3D Fluorescence Reconstruction Using Iterative Refractive Index Correction

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Solution Overview

Problem

Existing fluorescence reconstruction methods struggle with non-homogeneous refractive indices in biological samples, leading to inaccurate 3D fluorescence imaging, and the use of clarifying agents is invasive and disrupts sample integrity.

Innovation Solution

A non-invasive method for reconstructing the spatial distribution of fluorescence in a sample by iteratively assigning random phases and using light propagation algorithms to estimate complex amplitudes, accounting for incoherent fluorescence and refractive index variations, without the need for clarifying agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a clarifying agent is used to limit the influence of refractive index non-uniformity, then 3D fluorescence images can be obtained without refractive index non-uniformity artifacts, but the sample integrity is compromised and long-term monitoring is not possible

Engineering Contradiction:
Improvefluorescence image accuracyVSAvoidsample integrity
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent introduces an optical phase conjugation process as an intermediary method to correct refractive index non-uniformity effects without physically altering the sample. The phase conjugation acts as a computational-optical mediator that reverses the distorting effects of refractive index variations, allowing accurate fluorescence imaging while preserving sample integrity for long-term monitoring

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the optical parameters (phase conjugation) to compensate for refractive index non-uniformity rather than changing the physical state of the sample. By applying phase conjugation to the fluorescence signal, the method corrects imaging artifacts while maintaining the sample in its native state, enabling both accurate measurement and long-term monitoring

Inventive Principle:
Principle #35Parameter changes

2Device complexity

If traditional fluorescence reconstruction methods are used, then the imaging process is simple, but the results are inaccurate due to refractive index non-uniformity in biological samples

Engineering Contradiction:
Improveimaging process complexityVSAvoidfluorescence localization accuracy
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The patent inserts an optical phase conjugation step between fluorescence excitation and detection. This intermediary process corrects the wavefront distortions caused by refractive index non-uniformity, thereby improving localization accuracy without requiring complex sample preparation or invasive procedures

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs an iterative phase conjugation process that uses feedback from the detected fluorescence signal to progressively correct refractive index artifacts. By repeatedly applying phase conjugation and refining the correction based on measured deviations, the method achieves high accuracy while maintaining a relatively simple overall imaging workflow

Inventive Principle:
Principle #23Feedback

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 accurate 3D fluorescence imaging in biological samples with non-uniform refractive indices, preserving sample integrity and allowing for long-term monitoring.

Implementation Method 1

the spatial distribution of the refractive index of the sample, which may not be uniform, especially when the sample is a real biological tissue

Methodology Applied
Scientific EffectRefraction: Refraction

Implementation Method 2

Fluorescence imaging is a technique for locating fluorescent markers in a human or animal body

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP4205641B1Method for estimating a three-dimensional spatial distribution of fluorescence, inside an object
Publication Date: 2025.08.20 COMMISSARIAT A LENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
  • EP4205641B1 patent drawingFigure 1A
  • EP4205641B1 patent drawingFigure 1B
  • EP4205641B1 patent drawingFigure 2

AI summary

The invention describes an iterative reconstruction method for obtaining a spatial fluorescence distribution within an object. The method involves acquiring fluorescence images in different planes at different depths within the object to form a three-dimensional acquired image. It comprises an iterative reconstruction algorithm, whereby, at each iteration, an initial fluorescence distribution or one resulting from a previous iteration is taken into account, and the fluorescence light wave propagating through the object is simulated to obtain a reconstruction of the acquired image. The acquired image, or a differential image corresponding to a comparison between the acquired image and the reconstructed image, is then back-propagated within the object to update the fluorescence distribution. Figure 5B.