Fluorescence Signal Processing for Lifetime-Independent Spatial Distribution

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Solution Overview

Problem

Current fluorescence molecular imaging techniques face challenges in determining the spatial distribution of fluorophores in a diffusing medium without prior knowledge of the fluorescence lifetime, as this parameter can be sensitive to the environment and difficult to measure in vivo, leading to erroneous results.

Innovation Solution

A method and device for processing fluorescence signals that calculates a variable independent of the fluorescence lifetime, allowing for the determination of the spatial distribution of fluorophores by using normalized measurements, Mellin-Laplace transforms, and error function minimization, enabling the calculation of the first moment of the fluorescence signal and correction for background noise.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescence lifetime is used as a parameter for reconstruction, then the spatial distribution can be determined, but the results become erroneous due to environmental sensitivity and measurement difficulty in vivo

Engineering Contradiction:
Improvespatial distribution determinationVSAvoidmeasurement reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent extracts and eliminates the fluorescence lifetime parameter from the reconstruction process. Instead of using lifetime-dependent moments, the invention formulates a lifetime-independent reconstruction method that uses only intensity and spatial information, thereby removing the source of measurement errors associated with lifetime variability in vivo

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the parameter set used for reconstruction from lifetime-dependent moments to lifetime-independent variables. The method transforms the reconstruction problem to use parameters that are not sensitive to environmental changes, such as normalized intensity ratios and spatial coordinates, fundamentally altering the parameter space to eliminate reliability issues

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If fluorescence lifetime is assumed to be known for reconstruction, then the reverse problem can be solved, but this assumption leads to erroneous results when the lifetime is not accurately known

Engineering Contradiction:
Improvereconstruction processVSAvoidspatial distribution accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent makes the reconstruction method self-sufficient by eliminating the need for external lifetime information. The system uses only the fluorescence signals directly measured in the experiment, processing them through lifetime-independent moment calculations and reconstruction algorithms that do not require any a priori knowledge of fluorescence lifetime values

Inventive Principle:
Principle #25Self-service

3Productivity

If traditional moment extraction methods are used, then the reconstruction can be performed, but the results are sensitive to errors in fluorescence lifetime measurement

Engineering Contradiction:
Improvereconstruction efficiencyVSAvoidreconstruction reliability
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent introduces lifetime-independent moments as intermediary variables that mediate between the raw fluorescence signals and the final spatial distribution reconstruction. These intermediary moments capture the essential spatial and temporal information without being contaminated by lifetime variability, serving as a reliable bridge in the reconstruction process

Inventive Principle:
Principle #24Intermediary (Mediator)

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 allows for accurate determination of the spatial distribution of fluorophores without relying on fluorescence lifetime measurements, improving the precision and reliability of fluorescence molecular imaging by considering a normalized frequency function and minimizing errors, thus overcoming the limitations of existing methods.

Implementation Method 1

processing emitted fluorescence signals, after excitation by radiation from a radiation source, by at least one fluorophore with a lifetime τ

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS7977650B2Method and device for 3D reconstruction of the distribution of fluorescent elements
Publication Date: 2011.07.12 COMMISSARIAT A LENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
  • US7977650B2 patent drawing
  • US7977650B2 patent drawing
  • US7977650B2 patent drawing

AI summary

A device and method for processing fluorescence signals emitted after excitation by radiation coming from a radiation source, by at least one fluorophore with a lifetime τ in a surrounding medium, which signals are detected by detection means, and which method includes the calculation, on the basis of detected fluorescence signals, of values of a variable, independent of τ, of the position or the distribution of fluorophore in said medium.