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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
Outline Introduction
Objective
Methodology
Experiment and Results
Conclusions
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3
Introduction • Background
• Diagnosis tools
• Photoacoustic and imaging tools
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
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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
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
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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.
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Objective
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.
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Methodology • PAM
• 2D imaging
• 3D imaging
Optic-Acoustic Transmitter of OR-PAM
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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.
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
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
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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
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Experiments and Results • Specimen
• PAM System
Phantom with implanted copper wire
Specimen
Animal organ for ex vivo experiments
Chicken testicle (obvious vessel distribution)
Micro vascular distribution
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Copper wire at the same depth
1 mm
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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
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
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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
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
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
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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
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
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Ultrasonic probe with PZT film
• Frequency: 4.5 MHz
• Focal length 5 mm
Pulse-echo and receive ability
• Phantom with copper wire
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)
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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
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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
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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
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Conclusions
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.
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Thank you for attention
Taipei, Taiwan