Selective Stain Segmentation for Digital Pathology

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Solution Overview

Problem

Current digital image analysis methods for medical diagnosis struggle to accurately classify and segment specific cell types in membrane-stained tissue images, leading to incomplete or incorrect quantification of staining, especially when cells are intermixed or have shared membrane components.

Innovation Solution

A digital image analysis system that includes a membrane mask generation engine, a cell classification engine, and a selective stain segmentation engine, which uses machine learning approaches to detect cells, classify them, and generate selective stain segmentation images by splitting shared membrane components using techniques like Voronoi diagrams, enabling accurate separation of specific cell types.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If algorithms use predefined threshold to define neighborhood around nuclei for membrane detection, then detection process is simplified, but membrane staining may be missed if cells are intermixed or membrane lies outside predefined radius

Engineering Contradiction:
Improvedetection process simplicityVSAvoidmembrane staining detection accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The system dynamically adjusts the neighborhood radius around each nucleus based on the specific image content and cell density, rather than using a fixed predefined threshold. This allows the detection algorithm to adapt to varying cell configurations and ensure membranes are captured even when cells are intermixed or membranes extend beyond standard distances from nuclei.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The algorithm changes the detection parameters (neighborhood radius, threshold values) based on local image characteristics and cell morphology. By adjusting these parameters dynamically rather than using fixed values, the system maintains both operational simplicity and detection accuracy across diverse tissue samples.

Inventive Principle:
Principle #35Parameter changes

2Device complexity

If algorithms ignore regions with membrane staining in combination with other staining compartments, then processing complexity is reduced, but quantification of staining becomes incomplete or incorrect

Engineering Contradiction:
Improvealgorithm processing complexityVSAvoidstaining quantification accuracy
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The system segments the staining analysis into distinct compartments (nuclei, cytoplasm, membrane) and processes each compartment separately while maintaining awareness of their relationships. This allows the algorithm to handle complex multi-compartment staining patterns without overwhelming complexity, by breaking down the problem into manageable segments that can be analyzed independently and then integrated.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The algorithm is designed to universally handle multiple staining compartments and their combinations through a unified framework. Rather than creating separate specialized algorithms for each staining pattern, the system uses a multi-functional approach that can process nuclei staining, cytoplasmic staining, membrane staining, and their combinations through the same core detection and quantification pipeline.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Loss of information

If multiple information channels of image data are derived from scanned assay, then comprehensive information is captured, but each observed channel comprises mixture of multiple signals making analysis difficult

Engineering Contradiction:
Improveinformation completenessVSAvoidsignal separation difficulty
Core Design Contradiction:
Loss of informationVSDifficulty of detecting and measuring

Solution Approach 1:

The system extracts and separates the mixed signals within each image channel by identifying and isolating contributions from different staining compartments. Through sophisticated image analysis, the algorithm extracts pure membrane staining signals from channels that contain mixed signals from nuclei, cytoplasm, and membrane, enabling accurate quantification despite the inherent signal mixing in multi-channel imaging.

Inventive Principle:
Principle #2Taking out (Extraction)

Data Source

PatentEP3729371B1System and method for generating selective stain segmentation images for cell types of interest
Publication Date: 2023.09.06 VENTANA MEDICAL SYSTEMS INC
  • EP3729371B1 patent drawingFigure 1
  • EP3729371B1 patent drawingFigure 2
  • EP3729371B1 patent drawingFigure 3

AI summary

An image analysis system and method to generate selective stain segmentation images for at least one cell type of interest within a stained tissue image. The system and method may detect cells in the tissue image and generate a corresponding membrane mask image. They may classify the cells detected in the tissue image and generate a classified cells image of the cells. The system and method may further generate selective stain segmentation images for the at least one cell type of interest based on the membrane mask image and the classified cells image of the cells.