1. Characterization of Arterial Biomechanical Properties with Ultrasound for Coronary Heart Disease (CHD) Diagnostics Group 8 Laura Tanenbaum, Sam Tavakoli, Shea Thompson, Barbara Thorne-Thomsen, Michelle Thorson

2. Significance of CHD Primary cause of death in America ◦ 785,000 first-time heart attacks each year ◦ 470,000 recurrent heart attacks each year 33% of heart attacks result in sudden death The direct and indirect cost of this disease in this past year alone was $165.4 billion Developing a diagnostic tool to detect CHD before heart attack manifests would save lives and money

3. Project Overview Goal: To characterize biomechanical properties of human arteries after a stress test using ultrasound to diagnose CHD Aim 1: Determine Elastic Modulus Aim 2: Generate Blood Velocity Profile Aim 3: Determine Diagnostic Potential

4. Atherosclerosis Causes CHD Plaque build-up leads to stenosis ◦ Narrowing of the arteries Acute coronary syndrome : sudden occlusion blocks blood flow in the coronary artery ◦ Unstable, vulnerable plaques ◦ Varying degrees of stenosis Stable PlaqueUnstable Plaque High degree of stenosisLow degree of stenosis Image: www.heartonline.org/images/heartattack.jpg

5. Selected Parameters Elastic modulus reveals arterial wall stiffness Blood velocity profile changes with presence of plaques Carotid artery Determined after exercise stress test Image: http://graphics8.nytimes.com

6. Current Methods are Limited MethodEKG Catheter Coronary Angiography CTMRI Description Monitors electrical activity X-ray images track blood flow X-ray scans create 3D model Generates image from rotation frequencies of H + atoms Average cost of test $140$3,000$800$2,000 Weakness Limited to electrical activity High false positive rate Invasive Can’t detect all vulnerable plaques Invasive Long image acquisition time Expensive Long image acquisition time

7. Doppler Mode Ultrasound Transducer Skin Image: http://commons.wikimedia.org/wiki/ File:DopplerSonographyBloodFlowDiagram-de.svg Provides images of blood flow through arteries ◦ Noninvasive ◦ Real-time ◦ Average cost of echocardiogram = $300 Can be used to generate elastic modulus and blood velocity profile

8. Experimental Design All subjects age 40-60 Blind study design Cardiac coronary angiography used for preliminary diagnoses Exercise stress test procedure on treadmill ◦ 10% incline at steadily increasing rates ◦ 10 minutes or until target heart rate reached CHDControl Male25 Female25

9. Outline Aim 1: Determine the Elastic Modulus Aim 2: Generate the Blood Velocity Profile Aim 3: Determine the Diagnostic Potential

10. Project Outline Preliminary diagnosis with cardiac coronary angiography Elastic Modulus Velocity Profile Exercise stress test ULTRASOUND CHD Diagnosis Calculate sensitivity, specificity, accuracy EKG Check ultrasound results CHD Diagnosis Literature values for sensitivity, specificity, accuracy Determine superior diagnostic technique

11. Aim 1: Determine Elastic Modulus Decreased elasticity has been identified as a risk factor for cardiovascular disease Indicator of CHD and presence of plaques Experimental set-up ◦ Non-invasive technique ◦ Doppler ultrasound used to determine mean arterial radius and generate point force ◦ Laser vibrometer measures wall displacement

12. Aim 1: Vessel Model Viscoelastic Model ◦ Homogeneous, isotropic, 3D, linear, thick-shelled, cylindrical tube with constant thickness and radius Love's theory used to compute the ring resonant frequency matrix equation Elastic modulus calculated from resonant frequencies Only requires vessel diameter

13. Aim 1: Data Analysis Frequency response curve generated from laser vibrometer Maxima represent resonant frequencies Normalized curve used to determine quality factor for complex modulus Zhang 2006

14. Aim 2: Generate Blood Velocity Profile Blood velocity profile reflects presence and quantity of atherosclerotic plaque Plaque buildup is primary cause of CHD Experimental setup: Fast Fourier Transform Processor Digital Signal Processor Dirgenali 2006

15. Aim 2: Doppler Ultrasound 128 range gates along ultrasound beam Approaches real-time capabilities Digital signal processor collects backscattered signals Raw data: frequency as a function of depth Fast Fourier Transform converts spectral data to 3-D plot Tortoli 1996

16. Aim 2: Data Analysis Frequency of backscattered signal varies as a function of depth along the artery Maximum frequency per given depth correlates to maximum velocity of arterial blood flow where W, F, and θ are properties of transducer and Doppler ultrasound beam, λ is beam wavelength Generate velocity vs. depth profile

17. Aim 2: Significance Frequency varies significantly in healthy (left) vs. atherosclerotic (right) patients Noticeable differences with 5% stenosis Stress test magnifies effects Possible to determine plaque position in artery Potential for CHD diagnosis Dirgenali 2006

18. Aim 3: Diagnostic Potential Calculate parameter values using ultrasound Compare to literature values ◦ Generate diagnosis Compare to "true" diagnosis ◦ Calculate sensitivity and specificity Compare to EKG sensitivity and specificity ◦ Determine if ultrasound is a better diagnostic tool for CHD

19. Timeline 0-6 months Recruit subjects Obtain equipment 6-9 months Conduct testing Stress test Ultrasound EKG 9-18 months Determine parameter values Compare to literature values Generate diagnoses 18-24 months Calculate ultrasound sensitivity, specificity, accuracy Compare to EKG Determine superior technology

20. Advantages of Proposed Technique Biomechanical Relevance ◦ Blood velocity profile ◦ Elastic modulus ◦ Both indicators of CHD Strengths ◦ Non-invasive ◦ Real-time ◦ Biomechanical information ◦ Inexpensive Novelty ◦ Combined system to diagnose CHD ◦ Using ultrasound after stress test

21. Conclusion Characterization of elastic modulus and blood velocity profile of carotid artery Diagnosis of CHD using biomechanical parameters Potential for revolutionizing CHD diagnostics ◦ Save lives and money