Real-time Visualization of Clot Dissolution Using Doppler

UltrasoundGroup 38

Teammates: Debra Yen, Taylor Tso, Vera XiaoPresenter: Vera Xiao

Client: Michael Sabo, Pulse Therapeutics, Inc.

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

Outline

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

Background

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

Client and Client Needs

Design Specifications (1)

Design Specifications (2)

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

Design Overview

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

The Chosen Design : TCD Probe (1)

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

The Chosen Design: TCD Probe (2)

The Chose Design: TCD Probe (3)

The Chosen Design : Headset (1)

Ball and Socket Mechanism

70° full range of insonation angle

Single Thumb screw to lock mechanism

Probe screws in the ball

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

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

The Chosen Design: Headset (3)

The Chosen Design: Headset (4)

Straps

Primary fixture mechanism

Three straps 120° apart

Material: Nylon Young’s Modulus: 2-4

GPa

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

The Chosen Design : Headset (5)

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

The Chosen Design : Headset (6)

The Chosen Design: Probe & Headset Usage Workflow

1. Apply gel, and locate temporal window with probe while pedestal is locked at middle of the probe body

2. Twist down the pedestal and apply adhesives

3. Attach straps to pedestal, and allow adhesive to dry

4. Unlock the ball and socket, and alter probe insonation angle till optimal

The Chosen Design : Algorithm (1)

Algorithm Demonstration

The Chosen Design : Algorithm (2)

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

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

Material, Manufacturing and Cost (1)

Prototype

Component Material Method Lead Time Cost

Probe (M-Turbo P-21X)

Phased Array single probe 3 Weeks 11,500

PVC 3D Printing 8 Days 4070.4

Headset -- Ball PVC 3D Printing 8 Days 489.4

Headset -- Pedestal PVC 3D Printing 8 Days 1726.4Headset -- Thumb Screw Nylon Direct Purchase 1 Week 9.5

Headset -- Flat Hook PVC 3D Printing 8 Days 3.5

Headset -- Straps Nylon Elastic Strap Direct Purchase 1 Week 9.11

Headset -- Adhesive Collodion Direct Purchase 1 Week 6

Algorithm -- Coding N/A Coding 3 Days 480

Algorithm -- LCD N/A N/A N/A N/A

Total       18294.31

Material, Manufacturing, and Cost (2)

Note: 1st year cost includes initial tooling and 50 units of the imaging systems.

Manufacturing

Component Material Method manufacterLead Time Cost (1st Year)

Probe (M-Turbo P-21X) Phased Array Duplex Sonosite 3 weeks 1150000

  PVC Injection Mold ICOMold 2 weeks 2875

Headset -- Ball PVC Injection Mold ICOMold 2 weeks 3025.5Headset -- Pedestal PVC Injection Mold ICOMold 2 weeks 5389Headset -- Thumb Screw Nylon Direct Purchase

plastic nuts and bolts 1 week 19

Headset -- Flat Hook PVC Injection Mold ICOMold 2 weeks 502.5Headset -- Straps

Nylon Elastic Strap Direct Purchase McMaster-Carr 2 days 152

Headset -- Adhesive Collodion Direct Purchase Mehron 1 week 2400Algorithm -- Coding  N/A

Modification and Test  N/A 2 weeks 1600

Algorithm -- LCD  N/A Direct PurchaseIndustrial Image 2 weeks 65800

Total  N/A  N/A  N/A  N/A 1231762.8

DesignSafe ReportSummary

Item Counts

Total Users 2

Total Tasks 9

Total Hazards (Task-Hazard pairs) 21

Residual Risks

Number of residual risks that are:

High 0

Moderate 0

Low 20

Unspecified 1

Initial Risks

Number of initial risks that are:

High 2

Moderate 15

Low 4

Unspecified 0

Change in risk levels

High to Low 2

Moderate to Low 15

Low to Unspecified 1

No change in risk level 3

DesignSafe Report (examples)

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

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?

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

References

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/

Ball and socket mechanism