PEER into a cupboard in Kullervo Hynynen鈥檚 lab and you鈥檒l find a most unusual device. The metal hemisphere looks like the sort of old-fashioned hairdryer you sit under at the hairdresser鈥檚. But this is a top-grade research lab at Brigham and Women鈥檚 Hospital, part of the Harvard Medical School, and no one is interested in drying hair.
It鈥檚 what it can do to the inside of your head, not the outside that counts here, because Hynynen鈥檚 helmet can perform surgery on your brain. It鈥檚 part of a new wave in medicine: a generation of tools that diagnose and treat the body鈥檚 ailments using nothing more invasive than sound waves. Without breaking the skin, beams of high-intensity sound can patch holes in a damaged blood vessel, calm an arrhythmic heart or wipe out a deadly tumour. The beam does its work in a volume not much larger than a grain of rice, leaving all other tissue unaffected. Thanks to this revolution, patients are already going home straight after operations that used to involve a general anaesthetic and a stay in hospital.
Ultrasound is already familiar as a diagnostic technique, and for monitoring fetuses right from the early months of pregnancy. The sound is produced by a high-frequency loudspeaker known as a transducer, in which an oscillating electrical signal vibrates a piezoelectric crystal to generate ultrasound waves of anywhere between 1 and 20 MHz. Stick the transducer against the skin and the sound waves can travel deep into the body.
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Some waves are reflected back to the transducer, where their properties are analysed. The amplitude of the reflected pulse provides evidence about the density of the structure, while the time delay between emission and return reveals the structure鈥檚 position. Typically, dense structures like bone appear bright, while fluids look dark.
Imaging ultrasound waves are sent out at a low intensity, about 1.75 watts per square centimetre. That鈥檚 around one-tenth of the power of sunlight on Earth鈥檚 surface. But crank up the intensity by a factor of 10,000, and focus this intense beam by giving the transducer a concave surface, and you鈥檒l create a searing heat. 鈥淚t鈥檚 like focusing sunlight through a magnifying glass onto a dry leaf,鈥� says Gail ter Haar, who heads the therapeutic ultrasound group at the Royal Marsden Hospital in Sutton, on the outskirts of London.
Aim this high-intensity focused ultrasound (HIFU) beam at a small broken blood vessel in the liver, for instance, and the heat will dry and shrink the tissues, causing it to collapse and stop bleeding. Veins and arteries more than a couple of millimetres across don鈥檛 collapse so easily, but the heat does trigger the release of an insoluble protein, called fibrin, from the blood. This forms into a network of fibres that help to seal a wound. Again, any bleeding halts.
Shahram Vaezy, a bioengineering professor at the University of Washington in Seattle has performed some remarkable demonstrations of the healing power of sound. In studies in pigs, he and his team have shown they can stop the bleeding from a ruptured pelvic artery within a minute. For something like a stab wound, where the opening may be several millimetres long, the researchers move the focal point of the acoustic waves back and forth over the opening in the vessel, sealing it up like a healing ray. Hynynen鈥檚 group has even developed an array of piezoelectric crystals that can scan the ultrasound beam back and forth without any physical movement (see Graphic).
In itself, healing by heating is nothing new. Surgeons have used the technique since medieval days when they wielded red-hot pokers to cauterise wounds on the battlefield. Hot iron has now given way to lasers or electric currents, but even these modern techniques need a surgeon to slice open the body to get to the wound. Ultrasound, on the other hand, can reach deep into the body without a single cut.
It will revolutionise the treatment of many major medical problems. Take internal bleeding after an accident or on the battlefield. Blood spurts out of the circulatory system with every heartbeat, and the victim can die in minutes. 鈥淭he only thing one can do is hope a hospital is near,鈥� says Vaezy. Small wonder, then, that the US military is one of the primary sources of funding of the his research.
But before doctors can stop the bleeding, they have to find it, and ultrasound can help here too. Conventional ultrasound won鈥檛 do, though, as the shadowy images make it hard to pick out a pool of blood. But researchers have found ways around this problem. One involves upping the intensity of the ultrasound radiation. Sound waves are just pressure waves that compress and relax tissues as they spread through them. The pressure can cause blood and other fluids to move about, sometimes quite rapidly, a phenomenon known as acoustic streaming. If the area under examination contains pooled blood, acoustic streaming will make it move.
This moving blood shifts the frequency of sound waves that bounce off it, and this shift can be picked up by a portable Doppler ultrasound scanner. In this way images from a Doppler scanner can clearly show where the bleeding originates (快猫短视频, 2 March, p 19). By combining this imaging technique with their HIFU beam, the Seattle researchers have developed a system that keeps the healing beam focused on a bleeding internal wound.
But ultrasound can do more than just cauterise tissue. When the sound waves squash and stretch the body鈥檚 tissues and fluids, the rapid changes in pressure can draw out gases that are dissolved in the blood. The bubbles that form in this 鈥渃avitation鈥� process quickly grow and oscillate. They could prove useful for imaging because the gassy areas reflect sound waves particularly strongly鈥攕o they should show up prominently on a scan. But these bubbles can also help the healing process. By tuning the intensity, frequency and duration of the ultrasound pulses that create the bubbles, Vaezy and his colleagues can use shocks from their sudden growth and collapse to pummel part of a blood vessel wall into a paste. This stimulates the body鈥檚 healing response. The paste of tissue blocks the leak, while blood clotting factors move in and finish the job.
High-energy surgery is showing promise for more than treating haemorrhage. Take fibroid tumours of the uterus, for example. Although not cancerous, they can grow as big as a football if left unchecked. Dealing with them may require removal of the uterus, and women who have to undergo such drastic surgery may take weeks to recover. But women treated with acoustic surgery are leaving hospital the same day.
In a technique pioneered by Ferenc Jolesz of Harvard Medical School, the patient lies face-down on a cot fitted with an ultrasound transducer, which then slides into an MRI scanner. The scanner feeds images of the tumour and information about its location to the transducer, which focuses ultrasound energy onto the tumour cells and kills them. No further surgery is necessary, as the body鈥檚 own scavengers take care of the debris. The Israeli company InSightec, has combined these elements in a machine that has already treated forty women in Israel.
Jolesz is also targeting other kinds of tumour for ultrasound treatment, including cancerous breast tumours. These are much harder to deal with than non-cancerous tumours like uterine fibroids, because a single surviving malignant cell can start the cancer spreading again. Nevertheless, researchers across the world are reporting positive results from ultrasound cancer treatments. Feng Wu of the Institute of Ultrasound Engineering in Medicine at Chongqing Medical University in China has supervised the HIFU treatment of more than 1000 potentially fatal cancers affecting the liver, breast, lung and many other organs. It鈥檚 not perfect; there have been recurrences of the cancers, Wu says, but at a lower rate than with other treatments. At the Royal Marsden Hospital in Sutton, ter Haar and David Cunningham have treated 68 people with kidney, prostate and liver cancers without any need for general anaesthetic. One of the Chinese ultrasound systems will be installed this year for trials at Churchill Hospital, Oxford. Doctors from Oxford University and the Royal Marsden will go to China to learn to operate the system next month.
Hard targets
However, some of the targets that acoustic surgeons desperately want to treat will be much harder to reach. The upper lobes of the liver, for example, are tucked inside the rib cage. The heart is hidden behind the lungs. And the brain is encased in the skull. To reach them, the sound energy would have to pass through bone, pockets of air or gas, or thick layers of fat, all of which can distort ultrasound waves. To get at the heart, Transurgical, a company based in Setauket, New York, is working on an ultrasound catheter that snakes up through the veins into the heart to kill regions of heart muscle that are propagating deadly, irregular heart rhythms.
But the most sought-after treatment is one that can use sound to operate inside the skull. And this is where Hynynen鈥檚 acoustic helmet comes out of the cupboard and into the operating theatre. For years the brain was considered off limits to acoustic surgery because it is encased in such thick bone. 鈥淭he skull acts like a defocusing lens that weakens the wave by 10 to 20 times,鈥� Hynynen says. Cranking up the power won鈥檛 work because the ultrasound waves will simply heat up the skull and burn the scalp. The skull also distorts waves as they pass through, so that they end up several millimetres from the predicted focal spot.
Hynynen鈥檚 way round the problem was to assemble an array of 64 low-frequency, low-powered ultrasound transducers around the skull to direct a tightly focused hot spot of sound energy anywhere he wanted within the brain. Because everybody鈥檚 skull is a little different, Hynynen needs to program a computer to ensure that the transducers have the correct firing times for each patient. This has to take into account exactly how much each section of skull deflects the ultrasound wave, and then compensate for this by calibrating each transducer to fire at a slightly different moment. If the computer gets it right, all the waves will arrive in sync at just the right point in the brain.
To make sure this happens, Hynynen鈥檚 researchers are busy borrowing skulls from the medical school and using CT scans to take detailed measurements of their thickness at every point. They鈥檒l feed these into a computer that will then turn skull measurements into suitable firing patterns. When a patient has a brain tumour that needs treating, the acoustic surgeon will use CT to map the patient鈥檚 skull, and then feed these measurements into a computer that calculates the correct firing pattern. The Harvard researchers, collaborating with InSightec, are hoping to begin clinical trials by the end of this year.
More than 20 companies worldwide are now racing to develop tools for acoustic surgery technology. Routine walk-away treatments for non-cancerous tumours of the uterus and prostate could be just around the corner, and trials of trickier applications such as treating brain tumours are about to begin. It might not be long before hospitals replace their knives and sutures with the healing sounds of acoustic surgery.