Shorter-wave ultrasound pulses could open up new brain treatments

Neurological diseases could be treated more effectively with shorter-wave ultrasound pulses that help deliver therapeutics through the blood brain barrier with less risk of side-effects.

ultrasound pulses

These new findings from Imperial College London could have implications for how drugs are used to help people living with Alzheimer’s.

Neurological diseases like Alzheimer’s can be difficult to treat with drugs because they are often blocked by the blood brain barrier (BBB), the membrane that surrounds blood vessels in the brain and allows very few molecules to pass to the brain from the blood. This protects the brain from harmful substances but can also hinder drugs getting to where they can act.

One avenue of research involves prying open the BBB to let drugs into the brain. This is done by injecting mice with tiny bubbles, or ‘microbubbles’, before applying long-wave pulses of ultrasound radiation to the brain.

The ultrasound pulses change the pressure in the blood vessel, causing the microbubbles to expand and contract. As they do so, they gently open the BBB.

According to Imperial, the long pulses last at least ten milliseconds at a time, which can cause side effects. The longer the BBB stays open, the more chance there is for tissue damage and for harmful molecules to reach the brain.

In a new study published in Radiology, lead author Dr James Choi and colleagues at Imperial compared long-wave ultrasound with shorter-wave, more rapid ultrasound pulses. They found their new technique was more effective and potentially much safer than current methods.
The research is led by Imperial College London and funded by Alzheimer’s Research UK.

Dr Choi, from Imperial’s Department of Bioengineering, said: “We have now found a seemingly effective way of getting potentially effective drugs to where they need to be.”

The researchers injected 28 mice with microbubbles, before using short-wave pulses on 14 mice, and long-wave pulses on the others.

They found that the short-wave pulses delivered drugs effectively throughout the brain without the surrounding tissue damage that can be caused by longer waves. The BBB also returned to its usual closed state within ten minutes.

Dr Choi said: “The blood brain barrier is relatively simple to open but current techniques are unable to do so safely – which is why we haven’t been able to use them in humans without side effects.”

The researchers said the new findings could eventually lead to new techniques for getting drugs to human brains in cases like Alzheimer’s, brain cancers, and other neural disorders.

Dr Sara Imarisio, head of Research at Alzheimer’s Research UK, said: “Although this study exploring how we can penetrate the blood brain barrier was conducted in mice, it’s a critical step before technology like this can be tested in people.”

This study was supported by Biotechnology and Biological Sciences Research Council, the Wellcome Trust, and Alzheimer’s Research UK.

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