Digital Prostate Tissue Analysis for PSA Recurrence Prediction

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Solution Overview

Problem

Manual Gleason grading of prostate cancer tissue is challenging due to the need for consistent evaluation of numerous cancerous areas on highly magnified images, making it difficult to accurately determine the Gleason score, which is crucial for predicting prostate-specific antigen (PSA) recurrence after radical prostatectomy.

Innovation Solution

A system that analyzes duplex-stained digital images of prostate tissue slices to generate masks for intact and non-intact glands, stroma regions, and influence zones, and counts macrophage objects in these regions to determine a score indicative of PSA recurrence, using specific biomarkers like CK18, p63, CD68, and CD163 to differentiate between M1 and M2 macrophages and assess their distribution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If manual Gleason grading is performed by pathologists evaluating highly magnified images, then diagnostic accuracy can be maintained through expert visual inspection, but the process becomes time-consuming and difficult to perform consistently across numerous cancerous areas

Engineering Contradiction:
ImproveGleason score accuracyVSAvoidgrading time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces the manual mechanical process of visual inspection and manual scoring with an automated digital image analysis system. The system uses computer algorithms to automatically detect, segment, and evaluate glandular structures in tissue images, generating Gleason scores without manual intervention. This substitution of automated computational methods for manual visual assessment resolves the contradiction by maintaining diagnostic accuracy while dramatically reducing grading time.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent transforms the subjective visual assessment parameters into objective quantitative measurements. By converting glandular architecture evaluation into measurable features such as gland size, shape, spacing, and spatial distribution, the system enables automated calculation of Gleason scores. This parameter transformation allows the system to maintain the diagnostic precision of expert evaluation while eliminating the time-consuming nature of manual inspection.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If pathologists manually inspect and classify each cancerous area on magnified images, then accurate Gleason scoring can be achieved through consistent evaluation, but the complexity and difficulty of the task increase significantly

Engineering Contradiction:
ImproveGleason score consistencyVSAvoidevaluation process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the complex task of Gleason scoring into distinct automated steps: image preprocessing, gland detection, gland segmentation, feature extraction, and score calculation. Each step is handled by specialized algorithms that process specific aspects of the tissue architecture. This segmentation of the evaluation process reduces complexity by breaking down the overwhelming manual task into manageable automated components while ensuring consistent application of grading criteria.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces an intermediary computational layer between the raw tissue images and the final Gleason score. This intermediary system includes multiple processing stages that transform images into quantitative features, apply grading rules, and generate scores. This intermediary computational framework mediates the complexity by providing a structured, rule-based approach that ensures consistency while reducing the burden on pathologists.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If traditional Gleason scoring methods are used, then the process remains simple and quick, but the ability to predict PSA recurrence accurately is insufficient

Engineering Contradiction:
Improvegrading speedVSAvoidrecurrence prediction accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent adds another dimension to traditional Gleason scoring by incorporating spatial and contextual information beyond basic glandular patterns. The system analyzes the spatial distribution of glands, their relative positions, and the architecture of the tumor microenvironment. This dimensional expansion allows the system to maintain rapid processing speeds while significantly improving recurrence prediction accuracy through more comprehensive feature analysis.

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

Solution Approach 2:

The patent creates a composite scoring system that combines traditional Gleason grade group assessment with additional quantitative features derived from digital image analysis. By integrating multiple independent measurements including glandular architecture, spatial distribution, and microenvironment characteristics, the system produces a composite prediction model that maintains the speed of traditional grading while achieving superior predictive accuracy for PSA recurrence.

Inventive Principle:
Principle #40Composite materials

Data Source

PatentUS10579935B2System for predicting the recurrence of cancer in a cancer patient
Publication Date: 2020.03.03 DEFINIENS GMBH
  • US10579935B2 patent drawing
  • US10579935B2 patent drawing
  • US10579935B2 patent drawing

AI summary

A system predicts the recurrence of cancer. A first slice of a prostate tissue sample is stained so that luminal epithelial cells and basal epithelial cells are stained different colors. A first digital image is taken of the first slice. The second slice of the sample is stained so that M1 type macrophages and M2 type macrophages are differentially stained. A second digital image is taken of the second slice. The system analyzes the first digital image and defines regions of non-intact glands. Intact gland regions are then determined, and regions of stroma are identified. The system defines influence zones between non-intact regions and stroma regions. Using information from the second image, macrophages in the tissue corresponding to the influence zones are identified and counted. Based at least in part on this count, the system determines a score. The score is indicative of whether the patient will experience PSA recurrence.