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Cardiovascular applications of magnetic resonance imaging
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Mogneric Resonance Imaging. Vol. 2. pp. 167-186, 1984 Printed in the USA. All rights reserved.
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l Continuing Education CARDIOVASCULAR APPLICATIONS OF MAGNETIC RESONANCE IMAGING MICHAEL T. MCNAMARA, M.D., AND CHARLES B. HIGGINS, M.D. Department
of Radiology,
University
of California,
San Francisco,
California
94143
Magneticresonance
imaging (MRI)is a completely noninvasive modality that has shown significant promise for the evaluation of the cardiovascular system. Our imaging technique employed electrocardiographic (ECG) gating, which resulted in well-resolved images of the cardiac structures. Patients and animals with a variety of cardiovascular abnormalities were also assessed with this technique; the abnormalities included acute and remote myocardial infarctions and their sequelae, atherosclerotic plaques, hypertrophic cardiomyopathy, pericardial diseases, and aneurysms. The diagnostic utility of MRI includes direct tissue characterization, and such utility may be further extended by the use of paramagnetic contrast media. In addition, metabolic imaging of elements other than hydrogen may further increase the clinical potential of MRI for assessment of the cardiovascular system. Keywords: Nuclear magnetic resonance, Cardiovascular system, Blood flow, Chemical shift, Paramagnetic
contrast
media.
INTRODUCTION
of very low intensity, providing a high degree of natural contrast within the walls of the cardiac chambers and large blood vessels. Intravenous injection of contrast medium is therefore not required in MRI. However, depending on the rate of flow and the imaging pulse sequences employed, the intensity of blood may be represented by a spectrum of signal intensities ranging from nearly absent to very intense. MRI has several advantages over the conventional x-ray methods for the evaluation of the cardiovascular system. First, MRI affords natural contrast between cardiovascular structures and flowing blood. Second, the contrast among soft tissues afforded by MRI is several times greater than that attainable with x-ray computed tomography (CT). Third, MRI offers tissue characterization by the magnetic relaxation times T, and T,. Studies have shown that normal and ischemic or infarcted myocardium can be differentiated by their T, and T, relaxation times.4’35 Finally, MRI uses no ionizing radiation. The purpose of this work is to describe the techniques whereby cardiovascular images are obtained using MRI and to demonstrate the clinical utility of MRI for the visualization of normal cardiovascular anatomy and for the detection of pathologic lesions. Future prospects for cardiovascular imaging are also discussed.
Magnetic resonance imaging (MRI) has shown enormous potential for the evaluation of cardiovascular disease.‘3.‘6,24 It is a completely noninvasive modality for obtaining images of the heart and blood vessels. However, to obtain diagnostic images of the heart, technical difficulties had to be overcome. These difficulties are caused by cardiac motion, which diminishes the magnetic resonance (MR) signal intensity of cardiac structures. Moreover, images obtained without gating represent neither end-diastole nor end-systole but are instead a temporally unpredictable average image. Additionally, the relaxation time constants T, (longitudinal relaxation time) and T, (transverse relaxation time) cannot be obtained from such images. However, the application of a gating technique that synchronizes the MR pulse sequences to specific phases of the cardiac cycle have dramatically improved the cardiac image quality and provided sharp discrimination of internal cardiac anatomy (Fig. I). It may be possible to characterize myocardium by T, and T2 with gated imaging, but this has not yet been proven. MRI of the cardiovascular system benefits greatly from the effects of flowing blood on image contrast. In general, rapidly flowing blood generates an MR signal RECEIVED4/4/84;
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Magnetic
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1 80°
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RF Signal
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Second Spin Echo (56 msec)
Fig. 1. Schematic representation of the spin-echo imaging technique showing application of a 90” RF pulse followed by a 180° pulse at a given time interval. The receipt of the subsequent signal (spin-echo) occurs at a time interval equal to twice the interval between 90° and 180° RF pulses.
INSTRUMENTATION
MRI studies were performed with a superconducting magnetic operating at 0.35 T (3.5 kG), with a resonant hydrogen frequency of 15 MHz. The magnet consists of niobium-titanium (Nb-Ti) filaments embedded in a copper matrix. This metal is cooled to near absolute zero (- 40 K) using liquid helium and liquid nitrogen, thereby eliminating resistance to current flow. Other types of magnets are currently being used, including permanent magnets, iron core magnets, and air core resistive magnets, with field strengths ranging from 0.1 T (1 kG) to 0.5 T (5 kG).’ The parameters used for spin-echo images employed echo delays (TE) of 28 ms (first echo) and 56 ms (second echo) and pulse sequence repetition times (TR) varying from 0.5 to 2.0 s. The echo delay is the time between the initial radiofrequency (RF) excitation of the proton nuclei and the receipt of the spinecho signal from the nuclei. The pulse sequence repetition time is the interval between successive excitation sequences within each imaged volume. Figure 1 illustrates the application of RF pulses using the spin-echo technique. With gated acquisition of images, the TR interval is equal to the RR interval of the electrocardiogram; the TR can be doubled by gating to every second heart beat. The technique for gating will be discussed shortly. As the RF sequences are applied, simultaneous weak magnetic field gradients are also applied along the x, y, and z axes of the image by three sets of resistive gradient coils. The use of these gradients allows spatial encoding of the volume of tissue being imaged to facilitate accurate image reconstruction and display. The RF pulse transmitter and receiver antennae (which may be one antenna that switches between a transmission mode and reception mode) are at 90° Our
angles to the main magnetic field gradient (x, y plane). Imaging time for each patient is determined by the pulse sequence repetition time, the number of lines along the y axis, and the number of signal averages obtained for each volume. An increase in any of these parameters will proportionately prolong imaging time. We employ a multiplanar imaging technique whereby RF sequences are applied at five adjacent 7-mm-thick axial sections during each RR interval. The delay between each axial section image is 100 ms, and imaging proceeds in a cranial-to-caudal direction. Thus, each data acquisition cycle begins in enddiastole and proceeds at lOO-ms intervals into systole in a caudal direction. GATING A significant loss in MR signal intensity occurs with nongated cardiac imaging due to cardiac wall motion and the sampling of data for reconstruction at random phases of the cardiac cycle. This results in generally poor image quality (Fig. 2). However, the data acquisition pulse sequences can be physiologically gated to the events of the cardiac cycle to avoid this loss of signal.‘6 A major consideration in the selection of gating techniques is that ferromagnetic hardware within the confines of the shielded imaging system may contribute to image distortion. We have evaluated three different gating techniques: blood pressure cuff plethysomography, which is sensitive to limb distension with arterial pulsation; laser-Doppler velocimetry, which detects relative changes in tissue microcirculatory blood flow beneath a 1-mm3 light probe; electrocardiography (ECG) using low-resistance electrodes that contain very little metal and thus are safe for use in the presence of high electromagnetic fields and rapidly changing RF pulses. The use of low-resistance elec-
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Fig. 2. Transverse MRI of a normal volunteer. The poorly resolved images (top) are nongated. Note the excellent anatomic resolution afforded by electrocardiographic gating (bottom). Natural contrast results from normal intracardiac and intraortic blood flow. ECG _ Eating_ allows clear distinction of cardiac wall thickness, papillary muscles, and intracardiac valves.
trodes and nonmagnetic ECG lead cables does not contribute to any measurable increase in the image noise level and the ECG signal is not affected by the RF fields. Variations in the temporal relationships between the R-wave and the plethysmographic and laser-Doppler velocimetric signals produce inconsistencies in the timing of the imaging sequences. By using the R-wave of the ECG cycle for gating, more precise synchronization to a specific segment of the cardiac cycle is obtained, compared with the other two methods. Since data acquisition is determined by the patient’s heart rate, the pulse sequence repetition rate (TR) is defined by the RR interval of the cardiac cycle. For example if the heart rate is 60 beats/min, the TR will be 1 .O s by gating to every heart beat or 2.0 s by gating to every other heart beat. In general, the image quality for the 28-ms spin-echo is usually superior to the 56-ms spinecho because it encompasses a proportionately shorter gating window (335% of the cardiac cycle). As a result, less cardiac motion occurs during the first spin-echo image and, depending on the patient’s heart rate, this may affect image quality. The heart is at end-diastole, or maximal filling, at the R-wave when the first image is obtained with the multislice technique. The subsequent four images are obtained at lOO-ms intervals further into the cardiac cycle because this time interval is required to obtain each image. Thus, for a patient with a heart rate of 60
beats/min, each cycle is 1 s long and the fifth slice (completed 500 ms after the R-wave) will be obtained about halfway into the cardiac cycle. For more rapid heart rates, however, the time required to obtain these images will constitute a greater proportion of the cardiac cycle. Thus the middle three images may occur during systole while the fifth image may be acquired during early diastole. Gated MRI can be performed in patients with very rapid heart rates because the imaging sequence can be gated to every other or even every third heart beat. This results in a longer TR interval, thereby allowing more recovery of longitudinal magnetization between sequences. Patients with marked arrhythmias, especially atria1 fibrillation and frequent premature ventricular contractions, cannot be adequately gated. MRI AND BLOOD
FLOW
The signal intensity (I) produced by blood on MRI is affected by several factors, including the magnetic relaxation times T, and T,, mobile hydrogen density, and blood flow as described by the MRI intensity equation for spin-echo images: I = N(H)f(v) exp represents the tion of nuclei intensity that move through
W-0 (-TE/TJ[l - exp (-TRIT,)I. local hydrogen density;f(v) is the fracthat are moving and the effect on the speed of these nuclei have as they the imaging plane; TE is the echo delay
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[time delay between application of the initial 90” RF pulse and the receipt of the signal (spin-echo) from these nuclei]; TR is. the time interval between successive pulse sequence repetitions; T, is the longitudinal or spin-lattice relaxation time; and T, is the transverse or spin-spin relaxation time. Based on this equation, one can see that blood flow will affect the MRI signal intensity. T, and T2 alterations in the imaging parameters will also affect signal intensity, even if N(I~Z)jiiv) is constant. The direction of motion of the nuclei through the plane being imaged is yet another factor that will affect the signal intensity; it is discussed later. For different ranges of blood flow rates, there will be characteristic appearances on spin-echo images. Stationary blood, such as that which may be encountered in patients with vascular occlusive disease or extravasated blood, will receive full exposure to the perturbing RF pulses and thus will have a strong MR signal intensity. However, protons in rapidly flowing blood will not experience complete RF pulse and gradient pulse sequence because their velocity will carry them out of the imaging plane before the completion of the
pulse sequence. For example, if a particular sequence requires 70 ms and the imaging plane is 7 mm thick, then a flow rate of greater than 10 cm/s will carry the nuclei completely out of the plane and the signal intensity will be zero. A third flow-related appearance arises from slowly flowing blood, that is, blood with a flow rate of less than about 10 cm/s. A fraction of slowly flowing hydrogen nuclei will experience the complete RF pulse and gradient pulse sequence, and will therefore appear with a signal intensity characteristic of stationary blood that has recovered some of its equilibrium magnetization. However, the remaining fraction of this particular image plane will not have experienced the initial 90” RF irradiation; they will enter the plane during the imaging sequence and have full magnetization. The net result is a collection of protons, some of which have not previously been irradiated and have full magnetization because they are flowing slowly enough to interact with the entire imaging sequence, and some which have been previously irradiated and therefore have partial magnetization. The intensity of the previously irradiated popu-
Fig. 3. Sequential cross-sectional images of an asymptomatic patient with a normal aorta and vena cava. The cranial level images are on the left and the caudal level images are on the right. Paradoxical enhancement is present within the aorta on the second spin-echo (arrow) cranial entrance level image on the left. There is an intense intraluminal signal within the vena cava on the second spin-echo image at the caudal entrance level (arrowhead), which also represents paradoxical enhancement.
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Fig. 4. Gated transverse MRI of the heart of a normal volunteer reveals normal cardiac contour, myocardial wall thickness, and ventricular chamber size. lation will be similar to that of stationary blood, while the intensity of the fully magnetized population will be greater than that of stationary blood. Thus, the net additive result of these two populations of nuclei within this plane is a paradoxically greater MR signal intensity than that of stationary blood. This MRI phenomenon of slowly flowing blood has come to be known as paradoxical enhancement (Fig. 3). When a volume of the body is exposed to the RF pulse sequences, paradoxical enhancement is greatest
Fig. 5. Sequential cross-sectional MRI of a normal human volunteer. The ascending aorta (straight black arrow) and descending (curved black arrow) aorta has a normal contour and smooth endothelial wall. Also clearly visible are the main (solid, straight white arrow), right (open white arrow), and left (curved white arrow) pulmonary arteries and pulmonary veins.
at the initial transverse level into which blood is flowing. This is because all proton nuclei flowing toward this level have not been previously irradiated. Thus, for abdominal imaging, the greatest intensity for the flow signal appears at the most cranial (superior) level for arterial flow and at the most caudal (inferior) level for venous flow, which are the respective entrance imaging levels for these structures (Fig. 3). This is because blood flowing in each of these directions has not experienced previous 90° RF irradiation before
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Fig. 6. Nongated transverse image at the level of the great vessels shows the superior vena cava (arrowhead) which has been displaced medially by a mass (bronchogenic carcinoma). In addition, the right pulmonary artery (arrow) is narrowed distally as a result of encasement by the bronchogenic carcinoma.
Fig. 7. Sequential transverse MRI of the abdomen. The solid retroperitoneal mass (apudoma, arrow) can be distinguished from the adjacent aorta, which lacks an intraluminal signal. The aorta has been displaced but not invaded by the tumor. Note the presence of signal within the inferior vena cava (arrowhead) at all levels, which suggests sluggish flow.
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entering their respective initial imaging sections. Also, due to the relatively slower flow in venous structures, there tends to be greater paradoxical enhancement in veins compared with arteries. The variation in intensity with the different Bow rates has proven useful in MRI because of the high degree of natural contrast that it provides between the blood in cardiovascular system and the cardiac walls or the walls of blood vessels. Rapidly flowing blood has a characteristically low MR signal intensity and this contrasts quite well with the myocardial and vascular wall tissue (Fig. 4). The absence of MR signal roughly shows a normal blood flow rate, or at least confirms a flow rate of greater than lo-15 ml/s. Paradoxically enhanced low-velocity flow has a greater signal intensity than the surrounding vascular walls and perivascular tissue, and therefore also provides natural contrast on MRI spin-echo images. MRI therefore requires no contrast media to depict blood flow. For a multislice imaging technique, the signal intensity of blood varies among the different transverse levels. With the multisection imaging mode, the nuclei entering the first section have not experienced previous
173
irradiation and consequently show paradoxical enhancement. The nuclei that enter the remaining contiguous slices have already undergone previous irradiation and will have diminished paradoxical enhancement or even none at all.
VASCULAR
APPLICATIONS
OF MRI
The natural contrast provided by the absence of signal from rapidly flowing blood with MRI allows visualization of the large mediastinal blood vessels without contrast media. Thus it is quite easy to discriminate blood vessels without contrast media,12 including the ascending and descending aorta, the pulmonary vessels, and the superior vena cava (Fig. 5). This natural contrast distinguishes such vessels from adjacent solid structures such as hilar or mediastinal tumors and lymph nodes (Fig. 6). There are other exciting possibilities offered by natural vascular contrast with MRI. Abdominal blood vessels are easily distinguished from surrounding organs and soft tissue structures, including retroperitoneal masses (Fig. 7). The utility of MRI in demon-
Fig. 8. Nongated transverse second spin-echo (TE = 56 ms) image of a patient with Type B dissection of the aorta. The true lumen (straight arrow) and false lumen (open arrow) are separated by an intimal flap (curved arrow). Slow flow within the false lumen is represented by high signal intensity within this lumen.
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strating masses and other abdominal diseases and their effects upon abdominal vasculature has been previously reported.17 MRI has also been useful in demonstrating abnormalities of the aortic wall. These include aortic aneurysms, aortic dissections with displacement of intimal flaps into the aorta, the true and false lumens, and slow flow within the false channels of aortic dissections (Fig. 8). Images of abdominal aortic aneurysms have demonstrated the outer wall that defines the true diameter of the aneurysm, the size of patent lumen, and the presence of wall thickening due to atherosclerotic debris or engrafted thrombus upon the wall of the aneurysm (Fig. 9). It may even be possible to detect acute bleeding and hematoma from a leaking aneurysm by the presence of high MR signal intensity characteristic of fresh blood. The high contrast between flowing blood and the vascular wall makes it possible to visualize atherosclerotic lesions projecting into the low signal intensity (flow void) of the aortic lumen. The appearance of the aorta and iliofemoral vessels on transverse and sagittal
MRI is characterized by a smooth endothelial surface and a uniformly thin aortic wall. On the other hand, in patients with known atherosclerosis, MRI has demonstrated eccentric thickening of the vessel wall and in some instances discrete atherosclerotic plaques projecting into the vascular lumina (Fig. 10). MRI has displayed both concentric and eccentric narrowing of the aorta (Fig. 11). Atherosclerotic lesions detected by MRI have been confirmed by angiography.15 Since atherosclerotic lesions contain variable accumulations of lipid, smooth muscle, fibroblasts, and calcification, these lesions may have variable appearances on MRI that proportionately correspond to these various constituents. Ex vivo MRI of iliac arteries has depicted atherosclerotic plaques that correlated with postmorten examinations.23 Fatty deposits produce high signal intensity, while smooth muscle and fibroblasts are associated with low-intensity regions in the plaques. Calcification, like cortical bone, lacks mobile protons and therefore appears as a low-intensity structure. The usual appearance of calcification is an arc or circumferential rim of low intensity.
Fig. 9. Sequential transverse images of the aorta and vena cava in a patient with an abdominal aortic aneurysm that extends to the bifurcation. The outer wall of the aneurysm is well visualized. The aneurysm is lined with atherosclerotic debris and thrombus material. The low intensity within the residual lumen represents flowing blood.
Cardiovascular applications of MRI 0 M. T. MCNAMARA AND C. B. HIGGINS
Fig. IO. Sequential transverse images in a patient with diffuse aortoiliac atherosclerotic disease show multiple atherosclerotic plaques protruding within the lumen with eccentric narrowing. The residual lumen has low signal intensity due to rapidly flowing blood.
NORMAL Excellent
resolution
CARDIAC
I I
ANATOMY
of the cardiac
morphology
175
has
been attained with ECG-gated MRI. In general, most imaging is performed in the transaxial plane, but direct coronal and parasagittal imaging can also be performed. Due to the rapid rate of normal blood flow there is a high degree of natural contrast between the cardiac walls and the cardiac chambers. A similar degree of contrast exists between the epicardial surface and the lungs due to the very low hydrogen density of the lungs. This high degree of natural contrast allows
the measurement of wall thickness and chamber size at various sites in the heart. Figure 12 demonstrates five contiguous transaxial slices, each section being 100 ms further into the cardiac cycle and thus in a different state of contraction relative to the previous section. Internal cardiac anatomy has been well delineated on MRI, including the papillary muscles (Fig. 13), the proximal left and right coronary arteries (Fig. 14), the cusps of the aortic valve, and the moderator band of the right ventricle (Fig. 15). The pericardium can be seen as a l-2 mm thick curvilinear structure of low signal intensity between the higher intensity myocardium or
Fig. 1 1. Transverse MRI of the intrarenal abdominal aorta in a patient with eccentric wall thickening and stenosis of the aorta. The magnified first echo (28 ms) and second echo (56 ms) images are pictured at right.
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Fig. 12. Sequential cranial-to-caudal transverse images. The cranial image (upper left) is acquired at end-diastole and each adjacent 7-mm thick section is imaged at a lOO-ms interval further into the cardiac cycle.
subepicardial fat and the pericardial fat (Fig. 16). When sufficient pericardial fat is present, the pericardium can also be seen lateral to the right atrium and left ventricle. MRI OF CARDIAC ABNORMALITIES
Congenital malformations Various congenital cardiac malformations have been imaged with excellent depiction of intracardiac anomalies.’ The atrioventricular valves, interatrial and interventricular septa, and aortic root are all well visualized simultaneously on single axial images. This “four-chamber” view permits the evaluation of wall thickness and chamber size, which are often abnormal
Fig. 13. Transverse MRI shows excellent internal cardiac anatomy, including the papillary muscles. Also note the right coronary artery with low signal intensity lying within the fat in the right atrioventricular groove (arrow).
in these patients. Sagittal views permit excellent visualization of the thoracic aorta but do not usually provide any important additional anatomic information. The congenital anomalies that have been analyzed thus far with MRI include atria1 and ventricular septal defects, aortic stenosis, mitral stenosis, tricuspid atresia, Ebstein’s anomaly, transposition of the great vessels, persistent truncus arteriosus, and car triatriaturn. In general, the thicker interventricular septum is more easily identified on MRI than the interatrial septum but, nevertheless, atria1 septal defects have been distinguished from complete absence of the interatria1 septum. Difficulty has been encountered in
Cardiovascular
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Fig. 14. Image at the level of the aortic root shows a portion of the left anterior ascending coronary artery with low signal intensity (arrow). visualizing the right ventricular curved configuration.
outflow tract due to its
Myocardial wall abnormalities MRI permits the detection of focal myocardial wall thinning that results from previous myocardial infarctions.” The sites of previous infarcts are demonstrated by regions of myocardial thinning in the left ventricle and, by examining muliple adjacent axial images, it is possible to estimate the extent of infarcted left ventricle (Figs. 17 and 18). Left ventricular angiography and/or sector scan echocardiography have confirmed these findings. Several patients with aneurysms of the left ventricle had extreme wall thinning and bulging
that were readily identified with MRI. Posterior, anterior, and septal infarctions and aneurysms have also been identified. Some patients with such left ventricular wall aneurysms had findings on MRI suggestive of regional dyskinesis or akinesis with resultant stasis of blood flow. This appeared as a region of high signal intensity within the left ventricle lumen on the second spin-echo image (TE = 56 ms) (Fig. 18). Acute myocardial infarction: tissue characterization with magnetic relaxation times Investigators have shown that acute ischemia produces significant increase in T, relaxation times of myocardium relative to normal myocardium. Changes
Fig. 15. Transverse MRI shows excellent cardiac anatomic detail, including the moderator band of the right ventricle (arrow).
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Fig. 16. ECG-gated transverse image of normal volunteer shows the low-intensity thin curvilinear normal pericardium surrounding the left and anterior cardiac borders (arrows). The adjacent subepicardial fat and pericardial fat (high signal intensity) surround the pericardium and allow such visualization.
Fig. 17. ECG-gated transverse images of a patient with an old lateral wall myocardial infarction. Note the extreme wall thinning (arrow) on multiple levels, which allows the estimation of extent of the infarcted left ventricle.
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Fig. 18. Gated MRI of a patient who has suffered an old anterior wall myocardial infarction reveals the presence of a mural thrombus (left arrow) within the anterior left ventricle. This high-intensity thrombus can be distinguished from the adjacent thin anterior wall of the left ventricle. It is easier to distinguish the interface of thrombus and myocardium on the second spin-echo image (right arrows; TE = 56 ms). Note also the presence of increased signal intensity within the anterior left ventricle on the second spin-echo image that probably represents stasis of blood due to myocardial dyskinesis in addition to thrombus (curved arrow).
in magnetic relaxation times have been demonstrated as early as several minutes after coronary 0cclusion,35 but this finding is unconfirmed. An early imaging study suggested that acutely infarcted myocardium could not be detected without the injection of a paramagnetic contrast agent to demarcate perfusion.27 This report used a steady-state free precession technique for imaging. A more recent report utilizing the spin-echo technique showed that 24-h-old canine myocardial infarcts appear with a visibly greater signal intensity than adjacent myocardium due to a significantly longer T2 relaxation time of the infarcted myocardium (48.4 * 2.4 ms for infarcted myocardium versus 42.1 + 1.2 ms for normal myocardium). There was no overlap in the ranges of T, relaxation times for normal and infarcted myocardium.” In that report’* it was also noted that the mean T2 of infarcted myocardium (728 * 94.8 ms) was longer
than the mean T, of normal myocardium (650 + 87.4 ms). The T, of infarcted myocardium was longer than that of normal myocardium for each individual animal. There was a linear relationship between T2 values and percent water content (r = 0.90) but not between T, and water content (r = 0.47). More recently, in vivo gated
MRI
of I-7-day-old
myocardial
infarctions
has
shown increased signal intensity of the infarcted compared to normal myocardium (Fig. 19). High signal intensity was found in the anterior wall of the left ventricle following ligation of the left anterior descending coronary artery. No administration of contrast media was required.3’ Although the high degree of natural contrast between infarcted and normal myocardium results in good infarct detection without contrast agents, it is not possible to define myocardial perfusion without such agents. Recent work has demonstrated the potential
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for demonstrating acute ischemia following 1 min of coronary artery occlusion employing the paramagnetic complex gadolinium-DTPA (Gd-DTPA).** _
Fig. 19. Transverse ECG-gated spin-echo MRI of a dog with an anterior wall myocardial wall infarction produced by left anterior descending coronary artery occlusion 1 week prior to imaging. The infarct appears as a discrete highintensity segment within the anterior and anteroseptal walls of the left ventricle due to prolonged T2 relaxation time.
Cardiomyopathies MRI has shown significant promise in the evalua .tion of patients with hypertrophic cardiomyopath Y (HCM) (C.B. Higgins et al., unpublished data). MR I was able to clearly demonstrate the site and extent cIf hypertrophy (Fig. 20). In general, the distribution of hypertrophy varied from hypertrophy of the basal septum alone to hypertrophy of the entire septum with extension into the anteroapical segment. At the level of the left ventricular outflow tract most patients showed hypertrophy confined to the septal wall (nine patients) and a smaller number had involvement of the lateral as well as the septal wall (four patients). The longitudinal extent of hypertrophy was well demonstrated with sagittal MR images. Measurement of wall thickness was easily performed with the sharp images obtained with ECG gating (Fig. 19). While the thickness of septal and posterolateral myocardial walls in normal volunteers was 10.2 k 0.4 and 10.8 c 0.5 mm, respectively, all but one patient with HCM had a septal thickness of 15 mm or greater. The severity and distribution of hypertrophy were comparable on twodimensional echocardiography and MRI. Thus, MRI has proven to be an effective and completely noninvasive technique for demonstrating the presence, severity, and extent of hypertrophy in patients with HCM.
Fig. 20. Gated image of a patient with hypertrophic cardiomyopathy. There is extreme thickening of the anteroapical septum and lateral wall of the left ventricle. Gated MRI allows the measurement of myocardial wall thickness and the demonstration of the extent of involvement of hypertrophy.
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Fig. 21. Gated MRI of a patient with a pericardial effusion. The asymmetric effusion surrounds the anterior and lateral sides of the heart. Although the effusion in general has low signal intensity (arrow) there is some signal within, which presumably represents inflammatory debris and adhesions between parietal and visceral pericardium.
MRI of pericardial disease MRI has been effective in demonstrating the presence of abnormalities in patients with pericardial disease. The normal pericardium, a thin fibrous structure l-2 mm thick and of low signal intensity in normal patients (Fig. 16), appears thickened in patients with constrictive pericarditis. The low signal intensity probably reflects the mostly fibrous composition of this tissue. Inflammatory pericarditis, on the other hand, may appear differently on gated MR images. In addition to appearing thickened, the inflamed pericardium may produce a more intense signal owing either to the presence of edema or exudate or effusion, or a combination of all three elements. Figure 21 shows the pericardial effusion and inflammatory exudate, as well as adhesions between the parietal and visceral pericardium. Previous reports have indicated that MRI may be useful for the diagnosis of a variety of clinical pericardial diseases. Such useful information would entail anatomic (pericardial thickness, presence of effusion, etc.) and pathologic information based on T1 and T, relaxation times and signal intensity.
FUTURE
OF CARDIOVASCULAR
MRI
The role of MRI in cardiovascular imaging requires additional clinical experience before it can be clearly defined. It offers a distinct advantage over conventional x-ray techniques in that it does not require contrast media for imaging. MRI also offers tissue
characterization, which x-ray CT does not. And with the use of contrast media, it appears that noninvasive quantification of blood flow and perfusion defects may be possible. Studies have described characteristic T, and T2 relaxation times for normal and pathological tissues in animals and in humans.6.7,‘4 This includes characteristic relaxation times for normal and ischemic and infarcted myocardium in animals.4~“~‘6~27~33~3s Although characteristic ranges for myocardial T, and T2 relaxation times have not clearly been established on gated MRI in humans, it seems likely that further experience will lead to them in myocardial tissue as well as in other organs. Although acute canine myocardial infarctions have been seen on ex vivo spin echo MR images without contrast media,‘“,3’ it appears that paramagnetic pharmaceuticals offer significant promise in improving both diagnostic sensitivity and specificity in detecting such lesions. This may be particularly applicable to more acute perfusion abnormalities, which may otherwise be occult on MRI. Human clinical trials are presently being conducted in Europe using Gd-DTPA, a very powerful paramagnetic agent, for urographic enhancement and for enhancement of neoplastic lesions. Although MRI to date has been exclusively proton imaging due to hydrogen’s great natural abundance, investigators are also measuring chemical shifts of sodium-23, carbon- 13, and phosphorus-33.*’ Sodium imaging may prove to be useful in detecting ischemia
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because of the reversal of sodium and potassium levels that occurs in cells whose membranes have been damaged by ischemia.‘*‘* This application has been used with a very strong magnetic field strength.8 Carbon-l 3 for fatty acid metabolism may also prove to be useful in myocardial imaging,2934 and imaging of phosphorus-3 1 may be important in demonstrating myocardial high energy phosphate metabolism.‘0*20~ 2’.29*30*32 Studies have already demonstrated regional
changes in concentration of phosphorus compounds during ischemia20+29*30and a return to normal concentration as normal flow is restored.29 In vivo application of this technique using topical MRI has been performed but presently requires a great length of time for such images.’ Perhaps the combined use of hydrogen and chemical shift imaging with further improvement in instrumentation and higher field strengths may provide the optimal features for clinical use.
REFERENCES 1. Abraham, J.L.; Higgins, C.B.; Newell, J.D. Uptake of iodinated contrast material in ischemic myocardium as an indicator of loss of cellular membrane integrity. Am. J. Pathof. 101: 319-330; 1980. 2. Alger, J.R.; Sillerud, L.O.; Behar, K.L.; Gilles, R.J.; Shulman, R.G.; Gordon, R.E.; Shaw, D., Hanley, P.E. In vivo carbon- 13 nuclear magnetic resonance studies of mammals. Science 214: 660-662; 198 1. 3. Bottomley, P.A.; Smith, L.S.; Edelstein, W.A.; Hart, H.R.; Mueller, 0.; Lowe, W.M.; Darrow, R.; Redington, R.W. Localized 3’P, 13C, ‘H NMR spectroscopy studies of the head and body at 1.5 Tesla. Scientific Program of the Society of Magnetic Resonance in Medicine 53-54; 1983. 4. Brown, J.J.; Slutsky, R.A.; Gerber, K.H.; Strich, G.; Higgins, C.B. Nuclear magnetic resonance analysis of acute myocardial infarction in dogs: the effects of transient coronary ischemia and reperfusion on spin lattice relaxation times. (in press). 5. Crooks, L.E.; Kaufman, L. Imaging techniques. Margulis, A.R.; Higgins, C.B.; Kaufman, L.; Crooks, L.E., eds. Clinical magnetic resonance imaging. San Francisco: Radiology Research and Education Foundation, 1983: 25-30. 6. Davis, P.L.; Kaufman, L.; Crooks, L.E.; Margulis, A.R. NMR characteristics of normal and abnormal rat tissue. Nuclear magnetic resonance imaging in medicine. Tokyo: lgaku-Shoin; 198 1: 7 1. 7. Davis, P.L.; Kaufman, L.; Crooks, L.E. Tissue characterization. Margulis, A.R.; Higgins, C.B.; Kaufman, L.; Crooks, L.E., eds. Clinical magnetic resonance imaging. San Francisco: Radiology Research and Education Foundation; 1983. 8. DeLayre, J.K.; Ingwall, J.S.; Malloy, C.; Fossel, E.T. Gated sodium-23 nuclear magnetic images of an isolated perfused working rat heart. Science 212:935-936; 198 1. 9. Fletcher, B.D.; Jacobstein, M.D.; Nelson, A.D.; Riemenschneider, T.A.; Alfidi, R.J. Gated magnetic resonance imaging of congenital cardiac malformations. Radiology 150: 137-140; 1984. 10. Fossel, E.T.; Morgan, H.E.; Ingwall, J.S. Measurement of changes in high energy phosphate in the cardiac cycle by using sated P-31 nuclear magnetic resonance. Proc. Natl. Acad. Sci. U.S.A. 77: 3654; 1980. 11. Frank, J.A.; Feiler, M.A.; House, M.V.; Lauterbur, P.C.; Jacobson, M.J. Measurement of proton nuclear magnetic longitudinal relaxation times and water content in infarcted canine myocardium and induced pulmonary injury. C/in. Res. 27:217A; 1976 (Abstract). 12. Gamsu, G.; Webb, W.R.; Sheldon, P.; Kaufman, L.; Crooks, L.E.; Birnberg, F.A.: Goodman, P.; Hinchliffe,
13.
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W.A.; Hedgecock, M. Nuclear magnetic resonance imaging of the thorax. Radiology 147: 473-480; 1983. Hawkes, R.C.; Holland, G.N.; Moore, W.S.; Roebuck, E.J.; Worthington, B.S. Nuclear magnetic resonance (NMR) tomography of the normal heart. J. Comput. Assist. Tomogr. 5: 605-6 12; 198 1. He&ens, R.J.; Davis, P.L.; Crooks, L.; Kaufman, L.; Price, D.; Miller, T.; Margulis, A.R.; Watts, J.; Hoenninger, J.; Arakawa, M.; McRee, R. NMR imaging of the abnormal live rat and correlations with tissue characteristics. Radiology 141: 211-218; 1981. Herfkens, R.; Higgins, C.B.; Hricak, H.; Lipton, M.J.; Crooks, L.E.; Sheldon, P.E.; Kaufman, L. NMR imaging of atherosclerotic disease. Radiology 148: 16 l-l 66; 1983. He&ens, R.J.; Higgins, C.B.; Hricak, H.; et al. Nuclear magnetic resonance imaging of the cardiovascular system: normal and pathological findings. Radiology 147: 749-759; 1983. Higgins, C.B.; Goldberg, H.; Hricak, H.; Crooks, L.E.; Kaufman, L. Nuclear magnetic imaging of vascular abdominal viscera. Normal and pathologic findings. A.J.R. 147: 749-759; 1983. Higgins, C.B.; He&ens, R.; Lipton, M.J.; Sievers, R.; Sheldon, P.; Kaufman, L.; Crooks, L.E. Nuclear magnetic resonance imaging of acute myocardial infarctions in dogs: alteration in magnetic relaxation times. Am. J. Cardiol. 52: 184-188; 1983. Higgins, C.B.; Lanzer, P.; Stark, D.; Botvinick, E.; Schiller, N.B.; Crooks, L.; Kaufman, L.; Lipton, M.J. Imaging by nuclear magnetic resonance in patients with chronic ischemic heart disease. Circulation 69: 523-53 1; 1984. Hollis, D.P.; Nunally, R.L.; Jacobus, W.E.; Taylor, G.J. Detection of regional ischemia in perfused beating hearts by phosphorus nuclear magnetic resonance. Biothem. Biophys. Rex Commun. 75: 1086; 1977. Jacobus, W.E.; Taylor, G.J.; Hollis, D.P.; et al. Phosphorus nuclear magnetic resonance of perfused working rat hearts. Nature 26: 756; 1977. Jennings, R.B.; Sommers, H.M.: Kaltenbach, J.P.; West, J.J. Electrolyte alterations in acute myocardial ischemic injury. Circ. Res. 14: 260; 1964. Kaufman, L.; Crooks, L.E.; Sheldon, P.E.; Rowan, W.; Miller, T. Evaluation of NMR imaging for detection and quantification of obstruction in vessels. Invest. Radioi. 17: 554-60; 1982. Kaufman, L.; Crooks, L.; Sheldon, P.; Hricak, H.; Herfkens, R.; Bank, W. The potential impact of nuclear resonance imaging on cardiovascular diagnosis. Circulation 67: 251-257; 1983.
Cardiovascular applications of MRI 0 M. T. 25. Kramer, D.M. Imaging elements other than hydrogen. Kaufman, L.; Crooks, L.E.; Margulis, A.R., eds. Nuclear magnetic resonance imaging in medicine. Tokyo: Igaku-Shoin; 198 1. 26. Lanzer, P.; Botvinick, E.; Kaufman, L.; Lipton, M.J.; Schiller, N.B.; Crooks, L.; Higgins, C.B. Cardiac imaging using gated NMR. Radiology 1983 (in press). 27. Lanzer, P.; Lorenz, V.; Schiller, N.B.; Crooks, L.; Arakawa, M.; Kaufman, L.; Davis, P.L.; He&ens, R.; Lipton, M.J.; Higgins, C.B. Cardiac imaging using gated nuclear magnetic resonance. Radiology 1984 (in press). 28. McNamara, M.T.; Higgins, C.T.; Ehman, R.L.; Sievers, R.; Revel, D.; Brasch, R.C. NMR contrast enhancement of acute myocardial ischemia using the paramagnetic pharmaceutical complex Cd-DTPA. Radiology 1984 (in press). 29. Nunally, R.L.; Bottomley, P.A. “P NMR studies of myocardial ischemia and its response to drug therapies. J. Comput. Assist. Tomogr. 5: 296; 1981. 30. Pernot, A.C.; Ingwal, J.S.; Menasche, P.; et al. Evaluation of high energy phosphate metabolism during cardio-
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plegic arrest and reperfusion: a phosphrous-31 nuclear magnetic resonance study. Circulation 67: 1296; 1983. 31. Pykett, I.L. NMR 78; 1982.
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32. Salhany, J.M.; Peiper, G.M.; Wu, S.; et al. 3 1-P nuclear magnetic resonance measurement of cardiac pH in perfused guinea pig hearts. J. Mol. Cell. Curdiol. 11: 601; 1979. 33. Selwyn, A.; Jonathan, A.; Deanfield, J.; Pennock, J.; Bydder, G.M.; Steiner, R. Tomography of the heart and acute ischemia using nuclear magnetic resonance. Circulation (Suppl 2): 11-39; 1982. 34. Shalman, R.G.; Brown, T.R.; Ugurbil, K.; Ogawa, S.; Cohen, S.M.; den Hollander, J.A. Cellular applications of “P and “C nuclear magnetic resonance. Science 205: 160-166; 1976. 35. Williams, ES.; Kaplan, J.I.; Thatcher, F.; Zimmerman, G.; Knobel, S.B. Prolongation of proton spin lattice relaxation time of regionally ischemic canine hearts: effects of paramagnetic proton signal enhancement. Radiology 144: 343: 1982.
Mogneric Resonance Imaging. Vol. 2. pp. 167-186, 1984 Printed in the USA. All rights reserved.
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Copyright 0 I984 Pergamon Press Ltd.
l Continuing Education CARDIOVASCULAR APPLICATIONS OF MAGNETIC RESONANCE IMAGING MICHAEL T. MCNAMARA, M.D., AND CHARLES B. HIGGINS, M.D. Department
of Radiology,
University
of California,
San Francisco,
California
94143
Magneticresonance
imaging (MRI)is a completely noninvasive modality that has shown significant promise for the evaluation of the cardiovascular system. Our imaging technique employed electrocardiographic (ECG) gating, which resulted in well-resolved images of the cardiac structures. Patients and animals with a variety of cardiovascular abnormalities were also assessed with this technique; the abnormalities included acute and remote myocardial infarctions and their sequelae, atherosclerotic plaques, hypertrophic cardiomyopathy, pericardial diseases, and aneurysms. The diagnostic utility of MRI includes direct tissue characterization, and such utility may be further extended by the use of paramagnetic contrast media. In addition, metabolic imaging of elements other than hydrogen may further increase the clinical potential of MRI for assessment of the cardiovascular system. Keywords: Nuclear magnetic resonance, Cardiovascular system, Blood flow, Chemical shift, Paramagnetic
contrast
media.
INTRODUCTION
of very low intensity, providing a high degree of natural contrast within the walls of the cardiac chambers and large blood vessels. Intravenous injection of contrast medium is therefore not required in MRI. However, depending on the rate of flow and the imaging pulse sequences employed, the intensity of blood may be represented by a spectrum of signal intensities ranging from nearly absent to very intense. MRI has several advantages over the conventional x-ray methods for the evaluation of the cardiovascular system. First, MRI affords natural contrast between cardiovascular structures and flowing blood. Second, the contrast among soft tissues afforded by MRI is several times greater than that attainable with x-ray computed tomography (CT). Third, MRI offers tissue characterization by the magnetic relaxation times T, and T,. Studies have shown that normal and ischemic or infarcted myocardium can be differentiated by their T, and T, relaxation times.4’35 Finally, MRI uses no ionizing radiation. The purpose of this work is to describe the techniques whereby cardiovascular images are obtained using MRI and to demonstrate the clinical utility of MRI for the visualization of normal cardiovascular anatomy and for the detection of pathologic lesions. Future prospects for cardiovascular imaging are also discussed.
Magnetic resonance imaging (MRI) has shown enormous potential for the evaluation of cardiovascular disease.‘3.‘6,24 It is a completely noninvasive modality for obtaining images of the heart and blood vessels. However, to obtain diagnostic images of the heart, technical difficulties had to be overcome. These difficulties are caused by cardiac motion, which diminishes the magnetic resonance (MR) signal intensity of cardiac structures. Moreover, images obtained without gating represent neither end-diastole nor end-systole but are instead a temporally unpredictable average image. Additionally, the relaxation time constants T, (longitudinal relaxation time) and T, (transverse relaxation time) cannot be obtained from such images. However, the application of a gating technique that synchronizes the MR pulse sequences to specific phases of the cardiac cycle have dramatically improved the cardiac image quality and provided sharp discrimination of internal cardiac anatomy (Fig. I). It may be possible to characterize myocardium by T, and T2 with gated imaging, but this has not yet been proven. MRI of the cardiovascular system benefits greatly from the effects of flowing blood on image contrast. In general, rapidly flowing blood generates an MR signal RECEIVED4/4/84;
ACCEPTED 6/21/84.
Address Higgins. 167
correspondence
and reprint requests
to Dr. C. B.
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Magnetic
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1 80°
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Second Spin Echo (56 msec)
Fig. 1. Schematic representation of the spin-echo imaging technique showing application of a 90” RF pulse followed by a 180° pulse at a given time interval. The receipt of the subsequent signal (spin-echo) occurs at a time interval equal to twice the interval between 90° and 180° RF pulses.
INSTRUMENTATION
MRI studies were performed with a superconducting magnetic operating at 0.35 T (3.5 kG), with a resonant hydrogen frequency of 15 MHz. The magnet consists of niobium-titanium (Nb-Ti) filaments embedded in a copper matrix. This metal is cooled to near absolute zero (- 40 K) using liquid helium and liquid nitrogen, thereby eliminating resistance to current flow. Other types of magnets are currently being used, including permanent magnets, iron core magnets, and air core resistive magnets, with field strengths ranging from 0.1 T (1 kG) to 0.5 T (5 kG).’ The parameters used for spin-echo images employed echo delays (TE) of 28 ms (first echo) and 56 ms (second echo) and pulse sequence repetition times (TR) varying from 0.5 to 2.0 s. The echo delay is the time between the initial radiofrequency (RF) excitation of the proton nuclei and the receipt of the spinecho signal from the nuclei. The pulse sequence repetition time is the interval between successive excitation sequences within each imaged volume. Figure 1 illustrates the application of RF pulses using the spin-echo technique. With gated acquisition of images, the TR interval is equal to the RR interval of the electrocardiogram; the TR can be doubled by gating to every second heart beat. The technique for gating will be discussed shortly. As the RF sequences are applied, simultaneous weak magnetic field gradients are also applied along the x, y, and z axes of the image by three sets of resistive gradient coils. The use of these gradients allows spatial encoding of the volume of tissue being imaged to facilitate accurate image reconstruction and display. The RF pulse transmitter and receiver antennae (which may be one antenna that switches between a transmission mode and reception mode) are at 90° Our
angles to the main magnetic field gradient (x, y plane). Imaging time for each patient is determined by the pulse sequence repetition time, the number of lines along the y axis, and the number of signal averages obtained for each volume. An increase in any of these parameters will proportionately prolong imaging time. We employ a multiplanar imaging technique whereby RF sequences are applied at five adjacent 7-mm-thick axial sections during each RR interval. The delay between each axial section image is 100 ms, and imaging proceeds in a cranial-to-caudal direction. Thus, each data acquisition cycle begins in enddiastole and proceeds at lOO-ms intervals into systole in a caudal direction. GATING A significant loss in MR signal intensity occurs with nongated cardiac imaging due to cardiac wall motion and the sampling of data for reconstruction at random phases of the cardiac cycle. This results in generally poor image quality (Fig. 2). However, the data acquisition pulse sequences can be physiologically gated to the events of the cardiac cycle to avoid this loss of signal.‘6 A major consideration in the selection of gating techniques is that ferromagnetic hardware within the confines of the shielded imaging system may contribute to image distortion. We have evaluated three different gating techniques: blood pressure cuff plethysomography, which is sensitive to limb distension with arterial pulsation; laser-Doppler velocimetry, which detects relative changes in tissue microcirculatory blood flow beneath a 1-mm3 light probe; electrocardiography (ECG) using low-resistance electrodes that contain very little metal and thus are safe for use in the presence of high electromagnetic fields and rapidly changing RF pulses. The use of low-resistance elec-
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Fig. 2. Transverse MRI of a normal volunteer. The poorly resolved images (top) are nongated. Note the excellent anatomic resolution afforded by electrocardiographic gating (bottom). Natural contrast results from normal intracardiac and intraortic blood flow. ECG _ Eating_ allows clear distinction of cardiac wall thickness, papillary muscles, and intracardiac valves.
trodes and nonmagnetic ECG lead cables does not contribute to any measurable increase in the image noise level and the ECG signal is not affected by the RF fields. Variations in the temporal relationships between the R-wave and the plethysmographic and laser-Doppler velocimetric signals produce inconsistencies in the timing of the imaging sequences. By using the R-wave of the ECG cycle for gating, more precise synchronization to a specific segment of the cardiac cycle is obtained, compared with the other two methods. Since data acquisition is determined by the patient’s heart rate, the pulse sequence repetition rate (TR) is defined by the RR interval of the cardiac cycle. For example if the heart rate is 60 beats/min, the TR will be 1 .O s by gating to every heart beat or 2.0 s by gating to every other heart beat. In general, the image quality for the 28-ms spin-echo is usually superior to the 56-ms spinecho because it encompasses a proportionately shorter gating window (335% of the cardiac cycle). As a result, less cardiac motion occurs during the first spin-echo image and, depending on the patient’s heart rate, this may affect image quality. The heart is at end-diastole, or maximal filling, at the R-wave when the first image is obtained with the multislice technique. The subsequent four images are obtained at lOO-ms intervals further into the cardiac cycle because this time interval is required to obtain each image. Thus, for a patient with a heart rate of 60
beats/min, each cycle is 1 s long and the fifth slice (completed 500 ms after the R-wave) will be obtained about halfway into the cardiac cycle. For more rapid heart rates, however, the time required to obtain these images will constitute a greater proportion of the cardiac cycle. Thus the middle three images may occur during systole while the fifth image may be acquired during early diastole. Gated MRI can be performed in patients with very rapid heart rates because the imaging sequence can be gated to every other or even every third heart beat. This results in a longer TR interval, thereby allowing more recovery of longitudinal magnetization between sequences. Patients with marked arrhythmias, especially atria1 fibrillation and frequent premature ventricular contractions, cannot be adequately gated. MRI AND BLOOD
FLOW
The signal intensity (I) produced by blood on MRI is affected by several factors, including the magnetic relaxation times T, and T,, mobile hydrogen density, and blood flow as described by the MRI intensity equation for spin-echo images: I = N(H)f(v) exp represents the tion of nuclei intensity that move through
W-0 (-TE/TJ[l - exp (-TRIT,)I. local hydrogen density;f(v) is the fracthat are moving and the effect on the speed of these nuclei have as they the imaging plane; TE is the echo delay
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[time delay between application of the initial 90” RF pulse and the receipt of the signal (spin-echo) from these nuclei]; TR is. the time interval between successive pulse sequence repetitions; T, is the longitudinal or spin-lattice relaxation time; and T, is the transverse or spin-spin relaxation time. Based on this equation, one can see that blood flow will affect the MRI signal intensity. T, and T2 alterations in the imaging parameters will also affect signal intensity, even if N(I~Z)jiiv) is constant. The direction of motion of the nuclei through the plane being imaged is yet another factor that will affect the signal intensity; it is discussed later. For different ranges of blood flow rates, there will be characteristic appearances on spin-echo images. Stationary blood, such as that which may be encountered in patients with vascular occlusive disease or extravasated blood, will receive full exposure to the perturbing RF pulses and thus will have a strong MR signal intensity. However, protons in rapidly flowing blood will not experience complete RF pulse and gradient pulse sequence because their velocity will carry them out of the imaging plane before the completion of the
pulse sequence. For example, if a particular sequence requires 70 ms and the imaging plane is 7 mm thick, then a flow rate of greater than 10 cm/s will carry the nuclei completely out of the plane and the signal intensity will be zero. A third flow-related appearance arises from slowly flowing blood, that is, blood with a flow rate of less than about 10 cm/s. A fraction of slowly flowing hydrogen nuclei will experience the complete RF pulse and gradient pulse sequence, and will therefore appear with a signal intensity characteristic of stationary blood that has recovered some of its equilibrium magnetization. However, the remaining fraction of this particular image plane will not have experienced the initial 90” RF irradiation; they will enter the plane during the imaging sequence and have full magnetization. The net result is a collection of protons, some of which have not previously been irradiated and have full magnetization because they are flowing slowly enough to interact with the entire imaging sequence, and some which have been previously irradiated and therefore have partial magnetization. The intensity of the previously irradiated popu-
Fig. 3. Sequential cross-sectional images of an asymptomatic patient with a normal aorta and vena cava. The cranial level images are on the left and the caudal level images are on the right. Paradoxical enhancement is present within the aorta on the second spin-echo (arrow) cranial entrance level image on the left. There is an intense intraluminal signal within the vena cava on the second spin-echo image at the caudal entrance level (arrowhead), which also represents paradoxical enhancement.
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Fig. 4. Gated transverse MRI of the heart of a normal volunteer reveals normal cardiac contour, myocardial wall thickness, and ventricular chamber size. lation will be similar to that of stationary blood, while the intensity of the fully magnetized population will be greater than that of stationary blood. Thus, the net additive result of these two populations of nuclei within this plane is a paradoxically greater MR signal intensity than that of stationary blood. This MRI phenomenon of slowly flowing blood has come to be known as paradoxical enhancement (Fig. 3). When a volume of the body is exposed to the RF pulse sequences, paradoxical enhancement is greatest
Fig. 5. Sequential cross-sectional MRI of a normal human volunteer. The ascending aorta (straight black arrow) and descending (curved black arrow) aorta has a normal contour and smooth endothelial wall. Also clearly visible are the main (solid, straight white arrow), right (open white arrow), and left (curved white arrow) pulmonary arteries and pulmonary veins.
at the initial transverse level into which blood is flowing. This is because all proton nuclei flowing toward this level have not been previously irradiated. Thus, for abdominal imaging, the greatest intensity for the flow signal appears at the most cranial (superior) level for arterial flow and at the most caudal (inferior) level for venous flow, which are the respective entrance imaging levels for these structures (Fig. 3). This is because blood flowing in each of these directions has not experienced previous 90° RF irradiation before
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Fig. 6. Nongated transverse image at the level of the great vessels shows the superior vena cava (arrowhead) which has been displaced medially by a mass (bronchogenic carcinoma). In addition, the right pulmonary artery (arrow) is narrowed distally as a result of encasement by the bronchogenic carcinoma.
Fig. 7. Sequential transverse MRI of the abdomen. The solid retroperitoneal mass (apudoma, arrow) can be distinguished from the adjacent aorta, which lacks an intraluminal signal. The aorta has been displaced but not invaded by the tumor. Note the presence of signal within the inferior vena cava (arrowhead) at all levels, which suggests sluggish flow.
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entering their respective initial imaging sections. Also, due to the relatively slower flow in venous structures, there tends to be greater paradoxical enhancement in veins compared with arteries. The variation in intensity with the different Bow rates has proven useful in MRI because of the high degree of natural contrast that it provides between the blood in cardiovascular system and the cardiac walls or the walls of blood vessels. Rapidly flowing blood has a characteristically low MR signal intensity and this contrasts quite well with the myocardial and vascular wall tissue (Fig. 4). The absence of MR signal roughly shows a normal blood flow rate, or at least confirms a flow rate of greater than lo-15 ml/s. Paradoxically enhanced low-velocity flow has a greater signal intensity than the surrounding vascular walls and perivascular tissue, and therefore also provides natural contrast on MRI spin-echo images. MRI therefore requires no contrast media to depict blood flow. For a multislice imaging technique, the signal intensity of blood varies among the different transverse levels. With the multisection imaging mode, the nuclei entering the first section have not experienced previous
173
irradiation and consequently show paradoxical enhancement. The nuclei that enter the remaining contiguous slices have already undergone previous irradiation and will have diminished paradoxical enhancement or even none at all.
VASCULAR
APPLICATIONS
OF MRI
The natural contrast provided by the absence of signal from rapidly flowing blood with MRI allows visualization of the large mediastinal blood vessels without contrast media. Thus it is quite easy to discriminate blood vessels without contrast media,12 including the ascending and descending aorta, the pulmonary vessels, and the superior vena cava (Fig. 5). This natural contrast distinguishes such vessels from adjacent solid structures such as hilar or mediastinal tumors and lymph nodes (Fig. 6). There are other exciting possibilities offered by natural vascular contrast with MRI. Abdominal blood vessels are easily distinguished from surrounding organs and soft tissue structures, including retroperitoneal masses (Fig. 7). The utility of MRI in demon-
Fig. 8. Nongated transverse second spin-echo (TE = 56 ms) image of a patient with Type B dissection of the aorta. The true lumen (straight arrow) and false lumen (open arrow) are separated by an intimal flap (curved arrow). Slow flow within the false lumen is represented by high signal intensity within this lumen.
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strating masses and other abdominal diseases and their effects upon abdominal vasculature has been previously reported.17 MRI has also been useful in demonstrating abnormalities of the aortic wall. These include aortic aneurysms, aortic dissections with displacement of intimal flaps into the aorta, the true and false lumens, and slow flow within the false channels of aortic dissections (Fig. 8). Images of abdominal aortic aneurysms have demonstrated the outer wall that defines the true diameter of the aneurysm, the size of patent lumen, and the presence of wall thickening due to atherosclerotic debris or engrafted thrombus upon the wall of the aneurysm (Fig. 9). It may even be possible to detect acute bleeding and hematoma from a leaking aneurysm by the presence of high MR signal intensity characteristic of fresh blood. The high contrast between flowing blood and the vascular wall makes it possible to visualize atherosclerotic lesions projecting into the low signal intensity (flow void) of the aortic lumen. The appearance of the aorta and iliofemoral vessels on transverse and sagittal
MRI is characterized by a smooth endothelial surface and a uniformly thin aortic wall. On the other hand, in patients with known atherosclerosis, MRI has demonstrated eccentric thickening of the vessel wall and in some instances discrete atherosclerotic plaques projecting into the vascular lumina (Fig. 10). MRI has displayed both concentric and eccentric narrowing of the aorta (Fig. 11). Atherosclerotic lesions detected by MRI have been confirmed by angiography.15 Since atherosclerotic lesions contain variable accumulations of lipid, smooth muscle, fibroblasts, and calcification, these lesions may have variable appearances on MRI that proportionately correspond to these various constituents. Ex vivo MRI of iliac arteries has depicted atherosclerotic plaques that correlated with postmorten examinations.23 Fatty deposits produce high signal intensity, while smooth muscle and fibroblasts are associated with low-intensity regions in the plaques. Calcification, like cortical bone, lacks mobile protons and therefore appears as a low-intensity structure. The usual appearance of calcification is an arc or circumferential rim of low intensity.
Fig. 9. Sequential transverse images of the aorta and vena cava in a patient with an abdominal aortic aneurysm that extends to the bifurcation. The outer wall of the aneurysm is well visualized. The aneurysm is lined with atherosclerotic debris and thrombus material. The low intensity within the residual lumen represents flowing blood.
Cardiovascular applications of MRI 0 M. T. MCNAMARA AND C. B. HIGGINS
Fig. IO. Sequential transverse images in a patient with diffuse aortoiliac atherosclerotic disease show multiple atherosclerotic plaques protruding within the lumen with eccentric narrowing. The residual lumen has low signal intensity due to rapidly flowing blood.
NORMAL Excellent
resolution
CARDIAC
I I
ANATOMY
of the cardiac
morphology
175
has
been attained with ECG-gated MRI. In general, most imaging is performed in the transaxial plane, but direct coronal and parasagittal imaging can also be performed. Due to the rapid rate of normal blood flow there is a high degree of natural contrast between the cardiac walls and the cardiac chambers. A similar degree of contrast exists between the epicardial surface and the lungs due to the very low hydrogen density of the lungs. This high degree of natural contrast allows
the measurement of wall thickness and chamber size at various sites in the heart. Figure 12 demonstrates five contiguous transaxial slices, each section being 100 ms further into the cardiac cycle and thus in a different state of contraction relative to the previous section. Internal cardiac anatomy has been well delineated on MRI, including the papillary muscles (Fig. 13), the proximal left and right coronary arteries (Fig. 14), the cusps of the aortic valve, and the moderator band of the right ventricle (Fig. 15). The pericardium can be seen as a l-2 mm thick curvilinear structure of low signal intensity between the higher intensity myocardium or
Fig. 1 1. Transverse MRI of the intrarenal abdominal aorta in a patient with eccentric wall thickening and stenosis of the aorta. The magnified first echo (28 ms) and second echo (56 ms) images are pictured at right.
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Fig. 12. Sequential cranial-to-caudal transverse images. The cranial image (upper left) is acquired at end-diastole and each adjacent 7-mm thick section is imaged at a lOO-ms interval further into the cardiac cycle.
subepicardial fat and the pericardial fat (Fig. 16). When sufficient pericardial fat is present, the pericardium can also be seen lateral to the right atrium and left ventricle. MRI OF CARDIAC ABNORMALITIES
Congenital malformations Various congenital cardiac malformations have been imaged with excellent depiction of intracardiac anomalies.’ The atrioventricular valves, interatrial and interventricular septa, and aortic root are all well visualized simultaneously on single axial images. This “four-chamber” view permits the evaluation of wall thickness and chamber size, which are often abnormal
Fig. 13. Transverse MRI shows excellent internal cardiac anatomy, including the papillary muscles. Also note the right coronary artery with low signal intensity lying within the fat in the right atrioventricular groove (arrow).
in these patients. Sagittal views permit excellent visualization of the thoracic aorta but do not usually provide any important additional anatomic information. The congenital anomalies that have been analyzed thus far with MRI include atria1 and ventricular septal defects, aortic stenosis, mitral stenosis, tricuspid atresia, Ebstein’s anomaly, transposition of the great vessels, persistent truncus arteriosus, and car triatriaturn. In general, the thicker interventricular septum is more easily identified on MRI than the interatrial septum but, nevertheless, atria1 septal defects have been distinguished from complete absence of the interatria1 septum. Difficulty has been encountered in
Cardiovascular
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of MRI 0 M. T. MCNAMARA AND C. B. HIGGINS
Fig. 14. Image at the level of the aortic root shows a portion of the left anterior ascending coronary artery with low signal intensity (arrow). visualizing the right ventricular curved configuration.
outflow tract due to its
Myocardial wall abnormalities MRI permits the detection of focal myocardial wall thinning that results from previous myocardial infarctions.” The sites of previous infarcts are demonstrated by regions of myocardial thinning in the left ventricle and, by examining muliple adjacent axial images, it is possible to estimate the extent of infarcted left ventricle (Figs. 17 and 18). Left ventricular angiography and/or sector scan echocardiography have confirmed these findings. Several patients with aneurysms of the left ventricle had extreme wall thinning and bulging
that were readily identified with MRI. Posterior, anterior, and septal infarctions and aneurysms have also been identified. Some patients with such left ventricular wall aneurysms had findings on MRI suggestive of regional dyskinesis or akinesis with resultant stasis of blood flow. This appeared as a region of high signal intensity within the left ventricle lumen on the second spin-echo image (TE = 56 ms) (Fig. 18). Acute myocardial infarction: tissue characterization with magnetic relaxation times Investigators have shown that acute ischemia produces significant increase in T, relaxation times of myocardium relative to normal myocardium. Changes
Fig. 15. Transverse MRI shows excellent cardiac anatomic detail, including the moderator band of the right ventricle (arrow).
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Fig. 16. ECG-gated transverse image of normal volunteer shows the low-intensity thin curvilinear normal pericardium surrounding the left and anterior cardiac borders (arrows). The adjacent subepicardial fat and pericardial fat (high signal intensity) surround the pericardium and allow such visualization.
Fig. 17. ECG-gated transverse images of a patient with an old lateral wall myocardial infarction. Note the extreme wall thinning (arrow) on multiple levels, which allows the estimation of extent of the infarcted left ventricle.
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applications
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Fig. 18. Gated MRI of a patient who has suffered an old anterior wall myocardial infarction reveals the presence of a mural thrombus (left arrow) within the anterior left ventricle. This high-intensity thrombus can be distinguished from the adjacent thin anterior wall of the left ventricle. It is easier to distinguish the interface of thrombus and myocardium on the second spin-echo image (right arrows; TE = 56 ms). Note also the presence of increased signal intensity within the anterior left ventricle on the second spin-echo image that probably represents stasis of blood due to myocardial dyskinesis in addition to thrombus (curved arrow).
in magnetic relaxation times have been demonstrated as early as several minutes after coronary 0cclusion,35 but this finding is unconfirmed. An early imaging study suggested that acutely infarcted myocardium could not be detected without the injection of a paramagnetic contrast agent to demarcate perfusion.27 This report used a steady-state free precession technique for imaging. A more recent report utilizing the spin-echo technique showed that 24-h-old canine myocardial infarcts appear with a visibly greater signal intensity than adjacent myocardium due to a significantly longer T2 relaxation time of the infarcted myocardium (48.4 * 2.4 ms for infarcted myocardium versus 42.1 + 1.2 ms for normal myocardium). There was no overlap in the ranges of T, relaxation times for normal and infarcted myocardium.” In that report’* it was also noted that the mean T2 of infarcted myocardium (728 * 94.8 ms) was longer
than the mean T, of normal myocardium (650 + 87.4 ms). The T, of infarcted myocardium was longer than that of normal myocardium for each individual animal. There was a linear relationship between T2 values and percent water content (r = 0.90) but not between T, and water content (r = 0.47). More recently, in vivo gated
MRI
of I-7-day-old
myocardial
infarctions
has
shown increased signal intensity of the infarcted compared to normal myocardium (Fig. 19). High signal intensity was found in the anterior wall of the left ventricle following ligation of the left anterior descending coronary artery. No administration of contrast media was required.3’ Although the high degree of natural contrast between infarcted and normal myocardium results in good infarct detection without contrast agents, it is not possible to define myocardial perfusion without such agents. Recent work has demonstrated the potential
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for demonstrating acute ischemia following 1 min of coronary artery occlusion employing the paramagnetic complex gadolinium-DTPA (Gd-DTPA).** _
Fig. 19. Transverse ECG-gated spin-echo MRI of a dog with an anterior wall myocardial wall infarction produced by left anterior descending coronary artery occlusion 1 week prior to imaging. The infarct appears as a discrete highintensity segment within the anterior and anteroseptal walls of the left ventricle due to prolonged T2 relaxation time.
Cardiomyopathies MRI has shown significant promise in the evalua .tion of patients with hypertrophic cardiomyopath Y (HCM) (C.B. Higgins et al., unpublished data). MR I was able to clearly demonstrate the site and extent cIf hypertrophy (Fig. 20). In general, the distribution of hypertrophy varied from hypertrophy of the basal septum alone to hypertrophy of the entire septum with extension into the anteroapical segment. At the level of the left ventricular outflow tract most patients showed hypertrophy confined to the septal wall (nine patients) and a smaller number had involvement of the lateral as well as the septal wall (four patients). The longitudinal extent of hypertrophy was well demonstrated with sagittal MR images. Measurement of wall thickness was easily performed with the sharp images obtained with ECG gating (Fig. 19). While the thickness of septal and posterolateral myocardial walls in normal volunteers was 10.2 k 0.4 and 10.8 c 0.5 mm, respectively, all but one patient with HCM had a septal thickness of 15 mm or greater. The severity and distribution of hypertrophy were comparable on twodimensional echocardiography and MRI. Thus, MRI has proven to be an effective and completely noninvasive technique for demonstrating the presence, severity, and extent of hypertrophy in patients with HCM.
Fig. 20. Gated image of a patient with hypertrophic cardiomyopathy. There is extreme thickening of the anteroapical septum and lateral wall of the left ventricle. Gated MRI allows the measurement of myocardial wall thickness and the demonstration of the extent of involvement of hypertrophy.
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Fig. 21. Gated MRI of a patient with a pericardial effusion. The asymmetric effusion surrounds the anterior and lateral sides of the heart. Although the effusion in general has low signal intensity (arrow) there is some signal within, which presumably represents inflammatory debris and adhesions between parietal and visceral pericardium.
MRI of pericardial disease MRI has been effective in demonstrating the presence of abnormalities in patients with pericardial disease. The normal pericardium, a thin fibrous structure l-2 mm thick and of low signal intensity in normal patients (Fig. 16), appears thickened in patients with constrictive pericarditis. The low signal intensity probably reflects the mostly fibrous composition of this tissue. Inflammatory pericarditis, on the other hand, may appear differently on gated MR images. In addition to appearing thickened, the inflamed pericardium may produce a more intense signal owing either to the presence of edema or exudate or effusion, or a combination of all three elements. Figure 21 shows the pericardial effusion and inflammatory exudate, as well as adhesions between the parietal and visceral pericardium. Previous reports have indicated that MRI may be useful for the diagnosis of a variety of clinical pericardial diseases. Such useful information would entail anatomic (pericardial thickness, presence of effusion, etc.) and pathologic information based on T1 and T, relaxation times and signal intensity.
FUTURE
OF CARDIOVASCULAR
MRI
The role of MRI in cardiovascular imaging requires additional clinical experience before it can be clearly defined. It offers a distinct advantage over conventional x-ray techniques in that it does not require contrast media for imaging. MRI also offers tissue
characterization, which x-ray CT does not. And with the use of contrast media, it appears that noninvasive quantification of blood flow and perfusion defects may be possible. Studies have described characteristic T, and T2 relaxation times for normal and pathological tissues in animals and in humans.6.7,‘4 This includes characteristic relaxation times for normal and ischemic and infarcted myocardium in animals.4~“~‘6~27~33~3s Although characteristic ranges for myocardial T, and T2 relaxation times have not clearly been established on gated MRI in humans, it seems likely that further experience will lead to them in myocardial tissue as well as in other organs. Although acute canine myocardial infarctions have been seen on ex vivo spin echo MR images without contrast media,‘“,3’ it appears that paramagnetic pharmaceuticals offer significant promise in improving both diagnostic sensitivity and specificity in detecting such lesions. This may be particularly applicable to more acute perfusion abnormalities, which may otherwise be occult on MRI. Human clinical trials are presently being conducted in Europe using Gd-DTPA, a very powerful paramagnetic agent, for urographic enhancement and for enhancement of neoplastic lesions. Although MRI to date has been exclusively proton imaging due to hydrogen’s great natural abundance, investigators are also measuring chemical shifts of sodium-23, carbon- 13, and phosphorus-33.*’ Sodium imaging may prove to be useful in detecting ischemia
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because of the reversal of sodium and potassium levels that occurs in cells whose membranes have been damaged by ischemia.‘*‘* This application has been used with a very strong magnetic field strength.8 Carbon-l 3 for fatty acid metabolism may also prove to be useful in myocardial imaging,2934 and imaging of phosphorus-3 1 may be important in demonstrating myocardial high energy phosphate metabolism.‘0*20~ 2’.29*30*32 Studies have already demonstrated regional
changes in concentration of phosphorus compounds during ischemia20+29*30and a return to normal concentration as normal flow is restored.29 In vivo application of this technique using topical MRI has been performed but presently requires a great length of time for such images.’ Perhaps the combined use of hydrogen and chemical shift imaging with further improvement in instrumentation and higher field strengths may provide the optimal features for clinical use.
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Cardiovascular applications of MRI 0 M. T. 25. Kramer, D.M. Imaging elements other than hydrogen. Kaufman, L.; Crooks, L.E.; Margulis, A.R., eds. Nuclear magnetic resonance imaging in medicine. Tokyo: Igaku-Shoin; 198 1. 26. Lanzer, P.; Botvinick, E.; Kaufman, L.; Lipton, M.J.; Schiller, N.B.; Crooks, L.; Higgins, C.B. Cardiac imaging using gated NMR. Radiology 1983 (in press). 27. Lanzer, P.; Lorenz, V.; Schiller, N.B.; Crooks, L.; Arakawa, M.; Kaufman, L.; Davis, P.L.; He&ens, R.; Lipton, M.J.; Higgins, C.B. Cardiac imaging using gated nuclear magnetic resonance. Radiology 1984 (in press). 28. McNamara, M.T.; Higgins, C.T.; Ehman, R.L.; Sievers, R.; Revel, D.; Brasch, R.C. NMR contrast enhancement of acute myocardial ischemia using the paramagnetic pharmaceutical complex Cd-DTPA. Radiology 1984 (in press). 29. Nunally, R.L.; Bottomley, P.A. “P NMR studies of myocardial ischemia and its response to drug therapies. J. Comput. Assist. Tomogr. 5: 296; 1981. 30. Pernot, A.C.; Ingwal, J.S.; Menasche, P.; et al. Evaluation of high energy phosphate metabolism during cardio-
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