SFDI Fluorescence Imaging for Tissue Depth and Concentration

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Solution Overview

Problem

Current fluorescence-guided surgery methods struggle to accurately determine the depth and concentration of fluorophores below the surface of optically absorbing and scattering media, such as in tumor resection, due to limited penetration depth and distortion of fluorescence signals by tissue absorption and scattering.

Innovation Solution

The method employs spatial frequency domain imaging (SFDI) under red-light excitation to calculate the depth and concentration of fluorophores by analyzing the rate of decay of fluorescence-mode SFDI signal modulation with increasing spatial frequency, using a hyperspectral fluorescence imaging system to correct for tissue attenuation and provide topographic images of fluorophore depth and concentration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional fluorescence imaging is used to detect fluorophores in tissue, then the detection process is simple, but the depth accuracy and concentration measurement are compromised due to signal attenuation and scattering

Engineering Contradiction:
Improvedepth accuracyVSAvoidimaging system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The imaging system segments the detection process into multiple spatial frequency components. By acquiring images at different spatial frequencies and analyzing their modulation decay rates, the system separates depth information from concentration information, enabling accurate depth measurement despite optical attenuation and scattering in tissue.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system changes the spatial frequency parameter of the illumination pattern to encode depth information. By varying spatial frequency and measuring the corresponding fluorescence modulation decay, the system creates a parameter-based depth mapping that compensates for optical path length variations and tissue attenuation effects.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If conventional fluorescence imaging is used, then the device is simple, but concentration measurement is inaccurate due to inability to separate attenuation effects from fluorophore concentration

Engineering Contradiction:
Improveconcentration measurement accuracyVSAvoidimaging system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The system segments the fluorescence signal analysis into multiple spatial frequency components. By analyzing the modulation decay rates at different spatial frequencies, the system separates the effects of optical attenuation from the fluorophore concentration, allowing accurate concentration measurement even in the presence of varying tissue optical properties.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The spatial frequency domain acts as an intermediary that mediates between the raw fluorescence signal and the desired quantitative measurements. By transforming the signal into the spatial frequency domain, the system creates an intermediate representation where depth and concentration can be independently extracted through modulation decay analysis.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Length of moving object

If red-light excitation is used to increase penetration depth, then deeper fluorophore detection is enabled, but the fluorescence signal modulation decay rate analysis becomes more complex

Engineering Contradiction:
Improvepenetration depthVSAvoidsignal analysis complexity
Core Design Contradiction:
Length of moving objectVSDevice complexity

Solution Approach 1:

The system segments the signal analysis by spatial frequency, which simplifies the interpretation of red-light excitation signals. By analyzing modulation decay rates at different spatial frequencies, the system breaks down the complex interaction between light penetration and fluorescence emission into manageable components that can be quantitatively analyzed.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system utilizes the spatial frequency parameter to manage the complexity of red-light excitation signals. By changing the spatial frequency of the illumination pattern, the system creates distinct signal characteristics that simplify the extraction of depth and concentration information from the fluorescence modulation decay.

Inventive Principle:
Principle #35Parameter changes

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 accurate detection of sub-surface fluorophore depth and concentration up to 9 mm, improving tumor resection by providing surgeons with quantitative data to inform decision-making during surgery, enhancing the sensitivity and specificity of residual tumor detection.

Implementation Method 1

the spectrum of fluorescent light emerging from the tissue upon illuminating the tissue with light of a suitable excitation wavelength is the combination of tissue autofluorescence plus fluorescence from the exogenous fluorophore

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

the strength of the fluorescence signal is affected by the attenuation of the excitation and emission light due to the optical absorption and scattering of the light by the tissue

Methodology Applied
Scientific EffectAbsorption: Absorption (EM radiation)

Implementation Method 3

the strength of the fluorescence signal is affected by the attenuation of the excitation and emission light due to the optical absorption and scattering of the light by the tissue

Methodology Applied
Scientific EffectScattering: Scattering

Data Source

PatentUS11977027B2Device and method for determining the depth of a subsurface fluorescent object within an optically absorbing and scattering medium and for determining concentration of fluorophore of the object
Publication Date: 2024.05.07 TRUSTEES OF DARTMOUTH COLLEGE THE
  • US11977027B2 patent drawing
  • US11977027B2 patent drawing
  • US11977027B2 patent drawing

AI summary

A method and device for determining the depth and fluorophore concentration of a fluorophore concentration below the surface of an optically absorbing and scattering medium suitable for use in fluorescence-based surgical guidance such as in tumor resection is described. Long-wavelength stimulus light us used to obtain deep tissue penetration. Recovery of depth is performed by fitting measured modulation amplitudes for each spatial frequency to precomputed modulation amplitudes in a table of modulation amplitudes indexed by optical parameters and depth.