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Photoacoustic Computed Tomography with Applications to Breast Imaging

Mark A. Anastasio

Department of Biomedical Engineering

Washington University in St. Louis

St. Louis, MO

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Outline

• Introduction to photoacoustic computed tomography (PACT)

• Imaging models and iterative image reconstruction

• Success with small animal imaging

• PACT breast imaging » System design

» Preliminary clinical data

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

Ultrasound transducers

Tissue

Absorbed optical energy density

Image reconstruction

algorithm

Schematic of PAT

Optical pulse

Ultrasound transducers

Tissue

Absorbed optical energy density

Image reconstruction

algorithm

Photoacoustic physics

• Absorbed optical energy density:

» μa(r) optical absorption coefficient

» Φs(r) optical fluence rate

• Photoacoustic wave equation (can generalize to heterogeneous media)

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Grueneisen

parameter

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Canonical imaging model

• Conventional imaging model (assuming idealized transducers)

» 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)

where

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PACT reconstruction: Heterogeneous media

• If SOS variations are known, they can be incorporated into the PACT imaging model. Two general approaches:

• Geometrical-acoustics (“ray-based”) reconstruction:

• Full-wave equation-based model:

Action of wave equation

C. Huang, et al. IEEE Tran. Med Imaging, 32, 2013

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)

• Mitigating data incompleteness

• Inherently a 3D problem – computational issues

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Iterative image reconstruction

• Penalized least-squares objectives are commonly employed

• A variety of penalty terms have been explored in PACT

» Tikhonov regularization

» Quadratic smoothness penalties

» Sparsity promoted penalties

• 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.

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3D integrated PACT-USCT imaging

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System developer: Sergey Ermilov and colleagues at TomoWave Labs.

Goal: Incorporate USCT capabilities

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.

FBP PLS-Q PLS-TV

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61.6-mm

180 tomographic

views employed

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3D integrated PACT-USCT imaging: Mouse study

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Cryo photograph PACT Speed of sound

1 – Abdominal aorta/caudal vena cava, 2 – Right kidney, 6 – Intestines/abdominal fat, 7 – Vertebrae/back muscles, 8 – Left kidney

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2

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6

8

2

7

6

1

8

2

7

6

1

3D integrated PACT-USCT imaging: Mouse study

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Cryo photograph PACT Speed of sound

1 – Abdominal aorta/caudal vena cava, 7 – Vertebrae/back muscles, 9 – Urinary bladder, 10 – Iliac arteries/veins

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Rational for PACT breast cancer imaging

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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

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Biophotonic imaging of hemoglobin

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2

4

6

8

10

600 700 800 900 1000 1100

Absorp

tion

Cap

ab

ility

, µ

a (

cm

-1)

x %

co

nte

nt

Wavelength, nm

757 nm1064 nm

O2-Hb

H-Hb

H2O

800 nm

Possibility for tumor classification

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0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08

Tu

mor

Ab

sorp

tio

n a

t 1

06

4-n

m, 1

/cm

Tumor Absorption at 755-nm, 1/cm

Benign

Malignant

PACT breast imaging

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Collaboration with Dr. Alexander Oraevsky at

TomoWave Laborotories Inc.

• PACT/OAT breast imaging: • safe • high optical contrast and high

ultrasound resolution • structural and functional

information

• 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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• 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.

Clinical evaluation

7/15/2015 19

Phantom study

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10mm 760nm Sphere

10mm 1064nm Sphere

Final phantom

Breast phantom results: Backprojection

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(Work by: Yang Lou)

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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.

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Clinical PACT images for Patient B

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MIP along front-back direction

MIP along top-down direction

MIP along left-right direction

3D movie

Clinical PACT images for Patient A

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MIP along front-back direction

MIP along top-down direction

MIP along left-right direction

3D movie

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Summary

• PACT provides high contrast images based on optical contrast

• Physiological parameters related to Hb can be obtained by acquiring multi-wavelength measurements.

• Ultrasound imaging provides complementary contrast and yields high resolution structural information.

• Information from ultrasound image can be utilized to improve PACT image quality.

• Non-ionizing and compression free.

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7/15/2015 26

Fatima Anis

Trey Garson

Joe Poudel

Huifeng Guan

Kun Wang

Work supported by:

Acknowledgements

• NIH R01 EB010049 • NIH R01 EB016963 • NIH R01 CA1744601

http://anastasio.wustl.edu

Kenji Mitsuhashi

Collaborators

• Alexander Oraevsky/ Tomowave Laboratories • Lihong Wang (WUSTL)

Yujia Chen Yang Lou

Chao Huang

Depth limitations

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0

10

20

30

40

50

0 10 20 30 40 50 60 70 80

Opto

acoustic B

rightn

ess

Depth, mm

noise floor1-mm blood vessel

in 1% fat milk

ma=0.04/cm

ms’=12/cm

meff=1.2/cm

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Summary of advantages of hybrid PACT-US imaging

• PACT provides high contrast images based on optical contrast

• Physiological parameters related to Hb can be obtained by acquiring multi-wavelength measurements.

• Ultrasound imaging provides complementary contrast and yields high resolution structural information.

• Information from ultrasound image can be utilized to improve PACT image quality.

• Non-ionizing and compression free.

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Summary

• 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

• Numerous challenges for image reconstruction exist.

» Accurate modeling of physics and instrument response

» Shear waves

» Computational challenges

• Enhanced interactions between theoreticians and engineers are needed to address these challenges.

3D integrated PACT-USCT imaging

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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

Subject to initial conditions:

• Measurements are defined as

• Hybrid imaging system, collaboration with Tomowave Lab and MD Anderson Cancer Center

» Ultrasound imaging and PACT imaging

Ultrasound-informed PACT for breast imaging

7/15/2015 32