Measurement of cardiac output and blood volume by non-invasive detection of indicator dilution

• US 20050020891A1
• Filed: 06/10/2004
• Published: 01/27/2005
• Est. Priority Date: 05/22/2001
• Status: Active Grant

• Current Assignee: University of Southern California
• Original Assignee: Alfred E MANN Institute For Biomedical Engineering At The University of Southern California
• Inventors: Rubinstein, Eduardo H., Holschneider, Daniel P., Scremin, Oscar U., Maarek, Jean-Michel I.
• Granted Patent: US 7,611,470 B2
• Time in Patent Office: Days
• US Class Current: 600/315
• 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 5/029 Measuring or recording blood output from the heart, e.g. minute volume A61B8/065 takes precedence

Abstract

A system for evaluating the cardiovascular system parameters using indicator dilution and non-invasive or minimally invasive detection methods is disclosed. Intravascular indicators are stimulated, and emissions patterns detected for computation of cardiac output, cardiac index, blood volume and other indicators of cardiovascular health.

Claims

1. A method of measuring a parameter of the cardiovascular system of a subject in absolute physical units comprising:

administering to the cardiovascular system a detectable amount of an indicator that fluoresces when illuminated;

illuminating the indicator;

measuring the intensity of the illumination that is reflected by or transmitted through a portion of the cardiovascular system;

measuring the intensity of the fluorescence of the indicator that was administered while it is illuminated;

taking a blood sample from the cardiovascular circulatory system;

measuring the concentration of the indicator in the blood sample;

waiting a period of time;

administering a detectable amount of the indicator to the cardiovascular system for a second time;

illuminating the indicator for a second time;

measuring the intensity of the illumination for a second time that is reflected by or transmitted through a portion of the cardiovascular system;

measuring the intensity of the fluorescence of the indicator that was administered for the second time while it is illuminated;

determining the magnitude of the parameter in absolute physical units after the administration of the indicator for a second time based on the measured concentration of the indicator in the blood sample, the first and second measured intensity of the illumination, and the first and second measured intensity of the fluorescence.

2. The method of claim 1 wherein the determination of the parameter is based on the ratio of the first measured intensity of the illumination to the second measured intensity of the illumination.

3. A method of measuring a parameter of a cardiovascular system in a subject in absolute physical units comprising:

administering to the cardiovascular system a detectable amount of an indicator that fluoresces when illuminated;

illuminating the indicator;

measuring the intensity of the fluorescence of the indicator that was administered while it is illuminated;

taking a blood sample from the cardiovascular circulatory system;

measuring the concentration of the indicator in the blood sample;

waiting a period of time;

administering a detectable amount of the indicator to the cardiovascular system for a second time;

illuminating the indicator for a second time;

measuring the intensity of the fluorescence of the indicator that was administered for the second time while it is illuminated; and

determining the magnitude of the parameter in absolute physical units after the administration of the indicator for the second time based on the first and second measured intensity of the fluorescence and the measured concentration of the indicator.

4. The method of claim 3 wherein a blood sample from the cardiovascular system is not taken between the administration of the indicator for a second time and the determination of the magnitude of the parameter.

5. The method of claim 3 wherein measuring the intensity of the fluorescence includes measuring the intensity as a function of time.

6. The method of claim 3 wherein the period of waiting time is sufficient to allow substantially all of the indicator that was administered for the first time to be eliminated from the cardiovascular system.

7. A system for measuring a parameter of a cardiovascular system in a subject in absolute physical units comprising:

an illumination source configured to illuminate an administered indicator in the cardiovascular system;

a photo detector configured to measure the intensity of fluorescence from the indicator while it is illuminated; and

a computing system configured to determine the magnitude of the parameter in absolute physical units after a second administration of the indicator based on the measured intensity of the fluorescence after a first and the second administration of the indictor and a measured concentration of the indicator in a blood sample taken from the cardiovascular system after the first administration of the indicator.

8. The system of claim 7 wherein the illumination is configured to illuminate the indicator from the external surface of the skin and the photodetector is configured to measure the intensity of the indicator fluorescence from the external surface of the skin.

9. The system of claim 7 wherein the computing system is configured to base the determination of the magnitude of the parameter on the ratio of a measurement of the intensity of illumination after the first administration of the indicator to a measurement of the intensity of illumination after the second administration of the indicator.

10. A method of calibrating an indicator dilution curve measured after administration of a detectable indicator to the circulatory system in units of concentration comprising:

determining the indicator dilution curve using a sensor positioned transcutaneously, perivascularly or intravascularly, the indicator curve having a sharply rising initial portion and a slowly decaying subsequent portion;

back extrapolating the indicator dilution curve from the subsequent portion to a point on the initial portion;

calculating the concentration of the indicator in the blood by dividing the amount of the administered indicator by the blood volume in the circulatory system; and

relating the extrapolated point to the calculated concentration.

11. A method of measuring a parameter of a cardiovascular system in a subject in absolute physical units comprising:

determining the volume of blood in the cardiovascular system;

administering to the cardiovascular system a detectable amount of an indicator that fluoresces when illuminated;

illuminating the indicator;

measuring the intensity of the fluorescence of the indicator while it is illuminated; and

determining the magnitude of the parameter in absolute physical units based on the measured intensity of the fluorescence, the administered amount of the indicator and the determined blood volume.

12. The method of claim 11 further including:

determining a conversion factor that converts the measured intensity of the fluorescence to the concentration of fluorescence in the cardiovascular system; and

wherein determining the magnitude of the parameter is also based on the conversion factor.

13. The method of claim 11 further including determining the concentration of the indicator in the cardiovascular system based on the amount of the indicator that was administered and the determined volume of blood.

14. The method of claim 13 wherein:

measuring the intensity of the fluorescence includes measuring the intensity as a function of time;

measuring the intensity of the fluorescence as a function of time results in an initial fast rising portion and a subsequent slow decay portion; and

determining the conversion factor includes determining the point on the fast rising portion that is intercepted by an extrapolation of a portion of the slow decay portion.

15. The method of claim 14 wherein determining the conversion factor is based on the ratio of the determined concentration to the measured intensity of the fluorescence at the intercepted point.

16. A system of measuring a parameter of a cardiovascular system in a subject in absolute physical units comprising:

an illumination source configured to illuminate an administered indicator in the cardiovascular system;

a photo detector configured to measure the intensity of fluorescence from the indicator while it is illuminated;

a computing system configured to determine the magnitude of the parameter in absolute physical units based on the measured intensity of the fluorescence, the amount of the administered indicator and the blood volume of the subject.

17. The system of claim 16 wherein the computing system is configured to determine a conversion factor that converts the measured intensity of the fluorescence to the concentration of fluorescence in the cardiovascular system.

18. The system of claim 16 wherein the computing system is configured to:

measure the intensity as a function of time to create an intensity curve having an initial fast rising portion and a subsequent slow decay portion; and

determine the point on a fast rising portion of the intensity curve that is intercepted by the extrapolation of a portion of the slow decay portion of the curve.

19. The system of claim 18 wherein the computing system is configured to determine the conversion factor based on the ratio of the determined concentration to the measured intensity of the fluorescence at the intercepted point.