Imagine a small fast system that will be able to quickly determine not only whether a person has suffered a stroke but also when the stroke occurred. The latter determination is critical in knowing what kind of treatment to administer – because every passing minute holds a victim’s future and quality of life in the balance.
The potentially life-saving innovation is closer to a reality than you might think. And – in the creative explanation of Dr. William Scott Burgin, Professor and director of the Comprehensive Stroke Center in the USF Health Morsani College of Medicine Department of Neurology – it can be best described with the help of three elements: a shoe box, Snapchat and apple pie.
First, the shoe box. That refers to the basic size of the system, which made initial waves two years ago thanks to Dr. Burgin and USF alumna Dr. Maha Sallam. Her Tampa-based company, VuEssence, developed the invention that they hope will drastically reduce the time it takes to detect and diagnose a potential stroke – from hours, or sometimes days, to well under an hour.
Following data collection and intensive analysis, an exciting new development has emerged in providing a time stamp of that stroke. More testing is on tap to support the ongoing work. Yet the potential benefits of the research and development conducted by Dr. Burgin and Dr. Sallam are enormous.
“Employing our approach, we were able to use it, we think, reasonably as a clock,” Dr. Burgin said. “So not only can it tell us if it’s a stroke or not, but it can also give us an idea of how long ago it happened. And for us, that’s a very important question, because our treatments are predicated on how long ago somebody’s symptoms started.”
Burgin explained that knowing the best course of action is challenging if a person suffers a stroke but nobody witnessed it. That’s because the clot-busting drugs given to treat the most common types of stroke must be given quickly to be effective – and can create additional bleeding risks if not given quickly enough.
“What if you live alone or you fell down and somebody found you passed out?” he said. “We often can’t do anything because we don’t know how long ago it occurred. With our test, the first step would be to determine if it’s a stroke or not; the second would be to help us put a time stamp on when it started.”
Burgin notes that complex MRIs and CT scans can provide useful information, but are largely limited by cost, complexity, and general availability. But the system he and Dr. Sallam have been working on holds considerable promise for a complimentary test within a compact package.
“We have all the parts to make this into an even smaller device,” he said. “I mean, the Lego pieces aren’t yet put together. But we have all the Lego pieces needed to make a quick, mobile desktop unit longer term.”
Their efforts are vital because stroke is the No. 5 leading cause of death in the United States and the No. 1 cause of disability. Given those numbers, the stakes surrounding their research and inventive pursuit couldn’t be higher. Compared to a much slower MRI machine, their system's vastly reduced timeframe and improved precision could greatly accelerate the administration of clot-busting treatments, substantially improving recovery prospects.
Delays cause oxygen deprivation to the brain from the clot, and the results can be profound in impairing the ability to walk, speak, comprehend, and carry on life as normal.
In short, Dr. Sallam’s system is designed to analyze a tube of blood drawn from a possible stroke victim and quickly determine whether a stroke has occurred or whether the symptoms are unrelated, such as a migraine, seizures, tumors or blood sugar levels.
“Cutting-edge stroke treatments are still heavily predicated on some old-fashioned medicine – it’s talking to people, seeing them and laying hands on them,” Dr. Burgin said.
But complex technology is also part of the equation, he adds. And the advancements unfolding due to the collaboration with Dr. Sallam could take stroke assessment to a new level, thanks to the genetic codes of messenger RNA (which is also integral to the success of rapid COVID-19 diagnostic testing).
Enter Snapchat, the social media platform that records small slices of everyday life for a limited time.
“Messenger RNA is like the Snapchat of our genetics,” he said. “One part of our body sends a fading Snapchat message off to another place like a set of instructions. We thought, ‘You know, if we can intercept and decode them, we can if the body is effectively screaming, ‘I’m having a stroke.’ We look first at the ‘noise’ – all these millions of little ‘conversations’ taking place on a molecular level. Then, using statistics and complex computers, we can determine which messages are saying if it’s a stroke. And we can do that with a small sample of blood.”
Put another way, Dr. Burgin said their work is akin to “wiretapping” those conversations in search of clues.
“We have a system that can catch and study these messages,” he said. “We’ve been trying to identify the specific content of the messages that alerts body something has happened when you’ve had a stroke. And we can use some rapid, sophisticated approaches to do that.”
During their research, they were able to pinpoint between 150 and 250 different genes that changed in some way in response to a stroke. Then, using statistics, they narrowed the field to 117.
“We were able to mix and match and come up with the magic formula for what best identifies a stroke,” he explains. “Specifically, we found different panels containing unique combinations of genes. It was like looking for the secret blend of herbs and spices in Kentucky Fried Chicken. We got it down to a handful, and with further refinements, we’ve actually improved on our ability to identify stroke.”
They measure their effectiveness against other approaches utilizing a clinical assessment called the NIH Stroke Scale Score. The standard assessment method involves a neurological exam – how a person moves, talks, sees and looks.
“Its accuracy is .66, which in the realm of things is considered a poor discrimination tool – considering that if I flip a coin it’s .5,” Dr. Burgin said. “Our latest test is .9-plus. That is considered outstanding.”
Which leads us now to apple pie. Dr. Burgin’s culinary analogy helps explain his and Dr. Sallam's advances in the past two years. He likens the genomic properties they have studied and the data they have compared to finding the best way to make an apple pie.
“Say I made the greatest apple pie ever,” he said. “We tinkered around until we made the pie, then went back and wrote down the recipe. Now we must take the recipe and see if someone else can make that same exact pie repeatedly. In other words, if we have this definition, can we accurately predict strokes based on our diagnostic recipe? What we’ve found is it looks like it really works.”
But now comes the key next step – sending “the apple pie recipe” to other labs to see if they can replicate the outcome using the Burgin-Sallam definitions and data.
“We can continue to fiddle with the recipe – too much sugar, not enough cinnamon, too many apples – but for now we’re locking in,” Dr. Burgin continued. “No more tinkering. We’re taking it forward and seeing if others can make it.”
They are now fundraising to cover the costs of offering the system to hospital labs for stroke diagnosis on a limited scale, then they plan for an expanded study, which involves sending their test system to multiple centers across the country to support FDA approval.
“We’re throwing it out there to see if it sinks or swims,” Dr. Burgin said. “If it swims, it becomes a valid application and that’s when we can share it with others.”
And that would be one memorable apple pie, indeed.