Outline
• Introduction to photoacoustic computed tomography (PACT)
• Imaging models and iterative image reconstruction
Photoacoustic Computed Tomography with
Applications to Breast Imaging
• Success with small animal imaging
Mark A. Anastasio
• PACT breast imaging
Department of Biomedical Engineering
» System design
» Preliminary clinical data
Washington University in St. Louis
St. Louis, MO
Advantages of PACT
• PACT methods have been recently developed to overcome the
limitations of other existing modalities.
» Strong (hemoglobin-based) contrast similar to pure optical methods
» High spatial resolution similar to pure ultrasonic methods
• Anatomical structures can be imaged based on endogenous
hemoglobin.
• Hemoglobin can also serve as a functional contrast for imaging of
hemoglobin oxygen saturation (sO2).
• Molecular imaging is also possible by use of exogenous agents.
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Schematic of PAT
Optical
pulse
Schematic of PAT
Optical
pulse
Ultrasound
transducers
• Absorbed optical energy density:
Ultrasound
transducers
Image
reconstruction
algorithm
Tissue
Photoacoustic physics
» μa(r) optical absorption coefficient
» Φs(r) optical fluence rate
Image
reconstruction
algorithm
• Photoacoustic wave equation (can generalize to heterogeneous media)
Tissue
Absorbed optical
energy density
Absorbed optical
energy density
Grueneisen
parameter
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PACT reconstruction: Heterogeneous media
Canonical imaging model
• Conventional imaging model (assuming idealized transducers)
• If SOS variations are known, they can be incorporated into the
PACT imaging model. Two general approaches:
» Solution to PA wave equationa homogeneous lossless me
» Continuous-to-continuous mapping (C-C)
(mapping between infinite dimensional Hilbert spaces)
» Assumes uniform acoustic properties (SOS), constant density, no
acoustic attenuation
(i.e., input and output functions are defined on continuous domains.)
• Alternate form: spherical Radon transform (SRT)
• Geometrical-acoustics (“ray-based”) reconstruction:
Challenges in PACT image reconstruction
• Modeling of acoustic physics
»
»
»
»
Speed of sound (SOS) (dominant factor for breast imaging)
Mass density
Acoustic attenuation
Shear wave physics (e.g., transcranial brain imaging)
• Compensating for measurement system response
» Acousto-electrical impulse response (EIR)
» Spatial impulse response (SIR)
• Full-wave equation-based model:
C. Huang, et al. IEEE Tran.
Med Imaging, 32, 2013
• Mitigating data incompleteness
where
Action of wave equation
• Inherently a 3D problem – computational issues
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Iterative image reconstruction
3D integrated PACT-USCT imaging
• Penalized least-squares objectives are commonly employed
Reconstructed 3D images of the mouse body
• Collaboration with Tomowave Laboratories, Inc. (A. Oraevsky)
• Iterative image reconstruction produces images with better spatial
resolution and lower noise levels.
Goal: Incorporate
USCT capabilities
• A variety of penalty terms have been explored in PACT
FBP
» Tikhonov regularization
» Quadratic smoothness penalties
» Sparsity promoted penalties
PLS-Q
PLS-TV
• Depending on cost functions, a variety of optimization algorithms
are employed for PACT image reconstruction.
» For quadratic cost functions: conjugate gradient, LSQR, etc.
» For cost functions containing l1-type terms:
shrinkage/threshold type algorithms, etc.
System developer: Sergey Ermilov
and colleagues at TomoWave Labs.
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61.6-mm
180 tomographic
views employed
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3D integrated PACT-USCT imaging: Mouse study
Cryo photograph
3D integrated PACT-USCT imaging: Mouse study
Cryo photograph
Speed of sound
PACT
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“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
Speed of sound
PACT
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Rational for PACT breast cancer imaging
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1 – Abdominal aorta/caudal vena cava, 2 – Right kidney, 6 –
Intestines/abdominal fat, 7 – Vertebrae/back muscles, 8 – Left kidney
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1 – Abdominal aorta/caudal vena cava, 7 – Vertebrae/back muscles, 9 –
Urinary bladder, 10 – Iliac arteries/veins
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Possibility for tumor classification
1064 nm
757 nm
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800 nm
O2-Hb
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H-Hb
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2
H2O
600
PACT breast imaging
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Tumor Absorption at 1064-nm, 1/cm
Absorption Capability, µa (cm-1) x % content
Biophotonic imaging of hemoglobin
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800
900
• PACT/OAT breast imaging:
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• safe
• high optical contrast and high
ultrasound resolution
• structural and functional
information
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Benign
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• Problem: illumination of large
object, heavy computation
burden.
• We are developing effective
system set-ups and efficient
iterative methods for PACT
breast imaging.
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Malignant
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1100
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Collaboration with
Dr. Alexander Oraevsky at
TomoWave Laborotories Inc.
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Tumor Absorption at 755-nm, 1/cm
Wavelength, nm
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Clinical evaluation
Phantom study
• Our collaborators at Tomowave Lab have constructed a prototype
PACT imager.
• It has recently been installed at MD Anderson Cancer Center and is
being evaluated in clinical breast imaging studies.
Breast phantom results: Backprojection
Final phantom
10mm 1064nm Sphere
10mm 760nm Sphere
(Work by: Yang Lou)
7/15/2015
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7/15/2015
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Clinical PACT images for Patient B
Preliminary clinical results
• The following slides show some preliminary clinical images
obtained by the first-generation PACT breast imaging system built
by our collaborators at TomoWave Laboratories Inc. The images are
maximum intensity projection (MIP) images.
• Patient A collected 300 views of data, and the PACT images are
reconstructed using an accelerated iterative method incorporating
Total-Variation penalty.
• Patient B collected 1800 views of data, and the PACT images are
reconstructed using filtered back-projection method.
• We are actively working on the next-generation PACT breast
imaging system with better illumination and acoustic probe design.
MIP along
front-back
direction
MIP along
top-down
direction
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Clinical PACT images for Patient A
MIP along
left-right
direction
3D
movie
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MIP along
front-back
direction
MIP along
left-right
direction
MIP along
top-down
direction
3D
movie
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Acknowledgements
Work supported by:
• NIH R01 EB010049
• NIH R01 EB016963
• NIH R01 CA1744601
• PACT provides high contrast images based on optical contrast
• Physiological parameters related to Hb can be obtained by
acquiring multi-wavelength measurements.
Fatima Anis
• Ultrasound imaging provides complementary contrast and yields
high resolution structural information.
Trey Garson
• Information from ultrasound image can be utilized to improve PACT
image quality.
Collaborators
• Alexander Oraevsky/
Tomowave Laboratories
• Lihong Wang (WUSTL)
Depth limitations
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Optoacoustic Brightness
Summary
Huifeng Guan
Chao Huang
http://anastasio.wustl.edu
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noise floor
Joe Poudel
Kenji Mitsuhashi
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• Non-ionizing and compression free.
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Yujia Chen
Yang Lou
7/15/2015
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Depth, mm
Kun Wang
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70
1-mm blood vessel
in 1% fat milk
80 m =0.04/cm
a
ms’=12/cm
meff=1.2/cm
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Summary of advantages of hybrid PACT-US imaging
Summary
• PACT provides high contrast images based on optical contrast
3D integrated PACT-USCT imaging
• PACT is a rapidly emerging bioimaging modality with great potential
for important preclinical and clinical applications.
» Whole body small animal imaging
» Breast cancer detection and management
» Brain imaging
• Physiological parameters related to Hb can be obtained by
acquiring multi-wavelength measurements.
• Ultrasound imaging provides complementary contrast and yields
high resolution structural information.
• Numerous challenges for image reconstruction exist.
» Accurate modeling of physics and instrument response
» Shear waves
» Computational challenges
• Information from ultrasound image can be utilized to improve PACT
image quality.
• Enhanced interactions between theoreticians and engineers are
needed to address these challenges.
• Non-ionizing and compression free.
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•
•
LU emitter – acrylic half-rod with
curved surface painted black
Illumination via 600 µm fiberoptic
source offset by 15 mm from the flat
back surface of the emitter
Wide planar (transverse slice)
directivity, cylindric wavefront
Emit-receive directivity
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PACT imaging model in heterogeneous media
• Photoacoustic wave equation
Ultrasound-informed PACT for breast imaging
• Hybrid imaging system, collaboration with Tomowave Lab and MD
Anderson Cancer Center
» Ultrasound imaging and PACT imaging
Subject to initial conditions:
• Measurements are defined as
7/15/2015
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