Deep Tissue Red Light Therapy Dosing: Does High Intensity Increase Penetration?

Deep Tissue Red Light Therapy Dosing: Does High Intensity Increase Penetration?

Improving the penetration of light into the skin is a key area for direct treatments with Photobiomodulation.

However, many of the effects from Red Light Therapy are systemic in nature, particularly from non-contact LED panels that inherently have poor penetration. Meaning that even if the light doesn't directly penetrate deep enough, deeper tissues can benefit through indirect mechanisms. 

Which is why adhering to proper dosing protocols is more important than maxing out the penetration depth to speculatively deliver better results. 

Through the years, influencers have insisted that high intensity is essential for deep tissue treatments. These claims rarely come with citations or references.

What does the research say about how intensity affects penetration depth? Does an intensity of 80mW/cm^2 penetrate 4 times deeper than an intensity of 20mW/cm^2? How does that affect our dosing methodology?

Summary:

Penetration depth is primarily determined by wavelength. The exposure time, and ultimately the "dose" of J/cm^2 determines how much energy reaches the deeper tissues.

While having adequate intensity is certainly important for a therapeutic response, it does not significantly improve penetration depth within typical LLLT/PBM parameters. Too much intensity will simply cause heat without any apparent advantage to penetration depth or therapeutic response, which would need to by mitigated by pulsing, scanning, or other cooling techniques.

    A recent June 2024 systematic review article looked at the optimal parameters for Near-Infrared transcranial (through the scalp/skull targeting the brain) light therapy from a large number of studies. Their conclusion was that the lower intensity range tended to have better results than the higher intensity range. 

     "Our findings suggest that NIR light with low-power density (15–30 mW/cm2)

    is a more effective intervention than that with high-power density (40–90 mW/cm2)." [1]

    Results like this are shocking, as it is often claimed that higher intensities are unconditionally superior in many ways.

    Another recent June 2024 article also notes that the LED devices typically used for brain health are in this range:

    "LEDs have power densities between 10 and 30 mW/cm2." [61]

    Another recent June 2024 systematic review article on PBM for TBI summarizes:

    "In research on TBI, most studies have set the irradiance at 10–70 mW/cm2, with 22.2 mW/cm2 as the most commonly used."
    ...

    "In order to ensure patients’ safety, the values used in the medical field are usually low" [65]

    Influencers would claim that 10-30 mW/cm^2 is barely sufficient for superficial treatments, yet these review articles found trends that this intensity range was effective for a deep tissue treatment like the brain. What could really be going on here?

    Deep Tissue Penetration Diagrams:

    Lets quickly review some penetration diagrams that summarize these important dosing concepts. Then we can dig into the supporting articles.

    Lets follow along a rough example stated in one 2010 article. [2]

    They state that from an 810nm wavelength, about 10% of the intensity reaches 10mm deep, and 1% of the intensity reaches 20mm deep.

    A more recent 2022 article confirms this penetration profile from Near-Infrared lasers:
    "most of the initial light energy was lost in the first one to two millimeters,
    more than 90% of the light energy was absorbed within the first ten millimeters,
    and there was hardly any light energy left after 15–20 mm of tissue." [3]

    An insignificant amount of NIR would be expected to pass 20mm (2 cm, or 0.79 inches) of tissue thickness, since it is subjected to exponential absorption curves. 

    See the exponential absorption curves in this study and this study and this study.

    These percentages are the same regardless if a relatively high intensity or low intensity is being used. Thus, from this perspective we can say the penetration profile and depth are determined by the wavelength.

    Lets consider if we use 20mW/cm^2 versus 80 mW/cm^2 in these diagrams. The intensities being applied to the surface of the skin. 

    From this view, it is clear that the higher intensity gives better penetration. Even though we multiplied both surface intensities by the same percentages, it appears the 80mW/cm^2 delivers more intensity at the corresponding depths. 

    In this one specific perspective, it is fair to generalize to say that higher intensities do have better penetration.

    However, the depth of penetration does not significantly increase with intensity, since the percentage penetration beyond 20mm becomes exponentially small. 

    When we fit these initial skin intensities into this exponential model:

    Regardless of starting with 80 or 20 mW/cm^2 at the surface, both intensities are flatlined close to zero beyond 20mm. As we can see, at 30mm deep we would get 0.02 and 0.08 mW/cm^2, both of which would be negligible for a therapeutic response.

    It would require orders of magnitude (i.e. 100x) higher intensity to make a significant impact on the effective penetration depth. This is not achieved by simply doubling or even quadrupling intensity. We cannot solve an exponential problem with linear thinking. 

    Ultimately, the goal is that the proper dose (J/cm^2) must be reached for both the high intensity and low intensity exposure. As such, we adjust the Exposure Time to reach the same dose of Energy Density (J/cm^2).

    So lets say for both intensities we want to reach 24 J/cm^2. Which is a reasonable dose for deep tissues.

    For example one human case report series for TBI used LED cluster units delivering 8 to 20 J/cm^2 on the forehead. They used intensities between 22-26 mW/cm^2. [4]

    According to our dosing calculator, to reach 24 J/cm^2 the 20mW/cm^2 would take 20 minutes and with the 80mW/cm^2 would take 5 minutes.

    Now lets look at the penetration profile based on this dose:

    *A similar illustration can be found in Tuner & Hode's Phototherapy textbook, page 687-688 [5]

    As we can see, when we apply the same dose at the surface, then the penetration of this energy is exactly the same for both intensities. Based on the wavelength and dose we get the same penetration.

    Low intensities deliver the same penetration when applied for the proper amount of exposure time for the same dose. Which may be important to use low intensities and adequate exposure times to optimize the benefits of red light therapy. 

    So rest assured that even when influencers claim you need high intensities for deep penetration, this claim is not entirely accurate. It is based on a narrow perspective that conveniently ignores dosing and exposure time, and that penetration depth is mostly determined by wavelength. 

    Wavelength Determines Penetration Depth:

    It is fairly common knowledge that the wavelength is the primary determinant of penetration depth. 

    The "Optical Window" of the skin in PBM generally ranges between between 600nm to 1100nm. This is the lowest intersection of absorption coefficients for water, blood, and melanin that allows these wavelengths deeper into the skin. 

    A quote from a 2022 article on optimizing doses for deep penetration states the optimal wavelength ranges for deep penetration as:

    "The spectral ranges for maximal penetration depths

    are 800–900 nm and 1000–1100 nm." [6]

    The first step to optimize penetration is to use wavelengths in these ranges.

    It is most commonly accepted that the wavelength, and more specifically the interactions between wavelength and the optical properties of the skin, is the determining factor for the penetration profile. 

    As one review article puts it:

    "Wavelength affects tissue penetration."
    ...
    " Red wavelengths penetrate 0.5 to 1 mm and
    near-infrared energy penetrates 2 mm

    before losing 37% of its intensity." [7]

    Statements about penetration are often entirely dependent on the wavelength, regardless of intensity.

    Another study also clearly stating that the wavelength determines the depth penetration of the light. 

    "The wavelength is the most important.
    It determines the depth of the penetration by the light—
    the higher the wavelength, the greater the

    laser penetration through the tissues" [8]

    And yet another study says something similar:

    "Wavelength is therefore a very powerful determinant
    of the absorption component of the basic light/tissue
    reaction of light-based medical systems,13 
    determining not only the target chromophore for any laser system

    but also how deep that laser can intrinsically penetrate into tissue." [9]

    Another 2024 one:

    "The parameter wavelength determines tissue penetration

    and affects the corresponding biological functions." [10]

    And:

    "The wavelength of a laser will predominantly
    determine penetration depth and location of

    energy absorption[20]

    And:

    "Light wavelength influences the deep and superficial
    target tissues at long and short wavelengths, respectively [32]."
    ...
    "The penetration depth increases with

    increasing wavelength of light [35]. " [34]

    Also:

    "As noted in the section on wavelength,
    wavelength exerts a significant influence

    on the depth of penetration of light." [12]

    The scientific consensus is quite clear on this topic. The wavelength alone is the most influential parameter that determines the penetration depth. 

    Consider the following quote:

    "RL [Red Light] penetrates 6–50 mm deep.

    BL [Blue Light] likely has a maximum skin penetration of 0.5–1 mm." [11]

    Lets say we want to improve the penetration of Blue light beyond the maximum of 1mm. Could we simply increase the intensity to push more Blue Light deeper than 1mm? Perhaps, but not by much as it has extremely strong absorption by blood and melanin. Ultimately it would cause more problems than it is worth. 

    Similarly Red/NIR light is often limited to about 50mm, which cannot be overcome simply by increasing intensity in a linear fashion. As we know beyond about 20mm with NIR the exponential absorption takes over and the intensity becomes negligible.  

    Dose Determines The Energy that Reaches Deep Tissues:

    Most people have gotten the memo that different doses are used depending on the depth of the target tissue. Proper dosing (Energy Density, J/cm^2) determines how many photons reach the deeper tissues.

    Lower Energy Density is used for superficial tissues, while higher Energy Density is used for deeper tissue. 

    According to one excellent article on parameters used in Photobiomodulation:

    "Another respected source suggests that doses used for
    superficial targets tend to be in the
    region of 4  J/cm2 with a range of 1 to 10  J/cm2.
    Doses for deeper-seated targets

    should be in the 10 to 50/cm2 range." [7]

    The article says that superficial dosing ranges are 1 to 10 J/cm^2, and deeper tissue dosing ranges are 10 to 50 J/cm^2. The article notes that wavelength and dose determine the penetration depth, with no mention of requiring higher intensities for deeper penetration. 

    A recent 2024 systematic review article for PBM on the Brain notes these ranges of doses:

    "Concerning energy density, previous studies have pointed out that the most commonly used doses for treating neurological disorders are between 10 and 30 J/cm2, and for treating psychological disorders, between 12 and 84 J/cm2." [65]

    When we talk about the dose delivered then we are typically discussing the energy that lands on the surface of the skin. But for deeper tissues we need to consider the amount of photons that actually reach that depth.

    For example, we can consider a dose of 4 J/cm^2 compared to a dose of 40 J/cm^2 at the skin surface.

    In our Biphasic Dose blog, the graph shows that cells typically respond well to 2-10 J/cm^2. So for superficial tissues using 4 J/cm^2 at the surface can work very well.

    As we can see in the diagram above, the dose of 40 J/cm^2 on the skin surface will deliver 4 J/cm^2 to the cells that are 10mm deep. So the deeper tissue cells at 10mm are now receiving the optimal dose.

    However, higher-mitochondrial density cells respond well to even lower doses. Which is why using 10-20 J/cm^2 at the surface can do well for deep tissue treatments like the brain. 

    Other articles offer similar advice for utilizing the Dose and Exposure Time to promote deep tissue treatments. 

    "Moreover, increasing the duration of treatment increases
    the likelihood that a cumulatively larger quantity of photons or light energy

    will propagate to deeper tissue levels." [12]

    And another article: 

    "Because of the optical properties of brain and its surrounding tissues,
    the total dose of light will need to be increased to account
    for the loss of irradiance, as photons travel through various tissue layers

    to reach the targeted tissue." [13]

    Even if we have a wavelength or intensity that could be lacking in penetration, this can be compensated for by increasing the exposure time and thus the dose. 

    Another article aptly named Light Dosing and Tissue Penetration: It Is Complicated describes the need to get the proper energy to the target tissues.

    "One still needs to get the right amount of energy to the specific target.
    The time course over which this is delivered is also important.
    Mathematical reciprocity of exposure time and irradiance to achieve

    a specific light dose can be ineffective or be deleterious." [14]

    While proper energy delivery is key, the article above also emphasizes adequate intensity and exposure time over the fallacy of using "dosing" math. Which we covered in great detail in a previous blog.

    Ultimately, increasing the dose (J/cm^2) is also limited by the same exponential absorption curves. 

    This has led some authors to make statements like this:

     "Longer exposure times simply put more energy into the epidermis and dermis of the skin. They do not yield deeper penetration." [27]

    Essentially, this is why higher "doses" of Energy Density (J/cm^2) would not yield better results or significantly deeper penetration either, as most of the absorption would still occur superficially. It is generally best to stay within established therapeutic ranges, typically below 50 J/cm^2 on the skin surface.

    We can appreciate that discussions on penetration depths are often balanced with guidelines for proper dosing. Supposedly "higher penetration" is not more beneficial if it cannot be utilized within proper dosing thresholds. 

    (Relatively) Higher Intensities Preferred for Deeper Penetration:

    Within reason, higher intensities are more practical to reach a desired dose in a shorter amount of time. 

    • 5 mW/cm^2 will take 133.3 minutes to reach 40 J/cm^2
    • 40 mW/cm^2 will take 16.7 minutes to reach 40 J/cm^2

    Both intensities will deliver the same penetration at said dose as we illustrated earlier. However, it is preferred to use relatively higher intensities to deliver the higher dose in the ideal time range of 10-30 minutes.

    Hence, one reason why it is often oversimplified that higher intensities are preferred for deeper tissue treatments. Not that higher intensity necessarily penetrates deeper. 

    A Photobiomodulation textbook addresses this fallacy from marketing people promoting higher intensities that claim to penetrate deeper. They give an example that a 100mW laser obviously penetrates deeper than a 1mW laser. But more importantly is that an extremely low powered laser would not deliver a therapeutic effect, since it is not much more powerful than ambient indoor lighting. They grounded the discussion that it is more of an overall dosing parameter issue, not just a penetration issue. 

    "Therefore, technically speaking, a claim such as
    “this system penetrates deeper than others by virtue of extra-high power”

    may be true." [15]

    Based on a technicality, the authors begrudgingly concede that it is fair to say that higher powers penetrate deeper, especially if you 100x the intensity as in their example. As we showed earlier when we multiply the intensity times the percent penetration, it at least appears in that one context that the higher intensity penetrates deeper.

    Doctors Tuner and Hode comment on power and penetration as:

    "Output power is also of some importance to penetration."

    [5, Tuner & Hode, pg 95]

    Although this is the last sentence in a paragraph where they discuss how power is mostly important for dosing calculations and considerations. The authors are big proponents of skin contact method for deeper penetration. But most experts will certainly admit that power and intensity plays some role in penetration. 

    Dr. Calderhead does note how intensity is important for stimulating the target tissues at the correct depth. 

    "So, although wavelength is key, if there is insufficient photon intensity
    from the light source giving low irradiance, or a too high angle of divergence
    diluting the irradiance, then the photon intensity at the target

    will not be sufficient to get the optimum reaction." [18]

    Again highlighting that the wavelength is the the first key for penetration depth. But certainly proper PBM treatments require sufficient intensity.

    Dr. Enwemeka notes that increasing power density can compensate for poor penetration, however he also stresses that increasing the exposure time and dose will ultimately increase the energy reaching the deeper tissues that we quoted earlier:

    "For example, the brightness of a source with a
    relatively short wavelength can be enhanced at

    lower depths of tissue by increasing its power density." [12]

    These comments are almost always contextualized that power density must be used in conjunction with proper dosing methodologies and limited by heat.

    One article also notes the conflict between getting high enough power versus getting proper dosing and minimizing thermogenesis (heat). 

    "Therefore, the selection of appropriate power density and dose
    is crucial in PBM research. It is essential to strike a balance between
    using a high-enough power density and dose to trigger the
    desired biochemical effects while avoiding tissue thermogenesis
    and ensuring that the power density and dose are

    not too low to achieve therapeutic benefits." [16]

    Consider that if "high intensity" did indeed significantly penetrate deeper, then that means the Energy Density (J/cm^2) could be reduced when using high intensity vs low intensity. But that is typically not the case. 

    Penetration Depth not Affected by Intensity:

    In a previous blog we referenced several experts that have stated that power and intensity does not significantly improve penetration depth. At best it would be only a marginal improvement, and not worthwhile to chase recklessly high intensities that cause heating, require non-contact usage, and ignore proper dosing protocols like shortening the exposure time. 

    "the depth of penetration becomes totally independent of the laser's output, which means that the same depth value is achieved no matter how weak (or strong) the laser."

    [5, Tuner&Hode, pg 709]

    According to Doctors Tuner and Hode in their Phototherapy textbook, the penetration depth value has no correlation to power output, regardless of being weak or strong. They note that biological effects are typically observed between 1 to 4 cm of tissue, and even a 630nm laser has been shown to deliver a biological response at 1 cm deep. [5, pg709]

    But why do experts say that power/intensity doesn't affect penetration depth? Especially since it is so contrary to what many brands and their affiliate influencers have claimed over the years. Certainly they can't all be wrong... again. 

    Lets look at a few more references that plainly state that the penetration depth does not depend on power (or intensity). 

    "With the help of statistical analyzes, it has been determined that the optical
    penetration depth of the light in biological tissue does not depend on its
    optical power." [17]

    The study above clearly concluding that the penetration depth does not depend on power. Which seems to have set most of the current scientific consensus on the topic. 

    "While the wavelength and beam size are known to strongly affect the penetration of the emitted laser light in tissue [], the initial power should not influence the penetration depth []." [3]

    The above quote telling us that the wavelength and beam size will have a strong impact on penetration profile, but the initial power used at the skin surface has no influence. 

    "Measurements of light intensity transmittance have demonstrated that the optical penetration depth in biological tissue does not depend on the optical power []." [19]

    The above study also clearly stating that the penetration depth does not depend on power.

    "Greater irradiance is thought to be important because it allows greater light penetration, but this remains to be confirmed"

    [13]

    Despite the constant marketing claims that high intensities are essential for deeper penetration, according to the 2019 article above, this assumption has not even been confirmed. 

    The same paper continues on:

    "Increasing irradiance incrementally increased laser light penetration, but the percentage of laser light crossing the rabbit skull remained constant at 11% regardless of power density (Lapchak and Boitano, 2016). " [13]

    Confirming that regardless of intensity, the percentage penetration remains the same. Which is how we were able to make our penetration diagrams earlier. 

    Definition: With lasers it is common to only refer to just Power (Watts, or milliWatts (mW)). This is proportional to Intensity (Power Density, mW/cm^2), the difference is they don't divide by the spot size area (cm^2). 

    Examples of Varying Power for Penetration:

    One article tested the penetration of 660nm Red LED Light through different living and dead tissues at intensities ranging from 15 to 500 mW/cm^2. They found adequate penetration at 100mW/cm^2 or less for 50mm thickness of tissue. 

    "The results indicate that in live subjects, irrespective of skin tone, redlight readily penetrates tissues up to 50 mm of thickness at an irradiance of 100 mW/cm2 or less." [19]

    They found the maximal penetration was at 100mW/cm^2, and that higher intensities did not significantly improve penetration. Even a broken clock is correct twice a day.

    This at least gives us an upper limit that exceeding 100mW/cm^2 would be unnecessary as it would not increase penetration any further. 

    "We also demonstrated that increasing the red-light irradiance beyond 100 mW/cm2 did not greatly improve penetration, and we therefore propose the use of an irradiance of 100 mW/cm2 for red-light treatments and future research in tissues of 50 mm thickness or less." [19]

    However, the increased penetration did not actually increase the depth it could traverse beyond 50mm tissue. They note that the higher irradiances did not significantly increase the ability to penetrate thicker tissues. Likely hindered by exponential absorption beyond a certain point. 

    "While increasing the light irradiance increases penetration, it does not greatly increase the capacity for redlight to penetrate thicker tissues over the irradiances studied." [19]

    When we fit 500mW/cm^2 into our 810nm exponential model from before, the effective intensity only marginally goes beyond 20mm before getting flattened out. This would need to be pulsed or scanned to reduce heating. 

    Another study hypothesized that higher powers could penetrate deeper by affecting the absorption and scattering coeffients of the tissues. They found that as they increased the power from 150mW to 350mW, this led to an increase of penetration from about 3 mm to 4mm - an increase of 1mm. [30]

    So, when they increased the power by 2.33x, they found an increase in penetration of 1.33x. Again, note the lack of linearity or significance of increasing the power by over 2x only gets a 33% increase in depth. However, this appeared to be from a combination of laser measurements and mathematical modeling, which might not apply to real-world LED panel usage. [30]

    Intensity affects the "penetration" in a general sense, but does not significantly increase the depth of penetration. These studies show at-best a marginal improvement in penetration by increasing power. 

    As many studies have noted, there is surprisingly limited information on the role intensity plays affecting penetration depth, likely because it is already so clearly governed by wavelength and dose. Despite the lack of evidence, this has not stopped influencers from claiming that higher intensities penetrate deeper. Quite the opposite; in the absence of clear evidence, influencers are emboldened to fabricate claims that fit their sales narrative. 

    Does Pulsing Increase Penetration?

    Pulsing primarily allows for higher peak intensities, while allowing the skin to cool during the short periods of being "off" between pulses. Higher intensities with standard continuous wave would cause too much heat, thus pulsing is used to ensure treatments are non-thermal. 

    The textbook on LLLT and PBM states:

    "Fairly significant peak powers using short pulses (super pulses) can be
    applied without heating the tissue while at the same time keeping the average
    output powers similar to what lower-power continuous wave (cw) instruments
    would deliver." [15]

    Conventional pulsing does not increase penetration on its own, but only enables the usage of higher peak intensities that theoretically would promote deeper penetration. 

    When we 100x the intensity and apply 8,000mW/cm^2 into the same exponential model as before, now we get effective intensity at 30mm. Notice how an increase of intensity of 100x increases the effective penetration depth by only 3x, that is how insignificant intensity is to penetration depth. However, this creates an excessive heating problem that would need to be managed with additional pulsing, scanning, and/or cooling techniques. A similar scenario is described in [2]

    However, similar to merely increasing intensity, the penetration depth does not significantly improve even with pulsed high intensity levels.

    "In reality the increase in effective penetration depth obtained with pulsed lasers is more modest than simple calculations might suggest. " [2]

    The above quote stating that pulsed lasers may not be enhancing penetration as significantly as is often assumed. 

    The LLLT:PBM textbook reviews one study that compared 660nm, 808nm, and 940nm and found 808nm had the best penetration of about 40mm. They found there was no significant difference in penetration depth with pulsing. 

    "Pulsed light and continuous wave were also compared, and no differences were observed in the effective penetration depth." [15]

    We often assume that the higher peak pulses would deliver a proportional increase in penetration. However, these quotes in this section and below do not confirm a significant increase. 

    "Another hypothesis of why a difference in penetration depth between continuous wave and pulse-wave light exists is that at an identical average power output as a continuous-wave light system, the pulse wave mode may theoretically emit more photons deeper into the brain at pulsed peaks. However, this hypothesis has not been demonstrated in studies." [13]

    Similar to the intensity hypothesis, pulsing does not consistently lead to better penetration depths even at relatively higher peak outputs.  

    What Distance to Use Red Light Therapy Panels?

    Many "dosing guides" will imply that different intensities will have different penetration depths. Even though we now know there is poor evidence for this guidance and a very weak relationship between intensity and penetration depth. 

    As you move closer to the panel, the intensity will be higher. Further away and the intensity decreases as the light spreads out over a wider area.

    So, using the "highest intensity" panels at 6-12 inches away is recommended for a deep tissue treatment. Using them at 18-36 inches is recommended for superficial tissue treatment. Makes sense, if we accept the false assumption that different intensities modulate penetration depth significantly. 

    However, this is clearly not the case. Using 20mW/cm^2 at a far distance compared to 80mW/cm^2 closer to the panel, the effective penetration depth has not significantly changed. Even up to 500 mW/cm^2 has been shown to not make a significant improvement in effective penetration depth. [19]

    Let us provide a helpful diagram for clarification:

    what distance to use red light therapy panels 6 inches deep tissues 24 inches superficial skin care

    Relatively higher intensities from a non-contact LED panel will only increase superficial heating and not the penetration depth. Thus, this guidance is extremely misleading and only encourages people to overheat their skin for a false promise of deeper penetration.

    It is only with extraordinarily high intensities and pulse frequencies that it is possible to have an impact on penetration depth, as the next sections will cover. 

    Exception 1: High Wattage Pulsed Lasers Penetrate Deeper

    Dr. Henderson and Dr. Morries chronicled their efforts to utilize high wattage lasers to improve penetration and treat the brain - particularly TBI and the symptoms related to it like depression. Here are 3 of their papers on this topic. 

    [24] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627142/

    [25] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552256/

    [26] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550182/

    As well they have additional commentary in their contribution to a PBM Textbook.

    [27] https://www.sciencedirect.com/science/article/abs/pii/B9780128153055000063

    They note concerns that LED and typical laser devices for LLLT (<500mW) may not penetrate deep enough into the brain. Although many LLLT/PBM studies have successfully treated the brains of humans with low powered LEDs and Lasers, they remain concerned that the results are often transient (temporary). 

    Thus, they used high-powered lasers rated at 10-15 Watts at 810nm or 980nm. These were pulsed at 10 Hz and used in a sweeping motion (not stationary) over the treatment area to reduce heating. They ensured the skin temperature of human participants did not increase by more than 3 degrees C. Based on these parameters and technique used, this should be classified as HILT (High Intensity Laser Therapy) rather than LLLT (Low Level Light Therapy), which the authors seem to acknowledge. 

    They found that typical LED 20mW and 50mW devices did not penetrate 3 cm of tissue at all. But their high-wattage lasers could deliver 0.5% to 3% of their surface power at 3 cm deep. So with an extremely high increase in power, they were able to make a measureable improvement in penetration depth.

    They describe the power output as 9W or 13.2W in an 0.89cm^2 spot size. So that is a peak intensity of 10,112 mW/cm^2 and 14,831 mW/cm^2. Yes, over ten thousand mW/cm^2. 

    In the 2010 pulsing article, they also note that a peak intensity of 10 W/cm^2 would be required to penetrate 3cm deep.[2] Which is 10,000 mW/cm^2. This would need to be carefully administered with short pulses to avoid burning the skin. 

    These intensities are over 100 times higher than a typical "high intensity" LED Panel emitting 80mW/cm^2 at 6 inches away. So LED technology is still far away from achieving these levels of intensities that can make a significant impact on penetration. Yet many salespeople will invoke these HILT studies to give a false impression that their "high intensity" LED panels will penetrate deeper. Suddenly, they don't seem so high anymore. 

    Interestingly with the pulsing and sweeping, the Average Intensity is still between 34 to 50 mW/cm^2, which this average intensity is key to minimize heating. The dose was still delivered over a timeframe of 8 to 10 minutes, average dose of 14.1 to 28.3 J/cm^2, with treatments on 2-3 areas of the head over 10 visits. [26] So we can appreciate that even with extremely high intensities, they were able to adhere to having adequate exposure time. 

    Exception 2: High Intensity and Short Pulses Increase Penetration Depth

    The HILT studies in the previous section and the following PDT (photodynamic therapy) study have seemingly defied the rule that intensity does not significantly improve penetration. 

    The following study used femtosecond pulses (fs) with high peak intensities again on the scale of thousands of mW/cm^2. They showed a significant improvement in penetration over Continuous Wave lasers of 135 mW and 165 mW. They state the frequency is 71.4 MHz. The prefix Mega (upper case M) tells us it is 71.4 Million Hertz. That means it turns on and off 71.4 million times within each second.

    "As discussed in the introduction, the power of the laser does not affect the penetration depth [14]. Therefore, differences in penetration depth must be related to the wavelength, laser type (CW or PW) and the frequency of the PW." [28]

    The authors (along with editor Dr. Michael Hamblin) acknowledge above that they know the fact that power does not normally affect the penetration depth. So, they set out to provide an alternative explanation. 

    "A possible explanation for the results is that the high photon density of the PW laser (compare to the CW laser) excites a large percentage of electrons in the sample (close to saturation), rendering the irradiated zone transiently transparent for the rest of the incoming photons." [28]

    This is quite a feat of (quantum?) physics, that the electrons in our skin molecules would be excited into a state that temporarily increases their transparency. 

    Interestingly, another article mentions that femtosecond pulsed lasers would also be useful in specifically targeting the mitochondria. Although they believe this may be a costly technology to deliver such high pulsing frequencies. 

    "Thus, the smallest targets, such as CCO in the mitochondria for photobiomodulation, would require femtosecond lasers. Therefore, we believe pulsing may not be a factor for transcranial photobiomodulation as the current pulse widths of the lasers and LEDs currently used are too long to target the mitochondrial unit." [13]

    This phenomenon (or a similar one) has been discussed in PBM literature. A 2017 Handbook of Low Level Laser Therapy references a "photobleaching" effect from high intensities, high peak pulses, and/or longer exposure times. [29]

    The 2012 study they reference states:

    "It has previously been suggested that strong pulses may cause a photobleaching effect in the skin barrier over time." [31]

    Another study mentions the photobleaching effect, but also notes the high intensity pulses may also cause cellular destruction, micropores, protein rearrangements, or other structural changes in the skin or lipid tissues. These structural changes may result in a temporary transparency increase during treatment. [32]

    A study with multiple-watt lasers through dog skin also noted the conflict between their results and the general consensus that wavelength dictates penetration and the uncertainty about power affecting penetration. 

    "Although the depth of photon penetration is mainly determined by wavelength, the precise effect of power has yet to be elucidated. Anecdotally, power is thought to govern photonic saturation at the target depth via an increased wattage at the treatment surface, although a recent study showed that penetration depth in biologic tissue did not depend on wattage ()." [33]

    With quotes like "the precise effect of power has yet to be elucidated" from a 2020 article should raise red flags when salespeople claim that high intensities definitively increase penetration. The quote above again notes the depth of penetration is mainly determined by wavelength, with presumably little influence from power/intensity. 

    The authors explain this as a phenomenon of photonic saturation in the tissues that enabled deeper penetration with their high wattage treatments. 

    As with many other references, the LLLT Handbook balances the discussion that we have a tug-of-war between parameters that improve penetration versus appropriate dosing methodologies and avoiding excessive heat.

    "Clearly then, there are several opposing goals involved in capitalizing on this phenomenon: we want to increase penetration while mitigating any risks of tissue damage due to superficial thermal accumulation and avoid any dose saturation that may diminish the therapeutic efficacy. " [29]

    Exception 3: Temporal Tissue Optical Clearing

    Instead of calling it "photobleaching", one research group named this technique Temporal Tissue Optical Clearing (TTOC) in their 2022 study. 

    They proposed that ultrashort nanosecond or femtosecond pulses promote deeper penetration by modifying absorption and scattering properties of tissues. They modeled this with 750nm, 800nm, and 850nm lasers. 

    "According to the definition of light penetration depth, which is 1/µeff, using the TTOC method with pulses of 80 fs, the light penetration depth has been increased by about 40%." [35]

    By their calculations, their femtosecond pulses can increase penetration depth by 40%. That is quite significant, much more than merely increasing the intensity. 

    In a follow-up study, the same group also makes this comment. 

    "results show that absorption and scattering can be minimized at sufficiently short pulses (femtosecond and shorter pulses)." [36]

    So this technique of femtosecond pulses is just now being understood and utilized for deeper tissue delivery of Near-Infrared light. 

    Dosing Dermatology Lasers:

    Dermatology lasers often use similar wavelengths at extremely high intensities for various heat effects like ablation, which destructively removes various targets in the skin. 

    Lasers in dermatology are clear that they choose the wavelength and the "dose" (J/cm^2) of energy to determine the penetration depth.

    "Each wavelength penetrates to a specific depth. This diffusion also depends on the spot diameter, the fluence, and the pulse duration (the higher they are, the deeper the wave goes) [1,5-6]." [37]

    The quote above makes quite clear. The penetration depth depends on the wavelength, spot diameter, fluence (J/cm^2), and pulse duration (exposure time of each pulse). No mention of intensity or power determining penetration depth. 

    The Energy (dose) applied at the surface determines how much energy reaches the deeper tissues. 

    "Therefore, for a given wavelength, light with higher energy at the surface will have a slight increase in tissue penetration." [54]

    And another laser dermatology study:

    "There is a linear relationship between the energy delivered and depth of ablation"
    ...
    "with the depth of injury determined by energy level" [59]
     

    Power and Intensity levels are chosen based on the amount of heat they want to deliver. Different levels of intensity produce different heat effects:

    "The photothermal effect is the best known. The wavelength determines the penetration into the tissues based on the absorption and scattering of light. Temperature increases when the power density increases, thus causing different tissue effects. As the temperature rises, the effects may begin with a transient hyperthermia, and subsequently, desiccation, protein denaturation and coagulation, tissue coagulation fusion, then tissue vaporization, and finally, its charring []." [55]

    It is quite clear, the power density (aka intensity) determines the heat effects. If higher intensity actually penetrated significantly deeper, then it would be rather problematic for the dermatology laser industry. 

    Dermatology and Surgical laser procedures certainly do not lack in power or intensity. According to Tuner & Hode, 1-5 Watts is used for vapourising, 5-20 Watts is used for superficial cutting, and 20-100 Watts is used for deep cutting. [5, pg43]  If higher power actually penetrated significantly deeper, then these procedures wouldn't be able to exist the way they are being used today. 

    Similarly, in PBM/LLLT it is clear that the wavelength and "dose" play the most significant roles in penetration. Intensity can be used for different effects, but is most often purposely chosen to be low enough not to cause heat. Increasing intensity would only cause more heat effects, not significantly better penetration. As is already utilized therapeutically in laser surgery.  

    Case Study: The Entire LED Panel Industry

    Recall that most of the original dosing guidelines in this industry relied on improper Solar Power Meter measurements (leading to the erroneous >100mW/cm^2 claim) and failed to account for things like skin reflection losses.

    After accounting for the 2x false advertised intensity and the 60% reflection losses, consumers were likely absorbing less than 1/4th the intensity and dose that they thought. Most of which would be superficial absorption as it was delivered at a distance from the device and lacked skin contact compression.  

    Ironically, the influencers promising deep penetration have already proven the opposite. They demonstrated that poor penetration and underdosing still leads to good results. 

    Despite underdosing in terms of J/cm^2 and penetration depths; consumers likely got benefits from getting adequate Total Joules and Exposure Time for the systemic benefits.

    They managed to prove Dr. Hamblin's theory correct, as he has been stating for years that these LED panels are more systemic in nature. (i.e. not a direct deep-penetrating treatment like a skin-contact laser)

    https://www.youtube.com/watch?v=XAHpmZc4f7U&t=1476s

    https://youtu.be/yeAM1djssiE?si=SHJ4XRsDIwobGTBn&t=1020

    Even a typical 100mW LLLT laser will have high concentrated intensity. For example because the diameter and spot size is so small, when 100mW is divided by the area then the intensity becomes extremely large. Here are 3 articles with only 100mW lasers but with such small spot sizes their intensity becomes 1,500-3,500 mW/cm^2.[62][63][64]

    A Low Level Laser does not lack in intensity, so that was never the problem for penetration depth. Low power devices are chosen for the proper therapeutic response, not because the technology was ever limited. 

    So even compared to many typical LLLT lasers, the intensities from modern LED panels are severely lacking, which is why many experts like Dr. Hamblin have adopted the theory that treatment mechanisms are more superficial and systemic.

    Feeling Heat is a Sign of Superficial Absorption:

    Most of the intensity from Near-Infrared wavelengths is absorbed within the first 2 mm of the skin:

    "most of the initial light energy was lost in the first one to two millimeters" [3]

    Another recent article states: 

    "The scientific reports reveal that the red wavelength can penetrate up to 0.5–1 mm depth, whereas the NIR wavelength reaches up to 2 mm depth before losing 37 % of its original light intensity." [10]

    Higher intensities will increase the rate of energy absorbed in the first few millimeters of the skin. Leading to problems of thermoregulation that will cause heating. Especially since we now know about the backscattering problem from our previous blog.

    Whereas, skin compression will shorten the tissue thickness by a few millimeters and give reduced absorption and scattering properties in the underlying skin cells. Significantly increasing penetration depth without needing to increase the intensity. 

    Our thermoreceptors (nerves that sense heat) are primarily in the epidermis and dermis.

    "Diagram of the thermoreceptors in the skin. Note that on average hot receptors are found deeper in the skin." [41]

    "The thermoreceptors which function as thermal sensors are scattered between the dermis and epidermis []. " [42]

    Which the Epidermis and Dermis are only 2-6mm deep depending on the part of the body. [44] The sensation of heat in the skin is literally a superficial one. 

    For example, we do not have as many heat sensors in our deeper tissues like the fat, muscles, bones, or organs. So if the light was actually penetrating deeply, we would not be feeling as much of a sensation of heat. 

    "The photon intensity i.e., irradiance (W/cm2 or spectral irradiance), must be adequate. Using higher intensity, the photon energy will be transformed to excessive heat in the target tissue and, using lower intensity, photons absorption will be insufficient to achieve the goal." [11]

    Many references like the above certainly admit that the intensity must be adequate, but excessive intensity would only be converted to heat. Without any guarantee of deeper penetration or better benefits from high intensities.

    This phenomenon is the opposite of what most people assume. We may assume that feeling heat is a sign of deep penetration, when it is more likely a sign of a high amount of superficial absorption and conversion of photons into heat in the skin layers, especially from a non-contact device.  

    Conclusions:

    It is acceptable to generally say that higher intensity increases penetration based on a technicality. However, like most marketing claims used to sell LED Panels over the years, this statement is less than half of the truth.

    In standard LLLT and PBM intensity ranges (5 to 500 mW/cm^2), the intensity has at-best a marginal influence on the penetration depth. High intensities (typically >50mW/cm^2) would need to be pulsed for proper non-thermal light therapy, although it may not significantly improve penetration either.

    Proper wavelengths and dosing (J/cm^2) will primarily determine the energy delivered to the intended depth. Adequate, evidence-based, non-thermal intensity must be chosen for the best benefits. 

    The two techniques that have evidence for improving penetration depth are:

    1. Using skin contact method for direct deep tissue treatments. 
    2. Temporal Tissue Optical Clearing for increasing penetration seems to be some sort of combination high peak (>>1,000mW/cm^2*) intensities, short pulses (femtosecond, Millions of Hz), specific wavelengths, specific properties of lasers, and/or some other combination of factors that have not been discovered yet.

    These high intensities (~10,000 mW/cm^2) and femtosecond pulses are obviously a far-cry away from what current LED technology can achieve, despite false claims of deep penetration from non-contact LED panels.

    So, unless an influencer to comparing a Multiple-Watt Laser to an LED Panel, claims of deeper penetration from relatively small differences in intensity is extremely misleading. 

    As always, the goal of Red and NIR Light Therapy is to thread the needle of many conflicting parameters to achieve a stimulatory dose in the correct range. 

    "If the incident power is too high, heat will be the end product as with the surgical laser. If a too-low photon intensity is delivered, there will be very little or no reaction. The trick in LED phototherapy is to deliver just the right amount of photon intensity to achieve the desired clinical effect but in an athermal and atraumatic manner." [53]

    Recent articles and commentary from experts have cast doubts on the direct penetration of LED treatments. So they are discussing more how to view Photobiomodulation as a systemic treatment, which will change many ways we view dosing.

    When we can acknowledge the systemic mechanisms of Red Light Therapy are likely dominant in LED panels, viewing treatments as an indirect therapy instead of an direct therapy will enable optimal treatment protocols like low intensities, total joules considerations, adequate exposure times, and remote/systemic targets in addition to direct targets. 

    And now that we know that relatively higher intensities (<500mW/cm^2) do not significantly increase penetration depth, people can stop scorching their skin because influencers told them that was the only way to treat deeper tissues. 

    References:

    [1]

    Kai Su, Chunliang Wang, Jianbang Xiang,

    Exploring the key parameters for indoor light intervention in treating neurodegenerative diseases: A systematic review,Building and Environment,Volume 258,2024,111587,ISSN 0360-1323,

    https://doi.org/10.1016/j.buildenv.2024.111587.

    (https://www.sciencedirect.com/science/article/pii/S0360132324004293)

    [2]

    Hashmi JT, Huang YY, Sharma SK, Kurup DB, De Taboada L, Carroll JD, Hamblin MR. Effect of pulsing in low-level light therapy. Lasers Surg Med. 2010 Aug;42(6):450-66. doi: 10.1002/lsm.20950. PMID: 20662021; PMCID: PMC2933784.

    [3]

    Kaub L, Schmitz C. More than Ninety Percent of the Light Energy Emitted by Near-Infrared Laser Therapy Devices Used to Treat Musculoskeletal Disorders Is Absorbed within the First Ten Millimeters of Biological Tissue. Biomedicines. 2022 Dec 9;10(12):3204. doi: 10.3390/biomedicines10123204. PMID: 36551959; PMCID: PMC9775104.

    [4]

    Naeser MA, Saltmarche A, Krengel MH, Hamblin MR, Knight JA. Improved cognitive function after transcranial, light-emitting diode treatments in chronic, traumatic brain injury: two case reports. Photomed Laser Surg. 2011 May;29(5):351-8. doi: 10.1089/pho.2010.2814. Epub 2010 Dec 23. PMID: 21182447; PMCID: PMC3104287.

    [5]

    Hode, Lars. Tuner, Jan. Laser Phototherapy Clinical Practice and Scientific Background. 2014 Prima Books AB

    [6]

    Su C-T, Chiu F-C, Ma S-H, Wu J-H. Optimization of Photobiomodulation Dose in Biological Tissue by Adjusting the Focal Point of Lens. Photonics. 2022; 9(5):350. https://doi.org/10.3390/photonics9050350

    [7]

    Zein R, Selting W, Hamblin MR. Review of light parameters and photobiomodulation efficacy: dive into complexity. J Biomed Opt. 2018 Dec;23(12):1-17. doi: 10.1117/1.JBO.23.12.120901. PMID: 30550048; PMCID: PMC8355782.

    [8]

    Cios A, Cieplak M, Szymański Ł, Lewicka A, Cierniak S, Stankiewicz W, Mendrycka M, Lewicki S. Effect of Different Wavelengths of Laser Irradiation on the Skin Cells. Int J Mol Sci. 2021 Feb 28;22(5):2437. doi: 10.3390/ijms22052437. PMID: 33670977; PMCID: PMC7957604.

    [9]

    Calderhead RG.  Photobiological Basics of Photomedicine: A Work of Art Still in Progress.  Medical Lasers 2017;6:45-57.  https://doi.org/10.25289/ML.2017.6.2.45

    [10]

    Iruthayapandi Selestin Raja, Chuntae Kim, Nuri Oh, Ji-Ho Park, Suck Won Hong, Moon Sung Kang, Chuanbin Mao, Dong-Wook Han, Tailoring photobiomodulation to enhance tissue regeneration,

    Biomaterials, Volume 309, 2024, 122623, ISSN 0142-9612,

    https://doi.org/10.1016/j.biomaterials.2024.122623.

    (https://www.sciencedirect.com/science/article/pii/S0142961224001571)

    [11]

    Austin E, Geisler AN, Nguyen J, Kohli I, Hamzavi I, Lim HW, Jagdeo J. Visible light. Part I: Properties and cutaneous effects of visible light. J Am Acad Dermatol. 2021 May;84(5):1219-1231. doi: 10.1016/j.jaad.2021.02.048. Epub 2021 Feb 25. PMID: 33640508; PMCID: PMC8887026.

    [12]

    Intricacies of Dose in Laser Phototherapy for Tissue Repair and Pain Relief

    Chukuka S. Enwemeka

    Photomedicine and Laser Surgery 2009 27:3387-393

    [13]

    Erica B. Wang, Ramanjot Kaur, Manuel Fierro, Evan Austin, Linda Ramball Jones, Jared Jagdeo, Chapter 5 - Safety and penetration of light into the brain,

    Editor(s): Michael R. Hamblin, Ying-Ying Huang, Photobiomodulation in the Brain, Academic Press, 2019, Pages 49-66,ISBN 9780128153055,

    https://doi.org/10.1016/B978-0-12-815305-5.00005-1.

    (https://www.sciencedirect.com/science/article/pii/B9780128153055000051)

    [14]

    Lanzafame R. Light Dosing and Tissue Penetration: It Is Complicated. Photobiomodul Photomed Laser Surg. 2020 Jul;38(7):393-394. doi: 10.1089/photob.2020.4843. Epub 2020 Jun 5. PMID: 32503388; PMCID: PMC7374595.

    [15]

    Low-Level Light Therapy: Photobiomodulation

    Author(s): Michael R. Hamblin, Cleber Ferraresi, Ying-Ying Huang M.D., Lucas Freitas de Freitas, James D. Carroll

    Published: 2018

    https://doi.org/10.1117/3.2295638

    PDF ISBN: 9781510614161 | Print ISBN: 9781510614154

    [16]

    Zhang R, Qu J. The Mechanisms and Efficacy of Photobiomodulation Therapy for Arthritis: A Comprehensive Review. Int J Mol Sci. 2023 Sep 19;24(18):14293. doi: 10.3390/ijms241814293. PMID: 37762594; PMCID: PMC10531845.

    [17]

    Arslan H, Doluğan YB, Ay AN. Measurement of the Penetration Depth in Biological Tissue for Different Optical Powers. SAUJS. August 2018;22(4):1095-1100. doi:10.16984/saufenbilder.332802

    [18]

    Photobiological Basics and Clinical Indications of Phototherapy for Skin Rejuvenation

    WRITTEN BY

    Robert Glen Calderhead and Yohei Tanaka

    Submitted: 05 May 2016 Reviewed: 22 March 2017 Published: 17 May 2017

    DOI: 10.5772/intechopen.68723

    [19]

    Hu D, van Zeyl M, Valter K, Potas JR. Sex, but not skin tone affects penetration of red-light (660 nm) through sites susceptible to sports injury in lean live and cadaveric tissues. J Biophotonics. 2019 Jul;12(7):e201900010. doi: 10.1002/jbio.201900010. Epub 2019 Apr 1. PMID: 30851081.

    [20]

    Weber RJ, Taylor BR, Engelman DE. Laser-induced tissue reactions and dermatology. Curr Probl Dermatol. 2011;42:24-34. doi: 10.1159/000328241. Epub 2011 Aug 16. PMID: 21865795.

    [21]

    Sakata S, Kunimatsu R, Tsuka Y, Nakatani A, Hiraki T, Gunji H, Hirose N, Yanoshita M, Putranti NAR, Tanimoto K. High-Frequency Near-Infrared Diode Laser Irradiation Attenuates IL-1β-Induced Expression of Inflammatory Cytokines and Matrix Metalloproteinases in Human Primary Chondrocytes. J Clin Med. 2020 Mar 24;9(3):881. doi: 10.3390/jcm9030881. PMID: 32213810; PMCID: PMC7141534.

    [22]

    Salehpour F, Mahmoudi J, Kamari F, Sadigh-Eteghad S, Rasta SH, Hamblin MR. Brain Photobiomodulation Therapy: a Narrative Review. Mol Neurobiol. 2018 Aug;55(8):6601-6636. doi: 10.1007/s12035-017-0852-4. Epub 2018 Jan 11. PMID: 29327206; PMCID: PMC6041198.

    [23]

    Cronshaw M, Parker S, Arany P. Feeling the Heat: Evolutionary and Microbial Basis for the Analgesic Mechanisms of Photobiomodulation Therapy. Photobiomodul Photomed Laser Surg. 2019 Sep;37(9):517-526. doi: 10.1089/photob.2019.4684. Epub 2019 Jul 19. PMID: 31329512.

    [24]

    Henderson TA, Morries LD. Multi-Watt Near-Infrared Phototherapy for the Treatment of Comorbid Depression: An Open-Label Single-Arm Study. Front Psychiatry. 2017 Sep 29;8:187. doi: 10.3389/fpsyt.2017.00187. PMID: 29033859; PMCID: PMC5627142.

    [25]

    Henderson TA, Morries LD. Near-infrared photonic energy penetration: can infrared phototherapy effectively reach the human brain? Neuropsychiatr Dis Treat. 2015 Aug 21;11:2191-208. doi: 10.2147/NDT.S78182. PMID: 26346298; PMCID: PMC4552256.

    [26]

    Morries LD, Cassano P, Henderson TA. Treatments for traumatic brain injury with emphasis on transcranial near-infrared laser phototherapy. Neuropsychiatr Dis Treat. 2015 Aug 20;11:2159-75. doi: 10.2147/NDT.S65809. PMID: 26347062; PMCID: PMC4550182.

    [27]

    Theodore A. Henderson, Larry D. Morries, Chapter 6 - Near-infrared photonic energy penetration—principles and practice, Editor(s): Michael R. Hamblin, Ying-Ying Huang, Photobiomodulation in the Brain, Academic Press, 2019, Pages 67-88, ISBN 9780128153055, https://doi.org/10.1016/B978-0-12-815305-5.00006-3.

    (https://www.sciencedirect.com/science/article/pii/B9780128153055000063)

    [28]

    Barbora A, Bohar O, Sivan AA, Magory E, Nause A, Minnes R. Higher pulse frequency of near-infrared laser irradiation increases penetration depth for novel biomedical applications. PLoS One. 2021 Jan 7;16(1):e0245350. doi: 10.1371/journal.pone.0245350. PMID: 33411831; PMCID: PMC7790424.

    [29]

    Hamblin, de Sousa, Agrawal. Handbook of Low-Level Laser Therapy. Pan Stanford Publishing Pte. Ltd. (C) 2017

    [30]

    Hamdy O, Mohammed HS. Variations in tissue optical parameters with the incident power of an infrared laser. PLoS One. 2022 Jan 31;17(1):e0263164. doi: 10.1371/journal.pone.0263164. PMID: 35100314; PMCID: PMC8803203.

    [31]

    Skin Penetration Time-Profiles for Continuous 810 nm and Superpulsed 904 nm Lasers in a Rat Model

    Jon Joensen, Knut Øvsthus, Rolf K. Reed, Steinar Hummelsund, Vegard V. Iversen, Rodrigo Álvaro Brandão Lopes-Martins, and Jan Magnus Bjordal

    Photomedicine and Laser Surgery 2012 30:12688-694

    [32]

    Bordvik DH, Haslerud S, Naterstad IF, Lopes-Martins RAB, Leal Junior ECP, Bjordal JM, Joensen J. Penetration Time Profiles for Two Class 3B Lasers in In Situ Human Achilles at Rest and Stretched. Photomed Laser Surg. 2017 Oct;35(10):546-554. doi: 10.1089/pho.2016.4257. Epub 2017 Apr 21. PMID: 28436746.

    [33]

    Hochman-Elam LN, Heidel RE, Shmalberg JW. Effects of laser power, wavelength, coat length, and coat color on tissue penetration using photobiomodulation in healthy dogs. Can J Vet Res. 2020 Apr;84(2):131-137. PMID: 32255908; PMCID: PMC7088515.

    [34]

    Su CT, Chen CM, Chen CC, Wu JH. Dose Analysis of Photobiomodulation Therapy in Stomatology. Evid Based Complement Alternat Med. 2020 Sep 16;2020:8145616. doi: 10.1155/2020/8145616. PMID: 33014111; PMCID: PMC7519198.

    [35]

    Shariati B K B, Khatami SS, Ansari MA, Jahangiri F, Latifi H, Tuchin VV. Method for tissue clearing: temporal tissue optical clearing. Biomed Opt Express. 2022 Jul 19;13(8):4222-4235. doi: 10.1364/BOE.461115. PMID: 36032583; PMCID: PMC9408250.

    [36]

    Shariati B K B, Ansari MA, Khatami SS, Tuchin VV. Multimodal optical clearing to minimize light attenuation in biological tissues. Sci Rep. 2023 Dec 6;13(1):21509. doi: 10.1038/s41598-023-48876-x. PMID: 38057535; PMCID: PMC10700339.

    [37]

    El Arabi Y, Hali F, Chiheb S. Laser Management and Safety in Dermatology. Cureus. 2022 Jun 16;14(6):e25991. doi: 10.7759/cureus.25991. PMID: 35859982; PMCID: PMC9287998.

    [38]

    Yang, Marjorie & Tuchin, Valery & Yaroslavsky, Anna. (2009). Principles of Light-Skin Interactions. 10.1007/978-1-84882-328-0_1.

    [39]

    +++

    Kolari PJ, Airaksinen O. Poor penetration of infra-red and helium neon low power laser light into the dermal tissue. Acupunct Electrother Res. 1993 Jan-Mar;18(1):17-21. doi: 10.3727/036012993816357566. PMID: 8098894.

    [40]

    Esnouf A, Wright PA, Moore JC, Ahmed S. Depth of penetration of an 850nm wavelength low level laser in human skin. Acupunct Electrother Res. 2007;32(1-2):81-6. doi: 10.3727/036012907815844165. PMID: 18077939.

    [41]

    Ezquerra-Romano, Ivan & Martínez, Ángel. (2016). Highway to thermosensation: A traced review, from the proteins to the brain. Reviews in the Neurosciences. 28. 10.1515/revneuro-2016-0039.

    [42]

    Chen C, Ding S. How the Skin Thickness and Thermal Contact Resistance Influence Thermal Tactile Perception. Micromachines (Basel). 2019 Jan 25;10(2):87. doi: 10.3390/mi10020087. PMID: 30691019; PMCID: PMC6412694.

    [43]

    Oltulu, Pembe; Ince, Bilsev1; Kokbudak, Naile2; Findik, Sidika; Kilinc, Fahriye. Measurement of Epidermis, Dermis, and Total Skin Thicknesses from Six Different Body Regions with a New Ethical Histometric Technique. Turkish Journal of Plastic Surgery 26(2):p 56-61, Apr–Jun 2018. | DOI: 10.4103/tjps.TJPS_2_17

    [44]

    Hofmann E, Schwarz A, Fink J, Kamolz LP, Kotzbeck P. Modelling the Complexity of Human Skin In Vitro. Biomedicines. 2023 Mar 6;11(3):794. doi: 10.3390/biomedicines11030794. PMID: 36979772; PMCID: PMC10045055.

    [45]

    Ilic S, Leichliter S, Streeter J, Oron A, DeTaboada L, Oron U. Effects of power densities, continuous and pulse frequencies, and number of sessions of low-level laser therapy on intact rat brain. Photomed Laser Surg. 2006 Aug;24(4):458-66. doi: 10.1089/pho.2006.24.458. PMID: 16942425.

    [46]

    Oron U, Yaakobi T, Oron A, Hayam G, Gepstein L, Rubin O, Wolf T, Ben Haim S. Attenuation of infarct size in rats and dogs after myocardial infarction by low-energy laser irradiation. Lasers Surg Med. 2001;28(3):204-11. doi: 10.1002/lsm.1039. PMID: 11295753.

    [47]

    Jaroslava Joniová, Emmanuel Gerelli, Georges Wagnières,

    Study and optimization of the photobiomodulation effects induced on mitochondrial metabolic activity of human cardiomyocytes for different radiometric and spectral conditions, Life Sciences, 2024, 122760, ISSN 0024-3205, https://doi.org/10.1016/j.lfs.2024.122760.

    (https://www.sciencedirect.com/science/article/pii/S0024320524003503)

    [48]

    Loignon, A.E. Bringing Light to the World: John Harvey Kellogg and Transatlantic Light Therapy. J Transatl Stud 20, 103–128 (2022). https://doi.org/10.1057/s42738-022-00092-7

    [49]

    Pruitt T, Carter C, Wang X, Wu A, Liu H. Photobiomodulation at Different Wavelengths Boosts Mitochondrial Redox Metabolism and Hemoglobin Oxygenation: Lasers vs. Light-Emitting Diodes In Vivo. Metabolites. 2022 Jan 23;12(2):103. doi: 10.3390/metabo12020103. PMID: 35208178; PMCID: PMC8880116.

    [50]

    Luke C. GordonKristy L. MartinNapoleon TorresAlim-Louis BenabidJohn MitrofanisJonathan StoneCecile MoroDaniel M. Johnstone

    Remote photobiomodulation targeted at the abdomen or legs provides effective neuroprotection against parkinsonian MPTP insult

    First published: 22 March 2023

    https://doi.org/10.1111/ejn.15973

    [51]

    Blivet G, Roman FJ, Lelouvier B, Ribière C, Touchon J. Photobiomodulation Therapy: A Novel Therapeutic Approach to Alzheimer's Disease Made Possible by the Evidence of a Brain-Gut Interconnection. J Integr Neurosci. 2024 Apr 30;23(5):92. doi: 10.31083/j.jin2305092. PMID: 38812393.

    [52]

    Bicknell B, Liebert A, McLachlan CS, Kiat H. Microbiome Changes in Humans with Parkinson's Disease after Photobiomodulation Therapy: A Retrospective Study. J Pers Med. 2022 Jan 5;12(1):49. doi: 10.3390/jpm12010049. PMID: 35055364; PMCID: PMC8778696.

    [53]

    Calderhead, R.G. (2018). Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice. In: Nouri, K. (eds) Lasers in Dermatology and Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-76118-3_18

    [54]

    Boechat, A., Torezan, L., Osório, N. (2016). Lasers, Lights, and Related Technologies in Cosmetic Dermatology. In: Issa, M., Tamura, B. (eds) Daily Routine in Cosmetic Dermatology. Clinical Approaches and Procedures in Cosmetic Dermatology. Springer, Cham. https://doi.org/10.1007/978-3-319-20250-1_30-1

    [55]

    de Planell-Mas E, Martínez-Garriga B, Viñas M, Zalacain-Vicuña AJ. Efficacy of the Treatment of Plantar Warts Using 1064 nm Laser and Cooling. Int J Environ Res Public Health. 2022 Jan 12;19(2):801. doi: 10.3390/ijerph19020801. PMID: 35055623; PMCID: PMC8775824.

    [56]

    GaripovaI. A. DenissovVladimir Solodovnikov, and I. Digilova"Laser surgery in dermatology with application of superthin optical fiber by contact and noncontact method", Proc. SPIE 3590, Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems IX, (22 June 1999); https://doi.org/10.1117/12.351009

    [57]

    Barolet D, Christiaens F, Hamblin MR. Infrared and skin: Friend or foe. J Photochem Photobiol B. 2016 Feb;155:78-85. doi: 10.1016/j.jphotobiol.2015.12.014. Epub 2015 Dec 21. PMID: 26745730; PMCID: PMC4745411.

    [58]

    Photobiological Basics and Clinical Indications of Phototherapy for Skin Rejuvenation

    WRITTEN BY

    Robert Glen Calderhead and Yohei Tanaka

    Submitted: 05 May 2016 Reviewed: 22 March 2017 Published: 17 May 2017

    DOI: 10.5772/intechopen.68723

    [59]

    Jason N. Pozner, Barry E. DiBernardo, Jonathan Cook. 2021. "Laser resurfacing of the aging face" Plastic and Aesthetic Research. 8: 20. http://dx.doi.org/10.20517/2347-9264.2020.218

    [60]

    Barolet D. Near-Infrared Light and Skin: Why Intensity Matters. Curr Probl Dermatol. 2021;55:374-384. doi: 10.1159/000517645. Epub 2021 Oct 25. PMID: 34698043.

    [61]

    Nairuz T, Sangwoo-Cho, Lee JH. Photobiomodulation Therapy on Brain: Pioneering an Innovative Approach to Revolutionize Cognitive Dynamics. Cells. 2024 Jun 3;13(11):966. doi: 10.3390/cells13110966. PMID: 38891098; PMCID: PMC11171912.

    [62]

    Alves AC, Vieira R, Leal-Junior E, dos Santos S, Ligeiro AP, Albertini R, Junior J, de Carvalho P. Effect of low-level laser therapy on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation. Arthritis Res Ther. 2013;15(5):R116. doi: 10.1186/ar4296. PMID: 24028507; PMCID: PMC3979014.

    [63]

    Altan BA, Sokucu O, Ozkut MM, Inan S. Metrical and histological investigation of the effects of low-level laser therapy on orthodontic tooth movement. Lasers Med Sci. 2012 Jan;27(1):131-40. doi: 10.1007/s10103-010-0853-2. Epub 2010 Oct 31. PMID: 21038101.

    [64]

    Kingsley JD, Demchak T, Mathis R. Low-level laser therapy as a treatment for chronic pain. Front Physiol. 2014 Aug 19;5:306. doi: 10.3389/fphys.2014.00306. PMID: 25191273; PMCID: PMC4137223.

    [65]

    Zeng J, Wang C, Chai Y, Lei D, Wang Q. Can transcranial photobiomodulation improve cognitive function in TBI patients? A systematic review. Front Psychol. 2024 Jun 17;15:1378570. doi: 10.3389/fpsyg.2024.1378570. PMCID: PMC11215173.


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