Cath Lab Digest

Listen to the full podcast of this interview at http://vasculardiseasemanagement.com/content/dr-david-w-newell-speaks-vd...

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?