Medical applications of laser 3

1. Dr. Hossam Eldin Sayed Ali
Lecturer of medical Biophysics
The Research Institute of Ophthalmology

2.  An equal flow of energy can be supplied by changing
the exposure time and wavelength (λ) of the laser
radiation so that we can reach the high intensities like
1016 W/cm2.
 There are 4 types of interactions of the laser beam
with tissues:
 Photochemical.
 Photothermal.
 Photoablative.
 Photomechanical
interactions.

3.  PHOTO-CHEMICAL laser causes chemical change or
response; the light has a chemical impact on the
tissue being treated. Examples include: Photo
Dynamic Therapy (PDT) Cancer treatment,
ophthalmic treatments, and Laser therapy in pain
relief.
 PHOTO-THERMAL occurs when we use long pulses,
biological effect due to heating such as hair removal,
and most surgical lasers.
 PHOTO-MECHANICAL: Short-pulsed (q-switched)
lasers cause pressure waves that can stimulate the
lymph draining system leading to dissolution of
inflammatory mediators.
 Photoablation such as in tattoo removal.

4.  The interactions are based on the absorption of
radiation by :
 Water contained in the tissues.
 Hemoglobin in the blood
 Pigments or chromophores in some tissues normally
present (or externally administered).

5.  1-The photochemical (Photodynamic) interaction:
 occurs when the energy of photons is greater than that of
chemical energy bond, typically greater than 5 eV;
 Occurs at very low levels of intensity or irradiance (I ~ 1
W/cm2)) and for high exposure times (duration time
greater than a second).
 The field of action is that of ultraviolet radiation that
generates chemical fragmentation effects.
 (If the energy density deposited is very high it is possible to
achieve an ablation with high spatial control) (KrF laser,
ArF). In this case the contours of the spots must be well-
defined for the prevention of thermal spreads.
 The energy absorbed in the tissue is used for structural
modifications of the existing molecules, in fact the
reaction: hν + A + B →(AB) …. a molecule A and another
one B receives energy hν, a new product AB will be
produced.

6.  Fluence rates below the hyperthermia threshold can be
used for PDT (PhotoDynamic Therapy) , a two-step
modality in which the delivery of a light activated and
lesion-localizing photosensitizer is followed by a low,
non-thermal dose of light irradiation to kill cancer cells.
 Almost all photochemical reactions of biological
relevance are dependent on generation of reactive
oxygen species (ROS). The most important is 1O2
 1O2 (Singlet oxygen) is a high energy form of oxygen
 It is the lowest excited state of the dioxygen molecule.
Its lifetime in solutions is in the microsecond range (3
µsec in water).
 It undergoes several reactions with organic molecules.
 It is believed to be the major cytotoxic agent involved in
PDT.

7.  It is not possible to generate 1O2 by light of higher
wavelengths than about 800 nm. Thus, for PDT one
has to use radiation in the UV or visible range.
 Because of the optical window of tissue ‘between’ 620
and 1100 nm, yielding optimal penetration depths (∼1–
3mmat 630 nm), red light is most frequently used for
PDT.
 The red band of heme proteins is at 620 nm, so
chemicals (sensitizers) such as Porphyrins, chlorines
and phthalocyanins that absorb beyond 620 nm are
being used for laser PDT.
 Several lasers can be applied, notably dye lasers and
diode laser.

8.  Absorption of 10 light quanta can give as many as six 1O2
molecules, so the process is extremely efficient, and sub-
hyperthermal fluence rates can be satisfactory.
 Singlet oxygen has a short lifetime of 10–40 ns in cells and
tissues, and its radius of action is only about 10–20 nm.
 This means that PDT acts selectively on targets with high
concentrations of sensitizer . PDT Tumor selectivity is based
on this principle.
 The tumor selectivity of sensitizer accumulation can be
related to a number of factors:
 -Low tumor pH (several sensitizers protonate and get more
lipophilic below pH 7),
 -High concentration of lipoprotein receptors in tumours
(many sensitizers are bound to lipoprotein in the blood),
 -Presence of leaky microvessels with low lymphatic drainage
in tumors, and a high concentration of macrophages (taking
up aggregated sensitizers) in tumors

9.  Diagnostic uses of PDT:
 Based on the concept of photochemical reactions of
light, there are some biomedical techniques that allow
us to diagnose cancer of the larynx, esophagus and
bladder, they can show the differentiations of the
tissues, and their metabolic activities, which gives a
precise diagnosis of the disease by the analysis of the
fluorescence spectrum of the organ.
 Some examples of diagnostics based on the
fluorescence of different tissues as a function of the
wavelength emitted by them when they are hit by UV
light are shown here.

10.  Fluorescence spectrum emitted from different tissues
irradiated with UV light (a) and tumor tissues of the
bladder (b) which is injected with Photofrin 48 hours
before the investigation.
 By irradiating healthy tissue and the tumour with radiation
of a wavelength 405 nm, we observe a very strong reduction
of fluorescence in the blue-green region with respect to the
healthy tissue.

11. 2-Photothermal interactions:
 Occur when the energy of the used photons is lower
than the binding energy and by using infrared lasers,
such as Nd: YAG or CO2 lasers, and using power
densities above 100 W/cm2, or by irradiation with
pulsed lasers of durations between 1 ms and 5 sec.
 In infrared and visible ranges these interactions
produce thermal effects on the irradiated tissues.
 Chromophores in the tissue absorb the irradiation
photons, which bring it into an excited rotovibrational
state, this subsequently damps the inelastic collisions
with the surrounding molecules leading to an
increase of its own kinetic energy or thermal energy.
 Once the laser light is absorbed, a consequent rapid
non-radiative decay occurs inducing a local
temperature increase.

12.  The effects of temperature can cause different degrees of
damage as a function of irradiation time.
 For temperatures from 45°C - 50 °C the thermal damage
involves heating and hyperthermia of healthy tissue, and may
result in necrosis of the tissue.
 Denaturation occurs at temperatures between 50° and 100° C
the of the biomolecules and their aggregates (proteins,
collagen, lipids, hemoglobin) or irreversible coagulation of
proteins.
 High heating causes an irreversible deformation of these
structures and loss of protein function. The denatured
cellular material is absorbed by the body and replaced with
scar tissue. These processes of photocoagulation are used for
example in eye surgery for the reduction of retinal
detachments, and in dermatology for the treatment of
vascular lesions by using continuous Argon laser (488 and
514,5 nm).

13. Scheme of the thermal interaction in biological tissue for
different temperatures.
 When the temperature of the tissue reaches about 100 °C
the water constituting most of the soft tissues, vaporizes,
dehydrating the tissue. When the water present in the
tissue is completely evaporated, the tissue temperature
rapidly increases up to about 300 °C and the tissue burns.
In this case the vaporization together with the
carbonization gives rise to the decomposition of the
constituents tissue.

14. 3- The fotoablative interactions:
 Occurs when the intensity and wavelength of the laser exceed
certain threshold values that allow the removal of layers of
material from the irradiated target;
 Requires high power density (107-1010 W/cm2) and pulse durations
ranging typically from 10 to 100 ns.
 Many biomolecules absorb strongly in the UV band (200-320 nm)
and in the visible band (400-600 nm); such strong absorptions
involve a localized molecular dissociation that may be
accompanied by thermal effects like evaporation. Ionization with
the formation of plasma and removal of material from the target
usually happens with high power densities.
 The photoablation process is therefore the photodissociation of
macromolecules in repulsive photoproducts :
hν + AB → (AB)* → A + B*
and the transfer of energy to atomic and molecular species that
are emitted at high speed from the irradiated target.
 In the photoablation process the residual energy that is not used
to break molecular bonds in the photoproducts remains in in
tissue the form of translational kinetic energy.

15.  This translational kinetic energy causes the instant high-speed
ejection of photoproducts from the area irradiated by the laser
beam. Similar effects may also be obtained by visible lasers with
intensity of the order of 1010 W/cm2.
 The process of photoablation is related to the product of laser
intensity multiplied by the square of the wavelength (I λ2 )
 Laser pulses are focused on tissue with intensities greater than
108 W/cm2; the radiation is strongly absorbed by the molecules,
such as protein, starche and peptides, until a penetration
depths of about 1 μm. It is followed by a high excitation of
macromolecules with the formation of photodissocitation in
repulsive photoproducts; finally an expulsion of photo products
at supersonic speed without tissue necrosis or thermal effects
are produced in the case of UV band.

16.  The removal of atoms, molecules, clusters from
the tissue, through laser irradiation, can be
described by the curves of the ablation rate, which
represent the removal rate as a function of the
used laser fluence.
 The ablation threshold is the minimum level of
radiation above which the removal of tissue is
produced and below which only fluorescence
effect and heating, without any ablative effect
occur. This parameter is important for the analysis
of the ablation process, and it is generally
expressed by the laser fluence threshold (J/cm2).

17.  4-The Photomechanical interaction:
 Takes place when the laser pulses impinging the material
have high intensities greater than 1010 W/cm2 and the tissue
absorbs them.
 Ionization effects are induced; they generate a plasma which
causes cavitation effects

18.  In addition to the direct dynamic effect of shock waves
on interfaces, so-called cavitation occurs in certain
media such as water and sometimes body tissue as
well. Cavitation bubbles occur directly after the
pressure/tension alternating load of the shockwaves
has passed the medium. A large number of bubbles
grow and then violently collapse while emitting
secondary spherical shock waves.
 Cavitation is a biologically effective mechanism
produced by shockwaves, which can be selectively
used in localized areas, even in deeper tissue layers.
The physically induced energy causes biological
reactions via different mechanisms.