Device and method for measuring blood flow in an organ

• US 7,529,576 B2
• Filed: 04/01/2004
• Issued: 05/05/2009
• Est. Priority Date: 04/05/2003
• Status: Active Grant

• Current Assignee: ETH Zurich, Universität Zürich
• Original Assignee: ETH Zurich, Universität Zürich
• Inventors: Niederer, Peter, Keller, Emanuela, Nadler, Andreas
• Primary Examiner(s): Smith; Ruth S
• Assistant Examiner(s): Lauritzen; Amanda L.
• Application Number:
  US10/816,306
• Publication Number:
  US 20040249275A1
• Time in Patent Office: 1,860 Days
• Field of Search: 600407-480, 600/309, 600/310, 600/314, 600322-324, 600/317, 600/504, 356/39, 356/51, 356/300, 356/302, 356/303
• US Class Current: 600/431
• CPC Class Codes: A61B 5/0261 using optical means, e.g. infrared light
• CPC Class Codes: A61B 5/0275 using tracers, e.g. dye dilution
• CPC Class Codes: A61B 5/4064 Evaluating the brain A61B5/031, A61B5/369, A61B5/14553 take precedence

Abstract

A device has a source for emitting near infrared radiation into cerebral tissue, a sensor for detecting radiation exiting from the tissue, and an evaluation unit which detects the exiting radiation as an input signal having pulsatile and non-pulsatile components and is programmed to determine the concentration of an injected indicator in the tissue from the non-pulsatile signal component, iteratively determine an inflow function characterizing cerebral blood flow by varying a mean transit time until reaching a stop criterion, determine indicator concentration relative to cerebral blood volume from the inflow function and the pulsatile signal component, calculate cerebral blood volume by dividing indicator concentration in the tissue by indicator concentration relative to cerebral blood volume, calculate cerebral blood flow by dividing the cerebral blood volume by the mean transit time when the stop criterion has been reached, and scale the inflow function using values determined from the pulsatile signal component.

Claims

1. A device for measuring blood flow in an organ using an injected indicator comprising:

a radiation source for emitting near infrared radiation into tissue of the organ at a first location;

a sensor for detecting a proportion of the emitted near infrared radiation that exits from the organ at a second location; and

an evaluation unit that detects the proportion of the emitted near infrared radiation that exits from tissue of the organ as a single input signal, said evaluation unit being programmed to perform the following evaluation steps;

(a) dividing up said single input signal into a pulsatile component and a non-pulsatile component;

(b) determining an injected indicator concentration with reference to the organ tissue from said non-pulsatile component of said single input signal;

(c) iteratively determining, from said non-pulsatile component, an inflow function i(t) that characterizes blood flow through the organ by incrementally varying a mean transit time mtt until a stop criterion is reached;

(d) determining an injected indicator concentration with reference to blood volume in the organ from said pulsatile component of said single input signal and the iteratively determined inflow function i(t);

(e) calculating a blood volume in the organ as a quotient of the injected indicator concentration with reference to the organ tissue and the injected indicator concentration with reference to the blood volume in the organ; and

(f) calculating a blood flow in the organ as a quotient of the blood volume in the organ and the mean transit time mtt when the stop criterion has been reached.

2. The device according to claim 1, wherein each iteration step in iteratively determining the inflow function i(t) comprises a step-by-step calculation by approximation of the inflow function i(t) according to the equation

i(t)=d/dt(C_tissue(t))+o(t−

t_k)

and an outflow function o(t) by means of a convolution integral

o(t)=i(t)*g(t)

wherein d/dt (C_tissue(t)) is a term that describes a change in the injected indicator concentration with reference to the organ tissue, a value of the outflow function o(t) at a time t−

t_k is to be inserted for o(t−

t_k), and g(t) is a characteristic transport function in which the mean transit time mtt is included.

3. The device according to claim 2, wherein the stop criterion for iteratively determining the inflow function i(t) includes that the inflow function i(t) can be represented as a sum of a finite number of functions that are similar in form to the transport function g(t).

4. The device according to claim 1, wherein the stop criterion for iteratively determining the inflow function i(t) includes that a minimum of the inflow function i(t), determined by means of iteration, is greater than a threshold value.

5. The device according to claim 4, wherein the threshold value is 0.

6. The device according to claim 1, further comprising a non-invasive measurer of blood flow in the organ including means for radiating near infrared radiation in through a patient'"'"'s skin at the first location and means for capturing the exiting proportion of the emitted near infrared radiation through the patient'"'"'s skin at the second location.

7. The device according to claim 6, further comprising means for a local reduction of skin perfusion at the first location and the second location by means of applying a locally increased contact pressure.

8. The device according to claim 1, wherein the evaluation unit is programmed to take into consideration that the organ is a patient'"'"'s brain, the blood flow is cerebral blood flow CBF, and the blood volume is cerebral blood volume CBV.

9. A device for measuring blood flow in an organ using an injected indicator comprising:

a radiation source for emitting near infrared radiation into tissue of the organ at a first location;

a sensor for detecting a proportion of the emitted near infrared radiation that exits from the organ at a second location; and

an evaluation unit that detects the proportion of the emitted near infrared radiation that exits from tissue of the organ as a single input signal, said evaluation unit being programmed to perform the following evaluation steps;

(a) dividing up said single input signal into a pulsatile component and a non-pulsatile component;

(b) determining an injected indicator concentration with reference to the organ tissue from said non-pulsatile component of said single input signal;

(c) iteratively determining, from said non-pulsatile component, an inflow function i(t) that characterizes blood flow through the organ by incrementally varying a mean transit time mtt until a stop criterion is reached;

(d) determining an injected indicator concentration with reference to blood volume in the organ from said pulsatile component of said single input signal and the iteratively determined inflow function i(t);

(e) calculating a blood volume in the organ as a quotient of the injected indicator concentration with reference to the organ tissue and the injected indicator concentration with reference to the blood volume in the organ;

(f) calculating blood flow in the organ as a quotient of the blood volume in the organ and the mean transit time mtt when the stop criterion has been reached; and

(g) scaling the inflow function i(t) by means of values determined from said pulsatile component of said single input signal.

10. A method for measuring blood flow in an organ of a patient comprising the steps of:

injecting the patient with an indicator;

emitting near infrared radiation into tissue of the organ at a first location;

detecting a proportion of the emitted near infrared radiation that exits from the organ at a second location as a single input signal;

dividing up said single input signal into a pulsatile component and a non-pulsatile component;

determining an injected indicator concentration with reference to the organ tissue from said non-pulsatile component of said single input signal;

iteratively determining, from said non-pulsatile component, an inflow function i(t) that characterizes blood flow through the organ by incrementally varying a mean transit time mtt until a stop criterion is reached;

determining an injected indicator concentration with reference to blood volume in the organ from said pulsatile component of said single input signal and the iteratively determined inflow function i(t);

calculating a blood volume in the organ as a quotient of the injected indicator concentration with reference to the organ tissue and the injected indicator concentration with reference to the blood volume in the organ; and

calculating a blood flow in the organ as a quotient of the blood volume in the organ and the mean transit time mtt when the stop criterion has been reached.

11. The method according to claim 10, wherein each iteration step in iteratively determining the inflow function i(t) comprises a step-by-step calculation by approximation of the inflow function i(t) according to the equation

i(t)=d/dt(C_tissue(t))+o(t−

t_k)

and of an outflow function o(t) by means of a convolution integral

o(t)=i(t)*g(t)

wherein d/dt (C_tissue(t)) is a term that describes a change in the injected indicator concentration with reference to the organ tissue, a value of the outflow function o(t) at a time t−

t_k is to be inserted for o(t−

t_k), and g(t) is a characteristic transport function in which the mean transit time mtt is included.

12. The method according to claim 11, wherein the stop criterion for iteratively determining the inflow function i(t) includes that the inflow function i(t) can be represented as a sum of a finite number of functions that are similar in form to the transport function g(t).

13. The method according to claim 10, wherein the stop criterion for iteratively determining the inflow function i(t) includes that a minimum of the inflow function i(t)determined by means of iteration is greater than a threshold value.

14. The method according to claim 13, wherein the threshold value is 0.

15. The method according to claim 10, wherein the indicator has an absorption coefficient that decreases with an increasing indicator concentration and the absorption coefficient is used for determining the injected indicator concentration with reference to the blood volume in the organ.

16. The method according to claim 10, wherein a skin perfusion is reduced at the first location and the second location by means of applying a locally increased contact pressure.

17. The method according to claim 10, wherein the organ is a the brain, the blood flow is cerebral blood flow CBF, and the blood volume is cerebral blood volume CBV.

18. The method according to claim 10, wherein the indicator is indocyaningreen.

19. A method for measuring blood flow in an organ comprising the steps of:

injecting an indicator;

emitting near infrared radiation, into tissue of the organ at a first location;

detecting a proportion of the emitted near infrared radiation that exits from the organ at a second location as a single input signal;

dividing up said single input signal into a pulsatile component and a non-pulsatile component;

determining an injected indicator concentration with reference to the organ tissue from said non-pulsatile component of said single input signal;

iteratively determining, from said non-pulsatile component, an inflow function i(t) that characterizes blood flow through the organ by incrementally varying a mean transit time mtt until a stop criterion is reached;

determining an injected indicator concentration with reference to blood volume in the organ from said pulsatile component of said single input signal and the iteratively determined inflow function i(t);

calculating a blood volume in the organ as a quotient of the injected indicator concentration with reference to the organ tissue and the injected indicator concentration with reference to the blood volume in the organ;

calculating a blood flow in the organ as a quotient of the blood volume in the organ and the mean transit time mtt when the stop criterion has been reached; and

scaling the inflow function i(t) by means of values determined from said pulsatile component of said single input signal.

20. The method according to claim 19, wherein the step of determining the concentration of injected indicator with reference to the blood volume in the organ comprises back-extrapolating the scaled inflow function i(t) to a time of injection of the indicator.

21. A method according to claim 19, wherein the indicator is indocyaningreen.

22. A device for measuring blood flow in an organ using an injected indicator comprising:

a radiation source for emitting near infrared radiation into tissue of the organ at a first location;

a sensor for detecting a proportion of the emitted near infrared radiation that exits from the organ at a second location; and

an evaluation unit that detects the proportion of the emitted near infrared radiation that exits from tissue of the organ as a single input signal, said evaluation unit being programmed to perform the following evaluation steps;

(a) dividing up said single input signal into a pulsatile and a non-pulsatile component;

(b) determining an injected indicator concentration with reference to the organ tissue from said non-pulsatile component of said single input signal;

(c) iteratively determining, from said non-pulsatile component, an inflow function i(t) that characterizes blood flow through the organ by incrementally varying a mean transit time mtt until a stop criterion is reached;

(d) determining an injected indicator concentration with reference to blood volume in the organ from said pulsatile component of said single input signal and the iteratively determined inflow function i(t);

(e) scaling the inflow function i(t) by means of values determined from said pulsatile component of said single input signal;

(f) back-extrapolating the scaled inflow function i(t) to a time of injection of the indicator;

(g) calculating a blood volume in the organ as a quotient of the injected indicator concentration with reference to the organ tissue and the injected indicator concentration with reference to the blood volume in the organ; and

(h) calculating a blood flow in the organ as a quotient of the blood volume in the organ and the mean transit time mtt when the stop criterion has been reached.