Systems and methods described herein relate, among other things, to unmixing more than three stains, while preserving the biological constraints of the biomarkers. Unlimited numbers of markers may be unmixed from a limited-channel image, such as an RGB image, without adding any mathematical complicity to the model. Known co-localization information of different biomarkers within the same tissue section enables defining fixed upper bounds for the number of stains at one pixel. A group sparsity model may be leveraged to explicitly model the fractions of stain contributions from the co-localized biomarkers into one group to yield a least squares solution within the group. A sparse solution may be obtained among the groups to ensure that only a small number of groups with a total number of stains being less than the upper bound are activated.
Techniques for obtaining a synthetic histochemically stained image from a multiplexed immunofluorescence (MPX) image may include producing an N-channel input image that is based on information from each of M channels of an MPX image of a tissue section, where M and N are positive integers and N is less than or equal to M; and generating a synthetic image by processing the N-channel input image using a generator network, the generator network having been trained using a training data set that includes a plurality of pairs of images. The synthetic image depicts a tissue section stained with at least one histochemical stain. Each pair of images of the plurality of pairs of images includes an N-channel image, produced from an MPX image of a first section of a tissue, and an image of a second section of the tissue stained with the at least one histochemical stain.
The present disclosure is directed to a computer system designed to (i) receive a series of images as input; (ii) compute a number of metrics derived from focus features and color separation features within the images; and (iii) evaluate the metrics to return (a) an identification of the most suitable z-layer in a z-stack, given a series of z-layer images in a z-stack; and/or (b) an identification of those image tiles that are more suitable for cellular based scoring by a medical professional, given a series of image tiles from an area of interest of a whole slide scan.
A method includes accessing a digital pathology image that depicts tumor cells sampled from a subject. A plurality of patches may be selected from the digital pathology image, wherein each of the patches depicts tumor cells. A mutation prediction may be generated for each of the patches, wherein the mutation prediction represents a prediction of a likelihood that an actionable mutation appears in the patch. Based on the plurality of mutation predictions, a prognostic prediction related to one or more treatment regimens for the subject may be generated. The prognostic prediction may be based on determining one or more mutational contexts of the digital pathology image as an unknown driver or a tumor suppressor, an oncogene driver mutation, or a gene fusion.
G16H 20/00 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
A slide carrier includes: a base support; and a slide platform having a surface that is parallel to a first plane defined by a first vector and a second vector, wherein a vector extending in a direction opposite to the direction of gravity is normal with respect to a second plane defined by a third vector and a fourth vector, an angle between the first vector and the third vector is greater than zero degrees and less than 90 degrees, and an angle between the second vector and the fourth vector is greater than zero degrees and less than 90 degrees.
An automated specimen processing system is provided for performing slide processing operations on slides bearing biological samples. In some embodiments, the disclosed specimen processing system includes a barcode reader having a heated window. In some embodiments, the barcode reader having the heated window is configured to read information stored within a label affixed to a slide, whereby the barcode reader may be operated within a hot and/or humid environment. A method for automated processing of slides also is provided, whereby the method utilizes the information retrieved from a label affixed to determine which one or more slide processing operations to perform.
Single-stranded oligonucleotide probes, systems, kits and methods for chromosome enumeration, gene copy enumeration, or tissue diagnostics. The probes are particularly suited for detecting gene amplification, deletion, or rearrangement in tissue samples in a single, dual, or multiplexed assay. The probes exhibit improved performance compared to industry leading dual-stranded probes; particularly in terms of the rate of hybridization.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
The present disclosure provides a method of separating cellular particles from a tissue sample and then sorting the cellular particles into two or more cellular particle populations.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
Techniques for image segmentation of a digital pathology image may include accessing an input image that depicts a section of a tissue; and generating a segmentation image by processing the input image using a generator network, the generator network having been trained using a data set that includes a plurality of pairs of images. The segmentation image indicates, for each of a plurality of artifact regions of the input image, a boundary of the artifact region. At least one of the plurality of artifact regions depicts an anomaly that is not a structure of the tissue. Each pair of images of the plurality of pairs includes a first image of a section of a tissue, the first image including at least one artifact region, and a second image that indicates, for each of the at least one artifact region of the first image, a boundary of the artifact region.
The present disclosure is directed, among other things, to automated systems and methods for analyzing, storing, and/or retrieving information associated with biological objects including lymphocytes. In some embodiments, a shape metric is derived for each detected and segmented lymphocyte and the shape metric is stored along with other relevant data.
The present disclosure provides systems and methods which facilitate the prediction of an estimated time in which one or more fluids will optimally be diffused into a biological specimen, e.g., a tissue sample derived from a human subject. In some embodiments, the present disclosure provides systems and methods which facilitate the prediction of an estimated time until a biological specimen will optimally be fixed with one or more fixatives. In other embodiments, the prediction of a future time at which the biological specimen will be optimally fixed is based on time-of-flight data acquired at a particular point in time during the fixation of the biological specimen that has been deemed sufficiently accurate to predict the time at which the biological specimen will be optimally diffused with fixative.
Systems and methods relate to predicting disease progression by processing digital pathology images using neural networks. A digital pathology image that depicts a specimen stained with one or more stains is accessed. The specimen may have been collected from a subject. A set of patches are defined for the digital pathology image. Each patch of the set of patches depicts a portion of the digital pathology image. For each patch of the set of patches and using an attention-score neural network, an attention score is generated. The attention-score neural network may have been trained using a loss function that penalized attention-score variability across patches in training digital pathology images labeled to indicate no or low subsequent disease progression. Using a result-prediction neural network and the attention scores, a result is generated that represents a prediction of whether or an extent to which a disease of the subject will progress.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
Methods for in situ detecting proximity of two targets of interest featuring an antibody conjugated with a cleavable bridge component having a detectable moiety and an antibody conjugated with a non-cleavable bridge component. The bridge components each have a chemical ligation group adapted to form a covalent bond under particular conditions and when the targets are in close proximity. Following covalent bond formation, the cleavable bridge component can be cleaved from the antibody, effectively transferring the detectable moiety to the non-cleavable bridge component. Detection of the detectable moiety is indicative of the targets being in close proximity. The methods are compatible with both chromogenic and fluorogenic detection systems. The methods may be used to perform assays wherein one or more than one proximity event is detected on the same slide.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
G01N 33/542 - Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
G01N 33/543 - Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
14.
OPTIMIZED DATA PROCESSING FOR MEDICAL IMAGE ANALYSIS
A method for analyzing an image of a tissue section may include obtaining a plurality of image locations, each corresponding to a different one of a plurality of biological structures; obtaining a plurality of locations of a first biomarker in the image; and calculating a distance transform array for at least a portion of the image that includes the plurality of seed locations. The method may include, for each of the plurality of seed locations and based on information from the first distance transform array, detecting whether the first biomarker is expressed at the seed location, and storing, to a data structure associated with the seed location, an indication of whether expression of the first biomarker at the seed location was detected. The method may include detecting, based on the stored indications, co-localization of at least two phenotypes in at least a portion of the tissue section.
Disclosed are systems and methods for labelling one or more morphological markers in a biological sample that are characteristic of one or more molecular features. In particular, system and methods are described for labelling one or more morphological markers in a biological sample with covalently deposited narrow band detectable moieties. Narrow band detectable moiety labelling of the one or more morphological markers permits higher order multiplexed assays due to conservation of available spectral bandwidth. Furthermore, as compared to conventional counterstaining methods, covalent deposition of one or more detectable moieties can provide flexibility and robustness with regard to the order in which biomarkers and morphological markers are labeled in a given staining protocol.
The present disclosure relates to techniques for obtaining a synthetic immunohistochemistry (IHC) image from a histochemically stained image. Particularly, aspects of the present disclosure are directed to accessing an input image that depicts a tissue section that has been stained with at least one histochemical stain; generating a synthetic image by processing the input image using a trained generator network; and outputting the synthetic image. The synthetic image depicts a tissue section that has been stained with at least one IHC stain that targets a first antigen, and techniques may also include receiving an input that is based on a level of expression of a first antigen from the synthetic image and/or generating, from the synthetic image, a value that is based on a level of expression of the first antigen.
A slide carrier includes: a base support; and a slide platform having a surface that is parallel to a first plane defined by a first vector and a second vector, wherein a vector extending in a direction opposite to the direction of gravity is normal with respect to a second plane defined by a third vector and a fourth vector, an angle between the first vector and the third vector is greater than zero degrees and less than 90 degrees, and an angle between the second vector and the fourth vector is greater than zero degrees and less than 90 degrees.
A microscope scanner is provided comprising a detector array for obtaining an image from a sample and a sample holder configured to move relative to the detector array. The sample holder can be configured to move to a plurality of target positions relative to the detector array in accordance with position control signals issued by a controller and the detector array is configured to capture images during an imaging scan based on the position control signals.
An automated system is provided for performing slide processing operations on slides bearing biological samples. In one embodiment, the disclosed system includes a slide tray holding a plurality of slides in a substantially horizontal position and a workstation that receives the slide tray. In a particular embodiment, a workstation delivers a reagent to slide surfaces without substantial transfer of reagent (and reagent borne contaminants such as dislodged cells) from one slide to another. A method for automated processing of slides also is provided.
The invention provides anti-human pro-epiregulin and anti-human amphiregulin antibodies and methods of using the same. Anti-EREG antibodies raised against amino acids 148-169 and 156-169 of the human EREG protein, and anti-AREG antibodies raised against amino acids 238-252 of the human AREG protein are disclosed. Methods of using these antibodies to detect EREG and AREG and kits and other products for performing such methods are also disclosed.
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
Disclosed herein are novel quinone methide analog precursors and embodiments of a method and a kit of using the same for detecting one or more targets in a biological sample. The method of detection comprises contacting the sample with a detection probe, then contacting the sample with a labeling conjugate that comprises an enzyme. The enzyme interacts with a quinone methide analog precursor comprising a detectable label, forming a reactive quinone methide analog, which binds to the biological sample proximally to or directly on the target. The detectable label is then detected. In some embodiments, multiple targets can be detected by multiple quinone methide analog precursors interacting with different enzymes without the need for an enzyme deactivation step.
C07F 9/6561 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
C07F 9/12 - Esters of phosphoric acids with hydroxyaryl compounds
C07D 209/14 - Radicals substituted by nitrogen atoms, not forming part of a nitro radical
C07H 15/203 - Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
C07H 15/26 - Acyclic or carbocyclic radicals, substituted by hetero rings
C12Q 1/42 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving phosphatase
C07H 15/207 - Cyclohexane rings not substituted by nitrogen atoms, e.g. kasugamycins
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
The present disclosure is directed to a method of staining a biological specimen (e.g. a single serial tissue section derived from a biological sample) with one or more routine and/or special statins while concomitantly labeling the same biological specimen with one or more detectable moieties without the need for stripping any stain or evaluating different images of stained serial tissue sections of a biological specimen. In some embodiments, the present disclosure is directed to a biological specimen stained with one or more conventional dyes, and where the biological specimen further includes one or more biomarkers labeled with one or more detectable moieties.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
The disclosure relates to devices, systems and methods for image registration and annotation. The devices include computer software products for aligning whole slide digital images on a common grid and transferring annotations from one aligned image to another aligned image on the basis of matching tissue structure. The systems include computer-implemented systems such as work stations and networked computers for accomplishing the tissue-structure based image registration and cross-image annotation. The methods include processes for aligning digital images corresponding to adjacent tissue sections on a common grid based on tissue structure, and transferring annotations from one of the adjacent tissue images to another of the adjacent tissue images. The basis for alignment may be a line-based registration process, wherein sets of lines are computed on the boundary regions computed for the two images, where the boundary regions are obtained using information from two domains—soft-weighted foreground images and gradient magnitude images. The binary mask image, based on whose boundary the line features are computed, may be generated by combining two binary masks—a first binary mask is obtained on thresholding a soft-weighted (continuous valued) foreground image, which is computed based on the stain content in an image, while a second binary mask is obtained after thresholding a gradient magnitude domain image, where the gradient is computed from the grayscale image obtained from the color image.
Disclosed herein are caged haptens and caged hapten-antibody conjugates useful for facilitating the detection of targets located proximally to each other in a sample.
C07J 19/00 - Normal steroids containing carbon, hydrogen, halogen, or oxygen, substituted in position 17 by a lactone ring
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
In one aspect of the present disclosure is a method of contactlessly urging, directly, or moving a substance on the surface of a substrate, the method employing a gas knife configured to produce a gas curtain having parallelogram flow.
Immune context scores are calculated for tumor tissue samples using continuous scoring functions. Feature metrics for at least one immune cell marker are calculated for a region or regions of interest, the feature metrics including at least a quantitative measure of human CD3 or total lymphocyte counts. A continuous scoring function is then applied to a feature vector including the feature metric and at least one additional metric related to an immunological biomarker, the output of which is an immune context score. The immune context score may then be plotted as a function of a diagnostic or treatment metric, such as a prognostic metric (e.g. overall survival, disease-specific survival, progression-free survival) or a predictive metric (e.g. likelihood of response to a particular treatment course). The immune context score may then be incorporated into diagnostic and/or treatment decisions.
A method, system, and computer program product for an image visualization system (120) that includes a contextually adaptive digital pathology interface. At least one image of a biological sample stained for the presence of one or more biomarkers is obtained (300). The image is displayed on a display screen at a first zoom level (310), in which a first subset of user selectable elements is contemporaneously displayed (320). As a result of user input, the image being is displayed at a second zoom level (330), in which a second subset of user selectable elements are contemporaneously displayed with the image (340). The one or more elements within the second subset of user selectable elements are disabled or hidden at the first zoom level, or one or more elements within the first subset of user selectable elements are disabled Or hidden at the second zoom level.
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
G16H 30/20 - ICT specially adapted for the handling or processing of medical images for handling medical images, e.g. DICOM, HL7 or PACS
G06F 3/0482 - Interaction with lists of selectable items, e.g. menus
G06F 3/04845 - Interaction techniques based on graphical user interfaces [GUI] for the control of specific functions or operations, e.g. selecting or manipulating an object, an image or a displayed text element, setting a parameter value or selecting a range for image manipulation, e.g. dragging, rotation, expansion or change of colour
Disclosed herein are systems and methods of calibrating a microscope or an imaging system prior to acquiring image data of a sample. In some embodiments, a method is disclosed including the steps of (a) running a power output calibration module to calibrate an imaging apparatus for repeatability; (b) running an image intensity calibration module to calibrate the imaging apparatus for reproducibility and to mitigate differences in detection efficiency between channels; (c) collecting image data from a microscope or imaging system; (d) optionally running an unmixing module to unmix the collected image data into individual image channel images; and (e) optionally running a contrast agent intensity correction module to calibrate for differences in brightness between different contrast agents.
G01N 21/27 - Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection
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.
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
Disclosed herein are systems and methods for of assessing stain titer levels. An exemplary method includes generating a set of field of views for the image or the region of the image, selecting field of views from the set of field of views that meet predefined criteria, creating a series of patches within each of the selected field of views, retaining patches from the series of patches that meet predefined criteria indicative of a presence of the stain for which the titer is to be estimated, deriving stain color features and stain intensity features pertaining to the stain from the retained patches, estimating a titer score for each of the retained patches based on the stain color features and the stain intensity features, and calculating a weighted average score for the titer of the stain based on the estimated titer score for each of the retained patches.
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
G16H 70/60 - ICT specially adapted for the handling or processing of medical references relating to pathologies
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G06F 16/535 - Filtering based on additional data, e.g. user or group profiles
The present disclosure is directed to opposables including a body having a plurality of cavities disposed therein. Each cavity can be designed to contain one or more reagents, liquids, or fluids which may be applied to a specimen-bearing surface. In some embodiments, the cavities include one or more reagent chambers, the reagent chambers can have one or more seals such that the reagents, liquids, or fluids contained therein may be stored and released to the specimen-bearing surface.
G02B 21/34 - Microscope slides, e.g. mounting specimens on microscope slides
B01L 7/00 - Heating or cooling apparatus; Heat insulating devices
B05C 11/02 - Apparatus for spreading or distributing liquids or other fluent materials already applied to a surface; Control of the thickness of a coating
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor
32.
HYBRID AND ACCELERATED GROUND-TRUTH GENERATION FOR DUPLEX ARRAYS
Methods and systems can include: accessing a digital pathology image; generating, using a first machine-learning model, a segmented image that identifies at least: a predicted diseased region and a background region in the digital pathology image; detecting depictions of a set of cells in the digital pathology image; generating, using a second machine-learning model, a cell classification for each cell of the set of cells, wherein the cell classification is selected from a set of potential classifications that indicate which, if any, of a set of biomarkers are expressed in the cell; detecting that a subset of the set of cells are within the background region; and updating the cell classification for each cell of at least some cells in the subset to be a background classification that was not included in the set of potential classifications.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
33.
PREDICTION OF RESPONSE TO EPIDERMAL GROWTH FACTOR RECEPTOR-DIRECTED THERAPIES USING EPIREGULIN AND AMPHIREGULIN
Methods allowing prediction of a response to anti-EGFR therapies are provided, which include histochemical or cytochemical staining methods for staining amphiregulin (AREG) or epiregulin (EREG). Scoring algorithms are provided that may include but are not limited to determining a percent tumor cell positivity for each of EREG and AREG and comparing the determined percent positivity to pre-determined cut offs. The pre-determined cut offs can be either positive cut offs (in which case patients are treated with the EGFR-directed therapy if the percentage is greater than or equal to the cut off), negative cut offs (in which case patients are not treated with the EGFR-directed therapy if the percentage is less than the cut off), or both a positive and negative cut off.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 31/4745 - Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
34.
Methods, Systems, and Apparatuses for Quantitative Analysis of Heterogeneous Biomarker Distribution
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.
A system and method for treatment of biological samples is disclosed. In some embodiments, an automated biological sample staining system (100), comprising at least one microfluidic reagent applicator (118); at least one bulk fluid applicator (116); at least one fluid aspirator; at least one sample substrate holder; at least one relative motion system; and a control system (102) that is programmed to execute at least one staining protocol on a sample mounted on a substrate that is held in the at least one sample substrate holder.
Embodiments disclosed herein generally relate to identifying auto-fluorescent artifacts in a multiplexed immunofluorescent image. Particularly, aspects of the present disclosure are directed to accessing a multiplexed immunofluorescent image of a slice of specimen, wherein the multiplexed immunofluorescent image comprises one or more auto-fluorescent artifacts, processing the multiplexed immunofluorescent image using a machine-learning model, wherein an output of the processing corresponds to a prediction that the multiplexed immunofluorescent image includes one or more auto-fluorescent artifacts at one or more particular portions of the multiplexed immunofluorescent image, adjusting subsequent image processing based on the prediction, performing the subsequent image processing, and outputting a result of the subsequent image processing, wherein the result corresponds to a predicted characterization of the specimen.
G06V 10/44 - Local feature extraction by analysis of parts of the pattern, e.g. by detecting edges, contours, loops, corners, strokes or intersections; Connectivity analysis, e.g. of connected components
G06V 10/70 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning
G16H 30/20 - ICT specially adapted for the handling or processing of medical images for handling medical images, e.g. DICOM, HL7 or PACS
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
In one aspect of the present disclosure is a targeted sequencing workflow where an input sample comprising a sufficient quantity of genomic material is provided such minimal or no amplification cycles are utilized prior to sequencing.
The subject disclosure presents systems and computer-implemented methods for evaluating a tissue sample that has been removed from a subject. A change in speed of the energy traveling through the sample is evaluated to monitor changes in the biological sample during processing. The rate of change in the speed of the energy is correlated with the extent of diffusion. A system for performing the method can include a transmitter that outputs the energy and a receiver configured to detect the transmitted energy. A time-of-flight of acoustic waves and rate of change thereof is monitored to determine an optimal time for soaking the tissue sample in a fixative.
The present disclosure relates to techniques for transforming digital pathology images obtained by different slide scanners into a common format for image analysis. Particularly, aspects of the present disclosure are directed to obtaining a source image of a biological specimen, the source image is generated from a first type of scanner, inputting into a generator model a randomly generated noise vector and a latent feature vector from the source image as input data, generating, by the generator model, a new image based on the input data, inputting into a discriminator model the new image, generating, by the discriminator model, a probability for the new image being authentic or fake, determining whether the new image is authentic or fake based on the generated probability, and outputting the new image when the image is authentic.
A method is disclosed that permits calculation of reagent concentrations (in SI units) over time and space within a tissue sample as the sample is immersed in the reagent and the reagent diffuses into the tissue sample. The disclosed method has yielded the surprising result that once a formaldehyde concentration at all points within a tissue sample exceeds about 90 mM during a cold step of a cold+hot fixation protocol, the hot step of the fixation protocol can be commenced to provide reliable detection of molecular targets and preservation of tissue morphology in downstream analyses.
Methods and systems for predictive measures of anti-EGFR therapy response in wild type RAS/EGFR+ samples, e.g., histochemical staining methods for staining EGFR, AREG, and EREG, digital analysis of stained slides, and scoring algorithms that allow prediction of a response to anti-EGFR therapies. Analysis of the stained slides and scoring algorithms may include but are not limited to: a percent tumor cell positivity, computerized clustering algorithms, area density (e.g., area of tumor positive for one or more markers over total tumor area), average intensity (e.g., computerized methodology measuring average gray scale pixel intensity), average intensity broken down according to membrane, cytoplasmic, or punctate staining patterns), or any other appropriate parameter or combination of parameters. The methods of the present invention allow for resolving spatial expression patterns of the ligands and the receptor to determine what patterns are predictive for response to anti-EGFR therapies.
A method and system are described for processing tissues according to particular processing protocols that are established based on time-of-flight measurements as a processing fluid is diffused into a tissue sample. In one embodiment, measurement of the time it takes about 70% ethanol to diffuse into a tissue sample is used to predict the time it will take to diffuse other processing fluids into the same or similar tissue samples. Advantageously, the disclosed method and system can reduce overall processing times and help ensure that only samples that require similar processing conditions are batched together.
An aldehyde fixative solution at a first temperature is caused to contact a tissue sample for a first time period, additionally an aldehyde fixative solution is caused to contact the tissue sample at a second temperature higher than the first temperature for a second time period. The first time period typically ranges from about 15 minutes up to about 4 hours, and the first temperature typically is from greater than 0° C. to at least 15° C. The second temperature typically is from greater than about 22° C. to about 55° C., and the second time period ranges from about 1 hour to about 4 hours. Using this process, improved tissue morphology and IHC staining as well as superior preservation of post-translation modification signals have been accomplished in approximately 4 hours compared to 24 hours for room temperature protocols, and more even morphology and antigen preservation are observed.
Automated system configured to perform and methods for performing one or more slide processing operations on slides bearing biological samples. The system and methods enable high sample throughput while also minimizing or limiting the potential for cross-contamination of slides. The automated systems can include features that facilitate consistency, controllability of processing time, and/or processing temperature.
A method and system for classifying field of view (FOV) images of histological slides into various categories that include certain stain patterns, artifacts, and/or other features of interest are provided herein. Few-shot learning (e.g., a prototypical network) techniques are used to train a deep convolutional neural network using a small number of training samples for a small number of image classes for classifying stain images belonging to a larger number of image classes.
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
G06V 10/764 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using classification, e.g. of video objects
G06V 10/74 - Image or video pattern matching; Proximity measures in feature spaces
G06V 10/771 - Feature selection, e.g. selecting representative features from a multi-dimensional feature space
G06V 10/82 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using neural networks
Disclosed herein are detectable moieties and detectable conjugates comprising one or more detectable moieties. In some embodiments, the disclosed detectable moieties have a narrow wavelength and are suitable for multiplexing. Also disclosed are methods of labeling one or more targets within a biological specimen using any of the detectable conjugates and/or detectable moieties described herein.
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07F 9/6547 - Six-membered rings condensed with carbocyclic rings or ring systems
C07F 9/6561 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
C07F 9/655 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
C07D 401/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
47.
METHOD OF IDENTIFYING TREATMENT RESPONSIVE NON-SMALL CELL LUNG CANCER USING ANAPLASTIC LYMPHOMA KINASE (ALK) AS A MARKER
Disclosed herein are methods for identifying a subject as having NSCLC that is predicted or is likely to respond to treatment with an ALK inhibitor, for example crizotinib. The methods include identifying a sample including NSCLC tumor cells as ALK-positive or ALK-negative using immunohistochemistry (IHC) and scoring methods disclosed herein. A subject is identified as having NSCLC likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-positive and is identified as having NSCLC not likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-negative. According to certain embodiments of the methods, subjects predicted to respond to an ALK inhibitor may then be treated with an ALK inhibitor such as crizotinib.
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
48.
SYNTHESIS SINGLEPLEX FROM MULTIPLEX BRIGHTFIELD IMAGING USING GENERATIVE ADVERSARIAL NETWORK
A multiplex image is accessed that depicts a particular slice of a particular sample stained with two or more dyes. Using a Generator network, a predicted singleplex image is generated that depicts the particular slice of the particular sample stained with each of the expressing biomarkers. The Generator network may have been trained by training a machine-learning model using a set of training multiplex images and a set of training singleplex images. Each of the set of training multiplex images depicted a slice of a sample stained with two or more dyes. Each of the set of training singleplex images depicted a slice of a sample stained with a single dye. The machine-learning model included a Discriminator network configured to discriminate whether a given image was generated by the Generator network or was a singleplex image of a real slide. The method further includes outputs the predicted singleplex image.
A method for fixing a biological sample includes delivering energy through a biological sample that has been removed from a subject, while fixing the biological sample. A change in speed of the energy traveling through the biological sample is evaluated to monitor the progress of the fixation. A system for performing the method can include a transmitter that outputs the energy and a receiver configured to detect the transmitted energy. A computing device can evaluate the speed of the energy based on signals from the receiver.
The present disclosure is directed, among other things, to automated systems and methods for analyzing, storing, and/or retrieving information associated with biological objects having irregular shapes. In some embodiments, the systems and methods partition an input image into a plurality of sub-regions based on localized colors, textures, and/or intensities in the input image, wherein each sub-region represents biologically meaningful data.
G06K 1/00 - Methods or arrangements for marking the record carrier in digital fashion
G06V 10/25 - Determination of region of interest [ROI] or a volume of interest [VOI]
G06V 10/762 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using clustering, e.g. of similar faces in social networks
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
51.
Convolutional neural networks for locating objects of interest in images of biological samples
Convolutional neural networks for detecting objects of interest within images of biological specimens are disclosed. Also disclosed are systems and methods of training and using such networks, one method including: obtaining a sample image and at least one of a set of positive points and a set of negative points, wherein each positive point identifies a location of one object of interest within the sample image, and each negative point identifies a location of one object of no-interest within the sample image; obtaining one or more predefined characteristics of objects of interest and/or objects of no-interest, and based on the predefined characteristics, generating a boundary map comprising a positive area around each positive point the set of positive points, and/or a negative area around each negative point in the set of negative points; and training the convolutional neural network using the sample image and the boundary map.
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
G06V 10/44 - Local feature extraction by analysis of parts of the pattern, e.g. by detecting edges, contours, loops, corners, strokes or intersections; Connectivity analysis, e.g. of connected components
G06F 18/214 - Generating training patterns; Bootstrap methods, e.g. bagging or boosting
G06F 18/2413 - Classification techniques relating to the classification model, e.g. parametric or non-parametric approaches based on distances to training or reference patterns
G06V 10/764 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using classification, e.g. of video objects
G06V 10/82 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using neural networks
52.
MACHINE LEARNING MODELS FOR CELL LOCALIZATION AND CLASSIFICATION LEARNED USING REPEL CODING
The present disclosure relates to computer-implement techniques for cell localization and classification. Particularly, aspects of the present disclosure are directed to accessing an image for a biological sample, where the image depicts cells comprising a staining pattern of a biomarker; inputting the image into a machine learning model; encoding, by the machine learning model, the image into a feature representation comprising extracted discriminative features; combining, by the machine learning model, feature and spatial information of the cells and the staining pattern of the biomarker through a sequence of up-convolutions and concatenations with the extracted discriminative features from the feature representation; and generating, by the machine learning model, two or more segmentation masks for the biomarker in the image based on the combined feature and spatial information of the cells and the staining pattern of the biomarker.
A method for transferring digital pathology annotations between images of a tissue sample may include identifying a first set of points for a geometric feature of a first image of a section of a tissue sample; identifying a corresponding second set of points for a corresponding geometric feature of a second image of a same tissue sample, the second image being an image of another section of the tissue sample; determining coordinates of the first set of points and coordinates of the second set of points; determining a transformation between the first set of points and the second set of points; and applying the transformation to a set of digital pathology annotations on the first image to transfer the set of digital pathology annotations within the first image to the second image.
G06V 10/25 - Determination of region of interest [ROI] or a volume of interest [VOI]
G06V 10/44 - Local feature extraction by analysis of parts of the pattern, e.g. by detecting edges, contours, loops, corners, strokes or intersections; Connectivity analysis, e.g. of connected components
G06V 10/74 - Image or video pattern matching; Proximity measures in feature spaces
The present disclosure is directed to conjugates of a specific binding entity and an oligomer, i.e. [Specific Binding Entity]-[Oligomer]n, wherein n is an integer ranging from 1 to 12, and where the Oligomer includes, in some embodiments, a PNA sequence having at least one substituent at a gamma carbon position. In some embodiments, the substituent at the gamma carbon position, e.g. an amino acid, a peptide, a miniPEG, or a polymer, includes at least one reporter moiety.
C07K 14/00 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
55.
METHOD AND SYSTEM TO DETECT SUBSTRATE PLACEMENT ACCURACY
A method and system for measuring the alignment between a substrate and a platform upon which it is disposed by using image processing algorithms are described herein. These algorithms automate the detection of edges of a microscope slide and the platform in a digital image. A reference line pattern in an image of the platform can be used to detect platform edges based on a computed location of the reference line pattern in the image.
A machine learning model is accessed that is configured to use one or more parameters to process images to generate labels. The machine learning model is executed to transform at least part of each of at least one digital pathology image into a plurality of predicted labels; and generate a confidence metric for each of the plurality of predicted labels. An interface is availed that depicts the at least part of the at least one digital pathology image and that differentially represents predicted labels based on corresponding confidence metrics. In response to availing of the interface, label input is received that confirms, rejects, or replaces at least one of the plurality of predicted labels. The one or more parameters of the machine learning model are updated based on the label input.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The disclosure is directed to conjugates, e.g. PNA conjugates, as well as methods of employing the conjugates for detecting one or more targets in a biological sample, e.g. a tissue sample.
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
C07K 2/00 - Peptides of undefined number of amino acids; Derivatives thereof
C07K 14/00 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present invention concerns a method for predicting the potential for aggressive growth and/or the risk to progress to high grade cancer for tumors in cell based detection procedures. In one aspect the invention concerns the detection of overexpression of cyclin-dependent kinase inhibitor gene products as a tool for predicting the progression risk and/or potential for aggressive growth of tumors. In a second aspect the invention concerns predicting the progression risk and/or potential for aggressive growth in tumors on the basis of the simultaneous co-detection of the presence of overexpression of cyclin-dependent kinase inhibitor gene products together with the expression of markers for active cell proliferation. Further the invention concerns preparations of probes for diagnosis namely for predicting the progression risk and/or the potential for aggressive growth of tumors.
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
A method, system, and computer program product for an image visualization system (120) that includes a contextually adaptive digital pathology interface. At least one image of a biological sample stained for the presence of one or more biomarkers is obtained (300). The image is displayed on a display screen at a first zoom level (310), in which a first subset of user selectable elements are contemporaneously displayed (320). As a result of user input, the image being is displayed at a second zoom level (330), in which a second subset of user selectable elements are contemporaneously displayed with the image (340). The one or more elements within the second subset of user selectable elements are disabled or hidden at the first zoom level, or one or more elements within the first subset of user selectable elements are disabled or hidden at the second zoom level.
G06F 3/0482 - Interaction with lists of selectable items, e.g. menus
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
G16H 30/20 - ICT specially adapted for the handling or processing of medical images for handling medical images, e.g. DICOM, HL7 or PACS
G06F 3/04845 - Interaction techniques based on graphical user interfaces [GUI] for the control of specific functions or operations, e.g. selecting or manipulating an object, an image or a displayed text element, setting a parameter value or selecting a range for image manipulation, e.g. dragging, rotation, expansion or change of colour
The present disclosure is directed to methods and devices for reducing or otherwise mitigating accumulated reagent material and/or fluids within a dispense nozzle of a dispenser.
Techniques for acquiring focused images of a microscope slide are disclosed. During a calibration phase, a “base” focal plane is determined using non-synthetic and/or synthetic auto-focus techniques. Furthermore, offset planes are determined for color channels (or filter bands) and used to generate an auto-focus model. During subsequent scans, the auto-focus model can be used to quickly estimate the focal plane of interest for each color channel (or filter band) rather than re-employing the non-synthetic and/or synthetic auto-focus techniques.
Devices and methods for the deposition of reagents onto cells or tissue samples are disclosed. Also disclosed are reagent compositions suitable for dispensing via a droplet-on-demand system.
A racemic hematoxylin formulation is disclosed that includes one or both of a stabilizer compound and an antioxidant. The disclosed composition exhibits sufficient stability to be utilized in an automated staining process. Methods of using and making the stabilized composition also are disclosed.
Efficient methods for identifying biomarkers are described. The method may include identifying a tumor area. The method may further include identifying a plurality of regions. The method may also include defining, for each region, a bounding area for the region that encompasses the region. The method may include determining, for each region of a first subset of the plurality of regions, that the region is to be ascribed to the tumor, where the bounding area is fully within the tumor area. The method may further include determining, for each region of a second subset of the plurality of regions, whether to ascribe the region to the tumor based on an intersection of the region and the tumor area. The method may also include accessing a metric characterizing a biological observation and generating a result based on the metrics. The result may be used as a biomarker.
A microscope scanner is provided comprising a detector array for obtaining an image from a sample and a sample holder configured to move relative to the detector array. The sample holder can be configured to move to a plurality of target positions relative to the detector array in accordance with position control signals issued by a controller and the detector array is configured to capture images during an imaging scan based on the position control signals.
A computer implemented method for identifying at least one peak in a mass spectrometry response curve is provided comprising: a) providing at least one mass spectrometry response curve by using at least one mass spectrometry device; b) evaluating the mass spectrometry response curve by using at least one trained model thereby identifying a start point and an end point of at least one peak of the mass spectrometry response curve, wherein the model was trained using a deep learning regression architecture.
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 b 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.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
The present disclosure describes a method of foreground segmentation and nucleus ranking for scoring dual ISH images. The method has been developed to better identify those nuclei, within a selected field of view, that meet the criteria for dual ISH scoring.
Disclosed herein are systems and methods for of assessing stain titer levels. An exemplary method includes generating a set of field of views for the image or the region of the image, selecting field of views from the set of field of views that meet predefined criteria, creating a series of patches within each of the selected field of views, retaining patches from the series of patches that meet predefined criteria indicative of a presence of the stain for which the titer is to be estimated, deriving stain color features and stain intensity features pertaining to the stain from the retained patches, estimating a titer score for each of the retained patches based on the stain color features and the stain intensity features, and calculating a weighted average score for the titer of the stain based on the estimated titer score for each of the retained patches.
G06T 3/40 - Scaling of a whole image or part thereof
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
G16H 70/60 - ICT specially adapted for the handling or processing of medical references relating to pathologies
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G06F 16/535 - Filtering based on additional data, e.g. user or group profiles
The present disclosure relates machine learning techniques for segmenting non-tumor regions in specimen images to support tumor detection and analysis. Particularly, aspects of the present disclosure are directed to accessing one or more images that comprise a non-target region (e.g., a non-tumor region) and a target region (e.g., a tumor region), predicting, by a two-dimensional segmentation model, segmentation maps for the non-target region based on discriminative features encoded from the one or more images, a segmentation mask for the one or more images based on the segmentation maps, applying the segmentation mask to the one or more images to generate non-target region masked images that exclude the non-target region from the one or more images, and classifying, by an image analysis model, a biological material or structure within the target region based on a set of features extracted from the non-target region masked images.
A method for using a federated learning classifier in digital pathology includes distributing, by a centralized server, a global model to a plurality of client devices. The client devices further train the global model using a plurality images of a specimen and corresponding annotations to generate at least one further trained model. The client devices provide further trained models to the centralized server, which aggregates the further trained models with the global model to generate an updated global model. The updated global model is then distributed to the plurality of client devices.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
Automated methods for extracting nucleic acid from one or more tissue samples disposed on slides are disclosed. The methods utilize an automated slide staining apparatus that dispenses a plurality of nucleic acid extraction reagents onto the tissue sample, thus creating an extracted nucleic acid sample. The extracted nucleic acid sample may be used directly in downstream applications such as nucleic acid amplification or sequencing procedures, or may be further purified.
Automated systems to make target compounds from slide stainer waste streams inactive utilizing advanced oxidation processes are described herein. Advanced oxidation processes are promoted by UV irradiation and further accelerated by use of radical initiators, such as hydrogen peroxide. The automated systems further include mechanisms for segregating components of the waste streams.
A microscope slide holder comprising a slide support member and at least one acoustic source for introducing acoustic waves to a microscope slide in communication with the slide support member such that one or more fluids present on the surface of the microscope slide are contactlessly mixed.
Disclosed is a device for contactlessly mixing fluid present on the upper surface of the slide, where the device comprises a first nozzle array and a second nozzle array, the first nozzle array adapted to impart a bulk fluid flow to the fluid present on the upper surface of the slide, and the second nozzle array adapted to impart at least a first regional fluid flow to at least a portion of the fluid present on the upper surface of the slide
Automated systems to make target compounds from slide stainer waste streams inactive utilizing advanced oxidation processes are described herein. Advanced oxidation processes are promoted by UV irradiation and further accelerated by use of radical initiators, such as hydrogen peroxide. The automated systems further include mechanisms for segregating components of the waste streams.
The present disclosure is directed, among other things, to automated systems and methods for analyzing, storing, and/or retrieving information associated with biological objects having irregular shapes. In some embodiments, the systems and methods partition an input image into a plurality of sub-regions based on localized colors, textures, and/or intensities in the input image, wherein each sub-region represents biologically meaningful data.
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
G06K 9/62 - Methods or arrangements for recognition using electronic means
G06K 1/00 - Methods or arrangements for marking the record carrier in digital fashion
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
Immune context scores are calculated for tumor tissue samples using continuous scoring functions. Feature metrics for at least one immune cell marker are calculated for a region or regions of interest, the feature metrics including at least a quantitative measure of human CD3 or total lymphocyte counts. A continuous scoring function is then applied to a feature vector including the feature metric and at least one additional metric related to an immunological biomarker, the output of which is an immune context score. The immune context score may then be plotted as a function of a diagnostic or treatment metric, such as a prognostic metric (e.g. overall survival, disease-specific survival, progression-free survival) or a predictive metric (e.g. likelihood of response to a particular treatment course). The immune context score may then be incorporated into diagnostic and/or treatment decisions.
At least some embodiments of the technology are directed to an automated slide processing apparatus configured to apply at least one reagent to a specimen carried by a microscope slide. The slide processing station can include a support element with a support surface, at least one vacuum port, and a sealing member having a non-round shape. In an uncompressed state, the scaling member can extend upwardly beyond the support surface. In a compressed state, the scaling member can be configured to maintain an airtight seal with a backside of the microscope slide as the microscope slide is pulled against the support surface by a vacuum drawn via the at least one vacuum port.
Techniques relate to object classifications using bootstrapping of region-level annotations. For each of multiple images, regions within the image can be identified. For each region, a region-specific label can be identified, a set of objects within the region can be detected, and an object-specific label can be assigned to each object. The object-specific label can be the same as the region-specific label assigned to the region within which the object is located. A training data set can be defined to include, for each image of the multiple images, object-location data (indicating intra-image location data for the detected object) and label data (indicating the object-specific labels assigned to the objects). An image-processing model can be trained using the training data. Training can include learning values for a set of parameters that define calculations performed by the image-processing model.
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
G06V 10/764 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using classification, e.g. of video objects
G06V 10/774 - Generating sets of training patterns; Bootstrap methods, e.g. bagging or boosting
G06V 10/82 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using neural networks
G06V 10/22 - Image preprocessing by selection of a specific region containing or referencing a pattern; Locating or processing of specific regions to guide the detection or recognition
The present disclosure relates to techniques for segmenting and detecting cells within image data using transfer learning and a multi-task scheduler. Particularly, aspects of the present disclosure are directed to accessing a plurality of images of one or more cells, extracting three labels from the plurality of images, where the three labels are extracted using a Voronoi transformation, a local clustering, and application of repel code, training, by a multi-task scheduler, a convolutional neural network model based on three loss functions corresponding to the three labels, generating, by the convolutional neural network model, a nuclei probability map and a background probability map for each of the plurality of images based on the training with the three loss functions, and providing the nuclei probability map and the background probability map.
The subject disclosure presents systems and methods for automatically selecting meaningful regions on a whole-slide image and performing quality control on the resulting collection of FOVs. Density maps may be generated quantifying the local density of detection results. The heat maps as well as combinations of maps (such as a local sum, ratio, etc.) may be provided as input into an automated FOV selection operation. The selection operation may select regions of each heat map that represent extreme and average representative regions, based on one or more rules. One or more rules may be defined in order to generate the list of candidate FOVs. The rules may generally be formulated such that FOVs chosen for quality control are the ones that require the most scrutiny and will benefit the most from an assessment by an expert observer.
G06V 10/98 - Detection or correction of errors, e.g. by rescanning the pattern or by human intervention; Evaluation of the quality of the acquired patterns
G06V 10/22 - Image preprocessing by selection of a specific region containing or referencing a pattern; Locating or processing of specific regions to guide the detection or recognition
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
The present disclosure relates to automated systems and methods for quantitatively determining an unmasking status of a biological specimen subjected to an unmasking process (e.g. an antigen retrieval process and/or a target retrieval process) using a trained unmasking status estimation engine. In some embodiments, the trained unmasking status estimation engine comprises a machine learning algorithm based on a projection onto latent structure regression model. In some embodiments, the trained unmasking status estimation engine includes a neural network.
G16B 25/10 - Gene or protein expression profiling; Expression-ratio estimation or normalisation
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
The Board of Trustees of the Leland Stanford Junior University (USA)
Inventor
Barnes, Michael
Chukka, Srinivas
Knowles, David
Abstract
The subject disclosure presents systems and computer-implemented methods for assessing a risk of cancer recurrence in a patient based on a holistic integration of large amounts of prognostic information for said patient into a single comparative prognostic dataset. A risk classification system may be trained using the large amounts of information from a cohort of training slides from several patients, along with survival data for said patients. For example, a machine-learning-based binary classifier in the risk classification system may be trained using a set of granular image features computed from a plurality of slides corresponding to several cancer patients whose survival information is known and input into the system. The trained classifier may be used to classify image features from one or more test patients into a low-risk or high-risk group.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G06K 9/62 - Methods or arrangements for recognition using electronic means
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
Disclosed herein are embodiments of a signaling conjugate, embodiments of a method of using the signaling conjugates, and embodiments of a kit comprising the signaling conjugate. The disclosed signaling conjugate comprises a latent reactive moiety and a chromogenic moiety that may further comprise a linker suitable for coupling the latent reactive moiety to the chromogenic moiety. The signaling conjugate may be used to detect one or more targets in a biological sample and are capable of being covalently deposited directly on or proximally to the target. Particular disclosed embodiments of the method of using the signaling conjugate comprise multiplexing methods.
G01N 33/542 - Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
87.
CANCER RISK STRATIFICATION BASED ON HISTOPATHOLOGICAL TISSUE SLIDE ANALYSIS
The subject disclosure presents systems and computer-implemented methods for providing reliable risk stratification for early-stage cancer patients by predicting a recurrence risk of the patient and to categorize the patient into a high or low risk group. A series of slides depicting serial sections of cancerous tissue are automatically analyzed by a digital pathology system, a score for the sections is calculated, and a Cox proportional hazards regression model is used to stratify the patient into a low or high risk group. The Cox proportional hazards regression model may be used to determine a whole-slide scoring algorithm based on training data comprising survival data for a plurality of patients and their respective tissue sections. The coefficients may differ based on different types of image analysis operations applied to either whole-tumor regions or specified regions within a slide.
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G06K 9/62 - Methods or arrangements for recognition using electronic means
Applicants have developed an amplification system and methodology for IHC and ISH staining that utilizes “click chemistry” to covalently bind reporter molecules to tissue.
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
C07F 9/12 - Esters of phosphoric acids with hydroxyaryl compounds
C07F 9/553 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
C07F 9/6524 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having four or more nitrogen atoms as the only ring hetero atoms
The present disclosure relates to automated systems and methods for predicting an expression of one or more biomarkers in a sample of a biological specimen. In some embodiments, the sample is one which has an unknown fixation status, or one where the duration of fixation to which the sample was subject is unknown. In some embodiments, the predicted expression is a quantitative estimation of the percent positivity of one or more biomarkers. In other embodiments, the predicted expression is a quantitative estimation of the staining intensity of one or more biomarkers. In some embodiments, the systems and methods utilize a trained biomarker expression estimation engine which has been trained with a plurality of training samples, where the trained biomarker expression estimation engine is adapted to derive biomarker expression features from the sample.
G01N 21/3577 - Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing liquids, e.g. polluted water
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
G06V 10/774 - Generating sets of training patterns; Bootstrap methods, e.g. bagging or boosting
G06V 10/82 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using neural networks
G01N 21/35 - Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
The present application provides for systems and methods for detecting and estimating signals corresponding to one or more biomarkers in biological samples stained for the presence of protein and/or nucleic acid biomarkers. On particular aspect is directed to a method of estimating an amount of signal corresponding to at least one biomarker in an image of a biological sample. The method includes detecting isolated spots in a first image, deriving an optical density value of a representative isolated spot based on signal features from the detected isolated spots, estimating a number of predictive spots in signal aggregates in each of a plurality of sub-regions based on the derived optical density value of the representative isolated spot, and storing the estimated number of predictive spots and detected isolated spots in each of the plurality of generated sub-regions in a database.
Applicants have developed an amplification system and methodology for IHC and ISH staining that utilizes “click chemistry” to covalently bind reporter molecules to tissue.
C07F 9/12 - Esters of phosphoric acids with hydroxyaryl compounds
C07F 9/553 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
C07F 9/6524 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having four or more nitrogen atoms as the only ring hetero atoms
A real time assay monitoring system and method can be used to monitor reagent volume in assays for fluid replenishment control, monitor assays in real-time to obtain quality control information, monitor assays in real-time during development to detect saturation levels that can be used to shorten assay time, and provide assay results before the assay is complete, enabling reflex testing to begin automatically. The monitoring system can include a real time imaging system with a camera and lights to capture images of the assay. The captured images can then be used to monitor and control the quality of the staining process in an assay, provide early assay results, and/or to measure the on-site reagent volume within the assay.
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
G06V 10/764 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using classification, e.g. of video objects
93.
SYSTEMS AND METHODS FOR ASSESSING SPECIMEN FIXATION DURATION AND QUALITY USING VIBRATIONAL SPECTROSCOPY
The present disclosure relates to automated systems (200) and methods for quantitatively determining a fixation duration of a biological specimen using a trained fixation estimation engine (210). In some embodiments, the trained fixation estimation (210) engine includes a neural network. In some embodiments, the trained fixation estimation (210) engine includes a supervised classifier.
G01N 21/3563 - Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing solids; Preparation of samples therefor
G01N 21/39 - Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using tunable lasers
G01N 33/483 - Physical analysis of biological material
Single-stranded oligonucleotide probes, systems, kits and methods for chromosome enumeration, gene copy enumeration, or tissue diagnostics. The probes are particularly suited for detecting gene amplification, deletion, or rearrangement in tissue samples in a single, dual, or multiplexed assay. The probes exhibit improved performance compared to industry leading dual-stranded probes; particularly in terms of the rate of hybridization and the ability to achieve specific hybridization without blocking DNA.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
95.
PROTEIN PROXIMITY ASSAY IN FORMALIN FIXED PARAFFIN EMBEDDED TISSUE USING CAGED HAPTENS
Disclosed herein are caged haptens and caged hapten-antibody conjugates useful for enabling the detection of targets located proximally to each other in a sample.
C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
G01N 33/542 - Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
G01N 33/573 - Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
The present disclosure provides stabilized hematoxylin formulations having a pH of less than 2.4. The present disclosure also provides methods of using such stabilized hematoxylin formulations to stain biological samples.
A real time assay monitoring system and method can be used to monitor reagent volume in assays for fluid replenishment control, monitor assays in real-time to obtain quality control information, monitor assays in real-time during development to detect saturation levels that can be used to shorten assay time, and provide assay results before the assay is complete, enabling reflex testing to begin automatically. The monitoring system can include a real time imaging system with a camera and lights to capture images of the assay. The captured images can then be used to monitor and control the quality of the staining process in an assay, provide early assay results, and/or to measure the on-site reagent volume within the assay.
G01N 21/78 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
G06V 10/56 - Extraction of image or video features relating to colour
G06V 10/147 - Optical characteristics of the device performing the acquisition or on the illumination arrangements - Details of sensors, e.g. sensor lenses
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
Methods, systems, and compositions featuring a solid, dissolvable reagent composition for delivering the reagent, such as an antibody, probe, chromogen, etc., to a sample. The present invention also features methods of producing said compositions, and automated systems featuring the use of the solid, dissolvable reagent compositions. The solid, dissolvable reagent composition may comprise a water-soluble polymer film, such as a polyvinyl alcohol film, infused with the reagent, wherein when applied to the sample, the water-soluble polymer film with reagent contacts the sample (e.g., tissue) and dissolves.
A slide imaging apparatus that includes a copy holder moving system and an imaging system. The copy holder moving system includes a movable stage configured to move along first and second slide movement axes relative to the imaging system, wherein the imaging system is configured to form an image of a sample mounted on a slide located in the/each imaging location on the movable stage during an image forming process that includes the movable stage moving relative to the imaging system along the first and second slide movement axes. The copy holder moving system also includes a copy holder configured to be mounted to the movable stage, wherein the copy holder is configured to be mounted to the movable stage in each of a plurality of indexing positions.
THE FRANCIS CRICK INSTITUTE LIMITED (United Kingdom)
THE ROYAL MARSDEN NHS FOUNDATION TRUST (United Kingdom)
Inventor
Alexander, Nelson R.
Litchfield, Kevin Richard
Stanislaw, Stacey
Turajlic, Samra
Abstract
Disclosed herein is a method of deriving a plurality of genetic variants from a homogenized input sample. Also disclosed herein are methods of identifying a plurality of genetic variants in a sample comprising: homogenizing one or more input samples to provide a homogenized sample; preparing genomic material isolated from the homogenized input sample for sequencing; and identifying the plurality of genetic variants within sequencing data derived after sequencing the prepared genomic material.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material