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1. 发明申请

WO2011046807A3 MULTI-MODALITY CONTRAST AND BRIGHTFIELD CONTEXT RENDERING FOR ENHANCED PATHOLOGY DETERMINATION AND MULTI-ANALYTE DETECTION IN TISSUE 审中-公开
标题翻译：多模式对比度和亮度上下文呈现用于增强病理学确定和组织多分析检测
公开(公告)号：WO2011046807A3
公开(公告)日：2011-09-01
申请号：PCT/US2010051857
申请日：2010-10-07
申请人： VENTANA MED SYST INC , GARSHA KARL , PESTANO GARY , OTTER MICHAEL , NAGY ALEXANDRA DEA , NAGLE RAY B , MILLER PHILLIP , FROEHLICH JAN , DAY WILLIAM
发明人： GARSHA KARL , PESTANO GARY , OTTER MICHAEL , NAGY ALEXANDRA DEA , NAGLE RAY B , MILLER PHILLIP , FROEHLICH JAN , DAY WILLIAM
IPC分类号： G01N33/483
CPC分类号： G01N21/6456
摘要： Multiple modality contrast can be used to produce images that can be combined and rendered to produce images similar to those produced with wavelength absorbing stains viewed under transmitted white light illumination. Images obtained with other complementary contrast modalities can be presented using engineered color schemes based on classical contrast methods used to reveal the same anatomical structures and histochemistry, thereby providing relevance to medical training and experience. Dark-field contrast images derived from refractive index and fluorescent DAPI counterstain images are combined to produce images similar to those obtained with conventional H&E staining for pathology interpretation. Such multi-modal image data can be streamed for live navigation of histological samples, and can be combined with molecular localizations of genetic DNA probes (FISH), sites of mRNA expression (mRNA-ISH), and immunohistochemical (IHC) probes localized on the same tissue sections, used to evaluate and map tissue sections prepared for imaging mass spectrometry.
摘要翻译：可以使用多种形式的对比度来产生可以组合和渲染的图像，以产生与在透射白光照明下观察到的吸收波长的污渍产生的图像类似的图像。用其他互补对比方式获得的图像可以使用基于经典对比方法的工程颜色方案来呈现，该方法用于揭示相同的解剖结构和组织化学，从而提供与医学训练和经验的相关性。将来自折射率和荧光DAPI复染图像的暗场对比图像组合以产生与用常规H＆E染色获得的用于病理解释的图像相似的图像。这种多模式图像数据可以流式传输组织样本的实时导航，并且可以与基因DNA探针（FISH），mRNA表达位点（mRNA-ISH）和免疫组织化学（IHC）探针位于相同的组织切片，用于评估和映射为成像质谱准备的组织切片。

2. 发明申请

WO2012152747A3 SPECTRAL IMAGING FOR MEASUREMENT OF NUCLEAR PATHOLOGY FEATURES IN CANCER CELLS PREPARED FOR IN SITU ANALYSIS 审中-公开
标题翻译：用于测量原位分析中准备的癌细胞中核型病理特征的光谱成像
公开(公告)号：WO2012152747A3
公开(公告)日：2013-01-24
申请号：PCT/EP2012058356
申请日：2012-05-07
申请人： VENTANA MED SYST INC , HOFFMANN LA ROCHE , UNIV CORNELL , DEMICHELIS FRANCESCA , GARSHA KARL , MILLER PHILLIP C , NAGLE RAY B , OTTER MICHAEL , PESTANO GARY ANTHONY , RUBIN MARK A
发明人： DEMICHELIS FRANCESCA , GARSHA KARL , MILLER PHILLIP C , NAGLE RAY B , OTTER MICHAEL , PESTANO GARY ANTHONY , RUBIN MARK A
IPC分类号： C12Q1/68 , G01N33/574
CPC分类号： G01N33/57407 , C12Q1/6841 , C12Q1/6886 , C12Q2600/156
摘要： In general, the presently disclosed technology relates to identification of cancer subtypes. More specifically, the technology relates to methods for determining molecular drivers of cancer and/or progression using a multivariate image data and statistical analysis of in-situ molecular markers and morphological characteristics in the same cells of a biological sample suspected of cancer. This analysis takes place after a single acquisition that obtains the molecular and anatomic morphology data in parallel. The analysis compares specific morphological and molecular markers to known samples exhibiting particular genetic drivers of the cancer. This method provides statistical information that allows for an increased confidence in the identification of specific molecular drivers of the cancer.
摘要翻译：一般来说，目前公开的技术涉及癌症亚型的鉴定。更具体地说，该技术涉及使用多变量图像数据确定癌症和/或进展的分子驱动因素的方法，以及在怀疑患有癌症的生物样品的相同细胞中的原位分子标记物和形态特征的统计分析。这种分析是在单次采集后并行获得分子和解剖形态数据进行的。该分析将特定的形态学和分子标记与展示癌症的特定遗传驱动因子的已知样品进行比较。该方法提供统计信息，可以增加对癌症特异性分子驱动因子的识别的信心。

3. 发明申请

WO2014118326A3 SYSTEMS AND METHODS FOR CALIBRATING, CONFIGURING AND VALIDATING AN IMAGING DEVICE OR SYSTEM FOR MULTIPLEX TISSUE ASSAYS 审中-公开
标题翻译：用于多组织组织测定的成像装置或系统的校准，配置和验证的系统和方法
公开(公告)号：WO2014118326A3
公开(公告)日：2014-12-04
申请号：PCT/EP2014051920
申请日：2014-01-31
申请人： VENTANA MED SYST INC , HOFFMANN LA ROCHE
发明人： GARSHA KARL , OTTER MICHAEL , PESTANO GARY ANTHONY , VENTURA FRANK
IPC分类号： G01J3/28 , G01J3/10 , G01J3/44 , G01N21/27 , G02B21/36
CPC分类号： G01J3/0297 , G01J3/10 , G01J3/28 , G01J3/2823 , G01J3/44 , G01J3/4406 , G01J2003/2826 , G01N21/274 , G02B21/365 , G06K9/0014 , G06T7/80
摘要： A system and method for characterization and/or calibration of performance of a multispectral imaging (MSI) system equipping the MSI system for use with a multitude of different fluorescent specimens while being independent on optical characteristics of a specified specimen and providing an integrated system level test for the MSI system. A system and method are adapted to additionally evaluate and express operational parameters performance of the MSI system in terms of standardized units and/or to determine the acceptable detection range of the MSI system.
摘要翻译：用于表征和/或校准多光谱成像（MSI）系统的性能的系统和方法，其将MSI系统配备成与多种不同荧光样品一起使用，同时独立于指定样品的光学特性并提供集成的系统水平测试为MSI系统。一种系统和方法适于在标准化单元方面另外评估和表达MSI系统的操作参数性能和/或确定MSI系统的可接受检测范围。

4. 发明申请

WO2016189065A8 METHOD AND SYSTEM FOR ASSESSING STAIN QUALITY FOR IN-SITU HYBRIDIZATION AND IMMUNOHISTOCHEMISTRY 审中-公开
标题翻译：评估原位杂交和免疫组织化学质量的方法和系统
公开(公告)号：WO2016189065A8
公开(公告)日：2017-04-27
申请号：PCT/EP2016061859
申请日：2016-05-25
申请人： VENTANA MED SYST INC , F HOFFMANN-LA ROCHE AG
发明人： GARSHA KARL , OTTER MICHAEL , STEVENS BENJAMIN , TAFT JEFFERSON , VENTURA FRANK
IPC分类号： G06K9/00 , G01N1/30
CPC分类号： G06K9/00127 , G01N1/30
摘要： Immunohistochemistry (IHC) and in situ hybridization (ISH) have the aim of detecting, localizing and quantifying certain analytes for various diagnostic purposes. The quality of the stains which are analyzed may deviate for various reasons. Therefore, the present invention provides a method and system for assessing the stain quality and for establishing objective criteria for assessing the stain quality for application in the fields of in-situ hybridization and immunohistochemistry. In one possible embodiment, the invention comprises the steps of unmixing multi-spectral image data of a tissue specimen to obtain analyte intensity images, each analyte intensity image comprising signals from a single stain, computing metrics based on the analyte intensity images, wherein the metrics are uniformity, distribution and/or dispersion of pixel intensity values in the analyte intensity images and assessing a stain quality of a slide by comparing the computed metrics to pre-determined cutoff values regarding uniformity, distribution and/or dispersion of pixel intensity, wherein the stain quality of the slide is assessed as acceptable if the computed metrics meet or exceed the pre-determined cutoff values, and wherein the stain quality of the slide is assessed as unacceptable if the computed metrics do not meet the pre-determined cutoff values. In order to establish objective criteria for assessing stain quality, in one possible embodiment, the method and system includes the step of deriving cut-off values for uniformity, distribution and/or dispersion of pixel intensity by combining the computed metrics based on the analyte intensity images with pre-established data quantifying the stain quality.
摘要翻译：免疫组织化学（IHC）和原位杂交（ISH）具有检测，定位和定量某些分析物用于各种诊断目的的目的。由于各种原因，分析的污渍质量可能会有所偏差。因此，本发明提供了用于评估染色质量和建立用于评估染色质量的客观标准以用于原位杂交和免疫组织化学领域的方法和系统。在一个可能的实施例中，本发明包括以下步骤：将组织样本的多光谱图像数据解混以获得分析物强度图像，每个分析物强度图像包括来自单一染色物的信号，基于分析物强度图像计算度量，其中度量是分析物强度图像中的像素强度值的均匀性，分布和/或分散，并通过将计算出的度量与关于像素强度的均匀性，分布和/或分散的预定截止值进行比较来评估载玻片的染色质量，其中如果所计算的度量达到或超过预定的截断值，则将该载玻片的污点质量评估为可接受的，并且如果所计算的度量不满足预定的截断值，则将该载玻片的污点质量评估为不可接受。为了建立评估污渍质量的客观标准，在一个可能的实施例中，该方法和系统包括通过组合基于分析物强度计算的度量来获得像素强度的均匀性，分布和/或分散的截止值的步骤具有量化污渍质量的预先建立的数据的图像。

5. 发明申请

WO2014118326A9 SYSTEMS AND METHODS FOR CALIBRATING, CONFIGURING AND VALIDATING AN IMAGING DEVICE OR SYSTEM FOR MULTIPLEX TISSUE ASSAYS 审中-公开
标题翻译：用于校准，配置和验证用于多组织分析的成像装置或系统的系统和方法
公开(公告)号：WO2014118326A9
公开(公告)日：2014-10-16
申请号：PCT/EP2014051920
申请日：2014-01-31
申请人： VENTANA MED SYST INC , HOFFMANN LA ROCHE
发明人： GARSHA KARL , OTTER MICHAEL , PESTANO GARY ANTHONY , VENTURA FRANK
IPC分类号： G01J3/28
CPC分类号： G01J3/0297 , G01J3/10 , G01J3/28 , G01J3/2823 , G01J3/44 , G01J3/4406 , G01J2003/2826 , G01N21/274 , G02B21/365 , G06K9/0014 , G06T7/80
摘要： A system and method for characterization and/or calibration of performance of a multispectral imaging (MSI) system equipping the MSI system for use with a multitude of different fluorescent specimens while being independent on optical characteristics of a specified specimen and providing an integrated system level test for the MSI system. A system and method are adapted to additionally evaluate and express operational parameters performance of the MSI system in terms of standardized units and/or to determine the acceptable detection range of the MSI system.
摘要翻译：一种用于多光谱成像（MSI）系统的性能表征和/或校准的系统和方法，所述系统和方法使MSI系统与多种不同的荧光样本一起使用，同时独立于指定样本的光学特性并提供集成系统级测试为MSI系统。系统和方法适于根据标准化单元额外评估和表达MSI系统的操作参数性能和/或确定MSI系统的可接受检测范围。

6. 发明公开

EP2678446A4 PRESENCE OF ERG GENE REARRANGEMENTS AND PROTEIN OVER-EXPRESSION IN LOW GRADE PIN (LG-PIN) IN PROSTATE BIOPSIES 有权
标题翻译：天IT ON ON ON EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN EN
公开(公告)号：EP2678446A4
公开(公告)日：2015-07-15
申请号：EP12749229
申请日：2012-02-24
申请人： VENTANA MED SYST INC
发明人： PESTANO GARY , NAGLE RAY , SATHYANARAYANA UBARADKA , NAGY ALEXANDRA DEA , CORTEZ CONNIE , GARSHA KARL , DITTAMORE RYAN
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q1/6841 , C12Q2600/156 , G01N33/57434 , G01N2333/4703

7. 发明公开

EP2488860A4 MULTI-MODALITY CONTRAST AND BRIGHTFIELD CONTEXT RENDERING FOR ENHANCED PATHOLOGY DETERMINATION AND MULTI-ANALYTE DETECTION IN TISSUE 审中-公开
标题翻译： MULTIMODALITÄTSKONTRAST和增强的病理学测定的BREITFELD背景和MEHRANALYTERKENNUNG组织
公开(公告)号：EP2488860A4
公开(公告)日：2015-12-16
申请号：EP10823858
申请日：2010-10-07
申请人： VENTANA MED SYST INC
发明人： GARSHA KARL , PESTANO GARY , OTTER MICHAEL , NAGY ALEXANDRA DEA , NAGLE RAY B , MILLER PHILLIP , FROEHLICH JAN , DAY WILLIAM
IPC分类号： G01N33/483 , G01N21/64
CPC分类号： G01N21/6456

8. 发明专利

CA2896197C SYSTEMS AND METHODS FOR CALIBRATING, CONFIGURING AND VALIDATING AN IMAGING DEVICE OR SYSTEM FOR MULTIPLEX TISSUE ASSAYS 未知
公开(公告)号：CA2896197C
公开(公告)日：2019-10-15
申请号：CA2896197
申请日：2014-01-31
申请人： VENTANA MED SYST INC
发明人： GARSHA KARL , OTTER MICHAEL
IPC分类号： G01J3/28 , G01J3/10 , G01J3/44 , G01N21/27 , G02B21/36
摘要： A system and method for characterization and/or calibration of performance of a multispectral imaging (MSI) system equipping the MSI system for use with a multitude of different fluorescent specimens while being independent on optical characteristics of a specified specimen and providing an integrated system level test for the MSI system. A system and method are adapted to additionally evaluate and express operational parameters performance of the MSI system in terms of standardized units and/or to determine the acceptable detection range of the MSI system.

9. 发明专利

AU2016269085A1 Method and system for assessing stain quality for in-situ hybridization and immunohistochemistry 未知
公开(公告)号：AU2016269085A1
公开(公告)日：2017-10-12
申请号：AU2016269085
申请日：2016-05-25
申请人： VENTANA MED SYST INC
发明人： GARSHA KARL , OTTER MICHAEL , STEVENS BENJAMIN , TAFT JEFFERSON , VENTURA FRANK
IPC分类号： G06K9/00 , G01N1/30
摘要： Immunohistochemistry (IHC) and in situ hybridization (ISH) have the aim of detecting, localizing and quantifying certain analytes for various diagnostic purposes. The quality of the stains which are analyzed may deviate for various reasons. Therefore, the present invention provides a method and system for assessing the stain quality and for establishing objective criteria for assessing the stain quality for application in the fields of in-situ hybridization and immunohistochemistry. In one possible embodiment, the invention comprises the steps of unmixing multi-spectral image data of a tissue specimen to obtain analyte intensity images, each analyte intensity image comprising signals from a single stain, computing metrics based on the analyte intensity images, wherein the metrics are uniformity, distribution and/or dispersion of pixel intensity values in the analyte intensity images and assessing a stain quality of a slide by comparing the computed metrics to pre-determined cutoff values regarding uniformity, distribution and/or dispersion of pixel intensity, wherein the stain quality of the slide is assessed as acceptable if the computed metrics meet or exceed the pre-determined cutoff values, and wherein the stain quality of the slide is assessed as unacceptable if the computed metrics do not meet the pre-determined cutoff values. In order to establish objective criteria for assessing stain quality, in one possible embodiment, the method and system includes the step of deriving cut-off values for uniformity, distribution and/or dispersion of pixel intensity by combining the computed metrics based on the analyte intensity images with pre-established data quantifying the stain quality.

10. 发明专利

CA2774422C MULTI-MODALITY CONTRAST AND BRIGHTFIELD CONTEXT RENDERING FOR ENHANCED PATHOLOGY DETERMINATION AND MULTI-ANALYTE DETECTION IN TISSUE 未知
公开(公告)号：CA2774422C
公开(公告)日：2017-08-29
申请号：CA2774422
申请日：2010-10-07
申请人： VENTANA MED SYST INC
发明人： GARSHA KARL , PESTANO GARY , OTTER MICHAEL , NAGY ALEXANDRA DEA , NAGLE RAY B , MILLER PHILLIP , FROEHLICH JAN , DAY WILLIAM
IPC分类号： G01N33/483
摘要： Multiple modality contrast can be used to produce images that can be combined and rendered to produce images similar to those produced with wavelength absorbing stains viewed under transmitted white light illumination. Images obtained with other complementary contrast modalities can be presented using engineered color schemes based on classical contrast methods used to reveal the same anatomical structures and histochemistry, thereby providing relevance to medical training and experience. Dark-field contrast images derived from refractive index and fluorescent DAPI counterstain images are combined to produce images similar to those obtained with conventional H&E staining for pathology interpretation. Such multi-modal image data can be streamed for live navigation of histological samples, and can be combined with molecular localizations of genetic DNA probes (FISH), sites of mRNA expression (mRNA-ISH), and immunohistochemical (IHC) probes localized on the same tissue sections, used to evaluate and map tissue sections prepared for imaging mass spectrometry.

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