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(Circulation. 1995;91:1347-1353.)
© 1995 American Heart Association, Inc.

Articles

Noninvasive Determination of Infarct Artery Patency By Cine Magnetic Resonance Angiography

W. Gregory Hundley, MD; Geoffrey D. Clarke, PhD; Charles Landau, MD; Richard A. Lange, MD; John E. Willard, MD; L. David Hillis, MD; Ronald M. Peshock, MD

From the Department of Internal Medicine, Cardiovascular Division (W.G.H., C.L., R.A.L., J.E.W., L.D.H., R.M.P.), and Department of Radiology (G.D.C., R.M.P.), University of Texas Southwestern Medical Center, Dallas.

Correspondence to Ronald M. Peshock, MD, Mary Nell and Ralph B. Rogers Magnetic Resonance Center, University of Texas Southwestern Medical Center, 5801 Forest Park, Dallas, TX 75235-9085.

	Abstract

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Background In survivors of myocardial infarction, restoration of antegrade flow in the infarct artery reduces morbidity and mortality. At present, coronary artery patency must be assessed invasively with contrast angiography. A noninvasive method of evaluating infarct artery patency would be useful in managing survivors of infarction. This study was performed to determine whether magnetic resonance (MR) imaging could reliably assess infarct artery patency in this patient population.

Methods and Results Eighteen survivors of myocardial infarction (11 men and 7 women, aged 35 to 74 years) who were consecutively referred for cardiac catheterization underwent contrast coronary angiography and cine MR coronary angiography. Sequential overlapping images of the infarct artery were acquired with cine MR during 15- to 20-second periods of breath-holding. In each study, proximal, middle, and distal segments of infarct arteries were classified as having antegrade, collateral, or no flow. The infarct artery was the left anterior descending in 10 patients, the right anterior descending in 7, and the circumflex in 1. When compared with the results of contrast angiography, MR imaging correctly identified the presence or absence of antegrade flow in the infarct artery of all 18 patients. In addition, cine MR coronary angiography with presaturating pulses correctly established the presence or absence of collateral filling of the distal portion of occluded arteries in 6 of 7 subjects.

Conclusions In survivors of myocardial infarction, cine MR coronary angiography can reliably determine the patency and direction of flow in the infarct artery.

Key Words: myocardial infarction • magnetic resonance imaging • angiography

	Introduction

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In patients with myocardial infarction, the early restoration of antegrade flow in the infarct artery improves left ventricular systolic function and survival.^{1 2 3} In addition, late restoration of antegrade flow appears to improve survival independent of its influence on left ventricular performance,^{4 5} in that survivors of infarction with a patent infarct artery have a better long-term survival rate than that of survivors whose infarct artery remains occluded.^{6 7} At present, selective contrast coronary angiography is the only means of reliably assessing infarct artery patency, but it is invasive, expensive, and associated with some morbidity and mortality.⁸ A rapid, noninvasive method of assessing the patency of the infarct artery would be useful in determining which patients may benefit from subsequent invasive procedures.

Images of the carotid,⁹ peripheral,¹⁰ and renal¹¹ arteries have been obtained with magnetic resonance (MR) imaging (MRI). By applying multiple phase-encoding steps within each cardiac cycle, investigators have reduced imaging times and visualized coronary arteries during 15 to 25 seconds of breath-holding.^{12 13} However, these studies obtained single images of coronary arteries in diastole and could not be used to assess the direction of flow. We have developed a method of obtaining cine coronary MR angiograms by acquiring multiple images during a single breath-hold, thereby allowing an assessment of anatomy and direction of flow. The present blinded, prospective study was performed to assess the ability of this technique to determine the patency of the infarct artery in survivors of myocardial infarction.

	Methods

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Study Population
The study was approved by the Institutional Review Board for Human Experimentation at the University of Texas Southwestern Medical Center at Dallas, and all participants gave written, informed consent. The study population consisted of 18 adults (11 men and 7 women, aged 35 to 74 years), who had sustained a myocardial infarction, as assessed by each patient's primary physician,¹⁴ and who were consecutively referred for cardiac catheterization because of postinfarction angina, a positive submaximal exercise test, or depressed left ventricular systolic function on echocardiography. Patients were ineligible for the study if they had an indwelling pacemaker, intracranial clips, intra-auricular or intraocular implants, a history of metal fragments in the eye, claustrophobia, a heart rhythm other than normal sinus, or an unstable medical condition that precluded transport from an intensive care unit. Each patient underwent an MR coronary angiography study and contrast coronary angiography. In 14 of the 18 patients, selective contrast coronary angiography and MRI were performed within 24 hours of one another, in 3 patients within 2 days, and in 1 patient within 6 days. In 12 patients MRI was performed 1 to 2 hours before catheterization.

MRI Technique
MRI was performed with a 1.5-T Picker Vista HPQ whole-body imaging system (Picker International, Inc) with a standard quadrature spine coil (20x26 cm²) used as a radiofrequency receiver. Each patient underwent MRI in the supine position after placement of ECG monitoring leads, a respiratory gating belt, and the surface coil on the chest. The strategy for determining infarct artery patency was to (1) review the 12-lead ECG and, based on published criteria,¹⁵ select the likely infarct artery; (2) perform MR scout images to locate the left ventricle; (3) image the infarct artery from its origin to within 3 cm of the cardiac apex; and, in subjects in whom signal dropout occurred within the vessel, (4) presaturate the proximal portion of the vessel to determine the presence or absence of antegrade flow distal to the region of dropout.

Scout images were obtained using a fast field echo sequence with first-moment compensation in the readout and slice-select directions, a repetition time of 20 milliseconds, and an echo time of 9.4 milliseconds. Phase-encoding grouping was used to obtain multiple-phase encoding steps for each frame during a cardiac cycle. Coronal and long-axis views of the heart were obtained with a phase-encoding grouping size of 4 (yielding 6 frames per cardiac cycle) to 10 (yielding 4 frames per cardiac cycle). These localizing scans were 8-mm slices, had a field of view of 50 cm, a flip angle of 40°, and a resolution of approximately 3 mm in the phase-encoding direction and 2 mm in the readout direction.

After obtaining scout views, we imaged the infarct artery in short-axis, tangential, and longitudinal planes. The purpose of these scans was to visualize the infarct vessel from its origin to 3 cm from the cardiac apex. Images were obtained with the same number of phases and phase-encoding grouping sizes as those of the scout images, with two modifications: (1) the field of view was decreased to 22 to 26 cm, thereby decreasing pixel sizes to 1.0 to 1.2 mm in the phase-encoding direction and 0.8 to 1.0 mm in the readout direction, and (2) an in-plane presaturation pulse was applied at the first frame of each cardiac cycle (sequence A, Fig 1). The presaturation pulse suppresses the signal from the tissue in the slice so inflowing blood appears bright compared with stationary tissue. Applying the presaturating pulse in early systole provided good contrast in multiple frames during early and middle diastole when coronary flow is high. When viewing the images in a cine loop, we found this to be the best strategy for preserving important information in early diastole. The short-axis views were single-slice acquisitions, whereas the tangential and longitudinal views were four-slice acquisitions (8-mm slices, each with 4-mm overlap). All views of the infarct artery were obtained with sequence A, and no fat saturation pulses were used. Fig 2 illustrates the typical imaging strategy used for the left anterior descending artery.

View larger version (18K): [in this window] [in a new window]   Figure 1. Phase-encoding grouping is used to acquire multiple-phase encoding steps with each cardiac cycle. The small gray stripes indicate different phase-encoding steps, and the dark stripes indicate the application of presaturation pulses. Numbered brackets indicate that each group of phase-encoding steps is used for an image or frame at a particular point in the cardiac cycle. In the example shown, five frames are acquired, resulting in a cine loop with images at five different points in the cardiac cycle. Two different imaging sequences were used in this study. Sequence A was used to initially view the infarct artery. The groups of gray stripes indicate a phase-encoding grouping size of 7, meaning that seven phase-encoding steps were acquired for each frame in the cardiac cycle. The single dark stripe in sequence A indicates a single in-plane presaturation pulse applied before the first frame of the cardiac cycle. The presaturation pulse suppresses the signal from the tissue in the slice so inflowing blood appears bright compared with stationary tissue. In vessels in which significant signal dropout occurred along the course of the vessel, sequence B was used to determine the direction of flow within the vessel. Presaturation pulses (paired dark stripes) were applied prior to the acquisition of each frame acquired during the cardiac cycle. This reduced the signal from the proximal portion of vessels when all the frames were viewed in cine format.

View larger version (23K): [in this window] [in a new window]   Figure 2. The typical imaging planes for the left anterior descending artery (LAD) are shown. The short-axis plane was used to identify the LAD in cross section. The longitudinal and tangential planes represent sets of four 8-mm slices, each overlapped by 4 mm, which were used to identify the LAD along its long axis. The gray crossed slices schematically represent the presaturation pulses used in sequence B (see Fig 1), applied across the proximal LAD to distinguish antegrade from collateral flow in the distal vessel (see text).

Infarct arteries were imaged in two to three orthogonal planes. Arterial segments were divided into proximal, middle, and distal portions, according to previously published techniques,¹⁶ with two exceptions: (1) the posterior descending artery was included as a portion of the distal right or circumflex arteries, and (2) the circumflex artery was divided into two segments: proximal, which included portions of the artery up to the first obtuse marginal branch, and distal, which included portions of the artery past it. After these scans were finished, if an area of signal dropout was seen along the course of the vessel of interest, imaging sequence B (Fig 1) was used to determine whether the signal dropout was due to a stenosis or an occlusion.

Two aspects of the presaturation technique used for determining the presence or absence of antegrade flow in the cases in which signal dropout occurred (sequence B) were different from the technique used initially to image the infarct artery (sequence A). The first was that the presaturating planes in sequence B (the two gray slices in Fig 2) were not in the imaging plane of the vessel. They were positioned to intersect the vessel segment proximal to the point of signal dropout and to saturate blood flowing antegrade through the infarct artery. The flip angle of each presaturation slice was limited such that the proximal vessel segment (the point of intersection of the two pulses) received maximal saturation, and the proximal aorta or left ventricle received minimal saturation. In this way, blood flowing to other coronary beds from the proximal aorta or left ventricle was mixed with unsaturated blood. At any point during the cardiac cycle, blood flowing antegrade through the proximally presaturated region would cause signal loss in the distal vessel. If retrograde flow was present (via collaterals), blood filling the distal portion of the coronary artery would not have been exposed to proximal presaturation pulses and would therefore appear bright. This technique is fundamentally similar to standard MR angiography for suppressing signal in arteries or veins and determining the direction of flow.¹⁷

The second difference in the presaturation pulses used in sequence B was their temporal placement in relation to the imaging pulses during the cardiac cycle. As shown in Fig 1, the presaturation pulses occurred before each frame in the cardiac cycle, so blood in the proximal coronary artery was saturated just before each frame was imaged. The use of repeated saturation with multiple frames in the cardiac cycle was necessary to ensure that antegrade flow did not occur at some point during the cardiac cycle when the images were reviewed in cine format. If the vessel distal to the presaturation pulses became dark, this was interpreted as movement of saturated blood into that segment, thereby establishing the presence of antegrade flow through the original area of signal dropout. After application of sequence B, a bright residual signal seen in the distal vessel lumen was interpreted as collateral flow. Sequence B was repeated with the flip angles of the presaturation pulses set to 0°. In cases in which antegrade flow was present within the infarct artery, this led to return of signal in distal segments.

MR images were stored on optical disks for subsequent recall and analysis. To determine interobserver variability, images were reviewed in cine format by two investigators blinded to the results of contrast coronary angiography. Intraobserver variability was determined by one investigator (R.M.P.) who reviewed the studies a mean of 4 months after their completion. The proximal, middle, and distal segments of the infarct artery were assessed as having antegrade flow, no flow, or collateral flow.

Contrast Angiography
Selective coronary angiography was performed according to standard techniques. Images were interpreted by physicians blinded to the MRI results. In the infarct artery, flow was assessed according to the criteria described by the TIMI investigators.¹⁸ Antegrade flow was classified as absent for TIMI 0 or 1 flow and present for TIMI 2 or 3 flow.

	Results

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MR studies were well tolerated, and were completed in all patients enrolled in the study. The time from infarction to enrollment was 5 days to 15 years. The patients' mean height was 5'6" (range, 5'0" to 6'4"), and the mean weight was 180 pounds (range, 130 to 240 pounds). The left ventricular ejection fraction averaged 0.50 (range, 0.28 to 0.77). Detailed data for the 18 subjects are displayed in the Table. In patient 14, the infarct artery territory initially imaged was incorrect, and the patient underwent repeat MRI. In 17 patients, scans were performed during 13- to 24-second periods of breath-holding. Patient 3 could not hold her breath, and therefore was scanned with respiratory gating. All 18 patients were imaged with sequence A (Fig 1); in 6 patients, imaging sequence B was used to discriminate the direction of flow in distal vessels. Total MRI study time ranged from 20 to 76 (mean, 53) minutes. The infarct artery was the left anterior descending artery in 10 patients, the right coronary artery in 7, and the left circumflex in 1. In the 18 patients studied, infarct arteries were viewed in the short-axis slices within a mean of 2.7 cm from the cardiac apex.

View this table: [in this window] [in a new window]   Table 1. Summary of Patient Data

In all 18 patients, cine MR angiography correctly identified the presence or absence of antegrade flow in the infarct artery. In the 6 patients in whom imaging sequence B was used, 2 were correctly identified as having antegrade flow (TIMI grade 3 flow by catheterization) and 4 were correctly identified as having occlusions of the infarct artery (TIMI grade 0 flow at catheterization). When the 18 infarct arteries were divided into segments (proximal, middle, and distal for the left anterior descending artery and right coronary artery, proximal and distal for the circumflex), MRI correctly identified the presence or absence of antegrade or collateral flow in 50 of 53 segments. Although an abrupt cessation of flow was seen in the posterior left ventricular branch of patient 8, collateral flow distal to this was not seen on MRI. On angiography this distal vessel was seen to be less than 1 mm in diameter and to have sluggish flow. The proximal and middle segments of the left anterior descending artery in patient 12 were misclassified as being occluded with collateral flow. On angiography the proximal segment was seen to have 75% stenosis and a long thrombus extending into the middle portion of the artery. In the distal portion of the vessel, the artery was occluded, and extensive collaterals supplied the distal artery. MRI demonstrated the area of signal dropout in the proximal and middle segments with extensive collaterals and bright signal in the distal vessel. Thus, investigators using MRI knew an occlusion was present, but because an extensive area of signal dropout was noted in the proximal segment (due to thrombus), the proximal and middle segments were thought to be the site of occlusion.

MRI intraobserver variability was assessed by having one investigator read the studies without knowledge of the catheterization results at the time of their completion and then repeat his reading a mean of 4 months after the studies were performed. There was agreement between the readings in all 18 cases. Interobserver variability was assessed by having a second investigator read the studies without knowing the first reader's results or the catheterization findings. In 17 of 18 cases, there was agreement with the reading of the first investigator. There was disagreement regarding the reading of the case in patient 14. Upon review of the second investigator's analysis, it was determined that he had misread the left anterior descending artery as being the circumflex artery and had therefore classified the vessel as open. Representative studies from patients 7 and 5 are displayed in Fig 3 and Fig 4, respectively. Figs 5 and 6 demonstrate the presaturation technique for determining the source and direction of flow in a vessel.

View larger version (106K): [in this window] [in a new window]   Figure 3. Short-axis–view magnetic resonance image (A), tangential-view magnetic resonance image (B), and right anterior oblique–view selective contrast coronary angiography (C) in a patient with a patent left anterior descending artery (LAD) (patient 7). In A, the solid white arrow indicates the LAD. Solid arrows in B (tangential plane by magnetic resonance) and C (right anterior oblique projection at catheterization) show the LAD system. Open arrows in B and C demarcate the circumflex artery.

View larger version (117K): [in this window] [in a new window]   Figure 4. Short-axis–view magnetic resonance image (MRI) (A), tangential-view magnetic resonance image (B), and right anterior oblique–view selective contrast coronary angiography (C) in a patient with an occluded left anterior descending artery (LAD) (patient 5). In A, no signal is seen in the anterior interventricular groove (solid white arrow). The open arrow indicates the posterior descending artery with a cardiac vein posterior to it. In B, the LAD is absent in the tangential plane by magnetic resonance. In C, the solid arrow marks the site of a proximal LAD occlusion in the right anterior oblique projection at catheterization. The open arrows in B and C mark a diagonal branch.

View larger version (91K): [in this window] [in a new window]   Figure 5. Tangential-view images illustrating the use of presaturation pulses to determine the source of flow in the middle and distal left anterior descending artery (LAD) from patient 15. The solid white arrows in A point to the LAD. The arrow in B demarcates a region where no LAD can be seen after the application of presaturation pulses, proving that the flow in the vessel came through its proximal portion. The open arrows in A and B indicate a vein.

View larger version (65K): [in this window] [in a new window]   Figure 6. Tangential-view images of the distal left anterior descending artery (LAD) from patient 18 are shown with (A) and without (B) presaturation pulses. The solid white arrow in A marks the distal LAD. In B, the LAD can still be seen after the application of presaturation pulses, proving that there is an alternative source of flow. The open arrows in A and B indicate a vein.

	Discussion

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In the patient with acute myocardial infarction, restoration of antegrade flow in the infarct artery minutes to hours after the onset of chest pain improves left ventricular function and survival.^{1 2 3} Even if antegrade flow is restored days or weeks after infarction, survival is improved,^{4 5} possibly because of enhanced electrical stability in the peri-infarction zone^{19 20} or modulation of factors controlling infarct expansion and left ventricular remodeling.^{21 22} Knowledge of the status of the infarct artery may therefore be of prognostic and therapeutic importance. Although selective coronary angiography can reliably determine coronary patency, it is invasive and not free of risk. Unfortunately, clinical markers²³ and noninvasive techniques, such as continuous ST segment monitoring,²⁴ measurements of creatine kinase isoforms,²⁵ nuclear imaging with ^99mTc-labeled sestamibi,²⁶ and transesophageal echocardiography,²⁷ do not reliably assess vessel patency. With MRI, the coronary arteries can be visualized noninvasively without a contrast agent, and our data demonstrate that MRI can accurately assess infarct artery patency.

In previous MRI studies of the coronary arteries, epicardial vessels were successfully identified in 73% to 100% of subjects.^{12 13} To reduce motion artifact and improve the signal-to-noise ratio, patients were imaged in a prone position, which some could not tolerate. Furthermore, the distal segments of the coronary arteries, particularly the posterior descending artery, often were not visualized. Because only a single diastolic image was obtained, the differentiation of epicardial arteries from veins was sometimes difficult. Finally, these studies often could not determine whether flow (via collaterals) distal to a region of signal loss was antegrade or retrograde. Our imaging technique was designed to eliminate these shortcomings. First, our patients were in the supine position, with the surface coil resting on the chest; this was well tolerated. Second, we obtained multiple, overlapped 8-mm slices positioned in orthogonal planes, thereby allowing visualization of distal vessels, including the posterior descending artery, during cardiac motion. Third, incorporating cine imaging with four to seven frames per cardiac cycle permitted visualization of flow at several intervals during the cardiac cycle. This enabled visualization of flow in arteries during early diastole, facilitating the differentiation of arteries from veins. Fourth, in 6 patients we distinguished antegrade from retrograde (collateral) flow in middle and distal arterial segments by positioning presaturation pulses orthogonal to the imaging plane across proximal portions of vessels.

Our technique of coronary MR angiography has four limitations: (1) The study was limited to patients in sinus rhythm, because image acquisition must be gated to the cardiac cycle. Although patients with irregular rhythms could be studied with respiratory gating and arrhythmia rejection, the time required for image acquisition would increase. (2) We concentrated on imaging the infarct artery. Examination of vessels in other territories as well would prolong image acquisition time. (3) Signal dropout in vessel segments led to incorrect assessment of the direction of flow in 3 of 53 vessel segments. In patient 8, this was probably due to sluggish flow in the posterior left ventricular branch, which on angiography was seen to be less than 1 mm in diameter. Higher-resolution scanning would be necessary to view smaller vessels. In patient 12, a significant stenosis and thrombus proximal to the site of occlusion caused signal dropout such that this portion of the artery was not visualized. As postulated in the case of patient 8, sluggish flow may have been present in the proximal portion of the artery. The case was correctly identified as a closed artery on the basis of the direction of flow in the distal vessel segment. (4) In this study of survivors of myocardial infarction consecutively referred for catheterization, we enrolled only 1 patient in whom the circumflex was the infarct artery. This was not unexpected, because the circumflex artery is known to be the site of significant stenosis and infarction in only 7% to 15% of patients with myocardial infarction.^{6 28 29} Previous MR coronary angiographic studies¹² have noted decreased sensitivity and specificity for detecting vessels on the lateral wall of the left ventricle; however, special coils or phased-array units that improve the signal from the lateral and posterior walls could improve these results.

In conclusion, in survivors of myocardial infarction, MRI with fast field echo sequences can reliably determine the presence or absence of antegrade flow in the infarct artery. The use of cine MRI enables visualization of flow in epicardial vessels throughout the cardiac cycle. Our data indicate that presaturation pulses positioned across proximal vessels are useful for distinguishing the direction of flow in middle and distal vessel segments.

	Acknowledgments

 
This work was supported in part by National Institutes of Health Special Center of Research (Ischemic SCOR) grant HL-17669, the Moss Heart Fund, and a grant from Picker International, Inc. The authors thank Alison Russell, Dorothy Smith, and Ginny Vaughn for their assistance in preparing the figures for the manuscript.

Received July 6, 1994; revision received September 12, 1994; accepted September 28, 1994.

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