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Tissue optics, Light propagation

in tissue
11h January 2007

Material to cover
• Photothermal
• Photoablation
• Photon transport in tissue.

Good collection of absorption spectra in vivo


http://omlc.ogi.edu/spectra/index.html

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Light-Tissue Interaction
Note:
Optical Modification
1-1000 J g-1
Ionizing Radiation
50 Grey 0.05 J g-1

Long term effects


Selective Photothermolysis T= 10-4- 108
biological response
T= 1010- 1015
evolutionary effects

Diagnostic Threshold

Exposure Time Pulse Duration


• cw > msec linear effects

•Short pulses << msec Thermal confinement, e.g.


Τlaser < ΤDif
S∞
Non-linear absorption e.g.
S2 Τlaser < Τs1 or Τt1
ISC
Energy [eV]

S1
T1
Are other types of interactions
available at very short pulse
S0 durations?

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Resonance vs. multiphoton absorption

Determining Parameters
• Power density [Wcm-2] Irradiance or Fluence
rate
• Energy density [Wcm-2] Radiant Exposure or
Fluence
• Time [sec] Time
• Absorption coefficient
[cm-1] Extinction, Attenuation

Local absorbed energy density or power density

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Phototherapeutics
Thermal IR, vis
Chemical UV, vis (NIR)

}
Dissociation UV
Mechanical all need high power
Ionization all

Dominant mechanism depend on


Irradiation Geometry, Irradiance,
exposure time, tissue optical properties.

Light penetration and local


absorption (without scattering)
(− µeff d )
Φ (d ) = Φ 0 e Local fluence rate
(− µeff d )
RH = µ a Φ 0 e Local energy absorption rate

ln Φ (d ) ln Φ (d )
µ eff ln Φ (d ) µ eff ln Φ (d )

d d

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Light penetration and local
absorption with scattering

Possible >3 fold


increase of power
ln Φ(d ) density inside
µ a ln Φ(d ) scattering media.
Subsurface peak only
for index matched
cases.

Direct Photochemical effects

High Quantum
Energry Low Quantum Energy
Linear addition Photooxidation
Substitution reactions Cis-trans isomeration
Cycloadditions
Fragmentation

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Photochemical
• PDT

• Laser Biostimulation
(not enough science for 2 hours)

• PUVA (psoralen UVA)


– Thymidine crosslinking

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H&E micrographs of plantar aspect of the femoro-tibial joint sections, with the femur on the
right side of each image. A: Five hours after injection of 10 ul of PBS solution demonstrating
absence of cells in the joint. B: Ten microliters of PBS containing 300 lg of zymosan A
without LLLT with presence of granulocytes in the joint space. C: Five hours after zymosan A
injection followed by635 nm–mediated LLLT. D, E: Twenty-four hours after zymosan A
injection without LLLT (D) and at 24 h with LLLT (E), respectively.

Photothermal Effects
dT 1
= {(η H µ a Φ d ) − RL }
dt Cv ρ

Specific heat
η H µ a Φ d = RH
Fluence rate
Fraction converted
into heat
Rate of heat loss

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Pulse duration in Thermal effects

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Photothermal
• Skin resurfacing

• Selective
Photothermolysis

• Tissue
welding/modification

Cosmetic Examples: Resurfacing,


spider veins, Tattoo, Hair

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Clinical Examples:Port wine stain
haemangioma, scars

Tissue ablation
Goals Physical requirements
• Rapid removal of • Maximize
undesired tissue vaporization of water
• Prevention of open • Retaining a
wound coagulation zone
• Rapid healing • Minimal coagulation
zone
• Consider mechanical
properties of tissue

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Photoablative
• Ablation

• Vascular re-canalization
(myocardium perfusion)

• LASIK

• Pulsed Photothermal
Radiometry

Resonance vs. multiphoton absorption

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Photoablative Materials processing
in non-biological materials

Aluminum
substrate

PMMA or Boro-silica glass


Limited consideration for:
•Compressibility
•Limited tensile and shear strength

Hard Tissue Application

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Mechanical properties
of tissue

Cavity

Shockwave

Implosion followed by secondary


shockwave

Same effect for fsec pulses?

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e.g. corneal reshaping

PRK

LASIK

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Soft tissue application

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Approach for medical therapy
investigations
• Cellular component
only to investigate
response of genetic
content to
– Plasma
– Shockwave
– Soft x-ray

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9L glioma spheroid after
10nsec 1064 nm

Red Propidum Iodine


Green Annexin V

Single Cell application

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Scattering
• Rayleigh
S 1 + cos 2 ϕ 4 2
≈ ωα N=
1 + cos 2 ϕ 4 n 2 − 1
ω
(
ε02
)
2

2
S0 r r2 N
http://www-phys.llnl.gov/Research/scattering/

•Mie

http://scienceworld.wolfram.com/physics/MieScattering.html

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Towards Light Transport in
Tissue

Basics on Light Transport in


Turbid Media
(s∇ )L(r , s ) = − µt L(r , s ) + µ s ∫ p(s, s')L(r , s')dω + S (r , s )

E = ∫ L cosθdω Radiance, probability of scattering,


4π Sources

∫ p(s, s')dω = 1

Energy density
Scattering phase function, Isotropic
g= ∫ p(s, s')(s, s')dω

scattering
Heney-Greenstein function
g = (1 − β )g HG
1  1 − g HG
2 
p HG (cos Ω ) =  β + (1 − β ) 
4π 
 (
1 + g HG − 2 g HG cos Ω 
2 1.5
)

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Heney-Greenstein function

Rayleigh scattering d<< λ (no polar symmetric)


Mie Scattering d ~> λ (polar symmetric)

Boltzman To Diffusion Equation


(s∇ )L(r , s ) = − µ t L(r , s ) + µ s ∫ p(s, s')L(r , s')dω + S (r , s )

Require special cases for irradiation, boundary conditions


and scattering function. Delta Eddington here.

(s∇ )L(r , s ) = − µ t ' L(r , s ) + µ s ' ∫ L(r , s')[1 + 3g (s, s')]dω


4π 4π

L(r , s ) = Lcoll (r , s ) + Ld (r , s ) Assume that L is no


 − µt ' z
 more than linearly
Lcoll (r , s ) = (1 − rs )E0 (r )e γ0
δ (γ − γ 0 ) anisotropic, used
  Legendre polynomials
1 3 for zero and first order
Ld (r , s ) = ϕ d (r ) + Fd (r )s
4π 4π

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Diffusion Equation
∇ 2ϕ d (r ) − 3µ t 'ϕ d (r ) + 3µ t ' µ s E (r , s0 ) − 3µ s g∇(E (r , s0 )s0 ) = 0

Solutions of the Diffusion Equation:


Inverse Applications
Infinite media

Infinite media + collimated

Semi-infinite medium

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Monte Carlo Methods

108 Photons per simulation


Complex geometries and optical
properties.

Advanced Models

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Sample Applications:
Photocoagulation of vessels

Absorption within blood vessel

a'
Rtotal =
  3k   µs'
1 + 2k (1 − a ') + 1 +  3(1 − a ') 
a' =
 (1 − a ' ) µa + µs'
   

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Analytical models for R
and R(ρ’) but also
numerical.
Inverse solution using
NN or Lookup tables.

µ s ' = µ s (1 − g )
µ eff = 3µ a (µ a + µ s ' )
µs'
a' =
µa + µ s'

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Time or Frequency Dependent:
Reflectance/Transmittance
c=c0 / n n=1.35-1.45

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 −ρ 2 
 
R( ρ , t ) = 4πDc 3 z0t e (− µ a ct )e
 4 Dct 
 

d ln R( ρ , t ) 5 ρ2
= − t − µac +
dt 2 4 Dct 2
d ln R( ρ , t )
∴ lim t → ∞ = −µac
dt

Note Fourier Transform of R(ρ , t )results in M ( ρ , f ) and φ ( ρ , f )

For low f, phase shift


is related linearly to f
and the average
photon path length
(c,<t>)

φ (ρ , f ) = π (µ eff ρ 0 )2
f
(1 + µ eff ρ 0 )µ a c
ρ 0 2 = ρ 2 + z0 2

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time frequency
Advantage •Direct little •Fast
interpretation •Cheaper technology
•Complete time
profile data
Disadvantage •Slow data •Data interpretation
collection obscure
•Requires fast •Varied ρ required
pulses high cost •High f expensive
single electronics
wavelenght •Modulations of
lasers and or lamps

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