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For other articles and previous issues click here. September 13, 2004 Imaging
the Eye With Very-High-Frequency Ultrasound The technique can achieve resolutions of at least 100 microns for imaging the human eye—resolution at least 10 times better than either MRI or CT in clinical application. But the tradeoff at such high frequency is that sound waves don’t penetrate far into the tissue, which limits which parts of the body can be effectively imaged. The popularity of LASIK (laser-assisted in situ keratomileusis) vision correction surgery has been a major factor spurring interest in new ways to obtain more precise, high-resolution images of ocular structures. Very-high-frequency ultrasound (VHFU) is one area where researchers are demonstrating notable results. Two presentations at June’s annual meeting of the American Institute of Ultrasound in Medicine examined today’s leading edge of VHFU research. Ronald Silverman, PhD, director of bio-acoustic research for Weill Medical College of Cornell University, and Dustin Kruse, PhD, from the department of biomedical engineering at the University of California-Davis, presented recent findings from their VHFU studies of blood flow in the anterior of the eye. Why the Eye? The second attribute is safety. “VHFU operated within the limits dictated by the FDA does not cause any side effects,” Kruse says. “FDA limits for acoustic exposure of the eye are far lower than they are in soft tissue imaging. Furthermore, the likelihood of bioeffects related to cavitation [spontaneous formation and collapse of bubbles] is far less at high frequencies.” As Kruse points out, “High-frequency ultrasound is a somewhat misleading term in the sense that ultrasound is already considered ‘high frequency’ relative to what humans can hear. Sonographers and ultrasound engineers think about frequency relative to what most clinical ultrasound systems operate at, which is in the 1-megahertz to 7-megahertz range.” Until the mid-1990s, the typical frequency for ophthalmic ultrasound procedures was approximately 10 megahertz (which, as noted, other specialties would consider very high to begin with). As the operating frequency rises, resolution improves in a directly linear relationship, according to Kruse. New transducers allow using frequencies as high as 50 megahertz. So the newest transducers provide fivefold greater resolution than was previously available. While not especially good for studying the posterior areas of the eye, such as the retina, VHFU provides far superior viewing of the anterior structures, such as the ciliary body, cornea, and iris. The resolution improvement attainable with VHFU is striking. For instance, the average corneal thickness measures approximately 1/2 millimeter, or 500 microns. At 10 megahertz, in Silverman’s words, “you could see enough to say, ‘Well, there’s a cornea, alright.’” At 50 megahertz, in contrast, “we now have a resolution, axially, of about 30 microns. This allows us not only to image the cornea but also to make very precise measurements” of the entire anterior segment of the eye, he says. “With every doubling in frequency, the image resolution is also essentially doubled. At 20 megahertz, resolution is approximately 100 microns, or 0.1 millimeters,” adds Kruse. “VHFU can achieve resolutions of at least 100 microns for imaging the human eye... [That resolution is] at least 10 times better than either MRI or CT in clinical application.” Measuring Blood Flow Typically, acoustic echoes from blood cells increase significantly as the frequency rises, making it easier to detect blood cells and estimate velocities. So VHFU allows exploring blood flow in peripheral tissue with greater spatial resolution and depth penetration than ever before. However, notes Silverman, higher frequencies also mean greater attenuation. One problem with VHFU flow mapping is differentiating low-velocity blood flow echoes from tissue echoes with similar velocity magnitudes. To enhance the ultrasonic backscatter from the very small blood volume in small arterioles and capillaries, some tests employed a contrast agent consisting of a high-molecular-weight gas encapsulated in a lipid shell, ranging in diameter from 1 micron to 3 microns (red blood cells measure approximately 8 microns). “Contrast agents are required to detect blood flow in the smallest vessels only because currently available instrumentation isn’t sensitive enough to pick up the very weak echoes of blood cells under these conditions,” Kruse explains. Clinical Applications With current conventional optical instruments, Silverman adds, “it’s very difficult to reliably determine the internal dimensions of the eye from external measurements. If a lens implant is undersized, it may rattle around inside the eye, or if it’s oversized, it will push against internal structures and potentially cause cataracts, hemorrhaging, or other damage. So being able to visualize structures and measure the eye internally [with VHFU lets] you customize [each] lens before surgery.” The box below lists possible future ophthalmic application uses for VHFU. Perhaps most importantly, VHFU allows imaging potentially lethal pigmented tumors or lesions. That can be a vital capability for differentiating types of pigmented lesions that show up in the angle of the eye where the iris conjoins the sclera. For instance, according to Silverman, when a patient comes in with what’s basically a freckle on the iris, conventional optical tools limit the ophthalmologist’s diagnosis because they can’t image any changes occurring behind the iris’ natural opacity. While a pigmented melanoma restricted only to the iris is typically considered very benign, he says, “if we can visualize the underlying ciliary body and see that the tumor extends into it, then the prognosis is quite different—it’s a potentially lethal neoplasm that has to be treated aggressively.” At the same time, he adds, new capabilities for more accurately measuring the depth of any corneal scarring, as well as measuring how much viable cornea remains, can significantly impact the decision to perform a corneal graft or transplant. In addition to ophthalmic applications, Kruse points out that “VHFU could be used to study the effectiveness of skin grafts and associated vascular remodeling that takes place during the wound-healing process. And it can be used to monitor the effectiveness of skin cancer treatments.” As Kruse notes, “Limitations dictated by physics greatly restrict the achievable resolution of MRI and CT for imaging the human eye.” On the other hand, the doctors don’t expect VHFU to supplant other imaging methodologies for examining the eye. Instead, hopefully many more ophthalmologists and radiologists will come to consider adding VHFU as a complementary modality for a greater range of applications. Comparing Imaging Modalities Similarly, optical coherence tomography (OCT) images at higher resolution than traditional ultrasound and VHFU, which makes it good for imaging the macula (the retinal area where fine vision occurs). OCT is an optical method of cross-sectional scanning that measures reflectivity from structures; it’s being investigated for ophthalmic and other uses. Silverman points out, however, that OCT “has very limited penetration, maybe a millimeter into the tissue. Now within that millimeter it gets terrific resolution, but it can’t go through opacities like the sclera very well.” That limitation makes OCT unable to differentiate, as in the earlier example, between a benign melanoma on the iris or an invasive neoplasm penetrating into the areas behind it. As for CT, because its high contrast allows imaging precise location and size, it remains the most popular choice for viewing foreign metallic bodies lodged in the eye. But because the modality involves radiation, it can be potentially hazardous to the eye’s sensitive structures, including the retina. “There’s always a danger of cataracts [with CT],” notes Silverman. As clinical researchers, both investigators built their own VHFU systems by interfacing different components from various manufacturers. “Sometimes we go into frequency ranges beyond what the larger companies are interested in developing,” Silverman says. Silverman likens VHFU’s ophthalmic use to the situation still prevalent in cardiology. “The cardiologists generally do the imaging for their patients rather than the radiology department,” he says. “Similarly, most ophthalmic ultrasound is performed by the ophthalmologist.” As Silverman sees it, widespread adoption of VHFU by imaging departments won’t happen anytime soon, partially due to the limited usage and high cost of ophthalmic ultrasound equipment. “The market is relatively small,” Silverman says. “The reimbursement rates are relatively low; it’s a small niche with specific FDA guidelines [and] power limitations.” All these attributes may keep VHFU from finding its way into the radiology suite anytime soon, even as the technology and clinical know-how continues to advance exponentially. “The main disadvantage of increasing [ultrasound] frequency is that the depth of penetration is essentially halved with every doubling of frequency,” Kruse says. “[So] VHFU [remains] primarily limited to peripheral applications such as in the skin and eye.” In his estimate, “the technology needs to move away from scanning single-element transducers to a high-frequency transducer array operating at 25 megahertz or higher. Such an array combined with a real-time beam former would allow for truly real-time exams that clinicians are accustomed to with conventional ultrasound systems.” That said, Kruse believes routine clinical use of VHFU is at least five years away. — J. K. Bucsko is a healthcare writer and editor based in Westville, N.J., and a frequent contributor to Radiology Today.
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