LASERS IN GENERAL SURGERY 0039-6109/92 $0.00 + .

20

LASER-TISSUE INTERACTIONS
Photochemical, Photothermal, and
Photomechanical
Steven L. Jacques, PhD

When the novice medical laser practitioner first tries a laser, he or

she commonly follows a simple and very reasonable procedure. He
cautiously sets the laser at a modest power setting and delivers a laser
exposure to a test tissue. Nothing happens. He increases the power
setting and tries again. Again, nothing happens. A third try at a higher
setting achieves a "definite effect." Thus, the novice has introduced
himself to the concept of a "threshold laser exposure." He proceeds
systematically to test the variety of available lasers on a variety of tissue
types and map the threshold laser exposure over the operational range
of laser versus tissue. Now, he can achieve a definite effect predictably.
This is a pragmatic and logical approach.
If there were only one type of laser-tissue interaction, the above
lesson would be sufficient. But the variety of laser-tissue interactions
can make dosimetry a nonlinear, dynamic process. The definite effect
observed can actually involve one of several types of effect.
In this article, I discuss the variety of laser effects and how the
characteristics of various lasers and various tissues allow different
effects to occur. I shall approach the problem of laser-tissue interactions
just like the novice, by turning up the laser power until something
happens. However, in this article, I do not discuss thresholds but
rather concentrate on what is going to happen.

LASER-TISSUE INTERACTIONS: A SCHEMA

The complexity of laser-tissue interactions is schematically por-
trayed in Figure 1. The three axes (x, y, z) of this interaction cube are

From the Laser Biology Research Laboratory, University of Texas M. D. Anderson Cancer
Center, Houston, Texas

SURGICAL CLINICS OF NORTH AMERICA

VOLUME 72 • NUMBER 3 • JUNE 1992 531

532 JACQUES

Biologic
level of Cell z2
interaction y3 Long-tenn healing
-~
Organelle zl y2 Delayed response o~ !
yl Immediate physical effect ~~ ~
~
x3 Photomechanical
x2 Photothennal
x I Photochemical

Mechanism of
interaction
Figure 1. Laser-tissue interaction cube. The three axes are (x) the mechanisms of
interaction, (y) the time course of the tissue response, and (z) the level of biologic structure.

the interaction mechanism, the time course of the tissue reaction, and
the level of biologic organization. When a laser irradiates a tissue and
something happens, that event will map somewhere in this cube. The
mechanisms of interaction can be characterized as photochemical (Xl)'
photothermal (x2), or photomechanical (X3)' The time course of the
tissue reaction is described as either an immediate physical effect (YI),
a delayed biologic response (Y2)' or long-term healing (Y3)' The level of
biologic organization affected by the laser-tissue interaction can be
either organelles (Zl)' cells (Z2)' or tissues (Z3)'
Let us first consider some example laser-tissue interactions that
illustrate how to use the cube description. The reader should appreciate
that this cube is simply a mechanism for provoking and organizing a
discussion of laser-tissue interactions: it is not intended as a definitive
statement of fact. In following the examples, the reader should feel
encouraged to challenge statements and insert new ideas. The cube
simply draws lines of discrimination as one tries to dissect a single
complex process of interaction into its components. In the later section,
I consider the generic mechanisms of some photochemical, photother-
mal, and photomechanical effects.

EXAMPLES OF LASER-TISSUE INTERACTIONS

Photodynamic Therapy

Figure 2 illustrates one form of photochemical interaction called

photodynamic therapy. This form of light-activated chemotherapy in-
 LASER-TISSUE INTERACTIONS 533

Photochemical
mechanism
Figure 2. Schematic depiction of photodynamic therapy.

volves the reaction of a photon with a photosensitive dye and oxygen

to yield a toxic product that contributes to cell death (discussed again
later). The immediate effect occurs on the subcellular level, with
organelles such as the mitochondria or lysosomes often being the
primary target. Direct effects on membranes and DNA are also possible.
Therefore, the initial interaction is classified as photochemical, involving
subcellular or organellar structures (Xl' YI' Zl)' The delayed biologic
response to this toxic insult is cell death (Xl' Yz, zz). There is a subsequent
healing response that affects the tissue or organ as a whole (Xl! Y3' Z3)'

Hyperthermia

Figure 3A illustrates one form of thermal interaction, called hyper-

thermia. Generally, hyperthermia involves a long exposure to a mildly
elevated temperature, and the effects are not immediately apparent to
the eye but rather usually require at least 24 hours to develop into
necrosis. The thermal energy causes denaturation and irreversible
aggregation of macromolecules within the cell, which affects the meta-
bolic machinery (xz, YI' Zl)' Consequently, there is eventual cell death
(xz' Yz, zz)· The concept of hyperthermia is to cause minimal effect on
normal tissues but to stress cancer cells, making them more susceptible
to radiation or other therapeutic modalities. A healing response is not
shown in Figure 3A to emphasize this selective action on cancer cells.
However, one could easily justify including a healing response.

Photocoagulation

Figure 3B illustrates photocoagulation. The distinction between

photocoagulation and hyperthermia is not strictly defined, but gener-
ally, photocoagulation requires only a short exposure to a high temper-
ature and the effects are immediate and visible. Photocoagulation is a
534 JACQUES

on metabolic

A mechanism

fonnation
I
Fibroblasts
activated to
synthesize
collagen

_00)
cell and tissue
levels

Photothennal
B mechanism
Figure 3. Photothermal effects. A, Hyperthermia. B, Photocoagulation.

more obvious form of thermal injury than hyperthermia and causes

immediate visible changes in the tissue. As a specific example, consider
the photocoagulative procedure of using the argon laser to anchor a
detached retina. The immediate effects are coagulation of cells (X21 Yll
Z2) and extracellular collagen (X21 Yll Z3). The delayed biologic response
involves inflammation on both the cellular (X21 Y21 Z2) and the tissue
levels (X21 Y21 Z3). The healing response involves activation of fibroblasts
to synthesize collagen (X21 Y31 Z2), with scar formation on the tissue
level (X21 Y31 Z3). The subsequent scarring response strongly anchors the
retina to the underlying tissue.

ArF Excimer Laser Ablation

A rather complicated example of laser effects is the procedure for

ablation of skin tissue by the ArF excimer laser (ultraviolet wavelength
193 nm, pulse duration 14 nanoseconds). The interaction cube helps us
discuss the different aspects of this complex laser-tissue interaction
(Fig. 4).
 LASER-TISSUE INTERACTIONS 535

Sloughing of
ischemic tissue, and
subsequent healing.

Physical mel;hallisnls
of tissue ablation.

Cellular repercu
of genetic altera

Photochemically
induced genetic
alterations.
Photo- Photo- Photo-
chemical thermal mechanical
Figure 4. ArF excimer laser ablation of tissue (193-nm wavelength, 14-nanosecond pulse
duration).

The photochemical effects begin with the photochemical bond

breaking, which aids the ablation process at the tissue level (Xli YI' Z3)'
There is some degree of photochemical alteration of the DNA, either
by the original 193-nm photons or by the induced fluorescent photons
in the Ultraviolet (UV)C and UVB spectral region (Xl' YI' Zl)' The cellular
repercussions of such DNA effects may be described as Xli Y2' Z2' A
layer of several micrometers of unablated tissue receives photons that
lead to the delayed response of cellular death in a 7- to 9-fLm zone (Xli
Y2' Z2) .26
The photothermal effect involves the vaporization of tissue, which
achieves immediate tissue ejection (X2' Yll Z3)' Although one should
also consider thermal injury to the unablated tissue, the ArF excimer
laser causes negligible thermal injury unless high repetition pulse rates
are applied. Therefore, delayed thermal effects are not included in the
figure. The eventual healing process treats the wound like a simple
scalpel cut, with minimal scar formation, in contrast to the scar forma-
tion that occurs with thermal injury.24, 25 Therefore, carefully executed
ArF excimer laser ablation shows little of the signature of the healing
response of a thermal wound.
Photomechanical effects are involved, as mass is ejected from the
tissue at high speeds (X3' Yll Z3).15 Stress waves induced by ablation
cause deeper cellular injury characterized by nuclear and mitochondrial
disruption, which are immediate responses at the organellar level (X3'
Yt, Zt)·26 Photomechanical damage leads to delayed necrosis of the
photomechanically sensitive cells, especially the endothelial cells that
support blood vessels (X3' Y2' Z2)' The blood vessels subsequently
occlude to yield an ischemic tissue region, which is a delayed response
at the tissue level (X3' Y2' Z3)' The healing process is primarily a
neutrophil margination of the ischemic region (X3' Y3' Z3).4 Therefore,
the principal healing response appears to be the result of the delayed
biologic response and long-term healing response to the photomechan-
ical injury to the vasculature's endothelial cells that evolves into ische-
mia.
536 JACQUES

MECHANISMS OF LASER-TISSUE INTERACTION

This section is limited to a discussion of the mechanisms of laser-

tissue interaction (X123) from the perspective of immediate physical
effects (Yl)' The biologic response (Y2) and the long-term healing
response (Y3) to the three types of laser-tissue interaction are important
research and clinical topics but are not discussed here. The details of
effects at the organelle, cell, and tissue levels (Z123) could alone constitute
a paper. 21 The modest goal of this paper is to convey the laser dosimetry
that governs the three principal physical mechanisms of initial interac-
tion: photochemical, photothermal, and photomechanical.

Laser Sources

The common medical lasers (C02, Nd:YAG, argon) are continuous

and deliver 1 to 100 W of power, and usually, the laser exposures are
in the range of 0.1 to 100 seconds. Pulsed lasers have more recently
entered the clinic and deliver pulse energies of 0.01 to 10 J and pulse
durations from 100 femtoseconds to 500 microseconds. Pulsed-dye
lasers employ a dye solution as the lasing medium (e.g., the dye laser
for dermatology). Pulsed solid-state lasers employ a solid-state crystal
or glass as the medium (e.g., ruby, Nd:YAG, Er:YAG, Ho:YAG). If a
pulsed laser strikes special solid-state crystals, the laser's frequency can
be doubled to achieve a shorter wavelength. For example, the KTP
crystal halves the 1064-nm wavelength of the Nd:YAG laser to 532 nm.
Most of the pulsed lasers deliver about 0.1 to 10 J per pulse. One
joule of energy will raise the temperature of 1 cc of water only 0.24°C
and is not a lot of energy. However, this modest energy can be squeezed
into a very short pulse with high power as long as the product of
power and duration equals the total pulse energy
energy = (power)(duration) (1)
So pulsed lasers may not be so energetic, but they can be powerful if
the pulse is short. Confining a 1-J laser pulse to 1 nanosecond yields a
gigawatt laser!
Confinement can also occur spatially. A laser operates at a single
wavelength. The targeted tissue has optical properties at that single
wavelength that restrict the penetration of laser light. Both absorption
and scattering prevent light from penetrating tissue beyond a superficial
layer. If the penetration depth of the light is limited, then the laser is
spatially confined, and extremely high energy densities (energy per
unit volume) may be achieved during laser irradiation. The "optical
zone" of interaction for a particular laser depends on the depth of
penetration of the laser's optical energy into the target tissue. When
our 1-J laser pulse is spread out over a 1-cm2 surface area and penetrates
about 1 cm deep into an aqueous solution, the volume of interaction is
about 1 cc and the temperature rise is about 0.2°C. However, if that
 LASER-TISSUE INTERACTIONS 537

same laser pulse penetrates only 1 /-Lm, the volume of interaction is a

thin superficial layer, and the apparent temperature rise will be 2000°C!
The penetration depth of a particular wavelength into a particular tissue
is as important as the laser pulse energy itself.
The penetration depends on the optics of the tissue. For example,
an Ar laser may have no effect on the enamel of one's tooth but will
cause serious injury to the pigmented retinal epithelium of one's eye.
The penetration of laser light into the enamel is deep, and the laser
energy is distributed, whereas the absorption by the retinal melanin
pigment confines the energy to a thin layer, achieving a high energy
density that elicits injurious thermal effects.
"Confinement" is a key word that is used throughout this paper.
I have discussed confinement in time based on the laser pulse duration,
tp' and confinement in space of a laser's energy to the optical zone of
light penetration, B, at the laser wavelength, A. Later, I will discuss
confinement of laser-induced mechanical and thermal energy, which
depends on the combination of tp and B. Therefore, knowing a laser's
exposure energy is only half the problem: knowledge of the laser's
pulse duration and optical penetration into a target tissue is equally
important.

Tissue Optics and the Optical Zone

First, a brief discussion of tissue optical properties is presented.

Second, the "optical zone" of laser energy deposition is discussed.
Three aspects of tissue optics are mentioned: (1) light penetration from
a broad uniform irradiance; (2) light penetration from a narrow laser
beam; and (3) selective absorption by pigmented tissue structures. The
broad irradiance is essentially a one-dimensional problem of light versus
depth, and the tissue optics determine the optical zone. The narrow-
beam problem is a two-dimensional one in which light can diffuse both
down into the tissue and laterally to the side of the laser beam. The
geometry of the laser beam (e.g., an optical fiber delivery system), not
the tissue optics, may determine the optical zone. In the selective
absorption problem, energy is deposited in a pigmented target, and
the size of the pigmented structure, not the optics or the beam
geometry, determines the optical zone.

Tissue Optical Properties

The pertinent optical properties of a turbid tissue are its absorption
coefficient, /-L., and its effective scattering coefficient, /-Ls(l - g), which
is often denoted as /-L:. The latter term consists of two factors, the
scattering coefficient, /-Ls' and the anisotropy, g. The following para-
graphs define these terms.
The absorption coefficient, /-La' is in units of cm -1, and its inverse
value, l//-La' indicates the mean free path before absorption occurs. For
538 JACQUES

example, if f-La equals 0.3 cm-t, then the mean free path before
absorption is 110.3 or 3.3 cm.
The scattering coefficient, f-Ls' is also in units of cm -I, and its
inverse value, 1If-Ls', indicates the mean free path between scattering
events. For example, if f-Ls equals 40 cm -I, then the mean free path is
1140 or 0.025 cm or 250 f-Lm. On the average for our example, a photon
would be scattered every 250 fl-m and would scatter 133 times before
being absorbed.
The anisotropy, g, indicates the angular deflection of a photon's
trajectory caused by a scattering event. The anisotropy equals the
expectation value, <cose>, where e is the photon deflection angle.
For typical tissues, g is about 0.9, which corresponds to an average
photon deflection of e = 26°, which is only a modest deflection. 9 The
effectiveness of light scattering is described by the product f-Ls(1- g). A
g of 0.9 implies that scattering is only 10% effective (1 - g). A g of
zero, which occurs for isotropic scattering that scatters light randomly
in all directions, implies that scattering is 100% effective. If g equals
0.9, then a photon must be scattered 10 times to achieve the randomi-
zation equivalent to a single isotropic scattering event. Therefore, in
tissue optics, the term f-Ls(1 - g) is often used to describe scattering.
The effective scattering coefficient, f-Ls(1- g) or simply f-L.', is in
units of cm-t, and its inverse value, 1If-L.', indicates the mean free path
before a photon's trajectory has become randomized. Thereafter, the
photon movement is equivalent to a random walk with steps of 1If-L.'
between isotropic scattering events. For example, if f-Ls(1 - g) equals
40(1 - 0.9) or 4 cm-t, the mean free path is % cm or 2.5 mm.
Table 1 summarizes the optical properties of a typical soft tissue
for a variety of lasers with different wavelengths. 2 These values are
approximate as optical properties actually vary for different types of
tissues.
Broad-beam Light Penetration. The absorption and scattering by a
tissue will limit the penetration of laser light into it. If a tissue is simply
a transparent medium, then only its absorption will attenuate light. If
the tissue is turbid, then scattering will confine the light to a superficial

Table 1. TYPICAL OPTICAL PROPERTIES

Wavelength Absorption Scattering Penetration
Laser (nm) IL. (cm-') IL.' (cm-') Depth, I) (mm)
Er:YAG 2960 10,000 0.001
ArF excimer 193 6000 0.002
CO2 10,600 500 0.019
XeCI excimer 308 25 35 0.200
Argon ion 488 10 30 0.300
Nd:YAG/KTP 532 2 25 0.800
Photodynamic 630 0.3 4 5.1
Nd:YAG 1064 0.1 3 10

If fL. ;", fL.', then 1> equals 1/fL. else 1> equals 11"\1'3 fL.(fL. + fL.') in em; fL.' = fL.(1 - g).
 LASER-TISSUE INTERACTIONS 539

layer near the surface and thereby also attenuate the penetration of
light into the tissue.
Figure 5 illustrates light penetration into a clear versus a turbid
tissue. The clear and the turbid tissues have the same absorption
coefficient: the turbid tissue simply has added scattering. The attenua-
tion of laser light in both tissues follows a simple exponential decay,
but there are some differences. The expressions are summarized:
clear tissue: 'I'(z) = '1'0 exp( - J.Laz) (2a)
turbid tissue: 'I'(z) = '1'0 k exp( - z/8) for z > 8 (2b)
where '1'0 is the delivered laser irradiance in W/cm2, 'I'(z) is the fluence
rate (W/cm2) within the tissue as a function of depth, J.La is the absorption
coefficient cm- I , and 8 is the penetration depth (cm), which depends
on both absorption and scattering (see below). The term k is a constant
that accounts for the backscatter of light by the turbid tissue (see
below).
Note how light scattering causes laser energy to pile up near the
surface. In this example, k equals 4.4. Although only '1'0 is delivered to
the tissue, the accumulation of backscattered light near the surface
makes the apparent irradiance equal k'l'o' or 4.4'1'0' Near the surface,
Equation 2b is not accurate, but deeper in the tissue (z >8), it is quite

,.-...
N 5
a
u
~g 4
'-'~ ...... With scattering,
(I) ....
.... I=i light accumulates near surface.
~ ......
I-<..c::
/
3
(I) .-:::
u ~
§
-
~
::s 2 Without scattering,
light is absorbed as it penetrates.

\jf
0
= 1 W/cm2
... I
.. _---
0
0 10 20 30
Depth in tissue (mm)
Figure 5. Broad-beam laser penetration into clear versus turbid tissue. The penetration of
a broad beam is plotted as fluence rate (W/cm2) versus depth (mm) in a Monte Carlo
simulation with an air-tissue surface boundary. With scattering, the light is backscattered
toward the surface, where it accumulates. N.ote that the surface concentration of light
exceeds the delivered irradiance, '1'0 = 1 W/cm 2. The optical properties are absorption, fL.,
= 0.3 cm-'; scattering, /L" = 40 cm-'; anisotropy, g, = 0.9, and effective scattering, /L,',
= 4 cm-', which are typical for a red wavelength in tissue. The dashed line indicates the
approximate expression <I>(z) = <l>ok exp( - z/8) , for z > 8, where k is 4.4 and 8 is 5.1 mm.
540 JACQUES

accurate. Therefore, Equations 2a and 2b provide a simple prediction

of the optical zone of laser interaction for a broad beam.
To make use of Equation 2b for turbid tissues, both 8 and k must be
known. To specify the penetration depth, 8 (cm), diffusion theory
states:
1
8 = (3)
Y3l-1a(l-1a + 1-1.')
Equation 3 applies to a turbid tissue in which scattering predominates
over absorption (1-1.' > l-1a). Both absorption and scattering affect light
penetration.
To specify k, the constant that accounts for the accumulation of
backscattered light, the amount of diffusely reflected light, Rd , is the
only parameter needed:
k = 3 + 5.1Rd - 2 exp(-9.7 Rd) (4)
This equation was determined by computer simulations of light distri-
butions for a tissue with a refractive index of 1.37, typical of a tissue
with 80% water content (Monte Carlo).6 It does not depend on the
wavelength or the tissue optical properties but simply on the reflectance
and tissue refractive index.
The diffuse reflectance, Rd , depends on the tissue optical proper-
ties, which vary with wavelength. Saidi et aP9 have provided a simple
expression for diffuse reflectance from an optically thick tissue:
(5)
In summary, the above equations conveniently provide a good
approximation of the light distribution in a tissue irradiated with a
broad beam. Given optical properties of l-1a and 1-1.', first compute 8.
Then compute Rd' Then compute k. Finally, compute 'I'(z). These are
simple equations that are easily calculated on any computer spread
sheet.
Narrow Laser Beams. When a laser beam is narrow, the problem
becomes two dimensional: light will diffuse both laterally and as a
function of depth. At the edges of the area of laser irradiation, photons
can diffuse laterally and deplete the tissue irradiance. With a very large
beam, such edge losses are not important, and the W(z) along the axis
of the central region corresponds to the one-dimensional expression of
Equation 2b. However, when the laser spot become less than the value
of 48, the edge losses from one side of the beam superimpose on the
edge losses from the contralateral side of the beam. The overall
penetration of light becomes limited by the geometry of the beam, not
by the tissue optics. Most of the laser energy is deposited in a volume
whose cross-sectional area is the size of the beam itself. Figure 6
illustrates this effect.
In Figure 6, three situations are compared. The curves represent
isofluence contours, calculated by Monte Carlo simulations for our
example optical properties. Figure 6A illustrates the broad-beam dosim-
 LASER-TISSUE INTERACTIONS 541

20-mm diameter beam.

3142mW.1 W/cm 2
-20

1
W/cm 2
10

15
A
1-mm diameter beam.
3142 mW. 400W/cm 2
-20 -15 -10 -5 5 20 mm

10

B 15

I-mm diameter beam.

7.85 mW. 1 W/cm 2

10

15
C
Figure 6. Narrow-beam laser penetration into tissue. A. Broad beam, with a radius of about
41) where I) is the optical penetration depth, achieves the maximum penetration with the
minimum fluence rate near the surface. B, Narrow beam, with same total energy (3124
mW) as A, achieves similar penetration but causes a very high fluence rate near the
surface, which will ablate the tissue surface. C, Narrow beam, same irradiance (1 W/cm2)
as A, has low fluence rate near surface but very little total energy so the penetration is
shallow.
542 JACQUES

etry. The beam diameter is about four times the penetration depth, 3,
of 5.1 mm, or 20 mm. The beam irradiance is 1 W/cm2 , and the beam
energy is 3142 mW. Along the central axis, the maximum light penetra-
tion is attained. Diffusion losses at the edges of the beam deplete the
fluence rate around the beam periphery. The fluence rate directly under
the beam is just a little over 3 W/cm2 • Figure 6B illustrates a beam
diameter of 1 mm, but the total laser beam energy is maintained
constant at 3142 mW. Therefore, the irradiance becomes very high, 400
W/cm 2, because all the energy is confined to a small spot. Note that
the 0.1 W/cm2 isofluence contour is not too dissimilar from the same
contour in Figure 6A. Because the total beam energy is the same, the
fluence rates far from the central beam are comparable, but also note
that very high internal fluence rates (> 100 W/cm2) are achieved directly
under the beam. Such high rates would blow off the surface layer of a
tissue. Figure 6C illustrates a 1-mm laser beam, but the irradiance is
maintained constant rather than the total beam power. The total power
is only 7.85 mW. Note that the fluence rate directly under the beam is
only slightly above 1 W/cm2 , but laser penetration is shallow. In
summary, beam diameter greatly affects the laser penetration and hence
the optical zone of energy deposition.
Selective Absorption by Pigmented Tissue Structure. If the tissue
contains a pigmented structure, laser energy will be selectively depos-
ited in that structure. 1 Some examples of such pigmented targets of
laser irradiation are single melanosomes/ the pigmented retinal epithe-
lium, a single red blood cell (Fig. 7), or an entire blood vessel. Pigments
also may be artificially introduced into tissues. For example, one can
paint the edges of a cut blood vessel with a protein paste containing
indocyanine green dye, which selectively absorbs the optical energy of
a near-infrared diode laser (810 nm) during laser anastomosis. 14 In our
laboratory, we have injected indocyanine green into the blood volume
to convert a blood vessel into a pigmented structure that absorbs pulsed
alexandrite laser radiation (~785 nm) to allow selective thermal coagu-
lation of the vasculature. During such procedures, the optical zone of
laser interaction is defined primarily by the size of the pigmented
target, not by the optics of the surrounding tissue or the geometry of
the laser beam.

Summary

The significance of tissue optics is to specify the optical zone of

initial laser-tissue interaction. Once the laser's energy is absorbed in
this zone, the energy can participate in photochemical, photothermal,
and photo mechanical interactions. For our subsequent discussion, the
optical zone will be assumed to be approximated by the optical pene-
tration depth, 3, which is appropriate for a broad-laser beam. However,
keep in mind that for narrow beams, the optical zone is specified by
the size of the laser beam, not by 3. For small pigmented targets, the
 LASER-TISSUE INTERACTIONS 543

Q)
.....en
~ 200 °C
~

E Q)
0..
S
~ 100°C

-5 -1 +1 +5
position (/-Lm)
Figure 7. Selective absorption by a pigmented target. A red blood cell will selectively
absorb a pulsed yellow laser (e.g., a dye laser at 577 nm for removal of a port wine stain)
relative to the surrounding dermis. The figure shows the temperature rise and subsequent
thermal relaxation of a red blood cell with an internal absorption coefficient of 756 cm- 1
when irradiated with 1 J/cm 2 • Pulses shorter than 10 fJ.sec will pop red blood cells like
popcorn. Longer pulses allow thermal relaxation of the red cells and heat the blood vessel
as a whole.

optical zone is specified by the size of the. pigmented structure, not

by 8.

Photochemical Interactions

When a photon is absorbed by a molecular chromophore and

converts that molecule to an excited state, the laser energy has been
converted into a stored form of chemical energy. The excited state may
subsequently participate in a chemical reaction. The photon essentially
behaves as a reagent that is stoichiometrically consumed in the photo-
chemical reaction as a photochemical product is produced. A variety of
such photochemical reactions can occur, such as bond breaking, cross-
linking, radical formation that leads to oxidative injury, or photodes-
truction of the chromophore. The molecular chromophore may be
endogenous, such as amino acid side groups, peptide backbone link-
ages, or heme pigments, or it may be an exogenous molecule introduced
into the body, such as a photosensitive reagent.
544 JACQUES

The breadth of photochemical interactions is well developed in the

photobiology literature, but one particular type of laser-induced pho-
tochemical interaction deserves particular mention: photodynamic ther-
apy.s Photodynamic therapy is a form of light-activated chemotherapy
(Fig. 8). A photosensitive dye is injected into the body, where it
accumulates in certain cells, especially cancer cells. Irradiation with an
appropriate-wavelength light source causes photon absorption by the
dye, which yields an excited state. The excited state reacts with oxygen
to generate toxic products such as singlet oxygen. These toxic products
injure the local cellular environment, and the cells (e.g., cancer cells)
are killed. Therefore, three reagents are needed for photodynamic
therapy: photons, photosensitive dye, and oxygen.
The amount of photosensitive dye in the tissue may be expressed
as a concentration, C, in moles/liter. The extinction coefficient, E,
indicates the absorptivity of the dye at the laser wavelength and is in
units of liter/(mole em). The pathlength, L (em), indicates the path
length that photons travel through the tissue, although that path is a
random walk. The product, ECL, cancels all units to yield a dimension-
less factor called the optical density. Transmission over a path length
is given: T = lO- ECL • It is convenient to characterize dye concentration
in the tissue by the absorption coefficient attributable to dye in tissue:
I-La.dye = ECln(10), such that T = exp( - I-La.dyeL). For example, a typical
photosensitive dye such as a porphyrin molecule may have an extinction
coefficient of 104 LI(mole em). After injection of dye, the tissue concen-
tration of dye may typically reach 1.5 x 10- 6 moles/L. Therefore, the
I-La.dye equals 0.035 em-I.
The extent of necrosis caused by photodynamic therapy depends
on a number of factors. Let us assume that oxygen is plentiful, not a
rate-limiting factor (this is not always true, and oxygen concentration
is an important variable parameter). The depth of necrosis, Znecrosis'
depends on the laser irradiance ('1'0)' the time of exposure (t), the light

toxic product
(singlet oxygen)

Figure 8. Photodynamic therapy requires photons, a photosensitive dye, and oxygen. The
schematic diagram illustrates how photon absorption by the dye yields an excited-state
molecule that can react with oxygen to produce a toxic product (e.g., singlet oxygen). The
probability of excited-state reaction with oxygen is <I> and the probability of simply producing
heat or fluorescence is 1 - <1>. The injury by accumulated toxic product causes cell death.
 LASER-TISSUE INTERACTIONS 545

penetration into the tissue (k exp( - z/o); see Equation 2b), the absorp-
tion coefficient of the photosensitive dye (/-La.dye)' and the quantum
efficiency (<I» for producing toxic product (P). The threshold toxic
product that achieves photodynamic injury (Pth)' is summarized:
Pth = b <I> /-La.dye'l'o t k exp( - Znecrosis/o) (6)
where b is a constant that converts J/cm 3 into moles/cm3 of product (b
= ~/NAhc; NA is Avagadro's number, h is the Planck constant, and cis
the speed of light). P th is in units of moles/cm3 of generated product
in the tissue. Equation 6 can be rearranged to predict the depth of
injury:

Znecrosis -
_ (b 8 In
<I> /-La. dye '1'0 t k) (7)
Pth
Note that the depth of necrosis is proportional to the logarithm of most
of the terms but is linearly related to O.
The threshold toxic product, Pth , that will produce necrosis can
vary greatly with different photosensitive dyes and different tissues.
Patterson et aP6 report that chlorosulfonated phthalocyanine dye (Por-
phyrin Products, Logan, Utah) requires 3.8 x 1019 photons/cm3 to be
absorbed by dye in order to achieve cell death in rat liver. They
calculate, from work by Potterl7 in a variety of human tumors, that 8.6
x 1017 photons/cm3 must be absorbed by dihematoporphyrin ether
(Photofrin II; QuadraLogics, Inc., Vancouver, British Columbia) to
achieve cell death. The relation between photons/cm3 absorbed by dye
and moles!cm 3 of toxic product depends on the quantum efficiency, <1>.
For the following discussion, let us assume that a value of 3 x 1019
photons/cm3 must be absorbed by a generic photosensitive dye with a
quantum efficiency of 0.1. Then, the value of Pth is (3 X 1019)<I>/NA or 5
x 10- 6 moles/cm3 •
Let us illustrate a typical example of photodynamic therapy dosim-
etry, as summarized in Table 2. The values in Table 2 are hypothetical
but within actual typical ranges. The patient is injected with 5 mg/kg
of body weight of a photosensitive dye, causing the amount of dye
that accumulates in the tissue to be 1.5 x 10- 6 moles/L, which
corresponds to /-La dye equal to 0.035 cm- I • The irradiance, qro, is 0.2 WI
cm2 • The time of exposure is 20 minutes (1200 seconds). The optics of
our example tissue are the same as in Figure 5 (i.e., /-La = 0.3 cm- I and
/-Ls' = 4 cm- I ), which yields 0 = 5.1 mm and k = 4.4. The wavelength
of light is 630 nm (red light), so the value of the conversion constant,
b, is ~/NAhc or 5.3 x 10- 6 moleslJ. The quantum efficiency, <1>, is the
fraction of photons absorbed by the photosensitive dye that produce
toxic product (such as singlet oxygen) rather than heat and is assumed
to be 0.1. Assume the threshold toxic product that achieves necrosis,
P th , equals 5 x 10- 6 moles/cm3 • Then this photodynamic therapy
treatment will yield a depth of necrosis, Znecrosis' equal to 7 mm.
What happens if one doubles the irradiance, dye concentration, or
time of exposure? The Znecrosis will increase by 0In(2), or 0.690, which
546 JACQUES

Table 2. TYPICAL PHOTODYNAMIC DOSIMETRY WITH

RED LlGHT*
Name Symbol Value Units
Photons
Wavelength A 630 nm
Irradiance '1'0 0.2 W/cm2
Exposure time t (min) 20 min
Optical penetration depth 8 (mm) 5.1 mm
Optical backscatter constant k 4.4
Conversion constant b 5.23 x 10- 6 moles/J
Photosensitive dye
Delivered dose 5 mg/kg body weight
Tissue concentration C 1.5 x 10- 6 moles/liter
Extinction coefficient E 104 liter/(mole cm)
Dye absorption in tissue fLa-dye 0.035 cm- 1
Quantum efficiency <l> 0.1
Tissue necrosis
Threshold toxic product Pih 5 x 10- 6 moles/cm3
Zone of necrosis Znecrosis 7 mm

'These are hypothetical values in the typical range for photodynamic dosimetry, chosen to
demonstrate Equations 6 and 7. Oxygen is assumed to be in excess.

equals 3.5 mm in our example. If the irradiance, dye, or time is cut in

half, the Znecrosis will change by oln(1f2) or - 3.5 mm. In general, if one
increases dye, light, or time by a factor of X, then Znecrosis will increase
by oln(X). Note that oln(X) depends only on 0 and X and not on any
of the initial values of !-La.dye' '1'0' t, or even the initial Znecrosis' Therefore,
the optical penetration 0 is of primary importance when attempting
to adjust the photodynamic therapy dosimetry to achieve a desired
Znecrosis·

Photothermal Interactions

Heat deposited by the laser can cause thermal injury to a tissue

and desiccation. First, I briefly discuss desiccation, then the process of
thermal injury.

Desiccation
Evaporation of water is an important heat sink for laser energy,
and steam can carry heat away from the primary region of laser
exposure. For example, when an optical fiber is placed within the liver
and laser power is delivered through the fiber to cause local photoco-
agulation of a tumor nodule, steam can travel up along the fiber.
Matthewson et aP2 showed that increasing the amount of delivered
laser power above 1 W does not increase the amount of thermal injury
in a rat liver in vivo. Above 1 W, the laser simply induces evaporation,
and the energy is removed from the liver site by escaping vapor.
Evaporation is an important aspect of laser dosimetry.
 LASER-TISSUE INTERACTIONS 547

Thermal Injury
Let us now ignore evaporation and consider the process of irre-
versible thermal denaturation called either "hyperthermia" or "coagu-
lation," depending on whether delayed or immediate damage is ob-
served. Thermal injury occurs as a rate process of coagulation that
accumulates as a function of time. The native tissue may be character-
ized as having an initial number of a particular native species of
macromolecules, No. As the tissue is heated, thermal denaturation
proceeds, and the number of native species, N(t), decreases with time.
The damage is described by the term 0, called the "damage integral,"
which equals:
t

o = - In( ~:)) = Jk dt' (8)

o
where k is a rate constant (in units of seconds -I). Before denaturation
begins, 0 equals zero. When only 37% of the original native species
remain native (63% of the species have been denatured), 0 equals one.
When nearly all the native species are denatured, 0 approaches infinity.
The value of the rate constant, k, is temperature dependent. Higher
temperatures require less time to achieve a certain degree of coagulation
(large k), and lower temperatures require a longer time (small k).
Experimentally, we determine the value of k as a function of tempera-
ture. Then we plot the exposure time required to achieve a particular
amount of a particular type of damage as a function of the exposure
temperature. Figure 9 illustrates two types of thermal damage plotted
in such a manner for the example of thermal injury to liver. One type
of injury is immediate coagulation that yields a visually obvious effect.lO
The second type of injury is coagulation of heat-labile proteins, which
triggers delayed necrosis, obtained by analysis of the data on laser-
induced liver necrosis reported by Matthewson et alY Note that long
exposure times at moderate temperatures (e.g., 10 minutes at 55°C)
cause delayed necrosis to be achieved without producing visible coag-
ulation. This is the upper left zone labeled "necrosis" and is commonly
known as "hyperthermia." High temperatures for short times (e.g., 1
minute at 70°C) will achieve visible coagulation. While Figure 9 shows
only two types of injury, it illustrates that different temperature histories
will harm different structures at different rates.
The variety of types of thermal injury that can occur were recently
summarized by Thomsen/I as restated in Table 3. The approximate
threshold temperatures that achieve the different types of injury are
presented, but keep in mind that thermal injury is actually caused by
a temperature history, not a threshold temperature.
In general, the lower the apparent threshold temperature for
thermal injury, the more important is exposure time as a factor in the
accumulation of thermal injury. The higher the apparent threshold
temperature, the less important is exposure time, and the peak tem-
548 JACQUES

D Necrosis (rat liver): Matthewson et al. 1987

o Coagulation (pig liver): Jacques et al. 1991
1061m00~0000~~~~~n~ec~ro~si;is::~~~~~t
I"'u,"v/£····,··············c,H = 31.4 kcal mole-!
10 5 l>S = 29.4 cal mole-! K! 1 day
-----
r/.J :::::::. coagulation:
'-' ............ ,............. l>H = 61.4 kcal mole-!
(\) 10 4
S
......
......
1 hour
(\)
;.....
103
;::::l
r/.J
0
0.. 10
2
:><::
1 min
~

100~~~~TT~~~~~~+r~~~~-ls
40 45 50 55 60 65 70 75
Exposure temperature (OC)
Figure 9. Thermal coagulation. Thermal injury is a rate process and involves both exposure
temperature and exposure time. The threshold exposures required for two types of damage
in liver are shown as solid lines. One process is hyperthermia damage to vital heat-labile
macromolecules such as enzymes, which yields delayed cell necrosis after about 24 hours.
The second process is photocoagulation, which yields immediate visible effects, such as
whitening of the tissue. Modest temperatures for long times cause delayed necrosis without
visible coagulation. High temperatures for short times cause immediate coagulation. The
molar enthalpy, ~H, and entropy, ~S, for these two damage processes are given.

perature is more important. This phenomenon is understood by ex-

panding the thermodynamic expression for the rate constant, k, from
Equation 8:
kBT
k = h exp (LlS/R) exp( - LlH/RT) (9)

where kB' h, and R are the Boltzmann, Planck, and gas constants,
respectively. Temperature, T, is in degrees Kelvin. The terms LlS and
LlH are the molar entropy (cal/(mole degree» and molar enthalpy (call
mole) of the irreversible denaturation event. Entropy indicates the loss
of stored potential energy secondary to the randomization of structural
order during denaturation. Enthalpy indicates the bond energy that
tries to hold the molecule together. The LlS drives the denaturation
reaction forward, like a stack of blocks falling over. The LlH resists
denaturation, like support wires holding the stack of blocks in place.
For heat-labile proteins such as enzymes, the values of LlS and LlH in
Equation 9 are moderate, and the two exponential terms, exp(LlS/R)
and exp( - LlHlRT), are comparable in value over a temperature range
such that the two terms offset each other. Therefore, the rate constant,
 LASER-TISSUE INTERACTIONS 549

Table 3. PHOTOTHERMAL INJURY OF TISSUE

Photothermal Temperature
Interaction at Onset ee) Histopathologic Effect
Low-temperature 40-45 Deactivation of enzymes: reversible cell injury
damage 43-45 + Deactivation of enzymes: cell death
processes ? Cell shrinkage and hyperchromasia
43+ Birefringence loss in frozen-thawed myocardium
? Thermal denaturation of structural proteins
? Membrane rupture
58+ Hyalinization of collagen
69-72 Birefringence loss in fresh myocardium
70-75 Birefringence changes in collagen
140+ Thermal denaturation of elastin
Water vaporization 100 + Extracellular vacuole formation
>100 Rupture of vacuoles: "popcorn" effect
? Tissue ablation by explosive vaporization
High-temperature 300- Tissue ablation
ablation 1000 +
3550 Vaporization of carbon

From Thomsen S: Pathologic analysis of photothermal and photomechanical effects of laser-tissue

interactions. Photochem Photobiol 53:825-835, 1991; with permission.

k, increases gradually with increasing temperature, and the time of

exposure is an important factor. However, for structural proteins such
as collagen, the values of LlS and LlH are very high, and either one or
the other of the two exponentials will dominate. The value of k is either
extremely low or extremely large. Therefore, the value of k increases
suddenly as the temperature rises. The coagulation of collagen is more
like a melting process at a threshold temperature, and exposure time
is of little importance.

Photomechanical Interactions

Lasers can induce stress in tissues, and such mechanisms of

interaction are described as photomechanical. Stress is defined as force
per unit area and is commonly reported in units of newtons (N) per
square meter called either pascals (1 Pa = 1 N/m2), bars (1 bar = 105
N/m2) , or atmospheres (1 atm = 1.013 x 105 N/m 2). Under stress, a
tissue can be deformed, either reversibly or irreversibly. If the stress is
sufficient, the tissue can break. Such breakage may be macroscopic,
such as spallation of tissue3 or cracking of tooth enamel. 22 Alternatively,
the breakage may be microscopic, such as cellular disruption26 or the
accumulation of microfractures in a kidney stone during lithotripsy.13
There are two basic types of stress considered here: (1) transient
stress waves and (2) quasi-steady state stress. These are discussed in
the following paragraphs.
 -
550 JACQUES

Transient Stress Waves

Transient stress waves can be generated by several mechanisms:
(1) sudden thermoelastic expansion of tissue caused by rapid heating
by a pulsed laser; (2) recoil caused by ejection of ablated mass; and (3)
sudden expansion secondary to a phase change such as vaporization
of tissue waterll or formation of plasma. 13
Sudden Thermoelastic Expansion. A very short laser pulse will
rapidly heat the optical zone, which causes stress to develop by
thermoelastic expansion. This stress will propagate out of the optical
zone into the tissue as a stress wave. Figure 10 illustrates the propa-
gation of a stress wave into a tissue caused by a pulsed magnesium
cobalt laser (67-nanosecond pulse, 1.9-j.Lm wavelength, absorbed by
tissue water) using equations presented by Dingus and Sammon. 3 The
optical zone of light penetration is 100 j.Lm (8 = 1/j.La). As the laser
pulse is delivered, stress develops within the optical zone. The stress
wave propagates at the speed of sound, v = 1.5 X 105 cm/second.
Time is required for the stress to propagate out of the optical zone. The
propagation time is 8/v or (100 j.Lm)/(1.5 x 105 cm/second), which equals
67 nanoseconds. The rectangular laser pulse was chosen to equal 67
nanoseconds for this example. The stress accumulates during the 67-
nanosecond pulse. Thereafter, the stress wave propagates out of the
optical zone and into the tissue. Half of the laser-induced stress
propagates toward the tissue surface, where it is reflected by the air-
tissue boundary as a negative stress region that now propagates into
the tissue trailing the leading positive stress region. There is a steep
gradient between the leading compressive and trailing rarifractive stress
regions. If the stress becomes too negative, the tissue can break and be
ejected as ablated mass, a process called spallation. 3 Figure 10 shows
that stress in the range of 100 bars is achieved, which is estimated to
be sufficient to cause spallation. 3 As the stress wave propagates into
the tissue, it may also cause deep cellular injury.
Ablation Recoil. When mass is rapidly ejected by ablation, the
recoil sends an impulse of momentum into the tissue, which propagates
as a stress wave. For example, Watanabe et aF6 have reported photo-
mechanical disruption of cells in guinea pig skin following superficial
ablation with the pulsed ArP excimer laser (14-nanosecond pulse, 193-
nm wavelength, absorbed by tissue protein). The superficial 20 j.Lm of
the skin was ablated by the laser, but thephotomechanical injury
extended as much as 400 j.Lm deep. Figure 11 illustrates the photome-
chanical cellular injury. Photomechanical injury correlated with super-
ficial skin ablation. No injury was seen without ablation, suggesting
that ablation recoil generated the stress waves.
Sudden Expansion Secondary to Phase Change. During laser
lithotripsy of kidney stones, the laser induces plasma (the fourth state
of matter) at the stone surface. The sudden expansion of this plasma
initiates a stress wave that propagates into the stone. Nishioka et aP3
have observed that plasma is a requirement for breakage of the stone.
Often, the stone does not immediately break but requires many pulses
 LASER-TISSUE INTERACTIONS 551

r = 0.15 (Griineisen coefficient)

Il. = 100 cm· 1
$0 = 2.2 IIcm2 (70 mI, 2-mm dia. spot)

300

200

100

Stress -k-,L;;;;,~"'~=----=:=-iJ 0 bars

(J
-100
A

l't = 1& = 67 nsl 300

200
rlla$o
-2-

100

Stress 0 o bars
(J
-100
tp =~
B I)!..$o
--2-
0 100 200 300 400 500

Depth (Jim)
Figure 10. Transient stress waves induced by a pulsed laser. A. The thermoelastic
expansion of tissue caused by the heat from a very short laser pulse will create a stress
distribution. This example simulates an infrared laser (e.g., magnesium cobalt laser at 1.9-
II-m wavelength) delivering a pulse (pulse duration tp equals 67 nanoseconds) to a soft
tissue with an optical absorption, 11-., of 100 cm-'; 67 nanoseconds is the time required for
stress to travel across the optical zone, or T = 1/11-av, where v is the speed of sound (1500
m/second). At first, the stress builds up during the pulse. Thereafter, half the stress
propagates into the tissue and the other half propagates toward the surface, where it is
reflected by the air-tissue interface. The reflection inverts the stress into a negative stress.
The negative stress can cause tissue to break, an effect referred to as "spallation." B, If
the laser pulse, lp, equals T, the stress gradient will be relatively steep. Shorter pulses will
steepen the gradient, and longer pulses will decrease the gradient.
 r

552 JACQUES

Figure 11. Photomechanical disruption of cells. After superficial ablation of the superficial
20-lLm stratum corneum layer of guinea pig skin, pressure waves have propagated down
to the epidermal-dermal junction. A, Control site in unirradiated area. A keratinocyte (K),
fibroblast (F), and the junction (arrow) are indicated.
l1Iustration continued on opposite page

to accumulate damage before it suddenly pulverizes. A working hy-

pothesis is that each laser pulse generates a stress wave that propagates
throughout the stone and causes internal fractures of its crystalline
structure. The stone structure becomes progressively fatigued and
eventually falls apart.
Explosive vaporization of water is also a suddenly expanding phase
change. The "popcorn effect" is an example of explosive vaporization. l l
Walsh23 noted mechanical injury to artery wall that was aligned with
the collagen fibers, suggesting that mechanical injury occurred as
vaporized water attempted to escape the tissue around the delivery
fiber.
 LASER-TISSUE INTERACTIONS 553

Figure 11 (Continued). B, Photoacoustic injury by pressure waves has caused damage to

nuclei (N) and mitochondria. (Photographs courtesy of S. Watanabe, T. J. Flotte, D. J.
McAuliffe, and S. L. Jacques, similar to reference 26.)

Quasi-steady State Stress

Quasi-steady state stress occurs secondary to the thermoelastic
expansion of tissue caused by thermal heating. The term "quasi-steady
state" is introduced to emphasize that the thermoelastic expansion is
not a transient stress wave but rather a static distribution of stress that
depends on the temperature distribution. If the temperature distribution
were constant, the stress would be constant, but temperature distribu-
tions are rarely constant during laser irradiation, and therefore the
stress is not constant; hence the term "quasi."
An example of quasi-steady state stress is illustrated in Figure 12,
which shows the compressive and tensile stress generated in tooth
enamel during irradiation with a pulsed Er:YAG laser (2SD-microsecond
554 JACQUES

350-J.UIl radius

Figure 12. Quasi-steady state stress pro-

duced in tooth enamel by a pulsed Er:YAG
laser during the first 10 fJosec of irradiation.
A Compressive stress is indicated as nega-
tive and tensile stress as positive. A, Cir-
0.2 0.4 0.6 0.8 1.0 cumferential stress. The maximum tensile
stress occurs at a point outside the laser
beam radius. Studies in tooth enamel have
shown circumferential craze lines around
Er:YAG ablation craters that correlate with
the peak tensile stress. B, Radial stress.
The radial compressive stress may playa
role in ablation of enamel. (Adapted from
Rastegar S, Motamedi M, Anvari B: Ther-
-2.0e+5~+-.....,--r--r-..........- - I
momechanical effects of lasers on dental
0.0 0.2 0.4 0.6 0.8 1.0 tissue. Presented at the Third U.S.-China-
Japan Conference on Biomechanics, At-
B Radial Position [mm] lanta, August 1991; with permission.)

pulse, 2.9-j.Lm wavelength, absorbed by tissue water), as calculated by

Rastegar et al. 18 The convention in this figure is that compressive stress
is negative and the tensile stress is positive. The figure shows that
compressive stress occurs where the laser beam directly irradiates, but
tensile stress occurs outside the beam where tissue is being stretched
radially. Vickers et aP2 have shown using scanning electron microscopy
that Er:YAG laser irradiation of tooth enamel causes circumferential
craze lines that appear to correlate with the tensile stress predicted by
Rastegar et al.

A Map of Laser Dosimetry

Photochemical effects are confined to the optical zone where light

penetrates the tissue. Photothermal and photomechanical effects may
be confined to the optical zone or may be distributed outside that zone.
Stress waves can propagate. Thermal energy can diffuse. There is an
interplay between the optical zone, /), and the laser pulse duration, tp.
It is possible to summarize the relation in terms of three regimes: (1)
stress confinement; (2) thermal confinement; and (3) no confinement.
These are briefly summarized in the following paragraphs and in Figure
13. 7
Stress confinement occurs when the laser pulse is so short that it
 LASER-TISSUE INTERACTIONS 555

! stress thermal
i confinement; confinement
10 ·········i········+········,·····.····,··········f······
! ! Q-swNdYAG !
,·········1·······,········+·······;·········.·----;--......-:IP."
! .
i ' . 1 1 "KTP"

1 . :. !
~~~1r~:T
::
. . l·····T. . ·
! Q-sw 2xNdYAG.
HOYfGT··
! !

: :
quasi-CW 2xNdYAG

0.1 .........l..........~ .........l .......

: ' ! : --j

0.01 ·········i··········!·
,!
······l······ 1··········;··········:·········r···· rL-f~ .;" .~+-+-
~
u 1

'g, 0.001 ... : ... T" .... +... non

confinement
..... ..........
~

o
1~ 1~ 1~ 1~
Pulse duration, tp (s)
Figure 13. Mapping photothermal and photomechanical effects. Laser-tissue parameters
that achieve stress confinement, thermal confinement, and nonconfinement are mapped in
terms of the optical zone, Il, of laser energy deposition and the laser pulse duration, tp.
Shallow penetration requires shorter pulses to confine the stress or thermal energy. The
boundary for stress confinement is tp < Il/v, where v is the velocity of sound. The boundary
for thermal confinement is lp < 1l2/K, where K is the thermal diffusivity. Example lasers are
shown in terms of lp and approximate Il for typical tissues.

deposits its energy in the optical zone before the stress waves can
propagate out of the optical zone. Consequently, the laser-induced
stress accumulates prior to its propagation, which enables very large
stress waves to be generated. The criterion for a laser pulse, tp ' to fall
in the stress confinement regime is given by:

tp < ~v (10)

where 8 is the optical penetration and v is the velocity of sound.

Equation 10 is appropriate for stress induced by thermoelastic expan-
sion. The stress induced by recoil from ablation or sudden expansion
of plasma or water vapor would depend on the time course of the
explosive event itself and is still a topic of investigation in several
laboratories.
Thermal confinement occurs when the laser pulse is sufficiently short
that its energy is deposited in the optical zone before thermal energy
can diffuse out of that zone. Heat accumulates, and high temperatures
are achieved. The criterion for a laser pulse to fall in the thermal
confinement regime is given by:
t
p
< 8K2 (11)
556 JACQUES

where K is the thermal diffusivity (K = 1.3 X 10- 3 cm2/second). The

thermal relaxation time of the optical zone is approximately (2~W/4K,
where the factor of 2 accounts for thermal insulation at the air-tissue
interface of the tissue surface. This expression simplifies to Equation
11. Photo mechanical damage can still occur secondary to quasi-steady
state stress cause by the steep thermal gradients that may form when
heat is confined to the optical zone.
No confinement occurs when the laser pulse is relatively long and
stress and thermal energy can propagate out of the optical zone.
Thermal energy will diffuse over a larger tissue volume than just the
optical zone. Involving a larger volume of tissue requires a greater
threshold laser energy to achieve any effect. But recall that we are
simply turning up the laser energy until a definite effect occurs. Injury
will now involve a larger volume of tissue. The thermal and mechanical
effects may be different from those of the other two zones because the
gradients of temperature and stress are less steep, the volume of
interaction is larger, and the time periods of heating and cooling are
much longer. The criterion for no confinement is given by:

t > l)2
(12)
P K

Turning up the laser energy until a tissue effect occurs is a natural

first step toward dosimetry. However, when an effect occurs, it may
manifest via a photochemical, photothermal, or photomechanical mech-
anism. By understanding the different mechanisms and effects, it is
possible to design laser protocols that either enhance or mitigate
particular effects. For example, one may wish to enhance mechanical
effects but avoid thermal effects. Stern and colleagues have been
exploring the use of ultra-short laser pulses (nanosecond, picosecond,
and femtosecond pulses, which are in the zone of stress confinement)
to achieve localized retinal injury via a photo mechanical mechanism
while avoiding excessive thermal injury.20 A very short laser pulse can
cause significant photomechanical effect but contains only a small
amount of energy. This strategy hopes to minimize residual thermal
injury.

CONCLUSION

The study of mechanisms of laser-tissue interaction offers the

opportunity to optimize clinical laser protocols. The variety of lasers
available to medicine continues to grow, and more sophisticated pro-
tocols are under development. Industry has found that laser systems
designed for medicine can be commercial successes (e.g., ophthalmol-
ogy and dermatology), and its interest in the medical laser market is
increasing. The study of mechanisms of laser-tissue interaction can
 LASER-TISSUE INTERACTIONS 557

guide the laser industry in its development of new devices for medical
applications.

References

1. Anderson RR, Parrish JA: Selective photothermolysis: Precise microsurgery by selec-

tive absorption of pulsed radiation. Science 220:524-527, 1983
2. Cheong WF, Prahl SA, Welch AJ: A review of the optical properties of biological
tissues. IEEE J Quant Electron 26:2166-2185, 1990
3. Dingus RS, Scammon RJ: Griineisen stress-induced ablation of biological tissue. Proc
SPIE 1427:45-54, 1991
4. Flotte TJ, Yashima Y, Watanabe S, et al: Morphological studies of laser-induced
photoacoustic damage. Proc SPIE 1202:71-77, 1990
5. Gomer CJ (ed): Photodynamic therapy. Photochem Photobiol64(5), 1987
6. Jacques SL: Simple theory, measurements, and rules of thumb for dosimetry during
photodynamic therapy. Proc SPIE 1065:100-108, 1989
7. Jacques SL: Nonlinear optics during high-irradiance laser exposures [abstract]. Pro-
ceedings of the Annual Meeting of the Optical Society of America. San Jose,
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8. Jacques SL, McAuliffe OJ: The melanosome: Threshold for explosive vaporization
and internal absorption coefficient during pulsed laser irradiation. Photochem Pho-
tobiol 53:769-775, 1991
9. Jacques SL, Alter CA, Prahl SA: Angular dependence of HeNe laser light scattering
by human dermis. Lasers Life Sci 1:309-334, 1987
10. Jacques SL, Newman C, He XY: Thermal coagulation of tissues: Liver studies indicate
a distribution of rate parameters not a single rate parameter describes the coagulation
process. Proc Annual Winter Meeting of the American Society of Mechanical Engi-
neers. Atlanta, 1991
11. Langerholc J: Moving phase transitions in laser-irradiated biological tissue. Appl
Optics 18:2286-2293, 1979
12. Matthewson K, Coleridge-Smith P, O'Sullivan JP, et al: Biological effects of intrahe-
patic neodymium:yttrium-aluminum-garnet laser photocoagulation in rats. Gastro-
enterology 93:550-557, 1987
13. Nishioka NS, Teng P, Deutsch TF, et al: Mechanism of laser-induced fragmentation
of urinary and biliary calculi. Lasers Life Sci 1:231-245, 1987
14. Oz MC, Johnson JP, Parangi S, et al: Tissue soldering by use of indocyanine green
dye-enhanced fibrinogen with the near infrared diode laser. J Vasc Surg 11:718-725,
1990
15. Puliafito CA, Stern 0, Krueger RR, et al: High-speed photography of excimer laser
ablation of the cornea. Arch Ophthalmol 105:1255-1259, 1987
16. Patterson MS, Wilson BC, Graff R: In vivo tests of the concept of photodynamic
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Address reprint requests to

Steven L. Jacques, PhD
Laser Laboratory-17
The University of Texas M.D. Anderson Cancer Center
1515 Holcombe Boulevard
Houston, TX 77030