MIT implant could stop deadly brain tumors from coming back

By Stephen Beech

A new high-tech implant uses ultrasound to improve drug treatment for brain tumors.

Scientists say the tiny device, which is as thin as a sheet of card, could prevent the recurrence of the potentially deadly tumors.

Patients with glioblastoma, an aggressive type of brain tumor, usually undergo surgery to remove the tumor.

But it’s difficult for doctors to remove all of the cancer cells, and the tumor often recurs.

Researchers at Massachusetts Institute of Technology (MIT) have now designed an implantable drug-delivery device that they hope could help prevent the recurrence of glioblastoma.

The device contains a reservoir that can release drugs over an extended period, along with ultrasound transducers that use sound waves to help medicines spread farther through the brain and bypass the blood-brain barrier.

The researchers say such a device could be implanted in the brain during surgery, then gradually release drugs that would help kill the remaining tumor cells.

After implantation, a wireless controller can be used to program the exact ultrasound dosages to be delivered, enhancing the reach of the delivered therapy.

Study senior author MIT professor Canan Dagdeviren said: “We have 24 transducers in one ultrasound array, which can help a given drug bypass the blood-brain barrier and enhance the drug infusion.

“The device also gives doctors options in terms of the size, the length, and the number of infusions.”

The research team showed that their ultrasound device allowed molecules to spread farther after being released, in tissue models and in a mouse study.

On average, glioblastoma patients survive 12 to 15 months after diagnosis.

They usually undergo surgery to remove as much of the tumor as possible, followed by radiation and chemotherapy.

Chemotherapy drugs are often given either as pills or an intravenous infusion but, in recent years, scientists have developed drug-delivery wafers and hydrogels that can be implanted directly in the skull.

That can help to eliminate the side effects of chemotherapy and ensure that a higher concentration of the drug reaches the brain.

Those devices work by passive diffusion of drugs, but the MIT team wanted to design a new device that would allow for greater control of the timing of drug release.

They also wanted to incorporate ultrasound arrays to enhance the distribution of drug molecules.

Previous studies have shown that ultrasound helps drug molecules to disperse more widely, by creating convective flows that help travel them longer distances.

The mechanical oscillations generated by ultrasound waves also temporarily increase the permeability of the blood-brain barrier, helping drug molecules get into the brain.

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Dagdeviren had previously designed a tiny cannula, about as thin as a human hair, that could be implanted in the brain to deliver drugs.

She also built an implant called ImPULS, which uses tiny ultrasound transducers to deliver deep brain stimulation.

In the new study, published in the journal Device, her lab combined the technologies to create LUCID (Long-term Ultrasound-enhanced Convective Injection Device) — a flexible implant as thin as a sheet of card.

A drug-delivery cannula is 3D-printed directly onto an array of 24 miniature ultrasound transducers.

The transducers generate ultrasound waves right at the tip of the needle, helping drug molecules to diffuse farther into tissue after they are released.

Study co-lead author Jason Hou said: “Getting a drug into the brain is only part of the challenge.

“It also needs to spread through the surrounding tissue.

“We brought a delivery channel and a tiny ultrasound array together in one implant to help molecules reach a larger area, even during slow infusion.”

The implant’s reservoir carries about 100 microliters of fluid, and infusion is supplied by a passive osmotic pump, while ultrasound can be controlled wirelessly through Bluetooth.

The device also contains a small battery that can be recharged wirelessly.

In tests in a “tissue phantom” — a gel-like material engineered to mimic human tissue — the research team showed that ultrasound-aided delivery spread drug molecules much farther than when the drugs were delivered without ultrasound.

Co-lead author Sarah Ornellas said: “By enhancing that distribution locally and programmably with ultrasound, you can reduce systemic toxicity in nontarget organs, while the therapy that you’re using has a better chance of reaching whatever tumor cells are within the affected area.”

The research team also tested the system in mice, using it to deliver an MRI contrast agent.

When the ultrasound array was activated, the contrast agent spread farther through the brain than when ultrasound was not used.

Dagdeviren said that, if developed for use in patients, the drug cannula and ultrasound array would be placed inside the skull, while the part of the device containing the battery and other electronics could sit outside the skull.

She said, as well as delivering small-molecule drugs, the technology could also be used to deliver immunotherapies or nucleic acids, including gene therapies.

And it also has the potential to be used in other organs.

Dagdeviren added: “We started with the brain as a follow-up to our ImPULS technology, but eventually this can be used for other soft tissue treatments for different types of drugs, different types of interventions in deep body tissue.

“We are showing that we can make any kind of payload be distributed in a better way.”