Curing with light
was known and used in medicine in ancient times.
Red or ultraviolet light was successfully used
in the 19th century for the treatment of
pockmarks and lupus vulgaris by Danish
physician, N. R. Finsen, the father of
Biological phenomena induced by ultraviolet
light have been intensively investigated in
photobiology and photo medicine for several
decades. Ultraviolet light as a phototherapy for
some dermatological diseases (mainly psoriasis)
has been used since the early twenties. However,
ultraviolet light is an ionizing radiation, and
therefore has a damaging potential for
biomolecules and has to be used in photomedicine
with certain precautions.
Biological and healing phenomena induced by
optical wavelength (visible) and infrared
(invisible) light have been intensively
investigated in the last decade. Electromagnetic
waves with optical (visible light) and near
infrared (invisible irradiation) wavelengths
(.lambda.=400-2,000 nm) provide non-ionizing
radiation and have been used in vivo, in vitro
and in clinical studies, as such radiation does
not induce mutagenic or carcinogenic effects.
Low energy photon therapy (LEPT), also known as
LED photobiomodulation, is the area of
photomedicine where the ability of monochromatic
light to alter cellular function and enhance
healing non-destructively is a basis for the
treatment of dermatological, musculosketal, soft
tissue and neurological conditions.
Low energy photons with wavelengths in the range
of 400nm-2,000 nm have energies much less than
ultraviolet photons, and therefore, low energy
photons do not have damaging potential for
biomolecules as ionizing radiation photons have.
The area of LEPT research is controversial and
has produced very variable results, especially
in clinical studies. Almost every mammalian cell
may be photosensitive, e.g. could respond to
monochromatic light irradiation by changes in
metabolism, reproduction rate or functional
activity. Monochromatic light photons are
thought to be absorbed by some biological
molecules, primary photoacceptors, presumably
enzymes, which change their biochemical
activity. If enough molecules are affected by
photons, this may trigger (accelerate) a complex
cascade of chemical reactions to cause changes
in cell metabolism. Light photons may just be a
trigger for cellular metabolism regulation. This
explains why low energies are adequate for these
so called "photobiomodulation") phenomena.
However, it is difficult to induce and observe
these phenomena both in vivo and in vitro using
the same optical parameters. Specific optical
parameters are required to induce different
photobiomodulation phenomena (Karu, Health
Physics, 56:691-704, 1989; Karu, IEEE J. of
Quantum Electronics, QE23:1703-1717, 1987). The
range of optical parameters where "photobiomodulation"
phenomena are observed may be quite narrow. The
specificity and narrowness of the optical
parameters required for "photobiostimulation" in
LEPT therapy distinguishes LEPT therapy from the
photodestruction phenomena induced by hot and
mid power lasers (e.g. in surgery and PDT).
To meet the
changing requirements for optical parameters for
different experimental and clinical
applications, there is a need for an optical
system for "photobiomodulation" having flexible
parameters, adjustable for particular
applications. In particular, there is a need for
an apparatus capable of treating a range of
biological disorders by reliably providing light
to the affected three dimensional biological
tissue, which light has the optical parameters
necessary for inducing the appropriate
photobiomodulation for the particular disorder
and tissue to be treated. There is also a need
for a method for reliably providing light having
such parameters to a biological tissue having a
disorder in order to effect healing.
Intensity (Power Density)
Intensity is the
rate of light energy delivery to 1 cm.sup.2 of
skin or biotissue. Intensity is measured in
milliwatts per cm.sup.2 (mW/cm.sup.2). Real
intensity on the skin surface depends on light
reflection and scattering from the skin and
underlying tissue layers. The light intensity on
the skin surface can be calculated with the
where P (or Pav for pulsed mode) is the optical
power, d(cm) is the beam diameter and R is the
reflection coefficient. Coefficient R can vary
from 0.4 up to 0.75 for different wavelengths
and depends also on the skin type and condition.
For applications using non-contact techniques a
portion of the optical power (and dose) equal to
R.times.P is lost because of the reflection.
Back scattering has to be taken into account for
LEPT dosimetry as well. For contact technique
applications, less power is lost due to the
repeating light reflection back to the skin
surface from optical source parts. Therefore,
for the same optical source LEPT dosimetry would
be different depending on the type of technique
used (contact or noncontact). Particular "photobiomodulation"
phenomenon can best be activated within narrow
ranges of parameters (e.g. see Tables 2, 5,
which appear later in this description). For
example, collagen type 1 production is thought
to be affected by LEL in an inverse manner to
fibroblast proliferation: when cell
proliferation is increased, collagen type 1
production is decreased and vice versa (van
Breugel and Bar, 1992, Laser Surg. Med.
12:528-537). In cell culture experiments thin
cell layers are usually uniformly exposed to
light therefore intensity does not change
significantly within the sample. For biotissue
stimulation, the whole picture is different
because light intensity (and dose) decreases
with depth z. In the skin and subcutaneous
tissue layers light intensity can be
approximately described by the following formula
I(z)=I.sub.o (I-R)exp(-.alpha.z) ##EQU1##
where I(z) (w/cm.sup.2 or mw/cm.sup.2)--is the
fluence rate (intensity or power density) at the
depth z (mm); I.sub.o =P/S--incident intensity;
P--beam power; S=.pi.d.sup.2 /4 is a beam area
for a cylindrical parallel beam of diameter d
(cm); and .alpha. (mm.sup.-1) is the attenuation
coefficient which depends on light absorption
and scattering. This formula may be used to
calculate intensity and dose for every
particular tissue layer.
Suitable intensities for biostimulation are in
the range of from 0.1 to 5,000 mW/cm.sup.2. For
stimulating healing of chronic ulcers or wounds
intensity may preferably be in the range of from
0.2 to 10 mW/cm.sup.2, for ulcers or wounds in
acute inflammatory stage a preferred range is
from 10.0 to 30 mW/cm.sup.2 and for infected
wounds a preferred range is from 50 to 80 mW/cm.sup.2.
Table 2 below shows suitable ranges of
intensities for different tissue pathologies.
Beam Diameter and Divergence
Beam diameter and
divergence are important features of single
optical sources. Beam size affects light
intensity values on the skin surface and within
the tissue in accordance with formulae (3, 4).
Beam divergence affects light distribution and
dosimetry for different tissue layers. For
non-contact techniques light spot size and
irradiated area S on the skin surface depend on
the distance to the irradiated surface h as
where d is the beam diameter near the probe tip,
2.alpha. is the diverging angle, 2h.times.TAN
.alpha. is the additional beam diameter due to
Different optical sources (lasers, laser diodes,
light emitting diodes, etc.) have different beam
divergences. Lasers usually have small beam
divergency, laser diodes and LED's have bigger
divergences. For different applications
particular beam divergences are more convenient.
For example, for the treatment of wounds and
ulcers, almost parallel beams are less desirable
because of the large areas to be treated, and
optical sources with some particular divergence
are more convenient.
The beam diameter and divergence should be
selected based on the three dimensional size and
shape of the tissue area affected. Preferably,
the beam diameter and divergence should be
selected such that the area receiving LEPT is
just slightly larger in size than the area
affected. The appropriate radius of the beam may
be calculated by the following formula:
where R (cm) equals the radius of the area
affected by the disorder. In the case of
lesions, such as ulcers or other open skin
wounds, it is particularly important that too
large an area not be illuminated as, where the
illuminated area is much larger than the lesion,
the skin ulcer (wound) healing rate is not
optimized. As the ulcer is treated and healed
the area requiring treatment and the beam
diameter will have to be reduced.
The dose D is the light energy provided to the
unit of surface (1 cm.sup.2) during a single
irradiation and measured in J/cm.sup.2 or mJ/cm.sup.2.
The light dose received by the skin surface is
where I is the intensity on the skin surface,
and t is the exposure time (s). The dose
received by subcutaneous tissue layer at the
depth z for a parallel beam can be calculated by
the following formula:
where I(z) is given by formula (4).
As mentioned above, the dose alone does not
ensure particular photoeffect or healing
phenomenon. Only proper selection of the whole
set of optical parameters including dose will
provide the desirable therapeutic effect. The
selection of optical parameters depends on the
medical condition, location of the affected
areas, person's age, etc.
Frequency and Pulse Duration
frequencies of 0-200 Hz may sensitize release of
key neurotransmitters and/or neurohormones (e.g.
endorphins, cortisol, serotonin). These
frequencies correspond to some basic
electromagnetic oscillation frequencies in the
peripheral and central nervous system (brain).
Once released these neurotransmitters and/or
neurohormones can modulate inflammation, pain or
other body responses. Analogous phenomena can be
expected with "photobiomodulation" within the
same range of low frequencies. Certainly, the
interaction between living cell and pulsed
electromagnetic wave depends on wavelength as
well as pulse duration. Pulse repetition rates
within the range 1,000-10,000 Hz with different
pulse durations (milli-, micro- or nanoseconds)
can be used to change average power.
Three Dimensional Light
Depending on the
target tissue for LEPT (e.g. skin, muscle,
ligament) a proper three-dimensional light
distribution should be provided to get the
desirable physiologic and therapeutic response.
For single optical sources important parameters
affecting light distribution are beam size,
divergence, light wavelength as well as
biotissue optical properties (reflection,
absorption, scattering, refraction). Total
reflectance is equal to the sum of the regular
reflectance from the skin surface and the
remittance from within the tissue (see FIG. 4).
For cluster probes, additional contributive
parameters are the distance between diodes and
the cluster probe's three-dimensional shape. All
these parameters should be physiologically
justified to provide optimal biotissue response
and requirable three-dimensional light
distribution. For example, the distance between
diodes can affect vasoactive blood vessel
response and average energy density delivered to
the treated area. For proper vasoactive response
a definite distance between diodes has to be
provided depending on particular parameters of a
singular diode (power, beam, diameter,
The three-dimensional light distribution in
tissues such as the skin and underlying tissue
layers may be calculated based on diffusion
approximation and/or the Monte Carlo approach
(L. Wang and S. Jacques, Hybrid model of Monte
Carlo Simulation and diffusion theory for light
reflectance by turbid media, J. Opt. Soc. Am.
A/Vol. 10, No. 8, 1993, pp 1746-1752; A. Welch
et al., Practical Models for Light Distribution
in Laser-Irradiated Tissue, Lasers in Surg. Med.
6: 488-493, 1987). Wavelength
Wavelength.lambda. (nm) is the basic
electromagnetic wave feature which is directly
linked to the energy of an individual light
quantum (photon). The more wavelength the less
photon energy. Wavelength is also linked to the
monochromatic light color. Visible monochromatic
light changes its color with wavelength,
increasing from violet and blue (shorter
wavelengths) to orange and red (longer
wavelengths). Cell culture experiments have
indicated that there is a selectivity in
photoinduced phenomena related to wavelengths.
Experiments on different cell cultures (microbe
and mammalian) have revealed the ranges of
wavelengths (360-440 nm, 630-680 nm. 740-760 nm)
where photoinduced phenomena are observed (Karu,
Health Physics, 56:691-704, 1989; Karu, IEEE J.
of Quantum Electronics, QE23:1703-1717, 1987).
Photoeffect can be induced by monochromatic
light, only in cases, where a cell contains
photoacceptors, substances which are able to
absorb monochromatic light of this particular
wavelength. No photoinduced cell phenomena can
be observed if there are no wavelength specific
photoacceptors in a cell.
The following factors have to be taken into
account when considering LEPT dosimetry for
monochromatic light of a particular wavelength
.lambda.. The dose required for "photobiomodulation"
strongly depends on the wavelength. In general,
the longer the wavelength the more dose is
required to induce photoeffect. For example, in
experiments on cell cultures, doses required for
DNA synthesis stimulation are 10-100 times less
with blue light (.lambda.=404 nm) than with red
(.lambda.=680 nm) or near infrared (.lambda.=760
Wavelengths in the range of from 400 to 10,000
nm may be used for LEPT, preferably from 500 to
2,000, more preferably from 600 to 1,100, most
preferably from 600 to 700 nm and 800-1,100.
There appears to be some optimal wavelength
range to induce every particular photoeffect or
healing phenomenon. For example, light having a
wavelength of from 600 to 700, preferably from
630-680 nm, may be used for wound and ulcer
healing. For chronic soft tissue pathology
monochromatic light in near infrared wavelength
range (800-1,100) is more suitable.
Biotissue optical parameters (reflection,
scattering, refraction, absorption and depth
penetration) depend on wavelength. Therefore,
light wavelength affects three-dimensional light
distribution in biotissue. For example in a
specific wavelength range, the longer wavelength
the more light penetration depth. The darker
skin the more light absorption, therefore the
dose for a black skin has to be less then for a
Light source is
described by its spectrum, which shows the range
of wavelengths of the emitted light. Strictly
monochromatic light source is a source of
radiation with exactly the same wavelengths.
This is never achieved in practice even with a
laser. Every light source can be described by
its spectrum bandwidth .DELTA..lambda.(nm). The
smaller the bandwidth the more monochromaticity
of the light source. The following
considerations are important in regards to light
Biological objects became adapted to wide-band
solar radiation through evolution. Therefore,
pronounced photoinduced phenomena in living
cells can be observed only under irradiation by
a light source with narrow enough bandwidth. The
exact restrictions on light bandwidth may differ
for various biological objects.
Simultaneous irradiation by wide bandwidth and
monochromatic light can lead to decrease or even
disappearance of "photobiomodulation" effect.
Therefore, it is recommended to provide some
LEPT treatments in a darkened room.
Difference in wavelengths emitted by optical
source is leading to dispersion in light
reflection, scattering, refraction and
absorption which can affect three-dimensional
light distribution and LEPT dosimetry.
Bandwidth of the optical source can affect
optimal intensity and dose values required to
induce a particular healing phenomenon. The full
bandwidth of monochromatic light to activate
healing phenomena should not exceed 30-40 nm.