# Presentation: 701760

## Instrument for the non-invasive evaluation of human arterial endothelial function via measurement of changes in the transit time of an artificial pulse

- Jonathan S. Maltz, Ph.D.
- (_[jon](mailto:jon@eecs.berkeley.edu)__[@](mailto:jon@eecs.berkeley.edu)__[eecs](mailto:jon@eecs.berkeley.edu)__[.](mailto:jon@eecs.berkeley.edu)__[berkeley](mailto:jon@eecs.berkeley.edu)__[.](mailto:jon@eecs.berkeley.edu)__[edu](mailto:jon@eecs.berkeley.edu)_)
- Thomas F. Budinger, MD, PhD
- (_[tfbudinger](mailto:tfbudinger@lbl.gov)__[@](mailto:tfbudinger@lbl.gov)__[lbl](mailto:tfbudinger@lbl.gov)__[.](mailto:tfbudinger@lbl.gov)__[gov](mailto:tfbudinger@lbl.gov)_)
- Department of Nuclear Medicine and Functional Imaging
- Berkeley Lab
- University of California, Berkeley
- _[http://](http://muti.lbl.gov/relaxoscope/embs2003.ppt)__[muti](http://muti.lbl.gov/relaxoscope/embs2003.ppt)__[.](http://muti.lbl.gov/relaxoscope/embs2003.ppt)__[lbl](http://muti.lbl.gov/relaxoscope/embs2003.ppt)__[.](http://muti.lbl.gov/relaxoscope/embs2003.ppt)__[gov](http://muti.lbl.gov/relaxoscope/embs2003.ppt)__[/](http://muti.lbl.gov/relaxoscope/embs2003.ppt)__[relaxoscope](http://muti.lbl.gov/relaxoscope/embs2003.ppt)__[/embs2003.](http://muti.lbl.gov/relaxoscope/embs2003.ppt)__[ppt](http://muti.lbl.gov/relaxoscope/embs2003.ppt)_

## Instrument for the non-invasive evaluation of human arterial endothelial function via measurement of changes in the transit time of an artificial pulse

- Motivation
- Quantifying endothelial function
- Design of new instrument:                 “The Relaxoscope”
- Evaluation in human subjects
- Future enhancements

## -Kills  960,000 Americans each year 

- -Kills  960,000 Americans each year
- -40% of all deaths
- Disables 11 million Americans over age 65
- Costs $286.5 billion a year
*Source: US Centers for Disease Control and Prevention (1999).*

- Cardiovascular disease

## Monitoring of the effects on arterial function of:

- Routine evaluation of arterial system would allow:
- Detection of developing cardiovascular disease at a preclinical stage
- Monitoring of the effects on arterial function of:
- 	-cholesterol lowering therapy
- 	-vitamin supplementation
- 	-quitting smoking
- 	-exercise therapy

- Cardiovascular disease

## Currently the only routine physical method for monitoring the health of the arterial system is the Riva-Rocci spygmomanometer (1896):

- Blood pressure cuff

## Endothelial dysfunction:

**Endothelial dysfunction**:
- Is an early sign of developing artherosclerosis
- Correlates with all major cardiovascular disease risk factors
- Is a strong predictor of cardiovascular events such as heart attack and stroke
- Is ameliorated by factors that benefit cardiovascular health: exercise, quitting smoking, vitamin supplementation

## Flow-mediated vasodilation

## Measurement of vasodilation response by ultrasonic imaging of arterial diameter:

- Ultrasonic imaging of brachial artery diameter

## The procedure requires an experienced ultrasound technician to produce a high quality image.

- The procedure requires an experienced ultrasound technician to produce a high quality image.
- 2. The equipment is costly (> $50,000).
- 3. Measurements are highly variable (reported coefficients of variation 1.5% - 50%).

- Ultrasonic imaging of brachial artery diameter

- Not routinely performed because:

## Key idea:

- Measure flow-mediated **vasorelaxation** rather than flow-mediated **vasodilation**.
-  Theoretically greater sensitivity
-  Potentially easier to measure
-  Lower instrument cost

- The Relaxoscope

## Key principle:

**Key principle:**
- Quantify endothelium-mediated vasorelaxation by measuring the  transit time of an artificial pulse before and after endothelial stimulus
- By the Moens-Korteweg equation:

- The Relaxoscope

## After vasorelaxation: increased diameter, decreased wall thickness, decreased wall stiffness.

- The Relaxoscope

## The Relaxoscope

## The Relaxoscope

**Pulse-inducing actuator**

**Doppler**
**stethoscope**

## Force applied over artery

**Force applied over artery**

**Ultrasound audio output**

**Artery compression begins**

**Rising edge of received artificial pulse**

## Refinement

## Auto-detecting an artificial pulse signature

- Refinement

## Slide 18

## Time-frequency analysis using Wigner-Ville transform

## The Relaxoscope

## Preliminary testing: PTT versus distance

- Subject 1

- Subject 2

## Objective: Compare          to             in same 

- Comparison with arterial diameter measurements

| Diameter measurement | Relaxoscope |
| --- | --- |
| 1. Image baseline diameter (radius      ) | 1. Record baseline PTT: |
| 2. Occlude brachial artery for 5 minutes with cuff to generate maximal post occlusion reactive hyperemia |  |
| 3. Release cuff and resume measurement process.
for 5 minutes. Yields: |  |
|  |  |
| 4. Calculate:   | 4. Calculate: |

| Experimental protocol I |
| --- |

**Objective:** Compare          to             in same
-                   subjects.

## Diameter measurement apparatus

- Photograph courtesy Pie Medical

## Results

##               is correlated with         :     

-     A straight line fit yields:
-  Thus,               is **37%** more sensitive to flow-mediated vasodilation than

- Results

## Objectives: Ensure relaxoscope is sensitive

- Sensitivity to pharmacological vasodilators

| Record baseline PTT for 1 minute
Administer 0 or 0.6mg of sublingual nitroglycerin.
Measure PTT continuously for 7 minutes. |
| --- |

| Experimental protocol II |
| --- |

**Objectives: **Ensure relaxoscope is sensitive
- to arterial wall relaxation

## No dose of nitroglycerin (NG) given:

- Results

- 0.6mg sublingual NG at 1 minute:

## The relaxoscope PTT measurements are directly proportional to propagation distance.

- Conclusion

- The relaxoscope appears to be 37% more sensitive to endothelium-mediated vasorelaxation than artery diameter measurements.
- The relaxoscope PTT measurements increase after sublingual nitroglycerin, confirming that extravasation during occlusion is not the principal contributor to the decreases in PTT observed.

## Build high frequency switchable continuous wave (CW) / pulsed wave (PW) flowmeter optimized for artificial pulse rising edge detection.

- Future work

- More ergonomic design to accommodate different size arms.
- More convenient methods of pulse application: wristband, hydraulic coupling
- Better tolerated methods of endothelial stimulation than 5 minute cuff occlusion: 2-adrenergic agonists such as inhaled albuterol or salbutamol (Hayward et al. 2002, Wilkinson et al. 2002)

## This work was supported by the US Department of Energy and by the National Institute on Aging.

- Acknowledgements