Fluorescent Light Tomography for 3D Probe Distribution

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current light imaging technologies face challenges in obtaining a reliable three-dimensional representation of fluorescent probe distribution within scattering media, such as biological tissues, due to complex surface variability and autofluorescence noise, which complicates the determination of 3D location, size, and brightness of internal fluorescent probes.

Innovation Solution

The method employs fluorescent light emission data, surface representation, and computer-implemented photon propagation models to determine a three-dimensional representation of fluorescent probe distribution inside an animal, using structured light for surface topography and autofluorescence separation techniques to isolate the fluorescent probe signal.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional light imaging is used to capture photons from biological samples, then 2D spatial distribution of photons can be obtained, but reliable 3D characterization of fluorescent probe concentration cannot be achieved

Engineering Contradiction:
Improve3D characterization precisionVSAvoiddepth information
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent transitions from 2D surface imaging to 3D volumetric imaging by implementing fluorescent light tomography. The system captures fluorescent signals from multiple angles and positions around the biological sample, then uses iterative reconstruction algorithms to generate 3D representations of probe distribution, effectively adding the depth dimension to the imaging capability

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

Solution Approach 2:

The patent employs iterative reconstruction where the 3D probe distribution model is continuously refined based on comparison between predicted and actual measured fluorescent signals. The system adjusts the model parameters in each iteration to minimize the difference between simulated and measured data, achieving accurate 3D characterization through feedback-driven optimization

Inventive Principle:
Principle #23Feedback

2Reliability

If photons are used to image through scattering tissue, then internal fluorescent probes can be detected, but photons are absorbed and scattered resulting in diffusive propagation and signal loss

Engineering Contradiction:
Improvedetection reliabilityVSAvoidphoton loss
Core Design Contradiction:
ReliabilityVSLoss of energy

Solution Approach 1:

The patent replaces direct optical detection with a computational approach. Instead of relying on photons to travel directly from the source to the detector, the system uses detectors to capture diffused photons and then employs computer-implemented photon propagation models to reconstruct the original 3D distribution, substituting physical photon transport with computational modeling

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

Solution Approach 2:

The patent changes the detection parameters by measuring fluorescent signals at multiple wavelengths, angles, and positions. By collecting data across multiple parameters and using spectral unmixing techniques, the system can distinguish probe fluorescence from autofluorescence and scattering effects, maintaining detection reliability despite photon loss

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If 2D camera images are used to represent internal fluorescent sources, then surface photon distribution can be recorded, but accurate 3D location, size, and brightness of probes cannot be determined

Engineering Contradiction:
Improve3D probe characterizationVSAvoidimaging system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent makes the imaging system multi-functional by integrating capabilities to capture both 2D surface images and 3D volumetric data using the same hardware platform. The system can operate in different modes (direct imaging vs. tomographic reconstruction) and perform multiple functions including autofluorescence correction, spectral unmixing, and 3D reconstruction, reducing the need for separate specialized devices

Inventive Principle:
Principle #6Universality (Multi-functionality)

4Measurement precision

If multiple imaging sessions are conducted to improve 3D reconstruction accuracy, then better probe distribution characterization can be achieved, but significant delays occur between sessions

Engineering Contradiction:
Improve3D reconstruction accuracyVSAvoidimaging session time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary actions by collecting all necessary multi-angle and multi-position fluorescent images in a single imaging session. The complete dataset is acquired upfront, and the 3D reconstruction is performed computationally without requiring additional physical imaging sessions, eliminating time delays while maintaining accuracy

Inventive Principle:
Principle #10Preliminary 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

This approach enables real-time fluorescent tomographic imaging, providing accurate 3D characterization of fluorescent probe distribution within minutes, overcoming surface complexity and autofluorescence interference, and allowing for efficient multiple imaging sessions without significant delays.

Implementation Method 1

Fluorescent light emission data

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

Photons emitted by fluorescent cells scatter in the tissue of the mammal

Methodology Applied
Scientific EffectScattering: Scattering

Implementation Method 3

resulting in diffusive photon propagation through the tissue

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP2146752B1Fluorescent light tomography
Publication Date: 2022.05.18 XENOGEN CORP
  • EP2146752B1 patent drawingFigure 1
  • EP2146752B1 patent drawingFigure 2
  • EP2146752B1 patent drawingFigure 3

AI summary

Described herein are systems and methods for obtaining a three-dimensional (3D) representation of the distribution of fluorescent probes inside a sample, such as a mammal. Using a) fluorescent light emission data from one or more images, b) a surface representation of the mammal, and c) computer-implemented photon propagation models, the systems and methods produce a 3D representation of the fluorescent probe distribution in the mammal. The distribution may indicate - in 3D - the location, size, and/or brightness or concentration of one or more fluorescent probes in the mammal.