biomedical optics 5. lecture – tissue interactions ii
TRANSCRIPT
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
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 3/45 I 12/10/2020
5. Tissue Interactions II
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 4/45 I 12/10/2020
Literature
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 5/45 I 12/10/2020
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
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 6/45 I 12/10/2020
Exposure Times
• continuous wave (CW)
• min - µs
• µs - ns
• < 1 ns
12/10/2020
2
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 7/45 I 12/10/2020
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 8/45 I 12/10/2020
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)
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 9/45 I 12/10/2020
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
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 10/45 I 12/10/2020
Photodynamic Therapy (PDT)
Photosensitiser: Hematoporphyrin
Derivative
(3-4d after injection)
(slow in tumor cells)
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 11/45 I 12/10/2020
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
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 12/45 I 12/10/2020
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
12/10/2020
3
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 13/45 I 12/10/2020
Time-Resolved Fluorescence
Tumour versus healthy tissueFluorescence decay time
tumour selectivity• concentration dependent duration of the fluorescence decay
time-resolved fluorescence
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 14/45 I 12/10/2020
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 15/45 I 12/10/2020
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)
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 16/45 I 12/10/2020
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:
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 17/45 I 12/10/2020
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
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 18/45 I 12/10/2020
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
12/10/2020
4
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 19/45 I 12/10/2020
Coagulation: Human Cornea
Temperature ≥ 60°C
Coagulated tissue:
• becomes necrotic
• appears darker
than other tissue
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 20/45 I 12/10/2020
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
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 21/45 I 12/10/2020
Vaporisation: Human Tooth
Thermomechanical Effects
• vaporisation of water
• increase in pressure
• water expansion
→ microexplosions
• tissue ablation
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 22/45 I 12/10/2020
Carbonisation: Human Skin and Tooth
Temperature > 100°C Release of carbon
• blackening in colour
• reduces visibility during surgery
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 23/45 I 12/10/2020
Melting: Human Tooth
Temperature > 300°C
vaporisation
meltingmelting
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 24/45 I 12/10/2020
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
12/10/2020
5
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 25/45 I 12/10/2020
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 26/45 I 12/10/2020
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
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 27/45 I 12/10/2020
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:
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 28/45 I 12/10/2020
Wavelength Range
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 29/45 I 12/10/2020
Photoablation: Human Tooth
vaporisation
melting
photoablation
clean ablation, minor heat transfer to surrounding tissue
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 30/45 I 12/10/2020
12/10/2020
6
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 31/45 I 12/10/2020
Plasma-Induced Ablation
Characteristics
- power densities: 1011 - 1013 W/cm2
- 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.
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 32/45 I 12/10/2020
Plasma-Induced Ablation: Human Toothvaporisation
photoablation
plasma-induced ablation
increasingprecision
melting
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 33/45 I 12/10/2020
Plasma-Induced Ablation: Caries Diagnosis
healthy caries less minerals
spark: plasmaexplosion
Laser induced plasma sparking on tooth surface using a Nd:YLF laser.
Spectrometer
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 34/45 I 12/10/2020
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 35/45 I 12/10/2020
Photodisruption
Characteristics
- power densities: 1011 - 1016 W/cm2
- 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
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 36/45 I 12/10/2020
Photodisruption: Human Toothvaporisation
photodisruption
melting
photoablation
plasma-induced ablation
12/10/2020
7
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 37/45 I 12/10/2020
Repetition
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 38/45 I 12/10/2020
Calculations: Relevant for the exam
From previous lectures
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 39/45 I 12/10/2020
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
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 40/45 I 12/10/2020
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
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 41/45 I 12/10/2020
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*
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 42/45 I 12/10/2020
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!
12/10/2020
8
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 43/45 I 12/10/2020
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
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 44/45 I 12/10/2020
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
Biomedical Optics – Tissue Interactions II
Anne Adlung I Slide 45/45 I 12/10/2020
Next Lecture
6. Biomedical Applications