Fiberoptic Probe for Fluorescence Quantification in Turbid Tissue

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Solution Overview

Problem

Existing methods for quantifying fluorescence in turbid media like tissue face challenges due to variations in tissue optical properties, leading to inaccurate measurements, especially in the UV-blue-green spectrum where many fluorophores have absorption maxima, and current techniques are either invasive, time-consuming, or limited in applicability.

Innovation Solution

A fiberoptic probe device with a handle and a hypodermic needle-like tip, equipped with a linear array of fiberoptics, is used to measure fluorescence and white light reflectance at varying source-collector distances, applying a model of light interaction with tissue to determine optical properties and correct for distortions, allowing for in vivo quantification of fluorescence and fluorophore concentration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescence measurements are performed in tissue using conventional methods, then fluorescence signals can be detected, but measurement accuracy deteriorates due to tissue absorption and scattering effects

Engineering Contradiction:
Improvefluorescence quantification accuracyVSAvoidtissue optical property variations
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The system measures tissue optical properties (absorption and scattering coefficients) and uses these measurements as feedback to correct the fluorescence signal. The optical properties are determined from reflectance measurements at multiple source-detector distances, and these values are then used to compensate for the distorting effects on fluorescence, improving quantification accuracy.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent introduces an intermediate correction step using a fluorescence photon migration model. The model acts as a mediator that translates raw fluorescence measurements and optical property measurements into corrected fluorescence values. This intermediary process accounts for the complex light-tissue interactions and removes the distorting effects of absorption and scattering.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Device complexity

If single fiber method is used for fluorescence measurement, then device complexity is reduced, but measurement accuracy worsens due to minimal detection of fluorescence events

Engineering Contradiction:
Improveprobe structure simplicityVSAvoidfluorescence detection sensitivity
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The probe uses multiple separate optical fibers instead of a single fiber. The fibers are segmented into different functional groups: excitation fibers, collection fibers at various distances, and reference fibers. This segmentation allows simultaneous measurement of fluorescence at multiple source-detector separations, improving detection sensitivity while maintaining relatively simple probe construction.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system adds the dimension of spatial resolution by measuring fluorescence at multiple source-detector distances simultaneously. This multi-distance approach provides additional information about the fluorescence distribution and tissue optical properties, enhancing measurement sensitivity without significantly increasing device complexity.

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

3Adaptability or versatility

If excitation source operates in low tissue absorption region, then fluorescence measurement is feasible, but applicability worsens for UV-blue-green spectrum fluorophores

Engineering Contradiction:
Improvespectral range applicabilityVSAvoidtissue absorption loss
Core Design Contradiction:
Adaptability or versatilityVSLoss of energy

Solution Approach 1:

The system replaces the conventional approach of avoiding high-absorption wavelengths with a computational correction method. Instead of selecting excitation wavelengths based on low tissue absorption, the system can use any wavelength and then apply mathematical correction based on measured optical properties. This substitution of physical constraint with computational solution extends applicability to UV-blue-green spectrum fluorophores.

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

Solution Approach 2:

The system dynamically adjusts the correction parameters based on measured tissue optical properties. By changing the absorption and scattering coefficients used in the correction model to match the actual tissue being measured, the system can accurately quantify fluorescence even at wavelengths where tissue absorption is high, thereby extending spectral range applicability.

Inventive Principle:
Principle #35Parameter changes

4Measurement precision

If diffuse reflectance signal is used to correct fluorescence, then optical property variation is compensated, but device complexity increases due to multiple measurement requirements

Engineering Contradiction:
Improvefluorescence quantification accuracyVSAvoidmeasurement system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The system merges the fluorescence measurement and optical property measurement into a single integrated process. Both fluorescence and reflectance signals are collected simultaneously using the same probe and detection system, eliminating the need for separate measurement devices and reducing overall system complexity while maintaining correction accuracy.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The system continuously measures both fluorescence and reflectance signals to maintain accurate real-time correction. By maintaining continuous measurement of optical properties alongside fluorescence, the system ensures that correction parameters are always current, improving quantification accuracy without requiring intermittent or separate measurement cycles.

Inventive Principle:
Principle #20Continuity of useful 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

The device effectively compensates for tissue optical property variations, providing accurate, in vivo quantification of fluorescence and fluorophore concentrations, enhancing diagnostic capabilities and surgical guidance by reducing measurement geometry errors and improving sensitivity to tumor markers.

Implementation Method 1

A fluorescence photon migration model to produce a relation with the diffuse reflectance that can be exploited to extract the quantitative fluorescence in tissue

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

Fluorescence signals are strongly affected by variations in the tissue absorption and transport scattering properties

Methodology Applied
Scientific EffectLight scattering: Scattering

Implementation Method 3

The shape and intensity of the fluorescence spectrum contain useful information on the identity and abundance of fluorophores in tissue. However, accuracy of quantitative fluorescence measurement is complicated by the distorting effects of light absorption and scattering by the tissue

Methodology Applied
Scientific EffectLight absorption: Absorption (EM radiation)

Implementation Method 4

Many of these techniques use a diffuse reflectance signal to correct the fluorescence signal from optical properties variation

Methodology Applied
Scientific EffectDiffuse reflectance: Reflection

Data Source

PatentEP4160192B1Device, system and method for quantifying fluorescence and optical properties
Publication Date: 2024.05.29 UNIV HEALTH NETWORK
  • EP4160192B1 patent drawingFigure 1~2
  • EP4160192B1 patent drawingFigure 3~4
  • EP4160192B1 patent drawingFigure 5~6(b)

AI summary

Methods for quantifying fluorescence and optical properties in a turbid medium such as tissue. Devices and systems suitable for the methods are also disclosed.