Biomedical Optics 5. Lecture – Tissue Interactions II

12/10/2020

1

Biomedical OpticsAnne Adlung, M.Sc.

Computer Assisted Clinical Medicine

Medical Faculty Mannheim Heidelberg University

Theodor-Kutzer-Ufer 1-3D-68167 Mannheim, Germany

[email protected]/inst/cbtm/ckm

Biomedical Optics – Tissue Interactions II

Anne Adlung I Slide 2/45 I 12/10/2020

Outline: Biomedical Optics

1. Lecture – Basic Optics

2. Lecture – LASER Physics

3. Lecture – LASER Properties and Systems

4. Lecture – Tissue Interactions I

5. Lecture – Tissue Interactions II

• Photochemical Interaction

• Thermal Interaction

• Photoablation

• Plasma-Induced Ablation

• Photodisruption

6. Lecture – Biomedical Applications



5. Tissue Interactions II



Literature



Tissue Interactions II

• Photochemical Interaction

• Photosynthesis (6CO2 + 6H2O + hν C6H12O6 + 6O2)

• Thermal Interaction

• Tissue coagulation

• Photo Ablation

• Plasma-Induced Ablation

• Photodisruption

Reaction Types:

Energ

y D

ensity:

1-1

03

J/c

m2

Removing Tissue



Exposure Times

• continuous wave (CW)

• min - µs

• µs - ns

• < 1 ns

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Photochemical Interaction

Characteristics

- low power densities: 1 W/cm2

- long exposure times: CW - sec

Chemical effects and reactions within

macromolecules or tissues induced by light

exposure

Applications

- Biostimulation

- Photodynamic Therapy (PDT)



Biostimulation

• “Biostimulation” not scientifically well defined

• Red/infra-red low intensity light as stimulus for cell proliferation (e.g. wound healing, hair

growth)

• Controversial discussion about effects

→ no photochemical reaction path known



Photodynamic Therapy (PDT)

Photosensitiser: Hematoporphyrin

Derivative

(3-4d after injection)

(slow in tumor cells)



Photosensitiser Kinetics

radiative decay non-radiative decay

+ heat

ISC

non-radiative decay

+ heat

radiative decay Type II

Intramolecular exchange

Type I

hydrogen

transfer

electron

transfer

Free radicals cellular oxydation necrosis

Singlet oxygen (reactive!) cellular oxydation necrosis

fluorescence

phosphorescence

singlet/triplet state: s=0/s=1

non-radiative decay



Therapy + Diagnostics

620 nm

Fluorescence peak at 620 nm but…

• concentration (c) dependent peak height due to self-absorption at c > 10-3 mol/L

Absorption and fluorescence spectra of HpD dissolved in phosphate-buffered saline solution (Yamashita 1984)

Distinction between

healthy and tumor

cells

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Time-Resolved Fluorescence

Tumour versus healthy tissueFluorescence decay time

tumour selectivity• concentration dependent duration of the fluorescence decay

time-resolved fluorescence





Thermal Interaction

Characteristics

- CW or pulsed LASER irradiation

- effects depend on duration and peak temperature

- coagulation (blood changes from liquid to gel)

- vaporisation

- carbonisation (conversion of an organic substance to carbon)

- melting

Non-specific interaction with increase in local temperature

Applications

- LASER-induced thermotherapy (LITT)



Thermal Interaction

1. Absorption of a photon:

2. Deactivation by inelastic collision:

Bulk absorption at the microscopic level occurring in

molecular vibration-rotation bands followed by

nonradiative decay

Two-step Process:



Absorption Peak of Water at 3 µm

Water Absorption Spectrum

Erbium and Holmium doped LASERs

• Er:YAG at 2.94 µm

• Er:YLF at 2.80 µm

• Er:YSGG at 2.79 µm

Ho:YAG at 2.12 µm



Thermal Effects I

37°– 42°C No measurable effects in tissue

42°C – 50°C Hyperthermia (for several minutes: necrosis)

→ conformational changes of molecules: rearrangement of

rotatable bonds at carbon atom

→ bond destruction

→ membrane alterations

> 50°C Measurable reduction in enzyme activation

→ reduced energy transfer within the cell and cell immobility

→ certain cellular repair mechanisms disabled

→ fraction of surviving cells reduced

60°C Denaturation (structural changes) of proteins and collagen

→ coagulation of tissue

→ necrosis of cells

→ paling of tissue

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Coagulation: Human Cornea

Temperature ≥ 60°C

Coagulated tissue:

• becomes necrotic

• appears darker

than other tissue



Thermal Effects II

> 80°C Cellular membrane permeability drastically increases

→ destruction of the chemical concentration equilibrium

break down of sodium potassium pump

100°C Water vaporisation

→ phase transition with volume increase: gas bubbles

→ mechanical ruptures

→ thermal decomposition of tissue fragments

> 100°C Carbonisation

→ blackening of adjacent tissue and smoke generation

> 300°C Melting



Vaporisation: Human Tooth

Thermomechanical Effects

• vaporisation of water

• increase in pressure

• water expansion

→ microexplosions

• tissue ablation



Carbonisation: Human Skin and Tooth

Temperature > 100°C Release of carbon

• blackening in colour

• reduces visibility during surgery



Melting: Human Tooth

Temperature > 300°C

vaporisation

meltingmelting



LASER-Induced Thermotherapy

Liver tissue

(Nd:YAG, 5.5 W, 10 min)

Temperature evolution Localized tissue coagulation by LASER applicator(Nd-YAG at 1064 nm, diode LASERs at 800 – 900 nm)

⇒ tumour treatment (uterus, prostate, retina, brain, liver)

⇒ minimally invasive surgery

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Photoablation

Characteristics

- power densities: 107 - 108 W/cm2

- exposure times: ns

- precision of etching process

- lack of thermal damage to adjacent tissue

Applications

- refractive corneal surgery

Absorption of UV photons results in exceeding the bond

energy, which is followed by dissociation of the atoms due

to vibration



Absorption of high-energy

UV photons

Promotion to repulsive

excited states

→ Dissociation

Ejection of fragments

(no necrosis)Ablation

Simulation of ablation using Newton's equation of motion.

Ablation Process

Excitation:

Dissociation:



Wavelength Range



Photoablation: Human Tooth

vaporisation

melting

photoablation

clean ablation, minor heat transfer to surrounding tissue



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Plasma-Induced Ablation

Characteristics


- exposure times: 500 10-12 s (ps) - 10-15s (fs)

Applications

- refractive corneal surgery, caries therapy &

diagnostics

Well-defined removal of tissue by “optical breakdown” (plasma

explosion) without evidence of thermal or mechanical damage

to surrounding tissue.

Human tooth exposed to 16000 pulses from a Nd:YLF laser.



Plasma-Induced Ablation: Human Toothvaporisation

photoablation

plasma-induced ablation

increasingprecision

melting



Plasma-Induced Ablation: Caries Diagnosis

healthy caries less minerals

spark: plasmaexplosion

Laser induced plasma sparking on tooth surface using a Nd:YLF laser.

Spectrometer





Photodisruption

Characteristics


- exposure times: 100 ns – 100 fs

Applications

- lens fragmentation

- lithotripsy

Multi-cause mechanical effects:

• optical breakdown

• shock wave generation

• cavitation (formation of vapour cavities in a liquid)

• jet formation

LASER-assisted lens fragmentation



Photodisruption: Human Toothvaporisation

photodisruption

melting

photoablation

plasma-induced ablation

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Repetition



Calculations: Relevant for the exam

From previous lectures



Wave – Particle Duality

E = h·ν = p·c

p = h/λ

E: energy

p: linear momentum

h: Planck's constant = 4.1·10-15 eVs

Light Quantum

Photons (γ)

dispersion in vacuum

λ · ν = c

λ: wavelength

ν: frequency

c: speed of light = 299 792 458 m/s

Electromagnetic Wave

ψ(t)=A0⋅eiωt

t

λ

A0

Question:

What's the energy difference ∆E between violet (λ=400nm) and red light (λ=700nm)?

Solution: ∆E = 1.3 eV



Total Reflection

critical angle

n

n’

Normal

n’ > n

θc

sin(θ) =1

Question:

What is the critical angle for a light beam travelling from water to air?

Solution: ϴc = 49°

refractive index n

vacuum: 1

air: 1.0003water: 1.333lenses: 1.5



Directionality

∆θ

A

λQuestion:What's the opening angle in steradians, givenλ = 500 nm, A = 25 mm² ?

∆Ω λ

∆

Light bulb:Strongly divergent

Low irradiance

(intensity)

LASER:Slightly divergent

High irradiance

(intensity)

*steradians (sr): dimensionless variable for the solid angle related to the area „A“ it cuts out of a sphere: Ω=A/r2 [sr]

Solution:

∆Ω = 10-8 steradians*



Example: HeNe LASER

spot size at the waist: w0 = 1 mm

LASER wave length: λ = 632.8 nm w2 ≈ 202 nm

w2w0

focus : f = 1 mm

Gaussian beams significantly focused!

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Brewster Angle – Linear Polarisation

Brewster Angle

Snell's Law

Reflected ray polarized due to radiation charachteristic of Hertzian

dipole!

θB

Θ‘n`

n

E`=EII

E=E

E=E +EII



Reflection Coefficient and Reflectance

Fresnel Equation Reflection coefficient:Measure of the amount of reflected radiation

Reflectance: Intensity Ratio = (Reflection coefficient)2

Maxwell's Equation+

Boundary Condition: charge- and current-free surface

(polarised to plane of incident) (polarised || to plane of incident)

Brewster Angle: Rp = 0 (Water: 53°)

n=1.0003n=1.33

plane of incidence

E`

E



Next Lecture

6. Biomedical Applications

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Biomedical Optics 5. Lecture – Tissue Interactions II