lasers biomedical applications · • what are the medical applications of lasers, what kind of...

György Vereb – Lasers

György Vereb

Department of Biophysics and Cell Biology, University of Debrecen

LASERsand their

biomedical applications

126-131134-137141-144533-539 !541 !

Textbook pages: Interconnection with other lectures:

Lect. 3. Fluorescence applicationsLect. 5. Scanning image formation in microscopyLect. 24. Flow cytometry, confocal laser scanning microscopyLect. 27. Modern microscopic techniques


What do lasers give us?

What can we do with lasers?• Biomedical research• Laboratory diagnostics• Clinical diagnostics• Soft laser therapy• Laser surgery• Photodynamic therapy• Cosmetology• Other non-excelusively biomedical uses

• data processing, transfer and storage (printers, holography, CD/DVD/Blu-Ray, fiberoptics)• measurement, localisation and aiming devices• industrial applications

What is a laser?• A coherent monochromatic light source capable of delivering high photon energy into a

defined small spot over a short time• Light Amplification by Stimulated Emission of Radiation

What do we learn today?• The principles how lasers work• The different types and characteristics of lasers• How lasers interact with material• What medical applications are based on these interactions

Aim: To understand• how various lasers work and what kind of radiation they produce• how (and why) different lasers can be used for different medical therapeutic interventions


Coherence in time

Coherence

in space

(small divergence)

Spontaneous

emission

Incoherence in time

Incoherence in space

Polychromatic light

Small energy density

Non-polarized

Mono chromatic light

(small bandwidth)

High energy density

It can be polarized

Stimulated Emission

Conventional light sources vs. Laser radiation !


Spontaneous emission

E1

E2

Elight

electric

kinetic

Random

process

1. Interaction

2. E = hf = E2-E1

3. Polarity (p ~ cos2f)

SER: For coherence and monochromaticity, stimulated emission is needed

Spontaneous vs. Stimulated emission !


E1

E2

Initially (normally):

Boltzmann

( N2/N1= e - DE/kT )

(ΔE=E2-E1)

N1>>N2

DJ << 0

Absorption dominates

Amplification:

DJ > 0

N1 < N2

population inversion(inversion of normal population

proportions)

F

F + DF

DJ ~ N2-N1

Absorption Amplification

N1

N2

LA: Conditions of light amplification!

Change of photon flow: DJ


E1

E2

F

F + DF

DJ ~ N2-N1

Abs ~ N1 Em ~ N2

Optical pumping:

N2 increases, N1 decreases

N1 = N2

Equilibrium, DJ = 0

N1 < N2 population

inversion,

amplification

Impossible in a system with 2 levels

Condition for population inversion

N1>>N2 (Boltzmann)

DF << 0

Absorption

dominates

!


E1

E3

Creating population inversion

E1

E2

E = h fPumping

E = h f

Minimum condition: 3 energy levels

Fast, spontaneous transition

Pspontaneus relax. < Pstimulated em.

Inversion: N2=N1+1

!


E0

E3

E1

E2

E = h fE = h f

Optimal condition: 4 energy levels

Inversion: N2=1



Pumping

Creating population inversion!


Which four basic properties distinguish lasers from conventional light sources? • Coherence in space• Coherence in time• Monochromaticity• Polarized

Which photophysical phenomenon provides for these properties?• Stimulated emission

What are the condition(s) that make stimulated emission possible? • Photon interacts with excited electron• Energy of photon equals the energy liberated when this electron returns to a lower energy level• Polarity of the photon is appropriate

What’s the minimal and what’s the optimal condition for population inversion? (should also be ableto draw the relevant figure)• Minimal: 3-energy-level system• Optimal: 4-energy-level system

Why do we need population inversion for a laser to operate?• To achieve amplification

What else is needed for popluation inversion, when at least the minimum condition holds?• Pumping

So, to summarize….. !


E0

E3

E1

E2

Pumping

RESONATOR: Standing wave, L = n l / 2

LASER PLASMA

Front mirror

(outcoupling)

90 - 99 %

Rear mirror

99,9 %

From laser amplifier to laser oscillator!


Some types of lasers

State Material pumping l (nm) output E (W) t (ns)

gas He-Ne electric pulse 633 c.w. 0,1

Ar++ electric pulse 488, 514 c.w. 100

Kr++ electric pulse 657 752 c.w. 3

CO2 electric pulse 10600 c.w. 30

Excimer (ArF, XeCl) electric pulse 193, 308 pulsed 10 MW 1-3

liquid dye laser light various pulsed/c.w. 3

dye (Rh 6G) laser light 600 pulsed 10000 1 fs

solid Ruby (Cr+++ & Al2O3) flashlamp 694 pulsed 200 MW 100

Nd-YAG flashlamp 1065 pulsed 1 MW 10

Nd-YAG / KTP flashlamp 532.5 pulsed 2 MW 10

Nd-YAG Xe lamp 1065 c.w. 60

Er-YAG flashlamp 2900 pulsed 1 MW 10

Diode GaAs current 840 c.w. / pulse 5 HF

AlGaAs current 760 c.w. / pulse 50

GaInAsP current 1300 c.w. / pulse 20

5*


Guiding laser light

Infrared (eg. CO2 laser):

Mirrors

Targeting laser in the

visible range

(eg. He-Ne, diode)

CO2 laser

He-Ne laser

mirror

Dichroic

mirror

observer

micromanipulator

target

5*


Visible laser: mirrors, fiberoptics (coupling with lenses)

Guiding laser light

5*


Medical applications of lasers

flow cytometry

laser nephelometry

correlation spectosc.

microscopies, tweezer

endoscopy

laser doppler

fotodynamic diag.

hyperemisationcoagulation (60-90 C)

laserthermy

vaporization (100-

150 C)

carbonization (300 C)

photodynamic therapy

LOW POWER HIGH POWER

clinical diagnostics

lab diagnostics

thera

pylaser surgery

dia

gn

ostic

ssoft laser therapy

!


atomization

Shock waveFluores-

cence

Photochem.

reactions

Reflection,scatter

Absorption

Excitation ionization

Photo-

dissociation

40 oC 60-90 oC 100-150 oC 300 oC

Laserthermy Coagulation Vaporisation /

Cutting

Carbonisation /

Excision

Heating

Interaction of lasers with tissues !

Photothermal effects


What defines the applicability of various lasers?

Wavelength →where it is absorbed

how it penetrates

Energy →what it achieves

Pulse time →heat dissipation

affected volume

!

Absorption spectrum of tissue,

e.g. blood absorbs best between 400-580

nm (blue-green-yellow)

UV is absorbed at the surface, the longer

λ, the better light penetrates (up to NIR).

Effect is proportional to absorbed energy

High input rate → low dissipation →

localized effect

Low input rate → larger volume affected


COAGULATION

bleedingILPC (interstitial laserphotocoagulation)diabetic retinopathyRetinal detachmentglaucomaportwine stain

green: Ar, Ar-Krfar red: diode laser

!


TISSUE REMOVAL USING VARIOUS LASER EFFECTS

Nd-YAG

vaporisation

CO2

carbonisation

Excimer (ArF)

atomisation

5*


CARBONISATION, VAPORISATION

• CO2, Nd-YAG: bleed control, disinfection, sharp cut edges, tumor removal

burning an esophagus tumor

!


PHOTODISSOCIATION (ATOMISATION)

• Shaping the cornea – an alternative to spectacles (PRK = Photorefractive keratectomy)• Laser angioplasty• Excimer lasers (UV)

!


Methods for re-shaping the cornea: PRK, LASIK, LASEK

PRK: remove "skin of the apple", reshape surface. Epithelium grows back in 2-3 days. Advantage:

absolutely safe. Disadvantage: transient pain, light sensitivity and the feeling of having a foreign body

in the eye.

LASIK: cut a flap from the "apple", turn the flap to the side and reshape cut surface. Turn the flap back

to its original place. Advantage: no pain. Disadvantage: complications can occur during or after the

treatment. The flap will never grow back so it can be torn off, for example, in an accident.

LASEK: Losen"skin of the apple" into a flap (using alcohol), turn flap to the side, perform the

treatment, then turn the flap back. With this method we dramatically reduce the unpleasantness and we

do not need that potentially hazardous cut.

5*


MULTIPHOTON IONISATION

Basis: in the focus of the laser multiphoton and cascade ionisation takes places owed to

the high photon density (1012W/cm2), plasma is formed (1018/cm3 electrons) and shock

wave with GPa pressure creates a tiny discontinuity in the focus. Femtosecond pulsed

lasers (Nd-YAG) can be used.

The laser can be used to make a perforation

around the unnecessary piece of cornea, which

is then removed.

Femtosecond LASIK

!


MULTIPHOTON IONISATION Shock wave

Nd-YAGEr-YAG

secondary cataractlithotripsyarthrosisdrilling teeth

• Ho-YAG: alsophotothermal effect(fast vaporisation and cavitation)– lithotripsy– laser discdecompression

!


PHOTODYNAMIC DIAGNOSISFluorescent

dye (eg.

porphyrins)

Laser

Tumor

becomes

distinguish-

able from

normal

tissue

Tumor

takes

up dye

selectively

Fiberoptics

/endoscope

Green: vascular endothelial cells of a tumor

Red: photosensitizing agent localizes to vascular endothelial cells after intravenous injection

!


PHOTODYNAMIC THERAPY (PDT)

Laser

Fiberoptics

Tumor cells

accumulating the dye are destroyed by the radicals,

while normal cells not accumulating the dye are not

harmed. Radicals cause cell death by breaking

DNA and unsaturated lipids of the cell membrane.

Excited dye

produces

free

radicals

!


PDT in Cancer Treatment

• Minimally invasive

• Less damage to surrounding healthy cells

• PDT best suited for:

• Early stage tumors

• Inoperable for various reasons

• Limited success due to lack of specificity and potency of photosensitizing

agents

PDT for cancer of the esophagus

http://www.mayoclinic.com/health/photodynamic-therapy/MM00719

!


Take-home message

Ask yourself:

• In what aspects is laser light different from light from conventional sources?

• What are the mechanisms and conditions that make the generation of laser possible?

• In what ways do lasers interact with tissues and which properties define the type and

place of interaction?

• What are the medical applications of lasers, what kind of lasers are used for each and

what type of laser-tissue interaction(s) is each based on?

• As an MD (DMD):

• Is there a consequence of using a laser in a given treatment in terms of:

• therapeutic outcome/success

• patient comfort/quality of life

• financial aspects

lasers biomedical applications · • what are the medical applications of lasers, what kind of...

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