Ultrasound Implant Spreads Molecules Farther Through Brain Tissue in Early Tests

MIT researchers have developed an implant that combines drug delivery with ultrasound to help molecules travel farther through brain tissue, MIT News reported. The team hopes the technology could eventually help prevent glioblastoma from returning after surgery.

The findings, published in Device, come from experiments in tissue models and mice. They demonstrate improved molecular distribution, rather than an established treatment for patients.

According to MIT News, glioblastoma is an aggressive brain tumour that is difficult to remove completely. Patients generally undergo surgery followed by radiation and chemotherapy, but cancer cells left behind can contribute to recurrence.

The experimental device, called LUCID, could be implanted during surgery and gradually deliver drugs to the surrounding tissue. Its name stands for Long-term Ultrasound-enhanced Convective Injection Device.

MIT News described the implant as flexible and approximately as thin as a sheet of cardstock. It combines a drug-delivery cannula with an array of 24 miniature ultrasound transducers. The cannula is 3D-printed directly onto the array, positioning the sound-generating components at the needle’s tip.

A reservoir holds about 100 microlitres of fluid, which a passive osmotic pump supplies for infusion. Ultrasound settings can be controlled wirelessly through Bluetooth, and a small battery can be recharged wirelessly.

Canan Dagdeviren, an associate professor of media arts and sciences at MIT and the study’s senior author, said the design gives doctors options over the size, duration and number of infusions, according to MIT News.

The approach addresses a problem beyond getting medicine into the brain: helping it reach a wider area once delivered.

MIT News reported that ultrasound can generate fluid movements that carry molecules longer distances. Its mechanical oscillations can also temporarily increase the permeability of the blood-brain barrier, helping molecules enter brain tissue.

Existing implantable drug-delivery wafers and hydrogels rely on passive diffusion. The MIT team sought greater control over delivery timing while incorporating ultrasound to improve distribution.

In a gel-like material designed to mimic human tissue, molecules delivered with ultrasound travelled farther than those delivered without it, according to MIT News.

The researchers then tested the system in mice using an MRI contrast agent. Activating the ultrasound array again increased how far the agent spread through the brain compared with delivery without ultrasound.

MIT graduate student Sarah Ornellas and Jason Hou were the study’s lead authors. Ornellas said more controlled local distribution could reduce toxicity in organs outside the treatment area while improving the chances of reaching tumour cells, MIT News reported.

For a potential patient version, the researchers envisage placing the cannula and ultrasound array inside the skull. The battery and other electronics could sit outside it.

The team also sees possible applications beyond small-molecule drugs. According to MIT News, the technology could potentially deliver immunotherapies or nucleic acids, including gene therapies, and might be adapted for organs other than the brain.

The design builds on Dagdeviren’s earlier work on a hair-thin drug-delivery cannula and ImPULS, an implant that uses miniature ultrasound transducers for deep brain stimulation.

The research received funding from the MIT Media Lab Consortium and the National Institutes of Health, MIT News reported.

Sources

• MIT News: Implantable device uses ultrasound to improve drug delivery to the brain