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1. 发明授权

US07835786B2 Methods, systems, and computer program products for optimization of probes for spectroscopic measurement in turbid media 有权
标题翻译：用于优化浑浊介质中光谱测量的探针的方法，系统和计算机程序产品
公开(公告)号：US07835786B2
公开(公告)日：2010-11-16
申请号：US11493020
申请日：2006-07-25
申请人： Gregory M. Palmer , Nirmala Ramanujam
发明人： Gregory M. Palmer , Nirmala Ramanujam
IPC分类号： A61B6/00 , G01J3/30 , G02B6/06
CPC分类号： G01N21/4738 , G01N2021/4742 , G01N2021/4752 , G01N2201/1296
摘要： Methods, systems, and computer program products for optimizing a probe geometry for spectroscopic measurement in a turbid medium are provided. A probe geometry comprising one emitting entity and at least on collecting entity is selected. A simulation is performed to generate optical parameter values measured by the probe geometry. The measured optical parameter values are input to an inversion algorithm to produce corresponding optical properties as output. The produced optical properties are compared with known optical properties known and a degree of matching between the produced optical properties and the known optical properties is determined. The simulation and inversion steps are repeated for a plurality of additional probe geometries, each differing in at least one property. An optimization algorithm is applied at each iteration to select an optimal probe geometry.
摘要翻译：提供了用于优化用于浑浊介质中的光谱测量的探针几何的方法，系统和计算机程序产品。选择包括一个发射实体和至少在收集实体上的探针几何形状。进行模拟以产生由探针几何测量的光学参数值。测量的光学参数值被输入到反演算法中以产生相应的光学特性作为输出。将所产生的光学性质与已知的已知光学性能进行比较，并且确定所产生的光学性质和已知的光学性质之间的匹配程度。针对多个额外的探针几何重复模拟和反转步骤，每个不同于至少一个属性。在每次迭代中应用优化算法以选择最佳探针几何。

2. 发明授权

US07818154B2 Monte Carlo based model of fluorescence in turbid media and methods and systems for using same to determine intrinsic fluorescence of turbid media 有权
标题翻译：基于蒙特卡罗的浑浊介质中的荧光模型以及用于确定混浊介质的固有荧光的方法和系统
公开(公告)号：US07818154B2
公开(公告)日：2010-10-19
申请号：US11725141
申请日：2007-03-16
申请人： Gregory M. Palmer , Nirmala Ramanujam
发明人： Gregory M. Palmer , Nirmala Ramanujam
IPC分类号： G06F1/00
CPC分类号： G01J3/4406 , A61B5/0071 , A61B5/0084 , G01N21/49 , G01N21/6486 , G01N2021/6417
摘要： The subject matter described herein includes a method for modeling fluorescence in turbid media and methods and systems for using the model to determine intrinsic fluorescence of turbid media. According to one aspect, a method for modeling fluorescence of a turbid medium and for using the model to determine intrinsic fluorescence in the turbid medium is provided. The method includes illuminating a turbid medium of interest with an electromagnetic radiation source using a probe of a particular geometry and detecting measured fluorescence for the turbid medium using the probe. At least one set of Monte Carlo simulations is run to determine an escape energy probability map and an absorbed energy density map for the turbid medium. An indication of the intrinsic fluorescence of the turbid medium is determined using the escape probability density map and the absorbed energy density map in a manner that accounts for the geometry of the probe.
摘要翻译：本文描述的主题包括用于对混浊介质中的荧光进行建模的方法以及使用该模型确定混浊介质的固有荧光的方法和系统。根据一个方面，提供了一种用于对浑浊介质的荧光进行建模和使用该模型来确定混浊介质中的固有荧光的方法。该方法包括使用特定几何形状的探针用电磁辐射源照射感兴趣的混浊介质，并使用探针检测浊度介质的测量荧光。运行至少一组蒙特卡罗模拟来确定浑浊介质的逃逸能量概率图和吸收的能量密度图。使用逃避概率密度图和吸收的能量密度图以考虑探针的几何形状的方式确定混浊介质的固有荧光的指示。

3. 发明申请

US20110112435A1 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
标题翻译：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
申请人： Nirmala Ramanujam , Bing Yu , Jonathon Quincy Brown
发明人： Nirmala Ramanujam , Bing Yu , Jonathon Quincy Brown
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。

4. 发明申请

US20100301229A1 OPTICAL ASSAY SYSTEM FOR INTRAOPERATIVE ASSESSMENT OF TUMOR MARGINS 有权
标题翻译：用于肿瘤标志物进行评估的光学测定系统
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
IPC分类号： G01J1/58 , 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。

5. 发明授权

US07751039B2 Optical assay system for intraoperative assessment of tumor margins 失效
标题翻译：用于术中评估肿瘤边缘的光学测定系统
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。

6. 发明授权

US07236815B2 Method for probabilistically classifying tissue in vitro and in vivo using fluorescence spectroscopy 有权
标题翻译：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。

7. 发明申请

US20050203419A1 Side-firing probe for performing optical spectroscopy during core needle biopsy 审中-公开
标题翻译：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
申请人： Nirmala Ramanujam , Changfang Zhu , Carmalyn Lubawy
发明人： Nirmala Ramanujam , Changfang Zhu , Carmalyn Lubawy
IPC分类号： A61B5/00 , A61B6/00 , A61B10/00 , A61B10/02 , A61B17/00 , A61B19/00
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。

8. 发明授权

US09820655B2 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
公开(公告)号：US09820655B2
公开(公告)日：2017-11-21
申请号：US12680305
申请日：2008-09-29
申请人： Nirmala Ramanujam , Bing Yu , Jonathon Quincy Brown
发明人： Nirmala Ramanujam , Bing Yu , Jonathon Quincy Brown
IPC分类号： A61B5/00
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.

9. 发明申请

US20110295541A1 Systems and Methods for Performing Optical Spectroscopy Using a Self-Calibrating Fiber Optic Probe 有权
标题翻译：使用自校准光纤探头进行光谱分析的系统和方法
公开(公告)号：US20110295541A1
公开(公告)日：2011-12-01
申请号：US12989591
申请日：2009-04-27
申请人： Bing Yu , Nirmala Ramanujam
发明人： Bing Yu , Nirmala Ramanujam
IPC分类号： G01J3/40 , G06F19/00 , G01J3/28
CPC分类号： G01J3/02 , G01J3/0218 , G01J3/28 , G01J2003/2866 , G01N21/274 , G01N21/474 , G01N21/49 , G01N2201/082
摘要： Systems and methods for performing optical spectroscopy using a self-calibrating fiber optic probe are disclosed. One self-calibrating fiber optic probe includes a sensing channel for transmitting illumination light to a specimen and for collecting spectral data of the specimen. The spectral data includes the illumination light diffusely reflected from the specimen at one or more wavelengths. The self-calibrating fiber optic probe may also include a calibration channel for transmitting calibration light. The calibration light and the illumination light are generated simultaneously from a common light source. The calibration channel collects calibration spectral data associated with the calibration light contemporaneously with the collection of the spectral data of the specimen.
摘要翻译：公开了使用自校准光纤探针执行光谱的系统和方法。一个自校准光纤探针包括用于将照明光传输到样本并用于收集样本的光谱数据的感测通道。光谱数据包括在一个或多个波长处从样本漫反射的照明光。自校准光纤探针还可以包括用于传送校准光的校准通道。校准光和照明光从公共光源同时产生。校准通道与样品的光谱数据的收集同时收集与校准光相关联的校准光谱数据。

10. 发明申请

US20070232932A1 Monte Carlo based model of fluorescence in turbid media and methods and systems for using same to determine intrinsic fluorescence of turbid media 有权
标题翻译：基于蒙特卡罗的浑浊介质中的荧光模型以及用于确定混浊介质的固有荧光的方法和系统
公开(公告)号：US20070232932A1
公开(公告)日：2007-10-04
申请号：US11725141
申请日：2007-03-16
申请人： Gregory Palmer , Nirmala Ramanujam
发明人： Gregory Palmer , Nirmala Ramanujam
IPC分类号： A61B6/00 , G01J3/30
CPC分类号： G01J3/4406 , A61B5/0071 , A61B5/0084 , G01N21/49 , G01N21/6486 , G01N2021/6417
摘要： The subject matter described herein includes a method for modeling fluorescence in turbid media and methods and systems for using the model to determine intrinsic fluorescence of turbid media. According to one aspect, a method for modeling fluorescence of a turbid medium and for using the model to determine intrinsic fluorescence in the turbid medium is provided. The method includes illuminating a turbid medium of interest with an electromagnetic radiation source using a probe of a particular geometry and detecting measured fluorescence for the turbid medium using the probe. At least one set of Monte Carlo simulations is run to determine an escape energy probability map and an absorbed energy density map for the turbid medium. An indication of the intrinsic fluorescence of the turbid medium is determined using the escape probability density map and the absorbed energy density map in a manner that accounts for the geometry of the probe.
摘要翻译：本文描述的主题包括用于对混浊介质中的荧光进行建模的方法以及使用该模型确定混浊介质的固有荧光的方法和系统。根据一个方面，提供了一种用于对浑浊介质的荧光进行建模和使用该模型来确定混浊介质中的固有荧光的方法。该方法包括使用特定几何形状的探针用电磁辐射源照射感兴趣的混浊介质，并使用探针检测浊度介质的测量荧光。运行至少一组蒙特卡罗模拟来确定浑浊介质的逃逸能量概率图和吸收的能量密度图。使用逃避概率密度图和吸收的能量密度图以考虑探针的几何形状的方式确定混浊介质的固有荧光的指示。

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