Laser Education Center

Dr. Antonucci, Director of Rehabilitation at Plasticity Brain Centers, gave a wonderful presentation that answers many of the questions that clinicians have when they are considering adding laser therapy to their clinical practice. You can watch the entire presentation to the right, or click on any of the chapters below. The transcript is also available below for your review.

Chapters

History of Laser Therapy

Cellular Mechanisms of Laser Therapy

Interaction of Light & Matter

Light Sources & Dosimetry

Laser Side Effects?

Laser Therapy and TBI

Video Transcript

So the topic that I’d like to share today is a topic that’s very very intriguing to me and I first became kind of intrigued about laser or low light therapy or photobiomodulation, all of the things that it’s called these days, back in 2012 when I first started working at the Carrick Institute’s Clinic in Atlanta. I had a patient who was in for a concussion. Just in speaking, she said “You know what, I don’t know if you guys can help me with this, but I’ve got a really bad wart on my toe that will never go away. I’ve been trying for years and years and years, frozen medications, everything, they needled it, they abrased it, nothing made it go away.” So at that point, we had a pretty high powered laser and I just said, you know what, there seems to be a lot of talk about this for a dermal condition so let’s try it. So what we did is we applied that laser to her second toe, three times a day for about three minutes. At the end of the week, the wart became really red. Two weeks later she said it was completely gone. I’ve spoken with her since then as she said it’s never come back. So at that point my curiosity was piqued and I said there has to be something to this type of therapy but how do we apply in a practice for neurology, because I’m not in the business, neither are you, for treating warts but we treat brains, so let’s figure out how we can apply this to the brain.

But at that time everybody was saying you can’t penetrate the skull Light doesn’t go through the skull. You know there’s no way that you can target the brain. From there I kind of let it go to the wayside until a couple years ago when I became re-interested in it from an article that I read. I want to share just a little bit about my interest and my team’s interest in photobiomodulation. So we’re going to talk about shining light on TBI applications of transcranial low-level therapy. So at our facility, we do this. Some of the things that we’re going to talk about today are things that we actually do in clinical practice. So here you see somebody is doing transcranial photo-biomodulation with non-invasive neuromodulation for post-concussion syndrome, one of the different types of therapies that we’re doing with this one gentleman. Here is a woman that’s doing transcranial photobiomodulation with a visually evoked potential as well as a non-invasive neuromodulation for her post-concussive dysautonomia. So these are things that we’re doing in applications and many of us have lots of questions around this. Most of all how, can light aid the recovery of brain injuries.

So what our objectives are today? We have seven objectives. One of them is to review the history of photobiomodulation so we can see where this practice is evolving from and where it is at the current state. Discuss the cellular physiology of PBM. So whenever I try to assess whether I want to implant something into clinical practice, I want to understand it. I don’t like to just do things just because other people are doing them. I like to be able to understand why we’re doing what we’re doing because if something goes wrong, if you understand the basis of it, you can understand how to fix it. And also you can customize your treatments for your patient.

We’re going to talk a little bit about that today. We’re going to review a little bit of the literature that actually shows that transcranial light modulation or photobiomodulation is possible. Light can penetrate the skull if you have the right settings. We’re going to identify the factors to consider with PBM. We’re going to talk about a little bit about calculating dosage. We’re also going to discuss potential side effects. And finally, we’re going to compare and contrast proposed mechanisms of PBM, photobiomodulation, with the cellular mechanisms of traumatic brain injury to see if there is a feasible solution here or a feasible application of light.

History of Laser Therapy

So a little bit about the history of photobiomodulation. We won’t go through this whole thing but you see in the 60s is when laser therapy was really evolved. The first laser ever invented was the ruby laser, was in 1960. And you can see in the decade of the 60s many people were kind of experimenting with this type of laser. In 1965, Boston or actually a Harvard scholar destroyed cancerous tumors in a rat using laser therapy. And then Dr. Mester tried to reproduce the experiment, didn’t have the same results, but what he noticed is that the rats that he was treating actually grew hair back on the scar tissue where they had done some incisions.

Later they found out the reason why it didn’t help the tumors, but to help this skin the hair regrow is because his laser wasn’t strong enough. So he discovered low-level light therapy almost by accident. Later on, we started seeing that there are some studies that are once again supported by Mester and his colleagues on human healing and hair growth. We looked at adding infrared to the photobiomodulation spectrum all the way in the mid-70s and then from there Karu identified the target of photobiomodulation that we exist today which is Cytochrome c oxidase which we’ll talk about in just a minute, which is part of the mitochondrial or the electron transport chain. In the year 2009, there were some studies published about photobiomodulation for stroke. Now this began getting people thinking how can you treat stroke if the light doesn’t penetrate the skull. There is a feverious investigation about how light penetrates the skull. So in 2015, Jagdeo, who we’re going to talk a little bit later, discovered that light can actually penetrate the skull and we’re going to talk about how deep it actually can penetrate the skull. Then a little bit later in 2016, which is not so long ago, the whole terminology is beginning to evolve. Laser, low-level light therapy, we kind of started clustering them all together into photobiomodulation, because the spectrum goes from all the way from one milliwatt all the way into multiple watt lasers. So it’s not necessarily low-level light therapy as a treatment modality.

Cellular Mechanism for PBM

So that’s kind of where we are today and now to understand how light can actually affect cellular physiology, we have to dive into a little bit of a cellular mechanism. There’s something called a chromophore that exists inside of most species, bacteria included, most eukaryotes. What chromophores do is they are actually specialized portions of the cell that are responsible for absorbing photons. So light is packets of photons and we have to have some way to biologically accept those things. We know of a couple really common ones if we all think about it, melanin in our skin melanin is a chromophore. So when ultraviolet lights hits our melanin we have a chemical reaction that comes that creates pigmentation and we start tanning. So this does exist. It also exists in plants. Chlorophyll is a type of chromophore as well. It accepts sunlight and creates a cellular mechanism inside of that plant. Well there’s two different types of chromophore as you have specialized and non-specialised. The specialized ones you’re using right now which. We have rods and cones inside of our eyes and allow us to accept photons. You see down there in the middle we have three different types of cones in our eyes. We have red, we have greens, and we have blues. That allows us to see the visual spectrum. What’s interesting is these chromophore either absorb or reflect different wavelengths of light. So at the bottom we see that the red chromophore and our cones accepts the lights at 560 nanometers and it rejects or reflects everything else, so that we can see red when those chromophore are stimulated. Green, 530. Blue, 430. So we see the number starts to decrease as we go towards the blue end of the spectrum where the ultraviolet end of the spectrum. As the numbers start to get higher as far as the wavelength, as we go towards the infrared or microwave. Now speaking of microwaves, microwave is just a continuation of the electromagnetic spectrum. One of the things that we see with microwaves is anytime you put a piece of food in the microwave, what happens to the food as you turn it on? It heats! Does it on the outside? No, it heats all the way through even if it’s in a container. So microwaves can penetrate different types of aspects. So when we start a little moving a little bit further up that spectrum towards the ultraviolet spectrum, we should also assume that those wavelengths that are longer can also penetrate like microwaves can. So that’s something we should start thinking in the back of our mind. So we also started to see on the right side of the screen, we have some of the different cells that are in our eyes, some of them are photo acceptors which are the types that don’t have any participation in senses. And we have photoreceptors so photoreceptors talk about phototransduction and when we start looking at receptor-based therapies we always say that receptors have one job.  They are transducers. They take some sort of a physical energy and they convert it into electrical energy so that we can experience the world in which we exist. So the phototransduction occurs in the receptors and then the photobiomodulation occurs in the photo acceptors. Receptors versus acceptors. So when we start really getting into this electron transport chain there is a target of photobiomodulation. This is Cytochrome c oxidase. So Cytochrome c oxidase, when we start looking at the electron transport chain has a really really important role in mitochondrial function. It’s the last stage in reduction in the mitochondrial transport electron transport chain before we can produce ATP. So when we say when light hits Cytochrome c oxidase what it does is it implements the complex 4 of the mitochondrial transport chain. What that does is that takes hydrogen molecules and also we start looking at O2 molecules which are superoxide molecules and converts them into water. When it converts that into water inside the medic mitochondrial matrix, what it does is it releases hydrogen protons into the extracellular space. Well, when we start looking, that’s the first thing that happens is when light shines on this on this Cytochrome c oxidase it creates hydrogen molecules and as those hydrogen molecules start to increase in their numbers we can see there is an influx into complex five which the end result is ATP. We all know that ATP is super important for what? Life. For energy. However, we also know that free hydrogen molecules are not also the best thing for us either. So in an electron transport chain, we’re going to see that there’s going to be the release of network oxide, which as Dr. Jay was just talking about, is really important for vasoconstriction and dilation regulation or vasoregulation, I should say. But we also know that nitric oxide can have detrimental effects on cellular function as well, because it can actually block Cytochrome c oxidase.

So some of the research thinks the reason why we have this sharp drop off curve with a laser therapy or photobiomodulation is because you may exceed the metabolic capacity of the mitochondria, which is a term that we’ve been talking about for quite a while. The other thing that happens is we also have an elevation of temperature. Elevation of temperatures is anything in the realm of one tenth of one degree Celsius, has a big change in intracellular pressure. So you start having more changes in sodium potassium transduction and things of that nature. We also know that some of our cells have thermoreceptors or temperature gated channels that can allow influx or outflux of ions. So we have those primary effects of this photobiomodulation, then we start looking at secondary effects. There are many many many. There’s a little bit of a diagram on the side there and you can kind of go through that but realistically what ends up happening is protein kinase has become set into place which creates the release of calcium and cyclic amp which are signaling molecules. Nitric oxide, as well as the reactive oxygen species that are produced by the electron transport chain, are cellular molecules that signal for cellular processes to occur. Everything from immune activation with some of the reactive oxygen species we start activating superoxide dismutase which is a really strong antioxidant that promotes cellular health. But we also see that these secondary messengers also activate different types of metabolic pathways not on a mitochondrial layer, but on a nuclear layer such as transcription, translation and protein production for cellular health. There is also tertiary effects of photobiomodulation We see here in the bottom right hand corner,this is from a paper published by Hamblin and right now from what I’ve been able to read Hamblin seems to be one of the authorities in this area. One of our colleagues here today has a great poster presentation that he did with Hamblin. Dr Hamblin works at Mass General Hospital, Harvard trained, and they have a whole department on photobiomodulation there at Harvard. He is one of the main people in charge of this and what he found is that the tertiary responses to photobiomodulation mean that you increase more blood vascularization, angiogenesis, synaptogenesis which is a huge interest to us, right? We talked about superoxide dismutase upregulation and NF-kB, are big anti-inflammatory cytokines, get produced. We have up-regulation of mesenchymal stem cells which can differentiate in neural tissue. They can be created into fibroblasts for collagen and muscle tissue. Lots of changes that happen. We have increased lymphatic drainage. Then we get the dissociation of nitric oxide. So we produce it, then we dissociate it, so it’s not such a harmful chemical because at certain points the concentrations in nitric oxide can also change membrane potentials. We also see increased blood flow. So you see there’s primary, secondary and tertiary, and then there are systemic effects. So before I talk about the systemic effects there is a great study that was published by Johnstone done in 2014. They were a little bit skeptical of this transcranial stimulation. So what they did is they took a bunch of rodents, MPTP rodents. So these are rodents that they genetically and experimentally induced Parkinson’s disease with. What they did, and I couldn’t find a good picture of it, is that they put tinfoil hats on the rats, almost like the people from outer space are coming for them right? So they put tinfoil hats on them so that the light cannot penetrate the tinfoil and affect their brain but they shine the light on their body. What they realize in their controlled study is that the ones that had the lights that shined on their brain had the best results with some of their task speed and walking speed and maze test, but the ones that had their head covered with the aluminum foil also had significant improvements over the controls. So this leads a little more to question right what are the systemic effects of photobiomodulation at ulterior sites. The place where they actually shined the light on these rodents was actually on the tibia. So they shined it on their tibia. It wasn’t on their spinal cord, it wasn’t anywhere in the nervous system. It’s on their actual tibia. So some of the effects of photobiomodulation cannot be explained entirely by photons penetrating the skull and accessing brain tissue. However what they have shown is that in 2003, the calvarial bone has really high levels of mesenchymal stem cells that exist inside there. So maybe there is some photoactivation of mesenchymal stem cells. They also showed in 2011 with Andrew that the effects can last days to weeks, and potentially even months after the stimulation stops. So there are systemic long-term effects that happen there.

Interaction: Light and Matter

Now when we start looking at light there is a lot to understand about light. The most complex part and this is what kind of gets overshadowed by the ease of application, is the complexity of light. What I mean by that it seems pretty easy to go “beep”, wait 10 minutes and then something happens. But the complexity of it, the richness of it, is really understood in its complexity. So whenever we have photons hit matter, and we’ll call this tissue matter, at this point in time, there’s a couple of things that happen. The first thing that could potentially happen is the light is reflected. This is what you see when you shine laser. So anything that you see when you’re doing laser or photobiomodulation is energy that’s not getting into the tissue. If it was getting absorbed into the tissue you wouldn’t see it because 100 percent is getting absorbed. So the first thing we look at is the reflection. As it starts penetrating and transmitted through the surface, one of the other things you’ll have is refraction. So you think you’re pointing it there, but just like with x-ray it can scatter and go in a different direction. An important part of refraction is the internal reflection. So you can see that that reflects at a 90-degree angle to the vector and what does it go back towards? Your target tissue. So we actually use some of the scatter when we’re looking at a photobiomodulation. Other things that we have on the right side of the screen there, you see diffraction and scatter. This is energy that becomes wasted or absorbed by other tissue other than your target tissue. And then we also have backscatter. So when these light waves or these photons get in, they just go all over the place and a small percentage of them go right to where you are you’re trying to target them. So we always have a collateral influence on our tissue with photobiomodulation.

When you start looking at penetration, only light that is absorbed by the chromophore is actually utilized. So chromophore reflect or absorb certain wavelengths. What happens with sunlight, because a lot of people say “ What if I just stand outside in the sun? I’ll get tons of infrared, visible and UV.” When you have tons of light, especially non-coherent light, it scatters all over the place and reflects all over the place. You don’t get a concentrated dose of any one wavelength. When focusing on transcranial photobiomodulation we also have to consider impedance by both hair and skin. Different colors of skin, darker skin doesn’t transmit light as well as lighter skin. We have to consider the lack of transmission through bone, meninges, blood, water and tissue. Different tissues also have different impedances.  As a matter of fact, when you look at grey matter vs. white matter they have totally different impedances for this photoenergy. When you start looking at some of your different devices, wavelength has the greatest impact on penetration, not power. Everybody’s always trying to buy a powerful laser. It’s not always the right thing depending on what you’re trying to accomplish. So your target tissue should be the determining factor on what type of light you’re purchasing or what type of illumination source.

But penetrating the skull.. does it really happen? So we’ve talked in the beginning about how we were going to come back Jagdeo. He used human cadaver heads with the skull intact as well as soft tissue to measure penetration of 830 nanometre light. He found that the penetration depended on the anatomical region they were trying to shine the light through. So different skull bones or cranial bones have different transmissions of light. So less than 1 percent in the temporal region, 2 percent of the frontal region, 11 almost 12 percent at the occipital region. It’s said specifically in this report that 633-nanometre wavelength had hardly any penetration through the skull at all. Does that mean that 633 or in that spectrum doesn’t work for photobiomodulation? No it doesn’t mean that. It just means that maybe your intended target is different than the actual target being treated and we’ll talk about that in just a moment. Tedord in 2015 also used the human cadaver heads, compared penetration between three different wavelengths 660, 808, and 940.  They found that 808 was the best and it could reach a depth of up to 40 to 50 millimeters into the brain tissue. When we started looking at the cerebral cortex, some layers of the cerebral cortex are only 10 millimeters thick. So you start seeing some significant penetration into the brain tissue if you’re using the right wavelength and if you consider the impedance from other tissues.

So we know that about 2 to 12 percent of energy delivered trans-cranially will actually even reach the cortex. A twenty-fold higher efficiency of light is delivered through the sphenoid, so instra-nassalar. So you’ll see some applications of intranasal light. Twenty times more gets through the sphenoid because the sphenoid is not as big. We know what lives behind that spheroid and how beautiful and important it is, right? This is where you have structures like your nigra. This is where you have structures like your brain stem and oculomotor nuclei and all those things that sit right behind there; the thalamus, the basal ganglia. All of these different beautiful areas that allow us to interact with the world and you have a great pathway right through your nose. We also understand that when considering a tissue impedance it will really help you understand how to pick your instrument and target your tissue.

Light Sources and Dosimetry

So let’s maybe segway into light sources and dosimetry. The mechanisms behind photobiomodulation are not so controversial in the literature. People are pretty well understanding how this is working. We’ve been working and looking at it for over 50 years now. The most controversial aspect is “what light do you use and how much do you use it. What are the settings?”  What you’re going to see in just a few minutes is it that it gets pretty complex and now you’ve got to go back to grade school and start doing some math. So there’s two parts of dosimetry, the instrument, the second is the dose. The instrument generates power or irradiance and this is designated by watts per square centimeter. However, the dose is energy is also called fluence which is joules per centimeter squared. So watts per centimeters squared versus joules per centimeter squared. We’re gonna talk a little bit about what’s the difference between irradiance and fluence.

So when you’re looking at an instrument, there’s four factors you want to consider; the wavelength, the power, the coherence, and the pulse structure. So the wavelength is going to tell you what tissue, or you’re going ask yourself what tissue do you want to treat? The powers going to say, “how much tissue do you want to treat?” The coherence is going to say “well, should I use a light emitting diode or should I use a laser?” The pulse structure is important because it’s going to help you consider some of your power calculations and your dose calculations.

So here’s a diagram that I put together for you that really summarizes a lot of what people are talking about right now. I want to draw your attention to the left side of the screen where it goes from the 400-nanometer spectrum all the way down to 1100, and on the right side of the screen you’ll see the chromophore that is affected by that specific wavelength. So when we start looking in the 400 to 700 nanometer spectrum your target tissue is melanin. So when you’re in the tanning bed that’s at the higher end, the 400 spectrum ultraviolet, and also hemoglobin and myoglobin. So really, really important if you’re looking at superficial types of injuries when you’re looking at tissue repair, when you’re looking at aches and pains and blood flow and inflammation. Then there’s a gap of what the research has pretty well determined is completely unusable wavelength between 700 and 750 plus or minus about 15 nanometers of light.  It just doesn’t seem to be really absorbed by anything maybe a little bit by melanin and a little bit by hemoglobin, but it doesn’t really have a therapeutic consequence. And then from 750 on, our primary chromophore is the cytochrome C oxidase which is going to give us more ATP and all of those amazing things that we just talked about. And as you go farther down the list there, you start seeing that the major chromophore becomes water. This is why you put something dry in the microwave and you put it on for five minutes and it doesn’t do anything. Because as you start going down that spectrum, water seems to be the chromophore that’s absorbing most of that energy. So what that means, if water is the chromophore in that spectrum, then there is something we need to be considerate of. What is that? Heating. So heat becomes an issue, but we also said that heating can be a good thing because there are heat gated channels on these cells that allow us to have action potentials that allow us to create ATP and protein kinases. All of these different things. We also have to look at some of the depth.

So let’s go across the x-axis where we look at, it’s almost like an X-Y coordinate system here. When you have 400, looking at dermal. As we go a little bit higher in the wavelengths we are going to looks more at tissue in vascular aspects than bone and joint. Once we crossed that threshold we’re looking a little bit more brain as the primary target. As we go down into the real infrared spectrum we’re looking at deep brain tissue, is realistically our target for some of those different wavelengths. In the top right-hand corner, you can see a good graphical illustration of the difference between a short wavelength and a long wavelength. So you see the penetration of that short wavelength is only about 5 millimeters when we start looking at the distribution of that long wavelength, you see that there’s a whole lot more penetration of the longer wavelength.  

Laser Power

So power.  How much tissue do we want to treat? That’s the question we’re going to ask ourselves. The power of light used in photoneuromodulation, now we’re kind of focusing a little bit more on the neuro side of things, is about 1 milliwatt to 1000 milliwatts per diode. Okay, so you’re looking at about a 1 milliwatt to 1 Watts spectrum. Outside of this threshold the light is either too weak to have any effect or so strong that harmful effects may actually outweigh the benefits. This is from Chung in 2012. Power and time are inversely related to dosimetry, so the more power you have the less time you’ll treat for, but less isn’t always more, because we’re going to talk in a minute about tissue capacitance. Tissue can actually store energy. So maybe longer is better. So as we just said, higher power isn’t always better. Tissue can act as a capacitor and actually stores energy, over a period of time. Longer sessions of the same power can provide greater penetration without necessarily heating up the tissue as much. So higher power can produce more heat and causes a sharper hormetic curve. So everybody is familiar with that term, hormesis.  Same thing we see with radiation. X-ray has a hormetic curve. Some of it’s beneficial, some of its detrimental.  Light has the same exact curve. Here is a 3D rendering of that hormetic curve and what you’ll see there at the 0.0 seconds with zero radiance, as you go up that y-axis you’re going to start seeing that power starts to increase, but look at the shape of the mountain if you will.  Look at the shape of the mountain from one side to the other and what you’ll see is there’s a sharp drop off with the higher power. And then if we look at the bottom right-hand corner there’s almost like a plateau at the top before it starts to drop off. So lower power is actually a little bit more forgiving if the dose calculations aren’t actually right. You’ll see in just a moment how tricky it is to do some of these dosage calculations.

Right now the literature pretty well supports that a maximum tissue dosage for photoneuromodulation is about 6 joules per centimeter squared, but the average is about 2.2. So this is not what you’re delivering from your instrument. We have to look at the perspective of the tissue we are trying to treat. So we’re going to work backwards in calculating some of our dosages. Dose is usually in joules, and a joule is one watt per second. That’s the calculation of a joule. Here’s what you need to be cautious of when you’re looking through your laser catalogs. Most of the time these devices are displaying their power in milliwatts. So a milliwatt is 1/1000 of a watt. So which means that when you do that conversion you’re actually looking at 1/1000 of a joule per second. So we have to make sure we take that into consideration as somebody can say, “hey my device is 2500 milliwatts and you say wow, that’s pretty high!” It’s 2.5 watts, which is still significant but just don’t get caught up in the numbers. This is where we can deconstruct things and be educated physicians and know what we’re trying to accomplish with what we’re doing.

Coherence

Coherence was another thing that we were talking about. Coherence is essentially the type of wavelength that you have. So lasers emit monochromatic, meaning one color coherent wavelengths, that are coherent in time and space. So you get this one beam and that’s it. When we start looking at low-level light therapy and things like LED, they’re noncoherent but they’re also monochromatic. They have one color but there’s a bunch of different wavelengths. At the bottom right-hand corner, you see sunlight. It’s completely noncoherent and it’s multichromatic, so we have all of these different wavelengths there. When you start looking at some of the research from Rojas in 2011, he pretty well said that both are effective. However noncoherent light seems to be able to affect nervous tissue a little bit better. Specifically, because you can have lower energy densities with less heating and accomplish the task that you need to with neuromodulation.

Pulse Structure

Pulse structure is another thing that we need to consider. So this can factor into your usable power calculations. So one way is to look at this as a duty cycle.

So if you have a pulse that’s on 50 percent of the time and off 50 percent of the time and they’re advertising this is a thousand milliwatt light source. What’s your usable power? 500 milliwatts because it’s off 50 percent of the time, and on 50 percent of the time. So a lot of times when we see some of these pulsed lights we just have to be educated consumers and say “Okay what’s your duty cycle. How long is the laser on when I turn it on.” But some of the things that we need to really consider in calculations are what’s called spectral width. In camera terminology, it’s the aperture or also with your pupils as the aperture. How wide is the actual light? Because they wider it is the more it’s going to affect the surface and a lot of these calculations are in milliwatts per centimeter squared. So you to ask them, “How big is the beam if you’re telling me it’s a thousand watts per millimeter squared and the light is only a nanometre thick. That’s a really what low powered light source! You can see where it starts to get so confusing, right?

I think that there is a lot of time put into this so hopefully its beneficial to you. We also to consider peak wattage pulse width, pulse frequencies and there are some calculations there and I’m kind of running a little lower on time that I’ve wanted to so I’m going to run through some of these things so we can get to the good juicy stuff. However, one thing important on the slide is that pulsed photobiomodulation has been shown to be significantly more effective than constant waves. So light that’s always on is not as effective as pulsed. Now they think the reason why is that little bit of time, because remember the mitochondria. It’s not like this fast right. It’s a lot faster than any of these lights can actually pulse with. So the thing is is that if you have a constant light form there’s not really any time for that intracellular balance to occur, and for there to be a rest period in between the stimulation. So any type of pulsation seems to be more effective in the literature than constant.  When you start looking at pulse, there’s not a whole lot of literature surrounding what frequency the light should pulse at. But there are some people that are getting a little creative here and saying, “well, entrainment wavelengths of brainwaves exist.” This is the basis of neuromodulation, right? This is neurofeedback and things like that. We can entrain wavelengths. Well, if energy or electricity can entrain wavelengths, why can’t light? If we’re penetrating, which we’ve already established that we are, why can’t the flickering of a light or a dose of energy at a certain frequency, why can that not entrain wavelength? So you can actually maybe use this as a prescription cookbook for things that you’re trying to target.

Wavelengths

So Delta waves looking at 0.5 hertz to 3 hertz is associated with relaxation, sleep empathy. So somebody has a really high strung, anxious, maybe you want to pulse your laser between a 0.5 hertz to 3 hertz, Theta waves 3 to 8 Hertz. Associated with creativity, imagination. Alpha waves associated with the default mode network. This is the mode network that allows us to be present. It actually is one of the mode networks that are shown that learning or plasticity occurs the best in. Also with alertness and calmness. Beta waves associated with focus, judgment, decision-making, problem-solving. We all see patients that have some struggles in that area, so maybe that’s something we want to focus on. Gamma waves which are associated with love, consciousness, and also gamma waves have actually been shown to turn on glial cells. Which is kind of neat too because you can have an immunological influence using light waves.

Calculating the Dosage

So dosimetry. Let’s work backward. Let’s just say our target for the sake of this example is the right dorsolateral prefrontal cortex and not for any reason. As we go through this, what I don’t want you to do is say Dr. A said right dorsolateral prefrontal cortex needs 264 J, so that’s what I’m going to set my device at. This is a process by which we can break down how to calculate your dosage so you determine it. So the wavelength of 808, we see is greatest, or greater or more effective than other wavelengths so let’s just say that’s the wavelength that we’re going to use. We know that the frontal bone transmits about 2 percent of that activity. We need to consider probably the 20 percent impedance for hair follicles, for tissue melanin, things like that, especially if somebody is not shaved. In our target dosage, we said is at max 6 J per centimeter squared, but we’re going to want to shoot for 2.2. So we’ve got a math equation! 2.2 J per centimeter squared that’s our target tissue fluence.  So we’re gonna say if only 2 percent of the dose gets through we’re going to multiply that times 50. Right? And that equals 110 joules per centimeter squared. We’re gonna give an additional 20 percent for some interference with follicles and hair. So our estimated dosage is 132 J per centimeter squared. Now we say our surface area that we’re going to treat is 2 centimeters squared. Maybe that’s how big the aperture is of your light source. So what does that mean? If the dose that we had is 132 per 1 centimeter squared and we need to treat 2 what do we need to do to our dose? I just gave you the answer! We got to double it. So it 264 J, that’s what we want our light source to put out. So to target the dorsolateral prefrontal cortex, we need 264 J and needed to be spread over roughly a 2-centimeter square an area, and need the near the wavelength to be near infrared or infrared, so greater than 750 nanometers. So let’s talk about an instrument. Let’s just say our sample instrument, no brands associated, is 808 at 1 Watt per centimeter squared.  It’s pulsed at 20 hertz, 50 percent duty cycle which means that our effective output is 500 milliwatts per centimeter squared per second. Our aperture is 2 centimeters squared at the skin surface. So pretty good, easy statistics. But what if we needed to hit four-centimeter squared? What can we do? There are two options. We could either move our light source or what else? Pull it away from the skin, right? Because the light projection is conical, so as you pull the farther away the source is going to get bigger. But many types of non-coherent follows the inverse square law of like X-ray. So for every time you double your distance you have to double your power by 4 in order to get the same amount of energy hitting your source. So just something that you need to take into consideration. That also depends on a lot of different things, you’re spectral bandwidth, the laser lens focus, things the things you’re gonna want to ask the person you’re purchasing on a device from.

Laser Treatment Time

So now we need to calculate time. So 264 joules is what we want. So looking at the bottom of the screen, Joues is Watts times seconds. So 264 joules times our effective dose which is 500 milliwatts times a thousand to get it from milliwatts to Watts, means we need 528 seconds of stimulation, which is about 8.8 minutes. So that’s where you need to be in order to deliver the appropriate dose that is going to reach your target tissue. Do you see how we work to the target tissue and went back? We just didn’t go to a setting in our device that says “brain”, because that’s not going to be the best thing for your patient.

Laser Therapy Side Effects

Side effects. So this was pretty neat. Adverse neurological effect was seen in those with over 750 milliwatts per centimeter square, which is about a hundredfold of the optimal dose. Also, it was in the continuous wave mode. In the pulsed mode there was much less heating and no tissue damage there. So realistically there is very little risk or they’re pretty much are no real published side effects of using photobiomodulation as long as you have the right settings. So what the research is pretty well conclusive is that a less than optimal choice of parameters will reduce effectiveness but simply an inappropriate choice of light source and dosage is usually what causes the side effects.

How Can PBM help TBI Recovery?

Now taking a couple of seconds, just coming back where we started, how can photobiomodulation how TBI recovery. When we look at the screen here what we end up seeing is that down in this area during a concussion we start looking at an injury to the mitochondria, decrease ATP production, we have decreased energy synthesis. So right at the acute phase of the concussion laser can necessarily help the chemical cascade associated with that, but it can also help with the inflammation and also can help with the synaptogenesis. So in conclusion, photobiomodulation for brain disorders will become one of the most important medical applications in light therapy in the coming years. Looking at the brain influence and light. Dosimetry remains the most difficult and controversial element of photobiomodulation, however transcranial photobiomodulation may be able to mitigate cellular processes involved with chronic and acute concussion symptoms.

Thank you so much for all of your attention.

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