Fluorescence Cartography Reconstruction in Diffusing Media

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Solution Overview

Problem

Current time-resolved diffuse optical imaging techniques face challenges in accurately localizing fluorophores, especially in backscatter geometry, where different fluorophore distributions can result in identical measurements, making it difficult to reconstruct fluorescence maps in diffuse media.

Innovation Solution

The method involves using Green's functions and Monte-Carlo simulations to model photon propagation and absorption, allowing for the calculation of moments of the temporal distribution of fluorescence, which helps in reconstructing the fluorescence distribution by adjusting for contributions from known fluorophores and using specific a priori hypotheses such as localized fluorophores.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of information

If time-resolved diffuse optical imaging techniques are used to localize fluorophores, then temporal information about tissue is obtained, but reconstruction complexity increases and measurement ambiguity arises in backscatter geometry

Engineering Contradiction:
Improvetemporal informationVSAvoidreconstruction complexity
Core Design Contradiction:
Loss of informationVSDevice complexity

Solution Approach 1:

The patent changes the parameter used for reconstruction from raw temporal data to statistical moments (mean time of flight, variance) of the temporal point spread function. This transformation simplifies the reconstruction problem by converting complex temporal waveforms into a few key parameters that can be more easily inverted to obtain fluorophore location and concentration.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent extracts specific features (moments) from the complete temporal signal. By taking out only the most informative characteristics (mean time of flight, variance) rather than using the entire temporal waveform, the reconstruction complexity is reduced while retaining the essential information needed for fluorophore localization.

Inventive Principle:
Principle #2Taking out (Extraction)

2Measurement precision

If conventional moment-based localization is used, then fluorophore position can be estimated, but accuracy deteriorates in backscatter geometry due to measurement ambiguity

Engineering Contradiction:
Improvefluorophore localization accuracyVSAvoidmeasurement reliability in backscatter geometry
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent adds a new dimension to the measurement by incorporating the variance (second moment) of the temporal distribution in addition to the mean time of flight. This additional dimensional information helps disambiguate fluorophore locations in backscatter geometry, where single-moment methods fail due to the non-uniqueness of the inverse problem.

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

Solution Approach 2:

The patent uses an iterative reconstruction approach where initial estimates are refined by comparing measured moments with modeled moments and adjusting the fluorophore distribution accordingly. This feedback loop continues until convergence, improving the reliability of localization in challenging backscatter configurations.

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

This approach enables precise localization of fluorophores by minimizing residual criteria based on measured and modeled parameters, improving the accuracy of fluorescence reconstruction in diffusing tissues, particularly in applications like cancer detection in organs like the prostate.

Implementation Method 1

Optical techniques for molecular fluorescence imaging are therefore developing rapidly thanks to the use of specific fluorescent markers

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

For any medium, knowing its optical properties, we can calculate the photon density for a Dirac source, point-like and localized in rs and at t=0s, using Green's functions

Methodology Applied
Scientific EffectLight propagation: Light

Implementation Method 3

This document shows a process where a single fluorophore is localized by minimizing a parameter obtained by summing, for the various fiber-fluorophore relative positions, the differences between the measurement, for each position, of the first-order moment of the temporal fluorescence distribution, or time of flight

Methodology Applied
Scientific EffectTime of flight: Time of Flight

Data Source

PatentEP2302362B1Device and method for spatial reconstruction of a fluorescence cartography
Publication Date: 2019.10.02 COMMISSARIAT A LENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
  • EP2302362B1 patent drawingFigure 1A~1B
  • EP2302362B1 patent drawingFigure 1C~1D
  • EP2302362B1 patent drawingFigure 1E~2

AI summary

The method involves illuminating a diffusion medium (2) by a radiation source (L-1), and detecting a signal produced by the medium at fluorescence wavelength by a detector (PM-1) e.g. charged coupled device (CCD) detector. Temporal distribution of the signal is performed for source-detector pair, where the diffusing medium is discretized into voxels, where each of set of fluorophores (F-1) occupies one voxel. A basic parameter for temporal distribution is computed, and magnitude obtained from the moment of the distribution is combined with the estimation of the magnitude. The diffusing medium is an infinite-type diffusing medium. An independent claim is also included for a device for locating fluorophores in a diffusing medium using a pulsed radiation source and a detector.