PH880 Topics in Physics

Modern Optical Imaging (Fall 2010)Modern Optical Imaging (Fall 2010)

KAIST PH880 11/10/2010

Overview of week 11

• Monday:• Monday: 

‐ Digital Holographic Tomography

l h h‐ Optical Coherence Tomography

• Wednesday:

‐ PhotoacousticTomography

KAIST PH880 11/10/2010

Rotating the beam angle + high speed (Feld Group, MIT, Nat. Methods, 2006)

KAIST PH880 11/10/2010

Projection (Radon) Diffraction (exact)

ky

fmaxkz

SEM diffraction Radon

KAIST PH880 11/10/2010

Time-domain OCT

KAIST PH880 11/10/2010

Coherence gating

Optical Coherence Microscopy

KAIST PH880 11/10/2010J A Izatt et al, OPTICS LETTERS / Vol. 19, No. 8 / April 15, 1994

Optical Coherence Microscopy

OCT: Low NA

L t l l ti

xΔ4 fx

dλπ

⎛ ⎞Δ = ⎜ ⎟⎝ ⎠

Lateral resolution OCM: High NA

xΔ dπ ⎝ ⎠b

D th f f

xΔb

2

2 Rxb z π Δ

= =

Depth of focus

2R λ

f=focal length

8

f=focal lengthd= lens diameter

Fourier-domain OCTno scanning of reference mirrorno scanning of reference mirror

the spectrum of the backscattered sample light amplitude

FercherAF, HitzenbergerCK, DrexlerW, Kamp G, Strasser I, LiHC1993b Medical Optical Tomography: FunctionalImaging and Monitoring vol IS 11, ed G M¨uller et al (Bellingham: SPIE Press) pp 355–70

Parallel OCT set-up with a 2D detector array

Bourquin S, Seitz P and Salathe R P 2001 El Lett. 37 975–6

Overview of week 11

• Monday:• Monday: 

‐ Digital Holographic Tomography

l h h‐ Optical Coherence Tomography

• Wednesday:

‐ Photoacoustic Tomography*

KAIST PH880 11/10/2010* Slides are modified from L Wang’s lecture slides

High Relative Resolution:Depth-to-Resolution Ratio > 100Depth-to-Resolution Ratio > 100

Modality Max depth Axial resolution Depth / Resolution

Confocal/two-photon microscopy ~0.2-0.5 mm ~1-2 microns >100

Optical coherence tomography ~1 mm ~10 microns >100

Magnetic resonance imaging / Ultrasonography ~100-200 mm ~1 mm >100

X-ray CT ~200 mm ~0.1 mm >100

Photoacoustic imaging of cancer in‐vivo

MelanomaMelanoma

1 mm

MelanomaMelanoma

B-scan image at 764 nmHistology

1 mm

KAIST PH880 11/10/2010Nature Biotech. 24, 848 (2006).

Photoacoustic Tomography: principle

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

(2) Local heating(~ mK)

(4) Ultrasonic detection(scattering/100) (3) Ultrasonic emission(scattering/100) (3) Ultrasonic emission 

(~ mbar)

Physical Review E 71, 016706 (2005). Phys. Rev. Letters 92, 033902 (2004). Lihong Wang group, Washington University

Photoacoustic Tomography: principle

1. Short laser pulse (~ ns range) is spatially broadened and then used to irradiate biological tissueto irradiate biological tissue

2. Produces a temperature rise (~ mK in short time frame)

3. Thermo-elastic expansion causes emission of acoustic wave

(discovered by Alexander Graham Bell)(discovered by Alexander Graham Bell)

4. Acoustic wave is measured by wideband ultrasonic transducers

5. Acquired signal is combined mathematically to reconstruct the distribution of optical energy absorption

KAIST PH880 11/10/2010V Ntziachristos et al, Nature Biotechnology, 23 3, (2005)

Reflection-mode Photoacoustic Microscopy: IllustrationMicroscopy: Illustration

Sphere

ic

hoto

acou

sti

sign

al SurfaceSphere

Time

Ph

Reflection‐mode Dark‐field ConfocalPhotoacoustic Microscopy: SystemPhotoacoustic Microscopy: System

Tunable laser Nd:YAG pump laser

Motor driver Photodiode

Tunable laser Nd:YAG pump laser

Translation stages

Amplifier

C i l l

Ultrasonic transducer

Optical illumination

Sample holder AD

Conical lens

Mirrorp

Base

Heater &

ComputerMirror

D l f i A l ill i tiHeater & temperature controller

Dual foci

Sample

Annular illumination with a dark center

Optics Letters 30, 625 (2005) Nature Biotech. 24, 848 (2006).

Imaging Depth and Resolutionin Photoacoustic microscopyin Photoacoustic microscopy

B‐scan of a black double‐stranded cotton thread embedded 3 

mm

in rat

• Imaging depth:  ~3 mm

• Axial resolution:  ~15 microns

• Depth/resolution: ~200 pixels

• Lateral resolution: ~45 microns

• Acquisition time: 2 ms/A‐scan

• No signal averaging

Optics Letters 30, 625 (2005).

Volumetric Imaging of Rat Microvasculature In VivoMicrovasculature In Vivo

Maximum amplitudeprojection onto the skinprojection onto the skin

1 mm

Volume: 10 mm x 8 mm x 3 mm

Optics Express 14, 9317 (2006).

Imaging of Skin: Burn in Pigs

Acute thermal (175 oC, 20 s) burn in pig skin in vivo. Postmortem imaging at 584‐nm optical wavelength.

Coagulated Healthy 

Photograph Photoacoustic image

B‐scan image

1 mmHyperemic bowl

Coagu atedtissuetissue

Hyperemic bowl

1 mm1 mmHyperemic ring

0.2

] Burn depth~1 7Hyperemic ring

Histology0.1

itude

 [a.u.]

Hyperemic bowl

ki f

~1.7 mm

5 5 6 6 5 7 7 5 80PA

 ampl Skin surface

Hyperemic bowl5.5 6 6.5 7 7.5 8

Distance [mm]

J Biomed Optics 11, 054033 (2006).

Imaging of Hemoglobin Oxygen Saturation (SO ) In VivoSaturation (SO2) In Vivo

Total hemoglobin concentration SO2 in segmented venules and arterioles

14

0 85

0.95

2 53 0 75

0.85

3 0.751 mm

Histology Arterial microsphere perfusion

14A

25

3V

1 mm

3

Nature Biotech. 24, 848 (2006).

Hemodynamics In Vivo(578 584 590 and 596 nm)(578, 584, 590, and 596 nm)

Total hemoglobin Oxygen saturation Arteries and veins

1 mm

1

2 Artery

Change in oxygenation

0.8

Imaged

 SO2

Vein

Artery

monitor SO2 change over time.

Hypoxia Normoxia Hyperoxia

0.6

Physiological states

Appl. Phys. Lett.

90, 053901 (2007).

In Vivo Genetic Imaging:Gene Expression in Gliosarcoma Tumor in RatGene Expression in Gliosarcoma Tumor in Rat1. LacZ (gene)2 B t l t id ( )2. Beta‐galactosidase (enzyme )3. X‐gal (colorless substrate)4. Blue product

Image of blood vessels at 584‐nm wavelength

Image of expression of LacZ reporter gene at 635‐nm wavelength

Composite image

1 mmwavelength 1 mm

J Biomed Optics 12(2), 020504 (2007).

Imaging of Human Palm In Vivo

Ski f

Maximum amplitudeprojection onto the skin

Photo

1 2

3

4

5

6 70.3 mm

Skin surfacep j

0.13 mm

Skin surface Stratumcorneum

B‐scan image

corneum

1 mm1 52 3 4 6 7

Optical absorption

Nature Biotech. 24, 848 (2006).

Reading List

i h i i ll & i l d ( ) ki d li i li h1. Ntziachristos V, Ripoll J, Wang L, & Weissleder R (2005) Looking and listening to light: the evolution of whole‐body photonic imaging. Nature biotechnology 23(3):313‐320.

KAIST PH880 11/10/2010