Multi-modal Contrast Imaging for Tissue Context

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Solution Overview

Problem

Conventional histological stained tissue sections require serial preparation and evaluation, which increases costs and time, and can be difficult to correlate features between different sections, especially when using fluorescence-based imaging that lacks anatomical context.

Innovation Solution

The use of multi-modal contrast methods that combine refractive index properties with fluorescent labeling, allowing for simultaneous or sequential imaging of tissue sections, providing complementary contrast components that can be displayed in a digitally rendered brightfield context similar to conventional histological stains, eliminating the need for serial sections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescence-based imaging is used to detect molecular markers, then molecular information is enhanced, but anatomical context information is lost

Engineering Contradiction:
Improvemolecular marker detectionVSAvoidanatomical context
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent combines fluorescence-based molecular marker detection with brightfield imaging that preserves anatomical context. The multi-modal imaging system simultaneously captures fluorescence signals for molecular information and brightfield images for structural context, merging both types of information in a single integrated workflow rather than requiring separate serial sections.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The imaging system performs multiple functions simultaneously: it detects molecular markers via fluorescence while also providing anatomical context through brightfield imaging, and can generate both colored and grayscale images from the same specimen. This multi-functionality eliminates the need for separate staining and imaging procedures.

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

2Measurement precision

If serial tissue sections are prepared for conventional H&E staining and molecular marker staining, then comprehensive diagnostic information is obtained, but cost and time increase

Engineering Contradiction:
Improvediagnostic information completenessVSAvoidevaluation time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent merges multiple diagnostic functions into a single tissue section by combining H&E staining with molecular marker detection on the same specimen. This allows comprehensive diagnostic information to be obtained from one section rather than requiring multiple serial sections, thereby reducing processing time and cost.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The system performs preliminary H&E staining and molecular marker application on the same tissue section before imaging. This preliminary preparation allows both structural and molecular information to be captured simultaneously during the imaging process, eliminating the need for separate serial section preparation.

Inventive Principle:
Principle #10Preliminary action

3Adaptability or versatility

If serial sections are used for different staining purposes, then multiple diagnostic features can be evaluated, but correlation between sections becomes difficult

Engineering Contradiction:
Improvediagnostic feature evaluationVSAvoidspatial correlation
Core Design Contradiction:
Adaptability or versatilityVSLoss of information

Solution Approach 1:

The patent merges multiple diagnostic evaluations into a single spatial reference frame by imaging both H&E-stained structures and molecular marker locations on the same tissue section. This ensures that spatial correlations between anatomical features and molecular markers are preserved, as both types of information are captured from the identical physical location.

Inventive Principle:
Principle #5Merging (Combining)

4Loss of information

If conventional H&E staining is used to provide anatomical context, then structural information is preserved, but molecular marker detection capability is reduced

Engineering Contradiction:
Improveanatomical context preservationVSAvoidmolecular marker detection
Core Design Contradiction:
Loss of informationVSMeasurement precision

Solution Approach 1:

The patent merges H&E staining with molecular marker detection on the same tissue section, allowing both anatomical context preservation and molecular marker detection to occur simultaneously. The multi-modal imaging system captures both the colored H&E-stained structures and the fluorescent molecular markers from the same specimen without requiring separate sections.

Inventive Principle:
Principle #5Merging (Combining)

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

This approach enables physicians to navigate and interpret tissue structures with familiar anatomical and morphological context, correlating molecular information with structural features without the need for conventional staining, reducing costs and time while enhancing diagnostic accuracy.

Implementation Method 1

contrast is derived from the refractive index properties and fluorescent labeling of tissue specially prepared for markers of specific molecules

Methodology Applied
Scientific EffectRefraction: Refraction

Implementation Method 2

fluorescence based images can be used for detection of specialized molecular markers

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 3

a combination of transmitted-light darkfield refraction contrast imaging, with simultaneous incident light fluorescence imaging

Methodology Applied
Scientific EffectLight scattering: Scattering

Data Source

PatentUS9310302B2Multi-modality contrast and brightfield context rendering for enhanced pathology determination and multi-analyte detection in tissue
Publication Date: 2016.04.12 VENTANA MEDICAL SYSTEMS INC
  • US9310302B2 patent drawing
  • US9310302B2 patent drawing
  • US9310302B2 patent drawing

AI summary

Multiple modality contrast can be used to produce images that can be combined and rendered to produce images similar to those produced with wavelength absorbing stains viewed under transmitted white light illumination. Images obtained with other complementary contrast modalities can be presented using engineered color schemes based on classical contrast methods used to reveal the same anatomical structures and histochemistry, thereby providing relevance to medical training and experience. Dark-field contrast images derived from refractive index and fluorescent DAPI counterstain images are combined to produce images similar to those obtained with conventional H&E staining for pathology interpretation. Such multi-modal image data can be streamed for live navigation of histological samples, and can be combined with molecular localizations of genetic DNA probes (FISH), sites of mRNA expression (mRNA-ISH), and immunohistochemical (IHC) probes localized on the same tissue sections, used to evaluate and map tissue sections prepared for imaging mass spectrometry.