Laser Optoacoustic + Ultrasonic Imaging System Assembly...
Transcript of Laser Optoacoustic + Ultrasonic Imaging System Assembly...
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AAPM-2014, Austin, Texas, 23 July 2014
Alexander A. Oraevsky
Laser Optoacoustic + Ultrasonic Imaging System Assembly (LOUISA) for Functional-Anatomical Mapping
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
Students, Post Docs, Scientists, Engineers
and Faculty
Collaborators
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
AAPM-2014, Austin, Texas, 23 July 2014
Listening to Light with OptoAcoustics
Absorbing Object
NEAR-INFRARED
LASER PULSE
Array of
Acoustic Detectors
Absorbing Object
Acoustic
Waves
Acoustic
Waves
aap
S
V
FTFc
C
c
zabs
ET
V
VP
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)()(111
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AAPM-2014, Austin, Texas, 23 July 2014
Algorithm of OptoAcoustic Tomography
Laser
Pulse
Ultrasound
transducers
Tissue Absorbed optical
energy density
Image
reconstruction
algorithm
Finch et. al., SIMA 2004
3D OAT
2D OAT
AAPM-2014, Austin, Texas, 23 July 2014
Impulse Responses OA/US transducers
reverberations
accurate waveform
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0 10 20 30 40 50 60
WideBand Transducer
Resonant Transducer
Op
toA
co
ustic A
mp
litu
de, d
B
Frequency, MHz
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Impu
lse R
espo
nse
Sig
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Time, microsec
Ultrawide-BandOA transducer
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-0.5
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0.5
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Impu
lse R
espo
nse
Sig
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Time, microsec
Resonant UStransducer
Sensitivity = NEP = 1Pa
AAPM-2014, Austin, Texas, 23 July 2014
Biophotonic Imaging Technology based on Optical Absorption in Tissues
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600 700 800 900 1000 1100
Absorp
tion
Capabili
ty, µ
a (
cm
-1)
x %
co
nte
nt
Wavelength, nm
757 nm1064 nm
O2-Hb
H-Hb
H2O
800 nm
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AAPM-2014, Austin, Texas, 23 July 2014
Optoacoustic Detection of Erythrocytes: demonstration of a single red blood cell detection
Nd
-YA
G
las
er
=
53
2 n
m
red blood
cell
piezo- transducer
transient acoustic
wave
transient acoustic
wavesignal
to scope
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Opto
acoustic S
ignal, m
V
Time, µs
Depth, mm
laser-inducedacoustic wavefrom individualred blood cells
E=5 mJ
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
“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
Rationale for Imaging of Cancerous Tumors based on Angiogenesis
AAPM-2014, Austin, Texas, 23 July 2014
Breast Cancer Imaging (X-ray Mammography vs. LOIS)
OPTOACOUSTIC IMAGE
High Contrast: 2x-3x
Resolution: 0.5 mm
MAMMOGRAPHY IMAGE
Low Contrast: dense breast
Missing 20% of cancerous tumors
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AAPM-2014, Austin, Texas, 23 July 2014
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
[THb]=[Hb]+[HbO2]
[SO2]=[HbO2]/[THb]
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Tu
mor
Ab
sorp
tio
n a
t 1
06
4-n
m, 1
/cm
Tumor Absorption at 755-nm, 1/cm
Benign
Malignant
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AAPM-2014, Austin, Texas, 23 July 2014
Hand-held Opto-Acoustic / Ultrasound Probe and Method of Co-registered Functional+Anatomical Imaging
US B-mode
US+[SO2]
US+[tHb]
AAPM-2014, Austin, Texas, 23 July 2014
Invasive Carcinoma: Enhanced concentration of deoxygenated blood
[tHb] Total Hemoglobin
[SO2] Blood Oxygenation
[USI] B-mode Ultrasound
AAPM-2014, Austin, Texas, 23 July 2014
Benign FibroAdenoma: normal blood oxygenation, not significant angiogenesis
[tHb] Total Hemoglobin
[SO2] Blood Oxygenation
[USI] B-mode Ultrasound
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AAPM-2014, Austin, Texas, 23 July 2014
Invasive Ductal Carcinoma, malignant tumor
with high concentration of (deoxy)hemoglobin
Fibroadenoma, benign tumor
with normal blood oxygenation and and low total hemoglobin
Co-registration of OA and US for diagnostic imaging of breast cancer
AAPM-2014, Austin, Texas, 23 July 2014
KEY FEATURES OF BREAST IMAGING WITH IMAGIO™ VERSUS THE CURRENT STANDARD OF CARE*
Key
Properties
Gold Standard
(X-ray mammo)
Imagio
(OA+US)
Significance
Benefits
Morphology
and function
Only
morphology
Yes
Both
High sensitivity
and specificity
False
Negative
25% <3% Early detection
False
Positive
82% <36% Minimum
Negative biopsy
Safety Carcinogenic
radiation
Safe
Light & Sound
More frequent
procedures
Convenience Pain of
compression
No
compression
Better
acceptance
* 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
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Op
toa
co
ustic B
righ
tness
Depth, mm
noise floor
20 mm
40 mm
60 mm
80 mm
1-mm blood vessel
in 1% fat milk
a=0.04/cm
s’=12/cm
eff=1.2/cm
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AAPM-2014, Austin, Texas, 23 July 2014
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
Laser Optoacoustic Imaging System
LOIS-3D a new technology
for preclinical research
TomoWave
Laboratories, Inc.
AAPM-2014, Austin, Texas, 23 July 2014
Quantitative OptoAcoustic Tomography
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
𝑺𝒕 =2𝜋 𝑅 𝑐𝑜𝑠𝛽
𝑁𝑇𝑟𝑆𝑖
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AAPM-2014, Austin, Texas, 23 July 2014
Spatial Resolution in 3D
Image brightness shows Gaussian shape with FWHM of 300 micron.
A hair cross-section of the optoacoustic image acquired with LOUIS-3D
3 horse hairs with diam 150
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
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AAPM-2014, Austin, Texas, 23 July 2014
Functional OptoAcoustic Imaging
1064nm / 757nm - arterial/venous systems
757 nm 1064 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
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AAPM-2014, Austin, Texas, 23 July 2014
Molecular Imaging using Gold Nanorods
GNR-PEG Control GNR-Herceptin
Control GNR-PEG GNR-Herceptin
tumor
tumor
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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
Abs
orpt
ion
cros
s-se
ctio
n [1
0-1
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2 ]
Wavelength, µm
Absorption Spectra for Nanoparticles
multiplied x10
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=9.5
1064 nm
Nd:YAG AR=3.7
800 nm
Ti:Sapphire
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
GNR-PEG-Herceptin Angio-Endogenous
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AAPM-2014, Austin, Texas, 23 July 2014
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
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Viewed from the LU emitter perspective
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AAPM-2014, Austin, Texas, 23 July 2014
Co-registered OA & SoS Images liver/spleen level slice
Cryo photograph OAT Speed of sound
1 – Abdominal aorta/caudal vena cava, 2 – Right kidney, 3 – Liver, 4 – Spleen,
5 – Stomach, 6 – Intestines/abdominal fat, 7 – Vertebrae/back muscles
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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