How high-tech computer modelling could stop harmful blood clots

The latest 3D technology is helping to create personalised treatments for people with atrial fibrillation and other conditions, thanks to the BHF, as Sarah Brealey reports.

Image of a 3D model heart

Dr Bosi's scan of a 3D computer model heart, showing the speed and vorticity (the way flowing liquid rotates) of blood flow.

Virtual hearts to help people with atrial fibrillation

‘Personalised treatment’ is a trendy term in healthcare. The latest advances in science, maths and technology are bringing it to life in ways that previously seemed impossible.

At University College London, Dr Giorgia Bosi is an engineer creating personalised three dimensional (3D) computer models of people’s hearts, thanks to funding from the BHF. Her aim is to stop harmful blood clots, which can cause stroke, heart attack and vascular dementia.

She is currently studying atrial fibrillation (AF), the most common type of abnormal heart rhythm. If you have AF, blood may not be pumped out of your heart properly, which means clots can form and be carried to the brain, causing a stroke. That’s why people with AF need to take anticlotting medication for life.

“I am trying to apply mathematical models to healthcare to improve patient safety,” says Dr Bosi. “Using scans and other patient data, I create a virtual 3D shape of the part of the heart that is relevant in that patient.”

1.26m people currently diagnosed with atrial fibrillation in the UK

Dr Bosi is looking at the left atrial appendage – the part of the heart where clots form in people with AF. “Depending on the shape of your left atrial appendage, you have a higher or lower risk of clot formation,” she says.

“I am trying to classify patients according to their level of risk, which could help us know which patients require which medication. I want to work out if there is a better way to treat them.”

Her computer modelling shows speed and vorticity (the way flowing liquid rotates) of blood flow. Both can affect the chance of clots forming.

Dr Bosi has applied these modelling techniques to replacement heart valves, too. Valve replacements can give a new lease of life to people with heart failure caused by valve problems. But replacement can also come with risks, such as leakage, raised risk of clots and heart rhythm problems.

She has published studies showing that computational modelling can show how different artificial heart valves will fit in an individual patient’s heart, how much the valve will open up and how blood will flow through it. And she’s shown that engineering techniques can tell us more about how the location of the replacement will affect the valve.

So far, these studies have been based on previous patients, using data collected before their procedure, then checking whether the predictions of the computer models were accurate. The next step is to use simulations before treatment.

“We call it ‘personalised patient care’,” says Dr Bosi. “It is a patient-specific way of looking at data. You could call it a virtual clinical trial. “You can calculate how a new device will work in the patient to help the clinician make a decision. But also you could test and improve new devices with this modelling. That could reduce the work involved and the animals used in studies. “This technique could be useful for a lot of other things – stents for coronary arteries and brain aneurysms, and repairs for aortic aneurysm.”

There are still relatively few people working in this new field of research. “The BHF is one of the few funding bodies that have a real vision for this technology,” says Dr Bosi. “It is nice to be one of the people working in this niche. This is lifechanging technology.”

Professor Gibbins' team created a computer generated platelet model. The colours show chemical signals moving through the platelet (red is high concentration, blue is low).

A virtual platelet

Professor Jon Gibbins, an expert on blood clotting, is using computer simulations to see how platelets work and stop dangerous clots. He’s leading a team at the University of Reading, creating a virtual platelet to improve our understanding. “If you cut yourself, platelets will stop you bleeding,” says Professor Gibbins. “But if they work in the wrong place, they can cause heart and circulatory diseases.”

Professor Gibbins has devoted his life’s work to platelets. When these tiny cells clump together to form a clot inside your body, it can take a dangerous turn, leading to a heart attack, stroke and vascular dementia.

“The way platelets work is really complicated. It’s like trying to grapple with 100 things happening simultaneously and they are all connected in some way. You have to think in 3D, with everything moving at once. That makes it very difficult to predict what might happen if you have a drug or molecule to change the processes. “We are trying to turn our detailed molecular biology and cell biology into a computer program that allows you to visualise what’s going on in 3D.”   

Professor Gibbins’ team has already discovered differences in how people’s platelets behave – some are very active and others sluggish. And they found that a particular molecule influences the likelihood of platelets clumping together, and measured this in different people.

This is life-changing technology

Dr Giorgia Bosi

Unlike some other cells, platelets can’t reproduce themselves, so there are limited numbers for experiments. The virtual platelet helps solve this issue. Computer modelling also allows you to experiment with genetics. “Making genetic changes isn’t feasible in humans; it wouldn’t be ethical,” says Professor Gibbins. “But on a computer, you can mimic the effect of a particular genetic change and see what happens... The virtual platelet could help us pinpoint why that person’s platelets aren’t working properly.”

Professor Gibbins thinks it will take 18 months to build a website that can be used as a research tool. “We hope in the next five years or so to have something pretty comprehensive. If we understand which molecules control how platelets are activated, leading to clotting, then we could develop new medicines to stop that,” he says. “That is really exciting.”

Driven to beat heartbreak

Research is built on failure as much as success – inevitably, new techniques don’t always work. Dr Bosi says: “Sometimes it is difficult… you just aren’t reaching success with the simulation.”

Or as Professor Gibbins puts it: “I think all scientists have times when you’re hitting your head against a brick wall.”

£6.5m BHF funding for Professor Gibbins’ research into blood clotting, since 2002

But BHF researchers are driven by the need to solve problems that cause heart and circulatory disease. Dr Bosi says: “As a bioengineer, I decided to work behind the scenes,” she says. “But I still feel I have an impact on the patient and their family. “That is really important to me. You know you are doing something useful, not just for yourself but for the public. You’re aiming to improve the health of the population and help doctors by giving them information it wouldn’t be possible to have otherwise. You know that you’re just a small piece of something much bigger.”

Professor Gibbins adds: “We’re not doing it for the sake of it – it’s because there is a clear clinical need to increase understanding. Work you have done might improve people’s lives – that is quite rewarding.”

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