Quantification of absolute blood flow in tissue using fluorescence mediated photoplethysmography
A method and an apparatus for measuring a time-varying change in an amount of blood in a tissue 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 the 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.
1. A method for quantifying absolute blood flow through a tissue volume, comprising:
administering a volume of a fluorescence dye into the vasculature supplying the tissue volume;
obtaining a sequence of angiographic images of the tissue volume;
calculating average fluorescence intensities for the sequence of angiographic images of the tissue volume;
generating a plot of time-varying average fluorescence intensity;
determining an increase in thickness of a blood volume layer based on the plot of time-varying average fluorescence intensity and based on a graph of fluorescence intensity versus capillary diameter; and
determining absolute blood flow based in part on the determined increase in thickness of the blood volume layer.
2. The method of claim 1 , wherein determining the increase in thickness of the blood volume layer based on the plot of time-varying average fluorescence intensity and based on the graph of fluorescence intensity versus capillary diameter comprises:
projecting an envelope defined by a minima and a maxima of PPG fluorescence-intensity oscillations of the plot onto the graph of fluorescence intensity versus capillary diameter;
projecting the envelope from a curve of the graph onto an abscissa of the graph;
determining the increase in thickness of the blood volume layer based on a width of the envelope when projected onto the abscissa.
3. The method of claim 1 , wherein the fluorescence dye is indocyanine green (ICG).
4. The method of claim 1 , wherein the fluorescence dye is administered at a concentration of between 25-50 mg/mL.
5. The method of claim 1 , wherein the tissue volume comprises skin tissue.
6. The method of claim 1 , wherein the angiographic images are obtained at a frame rate of 20-30 frames per second.
7. The method of claim 1 , wherein the angiographic images are obtained by a fluorescence imaging system.
8. The method of claim 7 , wherein the fluorescence imaging system comprises a laser for excitation of the fluorescence dye and a camera for capturing images of fluorescence emitted by the fluorescence dye.
9. The method of claim 1 , wherein determining the increase in thickness of the blood volume layer based on the plot and based on the graph comprises making a first projection from the plot onto the graph.
10. The method of claim 9 , wherein the first projection from the plot onto the graph is a projection of an envelope defined by a minima and a maxima of PPG fluorescence-intensity oscillations of the plot.
11. The method of claim 9 , wherein determining the increase in thickness of the blood volume layer based on the plot and based on the graph comprises making a second projection from a curve of the graph onto an abscissa of the graph.
12. The method of claim 11 , wherein:
the first projection from the plot onto the graph is a projection of an envelope defined by a minima and a maxima of PPG fluorescence-intensity oscillations of the plot; and
the second projection is a projection of the envelope from a curve of the graph onto an abscissa of the graph.
13. The method of claim 12 , wherein determining the increase in thickness of the blood volume layer is based on a width of the envelope when projected onto the abscissa.
14. A system for quantifying absolute blood flow through a tissue volume, the system comprising one or more processors configured to execute instructions to cause the system to:
obtain a sequence of angiographic images of a tissue volume following administration of a volume of a fluorescence dye into vasculature supplying the tissue volume;
calculate average fluorescence intensities for the sequence of angiographic images of the tissue volume;
generate a plot of time-varying average fluorescence intensity;
determine an increase in thickness of a blood volume layer based on the plot of time-varying average fluorescence intensity and based on a graph of fluorescence intensity versus capillary diameter; and
determine absolute blood flow based in part on the determined increase in thickness of the blood volume layer.
15. The system of claim 14 , wherein determining the increase in thickness of the blood volume layer based on the plot of time-varying average fluorescence intensity and based on the graph of fluorescence intensity versus capillary diameter comprises:
projecting an envelope defined by a minima and a maxima of PPG fluorescence-intensity oscillations of the plot onto the graph of fluorescence intensity versus capillary diameter;
projecting the envelope from a curve of the graph onto an abscissa of the graph;
determining the increase in thickness of the blood volume layer based on a width of the envelope when projected onto the abscissa.
16. The system of claim 14 , wherein the angiographic images are obtained at a frame rate of 20-30 frames per second.
17. The system of claim 14 , comprising a fluorescence imaging system configured to perform the obtaining the sequence of angiographic images.
18. The system of claim 17 , wherein the fluorescence imaging system comprises a laser for excitation of the fluorescence dye and a camera for capturing images of fluorescence emitted by the fluorescence dye.
19. The system of claim 14 , wherein determining the increase in thickness of the blood volume layer based on the plot and based on the graph comprises making a first projection from the plot onto the graph.
20. The system of claim 19 , wherein the first projection from the plot onto the graph is a projection of an envelope defined by a minima and a maxima of PPG fluorescence-intensity oscillations of the plot.
21. The system of claim 19 , wherein determining the increase in thickness of the blood volume layer based on the plot and based on the graph comprises making a second projection from a curve of the graph onto an abscissa of the graph.
22. The system of claim 21 , wherein:
the first projection from the plot onto the graph is a projection of an envelope defined by a minima and a maxima of PPG fluorescence-intensity oscillations of the plot; and
the second projection is a projection of the envelope from a curve of the graph onto an abscissa of the graph.
23. The system of claim 22 , wherein determining the increase in thickness of the blood volume layer is based on a width of the envelope when projected onto the abscissa.
24. A non-transitory computer-readable storage medium storing instructions for quantifying absolute blood flow through a tissue volume, the instructions configured to be executed by a system comprising one or more processors to cause the system to:
obtain a sequence of angiographic images of a tissue volume following administration of a volume of a fluorescence dye into vasculature supplying the tissue volume;
calculate average fluorescence intensities for the sequence of angiographic images of the tissue volume;
generate a plot of time-varying average fluorescence intensity;
determine an increase in thickness of a blood volume layer based on the plot of time-varying average fluorescence intensity and based on a graph of fluorescence intensity versus capillary diameter; and
determine absolute blood flow based in part on the determined increase in thickness of the blood volume layer.
25. The non-transitory computer-readable storage medium of claim 24 , wherein determining the increase in thickness of the blood volume layer based on the plot of time-varying average fluorescence intensity and based on the graph of fluorescence intensity versus capillary diameter comprises:
projecting an envelope defined by a minima and a maxima of PPG fluorescence-intensity oscillations of the plot onto the graph of fluorescence intensity versus capillary diameter;
projecting the envelope from a curve of the graph onto an abscissa of the graph;
determining the increase in thickness of the blood volume layer based on a width of the envelope when projected onto the abscissa.
26. The non-transitory computer-readable storage medium of claim 24 , wherein the angiographic images are obtained at a frame rate of 20-30 frames per second.
27. The non-transitory computer-readable storage medium of claim 24 , wherein the system comprises a fluorescence imaging system configured to perform the obtaining the sequence of angiographic images.
28. The non-transitory computer-readable storage medium of claim 24 , wherein the fluorescence imaging system comprises a laser for excitation of the fluorescence dye and a camera for capturing images of fluorescence emitted by the fluorescence dye.
29. The non-transitory computer-readable storage medium of claim 24 , wherein determining the increase in thickness of the blood volume layer based on the plot and based on the graph comprises making a first projection from the plot onto the graph.
30. The non-transitory computer-readable storage medium of claim 29 , wherein the first projection from the plot onto the graph is a projection of an envelope defined by a minima and a maxima of PPG fluorescence-intensity oscillations of the plot.
31. The non-transitory computer-readable storage medium of claim 29 , wherein determining the increase in thickness of the blood volume layer based on the plot and based on the graph comprises making a second projection from a curve of the graph onto an abscissa of the graph.
32. The non-transitory computer-readable storage medium of claim 31 , wherein:
the first projection from the plot onto the graph is a projection of an envelope defined by a minima and a maxima of PPG fluorescence-intensity oscillations of the plot; and
the second projection is a projection of the envelope from a curve of the graph onto an abscissa of the graph.
33. The non-transitory computer-readable storage medium of claim 32 , wherein determining the increase in thickness of the blood volume layer is based on a width of the envelope when projected onto the abscissa.