00PAT 60min MSRI 2010 - University of Washingtongunther/MSRI_IPSeminar_files/... · r21 eb000319: moct

© 11/20/2010, LV WANG

PHOTOACOUSTIC TOMOGRAPHY:Ultrasonically Breaking through the Optical Diffusion Limit

Lihong V. WangGene K. Beare Distinguished Professorg

Optical Imaging LaboratoryDepartments of Biomedical Engineering,

Radiology andRadiology, andElectrical & Systems EngineeringWashington University, St. Louis

http://oilab.seas.wustl.edu -- 1Email: [email protected]

© 11/20/2010, LV WANG

Financial Interest Disclosure and Funding Sources

FINANCIAL INTEREST• Microphotoacoustics, Inc.• Endra, Inc.

COMPLETED GRANTS• NIH

R21 CA83760: SLT

ACTIVE GRANTS• NIH/NCI

R01 CA71980: UOT R29 CA68562/FIRST: UOT R21 EB000319: MOCT

U54 CA136398/NTR Ctr: SLN PA R01 CA134539: Chemo TAT/PAT R01 CA157277: PA endoscopy

R01 EB000712: PAM R33 CA094267: UOT R01 CA092415: OCT

• NIH/NIBIB R01 EB000712: PAM R01 EB008085: DOT/PAT

R01 NS46214/BRP: PACT R01 CA106728: OIR

• NSF R01 EB010049: Brain TAT BES-9734491/CAREER: UOT

• DOD Breast Program DAMD17-00-1-0455: TAT

http://oilab.seas.wustl.edu -- 2

• Whitaker Foundation RG-96-0221: OIR

© 11/20/2010, LV WANG

Outline

• Motivation and challenges

• Photoacoustic computed tomography

Circular geometryg y

Linear geometry

• Photoacoustic microscopy

Acoustic resolution

Optical resolution

Di i dhttp://oilab.seas.wustl.edu -- 3

• Discussion and summary

© 11/20/2010, LV WANG

Motivation for In Vivo Optical Imaging (Partial List)

Safety Non ionizing radiation: photon energy is 2 eV• Safety — Non-ionizing radiation: photon energy is ~2 eV• Physics — Molecular structure and composition of tissue • Optics — High intrinsic contrast. E.g., absorption probes

Oxy-hemoglobin & deoxy-hemoglobin Melanin LipidLipid Water DNA & RNA

Physiology Endogenous contrast for functional imaging• Physiology — Endogenous contrast for functional imaging Concentration of hemoglobin (angiogenesis) Oxygen saturation of hemoglobin (hyper-metabolism) Cell nuclei Blood flow (Doppler)

• Biology — Exogenous contrast for molecular imaging


o ogy oge ous co t ast o o ecu a ag g Biomarkers (Integrin, VEGF, HER2, etc.) Reporter genes

© 11/20/2010, LV WANG

Fundamental Challenges in High-resolutionOptical Imaging: Diffraction and Diffusion

• Diffraction (wave phenomenon)

Limits the spatial resolution of ballistic imaging (planar, confocal,

& two-photon microscopy, optical-coherence tomography).

Has been overcome for super-resolution imaging (PALM/STORM).

• Diffusion (scattering phenomenon)

Limits the penetration of ballistic imaging to ~1 mm in skin.p g g

Has been overcome for super-depth imaging (PAT).Laser


© 11/20/2010, LV WANG

High-resolution Imaging by Clear Detection Despite Diffuse Illumination

(a) Diffuse light out (b) Clear light out (invasive surgery)

( ) C ( ) C


(c) Clear light out(toxic optical clearing)

(d) Clear sound out(photoacoustic conversion)

© 11/20/2010, LV WANG

Alexander G. Bell’s Photophone Based on Photoacoustics

Photoacoustic effect:1. Light absorption2. Temperature rise

[1] A G B ll “O th d ti d

p3. Thermoelastic expansion4. Acoustic emission[1] A. G. Bell, “On the production and reproduction of sound by light,” American J. of Science, vol. 20, pp. 305-324, 1880.[2] “Production of sound by radiant energy,”


[ ] y gy,Manufacturer and Builder, vol. 13, pp. 156-158, 1881.

© 11/20/2010, LV WANG

Outline




Linear geometry


Acoustic resolution

Optical resolution



© 11/20/2010, LV WANG

Photoacoustic Computed Tomography in Circular Geometry

(1) L l ( ANSI li i(1) Laser pulse (<ANSI limit:e.g., 20 mJ/cm2)

(2) Light(2) Light absorption & heating (~ mK)

1 mK 8 mbar

(4) Ultrasonic

= 800 Pa

(4) Ultrasonic detection(optical scatter/1000)

(3) Ultrasonic emission (~ mbar)


scatter/1000) (~ mbar)

Nature Biotech. 21, 803 (2003).

© 11/20/2010, LV WANG

Imaging of a Single Sound Sourceby Triangulation

Ob 22tvs

Observer 21tvs

Observer 1 Source

3tvs

Obse e

Observer 3


© 11/20/2010, LV WANG

Spherical Radon Transform and Spherical BackprojectionDetection

Integration

Detectionsurface

tvs

sphere

Object Physical Review Es y71, 016706 (2005).

Physical Rev. Lett.92 033902 (2004)

lS lidfd ih i l and l,cylindrica planar,for tion backprojec Universal

92, 033902 (2004).

/),(),(2)(

:angleSolid :surfacesdetection spherical

0000

0

dttrpttrprp vrrt High-frequency


),(),()( 0000

0 0 pppsvrrt

Beamforming DelayOptical contrast

© 11/20/2010, LV WANG

Non-invasive Functional Photoacoustic Imaging of RatWhisker Stimulation In Vivo: Hemodynamic Response

Left-whisker stimulation

2.0

(cm

)

2.0

(cm

)

Right-whisker stimulation

1.5

(

1.5

(

1.0

1.0

0.5

0.5

0 0.5 1.0 2.0

0

(cm)1.5 0 0.5 1.0 2.0

0(cm)

1.5

Through intact scalp and skin


Differential absorption MaxMin

Nature Biotech. 21, 803 (2003).

Through intact scalp and skinIn-plane resolution: 0.2 mm

© 11/20/2010, LV WANG

Growth of Photoacoustic Tomography:Data from Conference on Photons plus Ultrasoundp

Chaired by Oraevsky and Wang

Number of Presentations versus Year

140160180

100120140

406080

020


© 11/20/2010, LV WANG

Functional and Molecular Photoacoustic Imaging:Nude Mouse with a U87 Glioblastoma Xenograft in the Brain

(b) Molecular imaging:Tumor over-expression of integrin

Max

(a) Functional imaging:Tumor hypoxia

60%

80%

xyge

n SO

2)

Max

ontr

ast

pept

ide)

40%

60%

glob

in o

xur

atio

n (S

ecul

ar c

oye

800

+ p

20% Hem

ogsa

tu

Min

Mol

e(IR

Dy

1 mm

Structural resolution: 60 mSpeckle free

Resolution: 312 mSensitivity: 4 fmol/voxel (40 nM)

P f IEEE 96 481 2008


Proc. of IEEE 96, 481, 2008.* Contrast agent provided by Chun Li’s Group (MD Anderson)

© 11/20/2010, LV WANG

5-MHz Ring Ultrasonic Array

Transducers:• Transducers: Elements: 512-elements. Center frequency: 5 MHz.

Bandwidth: 80% of center freq Bandwidth: 80% of center freq.• Geometry:

Shape: Ring with 50 mm diam. Pitch: 0.308 mm. Kerf: 0.1 mm.tc 0 308 e 0 Elevation height: 10 mm. Elevation focal length: 19 mm.

• Data acquisition: Channels: 64 channels A/D

(8:1 MUX) Sampling rate: 40 MHz.

S li d i 12 bit Sampling dynamic range: 12 bits. Frame rate: 0.9 Hz with a 7-Hz laser pulse repetition.

• Resolution: In plane: ~200 µm

J. Biomed. Optics 13, 024007, 2008.


In plane: ~200 µm. Elevation: ~1.9 mm.

Optics Express, 17 (13), 10489, 2009.Collaboration: Q. Zhu’s Group @ UConn.

© 11/20/2010, LV WANG

Noninvasive Photoacoustic Image of a Mouse Brain:360o View, 0.9 Hz Frame Rate and Gel Coupling, p g

NoninvasivePhotoacoustic Image

InvasivePhotographPhotoacoustic Image Photograph

view

: 4

mm

el

d of

vm

m x

1Fi

e10

m

http://oilab.seas.wustl.edu -- 16J Biomed Optics 15, 010509 (2010).

© 11/20/2010, LV WANG

Photoacoustic Tomography of Monkey Brain with Intact Cranium

Photo with cranium removed

Photoacoustic tomography imagewith cranium intact

http://oilab.seas.wustl.edu -- 17L. Nie, et al., unpublished.

© 11/20/2010, LV WANG

Outline




Linear geometry


Acoustic resolution

Optical resolution



© 11/20/2010, LV WANG

Photoacoustic Imaging usingHigh-frequency (30 MHz) Ultrasound Array

# elements 48Center frequency 30 MHz

A f ti l b d idth 50%

1 cm

Average fractional bandwidth 50%Elevation focal depth 8.2 mm

Elevation aperture 2 mmNearest element crosstalk < -25 dB

Element-to-element spacing 0.1 mmLaser pulse energy 1 mJLaser pulse energy 1 mJ

Laser fluence (578 nm) 18 mJ/cm2

Lateral spatial resolution < 50 mA i l ti l l ti 25Axial spatial resolution 25 m

Imaging depth > 3 mmB-scan frame rate 50 frames/s


Optics Express, 16, 7915, 2008.Collaboration: K. Shung’s Group @ USC.

© 11/20/2010, LV WANG

Real-time Photoacoustic Imaging of the Heart Beating of a Nude Mouse In Vivo: g50 Frames/s at 30 MHz Ultrasonic Frequency


Optics Express, 16, 7915, 2008.Collaboration: K. Shung’s Group @ USC.

© 11/20/2010, LV WANG

Photoacoustic Angiography using Evans Blue Dye

http://oilab.seas.wustl.edu -- 21L. Song, K. Maslov, L. WangOptics Letters, accepted.

249 B-scans/sec.

© 11/20/2010, LV WANG

Scalability of Resolution and Penetration:Multiscale Imaging

frequency.center:h;wavelengtacousticcenter:

1NA

71.0NA

71.0 resolution lateral FWHM

00

00

0

fff

vs

1

sound. of speed : f/2);(# aperture numerical :NAfrequency.center : h; wavelengtacousticcenter : 00

vf

s

constant).(~bandwidth acoustic fractional : bandwidth; acousticway -one :

188.0 88.0 resolution Axial00

fff

vf

v ss

1dB/cm/MHz 5.0~;frequency acoustict coefficien n attenuatio Ultrasonic afa

li itP t ti

.Resolution1limit n Penetratio0

f


n).penetratio optical(within 200Constant resolution Axial

limitn Penetratio

© 11/20/2010, LV WANG

Hand-held Photoacoustic/Ultrasonic Imaging Probeusing Modified Clinical Ultrasound Scanner

DAQPA

imageUSi

US Scan

US system

imageimage

US probeScanner

system

Hand-held PA/US probe

Fiber bundles Patient bed

probe

http://oilab.seas.wustl.edu -- 23Biomed Optics Express 1, 278 (2010).Collaboration: Philips Research

© 11/20/2010, LV WANG

In Vivo Photoacoustic Molecular (Reporter Gene) Imaging:Gene Expression in Gliosarcoma Tumor in Mouse

1. LacZ (gene)2 Beta galactosidase (enzyme )2. Beta-galactosidase (enzyme )3. X-gal (colorless substrate)4. Blue product

5.0 cm

• Philips US array: L8-4• 2 mJ/cm2 @ 650 nm• 1/10 of ANSI exposure limitTumor • 1/10 of ANSI exposure limit• 100X averaging• Contrast: ~2.5

http://oilab.seas.wustl.edu -- 24L. Li, et al., unpublished.Collaboration: Philips Research

© 11/20/2010, LV WANG

In Vivo Dynamic Photoacoustic Imaging of Sentinel Lymph Node in Rats With Indocyanine Green

en

• ICG:

Chi

cke

reas

t

ICG: 0.1 mL @ 1 mM

• 810 nm<1 5 mJ/cm2

2-cm

B • <1.5 mJ/cm2

• 10 Hz data acquisition

Rat

• 1 Hz online display

Sentinel lymph node


Sentinel lymph node J Biomedical Optics 15, 046010 (2010).Collaboration: Philips Research

© 11/20/2010, LV WANG

In Vivo Image-guided Needle Biopsy

Photoacoustic

n B

reas

t Needle (18 gauge = 1.27 mm)Photoacoustic

C t t f dl 8 5 ± 4

m C

hick

en

Ultrasonic

Contrast of needle: 8.5 ± 4

2-cm

Rat

Sentinel lymph node w/ICG

R

Sentinel lymph node w/ICG


Contrast: 1.2 ± 0.04J Biomedical Optics 15, 046010 (2010).Collaboration: Philips Research

© 11/20/2010, LV WANG

Deeply Penetrating Photoacoustic Imagingin Biological Tissue Enhanced with Methylene Bluein Biological Tissue Enhanced with Methylene Blue

S5 1 transducer• S5-1 transducer• Beam size: 2.5 cm• Fluence: 20 mJ/cm2

>7 cm• Methylene blue at 1%• 200X averaging• 1/e penetration depth: 0.69 cmp p• Target depth: >7 cm

H Ke T Erpelding et al unpublished


H. Ke, T. Erpelding, et al., unpublished.Collaboration: Philips Research

© 11/20/2010, LV WANG

Outline




Linear geometry


Acoustic resolution

Optical resolution



© 11/20/2010, LV WANG

Reflection-mode Photoacoustic Microscopy: Illustration

Surface B-scan

Target

ic

acou

sti

gnal

Optical absorption

A-scan

http://oilab.seas.wustl.edu -- 29Time of arrival or depth Phot

oa si

© 11/20/2010, LV WANG

Dark-field Confocal Photoacoustic Microscopy:3 mm Penetration at 50-MHz Ultrasonic Frequency

y

x Tunable laser Nd:YAG pump laseryz

Motor driverTranslation

t

Photodiode

Ultrasonic Optical illuminationstages Amplifier

Conical lenstransducer

p

Sample holder

Base

AD

ComputerMirror

Heater & temperature controller

Dual foci

Sample

Annular illumination with a

dark center Optics Letters 30 625 (2005)


pOptics Letters 30, 625 (2005).Nature Biotech. 24, 848 (2006).Nature Protocols 2, 797 (2007).

© 11/20/2010, LV WANG

Photoacoustic Imaging Depth and Resolution: 50 MHz System (High Ultrasonic Frequency)y ( g q y)

B-scan of a double-stranded cotton thread

• Imaging depth: ~3 mmstranded cotton thread embedded in a rat • Axial resolution: ~15 microns

• Depth/resolution: ~200 pixels

• Lateral resolution: ~45 microns• Acquisition time: 2 µs/A-scan3

mm Surface

Acquisition time: 2 µs/A-scan• Signal averaging: None

3

Thread

Super-depths for high-resolution optical imaging


Optics Letters 30, 625 (2005).(beyond diffusion limit)

© 11/20/2010, LV WANG

Photoacoustic Imaging of Hemodynamicsin a Small Animal In Vivo

Concentration Oxygen saturation Arteries (red)&

Veins (blue)Veins (blue)

1n ArteryOxygenation versus physiological state 1 mm

0 6

0.8

d ox

ygen

urat

ion Vein

Artery

Appl. Phys. Lett.

a xia

oxia


0.6

Imag

edsa

tu 90, 053901 (2007).

Hyp

oxi

Nor

mox

Hyp

ero

© 11/20/2010, LV WANG

Photoacoustic Oximetry of Single Vessels in Brain

Enveloped BScan along line

Scalp

1mm 0.5 mmCortical vessels1mm

30

40

sign

alm

) 80

100• PAM used to track

oxygenation of multiple

10

20e

in P

A s

1/57

0 nm

40

60

% [O

2]

oxygenation of multiple cortical vessels

• Dual-wavelength images 561 nm (Hb-dominant)

-10

0

10

% C

hang (561

0

20

40 % 561 nm (Hb-dominant)570 nm (Isosbestic)

• Step changes in [O2]100% and 5%


-10%

0 10 20 30 400

Time (min)

100% and 5%• Time resolution < 1 sec

J. Biomed. Optics 14, 020502 (2009).

© 11/20/2010, LV WANG

Photoacoustic Imaging of a Melanoma Tumorin a Small Animal In VivoC it h t ti B t 764Composite photoacoustic

image with 584 and 764 nm

1

Melanoma

Photograph

B-scan at 764 nm

Melanoma1 mm

MelanomaPhotograph

Histology

1 mmMelanoma

Surface rendering3D M iSkin surface

x

1 mm Surface rendering3D Movie

Contrasts:Blood: 13±1

3 mmzxy

8 mm

Melanoma: 68±5


8 mm8 mm

Nature Biotech.24, 848 (2006).

© 11/20/2010, LV WANG

Photoacoustic Microscopy of Human Palm

Ph tPhoto Max amplitude projection5

4

B S @ 5842

3

B-Scan @ 584 nmEpiderm.-derm. junction Stratum corneum 1 mm

1

C F bli h d

Epidermis


C. Favazza, unpublished.Collaboration: L. CorneliusDermis Subpapillary plexus 1 mm

1 23 4 5

© 11/20/2010, LV WANG

Photoacoustic Imaging of Human Skin In Vivo:Junctional and Blue Nevi

http://oilab.seas.wustl.edu -- 36E. Stein, unpublished.Collaboration: L. Cornelius

© 11/20/2010, LV WANG

In Vivo Molecular Photoacoustic Imaging of B16 Melanomain a Rat Using Targeted Gold Nanocages (AuNCs)

[Nle4,D-Phe7]-α-MSH-AuNCs 38 ± 3 (%) at 6 hr (3X control)

0 h 3 h 6h

[%]

50

PA s

igna

l [

30

40

50

PEG AuNCs 13 ± 1 (%) at 6 hr

2mmTumor Tumor

reas

e in

P

10

20

30

PEG-AuNCs 13 ± 1 (%) at 6 hr

S iti it

0 h 3 h Tumor 6 h Tumor Incr

0

Sensitivity :~ 5000 AuNCs / voxel

http://oilab.seas.wustl.edu -- 37ACS Nano 4, 4559 (2010). Collaboration: Y. XiaControlled drug release: Nature Mat. 8, 935 (2009)

MSH: melanocyte-stimulating hormone

© 11/20/2010, LV WANG

Photoacoustic Endoscopy of Rabbit Esophagus In VivoScanning MagnetsUltrasonic Scanningmirror

NS N

S

MagnetsUltrasonictransducer

Optical fiber Micromotor

Lung Trachea

Photoacoustic

Ultrasonic

Axial resolution: 50 micronsLateral resolution: 250 micronsDiameter of probe: 3.8 mm

http://oilab.seas.wustl.edu -- 38Yang et al., unpublished.Optics Letters 34, 1591 (2009).

Collaboration: Zhou & Shung, USCUltrasonic frequency: 43 MHz

© 11/20/2010, LV WANG

Outline




Linear geometry


Acoustic resolution

Optical resolution



© 11/20/2010, LV WANG

Optical Resolution PhotoacousticMicroscopy: 1.2 mm Penetration

CLCL: Condenser lensPH: Pinhole

CL

LightS OL: Objective lens

UT: Ultrasonic transducerDL: De-aberrating lensPH

Sound

DL: De aberrating lensIP: Isosceles prismAL: Acoustic lensLight transmitting

& sound reflectingi t f

OLDL

• Optic NA = 0.1• Lateral resolution = 2.6 µm

interface

DLUTIP • Acoustic NA = 0.45

• Center f ~ 85 MHz


AL • Axial resolution < 15 µmOptics Letters 33, 929 (2008).

© 11/20/2010, LV WANG

Spatial Resolution and Maximum Penetration

1.2 mm

Black needle

plitu

de

(0.25-mm diameter)

Lateral resolution: 2 6 µm

1 2 3 4 5 6PA a

m

Element number

Lateral resolution: 2.6 µm Maximum penetration: 1.2 mm


Element number

S. Hu et al., unpublished.

© 11/20/2010, LV WANG

In Vivo Monitoring of HIF-Mediated Angiogenesis usingOptical-Resolution (5 Micron) Photoacoustic Microscopy

D 30D 0 D 1 D 60D 3 D 14 Day 30Day 0 Day 1 Day 60Day 3 Day 14

http://oilab.seas.wustl.edu -- 42S. Hu et al., unpublished (Collaboration: Arbeit).

200 µmHIF: hypoxia-inducible factor

Perifollicular microdomain

© 11/20/2010, LV WANG

In Vivo Label-Free Optical-Resolution (5 Micron)Photoacoustic Microscopy of Ocular Microvasculature

CP: ciliary process; LIC: lesser iris circle; MIC: major iris circle;

RIA: radial iris artery; RCB: recurrent choroidal branch;RBC: red blood cell;


j ;PA: photoacoustic signal;

S. Hu et al., unpublished.

;sO2: hemoglobin oxygen saturation.

© 11/20/2010, LV WANG

In Vivo Optical-Resolution Photoacoustic Microscopyof Mouse Ear: 2.6 Micron Lateral Resolution

Capillary bed50 µm

500 µmRBCs

5 mm x 5 mm x 0 45 mm

Cs


S. Hu et al., unpublished.0.45 mm

© 11/20/2010, LV WANG

Photoacoustic Microscopy with Submicron Resolution:Intussusceptive Angiogenesis in a Living Mouse

Fi t i iFirst in vivo imaging of intussusception

http://oilab.seas.wustl.edu -- 45K. Maslov, S. Hu et al., unpublished.Collaboration: J. Arbeit

100 µm

© 11/20/2010, LV WANG

Transcranial Imaging in Living Mouse with Intact Skull

Hemoglobin @ 570 nm(before methylene blue injection)

Methylene blue @ 650 nm(after methylene blue injection)

500 µm


500 µ

S. Hu et al., unpublished.Collaboration: JM Lee

© 11/20/2010, LV WANG

In Vivo Photoacoustic Microscopy of Human Finger Cuticle1.0

0 5

sO2Capillary

loop

Eponychium 0.5 mm

0 3

2 loop

0.3


S. Hu et al., unpublished.1 mm

Cross section

© 11/20/2010, LV WANG

O ti l bj ti

Photoacoustic Microscopy with Submicron Resolution

Spread f nction of nanoparticleOptical objective: NA=0.60 @ 40X

Lateral resolution: 0 45 µm @ 528 nm

Spread function of nanoparticle

litud

e Theory

Melanoma cells

0.45 µm @ 528 nm

gnal

am

p

Experiment

-2.0 -1.0 0 1.0 2.0

R d bl d ll

Displacement (µm)

Sig

Red blood cells

5 µm


5 µm

K. Maslov et al., unpublished.

© 11/20/2010, LV WANG

Photoacoustic Microscopy with 220-nm Resolution

http://oilab.seas.wustl.edu -- 49K. Maslov, C. Zhang, et al., unpublished.

© 11/20/2010, LV WANG

Photoacoustic Microscopy of DNA & RNAin Cell Nucleiin Cell Nuclei

Photoacoustic microscopy without staining

Histology with hematoxylin and eosin stainingwithout staining eosin staining

20 µm 20 µm


µ

D. Yao, K. Maslov, et al., unpublished.

© 11/20/2010, LV WANG

Doppler Photoacoustic Microscopy of Blood Flow in Mouse

12

s)

1 mm 250 µm 250 µm

ArteryV i6

8

10

peed

(mm

/s

VeinVein

02

4

Flow

sp

Measureable range:

Normalized CHb

0 1 0 10.4 0.6 0.80.2 10.0-3.0sO2 Velocity (mm/s)

C : concentration of total hemoglobin

0 100 200 300 4000

Position (microns)

J. Yao et al., unpublished.

Measureable range: 0.1-12 mm/s

CHb : concentration of total hemoglobin

sO2: oxygen saturation of hemoglobin


J. Yao et al., unpublished.PRL 99, 184501, 2007.Metabolic rate of oxygen quantified

© 11/20/2010, LV WANG

Outline




Linear geometry


Acoustic resolution

Optical resolution



© 11/20/2010, LV WANG

Microwave-induced Thermoacoustic Tomography:Images of Mastectomy Specimens

Water tankUltrasonic transducers Step motor

1 cm

Waveguide

Amplifiers Oscilloscope

Microwave:• 3 GHz freq.• 500 ns pulse width

5 J l


Amplifiers Oscilloscope• ~5 mJ pulse energy• 9 cm penetration in fat 6 mmIEEE TBE 55, 2741 (2008). Collaboration: J. Li @ UF

© 11/20/2010, LV WANG

Multiscale Photoacoustic Tomography In Vivo with Consistent Contrast

102

L t l l ti LA PACT LA: Linear array

101

mm

)

Lateral resolutionAxial resolution

LA-PACTAR-PAMac

LA: Linear arrayPA: PhotoacousticCT: Computed

tomographyDepth-resolution ratio = 200

100

n tis

sue

(m

OR-PAM

AR-PAM AR: Acoustic resolutionMac: Macroscopy

10-1

10

etra

tion

in

SM-PAM

OR-PAM

SW PAM

PAM: PA microscopyOR: Optical resolutionSM: Sub-micronSW S b l th

-2

10

Pen SW-PAM SW: Sub-wavelength

Organelle Cell Tissue Organ

10-1 100 101 102 10310-2

Resolution (m)

1. Enable systems biology at multiple length


Nature Photonics 3, 503 (2009).

1. Enable systems biology at multiple length scales

2. Accelerate translation of microscopic lab discoveries to macroscopic clinical practice

© 11/20/2010, LV WANG

Preclinical Imaging Applications

1. Non-fluorescent pigments (red blood cells & melanin)2. Angiogenesis and anti-angiogenic response3. Microcirculation physiology and pathology4. Drug response for screening5. Brain functions6. Biomarkers7 Gene activities through reporter genes7. Gene activities through reporter genes


© 11/20/2010, LV WANG

Clinical Imaging Applications

1. Melanoma cancer screening2. Gastrointestinal tract and colon endoscopy3. Neonatal brain (fontanel) and adult brain mapping4. Breast cancer detection5. Prostate cancer detection6. Guided sentinel lymph node needle/core biopsy for

cancer stagingcancer staging7. Early response to chemotherapy8. Dosimetry in thermal therapy9. Blood flow, oxygenation, and tissue metabolism

imaging


© 11/20/2010, LV WANG

Summary1. Photoacoustic tomography by optical excitation and ultrasonic detection2. Diffusion limit (~1 mm) broken: Super-depths (up to 7 cm) reached3. Single capillaries and single cells resolved in vivo (0.22 micron resolution)4. Multiscale imaging achieved by scaling depth and resolution5. Background-free detection built-in (no absorption, no signal)6. Highest sensitivity to optical absorption (100%) among all modalities7. Either non-fluorescent or fluorescent pigments detected8. Multiple chromophores resolved spectrally9. Functional imaging derived from endogenous chromophores10. Molecular imaging enabled by targeted contrast agents11. Reporter genes imaged12. Doppler imaging of flow demonstrated13. Frame rates of 50 and 249 Hz achieved online and offline14. Speckle artifacts avoided15. Non-ionizing radiation used16. Costs relatively low


y17. Contact acoustic detection through gel or liquid18. Cavity and thick bone attenuations to ultrasound

© 11/20/2010, LV WANG

Credits to Lab Members

CURRENT RECENT ALUMNICURRENTAlejandro Garcia-UribeAmos DanielliArie KrumholzBin Huang

Hui FangChul-Hong KimGeng KuM jit P ik

Liang SongLidai WangLiming NiePuxiang Lai

Bin RaoChi ZhangChris FavazzaDa Kang Yao

Manojit PramanikKwanghyun SongEric SteinXueding Wang

Rameez ChatniRobert BerrySong HuWenxin Xing

Dongsu DuGuo LiHaixin KeHonglin Liu

Xueding Wang Minghua XuYuan XuXinmai YangRoger Zemp

Xiao XuXin CaiYan LiuYu Wang

Joon Mo YangJun XiaJunjie YaoKarthik Omanakuttan

Roger ZempHao Zhang

BME Dept

Yuchen YuanYuta SuzukiZhen JiangZhun Xu

Konstantin MaslovLi Li

Washington U

Zijian Guo


© 11/20/2010, LV WANG

Chapters1. Introduction to biomedical optics2 Single scattering: Rayleigh theory and

2007Source codes

2. Single scattering: Rayleigh theory and Mie theory

3. Monte Carlo modeling of photon transport

4. Convolution for broad-beam responses5. Radiative transfer equation and

diffusion theory6 Hybrid model of Monte Carlo method6. Hybrid model of Monte Carlo method

and diffusion theory7. Sensing of optical properties and

spectroscopy8. Ballistic imaging and microscopy9. Optical coherence tomography10. Mueller optical coherence tomography11. Diffuse optical tomography11. Diffuse optical tomography12. Photoacoustic tomography13. Ultrasound-modulated optical

tomography


Homework solutions provided for instructors

Joseph W. Goodman Book Writing Award

© 11/20/2010, LV WANG

• JOB OPENINGS: Postdoctoral Predoctoral

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Documents

00PAT 60min MSRI 2010 - University of Washingtongunther/MSRI_IPSeminar_files/... · r21 eb000319: moct