公开(公告)号：WO2019074491A1

公开(公告)日：2019-04-18

申请号：PCT/US2017/055918

申请日：2017-10-10

Applicant: FLAGSHIP BIOSCIENCES, INC.

Inventor： BLACK, Joshua ,  SCHNATWINKEL, Carsten ,  WILSON, Kristen ,  MARTIN, Nathan T. ,  KRUEGER, Joseph ,  LANGE, Holger

IPC: G01N33/50 ,  G01N33/567 ,  G06F19/26 ,  G06K9/34 ,  G06T1/00 ,  G06T7/00

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.

公开(公告)号：WO2019009893A1

公开(公告)日：2019-01-10

申请号：PCT/US2017/040777

申请日：2017-07-05

Applicant: FLAGSHIP BIOSCIENCES INC.

Inventor： POTTS, Steven J.

IPC: G01N33/569 ,  G06K9/00 ,  C12Q1/68

CPC classification number: G01N33/574 ,  C12Q1/6841 ,  G01N1/30 ,  G01N33/543 ,  G01N33/569 ,  G01N2800/7014 ,  G01N2800/7038 ,  G06K9/00147

Abstract: The disclosure concerns 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.

公开(公告)号：WO2018009202A1

公开(公告)日：2018-01-11

申请号：PCT/US2016/041373

申请日：2016-07-07

Applicant: FLAGSHIP BIOSCIENCES INC.

Inventor： LANGE, Holger

IPC: G06K9/00

CPC classification number: G06K9/6227 ,  G06K9/00147

Abstract: A method for a continuous scoring scheme used for the assessment of biomarker expressions in the analysis of tissue sections, and digital images thereof, is based on cell classifications.

Abstract translation: 在分析组织切片及其数字图像时用于评估生物标志物表达的连续评分方法的方法基于细胞分类。

公开(公告)号：WO2019108230A1

公开(公告)日：2019-06-06

申请号：PCT/US2017/064276

申请日：2017-12-01

Applicant: FLAGSHIP BIOSCIENCES INC.

Inventor： BLACK, Joshua C. ,  CERKOVNIK, Logan Jerome ,  HARNEY, Allison S. ,  RYALL, Karen ,  KRUEGER, Joseph

IPC: G06K9/00 ,  G06T7/00

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.

公开(公告)号：WO2018017097A1

公开(公告)日：2018-01-25

申请号：PCT/US2016/043318

申请日：2016-07-21

Applicant: FLAGSHIP BIOSCIENCES INC.

Inventor： LANGE, Holger ,  KRUEGER, Joseph ,  YOUNG, George David ,  JOHNSON, Trevor ,  VOELKER, Frank

IPC: G06E1/00

CPC classification number: G06T7/0012 ,  G06F16/583 ,  G06K9/0014 ,  G06K9/00147 ,  G06N20/00 ,  G06T7/70 ,  G06T2207/10056 ,  G06T2207/20081 ,  G06T2207/20104 ,  G06T2207/30024 ,  G06T2207/30096 ,  G16H30/40

Abstract: Systems and methods relating to a cell-based pattern recognition tool for microscopy images from tissue sections are described, wherein cell features are extracted and a classifier is built in accordance with a particular application using an interactive training tied to a computerized platform, the result is an application-specific classifier that further processes images in accordance with the specific application, thereby tuning an automated process for cell based pattern recognition.

Abstract translation: 描述了与来自组织切片的显微镜图像的基于细胞的模式识别工具相关的系统和方法，其中提取细胞特征并且使用绑定到计算机化平台的交互式训练根据特定应用建立分类器，结果是 根据特定应用程序进一步处理图像的应用程序特定分类器，从而调整基于单元格模式识别的自动化过程。

公开(公告)号：WO2017171720A1

公开(公告)日：2017-10-05

申请号：PCT/US2016/024598

申请日：2016-03-29

Applicant: FLAGSHIP BIOSCIENCES, INC.

Inventor： PELJTO, Mirza ,  MILICI, Anthony J. ,  LANGE, Holger ,  KRUEGER, Joseph ,  AEFFNER, Famke ,  YOUNG, George David

IPC: G01N33/567 ,  G01N33/50 ,  G06K9/34 ,  G06F19/26 ,  G06T1/00

CPC classification number: G06K9/00147 ,  G06K9/0014 ,  G06T7/0012 ,  G06T2207/10024 ,  G06T2207/10056 ,  G06T2207/30024 ,  G16B45/00

Abstract: This disclosure concerns methods for evaluating inflammatory cells and modulators of the inflammatory response in tumor tissue and other relevant tissue types. The methods entail: obtaining a tissue sample and processing said tissue sample to produce histologic slides of tissue sections; staining of the tissue sections to identify inflammatory cells and modulators of the inflammatory response; digitizing slides to produce an image of the stained tissue sections; digitally stratifying the tissue sample into tumor and other relevant tissue compartments; and using digital image analysis to quantify cell-based and cell population-based features. The quantification of cell-based and cell population-based features within a tissue compartment of interest is used to develop a summary score of the immune system-tissue compartment of interest interaction. Patient stratification and selection as candidates for a therapeutic approach is ultimately based on the summary score value.

Abstract translation: 本公开涉及用于评估肿瘤组织和其他相关组织类型中炎性细胞和炎性应答调节剂的方法。 该方法需要：获得组织样本并处理所述组织样本以产生组织切片的组织切片; 对组织切片进行染色以鉴定炎性细胞和炎性应答的调节剂; 数字化幻灯片以产生染色组织切片的图像; 将组织样本数字分层到肿瘤和其他相关组织区室中; 并使用数字图像分析来量化基于细胞和细胞群体的特征。 定量感兴趣组织区间内的基于细胞和细胞群体的特征被用于开发免疫系统 - 感兴趣相互作用的组织区间的总结评分。 患者分层和选择作为治疗方案的候选者最终基于总分值。

公开(公告)号：WO2017151989A1

公开(公告)日：2017-09-08

申请号：PCT/US2017/020546

申请日：2017-03-02

Applicant: FLAGSHIP BIOSCIENCES, INC.

Inventor： KRUEGER, Joseph ,  MARTIN, Nathan

IPC: G01N33/48 ,  G06K9/20 ,  G06T7/40

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.

Abstract translation: 组织染色是用于在组织背景下显现基因产物的常用方法。 在某些应用中，有必要将组织内的事件总和报告为靶组织区域的特定功能，该组织区域是整个组织的子区域，作为用于报告定量的标准化因子。 在这里，我们描述了确定目标组织区域并利用计算机算法报告与目标组织区域成比例的量化的方法。 为“目标组织区域”分配值是很重要的。 在应用组织图像分析期间以最大病理学相关方式需要组织区域归一化因子的情况下。 我们已经创建了用于确定和报告“目标组织区域”的方法。 作为归一化因子，在利用图像分析的诊断应用中是有用的。