Dr. David W. Newell Speaks with VDM About the First Successful Use of Ultrasound Technology to Treat Hemorrhagic Stroke Within the Brain

Your recently published article in the Journal of Neurosurgery describes a new study that made you the first to report successful use of ultrasound technology to treat hemorrhagic stroke. How did the study get started?

The study got started due to the fact that a company in the Seattle area called EKOS had an exciting new technology involving ultrasound for breaking up blood clots and they designed a number of catheters for breaking up blood clots in different areas of the body. The one that we utilized was one that they had previous experience with threading up the middle cerebral artery in the brain to break up blood clots that were large for ischemic stroke. The research scientist there contacted Dr. Dan Hanley at Johns Hopkins and me to explore the possibilities that this could be used for treating hemorrhage in the brain. We designed a protocol to take the small catheter, which was designed for use threading up inside arteries with the idea of placing it stereotactically in hemorrhages in the brain and then using the ultrasound plus TPA, which is the thrombolytic, to directly liquefy clots in the brain and drain them out through a small catheter.

How does the procedure take those clots and liquefy them so that they can be removed?

Many of the applications that I mentioned before that the EKOS Corporation is involved with are based on experimental work where a phenomenon called sonothrombolysis is activated, which is the use of ultrasound to break up blood clots in conjunction with TPA. The ultrasound causes what is called acoustical streaming of the thrombolytic through the clot so like putting an ice cube in water, if you put the TPA just around the blood clot, it works on it from the outside slowly and melts it, which takes quite a long time. If you apply the ultrasound, it pushes the TPA through the intricacies of the clot and experimentally, it breaks the clot up much faster. We saw this as an opportunity to utilize the technology to break up the blood clots in the brain a lot faster. Then, we’re able to drain them out through what we call a minimally invasive approach where we put a hole in the head and introduce the catheter inside to evacuate the clot without having to do an open cranial procedure.

Is the minimally invasive approach much safer for patients?

In this study, we just did a small safety study because it hadn’t been used in the brain in humans before, so we didn’t know what the effects were going to be. Based on use of the catheter in humans in the middle cerebral artery, the initial data indicated that it was safe. There were also studies in pigs where the catheter was placed in pig brains, turned on, and the histological parameters were examined. There was no evidence of neuronal damage or damage to the brain tissue from the ultrasound at these doses so we had some preliminary data that appeared to be safe but it hadn’t really been done in humans for this particular application before.

The way to proceed with a new technology is to first do a small safety study. We ended up only utilizing 9 patients here to see if there was 1) any increased infection rate, 2) any evidence of rebleeding or the hemorrhage expanding or bleeding again as we initiated the treatment, and 3) to see if there was any evidence that the procedure was causing any harm or increased mortality rate. What we did find was that there were no infections and the hemorrhage reduction rate looked like it increased dramatically when we compared it to hemorrhages that were treated with the TPA alone without the ultrasound. That wasn’t a comparison where we looked at patients side by side but we looked at previous series’ of patients that were treated with the same protocol without the ultrasound and it appeared that adding the ultrasound helped lyse the hemorrhage much faster than just using the TPA alone through a catheter. We didn’t find any evidence of any increased mortality by using the catheter. That gave us the information that we needed to look at the lysis rates of these hemorrhages and based on this work, the EKOS Corporation, which makes the catheter, received a $2.7 million NIH grant to redesign the catheter specifically for the purpose of removing intercerebral hemorrhages.

Of the 9 patients entered into the initial trial, how many ultimately had a successful procedure? What defines a successful procedure?

All of them had a successful procedure in that the hemorrhage size was reduced early on within the first 24 hours. If you take them all as a group, the rate of reduction of the hemorrhage size was much greater than just using the TPA alone with a protocol that’s very similar but does not involve the ultrasound. It was successful in reducing hemorrhage size but it was too small a group of patients to look at any kind of improvement in outcome. Although we did follow the outcome, it’s not appropriate to make any claims about improved outcome until you do a larger trial that’s designed to look at that as a key parameter compared against a different type of therapy. When we look at the effectiveness of the therapy to reduce hemorrhage size, which was one of the outcome measures, it looks very promising. We have evidence that minimally invasive early reduction in hemorrhage size is very promising to try to improve the outcome from intercerebral hemorrhage by preventing secondary edema, swelling, and delayed pressure effects from the hemorrhage.

Given what you’ve recently discovered with the initial trial and wanting to expand, what is your next step for this study to help those suffering from this disease?

The next step is to complete the design of a catheter that is specifically designed for this purpose. The catheter we used was actually designed to deliver ultrasound to clots within the arteries so it’s quite small. We had to put it side by side next to a drainage catheter called a ventriculostomy catheter, which is designed to drain spinal fluid out from the ventricles. These were two devices that were put together for this purpose. The goal is to engineer a single device, which delivers the ultrasound and provides a mechanism to drain the liquefied clot out into a drainage bag and be able to deliver that into a specific site in the brain, right into the center of the hemorrhage, with very precise coordinates. We want to be able to place the device exactly where we want and then tunnel it out to the scalp, hook it up to a drainage bag, and hook it up to the machine that delivers the ultrasound, so the catheter is being engineered for those specific purposes. When that design and approval to use is completed, we’ll conduct a second trial with a larger number of patients to prove the safety and efficacy of that redesigned catheter for this specific purpose.

What do you hope to accomplish in the long term with your research to help prevent this from happening to people?

Currently there’s no really good proven treatment for improving the outcome of intercerebral hemorrhage. It constitutes about 15% of all strokes or hemorrhagic strokes versus ischemic strokes. The annual incidence is between 10 and 30 cases per 100,000 people per year and accounts for about 2 million strokes annually worldwide. The condition is fatal in about 30–50% of cases. These patients often stay in intensive care or a hospitalized setting for an extended period of time so we would hope to make an impact by early reduction in hemorrhage size, which would hopefully prevent secondary swelling and pressure effects. This would get patients out of the ICU setting faster and try to institute treatments that would reduce the number of secondary complications that they get from being in the hospital so long and being unconscious, in many cases, for a long time. This would hopefully improve outcome by being able to reduce pressure, reduce secondary complications, and improve the course of treatment.

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Dr. David W. Newell, MD, is the Co-Executive Director of the Swedish Neuroscience Institute in Seattle, Washington. He was also a Professor of Neurological Surgery at the University of Washington and former Chief of Neurosurgery at Harborview Medical Center. Dr. Newell would like to credit the Swedish Neuroscience Institute, EKOS Corporation (Bothell, Washington), amd Johns Hopkins University School of Medicine as the primary executors of the study.