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公开(公告)号:US20190178867A1
公开(公告)日:2019-06-13
申请号:US16271525
申请日:2019-02-08
Applicant: Flagship Biosciences, Inc.
Inventor: Cris L Luengo Hendriks , Roberto Gianani
IPC: G01N33/483 , G01N1/30 , G01N33/52 , G01N21/64
Abstract: The present invention concerns detection of specific tissue objects within thin sections of tissue samples as imaged in a brightfield microscope, such as a predetermined type of immune cells, without using a chromogenic stain that is specific to those tissue objects. The invention uses fluorescent stain and fluorescence imaging to detect these tissue objects. By combining a brightfield and a fluorescence image of the same tissue sample, it is possible to automatically identify objects in the brightfield image that have been stained for in the fluorescence image. The fluorescence stain does not affect the appearance of the tissue sample under the brightfield microscope. Therefore, the invention is ideal to automate the collection of training data for machine learning systems that are to be trained to detect these specific tissue objects in brightfield images of tissue that has not been stained to specifically highlight these tissue objects.
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公开(公告)号:US20180040120A1
公开(公告)日:2018-02-08
申请号:US15220393
申请日:2016-07-27
Applicant: Flagship Biosciences, Inc.
Inventor: Crystal Dawn Faelan , Anthony J. Milici , Joshua C. Black , Nathan T. Martin
CPC classification number: G06T7/0012 , G01N1/30 , G01N33/6887 , G01N2333/4712 , G01N2800/10 , G06K9/0014 , G06K9/00147 , G06T11/60 , G06T2207/10024 , G06T2207/10056 , G06T2207/30024
Abstract: In accordance with the embodiment described herein, we describe a method for evaluating muscle fiber nuclei and non-muscle fiber mononuclear cells, and biomarkers expressed within these and muscle fibers, within the context of muscle tissue using digital tissue image analysis. An algorithm process is applied to histologically stained tissue sections to extract the morphometric, staining, and localization features of a plurality of tissue objects. These features can be further analyzed to describe relationships between tissue objects or tissue object image analysis features. One or more of these image analysis features or relationships between objects and features are summarized to derive a patient-specific score. Patient stratification criteria are applied to the patient-specific score and patient strata membership is evaluated to infer presence of disease, natural course of disease, disease severity, treatment efficacy, or response to a therapy and eligibility for said therapy.
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公开(公告)号:US20180011000A1
公开(公告)日:2018-01-11
申请号:US15696148
申请日:2017-09-05
Applicant: Flagship Biosciences, Inc.
Inventor: Anthony J. Milici , George David Young , Holger Lange , Joseph Krueger , Nathan T. Martin
CPC classification number: G06T7/0012 , G01N1/30 , G01N33/6887 , G01N2333/4712 , G01N2800/10 , G06K9/0014 , G06K9/00147 , G06T2207/10024 , G06T2207/10056 , G06T2207/10064 , G06T2207/30024
Abstract: The disclosure concerns a method for assessing muscular dystrophy-linked protein expression in muscle fibers using digital image analysis of tissue. The method relates to assessing disease severity in individuals with muscular dystrophy. Muscle tissue samples are obtained from patients submitted for evaluation and processed to produce tissue sections mounted on glass slides which have been stained for a muscular dystrophy-linked protein. Digital images of the stained tissue sections are generated and analyzed by applying an algorithm process implemented by a computer to the images. The algorithm process extracts the morphometric and staining features of the muscular dystrophy-linked protein staining in the tissue, and parameters relating to these features are used to score the disease status for each patient submitted for evaluation. The score of disease status is ultimately used to infer disease severity, monitor the efficacy of a therapeutic approach, or select patients as candidates for a therapeutic approach.
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公开(公告)号:US20170270660A1
公开(公告)日:2017-09-21
申请号:US15448550
申请日:2017-03-02
Applicant: Flagship Biosciences, Inc.
Inventor: Joseph Krueger , Nathan T. Martin
IPC: G06T7/00
Abstract: Staining of tissue by is a common approach utilized to visualize a gene product in tissue context. In certain applications, it is necessary to report a sum of events within the tissue as a specific function of the target tissue area, which is a sub-area of the total tissue, as a normalization factor for reporting the quantification. Here, we describe methods of determining target tissue area and reporting a quantification which is ratiometric to the target tissue area, utilizing computer algorithms. It is important to assign a value for the “target tissue area” in scenarios where a tissue area normalization factor needed in the most pathologically relevant fashion during the application of tissue image analysis. We have created methods for determining and reporting “target tissue area” as normalization factor which are useful in diagnostic applications utilizing image analysis.
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公开(公告)号:US20210343004A1
公开(公告)日:2021-11-04
申请号:US16862098
申请日:2020-04-29
Applicant: Flagship Biosciences, Inc.
Inventor: Cris L Luengo Hendriks , Joseph Krueger , Nathan T. Martin , Joshua C. Black
IPC: G06T7/00 , G16H50/30 , G06N20/00 , G01N33/53 , G01N33/483
Abstract: One type of tissue-based assay, the companion diagnostic (“CDx”) allows for the identification of individuals within a larger patient population who are more likely to respond to a therapy. The CDx paradigm typically applies to drugs that target a specific gene product or biologic pathway involving a gene product of interest. It is possible, especially for popular therapeutic targets, for multiple drugs and multiple associated CDx to be developed for a single gene product or biologic pathway involving the gene product. Currently, each of these similar CDx must be applied to identify the best therapy. The present invention can determine the outcome of one CDx using an image of a tissue section used for another CDx. Using a single tissue section and a single CDx, it becomes possible to obtain the outcome of multiple, related CDx.
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公开(公告)号:US10733732B2
公开(公告)日:2020-08-04
申请号:US16050907
申请日:2018-07-31
Applicant: Flagship Biosciences, Inc.
Inventor: Joseph Krueger , Allison S. Harney , Chris L. Luengo Hendriks
Abstract: In accordance with the embodiments herein, a method for displaying differences and similarities between tissue samples utilizing a reference database consisting of tissue images, image analysis features, and derived score from patient tissue samples assayed with a tissue-based test for the purpose of scoring said patient sample and guiding treatment based on said score. The method described herein utilizes digital image analysis of a tissue image of one or more tissue sections to extract features which generates a dataset mathematically representing the image. This dataset is then compared to the reference database to determine reference images with similar and different feature values. Those images are then displayed with the similar and different features highlighted.
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7.
公开(公告)号:US20170364664A1
公开(公告)日:2017-12-21
申请号:US15696159
申请日:2017-09-05
Applicant: Flagship Biosciences, Inc.
Inventor: Joshua Black , Carsten Schnatwinkel , Kristin Wilson , Nathan T. Martin , Joseph Krueger , Holger Lange
CPC classification number: G06F19/3481 , G06K9/00147 , G06K9/6277 , G06T7/0012 , G06T2207/20076 , G06T2207/20104 , G06T2207/30024
Abstract: The disclosure concerns a method for patient stratification and selection of patients who are candidates for a specific therapy is described which is based on quantifying one or more digital image analysis feature distributions from stained tissue. The method extends beyond the abilities of a manual observer and a microscope, and generally comprises: acquiring digital images of stained tissue sections from patients submitted for evaluation, applying an algorithm process to said images with a computer to extract the morphometric and staining features of image pixels and tissue objects, deriving one or more distribution function for one or more image analysis features, calculating a summary statistic of the one or more distribution functions, and using said summary statistic along with an associated predefined patient stratification paradigm to separate a patient cohort into distinct strata which correspond to a decision to include or exclude a patient for a specific therapy.
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公开(公告)号:US09725766B1
公开(公告)日:2017-08-08
申请号:US14588319
申请日:2014-12-31
Applicant: Flagship Biosciences, LLC
Inventor: Steven J. Potts
IPC: G06K9/00 , C12Q1/68 , G01N33/569
CPC classification number: G01N33/56966 , G01N33/5044 , G01N33/5064 , G01N33/56972 , G01N2800/7014 , G01N2800/7038 , G06K9/00127 , G06T7/0012 , G06T2207/10024 , G06T2207/10056 , G06T2207/30024 , G06T2207/30101
Abstract: The instant disclosure describes a method for measuring and reporting vascularity in a biological tissue sample. The method generally includes: within a digital image of a tissue section, (i) identifying endothelial cells, lymphatic cells, or a combination thereof; (ii) mapping one or more proximity regions, each of the proximity regions defining an area between detected vessels and a first distance outwardly therefrom; and (iii) calculating one or more of: a vessel proximity score or a hypoxia score, wherein the vessel proximity score relates a composition of objects within the proximity regions, and wherein the hypoxia score relates a composition of tissue within or outside of the proximity regions, respectively.
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公开(公告)号:US11568536B2
公开(公告)日:2023-01-31
申请号:US16862098
申请日:2020-04-29
Applicant: Flagship Biosciences, Inc.
Inventor: Cris L Luengo Hendriks , Joseph Krueger , Nathan T. Martin , Joshua C. Black
IPC: G06T7/00 , G16H50/30 , G06N20/00 , G01N33/483 , G01N33/53
Abstract: One type of tissue-based assay, the companion diagnostic (“CDx”) allows for the identification of individuals within a larger patient population who are more likely to respond to a therapy. The CDx paradigm typically applies to drugs that target a specific gene product or biologic pathway involving a gene product of interest. It is possible, especially for popular therapeutic targets, for multiple drugs and multiple associated CDx to be developed for a single gene product or biologic pathway involving the gene product. Currently, each of these similar CDx must be applied to identify the best therapy. The present invention can determine the outcome of one CDx using an image of a tissue section used for another CDx. Using a single tissue section and a single CDx, it becomes possible to obtain the outcome of multiple, related CDx.
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公开(公告)号:US20180089495A1
公开(公告)日:2018-03-29
申请号:US15828587
申请日:2017-12-01
Applicant: Flagship Biosciences, Inc.
Inventor: Joshua C. Black , Logan Jerome Cerkovnik , Allison S. Harney , Karen Ryall , Joseph Krueger
CPC classification number: G06K9/00134 , G06K9/0014 , G06K9/00147 , G06K9/46 , G06K9/52 , G06K2209/05 , G06T7/0012 , G06T7/11 , G06T2207/10024 , G06T2207/10056 , G06T2207/20076 , G06T2207/30024 , G06T2207/30096 , G16B45/00
Abstract: The disclosure concerns a method for extracting spatial distribution statistics from patient tissue samples assayed with a tissue-based test for the purpose of scoring the patient tissue samples and guiding treatment based on the score(s). The method described herein utilizes digital image analysis of an image of one or more tissue sections to extract object-based (e.g., cells) features. The object-based features within the image of the tissue section is further processed using one or more algorithm processes to extract sophisticated spatial distribution features of one or more object type or sub-type in the tissue. Statistics describing the spatial distribution features are summarized to generate a patient-specific diagnostic score, and this score can be evaluated to guide patient treatment decisions.
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