Creating Biomedical Technologies to Improve Health


Science Highlight: October 30, 2009

New Stroke Treatments on the Horizon

Once a stroke occurs, prompt treatment often means the difference between a return to normal life and months of rehabilitation, severe disability, or even death. Take the case of a 37-year-old woman who kissed her husband goodbye one morning as he left for work. Just outside the door, the husband realized he had forgotten his lunch. On returning he found his wife unconscious on the floor. She had experienced an ischemic stroke. Two blood clots blocked a main artery in her brain. With prompt treatment to remove the clots, the woman left the hospital two days later with no neurological damage.

A model of the middle cerebral artery shows (A) an artery without a blood clot and (B) the artery blocked by a clot. In (C), the model artery is shown 15 minutes after inserting a stroke wire; the majority of the clot mass has been obliterated and minimal blood flow restored. Current research is focused on decreasing the time required to remove a blood clot and fully restore blood flow.

A model of the middle cerebral artery shows (A) an artery without a blood clot and (B) the artery blocked by a clot. In (C), the model artery is shown 15 minutes after inserting a stroke wire; the majority of the clot mass has been obliterated and minimal blood flow restored. Current research is focused on decreasing the time required to remove a blood clot and fully restore blood flow.

The U.S. Food and Drug Administration has approved two therapies to treat ischemic strokes, which affect about 750,000 people in the United States every year. Patients may receive either tissue plasminogen activator, a drug delivered intravenously that breaks up blood clots, or undergo a procedure in which the clot is mechanically removed from the blood vessel. Both procedures have their drawbacks. Tissue plasminogen activator (tPA) must be administered within four and a half hours following the onset of stroke symptoms; but bleeding in the brain may occur with the use of tPA. The mechanical approach can damage surrounding tissue and may not remove all clot fragments.

Scientists at the University of Massachusetts Medical School, Worcester, are developing an alternative to these therapies. A team led by Matthew Gounis, Ph.D., director of the New England Center for Stroke Research, is investigating the application of an ultra-thin wire technology that delivers localized ultrasound directly to a clot for the treatment of stroke. After threading the wire into the affected artery, the wire begins quivering like a tiny rattlesnake tail as ultrasonic energy pulses through the wire. This action creates microscopic bubbles that, when they pop, cause the clot to break apart, thereby restoring blood flow. “The particles are so small that the blood flow washes them out of the capillary bed. It’s like emulsifying the clot,” explains co-investigator Ajay Wakhloo, M.D., Ph.D., director of Neuroimaging and Intervention at the University of Massachusetts Memorial Medical Center.

“This is a big step in endovascular stroke therapy,” adds Gounis. “This technology will enable physicians one day to treat strokes more quickly once the decision is made to recanalize [restore flow to] the artery.” The device could play an important role in cases of severe stroke. Often very large clots are involved and tPA therapy is ineffective. “About 10 to 15% of these patients would benefit from immediate reopening of the vessel,” says Wakhloo.

Although the neurovascular stroke wire has had success in large animal models, Gounis says many questions still must be answered before moving the device into clinical trials. Among the questions under investigation:

  • How does the energy from the wire affect the arteries and brain tissue?
  • Can the device move easily through brain vessels that twist and turn sharply?
  • Can brain tissue be saved using the device?

Working in the brain also poses unique challenges because “the blood vessels in the brain are very different from those in the rest of our body,” Gounis says. “They are not tethered to muscle, are fragile, and have a lot of turns.” To accommodate the brain’s unique landscape, the researchers are also experimenting with different designs of the wire itself.


Double-Duty Research

Gounis and Wakhloo made a compelling discovery while investigating the neurovascular stroke wire. They found that currently available off-the-shelf retrievable stents (small metal cages used to keep blood vessels open) could be used to remove clots or lessen their effects. Retrievable brain stents are normally used to fill the gap created in an artery when an aneurysm or ballooning of the artery occurs. The stent holds metal coils in place in the aneurysm to prevent the space from filling with blood or bursting. Although the stent is permanently implanted in the vessel, being able to retrieve it helps physicians optimally position the stent prior to final deployment.

In their experiments, Gounis and Wakhloo showed that the retrievable stent could push a clot up against the wall of the blood vessel, reestablishing blood flow quickly, or the stent could be used to capture and remove the clot. Because the tubes that guide the stent into position are just a few millimeters in diameter and highly flexible, they can move easily through the brain’s winding vessels. While the approach has not received FDA approval in the United States, European doctors are using the procedure in the clinic to treat patients with strokes caused by clot formation.


Modeling Vessels

In addition to developing the stroke wire, Gounis and his group are investigating new ways to improve all stroke-related devices. To this end, the researchers have developed silicone models of the brain’s key arteries – the internal carotid and the middle cerebral arteries. These models were based on data from magnetic resonance angiograms of 20 patients. The images of the blood vessel networks were used to determine the length of each vessel as well as where to locate bends within each vessel in their silicone models. The silicone models are an important advance because they replicate the twisty nature of human vessels and reduce the need for animal models.

By compiling details from a group of patients, the researchers created a model representative of an average patient rather than one specific individual. “We can now be confident that the device will work in a given patient population,” says Gounis. In the future, Gounis hopes to generate libraries of patient data to create a range of models that depict a variety of patient groups.


Improving Patient Outcomes

Stroke is the number one cause of disability in the United States and carries a price tag of about $70 billion. “People don’t usually die from strokes but are extremely disabled by them,” says Gounis. Developing new ways to rapidly and reliably restore blood flow to the brain could dramatically change the quality of life for stroke survivors.

Although currently available mechanical clot retrieval devices give doctors a much-needed alternative to drug therapy, they are cumbersome and only about 500 physicians are trained in their use, says Wakhloo. Easy-to-use approaches such as the stroke wire and retrievable stents not only will increase the number of clinicians who can perform clot removal but also sharply reduce the time it takes to remove a clot. From their current studies, Gounis and Wakhloo estimate the stroke wire could remove a clot in about 15 minutes, a significant improvement over the 2 hours it can take for therapies presently in use.

“Our goal is to create user-friendly devices so that a broad-range of physicians can use them,” he says. “The faster we open vessels, the more brain cells we save.” Adds Gounis, “Time is brain.”

This work is supported by the National Institute of Biomedical Imaging and Bioengineering.


Chueh JY. Wakhloo AK. Gounis MJ. Neurovascular modeling: Small-batch manufacturing of silicone vascular replicas. AJNR. 2009: 30:1159-64.

Wakhloo AK. Gounis MJ. Retrievable closed cell intracranial stent for foreign body and clot removal. Neurosurgery. 2008: 62(5 Suppl 2) ONS390-394.

Health Terms: 
Heart Disease,