair. Finally, stimulation with optical energy does not require physical contact with the nerve which may be an advantage clinically when physical manipulation of neural tissue is not desired.
摘要翻译： 本发明提供了用光能直接刺激神经组织的方法。 通过刺激本文公开的波长，激光脉冲和斑点尺寸的神经组织，可以使用神经刺激来以不能被其他刺激方式提供的方式唯一地刺激神经组织。 它可以允许基础科学家研究单个神经元或神经元群体的性质，而不刺穿脆弱的微电极组织。 此外，可以以纯粹的方式研究神经组织的反应，而不会通过电刺激常见的电赝像而被污染。 关于临床用途，可以使用光学刺激来将外周神经的子部分中的功能作为辅助手术修复。 最后，用光学能量刺激不需要与神经的物理接触，这在神经组织的物理操作是不希望的时候临床可能是有利的。
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公开(公告)号：US20140024902A1
公开(公告)日：2014-01-23
申请号：US13117850
申请日：2011-05-27
申请人： Anita Mahadevan-Jansen , Jonathon D. Wells , E. Duco Jansen , Peter E. Konrad , Changquing C. Kao
发明人： Anita Mahadevan-Jansen , Jonathon D. Wells , E. Duco Jansen , Peter E. Konrad , Changquing C. Kao
IPC分类号： A61B5/00
CPC分类号： A61N5/0622 , A61B5/0048 , A61N5/0601 , A61N5/0613 , A61N5/0619 , A61N2005/063 , A61N2005/0659 , A61N2005/0665 , A61N2005/067
摘要： The present invention, in one aspect, relates to a system for stimulating neural tissue of a living subject. The system comprises an energy source capable of generating optical energy, a connector having a first end and a second end capable of transmitting optical energy, and a probe operably coupled to the second end of the connector and having an end portion for delivering optical energy to a target neural tissue. In one embodiment, the energy source comprises a tunable laser.
摘要翻译： 本发明在一个方面涉及一种用于刺激活体的神经组织的系统。 该系统包括能够产生光能的能量源，具有第一端和能够透射光能的第二端的连接器，以及可操作地耦合到连接器的第二端的探针，并具有用于将光能传递到 目标神经组织。 在一个实施例中，能量源包括可调激光器。
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