Arterial endothelial function measurement method and apparatus

• US 8,666,472 B2
• Filed: 02/23/2006
• Issued: 03/04/2014
• Est. Priority Date: 09/12/2003
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Maltz, Jonathan S., Budinger, Thomas F.
• Primary Examiner(s): Chen, Tse
• Assistant Examiner(s): REMALY, MARK DONALD
• Application Number:
  US11/362,326
• Publication Number:
  US 20060264755A1
• Time in Patent Office: 2,931 Days
• Field of Search: 600/300, 600/437, 600/438, 600/449, 600/450, 600/454, 600/455, 600/485, 600500-504
• US Class Current: 600/407
• CPC Class Codes: A61B 8/08 Detecting organic movements or changes, e.g. tumours, cysts, swellings A61B8/02 - A61B8/06 take precedence
• CPC Class Codes: A61B 8/488 involving Doppler signals

Abstract

A “relaxoscope” (100) detects the degree of arterial endothelial function. Impairment of arterial endothelial function is an early event in atherosclerosis and correlates with the major risk factors for cardiovascular disease. An artery (115), such as the brachial artery (BA) is measured for diameter before and after several minutes of either vasoconstriction or vasorelaxation. The change in arterial diameter is a measure of flow-mediated vasomodification (FMVM). The relaxoscope induces an artificial pulse (128) at a superficial radial artery (115) via a linear actuator (120). An ultrasonic Doppler stethoscope (130) detects this pulse 10-20 cm proximal to the point of pulse induction (125). The delay between pulse application and detection provides the pulse transit time (PTT). By measuring PTT before (160) and after arterial diameter change (170), FMVM may be measured based on the changes in PTT caused by changes in vessel caliber, smooth muscle tone and wall thickness.

Claims

1. A method of arterial endothelial function measurement, the method comprising:

a) imparting a first set of one or more artificial pulses into an artery endothelium using an actuator, said artery endothelium having an initial pulse transit speed;

b) detecting the arrival of at least one of the one or more artificial pulses at a detector to determine the initial pulse transit speed;

c) modifying the artificial pulse transit speed of said artery endothelium;

d) imparting a second set of one or more artificial pulses using an actuator into said artery endothelium;

e) detecting the arrival of at least one of the one or more artificial pulses with said detector to form a modified pulse transit speed;

f) calculating a difference between said modified pulse transit speed and said initial pulse transit speed; and

g) calculating a ratio between said modified pulse transit speed and said initial pulse transit speed, wherein said ratio is a measurement of arterial endothelial function.

2. The method of claim 1 wherein said detecting steps take place with said detector at substantially the same distance from where said pulses are imparted.

3. The method of claim 1 wherein said detecting steps take place with said detector at different distances from where said pulses are imparted.

4. The method of claim 1 further comprising:

a) outputting as a signal output one or more signals selected from the group consisting of;

i) the initial pulse transit speed,

ii) the modified pulse transit speed,

iii) a difference of pulse transit speeds, formed by calculating a difference between said modified pulse transit speed and said initial pulse transit speed, and

iv) a ratio of pulse transit speeds formed by dividing said modified pulse transit speed with said initial pulse transit speed.

5. The method of claim 1 wherein said modifying step is accomplished by relaxing said artery with one or more of the group consisting of:

electrostimulation, reactive hyperemia, applying vasorelaxant sodium nitroprusside, nitroglycerin, albuterol, salbutamol, nicotine, and carbon dioxide.

6. The method of claim 1 wherein said detector in said detecting step is a high frequency Doppler ultrasonic stethoscope, a pulsed wave flow measurement device, an ultrasonic imager, electromagnetic detector, an optical detector, a force sensor, a microphone, or a nuclear magnetic resonance imager.

7. The method of claim 1 wherein said first and second sets of artificial pulses in said imparting steps are effected by a force-displacement controlled linear actuator.

8. The method of claim 7 wherein said modifying step is accomplished by constricting said artery with one or more of the group consisting of:

electrostimulation, L-NAME, L-NMMA, nicotine, nitric oxide synthase inhibitors, carbon dioxide, epinephrine, and norepinephrine.

9. An article of manufacture for arterial endothelial function measurement using a computer, said article comprising:

a non-transitory computer readable medium comprising instructions for said computer to execute or control a set of steps comprising the steps of claim 1.

10. The article of manufacture for arterial endothelial function measurement of claim 9 further comprising:

(a) an actuator to create one or more artificial pulses in an artery endothelium;

(b) a detector of said pulses in said artery endothelium;

(c) a signal output of a differential pulse transit time, said differential the difference between pulse transit time before and after modification of pulse transit time, and (d) means for connecting the computer to said actuator, detector and signal output.