I’m back again for my fourth conversation with Dr. Mark Cronshaw, an expert in the world of photobiomodulation (PBM), aka red light therapy. You know that when I have multiple conversations with a guest, I highly value their knowledge and want to go deeper with what they have to share.
If you want to get VERY technical and go deep with the topic of PBM, this episode is for you, and I recommend you listen to the prior 3 episodes we’ve recorded together.
In this conversation, Dr. Cronshaw presents what he calls his “philosophy of care” for using photobiomodulation to enhance healing, manage pain, and prevent injury. His approach focuses on a few fundamental questions:
- Are you treating surface or deep tissues?
- Are you seeking to stimulate healing/tissue repair or provide pain relief?
His multi-dimensional approach explains why different devices produce different results, enabling more strategic use of both professional and at-home light therapy tools.
WARNING: My conversations with Dr. Cronshaw are NOT a simple or practical how-to guide of “go buy this device and use it this way.” This podcast series intends to go deep into the scientific, technical, and theoretical nuances of PBM science. So it’s NOT for everyone. These podcasts are for people who want to nerd out on PBM science. So please don’t say I didn’t warn you! 🙂
Table of Contents
In this podcast, Dr. Cronshaw and I discuss:
- Why inflammation is necessary for healing, but can be managed with the right light approach
- The critical difference between superficial tissue targets versus deeper treatments (and why most devices get this wrong)
- How the skin acts as “a brain on the outside,” transforming light into powerful healing signals throughout your body
- The overlooked truth about irradiance: why higher power isn’t always better (and when it actually matters)
- Why blue light isn’t just harmful and how it can deactivate pathogens when used correctly
- The shocking revelation about “photon is a photon” versus wavelength-specific effects (hint: the truth lies somewhere in between)
- What common PBM devices are missing when they make unrealistic penetration depth claims
- Why tissue heating isn’t always harmful and the surprising benefits of controlled thermal effects
- The “Gaussian effect” that may have contributed to methodological errors in PBM research
- Dr. Cronshaw’s simple but profound framework for treating different conditions (from pain to wound healing)
- The revolutionary concept of “bioenergetic entrainment” that explains why light therapy works at a systemic level
- Why most research focusing solely on the mitochondrial mechanism is missing the bigger picture
- How light therapy triggers the production of mood-enhancing neurotransmitters directly in your skin
- Why prevention with light therapy can be more powerful than treatment (especially for certain conditions)
- The shocking truth about popular pad-style devices and whether they can truly deliver therapeutic effects
- How timing your light therapy intervention can dramatically change your results
- Dr. Cronshaw’s finding of two dose windows that explain why some treatments work for stimulation while others work for inhibition
- Why understanding “3D effects” changes how you should approach treatment
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Transcript
Dr. Cronshaw: Right. Okay. I’m going to talk to you a little bit about the way that I do with my own students when I’m teaching this/ I should explain, I’ve got a dental training facility that I work with dentists and hygienists, and therapists, and what have you, and we induct them in how to do PBM practically for dental applications. I’m not going to talk so much about dental applications. These are some of my dental friends and colleagues, right? It’s an international group because we all have the same problems. We’re all having to either deal with people who are in pain or deal with the after effects of people who’ve had pain and then they’ve lost some function.
We seek to try and do things as gently as we possibly can and, also, to try if possible, not just to stop what’s happened, which has led to the problem, but if possible to reverse it and to regenerate tissues. At the same time we need to match the needs of our patients, which is something which is going to be reliable, simple, and not too expensive, and something which is going to last. It’s quite a demanding set of challenges.
What I’m seeking to do is to increase the ability of the tissues to heal and repair. Although I’m doing some directed clinical care, which may be triggering off some issues associated with healing, I want to try and direct that healing so that the tissues are dealt with as gently as possible in order to increase their resistance to the type of trauma that can lead to more tissue damage. I want the tissues afterwards to get the best possible healing and repair with the minimum amount of trouble after my intervention. If I can start to manage inflammation using PBM, this is great.
The pictures that you can see there is of a daughter, actually of a dentist, who decided to take a drink from a hot tap and she ended up with a really bad burn on her commissure here, in the corner of her lips. Her dad, who’s a student and a friend of mine, contacted me saying, “Hey Mark, what do I do? What do I do?” This is his 10-year-old daughter. I gave him instructions and care, which I’ll share with you later on if you wish. We managed that on a daily basis, where he did some treatment at home, doing some PBM every day. Over a process of six days, you can see how rapidly the inflammation is resolved and how good the quality of the wound healing.
How do we manage to do this? This something you can turn into a transferable skill? The short answer to that is well, absolutely, you can. You see, what we’re trying to do is whenever we’re thinking about using PBM, photobiomodulation, it’s going to be within a bigger context. There has to be a good management of the problem. This is where some professional input can be helpful because if you’ve got a good diagnosis, then this may be just one element of what’s happening. You may have people who want to treat themselves at home after they’ve had some surgery, doing some PBM in order to help enhance the quality of their healing and repair.
Although I’m talking from a clinician’s perspective, I’m very happy to indicate to people some things where they might be able to add to the benefits of the care that they’re receiving from their clinicians. These are all sorts of stuff that we clinicians look for. We need someone who’s essentially as healthy as they possibly can be, not like the guy in the picture. We may have to do all sorts of things to help set the frame for good wound healing. We want to, at the same time, to design it in such a way that you’re going to get the optimum response.
As part and parcel of that, as a model of care, there’s this idea that we may be able to instruct our patients in how to use home use PBM devices as a support at home on a daily basis. This is a new concept, something which I think is very exciting for me as a clinician, where we’re working with the patients, where we’re doing certain things which may be more intensive treatments and may involve some invasive stuff in our surgeries. The patient, at home, is managing their complaint using some PBM.
What’s the problem? Whenever you do something, say, you twist your ankle, you get acute inflammation. Now that acute inflammation, that causes you pain. There’s some swelling. If you try and load it, there’s reduced mobility of the joint. That pain can last for anything up to 10 days. Typically, it peaks at about 24 hours. I asked myself the question, well, why? What does inflammation do? Without inflammation, you don’t get healing. Inflammation is the thing which sends out the primary signal to the body’s repair mechanisms. It calls in all the repair troops. Without that, then you just don’t get the attraction of all of the repair cells to the site of the injury to repair.
Then after a day or so, there’s some initial deposition of wound matrix, which is the basis of healing and repair. The MoPOC crew, as it were, is there on site dealing with the site of the damage and removing damaged tissues and remodeling them. That process then can go on for 30 days or more. Then there’s a remodeling phase where the initial temporary repair is replaced with something which is more permanent. This is very characteristic of wound healing, right? With that model of wound healing in your mind, what we’re seeking to do with PBM is we’re seeing if we can reduce the peak, as well as the duration of the acute inflammatory phase.
This is the point where you’re getting the pain, the acute swelling. It might feel hot to the touch. You’ve got reduced mobility, say, the joint which has been damaged. If you can reduce the peak so there’s less pain and then reduce the duration of acute inflammatory phase, this is really useful clinically. You’ve had an injury, you’re in pain, you want some help. Okay, so you can do some PBM. There’s no reason why you couldn’t be doing some of this at home using some home devices that you can buy for home use.
Then after that, in terms of the repair, you want to encourage the repair cells so that there’s the maximum number of repair cells present and that the quality of the healing repair is going to be really, really good. If you’ve got a history of prior sports injuries, you may want to see if you can build a better tendon, build a stronger bone, build some more tissue there so you’re less susceptible to future injury. The quality and stability of the wound is really good.
This is where PBM can really score because when you understand the dynamics of what’s happening when you shine that light onto the tissues, then you’ve got a very potent anti-inflammatory. They can stimulate the cells so you can get more of them and so you’re going to get more matrix, and thus see some direct healing and repair towards the optimum, within the range of possibilities for the individual. That will depend on their health.
If you’ve got some of these elderly, who’s got an impaired immune system, who’s got all sorts of other pathologies, then it’s very much more difficult. That’s not to say PBM doesn’t work. In fact, actually the contrary, because in these groups, this is where there’s a better chance can help to stimulate the cells to do a better job. Whether you’re healthy or unhealthy, PBM is still very helpful, but there are certain things which will hinder your ability to heal.
This is where within the context of healing and repair, it helps if you just understand that you need to have, basically, a healthy body. You need to have a good diet. You need to make sure there’s a good blood supply there, that the wound is stable. You’re not going to damage it and let it get infected. There are other factors there which medically may make it more difficult for you to heal and repair.
If you understand that, then you can start to appreciate the limits of what you might be reasonably expected to be able to achieve because for some conditions it’s like magic. You’ve got someone who’s healthy, who’s got a sports injury, they do some PBM and, hey, they recover really fast. Whereas if you’re ill, maybe you’ve had some cancer chemotherapy and radiotherapy, you’re not so good, it’s going to take longer and it’s a more arduous route and you can’t expect to see instant results, but it will still be of benefit.
PBM affects all the different cell types. It affects every single type of living cell. Whether you want to grow a new nervous tissue, whether you’re looking at stimulating the white blood cells, which are associated with your immune system and your ability to combat infection, whether you just wanted to generate more bone, whatever it is, these are all things where PBM applied appropriately, you can get all of this.
This is all really good stuff, especially with people who’ve got an impaired ability to heal and to repair, who are medically compromised, say they’ve got diabetes, or they’re obese, or they’re on a whole bunch of drugs which can impair healing. Lots of prescription medications have got this effect of impairing healing. This will help just promote the ability of the cells to operate to their best capacity within the ability of that individual to heal and to repair.
The clinical applications of this are huge. As you know, it’s everything from central nervous system conditions, through to the management of cardiovascular disease, respiratory infections, arthritis, sports injuries, as a support for people who are having various forms of surgeries, dentistry, it goes on, anything which has got an -itis in it, which is related to inflammation. This is an anti-inflammatory, so all of these medical conditions.
Inflammation is the name of the game in medicine. Most stuff that’s happening, which is causing people ill effects, whether it’s Alzheimer’s, whether it’s traumatic brain injuries or whatever, most of it is related to inflammation. If you’ve got a tool which you can use to manage that inflammation, but without damaging the ability to heal and repair, that’s fantastic because you actually need inflammation. If you haven’t got inflammation, you don’t get that signal that calls in all the repair troops to the site. This is where people who are on steroids, that systemically reduce the whole body’s ability to have this inflammatory response, they suffer. They just don’t heal so good, I think the selective application to the area is working on exactly the same targets as powerful drugs like steroids [crosstalk]
The impact of the disease process on PBM results
Ari: Dr. Cronshaw, if I can interject one point to this topic. I feel there’s a lot of confusion around this topic of inflammation and its role in disease, its role in aging and longevity. There’s even researchers who have promoted the concept of inflammaging that sort of chronic low level inflammation is a major driver of biological aging itself and therefore longevity.
It’s been, as you mentioned, implicated in many different disease processes, but to some extent, to a large degree, it’s like if you’ve got a house on fire or a neighborhood on fire, and the fire department shows up and you’ve got firemen in there, with battle axes chopping down doors and with fire hoses spraying stuff and using fire extinguishers, and then you go in and you measure that, from the outside, and you say, “Well, these firemen and these fire trucks really seem to be associated with these disease processes,” but the firemen and the fire trucks are not what’s causing that situation in the first place.
There’s a lot of misattributed cause to inflammatory cytokines, to inflammation itself as being the cause of these events. Yes, it’s circular, yet there’s a case to be made for that kind of thing. I think that this very idea of the inflammation itself being the cause can be debunked very easily in a science 101 sort of way. Let’s say you take non-steroidal anti-inflammatory drugs, which lower inflammation. Well, they don’t actually positively affect most disease processes. Yes, they can temporarily alleviate symptoms like pain, but they don’t actually positively affect any of the disease processes that are supposedly caused by inflammation. They also don’t translate into increased longevity.
We know that taking drugs to block inflammation doesn’t actually translate into lower rates of disease or improved longevity, which I think gets at this idea that the attributing cause to the inflammation itself is probably [unintelligible 00:16:59]. I think that there’s an important distinction here, which I think you were alluding to, between something that is combating inflammation by simply blocking it or suppressing it, like a drug might do, versus something that might reduce inflammation by actually promoting better cellular health and healing processes. Would you agree or how would you sort of comment on what I just presented there?
Dr. Cronshaw: There’s a lot that I’d agree with. The issue really is not with eliminating inflammation because if you eliminate inflammation, that’s the body’s response to injury and trauma and insult. Inflammation is crucial to health, and people who can’t trigger that inflammatory response for one reason or another, they’re severely mentally compromised, and they’re much more at risk for all sorts of problems, including infection. The objective really is to manage inflammation, to improve the experience of the patient. At the same time the issue is how to deal with chronic inflammation because there’s a difference between an acute and a chronic inflammatory condition.
When inflammation goes chronic, this is where it’s failed wound healing and this is where there’s a persistent problem which the bodies can’t deal with and so all that happens is that, progressively, you get tissues that get removed. There can be progressive loss of damage. In dentistry, this is where people who’ve got gum and bone disease gradually lose all the attachment in all the bone around their teeth and then they end up with no teeth. It can happen in the joint where all the cartilage disappears and then you can lose the bone, and then you’re in trouble.
I think this concept of managing inflammation is essential. It’s certainly true to say that the manifestations, the things that cause people to go and see their doctor or to seek help, whether it’s self-help or within a medical context, a lot of it revolves around the issues that they experience because of inflammation. They’re experiencing pain, they’ve got swelling, they’ve got some persistent issues which you’re just failing to resolve. My point really is that PBM is a tool. It’s what I would call an adjunct, which is something which you can bolt on to other stuff that you can do to try and help both relieve the symptoms, as well as stimulate a healthy pathway towards healing and repair.
Timing matters in photobiomodulation treatment
Ari: Right. I think as a simple example of this, I know that there’s some research in athletes who, let’s say soccer players, who get ankle sprains, and it’s been shown that applying photobiomodulation improved the rate of healing by about 100% or 200%, meaning, they got back on the field, let’s say, in two weeks instead of four weeks, like the control group that didn’t use photobiomodulation, which, again, I think, gets at this distinction of this isn’t just something that is alleviating symptoms associated with inflammation. It’s actually speeding up cellular regeneration. As a byproduct of enhancing the actual regeneration at the cellular level, the inflammatory processes, that process is sped up or is optimized in a way where it’s made much more efficient and effective. The time of its presence is shortened rather than simply taking a drug that suppresses inflammation and reduces pain.
Dr. Cronshaw: Exactly, and those are– There’s one other exciting thing you could add, which is the timing of the intervention. The sooner you do it following the injury, the less acute inflammation you get because you never totally eliminate inflammation with PBM, and which then can help reduce the amount of tissue trauma. Also, if you preventatively treat someone, so if you condition them before the event, then, again, you can reduce both the severity, as well as the frequency of them having an injury.
The timing of PBM intervention is the same, which is very exciting as I’ll discuss later. This has got some very important implications for patients who are undergoing cancer therapies, one form or another, where they can suffer the ill effects of radiotherapy and chemotherapy. The timing of the intervention can be critical, a critical factor. Let’s carry on a little while longer but, no, I welcome your quite astute comments there. You’re right. You need information, but you can have too much of a good thing. That’s the message.
When I got involved in the clinical research in this, I wanted to know, well, how does it work? How much of it do you give? How do you go about doing it? Is it a specific device I need? Is it a magic wavelength? Can it be a laser? Can it be an LED? How often do you do it? What’s the sort of things that are going to screw me up, and make it difficult for me? What are the complications and things I need to know about?
`Right at the outset of when I started my doctoral research, I wrote a review with colleagues, Stephen Parker and Praveen Arany, where I was trying to get a handle on dissymmetry, as well as trying to understand how it is that you can achieve pain relief, which is analgesia, using this very useful effect. When I delved into the literature, I found that in the literature, in the peer-reviewed scientific reviews and meta-analysis and what have you, that there were two dose windows, that there was a lower dissymmetry, which was associated with the increase in activity of the cells and enhanced production of biometrics and better healing and good quality of immune response.
Then the higher window, you didn’t see that increased activity, you saw inhibition, but also this was associated with pain relief. You could use a higher intensity of energy, and this would be very useful in relieving pain. I thought, okay, great. I’ve got some initial ideas of what the previous research have done, but I still don’t understand how best to do it. The lady in the picture, she’s got a [unintelligible 00:24:02]. She’s got a hepatic lesion on the lip. There I’m actually using a laser rather than LED, but you could use an LED for this. What I’m trying to do there is to arrest the progress of that hepatic lesion and to help stimulate the immune response. Also, to see if I can turn it around so that we’ll have very rapid wound resolution, which you can do when you can start to understand how you can selectively apply the parameters.
Let’s build on this. I was thinking about, okay, what are you trying to achieve? Here I’m thinking with a clinician’s brain, which you could do this at home. What am I seeking to do? Am I looking to prevent a problem or am I trying to manage a problem? Is the management issue one of relieving pain and inflammation, or do I just want, after I’ve had some surgery, just so I get really good healing? Maybe a combination of them all.
The images in the picture show a patient of mine who had a really bad traumatic ulcer in their lip. They bit themselves really badly and it got very inflamed. It’s very painful. I applied some PBM. It took me two minutes. You can see there’s already some signs of reduction in the inflammation. There’s a reduction in the edema, which is the swelling associated with the wound. The wound itself is already beginning to contract slightly. All of that’s happened inside of two to three minutes. That says this is a very powerful thing, and that’s something which both relieves the patient’s pain and at the same time, it’s stimulating the heat and promoting resolution of a wound, which otherwise was just going to persist for a while, which is a nuisance to the patient, which is why they’re there to see me.
Lots of my patients, unfortunately, aren’t well. They’ve got all this stuff going wrong. They’ve got multiple pathologies. Virtually all of my patients over the age of 50 are on 3 or 4 different prescription medicines of one form or another. Within the ability to heal, you can’t just look just at the condition, the specific problem that you might have. It’s got to be within a bigger context, because quite often you might have people who’ve got maybe heart disease, but they may also be depressed as well. There can be other illnesses there too. They may have some diabetes. There can be this complication of these different pathologies, all of which then, as a patient, add up to a lot of separate problems.
When you start to think about doing PBM, you may be thinking not just of treating the immediate condition, which might be the ulcer that’s not healing, or your bedsore, or carpal tunnel syndrome, what have you. It might be within the greater context so seeing if you can help systemically as well. This is where PBM can score because you can use it either locally and also you can start to think about treating the whole person. It’s a concept that I describe as bioenergetics, where we’re starting to have an effect on the systemic health of the patient, as well as a local effect on the targeted tissues. Hang on to that thought for a minute, Ari.
Depth of injury matters
When you start to think about doing this, you need to know a little bit about where is the problem. Is it on the surface or is it deeper? The lady in the picture has got a muscle related problem, which has got some pain, which is causing her headaches. It’s a muscle that’s gone into spasm. I’m using a device there, which is actually a laser to get that muscle to relax and to improve the blood flow there. To treat this, I’ve got to know where is it.
Ask yourself the question, is this on the surface or is it beneath the surface? It’s a very simple question. If it’s a skin condition, then it’s a very different thing than if it’s a subsurface target. That will then affect your dissymmetry, as well as perhaps the type of device you use and the wavelengths that you use. It’s got some implications for the technique. It’s a fundamental question. Ask yourself, what am I trying to achieve? Is it pain relief, inflammation management, or healing, as well as what is it that is the outcome I’m seeking?
When you start to come down to the, how do I do it? There’s some basics you have to understand. I know listeners to this podcast will probably know this, but just to reiterate it so we’re talking the same language. There’s the unit of currency when we’re talking about dissymmetry is a joule, which is a unit of energy. The metric for photobiomodulation’s therapy is the number of joules we’re administering to an area, which by convention is the joules per square centimeter. Some people call this the dose. Some people refer to it as fluence. Some people call it radiant exposure, which is its proper technical term.
Now, the rate at which you deliver it is the power. There’s a very important concept of irradiance, which is the concentration of the power in the unit area. A joule in one second is a watt. A watt is the unit of power. Now, don’t worry, because we’re going to reiterate this and we’ll explore this a little bit more clearly, just so it’s a little bit more obvious as we’re going along.
Then you can think about, well, what tool am I going to use. Am I going to use a big flatbed LED? Am I going to use a small torch device? Am I going to be using an LED? Am I going to be using a laser? There’s a whole string of questions then you have to answer as to, what is it that I need to use to best treat this condition. Then you then think, okay, well, I’ve got a range of tools available to me. Maybe I’ll use a small applicator just for a little [unintelligible 00:29:59] lip or alternatively maybe I’ll need to use a big flat LED to start to deal with large areas associated with other conditions.
With some issues which are related to parametry, this is where it starts to get head spinningly complicated because there’s all these different elements to it, and this is where it can be really quite daunting because there’s issues to do with do you keep it static or do you move? How big an area do you expose the surface of the tissue? Are you going to hold it in contact with the skin or at a distance from it? Are you going to press it into the skin? Then the beam itself, the light, it can diverge. If you’re further away, then it’s a bigger spot than if you’re closer up.
Then there’s, you can do things with the beam so you can turn it on and off, which is what we refer to as the emission mode, and you can gate it so that you can have peaks and troughs sometimes when it’s not on. Then there’s the amount of energy you’re delivering and all the rest of it. Then there’s all these other parameters and you think, oh my goodness, this is so awkward. Actually, in essence, you can reduce this quite a lot to some fundamentals when you start to think about what is it that I’m actually doing.
Although there are all these parametry, when you go into the literature, there’s a huge amount of confusion in the scientific literature. How normal people are supposed to expect this, goodness knows, it’s a head spinningly complex because each of these things can be interrelated and it can affect the outcome. If you’re not careful in the scientific study, you can put too much importance to the magic formula, which gave you the result that you’re seeking, and you can claim, “Eureka, this is the way to do it,” whereas, actually, it’s just because of the way in which you packaged the energy in the form of delivery. There are many, many problems in the literature because of that. In an effort to try and remove the fog and that you see more closely, rather than focusing on all these complex parameters, let’s just move a little bit further forward in this conversation just so we get a better handle on what we’re doing and what we’re trying to achieve.
There’s a general concept of what happens to the light when it enters the tissues. A number of things can happen. It can just be spread, which would be called scatter. You can see those images of somebody’s lip where the red light that’s being applied is just spreading throughout the tissue. Then you can take a red LED and put it into your mouth and it looks like your whole face is lit up. That’s scatter. That can be associated with what we refer to as attenuation. This is where the energy is falling off quite rapidly because the energy has been diffused into quite a large area. When you start to apply it to something like skin, it rapidly falls off.
These are some figures from a colleague who suggests that just a centimeter deep you’re down to a third. In fact, I could show you other studies depending on wavelength, and other one of those parameters I was talking about, you can have between 2% to 10% of the energy at depth, depending on the source. There are all these depending on aspects of it. Scatter is something which is a feature, particularly with red visible to near infrared wavelengths, because these wavelengths are quite poorly absorbed. As opposed to the energy being absorbed by the molecule, most of it is scattered in these wavelengths. You get a big optic footprint. When you shine that light, even if you can’t see it because it’s near infrared, the whole area can be illuminated like a light bulb if it’s just outside of our capacity to see.
Now, some sources are concentrated so that the energy is in the middle of the beam. This is particularly important when you’re dealing with lasers. The video picture you can see there, it’s a chiropractor. He’s probably not a million miles away from where you are, Ari. He’s in California. He’s doing some PBM using a high intensity laser there. The different colors indicate temperature of the tissues and you can see that in the middle of the beam there’s a lot more heat. It’s hotter in the middle of the beam than on the periphery. This is what we refer to as a Gaussian effect.
The Gaussian effect is something which is very important in laser therapies. Now members of the public, generally, are not able to access lasers apart from very weak laser pointers, and things, which aren’t really going to be therapeutic, but even an LED there’s going to be some Gaussian effect. As opposed to it being a strong effect, this is less of an issue for LEDs. Anyway, let’s say that with a laser, you’re going to have maybe 68% of the energy in the middle of the beam. That’s something which I’m mentioning now, because this has impacts on some of the research findings, which, no doubt we’ll be discussing later on in regards to temperature and heat and the significance of those in regards to PBM. The Gaussian effect is something which is–
Ari: Sorry. Actually, I’ll let you complete your thought. Before you move on from this slide, I want to ask you something about it.
Dr. Cronshaw: Yes, sure. When you’re thinking about delivering the dose, you might think, okay, I’ve got this set up at 1 watt per square centimeter, which would be a dose I wouldn’t use for PBM but just for convenience, just for numbers. I’ve got a device there where in the middle third of the beam, 70% of that 1 watt is being concentrated. Now because it’s a big beam I’ve got a stick, a lot more power into it to provide that 1 watt per square centimeter, because the example you can see there, it’s got seven square centimeters so it’s quite a large beam.
If I was wanting to have it as an average of 1 watt per square centimeter, I’d have to have the power output up to 7 watts, which is a lot of juice, isn’t it? Then I’m thinking, okay, well I’m just going to go for 1 watt per square centimeter. You turn it up to 7 watts and then 70% of that 7 watts is in the middle of the beam. That, basically, means that about 6.5 watts is being delivered to that central area. That’s a lot of juice to a small area. Then you’re going to start to get some photothermal effects.
As in the middle of the beam, particularly if it’s a really big area, it carries on peaking because a Gaussian beam, it comes to a point but like a traffic cone. Then in the central area of that middle third, again, it’s another 70%. This is where you can seriously start to overheat things which is why with high intensity laser therapy devices, it’s really important with big beams to move because if you don’t, you’re going to cook things in the middle of the beam. That mistake has been made in some very important scientific studies which have led to some conclusions being reached with which I profoundly disagree. [crosstalk]
Ari: You’re hinting at that certain studies have found a negative result, let’s say overt tissue harm or at the very least that a particular treatment using a laser was ineffective, failed to show benefits, and you think the big confounding variable is how they use the device itself, and therefore they overheated the tissues.
Dr. Cronshaw: Absolutely. They come to a false conclusion because they’ve assumed that this is a phototoxic response, whereas, really, it’s a photothermal rather than a phototoxic effect. Basically, all they’ve done is just overheated the tissues. That’s a methodological problem. This is from a paper I published under two years ago. When you’re looking retrospectively, you’re looking at previously published papers going back 10 years ago, when people were less alert to this, then it’s entirely understandable why people might have jumped for the wrong conclusion.
It’s the nature of science. It’s not bad science. It’s just that you get somebody awkward like me comes along says, “We thought about this,” and it changes their conclusion, but the conclusions that they’ve derived from that are having some important impact on dissymmetry, particularly in regards to pain relief. I’m on a mission to try and get this message out. The Gaussian beam is something which, particularly with lasers, is really importan,t with an LED, because with an LED, unless you’ve got some special optics screwed onto the LED, then generally the size and divergence of the beam is huge, as opposed to it being quite relatively small area. As opposed to it coming to a really high peak, it’s almost like a little plateau, like a little speed bump, really, as opposed to it being a big mountain. Then it’s less of a biohazard to intense to symmetry in the center of the beam, depending, of course, on the output power of the LED. Generally, with the LEDs you’re looking at, what, 25 to 50 milliwatt output devices and so you’re not really going to start putting high wattage in order to fill large beams.
[unintelligible 00:39:49] that a little bit, ask your question, Ari, because I’m all [unintelligible 00:39:52]. What were you going to ask me?
Heating tissue in PBM
Ari: I want to point out something obvious here, which is that, as you’re showing in this image, the tissue, where you’re applying this laser is heating up. It looks like, based on the graph, it’s somewhere, I would guess 41, 42, 43 degrees Celsius, somewhere in there. Now, in certain literature that you see in the field of photobiomodulation, and in, for example, my podcast with Dr. Praveen Arany, he makes the argument that photobiom– I know you know where I’m going with this, and I know that this is a topic we could spend a lot of time on, we’ve already touched on a bit, but I just want to bring it to people’s attention in the context of what you’re presenting here.
Certain people have made the argument that photobiomodulation is sort of by definition, the way we define photobiomodulation is that it is non-thermal. I believe Dr. Arany’s exact words in the podcast that I did with him were, “I think that there is no place for tissue heating in photobiomodulation.” Presumably, he would– This [inaudible 00:41:10] doesn’t make sense to me. I certainly don’t want to misrepresent his position, but based on those statements, it would seem that this would not classify, based on this definition, as photobiomodulation, and that it would be put in the category of let’s say photothermal effects.
Therefore, basically, [unintelligible 00:41:31] effect is purely based on tissue [unintelligible 00:41:34] rather than PBM effects. Once you start going down that train of thought, then you start to wonder, well, if this is only about tissue heating, you’re only getting [unintelligible 00:41:45] versus let’s say a hot pack, just this little bag of sand that you might throw in a microwave and slap a hot pack on an area, right? There’s a number of layers to this story, and I think a big part of this is semantic, is just how we define what photobiomodulation is or isn’t based on how we are saying it’s these sets of mechanisms but not these other sets of mechanisms, photobiomodulation is only below X temperature and so on. How would you describe that picture?
Dr. Cronshaw: To say that there is zero heat associated with any photochemical process or photon transduction as we refer to the energy transfer between the light, the photon and the living portion of the cell, as being without any heat is just impossible. Inevitably, particularly with red to near infrared wavelengths, you are going to get some heat. It might be a micro scale event, where you’re looking at things where you need special probes to scientifically see the rise in temperature inside the cell point where the energy is being absorbed, as opposed to overtly heating up the whole cell or the whole tissue.
I would support the idea that you’ve got to be really careful not to overheat tissues. I’m completely empathetic to that. That’s part and parcel of any kind of energy transfer process, you are always going to have some heat. I don’t think Dr Arany would argue with that, because he’s– I think the distinguishing feature is that PBM, photobiomodulation is not heat. It could be associated with heat, but it’s not the same effects. PBM has a whole variety of other effects. It’s got a selective effect on specific areas of the cell.
Although, again, you may get some localized heating, for instance, with some of the iron gates around the membrane, the TRPVs, you can get some localized heating, which will then stimulate those iron gates to open. You’re thinking, well, is that a PBM effect or is that heating effects? This is where you’re starting to split hairs. You’re starting to argue really about how many angels are going to sit in the pin. The issue really is energy transfer, duh. You’re going to get multiple overlaying effects. To be too purist on this and say that there is absolutely no place for a photothermal response in PBM, well, good luck with that because I don’t believe it.
To give you an example, I do surgery using surgical lasers, and the healing is fantastic. It’s what got me interested in PBM because outside of the zone of surgical destruction, the energy is low enough to start to have a two-for-one PBM benefit, where I’m conditioning the [unintelligible 00:44:49] but at the same time that I’m doing my very selective surgery. The surgery will involve some photothermal events, which may disrupt tissues and break it up and heat them up above 100 degrees centigrade or higher. Yet beneath that, you get fantastic healing.
Trying to separate out photothermal effects totally from PBM, I think you’re throwing the baby out in the bathwater. I would emphasize that PBM is not the same as heating. It’s a different effect. The two effects themselves, especially when you start to think about three-dimensional models. We’re big creatures, people. If you start to have high intensity, as you can see in the image there, the lady who’s having some laser therapy to presumably help her with some fasciculation on a muscle. At the surface, that will be potentially producing some minor disruption in the tissues, which might trigger some remodeling.
That’s almost like diathermy as opposed to PBM. Whereas, in the depths of the tissues, because the energy will fall off quite sharply because of this effect of scatter and attenuation, then you can be having some PBM effects and you’re getting a two-for-one benefit. When we’re talking about surgery, we say, “Well, it may look ugly, but the healing is beautiful.” For some of the things that people are using at home, we certainly wouldn’t encourage them to start overheating things. This is not what you want. You want to be gentle.
The devices that are generally available for the public to use, intentionally, are very safe. You really would have to go out of your way to cause yourself some photothermal damage. The safety factor is one of the reasons why they’re available to people who are relatively untrained. Whereas, when it comes to high-intensity laser devices, there is the need for special training and awareness and all sorts of safety precautions. The devices that we’re using now, they’ve got built-in photothermal cameras and there’s all manner of things which, by design, let us more safely apply really high energy, but without causing the damage that causes Dr. Arany to lose sleep. Hopefully, we’ll move on to that one. We can talk more about this as we go on, because it’s a great conversation.
Ari: Yes, and I know we previously discussed this in some of the irradiance parameters that are 500 milliwatts per square centimeter in the near-infrared range and about 300 in the red wavelengths. I know that, also, there’s more complexity to that as far as the method of application, laser versus LED, and spot size and things like that. More broadly, those were the parameters we discussed and are also discussed in– What was it, the paper by your student, Zane and Dr. Hamblin? I think that’s the one where they review the photobiomodulation parameters that are involved in overheating the tissues.
Dr. Cronshaw: Absolutely. When you’re thinking about applying the energy, you might think, “Okay, I’m going to use a fixed irradiance. I’m going to go for–” Just for example, you might think, “I’ll use maybe 500 milliwatts,” which is top end for maybe an 810 nanometer near-infrared source, based on the Zein paper, but then the spot size is quite small. You may be using a surface spot, surface light application around about a centimeter.
You set the device to half a watt, which will deliver 500 milliwatts per square centimeter because it’s half a joule per second. Then you can start to think, “Okay, I’m applying that on the surface. I want to deliver 5 joules to depth.” Then you can calculate how many seconds it will take you, right? You think, “Oh, great.” If you use a bigger applicator, then you might then start to think, “Well, I really do want to deliver 5 joules, but I want to deliver it so it’s not going to take me quite so long to a bigger volume.”
You use a larger applicator, and then you’re starting to step up the amount of power that you’re applying by a factor of 10. Then you need to, more realistically, deliver your 5 joules per square centimeter at a centimeter depth. Then if you use a really big spot size, because of this Gaussian effect, particularly if it’s a laser, then because the energy in the mid-third of the beam is so much higher, then you need to be careful with your dosimetry, because otherwise you can be doing a bit more down there than you realize.
You can start to over-energize the tissues, and you’ll be delivering more energy to depth. This is my explanation of why it is that big spot size devices, particularly if it’s a single source like a laser, can start to really deliver a lot of energy to depth. Whereas with LEDs, these things can still be therapeutically beneficial. We’ll have this conversation later on in this presentation, if you wish, where we’re looking at the pros and cons of LEDs and lasers.
Then, as opposed to it being one big LED, you’ve got multiple LEDs, and the effects in terms of the tissue saturation of the photons and the distribution of the energy is quite different. I think, when you’re thinking about dose delivery, you’ve got to think about spot size. When you’re thinking about irradiance, then that is something where the amount of power that you’re delivering, if it’s going to have this Gaussian effect, you’ve got to take into account with big beams, the fact that the middle of the beam is going to be a lot more energy. With all the spots cumulatively, then you can do this but without so much of a risk of over-energizing tissues in the middle of the beam.
Ari: You can get it from purple LEDs because the energy, it’s spreading out. You can get some overlap of these areas, as I understand it, interference essentially of the light before the light reaches the skin and after, beneath the skin. As opposed to just one single source of that light, having multiple sources adjacent to each other creates, I don’t know if you’d sort of say it’s a different effect, but it seems, basically the light, it enhances the penetration of light to depth.
Dr. Cronshaw: Well, I’ve got a great slide on this later on. We’ll come back to that one. Hang on to that for, Ari, we’ll return to it, okay? Because I’ve got a nice slide to discuss this with.
Ari: Can I mention one more thing while we’re on this slide here?
Dr. Cronshaw: Yes.
The dose matters
Ari: I think this three-dimensional picture here is really important to understand because sometimes we see particularly when the biphasic dose response is discussed. I know that’s something that we’re going to touch much more upon in the multiphasic dose response. You see these numbers thrown out in many of these biphasic dose responses, like 1 to 5 joules per square centimeter is the stimulatory range, and then above 10 joules per square centimeter is the inhibitory range.
This is the dose that it’s basically the dose that’s delivered to the tissue where that would be the case. Sometimes people get confused as to the surface dose versus the dose that is being delivered to depth. Let’s say you’re trying to treat a knee joint, for example, and you’re trying to deliver light to, let’s say, a centimeter, 2 centimeters of depth, 3 centimeters of depth, as you outlined in this image here, the percentage of light of the surface dose that’s reaching those different depths. In order to deliver, let’s say, 5 joules per square centimeter to 2 or 3 centimeters of depth, you need a hell of a lot more at the surface to be able to reach that. Is that correct? How would you speak to this distinction?
Dr. Cronshaw: This is all great because you’re following very much the logical processes that I went through when I was studying this for my thesis. As I thought, “Okay, so we’ve got this target. We’ve got to get these photons down to 3 centimeters. This means we’re really going to have to deliver a lot of energy at the surface,” but then you’re going to end up overheating the surface tissues, and what’s going to happen?
I did a paper, which is all about photothermal aspects of photobiomodulation therapies, where I did some thermography under different conditions, using lasers, trying to define ways in which you could compensate for this. One of the ways is by optical scanning, so then you’re spreading it over a larger area and cumulatively starting to feed the photons into the target. Another concept is that with lasers, the beam is quite a tight one.
In the core of the area, then this is like a probe which is reaching into the tissue, and you can move it around. You’re delivering photons over a period of time, but you’re not sort of overheating the whole volume of the tissue. Because the scatter is less lateral, it is more coming down to a point. It’s an optical effect. When the light enters the target, it’s entering a tissue which has got a higher refractive index.
Then the light is bent towards the normal. The normal is the vertical. You come in like this, and it bends light like this, so you get forward transmission of the energy, which is one of the reasons lasers which are a coherent beam, where all the photons in the same phase and time have got to better capacity for reaching deeper into the tissues than an LED. There’s all sorts of finesse to this, but let’s carry the conversation on because we’re in danger of getting in too deep.
Then LED, the beam is divergent, and what that means is if you look at that image there, that’s actually a laser I’m using. When you’re far away, it’s a big spot. When you’re close up, it’s a very tight spot. Now, what we call the beam divergence angle, which is the size of the spot with an LED, can be huge, much bigger than with a laser. As soon as you’re any kind of distance away, then the size of the area you’re treating is very much greater.
That has a big impact on the symmetry because if you’re trying to apply a dose at the surface, as opposed to one which is an inch or 2 away, then the intensity of the source really falls off very sharply. When you’re 2 centimeters away, which is roughly just under an inch, then there’s about 4 times the area, whereas with laser, it’s a smaller beam divergence angle.
All these LEDs unless they’ve got a special lens screwed onto them and you can get LEDs that got that, you don’t tend to see them very often in PBM devices, then distance is a critical parameter. I did a paper looking at torch-type LED papers that came out recently. I looked at the instructions and people were saying, “Well, hold them 1 to 2 inches away,” and this is just not good because that completely screws up any hope of getting the dose right because the further away you are, then you markedly reduce the surface dose.
That will then have a big effect on how effective you’re going to be unless it’s a very superficial condition. Moving on. Which wavelength is it? Now, this is a hot topic. I think everybody’s got their favorite wavelengths. “Oh, I really like a 1064.” “No, no, no, I like using a red wavelength.” “No, no. You want to use an 810.” I did some measurements using a thing called the beam profilometer, which is like a camera. It just measures the amount of power that emerges when you shine it through tissues.
Those pictures on the left, on the top, that’s a 1064 nanometer. I’ve got 10 watts of power going through that. That’s a lot of power. It’s barely getting through into the tissues, into a 3-millimeter thickness of tissue. Whereas with shorter wavelengths, you can see there’s an appreciable volume of tissue, which is getting exposed to it. This concept of this optic window, which you can see in the middle slide there, where from about 600 through to about 1,000, it’s like a funnel like this.
The wavelength which has got the least scatter and the least absorption is around about 800 to 810 nanometers. If you want to go deep, that’s a good wavelength. Any of those wavelengths will do it. It’s just it might take you longer to deliver photons to depth using a shorter or a longer wavelength than it would be if you used an 800 to 810. There are other aspects related to your choice of wavelength because the amount of energy associated with the photon, which is the unit of light, is dependent on the color.
Really short wavelengths like blue wavelengths or ultraviolet wavelengths, there’s a lot of power there. It’s a short wavelength, so all the power is condensed into a very short cycle. This is where you can start to generate a lot of heat. There’s also a lot of energy there available for photochemical events, such as converting dehydrocholesterol into provitamin D in your skin with UVB.
Whereas with the longer wavelengths, there may not be enough energy there to produce these photochemical effects, but you can start to have other effects, which can include photothermal effects, photoacoustic effects, photomagnetic effects, photofluorescent effects, and cumulatively, you can then start to build up sufficient energy there to start to generate enough energy to drive forward the chemical change that you’re seeking.
The choice of wavelength, in part, is to do with, well, what is it you want to do with it? If you want to heat something up, then great, use a blue wavelength or an ultraviolet one. If you want to kill some pathogens, some staph aureus, or a herpetic lesion or something like that, then a blue wavelength is very hot. Very quickly, you’ll be able to deactivate that virus.
Whereas if you’re seeking to enter the tissues and penetrate deeply, but without heating things up, then something which has got really quite poor absorption and not so much scatter, like the 800 to 810 nanometer, this is a good choice. In an effort to make it easier to get the dosimetry right, then Praveen has done some work where he’s come up with this calibration scale, which he calls the Einstein dose, which you can love or leave.
The difference it makes in the red to near-infrared is around about 10% either side. It’s not a mega difference. If you’re doing things which are high-intensity laser therapies, then it makes a big difference because you might be doing that for quite a long time, and that extra 10% or minus 10%, that can then be a significant factor in dosimetry. I’m not saying that Praveen is wrong to come up with this concept; it’s just that for LED treatments, I don’t think you need to get too hung up about Einstein dose. This isn’t something which is really going to be terribly germane to the sort of stuff that you can achieve with an LED.
Wavelength and penetration depth
Ari: Dr. Cronshaw, one second before you go on. I want to point out one thing here: on depth. You see a lot of these on the previous slide. You see a lot of these types of images online. A quick Google search will bring up many similar images showing different wavelengths and how deeply they penetrate. What’s important to note here is the scale. You’re seeing wavelengths penetrate no more than a few millimeters.
They’re showing in the 600 to 700 nanometer range, which is red wavelengths. They’re showing roughly 2 millimeters of penetration depth. You’re not even making it to the hypodermis. You’re not making– This, basically, to most people would be interpreted as, “Oh, this light doesn’t even make it through the skin.” The same is true even in the 800 and the near-infrared, where, for example, you just gave an example of if you want to deliver light to tumor tissues, you’d use the, let’s say, 810 nanometers.
Based on this image, it’s only showing, let’s say, 3 to 4 millimeters of depth of penetration, still not even making it all the way through the layers of the skin. This is something we touched on previously, but I think there’s enormous amount of confusion around this whole topic of penetration depth of light because of images like this that suggest this light is not even making it through the skin and yet you can do that simple at-home experiment that kids do in a closet with a flashlight shining light through your hand.
You can see. Yes, there you go. You can see it clearly penetrating all the way through the skin on one side through the entire hand and out the skin on the other side. We have studies showing 50 millimeters, 75, 90, or even in some cases, up to 100 [inaudible 01:02:50] which don’t penetrate as deeply as, let’s say, the 800s or something like 810, 830. I just find this really bizarre that you see so many images that imply only 2 or 5 millimeters of penetration depth when the reality is so different.
Dr. Cronshaw: Well, the issue is partly the sensitivity of the human eye when it comes to viewing visible wavelengths. Praveen says that the retina can detect something as low as one single photon, which I found is extraordinary, so the exceptional sensitivity of the human eye is such that you can detect really low levels of energy.
When you’re looking at something like this, you may think, “Oh, that’s it. There is no light getting beyond about 2.5, 3 millimeters with these red wavelengths.” That’s a threshold, which is around about 37% because, by convention, below that level, it’s regarded as being the convention depth for penetration. Whereas [crosstalk]
Ari: Referencing the 1 over E discussion we had previously.
Dr. Cronshaw: That’s right. This is where the energy carries on because you can detect photons visually in the visible spectrum like that red image down to the micro watt range, which is a millionth of watts, it’s 10 to the -6 watts. It can appear that the whole thing is just illuminated like a light bulb, and the amount of energy you’re actually delivering at a distance is very small, but you can still see it, so the photons just keep going.
There will be tiny amounts of energy way beyond anything that this image is showing. This is where when you have high-intensity devices, like high-output devices at the surface, that 37% becomes really significant and because that 37% might be well into the therapeutic range and beyond for tissues far beyond that cutoff point in which, by convention, you’ve reached the limit of how deep that that particular light wavelength can go.
Let’s keep going because we’ve got a journey ahead of us. I’ve tried to sum it up. This is something I look at, and I understand it, but hey, I’m sorry it’s complicated. Basically, you’ve got all the different colors on the left from the shorter wavelengths, which are high-energy, through to the longer wavelengths, which are lower-energy. Then I’m looking at the dose, which is the X-axis, where you’re stepping up the dose.
Then I’ve got the different effects I’m trying to achieve, where you’re looking at stimulation as opposed to inhibition because I would argue that, as opposed to it being an all non-response, you’ve got a stimulatory zone. You’ve got an inhibitory zone associated with analgesia, and then you’re into the area where there’s a hazard, you can start to get tissue damage. The point of this shows that the shorter the wavelength, the smaller the dose before you start to get over to adverse effects.
If you use something which has got a very short wavelength, ultraviolet light, then it doesn’t take long, and you start to damage tissues. Whereas if you’re using a much longer wavelength, it can be a much higher dose, and you’ll still be in the stimulatory zone and it has to be an even higher dose again before you get an inhibitory zone. This is where you can start to understand the merits and the disadvantages and advantages of different wavelengths.
I think it’s less to do with a specific photon being the magic bullet that pushes the switch. It’s more to do with the transfer of energy associated with that photon to the cellular target, which can produce a variety of effects depending on the accumulated energy of the photon. That’s quite a complex statement, and we’ll revise that when we go back into this. The point is really that each of these different colours can have different effects, but in part, it relates to the dosimetry that you apply.
People say, “Oh, don’t use blue wavelengths. That’s going to be damaging to your skin. It’ll age your skin,” but it depends on the dose, and a very low dose is actually stimulatory. There is this inverse response where the shorter the wavelength, the more intense the source. Then if you start to think about this sort of graphic here, where you’re trying to work out whether you’re trying to be in the low-end stimulatory zone or the inhibitory zone, certainly you want to avoid the damage zone.
The shorter the wavelength, then the more the hazards and the smaller the dose you need to administer. It’s not an absolute that some of these wavelengths, unless they’re very short wavelengths like ultraviolet, will inevitably lead to tissue damage.
Ari: Are you trying to make the case for use of screens and computers, blue light emission from them as being anti-aging for the skin?
Dr. Cronshaw: No, absolutely not. No way. No, no, no. In fact, they can be things which can start to really screw up your circadian cycle. Also, cumulatively, there is even concern that they may progressively contribute towards retinal issues. This is an area of continued research. At the moment, there’s no consensus on this, but there is concern that some of these blue wavelengths may represent a biohazard.
No, I’m certainly not gung-ho about using blue wavelengths near my eyes. I think if you’re using blue wavelengths, even if it’s a blue wavelength LED, I suggest that you put some sunglasses on just to protect your eyes. Because there are examples in literature of people, children, who’ve used blue LED laser pointers and things and permanently damaged their retina. That’s [unintelligible 01:08:55]
Ari: There are some LED-based PBM products that are now putting blue light in some of these devices.
Dr. Cronshaw: Oh, absolutely. That can be something which you could actually maybe benefit from if you’ve got an understanding of what it is that the blue light is actually doing because each of these wavelengths has got certain attributes which can help you. Blue light is something which is the best wavelength of all for generating nitric oxide in your skin. Nitric oxide is a vasodilator. That’ll help enrich the blood supply in the deeper tissues.
Those blue wavelengths are very good at deactivating pathogens because they’ve got enough energy there to be absorbed by the protein of the virus and the fungus and the bacteria. It can switch off that pathogen. For the treatment, so it saves some skin disorders like acne and things. Dermatologists use shorter wavelengths. They use ultraviolet or blue wavelengths specifically for that reason.
There are advantages and disadvantages, but the issue is you have to understand what it is that you’re doing. As opposed to just willy-nilly pointing all the mixed wavelengths, there is a selection process when you understand what these different wavelengths can do, which you can then start to select, “Which effects am I trying to achieve?”
Ari: Yes, I think most of what’s going on right now in some of these devices is in the willy-nilly category, squarely in the willy-nilly category rather than is being done in a very targeted and precise way for a specific purpose. To be honest with you, I think most of it is just marketing gimmicks to say, “Our device has X number of wavelengths more than such-and-such other device.”
Dr. Cronshaw: Yes, well, to be fair, there is the potential with something which could be conditioned, prescribed to a patient for some of these other wavelengths. For instance, blue wavelengths used together with curcumin, which is basically a tumric extract, that’s a photosensitizer, and the blue [crosstalk]
Ari: I’ve seen it used in PDT, photodynamic therapy.
Dr. Cronshaw: Yes, that’s right. That’s photodynamic therapy. If you’ve got someone who’s got a persistent infection with a multi-drug resistant bug, then that could be really useful, and you could be prescribed an LED of that, right? I wouldn’t say these things are useless, but the way that they’re marketed at the moment, I quite agree with you.
Ari: Yes, to be clear, I’m not talking about specific devices used in a specific medical context. I’m talking about the devices for the general consumer just with some vague notion that sort of more wavelengths is better and having some blue LEDs interspersed in there is better than not having them.
Dr. Cronshaw: Absolutely. When I’m starting to think about my clinical dentistry, I’m thinking, “Well, am I trying to stimulate things, or am I trying to inhibit them? Am I trying to do both?” All right? For some things, definitely, I just want to keep the dosimetry lower. Then I’m stimulating fibroblasts and osteoblasts and all the other tissues associated with the healing of the things that I’m doing.
On high dosimetry, I may be trying to inhibit pain, or I may be trying to do both, which is confusing. Hang on to that thought because you can get two for one effect. It’s a bit like I was talking about earlier in dealing with when I’m doing surgery. I’ll just cut through these videos. When you’re thinking about a 3D effect, you’re looking at a volumetric system, right? Now, this is one of the things that I really seriously critique in my thesis, is this concept of 2D planar dosimetry, right?
So much of what’s been done in the literature is based on tissue culture and small animal studies, right? Out of that have been given grand pronouncements in regards to dosimetry and harmful effects and beneficial effects and what have you. Whereas in a large mammal, like a person, you’ve got some volume to consider. Your target might be at a distance away from the surface.
In order to reach that, you’ve got to deliver a higher dose, which might be an inhibitory dose. You need to do that safely within the parameters that we have devised, adopting strategies in order to help avoid overheating superficial tissues. Now, that may coincide with where you’ve got a wound where, at the surface, it’s painful, and there may be some pathogens, and that higher dose can both inhibit pain as well as deactivate the pathogens.
Whereas at depth, you’re stimulating the wound base, and you start to get healing repair. When you start to think of it in three dimensions, this whole concept of doses joules per square centimetre starts to get a bit twisted because you’re thinking about delivery of the dose at depth, but then there’s layers, and you can have multiple effects happening simultaneously. This is where you can start to be quite creative in terms of your application, particularly if you’ve got a superficial problem.
When you’re thinking about pain relief, well, you can get pain relief at really low dosimetry, or you can get pain relief at really high dosimetry. I then ask myself, “Well, how does this thing work?” It’s what I regard as a Janus effect. Of course, Janus is the god of the two faces. On the lower end of it, the effect of low dosimetry is to increase the resistance of the cell to stress, as well as promoting good blood flow there because you get a lot of good blood flow there because you get some vasodilatation, and you’re getting an enriched blood supply.
The cells are in an oxidative cycle of metabolism, so that basically means, as opposed to having an acidic cell, it’s producing lots and lots of ATP. Take this for a figure that I picked out of literature, Ari. I was reading from a really great paper when I was in the gym this morning, the way that you do, I was reading a scientific paper, aren’t I, Sam? It was from a lovely Italian researcher at Cambridge University, and she came up with something related to the generation of ATP.
She said, “Each day, the average adult produces 70 kilograms of ATP.” 70 kilograms? I nearly fell off my exercise bike when I read that. I thought, “That’s phenomenal. What a huge amount of product it’s producing.” It just goes to show how busy those mitochondria are in producing energy. When they’re in an oxidative cycle of metabolism, it’s producing maybe 30 to 32 molecules of ATP per glucose, whereas if it’s poorly perfused and you’ve got an acidic cycle of anaerobic metabolism, you’re only going to get maybe two to four molecules of ATP, which is a step order of difference.
There’s lots of ATP there. You’ve got a really vigorous active cell, which is going to be hugely active in producing matrix. The immune system is going to be really vigilant. It’s really going to go for those pathogens. A lot of good things can happen on low dosimetry. Now, associated with that can be a reduction of some of the mediators which because pain because pain is associated with inflammation.
If you’re doing something which is an anti-inflammatory, and low dosimetry can be anti-inflammatory, you’re going to have specific activation of anti-inflammatory gene transcription sequences. The cell moves away from this acute inflammation and towards a resolution of matrix production cycle. Then that’s associated with a reduction in pain because the mediators of pain, like histamine, like bradykinin, like calcitonin gene-related peptide, like substance P, along with a whole bunch of other stuff which I could mention, these are all being suppressed.
COX-2, the site production for prostaglandin E2, is suppressed. You’re getting less of these pro-inflammatory factors. Low dosimetry, this can be helpful for pain relief. In higher dosimetry, you’re starting to produce, basically, a nerve block. You can put the cell, basically, to sleep, so then the axon, the nerve fiber, shuts down activity, the mitochondria basically are turned off. There’s no ATP there.
When it comes to trying to activate that axon so that you get a wave of depolarization, you get this transmission of the pain signal along the fiber, it’s blocked. Higher dosimetry, you can produce a selective nerve block, which is terrific, particularly in some chronic pain conditions, and that can be lasting. Plus, it also stimulates a protective sequence, which is what we refer to as hormesis. These hormetic effects don’t just protect the cell at the time from the stressor, because the cell’s being really stressed by this higher intensity PBM irradiation.
It also encourages production of materials like heat shock proteins, as well as some stuff called ATF4, as well as activating various gene sequences, which then, should that event happen again, will then increase the resistance of the cell to the shock. It becomes more robust. It’s preconditioning the cell. Preconditioning can work either at low dosimetry or higher dosimetry, but preconditioning is another benefit of an inhibitory dose because the stress event, the stressor, is triggering the production of things, which just help the cell survive, should this occasion happen in future.
When you’re looking at pain relief, it can be both ends of the spectrum. For my money, if I’m wanting to block pain, I’m going to use a laser. Every time, I use a laser. It’s a more intense source. I can more easily deliver photons to the depth of the nerve, whereas it’ll take longer and may be associated with an extended treatment time and maybe a less beneficial effect than those associated with some of the wavelengths of lasers I’m using.
That’s not to say you can’t get pain relief with an LED. For pain relief, lasers, I think, have got a great place, if you’ve got access to them. If you haven’t, you can certainly use an LED, it’s just then you may take a lot longer to start to achieve the sort of results that you’re wanting, and it may be a less marked event. I can get a patient who’s in pain, like the guy in the picture. I can fire a laser at it, and I can switch that pain off inside of two to three minutes, whereas with an LED, you can work out a way for a while with an LED.
Eventually, you’ll get some basal dilatation. You’ll get some benefits that will happen. It just takes an awful lot longer, and it’s a less marked event. The big question there is, how long will that effect benefit the patient? Is it just a temporary effect, or is it going to be more lasting? This is one of the big questions associated with analgesia, which I know people like Juanita Anders and various other groups in Australia, for instance, are investigating. We’re still learning. Okay, so let’s talk about preconditioning. One of the interests I have is in cancer care.
Now, cancer is a plague. We all know someone who’s had cancer. 50% of us, one time or another, get cancer, which is a seriously frightening figure, isn’t it? We all witness friends and partners and relatives who go through cancer treatments, which can include chemotherapy and radiotherapy, which can have some really unfortunate side effects, because along the way of killing the cancer, it can disrupt healing, and you can end up with some painful conditions like oral mucositis, or a radiation-induced inflammation of the skin called radiodermatitis.
You can have effects on the nervous system where you can get lasting nerve damage called neuropathy and what have you. There’s been a lot of interest from the cancer community in how we can best use PBM in order to help these patients both to heal as well as to prevent it. I did a paper on this with colleagues investigating this because this, for me, was an interesting model for dosimetry.
What I found was that the most effective intervention was to prevent it in the first place. On the day the patients were going in for their chemo, their radiotherapy, if they pre-treated themselves first, then the incidence and the severity of things like that horrible picture there where this patient’s got a really bad ulceration associated with chemo, it’s not quite eliminated, but more or less, it’s very low-grade. That was a very strong event.
It was a statistically very powerfully supported outcome of my research. Whereas if you’ve got somebody who’s in pain, like the person in the picture, if you step up the dose, then you can then start to inhibit pain, but that’s not going to necessarily promote healing and repair. It’ll inhibit pain. Then you might need to inhibit the pain, but then step the dose down later on after you’ve done the treatment to start to get onto the sort of level of dosimetry associated with healing.
I came up with this little algorithm, and you could apply that to anything. It’s not just for cancer care. The philosophy of care there is prevention is really the best thing to do. If you’ve got pain, then do a higher dose. For something which is a surface condition like this, 10 to 15 joules per square centimetre is a good dose to go for or higher. For healing, when you’re no longer in pain and you want it to stimulate healing repair, step the dose down to about 2 to 5 joules per square centimetre, and then you’re going to get good wound resolution.
Now, I don’t see any reason why people can’t treat themselves at home because the availability of PBM in cancer care is really poor at the minute. There are very few specialist centres that have got that kind of equipment and access to equipment. People that are enduring these sort of conditions where I can’t see no sound reason why they shouldn’t be self-treating, and this is the sort of thing where you could really use these little LED torches to good effect because you’re not going to stimulate the cancer.
You’re not going to cause any damage, and one thing you can do is maybe help yourself. With things like this, this can be very, very deeply unpleasant. It can be extremely painful. The studies on this condition, oral mucositis, show one of the things that people are most frightened of is oral mucositis because of the discomfort that it causes them. Enough said. When you’re thinking about using it for things like cancer care, yes, this is more specialist.
Sure, it’d be good to be able to have this under the direction of someone who’s really au fait with this as a subject. There are distinct benefits. I think this is something very much for the future because this is where maybe a good dental therapist inside of a dental practice in general dental practice can do it. The pictures on the top on the right are of a patient who came in to see her hygienist in London, who contacted me and said, “Hey, Mark, what do I do to help this patient with their oral mucositis? She’s having chemotherapy.”
I told her. I gave her that little treatment wheel, and she did it, and she can see the wound resolution going through that cycle. Subsequently, she treated them on a regular basis before they had the chemotherapy using her equipment. The incidence and severity in the later rounds of chemotherapy was virtually zero. I think this is something which is quite exciting, from my professional point of view.
In terms of inducting people more generally, this is definitely something for the future. This is where self-help really can help because it’s one of those areas where it’s such a common problem. I actually did a webinar on it. If you want to watch a webinar on it, there’s a link. I spent an hour talking about cancer and cancer care. We showed you this picture earlier of this child. It’s got a lot of inflammation. There’s pain. There’s surface infection.
I recommended that he use a fairly high dose at the surface, looking at 50 joules per square centimetre at the surface in order to suppress the inflammation and the pain. Because of the attenuation, and this is the loss of energy through to the wound bed, this was also having this additional effect of stimulation, and that was done every day over a period of about six days. You can see the progression of the wound resolution.
For burns, it works great. This is a child who had an incident with a dog. The dog injured them. You can see that the local hospital had sutured it. There was a lot of swelling and inflammation associated with it. Understandably, the mother was very upset because this is her gorgeous three-year-old, who’s gotten this awful injury. This is another student of mine in Belgium, Charlotte, who contacted me saying, “What do I do?” It was the same process.
Over a period of about a month, she was doing very regular treatments, again, starting off in high dosimetry, and then later on, at about 10 days, when the acute inflammation subsided, we then very much reduced the dose in order then to stimulate healing and repair. You can see the onward progress over 20 days. This is what’s coming to some very nice wound resolution in that case. It works on nerves, too.
If you’ve got people who’ve got nerve damage, this can be helpful, but this is more for sort of lasers and sort of stuff that we dentists would do. Just be aware that there are people who’ve been left permanently numb following surgery to, say, have a dental implant and being told, “Sorry, it’ll never come back again.” That’s not true. We’ve got cases now where we’re actually encouraging and regenerating nerves that have been severed years before.
Lasers vs LED
I think this is a very exciting application, very much under research, but we’ve got some clinical cases that indicate it can work. Last summer, I was at the WALT meeting, the World Association of Photobiomodulation meeting in London. There I am with my friends: Steven Parker, who’s my co-director of the training academy I run and quite an eminent professor; with Juanita Anders, who’s in the Armed Forces University in the States, who’s got a great interest in the treatment of injuries associated with armed forces personnel; and myself.
We were listening to an awful lot of presentations about lasers and LEDs and all the rest of it. The question that we posed was, well, what’s the difference between laser and LED? Can LEDs work, and can these be effective? Because, as you know, the majority of the research that’s been done has been about lasers rather than LEDs. There’s huge literature about lasers and their benefits, but unfortunately, these aren’t accessible to the public except for really low-dose ones, which are not much use, whereas LEDs are optically a lot safer.
There’s all sorts of pros and cons that we have to consider in regards to the ability of different sources to be able to deliver energy to depth, as well as the safety factors. Of course, lasers are very much more expensive than LEDs. LEDs are relatively inexpensive, and maybe these are things that are good for patients to self-deliver. There are all sorts of devices. The guy in the picture there is actually my brother-in-law in France.
He’s self-administering some PBM because he’s tired, and he’s wanting to improve his cerebral performance, bless him. As he gets a lot of headaches [unintelligible 01:30:14] well, he might.
Ari: It looks like while he’s on an important business call there.
Dr. Cronshaw: Oh, he’s too warm. Oh, he’s a great character.
Ari: Maybe I could try that. I have one of those devices, the same device right next to me. Maybe I’ll try it.
Dr. Cronshaw: We both. Then there are little torchlight devices as well, which are less expensive, but they have got a much smaller footprint, and they’re of quite poor build quality but do possibly offer some potential. I did a study on this, looking to see what they could do. My conclusion was that, with LEDs, it really is not going to get deep into the tissues because although you can see these visible effects, you’re down to microwatts.
You’re down to some tens or single-figure millionths of a watt at a distance. Whereas with a laser, because it’s a more focused beam and because of this nature of how the energy is behaving as it enters the tissues, you end up with images like that, where it’s almost like little stiletto needles with a small probe, which should be reaching very deep into the tissue, but without much lateral scatter.
Whereas with the LEDs, particularly if they’re overlapping, which is what you were referring to earlier, you can then start to produce quite an even mass of energy. These overlapping beams can then produce a fairly dense layer of photons at the dermal-epidermal boundary. You can get quite a rich layer of photons there, which would appear if you’ve got a large enough LED area to produce some therapeutic effects.
Whereas if you’ve got a really big single point laser with a powerful, professional, high-energy PBM device, then you’ve got a tool where you can really start to reach very deeply into the tissues, to reach that damaged tendon, what have you, without too much trouble, with a more focused response.
Ari: Hold on one second, Dr. Cronshaw. I want to ask you. On this slide, this seems to not match up well with, for example, Tom Kerber’s penetration research, where I think two key points. Number one, the way that you’re illustrating the laser’s light as penetrating the tissue, it’s remaining very focused and even actually getting narrower, whereas [inaudible 01:32:42] was that it scatters and diffuses once in the tissue.
It doesn’t necessarily retain those characteristics. This also is relevant to a point you brought up from– I forget the name of the researcher, but shining it through a piece of steak where it retained its characteristics, but from at least the way Tom Kerber has done penetration depth studies, he’s even shined a laser at it to see the light diffusing. That’s one point I want to flag here. The second one is he’s also compared lasers and LEDs of similar parameters, and I’ve seen a number of different tissue samples where he’s done these tests, different wavelengths, and so on. It shows very similar depth of penetration with laser and LED at similar parameters. I’m curious what your thoughts on why is there a discrepancy, and maybe this also relates to how you designed this particular study.
Dr. Cronshaw: I’ve looked at some figures from Tom’s study where he took some chicken breast and he irradiated it with some LEDs. He was taking measurements, looking at the amount of energy that was penetrating down to five centimetres and then down to seven and a half centimetres using his LED. He was detecting the presence of photons from his red wavelength laser. When you actually looked at the energy associated with that, he was looking at around about 0.4 to 0.8 milliwatts per square centimetre. Now, that means then to deliver four joules, that would take you just short of two and a half to three hours to get it up to the level where you might be producing a therapeutic effect.
Yes, you can deliver photons to depth using an LED, but the energy level that you’re achieving at depth is going to be really low, and that means that then your exposure time in order to achieve the therapeutic dose that you may need to get to to trigger the event that you’re seeking through PBM may take you an inordinately long time. Whereas with a laser it’s a much more intense source. Because of the optic properties of the laser, the beam is quite tight. It doesn’t tend to scatter to the same degree because the wavelength’s all within a very narrow spectral range, within a nanometre, and so all the photons are in the same phase and time, and they enter the tissues, and when they do scatter, they scatter forwards.
You start to get these needle-like appearances because those images at the bottom, they’re of some– using a device which is called a beam profilometer, which is a camera, and then there’s a sample tissue, and down here I’m either using an LED or I’m using a laser. You can see the different patterns of energy distribution that’s coming through the other side, whereas with a laser with a small diameter probe, particularly if it’s a cluster, and there I’ve got a cluster of 200 milliwatt devices, you end up almost like it’s needles going into the tissues. Unlike the LED where it’s more diffused, whereas with the big source there’s more power in the middle of the beam. Then you’re starting to deal with a bigger volume of tissues. It all depends on the parametry and what it is actually you’re looking at because it’s like comparing apples and bananas. I wouldn’t say you can make a banana look like an apple, but Tom will give it a good go. Bless him.
Irradiance
Ari: Let me ask you one more point that speaks to something you were just alluding to a moment ago as far as the parametry and the amount of energy at a given depth. This relates to a controversy around irradiance. What is the role of irradiance in penetration depth. An important distinction here and point of confusion around the degree to which higher irradiance leads to “higher penetration depth” as defined by the maximal depth of tissue where we could detect any photons versus, I don’t know if there’s a proper term for this, but let’s say effective penetration depth or something along those lines, where we might define it by the amount of energy present at a given depth.
As distinct [inaudible 01:37:29] makeup numbers, let’s say the maximal depth that light could reach is five centimeters or eight centimeters, that 600 meter light source could reach. We could say, well, it didn’t cause any photons to be detectable below that eight centimeters of depth. Therefore, irradiance has no real relationship to penetration depth. It failed to increase maximal penetration depth. With a 100 versus 300 milliwatt per square centimeter device, there was no meaningful difference in that maximal penetration depth.
If you compared a difference in irradiance to, let’s say, something below that maximal depth, let’s say three centimeters, two centimeters, three centimeters of depth, there’d be a large difference in the amount of energy present at, let’s say, two or three centimeters of depth with a low versus a high irradiance device. You follow the distinction I’m presenting here?
Dr. Cronshaw: I do. When it comes to irradiance, yes, this is something which causes a lot of confusion. Irradiance is certainly related in regards to optical penetration to wavelength. Also it’s related to the size of the optic spot, and then there’s also the issue of what we call the spectrum beam profile, which is the energy distribution across that spot. If you look at those images in the bottom, they’re Gaussian beams, where there’s not an even energy distribution, whereas with your LEDs because it’s got this big wide beam divergence angle, it doesn’t come to that sharp spike in the middle. That’s going to affect the delivery of energy into deep layers, because there’s a lot more energy in that middle third of the beam.
Then because of this 1/e effect, you’re then delivering more energy to depth. Beyond about a centimeter, that doesn’t really start to make an awful lot of difference because, for instance, some people buy devices which are gated. They switch them on and off, and they can have a period where the arm, which might only be less than 1% of the total time using the device, but when it’s on you might have 300 watts that’s being delivered via that device.
For a fraction of a second, which can be down to millions of a second with some of these devices, or tens of thousands of a second, you suddenly got 300 watts there, and then it’s gone. The argument is well, this is going to drive photons deeper into the tissue. Some on-the-bench studies have been done, not by me, by another group using a similar model to myself. What they found was that comparing the same average power but at different peak powers, beyond about a centimeter, it made absolutely no difference whatsoever to the optic penetration.
You can extrapolate from that to this cut off with your irradiance where the benefits of increasing the irradiance eventually is going to be limited by the capacity of the photon because of its physical properties in relation to the tissues, because of scattering and absorption.
Ari: To the wavelength.
Dr. Cronshaw: Absolutely, which is also-
Ari: The relationship of the wavelength and the optical properties of the tissues themselves.
Dr. Cronshaw: The whole thing is limited. When you start to think about delivering energy to considerable depth, this still poses a challenge, which is why they’ve been experimenting using catheters with a laser or an LED built into them in order to deliver it to close proximity, say spinal nerves and things like this, in an effort to help overcome this problem. Then, as we’ll discuss later on, there are other aspects related to PBM, which are perhaps very much under-discussed in the literature because when you start to think about the mechanisms, there’s this incredible focus on photochemical reactions happening inside of mitochondria at a cellular level, but there’s a whole deal more going on there. It’s what I refer to as bioenergetics entrainment. This is something that we’ll progress to discuss too, if you wish, later in this presentation.
Hopefully that’s answered your question on irradiance. Is that okay, Ari? Are you happy about that?
Ari: Can you just more directly speak to the distinction that I was bringing up? The degree to which irradiance affects maximal penetration depth versus the effective dose of energy delivered at a depth of tissue that is more superficial than that maximal depth?
Dr. Cronshaw: Yes. Well, the issue with irradiance is when you’ve got a more intense source, which is what irradiance is, you’re packing more photons into the area, so it’s a higher number of watts per square centimetre, then the effect on the tissues is going to change because beyond a certain level, you’ll be changing the tissues quite profoundly. You can be heating things up, for instance. There’s a cutoff, there’s a limit to what you might be able to achieve by stepping up the irradiance because you can then start to see some photothermal effects, which can start to change the characteristics of the tissues.
Now, biological tissues, when they’re dealing with a living system, are very sensitive to temperature and a little small rise. This is all good, it stimulates enzymic activity. Above that, then, you see the cell go to sleep. It’s like a protective stasis. Beyond that then, you can start to see progressive signs of tissue damage. In response, the biology, because temperature is very strictly controlled by the cell, is intended to protect the viability of the cell and the tissue.
Initially, in response to a rise in temperature, you see vasodilatation. Blood vessels dilate and there’s a heat sink there as the bloodstream tries to diffuse away the heat from the surface. When it gets above 46 degrees centigrade, as opposed to seeing vasodilatation, you see vasoconstriction. The blood vessels actually close down. This confines that heat. This is intended, I guess, if you’re looking at it from this point of view, to reduce the collateral tissue damage and to confine it to a smaller area.
Then you’re starting to get into an area where you’re going to get an ascending level of damage because progressively, because the energy has been confined into that area, then you’re going to get more and more and more damage to the point where you’re going to get coagulation. Then you start to see all sorts of adverse effects. When you’re looking at irradiance, you have to think about, okay, if you’ve got more power per square centimeter, this is increasing the potential for that concentration of photons for more photons to be delivered to depth. Then in the superficial layers, you could then start to over-energize tissues and start to produce some harmful effects.
Ari: This relates to some of the irradiance parameters we previously discussed in relationship to skin overheating.
Dr. Cronshaw: Again, closely related to wavelengths and then beyond a certain level– Here you’re looking at most at two centimeters, but probably one to two centimeters. It makes very little if any difference because it’s more to do with the physics and the optical properties of those particular wavelengths.
Ari: What makes little difference?
Dr. Cronshaw: Beyond a certain depth, because of the very high irradiance you’re applying at surface, then you’re starting to change the optical characteristics of the tissue and that will then affect it. The research shows that if you heat things up, this can then affect the refractive index of the tissues. If you heat them up beyond a certain point, then you’ll be increasing both the scattering as well as the absorption coefficient. Then more energy will be absorbed in superficial layers. Then you’re starting to get more damage up to the point where you see signs of hypothermia and dermatitis and all the bad stuff that you’re trying to avoid.
Ari: Dr. Cronshaw, I think you’re introducing a lot of layers of complexity, and I’m trying to present just a more simplistic scenario that I want you to speak to the role of irradiance in. That is, let’s say I’m trying to effect change in 2 centimeters of depth with an 810 nanometer wavelength. What is the role of irradiance in influencing the ability to deliver an effect to that 2 cemtimeters of depth?
Dr. Cronshaw: If you’ve got more power, then because of this 1/e effect, there are more photons at a level beyond which you normally, by convention, think it was less than that 7% level. Up to a point, you will then be better able to deliver the energy to depth. This then comes into the concept of total joules as opposed to irradiance because the total amount of energy you’re delivering, that too can start to have an effect. Is that to do with penetration or is that more of a systemic effect? That’s a different issue.
To answer the question, really, when it comes to irradiance, the cut off with an 810 really is round about 500 milliwatts per square centimeter. Beyond that, then there is an ascending risk of starting to produce some photothermal effects. That’s not to say you can’t have a large applicator, say one of these four centimeter diameter laser devices used by the physiotherapy community, where you might be putting as much as six and a half watt into that, and we’ll call that beam. You then have to optically scan in order to avoid over energizing the mid third of the beam.
Even then, at roundabouts of two centimeters at depth, the ability to start to drive those photons really deep is reduced. It’s not an absolute. Like Tom Kirby showed with his little red LEDs, you’ll still have photons getting very deep. It’s just that the number of photons that’s getting through is going to be remarkably small. Then it takes a very long time to get up to the dissymmetry that you need to produce the changes that some traditional PBM therapies recommend.
Ari: That’s where irradiance factors into this. You’ve mentioned the upper end of this, which we’ve touched on a number of times and we’ve discussed at depth in a previous conversation, that 500 milliwatt cutoff where you start to get so high in irradiance that you overheat the tissues. On the other end, on the low end, let’s say there are a lot of devices like this on the market, these flexible, pad style devices, and many of these devices are 7, 10, maybe 15 or 20 milliwatts per square centimeter. The highest I’ve seen is maybe close to 30 milliwatts per square centimeter in this style of device. With those kinds of irradiances, how does that factor into this picture of, let’s say, trying to affect tissue at two centimeters of depth in my knee joint?
Dr. Cronshaw: I hate to depress you, but you’re probably only going to be delivering something like 0.2% of surface energy per centimeter depth. That being the case, if you’ve got a really low power device, then the number of milliwatts, it’ll be not milliwatts, it’ll be micro watts, it’ll be millions of watts. That then means that the treatment time is very extended in order to produce it. Now when it comes to things like wearables, perhaps that’s the way of going about it, or repeated exposure over a number of sessions during the day where cumulatively you may be able to achieve that threshold. It is going to take hours-
Ari: Meaning if the irradiance is so low, basically you have to compensate by massively expanding the duration of treatment. With that low of irradiance device, you’re saying essentially you would have to make it into a wearable, but you’ll have to wear it for hours, something along those lines. Is that what you’re saying?
Dr. Cronshaw: There’s a study by Shen, for instance, who was looking at tissue culture using some fiber optic impregnated materials. He was showing activation of fibroblasts to produce collagen when he had an exposure time just short of six hours. That was around about 0.25 of a milliwatt, so very low levels of power. Yet for hours and hours and hours and hours, eventually he got there. That’s in tissue culture. When you start looking at the human body and its complexities, it would take a long time to get to those levels.
Then you have to think about, well, maybe there are other effects that are happening here because I’m not saying to you things like that can’t help. It’s just it might not be working in the pathway that you think. Okay. This is where I think there’s been a paradigm shift which is emerging in the PBM community where we’re starting to think about different processes operating simultaneously to produce it. This is this concept of bioenergetics and what I call entrainment. This is where we’re introducing energy into an energized biological system, which is then having a ripple effect on the organism, not just on the immediate target.
Let’s keep going, Ari, because this is great conversation. I looked at these things and some of them were better than others. They certainly had potential. They’re very crude devices. They’re very basic. They’re really inexpensive. They’re widely on sale. Do they do what they say in the tin? The consumer feedback was really positive on them. How much of that was a photothermal effect and how much of it was PBM? I’ve got my doubts. These are the devices which we’ve got some going out to undergo some clinical trials. Once we’ve defined some benefits, these may be the things which in time, with some added bells and whistles, little minor tweaks to the design, could be something which might even be useful.
At this stage, there’s no harm in using them. You’re certainly not going to do any harm, apart from maybe to your back balance, but it may help you. On the other hand, it may not. It certainly doesn’t do the great things. These things are advertisers curing everything. It’s only a little device, little LED and less. People using them. If they’re really assiduous, it can produce some clinical benefits. As I say, how much of that’s photothermal and how much that is PBM? I’ve got my doubts.
Can things like LEDs work? There’s a lot of flat panel systems out there. This is from a medical device made by a company in Switzerland called the ATP38, which has been adopted by some world-leading oncologists in France. They’re using this to treat conditions like neuropathy, which is nerve damage, associated with chemotherapy, as well as in radiodermatitis and stuff. I listened to presentations on this at WALT in London. The irradiance that they’re using there was 20 milliwatts per square centimeter using a near-infrared and 840 nanometer LED. They reckon that at about 2 millimeters through the dermis, they’re around about at a milliwatt per square centimeter. I thought, well, that’s just nothing.
In order to get it up to 5 joules, it’s going to take you a long time. That’s an extended treatment time. Yet, they’ve got quite large areas, and they seem to be producing some interesting effects. This is a guy who’s got some radiodermatitis. He’s got a burn basically generated by the radiotherapy that’s been applied to treat his throat cancer that’s being treated using this exact device. It’s produced a great effect. It’s produced really good resolution of the inflammation and very good wound healing in the hands of Professor [unintelligible 01:55:30], who’s a world-leading authority on this.
Then I had to start to rethink a lot of the things that I thought I knew because up to this point, I really was a very strong fan of laser, laser, laser. If you want to reach depth, use a laser. I thought, well, these things clearly can work. How is that possible? I went right back to basics. I thought, well, what is actually happening when you put a photon into tissue? There’s a variety of effects that can occur. The emphasis in literature is on this photochemical effect where unit four of the electron transport chain is booting the cells to produce more ATP. Then there are also some photothermal effects, even though Praveen would probably decry that, but there are undoubtedly some low-level photothermal effects. Maybe the higher level photothermal effects can be beneficial.
Photoelectric and photofluorescent effect
There’s also a photoelectric effect. Einstein got his Nobel Prize not for the special theory of relativity. It was for basically the essence of solar PV. He was shining bright light onto aluminum and it was generating electricity. The light was stimulating electrical flow. In PVM, you are going to get some photoelectric effects because some of the things that you’re exposing are metals. When you expose those metals, you get a release of electrons and that can then be a catalyst.
You can get some photofluorescent effects where the energy is absorbed and then it’s re-emitted. This is something we definitely see in nature. You can see both fluorescence as well as phosphorescence. There are marine animals that use this as a type of signaling and there’s certain marine algae where at night you see this really weird greenish glow in the sea. As the waves break, you see little bright flashes. It’s extraordinary. This is a photofluorescent effect where the light during the day is being re-emitted as little packets of energy. Perhaps this is another pathway, as I’ll discuss later, which may be associated with PBM.
Then you can get some photomechanical effects where it creates like a shock wave. That shock wave then shakes open the iron gate. A little bit like when you clap your hands you can feel the vibration of the air and that can be transmitted through to the tissues. Then there’s some photomagnetic effects. This is where things which contain ferrous compounds, you can start to realign the dipoles and that can change the configuration of the enzyme. There are all these different pathways, all right, so rather than thinking simply of photochemistry and that photon-producing ATP at unit four, when you start to think about all this multiple effects and all the different constituents of the cells, then it’s a multi-planar thing.
Now in the skin you’ve got certain cell types which include keratinocytes and they produce the squames that form the keratin, which is the outer layer of your skin. There are also some little cells called melanocytes. The melanocytes are things which produce pigment when you’re exposed to light, which is melanin, but also they produce a whole load of other biologically very active things. In skin it’s been suggested this is almost like another brain because there is a neuroendocrine axis where by exposure of skin you can start to produce some quite important increases in production of neurotransmitters like serotonin, noradrenaline, dopamine, as well as a whole bunch of very important hormones like growth hormone and adrenocorticotropic hormone and prolactin and things like this which can peak at some hours.
The skin isn’t just a sort of an inert wrapper around the tissues, the skin itself there’s production of all sorts of steroids. It’s the site where with UV you get to manufacture vitamin D. It’s quite a dynamic organism where there’s a correspondence between skin and the central nervous system in both directions. It’s not just got sensors to detect pressure and temperature and pain and things like this, it’s a two-way process. It’s reporting back to the CNS and the CNS is also responding to some of the products produced inside of skin. These things are all photo products. When you expose the skin to light, it can start to produce all these very important biologically active substances, and this is happening right at superficial layers of your skin.
Serotonin, this is something which affects mood. Anybody who’s suffered from depression, they’re given serotonin uptake inhibitors to elevate their CNS serotonin levels and a bright sunny day, you feel good. There’s a reason for this. Noradrenaline, this is the fear, fright and flight thing. It’s the thing that gives you the go-go-go, as it were. This is another neurotransmitter which just changes mood. As for dopamine, well, this is the thing which is associated with motivation and reward and addiction and things. These things are producing a systemic effect.
As for these hormones, each of these hormones again produces a systemic effect. This is where by irradiating the skin, maybe with a big flat panel or with a large LED, you may be doing a little bit more than you realize because it’s not just the tissue that you’re exposing, you may also then start to trigger off the generation of some appreciable levels of some quite powerful systemic agents which can affect your brain as well as your endocrine system. This is then producing distant effects because often illness isn’t something which is just associated with a specific area, it can be associated with systemic conditions. People who’ve got inflammation are more prone to Alzheimer’s and things like this.
There’s a question really about should you be targeting the particular area where there’s the problem or should you be treating the whole person? This is a concept which I think is quite useful, particularly in regards to LEDs because you have these LED-impregnated mats like yoga mats. Then you’ve got much more expensive LED pods where you can do full body irradiation using red and near-infrared wavelengths.
These can be producing some quite profound physiological effects which are recognized to be treating very unpleasant conditions like fibromyalgia, for instance. Even though in theory the photons that are reaching those deep levels of the muscle after 20-30 minutes inside the pod is really quite low, it is producing something which is clinically of benefit, and so maybe it’s through these systemic effects it’s being mediated in part. We don’t know.
Ari: Dr. Cronshaw, I think I’m pretty close to out of time here. It sounds like maybe we’ll have to continue the rest of this in another session.
Dr. Cronshaw: We’re about three minutes away from the end.
Ari: Are you? Okay, great. [crosstalk] I want to quickly mention, I don’t know if you saw the 2022 review on the serotonin deficit theory of depression and the idea that SSRIs work to combat depression based on increasing serotonin levels. Most of that has largely been debunked. What’s really interesting about it is that there was like 30 years of research based on this idea that serotonin is the thing that controls our happiness. I don’t know how many hundreds of billions of dollars invested into drug development all based on that and then 30 years later they’re like, “Actually, there’s no real evidence to show that it’s a serotonin deficit.”
I’m just saying this as a random point here, but there’s no question that serotonin does stuff in human physiology that it’s clearly doing– it clearly has major roles but just as an interesting aside, the serotonin hypothesis of depression has largely been debunked at this point.
Dr. Cronshaw: Well, the treatment of depression with PBM is one of the active areas of research, and so I would suggest that it is maybe being mediated through neurotransmitters. When it comes to SSRIs which are drugs which are intended to slow down the metabolism of serotonin and retain higher levels, these drugs I can well believe are working at a level equivalent maybe to a placebo, maybe to a 30% event effect.
Ari: Yes, there’s a lot of research. I’m forgetting the name of that researcher. There’s a well-known depression researcher who’s done a ton of research where they’ve compared the effects of SSRIs versus [inaudible 02:04:47]. Anyway, I can look, but go ahead. Sorry to interrupt.
Dr. Cronshaw: Just to conclude my thought, because there’s a lot more we can say about this, if you start to take a larger frame, look through the other end of the telescope and look at the whole person. If you’re thinking about introducing energy then the photon, it’s an electromagnetic field. We’re full of electromagnetic fields, all biomolecules have got an electromagnetic field. These can resonate, and if they resonate and they’re on the same resonance frequency they can vibrate together or they can amplify so you’re getting a more profound effect or they can even tune each other so that external source then can start to reset the physiology of the cell.
In terms of health and disease, in the disease state you may have misfunctioning sequences of enzymes and things which you can then reset. A little bit like if you have a coronary and then they come along with the pads and they put an electric shock across your chest and then resets the firing electrical signal that starts your heart pumping back into sequence again at a less dramatic level. Maybe this is what PBM is doing, it’s harmonizing the physiology of the cell back to a healthier bioresonance.
When you’re thinking about bioenergetics, this is where we’re all very much full of elements which may then be resonating. It might not just be a chemical event, it may also be associated with bioenergetics. I think at that point we’ll call it the draw, because we’ve come to such a large area. I hope we’ve not completely exhausted your poor listeners. We’ve got so much more we could talk about, but we can pick the story up on another day.
Ari: Do you want to complete the last bit of your presentation here or you want to do it on another day? There’s still plenty to talk about and I still have lots of questions.
Dr. Cronshaw: I’ve got a couple of slides. Yes, I’ll finish up.
Ari: For anybody interested in the researcher I was mentioning, his name is Dr. Irving Karsch. Last name is K-A-R-S-C-H. He’s done a ton of research on antidepressant drugs and well worth looking at his research.
Dr. Cronshaw: What I was just going to finish was really looking at some light sensitive targets which are present in all of us, whether it’s at the surface or at depth. As opposed to it just being specific enzymes, there are pigmented materials which are broadband acceptors of photons. There are metals present in enzymes, such as heme groups and cuprous groups, copper groups, which are present in all sorts of key enzymes which are photosensitive.
Then there are specific clusters of cytochromes, such as there can be TRPVs in the outer membrane of the cell which are all photosensitive. These enzyme clusters can then start to activate iron gates to open and to close. Some of these are associated with important iron channels, so calcium, sodium, potassium, which can affect things like transmission of pain, as well as redirecting the physiology of the cell towards a different pathway.
Then there’s this intriguing possibility that those nerves themselves may actually be able to act in order to be conduits, to be like a passage of a pathway of transmitting photons into the cell body of the axon, maybe into deep tissues. We know this happens with naturally occurring biophotons, which are almost like quantum effects, tiny minuscule amounts of energy released through fluorescence within the mitochondria, which then gets carried along this outer sheath of the nerve down to the cell body. Maybe when we put an extrinsic light source on the outside of these myelinated nerves, maybe then some of those photons are being transmitted down the myelin. We don’t know, and so this could be a hidden pathway.
I was reading a paper over the weekend where somebody was using a 50 milliwatt laser device for doing laser acupuncture to treat kids with autism. He was applying one joule, one joule, just a couple of acupuncture points. They were producing effects which were clinical effects improving the behaviour and the ability of these children to cope. I thought, well, how’s this working? Maybe this is one of the pathways. There’s a lot that we don’t know.
As for this concept of skin being a mediator, well, apart from keratinocytes and melanocytes, hair, that may also be an optic pathway where light can pass down the hair shaft to the hair bulb, which is very richly innovated. Then there are a variety of other effects. These photothermal effects, forgive me, Praveen, but low level photothermal effects inside of the cell, as well as more tangible effects inside of a tissue at a low level can be beneficial to stimulate metabolism. At a higher level, but below the threshold necessary to start to lead to damage, these can be associated with pain relief.
It’s worth considering temperature effects because you can heat things up at the surface, as I’ve discovered from my studies, and two to three centimetres in depth, you can detect a rise in temperature. Even though the photons might not be getting through to depth, you may then be acting temperature sensitive iron gates like TRPVs at depth. Is that photobiomodulation or is it a photothermal effect? Who cares? [chuckles] It’s starting to turn into a semantic argument. It’s just there’s a panoply, there’s a multiple series of things that are all happening simultaneously. It’s not just one event.
Ari: I think that’s what you presented here and on the last slide as well, if you could go back to that one for a second.
Dr. Cronshaw: Yes, sure.
Ari: The previous one.
Dr. Cronshaw: There you go.
Ari: I think what this is presenting here is just a vastly more expansive picture of the way that photons interact with human biology as compared to the sort of the old school conception of photobiomodulation as being purely a photochemical reaction involving cytochrome C oxidase in the mitochondria and photons of light mechanically triggering CCO and then having this effect based on that.
What we can see from this, and I would guess, and I suspect you’d agree with me, that we’re probably still in our adolescence as far as understanding all of these different areas of human physiology that are in fact sensitive and affected by light. It would be interesting to revisit this 10 or 20 or 30 years from now because we’d probably find that this list of a dozen things is probably a hundred things, a hundred different ways we’ve discovered that different photons and different wavelengths of light are interacting with and triggering different mechanisms in human physiology.
Dr. Cronshaw: Absolutely, because some of these photosensors are deep inside of organs, way away from the light. Why? Nature abhors redundancy, and it’s quite complex, photosensitive things, opsins and things, which are present in the heart and various other key important organs. Far removed from anything which you might reasonably be able to expose from a surface application. Yet the photo-optic switch is there, so there’s a lot, I think, of hidden mechanisms here which are natural mechanisms, maybe to do with biophotons.
A little bit like cable, we may not be activated by light pathways. We don’t know, and that’s exciting that we don’t know because these are areas that we can investigate and see how we can best use them therapeutically. What we do know is sufficient to be able to start to produce some quite exciting effects, even with simple devices at home, use some LEDs and things. We’ve got a journey ahead of us, and it’s far from exhaustively researched by any means.
Ari: Yes.
Dr. Cronshaw: Just to wrap it up, if you’ve got something on the surface and you want to stimulate it, I suggest two to five joules per square centimetre is good. If it’s deeper, step up the dose by a factor of 10, and then you’ll stand a chance of being able to get down to that threshold level. If you’re trying to treat pain at the surface, like that painful ulcer associated with chemotherapy, 10 to 15 joules per square centimetre. If it’s a deeper structure, then it’s a very high dose indeed before you’d be able to deliver those sorts of energies. That’s not something you’re easily going to manage using a home device LED in one form or another.
If you’re using a laser, remember, it’s a Gaussian beam, so keep it moving, otherwise you’re going to end up overheating the tissues. That was my summary. If you’ve got a big applicator, you’ll be dealing with a big volume, not just at the surface. Watch out for the Gaussian effects of the laser and make sure you move, otherwise you’ll end up overheating things. When you’re looking at selection of wavelengths, there’s a good conversation we could have there about some of the mythology associated with this too, with pigments and blood and water. Maybe that’s a conversation for another day, Ari.
The optical window
Ari: Yes, we hinted at your skepticism of the optical window, so I flagged that as something that I wanted to dig into with you. That can be another day.
Dr. Cronshaw: Then there’s the issue to do with the timing of the intervention. Is this to prevent something or is it to treat it because sometimes it’s better to prevent something than to treat it. When it comes to producing analgesia, I’d suggest that the indication is that higher [unintelligible 02:15:31] is the way to go. Be aware that there can be some 3D effects and also, start thinking in terms more globally of what you’re doing to the organism. This is just a bioenergetic system and you’d be affecting localized, regional, as well as systemic effects, which will then mediate through the innovation or through the endocrine system.
It’s much more compound paradigm than simply firing that billion ball photon that’s for electron transport chain. We’ve moved a long way since then. Anyway, here I’m with a couple of my friends that I did my doctorate with at one of our congresses. You can see that it’s a very enthusiastic group that we’ve got going at the moment, and each of us are on the same pathway to try and make it successful. Thanks for your time, Ari. I hope it’s been of some benefit to you. At such time as you wish, I’m very happy to speak with you again. We’ve gone through an awful lot of materials tonight, so I think we’ll both sleep well. I hope you do, [unintelligible 02:16:38], and we’ll no doubt be speaking again soon.
Ari: It sounds great. I certainly have many more questions for you, and I look forward to digging into that. This was a wonderful presentation. Thank you so much, Dr. Cronshaw.
Dr. Cronshaw: It’s been very much my pleasure, and thank you to everybody who’s had the patience to go on the journey. All right. Thanks again. All right. Cheerio now. Bye-bye.
Show Notes
00:00 – Intro
00:44 – Guest intro
03:51 – PBM for tissue repair
15:27 – The impact of the disease process on PBM results
20:42 – Timing matters in photobiomodulation treatment
27:43 – Depth of injury matters
40:54 – Heating tissue in PBM
52:47 – The dose matters
1:29:14 – Lasers vs LED
1:37:25 – Irradiance
1:57:14 – Photoelectric and photofluorescent effect
2:15:14 – The optical window
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