Light Sources & Dosimetry
Light Sources & Dosimetry - Transcript
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 specialised 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 specialised and non-specialised. The specialised 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 super oxide 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 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 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.
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 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 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.
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.