Virtual IHC Staining via Deep Learning Autofluorescence Mapping

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Solution Overview

Problem

Current immunohistochemical (IHC) staining methods for tissue analysis are time-consuming, costly, and require specialized infrastructure and skilled operators, limiting their efficiency and accessibility for diagnostic purposes.

Innovation Solution

A deep learning-based label-free virtual IHC staining method that transforms autofluorescence microscopic images of unstained tissue sections into bright-field equivalent images, mimicking standard IHC stained images, specifically for HER2 biomarker analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional IHC staining is used, then diagnostic accuracy is maintained, but time consumption and cost increase significantly

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidtime consumption
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent creates a computational copy of the IHC staining process by training a deep neural network on paired images of stained and unstained tissue sections. The network learns to predict the stained appearance from the unstained autofluorescence images, effectively copying the staining effect without performing actual chemical staining. This resolves the contradiction by maintaining diagnostic accuracy through accurate reproduction of staining patterns while eliminating the time-consuming chemical staining process.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent replaces the mechanical/chemical staining system with a computational imaging system. Instead of using antibodies and chemical reagents to stain tissue sections, the system uses deep learning algorithms to computationally generate stained images from unstained autofluorescence images. This substitution eliminates the time-consuming laboratory procedures while maintaining the diagnostic information needed for accurate assessment.

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

2Measurement precision

If traditional IHC staining is used, then biomarker detection is achieved, but specialized infrastructure and skilled operators are required

Engineering Contradiction:
Improvebiomarker detection accuracyVSAvoidinfrastructure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent creates a computational copy of the IHC staining process by training a deep neural network on paired images of stained and unstained tissue sections. The network learns to predict the stained appearance from the unstained autofluorescence images, effectively copying the staining effect without performing actual chemical staining. This resolves the contradiction by maintaining diagnostic accuracy through accurate reproduction of staining patterns while eliminating the time-consuming chemical staining process.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent replaces the mechanical/chemical staining system with a computational imaging system. Instead of using antibodies and chemical reagents to stain tissue sections, the system uses deep learning algorithms to computationally generate stained images from unstained autofluorescence images. This substitution eliminates the time-consuming laboratory procedures while maintaining the diagnostic information needed for accurate assessment.

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

3Measurement precision

If chemical IHC staining is performed, then specific biomarker identification is achieved, but the process becomes laborious and costly

Engineering Contradiction:
Improvebiomarker identification accuracyVSAvoidprocessing efficiency
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent creates a computational copy of the IHC staining process by training a deep neural network on paired images of stained and unstained tissue sections. The network learns to predict the stained appearance from the unstained autofluorescence images, effectively copying the staining effect without performing actual chemical staining. This resolves the contradiction by maintaining diagnostic accuracy through accurate reproduction of staining patterns while eliminating the time-consuming chemical staining process.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent replaces the mechanical/chemical staining system with a computational imaging system. Instead of using antibodies and chemical reagents to stain tissue sections, the system uses deep learning algorithms to computationally generate stained images from unstained autofluorescence images. This substitution eliminates the time-consuming laboratory procedures while maintaining the diagnostic information needed for accurate assessment.

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

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The method achieves accurate and efficient virtual IHC staining, matching the quality of standard chemical IHC staining, and significantly reduces the time and labor required, while maintaining diagnostic accuracy.

Implementation Method 1

obtaining one or more autofluorescence images of the label-free tissue sample with a fluorescence imaging device

Methodology Applied
Scientific EffectAutofluorescence: Fluorescence

Data Source

PatentUS20250046069A1Label-free virtual immunohistochemical staining of tissue using deep learning
Publication Date: 2025.02.06 RGT UNIV OF CALIFORNIA
  • US20250046069A1 patent drawing
  • US20250046069A1 patent drawing
  • US20250046069A1 patent drawing

AI summary

A deep learning-based virtual HER2 IHC staining method uses a conditional generative adversarial network that is trained to rapidly transform autofluorescence microscopic images of unlabeled/label-free breast tissue sections into bright-field equivalent microscopic images, matching the standard HER2 IHC staining that is chemically performed on the same tissue sections. The efficacy of this staining framework was demonstrated by quantitative analysis of blindly graded HER2 scores of virtually stained and immunohistochemically stained HER2 whole slide images (WSIs). A second quantitative blinded study revealed that the virtually stained HER2 images exhibit a comparable staining quality in the level of nuclear detail, membrane clearness, and absence of staining artifacts with respect to their immunohistochemically stained counterparts. This virtual staining framework bypasses the costly, laborious, and time-consuming IHC staining procedures in laboratory, and can be extended to other types of biomarkers to accelerate the IHC tissue staining and biomedical workflow.