Dr. Hossam Eldin Sayed Ali

Lecturer of medical Biophysics

The Research Institute of Ophthalmology

Important Points to remember:

Laser pumping is the act of energy transfer from an external source into the gain medium of a laser. The energy is absorbed in the medium, producing excited states in its atoms. When the number of particles in one excited state exceeds the number of particles in the ground state or a less-excited state, a process known as population inversion is achieved. In this condition, the mechanism of stimulated emission can take place and the medium can act as a laser or an optical amplifier.

The pump power must be higher than the lasing threshold of the laser.

The pump energy is usually provided in the form of light or electric current, but more exotic sources have been used, such as chemical or nuclear reactions.

Population Inversion

A state of the gain medium where a higher-lying electronic level has a higher population than a lower-lying level, this is achieved after adequate pumping

In simple cases, a laser transition, on which optical gain occurs as a result of stimulated emission, can occur only when the population of the upper laser level is higher than that of the lower level (i.e. more laser-active atoms or ions are in the higher level). This condition of the laser medium is called population inversion.

Continuous wave (CW) Laser

Continuous-wave (cw) operation of a laser means that the laser is continuously pumped and continuously emits light. The emission can occur in a single resonator mode (single-frequency operation) or on multiple modes.

Pulsed lasers:

Pulsed lasers are lasers which emit light not in a continuous mode, but rather in the form of optical pulses. The term is most commonly used for Q-switchedlasers emitting nanosecond pulses. Versatile types of PL can be produced depending on: the pulse duration, pulse energy, pulse repetition rate and wavelength

The term Pulsed Laser is most commonly used for Q-switched lasers emitting nanosecond pulses. VIDEO

Nanosecond pulses in the ultraviolet spectral region are generated with excimer lasers.

The picosecond or femtosecond pulses are usually generated with mode-locked lasers. VIDEO

milli = 1E-3 micro = 1E-6 nano = 1E-9 pico = 1E-12 femto = 1E-15

atto = 1E-18.

Excimer Laser Excimer stands for excited di meris, a family of lasers that have

repetitively pulsed output, emit powerful pulses lasting for nanoseconds or tens of nanoseconds, at wavelengths in or near the ultraviolet, and the lasing medium is a diatomic molecule, or dimer, in which the component atoms are bound in the excited state but not in the ground state.

Sometimes more correctly called an exciplex laser

The most important excimer molecules are rare gas halides such as XeF and XeCl.

Average output power (in watts) is the product of the pulse energy (in joules) multiplied by the number of pulses per second (repetition rate). Typical average powers range from under a watt to over 100W.

Semi conductor (diode) lasers

An electrically pumped semiconductor laser in which the active laser medium is formed by a p-n junction of a semiconductor diode similar to that found in a light-emitting diode.

The laser diode is the most common type of laser produced with a wide range of uses that include fiber optic communications, barcode readers, laser pointers, CD/DVD/Blu-ray Disc reading and recording, laser printing, laser scanning and increasingly directionallighting sources.

The LED consists of a chip of semiconducting material doped with impurities to create a p-n junction. As in other diodes, current flows easily from the p-side, or anode, to the n-side, or cathode, but not in the reverse direction. Charge-carriers—electrons and holes—flow into the junction from electrodes with different voltages. When an electron meets a hole, it falls into a lower energy level and releases energy in the form of a photon.

Holography

How do Laser React With Tissue

Laser as one of the electromagnetic waves, reacts in one of the following ways when it strikes a surface:

Reflection,

Absorption

Scattering

Reflection occurs as a consequence of the change of the refractive index between air and tissue, a small fraction of the radiation is reflected back.

Absorption and scattering of the remaining fraction occurs when the beam is propagated into the tissue.

The absorption of light energy, and the transformation of the light into heat, is essential for the tissue reactions to occur.

The optical response of the tissue depends mainly on the effective absorption coefficient which takes account of absorption and scattering of the tissue at the used wavelength

Mechanisms Laser beam intensity is an important parameter for

the study of the effects of macroscopic and microscopic interaction of laser with matter and is defined as: The ratio of the emitted beam power (in watts) to the unit of irradiated area in square cm.

The laser intensities can be classified into:

High ( >1016 W/cm2),

Medium ( ~1010 W/cm2) and

Low ( <106 W/cm2). The latter in particular are used in medicine for diagnostic use, those intermediate for surgical use and those of high power mainly for research purposes.

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.

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.

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).

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.

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.

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.

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