Physics and physical properties to be considered when utilizing therapeutic laser energy for bio modulation of cellular and tissue function.
Written by Dr. Peter H. Eeg BSc, DVM, CVLF, FASLMS
Poolesville Veterinary Clinic, Poolesville, Maryland
The following are four keys to understanding therapeutic laser energy that I feel will provide you with the best opportunity to provide your patients with the best treatment outcome.
Key #1: Wavelength Penetration
Do not confuse the level of Power being applied and the penetration of energy into tissue as the same thing, because they are not.
It is important to remember that while certain wavelengths of Diode therapeutic laser energy penetrates much more deeply into tissues (Figure 1.) others have a much more limited penetration capability. The first thing to consider is which wavelength you are planning to use and if it will reach the tissue you are targeting.
Key #2: Power and Fluence
A critical factor to consider with the relationship of energy and its transfer to target tissues using Diode laser wavelengths is the effect of the Lambert-Beer Law.
About 60 to 80% of the energy is absorbed in the top 1-2cm of tissue during the transmission (Figure 2). High levels of Power applied at the skin surface from the therapy laser probe head does not necessarily correlate to deeper penetration into tissue.
The Lambert-Beer law shows that Power (W) is non-linearly absorbed by the variety of chromophores that absorb photonic energy in the first 2 cm of tissue. Thus it is far more important to select the appropriate wavelength to effectively transmit laser energy to deeper target tissues than increase total power at the surface.
A photo-thermal effect is seen more commonly with 980nm wavelengths due to their relatively shallow penetration depth (Figure 1) and its relative higher absorption by water, hemoglobin, oxy-hemoglobin and melanin. Photo-thermal effects may raise cellular temperatures above 45o C where cellular metabolism slows and enzymatic function decay. Continued increased power levels can cause rupture of protein bonds and fragmentation of cohesive molecular forces ultimately causing cellular damage or cellular death.
The use of Power in Watts (W) to express the energy going into tissue is an excellent descriptor in surgical lasers but a very poor descriptor of the actual energy to be imparted to tissues during exposure via a therapy laser. The optical therapeutic window that encompasses Diode laser energy is a critical factor in the transmission of energy to the deeper tissues (Figure 3).
Figure 3. Optical Therapeutic window of Diode laser wavelengths
Key #3: Time and emission modality
Appropriately describing therapy laser energy requires information about the previously discussed penetration of the wavelength, Joules and Fluence applied to the tissue. Equally critical is the total time duration of the energy application to the tissue, including the emission modality and then the total irradiance (Figure 4). Figure 4 gives a quick overview of the formulas needed to be confident about sharing information with other clinicians about cases that you are treating with therapy lasers. Clinicians should provide the total mille-Joules/Joules to be delivered, the total time of delivery and the total surface area to receive bio modulatory TLE. This produced the total irradiance (J/cm2/time) that can be rectified between any therapy protocol guideline given by varying companies and clinicians. To simply indicate the Watts applied will not allow other clinicians with different devices an opportunity to replicate your results.
These formulas indicate that energy density = Fluence which is the parameter that best permits us to interpret the protocols of varying therapeutic laser therapies. By example if we treat a 1 cm2 surface for 10 seconds with 10J/sec energy we will have a Fluence of 100J/ cm2. If we expose a 10 cm2 surface to the same power for the same time, then the Fluence will be only 10J/cm2 . Current research is showing that by varying all these factors changes the therapeutic value to the target tissue.
Equally important are the emission modalities available to apply the energy. By varying both the Hertz (Hz) and the total duty cycle (time of active output) of the laser energy being emitted (Figure 5) total energy application duration can be manipulated to maximize positive therapeutic effect. This is affected by changing the emission of the laser energy from a continuous output, to a chopped output (Figure 5, 808nm wavelength portion), or pulsed output (Figure 5, 905nm wavelength portion), or Q-switched ultra-pulsing (1064 nm). Further enhancing the total emitted energy is the synchronization (Figure 5) of one or more of these emission parameters to additional wavelengths. Synchronization and Q-switching can maximize the uniformity of energy dispersion into the targeted tissue and the energy delivery to specific cells and tissues thus giving a homogeneous and enhanced therapeutic effect.
Figure 5. Synchronous emission of continuous 808nm wavelength with a pulsed 905nm wavelength
Key #4: Laser/Tissue Interaction and the Bi-phasic Curve Effect
The bio modulatory effects on tissue from therapy laser energy are a combination of photo-chemical, photo-mechanical and photo-thermal effects. Depending on the wavelength, Fluence, emission modality and time the percentage of each effect varies to the target tissue and thus manipulated the bio modulatory effect.
Photochemical effects are most responsible for anti-inflammatory, anti-edema, analgesic and bio-stimulation and regenerative effects.
Photomechanical effects are most responsible for enhancing lymphatic peristalsis and realignment of damaged collagen fibers and connective tissues. This also can provide a regenerative component to TLE.
Photo-thermal effects can produce additional improvement in bio modulation when producing small incremental increases to the tissue temperature. High increases may raise cellular temperatures above 42o C where cellular metabolism slows and enzymatic function alters. Excessive energy release into tissue can cause rupture of protein bonds and fragmentation of cohesive molecular forces may occur.
Current basic research being done is finding that the selection of ultra-pulsed Q-switched 1064 nm and/or 800-810nm and 900-910nm near infrared wavelengths are recommended to maximize energy delivery to deeper target cells and produce the photo-bio modulation discussed above.
Photochemical effects associated with Q-switched 1064 nm ultra-pulsing and the 808nm wavelength are most responsible for anti-inflammatory, anti-edema, analgesic and photo-bio modulation effects.
Photomechanical effects associated with the 905nm wavelength are most responsible for enhancing lymphatic peristalsis and realignment of damaged collagen fibers and connective tissues.
Equally important is the fact that current research has shown that bio modulatory therapy laser energy has a biphasic dose response in the target tissue (Figure 6). This is just like the effect many medications have at the target. It is often termed the Arndt-Schulz curve. Too little produces no effect, the right amount produces a therapeutic photo-biostimulation effect and too much produces again no effect or a negative photo-biostimulation effect.
Figure 6: Idealized biphasic dose response curve (often termed Arndt-Schulz curve)
typically reported in Therapeutic Laser tissue application
The preceding four keys to a basic understanding of therapy laser/pathology interaction are fundamental to a fuller understanding of how laser wavelengths impacts the tissues and pathologies they are being utilized for in veterinary and human medicine and surgery.
As with other forms of medications, therapeutic laser energy has its active quantifiers that when combined together give the total bio modulatory picture for tissue interaction, modification and regeneration. Medicine (irradiation parameters) and Dose (the irradiation time), when thought of in way medications and radiation are calculated to produce the optimal therapeutic effect can give the veterinary clinician and technician a much clearer understanding of what they are doing when applying laser energy..
Irradiation parameters include; wavelength, irradiance, pulse structure, pulse time, wavelength penetration, coherence and polarization.
Irradiation time include: Energy (Joules, J), energy density (J/cm2) irradiation time (seconds to minutes) and treatment intervals (hours, days or weeks).
This clearly indicates the fact that energy has two components, power and time when discussing therapy laser-tissue bio modulation. Key to this is the realization that the two are not necessarily providing reciprocity between them, but a cumulative bio modulatory effect to the target cell type or tissue type. If the power doubled and the time is halved then the same energy is delivered but a different biological response is often observed to the pathology being treated.
For this reason the four keys must be viewed from two separate but equally important parameter settings to maximize the therapeutic window of the laser energy.
The medicine= irradiation parameters
The dose= irradiation time parameters
Cellular Chromophores are critical to the photo-biologic effect desired when using therapeutic laser energy. The photons must be absorbed by an electronic absorption band belonging to some molecular photo-acceptors or chromophores. A simple example is seen in chlorophyll used for plant photosynthesis, hemoglobin, cytochrome c oxidase, myoglobin, Flavin’s, flavo-proteins and porphyrins are also illustrations of such chromophores utilized by therapy laser energy application.
To optimize the effect there must be optical properties of the wavelength and tissue that allow the energy to reach the chromophores. This is known as the optical window where the penetration of the laser wavelength is maximized. This optical window runs approximately from 650nm to 1200nm. The absorption and scattering of light in tissue are both much higher in the blue region of the spectrum than the red, because the principle tissue chromophores in tissue are hemoglobin and melanin and have a high absorption band at shorter wave-lengths, tissue scattering of light is higher at shorter wave-lengths and furthermore water strongly absorbs infrared light at wave-lengths greater than 1100nm. Therefore the therapy laser energy use in animals is almost exclusively in the long visible red and near-infrared light ranges (600-1100nm)
Thus phototherapy is characterized by the ability to induce photo-biological processes in cells. Differing wavelengths produce differing action spectra. This is where research can identify where action spectrum can show specific wavelengths with the most effective and specific chemical reaction producing optimized cellular responses.
Tangential to this is the variation that pulse rated, and total time domain of TLE into a target tissue have on optimal bi-phasic maximization of bio modulatory effect. Here Q-switching for ultra pulse release of peak energy over extremely short time periods and synchronization of multiple wavelengths to maximize homogeneity of energy into the target cells and tissue are generating profoundly positive results.
Specific cellular structures and mechanisms revolve around mitochondria. Mitochondria plays a central role in energy generation and metabolism of the cell. This is where TLE can produce optimal positive energy release for improving or stimulating cellular respiration, cell wall stabilization and cell reformation if damaged. ATP formation via the process of oxidative phosphorylation is a central factor. Several pieces of evidence suggest that mitochondria are responsible for the cellular response to long red and near infrared light sources. Positive aspects include; increased proton electrochemical potentiation, more ATP synthesis, increased RNA and up regulation of protein synthesis. This enhances increased oxygen consumption, membrane potential, and enhanced synthesis of NADH and ATP.
The same COX (cytochrome c oxidase) we manipulate for anti-inflammatory mitigation, is proposed to be the primary photo-acceptor for the red-NIR range in mammalian cells (Karu and Kolyakov 2005).
Although the underlying mechanisms of TLE are still not completely understood, in vitro, in vivo and clinical studies have all tended to indicate that the delivery of appropriate doses of red-NIF light over appropriate time domains produce optimal photochemical and photo-biological effects to pathologies of mammalian tissue and thus a total bio modulatory enhancement of cellular function and proliferation, migration and adhesion in a variety of cell types from fibroblasts (Lubart et al. 1992, Yu et al. 1994), keratinocytes (Grossman iet al. 1998), endothelial cells (Moore et al. 2005), and lymphocytes (agaiby et al. 2000; Stadler et al. 2000). The enhancement of photo stimulatory effects to the mitochondria enhanced growth factor release and led to cell proliferation and attachment. All these positive cellular factors are dose-dependent with respect to the irradiance parameters and irradiance time parameters.
The extended positive tissue responses found in a large number of both animal trials and clinical studies have demonstrated that the above description of how therapeutic laser energy up regulates cellular respiration and cellular proliferation has a beneficial impact on a wide range of bio modulation to positively modify disease, injuries (chronic and acute) and tissue pathologies. Overwhelming research has determined that TLE can promote neovascularization, promote angiogenesis, increase collagen synthesis, promote healing of both acute and chronic wounds, stimulate improved nerve conduction and nerve regeneration, improve tendon re-alignment, promote cartilage regeneration, and even stimulate organ regeneration. These pro-regenerative effects promote reduction in pain directly and indirectly and the photomechanical effects promote reduction in inflammation and swelling.
There is no question that we do not yet have a very full understanding of the nuances that go into the symphony of interactions between the many three dimensional moving parts that make therapeutic laser administration. What is clear is that basic Diode wavelength effect research and a growing number of well done human and animal studies designed to identify the optimal proportions of all of the afore mentioned components that make up a photo-biostimulation effect by these near infra-red band wavelengths is very encouraging.
Therapeutic laser energy used alone or in concert with other therapeutic modalities can further enhance positive therapeutic outcomes for a host of current disease and pain processes. The time to think about using therapeutic lasers has passed. The time to use therapeutic lasers is now.
About Dr. Eeg
Dr. Peter Eeg grew up in Wheaton, Maryland and graduated from University of Maryland as an undergrad and graduate in Animal Science, Parasitology, and Immunology. He then attended and graduated with honors earning his veterinary degree from the Virginia-Maryland Regional College of Veterinary Medicine. Upon graduating, he interned at Peachtree Veterinary Clinic under the guidance of his lifelong friend; Dr. Chet Anderson. Dr. Eeg took over the reins of Poolesville Veterinary Clinic over 25 years ago, never looking back and always to the future.
To expanded his knowledge in veterinary medicine Dr. Eeg has obtained specialized training in laser surgery and therapy. Additionally, he worked in the first inter-disciplinary group related to pain management in people and animals, studied and lectured on the human-animal bond, quality of life issues and end of life care and euthanasia. He is an internationally recognized speaker in these areas and has traveled extensively at the request of National and International Veterinary Education Congresses.
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