Textbook of Cardiovascular Medicine
3rd Edition

Chapter 54
Cardiovascular Magnetic Resonance Imaging
Milind Y. Desai
Richard D. White
David A. Bluemke
Joao A. C. Lima
Introduction
Cardiovascular magnetic resonance imaging (MRI) is a rapidly evolving technology that is very well suited for the morphologic and physiologic evaluation of a wide range of acquired and congenital disease processes affecting the heart, pericardium, and great arteries and veins of the thorax. MRI is unique in its ability to provide four-dimensional (three spatial dimensions over the dimension of time) imaging of the cardiovascular system based on definition of high-detail anatomy, histologic characterization, intracardiac or intravascular blood flow, cardiac chamber contraction and filling, regional myocardial mechanics, and tissue perfusion. Hence, MRI is playing a major role as a diagnostic modality in all facets of cardiovascular medicine. Furthermore, its potential is clearly becoming evident in the fields of atherosclerosis imaging, molecular imaging, and interventional cardiovascular medicine.
Principles and Techniques
Brief History
Nuclear magnetic resonance is a phenomenon exhibited by certain atomic nuclei. It was introduced by Block et al. (1) and Purcell et al. (2) in 1946. In 1973, Lauterbur (3) first described a method for producing images using related techniques, and as early as 1977 human whole-body images were already being produced by MRI (4). By the early 1980s (5,6), high-quality static anatomic imaging of the cardiovascular structures was being accomplished by electrocardiogram (ECG)-gated MRI. The mid to late 1980s saw the development and clinical implementation of dynamic MRI techniques allowing physiologic assessment of cardiac function and blood flow (7,8); this was promoted by the use of the more rapid acquisition techniques (9). Since then, MRI has profited from technical advances allowing the following capabilities: near-real-time imaging (10,11), tissue tagging-tracking (12), and three-dimensional (3D) acquisition and display (13); the result has been improvement in the assessment of myocardial physiology and complex and/or fine-detail anatomy of the cardiovascular system.
Magnetic Resonance Imaging Principles
A detailed discussion of MRI principles is beyond the scope of this book. A brief discussion follows. Atomic nuclei with odd numbers of protons or neutrons spin about an axis and can be aligned along the direction of a magnetic field. This characteristic is vital because it causes nuclei to precess when tipped from alignment with the main magnetic field. The 1H proton has been most widely applied in MRI because of its natural abundance; therefore, this discussion will refer to hydrogen-based MRI. The MRI signal originates primarily from the hydrogen of water and less so from the small hydrogen content of lipids. The actual appearance of the image is affected by a variety of physical parameters. Some of these parameters are characteristic of the tissue sampled and others relate to the MRI sequences. An essential difference between MRI and other modalities is the control that the user has over how data are generated and utilized. The agent of this control is k-space (Fourier space), the platform onto which data are acquired, positioned, and then transformed into the desired image (14). Raw image data are obtained during sampling through k-space, which depicts the spatial frequency domain. High spatial frequencies encode fine details, whereas overall contrast is encoded in the lower frequencies. Data are acquired at discrete intervals to fill k-space as signal amplitude is stored as a function of the spatial frequencies along the read-out and phase-encoding directions. An
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image is simply the inverse Fourier transform of the sampled k-space (15).
MRI uses high-power static magnetic fields and radiofrequency (RF) pulses to generate tomographic images. Application of weak RF-modulated pulses of a specific frequency will partially align the magnetic moments of protons within the tissue sample against the magnetic field and will induce their resonance; the effect of this RF field is maximal when the nuclei have been deflected by 90°. When the RF pulse ceases, the protons return to equilibrium. During this process, they emit the RF energy of the same frequency, which is then Fourier transformed by a computer into a spatially accurate image whereby differences in signal intensity result in differences in gray levels. The signal intensity depends not only on hydrogen density, but also on the longitudinal relaxation time (T1), reflecting the rate of realignment with the external magnetic field (enhancing the signal), and on the transverse relaxation time (T2), indicating the rate at which nuclei lose coherence with each other (degrading the signal). In normal myocardium, T2 is much shorter (i.e., 60 msec at 1.5 T) than T1 (i.e., 500 msec). The characteristic T1 and T2 relaxation times are exploited to distinguish between normal tissues and to characterize disease processes. In general, MRI contrast improves with increasing hydrogen density, shortening of T1, and lengthening of T2.
Basically, an MRI scanner consists of five major parts: magnet, transmitter, antenna, receiver, and computer. Most modern clinical MRI scanners have magnets consisting of liquid helium–cooled superconducting solenoids operating at a field strength of 0.1 to 3.0 T and with a bore size of approximately 1 m; MRI is best performed with a magnet with higher field strength and homogeneity to improve the signal-to-noise ratio. The transmitter is used for transmitting RF pulses to an antenna or coil, which in turn transmits RF power to the patient and also receives the returning signal. The coil usually surrounds the patient or may be placed directly on the patient’s surface, depending on whether information is required from the whole body or from a selected organ of interest; although surface coils provide higher sensitivity and, therefore, excellent spatial localization of signal, they have the disadvantage of an inhomogeneous RF field, which produces an inhomogeneous signal intensity distribution on images. The receiver amplifies the signal picked up by the coil, and the signal is processed by a computer, which is also needed to operate the entire MRI system.
Specific Magnetic Resonance Imaging Techniques
A detailed discussion of MRI physics is beyond the scope of this chapter, but can be studied from many dedicated textbooks. We briefly discuss some features, including the commonly used imaging sequences in cardiac imaging.
Spin-Echo Sequence
Conventional spin-echo (SE) imaging was for a long time the workhorse of cardiac MRI studies. It has been supplanted by more modern techniques that allow for faster imaging. Nonetheless, spin-echo is still frequently performed with T1 weighting; T2-weighted sequences can be used to demonstrate tumors, inflammation, or myocardial tissue abnormalities. A typical cardiac MRI study is initiated by acquiring scout views through the chest. This is accomplished in a very short time interval, using a fast MRI pulse sequence that has a moderate spatial resolution. The scout views are used to prescribe a volume of interest that is studied with subsequent stacks of SE slices. Each stack has a different orientation (often the three orthogonal planes: coronal, sagittal, and axial) and is acquired in 3 to 5 minutes. Image (slice) thickness, gap, and orientation can be freely chosen. With SE MRI, flowing blood usually generates no signal, whereas myocardium and fatty tissue produce intermediate and high signal intensity. SE MRI is ideal for visualizing morphology, but its limited time resolution does not easily allow functional analysis. The turbo (fast)-spin-echo sequence (TSE) is a faster version of the spin-echo sequence. Instead of one spin-echo pulse, the 90° excitation pulse is followed by a series of 180° pulses that produce several echo signals, each with a different phase encoding. This means that instead of one k-line, several k-lines are measured. The number of 180° pulses is also referred to as the turbo factor. The acquisition time can be shortened with respect to spin-echo imaging by the turbo factor. The most frequent application of TSE sequences is in acquisitions with T2 contrast, in which high turbo factors can be used and the greatest reduction in measuring time can be achieved.
Gradient-Echo Sequence
Gradient-echo (GRE) imaging is a faster technique. In contrast to SE, orderly blood flow generates high signal intensities in GRE imaging. GRE is fast enough to “catch” the signal from previously excited magnetic spins in the blood volume of the image section under study before the blood flow has moved the spins out of the image section. With GRE, the same section can be measured with high repetition rate, enabling the reconstruction of a cine loop of that particular section. This can be achieved in the axial, long axis, short axis, or any desired plane, with a time frame interval of less than 25 msec. GRE can thus be used to detect turbulent blood flow occurring in stenosis, regurgitation, or shunts. Such lesions become particularly obvious when viewing the tomographic section in a cine loop. Turbulent blood flow causes loss of the signal, so stenosis, regurgitation, or shunt flow is detected by a jet of signal void. Cine GRE MRI can be used to assess left (LV) and right (RV) ventricular function in terms of volumes and myocardial mass without geometric assumptions regarding the shape of the ventricles (16). A complete stack that encompasses the heart consists of 10 to 12 adjacent GRE images (typically of 10 mm thickness), each with its own set of time frames, and can be acquired in 10 to 15 minutes. End-diastolic and end-systolic volumes can be measured, or if desired a complete ventricular time–volume curve can be obtained. Another modification of the gradient-echo sequence is the segmented (multishot) gradient-echo sequence, in which only a segment of the image is acquired. In order to achieve all segments, measurements must be made over several RR intervals. Each segment (sometimes also referred to as a “shot”) comprises a certain number of slice-selective RF pulses followed by phase encoding and signal measurement. The segments are distinguished from each other by different values of the phase-encoding gradients (ky values) and consequently provide different k-lines. The newer balanced steady-state free-precession sequences give the best image quality, particularly if the repetition and echo times are kept very short and there has been adequate shimming of the static magnetic field to the region of the heart (17).
Magnetic Resonance Imaging Prepulses
All of the basic pulse sequences (SE, GRE, TSE) can be extended by a prepulse that is transmitted before the actual excitation pulse. The prepulse can consist of one or more RF pulses, sometimes in combination with gradient switching (slice selection, dephasing, etc.). Prepulses can be used for various purposes, such as influencing the contrast and suppressing fat or blood signals. A 180° pulse (inversion pulse) can be used to increase the T1 contrast. The longitudinal magnetization is inverted, and the T1 relaxation does not start at zero, as in the case of a 90° pulse, but at –1. In other words, the contrast range is doubled. The strength of the T1 contrast can be controlled
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by the interval between the inversion pulse and the excitation pulse, known as the inversion time (TI). In addition, TI can be chosen in such a way that the magnetization of a tissue during excitation is equal to zero, so that the signal from the corresponding tissue disappears. In this way, the fat signal can be suppressed by using a short TI (e.g., short inversion time inversion recovery [STIR] sequence), or a longer TI can be used to suppress the fluid signal (e.g., fluid-attenuated inversion recovery [FLAIR] sequence). An inversion pulse can be combined with all of the basic pulse sequences. In segmented gradient-echo sequences, the interval between the inversion pulse and the k-line determining the contrast of the shots (ky = 0) is also referred to as the prepulse delay (pp delay). Similarly, a 90° pulse can be used to increase the T1 contrast. In ECG-triggered acquisitions, the relaxation state of the longitudinal magnetization depends on the RR interval. It can therefore have varying values in arrhythmic patients with RR intervals of differing length. If a 90° pulse is transmitted by systole, so that the longitudinal magnetization is reduced to zero, the same T1 relaxation state is ensured after the pp delay, regardless of arrhythmias.
Another prepulse that is applied in cardiovascular diagnosis is the black-blood pulse, which is used to suppress the blood signal. The black-blood pulse consists of a series of two 180° pulses. The first pulse is non–slide selective (so-called block pulse). It inverts the magnetism in the total range of the transmission coil (in heart examinations, this can be the whole chest). The second 180° pulse, which is transmitted after the first, is slice selective, and returns the magnetization in the acquisition slice back to its original value. The magnetization of blood flowing into the acquisition slice begins to relax and, after a delay dependent on TR (or the heart frequency), is equal to zero. If the contrast-relevant values of the sequence are measured at this point, the blood signal will be suppressed. The black-blood pulse is often used with TSE sequences (T1 and T2 contrast).
Myocardial Tagging
Regional myocardial function is best assessed using a unique MR technique called myocardial tagging (12), commonly acquired by spatial modulation of magnetization (18). Spatial modulation of magnetization is obtained by applying a radiofrequency prepulse perpendicular to the imaging plane. This prepulse induces local changes in saturation within their planes that label the heart muscle with a dark grid and enables three-dimensional analysis of cardiac rotation, strain (in the subendocardial, mid-wall, and subepicardial layers), displacement, and deformation of different myocardial layers during the cardiac cycle (19). The tags can be applied immediately after the R wave on the electrocardiogram to image systolic function or in late systole to image diastolic function. However, until recently it had not been widely used in clinical cardiac imaging, mainly because of the extensive postprocessing that is required because of the vast amount of information produced by MR tagging series. Recently developed postprocessing software has significantly reduced the time it takes to analyze these tags, making the technique clinically viable (20).
Conventional Magnetic Resonance Angiography and Blood Flow Quantification
MR angiography (MRA) techniques can be divided in time-of-flight (TOF) MRA, phase-contrast angiography (PCA), and contrast-enhanced MRA.
Time-of-Flight Magnetic Resonance Angiography
This is an older technique, which has been used less frequently since the emergence of contrast MRA. In gradient-echo sequences, the longitudinal magnetization of stationary tissue is reduced by repeated excitations. Due to the saturation of the longitudinal magnetization, the signal from the stationary tissue is low. When the blood vessel runs perpendicularly through the slice, “fresh” unsaturated blood (not previously excited, with full longitudinal magnetization) will produce the maximum signal in the excited slice. The overall result is higher contrast between the flowing blood and the saturated stationary tissue. If many overlapping slices are combined, or if 3D techniques are used, inflow MRA can also be used to cover larger volumes.
Phase-Contrast Angiography
With the use of this technique, blood flow velocity is encoded in the phase of the MRI signal and phase changes occur linearly with changes in velocity. An image displaying the phase values across a vessel lumen can therefore be regarded as a velocity map. The signal intensity on quantitative PCA images increases toward bright or dark, depending on the direction of the flow, linearly with the velocity. PCA can be performed across a perpendicular vascular cross section, which allows assessment of instantaneous peak velocity and (spatial) average velocity at frequent time points during a cardiac cycle. Alternatively, to study the jet across a stenotic lesion, the image plane can also be chosen along the longitudinal axis of a vessel. Because true spatial average velocity can be measured, volumetric flow (mL/second) can be calculated by multiplication with the corresponding vascular cross-sectional area. This unique feature of MRI is superior to deriving mean velocity from a sample volume as in Doppler echocardiography. The contour of a vascular cross section is traced by hand, or preferably automatically, using commercially available computer software. The contour is adjusted, if necessary, for changes in position and diameter in every time frame. From these data, velocity and volume of flow can be plotted against time, and stroke volume can be calculated. This technique is being used as an elegant and reliable method for quantifying aortic and pulmonary blood flow because it enables quantification of intracardiac shunts, valvular regurgitation, or differential pulmonary blood flow (21,22). It has also been used to assess endothelial function not only by measuring vessel diameter, as by ultrasound, but also by integrating anatomic and flow velocity data to quantify endothelial shear stress (23,24).
Contrast-Enhanced Magnetic Resonance Angiography
Gadolinium-diethylenetriamine pentaacetic acid (Gd-DPTA) is a contrast agent with no known nephrotoxicity that alters the magnetic properties of blood, allowing measurements of a volume of interest with short repetition time (25). Gd-enhanced MRA is now being used in a rapid 3D fashion.
Within one breath-hold, a tissue volume encompassing the entire thoracic aorta or pulmonary artery with their respective branches is imaged. Imaging is timed to the arrival of a Gd bolus (generally 30 mL) in the area of interest. If it is so desired, acquisition can be rapidly repeated to visualize early and late venous phases. This technique has proven to be very valuable in (postoperative) coarctation, pulmonary stenosis, and preoperative evaluation of pulmonary atresia. In particular, the use of maximum-intensity-projection (MIP) reconstructions allows visualization of the aortic and pulmonary branches from any desired angle. Three-dimensional views display complex spatial information to clinicians who are less trained in image interpretation.
Delayed Postcontrast Imaging for Myocardial Viability
The current technique involves the rapid infusion of a gadolinium chelate (doses are typically in the range of 0.1 to
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0.2 mmol/kg) followed approximately 5 to 30 minutes later by a high-resolution, cardiac-gated, multishot, inversion-recovery–prepared, T1-weighted gradient-echo sequence (26). Images are acquired 5 to 30 minutes after contrast agent infusion (27). Choice of the appropriate inversion time (approximately 200 msec) to null the signal intensity of normal myocardium is critical for accurate delineation of the infarcted region. The healthy myocardium appears dark, whereas the enhancing myocardium appears bright. However, the optimal inversion time will lengthen over time as the concentration of gadolinium in the blood and myocardium gradually diminishes. Phase-sensitive reconstructions render the technique less sensitive to the choice of inversion time and reduce the variation in apparent infarct size (28). Imaging too early (e.g., <5 minutes after contrast agent infusion) may result in an underestimation of the infarcted region, whereas imaging too late (e.g., after >30 minutes) may result in excessive washout of the contrast agent and a poor signal-to-noise ratio (SNR). Findings in acute myocardial infarction showed a substantial change in the portion of left ventricle that enhanced depending on the timing of the acquisition with respect to the contrast agent infusion, with overestimation of infarct size if imaging was performed too early (29).
Image Planes
The orientations traditionally used for cardiovascular MRI are the transaxial, sagittal, and coronal planes; they are orthogonal to the thorax but oblique to the heart and great vessels. Complete sets of these images are most useful in gaining a global perspective of the relationships of the cardiac chambers, great vessels, and adjacent structures. They also serve as important localizing images for oblique imaging along the natural axes of the cardiovascular structures, such as with the long axis of the thoracic aorta. With further axial rotation, double-oblique imaging also can be performed to acquire images of the heart equivalent to the 2D echo short-axis and long-axis orientations (e.g., two-chamber, four-chamber, LV outflow) (30). The limitations of orthogonal imaging relate to deficiencies in the MRI evaluation of some regions of the cardiac chambers for anatomic or physiologic abnormalities. In transaxial imaging, for example, the undersurface of the LV may be obscured due to volume averaging with the adjacent diaphragm, or its wall may have the appearance of being abnormally thickened because it is sliced tangentially (31). This problem with orthogonal MRI of the heart can be overcome by using either another orthogonal (e.g., coronal) or an appropriate oblique (e.g., short-axis) orientation.
Compensation of Cardiac Motion
The formation of an MRI image requires a number of measurements, typically 128 or 256 or a fraction of that. In stationary tissue, these measurements can be done continuously. The heart, however, requires a different approach. To compensate for cardiac motion, every measurement is performed at a fixed time delay after a trigger signal from the R wave of the ECG. An image (slice) can thus be reconstructed after acquiring data during several consecutive cardiac cycles. The remaining slices of the selected volume are measured simultaneously, all with a slightly different time delay after the ECG trigger. Thus, a stack of slices is obtained in several minutes, each slice representing a different time point of the cardiac cycle. With prospective ECG triggering, no measurements can be performed in a certain time interval before the next QRS complex to allow for variations in heart rate. This means that no data can be collected during end-diastole, a drawback when studying diastolic phenomena. With retrospective gating, measurements are being made continuously, with simultaneous registration of the ECG signal. After acquisition, the data are attributed to the corresponding time frame and a complete cine loop is reconstructed that displays the full cardiac cycle. Another problem with ECG gating occurs under the influence of a strong static magnetic field, the enhancement of the so-called magnetohydrodynamic effect. It leads to artifactual augmentation of the T wave and may frequently mislead the R-wave detection algorithm so that triggering is performed on the T wave instead of the R wave. Because this artifact increases with field strength, this presents a major challenge for 3T. However, by analyzing the ECG vector in 3D space using the vector ECG approach (32), the true T wave can be separated from the artifactual T-wave augmentation, and reliable R-wave detection has shown to be feasible even at higher field strength (33). In general, severe arrhythmias will cause image quality degradation and unreliable quantitative MRI studies.
Compensation of Respiratory Motion
The second major impediment to MRI is respiratory motion. To compensate for respiratory motion, breath-holding was implemented early to allow for suppression of respiratory motion. Breath-hold approaches offer the advantage of rapid imaging and are technically easy to implement in compliant subjects. However, breath-holding strategies have several limitations. Some patients may have difficulty sustaining adequate breath-holds, particularly when the duration exceeds a few seconds. In addition, it has been shown that during a sustained breath-hold there is cranial diaphragmatic drift (34), which is substantial in many cases (∼1 cm). Among serial breath-holds, the diaphragmatic and cardiac positions frequently vary by up to 1 cm, resulting in registration errors (35,36). To overcome limitations associated with breath-holding, different methods such as MR navigators (37) have been developed to allow for free-breathing coronary MRA. With vertical positioning of the navigator at the dome of the right hemidiaphragm (lung–liver interface), the diaphragmatic craniocaudal displacement can be monitored. Although navigator approaches greatly improve patient comfort and do not require significant subject motivation, their use prolongs MRI data acquisition, commonly collected during 50% of typical RR intervals (38).
Safety Concerns During a Magnetic Resonance Imaging Examination
MRI should not be performed in patients with vascular clips used for cerebral aneurysm surgery due to the potential risk of dislodgement from the vessel (39). Implanted cardiac pacemakers, cardiac defibrillators, and neurologic stimulators represent contraindications, and patients with these electronic implants should not undergo MRI due to the risks from malfunctioning of the device or current induction (39). However there are emerging data about the feasibility and safety of performing MRI in patients with modern pacemakers at 1.5 T (40,41). On the other hand, the vast majority of prosthetic heart valves are compatible with MRI. Only a few high-profile prosthetic valves containing large amounts of alloy (e.g., Starr-Edwards pre-6000 series) should be avoided (42). Hemostatic clips, metallic sternal suture wires, and retained surgical epicardial pacing wires are not known to lead to complications from MRI, aside from local imaging artifacts (39). Critically ill patients are less-than-optimal candidates for MRI because either they are dependent on life-support or continuous-monitoring systems that cannot be brought near the scanner or their clinical condition is too fragile for the limited monitoring that is compatible
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with the MRI environment. Nevertheless, such patients can be safely evaluated if physiologic monitoring is supplemented during close observation by trained personnel. Claustrophobia may impede MRI in up to 5% of patients. This problem can be controlled by premedication with sedatives. Finally, the use of gadolinium contrast agent might be associated with metallic taste in the mouth, tingling in the arm, nausea, or headache. These symptoms occur in less than 1% (<1 in 100) of patients undergoing MRI and subside quickly. Very rarely, there may be an allergic reaction, but there is less than a 1 in 300,000 chance that such reaction would be severe.
Specific Clinical Applications
Here we focus on the application of MRI to cardiovascular diseases (Table 54.1). We also discuss some emerging applications of MRI.
Evaluation of Ischemic Heart Disease
Evaluation of ischemic heart disease is one of the most important indications for cardiac MRI. Following is a brief description of the different aspects of MR evaluation for ischemic heart disease (IHD).
Assessment of Global Ventricular Function
MRI techniques have been used to estimate impaired ejection fraction (EF) as a result of ischemic heart disease. EF is obtained from the end-diastolic and end-systolic images of the LV, and the resulting values derived, using the area-length method, correlate well with those obtained by single-plane and biplane LV ventriculography (e.g., R = .79 and R = .95 for parallel and perpendicular to the interventricular septum, respectively) (43,44). EF determination in patients with IHD can be performed more efficiently and with better temporal resolution using multilevel-cine MRI (45,46). In patients imaged within 7 days of acute MI using cine, LVEF by MRI has been shown to correlate better with EF by contrast ventriculography (e.g., R = .94) than with EF by radionuclide ventriculography (e.g., R = .82) (47). Cine images show the motion of the heart and blood over multiple phases of the cardiac cycle (48,49) by using some form of a multishot (“segmented”) gradient echo. Use of a small number of phase-encoding steps in each breath-hold (encompassing a small portion of the cardiac cycle, e.g., 20 to 60 msec) minimizes blurring from cardiac motion. Accumulation of multiple segments over a typical breath-hold period of 10 to 20 heart beats results in a complete cine examination (10). The newer balanced steady-state free-precession sequences give the best image quality (17). Because of these, MRI has become a gold standard in assessing LVEF and LV volumes.
Assessment of Regional Ventricular Function
Regional myocardial function relates to the amplitude and rapidity of contractile deformation of a segment of the left ventricular wall in the face of a given load or stress. The assessment of regional function is crucial to the complete evaluation of patients with most types of cardiac disease. For example, the demonstration of functional recovery in injured segments or those partially involved by necrosis is important as parameters of viability, and the study of regional function is important to quantify the development or progression of left ventricular remodeling after ischemic and other types of myocardial injury.
Visual assessment of systolic endocardial motion and wall thickening have been used most frequently in previous acute and chronic studies of regional myocardial function. These studies have reported varying levels of intra- and interobserver variability, which may be acceptable in certain situations when the assessment is performed in a before-and-after setting by very well trained observers. Ideally, however, myocardial functional studies should be objectively quantified to allow for less biased comparisons. Commonly, endocardial motion is obtained from cine MRI studies by endo- and epicardial border delineation. These measurements are unfortunately also quite variable due to technical and geometric factors intrinsic to left ventricular architecture and function. More recently, MRI methods for measuring myocardial deformation objectively in multiple orientations have become available (12,18,50,51,52,53,54). These novel techniques have virtually eliminated the use of experimental sonomicrometer implantation for assessing local myocardial function in basic research and have more recently revolutionized the use of imaging methods for assessing left
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ventricular performance in clinical (50) and population-based research (50).
TABLE 54.1 Clinical Utility of Magnetic Resonance Imaging: Current Applications
Ischemic heart disease
Reversible
   Induced +++
   Stunned/hibernating +++
Irreversible  
   Acute (e.g., acute myocardial infarction) +++
   Chronic (e.g., post–myocardial infarction aneurysm) +++
Coronary artery disease
Anomalous coronary arteries +++
Atherosclerotic coronary artery disease ++
Valvular heart disease
Stenosis +++
Regurgitation +++
Myocardial disease
Dilated cardiomyopathy +++
Hypertrophic cardiomyopathy +++
Restrictive cardiomyopathy (primary and secondary) +++
Right ventricular cardiomyopathy +++
Pericardial disease
Pericarditis and constriction +++
Pericardial masses
Aortic disease +++
Aneurysm (true, pseudo, and mycotic) +++
Dissection
   Acute dissection +++
   Nonacute +++
Intramural hematoma +++
Pulmonary artery disease +++
Pulmonary emboli +
Pulmonary hypertension ++
Thrombi
Ventricular thrombi +++
Atrial thrombi ++
Cardiac masses
Intracardiac (benign and malignant) +++
Extracardiac (benign and malignant) +++
Adult congenital heart disease
Simple cardiac abnormality +++
Complex cardiac abnormality +++
Great vessel abnormality +++
+, minimal utility; +++, maximal utility.
Moreover, it is very important to emphasize the importance of local load or stress for the adequate interpretation of functional parameters based on myocardial deformation assessed as endocardial motion, systolic thickening, or myocardial strain by MRI. This local load or stress dependence is particularly complex in the regionally ischemic or infarcted left ventricle, where the interaction between infarcted subendocardial layers and preserved subepicardial tissue occurs frequently (55,56). Similarly, the interaction between preserved myocardium located adjacent to acute or chronically infarcted regions depends not only on its own contractile reserve, but also on the mechanical behavior of remote noninfarcted regions and global loading conditions (51,57,58,59). For these reasons, load interdependence at both the global and regional levels is frequently overlooked or completely ignored in clinical studies as parameters that are difficult or impossible to quantify. Their existence highlights the limitations of functional parameters as indices of myocardial viability, but on the other hand, it is also important to have in mind that the heart’s ultimate function is to develop tension and contract in order to eject blood at adequate circulatory pressures. For that reason, functional indices of systolic and diastolic performance will always remain crucial parameters in the evaluation of the heart in health and disease.
Regional myocardial wall thickening abnormalities are frequently observed on MRI in association with ischemic heart disease, starting as early as 5 minutes after coronary artery occlusion (60). Regional wall-motion abnormality appears to be the most predictive and specific MRI finding associated with either a recent or remote myocardial infarction (MI) (61). Cine MRI is suited for evaluation of regional ventricular function in patients with ischemic heart disease (47,49,62). Compared with contrast ventriculography, the concordance in regional wall motion has been similar for cine (e.g., 69%) and radionuclide ventriculography (65%) (47). Although a multilevel cine series gives the advantage of full representation of the ventricles, when patients with suspected coronary artery disease (CAD) have been studied using only biplane cine and biplane LV ventriculography, 96% agreement in the right anterior oblique view and 92% agreement in the left anterior oblique view have been demonstrated (63). Cine has been found to be more accurate than echo in the measurement of LV systolic wall thickening (64).
The ability to perform MRI tissue tagging is particularly advantageous because it can quantify local myocardial segmental shortening throughout the LV at sites across the LV wall (12,18). Tagging uses selective radiofrequency excitation to saturate the magnetization in a thin planar region perpendicular to the imaging plane before acquiring image data. The altered magnetization in the tagged region appears as a dark line in the subsequent image where it intersects the imaging plane, persisting during systole and most of diastole. If the underlying tissue moves between the times of tagging and imaging, the altered magnetization of the tag line deforms with it. Hence, motion of the tag line faithfully follows underlying tissue motion. In the assessment of postinfarct remodeling, myocardial tagging has been used to provide unique functional information about regions of MI and compensatory changes of noninfarcted portions of the LV (51). In patients with one-vessel disease leading to an acute MI, reduced intramyocardial circumferential shortening has been noted throughout the LV, including remote noninfarcted regions (65). Based on the use of tagging, LV dilation and eccentric hypertrophy from remodeling have been shown to be associated with persistent differences in segmental function and wall stress between adjacent and remote noninfarcted myocardium (65).
Similarly, in the assessment of myocardial viability, MRI with tissue tagging has provided important diagnostic information. The improved predictive value of dobutamine-tagged MRI in detecting chronic hibernation, for example, was examined in 10 patients with ischemic cardiomyopathy studied before and 4 to 8 weeks after revascularization (66). The presence of contractile reserve by dobutamine MRI was 89% sensitive and 93% specific for functional recovery. The detection of stunning was reported in a cohort of 20 patients with first acute reperfused MI who were studied with tagged MRI at 4 days and 8 weeks postinfarct (67). Tagged MRI had a sensitivity of 89%. Moreover, because of the spatial resolution of MRI, contractile reserve in the different layers across the myocardial wall could be assessed. A recent study directly compared quantitative stress tagged MRI to qualitative assessment of echocardiographic contractile reserve in 22 patients 3 days after acute reperfused MI (68). The outcome variable was 8-week postinfarct functional improvement by echocardiography. Echocardiography and MRI were concordant in 76% of the segments. Compared to echo, MRI had similar sensitivity (82% vs. 86%) but lower specificity (69% vs. 87%). However, the overall accuracy of MRI and echo was 76% and 85%, respectively, which was not statistically different. One reason for the lower specificity includes difficulties in cross-registering locations between the two imaging modalities. In addition, the subendocardial response to dobutamine by MRI is known to be lower (67). To more directly compare with echo, this study averaged the MRI response across the three transmural layers, which likely contributed to the difference.
In addition to assessing two-dimensional shortening, tagged MRI can be applied in three dimensions to assess regional function not only in the circumferential, but also in the radial and longitudinal directions (69,70). The sequential tag positions during the cardiac cycle can be fitted to a finite-element model of heart wall deformation. The components of strain (deformation) can then be separated from rigid-body motion (translation and rotation). This approach is an accurate and precise measure of mechanical function (52,69,71). In particular, it accounts for conformational changes of the heart during systole such as the base-to-apex shortening and twist.
Widespread clinical application of stress MRI, particularly with tagging, has been limited by relatively long imaging times and requirements for time-consuming postprocessing and off-line analysis. New approaches are available that decrease imaging and postprocessing time and potentially provide on-line quantitative assessment of wall motion in near real time (53,54,72,73). This may prove beneficial in detecting ischemia with higher sensitivity and at an earlier point in the stress protocol, improving both accuracy and patient safety.
Assessment of Myocardial Perfusion Using Magnetic Resonance Imaging
Myocardial perfusion by has been assessed in the following ways using MRI methods.
Dynamic First-Pass Imaging
This is a very practical method for evaluating myocardial perfusion (74,75,76,77,78) and is achieved with use of extravascular agents that are widely available (e.g., gadolinium-based agents), even though 30% to 50% of the agent leaks out of the vascular bed during the first pass (79). In patients, there is good correlation between the perfusion reserve with MRI and the coronary flow reserve with Doppler ultrasonography (R = .80) (80). From a theoretical point of view, the use of an intravascular contrast agent simplifies the modeling of tissue perfusion because one does not need to model tissue extravasation, but such agents are not yet available for routine clinical use. For quantification of myocardial perfusion, qualitative measures such as the maximum myocardial enhancement, transit time, or upslope of myocardial enhancement (i.e., slope of the initial portion of the signal
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intensity versus time curve after gadolinium administration) (81) have been implemented. In one study of 104 patients, MR imaging had a 90% sensitivity for depicting at least one coronary artery with significant stenosis and an 85% specificity in identification of patients with significant coronary artery stenoses (82). The authors found that stress enhancement at dynamic MR imaging correlated more closely with quantitative coronary angiography results than did stress enhancement at single-photon-emission computed tomography (SPECT).
Resting Perfusion
Imaging of resting perfusion is only moderately sensitive in CAD. For instance, a study of 12 patients with significant stenoses of major epicardial vessels demonstrated a sensitivity of only 77% (83). Early after acute myocardial infarction, the resting perfusion deficit correlates with the long-term severity of left ventricular functional abnormality, and one finds higher perfusion in segments that have a residual contractile reserve at stress echocardiography (84).
Stress Perfusion
To detect significant stenoses of the epicardial coronary arteries, it is helpful to stress the patient so that a measure of the coronary flow reserve, or similar other measures such as the myocardial perfusion reserve index, can be obtained. Although it is technically possible, it is awkward to perform a physiologic exercise stress test within the confined bore of an MR imager. Instead, a pharmaceutical agent, such as dipyridamole (typical dose, 0.56 mg/kg of body weight) or shorter-acting adenosine (typical dose, 140 μg/kg/minute), may be administered to induce coronary vasodilation. The safety profile and more consistent course of action make adenosine the preferred agent for stress perfusion MR imaging. An abnormal perfusion reserve at MR imaging helps distinguish patients with CAD from normal individuals (85). In a study of 34 patients with a stenosis of an epicardial coronary artery of at least 75%, a cutoff value of 1.5 for MR imaging perfusion reserve helped differentiate normal from ischemic myocardial segments (86). This cutoff value yielded high sensitivity (90%), specificity (83%), and diagnostic accuracy (87%) for CAD, with excellent inter- and intraobserver agreement. Perfusion MR imaging also demonstrates the effectiveness of coronary interventions. In a study of 35 patients with single- and multivessel CAD imaged within 24 hours of coronary revascularization, a myocardial perfusion reserve index (upslope index) was calculated from resting and stress perfusion MR imaging (87). The perfusion reserve index improved but did not normalize after successful revascularization. The improvement was greater in patients receiving stents than in those only undergoing angioplasty. The coronary flow reserve determined at contrast-enhanced MR imaging correlates well with that at nitrogen-13 ammonia positron emission tomography (PET) (88). Flow reserve values at MR imaging are lower than those at PET, in part owing to a low extraction fraction for extracellular agents such as gadopentetate dimeglumine. Findings of several studies have confirmed the sensitivity and specificity of stress perfusion MR imaging as equivalent or superior to those of SPECT. In the literature, sensitivity and specificity values of MR imaging range from 64% to 92% and from 71% to 100%, respectively (89,90,91,92,93,94). MRI would therefore appear to be a reasonable alternative to SPECT for the evaluation of patients suspected of having CAD, with the additional advantages of better depiction of wall motion, cardiac morphology, and myocardial viability, in addition to the lack of radiation intrinsic to nuclear methods. Nonetheless, MR imaging has yet to make much impact on routine clinical practice, in part because SPECT or dobutamine stress echocardiography can generally provide the needed diagnostic information and because of a lack of the large-scale multicenter trials that would validate any potential superiority of MRI.
Postinfarct Microcirculatory Function and Microvascular Obstruction by Magnetic Resonance Imaging
During routine coronary angiography, it is not possible to adequately assess the microvasculature (arterioles, capillaries, and venules). There are many instances of coronary arterial beds in which, despite the recanalization of the epicardial artery, there is persistently diminished blood flow because the microvasculature remains plugged by red blood cell stasis (95), myocardial edema, or endothelial cell damage from free radical formation. This is known as the “no-reflow” phenomenon, which indicates lack of reperfusion from microvascular impairment at the core of a reperfused infarct. In a study of 22 patients with acute myocardial infarction, contrast-enhanced imaging performed a few minutes after contrast agent infusion showed subendocardial hypoenhancement inside hyperenhancing myocardium in nearly 50% of the cases, which is consistent with no reflow and microvascular obstruction (96). Microvascular obstruction has been demonstrated to indicate a worsened prognosis (97) and may predict a larger amount of adverse left ventricular remodeling (98). Microvascular obstruction is also associated with an increased incidence of intramyocardial hemorrhage (99) and is more common after angioplasty than thrombolysis with or without angioplasty (100).
Assessment of Myocardial Viability by Magnetic Resonance Imaging
MRI has emerged as a powerful modality for assessing myocardial viability (Fig. 54.1), with a significant role in patients being considered for coronary revascularization. The following are the MR techniques that help assess myocardial viability.
Low-Dobutamine Stress Magnetic Resonance Imaging
Viability can be assessed without the need for contrast media by performing cine MR imaging during a low-dose infusion (5 to 10 μg/kg/minute) of dobutamine, which is comparable to dobutamine stress echocardiography. Improved left ventricular wall thickening with stress in a segment that functions poorly at rest indicates viability (101). In addition to the studies using MRI tagging cited previously, comparisons among dobutamine stress transesophageal echocardiography, dobutamine cine MRI, and fluorine-18 (18F)-fluorodeoxyglucose PET in 43 patients with chronic infarction and wall-motion abnormalities resulted in a respective sensitivity and specificity of 77% and 81% for echocardiography and 94% and 100% for MRI (102). Criteria for viability were a resting wall thickness greater than 5.5 mm or wall thickening of at least 1 mm with stress. Dobutamine stress MRI can also be used to detect ischemic myocardium (103). In patients with nondiagnostic echocardiograms, dobutamine stress cardiac MRI may have prognostic value (104). The presence of inducible ischemia or left ventricular ejection fraction of less than 40% was associated with future myocardial infarction or cardiac death, independent of the presence of risk factors for coronary arteriosclerosis.
Delayed Enhancement
Postcontrast myocardial delayed enhancement detected by MRI is the most accurate means of detecting myocardial infarction. Cellular degradation in the infarcted region results in an increase in the permeability and enlargement of the extravascular space and hence an increased distribution volume for the extracellular contrast agent. Gadolinium chelates wash out of infarcted tissue more slowly than out of healthy myocardium. The net result is that infarcted regions appear bright on delayed contrast-enhanced T1-weighted images. The size and location of the infarcted region, as demonstrated histochemically in animal models, correlate with the size and location of myocardial delayed
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enhancement. Delayed hyperenhancement correlates well with dobutamine stress echocardiography (105) and with areas of decreased flow and metabolism at PET (106). However, MRI appears to be more sensitive (in one study, 11% of segments called viable with PET showed delayed enhancement with MRI). Another study of 26 patients demonstrated a 96% sensitivity and 84% specificity for myocardial delayed enhancement, with18F-fluorodeoxyglucose PET as the standard (107). MRI is superior in detecting subendocardial infarction. There is also good agreement with SPECT, but myocardial delayed-enhancement MRI has the major advantage of superior spatial resolution by an order of magnitude and the capability of incorporating anatomic and cine imaging in the same imaging session. In a study of 91 patients, SPECT depicted all of the nearly transmural infarctions but missed 47% of subendocardial infarctions that were seen at myocardial delayed-enhancement MRI (108). Another study of 20 patients with equivocal stress-rest sestamibi SPECT examination findings found the presence of subendocardial infarction at myocardial delayed-enhancement MR imaging in 40% of the patients (109).
FIGURE 54.1. Patient with a diagnosis of ischemic cardiomyopathy. A: Short-axis gradient-echo image demonstrating a dilated left ventricle with prominent thinning (infarction) in the left anterior descending territory. B: Delayed gadolinium-enhanced short-axis image of the heart showing areas of hyperenhancement suggestive of myocardial fibrosis (infarction) in left anterior descending territory (arrow).
Studies have shown that the amount of delayed transmural enhancement predicts the degree of functional recovery after acute myocardial infarction. Extensive transmural myocardial delayed enhancement is highly predictive of a lack of functional improvement after revascularization; conversely, absence of myocardial delayed enhancement correlates with a likelihood of functional recovery (110). The presence of a high-grade perfusion deficit or delayed enhancement in the early-phase MR imaging study is highly predictive of scar formation and lack of functional recovery at 1 year. Increased signal intensity on T2-weighted images indicates myocardial edema but does not always indicate infarction (111). That distinction requires the additional use of myocardial delayed enhancement. In another study of acute myocardial infarction, 20 patients were imaged within 1 week of the acute event and 7 months later (50). Enhancement patterns correlated with regional circumferential shortening strain (a measure of myocardial function) as determined with the harmonic phase imaging technique. Absence of myocardial delayed enhancement had a positive predictive value of 77% for functional recovery, whereas presence of myocardial delayed enhancement had a negative predictive value of 66%. It was concluded that, compared with the lack of early hypoenhancement, lack of delayed hyperenhancement is more accurate in predicting functional improvement in dysfunctional segments. The early hypoenhanced regions, corresponding to regions with microvascular obstruction, resulted in substantial underestimation of the amount of irreversibly injured myocardium after acute myocardial ischemia. History of myocardial infarction greatly increases the mortality rate compared with that of the general population. MRI may be useful in detection of unsuspected myocardial infarcts. In a study of 82 subjects, myocardial delayed enhancement helped to predict the presence, location, and transmural extent of healed Q-wave and non–Q-wave myocardial infarction (112).
Myocardial Delayed Enhancement and Myocardial Stunning
Transient hypoperfusion can cause myocardial stunning, which is associated with wall-motion abnormalities in the clinical setting of suspected acute myocardial infarction. Myocardial delayed enhancement in combination with cine MRI helps to differentiate wall-motion abnormalities of myocardial stunning, which are reversible, from those of myocardial infarction, which are often irreversible, depending on the severity of the injury. Either condition may cause a wall-motion abnormality, but delayed enhancement occurs only with infarcts. Lack of delayed enhancement indicates stunning rather than infarction and a high likelihood that left ventricular function will fully recover (113). In a study of 30 patients imaged approximately 1 week and 13 weeks after a reperfused myocardial infarction, the likelihood of functional improvement of segments without hyperenhancement was 3, 14, and 20 times higher than that of segments with 26% to 50%, 51% to 75%, and more than 75% hyperenhancement, respectively. The likelihood of complete functional recovery of segments without hyperenhancement was 3.8, 11.1, and 50.0 times higher than that of segments
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with 26% to 50%, 51% to 75%, and more than 75% hyperenhancement, respectively (114). Thus, functional improvement of stunned myocardium is predicted with myocardial delayed-enhancement MRI.
Triage of Patients with Chest Pain
A study of 161 patients with more than 30 minutes of chest pain but a nondiagnostic electrocardiogram found that the combination of myocardial delayed-enhancement, cine, and perfusion MR imaging was the strongest predictor of CAD and added diagnostic value over clinical parameters (115).
Diagnosis of Ventricular Aneurysms
In addition to impairment of left ventricular function and arrhythmias, complications of myocardial infarction include true and false aneurysms. True aneurysms, which are composed of pericardium adherent to underlying epicardium and scar tissue from infarcted myocardium, do not usually rupture. However, false aneurysms, which consist of pericardium that contains a ruptured left ventricle, may enlarge over time and require surgical resection. MR imaging can help make this distinction based on morphologic criteria (e.g., a wide mouth and anterior location for true aneurysm) (116) but also through the detection of a typical scar in patients with a true aneurysm (117).
Right Ventricular Infarction
Right ventricular infarction occurs commonly in patients with ostial right coronary artery occlusion, but the diagnosis is elusive. Delayed-enhancement MRI is likely the best technique for the noninvasive identification of patients with this syndrome (118).
Evaluation of Coronary Arteries
The current gold standard for the diagnosis of coronary artery disease is x-ray coronary angiography. Approximately 1 million cardiac catheterizations are performed each year in the Western world. However, x-ray coronary angiography is expensive and invasive, exposing patients and operators to ionizing radiation, and a small but finite risk of serious complications exists. A more cost-effective, noninvasive, and patient-friendlier imaging modality like coronary magnetic resonance angiography (MRA) overcomes many of these problems. Therefore, the utility of coronary MRA has been investigated since the late 1980s (119,120). For successful coronary MRI, a series of major obstacles has to be overcome. The heart is subject to intrinsic and extrinsic motion due to its natural periodic contraction and due to breathing. Both of these motion components exceed the coronary artery dimensions by a multiple, and therefore coronary MR data acquisition in the submillimeter range is technically very challenging, and efficient motion suppression strategies need to be applied. In addition, an enhanced contrast between the coronary lumen and the surrounding tissue is crucial for a successful visualization of both coronary lumen and the coronary vessel wall. The details of cardiac and respiratory motion compensations were discussed earlier. Even though great progress has been made in motion suppression and MRI hardware, software, scanning protocols, and contrast agents, the spatial resolution obtained by MRI remains to be further improved to approach that of x-ray coronary angiography (<300 μm). Although an enhancement in spatial resolution is always accompanied by a penalty in SNR, this may partly be overcome by the use of high-field systems (33) and contrast agents (121).
Contrast Enhancement in Coronary Magnetic Resonance Angiography
Using MRI, one can manipulate the contrast between the coronary blood pool and the surrounding tissue using the in-flow effect (122) or by the application of MR prepulses. Nonexogenous contrast enhancement between the coronary arteries and the surrounding tissue has been obtained by the use of fat-saturation prepulses (122), magnetization transfer contrast prepulses (MTC) (123), or, more recently, T2 preparatory pulses (T2Prep) (124,125) that take advantage of natural T2 differences between blood and surrounding myocardium. With these techniques, the coronary lumen appears bright and the surrounding myocardium appears with reduced signal intensity. An alternative to the bright-blood visualization of the coronary arteries is black-blood coronary MRA, in which the coronary lumen appears signal attenuated and the surrounding tissue displays with high signal intensity (126).
With the use of MR contrast agents, the T1 relaxation of blood can be shortened, allowing for increased contrast-to-noise ratio (CNR) during coronary MRA (127,128). Examples of extracellular agents include gadopentetate dimeglumine (Magnevist; Berlex Laboratories, Wayne, NJ), gadodiamide (Omniscan; Nycomed-Amersham, Buckinghamshire, UK), and gadotetriol (Prohance; Bracco Diagnostics, Princeton, NJ) and intravascular agents such as iron oxide (AMI 227; Advanced Magnetics, Cambridge, MA), MS-325 (Angiomark; EPIX Medical, Cambridge, MA/Mallinkrodt, St. Louis, MO), NC100150 (Clariscan; Nycomed-Amersham, Buckinghamshire, UK) (127,128,129,130,131), and B-22956 (gadocoletic acid; Bracco Imaging SpA, Milan, Italy). Because extracellular agents quickly extravasate into the extravascular space, their use requires rapid first-pass imaging and thus necessitates breath-holding (132). First-pass coronary MRA with extravascular contrast agents is also limited by the need for repeated contrast injections when more than one slab is imaged. With each subsequent injection, the CNR will be lower because the signal from the extracellular space continuously increases after initial contrast administration. The use of intravascular agents has the inherent advantage of allowing image acquisition over longer time periods after intravenous administration of the contrast agent. Thus, non–breath-hold schemes can be used, and repeated scans have similar CNRs without the need for repeated injections (127). With the use of the intravascular contrast agent B-22956, a substantial (50%) SNR enhancement was accompanied by a 160% CNR improvement when compared to the non–contrast-enhanced technique used in previous international coronary MRA multicenter trials (121,127,133). Similar results were found in a parallel volunteer study using the contrast agent SH L 643A (Schering, Berlin, Germany) (134).
Identification of Coronary Stenosis
Although current breath-hold coronary MRA techniques have relatively limited in-plane spatial resolution, the technique has been shown to identify proximal coronary stenoses in several clinical series. Gradient-echo techniques depict focal stenoses as signal voids. In one of the earliest prospective patient studies comparing x-ray coronary angiography and coronary MRA (135), a segmented k-space, 2D, breath-hold, ECG-gated gradient-echo pulse sequence was used. Overall sensitivity and specificity of the 2D coronary MRA technique for correctly classifying individual vessels as having or not having significant CAD (50% diameter on conventional contrast angiography) were 90% and 92%, respectively. Subsequent studies (136,137,138,139,140) have reported variable sensitivity and specificity values for the detection of significant CAD. Explanations for this variability in these single-center studies include differences in the MR sequences used, inadequate patient cooperation with breath-holding, and irregular rhythms, all of which contribute to image degradation. Newer breath-hold (141) and non–breath-hold approaches for 3D coronary MRA have also demonstrated the ability of this technique to detect coronary stenoses. Previous multicenter trials that prospectively compared coronary MRA to the gold-standard x-ray coronary angiography demonstrated that free-breathing submillimeter 3D coronary MRA accurately identifies significant proximal and midcoronary disease, whereas
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nonsignificant coronary disease can be excluded with high confidence. The specificity (false-positive readings) remains to be improved, and quantitative stenosis grading remains to be investigated.
Evaluation of Valvular Heart Disease
MRI is generally considered second in line after echocardiography for evaluation of valvular diseases. However, MRI has the following advantages: Its 3D nature makes it operator independent; it may be less susceptible to missing or underestimating eccentrically directed flow through a diseased valve; and it is free from geometric assumptions if cardiac chamber volumes are to be calculated (142). Using a combination of cine images (for valve excursion, semiquantitative assessment of regurgitation), velocity-encoded phase-contrast techniques (for a more accurate determination of regurgitant fraction/volumes, pressure gradients, and valve areas), and standard anatomic imaging, MRI can provide much valuable information in evaluation of patients with valvular heart disease. Abnormalities of the adjacent chambers are easily detected with MRI. In the presence of stenosis, dilation of the recipient chamber, concentric hypertrophy of a proximal ventricle, and generalized dilation of a proximal atrium have been described; and with regurgitation present (142,143), generalized dilation of the proximal and distal chambers and eccentric hypertrophy of an associated ventricle have been noted.
Mitral Valve
Mitral Stenosis
The following anatomic abnormalities of mitral stenosis (MS) have been described by MRI: thickened leaflets with reduced diastolic opening, enlarged left atrium, abnormal left atrial signal, and abnormal diastolic transmitral signal (144). A signal-void jet begins at the site of the mitral valve level and extends into the cavity of the LV during diastole on cine (142,143). Cine MRI has demonstrated the ability to quantitatively evaluate the following physiologic abnormalities associated with MS: valve leaflet separation (R = .81 vs. area by Doppler by pressure half-time method) (144), relative distal signal-void jet area (R = .77 vs. peak transvalve gradient by catheterization) (145), and peak transvalve gradient (R = .89 vs. gradient by Doppler) (146). In a recent study of 17 patients with documented MS, velocity-encoded MRI was used to determine E wave, A wave, and pressure half-time, similar to Doppler echocardiography (147). There was highly significant correlation for valve size estimates, peak E, peak A, and pressure half-time measurements between MRI and Doppler echocardiography (R = .94, .99, .99, and .83, respectively; all p <.01).
Mitral Regurgitation
Mitral regurgitation is readily identified on cine because of the signal-void jet of turbulent flow extending from the mitral valve level into the left atrial cavity during systole. Based on the detection of a jet, mitral regurgitation is identified with a high degree of accuracy (94% to 100% sensitivity and 95% to 100% specificity vs. color Doppler) (148,149). Quantitative physiologic assessment by cine MRI has included the following: distal signal-void jet grade [70% concordance vs. grade by color Doppler (150) and R = .77 vs. ventriculography (151)]; distal signal-void jet size [length, R = .74 vs. color Doppler (151); absolute area, R = .71 vs. color Doppler (151); relative area, R = .74 to .87 vs. color Doppler (149,151); volume, R = .84 vs. regurgitant volume by cine volumetric analysis (148)]; volumetric regurgitant fraction [R = .84 vs. ventriculography (150)]; volume-flow regurgitant fraction [R = .87 to 0.96 vs. grading by color Doppler (152,153)]; and combined volumetric and volume-flow regurgitant fraction [R = .96 vs. ventriculography (153)].
Aortic Valve
Aortic Stenosis
The anatomic abnormalities of aortic stenosis (AS) evaluated by MRI have included concentric LV hypertrophy, dilation of the ascending aorta, reduced aortic valve area [R = .75 by SE vs. catheterization or Doppler (154)], and mean difference by velocity mapping of 0.2 cm2 versus catheterization by the Gorlin formula and of 0.1 cm2 versus Doppler by the continuity equation (155). A double-oblique cine image taken through the aortic valve plane best demonstrates the cusps and their coaptation and serves to differentiate acquired AS from congenital AS with a bicuspid aortic valve. Cine MRI has proved its ability to quantitatively evaluate physiologic abnormalities associated with AS. The following have been assessed: absolute distal signal-void jet length [R = .86 vs. peak transvalve gradient by catheterization (145)] and peak transvalve gradient [R = .96 vs. gradient by Doppler (155) and R = .67 to .97 vs. catheterization (155,156)]. In a recent study of 24 patients with documented AS, velocity-encoded MRI was used to obtain velocity information in the aorta and LV outflow tract; pressure gradients were estimated using the Bernoulli equation, followed by calculation of aortic valve area, similar to Doppler echocardiography (157). There was highly significant correlation for valve size estimates, peak pressure gradient, and mean pressure gradient between MRI and Doppler echocardiography (R = .83, .83, .99, and .87, respectively; all p <.01).
Aortic Regurgitation
The signal-void jet of aortic regurgitation (AR) on cine has been fully described and evaluated for its potential to stage the severity of disease (142,143,145). Qualitative assessment by cine has also involved proximal flow convergence detection (158) (87% sensitivity and 100% specificity vs. aortography) (159) and distal signal-void jet detection (89% to 92% sensitivity and 93% to 98% specificity vs. Doppler) (148). For quantitative physiologic assessment, cine MRI has been used for proximal convergent flow signal-void area (significantly greater than for all grades by echo) (159); distal signal-void jet grade (93% concordance vs. grade by aortography) (160); distal signal-void jet size [area significantly greater than for moderate to severe vs. normal to mild 2D echo grades (161); volume, R = .84 vs. regurgitant volume by cine volumetrics (148), significantly greater than for moderate versus mild and for severe versus moderate 2D echo grades (148)]; volumetric regurgitant fraction (significantly greater than for moderate to severe versus normal to mild 2D echo grades) (162); and volume-flow regurgitant fraction [R = .97 to .98 vs. cine volumetrics (216,229); R = .80 vs. grading by aortography (163)].
Tricuspid and Pulmonic Valves
The value of MRI in assessing the presence and severity of congenital tricuspid abnormalities, including Ebstein’s anomaly or pulmonic valve disease, has been well established (164). The techniques are similar to those used for assessment of left-sided valvular heart disease. Volume-flow regurgitant fraction of pulmonic regurgitation has been validated (R = .93 vs. cine volumetrics) (165).
Prosthetic Valves
Studies in vitro and in vivo have shown that patients with artificial heart valves can be safely examined in high-field magnets (39,42). On MRI, little image distortion outside the immediate area of the prosthetic valve and no patient discomfort have been observed in related studies (166). When the diagnostic value of cine for detecting regurgitation in prosthetic valves was
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compared with that of transesophageal color Doppler echo, excellent (e.g., 96%) agreement between the methods in distinguishing physiologic from pathologic regurgitation was observed (167). In addition, quantitative physiologic evaluation of the severity of regurgitation has been quite promising [75% concordance of grade vs. grade by Doppler (234); R = .85 distal signal-void jet length, and R = .91 distal signal-void jet vs. Doppler (167)].
Evaluation of Cardiomyopathies
Cardiomyopathies (CMPs) are chronic progressive myocardial diseases with distinct morphologic, functional and electrophysiologic characteristics. According to the classification issued by the International Society and Federation of Cardiology Task Force (1996), they are divided into dilated, restrictive, hypertrophic, and arrhythmogenic right ventricular dysplasia (1,168). MRI, because of a high degree of accuracy and reproducibility in visualization of LV and RV morphology and function, is superior to all other imaging modalities in determination of the left ventricular mass and volumes (169) and is fast becoming the gold standard for in vivo identification of CMPs. For delineating cardiac anatomy, “black-blood” T1-weighted spin-echo techniques provide excellent contrast between the myocardium and adjacent structures. Gadolinium administration followed by a repeat T1 study helps in defining infiltrative and inflammatory myocardial disease. Fluid accumulation in inflammatory and malignant diseases can be more easily identified because of the improved T2-weighted image quality due to shorter T1 inversion recovery techniques (170). Contrast-enhanced MRI is also being recognized as useful in intramyocardial fibrosis (171). MR spectroscopy using 1H and31P has also been applied in several studies of CMP, particularly those involving31P in dilated CMP (172) and hypertrophic cardiomyopathy (173). Although the technique is still experimental, there is growing evidence to support its utility.
Dilated Cardiomyopathy
The histologic hallmark of dilated CMP (DCM) is progressive interstitial fibrosis, decreased myocardial contractility. and relative wall thinning in the late disease stages (174). In DCM, MRI is useful in the study of LV morphology and function, using different MRI sequences with low inter- and intraobserver variability of LV mass and volumes (175). It is also useful for analyzing wall thickening (176), impaired fiber shortening (55) and end-systolic wall stress (which is a very sensitive parameter of changes in LV systolic function) (177). It can also accurately assess the morphology and function of the RV, which is also frequently affected in DCM (178). MRI is rapidly becoming the method of choice for longitudinal follow-up in patients with DCM who are undergoing therapeutic interventions (179). From a research perspective, the sample size needed to detect LV parameter changes in a clinical trial is far less, on the range of one order of magnitude, with MRI than with 2D echocardiography, which markedly reduces the time and cost of patient care and pharmaceutical trials (180). MR spectroscopy has also revealed changes in phosphate metabolism in patients with DCM (172). A ratio of phosphocreatine to ATP has some prognostic value in DCM. Use of contrast-enhanced T1-weighted images is also helpful in detecting changes of acute myocarditis (increased gadolinium accumulation is thought to be due to inflammatory hyperemia–related increased flow, slow wash-in/wash-out kinetics, and diffusion into necrotic cells). There is also evidence of similar changes in chronic DCM (181). Contrast-enhanced MRI could also increase the sensitivity of endomyocardial biopsy by visualization of inflamed areas, which would aid in determining biopsy site (182). Thus, MRI is very helpful in the diagnosis and follow-up of patients with inflammatory myocardial diseases presenting as DCM. However, further studies with improved imaging techniques are needed to augment the specificity of contrast-enhanced MRI.
Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate myocardial hypertrophy, loss of diastolic function, and, in many instances, the development of an LV outflow tract gradient. Histologically, the hypertrophic areas reveal myofibrillar disarray and areas of patchy necrosis (170) (Fig. 54.2). Due to its high accuracy, MRI is becoming useful for assessing morphology, function, tissue characterization, and degree of LV outflow tract (LVOT) obstruction in patients with hypertrophic cardiomyopathy. MRI is very accurate in assessing LV mass, regional hypertrophy patterns, and different phenotypes of the disease (e.g., apical HCM) (169). Similarly, postsurgical changes after myomectomy can also be reliably monitored (183). The turbulent jet during systolic LVOT obstruction is also easily detected by using suitable echo times (about 4 msec). MRI can also detect the systolic anterior motion of the mitral valve in the four-chamber view or a short-axis view at the valvular plane (184). Mitral regurgitation can also be well documented and quantified by MRI (170). MRI spectroscopy also reveals changes in the phosphate metabolism in patients with HCM (173). In addition, analysis of blood flow in the coronary sinus using MRI can be helpful in determining the alterations in coronary flow reserve in patients with HCM (185). A relatively newer technique relies on measurements of the effective LVOT area by MRI planimetry during systole. This method has the potential to overcome the problem of interstudy variability of the LVOT gradient due to its independence from the hemodynamic status (186). There are preliminary data indicating that assessment of diastolic function using MRI may be superior to conventional parameters using echocardiography (187). Analysis of early untwisting motion of the myocardium could be helpful in assessing diastolic function (188). Other functional changes using myocardial tagging include a reduction in posterior rotation, reduced radial displacement of the inferoseptal myocardium, reduced 3D myocardial shortening, and heterogeneity of regional function (170). MRI is also very useful in the follow-up of patients after surgical or pharmacologic interventions (184). MRI also easily detects the acute and chronic changes after septal artery ablation (189). MRI not only quantifies alcohol-induced endothelial and myocardial necrosis, but also easily detects the acute and chronic changes in left ventricular structure and function caused by septal artery ablation (189). Delayed postcontrast enhancement occurs with HCM, probably reflecting the presence of abundant connective tissue or foci of necrosis (190). When myocardial scar is visualized, it is generally present in hypertrophied regions as patchy and with multiple foci, predominantly involving the middle third of the left ventricular wall. It is correlated positively with regional hypertrophy and inversely with regional contraction. In this regard, the extent of hyperenhancement may have prognostic implications for the risk of progressive ventricular dilation and sudden death (191).
Arrhythmogenic Right Ventricular Dysplasia
Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by a progressive degeneration of the RV, morphologically leading to fibrous/fatty replacement of myocardial tissue, significant wall thinning, and atypical arrangement of trabecular muscles. These fibromuscular bundles, which are separated by fatty tissues, lead to reentry phenomena and ventricular arrhythmias, syncope, and sudden death (55).
MRI has become very useful in arriving at the diagnosis of ARVD (Fig. 54.3). In fact, it is rapidly becoming the diagnostic
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technique of choice for ARVD. T1-weighted SE images reveal an increased signal intensity due to fatty infiltration, thinned walls, and dysplastic trabecular structures. To differentiate the normal fat surrounding the heart from the fatty infiltration of the RV free wall, some authors have proposed imaging in prone position using phased-array coils (192). Axial, sagittal, and short-axis views are usually recommended for optimal results (170). Standard gradient field echo (GRE) or the newer steady-state free-precession (SSFP) techniques reveal characteristic regional wall-motion changes, localized early diastolic bulging, wall thinning, and saccular aneurysmal outpouchings (192,193). The working group classification proposed by Corrado et al. is the recognized standard for arriving at the diagnosis (194). Table 54.2 shows the major and minor MRI criteria for the diagnosis of ARVD. ARVD needs to be differentiated from RV outflow tract (RVOT) tachycardia. This disease is commonly associated with fixed focal wall thinning, regional decreased systolic wall thickening, and areas of wall-motion abnormalities during systole, usually located above the crista supraventricularis and in the anterior and lateral RVOT (195).
FIGURE 54.2. Patient with a diagnosis of hypertrophic cardiomyopathy. A: Short-axis gradient-echo image demonstrating severe thickening of the interventricular septum. B: Delayed gadolinium-enhanced four-chamber view of the heart of the same patient as in panel A showing areas of hyperenhancement suggestive of myocardial fibrosis in the distal septum (arrow). C: Delayed gadolinium-enhanced four-chamber view of the heart of another patient with apical hypertrophic cardiomyopathy showing areas of hyperenhancement suggestive of myocardial fibrosis in the apex.
Restrictive Cardiomyopathy
Primary infiltration of the myocardium by fibrosis or other types of tissues leads to the development of restrictive CMP, characterized by normal LV size and systolic function, severe diastolic dysfunction, and biatrial enlargement. It frequently requires differentiation from constrictive pericarditis, which can be done very effectively using T1-weighted spin-echo techniques by MRI. LV size and thickness are quantified using
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gradient-echo sequences. Atrial enlargement is assessed in a four-chamber view. Velocity-encoded cine-MR imaging can also be used to quantify and monitor the restrictive filling pattern of the ventricles during therapy in restrictive cardiomyopathy (RCM) patients by measuring diastolic flow across the mitral and tricuspid valves (196). Moreover, mitral or tricuspid regurgitation can likewise be demonstrated and quantified with cine-MR imaging.
FIGURE 54.3. Patient with a diagnosis of arrhythmogenic right ventricle cardiomyopathy. A: Fast spin-echo T1 axial image of the heart showing the right ventricle outflow tract (RVOT) dilation with increased T1 signal (arrow). B: Fast spin-echo T1 axial image of the heart showing dilation of the right ventricle (RV) with signal abnormality (arrow). C: Fast spin-echo T1 with fat saturation axial image of the heart confirming fat infiltration of the RV wall (arrow).
TABLE 54.2 Magnetic Resonance Findings of Arrhythmogenic Right Ventricular Dysplasia
Major criteria Minor criteria
High signal intensity of RV on T1-weighted images Mild RVOT dilation
Mild RV dilation
Diffuse myocardial thinning of the RV Regional contraction abnormalities
Severe dilation of the RVOT
Severe dilation of the RV with systolic dysfunction
Aneurysms of the RV and RVOT
Global diastolic dysfunction
RV, right ventricle; RVOT, right ventricular outflow tract.
The following different secondary CMPs can also be effectively assessed using MRI.
Sarcoidosis
The incidence of myocardial involvement in systemic sarcoidosis is 20% to 30% (197), and up to 50% (198) of the deaths in sarcoidosis may be due to cardiac involvement. MRI is becoming a useful tool in the assessment of sarcoidosis. Sarcoid lesions may lead to different signal intensities, most likely due to different stages of the disease. Previous studies have reported high-intensity areas in T2-weighted MRI, whereas other studies have reported a central low-intensity area on T1- and T2-weighted imaging surrounded by a high-signal ring (199). In a study of 16 patients with cardiac sarcoidosis, postcontrast images revealed enhancement in half of the cases, which diminished after steroid therapy (200). Occasionally, MRI may be useful in guiding endomyocardial biopsy 170.
Hemochromatosis
Extensive iron deposits leading to wall thickening, ventricular dilation, congestive heart failure (CHF), and death characterize cardiac hemochromatosis. Usually the iron deposits are subepicardial, and hence the endomyocardial
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biopsy may fail to confirm the diagnosis (170). MRI is used to detect iron deposits associated with hemochromatosis, which is possible due to the very strong paramagnetic properties of iron, which leads to extensive signal losses in native T1- and T2-weighted images (201). The pattern of focal signal loss within dysfunctional myocardium associated with an abnormally “dark” liver might be sufficient to confirm the diagnosis of systemic hemochromatosis. LV function can also be accurately assessed using MRI, which is also useful in the follow-up of these patients as they undergo intensified medical therapy (170).
Amyloidosis
Infiltration of the heart by amyloid deposits is found in almost all cases of primary amyloidosis and in 25% of familial amyloidosis. MRI can be useful in detection of amyloidosis and its differentiation from HCM. Interatrial septal thickening or right atrial posterior wall greater than 6 mm is fairly specific for amyloid infiltration and consistent with echocardiographic data (202). Tissue characterization in cardiac amyloidosis has not been well studied and few data are available.
Endomyocardial Fibrosis
Endomyocardial fibrosis (also termed Loeffler endocarditis) leads to posterobasal concentric wall thickening, followed by extensive subendocardial fibrosis, apical thrombus formation, with progressive obliteration of both apices, diastolic dysfunction, and reduced stroke volume (170). The morphologic and functional features of endomyocardial fibrosis and the mitral and tricuspid insufficiencies that can be associated with this condition are well quantified by MRI. The fibrosis may be visible as a dark, thick apical rim in bright-blood–prepared gradient-echo sequences. Delayed imaging after administration of gadolinium-DTPA might have a role in the detection of associated fibrosis.
Evaluation of Pericardial Disease
The pericardium is a two-layered membrane that envelops all four cardiac chambers and the origins of the great vessels. The parietal and visceral layers are separated by a small amount of serous fluid—normally, about 15 to 50 mL—that is mainly an ultrafiltrate of plasma. Many disease processes can affect the pericardium, including infection, neoplasm, trauma, primary myocardial disease, and congenital disease. The pericardial sac responds to an acute injury with (a) congestion, (b) increased exudation of fluid into the sac, (c) exudation of both fibrin and acute inflammatory cells into the sac, or (d) a combination of these reactions. Echocardiography is the imaging modality most often used for the initial evaluation of pericardial disease, especially in patients suspected of having pericardial effusion or tamponade. However, MRI (along with CT) offers distinct advantages in the imaging of the pericardium. They provide a larger field of view than echocardiography, thus allowing the examination of the entire chest and detection of associated abnormalities in the mediastinum and lungs. MRI provides excellent anatomic delineation and enables precise localization of pericardial masses. In addition, MRI is performed in standard imaging planes and does not require use of a transducer; therefore, it is less operator dependent than echocardiography. The thickness of the normal pericardium, as measured on CT scans and MR images, is less than 2 mm.
Effusion and Tamponade
Pericardial effusion originates in the obstruction of venous or lymphatic drainage from the heart. MRI is indicated when a complex effusion or pericardial thickening is suspected (203,204) or when findings at echocardiography are inconclusive. The appearance of pericardial fluid is different on SE and GRE cine MR images. Nonhemorrhagic fluid has low signal intensity on T1-weighted SE images and high intensity on GRE cine images (205), whereas hemorrhagic effusion is characterized by high signal intensity on T1-weighted SE images and low intensity on GRE cine images (205). When an effusion is secondary to malignancy, an irregularly thickened pericardium or pericardial nodularity may be depicted on MRI.
FIGURE 54.4. Patient with a diagnosis of constrictive pericarditis. Four-chamber gradient-echo images showing diffuse thickening of the pericardium, with a conical appearance of the heart and dilated atria.
Pericarditis and Constriction
Clinically, it is difficult to differentiate between constrictive pericarditis and restrictive cardiomyopathy. In both conditions, ventricular filling is restricted, leading to an increase in diastolic pressure in all four cardiac chambers. It is important, however, to distinguish between constrictive pericarditis (Fig. 54.4) and restrictive cardiomyopathy because patients with constrictive pericarditis might benefit from pericardial stripping, whereas those with restrictive disease would not. MRI provides crucial information on the differential diagnosis of constrictive pericarditis versus restrictive cardiomyopathy. Normal pericardial thickness is less than 2 mm (203,206). Pericardial thickness of 4 mm or more indicates abnormal thickening, and, when it is accompanied by clinical findings of heart failure, is highly suggestive of constrictive pericarditis. MRI has a reported accuracy of 93% for differentiation between constrictive pericarditis and restrictive cardiomyopathy on the basis of depiction of thickened pericardium (4 mm) (207). Pericardial thickening may be limited to the right side of the heart or to an even smaller area, such as the right atrioventricular groove. A disadvantage of MRI is its limited ability to detect pericardial calcification. It is important to remember, however, that neither pericardial thickening nor calcification is diagnostic of constrictive pericarditis unless the patient also has symptoms of physiologic constriction or restriction. The central cardiovascular structures may show a characteristic morphology in constrictive pericarditis. The right ventricle tends to have a narrow tubular configuration. In some patients, a sigmoid-shaped ventricular septum or prominent leftward convexity in the septum can be observed.
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Because of the higher temporal resolution provided with cine MRI, the abrupt limitation of late diastolic filling of the ventricles because of the abnormally thickened and confining pericardium in constrictive pericarditis is distinguishable from the delayed diastolic filling patterns of the ventricles caused by restrictive CM in the absence of significant pericardial thickening.
Pericarditis without Constriction
Pericardial thickening may occur in the absence of constrictive pericarditis. Pericardial thickening may result from inflammation caused by a variety of conditions, including acute pericarditis, uremia, rheumatic heart disease, rheumatoid arthritis, sarcoidosis, and mediastinal irradiation. Normal pericardium is composed primarily of fibrous tissue and has a low signal intensity on both T1- and T2-weighted MR images. The purely fibrous or calcified pericardium in chronic pericardial disease also has low signal intensity. However, in subacute forms of pericarditis, the thickened pericardium has moderate to high signal intensity on SE images. Enhancement of the thickened pericardium after the administration of gadolinium-based contrast material also suggests inflammation. The effusive-constrictive form of pericarditis involves both pericardial thickening and pericardial effusion.
Pericardial Masses
The differential diagnosis of pericardial masses includes pericardial cyst, hematoma, and neoplasm. Although pericardial masses are often detected initially with echocardiography, MRI is useful for the further evaluation of these masses. MR signal intensity characteristics, degree of contrast enhancement, and presence or absence of blood flow on cine MR images can help to differentiate among pericardial masses.
Cysts
Congenital pericardial cysts are formed when a portion of the pericardium is pinched off during early development. Pericardial cysts usually have thin, smooth walls without internal septa. On MRI, they typically have low or intermediate signal intensity on T1-weighted images and homogeneous high intensity on T2-weighted images. They are not enhanced with the administration of gadolinium chelates (208). Occasionally, a cyst may contain highly proteinaceous fluid, which may have a high signal intensity on T1-weighted images. Pericardial cysts may occur anywhere in the mediastinum, although they usually are found in the right cardiophrenic angle. A pericardial cyst in an unusual location may be indistinguishable from a bronchogenic cyst or thymic cyst.
Hematomas
MRI is particularly useful for the diagnosis of pericardial hematomas, which have a characteristic signal intensity on T1-weighted and T2-weighted MR images: Acute hematomas demonstrate homogeneous high signal intensity (209,210), whereas subacute hematomas that are 1 to 4 weeks old typically show heterogeneous signal intensity, with areas of high signal intensity on both T1-weighted and T2-weighted images (209,211). On T1-weighted and gradient-echo images, chronic organized hematomas may show a dark peripheral rim and low-signal-intensity internal foci that may represent calcification, fibrosis, or hemosiderin deposition (212,213). High-signal-intensity areas on T1-weighted or T2-weighted images often correspond to hemorrhagic fluid (214). Coronary or ventricular pseudoaneurysms or neoplasms may resemble hematomas on MR images. However, the administration of gadolinium chelates allows the differentiation of these entities because hematomas do not become enhanced. In addition, velocity-encoded cine MR imaging may be used to detect internal flow in pseudoaneurysms (215) and thus to differentiate pseudoaneurysms from hematomas.
Neoplasms
Pericardial metastases are much more common than primary pericardial tumors and are discovered at autopsy in 10% to 12% of all patients with malignancy (216,217). Tumors may seed the pericardium via the lymph system or the blood stream or may invade directly from the lung or mediastinum (218). Breast and lung cancers are the most common sources of metastases in the pericardium, followed by lymphomas and melanomas (217). On MRI, an intact pericardial line may be observed if an adjacent tumor extends to the pericardium but not through it. Tumors that have invaded the pericardium may be recognized by focal obliteration of the pericardial line and the presence of pericardial effusion. Hemorrhagic pericardial effusions secondary to metastases usually have high signal intensity on SE images (205). Most neoplasms have low signal intensity on T1-weighted images and high signal intensity on T2-weighted images (219). Metastatic melanoma is an exception; it may have high signal intensity on T1-weighted images because of the paramagnetic metals bound by melanin (220,221). Sites of malignant disease usually become significantly enhanced after the administration of contrast material (222). Primary neoplasms of the pericardium are rare. Benign pericardial tumors include lipoma, teratoma, fibroma, and hemangioma; malignant tumors include mesothelioma, lymphoma, sarcoma, and liposarcoma. Lipoma typically has high signal intensity on T1-weighted SE images. Fibroma characteristically has low signal intensity on T2-weighted images and often shows either no enhancement or heterogeneous enhancement because of poor vascularization (222,223). Primary malignant mesothelioma of the pericardium may manifest as pericardial effusion, occasionally accompanied by pericardial nodules or plaques. Malignant pleural mesothelioma also may invade the pericardium directly. Lymphoma, sarcoma, and liposarcoma typically appear as large heterogeneous masses frequently associated with serosanguineous pericardial effusion. Biopsy and histopathologic analysis are necessary to achieve a definitive diagnosis of most pericardial tumors.
Evaluation of Aortic Disease
MRI has come to play a significant role in the initial evaluation of diseases of the thoracic aorta (224), as well as for detecting postoperative complications from thoracic aortic surgery (225,226). Designing an MR imaging strategy for evaluating the thoracic aorta typically requires a combination of black-blood and bright-blood techniques along with contrast MR angiography (Fig. 54.5) and cine techniques. In addition, the protocol must be targeted for the primary regions of disease involvement, include proper imaging of the disease’s extent and pattern, and provide proper visualization of associated extravascular findings. Beginning at the aortic valve, the thoracic aorta can be divided into three distinct regions in the proximal-to-distal direction, namely, the aortic root, ascending aorta, aortic arch, and descending aorta.
Aortic Root
Sinuses of Valsalva
Discrete aneurysms involving one or more sinuses of Valsalva occur below the sinotubular ridge (227). In a nonacute setting, MRI may be used in the imaging evaluation to demonstrate the aneurysm, the donor sinus, and the recipient chamber of a small fistula. Bright-blood techniques are particularly well suited for these evaluations (227). Cine imaging might be useful in demonstrating a fistula.
Sinotubular Junction
Diseases involving the tubular portion of the ascending aorta typically spare the sinotubular junction with the exception of annuloaortic ectasia (228). Cystic medial necrosis is characterized histologically as myxomatous change
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of cardiac valves, with enlargement of the sinuses of Valsalva and annular dilation of the ascending aorta with a return to normal caliber by the innominate artery origin. Effacement of the sinotubular ridge and dilation of all three sinuses of Valsalva create the spring “onion bulb” appearance.
FIGURE 54.5. Contrast-enhanced MR angiogram in a patient demonstrating severe left subclavian artery stenosis.
Ascending Aorta
The ascending thoracic aorta extends from the sinotubular ridge to immediately proximal to the innominate artery origin. A serious and potentially life-threatening conditions involving the aortic root and ascending aorta is aortic dissection (229,230). The DeBakey and Stanford criteria divide aortic dissections into those that involve the ascending aorta or aortic arch (Stanford type A or DeBakey I and II) and those that are delimited to only the descending thoracic aorta beyond the left subclavian artery origin (Stanford type B or DeBakey III) (230). This distinction is important for deciding between a surgical or medical approach. The first goal is to determine the most proximal site of involvement. Dissection may be fatal if it extends proximally into the aortic root, the aortic valve, and the coronary arteries, potentially resulting in intrapericardial hemorrhage and cardiac tamponade, acute aortic insufficiency, and myocardial ischemia, respectively. In addition, extension of the intimal flap into one or more of the aortic arch vessels may produce cerebral ischemia or infarction. For this reason, Stanford type A dissections typically warrant acute surgical repair. Type B aortic dissections tend to be more stable and can be managed medically. Intramural hematoma results from bleeding from vasa vasorum of the aortic media (231,232). Subacute hemorrhage (methemoglobin) appears as crescentic or lentiform high intramural signal with adjacent normal signal void on non–contrast-enhanced T1-weighted sequences. The goals of MRI in aortic dissections, both acute and chronic, are to identify the intimal flap (by different imaging sequences), its extent, orientation, and involvement with aortic arch branch vessels and coronary arteries, and the location of entry and reentry tears of the intima and to assess for areas of flow and thrombus within the false channel (224,233,234). In addition, potential complications such as pleural effusion, pericardial tamponade, and aortic regurgitation must be assessed. A common hurdle is the distinction between a thrombosed false channel within a chronic dissection and an intraluminal thrombus adherent to the wall of an aneurysm. These are not always possible to differentiate because a chronic intraluminal thrombus may neoepithelialize, giving the appearance of an intimal flap overlying the chronic thrombus (224, 235). Signs that have been reported to be more consistent with a diagnosis of thrombosed false channel associated with dissection are a compressed or eccentric patent channel and extensive thrombus with associated wall thickening over a length greater than 7 cm; these signs are easily appreciated on MRI (235).
MRI is a highly sensitive and specific technique for the detection of aortic dissection that has proven to be superior to conventional angiography, computed tomography (CT), and transthoracic echo studies (233). It also has been compared with transesophageal echocardiography; they have demonstrated a similar high sensitivity (e.g., 98% to 100%), but MRI has a significantly higher specificity (e.g., 98% to 100%) than transesophageal echocardiography (e.g., 68% to 77%) in high-risk populations (233). The advantages of MRI include an ability to evaluate not just the intravascular space and walls of the aorta, but also the extravascular space, which may yield further information, particularly with regard to more serious complications of aortic dissection (224). However, artifacts may erroneously lead to the appearance of an intimal tear or, conversely, obscure it. Artifacts occur due to a number of reasons, such as the normal pulsatility of aortic blood flow, the movement of the aortic valve leaflets, and cardiac motion. The use of current bright-blood techniques, namely SSFP and 3D contrast-enhanced MRA, generally results in an accurate diagnosis. One additional aid in the recognition of an intimal flap is its configuration. Type A dissections typically spiral along the outer greater curvature of the aorta, with the false channel usually rightward in the ascending aorta and posterolateral in the descending aorta. When performing 3D contrast-enhanced MR angiography, the upper abdominal aorta should be included in the field of view. An oblique sagittal acquisition using a large field of view will usually enable reasonable coverage of the upper abdominal aorta, including the renal arteries.
Another common indication for thoracic MRI is the evaluation of a suspected or known aortic aneurysm (236,237,238). The normal aortic diameter on ECG-gated black-blood images has been reported (228) to be as follows: aortic root, 3.3 cm; midascending aorta, 3.0 cm; aortic arch, 2.7 cm; and descending aorta, 2.4 cm. Aneurysms that measure greater than 5 cm, that are expanding rapidly, or that are symptomatic will generally be repaired. Care must be taken to obtain aortic diameter measurements in a plane perpendicular to the aorta. On an axial image, measurement at the level of the horizontal portion of the right pulmonary artery will ensure that the aorta is generally vertical, and that diameter measurements accurately reflect the aorta’s cross-sectional size. In children, the ascending aorta is aneurysmal if the ratio of the ascending-aorta to the descending-aorta diameter is greater than 1.5 (239). Dilation of the ascending thoracic aorta can occur from intrinsic pathology that is acquired, such as atherosclerotic disease, or congenital, such as connective tissue disorders such as
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Marfan syndrome. Dilation of the ascending aorta can also occur owing to aortic valve disease.
Thoracic aortic aneurysms are classified as true aneurysms, meaning that all three mural layers of the aortic wall are involved, or as pseudoaneurysms, in which there has been a break in the intima and possibly media, leaving only the remaining wall to contain the intraaortic blood pool. These forms of aneurysm are characteristically represented by fusiform (i.e., circumferential enlargement of the involved segment) or saccular (i.e., asymmetric or focal outpouching of the involved segment) dilations, respectively. The saccular configuration connotes a less stable condition than the other configuration. These characteristics of a thoracic aortic aneurysm can be easily delineated with MRI for planning of therapy or for clinical monitoring (224). In addition, because of the abilities of MRI to depict the configuration and associated mural changes, it is critical in differentiating the various etiologies of thoracic aortic aneurysms (240). On MRI, the aortic wall is thickened and irregular, secondary to atherosclerotic plaque (241). Mural calcification is common and is manifested by areas of focal signal absence on both SE and cine, although it is better seen on CT. Intraluminal thrombus also is common and may be difficult to distinguish from atherosclerotic plaque, although thrombus usually has a smooth internal border, as opposed to atherosclerosis, which typically is irregular (224). In atherosclerotic aneurysms involving the ascending portion, the sinotubular junction and aortic valve function usually are preserved, which are important characteristics appreciated on MRI. Aortic aneurysms that may occur secondary to aortic valvular disease are also characterized by relative preservation of the aortic root and sinotubular junction on MRI (224). In cases of AS, the aneurysmal dilation usually is limited to the midascending aorta, where the poststenotic flow effects are most prominent (156). In AR, aneurysmal dilation of the thoracic aorta typically involves the ascending aorta but extends into the transverse arch because of the “water hammer” effect and, in long-standing cases, also may involve the descending thoracic aorta; often there is slight effacement of the sinotubular junction and dilation of the aortic root in primary AR because of their relationship (160). Another configuration of thoracic aortic aneurysms that is important to identify on MRI is saccular dilation from a mycotic or pseudoaneurysm. Mycotic aneurysms result from weakening of the aortic wall by infection (240), although pseudoaneurysms typically are caused by trauma (e.g., automobile accidents) and occur most commonly at the level of the ligamentum arteriosum or after surgery at anastomotic or cannulation sites (242).
The entity of noncommunicating dissecting intramural hematoma is being detected with increasing frequency with the development of tomographic imaging, including MRI. Technically, this may be described as dissection of the aortic wall without intimal rupture or tear; the etiology is unknown, but presumably it is related to a weakening of the media. Clinically, the presentation is almost always similar to that of aortic dissection; the diagnosis of an intramural hematoma is entertained once communicating aortic dissection has been excluded. On MRI designed to exclude communicating aortic dissection, an intramural hematoma is identified as a smooth crescentic to circumferential area of thickened aortic wall without evidence of blood flow in the false channel. Depending on the age of the hematoma, the area of thickening may be isointense or hyperintense relative to skeletal muscle on SE MRI; the signal intensity is relatively isointense in the acute phase and then becomes greatest in the subacute stage (232). If intramural bleeding stops, the intramural hematoma resolves with decreasing thickness and returns to SE isointensity in the more chronic stages. Knowledge is limited regarding the natural course of an intramural hematoma. However, complete resolution and evolution to dissection have been demonstrated on MRI (232,243). Involvement of the ascending aorta by intramural hematoma has been shown to predispose the development of communicating aortic dissection in most cases; rebleeding before development of communicating dissection has been detected based on SE intensity changes (232,243).
Aortic Arch
The aortic arch begins at the brachiocephalic, or innominate, artery and extends to the ligamentum arteriosus. The classic configuration of three aortic arch vessels, namely, the innominate artery, the left common carotid artery, and the left subclavian artery, in the proximal-to-distal direction is found in about two thirds to three fourths of individuals. Variant anatomy is common, particularly a common origin of the innominate and left common carotid arteries (so-called “bovine arch”), which has been reported in up to 22% of the population. Other variants to consider are a separate origin of the left vertebral artery from the arch.
Failure of the primitive aortic arches to fuse or regress can result in anomalous arch configurations called vascular rings that can encircle the trachea of esophagus and result in stridor, wheezing, or dysphagia (244,245). The most common vascular rings are a left aortic arch with an aberrant right subclavian artery, a right aortic arch with an aberrant left subclavian artery, and a double aortic arch. Aberrant subclavian arteries may also be associated with a diverticulum of Kommerell and are typically retroesophageal. Vascular rings are usually well demonstrated on black-blood imaging with supplemental cine MR. Three-dimensional contrast-enhanced MR angiography is often not necessary for diagnosing vascular rings but may be helpful for surgical planning.
Entities that involve the ascending aorta may also affect the arch and its branches, either as an extension with type A dissection or a large ascending aortic aneurysm or as its primary location. Atherosclerosis is a systemic process that can commonly result in aneurysms or branch vessel stenosis.
Ligamentum Arteriosum
The ligamentum arteriosum is the remnant of the fetal ductus arteriosus and approximates a boundary between the aortic arch and descending thoracic aorta. One of the most common entities that involve this region is coarctation of the aorta (see the section on congenital diseases). Pseudoaneurysms are typically posttraumatic and affect the lesser curvature of the aorta at the fixed point of attachment to the left pulmonary artery by the ligamentum arteriosum, the vestigial remnant of the ductus arteriosus (246). The risk of delayed rupture remains high even in stable patients with remote trauma. Pseudoaneurysms are typically saccular and can be well evaluated using 3D contrast-enhanced MR angiography.
Descending Aorta
The descending thoracic aorta extends from the ligamentum to the aortic hiatus of the diaphragm. True aortic aneurysms involve all three layers (intima, media, and adventitia) of the aortic wall and are typically atherosclerotic in nature or related to connective tissue disorders. Atherosclerotic aneurysms occur most typically in the descending thoracic aorta and may be fusiform or saccular in morphology (237,238,246). A penetrating aortic ulcer (246,247) is another entity that tends to present in the descending aorta where the bulk of atherosclerosis occurs. The natural history of penetrating atherosclerotic ulcers remains controversial, and its treatment generally parallels that of dissection. Penetrating atherosclerotic ulcers need to be differentiated from focal saccular aneurysm and intramural hematoma. In patients with a suspicion of a penetrating ulcer and aortic dissection, it is generally advisable that precontrast T1-weighted images be performed. Intramural
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hematomas (also called aortic dissection without an intimal flap) are often subtle and may only be evident on precontrast images as hemorrhages within thickened regions of the aortic wall.
Evaluation of Pulmonary Artery Disease
MRI can be used to detect intrinsic pulmonary artery disease and to evaluate the secondary effects of adjacent extravascular disease.
Pulmonary Emboli
Because of the signal void of normally flowing blood, thrombus within a pulmonary artery can usually be readily discerned on systolic SE images; the intensity of thrombus is variable, depending on its age. Recent reports have successfully demonstrated the potential of molecular targeted MRI of pulmonary emboli using low-dose application of a fibrin-specific contrast agent (EP-2104R; Epix Pharmaceuticals, Cambridge, MA) in a swine model (248,249).
Pulmonary Hypertension
The primary use of MRI in evaluation of pulmonary arterial hypertension (PAH) is the description of secondary changes (250). Anatomic findings include RV hypertrophy in proportion to the pulmonary artery pressures, reversal of septal curvature when pulmonary artery pressures approximate systemic pressures, and pulmonary artery dilation. The utility of MRI is clearly evident in the assessment of patients undergoing evaluation for possible lung transplantation or for monitoring after this surgery. Improved RV function and enhanced pulmonary artery flow in transplanted lungs have been shown (251).
Evaluation of Thrombi and Masses
MRI (252,253,254) plays an important role in the evaluation of patients with masses in the central cardiovascular system, not only for the primary diagnosis, but also for planning therapy. It also evaluates the paracardiac regions of the lungs and mediastinum with extreme accuracy. MRI is excellent in terms of soft-tissue contrast resolution, permitting better depiction of the morphologic details of a mass, including its extent, site of origin, and secondary effects on adjacent structures. Dynamic MRI (cine and tagging) also have the ability to provide functional images of the heart that can be used to study the pathophysiologic consequences of cardiac masses; another advantage of MRI is the depiction of cardiovascular structures without the use of contrast material, although use of MRI contrast (e.g., gadolinium-DTPA) for angiographic or ultrafast-tissue perfusion studies is becoming more commonplace. Because tumor hypervascularity due to angiogenesis can be detected, tissue studies have become commonplace in the assessment of masses and thrombi. The use of tissue-perfusion imaging is particularly helpful in distinguishing neoplasms from thrombi and in evaluating the extent of tumor (255,256). However, one disadvantage of MRI is its inability to detect calcification.
Cardiac and Paracardiac Masses
Primary cardiac tumors are rare. The cumulative prevalence is estimated to be between 0.002% and 0.3% in autopsy series (257). Approximately 75% of primary cardiac tumors are benign. The most common benign tumor is the myxoma, which accounts for approximately 30% of all primary tumors and 50% of benign tumors (257,258). Almost all primary malignant tumors of the heart are sarcomas; the most common are angiosarcomas and rhabdomyosarcomas. These tumors are clinically silent at first and produce symptoms only when blood flow becomes obstructed or valvular function is disrupted. Even then, symptoms are frequently nonspecific and may include chest pain and dyspnea (259). Primary malignant pericardial tumors are very rare and are mostly mesotheliomas. Metastatic cardiac and pericardial tumors are much more common, occurring in 1.5% to 0.6% of patients with malignant disease (260). Metastases usually involve the pericardium and myocardium, but rarely involve the valves and the endocardium. In addition, the right side of the heart is more frequently involved than the left side. Metastases may involve the heart via direct extension, hematogenous dissemination, or lymphatic spread. The most frequent primary malignancy that metastasizes to the heart is bronchogenic carcinoma followed by breast carcinoma, malignant melanoma, lymphoma, and leukemia (261).
Cardiac MRI does not unequivocally differentiate benign from malignant tumors; however, there are certain findings that suggest malignancy. Involvement of the right side of the heart, masses in the ventricles that infiltrate the myocardium, and associated hemopericardium support the diagnosis of malignant tumors. Conversely, benign tumors tend to occur on the left side of the heart along the interatrial septum and rarely cause pericardial effusion (262). MRI is capable of differentiating adipose from soft tissue and both from cystic fluid collections. Because myocardial tumors may be infiltrative, there may be difficulty in visualizing them. Contrast-enhanced MRI increases the sensitivity of tumor detection due to appreciation of vascularized areas in the areas of malignancy; generally, tumors become enhanced more intensely than the surrounding myocardium (263). However, the variable enhancement pattern of myocardial tumors complicates differentiating benign from malignant masses.
Cardiac Masses: Intracavitary
Myxomas are the most common benign primary cardiac tumor. Seventy percent of myxomas occur in middle-aged men and women. Myxomas are located within the cavity of the left atrium, attached to the interatrial septum at the border of the fossa ovalis in 85% of the cases. They originate from the posterior and anterior atrial walls, as well as from the atrial appendage (258). Usually myxomata are solitary tumors and are polypoid or pedunculated. Most patients present with one or more of the triad of embolism, obstruction, and constitutional symptoms (264). On MRI, variability in the appearance of myxomas may reflect their variable composition of water-rich myxomatous tissue versus fibrous tissue and calcification. Myxomata tend to have higher signal intensity than myocardium on T2-weighted imaging (T2WI) (265). Cine-MRI may show the characteristic mobility of the pedunculated tumor (223).
Lipomas are the second-most-common benign tumor of the heart, accounting for 10% of all cardiac tumors (223,266). There is no sex or age predisposition. About 50% arise subendocardially, 25% subepicardially, and 25% from the wall of a cardiac chamber to extend intracavitary (223). On MRI, lipomatous tissue has a uniquely short T1, and the signal intensity is similar that of subcutaneous fat, having a relatively high signal intensity on spin-echo T1-weighted imaging and a moderate signal intensity on T2-weighted imaging. A decrease in signal intensity using a fat presaturation technique verifies the diagnosis (223).
Overall, thrombi are the most common of intracardiac masses and typically occur along the posterolateral wall of the left atrial cavity or within the left atrial appendage (Fig. 54.6). Usually, a predisposing condition such as atrial fibrillation is present to promote the formation of the thrombus at these locations. Thrombus is also frequently observed in the apex of the impaired left ventricle due to slow blood flow in the region. On MRI, fresh thrombus often has higher signal intensity than
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myocardium on T1-weighted images. However, depending on the age of the thrombus, alterations in signal intensity are possible. After 1 or 2 weeks, paramagnetic compounds of the organizing thrombus such as deoxyhemoglobin and methemoglobin cause T1 and T2 shortening that may result in increased signal intensity on T1-weighted and decreased intensity on T2-weighted images (223,267).
FIGURE 54.6. Gradient-echo image demonstrating the presence of a thrombus in the right atrium. AoV, aortic valve; RV, right ventricle.
Intramyocardial Cardiac Masses: Malignant
Angiosarcomas, rhabdomyosarcomas, and fibrosarcomas are the most frequent primary malignant tumors of the heart. Angiosarcomas are the most common primary malignant tumor of myocardium in adults, accounting for approximately 33% of primary malignant cardiac tumors. They are typically found in patients between the ages of 20 and 50 years (259,268). Patients usually present with right-sided right failure and tamponade because this tumor exhibits a striking predilection for the right side of the heart, especially the right atrium. They also have a propensity to involve the pericardium, resulting in bloody pericardial effusion (268). Metastases occur in 66% to 89% of the cases, with the lungs being the most frequent site of spread (269).MRI of cardiac angiosarcoma most often reveals a mass arising from the right atrium accompanied by significant hemopericardium. MRI demonstrates a nonhomogeneous mass with hyperintense areas on T1-weighted images corresponding to hemorrhage (254,270). After the administration of gadolinium-DTPA, T1-weighted images typically show nonhomogeneous enhancement, especially in the periphery of the lesion (254). Rhabdomyosarcomas are malignant tumor of striate muscle. Rhabdomyosarcomas are the most common malignant tumors of infants and children, although they account for only 4% to 7% of all cardiac sarcomas. Frequently rhabdomyosarcomas extend beyond myocardium, causing a polypoid extension into a chamber cavity, simulating a myxoma (271). Although some reports suggest a predisposition for right-sided cavities (272), rhabdomyosarcomas have no strong predilection for a specific chamber, and multiple locations are frequently found (60%). A rhabdomyosarcoma is more likely than other sarcomas to involve or arise from cardiac valves (270). Pericardial involvement is also frequent (273). MRI signal intensity is intermediate on precontrast T1-weighted images, similar to that of adjacent myocardial tissue, but shows enhancement of the lesion after administration of contrast (273). Fibrosarcoma is another malignancy that diffusely infiltrates the myocardium. It often involves the left atrium and usually manifests as congestive heart failure due to blood flow obstruction. On MRI, a fibrosarcoma may be heterogeneous or isointense relative to myocardium on T1-weighted images (270), although the malignant nature can be depicted with T2-weighted images or contrast-based imaging.
Intramyocardial Cardiac Masses: Benign
Rhabdomyomas are the most common cardiac tumors of infants and children, with the majority occurring in newborns (274); they are associated with tuberous sclerosis in 50% of the cases. These benign tumors nearly always involve the myocardium or the ventricles, affecting both ventricles with equal frequency. At least half of the lesions are large enough to cause obstruction of a valve or cardiac chamber. There are multiple sites involved in 90% of cases; the atria are involved in 30% of cases of rhabdomyomas (274). On MRI, a rhabdomyoma may be slightly hypointense to slightly hyperintense to the myocardium on T1-weighted images and slightly hyperintense on T2-weighted images (219,223). Fibromas are a benign tumor primarily affecting children and are usually discovered before the age of 10 years. Almost all involve the myocardium, with a predilection for the anterior free wall and interventricular septum (223). These tumors usually cause blood flow obstruction, ventricular dysfunction, or conduction abnormalities (275). On MRI, fibromas are hypointense to slightly hyperintense on T1-weighted images when compared to skeletal muscle, but they have lower signal intensity than myocardium on T2-weighted images. This is because of their fibrous nature or due to deposits of calcium related to necrosis (252).
Paracardiac Masses
Many different sources of paracardiac masses, frequently unrelated to the heart (e.g., hiatal hernia) can be easily identified by MRI. The identification of such mass lesions potentially influencing the central cardiovascular structures is important. The relationship to the pericardium is a key issue. Metastases are by far the leading cause of pericardial masses. From 5% to 15% of patients with malignant neoplasm have pericardial metastases. Bronchogenic carcinoma, breast cancer, leukemia, and lymphoma account for 80% of pericardial metastases (276). Metastases may result in nodular deposits or local or diffuse pericardial thickening. Metastatic involvement may lead to hemorrhagic or serosanguineous pericardial effusions.
Evaluation of Congenital Heart Disease
MRI is a powerful modality for assessing the morphology and physiology of simple and complex congenital cardiac conditions (both before and after corrective/palliative interventions). With a growing adult congenital heart disease population, the requirements are likely to grow in the near future. Because of the wide range of anatomic and functional problems, a successful MRI study of a congenitally malformed heart requires a cardiovascular radiologist or cardiologist who has knowledge of the range of available MR pulse sequences (including standard spin-echo and gradient-echo sequences, cine sequences, and phase-contrast techniques) and also good expertise with regard to congenital heart disease. His or her presence near the scanner during the study is often necessary because imaging protocols often have to be tailored to the individual patient and adjustments are frequently made during the imaging session. The physician in charge of MRI needs to be in close
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contact with the referring physician and has to be informed about prior surgical or percutaneous intervention, and previous imaging studies should be available. The evaluation of various congenital diseases is discussed later.
Sequential analysis is the generally approved strategy for morphologic description of a congenital cardiac malformation. The first step in this approach is the determination of atriovisceral situs by reviewing the localization of inferior vena cava, abdominal aorta, liver, spleen and stomach, and the morphology of the atrial appendages and mainstem bronchi. This is followed by determining ventricular morphology, using the muscular outflow tract and the moderator band as landmarks of the anatomic RV. The aortic arch and the pulmonary bifurcation identify the great vessels. Then atrioventricular and ventriculoarterial connections are assessed to be either concordant or discordant. A concordant atrioventricular connection means that the anatomic right atrium is connected to an anatomic left ventricle. A discordant ventriculoarterial connection means that the anatomic right ventricle is connected to the ascending aorta (as in classic D-transposition of the great arteries [TGA]). Combined atrioventricular and ventriculoarterial discordance is the hallmark L-transposition. Finally, associated lesions such as septal defects or aortic arch coarctation are evaluated.
Aortic Anomalies
Bicuspid Aortic Valve
Congenital bicuspid aortic valve occurs in between 0.9% and 2% of all individuals in autopsy series. Although valve area may be reduced at birth, it is usually not responsible for severe stenosis until later in adulthood. About one third of patients with bicuspid aortic valves develop aortic regurgitation on the basis of organic structural abnormality or after a bout of acute bacterial endocarditis. MRI will demonstrate decreased aortic annular caliber, thickened valve leaflets, maldistribution of the three aortic sinuses of Valsalva by the unseparated valvular commissures, and aortic valve leaflet doming. In cases with mixed valvular stenosis and regurgitation, both the ascending aorta and left ventricle are dilated.
Coarctation of the Aorta
Coarctation of the presents with hypoplasia of the distal aortic arch and focal narrowing of the proximal descending aorta, most commonly at the junction of the ductus arteriosus and aorta. MRI demonstrates the location and length of the coarctation segment, the status of the aortic isthmus, and the degree of arterial collateralization present. It may be useful in delineating dilated intercostal arteries traveling along the underside of the posterior upper ribs or dilated internal mammary arteries running along the inner aspect of the anterior chest wall. MRI is useful for following the results of balloon dilation and surgical repair of coarctation (277). Serial examination allows close follow-up and assessment of residual stenosis and early demonstration of aneurysmal dilation.
Marfan Syndrome
MRI is very suitable for imaging the aorta in Marfan syndrome (228,278,279,280,281,282,283). The characteristically pear-shaped dilatation of the aortic root is well demonstrated with MRI, and its diameter can be accurately measured using only conventional SE techniques. The aortic root diameter is an important criterion in surgical decision-making. Associated dissection can be detected and aortic valve incompetence quantified with MRI. Furthermore, MR studies have looked at the compliance of the aortic wall, either by using conventional pulse sequences (284) or by measuring the velocity of the flow wave along the descending aorta (285). This can be used to monitor the effect of β-blocker medication that may slow down the loss of elasticity in Marfan patients (286). Very recently, MRI was reported to demonstrate dural ectasia, one of the rare diagnostic criteria, which occurs in 92% of Marfan patients, and therefore this is potentially very important.
Pulmonary Artery Anomalies
The preoperative evaluation of pulmonary atresia has been difficult with noninvasive imaging techniques predominantly because the patients of concern are mostly infants. MRI was successful and reported to be superior to echocardiography in demonstration of pulmonary artery branch anomalies (280,287,288,289,290,291). However, MRI is not easily performed in very young children, who often require sedation or anesthesia. Pulmonary artery stenosis can occur at the infundibular, valvular, or supravalvular level or in the peripheral branches, for instance, after previous systemic-to-pulmonary artery shunt. Obstructive hypertrophy of the RV infundibulum is adequately visualized with MRI. The pulmonary valve itself is difficult to demonstrate, although cusp movements are clearly shown on conventional cine sequences. A stenotic pulmonary valve, however, can be recognized by its doming configuration and by poststenotic dilation of the central pulmonary artery, a phenomenon not seen with infundibular obstruction.
Intracardiac Shunts
In addition to demonstrating the intracardiac defect, MRI also defines specific chamber dilation and hypertrophy, which is useful for characterization of the severity of the shunt and acquired complications. Shunt fraction calculation is generally performed using volume-flow analysis of great artery flow with velocity mapping. With this approach, quantitation of shunt size can be accomplished by measuring net blood flow volumes within the main pulmonary artery and ascending aorta over a cardiac cycle. Shunts produce discrepant pulmonary and systemic arterial flows, with the former exceeding the latter in left-to-right shunts, and conversely in right-to-left shunts (292). This difference can be expressed either in absolute terms (e.g., shunt volume) or in relative terms (e.g., pulmonary-to-systemic blood flow ratio, Qp/Qs). Values for shunting derived by volume-flow analysis have correlated well with the results from cardiac catheterization or nuclear first-pass ventriculography (292).
Atrial Septal Defects
Using a combination of various sequences (cine, spin-echo, gradient-echo, and phase-contrast), MRI can be used to classify atrial septal defects (ASDs). Secundum defect, the most common form of ASD, is usually large and centrally located in the septum. Primum ASDs are medially and inferiorly located, immediately superior to the atrioventricular (AV) valves. Sinus venosus defects are actually defects between the posterior inferior border of the inferior vena cava and the left atrium. These defects are almost always associated with anomalous drainage of the right upper-lobe pulmonary vein to the superior vena cava. Right ventricular myocardium in simple ASD is not hypertrophied. With imaging in the axial plane, MRI has an overall 97% sensitivity and 90% specificity for the detection of ASDs (293). MRI is excellent in detecting concomitant anomalous pulmonary venous return. It might be to the right atrium or coronary sinus, to the inferior vena cava or portal vein systemic veins, or to the innominate vein or superior vena cava. In a series of 56 patients with various types of congenital heart disease but normal pulmonary venous connection, axial spin-echo MRI showed the sites of connection of all four pulmonary veins in 88% of cases; in a parallel series of 22 patients with partial or total anomalous pulmonary venous return, pulmonary venous anomalies were identified in 95% of cases (294).
Ventricular Septal Defect
MRI can be used to diagnose the presence and characterize the size of ventricular septal defects (VSDs) (295,296). Large subaortic VSDs are readily demonstrated on axial MR spin-echo or double-inversion recovery images as a break in the interventricular septum to the left of
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the AV rings and to the right of the crest of the muscular interventricular septum. Visual separation of the actual defect from the inferior extension of an aortic sinus of Valsalva can be improved by obtaining images in oblique sagittal section. Membranous VSDs are identified by the absence of signal (or a break in the interventricular septum) in the posterior superiormost aspect of the interventricular septum, immediately below the aortic valve, and adjacent to the septal leaflet of the tricuspid valve. Cine MRI identifies left-to-right, right-to-left, and bidirectional shunts. AV septal defects (endocardial cushion defects) involve the AV septum and primum portion of the interatrial septum and may involve the anterior mitral and septal tricuspid leaflets and the membranous interventricular septum. MRI may be used to determine the size of the ventricular component of the defect as well as the presence of ventricular hypoplasia.
Evaluation of Complex Congenital Malformations
Tetralogy of Fallot
Tetralogy of Fallot is the most common cyanotic form of congenital heart disease, and surgical correction in early infancy has significantly improved survival. After repair, however, patients have residual defects or sequelae, and a comprehensive analysis of the postoperative status can be made with MRI (Fig. 54.7) (297). Residual or recurrent pulmonary stenosis, at either the infundibular or valvular level, frequently occurs. When clinically significant stenosis is relieved by placement of a transannular outflow patch, pulmonary regurgitation occurs. The RV is subsequently subjected to volume overload of varying severity, and the importance of detecting and measuring pulmonary regurgitation is increasingly being recognized. MRI, including phase-contrast techniques, has been shown useful and accurate for this purpose (165). Occasionally, residual ventricular septal defect requires quantitative analysis that is easily performed with MRI. The morphology of the central pulmonary arteries is crucial. After Fallot repair, for instance, after previous Blalock-Taussig anastomosis, patients often suffer from pulmonary artery branch stenosis, which is well visualized by SE MRI (289,298) or Gd-enhanced MRA. Finally, LV and RV systolic and diastolic function can be measured from a stack of cine images. Both LV and RV functional deteriorations were shown to be associated with pulmonary regurgitation (165,299,300).
FIGURE 54.7. A case of complex congenital heart disease. Patient has situs inversus, dextrocardia, is status-post tetralogy of Fallot repair, and presents with symptoms of right-sided heart failure. A: Axial gradient echo images showing dextrocardia and right ventricular dilation. B: Sagittal gradient-echo images showing free pulmonary regurgitation (arrow) at the site of previous infundibular resection.
Functional Single Ventricle: Tricuspid Atresia and Double Inlet Left Ventricle
Patients with tricuspid atresia or double inlet LV have functionally a single ventricle. Several surgical options have been developed to redirect the systemic venous blood to the pulmonary arteries. Some of these surgical procedures have already been abandoned, and others are still being modified. The Fontan procedure and all its variants have had a major impact on the treatment of single ventricle, but long-term outcome remains uncertain. The classic Fontan operation consisted of a conduit from the right atrium to the central pulmonary arteries. In particular, a valved conduit was prone to become stenotic. Sometimes the conduit only connected to the left pulmonary artery in combination with a Glenn procedure, a separate anastomosis of the superior vena cava to the right pulmonary artery. Occasionally, a conduit from the right atrium to a hypoplastic RV outflow tract was used, a mostly abandoned modification aiming at the development of a physiologic arterial type of pulmonary blood flow. Nowadays, the right atrium is mostly excluded by performing a bidirectional Glenn procedure (also named a hemi-Fontan), with secondary completion of the Fontan procedure (a complete cavopulmonary anastomosis) by establishing also a connection (sometimes a fenestrated baffle) between the inferior vena cava and the pulmonary arteries. MRI flow studies demonstrated that the success of RV incorporation could not be reliably determined on the basis of flow velocity measurements alone, but that volumetric flow also had to be taken into account. Furthermore, the ratio of left-to-right pulmonary artery flow was found to
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be reversed after Fontan surgery (301). The hypothesis of constant total heart volume and center of mass, promoting efficient use of cardiac energy, was tested in a cohort of patients during staged Fontan surgery. It was shown that total heart volume and mass center did not remain constant during the sequence of operations (302,303). Pulmonary artery size and confluence of the central pulmonary artery branches are crucial determinants of outcome after Fontan surgery, and MRI was shown to be superior to echocardiography in evaluating these parameters (304). Ventriculoventricular interaction has been studied with an MR myocardial tagging technique. This particular study showed differences in strain and motion of the RV in the systemic position after Fontan surgery when compared to a systemic RV that has an LV to support it, as in patients after Mustard or Senning repair for TGA (305). It was also demonstrated with MRI that a hemi-Fontan operation posed no significant changes in ventricular geometry or performance; however, a significant decrease of ventricular volume, mass, and performance was found 1 to 2 years after completion of the Fontan procedure (306). The relative cardiac and respiratory contribution to pulmonary blood flow after total cavopulmonary anastomosis has been studied using an MR blood-tagging technique (307). Fairly recently, also using an MR blood-labeling technique, it was elegantly demonstrated that after total cavopulmonary anastomosis, inferior vena cava blood is directed more toward the left pulmonary artery and superior vena cava blood more toward the right pulmonary artery (308). Others have used multidimensional quadratic principal component analysis (Q-PCA) to study pulmonary blood flow patterns after total cavopulmonary anastomosis and classic atriopulmonary Fontan connection. In the former category, pulmonary flow is more organized and uniform, suggesting that it is more hemodynamically efficient (309). A similar study showed reduced total pulmonary blood flow after both types of Fontan surgery compared to normal, attributable to the smaller size of the pulmonary arteries. In addition, swirling pulmonary artery flow patterns indicated increased shear stress in both categories (310).
Transposition of the Great Arteries: Postoperative Evaluation
Patients with D-type TGA (discordant atrioventricular connection) have to be separated into those who were treated with the older and nowadays mostly abandoned techniques that redirect blood at the atrial level (Mustard or Senning operation) and those who were treated with the arterial switch (Jatene) operation. The latter patients are generally younger, with the majority now reaching adulthood. The two categories have significantly different postoperative residua and sequelae. The Mustard or Senning procedures leave the anatomic RV in the systemic position, and we now know that this is at the base of a range of problems, with late sudden RV failure and death at the end of the spectrum. Other often-encountered hemodynamic problems are arrhythmias, (baffle) obstruction to pulmonary or systemic venous return, pulmonary hypertension, and tricuspid regurgitation. The post-Mustard anatomy has been successfully demonstrated with MRI (311,312,313). MRI has also been used for follow-up after stent placement for baffle obstruction (314). The function of the anatomic RV in the systemic circulation appears to be of particular interest. Late cardiac failure is a serious matter of concern in these patients, and diastolic dysfunction may be an early sign. After Mustard or Senning repair, cine MRI techniques were used to quantify RV hypertrophy, but RV volumes and ejection fraction were normal (315). Phase-contrast techniques have been used to study diastolic characteristics by measuring tricuspid flow in Mustard or Senning patients and demonstrating differences from normal volunteers (316). After the arterial switch procedure, common complications are RV outflow tract obstruction and pulmonary artery stenosis, either at the supravalvular or branch level. The postoperative status of the great vessels has been adequately assessed with SE MRI (298,317,318). The morphology of congenitally corrected TGA (CCTGA, combined atrioventricular and ventriculoarterial discordance) has been studied with conventional MRI techniques (319,320). This is a small category of patients, often detected at a later age. Furthermore, some patients with CCTGA suffer from arrhythmias or carry a pacemaker, making them unsuitable for MRI.
Controversies and Personal Perspectives
MRI is a rapidly emerging and complex noninvasive test of choice for patients with a multitude of cardiovascular problems. Its emerging role as one of the dominant imaging modalities in most facets of clinical cardiology cannot be understated. It has entered an important phase in its evolution, with an anticipated exponential growth in its current clinical applications and through the development of newer targeted molecular imaging and interventional applications. Furthermore, the availability of magnets with higher field strengths (e.g., 3 T and higher), improvements in coil design, and newer pulse sequences will be extremely important in enabling the success of this technology. For this potential to be realized, however, several types of obstacles must be overcome.
One of the biggest obstacles is the current medical environment with its increasing emphasis on cost containment and capitated reimbursement. Other obstacles include increasing demands on physicians involved in cardiac MRI to pursue clinical productivity in more basic diagnostic imaging areas, where reimbursement may be better established, and greater limitations on research time and institutional support for needed clinical investigation in cardiac MRI. Finally, for this technology to evolve further and flourish, a solid collaboration between cardiology and radiology, like the one that exists in our respective institutions, is the primary prerequisite.
The Future
Atherosclerosis Imaging
Atherosclerosis, a leading cause of morbidity and mortality in the Western world, is responsible for an estimated $112 billion in socioeconomic burden in the United States alone. It consists of a gradual process that begins as early as the second or third decade in the vessel wall as outward arterial thickening (positive arterial remodelling with a normal vessel lumen); significant obstruction to the arterial blood flow does not occur until the later stages of disease (321). Indeed, acute clinical events from atherosclerotic lesions have been shown to occur more often in mild to moderate than in severe stenoses (322,323). Therefore, focus is now beginning to shift toward the diagnosis and management of subclinical atherosclerosis and prevention of progression to overt disease (324). Because atherosclerosis progresses over decades, studies with clinical endpoints require long-term follow-up, participation of large populations, or both (325,326) to draw valid conclusions (327). Thus, to overcome these challenges, surrogate markers like imaging have gained immense attention (328) in the detection and longitudinal follow-up of the atherosclerotic plaque. If the following criteria (329) are met by an imaging modality, its use as a surrogate for clinical endpoints might be justified: (a) it is very sensitive and readily available, (b) it is easy to evaluate and noninvasive, (c) a causal relationship between the imaging modality and the clinical endpoint is well established, and (d) patients with and without vascular disease exhibit clear differences
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in surrogate marker measurements. The characterization of the different stages of atherosclerosis (from early positive arterial remodelling to overt atherosclerosis) can be made in vivo in humans using various invasive and noninvasive techniques [carotid ultrasound (330), electron beam or multislice computed tomography (331,332), intravascular ultrasound (333)].
MRI, because of its high resolution, 3D capabilities, truly noninvasive nature, and capacity for soft tissue characterization, has emerged as a powerful modality for assessing subclinical and overt atherosclerotic changes in different vascular beds (334,335). With regard to atherosclerosis, the surrogate criteria just described (329) appear to be fulfilled by MRI in a truly noninvasive fashion. However, there are many technical considerations, and the following factors need to be taken into consideration to accurately visualize the atherosclerotic plaque by MRI.
Technical Considerations of Magnetic Resonance–Based Atherosclerosis Imaging
A normal artery wall is extremely thin (around 1 mm for the coronaries and thicker for the aorta and carotids), but with progressive arterial remodeling, this thickness can vary from a few millimeters to greater than 1 cm. Using sophisticated receiver coils and improvements in hardware, it is now possible to achieve submillimeter in-plane spatial resolution on the order of 0.25 × 0.25 mm2 in the carotids, 0.8 × 0.8 mm2 in the aorta, and 0.46 × 0.46 mm2 in the coronaries, with a 2- to 5-mm slice thickness (336,337,338), using a 1.5-T magnet. The use of phased-array surface coil techniques has proven to be very effective in improving the signal to-noise-ratio (SNR) (339,340). The widespread availability of 3-T magnets will likely help to improve the SNR, which can be partially traded for an improved spatial resolution.
The next technical issue to consider is the presence of artefacts, including cardiac contraction, breathing, blood flow, and random motion as with swallowing or tremors, all of which can significantly degrade image quality. To counter that, cardiac gating is used to improve the quality of the scan. For aortic and coronary imaging, along with cardiac gating, breathing is also an issue, which is countered by breath-holding or use of respiratory navigators (337,338,341). In addition, perivascular fat, which can obscure signal from the vessel wall and lead to chemical-shift artifacts, can be suppressed using advanced fat-saturation techniques (123). Two other major steps in imaging atherosclerosis by MR include the quantitative analysis and the characterization of the atherosclerotic plaque: Accurate quantification of vessel wall dimensions depends on the ability to discern the inner and outer boundaries of the vessel wall. Use of techniques to suppress the blood-flow signal [e.g., double inversion recovery (342) combined with fast spin-echo) enhances the conspicuity of the vessel wall and its components against the backdrop of a hypointense lumen (336,337,338,343). Several semiautomatic image processing tools have been proposed for vessel boundary detection (344,345). In general, dimension measurement is preferred in continuous rather than categorical form to enable inferences about longitudinal regression/progression of plaque because atherosclerosis is generally not a uniform process, and accurate and reproducible determination of vessel wall dimensions is extremely important for valid conclusions to be drawn longitudinally. Arterial wall dimension assessment using MRI has been found to be highly reproducible in the carotid arteries (346,347), aorta (348), and the coronaries (349).
Another consideration is the ability to discern different plaque components including fibrous cap, lipid core, hemorrhage, and calcification. Based on histologic studies, it is known that different plaque components coexist, and these different components produce differences in the MR signal based on their physical properties (350). Thus, to achieve tissue contrast and hence plaque characterization, images obtained using different weightings are necessary (337,351). Different plaque components have been characterized by different (T1, T2, and proton density [PD]) weightings in animals (352,353), ex vivo specimens (354,355), in vivo carotids (354,356), in vivo aortas (337), and, more recently, the coronaries (338,340). The characteristic appearance of different plaque components by MRI has been previously validated (336,350,354). Generally, lipid components appear as isointense regions within the plaque on T1- and PD-weighted images but as hypointense on T2-weighted images. On the other hand, the fibrous cap appears bright, whereas calcium appears very hypointense on all three weightings. Thrombus appears hyperintense (albeit less than fibrous cap) on all three weightings. Perivascular fat, which predominantly has triglycerides, has a different MR appearance than lipid core, which generally consists of unesterified cholesterol and cholesterol esters (350,355). Recent studies have demonstrated that the use of paramagnetic contrast agents such as gadolinium would enable subtle distinctions among different plaque components. Increases in T1 relaxation by gadolinium leads to increased contrast enhancement on T1-weighted pulse sequences. There is evidence of neovascularization and inflammation in atherosclerotic plaque (357), and it has been proposed that contrast-enhanced MRI can further aid in plaque characterization by helping to detect these changes (358,359). In these studies, it was demonstrated that pre- and postcontrast MRI helped differentiate between the necrotic core and fibrous tissue. In another study, it was also demonstrated that postcontrast signal enhancement in carotid arteries and aorta was associated with elevated serum levels of interleukin-6, C-reactive protein, and cell adhesion molecules (360). Another interesting development in this field is the use of contrast agents to enhance plaque components, which generally involve gadolinium-based agents (358,359). The latter agents have proven usefulness in the assessment of plaque size and composition. Newer data, with the use of novel contrast agents like ultrasmall paramagnetic particles of iron oxide (USPIOs) or fibrin-specific agents, are emerging in this field at a rapid pace (361,362,363). USPIOs alter the relaxation times of adjacent tissue and are avidly taken up by macrophages. It has been demonstrated that that injection of USPIO into hyperlipidemic rabbits was associated with appearance of signal voids on the luminal surface of the aorta (364). Another active area of research is that of detection of thrombus or fibrin, which has been demonstrated to play a role in the progression of atherosclerotic plaque (365). Contrast agents that can detect and characterize thrombi have been developed, and fibrin has been identified by lipid-encapsulated perfluorocarbon paramagnetic nanoparticles in vitro (362,366) as well as in vivo (362).
Magnetic Resonance Imaging of Carotid Atherosclerosis
The carotid artery has become the most common target vessel for MR imaging of atherosclerosis. Reasons for this include the use of phased-array coils, well-validated multicontrast imaging protocols (336,354), and the existence of a reference based on histologic examination of atherosclerotic lesions obtained surgically during carotid endarterectomy (367). MRI has been used to demonstrate the state of carotid plaque substructure, including the fibrous cap (Fig. 54.8). In one study, the in vivo state of the fibrous cap was characterized based on its appearance on MR images (intact and thin, intact and thick or ruptured), and there was a high level of agreement between MR images and the histologic state of the fibrous cap (356). When multicontrast MR imaging was compared to histology, a sensitivity of 81% and a specificity of 90% were demonstrated for
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identification of an unstable fibrous cap (368). A ruptured fibrous cap identified on MR imaging was highly associated with a stroke or transient ischemic attack (369). MRI also has a high sensitivity and specificity in detecting lipid core, hemorrhage, and calcification in ex vivo imaging (90% to 100%) (370) and in vivo study (85% to 92%) (351) of endarterectomy specimens. Studies have demonstrated the ability of MRI to detect longitudinal changes in plaque size after aggressive therapeutic intervention using statins. A recent study compared the effects of aggressive and conventional lipid lowering by two different doses of simvastatin on early human atherosclerotic lesions using serial carotid and aortic (see subsequent discussion) MRI (371). Post hoc analysis showed that patients reaching a mean on-treatment low-density-lipoprotein cholesterol of 100 mg/dL or less had larger decreases in plaque size. In another study of 21 asymptomatic hypercholesterolemic patients, use of simvastatin resulted in 8% reduction in carotid wall thickness (372). In a recent study, we demonstrated the ability of MRI to show associations between cholesterol subfractions and atherosclerotic plaque components of carotid artery (347).
FIGURE 54.8. Carotid MRI in an atherosclerotic patient. Left: Precontrast T1-weighted image showing atherosclerotic plaque (AP) with lipid core (LC). L, lumen. Middle: Precontrast T2-weighted image showing atherosclerotic plaque with lipid core and lumen. Right: Postcontrast T1-weighted image showing atherosclerotic plaque with lipid core.
Magnetic Resonance Imaging of Aortic Atherosclerosis
Aortic atherosclerosis can be accurately detected using surface MRI when compared to histopathology (373) and transesophageal echocardiography (TEE) as a reference (337). It has been demonstrated that MR assessment of the aorta correlated well with TEE for the assessment of plaque thickness, extent, and composition. This technique has been found to be highly reproducible (343). In participants in the Framingham Heart Study, aortic plaque burden increases with age (374). MRI of the aorta demonstrated plaque regression by 8% after 1 year of lipid-lowering therapy using simvastatin without a change in the cross-sectional area of the arterial lumen (372,375). In another study of aortic atherosclerosis, the effects of 20-mg versus 5-mg atorvastatin was investigated on thoracic and abdominal aortic plaques in 40 hypercholesterolemic patients (376). The 20-mg dose reduced vessel wall thickness and area of thoracic aortic plaques (-12% and -18%, respectively; p < .001), whereas the 5-mg dose did not (+1% and +4%, respectively). In abdominal aortic plaques, even 20 mg could not reduce the vessel wall thickness or area (-1% and +3%, respectively), but instead progression was observed with the 5-mg treatment (+5% and +12%, respectively; p < .01). Another technique, transesophageal MRI (TEMRI), using a loopless antenna coil, has been developed for improved aortic MRI. The feasibility and utility of this technique were demonstrated in patients with aortic atherosclerosis (377). It was recently demonstrated that the addition of the TEMRI coil increased the signal by 157% to 225% in the aortic arch and descending aorta, respectively, above that attained by surface coils alone (348). Furthermore, using the combined surface MRI and TEMRI, it was recently demonstrated that aortic plaque regression of about 12% can be detected as early as 6 months (as compared to 1 year or longer) after lipid-lowering therapy (378).
Magnetic Resonance Imaging of Coronary Atherosclerosis
To successfully image coronary artery vessel wall and the atherosclerotic changes associated with it, a high contrast between the coronary lumen blood pool and the surrounding coronary vessel wall is mandatory. The first successful implementations of coronary vessel wall imaging in humans included the use of a dual-inversion fast spin-echo sequence. Using this method, single slices of the coronary artery vessel wall could be acquired during a prolonged breath-hold period, and relative thickening of the coronary arterial vessel wall could successfully be demonstrated in selected cases (338). Subsequently, and to remove the limitations associated with breath-holding, this technique was extended with the use of navigators for free-breathing data acquisition (379). More recently, the free-breathing navigator approach was combined with 3D spiral imaging in conjunction with a “local inversion” technique (380). This enables a larger anatomic coverage with reconstructed slices that are much thinner than those of the earlier 2D approaches. Therefore, it is now possible to visualize long, contiguous sections of the coronary artery vessel wall in a highly reproducible manner (381). This local-inversion 3D spiral technique was used to demonstrate positive arterial remodeling of the coronary vessel wall was (341). This novel approach has the potential of quantifying subclinical disease as well as following changes in the coronary vessel wall longitudinally.
Future developments will include the use of higher magnetic field strengths, contrast agents for plaque characterizations (358,359), and longitudinal studies of vessel wall thickness after interventions (382). Other potential applications include individually tailored therapy in patients based on their plaque characteristics and plaque burden, use as a screening tool to stratify patients based on their cardiovascular risk, and in vivo molecular imaging of the atherosclerotic plaque.
Molecular Imaging Using Magnetic Resonance Imaging
Technological advances in genomics, proteomics, and molecular biology are creating an unprecedented opportunity to change the current reactive medical paradigm of “see and treat” to an early “detect and prevent” strategy. Among these personal-medicine technologies, MRI is proving to be particularly advantageous, given its abilities to simultaneously elicit both anatomic and physiologic information with high spatial resolution as well as extract quantitative data from targeted contrast agents. Molecular imaging contrast agents take many
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forms, including the successful emergence of nanoparticulate systems. These contrast agents passively accumulate in clearance organ/cells or preferentially target biochemical signatures of disease via homing ligands. Nanoparticulate agents can be used to track cellular migration and tissue integration after local implantation or systemic injection. Contrast agents concentrate within a site by either passive or active targeting mechanisms. Passive targeting agents primarily highlight phagocytic cells and organs naturally responsible for particle clearance within the body, and are removed from the circulation in a size-dependent hierarchy by the lung (largest), spleen, liver, and bone marrow (smallest). Active targeting refers to ligand-directed, site-specific accumulation of contrast and/or therapeutic agents. A wide variety of ligands, including antibodies, peptides, polysaccharides, aptamers, and drugs, may be utilized to specifically home agents to cellular biomarkers. These ligands may be attached covalently (i.e., chemical conjugation) or noncovalently (e.g., avidin-biotin interactions) to the contrast agent.
Superparamagnetic Nanoparticles
In general terms, iron oxide particles are categorized based on their nominal diameter into superparamagnetic iron oxides (SPIOs; 50 to 500 nm) and ultrasmall SPIOs (USPIOs; <50 nm), which dictates their physicochemical and pharmacokinetic properties. SPIOs have been investigated with MRI for detection of atherosclerosis in ApoE-/- mice (383), and findings have been corroborated with histology. In these studies, SPIO particles were phagocytosed by macrophages and superficially restricted to the subendothelium of atherosclerotic plaques. Newly recruited macrophages represented most of the iron-laden cells, which explains the preferential targeting of superficial aspects of atherosclerotic lesions. The creation of USPIOs with a mean diameter of 10 to 50 μm (384) has resulted in increased intravascular half-life because these particles are not immediately recognized by the mononuclear phagocytic system in the liver and spleen. Although the concentration of USPIOs in macrophages has been confirmed histologically in atherosclerotic plaque, the particles are small enough to migrate through interendothelial junctions and capillary pores or fissures (385,386) and then potentially accumulate in the vascular wall. USPIOs are phagocytosed by macrophages in atherosclerotic plaque of Watanabe heritable hyperlipidemic (WHHL) rabbits (as confirmed by histology) in quantities sufficient to be detected by MRI (364), and accumulation of USPIOs in rat macrophages has been associated with cardiac allograft rejection (387). Recently, USPIOs have been used in humans to detect atherosclerotic plaques in vivo (361). Atherosclerotic lesions with high macrophage content in carotid arteries caused significant MR signal decreases in vivo. This finding correlated with histologic analysis after carotid endarterectomy.
Cell Tracking of Iron Oxides
The concept of cellular tracking takes advantage of the strong effects of iron oxide on T2 relaxation and the high spatial resolution that results from diminished background disturbance when individual cells are magnetically labeled before reaching their target location. MRI tracking of mesenchymal stem cell (MSC) implantation and engraftment into injured myocardium has been reported in a porcine myocardial infarction model (388). In these injured animals, magnetically labeled mesenchymal stem cells were injected into the myocardium via a catheter under x-ray fluoroscopy guidance, and conventional 1.5-T MRI was used to visualize the MR-MSCs over the next 3 weeks. MRI location of the superparamagnetic cells at 3 weeks was corroborated by histology. A recently developed MR-trackable intramyocardial injection catheter for implantation of MR-MSC has been successfully tested in two canine and one porcine closed-chest myocardial infarction models (389) and offers the possibility of a simpler, MR-based-only cell delivery technique.
Paramagnetic Nanoparticles
Although SPIOs produce dark or negative contrast effects that obscure image detail immediately around the particle, paramagnetic agents offer bright contrast in T1-weighted images.
Perfluorocarbon Nanoparticles
Liquid perfluorocarbon nanoparticle (PFC) emulsions provide a lipid surface area that can be functionalized with homing ligands, magnetic labels, and hydophobic drugs. The larger size of PFC nanoparticles (250 nm nominal diameter) focuses their utility toward vascular-accessible targets, such as thrombosis, atherosclerosis, restenosis, and other angiogenic-dependent diseases. Each bound paramagnetic nanoparticle delivers 50,000 to 90,000 or more gadolinium ions (362,390), which can be detected with low-resolution scans. PFC nanoparticles have been targeted to a variety of molecular epitopes, including high-density epitopes, such as fibrin in thrombi, and very sparse biomarkers, such as integrins in neovascular beds. One molecular signature, ανβ3-integrin, is expressed on the luminal surface of activated endothelial and smooth muscle cells in injured media but not on mature quiescent cells. In New Zealand White (NZW) rabbits bearing 12d Vx-2 tumors (<1.0 cm), ανβ3-integrin-targeted nanoparticles sensitively detect angiogenic endothelium at 1.5 T (391). Molecular images of ανβ3-integrin expression obtained with MRI paralleled those obtained with immunohistochemical staining, which revealed an asymmetric distribution along the border of the tumor capsule. The MRI signal from tumor neovasculature was enhanced by 126% within 2 hours of injection by ανβ3-integrin-targeted nanoparticles. Moreover, in vivo competition-blockade studies diminished targeted signal enhancement by more than 50%, which supports the specificity of the ανβ3-integrin-targeted paramagnetic agent. Angiogenesis is also central to the progression of atherosclerotic plaque development. Noninvasive, specific recognition of angiogenesis in early vascular disease is not possible with current medical imaging techniques. However, ανβ3-integrin-targeted paramagnetic nanoparticles have been demonstrated to spatially localize and quantify early atherosclerotic burdens in hyperlipidemic NZW rabbits (392). In addition, recent studies have demonstrated the unique capability of these agents to locally deliver antiangiogenic therapy via a process termed contact-facilitated drug delivery.
Interventional Cardiovascular Magnetic Resonance Imaging
In recent years, with the improvements in MR-scanner hardware, superfast interactive MRI, and development of miniature MR-compatible internal catheters, guidewires, and ablation catheters, the field of interventional and therapeutic MRI has been expanding at a very rapid rate. Furthermore, because of radiation-related issues, which are generally compounded in children, pediatric interventional MRI appears promising. The biggest stumbling block for real-time MR techniques was the inability of the imaging hardware to perform these tasks because they were not designed for this purpose. One of the most important developments has been that of real-time MRI.
Real-Time Magnetic Resonance Imaging
Advances in MR gradient hardware have made it possible to rapidly encode spatial information of the imaging data required to produce a 256 × 256 image of a 24-cm field of view (about
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1 mm spatial resolution) in about 120 msec. If the spatial resolution is reduced to 128 × 128, this time is further reduced to 50 msec (20 frames/second). The next important development in this field was the ability to perform real-time interactive manipulations of the imaging data utilizing a user interface in conjunction with a short-bore cardiovascular scanner and fast spiral imaging. Such developments lead to (a) rapid data acquisition, data transfer, image reconstruction, and real-time display, (b) interactive real-time control of the image slice, and (c) high-quality images without cardiac or respiratory gating. The real-time MR-hardware platform consists of a workstation and a bus adapter and can be adapted onto a conventional scanner at a reasonable cost.
Accurate visualization and positioning of the interventional devices in relation to the surrounding anatomy is critical for a successful and safe image-guided interventional procedure. There are primarily two methods that have evolved over the years to aid in navigation of endovascular navigation of the interventional devices: passive and active MR tracking (393,394). Passive MR tracking techniques are based on visualization of the signal void and susceptibility artifacts caused by the interventional instruments themselves due to displacement of the protons. This form of tracking constitutes the normal imaging process and does not require any extra postprocessing or hardware. The artifact generated by a particular material depends on a multitude of factors including the magnetic field strength, the spatial orientation of the device with respect to the magnetic field, the physical cross section of the device, the pulse sequence, and the imaging parameters. Active tracking requires the creation of a signal that is actively detected or emitted by the device to identify its location. This can be achieved by visualizing a signal from a miniature radiofrequency (RF) coil that is incorporated into the commercially available interventional devices such as embolization catheters and balloon catheters (394,395,396,397). The miniature coils are connected, through a fully insulated coaxial cable embedded in the catheter wall, onto the surface coil reception port for signal reception. A coil-tipped catheter is made by winding the miniature coil, which is a copper wire spiral, for 16 to 20 turns around the tips of interventional devices to actively identify their position (394,396). In the active tracking technique, the position of the device is derived from the signal received by a miniature RF coil that is attached to the instrument itself (394,398,399). Three-dimensional coordinates of the coil can be tracked in real time at 20 frames/second with a spatial resolution of 1 mm. The position of the coil is used to control the motion of a cursor over a scout (road map) image. Another technique in active tracking uses a loopless antenna (400) consisting of a conducting wire that is an extended inner conductor from a coaxial cable. A loopless antenna is particularly useful because it provides a superior field of view when compared to internal coils. In this regard, although it was first developed to guide endovascular procedures (400), it was adapted to support transesophageal MRI (401) and later the entire development of MR-guided electrophysiology (also see later discussion) (402). The entire body of the loopless antenna can be observed under MR imaging. This antenna can be either directly inserted into small or tortuous vessels or placed into the central channel of interventional devices. Because the loopless antenna is expected to function not only as an intravascular MR receiver probe for intravascular MR imaging and for creation of intravascular MR fluoroscopy, but also as a conventional guidewire for interventional MR imaging, it is called an MR imaging-guidewire (MRIG) (403). Indeed, for reasons of safety and for technical purposes, such as torque control and subselective placement as well as negotiation of hard atherosclerotic lesions, this antenna/guidewire must also function as an imaging receiver probe intravascular MR-guided interventional procedures are performed. The MRIG has been tested in vivo and found to be useful for both intravascular MR imaging and cardiovascular interventional MR imaging (404).
Applications of Interventional Cardiovascular Magnetic Resonance Imaging
Magnetic Resonance Imaging–Guided Balloon Angioplasty
The notion that endovascular procedures could be performed under MRI guidance stemmed from studies that tested (395,405,406) and validated (407) the use of intravascular coils. With the development of newer active and passive tracking techniques, ultrafast imaging, gadolinium-filled balloons, and small-diameter coils, performance and monitoring of balloon angioplasty using MRI has become technically feasible. A cable-tie created stenotic model has been used to test the monitoring of the inflation/deflation of an angioplasty balloon catheter of a rabbit aorta (403,404). In this study, a 1.5-F loopless antenna was used as a guidewire with a standard 4-cm, 4-F balloon angioplasty catheter. The intravascular antenna was also used as a high-resolution imaging probe to monitor vessel dilation using an MR fluoroscopy sequence. A subsequent study with the same stenotic model demonstrated the feasibility of performing intravascular MR-guided balloon angioplasty in vivo. Recently, the feasibility of using MR imaging to guide balloon angioplasty of renal artery stenosis generated by a constrictor has been demonstrated using a passive tracking approach with MR angiography (408). In addition, the success of MRI-guided percutaneous transluminal coronary angioplasty (PTCA) in living animals has been reported. Using active tracking methods, investigators performed the entire process, including (a) catheterization of the targeted coronary artery, (b) generation of selective coronary MR angiography, (c) creation of high-resolution MR images of the target coronary arterial wall, and (d) positioning and inflation/deflation of an angioplasty balloon under MRI guidance (409).
Magnetic Resonance Imaging–Guided Stent Imaging and Placement
The feasibility of stent deployment in coronary and peripheral vasculature using MRI has also been tested in both animals and humans. Buecker et al. demonstrated the feasibility of MRI-guided iliac Nitinol stent placement in pigs using radial scanning together with a sliding window reconstruction technique (410). Stainless steel balloon-expandable coronary stents have recently been placed in animals under real-time MRI guidance using a newly developed real-time steady-state free-procession sequence with radial k-space sampling (411). In a porcine model, 10 of 11 stents were successfully placed in the left main coronary artery without complication. Manke et al. described the first human MRI-guided Nitinol stent placement study in 13 patients with iliac artery stenosis (412).
Magnetic Resonance Imaging–Guided Interventional Electrophysiology
Ablation procedures in electrophysiology are typically very long, with significant radiation exposure. MRI could be a logical alternative to x-ray fluoroscopic techniques with the following advantages: (a) real-time catheter placement with detailed endocardial anatomic information, (b) rapid high-resolution three-dimensional visualization of cardiac chambers, (c) high-resolution functional atrial imaging for evaluating atrial function and flow dynamics during therapy, (d) the potential for real-time spatial and temporal lesion monitoring during therapy, and (e) elimination of patient and physician radiation exposure. Using a standard external surface coil, it has been shown that (a) MR images and intracardiac electrograms could be acquired during radiofrequency ablation therapy using special filtering techniques, (b) nonmagnetic, MR-compatible catheters could be successfully visualized and placed at right atrial and right ventricular targets using real-time MR imaging sequences with interactive scan-plane
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modification, and (c) regional changes in ablated cardiac tissue can be detected (413). Intracardiac spectroscopic measurements made at least two decades ago (414) were the foundations for applying developments originally conceived to enable endovascular procedures (see prior discussion) for the purposes of guiding electrophysiologic studies (402). MRI-guided ablation therapy can visualize and monitor lesion formation with high temporal and spatial resolution. Lesions appear as elliptical hyperintense regions (most likely due to interstitial edema) directly adjacent to the catheter tip on T2-weighted turbo spin-echo images. MRI can detect changes due to heat-induced biophysical changes in cardiac tissue, such as interstitial edema, hyperemia, conformational changes, cellular shrinkage, and tissue coagulation. In addition, lesion detection 1 to 2 minutes after ablation with subsequent formation over 10 to 15 minutes is consistent with the temporal physiologic response of local acute interstitial edema.
In Vivo Magnetic Resonance Imaging of Vascular Gene Therapy
Gene therapy is rapidly emerging as a viable modality and has shown a tremendous potential in the treatment of atherosclerotic diseases. Recently, MRI has been tested for monitoring and guiding vascular gene delivery, tracking vascular gene expression, and enhancing vascular gene transfection/transduction (415). Gene transfer into a target-specific cell is a major challenge in this field and has a very low success rate (1%). Several studies have shown that gene transfection or expression can be significantly enhanced one- to fourfold with heating (416,417). Local heat generation at the target site using an easily placed internal heating source could be a logical way of achieving that. An MRI guidewire called an MR imaging-heating-guidewire (MRIHG) (400) can be used to deliver external thermal energy into the target vessels, and has the following functions: (a) as a receiver antenna to generate intravascular high-resolution MR imaging of atherosclerotic plaques of the vessel wall (418), (2) as a conventional guidewire to guide endovascular interventions under MRI (28,403), and (c) as an intravascular heating source to deliver external thermal energy into the target vessel wall during MRI of vascular gene delivery and thereby enhance vascular gene transfection.
Tracking gene expression involves the use of imaging methods to assess gene function by detecting functional transgene-encoding proteins (referred to as “imaging downstream”) at the targets over time. MRI can be used to track overexpression of the transferrin gene, which produces a cell-surface transferrin receptor. The transferrin receptor is then probed specifically by a superparamagnetic transferrin that can be subsequently detected under MRI (419).
Safety of Interventional Magnetic Resonance Imaging
The obvious concerns with interventional MRI include electromagnetic exposure and internal heating in addition to intervention-related issues. Studies have found that conventional MRI is safe in this regard (420). Interventional procedures present new challenges, however, including the placement of monitoring equipment and surgical instruments in close proximity to a high magnetic field and in vivo placement of long conductive wires and electrical components in rapidly changing magnetic fields, all of which can lead to local heating (397). Such heating effects can be minimized by using a decoupling circuitry into the device, thus limiting the transfer of energy through the probe/wire by the transmit coil. In addition, the careful use of imaging sequences that limit RF power disposition and duration also helps to reduce the possibility of excessive heating. Existing studies do point toward the safety of this technology, but further comprehensive studies are required to further ascertain this.
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