Fluorescence Imaging Contrast via Dual-Agent Subtraction

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Solution Overview

Problem

Existing fluorescence-based medical imaging systems face challenges in enhancing contrast and discriminating between normal and abnormal tissues due to background fluorescence from normal tissue constituents and varying concentrations of exogenous fluorophores.

Innovation Solution

A method involving the administration of two fluorescent contrast agents, one targeted and one untargeted, with different emission wavelengths, where the tissue is illuminated at specific wavelengths to acquire data, and the untargeted agent's data is subtracted from the targeted agent's data to generate corrected fluorescence images, enhancing contrast and tissue discrimination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a single fluorescent contrast agent is used for imaging, then the imaging system is simple to operate, but the contrast between abnormal and normal tissues is insufficient due to background fluorescence

Engineering Contradiction:
Improvetissue discrimination accuracyVSAvoidimaging system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The imaging process is segmented into multiple wavelength channels, with separate stimulus and detection for targeted and untargeted fluorophores. This allows independent optimization of each channel for specific tissue types, improving measurement precision through spectral unmixing and background subtraction.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The imaging system is designed with multi-functionality to detect multiple fluorophore types simultaneously using different stimulus wavelengths. The system can switch between targeted and untargeted imaging modes, providing universal applicability for various tissue discrimination tasks while maintaining a unified hardware platform.

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

2Measurement precision

If multiple wavelength-selective devices are used to detect different fluorophores, then fluorescence contrast is improved, but the device complexity increases

Engineering Contradiction:
Improvefluorescence contrastVSAvoidoptical system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

Multiple wavelength-selective devices are merged into a single integrated optical system with shared components such as the photodetector array and imaging optics. The system combines multiple stimulus light sources and wavelength-selective devices into a coordinated configuration, reducing overall complexity while maintaining the ability to detect multiple fluorophores simultaneously.

Inventive Principle:
Principle #5Merging (Combining)

3Measurement precision

If background fluorescence from normal tissue is not subtracted, then the imaging process is simple, but the visualization of abnormal tissues is obscured

Engineering Contradiction:
Improveabnormal tissue visualizationVSAvoidimaging processing efficiency
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The system performs preliminary acquisition of untargeted fluorophore data that represents background fluorescence before final image generation. This preliminary data is then subtracted from the targeted fluorophore signal, removing background interference in advance and improving abnormal tissue visualization without requiring complex post-processing.

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 effectively improves contrast and discrimination between tissue types, allowing for better visualization of abnormal tissues by subtracting background fluorescence, thereby enhancing the accuracy of fluorescence imaging.

Implementation Method 1

Each molecule of fluorophore has the ability to absorb one or more photons of light of a first, or stimulus, wavelength, thereby raising the molecule to an excited energy state

Methodology Applied
Scientific EffectAbsorption (EM radiation): Absorption (EM radiation)

Implementation Method 2

the molecule may then drop to another energy state by emitting at least one photon of light at one or more second, or emission, wavelengths

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 3

the optical system has a receiving wavelength-selective device, such as a long-wavelength-pass receiving filter that blocks light at the stimulus wavelength, for excluding stimulus light from the detector while allowing fluorescence emissions-wavelength light reach the detector

Methodology Applied
Scientific EffectFilter (optical): Filter (optical)

Data Source

PatentUS11564639B2Method and apparatus for medical imaging using differencing of multiple fluorophores
Publication Date: 2023.01.31 TRUSTEES OF DARTMOUTH COLLEGE THE
  • US11564639B2 patent drawing
  • US11564639B2 patent drawing
  • US11564639B2 patent drawing

AI summary

A method of generating corrected fluorescence data of concentrations of a targeted fluorophore in tissue of a subject includes administering first and second fluorescent contrast agents to the subject, the first contrast agent targeted to tissue of interest, the second agent untargeted. The tissue is illuminated with light of a first stimulus wavelength and first data is acquired at an appropriate emissions wavelength; the tissue is illuminated at a second stimulus wavelength and second data is acquired at a second emissions wavelength associated with the second agent, the first and second emissions wavelength differ. Difference data is generated by subtracting the second data from the first data. A system provides for stimulus and capture at multiple wavelengths, with image storage memory and subtraction code, to perform the method. Corrected data may form an fluorescence image, or is used to generate fluorescence tomographic images.