Method for evaluating vascular endothelium function and a system therefor

• US 9,155,472 B2
• Filed: 05/30/2012
• Issued: 10/13/2015
• Est. Priority Date: 05/31/2011
• Status: Active Grant

• Current Assignee: Angionica SP Z OO
• Original Assignee: Angionica SP Z OO
• Inventors: Gebicki, Jerzy, Marcinek, Andrzej, Chlopicki, Stefan
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US13/483,625
• Publication Number:
  US 20120310057A1
• Time in Patent Office: 1,231 Days
• US Class Current: 1/1
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/02007 Evaluating blood vessel condition, e.g. elasticity, compliance
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/441 Skin evaluation, e.g. for skin disorder diagnosis
• CPC Class Codes: A61B 5/7271 Specific aspects of physiological measurement analysis A61B5/316, A61B5/349 and A61B5/374 take precedence

Abstract

A method for evaluating vascular endothelium function in a human subject comprises monitoring changes in intensity of NADH fluorescence signal emitted from skin tissue cells of an upper limb of said subject as a function of time, wherein said changes result from reactive hyperaemia caused by blocking and releasing blood flow in the same upper limb of said subject. A system for evaluating vascular endothelium function in a human subject comprises a means for illuminating a skin on an upper limb of said subject with exciting light, a means for measuring intensity of fluorescence signal emitted from the skin and recording changes of said intensity of the fluorescence signal over time; and a restriction means for blocking and releasing blood flow in the upper limb of said subject.

Claims

1. A method for determination of parameters for evaluating vascular endothelium function in a human subject, the method comprising:

(a) measuring and recording as a function of time the intensity of one NADH fluorescence emission wavelength signal emitted from skin tissue cells in a selected location on an upper limb of said subject to obtain a baseline, wherein said NADH fluorescence signal is emitted upon illumination with and absorption of one wavelength of UV exciting light;

(b) blocking blood flow in an artery to the upper limb upstream to the selected location, while continuing measuring and recording said intensity as it grows up as a function of time;

(c) releasing the block of blood flow while continuing measuring and recording said intensity as it changes as a function of time until obtaining a stationary state; and

(d) determining parameters indicative of endothelial function from the course of changes of said intensity, the parameters being one or more selected from the group consisting of;

the difference Δ

l between the maximum level of intensity of NADH fluorescence signal upon blocking blood flow and the minimum level of intensity of NADH fluorescence after releasing the block of blood flow in step (c);

the difference Δ

l₁ between the baseline intensity of NADH fluorescence signal in step (a) prior to blocking blood flow and the maximum level of intensity of NADH fluorescence signal upon said blocking blood flow in stet (b); and

the difference Δ

l₂, between the minimum level of intensity of NADH fluorescence signal and the stationary state of intensity of NADH fluorescence signal after releasing the block of blood flow in step (c).

2. The method of claim 1 wherein the selected location is a forearm or hand.

3. The method of claim 1 which further comprises determining the half-time t_1/2 required for increase of intensity of NADH fluorescence signal from its minimum level after releasing the block of blood flow in step (b) by a half of the difference Δ

l₂ between the minimum level and the stationary state of intensity of NADH fluorescence signal after releasing the block of blood flow.

4. The method of claim 1 which further comprises determining the time t_g between releasing the block of blood flow and reaching the stationary state of the intensity of NADH fluorescence signal in step (c).

5. The method of claim 1 wherein said blocking and releasing blood flow is obtained by tightening and releasing, respectively, a restriction means around said upper limb.

6. The method of claim 5 wherein said restriction means is an inflatable restriction means.

7. The method of claim 6 wherein said inflatable restriction means is a pressure cuff.

8. The method of claim 1 wherein said NADH fluorescence is obtained by illumination of said upper limb with the exciting light in the wavelength range from 300 to 400 nm.

9. The method of claim 8 wherein said the exciting light has the wavelength of about 350 nm.

10. The method of claim 1 wherein said NADH fluorescence signal is measured in the wavelength range from 420 to 480 nm.

11. The method of claim 10 wherein said NADH fluorescence signal, is measured at about 460 nm.

12. A system for evaluation of vascular endothelium function in a human subject, said system comprising

a means for illumination of a skin tissue of an upper limb of said subject with UV exciting light;

a means for measuring intensity of fluorescence signal emitted from the skin upon illumination with and absorption of UV exciting light and for recording changes of said intensity of the fluorescence signal over time, including measuring and recording as a function of time the intensity of one NADH fluorescence emission wavelength signal emitted from skin tissue cells in a selected location on an upper limb of said subject to obtain a baseline and measurement data, wherein said NADH fluorescence signal is emitted upon illumination with and absorption of one wavelength of UV exciting light;

a restriction means for blocking and releasing blood flow in an artery in the upper limb of said subject, including subsequent to obtaining the baseline, blocking blood flow in an artery on the upper limb upstream to the selected location, while said means for measuring continues measuring and recording said intensity as it grows as a function of time and releasing the block of blood flow while said means for measuring continues measuring and recording said intensity as it changes as a function of time until obtaining a stationary state;

a processor means for determining parameters indicative of endothelial function from the course of changes of said intensity, the parameters being one or more selected from the group consisting of;

the difference Δ

l₁ between the maximum level of intensity of NADH fluorescence signal upon blocking blood flow and the minimum level of intensity of NADH fluorescence after releasing the block of blood flow;

the difference Δ

l₁ between the baseline intensity of NADH fluorescence signal prior to blocking blood flow and the maximum level of intensity of NADH fluorescence signal upon said blocking blood flow; and

the difference Δ

l₂ between the minimum level of intensity of NADH fluorescence signal and the stationary state of intensity of NADH fluorescence signal after releasing the block of blood flow.

13. The system of claim 12 wherein said UV exciting light has the wavelength in the range from 300 to 400 nm.

14. The system of claim 13 wherein said UV exciting light has the wavelength of about 350 nm.

15. The system of claim 12 wherein said NADH fluorescence signal is measured in the wavelength range from 420 to 480 nm.

16. The system of claim 15 wherein said NADH fluorescence signal is measured at about 460 nm.

17. The system of claim 12 wherein the selected location is a forearm or hand.

18. The system of claim 12 wherein said processor means further determines the half-time t_1/2 required for increase of intensity of NADH fluorescence signal from its minimum level after releasing the block of blood flow by a half of the difference Δ

l₂ between the minimum level and the stationary state of intensity of NADH fluorescence signal after releasing the block of blood flow.

19. The system of claim 12 wherein said processor means further determines the time t_g between releasing the block of blood flow and reaching the stationary state of the intensity of NADH fluorescence signal.

20. The system of claim 12 wherein said restriction means is an inflatable restriction means.

21. The system of claim 20 wherein said inflatable restriction means is a pressure cuff.