Tubule Detection in Breast Cancer Histology Using Graph-Cut Segmentation

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Solution Overview

Problem

Current methods for automating the identification of tubule and non-tubule glandular regions in breast cancer tissue images are inefficient due to their inability to handle cases with multiple layers of nuclei and reliance on partial image analysis, leading to subjective and time-consuming manual estimation.

Innovation Solution

The method involves detecting nuclei and lumen candidates, applying a random forest classifier for classification, and using a graph-cut method to build a nuclei-lumen graph, which partitions the image into connected components to classify glandular regions as tubule or non-tubule, enabling accurate calculation of tubule percentage in whole slide images.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Extent of automation

If manual estimation of tubule percentage is used, then subjectivity and time consumption increase, but automation methods have not yet resolved the complexity of handling multiple layers of nuclei

Engineering Contradiction:
Improveautomation of tubule detectionVSAvoidaccuracy in handling multiple layers of nuclei
Core Design Contradiction:
Extent of automationVSReliability

Solution Approach 1:

The patent segments the complex task of tubule detection into distinct modules: (1) nuclei detection and classification, (2) lumen detection, (3) nuclei-lumen association through graph construction, and (4) tubule identification. This segmentation allows each module to handle specific complexities independently, particularly in managing multiple layers of nuclei through the graph-based association approach.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces a nuclei-lumen graph as an intermediary structure that mediates between the detected nuclei and lumens. This graph representation allows complex spatial relationships involving multiple layers of nuclei to be systematically modeled and processed, enabling accurate tubule identification without direct manual intervention.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Extent of automation

If existing automated methods are used, then some automation is achieved, but they rely on analysis of only small segments of whole slide tissue

Engineering Contradiction:
Improveautomation of tubule detectionVSAvoidcoverage area of tissue analysis
Core Design Contradiction:
Extent of automationVSArea of stationary object

Solution Approach 1:

The patent designs a universal processing framework that can handle entire whole slide images through the graph-based nuclei-lumen association approach. The methodology is scalable and can process varying sizes of tissue sections uniformly, making it applicable to both small segments and large whole slide images without requiring method modification.

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

3Device complexity

If connection of lumen to closest nuclei is used, then simple association is achieved, but cases with multiple layers of nuclei cannot be handled

Engineering Contradiction:
Improvesimplicity of nuclei-lumen associationVSAvoidaccuracy in tubule percentage estimation
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The patent transitions from simple 2D closest-neighbor connection to a multi-dimensional graph-based association approach. The nuclei-lumen graph captures complex spatial relationships in multiple dimensions, allowing accurate identification of tubules even when multiple layers of nuclei surround lumens, thereby improving measurement precision without excessive complexity.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Data Source

PatentEP3175389B1Automatic glandular and tubule detection in histological grading of breast cancer
Publication Date: 2024.05.15 VENTANA MEDICAL SYSTEMS INC
  • EP3175389B1 patent drawingFigure 1
  • EP3175389B1 patent drawingFigure 2A
  • EP3175389B1 patent drawingFigure 2B

AI summary

Methods, systems, and apparatuses for automatically identifying glandular regions and tubule regions in a breast tissue sample are provided. An image of breast tissue is analyzed to detect nuclei and lumen candidates, identify tumor nuclei and true lumen from the candidates, and group tumor nuclei with neighboring tumor nuclei and lumina to define tubule glandular regions and non-tubule glandular regions of the image. Learnt supervised classifiers, such as random forest classifiers, can be applied to identify and classify the tumor nuclei and true lumina. Graph-cut methods can be applied to group the tumor nuclei and lumina and to define the tubule glandular regions and non-tubule glandular regions. The analysis can be applied to whole slide images and can resolve tubule areas with multiple layers of nuclei.