The use of computed tomography (CT) to assess myocardial scar, viability, and perfusion has been the subject of ongoing investigation. Although initial animal studies were encouraging, the clinical application of myocardial imaging with single-detector CT met many obstacles.1-9 These included poor temporal and spatial resolution, extensive artifact due to cardiac motion, and unreliable intravascular contrast volume due to a signiﬁcant ﬁrst-pass effect.
is currently a third-year Cardiology Fellow at Northwestern
Memorial Hospital in Chicago, IL. She completed her medical school
training at Albert Einstein College of Medicine in Bronx, NY, in
2001. She completed her internship and residency training in
Internal Medicine in the Department of Internal Medicine, New
York-Presbyterian Hospital, Columbia Presbyterian Medical Center in
New York, NY. She completed her training in Internal Medicine in
2004. She completed her Cardiology Fellowship in June 2007 and will
complete an additional year in cardiac imaging training at
Northwestern Memorial Hospital during the academic year of
Multidetector computed tomography (MDCT) may be useful in
evaluating myocardial scar and viability in addition to its
current clinical use in assessing coronary artery disease and
coronary anatomy. Promising data suggest that MDCT may also be
used to assess perfusion. Therefore, electrocardiographic-gated
MDCT can potentially provide information on coronary anatomy,
myocardial infarction, viability, and perfusion with one
diagnostic test. Although clinical use is currently limited by
radiation and contrast doses, future modifications may permit
more widespread use of this technology.
The use of computed tomography (CT) to assess myocardial scar,
viability, and perfusion has been the subject of ongoing
investigation. Although initial animal studies were encouraging,
the clinical application of myocardial imaging with single-detector
CT met many obstacles.
These included poor temporal and spatial resolution, extensive
artifact due to cardiac motion, and unreliable intravascular
contrast volume due to a significant first-pass effect.
With the recent advent of the electrocardiographic (ECG)-gated
multidetector CT (MDCT) for the assessment of coronary artery
disease (CAD), there has been a renewed interest in the use of CT
to evaluate myocardial scar, viability, and perfusion.
Gating the cardiac structures to the ECG has improved the
temporal resolution of the conventional CT scanner to 82 to 165
msec. The use of ECG-gated MDCT permits a high-spatial-resolution,
single-breath-hold technique, which enables the reconstruction of
myocardial slices as thin as 0.5 mm. Both increases in spatial and
temporal resolution allow clinically practical anatomical
assessment of the coronary arteries in an intermediate- to
However, the anatomic assessment of obstructive CAD is only a part
of the overall evaluation of patients with heart disease. Given the
prognostic importance, research is being conducted to evaluate the
ability of MDCT to assess myocardial scar, viability, and perfusion
in addition to defining coronary anatomy.
In both acute and chronic myocardial infarct, the
revascularization of viable myocardium may result in improvement in
ventricular function and long-term survival.
To date, rest-redistribution thallium scans, dobutamine stress
echocardiography (DSE), and delayed enhanced cardiac magnetic
resonance imaging (DE-CMR) are the most accepted means to evaluate
myocardial infarction and viability.
Pharmacologic and exercise nuclear perfusion and PET scanning are
well-established modalities to assess myocardial perfusion. The
advantages of MDCT compared with these available imaging techniques
include a greater spatial resolution and shorter scanning times.
This article will review the literature to date on myocardial scar,
viability, and perfusion assessment with MDCT.
Characterizing myocardium on CT
After an intravenous (IV) bolus injection of contrast material,
2 techniques are available to evaluate the myocardium: first-pass
contrast-enhanced MDCT (CE-MDCT) imaging and delayed CE-MDCT
(DE-MDCT). Signal intensity differences (measured in Hounsfield
units [HU]) vary as a result of differential attenuation of the
X-ray beams on iodine molecules and various soft tissue components
within the myocardium. These differences in signal intensity may be
used to identify areas of myocardial scar and viability.
In first-pass CE-MDCT imaging, the MDCT is performed immediately
following an IV contrast bolus. A lower-than-normal signal
intensity area (a hypo-dense region) of the myocardium indicates
either the presence of microvascular obstruction or obstructive
epi- cardial coronary disease (Figure 1). Microvascular obstruction
represents regions of myocardium with no perfusion caused by
anatomic obstruction of capillaries by cellular debris secondary to
Delayed enhanced MDCT imaging is performed between 5 and 15
minutes after the administration of contrast. A higher-than-normal
signal intensity (a hyperenhanced region) indicates infarcted
myocardium (Figure 2). Hyperenhancement is recognized in patients
with recent and old infarctions.
In the acute setting, hyperenhancement results from cellular and
microvascular damage with leakage of contrast into the
extracellular space coupled with reduced outflow rates of contrast
agents in infarcted myocardium relative to normal myocardium.
In the chronic setting, hyperenhancement is thought to be secondary
to contrast accumulating within the interstitial space, which
comprises more of the total myocardial volume due to loss of
myocytes in the area of scarred myocardium.
Contrast-enhanced cardiac CT to assess myocardial scar
Most contemporary studies have used at least 16-slice MDCT for
Subjects have been pretreated with beta-blockers or antiarrhythmic
therapy. According to the available data, the amount of contrast
used varies in animal studies from up to a 150 mL bolus
to an equivalent of 200 mL in a 70-kg person.
A range of 120 to 140 mL of contrast has been used in studies
performed in humans, which is more than the usual dose for imaging
the coronary arteries with MDCT.
The contrast doses used in the human research trials are more
feasible for clinical use than are those used in the animal models,
although the increased contrast doses in the animal studies may
result in improved image quality.
During first-pass CE-MDCT images, the scanner is programmed to
begin imaging at the time the signal in the ascending aorta reaches
a predefined threshold of HU. Images are reconstructed in diastole
of the cardiac cycle with retrospectively or prospectively gated
cardiac MDCT, with or without dose modulation. Ten to 15 minutes
after contrast injection, another CT acquisition is acquired to
obtain DE-MDCT images.
The details of the CT protocols are provided in Table 1. The
radiation doses range from 7 to 8.2 mSv for men and 7 to 10.7 mSv
for women for the first-pass MDCT and from 2.4 to 2.7 mSv for men
and 2.4 to 3.8 mSv for women for the DE-MDCT (Table 2).
Typically, regions of hyperenhancement and hypoenhancement are
visually identified by experienced operators. Once regions of
delayed hyperenhancement are identified, investigators analyzed the
involved regions quantitatively.
Differing methodologies to quantitate regions of hyperenhancement
or hypoenhancement have been used. These include defining involved
myocardium according to a 16-segment
as the sum of the hyperenhanced and hypoenhanced regions,
by the Simpson's method,
or as a percentage of the left ventricular
Investigators have also measured CT attenuation values (expressed
in HU) of the hyperenhanced or hypoenhanced regions as compared
with remote myocardium
and determined maximum signal intensity, wash-in time, and slope
during the first pass of the contrast material to compare
differences between normal and infarcted myocardium
First-pass contrast-enhanced CT in defining infarct
Studies have evaluated first-pass CE-MDCT to identify myocardial
Mahnken et al
compared first-pass perfusion imaging between CE-MDCT and CE-CMR in
an acute infarction porcine model. Areas of hypoenhancement were
shown to correlate well with areas of myocardial infarction that
were identified on pathologic specimens treated with
triphenyltetrazolium chloride (TTC). Visual assessment of MDCT
revealed hypoenhancement in 10 of 36 segments. Triphenyltetrazolium
chloride staining proved the presence of myocardial infarction in
Nikolaou et al
retrospectively compared DE-CMR and perfusion CMR with first-pass
CE-MDCT in patients who had undergone all 3 examinations for the
assessment of myocardial perfusion and viability. First-pass
CE-MDCT was evaluated for areas of myocardial hypoenhancement.
First-pass CE-MDCT accurately detected chronic myocardial
infarctions, but ischemic perfusion defects were not reliably
This is because hypoenhanced regions can correspond to either a
poorly perfused region of myocardium or re-gions of microvascular
obstruction. More recent studies have compared first-pass CE-MDCT
to DE-MDCT. These studies indicate that DE-MDCT more accurately
detects areas of myocardial infarction.
These data will be discussed in the following section.
Delayed contrast-enhanced CT in defining myocardial infarct
Comparison with pathologic specimens-
Lardo et al
evaluated the accuracy of DE-MDCT for quantifying microvascular
obstruction and infarction in the acute and chronic setting. They
used a left anterior descending artery (LAD) occlusion/reperfusion
model of acute myocardial infarction in a canine model and chronic
myocardial infarction in a porcine model. Delayed CE-MDCT was
performed before the occlusion and after 90 minutes of vessel
occlusion in the acute infarction model. Delayed CE-MDCT was
performed 8 weeks after reperfusion in the chronic infarction
model. After the imaging protocol was completed, the animals were
euthanized for histopathologic analysis. Infarcted myocardium by
DE-MDCT was characterized by well-delineated hyperenhanced regions
that reached peak intensity 5 minutes after contrast injection.
Direct comparisons of reconstructed slice-matched DE-MDCT and
TTC-stained images showed excellent correlation with infarct
morphology and accurately predicted the actual transmural extent of
myocardial injury as determined by TTC in 35 of 35 postmortem
slices in the acute infarct canine model (Figure 3). Bland-Altman
analysis illustrated that MDCT infarct volume ratios matched well
with those measured by postmortem TTC in both the acute canine
infarct model (21.4% versus 20.8%, mean difference 0.7%, 95% CI
-2.04 to 3.44) and the chronic porcine infarct model (4.15 ±1.93%
versus 4.91 ± 2.06%, mean difference -0.763%, 95% CI -1.54 to 0.02)
Comparison with DE-CMR-
The extent of myocardial infarction and viability can be evaluated
Evidence of viability on DE-CMR has been correlated with recovery
of the left ventricular function after revascularization.
Kim et al
reported that viable myocardium, defined as myocardial scarring of
<25% of the total wall thickness, was associated with an
improvement in left ventricular contractility in 71% of
dysfunctional segments. In current clinical practice, CMR is not
usually performed in patients with cardiovascular disease who have
implanted cardiac defibrillators or pacemakers. Therefore, a
clinical need exists for alternative imaging strategies that
provide similar anatomic, functional, and viability imaging
capabilities. Despite the fact that contrast enhancement of
myocardium with MDCT and CMR acts by different physical properties,
image patterns produced in infarcted and noninfarcted myocardium
are similar. Consequently, DE-MDCT may detect acute and chronic
myocardial infarctions in a way similar to DE-CMR.
In a porcine model, the performance of DE-MDCT is in good
agreement with DE-CMR and TTC pathology.
Preliminary studies have also been promising in humans. Mahnken et
evaluated revascularized patients within 2 weeks of an acute
ST-elevation myocardial infarction. Patients underwent DE-MDCT and
DE-CMR. There was excellent agreement of myocardial infarction size
and location for DE-MDCT and DE-CMR. The extent of myocardial
infarction agreed in 415 of 448 (93%) (kappa = 0.878) of myocardial
segments. The mean size of myocardial infarction on MRI was 31.2 ±
22.5% per slice compared with 33.3 ± 23.8% per slice for
late-enhancement MDCT (Figure 5).
evaluated the correlation between CE-MDCT and CE-CMR in patients
with either acute or chronic myocardial infarctions. They performed
first-pass MDCT, first-pass CMR, DE-MDCT, and DE-CMR. There was
good agreement of delayed hyperenhanced regions between DEMDCT and
DE-CMR on a segmental basis (82%, kappa = 0.61,
<0.001), with slightly better concordance for acute (kappa =
<0.001) than chronic patients (kappa = 0.52,
<0.001). Concordance for identification of infarct location was
excellent if performed on a patient basis (kappa = 0.90,
Given the anatomic correlation between DE-MDCT and DE-CMR, findings
on DE-MDCT are expected to have similar prognostic implications as
DE-CMR. Furthermore, the improved spatial resolution of MDCT,
permitting slices 5 to 10 times thinner than those used for CMR
viability imaging, may allow for more detailed myocardial imaging.
This may be useful for improved scar localization for ablative
therapy in the treatment of arrhythmias.
Comparison with dobutamine stress echocardiography-
Habis et al
compared viability assessment between CE-MDCT and DSE.
Contrast-enhanced MDCT was performed immediately following
coronary angiography in patients with acute coronary syndromes
requiring urgent cardiac catheterizations. Additional contrast was
not administered. The extent of hyperenhancement was considered
sub-endocardial if <50% (Figure 6) and transmural if >50% of
the left ventricle wall thickness was involved (Figure 7). The
absence of hyperenhancement or subendocardial hyperenhancement was
expected to reflect viability. Patients were considered to have a
transmural in-farction if ≥2 adjacent segments exhibited transmural
late hyperenhancement on 64-slice CT. Low-dose DSE was performed 2
to 4 weeks following the acute infarction. There was agreement
between CT hyperenhancement and low-dose DSE results in 560 of 576
(97%) evaluated segments. Sixty-four-slice MDCT performed
immediately after coronary angiography offered good accuracy and
very good positive predictive values for viability assessment when
compared with low-dose DSE.
The initial investigations have found DE-MDCT to be a comparable
imaging technique to DE-CMR for evaluating infarct size. These
studies did not evaluate the prognostic implications of these
similarities. The above study conducted by Habis et al
is the first study to indicate that the anatomical extent of
infarction demonstrated on MDCT may reflect myocardial viability
(Tables 3 and 4).
Although the initial studies have been promising, additional
research is necessary to explore the clinical use of MDCT in
imaging myocardial infarcts. Scar on DE-MDCT may have similar
prognostic implications as scar identified with DE-CMR, but
prognostic data are not available yet. Although preliminary data
comparing DE-MDCT with DSE are promising,
no study to date has confirmed that the anatomic similarities seen
with DE-CMR and DE-MDCT translate into clinically meaningful
prognostic information. A larger study evaluating morphologic and
prognostic similarities between DE-CMR and DE-MDCT is
Further development of myocardial imaging techniques with MDCT
is necessary. Current use compares the relative differences between
normal and abnormal myocardium. Defining regions based on absolute
values may also be useful. This would permit the evaluation of more
subtle differences between normal and abnormal myocardium on the
basis of a systematic reduction in global flow reserve. This may
aid in the identification of microvascular disease, a disease
ubiquitous in diabetic patients, rather than limiting evaluation to
large epicardial arterial disease.
Contrast-enhanced cardiac CT perfusion stress
Pharmacologically induced coronary vasodilation with adenosine
is an established diagnostic tool to evaluate obstructive CAD.
Adenosine stress testing is routinely performed with
single-photon-emission CT (SPECT) imaging. Adenosine perfusion CMR
has also been reported to accurately detect significant coronary
occlusive disease when compared with invasive coronary angiography.
Preliminary research, described above, has established similarities
in infarct imaging between CE-CMR and CE-MDCT. Given these
similarities, the success of studying myocardial perfusion with CMR
may be applicable to cardiac MDCT. Multidetector CT has been shown
to accurately measure myocardial blood flow.
If MDCT perfusion can successfully diagnose obstructive CAD with
similar accuracy to available noninvasive stress imaging studies,
it will be the first noninvasive imaging tool to provide
complementary information on coronary anatomy and its physiologic
consequences with one diagnostic study.
Most contemporary studies have used a minimum of 16-slice
capability MDCT for perfusion imaging.
Subjects have been pretreated with beta blockers to lower resting
heart rates. Adenosine is then infused for a total duration of 5
minutes. Three minutes into the 5-minute adenosine infusion, the
stress images are obtained. If a rest scan is performed, it is done
20 minutes after the stress perfusion scan. The amount of contrast
given is 100 mL in animals and 70 mL per scan in humans. During the
first-pass contrast-enhanced imaging, a single 3-dimensional set of
images is acquired. The scanner is programmed to begin imaging at
the time the signal in the ascending aorta reaches a predefined
threshold of HU, or by calculating the scan delay using a test
dose. Images are usually reconstructed in diastole with
retrospectively gated cardiac MDCT.
Estimated radiation doses were not provided in these studies.
Myocardial perfusion studies using contrast-enhanced
Pharmacologically induced vasodilator coronary perfusion studies
with MDCT have been evaluated both in animal and human subjects.
George et al
evaluated the accuracy of first-pass CE-MDCT in measuring
differences in regional myocardial perfusion during adenosine
stress in a canine model of LAD stenosis. Eight dogs underwent LAD
stenoses to maintain baseline flow, but attained a ≥50% reduction
in hyperemic flow. Contrast-enhanced MDCT imaging was performed
once during a 5-minute adenosine infusion (Figure 8). Regional
signal densities were evaluated in stenosed and remote territories
and compared with microsphere-based myocardial blood flow measure-
ments. A significant linear association was found between the
regional signal intensity and myocardial blood flow in the region
of the myocardium supplied by the stenosed artery (Figure 9). This
study found that adenosine-augmented first-pass CE-MDCT can be
successfully performed in a canine model of LAD stenosis.
Kurata et al
performed a similar study in 12 human subjects without known CAD
who presented with new-onset angina, were asymptomatic with
multiple coronary risk factors, or had an abnormal exercise ECG.
The patients underwent conventional SPECT stress testing with an
exercise- or adenosine-induced stress thallium-201 and adenosine
CE-MDCT. The stress CE-MDCT was performed 3 minutes into a 5-minute
adenosine infusion, and the rest CE-MDCT was performed 20 minutes
after the first scan. Adenosine stress CE-MDCT was compared with
stress thallium-201 myocardial perfusion scintigraphy. There was
agreement between CE-MDCT and SPECT imaging in 30 of the 36 (83%)
evaluated vascular territories.
Although larger studies are necessary, this is the first published
data revealing promising results of the use of MDCT to evaluate
Contrast-enhanced MDCT perfusion is an attractive imaging
modality. With one diagnostic test, information on coronary anatomy
and its physiologic effects on myocardial perfusion, the presence
of myocardial viability, and an assessment of myocardial function
would potentially be available. Preliminary data suggest promising
results in a very select patient population. These studies have
indicated that perfusion defects can be identified with first-pass
CE-MDCT during adenosine infusion. The initial positive results are
tempered by many challenges that must be overcome be-fore the
widespread clinical use of this technique. Studies validating the
technique in larger clinical populations of patients with diverse
coronary anatomy and clinical presentations are necessary. Further
investigation is also necessary to validate the use of first-pass
imaging to accurately evaluate myocardial perfusion with CE-MDCT
and to define the appropriate use of CE-MDCT in clinical practice.
Future uses may include performing stress perfusion in patients
following the detection of an intermediate stenosis on CT
angiography. This would enable clinicians to evaluate for the
presence of ischemia in the region of myo-cardium supplied by an
artery with an intermediate lesion.
There are obvious limitations that require exploration prior to
widespread use of cardiac CT as the diagnostic modality of choice.
The largest problem to pursuing CT angiography and viability
assessment in patients is the risk associated with the increased
To evaluate myocardial perfusion and viability, there is an even
larger exposure to radiation due to the need for a minimum of 2
MDCT scans during 1 study. The second scan requires ap-proximately
2 to 4 mSv of radiation. Techniques are available to decrease the
amount of radiation, including ECG-dependent dose modulation and
the use of scanning protocols with lower tube voltages.
Other than radiation exposure, there are also potential nephrotoxic
risks associated with IV contrast.
In addition to the risks associated with performing the CT scan,
other limitations include the first-pass effect of contrast uptake
resulting in an unreliable intravascular content of contrast and
decreased signal-to-noise ratio when compared with CMR.
Although in some studies, the actual regions of hypo-perfusion are
evaluated both quantitatively and qualitatively, the region of
hypoenhancement is typically identified visually by experienced
observers. One would expect the area of hypoenhancement on
first-pass imaging to be larger than that of hyperenhancement on
delayed contrast-enhanced imaging. Regions of microvascular
obstruction and infarction as well as areas of hypoperfusion should
produce hypoenhancement on first-pass imaging. In the studies
described above, areas of hypoenhancement on first-pass imaging are
smaller than those seen on delayed enhanced imaging. This may be a
result of the poor signal-to-noise ratio associated with MDCT.
Observers may not be able to accurately identify regions of
hypoenhancement, as those areas may not produce a large enough
difference from the normal myocardium to be visually detected.
A reliable, reproducible method to evaluate the myocardium is
essential. Therefore, further research is necessary to determine
better methods to quantify signal differences between normal and
abnormal myocardium. Larger studies are also necessary to validate
the promising results found in the small initial studies that are
currently available. These studies should be performed in clinical
populations of patients with diverse coronary anatomy and clinical
presentations. Larger clinical trials should include a follow-up
period to evaluate patients' clinical outcomes.
CT viability and perfusion imaging are promising imaging
modalities in the early stages of investigation. Some of the
technical limitations described above may be overcome by emerging
technologies, including dual-source scanners, 256-slice scanners,
and flat-panel scanners. Although further research is necessary to
refine the technique, there is promise that cardiac CT will provide
complementary information, evaluating coronary anatomy and
myocardial imaging with one imaging modality. Further modification
and reduction in radiation exposure will be necessary before this
technology is applicable for widespread use.
I would like to thank Issam Mikati, MD, Francis Klocke, MD,
Edwin Wu, MD, Nirat Beohar, MD, James Carr, MD, Vera Rigolin, MD,
and Robert Bonow, MD, for their continued dedication to teaching
and their assistance in preparing this manuscript.