The pushing, the clawing, the preening! Is this the Miss America contest? No, it’s the annual competition for the angiography market. But the action’s just as fierce.
This year’s crown goes to – ta da – the same winner of the past 106 contests, X-ray. After Roentgen got things going in 1895, peering within the body via catheters and X-ray became, and remains, the gold standard. But the finalists are beauties: cancer-proof vermin, plaque-blasting rays, 3D veins in living, wiggling color, and a bevy of other contenders that until recently were still classified as science fiction.
Digital angiography technology clearly aced the talent event. David Siegel, M.D., chief of the vascular/interventional radiology division of Long Island Jewish Medical Center (New Hyde Park, N.Y.), says that digital angiography gives “better imaging, better detail. We can now see bleeding where we might not have been able to see it before, because we have good digital imaging, and now we can go after it and treat it. It has given us the ability to perceive more.”
Long Island Jewish handles about 140 angiography cases per month. One of its most popular procedures is the newly available technique of uterine fibroid embolization. First developed in France in 1995, it involves injecting particles into the vessels supplying blood to the fibroids, which causes them to shrink.
“If you had told me three years ago that I’d be treating a hundred patients a year for fibroids, I wouldn’t know what you were talking about. And now, all of a sudden, this is what I’m spending a good portion of my practice on,” says Siegel. “It’s very exciting work. It’s a very, very young field.” And one that’s catching on fast.
“One quarter of women develop fibroids, usually in their 30s and 40s,” says Timothy Murphy, M.D., associate professor of BioMed Diagnostic Imaging at Brown University (Providence, R.I.). “There are about 600,000 hysterectomies that are done annually. A third of those are done for fibroids. Uterine fibroid embolization is an alternative to hysterectomy, and less invasive. It’s done usually as an overnight hospital stay, or occasionally as an outpatient procedure. It’s very effective.”
Brown is a testing ground for many new angiography-based treatments, including one for high blood pressure and renal failure in patients with renal artery atherosclerosis. “Those procedures involve placing stents and doing balloon angioplasty in the kidney arteries,” says Murphy. “That’s being shown to be very effective for alleviating hypertension.” In another trial, Murphy said fabric-covered stents are being compared with standard, bare-metal stent material as “a new treatment for people with blocked arteries that supply the legs. That study is showing very good results with the vascular graft.”
Brown also is roadtesting a new endographic device for abdominal aortic aneurysms (AAAs). “About 5 percent of men over the age of 65 have an abdominal aortic aneurysm. When it ruptures, about 80 percent of the people die,” says Murphy. “A new procedure is done by placing a tube in the aorta through an incision in a leg artery, and it’s done using flouroscopic X-ray guidance. The standard treatment involves an abdominal incision and a week or two in the hospital. This procedure is done, with a one- or two-day hospital stay, through a leg incision.”
Last year, Brown and the University of Mississippi (Oxford) began testing the effectiveness of radiofrequency ablation (RFA) on malignant lung tumors as an alternative to surgical lung resection. Tumors have been dispatched with hot needles for a decade, but recent angiography advances have improved RFA’s effectiveness so much that it is now the preferred treatment for some unresectable cancers, surpassing even cryoblation.
In 2000, RITA Medical Systems, Inc. (Mountain View, Calif.) received the first FDA clearance to market RFA systems for treating liver lesions. M.D. Anderson Cancer Center in Houston now uses RFA as the standard treatment for unresectable liver cancer and is studying its use in colorectal cancer. St. George Hospital in Sydney, Australia, is testing it on pulmonary tumors.
Great things, small packages
Pediatric angiography has become a hotbed of gutsy experimentation. Earlier this year, a transcatheter coil designed to seal off brain aneurysms was repurposed to close off fistulas in a toddler’s heart artery at Advocate Hope Children’s Hospital (Oak Lawn, Ill.). The minimally invasive procedure involved a GDC SynerG Detachable Coil System made by Boston Scientific Corp./Target Therapeutics (BSC of Natick, Mass.).
And last May, the Hospital for Sick Children (HSC in Toronto) opened its Centre for Image-Guided Therapy, a multi-modality extravaganza featuring fluoroscopy, CT, ultrasound, laparoscopy, endoscopy, lasers and operating microscopy in four suites where procedures can be combined in one day, under one anesthetic. HSC’s customized IBR system from Toshiba America Medical Systems (Tustin, Calif.) combines a CT scanner and pulsed X-ray C-arm that travel over the table on floor and ceiling rails, and communicate with each other through fiber optics.
Overradiation and how to prevent it have become frequent topics in angio, especially in pediatrics. Patricia Burrows, M.D., chief of the interventional radiology division at Children’s Hospital Boston and a professor of radiology at Harvard Medical School, runs a big vascular anomalies program for small patients. “I do a lot of embolizations and procedures for venous malformations, as well as neuro interventional,” she says. “We have modern digital subtraction equipment. In one of our rooms we have a Philips SpectraBeam that has a special technology for extra filtration of the X-ray beam that allows you to use much lower radiation exposures. We use that plus grid-pulsed fluoro, which reduces the exposure by about 50 percent. And then we also can use the lowest frame rate on the pulsed fluoroscopy.”
Perhaps the greatest advance in magnetic resonance angiography [MRA], says Julianna Czum, M.D., director of vascular MR at the Heart and Vascular Institute (HVI of Morristown, N.J.), is the synchronization of table movement with imaging. “You can image multiple territories, or one extremely long territory, like the legs. That’s caused quite a shift in how patients are followed, diagnosed, and managed with their vascular problems.” In addition, she says, “The contrast material is much safer. The patient doesn’t need to be sedated and undergo the recuperation and preparation that they do for a conventional angiogram. Because MRAs are getting better and better, and people are being referred less and less for conventional angiography, more and more preoperative planning and diagnostic run-off studies are being done with MRA.”
Czum is developing a new MRA technology with Philips Medical Systems North America [Bothell, Wash.] called SENSE, an acronym of sorts for “sensitivity encoding.” It “allows you to basically do MRA as you normally do, but exploit the geometry of surface coils,” she says, by applying specialized MRI antennae directly to the patient’s body. “You can actually get even better image quality when you’re looking at smaller areas of interest,” even on patients who can’t hold their breath or remain still for long. “So it’s like
X-ray fluoroscopy, but with MR, which has a very fast frame rate [400 milliseconds].”
EBT for EBA
Some of the boldest strides in vascular imaging come from Imatron, Inc. of South San Francisco, the designer and sole manufacturer of EBT devices that received FDA clearance in 1999 for their use in minimally invasive angiography (EBA). The scanner fires beams of electrons at tungsten targets around the patient and acquires images in one-tenth of a second, compared with 1 to 2 seconds for other modalities; all scans are collected during a single breath-hold.
“What we do differently is that we’re fast, that we can freeze cardiac motion. No other CT can,” says Jeff Sorenson, director of marketing for Imatron. “Our fastest image is more than six times faster than any other CT imager out there.”
EBA is used for detecting stenosis and occlusions of the coronary arteries, monitoring revascularization procedures, evaluating congenital heart defects and pulmonary embolism, and for treating renal artery stenosis and diseases of the aorta. Because catheterization is unnecessary, the cost of an electron beam cardiac scan averages $1,900; a similar CT scan can cost $3,000 to 6,000, says Sorenson. But what’s causing a major stir is the technology’s ability to predict cardiac risk by measuring coronary artery calcification, a feature that has spawned a profitable new specialty and a ton of controversy [see sidebar “Preventive Scanning”].
Harvey Hecht, M.D., F.A.C.C., director of preventive cardiology and EBT (electron beam tomography) at HVI, has been using EBT with TeraRecon’s (San Mateo, Calif.) newest 3D workstation. By injecting contrast through a peripheral vein and collecting an EBA 3D image, he says, “you can see all three coronary arteries, and you can decide whether the arteries are normal or significantly narrowed. It’s also superb for evaluating bypass grafts. The patient’s in and out in a half hour, from start to finish.”
A rather huge surprise is the way recent improvements in angiography have propelled gene therapy, considered futuristic five years ago, into clinical use. The first federally approved protocol started in 1990, but precise insertion of genetic information into target cells couldn’t be controlled until real-time 3D angiography guidance became available in the late 1990s. This generated a tidal wave of new cancer and cardiovascular therapies, including: transvascular delivery of gene-carrying viruses through an angiographic catheter; treatment for transplant coronary vasculopathy (for which no known effective therapy existed); heading off post-angioplasty restenosis with angiogenesis (growing new blood vessels); and choking off cancers with anti-angiogenesis.
The Federal Trade Commission predicts the gene therapy market will exceed $45 billion by 2010. In 1998, the American Heart Association estimated 58 million Americans had cardiovascular disease. Angioplasty is performed on more than 400,000 patients every year. Go-getters are wasting little time.
As of June 2000, some 250 gene therapy clinical trials were underway. In New York, Memorial Sloan-Kettering Cancer Center successfully used anti-angiogenesis to create a strain of mice that are immune to cancer, and Cornell University grew new heart blood vessels in humans to bypass blocked ones. Collateral Therapeutics Inc., a biotech research company in San Diego, started phase I/II clinical trials in 1998 for an angiogenesis gene therapy for coronary artery disease that would replace surgical bypass or angioplasty. The company has developed many other proprietary genes as well, including one for heart muscle regeneration to treat heart attack, and another for use in nonsurgical treatment of congestive heart failure and peripheral vascular disease.
Surgi-Vision’s Endo-Esophageal MRI coil
images the heart and throat.
Johns Hopkins Medical Center (Baltimore) and Surgi-Vision (Columbia, Md.) have developed a .032-inch titanium alloy MRA guidewire for use in gene therapy. It helps to image the arterial wall and can remain within an artery for up to six hours without complications. Biotech giant BSC already owns one patent for a double-balloon catheter used in gene delivery to blood vessels, another for an angiogenic cardiac therapy, and it has applied for nine more. It also owns the only FDA-approved, fluid-cooled electrophysiology catheter ablation technology.
Angio: The next generation
Interventional radiology has only been sanctioned as a separate specialty by the Centers for Medicare and Medicaid Services since 1992, and 3D imaging has only been available commercially since 1998. Nevertheless, the competition is so overheated that in 2001, BSC had to squash a string of infringements of its angioplasty stent licenses, and RITA lost two RFA-related patent claim actions and initiated six more. But research still barrels along, and innovation springs eternal. Here are a few of the new kids in town:
UWGSP8 is the catchy project name for 3D Ultrasonic Angiography (3D USA), a new Doppler-based imaging system being developed at the University of Washington in Seattle. Two-dimensional color scans are reconstructed with proprietary software into volumetric renderings of vasculature structures and their spatial relationships.
Real-time catheter tracking: Researchers at the University Hospital (Freiburg and Bonn, Germany) have developed and tested a real-time, contrast-enhanced 2D MRA system for visualizing vascular catheters with high temporal and spatial resolution.
MPCE-VCATS: Not so short for “magnetization-prepared contrast-enhanced breath-hold volume-targeted imaging,” this new version of 3D MRA being developed at Northwestern University in Chicago. It combines an extracellular contrast agent with inversion recovery magnetization-preparation to resolve clarity issues caused by heartbeat and breathing noise.
Three-dimensional arteriography (3DA): Beth Israel Medical Center in New York, N.Y., uses a new type of neuroimaging that it believes will replace conventional angiography in treating carotid and intracranial vascular diseases, including aneurysms and arterio-venous malformations. The 3DA images are often clearer than DSA, and require less radiation, contrast and assembly time.
Multi-slice computed tomography (MSCT): A noninvasive method for detecting stenoses in coronary arteries, The Lancet recently reported that MSCT had the “potential to develop into a reliable clinical technique. MRI and EBCT [electron beam computed tomography] ? both have significant limitations in reliable visualisation of the coronary arteries. MSCT scanners ? allow noninvasive coronary angiography within a single breath-hold by use of a rotation speed of 0.5 s[econds] and sophisticated algorithms for retrospective electrocardiographic gating.”
Laser-assisted angioplasty: In 1998, a solid-state, pulsed-wave, mid-infrared laser was introduced that could vaporize and remove atheromatous and thrombotic plaques. It was tested on heart-transplant recipients considered unsuitable candidates for balloon angioplasty, with a procedural success rate of 100 percent.
Chronic pelvic pain in women: Often the result of faulty valves in ovarian veins that cause blood pooling, the condition can now be treated on an outpatient basis with embolization using stainless steel coils placed with a catheter.
Chemoembolization: Polyvinyl alcohol particles combined with chemotherapeutic agents are injected into blood vessels that feed tumors. The particles block off the vessels, and the drugs stay in the tumors.
ICG: Indocyanine green (ICG) angiography is retinal imaging with dye that fluoresces in infrared light. It can detect lesions too small to see with standard fluoresce in angiography. The recent availability of high-sensitivity fundoscopic cameras has transformed the treatment of age-related macular degeneration.
Clot busters: Ekos Corp. of Bothell, Wash., is testing Lysus, a miniaturized catheter containing a tiny ultrasound transducer that delivers a thrombolytic drug directly to blood clots of stroke patients. The ultrasonic energy induces a change in the clot that allows the drug to better penetrate it. Angiography is then used to monitor speed and extent of clot dissolution. Lysus also is being tested in gene therapy to prevent restenosis.
More than a fad
“The growth in radiology will largely be in the area of therapeutics,” predicts Joseph Fritz, Ph.D., Toshiba America’s senior manager of clinical development. “The use of intra-arterial techniques for treatment has become rather popular. Combining CT or tomography capability with that gives the opportunity to see the organ and understand the breadth of that pathology, and also then use the angiography system to be able to guide the catheter right up to the organ.”
Left: A customized Toshiba IBR combination CT/X-ray system mounted on floor and ceiling rails with a fiber optic communication system between the scanner and C-arm is installed at the Centre for Image-Guided Therapy at the Hospital for Sick Children in Toronto. Right:? A snapshot from a Toshiba America Medical Systems’ 3D Angio dataset, represents the posterior-to-anterior view of the left internal carotid circulation of the human brain.
In June at Johns Hopkins, Toshiba installed the next generation of the CT/angio system it installed last spring at HSC. The new one is capable of 0.5-second rotation speeds. Fritz says it is an “Aquilion CT system equipped with interventional capability. With that system, there have been RF ablations of tumors in kidneys, and biopsies. A number of standard techniques that are often done under ultrasound guidance are being done under CT guidance.”
“We have new angio systems that are going into Johns Hopkins soon. One is a neuro biplane system that has 3D capabilities and another, within the cardiology area, is a dual-plane system. It allows you not only to do imaging of the heart and standard coronary cath procedures, but also peripheral procedures. It has a configuration where one console can actually access two very different kinds of C-arms for two applications in one room. And we have new versions of that equipment that will be tapping into the flat-panel technology.”
Fasten your seatbelts, everyone.
Preventive Screening and EBA
How hot is electron beam angiography (EBA), the angiography application of the electron beam tomography (EBT)? Last spring Imatron Inc. (South San Francisco) introduced the C-300, a new PC-based, multi-phase beam model, and both the Cooper Clinic (Dallas) and California HeartScan (Sacramento, Calif.) claimed to be the first buyer.
A seven-year study by the Mayo Clinic (Rochester, Minn.) and the University of Michigan (Ann Arbor) completed last July showed that EBT could predict future cardiac events with only a coronary artery calcification measure and the patient’s age. EBT also proved more effective than a coronary angiogram in predicting cardiac risk. Another EBT study completed this year at the Arizona Heart Institute (Phoenix) proved that acceptable cholesterol levels for women 55 and older, as defined by the National Cholesterol Education Program guidelines, are dangerously miscalculated. Almost 1 million Americans die annually from heart disease, and 1.5 million more are disabled.
Imatron’s electron beam tomography (EBT) has proven helpful in predicting cardiac events using calcification as one indicator.
Bottom line, EBT is fast, noninvasive, could replace stress tests altogether and can prevent heart attacks. What’s the catch, then? There are several. For one thing, most insurance companies won’t pay for preventive scans. Heart disease “is a leading cause of death, and it can be detected early,” said Imatron’s Sorenson. “An insurance company isn’t going to get real excited about our ability to find a whole bunch of people who need treatment at their expense.”
The fact is, angiography for any reason is unpopular with insurers. An alarming report last year in the New England Journal of Medicine claimed that Medicare patients in managed-care plans were significantly less likely than those using fee-for-service coverage to receive coronary angiography following a heart attack, even when it was recommended (46 percent vs. 34 percent). The report noted that coronary angiography can lead to interventions, which Medicare would have to foot. The Ontario Hospital Association’s Hospital Report 2001 said things are even worse in Canada, where healthcare is nationalized: only 21 percent of heart attack patients receive angiography while hospitalized.
Therapeutic angiography, being such a hot potato, debate naturally rages over the value of preventive angiographic screening. Coronary calcium can occur in people with fairly clear arteries, and because scanners don’t actually measure plaque, a low score doesn’t necessarily mean a clean slate. Scanners also see anomalies in blood vessels that can appear to be cancerous growths, but in fact are benign. No standards have been set for these screenings, as they have for mammography.
The American College of Radiology, the American College of Cardiology and the American Heart Association all vigorously oppose CT scanning merely for preventive maintenance. However, doctors don’t discourage patients who request them; after all, they still have to pay for all that snazzy new equipment, which can cost upwards of $1 million.
Radiological Associates of Sacramento Medical Group Inc. is open six days a week and is booked solid for preventive CT screens. HealthView in Newport Beach, Calif., performs 6,000 scans per year. The Cooper Clinic has scanned more than 12,000 patients since it bought its equipment last year. Preventive imaging typically ranges from $300 for heart or lungs to $1,000 for a full-body scan.
“There’s a groundswell of people who want the test,” said Sorenson. “And there’s the Baby Boomer demographic, where people are retiring wealthy and all they need to hang on to is their health, and they’re willing to even pay for these types of tests.” Women have been convinced to have routine mammographies, said Sorenson, because insurance companies will reimburse for that. But most women won’t die of breast cancer. “They’re going to die of heart disease first, and lung cancer next, and colon cancer after that. Mammography is way down the list. So why not heart scanning?”