Ultrasound technicians often need as much finesse as couch potatoes adjusting the rabbit ears atop their fuzzy television sets.
Although ultrasound gear has improved with each passing year, getting useful results from the blurry flurry of video images still depends on a lot of operator technique and a little luck. As many as one in five cardiac ultrasound exams, for instance, isn't clear enough for a doctor to make a diagnosis, experts say.
Now ultrasonographers are about to get a helping hand from technology that their colleagues operating X-ray, computed tomography and magnetic resonance imaging machines have had for years: contrast agents. These drugs -- used to highlight an area of interest against its background -- are finally coming to ultrasound.
Besides breaking new clinical ground, however, the ultrasound imaging drugs might strain the budgets of hospital departments. Administrators are used to shelling out millions of dollars for contrast agents in X-ray, CT and MRI -- but not ultrasound.
The new era opened in January, when Molecular Biosystems, a San Diego-based drug company, won Food and Drug Administration approval for Optison. The injectable solution of microscopic gas bubbles brightens images when sonarlike waves hit them.
By this summer, Sonus Pharmaceuticals in Bothell, Wash., which has licensed U.S. marketing rights for its product to Abbott Laboratories, is expected to have the FDA's go-ahead for a contrast agent with both cardiology and general radiology uses. In the wings are a host of offerings from other drug companies.
For the record, Optison isn't the first contrast agent for ultrasound, but it's the first of a new generation of agents expected to be widely embraced. Since 1994 Molecular Biosystems has sold a primitive contrast agent called Albunex, which has failed to draw much attention because it works for less than 40 seconds. The new agents, however, last for minutes and make the difference between blurry shadows and anatomy shown in stark relief.
But the ultrasound imaging boost won't come cheap. Optison, being marketed by St. Louis-based Mallinckrodt, has a list price of $110 per patient. Sonus confirmed it will charge a similar amount, although pricing won't be determined until its agent, EchoGen, has FDA approval.
Even if contrast agents are used in only a fraction of the more than 50 million ultrasounds performed each year, the total direct costs to health systems are likely to be high. Analysts predict 20% to 25% of ultrasound exams ultimately will use contrast agents, up from essentially none today. At $100 per patient dose, the U.S. appetite for ultrasound contrast agents could top $1 billion within a few years.
Advocates of the agents say the cost is easily offset by clinical benefits and savings from eliminating other tests.
"There's a great potential for saving money," says Barry Goldberg, M.D., director of the ultrasound division at Thomas Jefferson University Hospital, Philadelphia. Fast, in-office diagnosis will lead to better outcomes in many cardiac patients, he predicts. And down the road, the contrast agents should allow easy visualization of blood vessels and perhaps even differentiation between malignant and benign tumors. "There is going to be a learning process for this to find its right place, but it will lead eventually to wide acceptance," Goldberg says.
To pave the way, drugmakers have bankrolled cost-effectiveness studies in tandem with the clinical trials needed for FDA approval.
"Each time someone uses it they save $119 . . . even after paying for the contrast agent," says Bobba Venkatadri, chief executive officer at Molecular Biosystems, citing a study of echocardiograms his company funded. "That's a powerful, telling story."
For potential customers, the trick will be balancing savings against the hard dollars flowing out of department budgets.
"I'm concerned about the potential for overutilization," says Andrew Rosenson, M.D., medical director at UtiliMed, a Northbrook, Ill.-based clinical utilization management company. A cardiac ultrasound with contrast agents could cost as much or more than a nuclear imaging scan, the current gold standard, Rosenson says.
Drugmakers counter that ultrasound studies, even with contrast agents, look positively thrifty compared with high-priced angiography or MRI. And better ultrasounds should lead to savings by dramatically reducing the need for more expensive second-line exams, such as nuclear medicine.
Until the drugs are used widely, however, those claims must rest on limited clinical studies and simulation by spreadsheet.
"It's always hard to quantify something you don't do," concedes Terry Willard, a vice president at Sonus Pharmaceuctical. "The best we can do is develop some comprehensive models in a patient population and calculate the probable savings."
Ultrasound, like MRI before it, was once sold as the imaging gadget that didn't need contrast agents.
But savvy users have hungered for the drugs, which make scans easier to perform and potentially more useful.
"I'm a believer in ultrasound contrast," says J. Brian Fowlkes, a researcher in contrast agents at University of Michigan Medical Center, Ann Arbor. "There are and will be applications." But, he adds, potential buyers should proceed cautiously until they see "the results of people actually using the (agents)."
Administrators and clinicians should have time to adjust. It took three years for MRI contrast agents to hit 20% of all exams after the drugs were approved for marketing.
Mallinckrodt, a drugmaker that has licensed U.S. marketing rights to Optison, is unfazed. "As with any new launch with a whole new concept, you're dealing with the innovators and early adopters first," says Neal Mulhilly, vice president for ultrasound at Mallinckrodt. For now, he says, "we have to find the people who want to write the papers rather than read them."