Fluorescence-Mediated Photoplethysmography for Quantitative Blood Flow
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Solution Overview
Problem
Current photoplethysmography (PPG) technologies cannot provide quantitative measurements of blood flow in tissue in standardized units, limiting their ability to enable direct inter-site and inter-subject comparisons in clinical applications.
Innovation Solution
The use of a modified Beer-Lambert law in conjunction with a fluorescence agent like indocyanine green (ICG) to measure time-varying changes in blood volume, allowing for the determination of blood flow in tissue, including microvascular blood flow, by analyzing the fluorescence intensity and concentration-mediated spectral shifts.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional PPG technology is used to estimate changes in microvascular blood volume, then pulse rate and oxygen saturation can be measured, but quantitative measurements of blood flow in standardized units cannot be provided
Solution Approach 1:
The patent introduces an indocyanine green (ICG) fluorescence agent as an intermediary substance that binds to plasma proteins and circulates with blood flow. This mediator enables quantitative measurement by providing a fluorescent signal that can be correlated to blood volume and flow rate through the modified Beer-Lambert law, thereby converting qualitative PPG signals into quantitative blood flow data in standardized units
Solution Approach 2:
The patent changes the measurement parameter from direct light absorption by blood (conventional PPG) to fluorescence emission from ICG-bound plasma. By measuring the fluorescence intensity and applying the modified Beer-Lambert law, the system transforms the measurement into quantitative blood flow values with standardized units, resolving the limitation of conventional PPG
2Measurement precision
If fluorescence-mediated photoplethysmography with ICG is used to measure blood flow, then quantitative measurements in standardized units are achieved, but the device complexity increases due to fluorescence excitation and detection requirements
Solution Approach 1:
The patent utilizes the periodic nature of blood flow (pulsatile flow with diastolic and systolic phases) to simplify the measurement process. By sampling fluorescence intensity at specific phases of the cardiac cycle and applying the modified Beer-Lambert law, the system can derive quantitative blood flow without requiring continuous complex monitoring, thereby reducing device complexity while maintaining measurement precision
Solution Approach 2:
The ICG fluorescence agent serves multiple functions simultaneously: it acts as a blood flow tracer, provides the fluorescent signal source, and its concentration variations directly indicate blood volume changes. This self-service capability eliminates the need for separate reference measurements or additional tracers, simplifying the overall system despite the fluorescence detection requirements
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 the measurement of blood flow in standardized units (volume/unit time) without the need for trans-illumination, providing accurate and comparable perfusion and microvascular blood flow data.
Implementation Method 1
exciting a fluorescence agent in the blood, such as for example indocyanine green (ICG), acquiring a time-varying light intensity signal during a pulsatile flow of the blood through the tissue volume
Implementation Method 2
a modified Beer Lambert law is applied at the diastolic and systolic phases of the pulsatile flow of blood through tissue volume
Data Source
AI summary
A method, an apparatus, and a kit including the apparatus and a fluorescence agent are provided for measuring a time-varying change in an amount of blood in a tissue volume, and include exciting a fluorescence agent in the blood, acquiring a time-varying light intensity signal during a pulsatile flow of the blood through the tissue volume, the pulsatile flow having a systolic and a diastolic phase resembling a conventional photoplethysmogram, and processing the acquired signal by applying a modified Beer-Lambert law to obtain a measurement of the time-varying change in the amount of blood in the tissue volume. The instantaneous molar concentration of the fluorescence agent is determined by utilizing a concentration-mediated change in a fluorescence emission spectrum of the fluorescence agent. There is further provided a fluorescence agent for use in the method.