Ultrasound’s changes are incremental, not revolutionary,” says A. Thomas Stavros, MD, medical director of ultrasound and noninvasive services at Radiology Imaging Associates in Englewood, Colo.

Technological change, nonetheless, is transforming the landscape of ultrasound, and many of its practitioners believe that further breakthroughs are on the horizon. New contrast agents, advances in harmonics, and real-time imaging are expected to be solidly established in the field within 3 to 5 years, leading radiologists into diagnostic and even treatment areas unimagined not so long ago.

Shadowing the modality’s advances, however, are concerns that the rising cost of equipment and tightening reimbursements will thwart the promise of state-of-the-art technology.


One advance that is already here (although not fully utilized) is reliable, real-time, compound imaging. Real-time imaging, which is as different from the old B-scanners as movies are from still pictures, has been available for more than

20 years, according to Christopher R. B. Merritt, MD, professor of radiology, Thomas Jefferson University Hospital in Philadelphia. Radiologists who remember the old scanners acknowledge that the change came with a downside: clarity of image was sacrificed. Adding compounding to the equation now gives the radiologist the best of both worlds: clarity plus numerous angles (Merritt says as many as nine), providing better definition of margins of lesions.

“The compound concept has been around for years, but it was not possible to truly implement it because of the intense computational ability needed,” Merritt says. “With ultrasound, unlike other imaging technologies, a huge amount of rapid calculations have to be made to process images. That is why ultrasound has been particularly suited to expand its [diagnostic] capabilities as computer technology not only speeds them up, but the cost of such speed continues to come down.”

He acknowledges that real-time compound imaging is presently limited to viewing fairly superficial structures. That means areas two to three inches beneath the skin, such as muscles and ligaments in the wrist and ankle, or the thyroid gland. “We already do ultrasound on the Achilles and patella tendons,” Stavros notes, but adds that it is feasible to do because those tendons are large and easy to read.


The real excitement, in terms of compound imaging having a significant impact on a large number of patients, is in evaluating breast tissue. It is an area, Merritt says, in which compound imaging will have a powerful impact.

Ultrasound technology that has been available for about 15 months already offers radiologists better definitions of margins of masses found within the breast, which in turn is helping to define treatment modalities, Merritt says. “Compounding reduces artifacts and noise that previously would have confused evaluation of masses that contain fluids, like cysts.” Today, radiologists can feel much more confident in determining that masses even less than 1 cm are benign, Merritt asserts.

One area in which compounding’s usefulness is still to be proven is in examining small calcifications within the breast. There is some evidence, first being explored, that “compounding reduces speckle in imaging,” says Merritt, who notes that identifying calcifications in certain masses will further allow radiologists to be much more accurate in deciding the probability that those masses are malignant.


Advances in high frequencies offer another step forward in further diagnosing breast cancers. “The big shift I have seen is in high-frequency (10-15 mHz) transducers,” comments Beverly Hashimoto, MD, section head of ultrasound, Virginia Mason Medical Center, Seattle. “Just 3 years ago, people were very hesitant to make a diagnosis of breast cancer with ultrasound. We did not have the kind of high-frequency transducers we needed to see the breast clearly. Now radiologists with newer training and up-to-date equipment are more confident in diagnosing cancer.”

According to Stavros, there are still penetration problems even at high frequencies, including artifactual echoes and clutter artifacts. That is why he believes real-time compounding needs the addition of coded harmonics. “The two are not mutually exclusive,” he notes, “and coded harmonics clean out artifactual echoes without degrading resolution.”

Stavros emphasizes that breast ultrasound will enhance, but not replace, mammography. “The vast majority of cancers found by ultrasound and missed by mammography occur in an area of the breast that contains dense tissue that obscures the lesion when using mammography alone,” Stavros notes. “It is therefore possible to select patients with these dense nodules whom we know to be at high risk for false mammograms for evaluation via sonography alone.”

Stavros adds that the latest evaluations (in findings to be released this spring) indicate that where using sonagraphy alone used to lead to five negative biopsies for every one, it is now possible to reduce the negative to positive ratio with ultrasound alone to 2:1. “Thus negative biopsies on solid nodules are being decreased without missing cancers,” he concludes.


There have been a number of advances regarding frequencies, or harmonics, experts acknowledge, but there is still much to learn. Jonathan Rubin, MD, professor of radiology and division director of ultrasound at the University of Michigan in Ann Arbor, notes that simply agreeing on certain definitions has not been achieved.

The harmonics of sound are like refractions of light, he points out. If a light is shone through a prism, it yields one bright beam in the center and then refractions that get progressively weaker moving away from the center. The same principle applies to sound waves.

“The only place you get harmonics is in the center beam, where the sound is strongest,” Rubin explains. That higher harmonic beam obliterates extraneous noise and gives a more accurate picture in coming back than the fundamental beam, the beam that was initially transmitted.

Higher frequency harmonics have been discussed for 2 decades, although they have been used in clinical scanners for just 2 to 3 years. There is no consensus, however, on how to define higher harmonics, Rubin notes. “Some people say the initial beam is the fundamental beam and the higher beam is the first harmonic,” he explains. “Others say the initial beam is the first harmonic and the higher level is the second harmonic.”

As might be imagined, this causes many areas of confusion when experts interpret and exchange information. “We will need an organizing body, like the AIUM (American Institute of Ultrasound in Medicine), to set a standard definition,” Rubin believes.

Higher frequencies, nonetheless, have limitations. “You want a lot of information in the beam, but your amplifier is limited,” he explains. “You cannot put out an infinite amount of energy in your amplifier; you will blow it up. But you can put out a finite amount of energy for long periods. You just run the amplifier for longer periods of time.”

Another problem is that while higher frequencies may be stronger in resolution, they do not penetrate as far as lower frequencies. That is why the issue of coded harmonics is generating a lot of interest. Coding the signal, Rubin says, means it will exhibit different properties at different points in its return. “You can keep track of exactly where the signal’s coming from. [The same principle is used to find objects through sonar.] The codes provide higher spatial resolution,” Rubin says. They also contain frequency information that allows the operator to use harmonics at high frequencies.


The arrival of contrast agents approved specifically for use in ultrasound is eagerly anticipated by many radiologists. Michelle Robbin, MD, chief of ultrasound, University of Alabama Hospital at Birmingham, is particularly enthusiastic about the possibilities. “I think we will have a new contrast agent approved by the Food and Drug Administration this year,” she predicts. Robbin foresees the approval of many more agents, each opening up numerous diagnostic opportunities in ultrasound.

One such opportunity is in vascular ultrasound, such as chemodialysis graft ultrasound, an area in which Robbin works. “I think new agents will improve our ability to see deep and small vessels,” she says.

Robbin is involved in a study using ultrasound to map arteries and veins in patients with end-stage renal disease. “We are evaluating arteries and veins of patients before they need hemodialysis so surgeons can place grafts or fistulas for optimal access.,” she describes. “That way there is less likelihood of discovering that the vein utilized is occluded higher up. We have a National Institutes of Health grant to evaluate whether ultrasound every 4 months will detect stenoses. If we can detect narrowing before a clot develops, we can perhaps improve the life of the graft.”

Contrast agents may also help radiologists utilize both coded harmonics and the field of subharmonics. “Right now, we can generate a very simple code, called pulse inversion, but not very sophisticated codes,” Rubin explains.

Similarly, he adds, subharmonics are very difficult to generate. “They take more energy to produce,” he explains. “Tissue has a very predictable, limited response, and the bubbles have a higher amplitude.” The technique, however, yields beautiful imaging results, he says. “You could look at the size of the bubbles and tell the pressure at certain sites. Right now the only way to measure that is through catheterization.”

Rubin adds that the exciting possibilities of bubble sizing and bubble generation are essentially ultrasound’s exclusive domain. “You cannot do these things with MRI or CT contrasts because of the way the beam interacts with the contrast,” he says.


Picking up and characterizing lesions is another anticipated benefit of new contrast agents, especially when combined with ultrasound’s real-time capabilities, according to John P. McGahan, professor of radiology and director of abdominal imaging and ultrasound at University of California Davis Medical Center. “You could put a probe on the abdomen and watch as the contrast comes into and exits the lesion,” he explains. “By observing different parameters, it might be possible to tell a malignant hepatoma, in which the blood flows more rapidly, from a cavernous hemangioma.” Using ultrasound for such screening, say all the experts, could significantly reduce expenses and patient anxiety.

McGahan also points to another exciting (though not immediate) possibility: “We might be able to put a therapeutic agent inside the contrast agent, inside a microbubble.Then using ultra-high-frequency ultrasound, we could pop that bubble right within the tumor and deliver the therapy exactly where needed.”

One of the limiting factors to this application, Rubin says, is that subharmonics requires a lot more energy to hit those bubbles hard enough to allow them to burst in such a way as to accurately deliver drugs, or even genes. On the other hand, he adds, it may be the bursting of the bubble that produces the energy needed.

Hashimoto does offer one caution regarding all the excitement surrounding contrast usage: “It looks like [the new contrast agents] will allow us to pick up a significant number of cases we used to miss. Whether it will be cost-effective or not is still to be determined.”

Hashimoto believes that whatever the cost, improvement in contrast is not enough, in itself, to hold the key to improving ultrasound diagnostics. “You can see some effect of contrast with plain imaging or plain color Doppler,” she notes, “but to truly take advantage of contrast’s capabilities you need harmonics.” Sophisticated harmonics, she says, “make a tremendous difference in how contrast boosts the gray-scale imaging,” and that in turn may lead to ultrasound being better utilized in areas such as liver scans. “Ultrasound is excellent for scanning the liver,” she notes, “but CT is better still. With ultrasound, you will get 90% of the lesions, but CT still picks up 99.9%.” If that gap could be closed, then ultrasound has the potential to be a truly competitive diagnostic tool in this realm.


McGahan notes that while delivering therapeutic agents directly to tumors is still on the horizon, he and his colleagues are already using high-frequency ultrasound for radio frequency (RF) tumor ablation. “We insert an RF probe into the body and [in many cases] use ultrasound guidance to treat various lesions.” Hepatomas are the main candidates for this procedure, though RF through ultrasound guidance is also utilized in treating metastatic liver tumors and renal cell carcinomas, enabling physicians to treat more tumors than previously possible. “You might have a tumor in an area that the surgeon cannot resect, or have a patient who, for whatever reason, might not survive the surgery,” McGahan explains. “Using this technique, we can ablate those tumors about 90% of the time.”

He adds that primary tumors, such as hepatomas, respond much better if they are less than 4 cm in size and if there are fewer than four tumors present. Also, because these tumors can reappear, it is critical to do follow-up using CT every 3 months. “The beauty is that we can use RF to re-treat the tumors if they do reoccur,” McGahan says.

Questions beyond the clinical arise with all of these advances, now and in the future. For example, there is the potential problem of interspecialty rivalry. Even when all the evidence indicates that ultrasound will work as well as angiography or MRI, Robbin always checks with colleagues in those areas. She rarely finds an objection to her treating the patient. “Angiographers, for example, are so backed up they are grateful for the relief,” she notes.

In discussing ultrasound vs mammography or other diagnostic imaging modalities, Hashimoto also raises the question of whether training issues are being addressed as carefully as technological ones. “Handheld machines are too operator-dependent; that is a real problem in ultrasound as opposed to magnetic resonance,” Hashimoto states.


Perhaps the most critical issue facing radiologists is that of reimbursements. “Anything considered low-tech is not reimbursed well and, unfortunately, ultrasound has been lumped into that arena,” Stavros says. “We have seen excellent reimbursement for CT and MRI, and horrible reimbursements for plain films, mammography, and ultrasound. The latter three are essentially included in contracts as loss leaders.” Ultrasound’s inclusion in the package is particularly ironic, he notes, since the physics and engineering of ultrasound are, if anything, more difficult than those of CT and MRI.

“You have to improve your equipment to meet the standards, but you are losing money on every case you do,” he adds. Stavros says the situation is most critical in mammography, but warns that ultrasound is not far behind. Notwithstanding all his colleagues’ talk about the exciting possibilities for using ultrasound to open new eras in breast imaging, Stavros notices that this is an area that has been hammered the hardest. “Reimbursements are just unsustainable,” he pronounces. By performing a breast ultrasound, he is forestalling a $3,000 biopsy (and the possible cost of legal fees), but he is reimbursed a mere $60 for the study.

“The ultrasound environment here in Colorado is very discouraging,” notes Stavros, who explains that Colorado is one of the country’s most intensely managed states. Stavros places part of the blame for the economic burdens squarely on radiologists’ own shoulders. “The radiologists here have not been as strong in defending our position as perhaps in some other states,” he admits. “It is our fault for not stepping up to the line.”

Radiologists who want to take a stand on reimbursement will have a major struggle on their hands, he believes. “Radiologists are generally hospital-based and you have no say on inpatient contracts,” he says. “Then the fact that you are in-house makes it more likely that the hospital can force you to take that contract and accept it on an outpatient basis, too. In fact, having to accept the inpatient contracts really weakens us, and reduces our ability to negotiate at the outpatient level.

“The trend is bad,” he warns. “We are not going to be able to maintain quality if we cannot make enough to replace old equipment.”

Wendy Meyeroff is a contributing writer for Decisions in Axis Imaging News.