Nick Engerer 19/4/20 Nick Engerer 19/4/20

Full body MRI screening technology - Interview with Health Nucleus Part 3

In this post you’ll learn about:

The power of Health Nucleus MRI algorithms (e.g. early detection of brain aneurysms or quantifying visceral fat levels)
Same examples of how multiple Health Nucleus visits enable deeper personalised analytics
How the Health Nucleus is prevention focussed, rather than on optimisation (but that’s a good thing!)

Part 3 - MRI analytics & health optimisation

Be sure to read Part 1 and Part 2!

Longevity Blog (LB):

Q: What kind of data will you be pulling out of the MRI scans? Besides the heart analysis and some of the cancer detection, which we already discussed. What will be showing up in that data and what will you use it for?

The blood vessels of my brain as revealed by Health Nucleus MRI data. Aneurysm free and healthy :)

Dr Duchicela: I think primarily it’s used for detecting the big things that we don’t want to miss that we really want people to know about early on, so things like cancer or aneurysms. With the post processing that they do on it, they’re able to reconstruct vasculature and vessels to look for aneurysms, even without using contrast which i think is really neat.

And then we have these different imaging biomarkers, so for Alzheimers we do hippocampal volume assessment where we look at the volume of the hippocampus and the ventricles surrounding them, and essentially see how do you compare to a healthy peer group? Are you a little bit lower or a little bit higher in these volumes, which correlates with Alzheimer’s risk. That’s one aspect.

At left, my visceral fat levels are highlighted by Health Nucleus MRI algorithms. Visceral fat is known to increase with age, and increased levels are risk factor for many diseases.

With MRI we also get the body composition like visceral fat levels, liver fat levels, liver iron levels, and muscle composition. What we’re doing with the MRI data is essentially training algorithms to better detect the sorts of cancers that traditionally you can’t detect with a non-contrast MRI, one we are working on right now is pancreatic cancer. We’ve developed a screening tool to use in MRI for pancreatic cancer and we’re in the process of validating it which is really really exciting. But that will just add to the overall comprehensiveness of the scan and of the experience, so yeah there’s lots of different things we get from the MRi, it’s pretty amazing how much data you can get from it and how much you can start to train these algorithms.

LB: Diving deeper into MRI analytics - I have a full body scan from May 2018, I’m soon to have another scan from January 2020, and plan to continue to do these scans every 12 to 24 months depending on my travel schedule, so you’re going to get a bit of a time series going with the data.

You’ve talked about disease risk and obviously we’ll keep assessing those things but in terms of somebody who’s trying to optimise, like myself who’s a bit of a biohacker or maybe an athlete who’s thinking about their performance and their muscle composition…

Q: What kind of optimisation intelligence could we derive from MRI data over time?

“If you come back multiple times, year to year or every two years, we can trend many things and see how you’re doing. ”

MRI analytics of muscle mass. At left, my colour coded leg muscle groups in May 2018. At right, January 2020. I added 1.3L of muscle mass during that time. Note: the pictured images are from a slightly different ‘slice’ of the data. — MRI analytics of muscle mass. At left, my colour coded leg muscle groups in May 2018. At right, January 2020. I added 1.3L of muscle mass during that time. **Note**: the pictured images are from a slightly different ‘slice’ of the data.

Dr Duchicela: I would look at the imaging biomarkers, looking at the visceral fat measurements and subcutaneous measurements that we get and quantifying and trending that. The scanner software automatically marks out where your subcutaneous fat is, where your visceral fat is, we can trend your liver fat measurements, your liver iron measurements and then obviously your muscle composition too and where you’re distributing your muscle.

If you come back multiple times, year to year or every two years, we can trend many things and see how you’re doing. Some people, even if their metrics are “within a normal range”, they want to get them better, and so when you have such an accurate test like the MRI you’re able to make that quantification, you’re able to make those comparisons versus for example other machines out there that measure your visceral fat too and kind of trend it, but really MRI is pretty darn accurate for that and one of the most accurate assessments available, so if you really want to know the numbers and get that in addition to your cancer assessment and your aneurysm assessment, I think MRI is the way to go.

LB: That’s really spot on in terms of the answer I was looking for, one thing I’d like to prompt you on…

Q: Is there opportunity to analyse the strength or flow volumes of the heart from your MRI data?

Have you read the Longevity Blog post on how the Health Nucleus dives deep on heart health?

Dr Duchicela: We can see that your ejection fraction or how much blood you’re pumping out of your heart changes over time, now the question is does that actually translate into performance increases? We don’t necessarily think so for healthy individuals, because there’s lots of other things, like how fast your heart rate is going etc. So I would say not yet, I see where you're going with the question in terms of, could it be used to measure and trend athletic performance, not only for elite athletes, but for lay people who want to really maximise their athletic performance. I don’t think we’re there yet and I don’t think that’s necessarily the overall goal of this test. I think there’s a different series of tests that probably could do better than just the MRI for athletic performance trending and monitoring.

LB: Q: Are there any unique Health Nucleus tools that could be applied to assessing athletic performance and/or optimisation?

Dr Duchicela: I think with genetics we’ll start to get more information on that. There's already genetic predispositions to things like muscle tissue fibers and that sort of thing. What I would want to do as a medical director is to try to delve more into that and gather information on athletic history and get these metrics like VO2max and mile time etc and then start to work with the genetics to see if there are any predictors where we could make some correlations. That I think would be really exciting to do at some point in the future.

“I’m really excited what we have in the pipeline with this sort of scoring ... incorporating that with the coronary calcium score and putting it together and getting a global integrated risk score”

LB: Yeah I agree with you that it would be very exciting, and again it’s not your current focus, but I was curious to ask a few questions on the topic of optimisation, so thanks for that.

One of my big outcomes from my last visit to the Health Nucleus was a ‘prescription’ for cardio exercise and to increase my muscle mass on direct guidance from one of your doctors. I took that exceptionally seriously and have been dedicated to cardio fitness routinely since that time. So I’m really curious what you think might be evident in terms of one’s biometrics and data coming from their visit to help one measure their improvement in fitness over time.

Q: You’ve talked about MRI, and a bit about genetics, what else in there might show up in this visit compared to last time if I’ve done a good job at that cardio and exercise routine?

“ the best areas to look for changes and improvements would be in your imaging biomarkers, your core lab tests for metabolic biomarkers, lipids, a1c and fasting sugar. ”

My blood lipid panel over time; some great changes in between my first Health Nucleus visit (May 2018) and my second (January 2020).

Dr Duchicela: Yeah we’ve already mentioned the imaging biomarkers like your body composition, your liver fat level, those will definitely change with lifestyle change for sure, and then I would look at your traditional blood markers. You’ve probably already been measuring those, but making sure your [Hemoglobin] A1c is good, as well as your fasting sugars and your cholesterol numbers. In terms of trending data, that’s the kind of metabolic panel we would do. We can’t trend genetics so much, so I would say the best areas to look for changes and improvements would be in your imaging biomarkers, your core lab tests for metabolic biomarkers, lipids, a1c and fasting sugar. That’s where you’d probably best be able to see improvement and change.

LB: Cool, thanks for diving into that. And in terms of the genomic data that we’re pulling out, Q: what information in there will be actionable for somebody who wants to optimise? There’s examples of the ways you might metabolise certain precursors to vitamins, such as not being a good converter of beta carotene to retinol in the blood or the MTHFR mutation for methylation.

“It’s probably too early to hang your hat on these variants that tell you to eat a certain food or to do something very specific in terms of lifestyle unless you have one of these obviously high risk genes”

Dr Duchicela: Yeah I think that’s kind of the challenge with the genetics, the focus of the company from what I’ve seen so far is more on the hidden health risks with these high risk cancer genes, high risk cardiovascular disease genes or neurodegenerative disease genes.

In terms of optimising genetics, from what I’ve discussed with the clinical geneticist here and the genetics team, It’s probably too early to hang your hat on these variants that tell you to eat a certain food or to do something very specific in terms of lifestyle unless you have one of these obviously high risk genes, these monogenic findings. But I think it’s an area of consumer interest, what we're hearing from a lot of people is they want more specific lifestyle modifications based solely off genomics. I think that our genetics team needs to be a little more convinced that there are really good actionable things there.

It’s also a matter of prioritisation of where we put our resources, do we want to be more of a lifestyle service versus more of a medical service that’s catering towards physicians and the medical community? I think we’ll always have tension on where the focus should be. Right now the testing is looking for high risk medical issues that we can intervene on, like is there a BRCA mutation or a gene that puts you at high risk of colon cancer?

I am curious to know and to see where the science takes us with more of these lifestyle influenced variants, but i would say for right now for our testing [optimisation] is not one of the big focuses - we really want to try to prevent disease first and build off of that and then delve more into and put more resources toward lifestyle genomics.

LB: I think that that focus area is apparent from the way your suite of testing and reporting is arranged. In my view, everybody needs to be taking advantage of these proactive aspects of medical technology before thinking about health optimisation. You’ve got to take care of the core risk and any acute issues first, in order to maintain your wellness. So I don’t think that focus is misplaced at all. It’s intriguing to hear that your team is interested and noting increased demand for this sort of individual attention. I certainly think that that’s a growing market as well.

“what is the patient’s goal?”

Dr Duchicela: Totally. There’s a lot of companies out there that will do some direct testing and tell you exactly what to eat or avoid this food based off of you having this variant. I think we want to be a little bit more careful with that just because you really have to look at things holistically. I don’t think we really want to say - stop eating cucumbers based off your genetics, we really want to take into account what the patient’s preferences.

Like i was mentioning before with the wine example, really what is the patient’s goal, is their goal to have a super restricted diet so they can live forever, or is it to enjoy time with their family, or to be able to do a certain activity better, so I hesitate to hang everything onto genetics and dictate lifestyle just based on your genetics. We really want to develop something that's more holistic.

LB: That’s where the physician comes into the picture - in having a relationship with them that’s ongoing and aligned with your personal goals and values. I think it’s excellent you’re even mentioning personal values and thinking about them as a physician.

One of the things I think is totally rad is that - I’m sitting here interacting with you, I’m going to be talking to a doctor and several team members on my visit next week - Q: I was curious if you could remind me of how many medical professionals will be interacting with me directly or with my data as an outcome of my Health Nucleus visit?

I’ve split this interview into FOUR parts, due to its length! Part 4 will drop next week!

Previous Posts: Part 1 - Part 2

Follow-up Posts: Part 4

Note: the Health Nucleus has recently appointed a new Medical Director - Dr. Pamila Brar. Dr. Duchicela has transitioned to a role as full-time physician at the Health Nucleus, working directly with patients to optimise their healthcare!

FDA & TGA DISCLAIMER

This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.

Nick Engerer 12/4/20 Nick Engerer 12/4/20

Screening for cardiovascular sisease with MRI and CAC - Interview with Health Nucleus Part 2

In this post you’ll learn ABOUT:

Health Nucleus tools for assessing cardiovascular disease risk
The role of the Coronary Artery Calcification (CAC) score in assessing risk, particularly for younger people (30s, 40s)
How CAC scores might influence statin use
The limitations of MRI data in assessing risk
How genetic risk factors might influence risk
Combining imaging data, genetic factors and blood tests to further clarify risk

Part 2 - Cardiovascular disease

Be sure to read Part 1!

Longevity Blog (LB):

We’ve talked a little bit about cancer. Another big killer whose risk is a function of how old you are and a number of genetic factors is cardiovascular disease and in particular atherosclerosis.

I understand my risk as a man in his thirties is low for an acute event now, but the disease risk grows with time as the result of a decade on decade buildup of plaque, inflammation and wear and tear on the arteries…

Q: So how does coming to the Health Nucleus help inform someone about how their risk might change as they get older? What could a young person do using this information to minimise their risk of atherosclerosis and cardiovascular disease?

Coronary Artery Calcium Scoring. Credit: Cleveland Clinic

Dr Duchicela: Yeah that’s a great question. So in terms of cardiac assessments, one of the most powerful ones that we do here is the coronary calcium score. This is looking at calcified plaque buildup in the arteries of your heart. Essentially, the more plaque you have the higher your risk is of a heart attack.

You’re right, for someone in their thirties, who’s young, who is otherwise healthy, the chances of you finding plaque are low. Based on the general standard of care in the community, we wouldn’t be getting a coronary calcium score on somebody who’s 35 years old or younger. But here, because we’re under a research protocol, we have a little bit more leeway to push the boundaries in terms of testing in groups that may not otherwise be traditionally tested.

“we’re finding that actually about 15 to 17% of individuals around the age of 40 to 45 or younger actually have significant plaque build up. ”

And so for the coronary calcium score for example we are able to do it on a 35 year old, or 36 year old and we’re finding that actually about 15 to 17% of individuals around the age of 40 to 45 or younger actually have significant plaque build up. So we are probably missing a good amount of people out in the community who have atherosclerosis and calcified plaque in arteries of their heart which will predispose them to heart disease.

So when you come here to Health Nucleus and you if you meet the age requirement of 35 years or older (that’s what do here for the coronary calcium score), you’ll see what your plaque level, your score is, and then we will compare you to other people your same age and gender. So you get a sense of how you stack up to a healthy peer group as well and based on that, we take that into account with your cholesterol numbers and so, let’s say you have high cholesterol numbers, your LDL is elevated and your doctor is trying to push you to be on a statin or a cholesterol medicine.

If you get a coronary calcium score and your score is 0, there’s no calcified plaque seen, then you actually have a pretty good case to make that you shouldn’t be on a statin just yet . A lot of men and women come through here and their doctors are pushing and pushing them to be on a statin because their cholesterol is on the higher side, and we scan them and we get their coronary calcium score and it’s zero or very low that actually is pretty powerful in that it makes it not as urgent to be on a statin and you can talk more about lifestyle modifications and the diet, the exercise and maybe hold off on that statin for awhile longer.

A lot of men and women come through here and their doctors are pushing and pushing them to be on a statin because their cholesterol is on the higher side, and we scan them and we get their coronary calcium score and it’s zero or very low

LB: That’s a really clear answer Keegan, thank you for that.

Q: Could you comment a little bit on what the Health Nucleus can do with the MRI technology in terms of cardiovascular risk?

My heart beating, as observed by the Health Nucleus full body MRI scan and post-processing technology.

Dr Duchicela: For heart attack risk you get most of the assessment from the CT scan and the coronary calcium score. From the MRI what we’re doing is more structure of the heart so this is like what the chambers look like, how large the chambers are, or if they are hypertrophied or thickened because of high blood pressure or if it’s not pumping as well as it should be, like the ejection fraction is low because of early congestive heart failure or some sort of other heart failure. That’s what we get from the MRI. The MRI is more structural. It can find congenital abnormalities of the heart sometimes too, where as the CT scan, the one that involves a little bit of radiation, that is more for heart attack risk.

LB: That’s a good differentiation. Thanks for taking the time to answer that. And so in terms of a young person coming in, you’ve mentioned this kind of threshold of 35 years or older to do the calcium score, I don’t meet that criteria quite yet, but I’ll certainly do it when I get to that point.

Q: What other Health Nucleus tools can sit alongside the diagnostic imaging tests (MRI, CAC score) which can help a young person evaluate their lifetime risk of atherosclerosis?

Have you read the Longevity Blog post on assessing your cardiovascular risk?

Dr Duchicela: In terms of genomics, there are some genetic markers that predispose you to very high levels of cholesterol, that would be picked up not only in the blood screen testing, but also in the genetic testing.

Let's say you're twenty years old and we’re not doing a coronary calcium score, what we would use instead to help predict your overall risk would be the blood test, the lipid panel, your other metabolic markers like your haemoglobin A1c, your fasting sugar. And then from the MRI we’d be looking at your body composition, visceral fat deposition, visceral fat level. With MRI we’re now actually able to quantify pretty accurately your visceral fat volume and compare you to other people your same age and gender.

So those things would build into this risk profile, and then the traditional things like how much you drink, how much you smoke, how much sleep you’re getting, if you have signs of sleep apnoea. Even thirty year olds have sleep apnoea now, so those sorts of things all help build a risk profile for young people if you don’t have let’s say a coronary calcium score.

LB: Right and in terms of the genetic analysis, besides being predisposed to familial hypercholesterolaemia or other acute high LDL cholesterol genetics, Q: Is there another set or group of markers that you might be looking at at an early stage that can show someone’s risk?

Polygenic risk scores from my own Health Nucleus genomic report.

Dr Duchicela: What we currently have is a polygenic risk scale that tells you your relative risk. What we do is we look at gene variants that are more present in groups or individuals that have for example coronary artery disease, or who have had heart attacks and then we see if you share those same gene variants, there are weights given to each of these gene variants, and then you come up on a scale of low, medium or high risk.

“I’m really excited what we have in the pipeline with this sort of scoring ... incorporating that with the coronary calcium score and putting it together and getting a global integrated risk score”

But we’re not able to give specific numbers just yet, other than relative risk or absolute risk just because our dataset wasn’t large enough to do that. But what we’re developing right now, you’d essentially get a polygenic risk score or polygenic risk assessment that takes into account these genes associated with familial hypercholesterolaemia, but also other ones that on their own don’t dramatically increase your risk, but in aggregate if you take 20 or 30 of them together they can tilt you one way or the other.

So that’s actually the really exciting part, using polygenic risk scales and scores and building those models out. And we’re just at version one of this I’m really excited what we have in the pipeline with this sort of scoring and also incorporating that with the coronary calcium score and putting it together and getting like a global integrated risk score. So that's where we’re headed, but right now I’d say these polygenic risk scales can tell you you’re a little bit more like people with heart attacks or you’re a little bit less like people with heart attacks but it doesn’t give you an actual number just yet.

LB: That’s really clear and you’ve mentioned version one a few times so it’s clear that one of the things we need to do is get more and more people to come through the Health Nucleus and share their genetic information and family history etc.

One of the things I get really excited about and really enjoy in my visits to the Health Nucleus is going into the MRI machine. I think that’s one of the coolest things you guys do, I love picking the scene, the light color, the music, the things to look at. It’s really awesome.

Q: What kind of data will you be pulling out of the MRI scans and what will you be using it for? Besides the heart analysis and some of the cancer detection, which we already discussed. What will be showing up in that data and what will you use it for?

I’ve split this interview into FOUR parts, due to its length! Part 3 will drop next week!

Previous Post: Part 1

Follow-up Posts: Part 3 - Part 4

FDA & TGA DISCLAIMER

Nick Engerer 4/10/19 Nick Engerer 4/10/19

3 Technologies for Monitoring Heart Health

Three heart health technologies looking after your ticker

Monitoring heart health is a top priority. When it comes to listing your vital organs - those needed most for your overall well-being and the joy of being alive, the heart comes up at the top of the list (along with your brain, liver, kidneys…).

It should be at the top of the list for all longevity enthusiasts keen to look after their long-term health. But what technologies are accessible and valuable for this purpose?

Heart Health and the EKG

Health Nucleus EKG results for Nick were all fine and dandy!

An EKG is short for ‘electrocardiogram’. The EKG is on the frontlines for assessing heart health, and is particularly valuable in the case of an ongoing heart attack.

An EKG is completed by checking the electrical activity of the heart by attaching several small sticky electrode pads to your arms, chest and legs.

The EKG provides the following information:

Analysis of blood flow to your heart muscle
The electrical signals of heart rhythm
A first line of detection for abnormalities
Detect electrolyte imbalances

What’s fascinating about EKGs is how accessible the technology has recently become.

Perhaps the biggest impact on accessibility of this test has been made possible by the Apple Watch, for which Series 4 and above have EKG capabilities

But the Apple Watch is not alone! Several other ‘test at home’ technologies are also available. “Emay” is another technology brand which has entered the space.

They have an impressively compact and slick device, which we personally prefer over the Apple Watch due to its lower cost and dedicated function (does an iMessage on your wrist help your heart health?).

Don’t get confused about the “ECG” term, EKGs and ECGs are the same test.

Heart Health and Cardiac MRI

In an earlier post we discussed the merits of full body MRI and cardiac MRI.

Example of Nick’s cardiac MRI findings. Note the very particular measurements of the heart anatomy.

MRI stands for magnetic resonance imaging. A heart or cardiac MRI looks into the structures of the heart and its neighbouring blood vessels in great detail.

A Heart/Cardiac MRI is used to diagnose/check for:

early signs of heart disease
assess the the heart for any signs of damage
detect any imminent heart failure or defects
assess inflammation of the membrane lining the heart

While you certainly can’t perform a cardiac MRI at home, you can work with organisations like the Health Nucleus or a specialist to have these tests completed.

Heart Health and THE ZIO

heart-rate monitoring.jpeg — Wearing the Zio

Two weeks of detailed heart-rate data, under all conditions - exercise, rest, day-to-day activity. Including tracked events where Nick pushed the button for closer inspection in the report (see below).

As a part of Nick’s preliminary Health Nucleus visit, he was sent away with a small stick-on device called a ‘Zio’ that he wore for two weeks.

The Zio watches heart-rate in great detail and and includes the ability for the user to track events of interest by clicking the device.

Nick noted he ‘clicked’ the button on a few events where his heart-rate seemed to pick-up and beat hard after lying down in my bed.

He’d actually noticed these events for most of his adult life, and had passing concern about what that indicated about my heart/body health.

Those events have now been analysed in great detail and revealed no underlying heart driven worries.

The Zio device is attached with a gentle adhesive which did not cause any skin irritation.

Beyond having to ‘bag’ the device in order to take a shower (covering it with plastic and tape), it is a very easy device to manage.

Notes from Nick: “Those ‘Black dots’ are regions where I clicked the button for closer inspection. These were events where I noticed my heart-rate seeming to pick-up, or be more noticeable after lying down in my bed. I’d noticed these my whole life … — Notes from Nick: “Those ‘Black dots’ are regions where I clicked the button for closer inspection. These were events where I noticed my heart-rate seeming to pick-up, or be more noticeable after lying down in my bed.
I’d noticed these my whole life - now I know they have no underlying heart driven worries and can rest easy :)”

iRhythm-overall stats.png — Zio IRhythm overall report after two weeks

Nick’s Zio report. 175bpm during an intense workout. 52 bpm minimum recorded during the overnight.

Full body MRI screening technology - Interview with Health Nucleus Part 3

In this post you’ll learn about:

Part 3 - MRI analytics & health optimisation

I’ve split this interview into FOUR parts, due to its length! Part 4 will drop next week!

FDA & TGA DISCLAIMER

Screening for cardiovascular sisease with MRI and CAC - Interview with Health Nucleus Part 2

In this post you’ll learn ABOUT:

Part 2 - Cardiovascular disease

I’ve split this interview into FOUR parts, due to its length! Part 3 will drop next week!

FDA & TGA DISCLAIMER

3 Technologies for Monitoring Heart Health

Three heart health technologies looking after your ticker

Heart Health and the EKG

Heart Health and Cardiac MRI

Heart Health and THE ZIO

Wearing the Zio

Zio IRhythm overall report after two weeks

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