IP Library Granted Patent US 10,285,603
Granted Patent B2
US 10,285,603 · App. 14/305,950 · Granted May 14, 2019

Quantification of absolute blood flow in tissue using fluorescence mediated photoplethysmography

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Quick Facts
Patent No.
US 10,285,603
App. No.
14/305,950
Granted
May 14, 2019
Kind
B2
Abstract

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.

Claims (28)

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.

Assignments (18)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 26, 2023
From: STRYKER EUROPEAN OPERATIONS LIMITED
To: STRYKER CORPORATION
Reel/Frame 066140/0647 →
CORRECTIVE ASSIGNMENT TO CORRECT THE ERRONEOUSLY FILED AGAINST APPLICATION NO. 15/570,072 PREVIOUSLY RECORDED AT REEL: 053823 FRAME: 0445. ASSIGNOR(S) HEREBY CONFIRMS THE NUNC PRO TUNC ASSIGNMENT EFFECTIVE 11/29/2018. Recorded May 3, 2021
From: STRYKER EUROPEAN HOLDINGS III, LLC
To: STRYKER EUROPEAN HOLDINGS LLC
Reel/Frame 056426/0496 →
CORRECTIVE ASSIGNMENT TO CORRECT THE ERRONEOUSLY FILED AGAINST APPLICATION NO. 15/570,072 PREVIOUSLY RECORDED AT REEL: 052873 FRAME: 0548. ASSIGNOR(S) HEREBY CONFIRMS THE NUNC PRO TUNC ASSIGNMENT EFFECTIVE 11/30/2017. Recorded May 3, 2021
From: NOVADAQ TECHNOLOGIES ULC
To: STRYKER EUROPEAN HOLDINGS I, LLC
Reel/Frame 056425/0616 →
CORRECTIVE ASSIGNMENT TO CORRECT THE ERRONEOUSLY FILED AGAINST APPLICATION NO. 15/570,072 PREVIOUSLY RECORDED AT REEL: 052860 FRAME: 0900. ASSIGNOR(S) HEREBY CONFIRMS THE NUNC PRO TUNC ASSIGNMENT EFFECTIVE 12/31/2018. Recorded May 3, 2021
From: STRYKER EUROPEAN HOLDINGS LLC
To: STRYKER EUROPEAN OPERATIONS LIMITED
Reel/Frame 056426/0585 →
CORRECTIVE ASSIGNMENT TO CORRECT THE ERRONEOUSLY FILED AGAINST APPLICATION NO. 15/570,072 PREVIOUSLY RECORDED AT REEL: 044910 FRAME: 0507. ASSIGNOR(S) HEREBY CONFIRMS THE MERGER AND CHANGE OF NAME. Recorded May 3, 2021
From: NOVADAQ TECHNOLOGIES INC.
To: NOVADAQ TECHNOLOGIES ULC
Reel/Frame 056425/0530 →
CORRECTIVE ASSIGNMENT TO CORRECT THE ERRONEOUSLY FILED AGAINST APPLICAITON NO. 15/570,072 PREVIOUSLY RECORDED AT REEL: 053318 FRAME: 0612. ASSIGNOR(S) HEREBY CONFIRMS THE NUNC PRO TUNC ASSIGNMENT EFFECTIVE 09/05/2018. Recorded May 3, 2021
From: STRYKER EUROPEAN HOLDINGS I, LLC
To: STRYKER EUROPEAN HOLDINGS IV, LLC
Reel/Frame 056425/0731 →
CORRECTIVE ASSIGNMENT TO CORRECT THE ERRONEOUSLY FILED AGAINST APPLICATION NO. 15/570,072 PREVIOUSLY RECORDED AT REEL: 052873 FRAME: 0597. ASSIGNOR(S) HEREBY CONFIRMS THE NUNC PRO TUNC ASSIGNMENT EFFECTIVE 09/05/2018. Recorded May 3, 2021
From: STRYKER EUROPEAN HOLDINGS IV, LLC
To: STRYKER EUROPEAN HOLDINGS III, LLC
Reel/Frame 056426/0352 →
NUNC PRO TUNC ASSIGNMENT Recorded Jun 7, 2020
From: STRYKER EUROPEAN HOLDINGS I, LLC
To: STRYKER EUROPEAN HOLDINGS IV, LLC
Reel/Frame 053318/0612 →
NUNC PRO TUNC ASSIGNMENT Recorded Jun 7, 2020
From: STRYKER EUROPEAN HOLDINGS LLC
To: STRYKER EUROPEAN OPERATIONS LIMITED
Reel/Frame 052860/0900 →
NUNC PRO TUNC ASSIGNMENT Recorded Jun 7, 2020
From: NOVADAQ TECHNOLOGIES ULC
To: STRYKER EUROPEAN HOLDINGS I, LLC
Reel/Frame 052873/0548 →
NUNC PRO TUNC ASSIGNMENT Recorded Jun 7, 2020
From: STRYKER EUROPEAN HOLDINGS IV, LLC
To: STRYKER EUROPEAN HOLDINGS III, LLC
Reel/Frame 052873/0597 →
NUNC PRO TUNC ASSIGNMENT Recorded Jun 7, 2020
From: STRYKER EUROPEAN HOLDINGS III, LLC
To: STRYKER EUROPEAN HOLDINGS LLC
Reel/Frame 053823/0445 →
CONSULTING AGREEMENT Recorded Mar 28, 2019
From: FLOWER, ROBERT W.
To: NOVADAQ TECHNOLOGIES INC.
Reel/Frame 048742/0310 →
MERGER AND CHANGE OF NAME Recorded Dec 19, 2017
From: NOVADAQ TECHNOLOGIES INC.; STRYKER CANADA OPERATIONS ULC
To: NOVADAQ TECHNOLOGIES ULC
Reel/Frame 044910/0507 →
RELEASE OF SECURITY INTEREST Recorded Sep 8, 2017
From: MIDCAP FINANCIAL TRUST
To: NOVADAQ TECHNOLOGIES INC.; NOVADAQ CORP.
Reel/Frame 043788/0799 →
RELEASE OF SECURITY INTEREST Recorded Sep 8, 2017
From: MIDCAP FUNDING IV TRUST (AS SUCCESSOR AGENT TO MIDCAP FINANCIAL TRUST)
To: NOVADAQ TECHNOLOGIES INC.; NOVADAQ CORP.
Reel/Frame 043786/0344 →
SECURITY AGREEMENT (TERM) Recorded Jan 9, 2017
From: NOVADAQ TECHNOLOGIES; NOVADAQ CORP.
To: MIDCAP FINANCIAL TRUST, AS AGENT
Reel/Frame 041306/0189 →
SECURITY AGREEMENT (REVOLVING) Recorded Jan 9, 2017
From: NOVADAQ TECHNOLOGIES; NOVADAQ CORP.
To: MIDCAP FINANCIAL TRUST, AS AGENT
Reel/Frame 041306/0172 →
Cited By (4)
US 12,186,055 US 12,350,415 US 12,464,215 US 12,465,229