We will talk today a bit about how we can get different images of the heart to tell us different
things about what's going on inside the hearts and not just looking at heart anatomy and function,
but also looking at what's going on inside the heart cells to detect different types of cardiac diseases.
So cardiovascular disease is one of the major causes of death in the UK unfortunately.
So we have quite a few cases of cancer leading to death, 28% of death attributed to cancer.
But just shortly after that, 26% attributed to cardiovascular disease.
And that's things like myocardial infarction, heart failure and such like.
So it's very common. So heart attacks, everyone has heard of sudden, sudden pain in the chest,
calling 99 and and heart failure as a more kind of slow progressive disease and why there are imaging modalities available to detect those.
There's still a lot of improvement to be made to really get the right treatment for the patient because
we're moving more and more towards personalised medicine where it's not one shoe fits all sort of approach,
but more what is actually happening in this person and what is the best treatment for this particular person.
And we need good imaging to to to choose basically what we do.
So this is just very simple sort of cartoon images of the heart, just so that everyone knows what we're talking about.
So that's sort of showing the heart from the outside with the aorta as the major vessel in the heart that pumps the blood around the whole body.
And then the blue thing here is what brings the deoxygenated blood into the left and right lung for oxygenation.
And if you take a cross-section through the heart, we can see inside the heart. So this is the right chamber of the heart, the right ventricle.
And that pumps blood through this pulmonary artery into the lungs for oxygenation.
And this is our left ventricle, the left chamber of the heart, where we get blood, blood pumped through the aorta, into the general circulation.
So for the rest of the body.
And the question is, I don't know how many people know really exactly how the heart works and how that gets pumped around.
But you can sort of compare that to a mechanical pump.
So fluid flows into through one pipe and then does mechanical pump, turns it around and pushes it out.
Another pipe. Right. And if you now look at the heart, it's not that dissimilar.
So we have blood that comes through through one pipe and then gets pushed through another pipe, and that happens by muscle contraction.
So our mechanical pump here is the heart muscle itself keeps beating throughout the lifetime just
to make the circuit complete so that we get deoxygenated blood into the lung for oxygenation,
back through the left atrium, into the left ventricle, and out through the aorta, into the rest of the body.
And that just keeps going and keeps going and keeps going. And one way of looking at dysfunction in the clinic is with echocardiography.
So that's an ultrasound of the heart. It's reasonably cheap, very widely available.
And you can see some sort of blood movement across these different chambers here.
But the images aren't that great and it's mostly 2D. So it doesn't really give us that much information about what's really happening in
3D and not really much sort of information about the actual cells in the heart.
One other very powerful technique to look at the heart with is magnetic resonance imaging and this different
approaches using this machine to to give different information about what's going on inside the heart.
And this is what I'm now going to hand over to Justin, who will talk a bit more about MRI and then I'm back.
Yes. So just not being biased. MRI is one of my favourite imaging modalities.
I also work on it. So so with MRI, what you can do is you can actually acquire any kind of cross-section through the body.
So you can acquire slices that are kind of like this.
You can acquire slices that are centred. And so in the heart, what we usually do is we try to align to the natural axis of the heart.
And so here, this cross-section here, that's what we call the short axis.
And that's usually the most common way of looking at the heart with the MRI images.
So so the this cross-section here shows the two chambers to two lower chambers.
So you see the left ventricle here and the right ventricle here.
And because left ventricle has to work hard to pump the blood to the rest of the body,
whereas the right ventricle just has to pump the blood to the lungs.
So the left ventricle is more muscular. And that's characteristic of how hard the heart that the different parts of the heart have to work.
And so the heart has is contracting and relaxing, contracting and relaxing.
And so when it's fully relaxed, we call that diastole. And this is kind of representation of when the heart is fully relaxed.
So the the left ventricle, the wall is very thin, whereas when the heart is fully contracted, that's called systole.
And that's where the left ventricle has squeezed to its maximum position to expel as much blood as possible to the aorta and to the rest of the body.
And so the difference between the fully expanded and the fully contract.
It states that's called the ejection fraction and that that represents how effective the heart is at pumping blood around the body.
So the higher the ejection fraction, the more efficient the blood at the heart is pumping the blood.
So in MRI, what we look at is this cross-section.
So we look at the health of the left and the right ventricles.
And you can tell if the left ventricle in particular is thicker than usual, then that indicates that it's working a lot harder to do the same job.
And so that could indicate early an early sign of heart failure. And so I'll switch quickly to the the video, which is on the desktop here.
So here we have a four dimensional view of the heart.
So, so here we have the the heart going from the top to the bottom.
So from the what we call the base at the top near where the aorta comes out.
And then we move down the heart along its natural axis of symmetry, down to the bottom.
So here that's the top of the heart.
And as you move down, you see the the left ventricle here in the circular shape and then the right ventricle here on the side.
And then as you move towards the apex of the heart of the bottom of the heart,
you start to see the the chambers getting never work as the heart is kind of a bit of a cone shaped.
And then here you can see that the bottom of the heart.
And so so just as a reference, if you take the other plane, which is which we can do easily with MRI,
if you take the other cross-section, kind of like cutting through the heart the lot the long way.
So this is the top of the heart. So that's that corresponds to this image here.
And then this is the bottom of the heart. So as you go down from the top to the bottom, that's where we're going from this from left to right.
And then here that's towards the bottom of the heart. So it's so this apex here.
And so this is a relatively healthy heart.
So you can see the the walls are contracting, the left ventricle in particular, so that this round part here, it's contracting uniformly around.
So it's doing quite well. And that's pretty typical of of a healthy person.
So now we will look at what happens when you have a heart attack.
So so heart attacks happen when one of the arteries that supply the heart itself becomes blocked.
So the heart requires a lot of blood in order to continually contract it and expand.
And so the blood flow that gets diverted from the aorta into the heart.
And so there's branches of arteries that sometimes can become clogged.
And if there's a blockage, then that part of the heart no longer receives blood and it can become injured.
And so usually the symptoms are chest pain and shortness of breath.
And that's when you call nine and nine. And so the ambulance will take you to the John Radcliffe Hospital.
And then we can do imaging on the heart.
And so, again, I'll switch to the videos just to show you what the heart looks like after a heart attack.
So here you can see. So this is the left ventricle and this is the left atrium.
And what you can see here is the other video showed a nice ring that contracted and expanded,
whereas here you can see the side of the heart that's not really moving.
And also the top the left atrium that this is not really contracting either.
So the left left atrium usually is a lot smaller.
But here, because the left atrium is not as efficient at expelling the blood into the left ventricle,
and the left ventricle is not as efficient pumping the blood out of the aorta.
So there's a back pressure. So it really comes down to plumbing.
So there's this back pressure. And so that causes the heart to expand.
And so normally the heart can adapt is a very versatile organ.
But this is this is this can lead to heart failure if the heart becomes too over pressured.
So when it's working too hard to to to pump the blood around. And this is just another view.
So again, you see this bottom side of the heart is not really contracting.
So most of the work is just done on the top wall. And here as well, the left atrium.
This part is not really contracting. And so this is a bad sign.
And there are there are treatments to to hopefully restore some function to parts of the muscle.
Um, and so, um, next,
so I'm going to pass it back to Kristen and she'll talk about some new techniques that we can use for early detection of parts of the heart
that might be in trouble versus part of the heart that can recover so that we can give the most appropriate treatment to the patient.
So so far we've just talked about function, but unfortunately with a lot of diseases such as myocardial infarction,
it can take some time to really manifest itself as a difference in output from the heart.
So it takes some time until the heart is sort of scarred when you notice that
there isn't such a great movement of the heart muscle anymore on heart failure,
it takes quite some time for symptoms to manifest because the heart is very good at compensating.
So a better way of assessing someone's cardiac health would be to look a bit
more insight themselves and see what's actually going on on a molecular level.
And for that, we're very interested in cardiac metabolism.
So that means how the heart takes up different types of fuel sources and makes energy from it.
And that's essentially leading to for the heart to be able to contract for lifetime.
So energy generation through metabolism is incredibly important.
And it turns out that the heart to heart kind of likes all different types of food for energy generation,
but it preferentially uses a mix of fat and sugar with a slight preference for fat, but it needs that sort of versatility to really work properly.
So that's why I think showing a little a little scale, you know, you both need the fat and the sugar.
And if you now zoom inside the heart to a cardiac muscle cell.
So this is a heart muscle. So this green thing here represents the powerhouse of the cell, which is called a mitochondria.
This is where oxidative metabolism happens when you have oxygen available and you can fully burn fuel so that you can get
the maximum energy if oxygen is not available and you can't get that much energy out of fuel sources and in a normal,
healthy heart, we want to have, like we said, sugar in the form of glucose and also fat.
And all of the sugar metabolism goes through a key central metabolite pyruvate and that can lead either lactate or lactic acid,
which can be produced when there's no oxygen available,
when there's oxygen available and we can fully oxidise sugar and generate bicarbonate, which is sort of the soluble form of carbon dioxide.
So what happens is basically those fuel sources go inside the mitochondria and get fully oxidised, generate energy for a healthy beating heart.
Now, this picture changes slightly, like I said, when we don't have oxygen available.
So imagine there's no oxygen available because either we have had a heart attack
so this ischaemic myocardium or we're hypoxic because we had high altitude,
for example, even though we shouldn't go that high for that really to manifest itself in massively changed metabolism.
But yes. So what happens then is that basically we cannot use fat at work because fat goes right
into the mitochondrion and needs that oxygen very vitally for for for its metabolism.
It can't go via this pathway. So what we can do is use that glucose and chuck it into that lactic acid.
And I mean, acid is bad, right? Too much of it is fat acidify our blood.
It's not very good for us and certainly isn't very good for the myocardium either.
And it doesn't produce that much energy. So you can see from this animation heart doesn't pizza one so that's that's a bad sign and conversely there's
also scenarios where we could rely more on on on fat for energy generation and we can't use any glucose.
So there can be changes to the way that you take up glucose.
For example, if if we don't have enough insulin around like in a diabetic person, we don't have insulin.
We need insulin to get sugar into the cells. So if that's prevented, then we fully rely on fats and why we can oxidise them into mitochondria.
We don't get that maximum amount of energy that we would if we had both nutrients available.
So that's another sign that something's not quite right. So just to summarise, again, for metabolism, there's different diseases.
So in a in a myocardial infarction, we would rely more on sugar for anaerobic metabolism.
So no oxygen available, we generate acid, not enough energy generation and acid is bad.
If we have more energy requirements for sugar than fat, then we instead of heart failure.
So when the heart starts to fail, then it becomes less able of really using the fats efficiently.
And then when we are relying more on fats than on sugar, then we can have a diabetic heart.
So the diabetic heart again lacks insulin, can take up sugar as well, and relies more on on fatty acids.
All of those diseases are associated with inappropriate energy generation and that manifests itself in change function.
But the thing is that if you could catch that very early on,
so if you could see very early changes in fewer and fewer choice and how those fuels metabolised inside the cell.
And then there's a time when where we could offer some treatment to improve that
before we actually get those functional changes where you start becoming breathless,
you can't really do your normal day to day day life anymore.
So that's where the multidisciplinary effort comes in. So in our lab we have physicists, chemists, vets, medics,
all sorts of different people that put together expertise to sort of try to tackle this problem.
And Justin is now going to introduce a new technique that we can use to look at this metabolism inside the cells in a living person.
So and so normally in M.R imaging, you look at water because the water is the most abundant molecule in the body.
And so you can get nice images of structures like. How the heart looks.
But in order to look at function, we want to look at fuels such as sugars, and those are usually present at lower concentrations in the body.
And so what we would like to do is to increase the amount of signal that we can get.
And so this is governed by thermodynamics. And so thermodynamics says at body temperature, you don't really get much signal.
And that's why when you go inside a magnet, you don't stick to the magnet because we don't become strongly magnetised.
So the trick that we play is we would like to put the system out of thermal equilibrium in order to get up to 10,000 times more signal.
So how that's done is you can imagine the molecules as little bar magnets.
And so what we do is we put the bar magnets into a strong magnet, and that aligns the magnets either with or against the magnetic field.
And then we add some some electrons.
So that's kind of where the source of the additional magnetisation will come from.
And then we cool the whole thing down. So we cool it down so much that it's very close to absolute zero.
So just below one, Kelvin, we're not engaged anymore. Yeah.
So this is in. So this is in a machine called a polariser.
And and so what happens is all the electrons, suddenly they align with the magnetic field.
So they all point up. And what we want to do is we want the the molecules as well to point all point up.
And so we use microwaves to jumble up the system so that we, you know, we flip an electron, but then we flip a molecule up.
And so by doing this for about 3 hours, we can actually increase the amount of signal that we get.
And this is basically fighting against thermal dynamics.
But in the end, thermodynamics always wins.
And so we have to act quickly before the system goes back to thermal equilibrium and we lose all the signal.
And so what we do is we quickly melt it. And that's at and after we melt it, that's when we inject into the patient.
So just to give you kind of a an idea of how this process is done, we have a video of how we prepare the sample.
So this is the polariser. So this machine here, this is a strong magnet.
And what it's what we're doing here is we're about to insert the stick that has the hot water inside.
So this stick has hot pressurised water. And so the sample is inside.
It's very cold. And so when you stick the stick in and then you release the pressure,
the water goes in, quickly melts it, and then shoots it back up into the into the pot.
And then you have to act very quickly. So you run. So you take it into the syringe, you run and then you inject.
So you inject this into a person. And then what you can do is you can see the signal that comes out.
And that's that's that's a signal that we use to create our images. And so what can we get with this?
So we can get we can look at the different products of of the sugar.
So as Kirsten said. So this this pyruvate,
the sugar can either go down the the oxidative metabolism route so you get CO2
and bicarbonate or you can go down the non oxidative so you can get lactic acid.
So if we want to focus on looking at bicarbonate, what we can do is we can acquire signal.
So as as this goes between bicarbonate and lactate, we can look at the the various signals and luckily they show up at different frequencies.
And so they're like radio stations.
So what we can do is we can tune our detection equipment to the right station to look at the different products of of this metabolism.
And you can get images like this. So so basically what we're seeing is sugar.
So this image here being converted into carbon dioxide.
And so the sugar mostly shows up in the chamber because it's mostly in the blood, but it gets uptake in by the tissue as well.
And you can see here in this healthy subject, you see a nice ring of carbon dioxide.
And so this indicates that the heart is functioning nicely,
that it's contracting and very active and uniformly pumping the blood out into the rest of the body.
So where this will be useful is if we see a chunk without signal.
So if we see something like that, then we know that that part of the heart has has potentially lost its blood supply.
And so what we can do is we can try and restore that blood supply or we can decide if it's worth restoring the blood supply.
So we can we can tell very early on with this technique whether or not the tissue will recover.
And so that will help our cardiologists decide what to do with the patient to give them the best care that they can.
And so that brings us to the end. So that was just a very new technique of looking at the heart.
So if you have any questions, we'd like to answer them.