Ventana Medical Systems, Inc.

Oregon Health & Science University

Cornell University

Other

Karl Eric Garsha

Michael Otter

Gary A Pestano

Benjamin C Stevens

Michael S Barnes

Joe W Gray

Phillip C Miller

Christophe Chefd'hotel

Thomas M Grogan

David Chafin

Esteban Roberts

Kandavel Shanmugam

Brian Jay Druker

Franklin Ventura

Ray B Nagle

Thomas Jacob

Damien Ramunno-Johnson

Mark A Rubin

Francesca Demichelis

Alexandra Dea Nagy

Tothu Tania Vu

William Kenneth Day

Jefferson Taft

Chol Steven Yun

Jan Froehlich

Tania Vu

Ryan Dittamore

Frank Ventura

Dustin Karl Harshman

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.

System level calibration

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.

Methods, systems, and apparatuses for quantitative analysis of heterogeneous biomarker distribution

A system and method for characterization and/or calibration of performance of a multispectral imaging (MSI) system equipping the MSI system for use with a multitude of different fluorescent specimens while being independent on optical characteristics of a specified specimen and providing an integrated system level test for the MSI system. A system and method are adapted to additionally evaluate and express operational parameters performance of the MSI system in terms of standardized units and/or to determine the acceptable detection range of the MSI system.

Systems and methods for calibrating, configuring and validating an imaging device or system for multiplex tissue assays

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.

Image acquisition methods for simultaneously detecting genetic rearrangement and nuclear morphology

Immunohistochemistry (IHC) and in situ hybridization (ISH) have the aim of detecting, localizing and quantifying certain analytes for various diagnostic purposes. The quality of the stains which are analyzed may deviate for various reasons. Therefore, the present invention provides a method and system for assessing the stain quality and for establishing objective criteria for assessing the stain quality for application in the fields of in-situ hybridization and immunohistochemistry. In one possible embodiment, the invention comprises the steps of unmixing multi-spectral image data of a tissue specimen to obtain analyte intensity images, each analyte intensity image comprising signals from a single stain, computing metrics based on the analyte intensity images, wherein the metrics are uniformity, distribution and/or dispersion of pixel intensity values in the analyte intensity images and assessing a stain quality of a slide by comparing the computed metrics to pre-determined cutoff values regarding uniformity, distribution and/or dispersion of pixel intensity, wherein the stain quality of the slide is assessed as acceptable if the computed metrics meet or exceed the pre-determined cutoff values, and wherein the stain quality of the slide is assessed as unacceptable if the computed metrics do not meet the pre-determined cutoff values. In order to establish objective criteria for assessing stain quality, in one possible embodiment, the method and system includes the step of deriving cut-off values for uniformity, distribution and/or dispersion of pixel intensity by combining the computed metrics based on the analyte intensity images with pre-established data quantifying the stain quality.

Descriptive measurements and quantification of staining artifacts for in situ hybridization

The disclosure provides methods for automated characterization of circulating tumor cells (CTCs), for example using automated tissue strainers. In specific examples, such methods permit characterizing a prostate cancer sample by simultaneously or contemporaneously detecting ERG rearrangements and PTEN deletions in the same CTC. Also provided are kits that can be used with such methods.

Automated analysis of circulating tumor cells

A microscope-based system and method for simultaneous imaging of several object planes, of a three-dimensional (3D) sample, associated with different depths throughout the sample. The system includes a polyfocal optical portion, adapted to create a plurality of optical channels each of which is associated with an image of a corresponding object plane, and a spectrally-selective portion, adapted to transform the spectral distribution of the image-forming beam of light to a corresponding spatial distribution. The image, registered by a detector, includes an image of an object plane and an image of the spatially-coded spectral distribution. The method effectuates the simultaneous multispectral imaging of the several object planes. The required data-acquisition time is several fold shorter than that taken by a conventional multispectral microscope-based imaging system.

Polyfocal interferometric image acquisition wherein each image of substantially non-overlapping images corresponds to one of spatially-different optical channels

Spectral imaging for measurement of nuclear pathology features in cancer cells prepared for in situ analysis

Systems and methods of polyfocal hyperspectral imaging having a beam splitter with optical channels respectively corresponding to plural image planes

Multiple modality contrast can be used to produce images that can be combined and rendered to produce images similar to those produced with wavelength absorbing stains viewed under transmitted white light illumination. Images obtained with other complementary contrast modalities can be presented using engineered color schemes based on classical contrast methods used to reveal the same anatomical structures and histochemistry, thereby providing relevance to medical training and experience. Dark-field contrast images derived from refractive index and fluorescent DAPI counterstain images are combined to produce images similar to those obtained with conventional H&E staining for pathology interpretation. Such multi-modal image data can be streamed for live navigation of histological samples, and can be combined with molecular localizations of genetic DNA probes (FISH), sites of mRNA expression (mRNA-ISH), and immunohistochemical (IHC) probes localized on the same tissue sections, used to evaluate and map tissue sections prepared for imaging mass spectrometry.

Multi-modality contrast and brightfield context rendering for enhanced pathology determination and multi-analyte detection in tissue

Growing community of inventors

Sahuarita, AZ, United States of America

Karl Eric Garsha