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Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu, Tai-Chieh Wu, Masayuki Tanabe, Makiko Kobayashi and Che-Hua Yang National Taipei University of Technology Graduate Institute of Mechanical and Electrical Engineering

Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

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Page 1: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

Fiber Laser Based Optical-Resolution Photoacoustic Microscopy

Shao-Heng Liu, Tai-Chieh Wu, Masayuki Tanabe, Makiko Kobayashi and Che-Hua Yang

National Taipei University of Technology

Graduate Institute of Mechanical and Electrical Engineering

Page 2: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

Outline Introduction

Objective

Methodology

Experiment and Results

Conclusions

2

Page 3: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

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Introduction • Background

• Diagnosis tools

• Photoacoustic and imaging tools

Page 4: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

Cancer

Cancer is a group of diseases characterized by uncontrolled

growth and spread of abnormal cell. If the spread is not

controlled, it can result death.

Cancer

37%

15% 9%

8%

8%

6%

5%

4% 4% 4%

10 Leading Causes of Death in Taiwan (2015)

Malignant

Heart

Cerebral vascular

Pneumonia

Diabetes mellitus

Accident

chronic respiratory

hypertension

chronic liver and Cirrhosis

Nephrotic syndrome

Source: Ministry of Health and Welfare, Taiwan.

Symptoms of cancer

A change in bowel or bladder habit.

A sore that doesn’t heal.

A lump grows in elsewhere.

Unusual bleeding.

Obvious change in a wart or mole.

Color change of skin (Jaundice).

Source : American Cancer Society

4

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Cancer Diagnosis Methods

Cancer diagnosis tools

Invasive method

• Biopsy

• Blood test

• Bone marrow aspiration

• Pap test

Method Imaging Mechanism Drawback

X-Ray Transmission coefficient of X-Ray 1. High radiation

2. Insensitive on tumor

3. Expensive

MRI Half time of cell proton 1. Strong magnetic field

2. Long scanning interval

3. Expensive

PET Isotope absorption of cancer cell 1. Poor positioning

2. Must cooperate with CT

3. Expensive

UT Acoustic wave propagation 1. Poor transmission of bone

2. Resolution limited speckle

Noninvasive method

• X-Ray Computerized Tomography

• Magnetic Resonance Imaging (MRI)

• Position Emission Tomography (PET)

• Ultrasonography

• Photoacoustic Imaging (PAI)

Imaging mechanism comparison

X-Ray MRI PET UT

Page 6: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

Theory

First discovered by Alexander Graham Bell in 1880.

Photoacoustic effect

American Journal. Science, vol. 20, pp. 305–324, 1880.

“ A sound wave could be produced directly from a solid

sample if the incident light was rapidly interrupted. ”

Ultrasound Transducer

Incident Light

Photoacoustic waves

Photoacoustic source

“Production of sound by radiant energy.” Manufacturer and builder, Vol. 13, pp. 156-158, 1881.

Photoacoustic effect :

1. Laser / RF pulse

2. Optical absorption

3. Thermoelastic expansion

4. Pressure wave generation

5. Acoustic detection

6

Page 7: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

Characterization

Optical contrast and ultrasound depth

Low laser radiation

No chemical reactions in the tissue

Different optical absorption of molecule

Photoacoustic Characterization

Advantages :

High resolution image without speckle

Functional imaging

Less cost than CT, MRI and PET

Maslov K, Stoica G, Wang L.V. “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging.Zhang HF,” Nat Biotechnol. 2006 Jul; 24(7):848-51.

7

Page 8: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

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Objective

Page 9: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

Objective

Aiming at optical resolution photoacoustic microscopy (OR-PAM) modality for the image with high resolution and contrast.

Develop photoacoustic imaging system that con-focally and co-axially aligned of optical illumination and acoustic detection.

9

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Methodology • PAM

• 2D imaging

• 3D imaging

Page 11: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

Optic-Acoustic Transmitter of OR-PAM

11

Optic-acoustic transmitter

Consists of two optical prism and optical index-matching fluid

Con-focally aligning optical excitation and acoustic detection

1. J. C. Ranasinghesagara, Y. Jian, X. Chen, K. Mathewson, and R. J. Zemp, "Photoacoustic technique for assessing optical scattering properties of turbid media," J Biomed Opt 14, 040504 (2009).

2. R. J. Zemp, J. Ranasinghesagara, Y. Liang, X. Chen, and K. Mathewson, “A photoacoustic method for optical scattering measurements in turbid media,” Proc. SPIE 7177, 71770Q 2009.

The prism glass and the silicone oil have similar optical refractive

indices but very different acoustic impedances.

Refractive index Acoustic

impedance

(MRayl)

Speed of sound

(mm/ms)

Attenuation

(dB/cm at

25MHz)

BK-7 1.46 ZL = 12.9

ZT = 8.1

CL = 5.848

CT = 3.687 0.006

Index

matching

liquid

1.46 1.20 1.44 2.7

Water 1.33 1.51 1.51 1.38

Optical and acoustic properties of fused silica, index matching liquid, and water.

Page 12: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

0 1 2 3 4 5-1.0

-0.5

0.0

0.5

1.0

Am

pli

tud

e (

V)

Time (s)

0 1 2 3 4 5-1.0

-0.5

0.0

0.5

1.0

Am

pli

tud

e (

V)

Time (s)

12

90⁰ Right angle prism

Silicon oil

Phantom

PA Source

Objective lens

Ultrasonic

Transducer

Signal process

JAPAN

Plan N 4x /0.10

Imaging mechanism

Directly acquire photoacoustic signals

Form images by C-scan

PAM 2D Imaging

0 1 2 3 4 5

-1.0

-0.5

0.0

0.5

1.0

Am

plitu

de (

V)

Time (s)

Peak

Page 13: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

13 0 1 2 3 4 5 6 7 8-0.5

-0.4

-0.3

-0.2

-0.1

0.0

0.1

0.2

0.3

0.4

0.5

Am

plit

ud

e (V

)

Time (s)

0 1 2 3 4 5 6 7 8-0.5

-0.4

-0.3

-0.2

-0.1

0.0

0.1

0.2

0.3

0.4

0.5

Am

plit

ud

e (V

)

Time (s)

0 1 2 3 4 5-1.0

-0.5

0.0

0.5

1.0

Am

plit

ud

e (V

)

Time (s)

0 1 2 3 4 5-1.0

-0.5

0.0

0.5

1.0

Am

plit

ud

e (V

)

Time (s)

Signal Process of PAM

Maximum amplitude selection

Summation

Methods depend on:

1. Apparent peak of PA signal

2. Number of samples

0 1 2 3 4 5-1.0

-0.5

0.0

0.5

1.0

𝑨𝑴𝑨𝑿

𝚺(𝑨)

With absorber Without absorber

With absorber Without absorber

Page 14: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

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PAM 3D Imaging

Imaging mechanism

Based on depth-resolved signals

Wave velocity for propagating medium is a constant

Depth = wave velocity x time

Signal divided into 20 portion

Summation for each portion

Stack 20 images to 3D image

0.0 0.1 0.3 0.5 0.6 0.8 0.9 1.1 1.2 1.4 1.5

-3

-2

-1

0

1

2

3

Am

plit

ud

e (

V)

Time (s)

0.00 0.25 0.50 0.75 1.00 1.25 1.50 1.75 2.00 2.25 2.50

-3

-2

-1

0

1

2

3

Am

plit

ud

e (

V)

Depth (mm)

0.00 0.25 0.50 0.75 1.00 1.25 1.50 1.75 2.00 2.25 2.50

-3

-2

-1

0

1

2

3

Am

plit

ud

e (

V)

Depth (mm)

0.125 mm 0.25 mm 0.375 mm 0.625 mm 0.5 mm

0.75 mm 0.875 mm 1 mm 1.25 mm 1.125 mm

1.375 mm 1.5 mm 1.625 mm 1.875 mm 1.75 mm

2 mm 2.125 mm 2.25 mm 2.5 mm 2.375 mm

1 2

3 4

5

20

17

19 18

15 16

14 13

12 11

10 9

6

8 7

Page 15: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

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Experiments and Results • Specimen

• PAM System

Page 16: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

Phantom with implanted copper wire

Specimen

Animal organ for ex vivo experiments

Chicken testicle (obvious vessel distribution)

Micro vascular distribution

16

Copper wire at the same depth

1 mm

Page 17: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

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Ingredients of phantom fabrication

Phantom Fabrication

40% Acrylamide/Bis Solution

Ammonium persulfate, APS

TEMED (N,N,N,N-tetramethyl-ethylenediamine)

Phantom

Acoustic properties of phantom

Sound velocity

Pulse-echo testing

Phantom

10%

Density ρ

(g/cm3)

Velocity ν

(m/s)

Impedance Z

(Mrayl)

Attenuation α

(dB/cm)

Reference 1.024 1546 1.583 0.44

Handmade

Phantom 1.023 1528 1.563 0.52

A. F. Prokop, S. Vaezy, M. L. Noble, P. J. Kaczkowski, R. W. Martin and . A. Crum,” polyacrylamide gel as an acoustic coupling medium for focused ultrasound therapy” Ultrasound Med Biol, Vol.29(9), pp.1351-1358. 2003.

Attenuation

Substitution method

Density

Archimedes method

Acoustic impedance

Density x sound velocity

Page 18: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

Development of Co-axial Photoacoustic Transducer (CPT)

New transducer

Con-focal and co-axis

No prism to avoid multi reflection

High SNR and large amplitude

18

JAPAN

Plan N 4x /0.10

Characteristics of PZT in UT

Thick film structure

Controllable frequency response

Complex surface adaptability

Low cost installation

Transducer

PZT

film

Optical scanning

Optic and acoustic con-focus

Page 19: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

Piezoelectric Ultrasonic Transducer by Sol-Gel Process

19 1. M. Kobayashi and C.-K. Jen, “Piezoelectric thick bismuth titanate/lead zirconate titanate composite film transducers for smart NDE of metals”, Smart Materials and Structures, vol. 13, no. 4, pp.951-956, Aug. 2004.

2. M. Kobayashi, C.-K. Jen, and D. Lévesque, “Flexible ultrasonic transducers,” IEEE Trans. Ultrasound. Ferroelect. Freq. Contr., vol.53, pp.1478-1486, 2006.

PZT ( Lead Zirconate Titanate )

Significant higher sensitivity and capacitance

Wide variety of shapes possible

Direction of polarity

Fabrication process

Powders mixing with sol-gel solution

Spray coating

Heating process

Desired thickness

Poling

Yes

No

PZT powder Sol-gel solution

Ball milling machine PZT sol-gel

Page 20: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

PZT Film Ultrasonic Transducer

20 10mm 0 2 4 6 8 10

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

Am

plit

ud

e (

V)

Time (s)

pzpzss01

0 5 10 15 20 25

0.000

0.001

0.002

0.003

0.004

0.005

0.006

Am

p.

Frequency (MHz)

pzpzss01

Time domain signal and spectrum

Sol-gel Powder Substrate Thickness

of film

(mm)

Central

frequency

(MHz)

PZT PZT Stainless

steel

58 9.2

146 6.5

Flexible ultrasonic transducer

0 2 4 6 8 10

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

Am

plit

ud

e (

V)

Time (s)

pzpzss04

0 5 10 15 20 25

0.000

0.005

0.010

0.015

0.020

0.025

Am

p.

Frequency (MHz)

pzpzss04

6.5 MHz

9.2 MHz

20

Page 21: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

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CPT Geometry Design

CPT design

Soft tissue

Substrate PZT

• Probe height (H): 5 mm

• Curvature: 5 mm

• Probe diameter (D): 13 mm

• Hole diameter: 3 mm

• Sensor area: 43 mm2

Page 22: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

CPT Acoustic Performance Experiment Setup and

Specimen

Pulser / Receiver

• PRF: 1k Hz

• Energy: 25 uJ

• Gain: 40 dB

Horizontal Movement Stage

• Step: 0.1 mm

Vertical Movement Stage

• Step: 0.05 mm

25

Ultrasonic probe with PZT film

• Frequency: 4.5 MHz

• Focal length 5 mm

Pulse-echo and receive ability

• Phantom with copper wire

Page 23: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

4 5 6 7 8

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Off

set

fro

m p

han

tom

su

rface (

mm

)

Time (s)

23

Results of CPT in Pulse-echo Testing

CPT configuration

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.50.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

Peak t

o p

eak (

V)

Offset from phantom surface (mm)

1.5 mm

Vertical moving ( Step 0.1mm )

• Transducer Design

2 mm

R = 5 mm

• Front View

Axial resolution testing

• Top View

Parallel moving ( Step 0.05mm )

3.25 mm

• Front View

Lateral resolution testing

Waterfall graph of time domain signal in axial movement Waterfall graph of time domain signal in lateral movement

1.75 + 1.5 = 3.25

4 5 6 7 8

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Parr

allel M

ovem

en

t (m

m)

Time (s)

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.00.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

Pe

ak

to

pe

ak

(V

.)

Parrallel Movement (mm)

0.2

Axial resolution depends on the transducer frequency

Lateral resolution is determined by the optical focusing

Page 24: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

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Laser

• Wave length: 532 nm

• PRF: 50k Hz

• Energy: 0.6 uJ

Receiver

• Gain: 70 dB (With pre-amp)

Galvo-Mirror

• Scanning area : 1 x 1 mm

• Pixel: 100 x 100

OR-PAM Experiment Setup and Specimen

Step motor

• Scanning area : 4 x 4 mm

• Step : 0.1 mm

Specimen and Scanning Mode

Step motor for large area scanning

Galvo-Mirror for small area scanning

Vessels of chicken testicle

Page 25: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

25

Results of PAM Ex vivo Experiment

Vessel of the chicken testicle Reconstructed 2D image

The field of view is consistent with imaging area

0.6

4

0.5

8

Ve

ssel w

idth

≈ 0.0

6 m

m

Reconstructed 2D image at various depth Reconstructed 3D image

The vessel depth is 0.6 mm beneath the surface

Page 26: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

26

Conclusions

Page 27: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

Conclusions

1. The acrylamide based phantom is fabricated with the homogeneity and stability. It can make use of the

biomedical application because the acoustic properties of phantom is similar to soft tissue.

2. The co-axial photoacoustic transducer(CPT) is developed by the sol-gel spray method. The frequency and focal

length of transducer can be controlled by the PZT film thickness and the curvature of substrate.

3. The CPT takes advantages of con-focal and co-axis detection, directly receive PA signal without reflection and

minimize the volume of detection in PAM system.

4. For the CPT apply in PAM system, the 60 mm vessel can be imaged clearly in ex vivo experiment.

27

Page 28: Fiber Laser Based Optical-Resolution … › events › APCNDT2017 › app › content › Slides › ...Fiber Laser Based Optical-Resolution Photoacoustic Microscopy Shao-Heng Liu,

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Thank you for attention

Taipei, Taiwan