Five ways Imperial researchers are advancing stroke research
Stroke, which occurs when the blood supply to part of the brain is blocked or reduced, is a leading cause of death and disability worldwide, with one occurring every five minutes in the UK alone.
This World Stroke Day (29 October), we’re highlighting how researchers across Imperial are advancing stroke prevention, treatment and rehabilitation – identifying those at risk sooner, improving understanding of complex health risks, and supporting patients through cognitive and physical rehabilitation.
1. Earlier diagnosis through a glowing probe that detects an enzyme associated with stroke risk
Researchers at Imperial have developed a probe that glows when it detects heme oxygenase-1 (HO-1), an enzyme associated with vascular disease such as blood clots and strokes. Professor Joe Boyle, Professor of Chemical Systems Pathology at the National Heart and Lung Institute (NHLI) is leading the research that explores how artery inflammation, and specifically the enzyme HO-1, plays a role in stroke risk.
Professor Boyle explains that “many strokes result from an inflammatory disease of arteries known as atherosclerosis,” which is partly driven by fats leaking into the arterial walls from the bloodstream. This leakage drives inflammation, which can lead to a bleed within the vessel wall, and the formation of clots that can disrupt blood flow. These bleeds, especially in the carotid artery – which supplies blood to the brain – help predict future strokes, underscoring the urgency of understanding the mechanisms involved.
To address this, a team of researchers, from the NHLI and Department of Chemistry, are harnessing innovative methods to study the role of HO-1. Their approach involves a novel probe that glows in the presence of HO-1 activity. Professor Boyle explains, “We spent years demonstrating that the enzyme HO-1 acts on this probe in the same way it acts on our body’s own hemin, causing it to glow in the dark.” This discovery opens doors for potential clinical applications, allowing for the tracing of active carotid artery lesions in patients.
Currently, the team’s research is focusing on serum, and they are optimistic that even a small pinprick of blood will suffice to detect elevated enzyme levels. “Because this enzyme is elevated by bleeds within the artery supplying the brain, it may be a very useful rapid biomarker for assessing the likelihood of stroke,” Boyle explains. This enzyme is particularly elevated in ischemic strokes – the most common type – as well as haemorrhagic strokes, showing potential as a versatile diagnostic tool.
“Because this enzyme is elevated by bleeds within the artery supplying the brain, it may be a very useful rapid biomarker for assessing the likelihood of stroke”
Professor Boyle envisions a future where this enzyme can be measured in a simple blood test, similar to how diabetics monitor glucose levels. “Our idea is to use a light signal, so patients at risk could drop blood onto a plastic strip to assess how much of this enzyme is in their blood,” he describes. This method could be especially beneficial for individuals with sickle cell disease, who are at high risk for stroke due to blockages in small vessels and elevated levels of HO-1 due to inflammation.
As for the current state of research, Professor Boyle states, “We’ve shown that it works in a basic sense, and now we're looking for potential applications and validating it in patient groups.” Their studies include patients undergoing extracorporeal membrane oxygenation (ECMO), a procedure that elevates haemoglobin levels like a bleed would and therefore elevates levels of the enzyme in a similar way to those experienced in patients at risk of stroke. The team is now setting up new ethical clearances to work with this probe in sickle cell disease, stroke and heart disease.
2. Finding answers for vulnerable patients with atrial fibrillation and a history of brain bleeds
Prestige-AF Consortium
Prestige-AF Consortium
It’s not always clear how to treat stroke survivors to prevent further stroke, particularly if they have other conditions. One significant gap in clinical understanding is determining the safest ways to treat vulnerable stroke patients who suffer from both intracerebral haemorrhage (ICH), a bleed in the brain, and atrial fibrillation (AF), an irregular heartbeat. Led by Professor Roland Veltkamp, from the Department of Brain Sciences at Imperial, in collaboration with 11 partners across Europe, the PRESTIGE-AF project has been exploring this challenge.
Atrial fibrillation is a leading cause of stroke, affecting approximately six million people across Europe and 30 million worldwide. The condition raises the risk of ischaemic stroke, where arteries are blocked due to blood clots forming in the heart and travelling to the brain. Preventative treatment often includes anticoagulants to thin the blood and prevent clot formation. However, anticoagulants come with an increased risk of bleeding, a significant concern for those with a history of ICH – a form of stroke caused by bleeding in the brain. “Almost 390,000 people in Europe have an ICH and 20% of these patients also have atrial fibrillation, and yet we don’t know the best way to treat those with both conditions,” says Professor Roland Veltkamp. “We need to fill this gap in our clinical understanding in order to provide the best prevention stroke strategies for all patients.”
PRESTIGE-AF has been investigating multiple aspects of care for ICH patients with AF, focusing on the uncertainty clinicians face in deciding on treatment. This ambiguity stems from a lack of data, as patients with both ICH and AF are often excluded from major trials on anticoagulants.
At its core, PRESTIGE-AF is an international clinical trial designed to answer whether anticoagulants should be prescribed for these patients, where patients across six European countries were randomly assigned to receive either anticoagulant medication or no such treatment, monitoring them for future strokes. Additionally, several sub-studies have sought to deepen the understanding of these patients’ needs, including one that examines potential indicators in blood and DNA for stroke risk and another using MRIs to explore whether brain changes occur without any noticeable symptoms.
We need to fill this gap in our clinical understanding in order to provide the best prevention stroke strategies for all patients.”
The PRESTIGE-AF team has also conducted research on a population level, highlighting an anticipated rise in ICH cases and related deaths across Europe by 2050, especially among ageing populations. Gender inequality in stroke outcomes is another focus, with women generally experiencing higher stroke risks and lower representation in clinical trials.
Beyond research, PRESTIGE-AF has pioneered public engagement efforts to educate diverse audiences on stroke prevention. This includes ‘Escape the Clinic!’ an innovative pop-up escape room experience showcased across Europe. More than 500 participants learned about stroke and AF in this engaging format, showing how interactive experiences can be used as effective tools to connect audiences with research and make complex health issues accessible.
As the project approaches its conclusion in November 2024, researchers and clinicians are in the final stages of data analysis. Results from the clinical trials and sub-studies are expected in early 2025, promising to clarify treatment approaches for ICH patients with AF.
“It’s been wonderful to bring together experts from across Europe to help tackle this vital problem,” says Professor Veltkamp. “It would not have been possible without the hard work of the whole consortium, the clinical teams at our recruiting hospitals, and of course the patients and their families who volunteered to help improve treatment for others who may face the same challenges as them.”
“Now that the clinical trial is complete, we hope that we will soon have definitive answers on how to treat this underserved group of patients.”
3. Identifying blood pressure variability as a factor in stroke risk
It’s well-known that high blood pressure, or hypertension, increases the risk of heart attacks and strokes, but Professor Peter Sever, from the National Heart and Lung Institute (NHLI), is leading research that is reshaping how we identify stroke risks and improve patient outcomes.
New insights from the ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) study, led by Imperial researchers, have found that changes in blood pressure over time – referred to as blood pressure variability – could be a crucial predictor of stroke and heart attack risk. Professor Peter Sever explains, “We’ve long known that high blood pressure increases the risk of heart attacks and stroke, but our latest findings highlight the importance of tracking variability in blood pressure over time as well.”
In a group of over 8,000 UK patients followed for more than 20 years, those with highly variable systolic blood pressure (the top number in readings) were at a significantly greater risk of cardiovascular events, including stroke, compared to patients with more stable blood pressure, regardless of their average blood pressure readings. These findings suggest that addressing blood pressure fluctuations could be key to reducing stroke risk in a wide range of patients, including those whose blood pressure is otherwise considered controlled.
We’ve long known that high blood pressure increases the risk of heart attacks and stroke, but our latest findings highlight the importance of tracking variability in blood pressure over time as well”
Currently, clinical guidelines focus primarily on managing average blood pressure levels. However, the ASCOT study shows that even patients with well-controlled blood pressure can remain at high risk for stroke if their blood pressure fluctuates over time. “We need international guidelines for clinicians to be updated to reflect these latest findings and to include blood pressure variability as a major risk factor for heart attack and stroke” explains Professor Sever.
In the original ASCOT trial, researchers showed that amlodipine-based treatment was better than a beta blocker-based treatment strategy for preventing heart attacks and strokes and that this benefit was best explained by the effect of amlodipine on reducing blood pressure variability. “Whilst new trials are necessary to confirm the benefits of drugs which lower blood pressure variability, in the meantime our best evidence is that in patients with high variability, a treatment regimen that includes a long-acting calcium channel blocker such as amlodipine is the sensible option”, added Professor Sever.
The research team are also exploring new practical ways to assess blood pressure variability, including the possibilities of incorporating data from home blood pressure monitoring into clinical-decision making.
“The low cost and wide availability of digital blood pressure monitors and health apps means people can readily track their blood pressure over time and this could provide invaluable data for doctors to make the best treatment decisions” says Professor Sever, although he noted to “urge patients not to be overly concerned, as we would expect a degree of variation in their readings over time.”
4. Helping stroke patients keep OnTrack with their recovery
After a stroke, recovery is crucial for regaining independence and improving quality of life. Arm impairment is the most common type of disability for stroke survivors, affecting 450,000 people in the UK alone, and the resulting loss of independence and isolation can be challenging for both survivors and their relatives. OnTrack is a digital platform designed to assist stroke survivors in their arm rehabilitation through the use of wearable technology. The development of the platform has been led by a multidisciplinary team at the Institute of Global Health Innovation’s Helix Centre, including Gianpaolo Fusari (Project Lead), Brian Quan (Technology Lead) and Clare McCrudden (Engagement Lead).
The OnTrack platform enables patients to track purposeful movements of their arms throughout the day, promoting self-management and providing real-time feedback. Gianpaolo explains, “This helps patients engage in continuous therapy beyond their standard clinical appointments,” enhancing their recovery experience significantly.
The development of OnTrack has been a collaborative effort, as “stroke survivors, carers, and clinical teams have been actively involved throughout the development, testing and evaluation of OnTrack”, shares Clare. An active Patient and Public Involvement and Engagement (PPIE) group has played a vital role in defining research and development streams, participating in workshops, user testing, and training material development. Patients and clinicians have also contributed by participating in movement data collection and in clinical trials. Clare says, “We are proud to be working with a wide range of needs in our PPIE group too, from people who have had their stroke more recently to many years ago, alongside the carer perspective which is often lost in developing tools for stroke rehabilitation.” This diverse input has been crucial in ensuring that OnTrack meets patient needs and aligns with clinical workflows.
Clare McCrudden and Gianpaolo Fusari observe Sana, a stroke survivor, during a data collection project
Clare McCrudden and Gianpaolo Fusari observe Sana, a stroke survivor, during a data collection project
OnTrack collects data on arm movement and provides feedback on the quantity of purposeful movement completed. Brian says, “The data provided by OnTrack helps clinical teams monitor progress, adjust therapy plans, and personalise rehabilitation by allowing them to review the data and adjust daily targets, ensuring a customised approach. Additionally, OnTrack provides self-management tools that send personal notifications to encourage and motivate movement.” This allows healthcare teams to track how the patient is progressing each day through visual data provided by OnTrack Tools, which is a current gap in post-stroke rehabilitation.
The data provided by OnTrack helps clinical teams monitor progress, adjust therapy plans, and personalise rehabilitation by allowing them to review the data and adjust daily targets, ensuring a customised approach”
The impact of OnTrack on stroke patients has been significant. Many users have reported increased motivation and therapy intensity, achieving recommended activity levels and improving arm function. One patient from the PPIE group shared their experience in feeling a newfound confidence to throw the rugby ball back to their grandson for the first time thanks to OnTrack. Clinical trials have produced promising results, showing an impressive 89% engagement with the platform, a 64% increase in arm activity, and an 18% improvement in arm performance over a 12-week intervention period.
Currently, OnTrack is nearing commercial readiness in the UK, with ongoing clinical validation and real-world implementation planned across several NHS sites. Clare shares, “We are also excited about our new feature developments to make OnTrack even better for patients, co-designed in partnership with them.” Additionally, an Imperial spinout company is currently being established to support the broader deployment of the platform.
5. Improving diagnosis and treatment of stroke survivors’ cognitive health
Dr Fatemeh Geranmayeh from the Department of Brain Sciences sheds light on her research into post-stroke cognitive recovery and the complexities of predicting patient outcomes. According to her, “Of the 1.3 million stroke survivors in the UK, three-quarters experience some degree of cognitive difficulty, such as with memory, language, problem-solving, numbers or planning actions.”
Cognitive impairment after a stroke can severely affect a person’s daily life, impacting their mental health, employment, and overall quality of life. “Up to a third of stroke survivors may develop dementia within five years,” explains Dr Geranmayeh. Despite national guidelines highlighting the need for cognitive testing in patients with stroke, many remain undiagnosed due to the lack of standardised approaches and the strain on NHS resources.
Up to a third of stroke survivors may develop dementia within five years”
The Clinical Language and Cognition lab, led by Dr Fatemeh Geranmayeh.
The Clinical Language and Cognition lab, led by Dr Fatemeh Geranmayeh.
The Clinical Language and Cognition lab, led by Dr Fatemeh Geranmayeh.
The Clinical Language and Cognition lab, led by Dr Fatemeh Geranmayeh.
Addressing this gap is the focus of Dr Geranmayeh’s team at the Clinical Language and Cognition lab. Their IC3 study (Imperial Comprehensive Cognitive assessment in Cerebrovascular disease) is aimed at improving the prediction of post-stroke cognitive outcomes. “We use deep cognitive phenotyping – assessing and categorising participants based on their cognitive abilities, clinical characteristics and performance”, Dr Geranmayeh explains. The overall aim is to improve the prediction of stroke outcome through a holistic view, with multimodal brain imaging (both structural and functional), and blood biomarkers of neuroaxonal injury – damage to the brain’s long connecting nerve fibres, neurodegeneration as well as Alzheimer’s-specific pathology.
One of the exciting innovations from this research is the development of an online cognitive testing tool that could transform stroke care. Dr Geranmayeh notes that the tool has been tested in over 6,000 older adults and validated its use against standard clinical assessments, intending to make cognitive testing more accessible and affordable. “Many stroke survivors with cognitive impairment remain undiagnosed and untreated, with significant impact on their life and that of their carers”, she highlights.
The goal is for this tool to be adopted in clinical settings to provide personalised testing and triaging for patients with stroke and those with similar vascular conditions. In research, it could also help track the effects of drugs and rehabilitation in clinical trials and support large-scale studies on how these conditions affect brain function, becoming a standard way to measure cognitive outcomes.
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