Abstract: Methods, systems, and apparatuses for detecting and describing heterogeneity in a cell sample are disclosed herein. A plurality of fields of view (FOV) are generated for one or more areas of interest (AOI) within an image of the cell sample are generated. Hyperspectral or multispectral data from each FOV is organized into an image stack containing one or more z-layers, with each z-layer containing intensity data for a single marker at each pixel in the FOV. A cluster analysis is applied to the image stacks, wherein the clustering algorithm groups pixels having a similar ratio of detectable marker intensity across layers of the z-axis, thereby generating a plurality of clusters having similar expression patterns.

Abstract: Systems and methods discussed herein include, among other things, a method comprising quantifying analyte staining of a biological compartment in a region in which said staining is intermixed with analyte staining of an analytically-distinct distinct biological compartment. Disclosed systems and methods include, for example, a system and method for identifying membrane staining of an analyte of interest in regions where diffuse membrane staining is intermixed with cytoplasmic staining and/or punctate staining is disclosed. Disclosed systems and methods include, for example, a system and method for quantifying membrane staining of an analyte of interest in tissue or cytological samples having regions in which membrane staining is intermixed with cytoplasmic staining and/or punctate staining.

Abstract: The subject disclosure presents systems and methods for improved meso-dissection of biological specimens and tissue slides including importing one or more reference slides with annotations, using inter-marker registration algorithms to automatically map the annotations to an image of a milling slide, and dissecting the annotated tissue from the selected regions in the milling slide for analysis, while concurrently tracking the data and analysis using unique identifiers such as bar codes.

Abstract: The subject disclosure presents systems and computer-implemented methods for automatic immune cell detection that is of assistance in clinical immune profile studies. The automatic immune cell detection method involves retrieving a plurality of image channels from a multi-channel image such as an RGB image or biologically meaningful unmixed image. A cell detector is trained to identify the immune cells by a convolutional neural network in one or multiple image channels. Further, the automatic immune cell detection algorithm involves utilizing a non-maximum suppression algorithm to obtain the immune cell coordinates from a probability map of immune cell presence possibility generated from the convolutional neural network classifier.

Abstract: The subject disclosure presents systems and methods for improved meso-dissection of biological specimens and tissue slides including importing one or more reference slides with annotations, using inter-marker registration algorithms to automatically map the annotations to an image of a milling slide, and dissecting the annotated tissue from the selected regions in the milling slide for analysis, while concurrently tracking the data and analysis using unique identifiers such as bar codes.

Abstract: A system and method of displaying of multiple simultaneous views of a same region of a biological tissue sample. Logical instructions are executed by a processor to perform operations such as receiving a plurality of images of the biological tissue sample, converting the plurality of images to a common reference frame based on the individual metadata of each image, and arranging the plurality of images into a display pattern for simultaneous viewing of different aspects of the imaged biological tissue sample on a display screen. The plurality of images is produced by preprocessing images of the biological tissue sample. Each image shows a view mode of a same region of the biological tissue sample, and each image contains metadata that describe spatial orientation, such as the translation, rotation, and magnification, of the image to bring the plurality of images to a common view.

Abstract: Methods, systems, and apparatuses for detecting and describing heterogeneity in a cell sample are disclosed herein. A plurality of fields of view (FOV) are generated for one or more areas of interest (AOI) within an image of the cell sample are generated. Hyperspectral or multispectral data from each FOV is organized into an image stack containing one or more z-layers, with each z-layer containing intensity data for a single marker at each pixel in the FOV. A cluster analysis is applied to the image stacks, wherein the clustering algorithm groups pixels having a similar ratio of detectable marker intensity across layers of the z-axis, thereby generating a plurality of clusters having similar expression patterns.

Abstract: Methods, systems, and apparatuses for detecting and describing heterogeneity in a cell sample are disclosed herein. A plurality of fields of view (FOV) are generated for one or more areas of interest (AOI) within an image of the cell sample are generated. Hyperspectral or multispectral data from each FOV is organized into an image stack containing one or more z-layers, with each z-layer containing intensity data for a single marker at each pixel in the FOV. A cluster analysis is applied to the image stacks, wherein the clustering algorithm groups pixels having a similar ratio of detectable marker intensity across layers of the z-axis, thereby generating a plurality of clusters having similar expression patterns.

Abstract: Methods and systems for generating a heat map that reduces bias in selecting FOVs are disclosed. Some disclosed methods include annotating a primary stained image, registering the annotation to a secondary serial specific stained image, using an image analysis algorithm to compute a scoring criteria specific to the tissue and assay type for tiled regions in the image, using a sliding window in the annotated tumor region to compute values for each pixel in a heat map which correlate to the specific scoring criteria, displaying the heat map at low resolution, ranking and selecting hot spots, selecting FOVs from the hot spot regions which results in displaying the slide-level score for the FOVs. The systems comprise, among other things, software configured to perform the referenced method.

Abstract: A method of segmenting images of biological specimens using adaptive classification to segment a biological specimen into different types of tissue regions. The segmentation is performed by, first, extracting features from the neighborhood of a grid of points (GPs) sampled on the whole-slide (WS) image and classifying them into different tissue types. Secondly, an adaptive classification procedure is performed where some or all of the GPs in a WS image are classified using a pre-built training database, and classification confidence scores for the GPs are generated. The classified GPs with high confidence scores are utilized to generate an adaptive training database, which is then used to re-classify the low confidence GPs. The motivation of the method is that the strong variation of tissue appearance makes the classification problem more challenging, while good classification results are obtained when the training and test data origin from the same slide.

Abstract: The subject disclosure presents systems and methods for improved meso-dissection of biological specimens and tissue slides including importing one or more reference slides with annotations, using inter-marker registration algorithms to automatically map the annotations to an image of a milling slide, and dissecting the annotated tissue from the selected regions in the milling slide for analysis, while concurrently tracking the data and analysis using unique identifiers such as bar codes.

Abstract: Systems and methods discussed herein include, among other things, a method comprising quantifying analyte staining of a biological compartment in a region in which said staining is intermixed with analyte staining of an analytically-distinct distinct biological compartment. Disclosed systems and methods include, for example, a system and method for identifying membrane staining of an analyte of interest in regions where diffuse membrane staining is intermixed with cytoplasmic staining and/or punctate staining is disclosed. Disclosed systems and methods include, for example, a system and method for quantifying membrane staining of an analyte of interest in tissue or cytological samples having regions in which membrane staining is intermixed with cytoplasmic staining and/or punctate staining.

Abstract: Automated systems and methods are presented for retrospectively analyzing clinical trial data. A plurality of image derived from biological samples of patients in a cohort population are accessed. Image features are computed based on the plurality of images. A diagnostic feature metric is derived based on the computed image features. A cut point value is determined by applying a statistical minimization method using the derived diagnostic feature metric and patient outcome data from the cohort population, in which the cut point value identifies a patient in the cohort population as positive or negative for a diagnostic test.

Abstract: The subject disclosure presents systems and computer-implemented methods for automatic immune cell detection that is of assistance in clinical immune profile studies. The automatic immune cell detection method involves retrieving a plurality of image channels from a multi-channel image such as an RGB image or biologically meaningful unmixed image. A cell detector is trained to identify the immune cells by a convolutional neural network in one or multiple image channels. Further, the automatic immune cell detection algorithm involves utilizing a non-maximum suppression algorithm to obtain the immune cell coordinates from a probability map of immune cell presence possibility generated from the convolutional neural network classifier.

Abstract: Described herein are methods for co-expression analysis of multiple markers in a tissue sample comprising: computing a heat map of marker expression for each of a plurality of single marker channel images, wherein each of the plurality of single marker channel images comprise a single marker; identifying one or more candidate regions of interest in each heat map of marker expression; computing overlay masks comprising the identified one or more candidate regions of interest from each heat map of marker expression; determining one or more co-localized regions of interest from the overlay masks; mapping the one or more co-localized regions of interest to a same coordinate position in each of the plurality of single marker channel images; and estimating a number of cells in at least one of the determined one or more co-localized regions of interest in each of the plurality of single marker channel images.

Abstract: Systems and methods for automated analysis of histochemical or cytological samples stained for analytes having complex staining patterns are presented. Analyte staining of a biological compartment in a region is quantified, in which said staining is intermixed with analyte staining of an analytically-distinct biological compartment. The systems and methods further include identifying membrane staining of an analyte of interest in regions where diffuse membrane staining is intermixed with cytoplasmic staining and/or punctate staining is disclosed. The systems and methods further include quantifying membrane staining of an analyte of interest in tissue or cytological samples having regions in which membrane staining is intermixed with cytoplasmic staining and/or punctate staining.

Abstract: Methods, systems, and apparatuses for detecting and describing heterogeneity in a cell sample are disclosed herein. A plurality of fields of view (FOV) are generated for one or more areas of interest (AOI) within an image of the cell sample are generated. Hyperspectral or multispectral data from each FOV is organized into an image stack containing one or more z-layers, with each z-layer containing intensity data for a single marker at each pixel in the FOV. A cluster analysis is applied to the image stacks, wherein the clustering algorithm groups pixels having a similar ratio of detectable marker intensity across layers of the z-axis, thereby generating a plurality of clusters having similar expression patterns.

Abstract: The subject disclosure presents systems and computer-implemented methods for automatic immune cell detection that is of assistance in clinical immune profile studies. The automatic immune cell detection method involves retrieving a plurality of image channels from a multi-channel image such as an RGB image or biologically meaningful unmixed image. A cell detector is trained to identify the immune cells by a convolutional neural network in one or multiple image channels. Further, the automatic immune cell detection algorithm involves utilizing a non-maximum suppression algorithm to obtain the immune cell coordinates from a probability map of immune cell presence possibility generated from the convolutional neural network classifier.

Abstract: Methods, systems, and apparatuses for detecting and describing heterogeneity in a cell sample are disclosed herein. A plurality of fields of view (FOV) are generated for one or more areas of interest (AOI) within an image of the cell sample are generated. Hyperspectral or multispectral data from each FOV is organized into an image stack containing one or more z-layers, with each z-layer containing intensity data for a single marker at each pixel in the FOV. A cluster analysis is applied to the image stacks, wherein the clustering algorithm groups pixels having a similar ratio of detectable marker intensity across layers of the z-axis, thereby generating a plurality of clusters having similar expression patterns.

Abstract: A system and method of displaying of multiple simultaneous views of a same region of a biological tissue sample. Logical instructions are executed by a processor to perform operations such as receiving a plurality of images of the biological tissue sample, converting the plurality of images to a common reference frame based on the individual metadata of each image, and arranging the plurality of images into a display pattern for simultaneous viewing of different aspects of the imaged biological tissue sample on a display screen. The plurality of images is produced by preprocessing images of the biological tissue sample. Each image shows a view mode of a same region of the biological tissue sample, and each image contains metadata that describe spatial orientation, such as the translation, rotation, and magnification, of the image to bring the plurality of images to a common view.