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A correction has been published: N Engl J Med 1994;330(2):152.

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Volume 328:828-832 March 25, 1993 Number 12
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A Preliminary Report Comparing Magnetic Resonance Coronary Angiography with Conventional Angiography
Warren J. Manning, Wei Li, and Robert R. Edelman

 

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ABSTRACT

Background The ability to assess the patency of coronary arteries by noninvasive means would represent an important advance. We have developed a magnetic resonance imaging (MRI) coronary angiographic technique that permits the display of areas of abnormal coronary blood flow. We have compared this method with conventional contrast angiography for the identification of coronary-artery stenoses.

Methods MRI coronary angiography was performed with an electrocardiographically gated sequence in 39 subjects, 33 to 84 years of age, who were scheduled for elective cardiac catheterization with coronary angiography. Sequential overlapping transverse and oblique sections were acquired during periods of breath-holding and were displayed as cine loops for analysis. MRI and conventional angiographic data were compared in a blinded manner. The four major epicardial coronary arteries were classified by MRI coronary angiography as being normal (or having only minimal irregularities) or as having disease that was moderately severe to severe.

Results The sensitivity and specificity of MRI coronary angiography, as compared with conventional angiography, for correctly identifying individual vessels with >= 50 percent angiographic stenoses were 90 percent and 92 percent, respectively. The corresponding positive and negative predictive values were 0.85 and 0.95, respectively. The sensitivity and specificity of the technique were 100 percent and 100 percent, respectively, for the left main coronary artery, 87 percent and 92 percent for the left anterior descending coronary artery, 71 percent and 90 percent for the left circumflex coronary artery, and 100 percent and 78 percent for the right coronary artery.

Conclusions MRI coronary angiography provides a new approach to evaluating the patency of coronary arteries. These preliminary data suggest that this technique may provide a noninvasive means of evaluating patients with known or suspected coronary artery disease. At its current stage of development, this procedure may be most helpful for excluding clinically important stenoses in patients referred for diagnostic contrast angiography. .

Cardiovascular disease remains the leading cause of death in the United States, with more than 1.5 million myocardial infarctions and one fourth of all deaths attributed to coronary artery disease each year1. Invasive coronary angiography is currently the only clinical method available with which to visualize the epicardial coronary vessels. Despite the availability of numerous noninvasive tests for the detection of coronary-artery stenoses, coronary angiography remains a common diagnostic procedure, with up to 20 percent of the procedures performed each year in the United States demonstrating no evidence of serious coronary-artery stenoses2. The ability to assess the patency of the coronary arteries by noninvasive means would represent an important advance in patient care and might reduce health care costs. Information regarding the coronary arteries could then be acquired with minimal risk, both for patients with suspected coronary disease and for patients with known disease who are being followed.

Magnetic resonance imaging (MRI) is ideally suited for evaluating the heart, providing excellent soft-tissue contrast without the need for the administration of a contrast agent. Initial attempts at MRI of the proximal coronary arteries had limited success because of the occurrence of artifacts resulting from prominent cardiac and respiratory motion3,4. More recently, MRI angiography of vessels similar in caliber to the coronary arteries has been developed5,6. These gradient-echo techniques depict laminar blood flow as a bright signal, whereas regions of turbulent, markedly diminished, or absent flow are displayed as signal voids. We have recently developed an MRI pulse sequence that can image the coronary vessels7. The purpose of this prospective study was to compare the results of noninvasive MRI coronary angiography with findings obtained from elective cardiac catheterization with coronary angiography.

Methods

Study Population

The study population consisted of 39 adults (35 men and 4 women), ranging in age from 33 to 84 years (mean, 54), who were referred for elective cardiac catheterization with coronary angiography. The patients were recruited from among those scheduled for outpatient testing (as part of their precatheterization evaluation) at a time when the MRI unit was available for research. If no subject was available, then inpatients who had recently undergone catheterization were solicited. Patients with pacemakers, intraauricular or intraocular implants or debris, or intracranial clips were excluded. MRI coronary angiography was performed within one week before (21 subjects) or after (18 subjects) contrast angiography. All studies followed the guidelines of the committee on clinical investigations at the hospital, and informed consent was obtained from all participants.

MRI

MRI was performed with a superconducting 1.5-T Magnetom SP whole-body imaging system (Siemens Medical Systems, Iselin, N.J.); a standard planar elliptical spine coil was used as a radiofrequency receiver. The electrocardiographic leads were attached, and the patients were placed flat on their stomachs with their hearts positioned directly above the surface coil. The imaging technique employed an ultrafast gradient-echo sequence with incremented flip angle series and k-space segmentation, such that six or eight phase-encoding steps were acquired in rapid sequence, constituting one segment7. Sixteen or 20 interleaved segments were acquired in order to complete a 120-by-256, 128-by-256, or 160-by-256 matrix during a single period of breath-holding. A chemical shift-selective fat-saturation pulse was applied before each segment to void the signal from surrounding epicardial fat and thus enhance the signal from coronary blood flow. The sequence was electrocardiographically gated to allow the acquisition of each segment in mid-diastole. A repetition time of 13 msec and an echo time of 8 msec were used, resulting in an effective temporal resolution of 78 to 104 msec. For transverse imaging, we used a slice thickness of 5 mm and a 230-mm field of view (in-plane resolution, 1.4 to 1.9 mm by 0.9 mm). Transverse images were obtained over a vertical distance of 2 to 3 cm, beginning at the level of the aortic sinus, with an overlap of 2 to 3 mm. Single- and double-oblique imaging was conducted in a similar manner along the axis defined by the origin of the right and left main coronary arteries as identified on transverse sections. The total imaging time averaged less than 45 minutes per patient.

Interpretation of MRI Data and Statistical Analysis

Individual transverse and oblique magnetic resonance images were stored on optical disks for subsequent recall and analysis. Because only portions of a vessel were imaged in any one section, images from sequential images taken from transverse or oblique sections (or both) were displayed in cine format and analyzed independently by two observers without knowledge of the patient's name, age, sex, or other clinical data (including the results of contrast angiography). The four major epicardial coronary arteries (left main, left circumflex, left anterior descending, and right coronary arteries) were initially assessed as adequate or inadequate for evaluation and then individually graded as being normal or having only mild disease (minimal or no luminal irregularities) or as having disease that was moderately severe to severe (marked attenuation of luminal diameter or signal void). Differences in grading between the independent observers were resolved by consensus after the images were reviewed at a separate session (again without knowledge of any clinical data). The sensitivity, specificity, and predictive value of MRI coronary angiography were determined.

Contrast Angiography

Left-heart catheterization and conventional coronary angiography were performed according to standard techniques8. Contrast coronary angiographic images were recorded on 35-mm cineangiographic film, and multiple views of each coronary segment were obtained. Contrast angiographic images were interpreted by the staff of the cardiac catheterization laboratory, who were unaware of the MRI findings. Individual arteries were classified as being normal or having only mild disease if the maximal narrowing of the diameter was less than 50 percent and as having disease that was moderately severe or severe if the maximal narrowing was 50 percent or greater.

Results

MRI studies were successfully performed in all subjects without complication. The left coronary system was not imaged in two patients because of time constraints. Studies of three vessels (the left anterior descending, left circumflex, and right coronary arteries) were thought to be uninterpretable by both independent observers and were excluded from further analysis. Studies of three vessels were thought to be interpretable by only one of the observers at the initial reading, but by both observers at the consensus reading. The 147 arteries available for analysis included 52 with moderately severe or severe disease on contrast angiography: 2 left main, 23 left anterior descending (12 proximal and 12 middle segments), 7 left circumflex (5 proximal and 2 middle segments), and 20 right coronary (9 proximal, 11 middle, and 3 distal segments) arteries. Four vessels (one left anterior descending coronary artery and three right coronary arteries) had stenoses in two regions. Contrast angiography demonstrated that 10 patients did not have clinically important coronary-artery stenoses, whereas among the other 29 patients, 2 had left main and triple-vessel coronary artery disease, 13 had single-vessel disease, 10 had double-vessel disease, and 4 had triple-vessel disease.

An example of a series of MRI scans in a patient without clinically important stenosis of the right coronary artery is shown in Figure 1 with the corresponding contrast angiogram, whereas the same types of images from a patient with a tight stenosis of the right coronary artery are shown in Figure 2. The MRI scan and angiogram shown in Figure 3 are of normal left main and left anterior descending coronary arteries.


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  		Figure 1. Sequential Oblique MRI Scans (Panel A, Panel B, and Panel C) and Contrast Angiogram (Panel D) of the Right Coronary Artery (White Arrows) in an 84-Year-Old Patient without Substantial Stenoses on Angiography.

The open arrow identifies the catheter. LV denotes left ventricular cavity, RV right ventricular cavity, and A aortic root.

 

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  		Figure 2. Oblique MRI Scan (Panel A) and Contrast Angiogram (Panel B) of the Right Coronary Artery in a 35-Year-Old Patient with Stenosis of the Middle Segment of the Artery.

Note the abrupt loss of signal (open arrow) in the middle portion of the artery (the more distal vessel was not visualized in adjacent sections) in Panel A and the stenosis (solid arrow) in Panel B at the site of the signal loss.

 

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  		Figure 3. Transverse MRI Scan (Panel A) and Contrast Angiogram (Panel B) Demonstrating Normal Left Main and Left Anterior Descending Coronary Arteries (Solid Arrows) in a 47-Year-Old Patient with Angiographically Normal Vessels.

In Panel A, a segment of the great cardiac vein (open arrow) runs parallel to the left anterior descending artery.

 
The sensitivity and specificity of the MRI angiographic technique for correct identification of individual coronary vessels with moderately-severe-to-severe stenoses were 90 percent and 92 percent, respectively. The corresponding positive and negative predictive values were 0.85 and 0.95. The agreement between the two observers was 0.92. Of five coronary arteries erroneously classified by MRI as not having clinically important disease (false negative results), two vessels had moderate (50 to 60 percent) stenoses by contrast angiography. Another patient had an osteal occlusion of his left anterior descending coronary artery, with extensive collateral involvement, and the vessel was misclassified as not having clinically important disease. Five of eight coronary arteries that appeared abnormal on MRI had mild (20 to 40 percent) stenoses (false positive results). The sensitivity, specificity, and predictive values of each of the four vessels studied are summarized in Table 1. The sensitivity and specificity of the technique for correctly classifying individual patients as having or not having serious coronary disease were 97 percent and 70 percent, respectively. The positive and negative predictive values for patients in our study population, with an incidence of coronary artery disease of 0.74, were 0.90 and 0.88, respectively.

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  		Table 1. Sensitivity, Specificity, and Predictive Value of MRI Coronary Angiography.

 
Discussion

In this blinded study, we have demonstrated the ability of noninvasive MRI coronary angiography to identify substantial stenoses correctly within the major coronary arteries in a group of patients undergoing conventional contrast coronary angiography. Despite the small caliber, mobility, and tortuosity of the coronary arteries, their patency can be assessed with an ultrafast MRI angiographic technique during periods of breath-holding. Transverse sections permitted assessment of the left main, left anterior descending, and proximal right coronary arteries, whereas oblique imaging sections were best for depicting the left circumflex artery and the more distal segments of the right coronary artery. In patients with stenoses, there was a marked tapering of the luminal diameter or an abrupt cessation of the signal (a signal void) corresponding to the stenotic area identified on contrast angiography. These preliminary data suggest that in its current state of development, MRI coronary angiography may be most helpful as a screening test to exclude clinically important coronary stenoses in patients who might otherwise be referred for diagnostic contrast angiography. Although only two patients with disease of the left main coronary artery were studied, the technique accurately identified the more numerous stenoses in the proximal segments and midportions of the other major epicardial vessels.

With standard MRI spin-echo and gradient-echo techniques, visualization of the coronary arteries has previously been erratic and limited to the proximal segments of the vessels3,4. This was probably due to cardiac and respiratory motion. Cardiac motion can be divided into four phases, with rapid movement during ventricular systole and less vigorous motion during rapid ventricular filling in early diastole and during atrial systole9. Between these last two events, however, is a period of relative diastasis, with little intracavitary blood flow and minimal cardiac motion, while coronary blood flow remains high10. Our use of a breath-holding sequence eliminated respiratory motion, whereas cardiac motion and temporal resolution were minimized by obtaining the image during mid-diastole and using k-space segmentation, respectively. More recently, other MRI techniques have been used to image the proximal coronary arteries in healthy subjects, including MRI subtraction methods,11 three-dimensional MRI angiograms formed by stacking two-dimensional planar images,12 and fast spiral MRI13. The successful application of these methods in patients with coronary artery disease has not yet been reported.

The spatial resolution of MRI coronary angiography and the use of relatively thick sections currently preclude precise quantification of the severity of focal stenoses. The gradient-echo MRI angiographic technique distinguishes rapidly moving, nonturbulent blood flow (which appears bright in the images) from areas of turbulent or slow flow (which appear dark). Focal stenoses in the coronary arteries result in turbulence and signal voids. Similar findings have been well described with the use of MRI to evaluate the carotid arteries14.

Given the sensitivity of MRI coronary angiography in identifying abnormal blood flow as well as the severity of the stenosis, perfect concordance with contrast angiography would not be expected. Minor luminal irregularities or ulcers may cause substantial local turbulence, which may result in the loss of the MRI signal. In addition, there is an imperfect relation between the maximal extent of a stenosis and its hemodynamic consequences, with eccentric lesions having a different hemodynamic profile than symmetric lesions15. Despite these limitations, contrast angiography remains the clinical standard by which new techniques for the identification of coronary stenoses are validated. However, the ability of gradient-echo MRI coronary angiography to identify focal areas of turbulence within the epicardial vessels may be clinically useful. A basic tenet of one of the current theories of the pathogenesis of atherosclerosis is that chronic injury to the arterial endothelium is caused by abnormal blood flow in the arterial tree16. These regions of abnormal blood flow may be discernible by MRI coronary angiography, unlike other imaging techniques.

Echocardiography is the only other noninvasive technique that has successfully imaged portions of the coronary arteries. Conventional two-dimensional transthoracic echocardiography allows visualization of the left main and proximal right coronary arteries in 60 to 90 percent of patients17,18 but has had only limited success in imaging the left anterior descending and left circumflex coronary arteries17,19 .More recently, transesophageal echocardiography, performed with higher-frequency transducers, has been shown to detect stenoses of the left main coronary artery in 90 percent of subjects20. The clinical usefulness of this method is limited, however, given the relatively low incidence of disease of the left main coronary artery, and this approach would be more invasive than MRI coronary angiography.

A limitation of MRI coronary angiography is the requirement of a regular heart rhythm and of breath-holding for 12 to 18 seconds. Frequent extrasystoles result in the degradation of the quality of the image. None of our subjects had difficulty holding their breath, though this may be a problem for some. If so, a coarser matrix or an increased number of phase-encoding steps per QRS complex could be used. Finally, the current spatial resolution of MRI angiography precludes reliable identification of stenoses in branch vessels. The use of faster and stronger gradient coils and improved surface coils would improve spatial resolution and the signal-to-noise ratio.

In conclusion, MRI coronary angiography provides a new approach for the evaluation of coronary-artery patency. Although the approach requires further development and clinical testing before it can be recommended for routine clinical use, it may soon provide a noninvasive alternative for the detection of coronary disease in patients with chest pain or in asymptomatic persons with multiple risk factors for coronary disease. Moreover, MRI coronary angiography may be combined with MRI perfusion imaging21,22,23 and with anatomical and functional MRI to provide a comprehensive cardiac evaluation.

Supported by a grant from the National Institutes of Health (R01 HL45180). Dr. Manning is supported in part by a Physician-Scientist Award (AG00294) from the National Institute on Aging.

We are indebted to Drs. Deborah Burstein, William Grossman, and Sven Paulin for their valuable advice and helpful review of the manuscript and to the members of the Cardiovascular Division for assistance with patient recruitment and for angiographic interpretation.


Source Information

From the Cardiovascular Division of the Department of Medicine (W.J.M.) and the Department of Radiology (W.J.M., W.L., R.R.E.), Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory, Beth Israel Hospital, and Harvard Medical School, Boston.

Address reprint requests to Dr. Manning at the Cardiovascular Division, Beth Israel Hospital, 330 Brookline Ave., Boston, MA 02215.

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MRI Coronary Angiography
Bittl J. A., Paulin S., Manning W. J., Edelman R. R., Steinberg E. P.
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N Engl J Med 1993; 329:507-508, Aug 12, 1993. Correspondence

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