A variety of imaging techniques have been developed to evaluate various aspects of CAD. This article addresses the important role of MRI for myocardial viability determination and functional assessment. It has a high confidence in the determination of nonviable territories and has shown good results in its ability to predict recoverable function after a revascularization procedure.
is an Assistant Professor, and
is a Cardiovascular Imaging Fellow, Department of Radiology,
Stanford University Medical Center, Stanford, CA.
This article is based on the authors' July 2003 presentation
at the Second International Radiology Symposium on
State-of-the-Art Imaging, organized by the Stanford Radiology
Postgraduate Program at Stanford University.
Coronary artery disease (CAD) is the leading cause of death in
developed countries. In the United States, CAD accounts for more
than 30% of deaths. The economic burden of CAD is estimated to be
more than $60 billion per year.
In the past 30 years, great strides have been made in understanding
the molecular and genetic underpinnings of this disease.
Technologies in diagnostic imaging and therapeutic intervention
have also progressed tremendously. Together, these advances help
clinicians optimize care of their patients.
Various imaging techniques have been developed to evaluate
various aspects of CAD. In particular, the assessment of myocardial
viability and cardiac function is important for the following
purposes: 1) to determine the optimal interventional and surgical
treatment strategies for CAD, including revascularization, scar
reduction surgery, cardiac resynchronization with biventricular
pacemaker, and cardiac transplant; 2) to optimize medical therapy
by monitoring treatment response; 3) to predict long-term outcome;
and 4) to assess entrance criteria for clinical trials.
The ability of the myocardium to perform a certain level of
mechanical work is dictated by the balance between the supply and
demand of oxygen and other metabolites. The term
generally refers to the condition in which the oxygen demand of the
myocardium exceeds oxygen delivery, defined as the product of
perfusion and oxygen content. When oxygen delivery is adequate for
the demand at rest but not during stress, the affected myocardium
. If ischemia worsens to the point that oxygen delivery is
inadequate at rest, the myocardium may undergo infarction or
, or cell death, is a series of irreversible steps that begins with
apoptosis. The threshold of infarction as a function of ischemia
varies depending on the duration of ischemia and previous exposures
to ischemic insults, known as
. Myo-cardium that suffers from a gradual onset of ischemia or
episodic but brief instances of ischemia may avoid infarction and
instead enter an altered cellular state in which the contractile
function is depressed. This is likely a preservation mechanism in
an attempt to lower the metabolic demands. The depressed function
may recover after revascularization, and the corresponding
myocardium is called
. Hibernating myocardium often coexists with infarcted tissue. The
goal of myocardial viability imaging is to identify and to
differentiate the two.
is a nonspecific term that generally refers to the pumping ability
of the heart to move blood forward in the vascular system. Overall,
cardiac function incorporates a number of aspects, including:
diastolic function, which describes the ability to fill a
ventricle; systolic function, which describes the contractility of
the ventricle; cardiac output, which describes the actual amount of
blood delivered by the heart; and valvular function, which
describes the efficiencies of the valves as flow
regulators. Each of these functions is quantitatively defined by
physical parameters. For instance, diastolic function is often
estimated by measuring the rate of pressure drop in the ventricle
during diastole. Systolic function is commonly evaluated by
measuring the ejection fraction. Cardiac output is measured by
calculating the average rate of blood flow through the aortic
valve. Valvular function is assessed by measuring valvular pressure
gradients and calculating regurgitant fractions. Traditionally,
cardiac function has been narrowly identified with systolic
function and is sometimes used synonymously with ejection fraction.
Clearly, the concept of cardiac function is multifactorial. An
effective imaging technique should investigate as many aspects of
cardiac function as possible.
Several existing imaging techniques are used to evaluate
myocardial viability. Thalium rest-redistribution perfusion
scintigraphy is perhaps the best-known and the best-studied method.
A myocardial region that does not demonstrate thallium uptake on
redistribution images is considered nonviable scar. Positron
emission tomography (PET) imaging of fluorine-18 fluorodeoxyglucose
(FDG) determines metabolically active myo-cardium.
A reduction of FDG uptake indicates nonviable tissue. Although,
traditionally, these nuclear medicine methods do not resolve
cardiac motion, new generations of single-photon emission computed
tomography (SPECT) and PET scanners incorporate electrocardiography
(ECG)-gating to produce cardiac cine images for volumetric
Echocardiography relies on the visual impression of myocardial
wall thinning, dyskinetic wall motion, and a lack of increase in
contractility under stress as indications of infarcted tissue.
Echocardiography has excellent temporal resolution, and in patients
whose physiques are favorable to ultrasound imaging, subtle changes
in wall motion can be detected by experienced operators. Although
qualitative and semiquantitative assessments of ejection fraction
are routinely performed, echocardiography is intrinsically a
two-dimensional (2D) technique in which accurate volume
quantification is difficult.
Magnetic resonance imaging (MRI) is a relative newcomer to
myocardial viability imaging.
Interpretation of viability is based on results from two different
techniques: wall-motion cine and delayed-enhancement imaging. Wall-
motion cine identifies myocardial wall thinning and abnormal wall
contraction. Delayed-enhancement imaging identifies infarcted
myocardium. Quantification of ventricular volumes and ejection
fractions is also possible using wall motion cine images.
MR evaluation of wall motion
and cardiac function
Although cardiac cine was one of the first techniques
implemented for MRI, it has progressed tremendously in terms of
scan speed, volume coverage, and image quality over the last 10
years. Currently, the method of choice for visualizing myocardial
wall motion is the balanced steady-state free-precession (SSFP)
Different manufacturers implement this technique under different
names: FIESTA for GE (GE Medical Systems, Milwaukee, WI), true-FISP
for Siemens, and balanced-FFT for Philips (Philips Medical Systems,
Best, The Netherlands). For cardiac cine, balanced-SSFP is usually
designed to be a breath-held, 2D-multiplanar, cardiac-gated,
segmented k-space sequence. It offers T2-weighted contrast, which
yields exquisite native contrast between the myocardium and the
ventricular blood pool without exogenous contrast material. It is
also relatively immune to in-flow effects and spin-saturation,
allowing good image quality in any cardiac plane. The excellent
delineation of the blood-myocardial boundary permits detailed
observation of wall contractility and accurate boundary
segmentation for volume analysis. Additionally, ventricular mass
can be calculated from the measured myocardial volume multiplied by
myocardial density, which is approximately the density of water. A
typical protocol includes contiguous short-axis slices covering the
ventricles plus the principle long-axis slices. The former slices
are needed for volume quantifications, and the latter slices are
needed to evaluate the ventricular apices.
Although regional wall contractility can be quantified, it is
more commonly assessed qualitatively. A normal contraction of the
left ventricle should show uniform thickening and inward motion of
the myocardium. A hypokinetic region demonstrates decreased
thickening or inward motion compared with other regions. An
akinetic region shows an absence of thickening and motion. A
dyskinetic region shows an absence of thickening and paradoxical
motion during systole and diastole (Figure 1).
MRI can quantify cardiac output using the phase-contrast
technique. A number of implementations are available. A
nonbreath-held, cardiac-gated, respiratory-compensated, short echo
time (TE) and short repetition time (TR) 2D-cine approach is
preferred, since the act of breath-holding may alter cardiac
Typically, quantification of the left ventricular cardiac output is
performed by selecting a plane above the aortic valve perpendicular
to the aorta (Figure 2). Velocity is encoded in the through-plane
direction. Flow is calculated as the sum of velocities across the
vessel lumen. Reversal of flow in the cardiac output time-curve
reflects valvular regurgitation.
The pressure gradient across the aortic valve can be estimated by
applying the Bernoulli equation to the peak velocity similar to
echocardiography. By combining flow and volume measurements, mitral
regurgitation can be quantified by subtracting forward flow volume
per cardiac cycle from the ventricular stroke volume. Similar
techniques can be employed to determine cardiac output of the
right-side of the heart at the pulmonary trunk (Figure 3) and the
valvular functions at the pulmonary valve (Figure 4) and tricuspid
valve. An average shunt ratio can be calculated from the ratio
between the pulmonary output and the aortic output. Thus, MRI alone
can quantify many aspects of the cardiac function.
MRI of myocardial infarction
A number of MRI methods, including MR spectroscopy, have been
proposed to image infarcted myocardium.
Currently, the most effective and straightforward means of MR
infarct imaging is based on delayed enhancement of the infarcted
myocardium after the administration of a gadolinium contrast agent.
This process is nonspecific and, in fact, was first observed in
computed tomography after the administration of an iodinated
The delayed enhancement is a result of altered pharmacokinetics of
increased distribution volume and slowed wash-out of contrast
materials in the infarcted region. The most useful MRI technique
employs inversion-recovery nulling of the normal myocardial signal,
which accentuates the signal intensity of the retained contrast in
the infarcted region. The pulse sequence is typically implemented
as a breath-held, cardiac-gated, single cardiac phase, segmented
k-space, 2D-multiplanar, gradient-recalled echo sequence. Using
inversion-recovery nulling, a five-fold difference in signal
intensity has been reported between the enhancing and the
The spatial resolution of this technique usually suffices to
differentiate transmural from subendocardial infarcts. Published
experiments used from 0.1 to 0.2 mmol/kg of gadolinium contrast
agents. Imaging is typically performed 15 minutes after contrast
administration. Using Tc-sestamibi SPECT as a standard of
reference, experiments showed that the size of infarction as
determined by delayed enhancement is relatively stable from 10 to
However, the optimal inversion time (TI), typically 200 to 250
msec, increases with contrast delay time.
This is because the contrast material in the normal myocardium is
slowly being washed out, thus increasing the effective T1 value. If
the inversion time is not chosen properly, the normal myocardial
signal may not be adequately suppressed, and, in the worst case,
the delayed-enhancement signal is suppressed in error (Figure
Interpretation of viability
In chronic infarction, myocardial remodeling and subsequent
scarring results in regional thinning of the myocardium. This
process may take up to 4 months after the initial myocardial
infarction to complete. A thinned myo-cardial wall of <5.5 mm at
end-diastole together with an absence of wall thickening during
systole correlates with decreased FDG uptake on PET imaging,
In a study of 43 patients with chronic infarcts, a wall thickness
<5.5 mm at end-diastole had a negative predictive value of 90%
for recovery after revascularization. In contrast, the positive
predictive value for recovery in patients with wall thickness
>5.5 mm was only 62%.
Therefore, the presence of wall thinning is a good indicator of
chronic scar, while an absence of wall thinning alone does not
necessarily indicate viable myocardium.
In animal studies, the area of delayed enhancement has been
shown to correlate closely with areas of infarcts.
In human studies, delayed enhancement is found to correlate with
PET and SPECT findings of infarction.
Kim et al
examined 50 patients with MRI before and after revascularization
procedures and stratified their results according to percentage of
wall thickness show
ing delayed enhancement. An absence of delayed enhancement in
segments that exhibit abnormal contractility has a positive
predictive value of 78% for recovery after revascularization. A
<25% delayed enhancement has a positive predictive value of 71%.
In contrast, the presence of transmural delayed enhancement has a
negative predictive value of 98% for recovery. The presence of
>50% delayed enhancement has a negative predictive value of 92%.
An increasing extent of dysfunctional contraction but viable
myocardium before revascularization correlates with greater
improvement in ejection fraction after revascularization.
In our experience, chronically infarcted walls, as indicated by
end-diastolic wall thinning (<5.5 mm) and akinesia, can show
variable delayed enhancement. We consider thin, akinetic, or
dyskinetic walls to be nonviable. As discussed above, this
interpretation is 90% predictive for nonviable tissue. Walls
thicker than 5.5 mm but showing a >50% delayed enhancement are
also considered nonviable (Figure 6). This interpretation is 92%
predictive for nonviable tissue. This group likely represents more
acute infarction when remodeling is not complete. Walls thicker
than 5.5 mm and showing a <25% delayed-enhancement are
considered potentially viable (Figure 7). This prediction is not
perfect, however, since up to 30% of these segments will not
improve functionally after revascularization.
MRI is a valuable tool for myocardial viability determination
and functional assessment. It has a high confidence (>90%) in
the determination of nonviable territories. Its ability to predict
recoverable function after revascularization procedure is good (70%
to 80%), although not perfect. Performance of delay enhancement
imaging requires meticulous attention, especially with regard to
the choice of the inversion time. MRI is also capable of
quantifying many aspects of cardiac function, including ventricular
volumes, ejection fraction, cardiac output, shunt ratio, valvular
pressure gradients, and regurgitation fractions.