Why is this research needed?
In cerebral small vessel disease, or cerebral SVD, small blood vessels in the brain are narrowed, limiting blood supply to nearby areas of the brain. Having cerebral SVD increases your risk of both vascular dementia and stroke. In fact, about a quarter of all strokes are caused by cerebral SVD.
While we can easily see the spots of damaged brain tissue on a scan, there are no treatments that can reverse, stop or even slow down cerebral SVD. Currently, anyone who has it is also stuck with the increased risk of stroke and dementia.
Part of the reason we don't have treatments is because we don’t understand why cerebral SVD causes brain damage. There are many possibilities. For example, it might make it harder for blood vessels to open as much, cause uneven blood flow or tiny leaks in the blood vessels, or stop the brain getting rid of waste as effectively. It could even be a combination of several of these factors.
During his Postdoctoral Fellowship, Michael is investigating brain scans to understand how brain damage changes over time in stroke survivors with cerebral SVD. He's also exploring the role our body's waste clearance system plays in this disease.
Michael says, "Brain images produce a huge amount information, especially in research. Using special types of brain scan, which tell us about how well stroke survivors’ brains are working, for example we can assess how responsive their blood vessels are or whether the protective layer between blood vessels and brain tissue is leaky or not. I want to find out why the brains of some stroke survivors become more damaged than others, even though they are on the best available treatments."
What are the aims of this research?
To begin with, Michael is analysing brain scans from the Mild Stroke Study 3. The people who took part in this study had a stroke due to cerebral SVD and volunteered to have MRI scans of their brains shortly after their stroke, six months later and 12 months later.
On an MRI scan, we can see the damage caused by cerebral SVD, but it can change over time, growing larger or smaller. Sometimes new areas of damage appear, or existing ones disappear.
Michael is especially interested in whether changes like these are linked with different types of damage to nearby blood vessels and stroke risk factors like age and high blood pressure. Understanding these links will also help to reveal ways to slow or stop the brain damage caused by cerebral SVD.
Next, Michael will explore the role of the glymphatic system - the brain's waste clearance mechanism - in cerebral SVD. The glymphatic system helps to move fluids around brain cells, filtering it to remove things like bacteria and damaged parts of cells. Michael thinks the glymphatic system might not be working as effectively in people with SVD, so he’ll ask some of the Mild Stroke Study 3 participants to have an extra scan at their three-year follow up to see whether this is the case.
It’s becoming increasingly clear that the glymphatic system plays a role in stroke. However, the current method of scanning it involves an uncomfortable injection into the fluid around the spine. Michael will spend the last part of his Fellowship working on translating a new, less uncomfortable scanning technique from the lab to the clinic.
What is the benefit of this research?
Michael's Postdoctoral Fellowship will provide a much better understanding of how cerebral SVD causes brain damage and how to measure it.
This understanding has the potential to allow Michael and other stroke professionals to identify targets for treating this disease and which people are most likely to benefit from treatment.
In years to come, Michael's work could lay the foundation for making cerebral SVD treatable at last, hugely reducing the risk of stroke and dementia for people living with this disease.
Michael says, "Currently, we have no idea why some stroke survivors go on to have more strokes and others do not – even when they are on the best treatments and otherwise have similar characteristics. I hope this research will help find out whether there are local differences in how well the blood vessels are working, which may in turn help to develop ways of preventing stroke in future."
What PSP priorities does this research link to?
From 2019 to 2021, we worked with the James Lind Alliance on the Stroke Priority Setting Partnership (PSP). During the PSP process, we collaborated with people with lived experience of stroke and stroke professionals to find out what they thought were the top priorities in stroke research. From this, we identified the top ten priorities in two areas: prevention, diagnosis and short-term care, and rehabilitation and long-term care.
Now, when researchers apply to us for funding, we require that their work addresses at least one of these priorities, or a priority from the Childhood Neurological Disabilities PSP Top 10 as it relates to childhood stroke.
Michael’s project addresses the following priority from the Stroke PSP:
- Prevention 10: What are the effects of other health conditions and characteristics on stroke?
Meet the researcher
Michael is a Research Fellow in Medical Physics at the University of Edinburgh. He says, "This Fellowship is a key stage in my development as an independent researcher, allowing me to lead my own project while benefitting from the input of my mentors, stroke survivors and the University of Edinburgh’s extensive network of stroke research, much of it supported by the Stroke Association."
Michael's supervisors are Professor Joanna Wardlaw and Dr Michael Thrippleton, both at the University of Edinburgh. He'll also be working with a large group of collaborators, including Professor Maiken Nedergaarden (University of Rochester and University of Copenhagen), a world-leading expert in the glymphatic system. Michael will collaborate with her on the new glymphatic scanning technique.