Ernest Orlando Lawrence Berkeley National Laboratory
Instrument for the non-invasive evaluation of human
arterial endothel...
Ernest Orlando Lawrence Berkeley National Laboratory
Instrument for the non-invasive evaluation of human
arterial endothel...
Ernest Orlando Lawrence Berkeley National Laboratory
-Kills 960,000 Americans each year
-40% of all deaths
-Disables 11 mi...
Ernest Orlando Lawrence Berkeley National Laboratory
Routine evaluation of arterial system would
allow:
•Detection of deve...
Ernest Orlando Lawrence Berkeley National Laboratory
Currently the only routine physical method
for monitoring the health ...
Ernest Orlando Lawrence Berkeley National Laboratory
Evaluation of endothelial function is logical target
for routine moni...
Ernest Orlando Lawrence Berkeley National Laboratory
Flow-mediated vasodilation
Ernest Orlando Lawrence Berkeley National Laboratory
Ultrasonic imaging of brachial artery diameter
Measurement of vasodil...
Ernest Orlando Lawrence Berkeley National Laboratory
1. The procedure requires an
experienced ultrasound technician to
pro...
Ernest Orlando Lawrence Berkeley National Laboratory
Key idea:
Measure flow-mediated vasorelaxation
rather than flow-media...
Ernest Orlando Lawrence Berkeley National Laboratory
Key principle:
Quantify endothelium-mediated vasorelaxation
by measur...
Ernest Orlando Lawrence Berkeley National Laboratory
After vasorelaxation: increased diameter,
decreased wall thickness, d...
Ernest Orlando Lawrence Berkeley National Laboratory
The Relaxoscope
Ernest Orlando Lawrence Berkeley National Laboratory
The Relaxoscope
Pulse-
inducing
actuator
Doppler
stethoscope
Ernest Orlando Lawrence Berkeley National Laboratory
Force applied over artery
Ultrasound audio output
Artery compression ...
Ernest Orlando Lawrence Berkeley National Laboratory
Refinement
Ernest Orlando Lawrence Berkeley National Laboratory
Refinement
Auto-detecting an artificial pulse signature
Ernest Orlando Lawrence Berkeley National Laboratory
Ernest Orlando Lawrence Berkeley National Laboratory
The Relaxoscope
Ernest Orlando Lawrence Berkeley National Laboratory
Preliminary testing: PTT versus distance
Subject 1 Subject 2
Ernest Orlando Lawrence Berkeley National Laboratory
Comparison with arterial diameter measurements
Diameter measurement R...
Ernest Orlando Lawrence Berkeley National Laboratory
Diameter measurement apparatus
PhotographcourtesyPieMedical
Ernest Orlando Lawrence Berkeley National Laboratory
Results
Ernest Orlando Lawrence Berkeley National Laboratory
• is correlated with :
• A straight line fit yields:
• Thus, is 37% m...
Ernest Orlando Lawrence Berkeley National Laboratory
Sensitivity to pharmacological vasodilators
1. Record baseline PTT fo...
Ernest Orlando Lawrence Berkeley National Laboratory
Results
No dose of nitroglycerin (NG) given:
0.6mg sublingual NG at t...
Ernest Orlando Lawrence Berkeley National Laboratory
Results
Nitroglycerin study
Four subjects examined: • 3 times with no...
Ernest Orlando Lawrence Berkeley National Laboratory
Results
Nitroglycerin study: Effect of treatment with NG
Mean fractio...
Ernest Orlando Lawrence Berkeley National Laboratory
Results
Nitroglycerin study: MANOVA
• The effect of NG on was highly ...
Ernest Orlando Lawrence Berkeley National Laboratory
Results
Nitroglycerin study: Within-subject coefficient of variation ...
Ernest Orlando Lawrence Berkeley National Laboratory
Conclusion
1. The relaxoscope PTT measurements
are directly proportio...
Ernest Orlando Lawrence Berkeley National Laboratory
Future work
1. Build high frequency switchable
continuous wave (CW) /...
Ernest Orlando Lawrence Berkeley National Laboratory
Ernest Orlando Lawrence Berkeley National Laboratory
Acknowledgements
This work was supported by the US
Department of Ener...
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Evaluation of Vascular Reactivity in Alzheimer's Disease via ...

  1. 1. Ernest Orlando Lawrence Berkeley National Laboratory 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@eecs.berkeley.edu) Thomas F. Budinger, MD, PhD (tfbudinger@lbl.gov) Department of Nuclear Medicine and Functional Imaging Berkeley Lab, University of California, Berkeley http://muti.lbl.gov/relaxoscope/isbi2004.ppt
  2. 2. Ernest Orlando Lawrence Berkeley National Laboratory Instrument for the non-invasive evaluation of human arterial endothelial function via measurement of changes in the transit time of an artificial pulse 1. Motivation 2. Quantifying endothelial function 3. Design of new instrument: “The Relaxoscope” 4. Evaluation in human subjects 5. Future enhancements
  3. 3. Ernest Orlando Lawrence Berkeley National Laboratory -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
  4. 4. Ernest Orlando Lawrence Berkeley National Laboratory Routine evaluation of arterial system would allow: •Detection of developing cardiovascular disease at a preclinical stage •Monitoring of the effects on arterial function of: -statin therapy -dietary modification -vitamin supplementation -smoking cessation -exercise therapy Cardiovascular disease
  5. 5. Ernest Orlando Lawrence Berkeley National Laboratory Currently the only routine physical method for monitoring the health of the arterial system is the Riva-Rocci spygmomanometer (1896): Blood pressure cuff
  6. 6. Ernest Orlando Lawrence Berkeley National Laboratory Evaluation of endothelial function is logical target for routine monitoring 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
  7. 7. Ernest Orlando Lawrence Berkeley National Laboratory Flow-mediated vasodilation
  8. 8. Ernest Orlando Lawrence Berkeley National Laboratory Ultrasonic imaging of brachial artery diameter Measurement of vasodilation response by ultrasonic imaging of arterial diameter:
  9. 9. Ernest Orlando Lawrence Berkeley National Laboratory 1. 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:
  10. 10. Ernest Orlando Lawrence Berkeley National Laboratory Key idea: Measure flow-mediated vasorelaxation rather than flow-mediated vasodilation.  Theoretically greater sensitivity  Potentially easier to measure  Lower instrument cost The Relaxoscope
  11. 11. Ernest Orlando Lawrence Berkeley National Laboratory 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
  12. 12. Ernest Orlando Lawrence Berkeley National Laboratory After vasorelaxation: increased diameter, decreased wall thickness, decreased wall stiffness. The Relaxoscope
  13. 13. Ernest Orlando Lawrence Berkeley National Laboratory The Relaxoscope
  14. 14. Ernest Orlando Lawrence Berkeley National Laboratory The Relaxoscope Pulse- inducing actuator Doppler stethoscope
  15. 15. Ernest Orlando Lawrence Berkeley National Laboratory Force applied over artery Ultrasound audio output Artery compression begins Rising edge of received artificial pulse
  16. 16. Ernest Orlando Lawrence Berkeley National Laboratory Refinement
  17. 17. Ernest Orlando Lawrence Berkeley National Laboratory Refinement Auto-detecting an artificial pulse signature
  18. 18. Ernest Orlando Lawrence Berkeley National Laboratory
  19. 19. Ernest Orlando Lawrence Berkeley National Laboratory The Relaxoscope
  20. 20. Ernest Orlando Lawrence Berkeley National Laboratory Preliminary testing: PTT versus distance Subject 1 Subject 2
  21. 21. Ernest Orlando Lawrence Berkeley National Laboratory 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.
  22. 22. Ernest Orlando Lawrence Berkeley National Laboratory Diameter measurement apparatus PhotographcourtesyPieMedical
  23. 23. Ernest Orlando Lawrence Berkeley National Laboratory Results
  24. 24. Ernest Orlando Lawrence Berkeley National Laboratory • is correlated with : • A straight line fit yields: • Thus, is 37% more sensitive to flow-mediated vasodilation than Results
  25. 25. Ernest Orlando Lawrence Berkeley National Laboratory Sensitivity to pharmacological vasodilators 1. Record baseline PTT for 1 minute 2. Administer 0 or 0.6mg of sublingual nitroglycerin. 3. Measure PTT continuously for 7 minutes. Experimental protocol II Objectives: 1. Ensure relaxoscope is sensitive to arterial wall tone 2. Evaluate repeatability: endothelium-mediated relaxation has much higher day-to-day variability than NG-induced relaxation.
  26. 26. Ernest Orlando Lawrence Berkeley National Laboratory Results No dose of nitroglycerin (NG) given: 0.6mg sublingual NG at t=1 minute:
  27. 27. Ernest Orlando Lawrence Berkeley National Laboratory Results Nitroglycerin study Four subjects examined: • 3 times with no NG • 3 times with 0.6mg sublingual NG Measured quantities: • • • initial blood pressure (t < 0 min.) • final blood pressure (t = 7 min.) Analysis: • MANOVA of each measured variable with each trial contributing a dependent variable. • Lawley-Hotelling trace test with α=0.05
  28. 28. Ernest Orlando Lawrence Berkeley National Laboratory Results Nitroglycerin study: Effect of treatment with NG Mean fractional change (N=12) 0mg NG ± SEM 0.6mg NG Maximum PTT / baseline 5.26 ± 1.76% 21.24 1.90% Final PTT / baseline 0.53 ± 2.60% 6.20 ± 2.4% Final systolic BP / baseline -1.05 ± 1.88% -2.46 ± 2.25% Final diastolic BP / baseline -5.78 ± 3.46% -10.10 ± 3.57%
  29. 29. Ernest Orlando Lawrence Berkeley National Laboratory Results Nitroglycerin study: MANOVA • The effect of NG on was highly significant. (p=0.0036 < 0.05) • The effect of NG on was significant. (p=0.0433 < 0.05) • The effects of NG on systolic and diastolic blood pressures at the final time points of the studies were not significant. (p=0.3325 > 0.05 and p=0.0634 > 0.05, respectively) Considering all 4 subjects x 2 treatments x 3 trials
  30. 30. Ernest Orlando Lawrence Berkeley National Laboratory Results Nitroglycerin study: Within-subject coefficient of variation (CV) Within-subject day-to-day mean CV ± SEM 0mg NG studies 4.0 ± 1.7% (N=3) 0.6mg NG studies 4.1 ± 0.9% (N=3) Pooled studies 4.1 ± 0.9% (N=6)
  31. 31. Ernest Orlando Lawrence Berkeley National Laboratory Conclusion 1. The relaxoscope PTT measurements are directly proportional to propagation distance. 2. The relaxoscope appears to be 37% more sensitive to endothelium- mediated vasorelaxation than artery diameter measurements. 3. The relaxoscope PTT measurements increase after sublingual nitroglycerin, confirming that extravasation during occlusion is not the principal contributor to the decreases in PTT observed. 4. CV compares very favorably with most reported brachial artery diameter studies.
  32. 32. Ernest Orlando Lawrence Berkeley National Laboratory Future work 1. Build high frequency switchable continuous wave (CW) / pulsed wave (PW) flowmeter optimized for artificial pulse rising edge detection (software ultrasound). 2. More ergonomic design to accommodate different size arms. 3. More convenient methods of pulse application: wristband, hydraulic coupling 4. Better tolerated methods of endothelial stimulation than 5 minute cuff occlusion: β2-adrenergic agonists such as inhaled albuterol or salbutamol (Hayward et al. 2002, Wilkinson et al. 2002)
  33. 33. Ernest Orlando Lawrence Berkeley National Laboratory
  34. 34. Ernest Orlando Lawrence Berkeley National Laboratory Acknowledgements This work was supported by the US Department of Energy, the National Institute on Aging and the National Heart, Lung and Blood Institute. http://muti.lbl.gov/relaxoscope/isbi2004.ppt

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