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
"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
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
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
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
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
"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
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.