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The newspaper of The Johns Hopkins University December 4, 2006 | Vol. 36 No. 13
Fast Test for Low Blood Flow in Dogs Detects Early Heart Trouble

Cardiac stress CT could replace all other tests to catch blocked arteries

By David March
Johns Hopkins Medicine

Using the latest in imaging software and machinery — a 64-slice CT scanner — and working with dogs, Johns Hopkins heart specialists have developed a fast and accurate means of tracking blood that has been slowed down by narrowing of the coronary arteries.

Researchers say it took them less than half the time of exercise stress tests and echocardiograms currently used to find early warning of vessels more likely to become blocked and cause heart attack.

The Johns Hopkins team presented its initial findings Nov. 12 at the American Heart Association's annual Scientific Sessions in Chicago. Already, the technique, in which patients are given a drug to stress their heart during the scan, is undergoing clinical testing. Results among 60 patients are expected within a year.

If the human trials prove equally successful, senior investigator Albert C. Lardo, an assistant professor at the School of Medicine and its Heart Institute, says the new scanner "could dramatically change the way we diagnose coronary disease in patients with initial symptoms of chest pain, by providing a safe, noninvasive and fast method to detect blood-flow problems in heart tissue.

"Because it takes less than 15 minutes to perform and does not require patients to be stabilized ahead of scanning," he said, "it could replace most other more time-consuming tests that help find blockages, including not only exercise stress testing and echocardiograms but also positron electron tomography imaging or magnetic resonance imaging.

"The new technique could also help eliminate many unnecessary invasive catheterization procedures when there is no underlying blockage, or become a practical test to verify if treatments with drug therapies, surgical bypass or stented arteries have worked to improve blood flow," he said.

Lardo, a biomedical engineer who specializes in perfusion imaging, says the tiny size of blood vessels, many no bigger than 0.5 millimeters in diameter, often makes it difficult for physicians to pick up the subtle clues that signal the presence of arterial disease. He notes that blood vessels begin to narrow long before mild chest pain and other symptoms occur, leading to reduced blood flow that gradually starves the heart of needed oxygen and nutrients.

According to Lardo, blood flow in these tiny vessels can be readily detected by high-resolution equipment like 64-CT scanners.

The device produces precise 3-D diagnostic pictures within five to 10 seconds by quickly passing X-rays through the body. The resulting digitized signals, called "slices" — and there are 64 — are then reconstructed by a computer and used to build a three-dimensional image of the heart. The picture is so good, researchers say, it decreases the need for invasive, more risky procedures, such as angiograms or cardiac catheterization, to check for arterial blocks.

More than 1 million Americans undergo cardiac catheterization each year, and the procedures take much longer to perform, 30 to 45 minutes, and require several hours for recovery. Roughly one-third of the procedures will turn out to be unnecessary. These tests also carry rare potential complications from infection, heart attack and stroke.

Lead study investigator Richard George, a Reynolds Foundation postdoctoral cardiology research fellow at Johns Hopkins, says it takes between 45 minutes to one hour on average to perform a cardiac stress test with exercise and ultrasound, another common diagnostic procedure, to assess pumping function and blood flow.

"Even when patients have a normal exercise stress test, they may still be in the early stages of atherosclerosis, when vessels start to clog, narrow and harden, gradually straining circulation," he said. The main drawback to the Johns Hopkins test, George says, is that CT imaging, like PET, also exposes patients to radiation from X-rays, but PET takes nearly one hour to perform, whereas CT scanning is quicker.

To assess if blood flow in dogs could be accurately measured with 64-CT, researchers compared the new scanner with an existing test that is considered to be the gold standard and relies on muscle absorption of microscopic beads in the heart muscle.

Six dogs had surgery to place a clamp around a main artery, cutting in half the blood flow to the heart. After surgery, the dogs were injected with the drug adenosine to speed up their heartbeat and maximize circulation. The dose, the researchers note, was the same as that typically used in humans for routine stress testing: 140 micrograms per kilogram per minute, for five minutes.

When forced to pump faster, healthy heart tissue and surrounding blood vessels will adapt, while unhealthy blocked ones will slow blood flow. These changes are not usually perceptible to the human eye from the scanned images but can be detected and quantified with CT imaging and computer analysis. Adenosine is commonly used in stress testing, Lardo said, to relax blood vessels in the muscle, which enhances the contrast between normal and abnormal regions of the heart.

After being injected, each of the dogs had a 64-CT scan of its heart and then underwent the standard test for blood flow with chemical beads. The beads, no bigger than 20 micrometers in diameter and called microspheres, were injected into the animal's bloodstream. Previous research has shown that they will lodge into the heart muscle at a fixed rate compared to how fast blood is flowing. Researchers can actually count the number of beads absorbed into the heart tissue to calculate blood flow.

However, calculating blood flow from the 3-D scanned CT images was more complicated. Researchers used deconvolution mathematical formulas to gauge the speed of blood flow through the heart and its feeding arteries and made separate calculations for each of the organ's three major regions: the front, back and side walls.

When researchers compared the deconvolution measurements with those derived from the microspheres test, they found the two to be almost identical, with statistical R-values of 0.93 to 0.96, with 1.0 meaning a perfect match. Indeed, blood flows ranged from 0.3 milliliters per gram of heart tissue per minute to 8 milliliters per gram per minute.

"We think this is a natural evolution of the technology and a significant improvement in our ability to diagnose problems with blood flow," said George, who conducted the study from June to September. Larger clinical studies, he said, are planned at Johns Hopkins to further refine the use of the latest CT technology for diagnosis of heart disease and other ailments.

The 64-CT scan has been available in North America only since February 2005. Each machine costs between $1.5 million and $2 million. A single test costs approximately $700.

The study was supported by the Donald W. Reynolds Foundation; Toshiba, the manufacture of the 64-CT scanner used in the study; and Astellas Pharma, which makes adenosine, the chemical used in stress testing.

In addition to Lardo and George, Johns Hopkins investigators involved in this study were Caterina Silva, David Bluemke and Joao Lima. Also collaborating was Michael Jerosch-Herold, of the Oregon Health and Sciences University. George's research efforts were acknowledged and presented at the AHA meeting as a finalist for the Melvin Judkins Young Clinical Investigator Award.


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