#134 - Seeing Inside the Brain with Prenuvo

Hi there, it's Matt here and welcome back to the podcast. Today I want to step back from sleep and ask a broader question. What if you could see inside of your body? And more specifically, what if you could see something inside of your body before anything went wrong? Well, we live in an age of reactive medicine. I would say right now, I think that's fur. something hurts, we go to the doctor. If something shows up on a blood test, we investigate. But what if instead of waiting for symptoms, we simply looked? That is the premise of what we call whole body MRI preventative screening. And it is the mission of a company called Prennuvo. Now, for those unfamiliar, PNUO is the world's largest network of MRI clinics dedicated to proactive whole body MRI scanning, and it's designed to find abnormalities before they announce themselves to you in the form of disease and sickness. I should say upfront, I have chosen to out of pocket go and get two pre-neuvo scans myself in my lifetime. I started when I crested 40 and started to get into my middle age. I really started to take my health seriously and I got my first pneumo scan in 2022 and then just recently I got my second pre-neuvo scan in 2025. Why? Well, because I take my health seriously. I don't really go on like fancy vacations or buy fancy cars or anything like that. Where I invest any disposable income is usually on my health and my happiness. And with my medical background, I know how critical proactive screening is compared to reactive latestage treatment. and believing in this process as I do, I wanted to invite someone from PNVO because I just had such a great experience with them to come on to the show and explain to you what whole body imaging actually is, what it can do, what it cannot do, and why it matters. And before I forget, PNUO has generously provided a $300 off discount from your next PNO scan. If you just want to go after listening to this conversation, go to pneuo. com. That's P renu vo prennuvo. com/mattwalker. You'll get 300 bucks off your skin. Anyway, to the podcast. My guest today is Dr. Daniel Gurand or Dan as I'm going to call him. Dan is the chief medical officer and the president of the PNUO medical group and he is one of the most impressive physician leaders I have come across. Dan is dual board certified in adult and pediatric radiology. He trained at the legendary John's Hopkins medical school. He is a prolific researcher with over 80 peer-reviewed papers, including work in the New England Medical Journal, which is one of the hardest journals to get into. You have to be doing groundbreaking stuff, as well as JAMMA, which is another very prestigious journal. Before he joined PNO, he held senior leadership roles at John's Hopkins Medical School, at Lifebridge Health, and also and McKenzie and company. So, he is a rare combination of world-class clinical expertise, rigorous scientific credentials, and sharp strategic thinking. He's exactly the kind of mind basically you want steering the future of preventative medicine. Dan, it is a real pleasure to have you on the show. Thank you for coming here. — Thanks, Matt. It's a privilege to be here. I'm excited for our hour together. — Thank you. So this incredible movement that you and PNO have started in a way that is unique I think in our human medical timeline which is this notion of seeing inside of ourselves in a way that we really haven't been able to for so long or at least the only time we were doing that seeing inside of ourselves with advanced neuroiming and whole body imaging. not just neuro imaging but whole body imaging is when something was wrong. [clears throat] But the way that PNO has taken it and one of the things that motivated the company you know is this notion of preventative imaging and this philosophy of proactive health. So I wanted to start with perhaps you telling us a little bit more about the fundamental philosophy. Most people listening right now probably feel fine. They have their annual physical done. Blood work looks normal. doctor says everything looks good. Why should someone then who feels perfectly healthy

lie inside an MRI machine for an hour? I obviously know the reason because as I mentioned there at the start of the show, I've been through the pneumover experience twice myself out of pocket because I believe so powerfully in it. But help other people understand what's the case for seeing before symptoms. That's the way I think about it. How do we see before symptoms? Tell me a little bit about that. — Absolutely, Matt. It really comes down to one fundamental question and it could be different for different people, but the basic question is, do you want to know? And within that question, there's the idea that information, more information might be more for you. It might be more of a chance to get ahead of pathology that's going to impact you. It might be a deeper understanding of your health that's going to let you optimize your health better. But when I have some of the highest level physicians from the highest level AMC's in the world come talk to me or when I have interested patients or family members come talk to me, it actually all boils down to that same question. No, no one has any more or less insight. Do I want more information? If so, what might that get me? And to frame it for people another way, but a related way. I would say that most of the world in the proactive so-called sick care system, the legacy health system, it's as if we're living our lives with paper maps or at least binders of really good maps. And if you go back to the time before GPS and everybody had a map on their cell phone that was updated in real time, this is what the world, the physical world looked like. This is where medicine is today. We understand the map of disease very well. What we lack is an adequate amount and depth and periodicity of data from the individual to place them within that map. And without them, — not only can they get surprised by things, but it's also even when they have some sense of where they are, it can be challenging for them to get where they want to go. — It almost reminds me of when you're sitting in a kitchen and the refrigerator compressor goes off. And it's only when it goes off do you realize, gosh, it's been on all of the time. When you say it that way, it's funny. Why haven't we been thinking like that in medicine for the past 50, 60 years? And I love this notion of trying to go in search of information because in some ways that's really what you're trading in is early information that gets you to a place of better health, longevity, not just lifespan but health span. And I think this notion of longevity has now really come onto the map in the last couple of years. before we go further into that because I want to speak about exactly what it is that you capture with the scans and how people should think about that. But taking a step back, maybe people would love to know what is Preuvo for listeners who may not be familiar. Could you just tell us a little bit about what PNO actually is? How did the company come into being? And maybe what was the problem that it was really founded on? What were you trying to solve? And what drives the mission today? — Absolutely. Prrenuo is a collection of 25 allied clinics across the world. 22 of them are in the United States. And then we have one in London, England, one in Melbourne, Australia, and one in Vancouver, Canada. And at all these clinics today, it is the only set of clinics in the world that is exclusively dedicated to proactive care specifically with whole body MRI. And we've also added to that blood work at many of the locations as well. So MRI was what Prneuo really became well known for. And Prneo the word it's a word that's specific to our company. It doesn't exist in any language that we know of prior to Prouvo. And it's a combination of the word prevention and new. And also there's the word or the name Renew in the middle. And Renu was someone that our founders knew well uh who was diagnosed with latestage colon cancer and died young because of that. So the idea is that we're trying to take this new method and we're trying to prevent that from happening to anybody else. Everybody has a renew in their life at some level. And as a physician, you end up seeing hundreds or thousands of these people. It's a constant reminder of what we call the false negative problem. You know, people talk a lot about if you have too much information, you might be prone to false positives. the problems that happen when you have the information, but to look at that problem in a vacuum is an issue in and of itself. And we look at reactive medicine and we say, "My goodness, there is a tremendous false negative problem. " And we all know it because we've all lost someone who made every single doctor's appointment, every

single preventative appointment, and still missed something, whether it was cancer or an aneurysm or a neurodeenerative condition or a cardiac condition. We all know that this happens. We don't have to read a medical journal. We experience it throughout our lives. — You know, you bring up an interesting point and I hope you don't mind me sort of going a little bit further into that. I know some people would say well look information apparently is king but coming on to the false positive if something is identified in my pre-neuvo scan which requires a follow-up with my doctor and let's say I have a you know a hyperintensity on my right thyroid and we need to know if it's benign or not and it takes you know my medical care 2 weeks to set me up and finally determine that thankfully it is benign. You could say, well, there is some degree of an emotional cost to that two weeks of time when I'm left in a limbo state. And I know some people do have that sort of ostrich syndrome where I just prefer to bury my head in the sand. But I don't think honestly any of us do. And I love the fact that you say yes, there is the concern about a false positive, but truly the devastation, the tragedy of medicine is so many of the false negatives. And I'm so glad that you sort of brought that up. I just want to defend the false negative and away from the false positive. And thank you for bringing that up. — Yeah. And I do have one or two more thoughts. in all medical processes whether you go to a primary care doctor which you absolutely should or get the additional recommended more common screenings like mamograms and colonoscopies which you absolutely should prou doesn't replace any of that it augments it but in all those other scenarios there's still the possibility of finding something that takes a while to resolve and so for anyone engaging in screening of any sort it's important to have that mentality that there may be an area of discomfort to understand that going in that is part of the process and it's a healthy the quicker the health care system can resolve things the better. Obviously, as time goes on and we get more experience with different modalities, we tend to get quicker. This is medicine at large, not just at resolving these things. But what we do know from the literature is that in whole body MRI, there is no long-term psychological distress. And there's actually in our experience a prepoundonderance of people that received a deep level of reassurance either immediately or eventually knowing that you've gone deeper than the average person that you've put yourself out there and that at the end of it nothing really serious or concerning was found. Now not everybody gets that. We do find serious or concerning things but thankfully in most people we find low-level findings or just early chronic disease findings. It's similar if you went to a primary care doctor. So, I always use this analogy because I think it's very understandable. Everyone of a certain age has been the experience that they've gone to their primary care doctor and they've pointed to something on their skin and they've said, "Hey doc, what do you think of this? " And the primary care doctor, if they know you really well, they might say, "Hey, I remember that exact thing. It was there when you were 2 years old. You're fine. " But most of us don't have that relationship with primary care. And it's much more common that the primary care doctor looks at it and says, "Well, it's probably okay. But since you think it's new and since the edge of it is a little irregular, I want you to see a dermatologist. Maybe you're a little bit concerned, but you know they're just being extra cautious and you go to the dermatologist and that person looks at it and they say, "That's probably fine. Come back in six months and I'll see it again, but I think it's probably fine. " And then you go back in six months and it's stable. I mean, this is a really common thing. It's happened to me two or three times. And sometimes in there there's an option to have a biopsy to be extra safe if you'd like to since biopsying the skin is kind of low stakes. But that's really up to the individual. The bottom line is when you hear that scenario, nobody says, "Oh my goodness, that primary care doctor created a false positive. " — They don't say, "Oh my goodness. " You know, why would they go and get an unindicated screening? Because if you look at these evidence-based societies, many of them don't endorse skin screening because it hasn't been proven out long enough to have a mortality benefit. However, most of us make use of it. Majority of people I know have their doctor look at their skin or even go to specific dermatology appointments for it and we don't consider it to be a false positive when the primary care doctor is being dutiful and refers to get an expert set of eyes on it. And I would look at Prouvo much the same. We are essentially a primary care type scan. We're doing a lot of trade-offs and balances to make a comprehensive scan that you can get in the comfort of 40 minutes to an hour. And what that means is we're not going to go to the nth level of detail on any one particular organ, but we're going to do all the organs well enough to where we can see most of the things. And you know, it's all in what we mean by most of the things. But I think what people need to understand is there is no one scan that's perfect. But we don't know of a

better whole body MRI scan than Peruvo for detection. And whole body MRI based on the literature is the single most powerful test globally for detecting cancer and many other things. So if you look at whole body MRI and this is not just in gnuo's hands, but if you look at it when applied to a general population, it will find a pathologically proven cancer in about 1. 6% of people. That's 16 out of a thousand. To give you some references, mimography, which is excellent but only looks at the breast, finds about four cancers per thousand. Colonoscopy, which is excellent but only looks within the colon, finds about 11 can cancers per thousand. And papsmears, which are excellent but only look at samples of the cervix for a virus. And then a closer look is taken if it's positive, that only finds cancer about one in a thousand. So if you added up those other three, all of which are great tests that people should continue to get, you start to approach the power of whole body MRI. That's how powerful the method is. And that's why we think it is a great adjunct to medicine and a great potential solution for this false negative problem because you can add on not only that cancer detection power that I mentioned, but it is also the best modality for detecting anything that's going on in the soft tissue. So it has incredible detection potential for things like inflammation, infection, aging in the brain, and then aging throughout the body and other things like orthopedic issues or metabolic derangement within the liver. Just an incredible amount of conditions that you can detect with this method in addition to the cancer detection. Okay, admission time. I've probably eaten more protein bars in my life than I've blinked. and I'm always on the hunt for the very best. Then I found David Protein bars. Each bar delivers 28 gram of protein, just 150 calories, and zero sugar. That's the best protein to calorie ratio I've seen. And the taste is legitimately good. Protein isn't just about muscle. It's essential for metabolic health and for keeping you full. And David's unique ratio makes these the most satiating bars out there. Here's the kicker. Demand has been so high that the full lineup of eight flavors is currently sold out on the website. They'll probably be back in stock by the fall or autumn for us Brits. In the meantime, you can find them on Amazon or use the store locator on their website to grab them nearby. Try them out for yourself at davidproin. com/mattwalker for a special deal for all you folks. Again, that's davidproin. com/mattwalker. And maybe if I could combine two questions into one here, could you tell us a little bit more about the organisms, the structures, and the early changes that you can detect? So for someone who's never had a whole body MRI before, tells a little bit about what the scan actually captures the organ systems, the structures, how early you can detect. And then you touched on it before and this is the sort of second part of the question. Why is it that MRI specifically is so good? Because some people out there will have heard about, you know, a CT scan or an X-ray or a posetron emission tmography scan or ultrasound. And we all know that these are things that help us look inside of the body. What's so uniquely distinct about MRI that positions it so well for preventative screening? So two-part. Tell us a little bit about whole body MRI, what it captures and then why that over some of the other imaging methods. — Well, whole body MRI and I'll get into the details in a moment is the best modality for looking at soft tissues. It is essentially looking at the chemical compositions of the tissues and it does this without any radiation. When you lie down an MRI scanner, you're lying down within a very homogeneous and very powerful magnetic field. And then we're using photons and so technically radiation but not ionizing radiation. So not cancer-causing radiation. So the same types of wavelengths more or less that you might use with radio frequency waves or cell phone frequencies. Very similar wavelengths. And these are used to excite some of the chemicals within the body. And then the chemicals then relax back with magnetic field. So they absorb this energy and then they release it. And it is in measuring what's released that the computer is able to reconstruct an image of what's going on inside the body. And it can do it at a very high resolution with very good contrast which means you can see structures very well. You can see the normal structures very well and you can see abnormalities very well within soft

tissue. The mass majority of the tissues in your body are considered soft tissues. These are things like your organs, your brain being one of your organs. Your bones actually have a significant soft tissue component. From a total area perspective or volume perspective, they're mostly soft tissues with the marrow. However, there are parts that are very hard that are calcified and those show up as sort of dark areas on MRI, but they're very few and far between when you consider those areas versus the rest of the body. So MRI images really well where things like X-ray and CT don't do as well in distinguishing all those soft tissues which is where most of the action happens with health and disease. When it comes to things like fractures while we don't see the broken bone as well we can often see secondary impact. So in some ways MRI can even be more sensitive than CT and X-ray even if it is a hard part of the body like a hard tissue like the bone that's broken. So, it's a very exquisite modality, very flexible, doesn't have any ionizing radiation, which is super important for this application. We're essentially talking here about using an imaging machine to help us create the annual exam of the future. Or maybe it will be even more than annual, right? Who knows? You wouldn't want to be irdiating somebody constantly with ionizing radiation to get that same information because over the course of their life, you could actually cause a significant amount of cancers were you to do that. And so that's what we think is the problem. If you were to do CT scans on lots of healthy people, the entire body, or PET not only would the imaging be inferior in many ways to MRI, but you'd have that cancer risk resulting from the imaging itself, which would be problematic. The last thing you asked about, just to finish, I just want to make sure I get to all your questions, is ultrasound. Now, ultrasound also doesn't have radiation. However, if you've ever seen an ultrasound image, it's very grainy. It's very operator dependent. So you can think of MRI as kind of like whatever your favorite high-end car is. I'll just say Cadillac to give the old axiom that we use in America, but like it's the Cadillac of cross-sectional imaging. You get this really great full digitization of the person. Whereas an ultrasound is I guess riding along on an analog bicycle in a way. I mean it's very operator dependent. The image is lower quality. You're really not digitizing the patient in one block. So it's much harder to do meaningful artificial intelligenceoriented postacquisition reconstruction. So using the computers to help us tease out what's going on in there, maybe helping us find things, helping us quantify things like we're presently doing would be very challenging with ultrasound and it would probably take a lot longer to do the whole body and get really good ultrasound images. The ultrasound comparison is almost hard to make because I would never even think to make it. The CT1 is an important one and it really is about being able to see those soft tissues where the action is and being able to do it without any radiation. — And I think that part is probably lost on so many of us who are not familiar with these scans. We just go in, maybe we fill out a form. There's something about do you know that this has some degree of radioactive component to it. We say yes cuz we want the scan. But as we think about this with the resolution increasing and our sensitivity and specificity increasing with MRI as that happens it means that the opportunity to repeat scan an individual and expect a measurable change an accurate change. So let's say that I'm scanning the brain of someone. I typically am not going to scan their brain to look at structural gray matter differences. Probably anything sooner than 12 months apart, maybe six months depending on what their age is because there's just not enough resolution yet to know that I can observe identifiable changes between a six-month period. But as things progress, as the MRI scans improve, our sensitivity and specificity gets better. That means that the opportunity for us to scan people more frequently to be able to detect more consistent join the dots progression time-lapse photography of what's going on in the body also increases. If it's a radioactivebased scan, even if you had the opportunity because of sensitivity and specificity, you're still going to be shut down because of safety concerns because you can't irradiate someone so frequently within such a short time period. And we face this when we're doing our Alzheimer's disease research when we're doing PET scans and we have a specific radioactive tracer that maps to look at things like beta amalloid in the brain or tow protein in the brain. And even though we would like to sometimes map them more frequently, we can't much more than 12 months apart because of the safety concerns. So I think it's just great that people understand how safe and how it's not just non-invasive but it's also non-erradiating and don't underestimate that. Let me

come on to a slightly different question which may be popping up in people's minds. It's the silent risk and it's the part that maybe fascinates me most. And I don't want to be scaremongering here, but let's say that you're scanning people who walk in to your facility and they feel completely fine. All of their blood work so far has looked great. They've had their annual physical. Nothing seems to be problematic. But as you mentioned, every now and again at a small percentage of those people, you will find something. What are the most common things that you find and what are the most surprising ones? What's lurking in bodies I suppose is the question that traditional metrics like standard blood work, physical exam, prostate exam. What are those things missing that you will typically have sensitivity to? We say that in a healthy population of people in our clinics, about one in 20 or 5% are going to wind up having something that needs attention within days to weeks. And within that 5% there's a fair amount of variety, but there's two principal components. One is masses that may be cancer and that can range from 2 to 3% depending on the population in terms of the amount that we find that's worrisome. If you look at the meta analyses of full populations which tend to be I would say having a median age in the 50s so the population age matters a lot in this but as I mentioned before in those populations they find cancer about 1. 6% of the time with whole body MRI in our hands in our largest cohort we found it about 2. 2% of the time and again we believe that we have the best technique and so we think our sensitivity is probably a little bit higher than those with less experience. So of that 5% we'll say around half of it's going to be things related to potential cancer and we are almost never diagnostic of cancer. We raise the flag we categorize as highly concerning and then it goes to a follow-up test usually a contrast enhanced MRI that's specific to that organ and then if necessary would go to biopsy after that test typically. And lastly I didn't mention this in the front but we don't give contrast to the prouvo scan. So, not only is there no radiation, but you don't even have to have a pin prick or an IV started. It really is. You just come in and you get this scan of your body. The other half or so are aneurisms. And it is a bit surprising to me how common they are that more the body we image and the higher resolution we do it, I would say over time, medicine in general is finding more aneurysms in individuals. Not necessarily that people are getting more of them, but we're detecting more. And the word aneurysm, like the word cancer, I think elicits a little bit of an adrenaline surge. You know, I'm not going to lie, there's certainly some anxiety associated with this. I haven't met anybody who has been told they have an aneurysm that at least wasn't initially a little anxious or a lot anxious, particularly if they had a family history or knew someone who had one rupture and maybe even died. The vast majority of aneurysms that we find and that are out there in the world are going to be okay in the sense that they aren't going to grow very much. They're tiny and they're going to stay tiny or it's going to take them so long to grow that the person will live out their natural lifespan without an issue. — And maybe Dan, sorry, could you just mention what an aneurysm is for folks who may not know? — An aneurysm is an out pouching of a blood vessel. So if you think of a blood vessel as a predominantly cylindrical type shaped structure, if you had a spherical branch point coming off the side, like a little circle, a little dome coming off, that's an aneurysm. And the larger that dome gets, the thinner its wall gets and eventually it can break. The consequences, if it breaks, can be devastating because the person is bleeding into some part of their body. There are a variety of places you can have aneurysms. The places that are most commonly associated with mortality are aneurysms in the brain where they can be quite lethal, aneurysms in the aorta and the principal sites being in the thoracic region as well as the abdominal region. All of these things increase in frequency with age although some of these have a genetic or developmental component. So they so some of them do happen earlier in life and it's not one of the leading causes of death but certainly a cause of death for people in their 40s and 50s is dropping dead from having aneurysm burst and once you know a person or two to whom this has happened it's quite scary. Now the nice thing is that if they are detected early the interventions are very effective for keeping them small and preventing them from bursting and there is a whole literature and a rich field of study and an entire specialization called neuroendovvascular medicine where probably I would say half of their volume at this point is related to dealing with the brain aneurysms and then likewise there's been a lot of non-invasive progress with how vascular surgeons treat abdominal aneurysms and

how cardiothoracic surgeons and vascular surgeons treat thoracic aneurysm and even cardiologists can treat those. Now, so lots of progress and something that you do want to know early about. The truth is that if you have let's say x number of these, probably less than half are going to need an intervention eventually, but all need to be evaluated to determine if they fall within that group. I don't want to have an aneurysm, but what I want to have even less is an aneurysm and not know about it. Yeah. because it's just one of those things that if you get ahead of it, it should not be the thing that kills you. Right? That's another group of things. And again, what we find is that people are grateful for the knowledge and their referring physicians take it very seriously and most of them will get these things followed and will be less concerned about them over time because like a blemish on your skin or something or any other part of your body that sort of isn't exactly the way you want it, if it's at least stable, then it's easier to live with. And then the last piece of that 5%. So I said we got potential cancers in there. We have aneurysms of different sorts in there. And then we have what I call a long tale of other diagnoses. And what's in that set of diagnoses that people need to know quickly about? Many of them are actionable. I would venture to say most a lot of things like inflammation, infection, and neurodeeneration. And there's some overlap there. So we find people walking off the street with diverticulitis with abscesses in their liver with pneumonia in their lungs and although they didn't come to us for the symptoms there are often symptoms when they reflect on them as you can imagine. — So that's the surprising one. We wouldn't be surprised by the stuff we find a lot of because even if you're not at Prouvo and you're just doing a lot of ER scanning you're going to find a lot of cancers. aneurysms. So that's not surprising to me. What's surprising to me is people coming in off the street with walled off absesses and you're thinking to yourself, the human body is an amazing thing. I mean, this person had mild symptoms and they have an abscess that needs to be drained and they're otherwise healthy. How did they get there? How long would that have gone on for? And there are people that would say, well, maybe they would have been fine without the intervention and without the knowledge, perhaps. Or perhaps it could have been one of those deaths that nobody can quite understand, right? someone just shows up and we don't get autopsies on all of those, right? So, I think there's a lot of things lurking in folks bodies and this is a way to find out to a fair degree of certainty. Do you have one of those things or not? — And I think I know which side of the equation I want to be on regarding that question, which is well maybe you would have been fine without the diagnostics and the intervention. maybe, but I'd much prefer to know that I could get it seen to and no matter what, whether it was going to be fine or not, it's now. And in some ways, you've actually really answered so much about the next question I had, which was from scan to action, which is what happens as you escalate up the chain of needing to do something actionable based on the findings. Long-standing partner of today's podcast is Element, spelled L M N T. Element is a sugar-free electrolyte drink mix. And for me, it was the sugar-free part that made me start using it a while back. And again, I buy my own supply just to stay objective. Beyond having the electrolytes in the right balance, the other reason I'm a fan of Element is that it's scientific. If you look up the people who created the company, you'll find some pretty heavyhitting physiology, biochemistry, and pharmacology knowledge baked into the product. And again, all of that comes without any sugar. Now, here's the update. Elements lemonade salt flavor, which used to be seasonal, was so popular that it's now permanent. You can get it year round. Happily, I badgered them and they have agreed to give you fine folks a free 8-count sample pack with any purchase of element if you use the link drinklnt. com/mattwalker. So, for free product with your purchase, just visit drinklt. com/mattalker. And as I said, you'll get some free product. But I suppose another question since I've been through it twice now, people may not know. What does it look like to get your pre-neuvo results? We're talking about doing this process and why it's important, but just from a boots on the ground. What do people get? I go through it, then what happens? What do I get at the end of it all? You go through the scan and if there is a really alarming result, so something that's going to need action within let's say minutes to hours, which is extremely rare, that's about one in 10,000 scans.

When we see that, we will get directly in touch with people by phone, usually the radiologists themselves. These are really rare cases and not something people should think about, but it is in the realm of possibility. And so if something really bad is going on, we will contact directly. If something alarming but not immediately life-threatening is going on, you will still get outreach. It'll be from direct and from one of our preventive medicine physicians or nurse practitioners who will reach out on a level of days since your scan. Sometimes maybe a little over a week. Otherwise, once your scan is read, the information comes back to you and it comes directly you instantly have access to two different types of reports. One is a medical report that goes into great depth that if you're kind of fluent in that sort of medical linguistics would be interesting and if you show it to your doctor, they'll be able to translate it if you cannot. But we have another report that's made for everyday people and it takes the same information and crosswalks it to much more accessible language and really is focused on what does this mean and what is the action you should take next. Now once you have that information back, you also get access to all of your images. And people love this. They love being able to see with immediiacy their images. And if there are any abnormalities, these are spelled out in what we call key images. Images that the radiologist has made available to show where this abnormality is. Often has, you know, some text or an arrow associated with it. Then there's the opportunity to get a consultation. Interestingly, not every patient avails themselves of this. Even if the results are all within that kind of normal range and there's nothing alarming or needing immediate action, there is still the opportunity to walk through all of it with a licensed provider, either a preventive medicine physician or a nurse practitioner, and that just has to be scheduled. The wait times for that vary by geography. It is a challenge as we're growing so fast to keep them as tight as I'd like, but we're working on ways to get to a better level of availability in all of our geographies. It is an amazing service and you feel very taken care of at a concierge white glove level. At least I felt that both times that I've been through the scan. The scan itself, you know, it's almost like an MRI but with a spa like feeling included with it. It's not at all antiseptic for folks out there. It's a really fantastic experience. And I'm not just saying that of course because I'm speaking to Dan. I've been a Preuvo customer for many years before doing this show and I do love the insights, you know, and my wife and I recently did I did my second scan, she did her first scan and it's interesting how you speak about those two different levels of depth. I was able to go into it at a much more medical level and dig deep into all of the granular details, which I adored. For her, the other version of that was fantastic because it wasn't caught up in medical gobbledegook and sort of highutin word salad. It was fantastic. She got just as much out of it. And being able to see these images and rotate them into it's an incredible service. I suppose that brings me on to my next question, which is really a little bit about who is this for, you know, and I remember you mentioned there it's not surprising to find someone in their 40s with an aneurysm somewhere. And I know that when I transitioned into what I would call my the foothills of middle age, hitting 40, that was really where I thought, I think I'm going to take myself off and go and get a prenovan. I believe in this and I know just from my medical background. That's the time when things can start an inflection moment starts to change. But how do I think about age in my decision to take a pre-neuvo scan or not? How do I think about it? If I've got family history of things, timing, when should someone, let's say, get a first baseline and how should they then return? How frequently should they be returning for their scans? Would you recommend? — Peruvo thinks that the philosophy of proactive care will play out such that people will be gathering data at least annually on themselves and we think whole body is an important part of that. In some cases, like the pillar of this data set of the future. We cover anyone age 18 and up. I have a son who's 17 in a few months and he wants to get his Prouno scan on his 18th birthday. I'm not going to stand in his way as a CMO for sure. But you know it again it is for anyone at any age I would say a personal decision to be involved in proactive care and it has all of the advantages and tradeoffs and responsibilities that we've already discussed. That being said, anyone who's an adult can get this scan. You're certainly more likely to find things as you get into what we call the rising risk part of life. And that's when people start to accumulate one or more chronic conditions, but they're otherwise in very good health and they

don't have a predominant chronic condition that's hospitalizing them on a regular basis. In the population health pyramid, we call this group the rising risk group and that tends to be 30s, 40s, 50s, and increasingly 60s as people enjoy greater health in older age. That is certainly our sweet spot in terms of what we see people coming in. Our median age is probably in the low 50s, but we have people from both parts of it. Like I mentioned, we don't do anyone under age [clears throat] 18. So at the extremes of life, we see Yes. But we do have older people. And another personal story here, I don't sort of proitize within my family. I kind of keep church and state separate. — Smart man. — Right. you know, it's [clears throat] but I've had an increasingly number of family members come to me and this past year was very special. My mother asked for the scan. She asked shortly after my father passed away and it was really about her kind of doing a reset and thinking about herself for the first time in a while because she'd been taking care of him as his caretaker for about two years when things got, you know, really rough. And for her it was obviously she knows I can't tell her how many years to expect but she sort of wanted to turn that page and to sort of not be living under the sort of damma please you know this idea of well I just buried my husband and I'm 78 years old. She wanted to know. She wanted to know look if I'm only going to live a few more years and there's something lurking I want to know. And if there's not something visibly lurking that's really useful information to me. And so we did a scan on her at 78 and you know really very good results. No lingering anxiety, nothing that anyone would call a false positive, and honestly some good things for her to focus on to improve her health. At least two things, both of which were actionable. I'm not I want to go any more in detail than that. I was always a believer in the scan, but the longer I'm in the game, the more I get to be a believer about the extremes of life. Really good use for the scan as well. Absolutely. Because there's a lot of life to be lived after 80, after 90. Those people I think like everyone else have potential uses for this information. Absolutely. — It's an interesting case study to hear of your mother too. Therein lies that proactive relief which was I'm sure for you and I'm sure for her going into that especially at her age there is the anxiety but coming out of it such a proactive release and relief that alone I think is worth the cost of entry. Let me switch. I have two lifestyle questions before I want to ask you a little bit about the future of where we're going. Because for all of us now in this moment in time, the future seems to be coming at us with distinct rapidity. That hasn't been the case for many decades if not centuries. So I want to get to the future, but I want to in between that speak about lifestyle connection. I, as I said, had my first pre-nuvo. I think it was 2022. And one thing that struck me and of course when I going in there no one there knew who I was thankfully. What struck me is that during your intake questions there was a significant proportion about sleep which made me giddy. I was thrilled. You were speaking asking me questions about my sleep duration, my sleep quality, my snoring, my daytime sleepiness. Did I have a history of sleep disorders? For someone who spent a career studying sleep, it was quite a delight. I know to me why it makes sense. But why did prenuvo and why does prenuvo ask about sleep specifically? And I'll speak about other lifestyle factors too. How do you factor that into your interpretation of what you're seeing if at all? And maybe if you don't that's great too. It's just that you gather that information. Help me better understand your views on sleep. — Well, I think Peruvo's philosophy and it might not be the case with all proactive care companies, but at Prouvo we really buy into the philosophy of lifestyle medicine. So, as you were filling out that myth, you're going to notice that there are many pillars of lifestyle medicine reflected. And for those that aren't familiar with the framework, there is this thing called lifestyle medicine. And the idea is that the human body can keep itself incredibly healthy if it's treated the right way by its owner. And there are five pillars that are physical pillars and one sort of mental and spiritual pillar within conventional lifestyle medicine frameworks. And again, this isn't something PNO invented. This is more like American Board of Lifestyle Medicine mantra and doctrine but sleep is on there right so getting sleep is its own pillar and there's exercise is a pillar diet is a pillar avoidance of risky substances like alcohol and tobacco that's on our form right that's a pillar of lifestyle medicine as well and then there's the pillars of mental health and then there's a pillar of sort of meaning and social connection and spirituality that's sort of the combined pillar those are the six pillars of lifestyle medicine, sleep is one of the most important. And when I talk to some of our collaborators in the wearable space, and we should talk maybe at some point about wearables, the richness of data there, because it really is going

to relate in some exciting ways to the scan data and other data that we gather at the clinics. But when I talk to people in the wearable space and I say to them, what is the single biggest unlock for your device? Regardless of who I'm talking to, and I'm not going to get into names here, they've all sort of said the same thing. And they said sleep is just this incredible thing people want to know about. We were also wondering why that is. And we think they all seem to think that people respond so much to data about sleep because it's one of the few things that like as you optimize it, you immediately see results. You can't say that for most other things. Like if you're going to try to build muscle mass or preserve your brain volume regress your stenosis on your vessels or something, these things tend to take a lot of time and you have to kind of get indirect measurements. But if you optimize sleep, you within days will start to feel like a better, more functional and healthier human being, won't you? Right. — So true. — And it's because we sort of are really unnaturally depriving ourselves of sleep with all the trappings of modern life. you know, artificial lights and weird bedtimes and, you know, you name it. The substances, the caffeine, the alcohol and all these things are not what our evolutionary ancestors, you know, were designed to kind of accommodate, right? So, we don't get enough sleep. We all know that. And if you track it and you get better at it, you can become healthier. So, we're believers in that. You know a lot more about this than I do, Matt. Prouvo wants to understand these things because when we have conversations with people, we're not only talking about scan results. If the scan results are normal, we are also reminding them of healthy habits, right? That's another thing that we do and that we're starting to do even more formally within some of the reporting. And so it's part of the philosophy. And then from a research perspective, yes, we are interested in looking at brain volume and body composition. Both areas that are known to be related to either health in those areas is known to be related to good sleeping hygiene and habits. And degeneration in those areas and poor health is known to be linked to poor or broken sleep habits. So these are things that we want to be able to study at the population level for individuals. We also, one of the most common things we find that impacts sleep is deviated septums. A lot of people have never had a brain scan or if they've had one, it's been in an acute trauma setting and even if they had a deviated septum noted, that might not have been a big part of the outcome of that clinical encounter. But for us, when they come in and they're getting imaged at health, that is a very common finding is that we were able to find someone who's snoring. we find issues on the inside of their nasal sinuses and the nasal septum is deviated and getting that addressed can often be a big deal for patients. So that's a common postp pronneo story we hear is you diagnosed me with a deviated septum I had that taken care of and now I've never slept so well. — Honestly, it's funny you mentioned that. My first scan 2022, there it was. I had a deviated septum and it was non-trivial. It was quite the bend and went and had it corrected and breathing was not to be a pun as a sleep researcher but night and day different. I was one of those statistics. It was incredible. Over the past 18 months, I've committed to a serious hypertrophy program. My natural body type runs lean. Gaining mass doesn't come easily to me. So to move the needle, I've had to train with greater intensity, higher volume, and significantly more calories. But with that effort comes a concern I take seriously, which is inflammation. The kind that quietly undermines recovery before you ever feel it. You've heard me say that sleep is the Archimedes lever for bringing inflammation down. And I track mine carefully. But here's the question I had to ask myself. If I hold sleep to that standard, why wouldn't I hold inflammation itself to the same standard? That's why I use function health. I also personally know the team behind it. Genuinely highquality people making a genuinely high quality difference with product. Proud to call them supporters of this podcast and friends. over 160 lab tests a year, including HSC CRP, vitamin D, and glucose, giving me highresolution mapping of my inflammation, and so much more. I really could not recommend them more highly. Visit functionhealth. com/matwalker or use code mattwalker25 for $25 off. That's functionhealth. com/matwalker. or use code Matt Walker25 for $25 off. Coming on to that then that scan was a

good demonstration for me as to how it motivated me to do something and go and get something addressed that improved my health. How do you see other lifestyle factors you know beyond sleep, diet, exercise and stress? Firstly, how do they show up in imaging? So that's daytime lifestyle factors impacting imaging. But conversely to close the loop, do you find that having had imaging done above and beyond abstract statistics or numbers on blood worksheets? Does imaging conversely have a more powerful impact on changing someone's behavior? So, for example, seeing your own visceral fat or seeing white matter lesions in your brain because let's say you've been snoring a lot and you haven't taken it seriously and you just think I don't need to go and get my self tested for sleep apnoa and to help me understand firstly how other lifestyle factors can impact and maybe show up if you have that sensitivity and conversely does imaging change people's motivational drive to do something and do something different because behavioral change as I understand it the more I live this medical scientific lifestyle is so hard. We're so routinized in our behaviors. It's hard to make us do something that we're not normally doing. Help me understand that. — Well, I'm not a behavioral sciences researcher, so I don't have uh perfect confidence when I say the following. Based on what I've seen, seeing what's inside of your body, particularly if there's something wrong, can be one of the most deeply motivating things for a person, for a patient, for a customer, for a consumer, whatever you want to call them. And why is that? I think it's because people respond to precision medicine. They respond to knowing that something is about them, that there are consequences for them, because they've been told their entire lives that they should do this or that. and they probably noticed that they don't always see a consequence, but a lot of these consequences are actually lurking inside of them. And you can say to somebody, you should only drink alcohol with moderation and you shouldn't eat too many carbs and too many calories. And they may look in this themselves in the mirror and sort of see that they're putting on weight, but not necessarily be certain what type of weight it is. Maybe they tell themselves this happens with age. Maybe they just learn to ignore it. But when you have the quantitative data on body composition for an MRI and you can say to them, since your last scan, your muscle mass is down, your fat is up, and really your visceral fat is two standard deviations above what we expect to see in a person of your sex and age. And that is then associated with high risk of other things like diabetes, heart disease, brain degeneration. All of a sudden, the person can't look away from this, right? This is a quantitative deeply personal measurement that has real consequences for them. The most common thing we see as a condition is hpatic stytosis or fatty liver disease. This is known to impact about 38% of the American population. — Wow. — Of those 38% 96% of that 38% do not know they have it. All right. So that is a very big deal. And fatty liver disease is associated with type two diabetes is associated with the whole cardioabolic syndrome. It's also can actually cause cerosis on its own if it's bad enough. And there's more and more of this going around. So it is going to be a bigger deal in the future. And today most people don't know they have it. A 100% of people who come to Prouvo are going to know if they have it or not because MRI is exquisitly sensitive and essentially diagnostic for this. Technically speaking the gold standard is biopsy. I would say that is very rarely done if you have a good MRI because we can actually see the chemical fat shift and tell you not only if you have it but what percent is fat within the liver and then we can sort of grade the stattosis based on that and the converse is also true. So people see that and it has motivated a lot of people. These are direct relations like not just patients, tons of patients, but friends of mine that have come and gotten the scan who have then followed up and said that was super motivating. I saw my body composition wasn't where I wanted to be. I saw that I had paddic stastosis and I needed to get on top of that. And so that becomes then the catalysts for them making major changes in their lives. Sometimes it's lifestyle only, sometimes it's lifestyle plus pharmacologic. And I got to say I'm coming around on that, you know. So, this is part of my journey. I don't have paddic stoattoosis. My visceral fat levels, despite really making an effort to get into the gym well beyond the [clears throat] recommended amount and sort of eating almost a pescatarian diet, my visceral fat is still above average and I don't like to be in a spot like that because it's actually below average from a health perspective. For that reason, I am paying out of pocket for GLPS because Zetbound is known to reduce visceral fat. So, I have

a lot of friends who have either gone on GLPs or some similar type medicine in addition to lifestyle changes they've made. These are not medical recommendations for anyone. They should go out there and talk to their doctor. But there's a lot people can do these days is my point. So, I think back in the days when there wasn't as much data and the lifestyle recommendations were less clear. And this is not that long ago. I would say there was only so much you could do. And now you have great data. you have, I think, increasing consensus on what a healthy lifestyle is and what a healthy diet is. And then you have these extra things you can do that even if your genetic makeup or age group or whatever is making your metabolism not respond, there are now extra lengths people can go to try to get control of some of these things, whether it's visceral fat, muscular fat, or paddic stattosis. It does feel as though we're living in not just an AI revolution, but also some degree of a sort of a medical revolution right now with the number of tools that we have in the box to augment and manipulate our health. All of which I think as a secondary reminder to say it's never been more important to get preventative diagnostics considering there's so much preventative medicine that is now coming online. I mentioned the AI. It is the 500 pound silverback gorilla in the room. But tell me a little bit. I know you've thought a lot about AI in healthcare. I think you've got some of the most intelligent and but also very thoughtful ideas on it. How is AI changing what's possible in whole body imaging more specifically? And where do you see the field in five or 10 years? I know it's always hard because things either come at us much more quickly than we imagine or it's a much harder nut to crack and it takes 20 versus 2 years. Tell me a little bit about your thoughts of what's changing with whole body MRI with AI and where are we going? — Well, I'll just preface it by saying I was at a major imaging quality conference last week and got to hear some of the leading minds on AI. And one of the things that's striking about AI is people talk about Moore's law and how that sped up computing power. We were talking about this for most of the '9s and into the 2000s. At some point, I think Moore's law maybe stopped applying. It was always this anticipation, hey, the computers are great now, but they'll be even better in 18 months. And 18 months is never that far away. Well, AI apparently is doubling its capabilities every seven months. — So, so it really is this nonlinear and very exciting but also a little bit edge of our pants scary. I'll say that what it's already done is if you take a really experienced radiologist and they're reading an excellent best in the world type non-contrast whole body MRI scan. So, a prouvo scan that gets you a certain level of medicine, but it isn't quite what I would call radiomics. So this idea of attaching omix to something is what you do when you just have a massive amount of quantification going on that isn't possible at the human level. It has to be augmented usually by some sort of data acquisition tool that's technological but also an analytic tool and examples are things like genomics or metabolomics or proteomics if you're familiar with the basic sciences. There is a thing called radiomix and now there's whole body radiomix and we're doing it with this body comp product that I mentioned which we had cleared by the FDA last year and I think we've used it thousands of times maybe tens of thousands of times on individuals at this point and what this is doing is something a human being a radiologist could never really do in a realistic way. So, it's possible that if you had gotten your whole body scan, let's say last January, and you had a radiologist assigned to you, maybe if they spent like a couple days tracing out all your muscle and all your fat, they could have reported out this information to you, but it would have been mind-numbingly boring for them to do that. Like, they may have quit, but also it would have been super expensive for you to get that done. You'd have to pay full radiologist wages for like a week or a month or something. AI can do this once the radiologists train it, right? AI can do this in a click. We're talking about milliseconds and then you know the hardest part is QCing it and making sure everything went well with the calculation because there is a small failure rate but something we have to look at. So it doesn't always work but it works at this point greater than 90% of the time. We're able to report out on this information for people and we don't make the products but similar products are used for the neuroquantification that you referenced before measuring all the different areas of your brain such as the hippocampus and the various different loes and comparing them to what they were in the same person or what they are in age and sex match individuals and height adjusted individuals. So these data points are new data points and it's radiomics because we're using analytics to produce data we couldn't produce before and

there's just going to be so much more of this on down the line and we're developing a lot of these things internally and we're excited to see what the impact on human health is going to be and that's why you need to have AI not only to produce the information but to deal with all the information. So I see a future where the baseline is not only prouvo scan it's certainly genomics it's probably a number of other biomarkers as well and then the periodic testing is some amount of MRI maybe other modalities certainly additional things like metabolomics proteomics etc. This is a massive amount of data and the average practitioner will be lost in it and sort of unable to be effective without AI to help glean the most valuable insights, the most valuable patterns and bring them to the patient. And the goal of the physician increasingly becomes cognitive and partnering with the patient to figure out how to use all this information, not just sit there and identify patterns essentially. So broadly gathering data using AI analytics to find the patterns and then using the human being to walk that journey with the patient figure out what's relevant to them and how they can use that to live longer or better or however they want to live. And the last thing I'll say is the data availability is something AI is going to really turn the knob up on and it's already done it. We are able to do our scan today between 40 and 50 minutes on average and it was a little bit over an hour if you went back two or three years in the past. And that difference is almost entirely due to what we call casebased compression. So these are AI algorithms that the device manufacturers have created and gotten cleared by the FDA and it lets you get the same quality image in a shorter period of time. And so if we continue to see AI move forward, we would expect that scan time to come down even more. And then it gets really exciting because essentially what these AI algorithms are doing in case is it's making it easier to get more signal no matter how much noise you have present. It's possible that you might be able to do whole body MRIs in the future at even lower field strengths. And what that might mean is in 5 10 15 years you walk into a prouvo you lie down on a table you don't even have to get in an MRI maybe you're lying down for five minutes and we're getting the same information right so think then about what that does with cost access what that does with anxiety right it makes it even easier to come upon the information and then it gets wedded in AI space with all the other types of information that you might get genomics proteomics, etc. And then that's all brought home to you by your doctor who has the benefit of AI to sift through all that information and help you decide what you want to act on. That's the type of medicine I want. You know, I'm getting up there in years, right? I want to get ahead of things. I want to be able to swim in a vast sea of data with really smart AI to help me figure out what I need to be wary of within that vast sea. What actions I want to take in the next three months or 6 months or 12 months. — It's such an incredibly exciting future. You know, just that idea that you mentioned there for people who don't know when we speak about field strength within MRI, this is sort of how powerful this magnet is. the sort of big donut like shape that you get slotted inside of and there's different strengths of magnetic field and the stronger the magnetic field typically as long as you can deal with some of the noise the better the image but what you're saying there is that AI may even be not just from a software perspective beneficial but in terms of a hardware designing perspective we may be able to need a lot less strong magnetism to get the same resolution such that you wouldn't have this big donut, which is a wonderful thing to slide into. You could be on a table. I mean, this is the stuff, you know, of science fiction, but with AI, it may be science fact, not too far in the future. I want to be really mindful of your time, Dan. So, I'm going to ask just one last closing question, which is a takeaway. If someone's listening and is intrigued but let's just say unsure about PNO, what would you want them to understand about what PNUo offers and why it matters? Prenuvo offers the opportunity to get ahead of potential health risks that you may not know that you have. And while we don't replace primary care and other screenings, we can find things that they don't and we can take you beyond the level of reassurance that you get in your current medical paradigm and bring it to a different level. But we're also here to answer questions about it. This whole talk might have raised as many questions as it answered. So they can always reach out to us. They can email the website. They can speak with our staff and they can look on the website to understand

more about the scan. It also has information on there about patients and their journeys. It has information about physicians and patients they've helped. who are patients, right? So, I think if they don't know anyone in their life who's had the experience, which is still probably the case for most, going this at the testimonials can be quite powerful. And so, that's what we would recommend. And like I said, we're happy to answer questions and folks can always reach out to Bruno and we will do our best to answer their questions. H Dan, this has been genuinely illuminating. You're so good at explaining things. When you interview people, I think sometimes as scientists and medical doctors, we forget that it's so hard to disabuse ourselves over our knowledge and return to the naive state so that people who aren't of that educational direction can still understand. You do it so well. I don't know if you know that or not, but I'm telling you, you're fantastic. So, thank you so much for spending a significant part of your day with me. It's been absolutely fascinating for me. Thank you so much, Dan. — Thank you, Matt. Very flattering and it was super fun to do and I'll come back whenever you want me. — We would love it. And for listeners, I will provide links to Preuvo in the show notes. And as I mentioned in the introduction, PNUO has been so good. They have offered a $300 discount for listeners of this show. All you need to do is go to prenuvo. com/mattwalker and there you can find your $300 discount code. Dan, again, for all that you do in the world and for the many lives that it's hard because it's a preventative tool, but for the many lives that you will save by way of your preventative practice there at PNUO. Thank you. And I mean that very genuinely. — Thank you. It's our pleasure and our privilege. and thank you for helping us get the word out. We deeply appreciate that, Matt. — Thank you, Dan. As ever, folks, sleep well and perhaps from an imaging perspective, I hope you get the chance to see well, too. We will see you in the next episode. But for now, take care. Thanks for listening. Bye for now.