New Technology: Bioptigen SDOCT Boosts Flexibility

Technology features a hand-held probe, presenting new opportunities for researchers and clinicians.

DIANE DONOFRIO ANGELUCCI

With the introduction of spectral domain optical coherence tomography (SDOCT), clinicians and researchers now can noninvasively image ocular structures much more quickly and in unprecedented three-dimensional detail.

One contender in the growing spectral domain market, the Bioptigen SDOCT, provides a novel feature—hand-held imaging—opening a new world of capabilities to researchers and clinicians, in addition to the advantages of rapid acquisition of high-quality depth-resolved images, superior resolution and real-time imaging.

"We are focused on providing our system to specialists and lead adopters who really care about providing the most in-depth analysis of images for diagnosis and treatment of ocular disease," says Eric L. Buckland, Ph.D., co-founder, president and chief executive officer of Bioptigen, Inc. (Research Triangle Park, N.C.), also co-founded by Duke University Professor of Biomedical Engineering Joseph A. Izatt, Ph.D. "Our system is most appropriate for the practice that has difficult cases, where details in the images matter."

GREATER FLEXIBILITY

The Bioptigen system incorporates a variety of interchangable imaging probes, including a standard chin-rest probe, microscopic addition for research and a hand-held probe.

"We use it for research purposes principally," says Thomas B. Connor, Jr., M.D., associate professor of ophthalmology and researcher at the Medical College of Wisconsin, Milwaukee, who has been using the Bioptigen SDOCT since February 2008. "It's a state-of-the-art spectral domain that one could use for clinical purposes, but the hand-held capability is unique," he says. "We've used it in the operating room on adults. You can use it on children. We've used it on many animals, and that's where there's nothing that has its capabilities." Although traditional OCT systems require patients to sit upright and follow the examiner's instructions, the Bioptigen SDOCT hand-held probe can be used in patients who are lying down or in other positions or in patients who have been anesthetized. In the operating room, Dr. Connor says, ophthalmologists can use it to examine different ocular structures.

This composite shows retinal images obtained with the Bioptigen SDOCT system. A: High-resolution B-scan of optic nerve head; B: A B-scan of normal macula; C: An image of retina with pigment epithelial detachment; D: A volume intensity projection; E: A Doppler image. The images were acquired, processed and displayed at 17,000 lines per second (except the Doppler image, which was acquired at 4,250 lines per second). The axial resolution is 4-5 microns, and the images are displayed as acquired with no averaging. (Images courtesy of Bioptigen, Inc.)

Dr. Connor says researchers at his institution have used the system to examine primates and rodents, and the microscopic application has been used even to image zebrafish. "Our user capabilities are primarily for research purposes, and we find it's superb for that," he says.

Joseph Carroll, Ph.D., assistant professor and researcher with Dr. Connor at the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, believes the instrument's flexibility is one of its most important features. "There's not a single patient who walks through the door that you couldn't image if you needed to," he says. "If a patient can't sit up, if the patient needs to be lying down, you can do that. There's no other OCT that you can do that with." The hand-held probe is particularly ideal for retinoblastoma screenings they perform in children under anesthesia, he says.

Dr. Carroll explains that research presented by Scott and colleagues at the 2008 meeting of the Association for Research in Vision and Ophthalmology (ARVO) indicated the usefulness of the system in imaging the macula in infants with shaken baby syndrome. "Because you couldn't image these infants with the standard OCT, they used the hand-held probe," Dr. Carroll says.¹

In addition, he says, with a simple switch of the front-end optics, the Bioptigen SDOCT also can be used to examine the anterior segment. "So instead of having two different OCTs or an OCT that doesn't do everything you want, that does all the OCT you're going to need, which I think is its biggest virtue," Dr. Carroll says.

"The physician can look at the cornea in very high resolution, look at the angle in very high resolution, look towards Schlemm's canal and the trabecular meshwork, anywhere where high-resolution imaging of the ocular microstructure is valuable," Dr. Buckland says.

IMAGE QUALITY

Key advantages of the Bioptigen SDOCT are its image quality and resolving power, Dr. Buckland says. Bioptigen reports that its SDOCT system is capable of 40,000 A-scans per second but is set to acquire, process, and display optimal images at 17,000 scans per second.

With this system, Bioptigen has measured a standard axial resolution of 4.5 microns throughout the imaging depth, which can be improved to 2.5 microns with add-on sources. Bioptigen offers systems at two available wavelengths, 840 and 1310 nm. The company recommends the 840-nm wavelength to image the retina and cornea of humans and small and large animals, anywhere superior image resolution is required. The 1310-nm wavelength is recommended for imaging thicker tissues and has been shown to be valuable for deeper anterior chamber imaging.²

"I think it gives you really nice image analysis and nice depth of the retina," says Sunil Srivastava, M.D., assistant professor of ophthalmology at Emory Eye Center, Atlanta, Ga., who has been using the Bioptigen system for several months. However, he believes it is probably geared more toward academic retina specialists involved in clinical and bench research. "With the spectral domain with Bioptigen, we're imaging hundreds of slices through the macula, so you're going to pick up areas of subtle pathology that you probably would miss with the time-domain OCT that is available now," Dr. Srivastava says. For example, he says, because clinicians can image the entire macula, in a patient with exudative AMD, the technology may help clinicians detect subtle subretinal fluid that can't be detected with some other systems. "That's going to give you a reason to treat some of these patients, so I think higher quality imaging of very subtle changes and imaging more of the retina in a very short period of time is just going to give us more information about the patient," he says.

Dr. Srivastava also likes that the system can resolve smaller parts of the retina. "Bioptigen allows you to sum up multiple images of a particular cut," he says. "In an area where you want really high resolution, the machine will take several images in that one spot, allowing you to get an ultra high resolution cut. You can pick where you like, such as the central foveal area or in other parts of the macula. You can get some very high resolution images in multiple areas because of the Bioptigen system flexibility."

Dr. Carroll's group is evaluating the benefit of the external light source in increasing resolution. "One of the questions we're working on is to ask explicitly: What is the clinical benefit of that improvement in resolution? I don't think people quite know that yet." Although twice the resolution, for example, is clearly beneficial, he says, this benefit may not be as pronounced for some diseases as in others. "But for other diseases where maybe it's a more subtle disruption of say, the photoreceptor layer, it might be very valuable," he says. "So it's going to be disease specific, I think, where it really has its highest benefit."

The system also acquires large amounts of data very quickly. "We are in the middle of a normative study of about 500 or 600 patients currently," Dr. Carroll says. "We can do one patient in about 5 or 6 minutes, and that's taking 14 images—seven images per eye, seven volumes per eye, which for each patient amounts to 7 GB worth of data. It's incredibly user friendly, incredibly patient friendly."

REAL-TIME IMAGING

The Bioptigen SDOCT also offers real-time imaging. "It provides the photographer immediate feedback on the quality of the image so if retaking an image is required, there is zero wait time to make that decision," Dr. Buckland says. "Additionally, if the photographer or the practitioner wants to look at a different area of the eye, there's flexibility for either guiding the patient or guiding the system to look throughout the geography of the eye."

SOFTWARE CAPABILITY

Dr. Buckland also describes the software's flexibility, explaining that users have unlimited control of the scan parameters. Although the Bioptigen SDOCT does not yet have a full set of analytic tools, those will be forthcoming, he says. In addition, it has unlimited flexibility for ophthalmology practices involved in research and clinical trials. "We have protocol-driven software, so the practice can set up a series of images that they want to do repeatedly and, with one click, load a series of image scan settings that they want to take and have their photographer run through them very quickly," he says.

"The database is very intuitive," Dr. Carroll says. "I have all of my research protocols entered in there with my IRB numbers and all the retina doctors in there, all the examiners in there, so whenever a patient is imaged, I can look back and I know exactly who the person is, who their doctor was, who took the image, when they took the image and what study they were enrolled in or if they were simply a clinical patient. So that database is one of the better ones I've seen as well." In addition, he explains, he can add notes about the exam, so that when physicians access the images off line, they can review the imaging notes he recorded.

LOOKING FORWARD

High-resolution SD-OCT images are providing even more information than previous OCT systems, Dr. Connor says, helping clinicians to learn more. "We're now finding things that no one had appreciated before and the question is how many of them are variances of normal and how many of those are pathology?" he says. "As with any new imaging technique, we're learning, just as investigators have done with computed tomography and magnetic resonance imaging."

"I think with this technology the big question that everyone has to ask is, is it right for you?" Dr. Srivastava says. "It's a new toy and everyone always wants the new toy. I think this is going to give us a lot of information. But if you're not sure you're going to use the information, that's the concern that people should have about buying any of the new SDOCT machines; it's a pretty large expense to undertake. For an academic retina practice I think it makes a lot of sense because I think it's going to be used in future clinical studies. But because the technology is so young, it's not clear yet what the future holds for these machines."

"The system is really allowing our users today to identify very early signatures of disease," Dr. Buckland says. "So this is particularly attractive to users who are interested in more than routine patient through-put, but clinicians who are really looking at disease cases that require more detailed analysis and intervention and, finally, for those who have non-standard patient populations, such as children or immobile patients or who want to use it in an operating room. This system is probably unique on the market for supporting those applications." RP

Note: Dr. Buckland is co-founder, president and CEO of Bioptigen. Dr. Connor, Dr. Carroll and Dr. Srivastava do not have any financial interests related to their comments.

REFERENCES

1. Scott AW, Farsiu S, Toth CA. Novel techniques to evaluate the infant retina with portable handheld spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2008; 49: E-Abstract 5044
2. www.newsobserver.com/news/health_science/story/1141855.html