Scott Prahl

= graduated

Ricky Wang Steven Jacques Sean Kirkpatrick

Don Duncan

Tissue Optics

Steven L. Jacques jacquess@ohsu.edu http://omlc.ogi.edu

Depts. of Biomedical Engineering and Dermatology Oregon Health & Science University, Portland OR, USA

1.  Optical properties

2.  How to measure optical properties

3.  Light transport

4.  Complex tissues

Tissue Optics

Steven L. Jacques jacquess@ohsu.edu http://omlc.ogi.edu

Depts. of Biomedical Engineering and Dermatology

Oregon Health & Science University, Portland OR, USA

1. where tissue affects photons, used for diagnostic sensing, imaging, and spectroscopy of tissues and biomaterials

We replaced heel stick tests with pain-free opical measurement of bilirubin

(FDA approved, marketed as Bilichek)

Normal light

polarized light Guiding skin

cancer surgery with polarized light camera

True cancer margin

BCC = basal cell carcinoma

Cancer margin seen by Doctor’s eye

2. where photons affect tissue, used for surgical cutting , dissecting, machining, processing, coagulating, welding, and oxidizing tissues and biomaterials

Micromachining with lasers

Laser surgery Photodynamic therapy of cancer

Computer simulations of laser effects in

tissues

Our first veterinary patient:

A donkey about to lose eye to sarcoid.

Treated with photodynamic therapy (PDT), a light-activated chemotherapy.

before

Debride and treat with PDT

2 weeks after treatment.

Eventually cleared completely Collaboration with School of

Veterinary Medicine, Oregon State University.

tissue

air

5mmx5mm

esophagus @ 630 nm wavelength

Monte Carlo simulation of photon migration

A photon’s path is tortuous due to multiple scattering, like a ball of string.

Nevertheless, there is a total pathlength L, like the length of the string.

L

€

T = e−µa L

Mean free path = 1/µa

L

L

€

T = e−µa L

Mean free path = 1/µa

L

absorp'oncoeff.µa photonpathlength,L

cm2W

per Wincident

power

r [mm]

z [mm]

Monte Carlo

photon diffusion Fluence rate [W/cm2]

€

Wcm2

F

Flux passing through a 2-D window

€

Wcm2 =

Jcm3

cms

F = C c

Energy density within a 3-D volume

1 W cm-2

(c [cm/s])(44 ps)

1 cm

1 cm

1 cm

for λ = 488 nm, n = 1.33

Fluence rate = speed of light x photon concentration F = c C

€

Cph =Enc

λhc

= 1.1×1010 photons / cm3

=Enc

λhc

1000Nav

= 1.8×10−13moles / liter

€

1 W / cm2

€

(c [cm / s])(44 ps)

F = cC

C = F/c

Photochemical

Photothermal

Photomechanical

Concentration Fluence rate [W/cm2]

Speed of light [cm/s]

[J/cm3]

= C F

c

Concentration Fluence rate [W/cm2]

Speed of light [cm/s]

[J/cm3]

= C F

c

Concentration

[#photons/cm3]

= C F

c

€

λhc1000Nav

Wavelength [m]

Speed of light,[cm/s]

Planck’s constant [J m]

[ph/J]

€

1 J /cm3 = 1.1×1010 photons /cm3

= 1.8 ×10−13moles / literW

Concentration

= C F

c

€

λhc1000Nav

[moles/liter]

# [cm3/liter]

# [1/mole]

€

1 J /cm3 = 1.1×1010 photons /cm3

= 1.8 ×10−13moles / literW

Energy deposition

time [s]

Absorption coefficient [1/cm]

[J/cm3]

= Q Ft

Fluence rate [W/cm2]

µ a

ΔT = µ a Ft

Temperature rise

€

1ρCp

density [g/cm3]

specific heat [J/(g K) [°C]

Fluence rate [W/cm2]

Absorption coefficient [1/cm]

N = µ ax Ft

(moles/liter)/(J/cm3 absorbed)

# of photons participating in photochemistry

photochemistry

€

λhc1000Nav

Φ

Quantum efficiency

J/cm3 absorbed by photochemical reagent X

Absorption coefficient [1/cm]

of photochemical reagent X

P = µ a Ft

€

Γ

Grüneisen coefficient [dimensionless]

1 [J/cm3] = 10 bar

Stress, or pressure

Γ = 0.12 at 25°C

--> 0.5 at higher temperatures

A

B

Look… the properties of A and B are quite different!

No, they have the same properties, just different geometries. Absorption, µa

Scattering, µs and g

Refractive index, n

Observation versus properties

Electronic transitions (UV, visible, nearIR)

N

N

N

N

pyrroles

porphyrins

heme

(chlorophyll)

cytochromes

phycobiliproteins

carotenoids

ferredoxins

flavins

melanin

N

O

N N

N

O

N

O

OO

OO

Absorption

vibrational transitions (nearIR, midIR, farIR)

Absorption

absorption cross-sectional area efficiency

geometrical area

Ageometrical

cross-sectioneffective

cross-section

σ = Q Aa a

σa = Qa A

[cm2] [-] [cm2]

absorption coefficient

density cross-sectional area

µa = ρa σa

[cm-1] [cm-3][cm2] σa = Qa A[cm2] [-][cm2]

efficiency area

T = exp(-µaL)

1

10

100

1,000

10,000

100 1,000 10,000Abs

orpt

ion

coef

ficie

nt [c

m-1

]

Wavelength [nm]

KrFexcimer

XeClexcimer

ArFexcimer

Ho:YAG

Er:YAG

CO2

Vis

aorta

UV IR

Nd:YAG

whole blood

dye laserargon

skin

75% water

melanosomeepidermis

1 µm

10 µm

100 µm

1 mm

10 mm

1 cm

mfp = 1/µa

µa

€

mfp =1

µa

mean free path

Scattering

dipole

Constructive interference in

forward direction

Destructive interference in lateral

directions

Non-uniform density of dipoles yields scattering

Non-uniform density of dipoles yields scattering

Hierarchy of ultrastructure

striations in collagen fibrils

membranes

mitochondria

nuclei

cells 10 µm

1 µm

0.1 µm

lysosomes, vesicles Mie scattering

Rayleigh scattering macromolecular aggregates

0.01 µm

(1-f) λ-b

f λ-4

mitochondria

0.5 µm

Collagen fibrils, fibers

Ageometrical

cross-sectioneffective

cross-section

σ = Q As s

σs = Qs A

[cm2] [-] [cm2]

scattering cross-section efficiency

cross-sectional area

scattering coefficient

density cross-sectional area

µ s = ρ s σ s

[ c m - 1 ] [ c m - 3 ] [ c m 2 ] σ s = Q s A [ c m 2 ] [ - ] [ c m 2 ]

efficiency area

T = e x p ( - µ s L )

Anisotropy, g

cos(θ)cos(θ)

azimuthalangle ψψ

g = <cosθ> = ∫0

π p(θ)cosθ 2πsinθ dθ

∫0

π p(θ) 2πsinθ dθ = 1where

Anisotropy, g

Anisotropy, g

€

g = < cosθ > = S(θ)cos(θ) 2π sin(θ)dθ

0

π

∫

S(θ) 2π sin(θ)dθ0

π

∫

Henyey-Greenstein function

€

p(θ)cos(θ) 2π sin(θ)dθ = g0

π

∫

€

p(θ) 2π sin(θ)dθ = 10

π

∫

26°g = <cosθ> = 0.90

<θ> = 26°

µs’ = µs(1-g) = 0.10µs

mfp = 1/µs

mfp’ = 1/µs’

anisotropy, g

one mfp’

ten mfp

Reduced scattering coefficient, µs’ = µs(1-g)

equivalent Random Walk

Mie

Rayleigh

total µs’

skin

Reduced scattering coeff. of skin

µs‘ = µs(1-g)

€

µs' = µs.500nm

' f λ500nm

−4

+ (1− f ) λ500nm

−1

Mie

Rayleigh

total µs’

43 cm-1 0.62 1 - 0.62 0.7 < ~1 < 1.3

Rayleigh Mie

skin

Absorption µa [cm-1]

Scattering µs [cm-1]

Anisotropy g [-]

Refractive index n [-]

Reduced scattering µs’ = µs(1-g)

Absorption µa [cm-1]

Scattering µs [cm-1]

Anisotropy g [-]

Refractive index n [-]

Reduced scattering µs’ = µs(1-g)

€

µa = B Sµa.oxy + (1− S)µa.deoxy( ) +Wµa.water + f iµa.ii∑

Absorption µa [cm-1]

Scattering µs [cm-1]

Anisotropy g [-]

Refractive index n [-]

Reduced scattering µs’ = µs(1-g)

€

µa = B Sµa.oxy + (1− S)µa.deoxy( ) +Wµa.water + f iµa.ii∑

€

µs' = µs.500nm

' f λ500nm

−4

+ (1− f ) λ500nm

−1

1.  Optical properties

2.  How to measure optical properties

3.  Light transport

4.  Complex tissues

Tissue Optics

Steven L. Jacques jacquess@ohsu.edu http://omlc.ogi.edu

Depts. of Biomedical Engineering and Dermatology

Oregon Health & Science University, Portland OR, USA