General Electric Company

Leica Microsystems Cms Gmbh

Digital Pathco, LLC

Kevin Bernard Kenny

Alex David Corwin

David LaVan Henderson

Robert John Filkins

Arunkumar Natarajan

Anup Sood

Siavash Yazdanfar

David Andrew Shoudy

Lakshmi Sireesha Kaanumalle

Christine Lynne Pitner

Dashan Gao

Brion Daryl Sarachan

Robert William Tait

Dirk Ryan Padfield

Michael Christopher Montalto

Christopher Reynolds Hammond

Christine Lynne Surrette

Xiaofeng Liu

Stephen Eric Zingelewicz

Michael Adam Kinstrey

Megan Pearl Rothney

Elizabeth Lockenberg Dixon

Richard R McKay

Helena Goldfarb

Elizabeth Mary McDonough

Krenar Tasimi

Antti Seppo

Stephen John Angelovich

Mary Kathleen Callahan

Adriana Ines Larriera

Alexandra Jay Schmidt

John Espirito Santo Amaral

Ralph Andrew Minerva

Ying Li

Denise A Hollman-Hewgley

Ainura Kyshtoobayeva

Natalia R Jun

Thomas Ha

Christina Chirappuram Royce

Walter Vincent Dixon, Legal Representative

Vipul A Baxi

Christine Lynne Surette

A method for generating an image of a region of interest in a biological sample comprising the steps of: generating a first image including the region of interest of the biological sample having undergone a first protocol but not a second protocol; and generating a second image including the region of interest of the biological sample after having undergone a second protocol; wherein the region of interest is smaller than said sample. Also provided is a method of analyzing a biological sample, comprising providing an image of the biological sample according to the method for generating an image of a region of interest in a biological sample, and analyzing the biological sample from the image. Further provided are system and kit that comprise the means for executing the novel methods.

Methods for generating an image of a biological sample

Approaches are disclosed for calibrating a plurality of imaging devices, such as microscopes. In certain implementations, a calibration plate is employed that includes a variety of calibration features. The calibration features comprise a geometric calibration, an illumination calibration, and an optical calibration. Imaging devices calibrated in accordance with the present approaches may be used to generate images having consistent attributes, such as brightness, regardless of which imaging device is employed.

Calibration of microscopy systems

Referencing of image acquired in multiple rounds of imaging is disclosed. In certain implementations, a baseline round of images are acquired and registered to one another to establish a global transformation matrix. In a subsequent round of image acquisition, a limited number of field of view images are initially acquired and registered to the corresponding baseline images to solve for translation, rotation, and scale. The full set of baseline images is then acquired for the subsequent round and each image is pre-rotated and pre-scaled based on the transform determined for the subset of images. The pre-rotated, pre-scaled images are then registered using a translation-only transform.

Referencing in multi-acquisition slide imaging

Methods comprising probing multiple targets in an H&E stained biological sample are provided. The methods include the steps of providing a hematoxylin and eosin stained biological sample containing multiple targets, optionally detecting H&E staining of the sample, removing the hematoxylin and eosin signals, and detecting additional features or targets in the biological sample. The detecting step may include performing the steps of binding at least one probe to one or more targets to the sample, detecting a signal from the probe and contacting the sample with a bleaching agent. The process of binding, detecting and bleaching may be iteratively repeated.

Methods of analyzing an H and E stained biological sample

Approaches are disclosed for calibrating a plurality of imaging devices, such as microscopes. In certain implementations, a calibration plate is employed that include a variety of calibration features. Imaging devices calibrated in accordance with the present approaches may be used to generate images having consistent attributes, such as brightness, regardless of which imaging device is employed.

The invention provides a slide holder that utilizes edge detection algorithms to determine the location of various edges of a slide. From these edges, and integrating characteristic slide dimension, both linear offset of the edge of the slide in the holder and any rotation of the slide relative to the microscope stage axis are determined. The process of using the slide holder of the invention ensures precise and accurate placement of a slide during a first round of imaging and for reload in subsequent rounds.

Slide holder for detection of slide placement on microscope

Methods comprising the use probing multiple targets in a H&E stained biological sample are provided. The methods include the steps of providing a hematoxylin and eosin stained biological sample containing multiple targets, observing the sample, removing the hematoxylin and partially removing the eosin by washing the sample, contacting the sample with a borate salt, and irradiating the sample to remove the residual eosin fluorescence. The method further includes the optionally performing the additional steps of binding at least one probe to one or more targets to the sample, observing a signal from the probe and contacting the sample with a bleaching agent. The process of binding, observing and bleaching may be iteratively repeated.

Automated assessment of registration quality, focus, and area defects in sequentially acquired images, such as images acquired by a digital microscope, is disclosed. In one embodiment, acquired images are registered and whole-image defects are automatically detected based on a figure of merit generated by the registration process. In related implementations, area defects may be automatically detected by calculating correlations in localized image regions for images acquired in different imaging rounds.

Image quality assessment of microscopy images

In an imaging device having an objective and a stage for holding a sample to be imaged, a method for autofocusing is presented. The method includes determining a measured focus value corresponding to at least a first of a plurality of logical image segments. Further, the method includes imaging the first logical image segment using the measured focus value. The method also includes determining a predicted focus value for a second of the plurality of logical image segments using the measured focus value and a stored focus variation parameter. In addition, the method includes imaging the second logical image segment using the predicted focus value.

System and method for enhanced predictive autofocusing

A method for generating a brightfield type image, which resembles a brightfield staining protocol of a biological sample, using fluorescent images is provided. The steps comprise acquiring two or more fluorescent images of a fixed area on a biological sample, mapping said fluorescent image into a brightfield color space, generating a brightfield image, and optionally applying a sharpening transformation correction. Also provided is an image analysis system for generating a brightfield type image of a biological sample using fluorescent images.

System and methods for generating a brightfield image using fluorescent images

Image quality is assessed for a digital image that is a composite of tiles or other image segments, especially focus accuracy for a microscopic pathology sample. An algorithm or combination of algorithms correlated to image quality is applied to pixel data at margins where adjacent image segments overlap and thus contain the same content in separately acquired images. The margins may be edges merged to join the image segments smoothly into a composite image, and typically occur on four sides of the image segments. The two versions of the same image content at each margin are processed by the quality algorithm, producing two assessment values. A sign and difference value are compared with other image segments, including by subsets selected for the orientation of the margins on sides on the image segments. The differences are mapped to displays. Selection criteria determine segments to be re-acquired.

Image quality assessment including comparison of overlapped margins

A method for imaging is presented. The method includes acquiring a plurality of images corresponding to at least one field of view using an imaging device having an objective and a stage for holding a sample to be imaged. Furthermore, the method includes determining a figure of merit corresponding to each pixel in each of the plurality of acquired images, wherein the figure of merit comprises a discrete approximation to a gradient vector. The method also includes synthesizing a composite image based upon the determined figures of merit.

System and method for imaging with enhanced depth of field

A method of autofocusing includes capturing first, second and third images of a sample, at respective first, second and third sample distances and respective first, second and third lateral positions determined with respect to an objective; determining a quantitative characteristic for the first, second and third images; determining a primary sample distance based upon at least the quantitative characteristics for the first, second, and third images; and capturing a primary image of the sample at the primary sample distance and at a primary lateral position that is offset from the first, second and third lateral positions.

Predictive autofocusing

The invention provides method for locating one or more substantially circular-shaped tissue sample positioned on a solid support. The method involves the steps of transmitting light of a preselected wavelength onto a tissue sample, wherein the light induces the tissue sample to autofluoresce, identifying the center location of the tissue sample using the autofluoresced light, correlating the coordinates of the center location of the tissue sample on the solid support using an x, y-coordinate system, and mapping the coordinates of the tissue sample on the solid support to differentiate tissue sample containing regions from blank regions on the solid support. In a second aspect, the invention provides an apparatus for locating one or more substantially circular-shaped tissue sample positioned on a solid support.

Method and apparatus for ultraviolet scan planning

An Integration Controller integrates broadcast automation systems and thereby provides a single command and control center for monitoring production of the audio and video stream. An event-based schedule, or a &ldquo;playlist,&rdquo; specifies the segments to be played along with the necessary timing and hardware information. Each event in the schedule commands the playback or record of a video segment, generation of a special effect, transfer of a video segment from one device to another or closure of one or more video switches. Events may be launched automatically at a specified time, or manually by an operator. An Integration Controller (IC) communicates with an Event Scheduling System via a Scheduling System Interface. The Scheduling System Interface communicates with the Integration Controller via the IC server. The IC server utilizes various modules to communicate with Device Drivers, a Log Manager and one or more User Interfaces.

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Niskayuna, NY, United States of America

Kevin Bernard Kenny