Real-time Visualization of Clot Dissolution Using Doppler Ultrasound

1. Real-time Visualization of Clot Dissolution Using Doppler Ultrasound Group 38 Teammates: Debra Yen, Taylor Tso, Vera Xiao Presenter: Vera Xiao Client: Michael Sabo, Pulse Therapeutics, Inc.

2. Outline Background and Client Need Design Specifications and Concept Overview The Chosen Design Material, Manufacturing, and Cost Safety Conclusion

3. Background 795,000 strokes / year in US ( 87% are ischemic stroke ) Time is critical: - 1.9 million neuron die per minute - 7.5 miles of myelinated fiber damaged per minute tPA (tissue plasminogen activator) is only drug approved Limited access to clot due to lack of blood flow

4. Client and Client Needs Client: Pulse Therapeutics Inc. Magnetically-Enhanced Diffusion (MED) therapy for ER use tPA coded magnetite directed to clot location under magnetic effect real-time visualization of lysis: - monitor therapy - detect successful

5. Design Specifications (1)

6. Design Specifications (2)

7. Design Overview • TCD Probe - Phased Array • Headset - Ball and socket mechanism - Adhesive and three elastic straps • Algorithm - Compare affected and unaffected middle cerebral artery mean full velocity

8. The Chosen Design : TCD Probe (1) • Phased Array - All crystals are excited simultaneously - Electronic steering of beam provides different lines of sight • Advantages - Variable focal lengths, high resolution, high line density - Electronic steering and focusing enhanced with delay times - Small size

9. The Chosen Design: TCD Probe (2) Manufacturer: Sonosite M-Turbo P-21X with custom-made case Frequency range: 5 – 1 MHz 21 mm broadband phased array Scan depth: 35 cm Dimension: cylindrical case with length = 120 mm, diameter = 31 mm. Probe body is threaded for probe insertion

10. The Chose Design: TCD Probe (3)

11. The Chosen Design : Headset (1) Adhesive and Elastic Straps Probe positioned perpendicular to patient’s temporal window Three elastic strips across patient’s forehead, back head, and chin Adhesive : Collodion Ball and Socket Mechanism • 70° full range of insonation angle • Single Thumb screw to lock mechanism • Probe screws in the ball

12. The Chosen Design : Headset (2) • Physical constraints on pedestal size: <70 mm diameter • Socket size < 60mm • Probe diameter = 31 mm • Allow 70° insonation angle • Result: ball radius = 25 mm

13. The Chosen Design: Headset (3)

14. The Chosen Design: Headset (4) Adhesive Prevent Minor disturbance Material: Collodion - 5 minutes to dry - acetone to clean up Position most on zygoma, squamous portion of the temporal bone Safe for medical use Straps • Primary fixture mechanism • Three straps 120° apart • Material: Nylon • Young’s Modulus: 2-4 GPa

15. The Chosen Design : Headset (5)

16. The Chosen Design : Headset (6) Headset material: polyvinyl chloride (PVC) Strong, stiff, and head and weather resistant Density: 1.35-1.45 g/ Volume: 36324 Headset weight: volume x density ~ 52.67g Headset + Probe weight ~ 250 g  2.45 N Strap across sections: 30  816.7 Pa Nylon straps and collodion strength >> gravity force

17. The Chosen Design: Probe & Headset Usage Workflow • Apply gel, and locate temporal window with probe while pedestal is locked at middle of the probe body • Twist down the pedestal and apply adhesives • Attach straps to pedestal, and allow adhesive to dry • Unlock the ball and socket, and alter probe insonation angle till optimal

18. The Chosen Design : Algorithm (1)

19. The Chosen Design : Algorithm (2) Algorithm Demonstration

20. The Chosen Design: Algorithm (3) • Created algorithm based only on MFV - Neglects effects of magnetite particles • Ultrasound signal from particles must be filtered out before applying algorithm - Need experimental data Values to detect beginning of clot dissolution can differentiate completely occluded signal from partially occluded signal. If MCA is originally partially occluded, threshold may not apply Algorithm is therefore targeted towards severe cases involving initial completely occluded flow

21. The Chosen Design : Algorithm (4) • LCD Monitor from Industrial Image, Inc. • 6.4” Open Frame LCD Monitor - Contrast Ratio: 400:1 - Display Color: 262, 144 colors - Viewing Angle: -50~50 (H); 35~15 (V) - Resolution: 640x480 pixels - Input: VGA - Touchscreen: Resistive

22. Material, Manufacturing and Cost (1)

23. Material, Manufacturing, and Cost (2)

24. DesignSafe Report

25. DesignSafe Report (examples)

26. Conclusions Our device and algorithm will function well for severe cases of ischemic stroke from MCA occlusion - Algorithm may detect false positives in milder cases - We did not consider cases arising from occlusion in other arteries 10-20% of patients have too thick temporal windows to properly insonate

27. Future Direction • Conduct experiments comparing visibility of magnetite particles to that of blood - May use a contrast agent • Develop a digital filter for the algorithm • Ultrasound affect clot-dissolution?

28. Take-away Learned about the foundations of ultrasound and design dynamics We should manage our time better We should try to work in teams with a diverse technical background

29. References Ball and socket mechanism • Burgin, S. “TCD Criteria for Recanalization.” Stroke. Oct. 20 1999. • Halsey, J. and Tan, MJ. “Evaluation of Acute Stroke.” Transcranial Doppler, New York 1992. • http://www.industrialimage.net/openframe/openframe6-1.php • http://sentryair.com/blog/collodion-fumes/collodion-adhesive-possible-health-effects-fume-extraction-recommendations/ • DesignSafe software http://www.designsafe.com/