Laser Optoacoustic + Ultrasonic
Imaging System Assembly (LOUISA)
for Functional-Anatomical Mapping
Alexander A. Oraevsky
Seeing through the body
by listening to the sound of light
NIH Grants: R01CA167446, R43EB015287, R44CA110137,
R44CA110137-S1, R44CA128196, R43ES021629
AAPM-2014, Austin, Texas, 23 July 2014
Arrrays of OptoAcoustic Transducers:
Andre Conjusteau
Analog and Digital Electronics
Vassili Ivanov
FiberOptics and Mechanics
Peter Brecht
Firmware and Software
Pratik Talole, Ketan Mehta
Modeling, Math-Physics, Tomography
Sergey Ermilov, Slava Nadvoretsky,
Mark Anastasio, Wash U St. Louis
Experimental Imaging, Data Processing
Richard Su, Dmitri Tsyboulski
Animal Studies, Nanotechnology
Anton Liopo
Clinical imaging of breast cancer
Wei Yang, MD Anderson Cancer Cntr
Students,
Post Docs,
Scientists,
Engineers
and
Faculty
Collaborators
AAPM-2014, Austin, Texas, 23 July 2014
Listening to Light with OptoAcoustics
NEAR-INFRARED
LASER PULSE
Acoustic
Waves
Acoustic
Waves
Absorbing
Object
Absorbing
Object
Array of
Acoustic Detectors
P 
1 V
 V

1

T 
1  Eabs( z )
 CS2

F0  a   ( T ) F0  a
cV
cp

AAPM-2014, Austin, Texas, 23 July 2014
1
Algorithm of OptoAcoustic Tomography
Ultrasound
transducers
Laser
Pulse
Image
reconstruction
algorithm
Tissue
Absorbed optical
energy density
3D OAT
2D OAT
Finch et. al., SIMA 2004
AAPM-2014, Austin, Texas, 23 July 2014
Impulse Responses OA/US transducers
Resonant US
transducer
0
WideBand Transducer
0
-0.5
reverberations
-1
0
0.2
0.4
0.6
0.8
1
Time, microsec
Resonant Transducer
-20
-40
-60
-80
Ultrawide-Band
OA transducer
0.8
-100
0.6
0
10
20
30
40
50
60
Frequency, MHz
0.4
0.2
accurate waveform
Sensitivity = NEP = 1Pa
0
0
0.5
1
1.5
2
Time, microsec
AAPM-2014, Austin, Texas, 23 July 2014
Biophotonic Imaging Technology
based on Optical Absorption in Tissues
Absorption Capability, µa (cm-1) x % content
Impulse Response Signal
1
OptoAcoustic Amplitude, dB
Impulse Response Signal
1
0.5
10
1064 nm
757 nm
8
800 nm
O2-Hb
6
H-Hb
4
2
H2O
600
700
800
900
1000
1100
Wavelength, nm
AAPM-2014, Austin, Texas, 23 July 2014
2
Optoacoustic Detection of Erythrocytes:
demonstration of a single red blood cell detection
red
blood
cell
Depth, mm
transient
acoustic
wave
0
1
2
3
4
5
10
E=5 mJ
Nd-YAG
laser
=532 nm
Optoacoustic Signal, mV
5
transient
acoustic
wave
0
-5
-10
laser-induced
acoustic wave
from individual
red blood cells
-15
signal
piezoto
transducer
scope
-20
0
0.5
1
1.5
2
Time, µs
2.5
3
3.5
A.A. Oraevsky, E.V. Savateeva, A. Karabutov,
V.G. Andreev: “Optoacoustic imaging of blood for
visualization and diagnostics of breast cancer”,
Proc. SPIE 2002; 4619: 81-94.
L.D. Wang, K Maslov, L.V. Wang, Pros NAS 110, 5759, 2013
AAPM-2014, Austin, Texas, 23 July 2014
Rationale for Imaging of Cancerous
Tumors based on Angiogenesis
“Without a private supply of new microscopic blood vessels
cancerous tumors can not grow larger than the head of a pin
and are unlikely to become lethal. Without blood vessels to
feed them oxygen and nutrients, these tumors remain tiny
and unable to spread…”
Judah Folkman, MD
AAPM-2014, Austin, Texas, 23 July 2014
Breast Cancer Imaging
(X-ray Mammography vs. LOIS)
MAMMOGRAPHY IMAGE
OPTOACOUSTIC IMAGE
Low Contrast: dense breast
Missing 20% of cancerous tumors
High Contrast: 2x-3x
Resolution: 0.5 mm
AAPM-2014, Austin, Texas, 23 July 2014
3
Real-time Opto-Acoustic & Ultrasound Imaging
Ulnar Artery in Human Arm
Ultrasound – anatomical
information on tissue
structure (morphology)
Optoacoustics – functional
information about [tHb]
and [SO2] (molecular)
M. Frenz et al., Proc. SPIE, vol. 4960, 2003
A. Oraevsky, S. Emelianov et al., Proc. SPIE, vol. 5320, 2004
AAPM-2014, Austin, Texas, 23 July 2014
Co-registration of
OptoAcoustic and Ultrasound Images
 This technology combines and co-registers images based on optical
and acoustical contrast to improve the accuracy of cancer detection and diagnosis.
 Co-registered OA+US imaging has the merit of providing both, functional information
based on specificity of optical contrast in blood and morphological information with
high sensitivity and resolution of ultrasonic imaging.
AAPM-2014, Austin, Texas, 23 July 2014
Method of Tumor Differentiation
Tumor Absorption at 1064-nm, 1/cm
0.08
0.07
[THb]=[Hb]+[HbO2]
0.06
Benign
0.05
0.04
0.03
[SO2]=[HbO2]/[THb]
Malignant
0.02
0.01
0
0
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
Tumor Absorption at 755-nm, 1/cm
AAPM-2014, Austin, Texas, 23 July 2014
4
Hand-held Opto-Acoustic / Ultrasound Probe
and Method of Co-registered Functional+Anatomical Imaging
US+[tHb]
US+[SO2]
US B-mode
AAPM-2014, Austin, Texas, 23 July 2014
Invasive Carcinoma:
Enhanced concentration of deoxygenated blood
[tHb]
Total Hemoglobin
[USI]
[SO2]
Blood Oxygenation B-mode Ultrasound
AAPM-2014, Austin, Texas, 23 July 2014
Benign FibroAdenoma:
normal blood oxygenation, not significant angiogenesis
[tHb]
Total Hemoglobin
[USI]
[SO2]
Blood Oxygenation B-mode Ultrasound
AAPM-2014, Austin, Texas, 23 July 2014
5
Co-registration of OA and US
for diagnostic imaging of breast cancer
Invasive Ductal Carcinoma, malignant tumor
with high concentration of (deoxy)hemoglobin
Fibroadenoma, benign tumor
with normal blood oxygenation and and low total hemoglobin
AAPM-2014, Austin, Texas, 23 July 2014
KEY FEATURES OF BREAST IMAGING WITH IMAGIO™
VERSUS THE CURRENT STANDARD OF CARE*
Key
Properties
Morphology
and function
False
Negative
False
Positive
Safety
Gold Standard
(X-ray mammo)
Only
morphology
25%
Imagio
(OA+US)
Yes
Both
<3%
Significance
Benefits
High sensitivity
and specificity
Early detection
82%
<36%
Carcinogenic
radiation
Pain of
compression
Safe
Light & Sound
No
compression
Minimum
Negative biopsy
More frequent
procedures
Better
acceptance
Convenience
* Projections based on preliminary analysis of initial clinical data of 79 patients
Diagnoses BIRADS-4A and BIRADS-4B cases 30% more accurately
AAPM-2014, Austin, Texas, 23 July 2014
Depth Limit of OA System Sensitivity
Optoacoustic Brightness
50
20 mm
40
1-mm blood vessel
in 1% fat milk
a=0.04/cm
s’=12/cm
 =1.2/cm
40 mm eff
30
60 mm
80 mm
20
10
noise floor
0
0
10
20
30
40
50
60
70
80
Depth, mm
AAPM-2014, Austin, Texas, 23 July 2014
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Tomography with LOUISA
2D versus 3D
 2D is conveniently performed with hand-held probe,
but can not be used for full organ screening,
sensitivity (contrast) is limited.
 2D delivers real time video rate images that can be
important for imaging rapid physiological changes,
but small aperture of the ultrasonic transducer array
provides limited lateral resolution and relatively
inaccurate quantitative brightness of image pixels
 3D with provides solutions for problems of 2D
imaging (low background, high resolution in all
directions) at the cost of time for data acquisition
and image reconstruction.
AAPM-2014, Austin, Texas, 23 July 2014
TomoWave
Laboratories, Inc.
Laser Optoacoustic
Imaging System
LOIS-3D
a new technology
for
preclinical
research
AAPM-2014, Austin, Texas, 23 July 2014
Quantitative OptoAcoustic Tomography
𝑺𝒕 =
2𝜋 𝑅 𝑐𝑜𝑠𝛽
𝑆𝑖
𝑁𝑇𝑟
Specifications:
150 deg arc, 65mm dia array, 128 of wideband 0.1 to 8 MHz transducers
38400 virtual transducers on spherical surface – rigorous reconstruction
Minimal Imaging Time: 30 sec acquisition + 20 sec image reconstruction
AAPM-2014, Austin, Texas, 23 July 2014
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Spatial Resolution in 3D
3 horse
hairs
with
diam
150
micron
A hair cross-section of the optoacoustic
image acquired with LOUIS-3D
Image brightness shows Gaussian shape with FWHM of 300 micron.
AAPM-2014, Austin, Texas, 23 July 2014
Anatomical OptoAcoustic Imaging
tissue structures: organs, bones
AAPM-2014, Austin, Texas, 23 July 2014
3D OptoAcoustic Imaging
of blood vessels, internal organs and kidney
Kidney
AAPM-2014, Austin, Texas, 23 July 2014
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Functional OptoAcoustic Imaging
1064nm / 757nm - arterial/venous systems
1064
757 nm
Veins @ 760 nm
Arteries @ 1064 nm
AAPM-2014, Austin, Texas, 23 July 2014
Functional OptoAcoustic Imaging at 760 nm
gradual decrease of blood oxygenation
AAPM-2014, Austin, Texas, 23 July 2014
OptoAcoustic Imaging of Mouse Brain
Live Mouse, Total Hemoglobin Map
AAPM-2014, Austin, Texas, 23 July 2014
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Molecular Imaging using Gold Nanorods
Absorption Spectra for Nanoparticles
Absorption cross-section [10
-10
cm2]
10
8
Au-Sphere, r=20 nm
Shell, Si 0-17.4 nm, Au 17.4-20 nm
Au-ellipsoid, a=12.6 nm, b=50.4 nm
6
multiplied x10
4
2
0
0.5
Control
GNR-PEG
0.6
0.7
Wavelength, µm
0.8
0.9
GNR-Herceptin
J.A. Copland, M. Eghtedari, V.L. Popov, N. Kotov, N., A.A. Oraevsky: Bioconjugated gold nanoparticles as a molecular based contrast
agent: Implications for imaging of deep tumors using optoacoustic tomography, Molecular Imaging and Biology 2004; 6(5): 341-349.
AAPM-2014, Austin, Texas, 23 July 2014
GNRs as OptoAcoustic Contrast Agents
AR=3.7
800 nm
Ti:Sapphire
AR=9.5
1064 nm
Nd:YAG
AAPM-2014, Austin, Texas, 23 July 2014
Molecular OptoAcoustic Imaging of a Tumor
BT474 Tumor
HER2 receptors
Injected iv
200 L of targeted
GNR-Herceptin
C=7x1012/mL
Angio-Endogenous
GNR-PEG-Herceptin
AAPM-2014, Austin, Texas, 23 July 2014
tum
10
Design of Imaging Module
OA scan is followed by LU scan
Optoacoustic PLUS Laser Ultrasound Tomography enables 5 images:
Functional [Hb], [HbO2], [H2O] and morphology: SoS and UA
AAPM-2014, Austin, Texas, 23 July 2014
Laser Generated Ultrasound
LUE=5
kPa / [mJ/cm2]
AAPM-2014, Austin, Texas, 23 July 2014
OA-US Tube Phantom
• 300 rotation steps, 16 averages
• 3 4.7mm PTFE tubes filled with NaCl + CuSO4
• SoS: Tube1 – 1.7, Tube2 – 1.6, Tube 3 – 1.5 mm/µs
• a: Tube1 – 2.4, Tube2 – 2.2, Tube3 – 1.1 cm-1
3
2
1
3
2
2
3
1
1
Viewed from the LU emitter perspective
AAPM-2014, Austin, Texas, 23 July 2014
11
Co-registered OA & SoS Images
liver/spleen level slice
Cryo photograph
OAT
Speed of sound
6
6
3
6
3
3
2
4
2
5
1
7
4
2
4
5
1
5
7
7
1 – Abdominal aorta/caudal vena cava, 2 – Right kidney, 3 – Liver, 4 – Spleen,
5 – Stomach, 6 – Intestines/abdominal fat, 7 – Vertebrae/back muscles
AAPM-2014, Austin, Texas, 23 July 2014
From LOIS-3D to LOUISA-3D
translation to diagnostic imaging of breast cancer
Breast Screening,
Diagnostics and
Monitoring System
AAPM-2014, Austin, Texas, 23 July 2014
SUMMARY
 OptoAcoustic Tomography provides images with high optical contrast of
[Hb] and [HbO2] and excellent ultrasonic resolution (<0.3mm)
 Most sensitive and accurate approach to quantitative imaging
 Rapid image acquisition and reconstruction (down to 40 sec)
Multiwavelength spectroscopic capability
 Functional OptoAcoustic Imaging
Measurement of [Hb] and [HbO] (hematocrit) in tissues and blood
vessels, assessment of heart function and blood flow.
Assessment of tumor angiogenesis, angiography, detection and
characterization of stroke and traumatic injury of the brain
 Molecular Imaging
Distribution of cellular receptors with targeted nanoparticle agents
Studies into kinetic and dynamic distribution of contrast agents
Combination of OptoAcoustic and Ultrasonic Imaging
Provides coregistered maps of anatomy and functional parameters
Laser generated ultrasound: 3x resolution, 3x contrast, USI spectroscopy
AAPM-2014, Austin, Texas, 23 July 2014
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