Curb the surgery - non-invasive ultrasound and stroke treatment

14 March 2016



New research into the practical applications of non-invasive ultrasound could save millions, allowing radiologists to detect carotid stenosis and pre-empt unnecessary surgery with medication. Fisnik Jashari, neurology resident at the University Clinical Center of Kosovo, talks about how medical imaging could be helping to transform the treatment of stroke sufferers, and promote cures that are safer, more economical and less invasive.


For a disease with which we have been so familiar for so long, it may come as a surprise that WHO lists strokes as the number two leading cause of death. Every year, around 15 million people worldwide suffer some form of the disease, and around 6.7 million people die. Though incidences of stroke are declining in many developed countries, in the developing world, they are increasing. It remains, in the words of the World Stroke Campaign, "a silent epidemic".

One of the most common causes of stroke is atherosclerosis - a disease involving the gradual hardening of the arteries. Over time, different substances like cholesterol, calcium and cellular waste products, known collectively as plaque, can build up inside arteries, where they harden, narrow and restrict the flow of blood. If one of these plaques bursts, a blood clot can form, and if the supply of blood is then blocked from accessing the brain, it can trigger a stroke.

Though atherosclerosis can affect arteries in any part the body, including the legs, kidney and pelvis, it is in the neck - where the arteries supply the brain with blood - that the risk is particularly concerning. Carotid artery disease, also known as carotid stenosis, occurs when key arteries in the neck narrow, causing decreased blood flow to the brain and increased risk of ischemic stroke. According to the Society for Vascular Surgery, only 1% of adults aged 50-59 have significantly narrowed carotid arteries, but 10% of adults aged 80-89 have this problem. People that suffer from hypertension, diabetes, hypercholesterolemia obesity and smokers are at a particularly high risk.

Change the future

Preventing patients with carotid stenosis from suffering a future stroke is an important goal for medical practitioners. In symptomatic cases (those in which the disease is already associated with ischemic symptoms), patients are usually recommended carotid endarterectomy (CEA) intervention: a surgical procedure that unblocks the artery. In asymptomatic cases (those in which there is a narrowing in the artery but no immediate symptoms), things are slightly more complex. Although surgery is often considered unnecessary and costly, there remains a small subgroup of asymptomatic patients who are at higher risk of stroke, where invasive intervention is still considered worthwhile. Patients with bilateral carotid disease, multisite atherosclerosis disease and 'silent' brain infarction, for example, have all been shown to have a significantly higher annual risk of stroke. The challenge is identifying both sets of patients: those that need surgery and those that don't.

One solution, according to a new study by Fisnik Jashari, neurology resident at the University Clinical Center of Kosovo, is to use ultrasound. Jashari's study, 'Carotid artery disease: plaque features and vulnerability', was written during his time as a doctoral student at Umea University in Sweden. It shows that ultrasound can identify carotid plaque features, and arterial wall thickening and composition, and could therefore be the best way of measuring the risk of stroke in asymptomatic patients, as well as the need for carotid endarterectomy.

"There is an idea that there might be a small group of asymptomatic carotid stenosis patients that could benefit from surgery," Jashari says. "So we decided we could add to the research by helping doctors identify who this subgroup is, and who the larger group of patients that should be left alone are. We went to the biomedical engineering department at the university and they helped us do an analysis of ultrasound data. Using ultrasound carotid plaque analysis, the idea was to try to identify plaques that could be vulnerable and then predict future strokes in asymptomatic patients.

"For our research, we did a meta-analysis where we searched for studies that have evaluated carotid plaque echolucency and the risk of future stroke," he explains. "We realised that echolucent plaques - soft plaques with vulnerable features - have a three-times-greater risk of developing strokes within three years, compared with echogenic plaques, which are less associated with future symptoms.

"With ultrasound, what we can do is evaluate the degree of stenosis, he contours of the plaque and plaque composition, based on grey-tone distribution of the ultrasound machine. By using the machine, we can identify echolucent plaques, and do the intervention for the subgroup of patients that are at risk of future stroke."

The preventative payout

Not only does this mean being able to accurately identify those who need surgery and improve patient safety, but it also means avoiding costly, uneconomical surgical procedures. To understand the significance of this, it's worth considering how big an issue unnecessary preventive surgery can be for patients with asymptomatic carotid stenosis. A recent study published by J David Spence at the University of Western Ontario, called 'Management of Asymptomatic Carotid Stenosis', found that over 90% of patients would be better off with medical therapy such as high-dose statin, cholesterol-lowering drugs and effective blood-pressure control. For doctors, patients and the taxpayers footing the bill, avoiding carotid endarterectomy is therefore paramount.

Overall, using ultrasound has the benefits of speed, safety, portability and, of course, its radiation-free properties.

"Two or three years ago, there was an idea that by doing carotid endarterectomy in asymptomatic patients, we could prevent strokes from happening in the future," says Jashari. "But in the last three years, this idea has started to change. Advancement in treatment, the use of statin therapy and better control of blood pressure has decreased the risk of strokes in asymptomatic patients with significant carotid stenosis.

"In a recent study, it was found that around $2 billion is spent in the US every year on carotid endarterectomy intervention. So there is a significant cost associated with doing this kind of intervention, because it is an invasive treatment. The problem is not that carotid endarterectomy does much harm to the patient - the perioperative stroke risk is less than 0.5%. But the costs to the governments and taxpayers are significant, given that it just isn't necessary in a lot of patients."

Benefits and limitations

So, what are the benefits of using ultrasound in this field over other imaging techniques?

"There are several other methods in use, but they all have drawbacks," Jashari says. "There is CT angiography: using this method, you can detect the degree of stenosis, and you can also use it to evaluate plaque composition. But this involves radiation and is an expensive procedure. Then you have carotid magnetic resonance angiography, but this carries patient inconvenience and needs time to be applied for each patient.

"Compared with ultrasound, magnetic resonance is also very expensive. With ultrasound, we can evaluate patients at their convenience with real-time analysis, and we can even apply it using portable ultrasound machines. The vast advances around ultrasound technology mean it can be so small that we can put it in a pocket and carry it around with us. So, overall, using ultrasound has the benefits of speed, safety, portability and, of course, its radiation-free properties."

The clinical significance of these findings is clear, but Jashari insists his work can only be used for research as things stand. "If we're going to use this kind of method on patients, we hope to see a trial that will compare the endarterectomy intervention in asymptomatic patients with patients that have hard plaques," he says. "In other words, a comparison between echolucent and echogenic plaques is needed.

"There are several other steps it should also pass before coming into use: it needs to be compared with plaque histology, and it needs to show that it can change over time and as medication develops. And we need to see if doing surgery in this kind of plaque has better benefits for patients than endarterectomy in more stable echogenic plaques. There are several groups working on the latter of these issues at the moment, and we hope that there will be a multicentre study that will try to operate on this kind of patient."

Further issues that ultrasound will face before it can be used on a daily clinical basis for detecting carotid stenosis are its various technological limitations. Better ultrasound devices, special software and expertise, and computer-assisted analysis of plaque echogenicity are all needed if Jashari's findings are to become a reality.

"At the moment, echogenicity quantification needs plaque evaluation in offline software," Jashari explains. "After doing the ultrasound, we have to put the images on a disc and then put them on a PC, and evaluate the plaques using software. There are no conventional ultrasound machines that have the software already installed to allow us to just do the work online, so for the moment, it takes time to quantify the plaque echogenicity.

"Additionally, there are two methods for classifying plaques in the echolucent and echogenic groups.

They can be classified visually by just looking at the ultrasound and seeing how light or dark it is, but this method is subjective and not especially realistic. The other method is after-imaging normalisation: a process that takes several minutes to perform, which allows us to quantify the echogenicity of the plaque and quantify its composition. So this is why I'm saying we are really at the very beginning of its development, and it will take time before it will be applicable."

The cost benefit of putting these things into practice might put some people off, but the clinical benefits of Jashari's study are hard to ignore. Strokes remain a serious public health issue in the developed and developing world, and while little can be done to reverse the disability and dependency that often follows a serious incident, the right preventive steps really can make a difference. Whether it is determining the risk of a future stroke or simply selecting a more appropriate treatment strategy, ultrasound - Jashari hopes - will have plenty to offer the field in the coming years.

Ultrasound scans can identify the risk of a patient having a stroke and determine appropriate treatments.


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