Chronic myocardial ischemia is a major cause of cardiac injury, often leading to permanent dysfunction and mortality. However, in some cases, injured myocardium remains "viable": it will recover function if blood flow to it is improved. Identification of viable myocardium has prognostic and therapeutic implications in the management of chronic ischemic heart disease. Recent advances in imaging sequences for contrast-enhanced cardiac magnetic resonance (MR) imaging now allow for identification of the characteristic delayed enhancement in scar tissue with high resolution. This offers several advantages in assessment of viability over stress echocardiographic and nuclear medicine techniques currently in use. These include the fact that MR imaging can be performed at rest and its ability to distinguish subendocardial from transmural scar.
is a third-year Radiology Resident at the Johns Hopkins Hospital,
Baltimore, MD. He received his MD from the University of Virginia
School of Medicine in 1999, and will begin a Fellowship in
Neuroradiology at Johns Hopkins Hospital in 2004.
is an Associate Professor and Clinical Director of MRI in the
Department of Radiology, Johns Hopkins University School of
Medicine, Baltimore, MD.
Chronic myocardial ischemia is a major cause of cardiac
injury, often leading to permanent dysfunction and mortality.
However, in some cases, injured myocardium remains "viable": it
will recover function if blood flow to it is improved.
Identification of viable myocardium has prognostic and
therapeutic implications in the management of chronic ischemic
heart disease. Recent advances in imaging sequences for
contrast-enhanced cardiac magnetic resonance (MR) imaging now
allow for identification of the characteristic delayed
enhancement in scar tissue with high resolution. This offers
several advantages in assessment of viability over stress
echocardiographic and nuclear medicine techniques currently in
use. These include the fact that MR imaging can be performed at
rest and its ability to distinguish subendocardial from
Diseases of the heart are the leading cause of mortality in the
Of these, chronic ischemic heart disease is the most common, and is
responsible for more deaths annually than is acute myocardial
infarction. Cardiomyopathy results when chronic myocardial ischemia
leads to ventricular injury and dysfunction. The prognosis of
ischemic cardiomyopathy is poor, with 5-year survival rates of only
50% to 60%.
Fortunately, in some patients, injured myocardium will recover
function if blood flow to it is improved. This tissue is referred
to as viable myocardium. Noninvasive methods of identifying viable
myocardium are valuable, as they allow clinicians to target
revascularization efforts for maximum benefit to the patient.
Recent advances in MR imaging research have enabled the radiologist
to distinguish viable tissue from nonviable tissue with a speed and
precision unmatched by other modalities. This article discusses the
clinical assessment of myocardial viability, with emphasis on
contrast-enhanced cardiac MR imaging techniques.
Chronic ischemia of the myocardium may lead to either tissue
necrosis and scar formation or, if less severe, to induction of
myocardial "hibernation." Hibernation is a self-protecting strategy
of myocytes in which the function of a muscle segment is
down-regulated until it matches the diminished blood supply.
Histologically, decreases in cellular contractile apparatus and
glycogen stores have been documented in biopsies of hibernating
This decreased contractility results in diminished ejection
fraction and cardiac function. In effect, hibernating myocardium
may simulate infarcted tissue, with the crucial distinction that it
can regain some or all of its lost activity if revascularized. Its
existence was inferred from the reversal of cardiac wall-motion
abnormalities after coronary artery bypass graft surgery. Viability
assessment began when areas of functional improvement were
predicted preoperatively by findings on positron emission
Hibernation is distinct from myocardial "stunning," which refers to
transient myocardial dysfunction after acute ischemia is relieved,
though the two may coexist.
Extensive research has shown the therapeutic and prognostic
value of identifying hibernating, but viable, myocardium. Patients
with substantial regions of viability fare better with
revascularization than with medical therapy alone.
Viable tissue portends better survival in the perioperative period
and later, greater exercise tolerance following revascularization,
and improved measures of left ventricular function.
The degree of recovery is greater when larger zones of viable
myocardium are detected.
MR identification of viable myocardium
Viability has been identified by evidence of myocardial
metabolism on PET,
by delayed fill-in of myocardial perfusion defects on single
positron emission computed tomography (SPECT) imaging,
or by evidence of preserved contractile reserve as assessed by
dobutamine stress echocardiography.
These will be discussed briefly below.
Contrast-enhanced MR imaging identifies viable tissue by taking
advantage of an unusual feature of myocardial enhancement after
infarction. Beginning several minutes after gadolinium-chelate
contrast injection, contrast agent that has accumulated in the
normal myocardium begins to "wash out." However, the wash-out of
gadolinium-chelate from nonviable myocardium is delayed. Thus,
there is progressive relative enhancement of chronically infarcted
This is true regardless of infarct age, extent of resting wall
motion, or reperfusion status.
The mechanism of this delayed enhancement is not entirely clear,
but it appears to be due to differing volumes of distribution. In
chronic myocardial infarction (older than 4 weeks), there is
progressive replacement of myocardium by fibrous scar, which has
increased interstitial space compared with normal myocardium.
Gadolinium-chelate contrast agents are extracellular. Presumably
they diffuse more slowly through tissues with larger interstitial
volumes. This may explain the slower wash-out of these agents from
areas of scar than from areas of intact myocardium. The delayed
enhancement, which can persist for up to 40 minutes, forms the
basis for distinguishing infarct from viable tissue using MR
Clinically, if a myocardial segment is dysfunctional on
wall-motion imaging but does not display delayed enhancement, it is
The sensitivity of nonenhancement for viability in the setting of
chronic infarction was 98% in one study.
However, early research on the utility of contrast-enhanced MR
imaging in assessing viability was muddied both by conventional MR
pulse sequences, which resulted in poor visualization of
enhancement, and by the observation that some cardiac segments with
nontransmural delayed enhancement also show improved function after
The central role of MR imaging for infarct delineation has been
clarified by the introduction of electrocardiogram-segmented fast
inversion recovery gradient-echo pulse sequences. Similar sequences
have been commercially distributed for several years, though they
were not initially applied to cardiac imaging. The resolution and
contrast-to-noise ratio they provide for infarct imaging is
superior to spin-echo, steady-state free precession (SSFP), or
short-T1 inversion recovery (STIR) sequences.
One important aspect of these sequences is the use of a segmented
k-space approach, so-called because several lines (segments) of
k-space are acquired during each cardiac cycle, rather than a
single line. When combined with short TEs (2 msec) and TRs (<10
msec), this allows high-resolution, breath-hold images of the heart
to be obtained.
Also important is the selection of an inversion time, TI, that
nulls normal myocardium. This is achieved by performing a
preliminary sequence using a range of inversion times and then
choosing the optimal parameter for a particular patient from among
the range of resulting images. Myocardial viability imaging with MR
is often termed myocardial delayed enhancement (MDE) imaging. This
term reflects the improved delineation of nonviable segments at 10
to 40 minutes following gadolinium-chelate contrast injection.
Kim and colleagues
used MDE imaging to prospectively assess viability in a series of
42 patients with ischemic cardiomyopathy. Cardiac wall motion
abnormalities were evaluated by cine MR imaging, and the degree of
delayed transmural enhancement in each segment was stratified (eg,
none, 1% to 25%, 75% to 100%). Using post-revascularization
improvement in function as the gold standard, these investigators
found that lesser transmural enhancement in a dysfunctional segment
predicted increasing likelihood of improved wall motion after
A particular strength of this study was that the positive
predictive value for recovery increased to 88% when analysis was
limited to severely dysfunctional segments. Such segments are
typically the most difficult to evaluate with other modalities.
The findings were also in concordance with myocardial biopsy
studies that showed that the percentage of transmural scar
correlates with degree of post-revascularization improvement in
Gerber et al
further clarified the question regarding post-revascularization
"recovery" of hyper-enhancing (and therefore nonviable) segments on
MDE imaging. Using MR tagging techniques, they found evidence of
"tethering" of the edges of infarcted tissue to myocardial segments
that regained function after revascularization.
First-pass myocardial perfusion is often measured as a way of
assessing coronary artery disease, but it can be misleading in
delineating chronic myocardial infarction with MR imaging.
Areas of decreased signal during the first minute of perfusion
imaging may represent either scar/fibrosis or rest occlusion of a
stenotic coronary artery segment.
First-pass perfusion imaging is useful in acute infarction, as
there may be areas of decreased perfusion in the central infarct
core due to microvascular obstruction by necrotic and/or
inflammatory cells (sometimes called the "no-reflow" phenomenon).
Such areas, if present, represent tissue that will not recover
function and is, therefore, nonviable.
Myocardial delayed enhancement imaging is performed with the
patient at rest. Cardiac gating and a cardiac coil are necessary.
Table 1 details the generic post-myocardial infarction protocol at
our institution. Although it includes first-pass perfusion imaging,
this sequence is relevant only when the protocol is performed in
the setting of acute infarction, as noted above, and it may be
omitted as appropriate. Scout images are obtained in sagittal,
axial, and oblique planes. Then, during the injection of 0.1
mmol/kg gadodiamide (Omniscan, Amersham Biosciences, Piscataway,
NJ) at a rate of 5 mL/sec, an inversion recovery-prepared fast
gradient-echo pulse sequence is performed to assess first-pass
perfusion. An additional 0.1 mmol/kg is then administered. The
split contrast dose avoids oversaturation during the first-pass
perfusion imaging, but achieves a more optimal intravascular
concentration for later MDE imaging. Cine images in short and long
axis are obtained using SSFP sequences to evaluate morphology and
function (eg, ejection fraction, cardiac output, wall thickness,
ventricular mass). Myocardial delayed imaging is performed 10 to 20
minutes after contrast administration, using an inversion recovery
prepared fast-gradient-echo sequence with blood suppression and
nulling of normal myocardium (Figures 1 and 2). The total duration
of the imaging protocol can be as brief as 20 minutes under ideal
circumstances. It may be longer, particularly when the patient is
severely ill or debilitated, and physically less able to
Contraindications to MDE imaging are the same as for any MR
imaging examination. Patients with implantable
defibrillator-pacemakers or orbital metallic fragments should not
be imaged. While gadolinium is not nephrotoxic and has a low
incidence of side effects, its safety in pregnancy is unknown.
MR compared with other modalities
Before comparison is made to MDE imaging, a brief review of the
other noninvasive modalities for assessing myocardial viability is
in order. All of these have been proven to have prognostic utility
in evaluating viability.
Positron emission tomography exploits the fact that ischemic
myo-cardium preferentially metabolizes glucose over fatty acids. In
this technique, [
F]fluorodeoxyglucose is used as a radiotracer, and normal or
increased uptake by a segment which demonstrates decreased
perfusion (as measured by a PET or SPECT perfusion agent) is
interpreted to indicate viability of that tissue.
Positron emission tomography has higher spatial resolution than
SPECT, and allows attenuation correction and the quantification of
some physiologic parameters.
The positive predictive value of a perfusion-metabolism mismatch
for functional improvement after revascularization has been
reported to from 76% to 85%.
Negative predictive value for the technique has been found to be as
high as 92%.
Single-positron emission computed tomography studies can employ
either thallium-201 or technetium-99m sestamibi uptake to measure
myocardial perfusion. Early perfusion defects that fill-in on
images obtained hours later are interpreted to represent viable
myocardium. Thallium is a potassium congener and enters cells
through energy-dependent transport.
Technetium sestamibi uptake relies on active mitochondria.
Neither agent will be taken up by dead myocardium. Two different
protocols are reported in the literature. In the
rest-redistribution technique, cardiac SPECT is performed
immediately after injection of radiotracer, again after a delay of
3 to 4 hours (a second dose may be injected just prior to delayed
imaging), and possibly again after a 24-hour delay.
Alternatively, a stress-redistribution-reinjection technique can be
used, with initial injection of radiotracer at peak stress, and
delayed images as with the prior technique.
While the delayed fill-in can be assessed qualitatively, some
researchers have quantitated it. Delayed uptake of more than 60% of
peak activity had a sensitivity of 78% and a specificity of 58% in
predicting functional recovery after revascularization, in one
study that employed thallium and the rest-redistribution protocol.
Pooled study results for both techniques have reported positive
predictive value of 69% and a negative predictive value of 89% to
Technetium viability studies offer the possibility of excellent
gated wall-motion imaging due to the long half-life of the isotope.
However, this radiotracer is especially susceptible to attenuation
artifacts, especially in the inferior wall.
Dobutamine stress echocardiography measures contractile reserve,
which is the ability of myocardium to increase its thickening after
stimulation with dobutamine (or another inotropic agent).
Myocardium that is dysfunctional but demonstrates sufficient
contractile reserve is interpreted to be viable.
Sensitivity for post-revascularization improvement has been
reported from 74% to 88%, with specificity ranging between 73% and
Dobutamine stress examinations may also be performed in conjunction
with MR imaging. This is of particular use for patients with poor
acoustic windows for echocardiography.
The chief advantage of MR imaging in comparison to other
noninvasive methods is its higher spatial resolution, up to 1.5 mm
in-plane, which allows for assessment of the percentage of
transmural extent of scar.
By contrast, when assessed by PET, SPECT, or echocardiography,
viability of an individual dysfunctional segment is an
"all-or-none" phenomenon. This additional clinical
information--small subendocardial versus large subendocardial
versus transmural infarct--may change patient management. In
addition, the high spatial resolution is of benefit when using MR
cine images to quantitatively evaluate cardiac morphology and
While the gold standard in viability assessment is improvement
of function after revascularization, PET has been used in many
clinical studies as a reference modality for assessing
A recent study of 31 patients showed that MDE imaging findings not
only agreed closely with findings on PET but showed additional
areas of scar which PET did not, due to the higher resolution.
If clinical trials find prognostic or therapeutic significance to
this extra level of detail, MR imaging may come to be the preferred
modality for assessing viability.
MR imaging has the potential to reliably produce complete,
high-quality examinations regardless of operator or patient body
habitus. Approximately 15% to 20% of echocardiography examinations
are limited by incomplete visualization of segments, primarily due
to dependence on acoustic windows.
Attenuation artifacts limit the sensitivity of SPECT imaging,
particularly in the inferior wall of the heart and in obese
In the studies cited above, no patients were excluded due to
poor MR image quality. However, patients who are unable to lie
supine or to hold their breath for appropriate periods may be poor
candidates for MDE imaging.
An advantage of SPECT imaging and dobutamine stress
echocardiography for evaluating myocardial viability is that the
expertise to perform and interpret such studies is widely
available. Cardiac MR imaging is still relatively novel in many
communities. However, MDE imaging can be performed using hardware
and software that has been offered commercially for several years,
and the use of intravenous contrast and cardiac gating is not new.
Positron emission tomography remains somewhat limited by high cost
and lack of broad availability.
Dobutamine stress echocardiography (and in some cases SPECT
imaging) derives its information from comparison of stress and rest
physiology. The need for either exercise or pharmacologic stress
adds time, cost, and complexity to those examinations. Like the
SPECT rest-redistribution technique and PET, MDE imaging has the
advantage of being performed at rest, and may be substantially
faster than those modalities in many instances. The protocol at our
institution can be completed in 20 minutes under optimal
conditions. It is now also possible to obtain postcontrast
three-dimensional whole-heart images in a single breath-hold,
further accelerating the examination (Figure 3).
It is worth noting that much research has been completed and is
ongoing with regard to dobutamine stress cardiac MR imaging. It has
proven prognostic value in assessing viability, and provides a
greater degree of quantitative accuracy than echocardiography.
However, like dobutamine stress echocardiography, it adds an
additional level of complexity when compared with the MDE
Large prospective studies of MDE imaging, with attention to the
prognostic implications of partial-thickness scar, could clarify
the clinical significance of this technique in relation to other
Other MR imaging techniques of assessing myocardial viability are
under investigation, though they may not have potential of MDE
imaging for prompt impact. Necrosis-avid MR imaging contrast
agents, metalloporphyrins, are paramagnetic and have high
specificity for scarred myocardium. Imaging is performed hours
One manganese-based MR contrast agent has been shown to accumulate
in normal myocardium but not infarct.
MR imaging using sodium-23 and MR spectroscopy of phosphorus-31 can
also distinguish viable from nonviable myocardium.
The latter techniques may be primarily of research interest due to
low resolution (sodium-23 MRI) or highly specialized equipment
requirements (phosphorus-31 MR spectroscopy).
The future development of MR imaging of viable myocardium will
also be influenced by the concurrent evolution of other cardiac MR
imaging applications, such as MR perfusion and MR coronary
angiography. These are areas of much research ferment, and the goal
of cardiac MR imaging as a comprehensive modality for evaluation of
coronary heart disease remains an active pursuit.
Myocardial delayed enhancement imaging has many features that
make it competitive with existing modalities in the assessment of
viable myocardium in chronic ischemic heart disease, including
relative simplicity and potential speed. Foremost among these is
its uniquely high level of spatial resolution, which may provide
information about myocardium that can change patient