Iodinated Oil Contrast Medium for Microangiography

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Solution Overview

Problem

Current contrast agents for microangiography struggle to visualize capillaries with diameters less than 3-4 µm due to inadequate penetration and high viscosity, limiting the resolution and completeness of vascular imaging in micro-CT scans.

Innovation Solution

A contrast agent comprising iodinated, esterified oil, polyurethane, and a ketone solvent, specifically iodinated linseed or poppy seed oil with a polyurethane hardener, which is designed to penetrate deeper into capillaries and harden within the vascular system for improved visualization in micro-CT imaging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional contrast agents are used for microangiography, then the vascular system can be visualized, but the resolution is limited and capillaries with diameter less than 3-4 µm cannot be adequately penetrated

Engineering Contradiction:
Improvevisualization resolutionVSAvoidcapillary penetration completeness
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent modifies the physical and chemical parameters of the contrast agent by formulating a low-viscosity iodinated contrast medium with specific rheological properties. The contrast agent contains iodinated oil (20-40% w/v), non-ionic surfactant (5-20% w/v), and water, creating a formulation with optimized viscosity and surface tension that enables penetration into capillaries with diameter of 3-4 µm and smaller, thereby improving both resolution and penetration completeness

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite contrast agent formulation combining multiple components: iodinated oil for radiopacity, non-ionic surfactant for reducing surface tension and viscosity, and water as the continuous phase. This composite structure allows the contrast medium to achieve both adequate capillary penetration and sufficient X-ray attenuation for high-resolution visualization

Inventive Principle:
Principle #40Composite materials

2Reliability

If the viscosity of the contrast agent is reduced to improve capillary penetration, then smaller vessels can be reached, but the radiopacity and contrast quality may deteriorate

Engineering Contradiction:
Improvecapillary penetration abilityVSAvoidradiopacity
Core Design Contradiction:
ReliabilityVSIllumination intensity

Solution Approach 1:

The patent carefully balances the concentration of iodinated oil (20-40% w/v) to maintain adequate radiopacity while adjusting the surfactant content (5-20% w/v) and water proportion to control viscosity. This parameter optimization ensures the contrast agent has both low enough viscosity for capillary penetration and sufficient iodine concentration for X-ray attenuation

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The non-ionic surfactant acts as an intermediary substance that reduces the surface tension and viscosity of the iodinated oil-water mixture. The surfactant molecules form micelles that solubilize the hydrophobic iodinated oil in the aqueous phase, creating a homogeneous low-viscosity formulation that maintains radiopacity while enabling deep capillary penetration

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If manual dilution of contrast agent is performed to achieve capillary penetration, then smaller vessels can be visualized, but the process is time-consuming and lacks standardization

Engineering Contradiction:
Improvecapillary visualization capabilityVSAvoidpreparation time and standardization
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent performs preliminary optimization of the contrast agent formulation during the development phase, creating a pre-formulated low-viscosity contrast medium with optimized composition (iodinated oil 20-40% w/v, surfactant 5-20% w/v, water). This preliminary action eliminates the need for manual dilution and adjustment during actual microangiography procedures, saving time and ensuring consistent, standardized results

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent establishes fixed concentration ranges for each component (iodinated oil 20-40% w/v, surfactant 5-20% w/v) that have been pre-optimized to achieve the desired balance between viscosity and radiopacity. These standardized parameters allow direct use of the contrast agent without manual dilution, improving productivity while maintaining capillary visualization capability

Inventive Principle:
Principle #35Parameter changes

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

Enables reproducible and high-resolution visualization of capillaries down to 3-4 µm diameter, allowing for detailed morphometric analysis and maintaining tissue integrity for subsequent histological examination, while providing autofluorescence for easier monitoring and localization.

Implementation Method 1

a contrast agent that can penetrate sufficiently far into the smallest vessels and enables visualization of the microvasculature that is as artifact-free as possible or morphometric 3D image analysis using micro-CT

Methodology Applied
Scientific EffectX-ray absorption: Absorption (EM radiation)

Implementation Method 2

A contrast agent comprising iodinated, esterified oil, polyurethane, and a ketone solvent, specifically iodinated linseed or poppy seed oil with a polyurethane hardener, which is designed to penetrate deeper into capillaries and harden within the vascular system

Methodology Applied
Scientific EffectPolymerization: Photopolymerisation

Implementation Method 3

A contrast agent comprising iodinated, esterified oil, polyurethane, and a ketone solvent, specifically iodinated linseed or poppy seed oil with a polyurethane hardener

Methodology Applied
Scientific EffectSolvation: Solvation

Implementation Method 4

providing autofluorescence for easier monitoring and localization

Methodology Applied
Scientific EffectAutofluorescence: Fluorescence

Data Source

PatentEP3592331B1Contrast medium for microangiography
Publication Date: 2020.12.30 PITENGO GMBH
  • EP3592331B1 patent drawingFigure 1A~1F'
  • EP3592331B1 patent drawingFigure 2A~2D'
  • EP3592331B1 patent drawingFigure 3a~3c'

AI summary

The invention relates to a contrast medium for ex vivo microangiography for digital imaging of the vascular system of a mouse or rat or other laboratory animals, and of individual animal and human organs, comprising an iodized, esterified oil, a polyurethane, and a hardener. The invention further relates to a method for producing the contrast medium; to a kit of parts, comprising the various containers having the components of the contrast medium according to the invention that are to be mixed; and to a preferred use of the contrast medium according to the invention for imaging by means of a micro-CT device.