SLIME Microvascular Imaging via OCT and Contrast Agents

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Solution Overview

Problem

Current 3D microvascular imaging methods are complex, expensive, and time-intensive, making them unsuitable for large-volume and large-sample population studies, such as drug screening and diverse phenotype studies.

Innovation Solution

The development of a method called 'scatter labeled imaging of microvasculature in excised tissue' (SLIME) using optical coherence tomography (OCT), which involves perfusing tissue samples with a contrast agent, cross-linking it to prevent leakage, and then using optical clearing agents to enhance imaging depth and contrast, allowing for fast and cost-effective 3D microvascular imaging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional 3D microvascular imaging methods (micro-CT, confocal microscopy) are used, then imaging resolution and detail are improved, but device complexity, cost, and time consumption increase significantly

Engineering Contradiction:
Improveimaging resolutionVSAvoidmethod complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical imaging systems (micro-CT scanners, confocal microscopes) with a simpler optical coherence tomography (OCT) system. By using OCT technology with scatter-labeled contrast agents, the method achieves high-resolution 3D microvascular imaging without requiring the complex mechanical scanning and reconstruction systems of conventional methods, thus reducing device complexity while maintaining imaging precision

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

Solution Approach 2:

The patent changes the optical parameters of the tissue by introducing scatter-labeled contrast agents that modify light scattering properties. This allows OCT to achieve enhanced contrast and resolution for microvascular imaging, transforming the tissue's optical characteristics to be more suitable for the simpler OCT modality rather than requiring complex imaging equipment

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If conventional 3D microvascular imaging methods are used, then imaging quality is improved, but processing time and cost increase

Engineering Contradiction:
Improveimaging qualityVSAvoidprocessing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces time-consuming conventional imaging methods with OCT, which provides rapid volumetric data acquisition. The scatter-labeled contrast agent enables real-time or near-real-time imaging with high quality, dramatically reducing processing time while maintaining or improving imaging quality through the inherent speed advantages of OCT technology

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

Solution Approach 2:

The patent performs preliminary labeling of the vasculature with scatter-labeled contrast agents before imaging, which simplifies the subsequent imaging process. This pre-preparation step enhances the signal-to-noise ratio and enables faster, higher-quality imaging without requiring complex post-processing or repeated scanning, thus reducing overall processing time

Inventive Principle:
Principle #10Preliminary action

3Loss of information

If conventional 3D microvascular imaging methods are used, then detailed vascular structure visualization is improved, but cost and complexity increase

Engineering Contradiction:
Improvevascular structure detailVSAvoidmethod cost
Core Design Contradiction:
Loss of informationVSEase of manufacture

Solution Approach 1:

The patent replaces expensive conventional imaging systems with a more cost-effective OCT system. By using scatter-labeled contrast agents that enhance the OCT signal, the method achieves detailed vascular structure visualization at a lower cost, making high-quality microvascular imaging more accessible and economically viable

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

Solution Approach 2:

The patent modifies the optical scattering parameters of blood vessels through contrast agent labeling, enabling detailed vascular structure visualization using the cheaper and simpler OCT modality. This parameter transformation allows cost-effective imaging to achieve the same informational detail as expensive conventional methods

Inventive Principle:
Principle #35Parameter changes

4Volume of moving object

If large volume tissue imaging is performed with conventional methods, then complete vascular mapping is improved, but time consumption and complexity increase

Engineering Contradiction:
Improvetissue volume imagedVSAvoidimaging speed
Core Design Contradiction:
Volume of moving objectVSProductivity

Solution Approach 1:

The patent replaces slow conventional imaging methods with high-speed OCT technology that can rapidly acquire volumetric data. The scatter-labeled contrast agents enhance the OCT signal throughout the entire tissue volume, enabling complete vascular mapping of large samples at high speeds, thus improving productivity while maintaining comprehensive coverage

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

Solution Approach 2:

The patent performs preliminary uniform distribution of scatter-labeled contrast agents throughout the vasculature of the entire tissue volume before imaging. This pre-labeling ensures that all vascular structures throughout the large volume are equally visible, enabling rapid complete mapping without requiring sequential sectioning or repeated imaging, thus dramatically improving imaging speed and productivity

Inventive Principle:
Principle #10Preliminary action

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

SLIME provides high-speed, high-resolution, and wide-field 3D microvascular imaging without shadowing artifacts, enabling efficient visualization and quantification of microvascular morphology, suitable for large cohort studies and diverse biological samples.

Implementation Method 1

the tissue sample can then be immersed in a solution comprising an optical clearing agent

Methodology Applied
Scientific EffectOptical clearing:

Implementation Method 2

scatter labeled imaging of microvasculature in excised tissue (SLIME) based on optical coherence tomography (OCT)

Methodology Applied
Scientific EffectLight scattering: Scattering

Data Source

PatentUS11845955B2Scatter labeled imaging of microvasculature in excised tissue (SLIME)
Publication Date: 2023.12.19 CASE WESTERN RESERVE UNIV
  • US11845955B2 patent drawing
  • US11845955B2 patent drawing
  • US11845955B2 patent drawing

AI summary

The present disclosure relates to a simple, fast, and low cost method for 3D microvascular imaging, termed “scatter labeled imaging of microvasculature in excised tissue” (SLIME). The method can include perfusing a contrast agent through vasculature of a tissue sample. The contrast agent can include colloids and a dispersant. After the contrast agent is perfused through the vasculature, the vasculature of the tissue sample can be treated with a molecule that cross links with at least a portion of the dispersant to form a sticky, non-Newtonian polymer that prevents leakage of the contrast agent out of the vasculature of the tissue sample. The tissue sample can then be immersed in a solution comprising a clearing agent and subsequently imaged.