Spectral-domain OCT wows interventional cardiologists

(From Bio Optics)

A live demonstration of a next-generation optical coherence tomography (OCT) system from LightLab Imaging (Westford, MA) drew rave reviews from a crowd of more than 1000 interventional cardiologists attending the Transcatheter Cardiovascular Therapeutics (TFT) conference in Washington D.C. last October. Performed in Germany by Prof. Dr. Eberhard Grube of the Helios Heart Center (Siegburg, Germany) and beamed live to the main hall of the Washington Convention Center, the procedure provided real-time OCT images of a recently implanted stent and the tissues covering the stent struts with a resolution of 15 to 20 µm—more than 10 times the resolution of intravascular ultrasound (IVUS), the dominant intracoronary imaging technology these days (see figure). The images were provided by LightLab’s next-generation spectral-domain scanning-laser OCT system (SL-OCT).

According to Gregg Stone, M.D., professor of medicine at Columbia University and chairman of the Cardiovascular Research Foundation (CRF), which sponsors the TFT meeting, many in the crowd were “amazed” at the OCT images. Gary Mintz, chief medical officer of the CRF, said it was the most excitement he’d seen at the meeting in recent years.

“The difference in resolution between OCT and IVUS is extraordinary,” Dr. Stone says. “This should significantly improve our ability to make accurate decisions for patients.”

The SL-OCT system from LightLab Imaging provides in vivo images of intravascular stents at much faster rates and higher resolution than competing technologies such as intravascular ultrasound. (Courtesy of LightLab Imaging)

The 1300 nm LightLab SL-OCT device is based on the fundamental Fourier-domain modelocking technology developed at the Massachusetts Institute of Technology (Cambridge, MA) by James Fujimoto (see related story, p. 20). LightLab’s first-generation system, the M2 OCT, is a time-domain OCT system. Compared to the M2 system, the SL-OCT system is much faster and provides higher-resolution, higher-quality images, according to Joe Schmitt, chief technology officer at LightLab. The SL-OCT system collects about 45,000 lines/s at 100 frames/s, compared to the M2, which collects about 4800 lines/s at 15 frames/s. In addition, the SL-OCT system takes a different approach to resolving a fundamental issue in cardiovascular applications: OCT cannot image in blood because the components of red blood cells cause diffuse reflection of near-infrared light.

“Our earlier generation of this product (the M2) uses an occlusion balloon to briefly stop the blood flow while doing OCT imaging in the arteries,” Schmitt says. “With the new system we are using a rapid-flush method that is auto-triggered. When you press the syringe (to deliver the saline), image acquisition begins. The catheter begins to spin, the sheath moves back, and you end up with a full spiral scan. Because you can pull back about 20 mm/s, you only need two to three seconds to cover the entire image area.”

The SL-OCT system possesses a higher sensitivity than the M2 system and its resolution is approximately three times higher, he adds, allowing for even more detailed intravascular observation and paving the way to 3-D intravascular imaging. Potential applications in clinical diagnostics include improved diagnosis of vulnerable plaques, identification of the presence of thrombus following coronary stent treatment and image diagnosis that helps to decide endpoints for the treatment of incomplete stent apposition, and auxiliary diagnosis for determining the period to discontinue antiplatelet therapy in drug-eluting stent patients.

The market potential for OCT imaging in cardiology is significant; currently, IVUS is a $400 million market with only 14% market penetration, according to Volcano (San Diego, CA), a leading provider of IVUS technologies. Given that OCT offers 10 times the resolution of IVUS, the future looks quite bright indeed for companies like LightLab Imaging and even Volcano. In mid-December Volcano announced that it will pay $25 million to acquire CardioSpectra (San Antonio, TX), a small company founded to commercialize OCT technology developed at the University of Texas (see related story, p. 14).

The LightLab SL-OCT system is in preclinical trials. The company is preparing to begin U.S. clinical trials and hopes to launch the system commercially by the end of 2008.

“Five years ago, intravascular imaging was a $150 million to $200 million market,” Schmitt says. “Now it is double that because of stents. But ultrasound doesn’t have enough resolution to image the thrombosis that can occur with stents. So our OCT product is quite timely.” —KK

A commercial available profuct could be seen from here.

The sound of light

Jun 4th 2009
From The Economist print edition

Biomedical technology: A novel scanning technique that combines optics with ultrasound could provide detailed images at greater depths

Mary Evans Picture Library

IF LIGHT passed through objects, rather than bouncing off them, people might now talk to each other on “photophones”. Alexander Graham Bell demonstrated such a device in 1880, transmitting a conversation on a beam of light. Bell’s invention stemmed from his discovery that exposing certain materials to focused, flickering beams of light caused them to emit sound—a phenomenon now known as the photoacoustic effect.

It was the world’s first wireless audio transmission, and Bell regarded the photophone as his most important invention. Sadly its use was impractical before the development of optical fibres, so Bell concentrated instead on his more successful idea, the telephone. But more than a century later the photoacoustic effect is making a comeback, this time transforming the field of biomedical imaging.

new technique called photoacoustic (or optoacoustic) tomography, which marries optics with ultrasonic imaging, should in theory be able to provide detailed scans comparable to those produced by magnetic-resonance imaging (MRI) or X-ray computerised tomography (CT), but with the cost and convenience of a hand-held scanner. Since the technology can operate at depths of several centimetres, its champions hope that within a few years it will be able to help guide biopsy needles deep within tissue, assist with gastrointestinal endoscopies and measure oxygen levels in vascular and lymph nodes, thereby helping to determine whether tumours are malignant or not. There is even scope to use photoacoustic imaging to monitor brain activity and gene expression within cells.

To create a photoacoustic image, pulses of laser light are shone onto the tissue being scanned. This heats the tissue by a tiny amount—just a few thousandths of a degree—that is perfectly safe, but is enough to cause the cells to expand and contract in response. As they do so, they emit sound waves in the ultrasonic range. An array of sensors placed on the skin picks up these waves, and a computer then uses a process of triangulation to turn the ultrasonic signals into a two- or three-dimensional image of what lies beneath.

The technique works at far greater depths (up to seven centimetres) than other optical-imaging techniques such as confocal microscopy or optical-coherence tomography, which penetrate to depths of only about a millimetre. And because the degree to which a particular wavelength of light is absorbed depends on the type of tissue and, in the case of blood, on whether it is oxygenated or deoxygenated, there is, in effect, a natural contrast agent. This makes the technique superior to ultrasound alone when it comes to picking out detailed features such as veins.

MRI and CT scans are also capable of delivering this kind of detail. But they usually require contrast dyes to be injected into the bloodstream, says Lihong Wang, a photoacoustic researcher at Washington University in St Louis, Missouri. CT scans also involve potentially harmful ionising radiation. And MRI and CT scans are very expensive, using machines that cost millions of dollars and require dedicated staff to operate them. Photoacoustic tomography, by contrast, could eventually be performed using portable hand-held devices, similar to those used for ultrasound scanning. This would allow doctors to diagnose and monitor patients in clinics, and reduce the need to refer them to consultants. “Photoacoustics provides greater access at a much lower cost than these other technologies,” claims Michael Thornton of Endra, a medical-imaging company based in Ann Arbor, Michigan.

Shining a light

A pioneer of the technique in the late 1980s was Alexander Oraevsky, who was based at the Soviet Academy of Sciences in Moscow at the time. He had been evaluating lasers as a means of removing tissue, but in the course of his experiments he realised that his samples were producing ultrasound, and began exploring the potential of this effect for imaging. Since then the technology has come a long way, not least because of the development of nanosecond pulsing lasers. Being able to deliver such brief pulses of energy to the sample being imaged—a nanosecond is a thousand-millionth of a second—has helped improve the resolution of the resulting images. Dr Oraevsky and other researchers have shown that it is possible to image the entire blood-supply system of a mouse, for example, down to a resolution of about half a millimetre.

One of the most promising applications for photoacoustics is in the treatment of cancer. Since blood cells are natural absorbers of light, photoacoustics is particularly good at providing high-contrast images of the formation of blood vessels (angiogenesis) and detecting increased metabolic activity (hypermetabolism), both of which are hallmarks of cancer, notes Dr Wang. Preliminary clinical research is now under way to look at how the technology can be used to monitor the development of breast cancer and identify how far it has progressed.

Even with mammography and ultrasound, the current gold standards for breast-cancer screening, doctors cannot tell if a tumour is malignant or benign without performing an invasive and expensive biopsy. “About eight out of ten patients who undergo a biopsy come back negative,” says Dr Oraevsky, who now works for Fairway Medical Technologies, a company based in Houston, Texas. Photoacoustic tomography could potentially be used to diagnose women in the doctor’s surgery.

One approach being explored by Michael Pashley, head of ultrasound imaging and therapy at Philips Research in Briarcliff Manor, New York, is to develop a hybrid ultrasound scanner that can produce ordinary ultrasound scans as well as photoacoustic images. In theory the two images could even be superimposed, he says. At the moment the work, which is being carried out in collaboration with Dr Wang, is geared towards monitoring the development of breast cancers that have already been diagnosed, says Dr Pashley. But if the technology proves successful, he hopes to move on to using it for the initial diagnosis.

Lihong V. WangGetting the picture

Although the different absorption characteristics of oxygenated and deoxygenated blood provide an extremely good natural contrast agent, this approach has its limits. So some companies are exploring the use of photoacoustics in conjunction with artificial contrast-agents introduced to the bloodstream. VisualSonics, an ultrasound-imaging company based in Toronto, has been evaluating contrast agents made up of gold nanorods attached to antibodies that bind to specific targets found in cancer cells. Ultrasound is already used to detect such agents but its resolution is sufficient to show only the structure of blood vessels. Dr Wang reckons that if contrast agents that are too small to be picked up by ordinary ultrasound were introduced into a patient’s bloodstream, they could be detected using photoacoustic imaging. Furthermore, it would be possible to see where the contrast agents built up, and hence determine the extent of a tumour. And by creating contrast agents that bind to specific genetic targets, the same technique could be used to monitor gene expression, he suggests.

Room for improvement

Despite its potential and its many advantages over other methods, there are some difficulties with photoacoustic imaging that have not yet been resolved. As light penetrates deeper into tissue, the resulting ultrasonic signal diminishes. This is partly because some of the light has been absorbed by the preceding tissue, but it is also because the laser light is dispersed, diffused and back-scattered. This places limits on just how deeply photoacoustic imaging can delve. In the future it might be possible to go a little deeper, says Dr Wang, but probably not by much. “If light is delivered from both sides of the tissue, ten-centimetre-thick tissue can potentially be imaged,” he says.

Bone tissue represents another obstacle to the technology, but not for the reason you might think. Laser light usually passes easily through bone, but sound does not. The speed at which sound travels through bone is different from the speed at which it travels through soft tissue, and as the ultrasound passes from one medium to the next it is distorted. Air cavities, many of which are found inside the human body, pose a similar problem, says Dr Wang.

Even so, VisualSonics and other companies are keen to explore the use of photoacoustics for neuroimaging. It is not an insurmountable problem, says Dr Wang, who is working on a technique to model the skull so that its effects on the ultrasonic waves can be predicted and eliminated in software, restoring clarity to the signals. If he can get this approach to work, it would further extend the revolutionary potential of photoacoustic imaging in the coming years. Doctors would not merely be able to diagnose cancer in the comfort of their own surgeries—they would be able to perform brain scans, too. A technology that traces its roots to a stillborn 19th-century communications device would have taken another step towards the futuristic dream of the all-purpose hand-held medical tricorder seen in “Star Trek”.