Abstract: One type of tissue-based assay, the companion diagnostic (“CDx”) allows for the identification of individuals within a larger patient population who are more likely to respond to a therapy. The CDx paradigm typically applies to drugs that target a specific gene product or biologic pathway involving a gene product of interest. It is possible, especially for popular therapeutic targets, for multiple drugs and multiple associated CDx to be developed for a single gene product or biologic pathway involving the gene product. Currently, each of these similar CDx must be applied to identify the best therapy. The present invention can determine the outcome of one CDx using an image of a tissue section used for another CDx. Using a single tissue section and a single CDx, it becomes possible to obtain the outcome of multiple, related CDx.

Abstract: The present invention concerns identifying matching tissue objects in two sections of a tissue block, as imaged using a microscope, for the purpose of mapping the biomarker-specific staining in one section onto the other section. The invention is useful because, in many workflows, it is not possible to add a sufficient number of different biomarker-specific stains to a single slide. By staining instead multiple slides, and mapping the staining data obtained across the slides, one obtains a data set that is similar to what one would be able to obtain by staining a single slide with all those stains. The invention first identifies a set of obviously correct matches, then propagates from those matches, using a priority queue driven process, to optimally match up all fibers in the two sections. The matching is based on the shape and neighborhood configuration of each tissue object.

Abstract: In digital pathology, obtaining a labeled data set for training, testing and/or validation of a machine learning model is expensive, because it requires manual annotations from a pathologist. In some cases, it can be difficult for the pathologist to produce correct annotations. The present invention allows the creation of labeled data sets using fluorescent dyes, which do not affect the appearance of the slide in the brightfield imaging modality. It thus becomes possible to add correct annotations to a brightfield slide without human intervention.

Abstract: One type of tissue-based assay, the companion diagnostic (“CDx”) allows for the identification of individuals within a larger patient population who are more likely to respond to a therapy. The CDx paradigm typically applies to drugs that target a specific gene product or biologic pathway involving a gene product of interest. It is possible, especially for popular therapeutic targets, for multiple drugs and multiple associated CDx to be developed for a single gene product or biologic pathway involving the gene product. Currently, each of these similar CDx must be applied to identify the best therapy. The present invention can determine the outcome of one CDx using an image of a tissue section used for another CDx. Using a single tissue section and a single CDx, it becomes possible to obtain the outcome of multiple, related CDx.

Abstract: The present invention concerns identifying matching tissue objects in two sections of a tissue block, as imaged using a microscope, for the purpose of mapping the biomarker-specific staining in one section onto the other section. The invention is useful because, in many workflows, it is not possible to add a sufficient number of different biomarker-specific stains to a single slide. By staining instead multiple slides, and mapping the staining data obtained across the slides, one obtains a data set that is similar to what one would be able to obtain by staining a single slide with all those stains. The invention first identifies a set of obviously correct matches, then propagates from those matches, using a priority queue driven process, to optimally match up all fibers in the two sections. The matching is based on the shape and neighborhood configuration of each tissue object.

Abstract: We present a method to detect dots in microscope images of tissue samples for the purpose of diagnosis or therapy selection. Dots in tissue arise trough CISH or FISH staining, but also through staining of small cellular compartments, or in other ways. The method is applicable to both brightfield and fluorescence modalities, as well as mass spectrometry imaging methodologies. The method is based on the use of first and second derivatives of the image along the image axes, computed using regularized derivative operators, i.e. Gaussian derivatives. The outputs of these operators are examined at appropriate distances from each location in the image. The found values must have specific signs. If the signs are all correct, these values are multiplied together to obtain a confidence measure for a dot being present at that location. If the signs do not match, no dot is present, and a zero is output.

Abstract: We present a method to detect dots in microscope images of tissue samples for the purpose of diagnosis or therapy selection. Dots in tissue arise trough CISH or FISH staining, but also through staining of small cellular compartments, or in other ways. The method is applicable to both brightfield and fluorescence modalities, as well as mass spectrometry imaging methodologies. The method is based on the use of first and second derivatives of the image along the image axes, computed using regularized derivative operators, i.e. Gaussian derivatives. The outputs of these operators are examined at appropriate distances from each location in the image. The found values must have specific signs. If the signs are all correct, these values are multiplied together to obtain a confidence measure for a dot being present at that location. If the signs do not match, no dot is present, and a zero is output.

Abstract: The present invention concerns detection of specific tissue objects within thin sections of tissue samples as imaged in a brightfield microscope, such as a predetermined type of immune cells, without using a chromogenic stain that is specific to those tissue objects. The invention uses fluorescent stain and fluorescence imaging to detect these tissue objects. By combining a brightfield and a fluorescence image of the same tissue sample, it is possible to automatically identify objects in the brightfield image that have been stained for in the fluorescence image. The fluorescence stain does not affect the appearance of the tissue sample under the brightfield microscope. Therefore, the invention is ideal to automate the collection of training data for machine learning systems that are to be trained to detect these specific tissue objects in brightfield images of tissue that has not been stained to specifically highlight these tissue objects.