Sharyn Sowell was exhausted and anaemic from the daily bleeding caused by her uterine fibroids, benign tumours that had grown to the size of a 6-month-old fetus. Her doctor urged her to have a hysterectomy, but instead in May she chose to undergo a non-surgical procedure that spared her uterus. She walked home from the hospital and was at work 36 hours later. Since then, she has had no bleeding. 鈥淚鈥檝e got my life back,鈥� she says.
What did the trick was a new approach to killing tumours using precisely targeted radiation or high-intensity ultrasound, leaving surrounding healthy tissue untouched. Such treatments are finally becoming possible thanks to advances in real-time imaging that let doctors see exactly what they are targeting rather than relying on scans taken prior to treatment.
The idea is to use magnetic resonance imaging (MRI) or computed tomography (CT) to create three-dimensional images precise enough to guide a tumour-zapping beam to its target. Crucially, the zap-while-you-scan approach means surgeons can also be confident they have hit all of the tumour and spared the surrounding tissue, says Jeffrey Siewerdsen of the Ontario Cancer Institute in Toronto, Canada. 鈥淲hen it comes to delivering therapies, there are geometric uncertainties that we have to account for, and that limits how aggressive we can be. Usually that means there is tumour left behind.鈥�
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Siewerdsen and colleagues have integrated a CT scanner into a radiation linear accelerator that can compute 3D CT images of soft tissue in real time. The device then targets the tumour site with radiation to an accuracy of less than 1 millimetre off true. This compares with around 1 centimetre when using images taken prior to treatment.
Delivering radiation more precisely also means doctors can give bigger doses without worrying about damaging healthy tissue. This should lead to faster, more effective treatment, says Cihat Ozhasoglu of the University of Pittsburgh Medical Center in Pennsylvania. Ozhasoglu has been testing a device called Cyberknife, which targets lung tumours with a powerful X-ray source mounted on a robotic arm, combined with a vision system that tracks the rise and fall of the tumour as the patient breathes.
The vision system, called Synchrony, uses X-ray images gathered at the beginning and at points throughout the treatment to track the movement of gold 鈥渟eeds鈥� implanted into the tumour site. To let the software track the tumour between X-rays, the patient also wears a vest fitted with blinking red LEDs, so the system can calibrate the position of these gold seeds relative to the LEDs and thereby follow the tumour. The robotic arm of Cyberknife then fires its X-rays, targeting the tumour to within 1 millimetre.
This precision means Ozhasoglu can deliver more than 10 times the typical dose in one go, so patients face only two or three sessions rather than 20 or 30. He presented his results at the meeting of the American Association of Physicists in Medicine in Orlando, Florida, last week. 鈥淚n some patients, after 2 to 3 months the tumour is completely gone,鈥� he says. Both Cyberknife and Synchrony were developed by Accuray of Sunnyvale, California.
鈥淚n some patients, after two to three months the tumour is completely gone鈥�
It is not just traditional radiation therapies that are benefiting from real-time image guidance. This approach also opens up the possibility of treating tumours with focused ultrasound, which avoids the side effects of radiation exposure.
The idea of using high-intensity ultrasound to destroy tumours by heating them has been around for more than 50 years. Focusing ultrasound beams 10,000 times stronger than those used in pregnancy scans onto a single point in the body can heat tissues to 55 掳C. At this temperature cellular proteins fall apart and the tissue dies (快猫短视频, 6 April 2002, p 34). However, without a way to see what you are targeting, it hasn鈥檛 been possible to deliver the treatment safely.
Combining focused ultrasound with magnetic resonance imaging allows doctors to pinpoint the exact location of the tumour and aim the ultrasound at the right spot, without accidentally cooking healthy tissues. What is especially useful about combining these technologies is that the scanner can also measure real-time tissue temperature, so the doctor knows exactly when the target has received a sufficient dose.
鈥淚t鈥檚 like a colouring book for children,鈥� says Ferenc Jolesz of Brigham and Women鈥檚 Hospital in Boston, Massachusetts, who is developing a number of procedures using focused ultrasound. 鈥淲ithin the outline of the tumour, you colour it in.鈥� Even after the tissue has cooled, the dead material appears different on the MRI, Jolesz says, allowing doctors to confirm that the target has been hit.
鈥淚t鈥檚 like a colouring book for children: within the outline of the tumour, you colour in鈥�
The proving ground for the technique has been in treating patients with uterine fibroids, like Sowell. The ultrasound can be administered on an outpatient basis, and the patients have 鈥渁lmost no pain post-procedure鈥�, says Wladyslaw Gedroyc of St Mary鈥檚 Hospital and Imperial College London. Gedroyc is testing the technique in the UK, where he expects the treatment to be approved within a year (it is already approved in the US).
Now Gedroyc and others are turning their attention to treating cancerous tumours with this approach. One such system made by InSightec of Tirat Carmel, Israel, is currently in trials in Germany and Japan, and Gedroyc and others also plan to test the method on prostate, liver and kidney tumours.
Already there are promising results from the first stage of a Japanese trial in which the technique was used to treat breast tumours prior to surgery. Hidemi Furusawa of the Breastopia Namba Hospital in Miyazaki, Japan, and colleagues found that the ultrasound procedure killed an average of 97 per cent of the treated tumour tissue, and in more than half of patients it killed 100 per cent of the total tumour tissue (Journal of the American College of Surgeons, vol 203, p 54).
It is too early to tell how ultrasound treatment will perform in the long term, but as with radiation therapy, researchers agree that the key to whether the method succeeds in treating cancer is whether the imaging can accurately identify the entire tumour. 鈥淚f you see it, you can kill it,鈥� Jolesz says.
Although tumours can show up more clearly in an MRI scan than they do visually on the operating table, it remains to be seen whether imaging can effectively resolve the entire tumour boundary. Still, as imaging improves, so should these imaging-based therapies too, and any non-invasive technique only has to match the performance of more invasive techniques to be considered a success, says Jolesz. 鈥淚f it鈥檚 equal to surgery, it鈥檚 already better.鈥�
Through the keyhole
Not all treatments can be carried out without going under the knife, so surgeons often use minimally invasive 鈥渒eyhole鈥� operations instead, and the developments in real-time imaging are also expanding the range of these techniques at their disposal.
Many minimally invasive procedures are carried out with the help of X-ray fluoroscopy, effectively an X-ray video, which generates 2D images at a rate of 30 frames per second. The surgeon can watch the medical instruments inside the body as they are guided to the target site. But 2D X-rays do not visualise soft tissue well, limiting which procedures can be guided by the method.
To get around this problem, Rebecca Fahrig of Stanford University in Palo Alto, California, has integrated an X-ray fluoroscopy instrument into an MRI scanner, which can create 3D images of soft tissue.
Ensuring the X-ray machine would work inside the strong magnetic field of the MRI scanner was a considerable engineering challenge. Fahrig鈥檚 group replaced a number of parts with non-magnetic materials, and positioned magnets beneath the X-ray detector to counteract its distortion of the magnetic field. What鈥檚 more, surgeons working in the field cannot use any magnetic instruments 鈥� no flying scalpels, please.
The hybrid instrument has been used for a number of keyhole procedures that would otherwise have been major operations. In one procedure, for example, the device was used to operate on a woman with two small extra uteri that were not connected to her true vagina. Because her bladder was also abnormally shaped, being able to see the soft tissue during surgery allowed doctors to find their way through the unusual anatomy without doing any damage.
The device is also being used for otherwise tricky liver bypass operations in patients waiting for transplants. The ability to see the soft tissue while guiding the bypass shunt to the appropriate blood vessels allows the surgeon to avoid puncturing crucial parts of the liver that would preclude a future transplant, or rupturing cysts, which could cause infections.
Other groups are working to develop robotic surgeons that can function in the MRI鈥檚 magnetic field, eliminating the need for a doctor to work in this environment. Garnette Sutherland of the University of Calgary in Alberta, Canada, has developed neuroArm, a two-armed robot that can operate in an MR environment.
Like Fahrig鈥檚 combination imager, it uses magnet-compatible materials, including ceramic piezoelectric motors to control its movements. All incision tools are made of a tough plastic that does not distort the image. To allow them to be tracked, the tools have titanium markers, which are virtually non-magnetic and so are safe to use within the intense field, but still show up on MR images.
NeuroArm is designed for intricate procedures such as brain, eye or plastic surgery. By combining the robot with MR imaging during neurosurgery, for example, the robot can compensate for any displacement of the brain when the skull is opened. The instrument is still under construction, and once it is completed Sutherland is planning to test it in competition against surgeons.
