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(Image: Patrick George)

From brain to prostate, focused waves of sound can reach places a scalpel can’t, putting us on the brink of a surgical shake-up

PHYLLIS is having brain surgery. But she is wide awake. There are no scalpels and no blood, sliced flesh or bone in sight. Instead, the surgeon carefully places a cap on top of Phyllis’s head and flicks a switch. Deep inside her brain, a tiny region of tissue heats up and begins to burn, while surrounding brain cells are left unscathed. Later that day, Phyllis is able to go home, free from the neurological disorder that for the past 30 years has made her right hand tremble violently whenever she tried to use it.

She has a form of ultrasound to thank for her remarkable recovery. Just as the sun’s rays can be focused by a magnifying glass to burn a piece of paper, high-intensity ultrasound waves can be concentrated to burn human tissue. The waves are harmless until they converge at the focal point, so a surgeon can operate deep inside the body without harming the surrounding tissue.

This high-intensity focused ultrasound (HIFU) requires no cuts to be made, and many operations don’t even need an anaesthetic, so the patient can be in and out of hospital within a day. “When you’re dealing with a lot of very sick people, that’s a huge advantage,” says , who studies ultrasound at the Institute of Cancer Research in London.

After promising trials treating prostate cancer, it is now looking as if HIFU could become a medical Swiss army knife for all kinds of procedures. And even in parts of the body where the focused waves can’t burn away tissue directly, they can still boost the uptake of drugs in specific organs. The method has even been used to prevent severe illness in fetuses in the womb.

See how surgery became surgical: “The gory details: Pictures of surgery through the ages“

Phyllis’s success story is the latest step of a journey that began 70 years ago. John Lynn and his colleagues at Columbia University in New York were the first to try targeting ultrasound waves to destroy biological tissue, in the 1940s. Although they managed to create lesions in cat brains with minimal disruption to non-targeted areas, the need for a craniotomy – in which a bone flap is removed from the skull – together with a lack of sophisticated imaging technologies, meant there was limited interest in the technology for general surgery. Now, with more advanced transmitters that can focus beams behind hard tissue like bone, and imaging technology such as MRI, doctors can operate more accurately, targeting areas of tissue sometimes just fractions of a millimetre across.

That precision looks set to revolutionise the treatment of prostate cancer. Conventionally, when tumours need to be eliminated, the entire prostate is removed, which can damage nerves and the muscles that control the ability to relieve yourself on demand. The result is that 70 per cent of patients lose the ability to get erections, and about 15 per cent become incontinent. A less-invasive option is radiotherapy, but it can still cause some damage to surrounding nerves. What’s more, radiotherapy is unlikely to be repeated if the cancer returns, because the risk becomes too great that DNA damage from the radiation will cause secondary tumours.

With focused ultrasound, however, surgeons can burn away tumours bit by bit, targetting areas the size of a grain of rice (see “No blood, sweat or tears“). Trial results so far have been impressive: in a 2012 study of about 40 men receiving HIFU, 90 per cent could maintain an erection by the end of the study, and no man was left incontinent. One year later, 95 per cent showed no signs of the disease ().

The recovery times are particularly notable. “We’ve had some people who’ve said they’ve been shopping the same day as the procedure,” says Louise Dickinson at University College London, who is investigating the . “One man said it was easier than going to the dentist for a filling.” Widespread clinical trials of ultrasound treatment for prostate cancer are now under way, but further evidence of its long-term effectiveness will be needed before it is a recommended treatment.

Buoyed by the promising results for prostate cancer, a range of trials are now investigating using sound to treat other disorders, including pancreatic cancer and lumps that form in the thyroid gland that can lead to cancer. One of the more ambitious ideas is to use HIFU to tackle problems deep in the brain. The technique has huge advantages, not least because you avoid cracking into the skull. What’s more, you can bypass the healthy layers of brain, preserving normal functions.

That’s not to say it is simple. The rate at which ultrasound passes through different tissue types varies – bone absorbs a lot of sound, whereas the jelly-like tissue of the brain takes in much less. To make matters worse, our skulls are not a uniform thickness all the way around. So surgeons have to use CAT scans to measure the bone density at thousands of points around the scalp. Later, a cap full of ultrasound emitters, called transducers, will be placed on the patient’s head. Each transducer is tuned using information about the bone density underneath so that it emits just the right frequency, for just the right amount of time, to focus the waves at the desired point in the brain.

Last year, the technique was used to treat 15 people with essential tremor, Phyllis among them (). To do so, the doctors singed a tiny area of the thalamus that relays motor signals to the cortex – thus blocking some of the abnormal neuronal activity that would otherwise be transmitted to the muscles and cause shaking. “The whole procedure probably took less than 2 hours, and apart from a strange buzzing sensation, it was completely painless,” says Phyllis. Because the trial was designed to test the safety of the procedure, they only aimed to treat the movements in her right hand. The results were immediate. “As soon as I came out of hospital, my handwriting was perfect, like it used to be,” she says. “It’s got a little worse over time but it’s so much better than my left hand.” The other 14 patients in the trial experienced similar improvements, and although side effects included temporary problems with speech, and for four patients, minor but persistent alterations to sensations in their face or fingers, all agreed that it significantly improved their quality of life.

“There was a strange buzzing sensation, but the brain surgery was completely painless”

The hope is that we might be on the cusp of a new wave of non-invasive brain surgery. “Soon, we’ll be starting a trial that will attempt to reduce movement problems in Parkinson’s and treat brain tumours,” says Neal Kassell, director of the in Charlottesville, Virginia.

Despite these successes, HIFU has its limitations. Bone cancer, for instance, is almost untouchable, because skeletal tissue quickly absorbs the ultrasound waves. “It’s hard to get any energy deep into the bone,” says , a consultant radiologist at St Mary’s Hospital in London. Conventional surgery, too, struggles to remove this kind of cancer, because it is difficult to bypass vital nerves, and any bone that is removed has to be reconstructed with a graft or prosthesis.

Bursting bubbles

Focused ultrasound may be much more than a replacement for the scalpel, however. It could open doors to procedures that would be impossible by conventional methods. Of particular interest is using ultrasound to direct the delivery of drugs. One approach would be to create medicines that are injected in an inert form, and then activated near to a tumour using heat from HIFU. The idea is to boost the dose where it is most needed while reducing side effects in the rest of the body.

In other instances, the treatment could be aided by “microbubbles”. This phenomenon was discovered by accident, or so the legend goes, says at the University of Oxford. “They used to be made just by shaking blood about and putting it back in.” Now, you can buy ready-made microbubbles that are between 1 and 10 micrometres across. They are comprised of a bubble filled with gas, supported by an outer shell made of lipids, proteins or polymers. The bubbles are often used during ultrasound scans, since they increase the contrast of the blood supply compared with the surrounding tissue. Once they are placed in the path of an ultrasound wave of the right frequency and intensity, however, they expand and contract until they suddenly collapse, creating a shockwave.

Do this in the brain, and you could perforate the blood-brain barrier – the layer of membranes around capillaries that separate the blood from the extracellular fluid that flows around the brain. This barrier makes it difficult to deliver drugs into the brain during chemotherapy, for instance – but puncturing it is a tricky procedure, because permanent damage would weaken the brain’s defences against bacteria. A 2012 study in macaques, however, identified the specific frequency necessary to induce a reversible disruption to this barrier for just a few hours – enough time to allow drugs to be delivered to the brain with a minimal risk of infection ().

Elsewhere in the body, it might be possible to place traditional chemotherapy agents into microbubbles and direct their implosion at the site you want destroyed. “It’s not been done yet, but we’re getting very close,” says Stride. Her colleague is about to take the first step. This year, his team will inject a chemotherapy drug into people with liver cancer. The drug will be encased in a lipid wrapper that can be broken down using ultrasound. If that works, they will then try to use microbubbles, filled with gas and the drug, as a vehicle – with the added advantage that the shockwave of the imploding bubbles would drive its chemical load deeper into the tumour, where it can do more damage. A similar approach would be particularly useful to push drugs into the bone cancers that are so difficult to reach with traditional surgery.

“The shockwave of the collapsing bubbles pushes the drugs deeper into the tumour”

Focused sound can even help doctors to treat patients at times when they were thought to be untouchable – such as when they are still in the womb. This was demonstrated for the first time in 2013, with a condition known as “twin reversed arterial perfusion”. This rare disorder involves two fetuses – one of which develops normally, while the other fails to develop a head, arms or heart. The two fetuses are connected by an umbilical cord that passes through the placenta, and the twin without a heart relies on blood pumped from its twin to stay alive. As a result, the healthy twin has to work extra hard to sustain both, which often results in heart failure and death.

Surgeons used HIFU, between 13 and 17 weeks after conception, to sever the abnormal fetus from the placenta and release the healthy twin of this burden. The baby boy was later delivered successfully ().

The success of such a delicate procedure offers a glimpse of what the future might hold. Kassell, for one, is sure that we are only just beginning to understand the potential of this technology. “It’s a stick that we’re still working out how to wield,” he says.

Gedroyc agrees. “You have here a very powerful tool,” he says. “Once you start thinking about it, you’re really only limited by how imaginative you are.”

This article appeared in print under the headline “Surgery’s new sound”