Quantification of absolute blood flow in tissue using fluorescence mediated photoplethysmography
View Patent ↗There is provided a method and a system for quantification of absolute blood flow in tissue using near-infrared fluorescence angiography in conjunction with photoplethysmography (fluorescence-mediated photoplethysmography). The method and system of the present invention provide absolute, real-time measurements of flow in terms of volume/time/area based upon measurement of fluorescence intensity.
1. A method for measuring a time-varying change in an amount of blood in a tissue volume of tissue of a subject, comprising:
administering a fluorescence agent into vasculature supplying the tissue volume of tissue of the subject;
exciting a fluorescence agent in the blood, the fluorescence agent having an instantaneous molar concentration in the blood;
capturing a sequence of fluorescence images of the tissue;
acquiring, from the sequence of fluorescence images of the tissue, a time-varying fluorescence intensity signal emitted by the fluorescence agent during a pulsatile flow of the blood through the tissue volume, wherein:
the pulsatile flow has a diastolic and a systolic phase resembling a conventional photoplethysmogram,
the acquired fluorescence intensity signal comprises a first fluorescence intensity emitted by the fluorescence agent in the blood in the tissue volume during a diastolic phase minimum,
the acquired fluorescence intensity signal comprises a second fluorescence intensity emitted by the fluorescence agent in the blood in the tissue volume during a systolic phase maximum, and
the first and second fluorescence intensities are respectively associated with measures of blood volume during the diastolic phase and the systolic phase; and
computing a change in an aggregate blood layer thickness in the tissue volume based on the first and second fluorescence intensities, wherein the change represents a quantitative measure of tissue blood perfusion in the tissue volume; and
displaying the quantitative measure to facilitate clinical assessment of the tissue of the subject.
2. The method of claim 1 , wherein the fluorescence agent is indocyanine green (ICG).
3. The method of claim 2 , wherein the ICG is administered at a concentration of between 25-50 mg/mL.
4. The method of claim 1 , wherein the fluorescence images are obtained at a frame rate of 20-30 frames per second.
5. The method of claim 1 , wherein the fluorescence images are obtained by a fluorescence imaging system.
6. The method of claim 5 , wherein the fluorescence imaging system comprises a laser for excitation of the ICG and a camera for capturing images of the fluorescence emitted by the ICG.
7. The method of claim 1 , wherein aggregate blood flow, F, is derived according to the formula:
F =( A )(Δ L )( P DC )/Δ t,
wherein
A is a cross-sectional area of the tissue volume end, ΔL is the derived change in the aggregate blood layer thickness, P DC is a pulse duty cycle, and Δt is a duration of a single pressure pulse.
8. The method of claim 1 , wherein the fluorescence imaging protocol further comprises administering a saline flush, following administering the fluorescence agent, to achieve a circulating peak dye concentration in excess of a predefined molar concentration.
9. The method of claim 1 , further comprising:
acquiring additional fluorescence wavelength data simultaneously with obtaining the fluorescence images; and
using the additional fluorescence wavelength data for dual-wavelength ratiometric analysis for determining an intravascular concentration of the imaging agent.
10. The method of claim 9 , wherein acquiring additional fluorescence wavelength data comprises:
measuring a fluorescence intensity signal from a first wavelength range longer than the wavelength range used for the fluorescence imaging; and
measuring a fluorescence intensity signal from a second wavelength range longer than the wavelength range used for the fluorescence imaging.
11. The method of claim 10 , wherein the first wavelength range and the second wavelength range are within the near infrared spectrum.