Clinical Bulletin

Mechanisms of Action of Fractionated 532nm and

1064nm Picosecond Laser for Pigmentation, Skin
Irregularities and Signs of Aging
Kevin Schomacker, Ph.D.
Jayant D. Bhawalkar, Ph.D.

BACKGROUND subsurface laser induced optical breakdown (LIOB),

leading to subsurface ablation voids or vacuoles.
Full face ablative resurfacing and fractional ablative
Fractional subsurface resurfacing is possible with two-
resurfacing techniques are treatments of choice for
dimensional scanning of the focused laser beam, or
facial rejuvenation of aged and photoaged skin. Both
with diffractive microlens or holographic diffractive
techniques were shown to be highly effective for
beam-splitter technologies, used in a stamping or
dyschromia, fine lines and wrinkles [1-3]. Although better
painting mode.
results are obtained with full resurfacing procedures, it
comes with more downtime and more serious risks,
Resolve uses holographic diffractive beam-splitter
when compared to fractional resurfacing techniques[3].
technology to create a two dimensional array of
Because of the higher risk, fractional resurfacing
LIOBs. The LIOBs can be focused in the epidermis,
techniques have essentially replaced full resurfacing
using the 532nm wavelength, or in the upper papillary
techniques today for facial rejuvenation. Albeit,
dermis, using the 1064nm wavelength. Picosecond
fractional resurfacing is not without risk, and scarring
treatments have been used to treat dyspigmentation,
and infections, although rare, have been reported [4].
skin irregularities, add volume for wrinkles and acne
scars, or both. [5,6,7]
With the advent of picosecond laser pulses, it is now
possible to safely generate optical breakdown in tissue,
Table 1 compares the mechanism, patient preparation,
leading to a novel approach to facial rejuvenation
procedural time, treatment downtime and expected
that has little to no downtime and greatly reduced
results for full face ablative resurfacing, fractional
risk for complications. Superficial focusing of these
ablative resurfacing, and picosecond fractional
high peak power laser pulses is sufficient to promote
subsurface ablative resurfacing, when used for facial
Table 1: Comparison of full resurfacing, fractional resurfacing, and subsurface fractional resurfacing.

Technique Mechanism Patient Prep Procedural Downtime Results

Time
Full ablative Thermal ablation Wash skin 1 hour (mostly 1 week or longer. Best results for
resurfacing of entire surface surface, lidocaine/ due to pre- - Risk of serious facial rejuvenation
of skin, some epinephrine procedural infections, - clearing dyspig-
residual thermal injection or prep and post- potentially leading mentation and fine to
damage on regional block procedural care) to scarring. moderate wrinkles.
ablative surface -Risk of Some effect on deep
depigmenting skin wrinkles
Fractional ablative Thermal ablation Wash skin 1 hour (mostly Several days. Good results for
resurfacing of 0.2mm surface, Lidocaine due to pre- Discomfort facial rejuvenation
diameter columns injection or procedural requiring pain - clearing dyspig-
of tissue, typically regional block prep and post- management mentation and fine
2-5% tissue procedural care) following the wrinkles, with some
coverage, some procedure. effect to moderate
residual thermal -Crusting a wrinkles, and acne
damage along couple of days scars
fractional craters after treatment.
-Makeup can
be applied 2
to 3 days after
treatment
PicoWay Tissue ablation Wash skin 20 – 30 minutes No downtime. Good results for
Fractional via laser surface (mostly due to - 8 - 36 hours of dyspigmentation,
Resolve induced optical requiring 4-6 mild erythema. skin and textural
(subsurface breakdown passes over full -Little irregularities, and
fractional (LIOBs), face) discomfort signs of aging
ablative typically 4 to following the
resurfacing) 25% tissue procedure.
coverage, no -Makeup can be
residual thermal applied the next
damage day

rejuvenation. forming a cavitation bubble.

LASER-INDUCED OPTICAL BREAKDOWN
– PRIOR STUDIES
Tissue ablation via laser induced optical breakdown
(LIOB), also known as laser induced plasma ablation,
has been studied in biological tissue for some time
now with some of the earliest work aimed at precise
surgical cutting within the eye [8]. Early ophthalmic work
in the 1970’s started with nanosecond pulses, which
led to the use of more precise picosecond laser pulses
in the mid 1980’s, to today’s use of femtosecond laser
pulses.
Laser induced optical breakdown (LIOB) can effect
tissue in numerous ways. This phenomenon occurs
when the pulse intensity is high enough to strip electrons
from the exposed material, generating plasma. Once
formed, the plasma absorbs the remaining laser
energy, which rapidly heats and expands the plasma,
The high temperature plasma effectively ablates tissue
collocated with the plasma. Collapse of the cavitation
bubble generates strong local mechanical forces
that can further disrupt tissue in the local vicinity. The
supersonic expansion of the cavity also generates a
shock wave, with sufficient forces to further disrupt
tissue, and which can travel some distance away
(0.1 to 0.2mm) from the cavitation zone.
Habbema et al. were the first to propose using a highly
focused picosecond pulse, to create subsurface
damage via LIOB for skin rejuvenation [9]. In vivo tissue
samples were irradiated with 0.15mJ of focused
1064nm laser radiation having subnanosecond
pulses. The focal spot diameter was 10µm, and the
pulse intensity was estimated to be 380 GW/cm2. The
laser beam was scanned horizontally to create multiple
evenly spaced vacuoles in skin. Their system also
allowed adjusting the focal depth in skin from 0.1mm to
Figure 1 (Left panel): H&E stain section of skin tissue showing 0.2mm diameter vacuoles in the upper dermis caused by
laser-induced optical breakdown. The tissue section was taken immediately after laser irradiation. (Right panel): Tissue
section stained with Herovici stain to show new collagen formation from healing of LIOB damage. The sample was biopsied
30 days after laser irradiation.9
0.75mm from the skin surface. Although at some point,
tissue scattering will reduce the efficiency at deeper
depths. Immediately after irradiation, vacuoles (empty
voids) were seen in the upper dermis and corresponded
to the location for the focused laser beam, which was
about 0.2mm deep into skin (FIG. 1). Thirty days after
treatment, new collagen was seen in the region of the
LIOBs, which is a natural healing response to this type
of dermal injury. Habbema’s research demonstrates
the feasibility of creating subsurface dermal injury,
while leaving an intact epidermis that with healing
leads to new collagen growth, showing promise for
skin rejuvenation.
Habbema’s proposed technique for skin rejuvenation
has since been demonstrated by others via studies
showing improvement in the appearance of facial
acne scars [7] and facial wrinkles [5]. In both studies,
a diffractive microlens array was used to fractionate
picosecond 755nm laser pulses into multiple beamlets.
The beamlets were softly focused onto skin, creating
a matrix of LIOB damage zones. Unlike Habbema’s
work, the LIOB damage zones in these studies were
located in the epidermis, primarily due to the higher
absorption of 755nm light by melanin in melanosomes,
but also due to the soft diffractive focusing.
In the acne scar study [7], 17 patients completed the
study after receiving six full face treatments. Masked
assessment of 2-dimensional photography was
performed, using a scale from 0 (0-25% improvement)
to 3 (>75% improvement). At the 1-month and 3-month
follow-ups, the acne scar improvement scores were
1.5 and 1.4, respectively. Scar volume was also
assessed, with 3D image analysis, and showed a
24% improvement in scar volume. Histologic analysis
demonstrated an elongation and increased density
of dermal elastic fibers, and an increase in dermal
collagen and mucin. This is particularly interesting
because it shows that laser-induced damage, within
the epidermis, promotes a healing response in the
dermis, either by direct stimulation or injury from
scattered laser energy, or via some other indirect
mechanism such as cytokine signaling or stresses
caused by traveling shock waves. The underlying
mechanism for dermal stimulation is not known at this
time. Treatments in the acne study were found to be
safe, with no severe clinical observations other than
transient erythema, which persisted for one day after
treatment. Pain from the treatments was mild, starting
at 2.7 (out of 10) for the first treatment and increasing
to 3.2 for the 6th treatment.
For the wrinkle study [5], 20 female patients with
perioral and periocular wrinkles received four full face
treatments, with 4,000-6,000 pulses per treatment. A
fractionated 755nm picosecond laser was used, with
an average fluence of 0.71 J/cm2. Wrinkle improvement
was assessed at six months after the final treatment.
The average Fitzpatrick wrinkle score (1-9) was 3,
showing an average improvement of 2.7. The majority
(94%) of subjects were satisfied with their improvement
and 78% were likely to recommend the treatment to
a friend. All patients tolerated the procedure with no
major complications.
Finally, Tanghetti reported on the histological changes
in skin following treating with the fractional 755nm
picosecond laser [6]. Biopsy samples, taken immediately
after treatment, showed focal vacuoles in the epidermal
layer and, unlike Habbema’s results using 1064nm light,
no immediate changes were seen in the dermis. The
direct focal damage in the epidermis at 755nm is most
likely due to the higher relative absorption of melanin
compared to other tissue chromophores. Although
there was no thermal damage noted in the dermis
following treatment, focal regions of inflammatory cells
were noted in the dermis 24 hours after treatment. The
mechanism for this dermal response is not known at
this time; however, such observations of inflammation
would be consistent with the observation of new
collagen, elastin and mucin seen in the acne scars
study described above.

Ten minutes post:

Demonstrates vacuoles (voids) in the epidermis where optical breakdown
occurred using Fractional 755nm picosecond laser pulses.

24 hours post:
Melanin staining shows focal injuries in melanin bearing cells limited to epidermis.
No thermal injury noted to dermis.

24 hours post:
Standard H&E staining showing inflammatory response in dermis leading to
deposition of new collagen and elastin.

Figure 2: Histologic assessment of skin changes from fractional 755nm picosecond

laser pulses.6
MECHANISMS OF ACTION
The mechanism of generating subsurface ablation
zones via LIOB has been well studied [10-13]. Generally
very high laser intensities (many GW/cm2) are required,
so that initiating the process usually requires a
combination of short laser pulses and focused beams.
The process starts with the stripping of a few free
electrons from the biological tissue (seeding). For
ultrashort laser pulses, the seeding occurs via a
multiphoton ionization process, which can occur
in colorless media. For subnanosecond pulses
and colorless media, seeding is most likely a
combination of multiphoton ionization and cascade
avalanche processes (See FIG. 3). For low intensity
subnanosecond laser pulses, seeding is most likely
initiated by a chromophore required to be present in the
focal volume that is absorptive to the laser wavelength.
Figure 3: (A) Seeding of a free electron. Seeding occurs
within the beam focus where the intensity is high. (B)
Once there are sufficient seeded free electrons, avalanche
ionization occurs, greatly accelerating the production of
free electrons. (C) The free electrons form a plasma cloud
that absorbs the remaining laser energy and expands
explosively. In the process a shock wave is launched (green
circle). (D) At the end of the process, a vacuole is formed in
tissue from plasma ablation. Nearby blood vessels become
dilated and an inflammatory process is started which
includes fibroblast activation.
Once a sufficient number of free electrons are available,
a free electron plasma cloud is formed, which is
extremely absorptive and absorbs the remaining
energy in the laser pulse. In the process, more free
electrons are stripped from tissue, due to an avalanche
cascade process, and the plasma cloud grows
supersonically, launching a shock wave. In soft tissue
such as skin, the plasma cloud ablates tissue within the
cloud leaving behind a vacuole. In liquid, a cavitation
bubble is formed, which rapidly collapses following the
laser pulse, causing further mechanical stress on the
tissue. Interestingly, Candela Laser Corporation’s first
commercial medical lasers were designed for kidney
stone laser lithotripsy. Fracturing of the kidney stones
was caused by a generated shock wave and high
pressure fluid jets caused by cavitation collapse; all
initiated by a LIOB process.
Optical breakdown thresholds have a complex
dependence on laser treatment parameters. Generally,
the LIOB threshold intensity increases with decreasing
pulse duration, increases with smaller beam focus
diameters, and for colorless samples decreases for
shorter wavelengths [10-11]. For chromophore assisted
breakdown, the threshold would follow the absorption
spectrum for the chromophore and the dependence
on spot size disappears [13]. Therefore, it is difficult to
find or extrapolate, from data in the literature, LIOB
threshold values that are relevant for skin to determine
optical treatment parameters to be used with the
two PicoWay Resolve fractional hand pieces, 532nm
and 1064nm. In general, LIOB threshold can range
from 10 to 1000 GW/cm2 for a colorless sample. For
chromophore-aided seeding, the optical breakdown
threshold can be between 1 and 10 GW/cm2. For
porcine epidermis, thresholds of 2.7 and 1.2 GW/cm2
were reported for 1064nm and 532nm, respectively [13].
The Picoway picosecond laser device, when focused,
can easily generate laser intensity of TW/cm2 and
higher, and, therefore, has the capabilities to easily
generate optical breakdown in tissue. The PicoWay
Resolve fractional 1064nm and 532nm hand pieces
are capable of delivering laser intensities of 50 GW/cm2
and 30 GW/cm2, respectively. Optical breakdown has
been noted with both 1064nm and 532nm hand pieces.
The breakdown threshold is most likely chromophore-
assisted for 532nm with epidermal melanosomes being
the origin for seeding free electrons. For 1064nm, it is
unclear whether it is chromophore-assisted, and if so,
what the chromophore target is. This process will be
elucidated when histological assessment is available.
Histologic assessment of skin samples, treated
with 755nm subnanosecond pulses, are consistent
with free electron seeding from melanosomes in the
epidermis [6].
As mentioned previously, new collagen, elastin and
mucin were observed in the upper dermis, following
755nm fractional subsurface resurfacing, even though
the primary injury was located in the epidermis.
A plausible explanation for this is dermal remodeling,
including fibroblast activation that is stimulated by an
epidermal injury-induced cytokine release [14]. However,
it is also possible that dermal remodeling is stimulated
by the traveling shock wave that is initiated in the
epidermis. There are reports in the literature that show
fibroblast proliferation [15] and angiogenesis [16] induced
by extracorporeal shock waves, so it is quite possible
that intracorporeal shock waves would induce a similar
effect.

In addition to cytokine release and shock waves, it is

conceivable that light from the focus beam is directly
interacting with the dermis and stimulating the dermal
response. Therefore, although there is currently some
evidence to support dermal remodeling following
fractional subsurface ablation at 755nm, further data is
warranted to identify the mechanism that causes this
effect.

We propose that 1064nm fractional subsurface

ablation, as demonstrated by Habbema, has the
potential to directly injure the dermis, inducing dermal
remodeling, independent of an indirect method.

PICOWAY RESOLVE FRACTIONAL HAND-
PIECE
Resolve was designed to deliver a 10 x 10 array
of focused microbeams. The size of the array is
6mm x 6mm. Handpieces are available for both
532nm and 1064nm. Resolve uses holographic
diffractive beamsplitter technology to create the
10 x 10 microbeam array. While more expensive
compared to diffractive microlens technology,
holographic beamsplitters have some benefits.
Figure 4: (Top) Microbeam intensity pattern from hexagonally
packed microlens array.
(Bottom) Microbeam intensity pattern from holographic
diffractive beamsplitter. Both profiles calculated from an
input beam having a Gaussian spatial profile.
Of course, the energy in each microbeam is halved
when compared to the full input beam. With diffractive
microlens, half of the microbeams would be missing so
a 10 x 10 microbeam array would only deliver a 5 x 10
microbeam array.

The most important benefit is a flat field response,

where the intensity is consistent across all microbeams.
The intensity of the microbeams from a microlens are
dependent on the spatial distribution of the incoming
beam, so a Gaussian-shaped input beam would create
a matrix of microbeams having this Gaussian shape
(See FIG. 4).

Holographic diffractive beamsplitters are much more

forgiving towards the incoming beam. Taken to an Figure 5: Insensitivity of microbeam array pattern for

extreme, if half the input beam was blocked, the holographic beamsplitters.

holographic beamsplitter would still form a complete

10 x 10 microbeam array with equal energies in all Another benefit of holographic beamplitter technology
microbeam (See FIG. 5). is more efficient use of the beam energy. With microlens
technology, about 30% of the beam energy is lost to
the space between the microlens. The lost light is
delivered to tissue as unfocused background light. The
background light has insufficient energy to generate
plasma and although some claim the warm heating
from this background light is beneficial to treatment,
no data exist today to support such an argument.
CONCLUSION
In conclusion, reports in the literature support LIOB as
a mechanism of action for Resolve. The holographic
diffractive beam-splitter technology is used to create
two dimensional arrays of LIOBs in the superficial skin.
The LIOBs can be focused in the epidermis, using the
532nm wavelength, or in the upper papillary dermis
using the 1064nm wavelength. In this way, treatments
can be specifically tailored to treat dyspigmentation,
skin and textural irregularities and signs of aging.
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