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
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