is an Instructor, and
is an Associate Professor of Radiology and Medicine and the
Clinical Director of MRI, Russell H. Morgan Department of
Radiology and Radiological Sciences, The Johns Hopkins University
School of Medicine, Baltimore, MD.
Gadolinium-enhanced MRI of the heart is off-label use of a
In the past decade, great strides have been made in magnetic
resonance imaging (MRI) of the heart and cardiovascular system.
Faster pulse sequences as well as extensive clinical and laboratory
research have rendered MRI an increasingly important tool in the
cardiac imaging arsenal. Cardiac MRI can provide the clinician with
valuable structural, anatomic, and functional information that
directly impacts subsequent patient management.
As a single examination, MRI is exceptionally versatile;
however, it may have found its most important cardiac application
in the determination of myocardial viability. The goal of
diagnostic tests to determine myocardial viability is to
distinguish myocardium that has the ability to contract versus
myocardium that is replaced by fibrosis or scar. MRI is rapidly
becoming the clinical gold standard for this assessment.
Approximately 3 decades ago, it was noted that regions of
abnormal myocardial function could recover contractility after
revascularization. Two subtypes of abnormally functioning
myocardium that retain the potential for recovery have subsequently
been described. Segments that lose function as a result of an acute
ischemic insult despite the restoration of normal perfusion are
. These segments have a mismatch between flow and function and are
likely to recover function spontaneously over time.
is the term used to refer to segments rendered dysfunctional
secondary to chronic ischemia. In these segments, there is a match
between low blood flow and low function.
The precise pathogenesis of stunned and hibernating myocardium
remains somewhat controversial and is beyond the scope of this
article. However, it is critically important to recognize that both
stunned and hibernating myocardial segments can regain function,
and are, therefore, collectively referred to as
Accurate identification of viable myocardial segments is
critical in deciding whether to pursue medical or surgical
treatment for left ventricular dysfunction caused by coronary
artery disease. Accurate preoperative assessment of myocardial
viability will predict which patients will regain left ventricular
function and which will not. Clearly, patients with little or no
viable myocardium should not be subjected to the risks of invasive
surgery. Studies have shown that preoperative myocardial viability
is an important predictor of clinical outcome after surgery. In a
1997 study, Pagley et al
showed that the extent of preoperative myocardial viability was the
best indicator of 3-year cardiac-event-free survival after
revascularization. Additionally, studies have suggested that
revascularization of patients with viable myocardium may improve
outcome independent of whether viable segments regain function
postoperatively, although the mechanism by which this occurs
Management of patients with coronary artery disease, therefore,
depends on precise determination of myocardial viability.
Imaging modalities for assessment of myocardial
There are essentially 4 methods of assessing myocardial
viability in clinical practice today. Single-photon emission
computed tomography (SPECT) with
Tl) has been widely utilized for this purpose.
Tl functions as a potassium analogue that is actively transported
into myocytes via the Na
ATPase located on the myocyte cell membrane. Initial images after
injection indicate areas of decreased perfusion, while images
obtained after a delay or redistribution phase show that these
areas are filled in, revealing myocardium that retains viability
despite diminished initial perfusion. This technique offers the
benefit of being fairly easy to perform with widely available
equipment. However, a meta-analysis has shown that it can
overestimate viability with a specificity of 49%, although the
sensitivity is high (88%).
Stress echocardiography (either with low-dose dobutamine or
dipyramidole) has also been widely used to assess myocardial
viability. Infusion of the "stress" agent, either a direct inotrope
or a vasodilator, causes previously dysfunctional but viable
myocardium to resume contractile function. This is referred to as
stress-induced contractile reserve.
The same meta-analysis referred to above reported a sensitivity of
84% and a specificity of 81% with this technique.
However, it is important to note that the sensitivity and
specificity of echocardiography decreases with increasing left
ventricular dysfunction--precisely the population that stands to
benefit most from myocardial viability assessment.
Advantages of echocardiography include portability, speed, and its
relative low cost; however, it is commonly limited by poor acoustic
windows and is interpreted subjectively, often with high
The gold standard for assessing in vivo myocardial viability has
been functional imaging with fluorodeoxyglucose (FDG) PET. This
technique involves comparing myocardial perfusion using a perfusion
agent with functional metabolic images obtained with FDG.
Myocardial segments that indicate normal or decreased perfusion but
maintain metabolism are classified as viable. Because PET is the
gold standard, MRI techniques are judged comparatively and have
been shown to be approximately 95% concordant.
While generally agreed to be a quite accurate technique, PET
imaging requires equipment and radiotracers that may not be readily
available. Additionally, as currently practiced, it is a
comparatively low-resolution study with pixel size of 8 mm, and it
does not routinely provide functional information regarding wall
motion and ejection fraction. Examination time for the patient is
long, requiring several hours for a complete perfusion and
Delayed contrast-enhanced MRI
As opposed to nuclear methods, viability assessment by MRI is a
nonstress examination that provides high-resolution detail,
including functional assessment of the left ventricle in
approximately 30 minutes. Assessment of myocardial viability is
performed using 5- to 20-minute delayed, gadolinium-enhanced MRI.
On delayed MRI, there is a relatively decreased washout of the
gadolinium contrast agent in areas of myocardium that have been
replaced by fibrosis or scar. In normal viable myocardium, the
gadolinium contrast agent washes out more rapidly than it does from
the fibrosis or scar. Since the difference between normal and
abnormal myocardium is based on washout kinetics, images that are
delayed by 5 to 20 minutes after contrast injection will optimally
depict the fibrosis or scar.
The differences in gadolinium enhancement on MRI of viable
myocardium and fibrosis or scar have been known for many years.
Recently, however, MRI pulse sequences have been developed that
greatly improve the conspicuity of the enhanced areas of myocardium
that have been replaced by fibrosis or scar. The pulse sequence
used is an inversion-recovery prepared gradient-echo sequence.
In this method, an inversion pulse is used to null the signal from
normal myocardium. Myocardium that is replaced by fibrosis or scar
retains gadolinium and shows very high signal intensity compared
with the suppressed, darker myocardium (Figures 1 through 3).
This relationship of high signal on delayed gadolinium-enhanced
MRI to fibrous or scar tissue has been repeatedly proven, and its
accuracy has been confirmed. In a canine model, Kim et al
reported that infarcts exhibited hyperenhancement whether acute or
chronic, whereas stunned or hibernating myocardium did not.
Additionally, they showed that the extent of myocardial
hyperenhancement matched the histologic extent of myocyte
In human trials, delayed contrast-enhanced MRI was found to be
an accurate method for determining myocardial viability in which
recovery of myocardial function after coronary bypass surgery was
the reference standard. In 52 patients who underwent coronary
revascularization, investigators identified improved regional
function in 82% of segments with no preoperative hyperenhancement,
64% of segments with 1% to 25% hyperenhancement, and 37% of
segments with 26% to 50% hyperenhancement.
Indeed, studies have shown that the ability of MRI to predict
restoration of myocardial function after revascularization is
actually best in segments with the most severe initial
dysfunction--exactly the opposite of stress echocardiography. When
investigators considered only segments with severe preoperative
dysfunction, the positive and negative predictive values for the
recovery of function were 81% and 72%, respectively.
The high spatial resolution of MRI allows for a more accurate
determination of the transmural extent of viability as opposed to a
binary classification of a myocardial wall segment as either viable
or not, as determined by nuclear medicine techniques and
This distinction is critical because it has been repeatedly shown
that revascularization of patients with viable myocardium leads to
significant improvement in clinical outcome.
As an example of the use of MRI for viability imaging, surgical
ventricular reconstruction (the "Dor procedure") is being performed
in patients with congestive heart failure and a left ventricular
aneursym. In this procedure, a left ventriculotomy is performed,
and the ventricular aneurysm is reduced in size by exclusion of the
scar from the endocardial volume of the left ventricle. The goal of
the cardiac surgeon is to incise only that part of the ventricle
that is fibrosis or scar; myocardium that is viable may recover
function from coronary artery bypass alone. Viability MRI is used
to determine 1) the site of the fibrosis or scar, 2) whether it is
transmural or subendocardial, and 3) the extent and coronary artery
territory of the fibrosis or scar (Figure 4). In addition,
incidental findings (such as left ventricular thrombus, mitral
valve regurgitation, and left ventricular volumes) are routinely
assessed with MRI in the same setting.
Delayed enhancement of the myocardium is not specific for prior
fibrosis or scar from myocardial infarction. Prior myocarditis or
fibrosis in association with hypertrophic cardiomyopathy, for
example, also exhibits delayed enhancement when the same MRI
technique is used. In addition, acute inflammation, tumors, and
granulomatous disease show delayed enhancement. Recently, delayed
enhancement has been shown to be found in arrhythmogenic right
Although the patterns of enhancement of the myocardium usually
differ in these conditions when compared with enhancement from
prior myocardial infarction, the correct diagnosis requires
knowledge of the clinical context of the MRI examination.
The ease of use and interpretation of MRI for myocardial
viability assessment has resulted in rapid growth in the use of
this technique. As such, the method has become one of the most
important cardiac imaging tests and a clinical gold standard for
identification of fibrosis or scar in the ventricle. In a single
examination, MRI provides the critical anatomic, functional, and
viability information required by the clinician to optimize patient