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Last Updated: Monday, 19 November 2007, 23:24 GMT
'Popping' bubbles to treat cancer
By Paul Rincon
Science reporter, BBC News

3D model of Haifu Treatment Machine. Image: Haifu System/UTL
The technique is to be brought into clinical trials
Scientists at the University of Oxford are trying to harness the energy released when bubbles collapse as a way of killing off cancer cells.

They have built a device to beam waves of ultrasound into the body, generating bubbles at the site of a tumour.

When these bubbles "pop", they release energy as heat - killing rogue cells.

The UK team plans to apply its new technique in clinical trials; it will be used in treating patients with kidney and liver tumours.

These clinical trials of High Intensity Focused Ultrasound (Hifu) are being conducted at the Churchill Hospital in Oxford.

No surgery required

Hifu is non-invasive: studies have shown that it is at least as effective as surgery, without the risks of opening up the patient. It also limits the damage to healthy tissue which occurs in radiotherapy.

But by harnessing the energy released by the bubbles that form when tissue is exposed to intense ultrasound waves, the researchers say they can provide faster and better targeted Hifu treatment.

Dr Constantin Coussios holding tubes filled with water to demonstrate the principle of cavitation. Image: Paul Rincon/BBC
I like to call it the 'energy shovel', because it allows us to grab this energy and use it where it is needed
Constantin Coussios, University of Oxford
So far, the trials have mainly involved terminal patients with isolated tumours in the liver and kidneys - organs which can be most difficult to reach with surgery.

When any wave moves through matter, it weakens; and some of the energy is turned into heat. This is why microwaves heat up food and light waves from the Sun warm the Earth.

In Hifu, ultrasound waves from outside the human body are brought to a focus inside the body, causing intense local heating which kills cells.

The principle is the same as burning a hole in paper by focusing sunlight through a magnifying glass.

But the existing Hifu technique has two important limitations compared with surgery that are hindering its clinical uptake. First, it is very slow: it takes up to five hours to treat a 10cm tumour, compared with the 45 minutes or so it takes a surgeon to cut the tissue out.

Secondly, clinicians are working in the dark: without invasive surgery, the results can only be assessed after the treatment is over.

Temperature boost

By harnessing the tiny bubbles that form in tissue when it is exposed to focused ultrasound, the researchers found they could boost the heating effect by factor of 6-10 compared with conventional Hifu treatment.

The enhanced technique, being pioneered by Dr Constantin Coussios from Oxford's Biomedical Ultrasonics and Biotherapy Laboratory (BUBL), is based on a principle called inertial cavitation.

Phantom tissue. Image: Paul Rincon/BBC
"Phantom", a gel that mimics the properties of tissue, is used in tests
Hifu uses relatively low-frequency ultrasound, which allows clinicians to treat tumours deep inside the body. These low-frequency waves also generate bubbles in the fluid that infuses tissue.

The bubble continues to grow until it reaches a critical pressure threshold. It then collapses and redistributes the energy as high-frequency "broadband noise" - effectively triggering a miniature explosion.

The energy from this little bang gets absorbed locally, so that tumour cells are killed, but healthy tissue is left unscathed.

"I like to call it the 'energy shovel', because it allows us to grab this energy and use it where it is needed, delivering it as heat," Dr Coussios told BBC News.

Treatment and diagnosis

While bubbles are created spontaneously when ultrasound is focused on a target inside the body, these bubbles normally form and collapse very quickly.

Coussios lab, University of Oxford.
The ultrasound technique is tested in a tank of water
In order to achieve the effect Dr Coussios and his team are aiming for, they need to keep the tissue bubbling long enough to heat it beyond 45C, the temperature threshold at which cells start to die.

Their solution is a machine that beams ultrasound waves into the body and also has a highly-tuned sensor at its centre. The sensor can "hear" the tiny bubbles collapsing - a sound which is a thousand times too high for dogs, let alone humans.

Currently, temperature changes in tissue are used as an indication of the success of Hifu treatment. But by the time these can be picked up, tissue in the focal region - and sometimes healthy tissue surrounding it - has often boiled.

Clinical trials

Dr Coussios commented: "If we can use cavitation to accelerate the treatment, better localise the treatment - meaning that you will never get pre-focal damage - deliver the treatment at a lower frequency so you can go deeper in the body, and if we can also use these bubbles to monitor the treatment in real time, we have solved all the major limitations of Hifu in one go."

However, the treatment is not suitable for all types of tumour. Where the cancer has "metastased", or spread to other tissue, the therapy would probably not be effective, said Dr Coussios.

Dr Coussios said he was working with a team at the Churchill Hospital to incorporate the technique he has developed into clinical Hifu trials currently underway there.

He said candidates for the procedure would generally be patients with isolated solid tumours in the kidneys or liver.

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