(Radiographics. 2001;21:1047-1074.)
© RSNA, 2001
Imaging & Therapeutic Technology |
Advanced Cardiac MR Imaging of Ischemic Heart Disease1
Scott B. Reeder, MD, PhD,
Yiping P. Du, PhD,
Joao A. C. Lima, MD and
David A. Bluemke, MD, PhD
1 From the Department of Radiology, Rm H1306, Stanford University, 300 Pasteur Dr, Stanford, CA 94304 (S.B.R.); GE Medical Systems, Milwaukee, Wis (Y.P.D.); and the Departments of Medicine (J.A.C.L.) and Radiology (D.A.B.), Johns Hopkins University, Baltimore, Md. Presented as a scientific exhibit at the 1999 RSNA scientific assembly. Received March 23, 2000; revision requested June 7; final revision received March 2, 2001; accepted March 19. Address correspondence to S.B.R. (e-mail: sreeder@stanford.edu).
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Abstract
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Important advances in rapid magnetic resonance (MR) imaging technology and its application to cardiovascular imaging have been made during the past decade. High-field-strength clinical magnets, high-performance gradient hardware, and ultrafast pulse sequence technology are rapidly making the vision of a comprehensive "one-stop shop" cardiac MR imaging examination a reality. This examination is poised to have a significant effect on the management of coronary artery disease by means of assessment of wall motion with tagging and pharmacologic stress testing, evaluation of the coronary microvasculature with perfusion imaging, and direct visualization of the coronary arteries with MR coronary angiography. This article reviews current state-of-the-art pulse sequence technology and its application to the evaluation of ischemic heart disease by means of MR tagging with dobutamine stress testing, MR perfusion imaging, and MR coronary angiography. Cutting edge areas of research in coil design and exciting new areas of metabolic and oxygen leveldependent imaging are also explored.
Index Terms: Coronary vessels, stenosis or obstruction, 54.76 Heart, ischemia, 51.771 Heart, MR, 51.1214 Magnetic resonance (MR), perfusion study, 51.12143 Magnetic resonance (MR), pulse sequences, 51.1214 Magnetic resonance (MR), vascular studies, 51.12142 Myocardium, infarction, 511.771 Myocardium, ischemia, 511.771
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Introduction
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Cardiovascular disease is the leading cause of death in the United States (1). Each year, over 1.5 million U.S. residents have myocardial infarctions, roughly one-third of whom die. Although there has been a dramatic reduction in the death rate due to cardiovascular disease over the past 30 years, it still accounts for 22% of all deaths.
Diagnostic imaging has played an important role in the proper assessment and management of coronary artery disease. Advances in rapid magnetic resonance (MR) imaging technology and its application to cardiac imaging have shown that MR imaging has tremendous potential for evaluation of coronary artery disease and cardiac disease in general.
The concept of a comprehensive cardiac MR imaging evaluation has been an evolving theme during the past decade, with the vision of a complete cardiac examination that could be performed in a relatively short time (eg, <1 hour). A single examination that provides information on regional myocardial contractility and contractile reserve, regional perfusion reserve, and the detailed anatomy of the coronary arteries can be envisioned on the basis of MR imaging with tagging and dobutamine stress testing, gadolinium-enhanced measurement of regional perfusion, and advances in MR coronary angiography, respectively.
This article reviews the clinical state of the art in cardiac imaging for evaluation of coronary artery disease at 1.5 T. An overview of pulse sequence technology is followed by a description of cardiac MR imaging applications in evaluation of myocardial infarction, evaluation of myocardial ischemia, and coronary angiography. Finally, some examples of exciting advances that demonstrate promising new roles for cardiac MR imaging in management of coronary artery disease are explored.
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Technical Issues
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The greatest hurdle for cardiac MR imaging was the development of gradient hardware and pulse sequence technology that allows imaging sequences to "freeze" the motion of the heart during the cardiac cycle. In addition, it was necessary that these techniques be insensitive to the high velocities of the myocardium and ventricular blood, which manifest as ghost artifacts with traditional pulse sequences. The development of rapid pulse sequences facilitated breath-hold imaging, which was necessary to accommodate the wide range of motion the heart experiences during respiration. The greatest challenges in the acquisition of MR imaging movies, or cine imaging, have been twofold: (a) cardiac motion caused by diaphragmatic motion during breathing and (b) flow artifacts from myocardial and blood pool velocities.
Improvements in gradient hardware technology, as well as the ability of MR imaging systems to manipulate and process raw data more rapidly, have brought significant advances to cardiac MR imaging. Although rapid imaging techniques are routinely used to capture motion of the heart, areas of active investigation in cardiac MR imaging necessitate reductions in total imaging time, such as bolus tracking of contrast agents through the myocardium (2). Accurate characterization of perfusion defects requires sampling of three to six imaging planes with single-heartbeat temporal resolution (3). In addition, MR dobutamine stress testing requires acquisition and reconstruction of complete cardiac cine loops within one to five heartbeats. Finally, real-time MR "fluoroscopy" is now capable of cine refresh rates on the order of 2040 frames per second (4,5).
The diaphragm can move 23 cm during quiet breathing, causing substantial displacement of the heart, and strategies are needed to compensate for this phenomenon. Breath-hold imaging has been the most widely used approach and has been demonstrated to be a reliable method of obtaining sets or subsets of images that are well registered and unaffected by respiration. Breath-hold imaging requires very rapid imaging techniques that can acquire a full set of images in about 20 seconds. This approach implicitly assumes that cardiac motion is highly reproducible. In practice, this assumption is generally true, although there are some notable exceptions, including arrhythmias and pericardial effusions, when cardiac motion may vary from beat to beat. The latter phenomenon, known as "swinging heart," occurs as a result of excessive motion of the heart within the pericardial sac in the presence of a large effusion (6). State-of-the-art sequences performed on imaging units with high-performance gradients can now acquire cine data sets in as few as one to three heartbeats, and real-time acquisitions eliminate the need for breath holding altogether, facilitating the capture of beat-to-beat variations in cardiac physiology.
The velocities of ventricular blood during systole and early diastole are approximately 200 cm/sec and 150 m/sec, respectively (7). Traditional imaging sequences are highly susceptible to first moment phase shifts caused by these high velocities. The ghost artifacts that result have been successfully addressed by using sequences with ultrashort acquisition windows with very small first moments, as well as first moment nulling techniques. Blood signal suppression techniques that null the signal from the blood pool are also highly effective for artifact reduction. Fortuitously, imaging sequences with small first moments often have the best speed performance and are best suited for rapid cardiac imaging.
Although a variety of rapid imaging sequences have been applied to capture cardiac motion, two pulse sequence strategies are particularly effective for the demands of cardiac imaging: single- and multiecho gradient-echo (GRE) imaging and spiral imaging.
Single- and Multiecho GRE Segmented k-Space Imaging
The first reliable breath-holding techniques applied to cine cardiac imaging were ultrafast spoiled GRE sequences (8,9). Spoiled GRE imaging is well suited to imaging the heart because it is a robust imaging technique with excellent reproducibility and adequate signal-to-noise ratio (SNR). Short echo times impart insensitivity to motion and minimize the off-resonance effects of susceptibility and chemical shift. The effects of short T2* commonly observed in tissue from the thorax and mediastinum are also minimized. Acquisition begins when the imaging unit is triggered by the electrocardiogram, synchronizing image acquisition with the heart cycle. Multiple repetition times (TRs) are played through the heart cycle, and sequential lines of k-space data from each TR are segmented into individual raw data sets that will form the final frames of the cine acquisition. For single-echo imaging, the number of lines (views) of k space per segment (NVS) determines both the time resolution of the cine acquisition (TR x NVS) and the total number of heartbeats required for the acquisition, which is the total number of k-space lines acquired (Ny) divided by NVS. Images with improved time resolution can be acquired by means of reductions in NVS at the cost of longer breath holds. An acquisition becomes "real time" when all lines of k space are acquired during one heartbeat (ie, NVS = Ny).
An important variation of GRE imaging, generically known as steady-state free precession (SSFP) and commonly known as fast imaging with steady-state precession (FISP) or "true FISP," has recently seen a resurgence in interest. Introduced in the late 1980s (10), this technique preserves the coherence of the transverse magnetization by refocusing the gradients in all three axes. Both the transverse and longitudinal magnetizations reach a steady-state equilibrium that results in image SNR greater than with spoiled GRE sequences (11). Unlike the signal intensity of spoiled GRE sequences, which is primarily T1 dependent, the image intensity with SSFP also depends on T2 as a result of the coherence of the transverse magnetization. The usefulness of this pulse sequence was not fully realized until recently, as a result of severe artifacts caused by field inhomogeneities. With the advent of high-performance gradient hardware and improved field homogeneity, SSFP has had a recent revival with applications in MR fluoroscopy and cardiac imaging (1214). For cardiac imaging, the increased T2 weighting improves the contrast between myocardium and ventricular blood, potentially eliminating the need for black-blood techniques.
In comparison with standard spin warp imaging, single-echo segmented k-space imaging or SSFP requires little additional postprocessing. Oblique imaging plane optimization schemes for maximizing sequence efficiency by means of reduced sequence dead times have allowed substantial improvements in sequence efficiency and time performance (15).
More recently, the use of multiple echoes after each radio-frequency (RF) excitation has been used to improve both time and SNR performance. The concept is based on the original echo-planar imaging technique, in which an entire image data set is acquired after a single RF excitation (16). The efficiency of echo-planar imaging is very high, unlike that of GRE sequences, which require one RF excitation for every ky line sampled.
Although echo-planar imaging is capable of high SNR and very low imaging times (40120 msec), it is inherently sensitive to field inhomogeneities, chemical shift, and short relaxation times (T2*), all of which are problematic when imaging the heart. To circumvent these problems, McKinnon (17) applied interleaved echo-planar imaging to cardiac imaging with an image data set segmented over several "shots," usually one-eighth to one-fourth of the raw data per heartbeat. Interleaving reduces image artifacts caused by field inhomogeneities and short relaxation times. When echo-planar imaging is applied to the heart for cine acquisitions, sequential excitation or sampling of imaging planes is performed in a similar manner as with segmented k-space acquisitions. This fact implies that the magnetization behavior of cardiac echo-planar imaging and spoiled GRE imaging is very similar and can be analyzed on a continuum of echo train lengths.
In this light, an alternative paradigm approaches the situation from the bottom up by adding echoes to fast GRE sequences (18). In this paradigm, multiple TRs, each with multiple echoes, are acquired for each phase of the cine animation. SNR gains with multiecho GRE imaging and echo-planar imaging are achieved mainly by means of improvements in sequence efficiency and the increased recovery of longitudinal magnetization (T1) permitted by a longer TR. State-of-the-art multiecho sequences can now produce good-quality real-time acquisitions. For example, a newly developed multiecho sequence (19) run on a high-performance imaging unit can acquire good-quality real-time images at a rate of 23 frames per second. This sequence has a TR of 10.7 msec, an echo train length of eight, a 125-kHz bandwidth, and a 36 x 18-cm field of view. The matrix size is 160 x 48 with partial ky acquisition, and an entire image is acquired every 43 msec. When new postprocessing algorithms (20) are used, this acquisition can produce effective frame rates of around 40 frames per second.
Figure 1 is a schematic of k-space segmentation for a multiecho sequence, which is similar to k-space segmentation for single-echo sequences (8,9). The number of views per segment (NVS) is the product of the number of echoes per RF excitation, or echo train length, and the number of TRs in each segment (NVS = echo train length x number of TRs per segment). In this figure, NVS is nine, the echo train length is three, and the number of TRs is three. Depending on the imaging parameters, a single line of k space is acquired, on average, every 0.51.5 msec in imaging units with high-performance gradients. The time resolution of a multiecho image (in milliseconds) is equal to TR x NVS/echo train length.

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Figure 1. Schematic of a cine acquisition with corresponding k-space trajectory for a three-echo spoiled GRE sequence, with nine lines of k space per movie frame (NVS) and Ny = 27. Only 27 lines are shown for clarity; typical acquisitions use an Ny of 60-120. Consecutive echo trains are offset horizontally in the diagram for clarity. Temporal resolution (in milliseconds) is equal to TR x NVS/echo train length. RF pulses are represented by solid boxes, and each echo is read out during open boxes. Typical short-axis cine images are shown. 2D = two-dimensional.
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For multiecho sequences, the optimal TR that maximizes image SNR is approximately the T2* of the tissue (18). This fact reflects the optimal balance between increased signal from T1 recovery as TR is increased by lengthening the echo train and the decreased signal from T2* losses as the echo train length increases. Values of TR longer than the T2* of the tissue can result in substantial loss of signal. For the heart, T2* is approximately 3040 msec at 1.5 T, but drops to 10 msec in the posterior wall of the heart (21). Therefore, the optimal TR is approximately 10 msec, which usually allows an echo train length of four to eight. Distortion also worsens as echo train length increases, although experience has shown that T2* losses generally become apparent first.
An advantage of multiecho sequences when used in conjunction with myocardial tagging (which is discussed later in this article) is improved tag contrast. The closely spaced RF pulses of single-echo imaging drive magnetization toward steady state, causing rapid tag fading. Without special strategies, diastolic motion becomes difficult to sample as a result of tag fading. Single-echo echo-planar imaging has the best tag contrast (22), and multiecho spoiled GRE imaging has improved tag contrast characteristics over single-echo imaging.
Single- and multiecho spoiled GRE sequences are well suited to gadolinium-enhanced perfusion imaging for two reasons. First, they are sufficiently rapid to acquire two to six imaging planes every one to two heartbeats. Second, they are inherently T1 sensitive, making them ideal for perfusion imaging with contrast agents because these agents act by modulating T1 in a concentration-dependent fashion, as described later in this article.
Spiral Cardiac Imaging
Spiral imaging is an alternative imaging modality (23,24) that samples k space along trajectories that start at the center of k space and spiral outward. This scheme is a more natural sampling pattern that has high sampling densities near the center of k space, where the power spectrum of the image is generally highest. Spiral imaging, like echo-planar imaging, is highly efficient, but it is less sensitive to T2* losses than echo-planar imaging owing to the fact that sampling begins at the center of k space immediately after RF excitation. With echo-planar imaging, a significant fraction of signal is lost due to T2* decay by the time the center of k space has been sampled. In addition, spiral imaging is inherently insensitive to motion artifacts, unlike most spin warp techniques. This insensitivity is a result of the fact that all moments of spiral gradient waveforms naturally refocus. For a detailed explanation, see the article by Meyer et al (24).
Despite the intuitive appeal and theoretical advantages of spiral imaging, its implementation has been technically challenging. The use of spatial-spectral pulses has been necessary for eliminating chemical shift from fat to prevent blurring artifacts (25). This approach has the added advantage of eliminating the signal from pericardial fat in which coronary arteries lie, providing excellent vessel-wall contrast. In addition, new developments in the use of rapid field map correction algorithms (26) and rapid non-Fourier grid reconstruction algorithms (24,27) have helped spiral imaging mature into a viable and robust technique for cardiac imaging, especially in the area of coronary angiography (24,28,29). For motion studies, a spiral sequence can produce a high-quality cine loop in approximately 1020 heartbeats with 1520-msec temporal resolution and 1 x 1-mm in-plane spatial resolution. Spiral imaging is well suited to real-time fluoroscopic cardiac imaging (4,30,31), and the recent application of spiral imaging with high-performance gradients (Gmax = 4 G/cm, dG/dT = 150 T/m per second) has produced real-time images at frame rates of 2030 frames per second (31). Figure 2 is a schematic of cine spiral k-space trajectories, with examples of cine spiral images.

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Figure 2. Spiral k-space cardiac cine acquisition. Three spiral arms are segmented into each frame with every heartbeat. In three heartbeats, all nine spiral arms have been acquired. Spatial-spectral pulses are represented by solid boxes, and each spiral arm is read out during open boxes. (Images courtesy of Craig H. Meyer, PhD, Stanford University, Stanford, Calif.)
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Measurement and Detection of Myocardial Wall Motion Abnormalities
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Cardiac MR Imaging with Tagging
Myocardial tagging is an MR imaging method that uses a sequence of RF pulses to presaturate thin planes of myocardium prior to imaging. These "tags" persist in the myocardium through the heart cycle and can be used to track motion of the heart by acquiring images perpendicular to the tagging planes. Detailed descriptions of tagging methods can be found in the literature (32). The implementation of tagging pulses with rapid breath-hold imaging (9) has enabled reconstruction of a full three-dimensional (3D) strain field with great accuracy and precision if orthogonal tagging planes are acquired from a sufficient number of imaging planes (32). Strain can be defined as the local fractional change in length of the myocardium as it shortens (negative strain) or lengthens (positive strain). A high-resolution tagging experiment acquires cine loops in six to eight short-axis imaging planes and six to nine long-axis imaging planes. Figure 3 shows tagged images of a human heart with tags in three orthogonal directions (33). Although grid tag patterns are easily generated, parallel tag acquisition offers superior speed performance, since the power spectrum of parallel tags lies near a single k-space axis. Orientation of the readout gradient perpendicular to the parallel tags allows substantial reductions in the number of phase-encoding steps necessary to preserve accurate sampling of tag motion (9).

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Figure 3. Breath-hold tagged cine MR images obtained in a healthy human volunteer. Two short-axis views of the same imaging plane (top two rows) and one long-axis view (bottom row) are shown; each displays tag lines from a different set of mutually orthogonal planes. Only three (of 25) phases during the cardiac cycle are shown (early, middle, and late systole [left, middle, and right columns, respectively]). LA = left atrium, LV = left ventricle, RA = right atrium, RV = right ventricle. (Courtesy of Cengizhan Ozturk, MD, PhD, Johns Hopkins University, Baltimore, Md, and Elliot R. McVeigh, PhD, National Institutes of Health, Bethesda, Md, and Johns Hopkins University; reprinted, with permission, from reference 33.)
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Quantitative measurement of strain pattern changes requires determination of precise tag positions by using tag detection algorithms (3436). Postprocessing software can be used to obtain highly accurate estimates of tag displacementas little as 0.1 mm (34). Three-dimensional strain pattern calculations are then performed to provide detailed strain maps of the entire left ventricle in both time and space (32,36).
Cardiac MR Dobutamine Stress Testing
Dobutamine stress echocardiography and dobutamine stress nuclear cardiography have been routinely employed over the past decade for evaluation of coronary artery disease by means of detection of wall motion abnormalities under pharmacologic stress (37,38). Dobutamine increases both contractility and heart rate, eliciting significant increases in myocardial oxygen consumption. Typically, the patients heart is monitored in real time with an ultrasound (US) imaging probe (37,38) while the rate of intravenous administration of dobutamine is stepped from 0 µg/kg per minute to 5, 10, 20, and 40 µg/kg per minute, with 3 minutes at each level. If a wall motion abnormality develops before the maximal rate is reached, dobutamine administration is stopped and the test is considered positive for hemodynamically significant coronary artery disease. Dobutamine administration is discontinued for new onset of symptoms such as chest pain or dyspnea or if the target heart rate of the patient has been reached ([220 - age] x 0.85). Blood pressure is checked frequently throughout the examination.
There are two general responses that are detected with dobutamine stress testing. First, wall motion abnormalities can be induced in coronary beds fed by arteries with subcritical but hemodynamically significant stenoses. This situation occurs when the coronary reserve is insufficient to increase blood flow to match increased oxygen demands during pharmacologic stress. Detection of induced wall motion abnormalities with high-dose dobutamine echocardiography (040 µg/kg per minute) has been shown to have a sensitivity of 83% and specificity of 85% for detection of ischemic heart disease (39).
Thallium-201 and technetium-99m scintigraphy have similar sensitivity and specificity for detection of coronary artery disease, albeit at higher cost and with radiation exposure, which may limit repeat use of this technique (40). In addition, gated wall motion imaging during resting states is routinely performed in nuclear cardiology. The presence of resting wall motion abnormalities in combination with reversible perfusion defects may enhance the specificity and sensitivity of nuclear medicine in detection of coronary artery disease.
The second response seen with dobutamine is directly related to assessment of myocardial viability. Tissue that contracts normally during rest is viable. Myocardium that is dysfunctional during rest in the setting of recent or ongoing ischemia is of great interest, since the viability of this tissue is uncertain. Contractile dysfunction of viable tissue comes in distinct entities. Hibernating myocardium is viable myocardium with depressed contractile dysfunction resulting from chronic ischemia (months to years) insufficient to cause tissue necrosis. Contractility recovers quickly once coronary flow is restored. Stunned myocardium exhibits sustained (hours to days) reduced regional contractility after coronary reperfusion from an acute ischemic insult. However, it will respond to inotropic stimulation, and this behavior of the myocardium can be exploited to differentiate between stunned and infarcted myocardium (37). Low-dose dobutamine stress echocardiography (020 µg/kg per minute) has been used to test for viability in the form of transient recovery of function (41). Assessment for reversible dysfunction is important for prognosis and to identify high-risk patients, who may benefit most from aggressive revascularization therapy.
Unfortunately, transthoracic echocardiography is inherently limited by poor image quality and provides only qualitative estimates of myocardial motion. (In dobutamine echocardiography, a qualitative "wall motion index" is used to assess contractility.) Use of this technique leads to subjective measures of wall motion abnormalities rather than quantifiable assessment of the significance of detected abnormalities. The presence of multivessel disease may also affect the sensitivity of this test. Approximately 10%15% of dobutamine echocardiographic studies are considered "technically poor," and studies are often unsuccessful due to lack of adequate acoustic windows (37,42). Cardiac MR imaging has consistently superior image quality over that of echocardiography and has the added advantage of tissue tagging, providing accurate quantitative motion estimates that allow detection of subtle wall motion abnormalities. Preliminary results of MR dobutamine stress testing in 208 patients have demonstrated sensitivity and specificity superior to those of dobutamine stress echocardiography in detection of coronary artery disease (43).
Accurate measurement of regional strain requires that movie loops of seven to nine imaging planes (four or five short-axis planes and three or four long-axis planes) be acquired during the plateau phase of each 3-minute dobutamine titration, which is necessary for the heart to reach a stable hemodynamic state. During this interval, approximately three 15-second breath holds can be performed, requiring that a cine loop of each imaging plane be acquired in five or fewer heartbeats. Multiecho spoiled GRE imaging with high-performance gradients (18) can easily provide the speed performance necessary for MR dobutamine stress testing.
Figure 4 is a panel of short-axis images acquired in a healthy human volunteer at rest and during dobutamine-induced stress (20 µg/kg per minute). Five (of eight) movie frames acquired through systole are shown in this figure, each with a time resolution of 41 msec. In this particular examination, movies from eight imaging planes were acquired at four dobutamine levels. Increased tag detection and cavity obliteration are seen with dobutamine administration, indicating an increase in contractility. Less than 2 minutes was needed at each stress level to perform cine acquisitions of all eight imaging planes.

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Figure 4. Cine short-axis images acquired in a healthy volunteer at rest and during 20 µg/kg per minute of dobutamine stress. The first five of eight time frames are shown, each separated by 41 msec. A noticeable increase in contractility, evident as increased tag deflection and cavity obliteration, is seen in the bottom row, where end-systole has been reached by 173 msec after the QRS complex. LV = left ventricle, RV = right ventricle. (Courtesy of Elliot R. McVeigh, PhD.)
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Figure 5 plots maximal strain in the midwall at rest, at two levels of dobutamine stress, and at recovery during the stress examination of the same volunteer as in Figure 4. A clear increase in maximal strain is seen with increasing dose, followed by a decrease in strain with cessation of dobutamine administration. Similar calculations can be performed in all imaging planes and can be localized to the endocardium, epicardium, or midwall; an arbitrary number of segments around the left ventricle can be analyzed.

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Figure 5. Maximal strain calculated at five locations around the left ventricle in the midwall at different levels of dobutamine. Ant = anterior, Inf = inferior, Lat = lateral, Pos = posterior, Sep = septal. (Courtesy of Michael A. Guttman, MSE, National Institutes of Health, Bethesda, Md.)
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Figure 6 compares a sequence of tagged short-axis images obtained at rest and during 40 µg/kg per minute of dobutamine administration. Normal contraction patterns are seen in the rest images. Under stress, however, a wall motion abnormality in the anteroseptal wall has developed as a result of dobutamine-induced ischemia. This abnormality is subtle and may have been missed without tags. This test would be read as positive for coronary artery disease, probably in the left anterior descending coronary arterial vascular bed.

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Figure 6. Cine short-axis images acquired in a patient with coronary artery disease at rest (top row) and during 40 µg/kg per minute of dobutamine stress (bottom row). During dobutamine administration, abnormal tag deflection, as evidenced by reduced tag curvature, is seen in the anteroseptal region (black arrow) but not in the lateral wall (white arrow) on the end-systolic images. This wall motion abnormality is a result of dobutamine-induced ischemia.
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Myocardial Infarction
As described earlier, standard cine imaging with myocardial tagging is helpful in identifying abnormalities of strain patterns. Wall motion abnormalities at rest are easily detected, and the spatial extent of an infarction can be estimated indirectly by its effect on strain patterns. More important, the impact of an infarction on cardiac function can be directly assessed by means of imaging. Assessment of myocardial remodeling that takes place after infarction and establishing the extent of infarction may be important for management and prognosis. Figure 7 contains a tagged short-axis cine movie of a heart with a resting wall motion abnormality after acute myocardial infarction.

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Figure 7. Acute myocardial infarction with myocardial tagging. The end-systolic image shows abnormal poor wall motion in the anteroseptal distribution (black arrow). Normal contraction of the myocardium is seen in the lateral wall (white arrow).
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Highly detailed plots can be made of the progression of strain with ejection fraction or time at different regions within the heart (32). Figure 8 plots circumferential myocardial strain against time for segments of myocardium from apex to base and septal wall to inferior wall. A global reduction in circumferential strain as well as a focal reduction in the septal region (base to apex) are evident by comparing the patients strain evolution (red line) with the limits of the normal population (green lines). Paradoxical stretching is seen as red lines that deflect positively, especially in the apical septal-inferior myocardium.

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Figure 8. Plot of circumferential strain for a patient (red line) during the cardiac cycle shows paradoxical stretching in the septal region from apex to base. In other areas, circumferential strain is reduced from the strain evolution of the normal population (green lines span two standard deviations), indicating global hypokinesis. (Courtesy of Elliot R. McVeigh, PhD.)
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Contrastenhanced Perfusion Imaging
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During the past decade, substantial research effort has been dedicated to studying the kinetics of contrast materialenhanced perfusion in ischemic and infarcted myocardium. The most commonly used agent is the lanthanide heavy metal gadolinium chelated to diethylenetriaminepentaacetic acid, a compound known as gadopentetate dimeglumine. Gadolinium has the effect of shortening T1 by enhancing the relaxation of protons on a microscopic scale. The effects of gadolinium in a single-compartment model at equilibrium are relatively well understood (44); however, in vivo the situation becomes substantially more complex during bolus injections, where variables such as compartmentalization, extravasation fraction, water exchange rates, and pulse sequence physics complicate the precise interpretation of enhancement patterns seen in normal and diseased tissue (45). Despite its complicated nature, there has been enormous interest in gadolinium-enhanced imaging owing to the ease of acquisition of high-quality images with good SNR characteristics. Indeed, the overall sensitivity and specificity of first-pass bolus MR imaging for detection and identification of perfusion defects are 74%92% and 87%96%, respectively, when compared with results of conventional coronary angiography (40). By contrast, conventional nuclear medicine scanning has sensitivity and specificity of 65%82% and 75%81%, respectively (46).
Accurate characterization of regional myocardial perfusion necessitates repeated acquisition of images over the entire heart with high temporal resolution to capture the first pass of contrast agent through the myocardium (3). Advances in hardware and pulse sequence technology now allow acquisition of multiple imaging planes every heartbeat during the tracking of a contrast agent bolus. Figure 9 diagrams the timing of a typical single- or multiecho spoiled GRE perfusion imaging sequence. In this example, a complete k-space data set composed of Ny echoes is acquired, followed by Ny echoes for a second imaging plane and finally a third plane. Depending on the heart rate, image resolution, and imaging unit performance, current technology allows acquisition of two to six complete images every heartbeat, permitting accurate tracking of the contrast agent bolus through the myocardium. An added advantage of single-heartbeat acquisition is that breath holding is no longer required during administration of the bolus and subsequent image acquisition. Trade-offs for higher image resolution can be made by reducing the temporal sampling rate. Segmentation to more than one heartbeat per image requires breath holding, however.

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Figure 9. Timing schematic for perfusion imaging with saturation recovery. Here, two imaging planes are acquired every heartbeat with a single-echo GRE sequence (Ny = 96, Nx [matrix size in the readout direction] = 256, TR = 3.1 msec, echo time = 1.2 msec, field of view = 36 cm). Two additional imaging planes are acquired in the next heartbeat, so that four planes are acquired with two-heartbeat resolution. Each acquisition is preceded by a 90° nonselective presaturation pulse to zero longitudinal magnetization and to enhance T1 contrast. Breath holding was not required for this acquisition. (Images courtesy of Anthony Z. Faranesh, MSE, Johns Hopkins University, Baltimore, Md.)
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Coronary blood flow and volume are both known to change during the cardiac cycle. Although these factors are not known to affect gadolinium-enhanced perfusion images, this is an area that has not been rigorously investigated. Indeed, the temporal resolution needed to track small perfusion changes throughout the cardiac cycle during a bolus injection is beyond the capability of current pulse sequence technology.
The acquisition of each imaging plane is preceded by a 90° saturation pulse or a 180° inversion pulse to enhance the sensitivity of the pulse sequence to changes in T1. Sequences that use the 90° saturation pulse are insensitive to variations in heart rate, whereas inversion preparation increases sensitivity to T1 but is more susceptible to image artifacts and variations in heart rate. Increasing the imaging tip angle also increases the T1 sensitivity, as does centric phase encoding, which delays acquisition of the central lines of k space to the last few TRs, where T1 contrast is the highest.
Figure 10 is an example of a first-pass perfusion acquisition in a patient with an old infarction of the left circumflex arterial distribution. The bolus of gadopentetate dimeglumine can be followed as it passes through the right ventricle, pulmonary vasculature, and left ventricle and finally into the left and right ventricular myocardium. A well-defined, crescent-shaped defect correlates with the left circumflex artery occlusion, as confirmed with conventional angiography.

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Figure 10. Eight time frames of a midventricular imaging plane of a human heart, obtained by using the saturation recovery technique after bolus intravenous injection of gadopentetate dimeglumine. The time interval between images is four heartbeats. A large, crescent-shaped defect is visible in the lateral wall of the left ventricle (arrow), which corresponds to a documented old occlusion of the left circumflex artery. LV = left ventricle, RV = right ventricle. (Courtesy of Anthony Z. Faranesh, MSE.)
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Perfusion Imaging after Acute Myocardial Infarction
Viability after Acute Infarction.
After intravenous bolus administration of contrast agent, normal myocardium will show increased signal intensity, followed by washout from the tissue. This is the normal enhancement pattern. After a recent myocardial infarction, there are two enhancement abnormalities that are commonly seen. First, in the center of the affected myocardium, there is often a core of myocardium that does not enhance, remaining at the same signal intensity as normal myocardium prior to gadopentetate dimeglumine injection. This area is commonly referred to as the "hypoenhanced" or "no reflow" zone and is most apparent on early (first-pass) images, although it may be seen on delayed images. Complete obstruction of flow due to microvascular obstruction has occurred, and most investigators agree that this tissue is nonviable. The surrounding zone, however, often shows large areas of enhancement that persists on delayed images. Contrast agent in this tissue follows different washout kinetics than in normal myocardium. This tissue is widely termed "hyperenhanced," although this term is a misnomer, and the retention of gadopentetate dimeglumine in this region indicates some degree of myocardial damage and leakage into the interstitial space and ruptured myocytes (47). This situation dramatically increases regional extravascular volumes of distribution, lengthening the washout time of the contrast agent. As an example, Figure 11a shows first-pass and delayed images from four imaging planes through the left ventricle. In the first-pass images, an obvious perfusion deficit is evidenced by a darker region. The delayed images show areas of hyperenhancement. Images from a cine tagging examination in this patient are shown in Figure 11b. They reveal a resting wall motion abnormality in a single midventricular imaging plane, which correlates with the same spatial location as the perfusion abnormalities seen in Figure 11a.

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Figure 11a. (a) First-pass (top row) and delayed (bottom row) images through four imaging planes of the ventricle, obtained in a patient 5 days after a documented inferior wall myocardial infarction. A region of hypoenhancement is seen on the first-pass images (arrows), and a larger area of hyperenhancement is evident on the delayed images (arrows). (b) Images from a cine tagging study of the same patient in a midventricular imaging plane. A wall motion abnormality (arrows) is seen in the same region as the perfusion abnormality in a. The tag pattern in this area shows poor contractile function. (Reprinted, with permission, from reference 33.)
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Figure 11b. (a) First-pass (top row) and delayed (bottom row) images through four imaging planes of the ventricle, obtained in a patient 5 days after a documented inferior wall myocardial infarction. A region of hypoenhancement is seen on the first-pass images (arrows), and a larger area of hyperenhancement is evident on the delayed images (arrows). (b) Images from a cine tagging study of the same patient in a midventricular imaging plane. A wall motion abnormality (arrows) is seen in the same region as the perfusion abnormality in a. The tag pattern in this area shows poor contractile function. (Reprinted, with permission, from reference 33.)
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Figure 12 shows a delayed perfusion in vivo image of a canine heart, obtained 48 hours after 90 minutes of occlusion and reperfusion of the left anterior descending coronary artery and 15 minutes after bolus injection of gadopentetate dimeglumine. This long-axis image demonstrates a perfusion abnormality in the apical anteroseptal region, which corresponds to the vascular bed of the left anterior descending artery. Both a hypoenhanced core and a hyperenhanced peripheral zone are well demonstrated.

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Figure 12. Long-axis delayed perfusion image of a canine heart, obtained 48 hours after 1-hour occlusion of the left anterior descending coronary artery followed by reperfusion and 15 minutes after bolus injection of gadopentetate dimeglumine. A zone of hyperenhancement surrounds a dark no-reflow core (arrows). LV = left ventricle, RV = right ventricle.
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The viability of the hyperenhanced zone has been an active research question, and current results are conflicting. Judd et al (47) showed that, after 90 minutes of occlusion and reperfusion of the left anterior descending coronary artery, approximately 90% of late hyperenhanced tissue in canine hearts was nonviable. Kim et al (48) have shown similar results; however, Rogers et al (49) recently demonstrated that hyperenhanced regions showed partially reversible dysfunction. Their results also suggested that border zones between hypo- and hyperenhanced regions (the "combination" zone) were likely an admixture of viable and necrotic myocardium. Additional studies will be needed to resolve this interesting and important issue.
Progression.
It is well documented that the extent of residual small-vessel obstruction plays an important role in left ventricular remodeling and long-term clinical outcomes (50). Initially, microvascular obstruction was believed to finish shortly after the onset of arterial reflow, but later experiments suggested that this process is dynamic and develops up to 3.5 hours after reperfusion (51). The ability to assess accurately regions of no reflow with contrast-enhanced MR imaging has been demonstrated (47,52). In addition, it has been shown that infarct size and the extent of microvascular obstruction increase significantly over the first 48 hours after 90 minutes of coronary artery occlusion and reperfusion (53). These results demonstrate that progressive microvascular and myocardial injury occurs well beyond the period of coronary artery occlusion and reperfusion.
Outcomes.
The risk of future adverse events increases with infarct size, and the presence of hypoenhanced areas is associated with fibrous scar formation and left ventricular remodeling. Wu et al (54) recently determined that the presence and size of a hypoenhanced core seen during the first pass correlate with outcome. This study showed that after infarction, the degree of microvascular obstructiondetermined by the size of hypoenhanced zones (if present)allows prediction of future cardiovascular complications. Patients with hypoenhanced regions were found to have an increase in future cardiovascular events relative to those with no hypoenhanced regions (45% vs 9%). Infarct size, defined by the size of late hyperenhanced areas, was also shown to correlate directly with long-term prognosis in patients with acute myocardial infarction. Interestingly, the size of the microvascular obstruction was the strongest prognostic marker, independent of infarct size.
Stress Testing for Perfusion Reserve
Perfusion imaging can be used in assessment of perfusion reserve by means of potent vasodilators, usually dipyridamole or adenosine. Preliminary studies in a swine model are being performed by using dipyridamole stress testing (55). Coronary artery stenosis is created by placing a custom-made nylon flow-reducer fitting in the left anterior descending artery with standard coronary angiographic techniques. Dipyridamole is administered at 0.57 µg/kg per minute for 4 minutes. At 68 minutes after initiation of dipyridamole administration, Tc-99m sestamibi is injected. Immediately after injection of the radiotracer, an intravascular gadolinium T1 contrast agent (AngioMARK; EPIX Medical, Cambridge, Mass) is injected at 5 mL/sec with a power injector and MR perfusion imaging is started. After 30 minutes, resting perfusion images are obtained in the same manner. Figure 13 is an example of early-phase gadolinium-enhanced images in four (of five) imaging planes spanning the left ventricle and corresponding Tc-99m sestamibi single photon emission computed tomographic (SPECT) images, obtained during dipyridamole administration. A well-defined perfusion defect is seen in the anterolateral wall on the MR images, which correlates closely with the large defect seen on the SPECT images. No perfusion deficit was seen on resting images. Preliminary human myocardial stress perfusion studies with dipyridamole and adenosine have shown high sensitivity and specificity in detection of coronary artery disease (40).

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Figure 13. Gadolinium-enhanced perfusion images and Tc-99m sestamibi SPECT images acquired during dipyridamole stress. The MR images were acquired with a multiecho spoiled GRE sequence (echo train length of four, TR = 6.2 msec, echo time = 1.2 msec) during the early phase after bolus injection. A well-defined perfusion defect (arrows) in the anteroseptal region is clearly seen on the MR images, which correlates closely with defects on the SPECT images. LV = left ventricle, RV = right ventricle. (Courtesy of Dara Kraitchman, VMD, PhD, Johns Hopkins University, Baltimore, Md.)
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Coronary MR Angiography
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Direct anatomic visualization of coronary atherosclerotic plaques and stenoses is essential for definitive diagnosis and treatment of coronary artery disease. Not only is coronary angiography critical in identification of the location and severity of atherosclerotic stenoses, it is also necessary for planning bypass surgery, as well as identification of congenital abnormalities of the coronary arteries and myocardial bridging.
Cardiac catheterization is the current standard of reference for assessment of the coronary arterial circulation; over 1 million diagnostic catheterizations are performed every year in the United States (1), at a cost of about $4,000$5,000 per procedure. Of all patients undergoing coronary artery catheterization, 20% have normal coronary artery anatomy, whereas 30% are diagnosed with coronary artery disease but no intervention is pursued (56). In the remaining 50%, lesions are present and attempts at revascularization are made, either with percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. This situation has important implications for potential revascularization therapy, which is very expensive and carries a high risk of morbidity and mortality (56). A screening examination that allows accurate assessment of coronary artery disease and myocardial viability would reduce the number of patients undergoing unnecessary catheterization and those undergoing unnecessary revascularization, greatly reducing morbidity and mortality. Such an examination could allow assessment of the outcomes of interventions and presents an opportunity for tremendous reductions in medical expenditures. (The cost of a typical MR imaging examination is
$1,000.) Reduction of unnecessary procedures and accurate assessment of revascularization prognosis is dependent on knowledge of the status of the myocardium: Is the tissue in question salvageable, and, if so, will it recover function on revascularization?
Tremendous advances in MR coronary angiography during the past decade have demonstrated promising potential for noninvasive diagnosis of coronary artery disease. The in-plane image resolution of current coronary artery MR imaging techniques is about 1 mm, sufficient for detection of stenoses in large coronary arteries but inadequate for accurate detection of disease in smaller branches of the coronary vasculature. Accordingly, the future role of MR coronary angiography will likely be as an important adjunct to the comprehensive cardiac MR imaging examination, which combines angiography with stress tagging and perfusion imaging. Direct correlation of MR angiographic abnormalities with perfusion and wall motion abnormalities may prove to be a powerful combination in evaluation of coronary artery disease.
Figure 14 shows several maximum-intensity projection images from a high-resolution 3D spoiled GRE study of an ex vivo human heart, performed after injection of gadopentetate dimeglumine into the coronary vessels. Exquisite detail of the coronary anatomy is visualized, especially when it is rotated in three dimensions. These images offer insight into the best-possible coronary angiogram that MR imaging might produce in the future.

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Figure 14. Maximum-intensity projection images of an ex vivo human heart after injection of gadopentetate dimeglumine into the coronary vasculature, viewed from above (left) and the side (middle and right). The heart was imaged with a high-resolution 3D spoiled GRE sequence at 1.5 T. (Courtesy of Guy Shechter, BS, Johns Hopkins University, Baltimore, Md.)
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In vivo coronary angiography is a challenging prospect, however, largely as a result of image artifacts caused by cardiac and respiratory motion. Although cardiac motion artifacts can be effectively reduced by proper cardiac electrocardiographic gating, compensation for respiratory motion has been a significantly greater challenge and respiration may severely degrade the image quality of an MR coronary angiogram. The difficulties associated with respiratory motion artifacts are related to the fact that, unlike cardiac motion, motion of the diaphragm is highly unreproducible (57). A complete coronary angiogram requires sampling across the entire heart, which is difficult to achieve within a single breath hold. The facts that the coronary arteries are embedded within the pericardial fat and the mediastinum is a highly inhomogeneous magnetic environment have made MR coronary angiography very challenging. Several strategies that have been pursued are described in the remainder of this section: 2D breath-hold imaging, spiral imaging, and 3D imaging with navigator techniques.
Two-dimensional Spoiled GRE Coronary Angiography
Standard 2D spoiled GRE imaging has been successfully used to image the coronary arteries by relying on the inflow of fresh spins into the imaging plane. The "2D time of flight" inflow phenomenon is used in many areas of MR angiography and relies on spins outside the imaging plane, not previously saturated from RF pulses. As these spins flow into the imaging plane, they generate high signal, which produces excellent vessel-myocardial contrast. By using multiple breath holds, several planes that span the heart are acquired during diastole, when coronary arterial flow is maximal (5759). Increased tip angles, chemical presaturation of epicardial fat, and first-order flow compensation are often used to improve vessel-myocardial contrast.
Venous injection of gadopentetate dimeglumine prior to imaging will enhance the coronary vasculature by shortening the T1 of the blood pool, further increasing the vessel-myocardial contrast (60,61). Recently developed intravascular gadolinium contrast agents, such as MS-325, have reduced extravasation with high relaxivities. These agents are highly effective for shortening blood T1 and significantly improving vessel-myocardial contrast for both 2D and 3D MR coronary angiography (62). Figure 15 shows some examples of anomalous coronary arteries imaged with a 2D spoiled GRE sequence with high tip angle, first-order moment nulling, and intravenous gadolinium contrast material.

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Figure 15a. Anomalous left main coronary artery (arrows) arising from the right coronary artery origin. The images were acquired with a 2D spoiled GRE sequence after intravenous injection of gadolinium contrast material. Ao = aorta, LV = left ventricle, PA = pulmonary artery.
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Figure 15b. Anomalous left main coronary artery (arrows) arising from the right coronary artery origin. The images were acquired with a 2D spoiled GRE sequence after intravenous injection of gadolinium contrast material. Ao = aorta, LV = left ventricle, PA = pulmonary artery.
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The main limitation of this technique stems from the fact that the coronary arteries are tortuous and are difficult to capture in a single 2D imaging plane. Only short segments of the coronary arteries are displayed in each image; splicing contiguous imaging planes together may be problematic if the planes are acquired during different breath holds, because the images may not be well registered. Vessel-tracking techniques that partially compensate for this problem by adding imaging plane offsets to track the motion of the coronary arteries have been developed (63).
Spiral Coronary Artery Imaging
As described earlier, spiral imaging is well suited to coronary artery imaging because of its insensitivity to flow and motion artifacts and high data acquisition efficiency. Initial efforts toward coronary angiography with spiral imaging involved 2D cine acquisitions, in a manner similar to that described earlier (24). More recently, 3D spiral stack imaging has been applied to 3D spiral coronary imaging (29). Acquisition times exceed that allowed by breath holding, and respiratory compensation methods are necessary (29). The application of high-performance gradient systems with 3D spiral imaging may provide complete coronary angiograms within a breath hold. Preliminary efforts with "fluoroscopic" spiral coronary angiography have shown promise (30).
Vessel-myocardial contrast is enhanced in spiral imaging by means of spatial-spectral pulses, which eliminate signal from pericardial fat (24,25). In addition, T2 preparation with spiral imaging has been shown to be an effective method of suppressing myocardial and venous structures, improving the contrast between arteries and surrounding structures (64). Although not limited to spiral imaging, these methods are used most frequently in conjunction with this technique.
Figure 16 contains examples of spiral coronary angiograms obtained in healthy volunteers.

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Figure 16a. Spiral coronary angiograms of the left anterior descending artery (LAD) and several of its diagonals (a) and the right coronary artery (RCA) (b). (Courtesy of Craig Meyer, PhD.)
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Figure 16b. Spiral coronary angiograms of the left anterior descending artery (LAD) and several of its diagonals (a) and the right coronary artery (RCA) (b). (Courtesy of Craig Meyer, PhD.)
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Navigator-gated 3D Coronary Imaging
An alternative approach to MR coronary angiography involves the use of 3D imaging. In addition to the traditional readout and phase-encoding directions, a third dimension of k space is acquired by means of "depth" encoding. Three-dimensional Fourier transform of a 3D data set produces a true 3D image that can be viewed by extracting planes in any orientation.
Three-dimensional imaging eliminates the problem of imaging plane misregistration and is better suited for imaging tortuous vascular structures. In addition, prescription of image volumes is simplified because an image volume containing the coronary arteries is easy to define. The SNR of 3D acquisitions increases by a factor of
Nz (Nz is the number of depth-encoding steps), further enhancing image quality.
Unfortunately, an entire Nx x Ny x Nz 3D data set must be acquired free from the effects of breathing. Recent efforts have been made to acquire a 3D coronary image within a breath hold (61), although the imaging time is still too long for many patients. Novel approaches with directed double-oblique 3D volumes and multiecho spoiled GRE sequences have helped reduce total imaging time (65), but 3D data sets are generally beyond acquisition within a breath hold.
To overcome this problem, "navigator" echo techniques have been developed to compensate for respiratory motion (6567). The principle behind most navigator techniques is to track the precise position of the diaphragm during respiration by using a pencil beam excitation and single readout. Lines of k space are accepted only when the position of the diaphragm falls within a narrow window. It has been shown that the position of the diaphragm correlates closely with the position of the heart during respiration (67). Thus, 3D data sets can be acquired during free breathing by accepting data only when the diaphragm is in the same position. In a typical examination, a navigated 3D acquisition accepts data about 20%25% of the time. An alternative approach has been to provide feedback to patients with a light-emitting diode monitor, which allows the patient to adjust the position of the diaphragm (67). Navigator techniques are well tolerated by patients, particularly patients who find it difficult to hold their breath, even for short periods.
Figure 17 contains reformatted images from a 3D navigator acquisition of the right and left coronary arterial structures in a healthy volunteer (65). Figure 18 contains zoomed MR and conventional angiograms of the right coronary artery in a patient with known disease (65). Three stenotic regions are identified in both images.

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Figure 17a. Three-dimensional reformatted images of the right and left coronary arteries in a healthy volunteer. The in-plane resolution is 0.7 x 1 mm. (a) Image shows the left circumflex artery (LCx), left main coronary artery (LM), right coronary artery (RCA), acute marginal artery into the right ventricle (RV), and sinus node (SN). (b) Image shows the aorta (Ao), first diagonal (D1), left anterior descending artery (LAD), left circumflex artery (LCx), left main coronary artery (LM), and right ventricular outflow tract (RVOT). (Courtesy of Matthias Stuber, PhD, Beth Israel Deaconess Medical Center, Boston, Mass; adapted and reprinted, with permission, from reference 65.)
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Figure 17b. Three-dimensional reformatted images of the right and left coronary arteries in a healthy volunteer. The in-plane resolution is 0.7 x 1 mm. (a) Image shows the left circumflex artery (LCx), left main coronary artery (LM), right coronary artery (RCA), acute marginal artery into the right ventricle (RV), and sinus node (SN). (b) Image shows the aorta (Ao), first diagonal (D1), left anterior descending artery (LAD), left circumflex artery (LCx), left main coronary artery (LM), and right ventricular outflow tract (RVOT). (Courtesy of Matthias Stuber, PhD, Beth Israel Deaconess Medical Center, Boston, Mass; adapted and reprinted, with permission, from reference 65.)
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Figure 18a. MR (a) and corresponding conventional (b) angiograms of the right coronary artery in a patient with known right coronary artery disease. Three stenotic areas are identified on both images (arrows). (Courtesy of Matthias Stuber, PhD; adapted and reprinted, with permission, from reference 65.)
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Figure 18b. MR (a) and corresponding conventional (b) angiograms of the right coronary artery in a patient with known right coronary artery disease. Three stenotic areas are identified on both images (arrows). (Courtesy of Matthias Stuber, PhD; adapted and reprinted, with permission, from reference 65.)
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Future Directions
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There are more new and exciting areas of cardiac MR imaging research than can be covered herein, but some notable examples relevant to coronary artery disease are worth mention. The following is an incomplete glimpse of areas of research that hold promise for future clinical applications in evaluation of coronary artery disease.
Coil Design Innovations
Key to the success of cardiac MR imaging has been the tremendous improvement in RF coil technology, most notably the use of phased-array coils (68), which provide improved SNR and signal homogeneity across the heart.
Two new exciting areas of coil development technology involve intravascular catheter coils for direct in situ imaging of vessels and atherosclerotic plaques and the development of coil technology that permits simultaneous acquisition of multiple lines of k space, reducing total acquisition times by a factor of two to four.
Intravascular Catheter Coils.
Developments in catheter coil technology during the 1990s have led to the ability to image vessels from within the vessel itself (69). Not only does this technique have important implications for the development of interventional MR imaging, it also has tremendous potential for direct imaging of atherosclerotic disease. By placing a coil directly adjacent to an atherosclerotic plaque, detailed imaging and even spectroscopic measurement of lipid content can be performed (69). Figure 19 contains an image of an ex vivo human aorta acquired with a catheter coil. An atherosclerotic plaque is easily visualized; a histologic section of the plaque is shown for comparison (70).

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Figure 19a. (a) Catheter coil image of an ex vivo human aorta with an atherosclerotic plaque (arrow). The intraluminal black spot in the aorta is the coil. (b) Photomicrograph of a histologic section of the plaque. (Courtesy of Ergin Atalar, PhD, Johns Hopkins University, Baltimore, Md.)
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Figure 19b. (a) Catheter coil image of an ex vivo human aorta with an atherosclerotic plaque (arrow). The intraluminal black spot in the aorta is the coil. (b) Photomicrograph of a histologic section of the plaque. (Courtesy of Ergin Atalar, PhD, Johns Hopkins University, Baltimore, Md.)
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The use of projection imaging in combination with injection of gadopentetate dimeglumine and high tip angles can be very useful for positioning catheter coils, in a manner analogous to traditional fluoroscopy. Figure 20 shows several T1-weighted projection images acquired with an external coil during injection of gadopentetate dimeglumine from a catheter positioned at the base of the aorta (71). Visualization of the large coronary arteries is possible. In addition, large coronary veins can be seen during the venous phase of contrast material washout. This technique is most effective when images are displayed as a continuous movie and may prove particularly useful when acquisitions incorporate stereoscopic MR imaging (72). Once the catheter coil is positioned, direct intraluminal imaging of coronary vessels would be performed with the coil itself.

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Figure 20. Multiple projection images of in vivo coronary vasculature obtained during injection of gadopentetate dimeglumine into the left coronary artery. Note the early visualization of the left coronary artery, followed by filling of the venous vasculature. CS = coronary sinus, Diag = diagonal, GCV = great cardiac vein, LAD = left anterior descending artery, LCx = left circumflex artery. (Courtesy of Jean-Michel Serfaty, MD, Harald H. Quick, MS, and Xiaoming Yang, MD, PhD, Johns Hopkins University, Baltimore, Md; adapted and reprinted, with permission, from reference 71.)
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Continued development of in situ imaging with catheter coil technology will allow direct imaging and possibly even spectroscopy of coronary atherosclerotic plaques. Will intraluminal imaging of plaque morphology and composition allow us to determine whether a plaque is stable or unstable? Plaque stability is of critical importance because the risk of developing intraluminal thrombosis and resulting myocardial infarction increases significantly with unstable plaques. The ability to answer this critical question would have an immense effect on the management of coronary artery disease.
Simultaneous Acquisition of Multiple k-Space Lines.
As described by Sodickson and Manning (73), arrays of RF coils can be used for simultaneous acquisition of multiple k-space lines (simultaneous acquisition of spatial harmonics [SMASH]). Detailed descriptions of the theoretical basis of the SMASH technique are given elsewhere (73). This technique uses linear combinations of signals from receive coils positioned adjacent to one another. By strategically combining weighted coil signals, spatially varying sinusoidal sensitivity profiles can be created, which are analogous to a phase-encoding step. With this method, imaging time can be reduced by an integral "acceleration factor" less than or equal to the number of component coils in the array used for imaging. Typical acceleration factors of two to four have been achieved in vivo, and acceleration factors of as high as eight have been obtained in phantoms. This method has obvious implications for all forms of fast imaging and will facilitate dramatic improvements in speed performance, particularly for 3D coronary imaging and real-time cardiac imaging, if the technical challenges of this approach can be surmounted. For example, free-running real-time cine acquisitions at echocardiographic frame rates (23 msec per frame) have been achieved by using ultrafast multiecho spoiled gradient imaging and SMASH with an acceleration factor of three (5). A related method for acquisition of multiple k-space lines, sensitivity encoding (SENSE), was recently introduced by Weiger et al (74). This technique relies on linear combinations of spatial harmonics from receive coils in a volume array.
Blood Oxygenation Leveldependent Imaging
The blood oxygenation leveldependent (BOLD) effect has been exploited in estimation of regional oxygen concentration in isolated blood-perfused rabbit hearts (75), as well as in vivo applications (7678). The approach relies on the fact that deoxygenated hemoglobin, unlike oxyhemoglobin, is paramagnetic. Hemoglobin is concentrated in erythrocytes, which are in turn confined to the intravascular space. This compartmentalization in concert with the paramagnetism of deoxygenated hemoglobin generates spatially dependent susceptibility gradients when oxygen tension is low. These gradients enhance transverse magnetization dephasing (T2*), which manifests as reduced signal intensity at T2*-weighted GRE imaging, as well as T2-weighted spin-echo imaging. Boxerman et al (79) showed that spin-echo imaging is most sensitive to compartmentalization of deoxygenated hemoglobin in capillary-sized vessels, which implies that T2-weighted spin-echo imaging is sensitive to the oxygen tension in myocardial capillary beds.
Preliminary studies in hypertensive hypertrophic patients showed a threefold reduction of the oxygenation-dependent response to dipyridamole, demonstrating a reduced ability to augment tissue oxygen delivery (78). This reduction in oxygen delivery reserve may underlie the ventricular dysfunction and altered high energy metabolism commonly seen in this condition.
Spin-Echo Imaging
Areas of myocardial infarction and prolonged ischemia become edematous, increasing the water content of the tissue. Increases in water content increase tissue T2, and this phenomenon can be exploited to detect injured myocardium with fast spin-echo imaging (80). Particularly interesting are "double inversion-recovery" sequences, which use preparatory inversion pulses to null blood pool signals that would normally overwhelm images with motion artifacts (81). In addition, "triple inversion-recovery" sequences can be used to null the signal from pericardial fat. Figure 21 contains short-axis double inversion-recovery T2-weighted fast spin-echo images obtained in a patient with a recent myocardial infarction and a documented occlusion of the left anterior descending coronary artery. Brightening is clearly seen in the anteroseptal region through several imaging planes. These images show excellent spatial detail of injury extent; however, it may be difficult to distinguish between necrotic and viable tissue in an acute ischemic episode.

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Figure 21. T2-weighted fast spin-echo images obtained in a patient with a documented acute anteroseptal myocardial infarction show brightening in the anteroseptal region (arrow). The images were acquired with an echo time of 40 msec, an echo train length of 24, and a 256 x 256 matrix. Each imaging plane required a 20-heartbeat breath hold.
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The oxygen consumption of infarcted reperfused tissue drops, and the deoxygenated hemoglobin concentration would be expected to decrease. As described earlier, this decrease in deoxygenated hemoglobin level would contribute to an increase in T2, although the magnitude of this effect has not been determined clinically in the setting of acute myocardial infarction. Stunned myocardium, unlike infarcted myocardium, however, consumes oxygen at the same rate as normal contracting myocardium (82), and the venous deoxygenated hemoglobin concentration would be similar to that of normal myocardium. Stunned tissue and infarcted tissue both show wall motion abnormalities, which are difficult to distinguish. It is interesting to speculate whether T2-weighted fast spin-echo imaging may be capable of differentiating stunned from infarcted tissue in areas that exhibit wall motion abnormalities.
Electrolyte Imaging
Another interesting area of research in the field of cardiac imaging involves nuclear species with physiologic relevance other than H-1. Recent work in the area of sodium imaging (83) and potassium imaging (84) has produced some exciting results in ischemic animal models. Intracellular space normally makes up about 75% of myocardial volume. Sodium exists in high concentrations outside cells (
140 mmol/L) and in lower concentrations inside. During an ischemic event, decreases in cellular adenosine triphosphate reduce the activity of sodium-potassiumadenosine triphosphatase ion pumps, and intracellular concentrations rise. After infarction, cell membranes rupture and cytoplasmic sodium concentration approaches that in the serum, and areas of injured myocardium appear bright on sodium images. The opposite occurs with potassium, which normally exists in high concentrations inside cells (
140 mmol/L) and in lower concentrations outside. After an episode of ischemic injury, potassium leaks from cells and injured myocardium appears darker than normal tissue on potassium images.
Figure 22 shows axial in vivo Na-23 canine cardiac MR images obtained after occlusion of the left anterior descending coronary artery (85). The sodium images are masked with binary masks generated from proton images to eliminate the bright sodium blood pool signal and correct for blood spillover effects, and images are scaled to account for falloff of surface coil B1 sensitivity. An obvious increase in sodium intensity is seen in the anterior wall, which correlates closely with postmortem sections stained with triphenyl tetrazolium chloride (TTC). TTC stains viable tissue red-pink, whereas lysed cells remain white. The areas of infarction demonstrated by TTC show close correlation with the defects seen on the MR sodium images. Proton scout images are also shown.

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Figure 22. Na-23 MR images of a canine heart after occlusion of the left anterior descending coronary artery (middle column). The Na-23 images are masked by using proton images, and falloff of surface coil B1 sensitivity has been corrected. An increase in signal from the anterior wall is apparent, which correlates closely with the infarction seen in the TTC-stained sections (right column). Proton scout images (left column) are shown for comparison. The proton images, Na-23 images, and photographs of TTC-stained sections are not to scale. LV = left ventricle, RV = right ventricle. (Courtesy of Chris D. Constantinides, MSE, Johns Hopkins University, Baltimore, Md; adapted and reprinted, with permission, from reference 85.)
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Finally, myocardial phosphorus imaging and spectroscopy have been active areas of research owing to the critical role of phosphorus in myocardial oxidative metabolism. Detailed descriptions of myocardial phosphorus spectroscopy and imaging can be found in the literature (86).
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Conclusions
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In this article, issues involved with rapid cardiac imaging, which is necessary to capture cardiac motion with high-quality images free from image artifacts, were discussed. Two approaches to rapid cardiac imaging, multiecho spoiled GRE imaging and spiral imaging, were reviewed in detail. With high-performance gradient systems, these techniques are capable of real-time imaging applications at speeds comparable with that of echocardiography. Most high-performance gradient systems have reached Food and Drug Administration limits on magnetic field switching rates; further speed improvements in gradient hardware technology will provide minimal additional speed benefit. Large improvements in speed performance will be made if the realization and integration of SMASH and related technologies is successful.
The developing concept of the comprehensive "one-stop shop" cardiac MR imaging examination has materialized during the past decade. The components of this examination will provide comprehensive testing of wall motion and contractile reserve by means of stress tagging, as well as evaluation of myocardial microvascular status and perfusion reserve with contrast-enhanced perfusion imaging. Direct anatomic imaging of the coronary arteries with MR coronary angiography will complement functional information garnered with stress tagging and perfusion imaging. Complete clinical evaluation and implementation of the comprehensive cardiac MR imaging examination will provide the experience necessary to determine its precise role, possibly for screening, evaluation of disease severity, surgical planning, follow-up after revascularization, and evaluation of new medical therapies.
A major remaining problem with cardiac MR imaging is the lack of an appropriate user interface for data acquisition. Current imaging unit technology often limits the ability to process, store, and display large quantities of image data. A true real-time imaging unit will require an interface that enables the operator to rapidly maneuver imaging plane orientation and change imaging parameters with minimal delay. Immediate feedback is essential for real-time adjustment of imaging plane orientation and imaging parameters as physiologic conditions change. For example, real-time monitoring of wall motion abnormalities during pharmacologic stress is necessary from a safety perspective and would permit the operator to focus more closely on new abnormalities. This feature would likely enhance the ability of stress testing to characterize stress-induced abnormalities with greater sensitivity and specificity. A real-time imaging unit console will likely encompass features similar to those on US platforms used for echocardiography. Stereoscopic goggles for display of stereo projection data will assist operators positioning intravascular catheter coils, and joystick controls may facilitate easy and rapid adjustment of imaging planes. Postprocessing data buses, computers, and storage devices must have the ability to transmit, process, store, and display large amounts of data. As an example, real-time cine MR imaging might require a 256 x 256 2D fast Fourier transform every 2030 msec. This requirement is beyond the capabilities of modern imaging unit platforms.
Despite remarkable improvements in the understanding of the natural history of coronary artery disease and advances in medical therapies, prevention, and revascularization interventions, coronary artery disease continues to have an enormous health impact in our society. Cardiac MR imaging is poised to drastically change current methods of diagnosis and management of coronary artery disease.
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Acknowledgments
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Many of the results reported in this article were obtained by means of the collaborative efforts of the Cardiac MRI Research Group at the Johns Hopkins University School of Medicine. The authors especially thank Ergin Atalar, PhD, Michael Atalay, MD, PhD, Garth Beache, MD, Jerrold Boxerman, MD, PhD, Chris Constantinides, MSE, Anthony Faranesh, MSE, John Forder, PhD, Michael Guttman, MSE, Dara Kraitchman, VMD, PhD, Elliot McVeigh, PhD, Chris Moore, MD, PhD, Ogan Ocali, PhD, Nael Osman, PhD, Cengizhan Ozturk, MD, PhD, Carlos Rochitte, MD, Jean-Michel Serfaty, MD, Guy Shechter, BS, Xiaoming Yang, MD, PhD, and Elias Zerhouni, MD. The authors also thank David Fieno, PhD, Robert Judd, PhD, Ray Kim, MD, Craig Meyer, PhD, Daniel Sodickson, MD, PhD, and Matthias Stuber, PhD.
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Footnotes
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Abbreviations: GRE = gradient echo, NVS = number of views per segment, Ny = matrix size in the phase-encoding direction, RF = radio frequency, SMASH = simultaneous acquisition of spatial harmonics, SNR = signal-to-noise ratio, TR = repetition time, 2D = two-dimensional, 3D = three-dimensional
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