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Transcript
JOURNAL OF MAGNETIC RESONANCE IMAGING 26:3–13 (2007)
Invited Review
Magnetic Resonance Imaging for Ischemic Heart
Disease
Hajime Sakuma, MD*
identification of subendocardial infarction with late
gadolinium (Gd)-enhanced MRI. MRI is noninvasive
and does not require injection of iodinated contrast
medium, which is potentially nephrotoxic for patients
with cardiovascular disease. In addition, MRI does not
expose the patient to ionizing radiation. Therefore, cardiac MRI is suited for serial assessments of patients
with heart disease. Recently, late Gd-enhanced MRI
has been shown to be useful in detecting infarct tissue
and in predicting myocardial viability and prognosis of
the patients, and is routinely performed in many hospitals to evaluate patients with MI. Stress myocardial
perfusion MRI and coronary MR angiography (MRA) are
mainly performed by a growing number of early adopters at this point. While several important issues remain
to be resolved, such as education and training for technologists and physicians, standardization of study protocols, and reimbursement for cardiac MRI, combined
stress myocardial perfusion and late CE-MR studies
will eventually play a central role in therapeutic decision-making for patients with ischemic heart disease.
This article reviews recent advances in CE and non-CE
cardiac MR applications from a clinical perspective in
the areas of stress MR studies for detecting myocardial
ischemia, MRI of MI and viability, coronary MRA, and
MR assessment of coronary artery bypass graft.
Cardiac MRI has long been recognized as an accurate and
reliable means of evaluating cardiac anatomy and ventricular function. Considerable progress has been made in the
field of cardiac MRI, and cardiac MRI can provide accurate
evaluation of myocardial ischemia and infarction (MI). Late
gadolinium (Gd)-enhanced MRI can clearly delineate subendocardial infarction, and the assessment of transmural
extent of infarction on late enhanced MRI has been shown
to be useful in predicting functional recovery of dysfunctional myocardium in patients after MI. Stress first-pass
contrast-enhanced (CE) myocardial perfusion MRI can be
used to detect subendocardial ischemia, and recent studies
have demonstrated the high diagnostic accuracy of stress
myocardial perfusion MRI for detecting significant coronary artery disease (CAD). Free-breathing, whole-heart
coronary MR angiography (MRA) was recently introduced
as a method that can provide visualization of all three
major coronary arteries within a single three-dimensional
(3D) acquisition. With further improvements in MRI techniques and the establishment of a standardized study protocol, cardiac MRI will play a pivotal role in managing
patients with ischemic heart disease.
Key Words: ischemic heart disease; coronary artery; myocardial infarction; myocardial ischemia; left ventricular
wall motion
J. Magn. Reson. Imaging 2007;26:3–13.
© 2007 Wiley-Liss, Inc.
MR Assessment of Cardiac Function
ISCHEMIC HEART DISEASE is one of the leading
causes of morbidity and mortality in many industrialized countries. Evaluation of ischemic heart disease
requires measurement of regional and global ventricular function, identification of the presence and extent of
myocardial ischemia, visualization of luminal narrowing of the coronary arteries, and assessment of myocardial infarction (MI) and viability. MRI has several important features for the assessment of ischemic heart
disease. Cardiac MRI offers high spatial resolution, permitting direct visualization of subendocardial ischemia
with stress first-pass contrast-enhanced (CE)-MRI and
Cine MRI is now generally recognized as the most accurate and reproducible technique for assessing global
ventricular function and left ventricular (LV) mass (1).
The development of steady-state free precession (SSFP)
sequences provided substantially improved blood–myocardial contrast on cine MR images in a reduced imaging time, allowing more accurate and reproducible delineation of the endocardial borders (2,3). Thus cine
MRI is ideally suited for serial assessments of LV function in patients who have undergone therapeutic interventions. The sample size required to detect significant
changes in clinical trials can be substantially reduced
in comparison to other imaging modalities (4).
In patients with impaired LV function after MI, the
reliable differentiation of irreversibly damaged tissue
and potentially salvageable viable myocardium is of
major clinical importance. Cine MRI with SSFP sequences can provide accurate determination of regional
LV wall thickness and systolic wall thickening in dys-
Department of Diagnostic Radiology, Mie University Hospital, Mie, Japan.
*Address reprint requests to: H.S., Department of Diagnostic Radiology,
Mie University Hospital, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
E-mail: sakuma@clin.medic.mie-u.ac.jp
Received May 1, 2006; Accepted January 26, 2007.
DOI 10.1002/jmri.20976
Published online in Wiley InterScience (www.interscience.wiley.com).
© 2007 Wiley-Liss, Inc.
3
4
functional myocardial segments in patients with MI.
However, rest cine MRI cannot distinguish between viable and nonviable myocardium, since both potentially
viable and necrotic myocardia may demonstrate impaired regional myocardial contraction. Inotropic stimulation with low-dose (10 ␮g/kg/minute) dobutamine
infusion has been established as a reliable and safe
means of predicting functional recovery of dysfunctional LV segments in patients with MI. Compared with
echocardiography, MRI can be more suitable for predicting recovery of myocardial contraction because it is
relatively independent of the operator’s skill, and the
entire LV wall can be imaged with optimal imaging
planes (5). Recent studies demonstrated that low-dose
dobutamine stress cine MRI can provide more accurate
prediction of functional recovery than late Gd-enhanced MRI in patients with MI (6,7).
High-dose dobutamine stress (40 ␮g/kg/minute)
augments both myocardial contractility and the ratepressure product, thus increasing myocardial oxygen
demand and causing ischemia in areas perfused by
coronary arteries with flow-limiting stenoses. Highdose dobutamine stress echo has become a well-established modality for diagnosing myocardial ischemia.
One of the limitations of stress echocardiography is that
a substantial number of subjects yield suboptimal or
nondiagnostic images. Stress-induced wall motion abnormalities can be detected with a significantly higher
diagnostic accuracy by using dobutamine stress cine
MRI compared to dobutamine stress echocardiography
in patients with coronary artery disease (CAD). The
sensitivity and specificity of high-dose dobutamine
stress MRI for detecting significant CAD were reported
to be respectively 83% and 83% by Hundley et al (8),
and 86% and 86% by Nagel et al (9). The improved
accuracy with stress MRI is generally explained by an
improved delineation of the endocardial and epicardial
borders, and superior quality of MR images in patients
with obesity and pulmonary emphysema. High-dose
dobutamine stress is superior to adenosine stress for
detecting significant luminal narrowing in the coronary
artery as a stress-induced wall motion abnormality
(10). While adenosine induces myocardial blood flow
inhomogeneities by vasodilation, and is useful for evaluating perfusion abnormality on first-pass CE-MRI, it
does not induce increased oxygen demand because
myocardial contraction is not augmented. In contrast,
high-dose dobutamine stress can cause “true ischemia”
due to increased myocardial contraction and oxygen
demand.
Complex intramyocardial contractile pattern can be
evaluated by using a myocardial tagging technique. A
radiofrequency (RF) prepulse labels the myocardium
with dark grids, and enables detailed analysis of rotation, shortening, and strain of regional myocardium
(11,12). Myocardial tagged MRI with strain quantification allows for more accurate assessment of regional
wall motion abnormality compared to a wall-thickening
analysis on cine MRI without tagging (13,14). A recent
study by Bree et al (15) demonstrated that 3D strain
analysis of low-dose dobutamine stress tagged MRI can
provide precise identification, quantification, and display of regionally varying ventricular function in pa-
Sakuma
Figure 1. First-pass CE perfusion MR images with dipyridamole stress acquired with a saturation recovery GRE sequence
with echo-planar readout in a patient with significant luminal
narrowing in the left anterior descending artery (LAD). The
hypoperfused region (arrows) in the anteroseptal wall is depicted as a region of lower enhancement.
tients with ischemic cardiomyopathies. Fast harmonic
phase (HARP) MRI combined with a rapid HARP postprocessing technique is one of the promising methods
that permit rapid and operator-independent monitoring
of strain abnormalities (16). Myocardial tissue tracking
with two-dimensional (2D) cine displacement-encoded
(DENSE) MRI is a new technique for quantitative motion tracking of the myocardium (17). Advantages of the
DENSE approach include high spatial resolution of
strain mapping and direct extraction of tissue displacement from phase-reconstructed images.
Rest-Stress Perfusion MRI
Accurate assessment of myocardial ischemia caused by
flow-limiting stenosis in the coronary artery is important for evaluating patients with chest pain syndromes
and in managing patients after therapeutic interventions. Dynamic MRI following a bolus injection of contrast material enables assessment of first-pass myocardial enhancement during pharmacological stress,
which can provide information regarding the presence
and the extent of CAD (Figs. 1 and 2). Rest-stress perfusion MR images are usually evaluated with semiquantitative approaches, such as an upslope analysis
of myocardial time-intensity curve, or with a visual assessment. Myocardial blood flow in the resting state is
not altered unless the luminal diameter stenosis in the
epicardial coronary artery exceeds 90%, due to an autoregulation of coronary circulation that is regulated by
the resistance in the arteriolar level. Vasodilator stress
with adenosine or dipyridamole relaxes the arteriolar
tonus and induces a perceptible difference in perfusion
between normal and ischemic myocardia (18). Inotropic
stress with high-dose dobutamine is widely employed in
stress function studies and theoretically can be useful
for inducing myocardial ischemia in stress perfusion
MRI for Ischemic Heart Disease
Figure 2. First-pass CE perfusion MR images with dipyridamole stress acquired with a saturation recovery GRE sequence
with echo-planar readout in a patient with triple vessel disease
before (a) and after (b) coronary artery bypass graft surgery.
Subendocardial hypoenhancement encompassing the entire
circumference of the LV myocardium is observed before bypass graft surgery, which is markedly improved after successful bypass grafting.
MR studies. However, high-dose dobutamine stress is
not usually used for rest-stress perfusion MRI, because
increased heart rate induced by high-dose dobutamine
leads to substantial motion artifacts and image degradation on perfusion MR images. Currently, no consensus has been established regarding the optimum dose
of Gd MR contrast medium for stress perfusion MRI. A
lower dose of the contrast medium (0.025– 0.05 mmol/
kg) is preferable to maintain the linear relationship between blood Gd concentration and MR signal intensity
that is critical for quantitative assessment of myocardial perfusion. Administration of a higher dose (0.075–
0.1 mmol/kg) is beneficial to achieve an increased myocardial enhancement and a better contrast between
normal and ischemic myocardium. A dual-bolus administration of Gd contrast medium (0.0025 mmol/kg
followed by 0.1 mmol/kg) is an approach that enables
quantitative assessment of myocardial perfusion while
maintaining excellent contrast enhancement in the
myocardium (19). Myocardial perfusion MR sequences
need to satisfy several conflicting requirements, including high spatial resolution, high temporal resolution,
sufficient coverage of LV myocardium, high contrast-tonoise ratio (CNR), and reduced artifacts. Saturation recovery fast gradient-echo (GRE) sequences and hybrid
echo-planar sequences have been widely used in perfusion MR studies (20). Recently, saturation recovery
SSFP sequences were introduced as a method that can
provide improved signal-to-noise ratio (SNR) (21). However, the sequence of choice for perfusion MRI has not
been determined at this point, and the image quality of
saturation recovery myocardial perfusion MR images
generally needs further improvements. Suppression of
a dark artifact in the subendocardium, which is most
apparent during first-pass transit of MR contrast medium through the LV cavity, is particularly important
because it may mimic the subendocardial perfusion
abnormalities observed in CAD. This artifact is primarily caused by Gibbs ringing and cardiac motion during
image data acquisition. Improved spatial resolution of
perfusion MR images, and shorter acquisition times per
image to reduce motion artifacts seem to be important
to reduce the artifact. A comparison of rest and stress
5
perfusion MR images is sometimes useful to distinguish
stress-induced subendocardial hypoperfusion from a
dark subendocardial artifact.
Recent studies demonstrated that first-pass perfusion MRI with pharmacological stress allows the detection of hemodynamically significant CAD with high diagnostic accuracy. Schwitter et al (22) obtained stress
perfusion MR images in 48 patients and 18 healthy
volunteers by using a multislice hybrid echo-planar MR
pulse sequence. Stress perfusion MRI showed a sensitivity of 91% and specificity of 94% for detecting CAD as
defined by positron emission tomography (PET), and a
sensitivity of 87% and specificity of 85% in comparison
with quantitative coronary angiography. In a more recent study, Nagel et al (23) obtained first-pass CE MR
images in 84 patients by using a fast GRE/echo-planar
hybrid sequence. By assessing myocardial perfusion
reserve index, MRI yielded a sensitivity of 88%, specificity of 90%, and accuracy of 89%. In a multicenter
dose-range study reported by Wolff et al (24), the highest area under the receiver operating characteristics
(ROC) curve of 0.90 ⫾ 0.04 was obtained at a relatively
low injection dose of 0.05 mmol/kg. The sensitivity,
specificity, and accuracy of stress perfusion MRI with
this dose were 93%, 75%, and 85%, respectively. Atherosclerosis in multiple vascular areas is a major problem in the care of patients with vascular diseases, and
significant CAD was found in approximately 31% to
53% of patients with aortic aneurysms. The use of routine coronary angiography in all patients with aortic
diseases, however, may increase unnecessary risk and
costs. A recent study by Ishida et al (25) demonstrated
that stress CE-MRI is useful for noninvasive detection
of CAD in patients prior to elective repair of aortic aneurysms. The overall sensitivity, specificity, and accuracy of combined stress perfusion MRI and late Gdenhanced MRI for detecting patients with significant
CAD were 88%, 87%, and 88%, respectively.
Stress myocardial perfusion single-photon emission
computed tomography (SPECT) has been widely used to
demonstrate reduced regional myocardial perfusion in
patients with CAD. First-pass MR perfusion assessment has several potential advantages over nuclear
medicine techniques in terms of good spatial resolution, no ionizing radiation, and no attenuation or scatter artifacts. The improved spatial resolution of MRI
permits the detection of small subendocardial ischemia
in patients with mild to moderate CAD, and the delineation of diffuse subendocardial hypoenhancement in
patients with multivessel CAD. In a study that directly
compared stress perfusion MRI and stress SPECT, the
diagnostic accuracy of stress perfusion MRI was significantly better than that of stress SPECT when results
from quantitative coronary angiography were used as
the reference standard (26). In another recent study,
the areas under the ROC curve for detection of significant coronary stenosis was 0.84 – 0.86 for stress perfusion MRI and 0.72-0.79 for stress 201Tl SPECT (27).
Viability Assessment With Late Gd-Enhanced MRI
Assessment of myocardial viability is important in the
prediction of functional recovery after revascularization
6
Sakuma
Figure 3. Late CE-MR images from a patient with old MI acquired with an IR 3D turbo-field-echo (TFE) sequence using
sensitivity encoding (SENSE). a: Short-axis image. b: Vertical long-axis image. c: Four-chamber view. Late Gd-enhanced MR
images show transmural high signal intensity in the anteroseptal wall and apex. No myocardial viability was preserved in the
infarcted area.
and in the risk stratification of patients with CAD. Myocardial viability has several different definitions, including functional viability that can be assessed by
monitoring responses to dobutamine stress using echocardiography or cine MRI, cellular viability indicated by
Tl-201 SPECT as a preserved intracellular fraction,
metabolic viability assessed by FDG (fluorodeoxyglucose) PET as preserved glucose metabolism, and histological viability determined by late Gd-enhanced MRI.
Among these definitions, the one closely related to histology seems to be the most definite criterion for determining whether a myocardial cell is alive or not. Myocardial uptake of Tl-201 on SPECT does indicate the
presence of viable myocardial cells, since there is an
apparent similarity between the transport of ionic thallium and potassium through myocardial cell membranes. However, spatial resolution of SPECT is limited,
and Tl-201 uptake in viable myocardium can be substantially influenced by myocardial blood flow as well.
Late Gd-enhanced MRI of the myocardium has become
increasingly important as a noninvasive MR method for
demonstrating MI and assessing myocardial viability.
CE-MRI has high spatial resolution and can clearly
demarcate infarcted tissue and viable myocardium
within the LV wall. An animal study demonstrated that
the spatial extent of enhancement on late Gd-enhanced
MRI showed a good agreement with that of MI defined
by TTC (triphenyl-tetrazolium chloride)-stained slices
in both acute and chronic states (28).
Late CE-MR images were acquired 10 –15 minutes
after contrast injection (29). In the equilibrium phase,
Gd contrast medium nonspecifically distributes in the
extracellular space that constitutes about 20% of water
fraction in normal myocardial tissue. In infarcted tissue, however, the distribution volume of extracellular
contrast medium is substantially increased due to loss
of intracellular fraction of myocardium (30), resulting in
enhancement of MI on inversion recovery (IR)-prepared
MR images (Fig. 3). Typically a patient is given a 0.1–
0.2-mmol/kg intravenous administration of extracellular Gd contrast medium, and images are acquired with
IR GRE sequences (29). The inversion time (TI) needs to
be adapted individually for each examination to null the
signal of the normal myocardium in order to ensure an
optimal contrast between infarction and viable myocardium. The Look-Locker pulse sequence acquires multiple GRE MR images at different TI values after the IR
pulse, which is useful for determining an optimal TI
value for late Gd-enhanced MR images (31). Phasesensitive image reconstruction allows the use of a nominal TI value and eliminates the precise adjustment of
TI in each patient (32–33). With two-dimensional (2D)
IR GRE sequences, repeated breath-holds are required
to cover the entire LV for a comprehensive evaluation of
myocardial viability of the heart. This procedure is
time-consuming and difficult for some patients with
advanced heart failure. The three-dimensional (3D) IR
GRE sequence allows rapid and complete acquisition of
3D images and covers the LV within one breath-hold.
The CNR of late Gd-enhanced MR images was found to
be threefold larger with the 3D sequence than with the
2D sequence (24). A high level of agreement was found
between 2D and 3D sequences for evaluating the presence of MI, while the transmural extent of enhancement
can be overestimated with the 3D sequence if the spatial resolution is not sufficient without using parallel
imaging acquisition.
Late Gd-enhanced MR images have been assessed by
measuring the transmural extent of infarction for predicting recovery of impaired contractile function in patients after MI. In a study that evaluated 50 chronic
patients with ventricular dysfunction before revascularization, the likelihood of improvement in regional
contractility after revascularization negatively correlated with the transmural extent of enhancement (35).
The contractility improved by revascularization in 78%
of dysfunctional segments without enhancement, but
the improvement was found in only 2% of the segments
that exhibited transmural extent of more than 75%. The
transmural extent of infarction on late CE-MR images
can predict improvement in contractile function in patients with acute MI as well. Choi et al (36) studied 24
patients who presented with their first MI and underwent successful revascularization. The percentage of
segments that showed improvement in contractile
function eight to 12 weeks later progressively reduced
MRI for Ischemic Heart Disease
Figure 4. A patient with inferior MI six days after onset. Balanced TFE cine MR images in the diastole (a) and systole (b)
demonstrate mild hypokinesis in the inferior wall. c: T2weighted black-blood FSE MR image exhibits transmural high
intensity in the inferior wall, indicating myocardial edema. d:
3D late CE-MR image reveals subendocardial MI in the inferior
wall with preserved non-necrotic myocardium in the epicardial
side of the LV wall. Notice that the area showing edema is
substantially larger than infarcted myocardium on the late
CE-MR image.
as the transmural extent of infarction increased. The
percentage of the segments that showed recovery was
77% for the segments without infarction, 67% for the
segments with 1% to 25% transmural extent, 56% with
26% to 50% transmural extent, 35% with 51% to 75%
transmural extent, and 5% with 76% to 100% transmural extent in their study. Differentiation between acute
and chronic MI is a frequent demand for clinical decision-making in patients with MI, but both acute and
chronic MI exhibit late enhancement regardless of their
age. T2-weighted MRI depicts infarct-related myocardial edema as a marker of acute MI, and is useful for
differentiating acute from chronic MI (37) (Fig. 4). In
addition to the patients with a diagnosis of MI, late
Gd-enhanced MRI is of great value for classifying patients with heart failure in relation to the presence or
absence of underlying CAD. Soriano et al (38) reported
that 81% of the patients with coronary arterial stenoses
on X-ray coronary angiography showed subendocardial
and/or transmural enhancement, whereas only 9% of
an angiographically negative group demonstrated late
enhancement. Thus late CE-MRI offers a valid alternative to X-ray coronary angiography for the detection of
CAD in patients with heart failure.
First-pass CE-MRI in the resting state has been
shown to be useful in predicting functional recovery in
patients with acute MI. An area of perfusion defect on
first-pass CE-MR images, which is related to “microvascular obstruction” or “no reflow,” indicates greater myocardial damage, and poor functional recovery and prognosis (39). Gerber et al (40) evaluated the diagnostic
accuracies of first-pass CE-MRI and late CE-MRI in
7
predicting functional improvement in patients with
acute MI. The presence of early hypoenhancement had
a high positive predictive value of 68% and a high specificity of 89% for predicting persistent dysfunction.
However, the absence of early hypoenhancement had a
low specificity of 19%, resulting in a limited accuracy of
49%. Late Gd-enhanced MRI demonstrated a sensitivity
of 82%, specificity of 64%, and accuracy of 74%, and
they concluded that lack of late enhancement has better diagnostic accuracy for predicting functional improvement in dysfunctional segments in acute MI
(Fig. 5).
Myocardial perfusion SPECT is an established procedure for diagnosing infarction. However, subendocardial MI is frequently missed by SPECT. In a study done
by Wager et al (41), late CE-MRI identified 92% of the
segments with subendocardial infarction in animal
models, whereas SPECT detected only 28%. A reason
for this poor sensitivity is that the spatial resolution of
SPECT images is nearly comparable to the entire thickness of LV wall. In contrast, MRI typically yields 5–10
pixels within the LV wall, which makes it possible to
reliably detect subendocardial infarction. In a study by
another group (42), the diagnostic accuracy of late CEMRI and rest Tl-201 SPECT were compared in the prediction of functional recovery of regional myocardial
contraction in patients after acute MI. The sensitivity,
specificity, and accuracy of late CE-MRI in the prediction of functional recovery were significantly higher
compared to Tl-201 SPECT. In addition, because of the
high negative predictive value of late enhanced MRI
(92.7%) as compared to Tl-201 SPECT (66.1%), segments with a low likelihood of recovery can be identified
with high confidence by using CE-MRI instead of
SPECT. The false-negative segments on Tl-201 SPECT
images were frequently found in the inferior wall, in 14
of 19 segments (74%), which is most likely related to
Figure 5. Late CE-MR images from a patient with acute inferior MI acquired with an IR 3D TFE sequence using SENSE.
MR images were obtained six days after onset of MI. Late
Gd-enhanced MR images show high signal intensity in the
posterior wall extending to the epicardial border of the LV wall.
Non-enhanced tissue is observed in the subendocardial side of
this transmural infarction, indicating the presence of microvascular obstruction.
8
attenuation artifacts on SPECT. These results indicate
that late CE-MRI can substitute for 201Tl SPECT in
evaluating patients with MI.
Infarct size on late Gd-enhanced MRI in patients with
acute MI appears to diminish on follow-up CE-MRI (43).
In a recent study that assessed changes in enhanced
tissue and non-enhanced myocardium from acute to
chronic states (44), the total volume of abnormally enhanced tissue was significantly reduced by approximately 32%. Segmental analyses revealed that the
mean thickness of enhanced tissue in the infarct segments decreased by 30%, and the mean thickness of
non-enhanced myocardium in the infarct segments increased by 27%. As mentioned previously, viable myocardium with preserved intracellular space is shown as
non-enhanced myocardium on late enhanced MR images. Thus, regional myocardial viability can be assessed by measuring the amount of non-enhanced tissue rather than the transmural extent of necrotic
tissue. One study indicated that the diagnostic performance of late enhanced MRI for predicting normal contractile function in the chronic state can be improved by
measuring the thickness of non-enhanced myocardium
instead of measuring the transmural extent in patients
with acute MI (44).
Coronary MRA
Catheter X-ray coronary angiography has been used as
the gold standard for identifying CAD. However, this
method entails small but definable risks (45), and a
considerable number of patients undergoing elective
X-ray coronary angiography are found to have no significant CAD. CE multislice CT has rapidly emerged as
a noninvasive method that can provide reliable detection of the CAD (46). In a recent work by Mollet et al (46),
the estimated radiation dose during 64-slice CT coronary angiography (15.2 and 21.4 mSv for men and
women, respectively) was higher than the radiation
dose associated with conventional coronary angiography. While coronary MRA does not expose the patients
to radiation, noninvasive MRI of the coronary artery is
technically demanding due to the small size and tortuous course of the coronary arteries and their complex
motion caused by cardiac contraction and respiration.
In the past few years the image quality, volume coverage, acquisition speed, and arterial contrast of 3D coronary MRA have been substantially improved with the
use of SSFP sequences and parallel imaging techniques, permitting the acquisition of high-quality 3D
MR angiograms encompassing the entire coronary arteries within a reasonably short imaging time.
Breath-hold 3D coronary MRA has advantages in
terms of time efficiency compared to free-breathing 3D
coronary MRA (47). In a study reported by van Guens et
al (48), 69% segments were assessable by breath-hold
3D coronary MRA with a volume-targeted imaging approach, with a sensitivity and specificity for detecting
⬎50% luminal stenoses of 92% and 68%. Another benefit of breath-hold 3D coronary MRA is that this method
can utilize first-pass contrast enhancement of the coronary arteries following an intravenous injection of conventional extracellular MR contrast medium. Regenfus
Sakuma
et al (49) obtained breath-hold 3D coronary MRA in 50
patients by injecting extracellular MR contrast medium
at a flow rate of 1 mL/second. The sensitivity and specificity of this approach were 94% and 57%, respectively,
for detecting patients with significant CAD. Breath-hold
3D coronary MRA has several important limitations. A
short imaging time is achieved at the expense of spatial
resolution and 3D volume coverage, and patients with
heart or pulmonary disease cannot hold their breath for
a long time. Another limitation is that breath-holding
does not completely eliminate respiratory blurring of
the coronary artery on 3D MRA, as a continued drift of
the diaphragm position was observed during breathholding (50). Free-breathing, respiratory-gated 3D coronary MRA is currently the most commonly used MR
approach for assessing coronary arteries in patients
with heart disease. In a multicenter study reported by
Kim in 2001 (51), free-breathing 3D coronary MR angiograms were obtained with a double oblique targeted
volume method and 3D GRE sequence. The sensitivity
and specificity were respectively 93% and 42% for identifying patients having significant CAD, and 100% and
85% for detecting patients with left main CAD and triple
vessel disease. Reliable detection of CAD beyond the left
main coronary artery and proximal coronary arteries
necessitates further improvements in MRI sequences.
With the introduction of SSFP sequences, the blood
signal intensity on 3D coronary MRA is considerably
augmented without the use of MR contrast medium in
comparison to 3D GRE sequence (52). In a study done
by Spuentrup et al (46), radial k-space sampling was
shown to be useful for reducing motion artifacts and
improving vessel sharpness on steady-state 3D coronary MRA (53). Jahnke et al (54) compared the diagnostic performances of breath-hold 3D coronary MRA and
free-breathing 3D coronary MRA by utilizing the same
SSFP sequence. Free-breathing coronary MRA was superior to breath-hold coronary MRA in terms of both
image quality and diagnostic accuracy, with an overall
sensitivity and specificity of 72% and 92% for the freebreathing approach, and 63% and 82% for the breathhold approach. Kefer et al (55) compared the diagnostic
accuracy of free-breathing 3D coronary MRA using an
SSFP sequence with that of 16-slice multislice CT in 42
patients. By using quantitative coronary angiography
as a gold standard, the sensitivity and specificity of
coronary MRA for the detection of luminal narrowing
were 75% and 77%, respectively. These MR results were
similar to the sensitivity (82%, P ⫽ n.s.) and specificity
(79%, P ⫽ n.s.) of 16-slice multislice CT.
SSFP sequences permit the acquisition of a 3D axial
volume that encompasses the entire heart without losing arterial contrast, because signal intensity on
steady-state 3D coronary MRA is primarily determined
by the T2/T1 ratio, instead of the in-flow effect of the
blood (56 –58) (Figs. 6 and 7). By using the whole-heart
approach, one can visualize all three major coronary
arteries with a reduced total examination time in comparison to targeted double oblique 3D GRE MRA. In
addition, planning of whole-heart coronary MRA becomes quite simple, eliminating the time-consuming
three-point planning required for the targeted double
oblique approach. Coronary MRA acquired with this
MRI for Ischemic Heart Disease
Figure 6. Whole-heart coronary MRA acquired with a freebreathing SSFP sequence in a subject with normal coronary
arteries. The volume-rendered image from whole-heart coronary MRA is useful for 3D anatomical recognition of the RCA
and the LAD and its branches.
approach is useful in the evaluation of the luminal
narrowing of the coronary artery that exhibits heavy
calcification in the vessel wall on multislice CT (Fig. 8).
A recent study demonstrated that acquisition of wholeheart coronary MRA was successful in 34 of 39 patients
(87.2%), with an average acquisition duration of 13.8 ⫾
3.8 minutes (58). In that study, a trigger delay time and
an interval of minimal motion of the right coronary
artery (RCA) were determined on cine MR images for the
subsequent whole-heart coronary MRA acquisition.
The use of a subject-specific acquisition window (59) is
important to reduce motion blurring of the coronary
artery on whole-heart coronary MRA. In a more recent
study evaluating 113 patients (60), whole-heart coronary MRA allowed for the noninvasive detection of significant narrowing in coronary arterial segments with a
diameter of 2 mm or greater, with moderate sensitivity
of 82% and high specificity of 90% in a patient-based
analysis. In a vessel-based analysis, the sensitivity was
85% for the RCA, 77% for the anterior descending artery, and 70% for the circumflex artery. However, MR
acquisition was not successful in approximately 14% of
the patients who demonstrated an unstable breathing
Figure 7. Reformatted whole-heart coronary MRA in a subject
with normal coronary arteries. a: Curved MPR (multiplanar
reformation) image clearly depicts the RCA and left circumflex
(LCX) arteries. b: Oblique axial curved multiplanar reformatted image visualizes the left main coronary artery, LAD, proximal RCA, and LCX arteries.
9
Figure 8. A 61-year-old-male with chest pain on effort. a: A
curved MPR image of CE-CT coronary angiography acquired
with a 64-slice scanner demonstrates heavy calcification of the
arterial wall in the proximal LAD, which makes it difficult to
evaluate luminal narrowing of the coronary artery. b: A curved
MPR image of free-breathing 3D whole-heart coronary MRA
clearly reveals luminal narrowing in the proximal LAD.
pattern or drift of the diaphragm position during the
scan. A low navigator efficiency of less than 20% generally indicated unsuccessful acquisition of freebreathing coronary MRA.
Coronary MRA has been shown to have high sensitivity and specificity for detecting anomalous coronary
arteries and delineating proximal courses of the vessels
(61). It should be also noted that anomalous coronary
arteries can be accurately assessed by CE multislice CT
as well (62). Coronary MRA provides noninvasive detection and size measurement of coronary artery aneurysms in patients with Kawasaki disease, and can be
used as an alternative imaging method when the image
quality of transthoracic echocardiography is insufficient (63). Coronary MRA and X-ray coronary angiography show excellent agreement in the diagnosis of coronary artery aneurysm, and also in the measurements of
the maximal diameter and length of the aneurysm (64).
Noninvasive visualization of the coronary vessel wall
may enhance risk stratification by quantifying subclinical coronary atherosclerotic plaque burden. However,
MR visualization of coronary atherosclerotic plaque is
highly challenging because it is much thinner than
carotid plaque and exhibits complex motion due to respiration and cardiac contraction. Fayad et al (65) initially demonstrated the feasibility of plaque MRI of the
human coronary arteries by using breath-hold 2D
black-blood fast spin-echo (FSE) MRI. The free-breathing black-blood spiral MR approach proposed by Kim et
al (66) allows for isotropic 3D visualization of the coronary vessel wall. Recently there has been increasing
interest in molecular MRI with tissue-targeted contrast-agents. Spuentrup et al (67) demonstrated that
fibrin-targeted contrast medium permits selective visualization of acute thrombi in the coronary and pulmonary arteries. MRI of coronary thrombosis with tissuetargeted contrast medium may be an ideal noninvasive
imaging approach for the visualization of thrombi associated with plaque rupture.
10
There is an increasing interest in high-field coronary
MRI because the SNR increases approximately linearly
with field strength, and improvement in the SNR is
expected with 3.0T MR imagers. Stuber et al (68) demonstrated the feasibility of coronary MRA using a 3.0T
MR imager in healthy volunteers. Coronary MR angiograms with submillimeter spatial resolution were demonstrated at 3.0T. Sommer et al (69) evaluated the feasibility, image quality, and accuracy of coronary MRA at
3.0T in patients with suspected CAD. The average increase in CNR at 3.0T with respect to 1.5T was 21.8%
for the left coronary artery (LCA) and 23.5% for the
RCA. However, coronary MRA at 3.0T did not result in
significant improvement in the overall image quality
score by visual assessment, and no significant difference was observed in the diagnostic accuracy between
1.5T and 3T. Susceptibility-related local magnetic field
variations, increased sensitivity to motion artifacts, and
impaired ECG R-wave triggering are cited as factors
related to increased artifacts at 3.0T. Another major
limitation of 3.0T for cardiac MRI is RF-induced heating. With further advances in hardware and optimization of pulse sequences for high-field cardiac MRI, the
3.0T MR imager might become a platform of choice for
high-resolution coronary MRA and vessel wall imaging.
MR of Coronary Artery Bypass Graft
The assessment of occlusion and stenosis of coronary
artery bypass grafts is required postoperatively in many
circumstances. While the patency and stenosis of coronary artery bypass grafts can be assessed reliably with
conventional X-ray angiography, this technique is invasive and involves some risk. MRI has been shown to be
useful for demonstrating the occlusion of coronary artery bypass graft with the use of spin-echo MRI (sensitivity/specificity of 90%/72%) (70), cine MRI (88%/
100%) (71), and CE 3D MRA (95%/81%) (72). Recently
Bunce et al (72) evaluated the accuracy of SSFP multislice MR images and CE 3D MRA for the detection of
coronary artery bypass patency in 25 patients. Although the sensitivity values of steady-state MRA and
CE-MRA were similar (84% vs. 85%), SSFP MRI resulted in more false-positive findings for occlusions and
reduced visualization of the arterial grafts.
In addition to the detection of graft occlusion, noninvasive identification of graft stenoses is important for
evaluating patients who present with chest pain after
bypass graft surgery. Langeral et al (74) evaluated the
accuracy of high-resolution navigator-gated 3D MRA
for detecting vein graft disease. The averaged sensitivity
and specificity for identifying graft occlusion, graft stenosis ⱖ 50%, and graft stenosis ⱖ 70% were 83/99%,
74/85%, and 73/84%, respectively, indicating that
high-resolution free-breathing 3D MRA enables the assessment of vein graft stenoses with a fair diagnostic
accuracy.
MR Flow Measurement in Coronary Circulation
Phase-contrast cine MRI can provide flow quantification in the coronary artery bypass graft and native coronary artery. MR flow measurement in coronary artery
Sakuma
bypass graft was validated with Doppler flow measurement using a flow phantom by Langerak et al (75).
Excellent correlations in average peak velocity (r ⫽
0.99, P ⬍ .001) and diastolic peak velocity (r ⫽ 0.99, P ⬍
.001) were demonstrated in vitro between MR and
Doppler flow measurements, with less than 5% interstudy variability. In order to validate the accuracy of MR
flow quantification of the coronary artery bypass grafts
in patients, the maximal diastolic blood flow velocity in
the bypass graft was compared with the diastolic peak
velocity measured by using a Doppler guidewire (76).
The diastolic peak velocity measured with MRI showed
a significant linear correlation with the diastolic peak
velocity obtained by using the Doppler guidewire, with a
correlation coefficient of 0.78 and slope of 0.85 (P ⬍
.05). One study evaluated the diagnostic value of
breath-hold MR flow measurement for detecting significant stenosis in the internal mammary artery to the
coronary artery bypass conduit, with conventional Xray angiography used as the reference standard (75).
The mean diastolic-to-systolic peak velocity ratio
(0.61 ⫾ 0.44 ) and the mean blood flow (16.9 mL/
minute ⫾ 5.5) in the subjects with graft stenoses were
significantly lower than in those without stenoses
(1.88 ⫾ 0.96, P ⬍ 0.01 and 79.8 mL/minute ⫾ 38.2, P ⬍
0.01), and the authors concluded that MR blood flow
measurement in the baseline state is useful for predicting significant stenosis in the internal mammary arterial graft. The value of MR measurements of graft flow
and flow reserve in differentiating significant from nonsignificant vein graft disease was evaluated by Bedaux
et al (77). By combining basal volume flow ⬍20 mL/
minute and graft flow reserve ⬍2, MR flow measurements showed a sensitivity of 78% and specificity of
80% for detecting grafts with significant stenosis or
impaired run-off . In a study recently reported by Salm
et al (78), a head-to-head comparison between SPECT
perfusion imaging and MR determined flow velocity reserve was performed for the detection of significant angiographic lesions in bypass grafts. Excellent agreement was found between SPECT and MR flow velocity
reserve measurement in 80% of all grafts. When the
grafts that perfused a territory with myocardial scar
were excluded, the agreement between SPECT and MR
improved to 84%. They also reported that MR flow velocity mapping can provide excellent detection of graft
stenoses by measuring either volume flow or flow velocity, with a sensitivity of 92% and 93%, respectively (79).
MR flow quantification can be used for the functional
assessment of native coronary arteries (80,81). Serial
changes in the coronary flow velocity reserve were evaluated for noninvasive detection of restenosis after coronary stent implantation by using fast phase-contrast
cine MRI (82). A significant reduction of MR-determined
coronary flow velocity reserve in the arterial lumen distal to the stent was observed in patients with restenosis. The flow velocity reserve was 2.26 ⫾ 0.49 at one
month and 1.52 ⫾ 0.09 (P ⬍ 0.05) at six months after
stent implantation in subjects with restenosis. In a recent study by Nagel et al (83), coronary flow velocity
reserve in the artery distal to the stent was measured
with MR in 38 patients after successful stent placements. Using a threshold of 1.2 for MR flow velocity
MRI for Ischemic Heart Disease
reserve, a sensitivity of 83% and a specificity of 94%
were achieved for detecting ⱖ75% stenoses on coronary
angiography.
CONCLUSIONS
With recent technical advances and an increasing number of publications, cardiac MRI is now recognized as a
method that can provide valuable information that may
not be obtained from other diagnostic modalities, such
as echocardiography and nuclear cardiology, in patients with ischemic heart disease. The high spatial
resolution of MRI can distinguish transmural from subendocardial ischemia or infarction. Cardiac MRI is noninvasive and does not require the use of potentially
nephrotoxic iodinated contrast agents or radiation.
However, MRI has a substantial functional overlap with
echocardiography, nuclear SPECT imaging, and multislice CT. For example, stress myocardial perfusion MRI
is not the only alternative approach to stress myocardial perfusion SPECT for the detection of myocardial
perfusion abnormalities in CAD. A multicenter study by
Jeetley et al (84) demonstrated that myocardial contrast echocardiography with vasodilator stress is comparable to stress SPECT in the detection of CAD. George
et al (85) recently determined the accuracy of multislice
CT to measure differences in regional myocardial perfusion during stress in a canine model of coronary artery stenosis, and found that stress myocardial perfusion CT provides semiquantitative measurements of
altered myocardial perfusion. There are several important points that currently influence the expansion of
cardiac MRI in clinical practice. The acquisition of cardiac MR images is time-consuming and the patient
throughput with MR is substantially lower compared to
multislice CT. Acquisition techniques for cardiac MRI
are still complicated, and a relatively small number of
institutions perform cardiac MRI on a day-to-day basis,
which has limited recognition of the usefulness of MRI
by physicians. Other factors that considerably affect
the expansion of cardiac MRI are the limited availability
of MR imagers and insufficient reimbursement. Most
importantly, administration of Gd contrast medium in
cardiac MRI has been considered off-label use in the
United States. Practical education and training for physicians and technologists, standardization of MRI protocols, cost-effectiveness studies to improve reimbursement, and efforts to raise awareness of the value of
cardiac MRI among clinicians and the general public
seem to be essential for expanding the use of cardiac
MRI in clinical practice.
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