20 Bio Medical Lasers

8/14/2019 20 Bio Medical Lasers

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D r . N . v e n k a t a n a t h a n

BIOMEDICAL LASERS


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Femto Second Lasers

The development and commercialization offemto - second lasers has opened up newapplications in biomedicine.

Particularly in surgery, Femto-second pulsesallow for much more precise cutting than donanosecond lasers.

Two-dimensional images of biological tissuecan be recorded using an ultrafast electronic-gated imaging camera system.


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This imaging typically uses 120 fs pulses at a 1kHz repetition rate from ultrafast laseramplifiers.

The biggest advantage of ultrafast lasers insurgical applications is limiting biologicaltissue damage.

The pulse interacts with the tissue faster thanthermal energy can diffuse to surroundingtissues.


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It simply means it hardly burnsor destructs the neighboring

tissue.The main components of biological tissue that contributeto the absorption are melanin,hemoglobin, water and proteins.


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Absorption spectra of mainabsorbers in biological tissue.


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The absorption in the IR region (200010000 nm)originates from water.

Which is the main constituent of most tissues.

Proteins absorb in the UV region (mainly 200300nm).

Pigments such as hemoglobin in blood and melanin,the basic chromophore of skin, absorb in the visible

range.The absorption properties of the main biological

absorbers determine the depth of penetration of alaser beam.


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Properties of Nd:YAG Laser

The Nd:YAG laser (1064 nm) for whichabsorption of water, pigments and proteins islow.

This property is therefore obviously importantfor medical applications.

For example, the Nd:YAG laser can penetrate

deeper A cut made with the Nd:YAG laser will notbleed due to tissue coagulation.


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Properties of CO2 Laser

The CO2 laser (10.6 m) does notpenetrate deeply because of waterabsorption in this region.

The CO2 laser which is a better knife

For precise thermal cutting of tissue

due to vaporization by focusing on thetissue along a short optical path.


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INTERACTION MECHANISMS


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Double logarithmic plot of the power density as a function ofexposure time. The circles show the laser parameters requiredfrom a given type of interaction with biological tissue.


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All types of interactions can be placed betweentwo diagonals illustrating the energy fluences o1 J/cm2 and 1000 J/cm2.

This indicates that lasers used for medicalapplications must have fluences ranging from 1J/cm2 to 1000 J/cm2.

The fluences are controlled both by the energy(controlled by exposure time) and degree ofocusing the laser beam on the tissue.


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Various interactions and Laser Sources

With cw lasers or exposure time >1 s, onlyphotochemical interaction can be induced.

Powers of only a few mW can be used for

these purposes.For thermal interactions shorter exposure

times (1 min1 ms) and higher energies must

be used.Thermal effects can be induced both by cw or

pulsed lasers of 1525W power.


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Photoablation occurs at exposure time between1 ms and 1 ns.

In practice, nano-second pulses of 106 109

W/cm2

irradiance should be employed.Plasma-induced ablation and photo disruption

occur for pulses shorter than nano seconds.

In practice, Pico - and femto second lasers withan irradiance of 1012 W/cm2 should be used.


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Note that although both phenomena occur at asimilar time exposure and irradiance.

They differ according to the energy densities

that are significantly lower for plasma-inducedablation.

The plasma-induced ablation is solely based on

tissue ionization. Whereas photo disruption is primaril

mechanical disruption.


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PHOTOCHEMICAL INTERACTIONS

Photochemical interactions do not need ahigh power density.

Lasers of 1 W/cm2 power density andlong exposure times ranging fromseconds to cw light are sufficient.

For this category of interactions, a laserinduces chemical effects by initiatingchemical reactions in tissue.


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For example, vision processes inrhodopsin or proton pumping inbacteriorhodopsin are initiated by a laser

beam from the visible range.Photochemical interactions are used in

photodynamic therapy (PDT).

Another application of very loirradiance of a laser beam isbiostimulation.


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Photodynamic Therapy

Photodynamic therapy utilizes the laser lighteffect on various chemical substances in anoxygen-rich environment.

Light induces a sequence of reactions thatproduce toxic substances such as singletoxygen or free radicals.

These substances are very reactive and candamage proteins, lipids, nucleic acids as wellas other cell components.


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It is found that some porphyrins are accumulated atmuch larger concentrations and for a much longertime in cancer cells compared to healthy cells.

It was suggested that this effect can be used for killingcancer cells.

If porphyrins are transferred to toxic states in any way, e.g., by light, cancer cells would be damaged

first.The method is very selective because it does not

destroy healthy cells.


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THERMAL INTERACTION

Thermal interactions are induced in atissue by the increase in localtemperature caused by a laser beam.

In contrast to photochemicalinteractions, thermal interaction mayoccur without only specific reaction pathand is highly non-selective and non-specific.


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THERMAL EFFECT ON THE TISSUE

Reversible hyperthermia (T>31o C) some functionsof the tissue can be perturbed but the effect isreversible,

Irreversible hyperthermia (T>42o C) somefundamental functions of the tissue can be destroyedirreversibly,

Coagulation (T>60o C) the tissue becomes necrotic,

Vaporization (T100o C),Carbonization (T>150o C),

Pyrolysis (T>300o C).


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PHOTOABLATION

A molecule is promoted to the repulsiveexcited state or to the Franck-Condon vibrationally hot state and followed by

dissociation.The chemical bond is broken, leading to the

destruction of biological tissue.

As electronic transitions occur usually in theUV range, the photo-ablation process is usuallylimited to UV lasers.


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Therefore, excimer lasers(ArF, KrF, XeCl, XeF) are

mainly employed.But higher harmonics of

other lasers can also beapplied.


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PLASMA-INDUCED ABLATION

An ultra short pulse from a Q-switched ormodelocked laser ionizes biological tissue.

This generates a very large density of free

electrons in a very short period of time withtypical values of 1018 cm-3 due to an avalancheeffect.

Free electrons from ionization accelerate tohigh energies and collide with molecules,leading to further ionization.


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Typical lasers used for plasma-inducedablation are Nd:YAG, Nd:YLF,Ti:sapphire with Pico- or femto second

pulses generating irradiance at about1012 W/cm2.

Such a high power density leads to fields

of 10

7

V/cm, comparable with theenergies of electrons revolving in atoms.


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Therefore, the Q-switched ormodelocked lasers can ionizemolecules in biological tissue.

Light electrons and heavy ions moveat different velocities, leading to theeffect similar to that in the acoustic

wave with areas of compression anddilation.


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APPLICATION OF LASERS IN MEDICINE

Lasers have many applicationsDENTISTY,

CARDIO VASCULAR MEDICINE,

DERMATOLOGY,GASTROENTEROLOGY,

GYNECOLOGY,

NEUROSURGERY, andOPHTHALMOLOGY


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BIOLOGICAL EFFECTS OF THE LASER BEAM.

EYE INJURY: Because of the high degree of beam collimation, a laser serves as an almostideal point source of intense light.

A laser beam of sufficient power cantheoretically produce retinal intensities atmagnitudes that are greater than conventionallight sources, and even larger than those

produced when directly viewing the sun.Permanent blindness can be the result.


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THERMAL INJURY

The most common cause of laser-inducedtissue damage is thermal in nature.

Where the tissue proteins are denatured due

to the temperature rise following absorptionof laser energy.

The thermal damage process (burns) is

generally associated with lasers operating atexposure times greater than 10 microseconds.


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In the wavelength region from the nearultraviolet to the far infrared (0.315 m-103 m).

Tissue damage may also be caused by thermally

induced acoustic waves following exposures tosub-microsecond laser exposures.

With regard to repetitively pulsed or scanninglasers, the major mechanism involved in laser-

induced biological damage is a thermal processwherein the effects of the pulses are additive.


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Factors for the Thermal Effects

The absorption and scattering coefficientsof the tissues at the laser wavelength.

Irradiance or radiant exposure of the laser

beam.Duration of the exposure and pulse

repetition characteristics.

Extent of the local vascular flow.Size of the area irradiated.


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The biological effects of non-ionizing laserradiation

Effect Non Ionizing laser radiationinclude the action of visible, ultraviolet(UV), or infrared radiation upon tissues.

Generally, lasers in the UV regioninduce photochemical reactions.

Lasers in the infrared region inducethermal effects.


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Damage can occur when a laser beamencounters tissue, depending on thecombined characteristics of both

the incident laser beam and

the properties of the tissue involved.

Laser wavelength, power density, and pulseduration.

Tissue property to reflect, transmit, orselectively absorb the laser radiation.


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Effect on Eye

The retina, cornea, and lens are the areasmost commonly damaged.

Laser light in the visible to near infrared

spectrum can cause damage to the retina.These wavelengths are also know as the"retinal hazard region.

Laser light in the ultraviolet or far infraredspectrum can cause damage to the cornea orthe lens.


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Laser effects on the skin

Thermal (burn) injury is the mostcommon cause of laser induced skindamage.

Thermal damage is generally associated with lasers operating at exposure timesgreater than 10 microseconds and in the

wavelength region from the nearultraviolet to the far infrared.


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Low level laser therapy

Photo bio-modulation, also known as lowlevel laser therapy (LLLT), cold lasertherapy, and laser biostimulation.

It is an emerging medical and veterinarytechnique in which exposure to low-levellaser light or light emitting diodes might

stimulate or inhibit cellular functionpossibly leading to beneficial clinicaleffects.


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Certain wavelengths of light at certainintensities will aid tissue regeneration,resolve inflammation, relieve pain and boost

the immune system.Observed biological and physiological effects

include changes in cell membranepermeability, up-regulation and down-regulation of adenosine triphosphate andnitric oxide.


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Bio-stimulatory effects of laser

The promotion of healing ofwounds.

Treatment of skin infections.Treatment of ulcers.

Laser may have an enhancing

effect on healing whereverinflammation is present.


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Effects of Laser Light on Tissue

Accelerated Tissue RepairRapid Formation of Collagen

Beneficial Effect on Nerve Cells and

the Production of B-EndorphinsAccelerated Lymphatic System Activity

and Reduction in Edema

Formation of New Capillaries andIncreased Blood Flow


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Accelerated Tissue Repair

Photons of light from a laser penetratedeeply into tissue

This power the synthesis of adenosine

triphosphate (ATP). ATP is a molecule that is a major carrier oenergy from one reaction site to another in allliving cells.

So that the cell can take in nutrients fasterand get rid of waste products.


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Collagen is the essential protein required toreplace old tissue or to repair tissue injuries.

Perhaps the most common example of

collagen is the clear sticky substance foundaround open wounds. Wounds are healed or closed over very

rapidly by the application of laser light.

There is also less scar tissue formed whenlaser light is applied to the area.

B fi i l Eff N C ll d h


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Beneficial Effect on Nerve Cells and theProduction of B-Endorphins

Laser light has a highly beneficial effect on nerve cells which block pain transmitted by these cells to thebrain.

In this case, laser light increases the potential

difference across the cell membrane, thus, decreasingnerve ending sensitivity.

Pain blocking mechanism involves the production o

high levels of painkilling chemicals such asendorphins and enkephelins from the brain, adrenalgland and other areas as a result of exposure to laserlight.


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Accelerated Lymphatic System Activity andReduction in Edema

The problem is that the veins in the legare only capable of removing onecomponent of the swelling.

Blood vessels can remove the water butnot the dirty protein solution that ispresent.

The lymphatic system is required totake away dirty proteins from edema.


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Laser light is capable of doubling the size othe lymphatic ducts in the area of exposureand rapidly removing the protein waste.

Another important aspect of the studyshowed that laser light was capable operfect regeneration of the lymphaticsystem in the immediate area with noleakage and no confused network of ducts.

F ti f N C ill i d


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Formation of New Capillaries andIncreased Blood Flow

Laser light does this extremely well inincreasing blood flow.

The laser light will significantly increase

the formation of new capillaries indamaged tissue.

It is the formation of new capillaries thatspeeds up the healing process, closeswounds quickly and reduces scar tissue.


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Nano Manipulation

Using Nanotechnology and Lasertechnology, manipulation of individualatoms and molecules to build structures

to complex, atomic specifications ispossible.

The atomic force microscope (AFM) is

one of the foremost tools for imaging,measuring and manipulating matter atthe nano scale.


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AFM

The AFM consists of a micro scale cantilever with asharp tip (probe) at its end that is used to scan thespecimen surface.

The cantilever is typically silicon or silicon nitride

with a tip radius of curvature on the order onanometers.

When the tip is brought into proximity of a samplesurface, forces between the tip and the sample leadto a deflection of the cantilever according to Hooke'slaw.


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Forces that are measured in AFM includemechanical contact force, Van der Waals forces,capillary forces, chemical bonding, electrostaticforces, magnetic forces etc.

As well as force, additional quantities maysimultaneously be measured through the use ofspecialized types of probe.

Typically, the deflection is measured using alaser spot reflected from the top surface of thecantilever into an array of photodiodes.


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If the tip was scanned at a constant height, a risk would exist that the tip collides with the surface,causing damage.

In most cases a feedback mechanism is employed

to adjust the tip-to-sample distance to maintain aconstant force between the tip and the sample.

Traditionally, the sample is mounted on apiezoelectric tube, that can move the sample in thez direction for maintaining a constant force, andthe x and y directions for scanning the sample.


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The AFM can be operated in a number ofmodes, depending on the application.

In general, possible imaging modes are divided

into static modes and a variety of dynamicmodes where the cantilever is vibrated.

The static mode can also be called as Contactmode.

The dynamic mode is otherwise called as NonContact Mode.

AFM til i th S i El t


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AFM cantilever in the Scanning ElectronMicroscope, magnification 3,000 x


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Static mode

The static tip deflection is used as a feedbacksignal.

Because the measurement of a static signal is

prone to noise and drift.Low stiffness cantilevers are used to boost

the deflection signal.

However, close to the surface of the sample,attractive forces can be quite strong, causingthe tip to 'snap-in' to the surface.


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Thus static mode AFM is almost alwaysdone in contact where the overall force isrepulsive.

Consequently, this technique is typicallycalled 'contact mode'.

In contact mode, the force between the

tip and the surface is kept constantduring scanning by maintaining aconstant deflection.


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Dynamic Mode

The cantilever is externally oscillated at orclose to its fundamental resonance frequencor a harmonic.

The oscillation amplitude, phase and

resonance frequency are modified by tip-sample interaction forces.

These changes in oscillation with respect to the

external reference oscillation provideinformation about the sample's characteristics.


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Schemes for dynamic mode operationinclude frequency modulation and themore common amplitude modulation.

In frequency modulation, changes in theoscillation frequency provide informationabout tip-sample interactions.

In amplitude modulation, changes in theoscillation amplitude or phase provide thefeedback signal for imaging.


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Identification of individual surface atoms

The AFM can be used to image andmanipulate atoms and structures on a varietyof surfaces.

The atom at the apex of the tip "senses"

individual atoms on the underlying surface when it forms incipient chemical bonds witheach atom.

Because these chemical interactions delicatelyalter the tip's vibration frequency, they can bedetected and mapped.

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Application in Cell Biology

Forces corresponding tothe unbinding of receptor

ligand couplesunfolding of proteins

cell adhesion at single cell scalehave been gathered.


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Biomedical Laser Beam Delivery Systems

Beam delivery systems for biomedicallasers guide the laser beam from theoutput mirror to surface of the tissue.

Beam powers of up to 100 W aretransmitted routinely.

All biomedical lasers incorporate a

coaxial aiming beam, typically from a He-Ne Laser (632.8 nm) to illuminate thetissue.

BEAM GUIDING METHODS


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BEAM GUIDING METHODS

A flexible fused silica (SiO2) optical fibergenerally available for laser beam wavelengths between 400 nm and 2.1 m, where SiO2 is

essentially transparent.

An articulated arm having beam guidingmirrors Can be used for wavelengths greater than~2.1 m (e.g. CO2 lasers), for the Er:YAG (erbium

doped YAG laser) and for pulsed lasers having peakpower outputs capable of causing damage to opticalfiber surfaces due to ionization by the intense electricfield (e.g. pulsed ruby).


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The arm comprises straight tubular sectionsarticulated together with high quality powerhandling dielectric mirrors.

The mirrors are present at each articulationjunction to guide the beam through each of thesections.

Fused Silica optical fibers usually are limitedto a length of 1 3 m and to wavelengths inthe visible - to low midrange IR (< 2.1 m).


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Fused silica fibres cannot be used for longer

wavelengths of IR radiation, since longer radiationare absorbed by water impurities ( 5 m).

Since the flexibility, small diameter, and smallmechanical inertia of optical fibers allow their usein either flexible or rigid endoscopes.

They offer significantly less inertia to handmovement, fibers for use at longer IR wavelengths.


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Material systems showing promise are fused Al2O3fibers in short lengths for near - 3 micro meterradiation of the Er:YAG laser

Ag halide fibers in short lengths for use with CO2

laser emitting at 10.6 m. A flexible hollow Teflon waveguide 1.6 mm in

diameter having a thin metal film overlain by a

dielectric layer has transmitted 10.6 m CO2radiation with attenuation of 1.3 and 1.65 dB/m forstraight and bent (5 mm radius, 90 degree bend)sections respectively

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20 Bio Medical Lasers