Fluorescence Tissue Measurement Using Remission and Autofluorescence Correction
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Solution Overview
Problem
Accurate measurement of blood analytes in tissue is hindered by variations in tissue structure and optical properties, which affect fluorescence intensity, making it difficult to determine concentrations of fluorophores like zinc protoporphyrin and protoporphyrin IX.
Innovation Solution
An apparatus and method that utilize excitation light at specific wavelength ranges to measure fluorescent light, autofluorescence, and remitted light, allowing for the derivation of tissue parameters like blood volume fraction and epithelial layer thickness, enabling correction of fluorescence intensity for reliable quantitative analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If fluorescence measurements are performed on intact tissue in vivo, then non-invasive diagnostic capability is improved, but measurement precision deteriorates due to unknown tissue parameters
Solution Approach 1:
The patent introduces remission measurements and autofluorescence measurements as intermediary measurements that provide information about tissue parameters (epithelial thickness, blood volume fraction, scattering properties). These intermediary measurements act as mediators that connect the non-invasive fluorescence measurement to the underlying tissue characteristics, enabling correction of the fluorescence signal without requiring invasive tissue sampling.
Solution Approach 2:
The system performs feedback by using the measured remission and autofluorescence signals to calculate tissue parameters, then using these parameters to correct the fluorescence intensity measurements. This closed-loop feedback mechanism allows the system to adapt to individual tissue variations and achieve accurate quantitative measurements in vivo.
2Reliability
If tissue parameters are determined by white light reflectance measurements, then tissue characterization is improved, but device complexity and cost increase
Solution Approach 1:
The patent merges the fluorescence excitation light source with the remission and autofluorescence measurement functions. The same blue light source (350-450 nm) used for exciting the fluorophores also enables remission measurements, and the emitted light contains both fluorescence and autofluorescence components that can be measured simultaneously. This integration eliminates the need for separate white light reflectance measurement systems, reducing device complexity while maintaining tissue characterization capability.
Solution Approach 2:
The measurement system is designed with multi-functionality, where a single optical setup performs multiple functions: exciting fluorophores, measuring remission, and detecting autofluorescence. This universal system replaces the need for multiple specialized measurement devices, simplifying the overall system while providing comprehensive tissue characterization.
3Ease of operation
If fluorescence intensity is measured without correcting for tissue parameters, then measurement simplicity is improved, but quantitative accuracy deteriorates
Solution Approach 1:
The system performs preliminary measurements of remission and autofluorescence before final fluorescence quantification. These preliminary actions provide the necessary tissue parameter information (epithelial thickness, blood volume fraction, scattering coefficient) that are used to correct the fluorescence signal, ensuring accurate quantitative results while maintaining operational simplicity through automated processing.
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 and reliable measurement of blood analytes by accounting for tissue-specific factors, improving the precision of diagnostic ratios such as ZnPP/heme and PP/heme, even at low blood volume fractions.
Implementation Method 1
emitting excitation light at least at a first wavelength range between 350 nm and 450 nm to the tissue... measuring: a) a portion of the fluorescent light emitted by the fluorescent blood analyte excited at the first wavelength range... b) a portion of the autofluorescence emitted by the tissue
Implementation Method 2
measuring: c1) a portion of the remitted excitation light at the first wavelength range, and c2) a portion of the remitted light at a second wavelength range
Implementation Method 3
Since the tissue autofluorescence is partially absorbed by the blood before it reaches the detector, the autofluorescence can serve as a measure of the amount of blood in the tissue volume
Data Source
AI summary
The present invention is directed to an apparatus (10) for reliable quantitative measurement of a fluorescent blood analyte in tissue (12) comprising: at least one light source (14), the light source (14) emitting excitation light at least at a first wavelength range between 350 nm and 450 nm to the tissue (12); a detection unit (16), the detection unit (16) measuring: a) a portion of the fluorescent light emitted by the fluorescent blood analyte excited at the first wavelength range; and b) a portion of the auto fluorescence emitted by the tissue (12); and/or c1) a portion of the remitted excitation light at the first wavelength range, and c2) a portion of the remitted light at a second wavelength range; and a control unit (18), the control unit (18) operating the light source (14) and detection unit (16). The present invention is further directed to a method for quantitative measurement of a fluorescent blood analyte in tissue (12).