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Published online before print July 19, 2002, 10.1148/radiol.2243010945
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(Radiology 2002;224:845-851.)
© RSNA, 2002

Cardiac Imaging

Real-Time MR Image Acquisition during High-Dose Dobutamine Hydrochloride Stress for Detecting Left Ventricular Wall-Motion Abnormalities in Patients with Coronary Arterial Disease1

Simon Schalla, MD, Christoph Klein, MD, Ingo Paetsch, MD, Hans Lehmkuhl, MD, Axel Bornstedt, PhD, Bernhard Schnackenburg, PhD, Eckart Fleck, MD and Eike Nagel, MD

1 From the Department of Internal Medicine-Cardiology, German Heart Institute Berlin, Augustenburger Platz 1, 13353 Berlin, Germany (S.S., C.K., I.P., H.L., A.B., E.F., E.N.); and Philips Medical Systems, Hamburg, Germany (B.S.). Received May 23, 2001; revision requested June 25; final revision received February 15, 2002; accepted March 5. Supported in part by the German Heart Institute Berlin Foundation and Philips Medical Systems, Hamburg, Germany and Best, the Netherlands. Address correspondence to E.N. (e-mail: eike.nagel@dhzb.de).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To compare the accuracy of real-time magnetic resonance (MR) imaging with that of standard echo-planar MR imaging for detecting myocardial wall-motion abnormalities at rest and during dobutamine hydrochloride–induced stress in patients with coronary arterial disease.

MATERIALS AND METHODS: In 22 patients with coronary arterial disease, left ventricular wall motion was examined at rest and during dobutamine hydrochloride stress, by using echo-planar MR imaging and a new technique with real-time segmented k-space turbo gradient-echo echo-planar MR imaging (repetition time, 16.5 msec; echo time, 6.8 msec). Wall-motion abnormalities were determined visually for each perfusion territory, and Cohen {kappa} coefficients were calculated for real-time imaging in comparison with echo-planar imaging. Coronary angiography was performed in all patients. Sensitivity and specificity for real-time and echo-planar imaging were calculated for detecting significant coronary arterial stenosis.

RESULTS: {kappa} values for detecting wall-motion abnormalities at real-time imaging, in comparison with echo-planar MR imaging, were 0.97 at rest and 0.94 at maximum dobutamine hydrochloride stress. At comparison with those of angiography, the sensitivity and specificity for detecting significant coronary arterial stenosis were 88% (14 of 16 patients) and 83% (five of six patients), respectively, for echo-planar imaging and 81% (13 of 16 patients) and 83% (five of six patients), respectively, for real-time imaging.

CONCLUSION: Real-time MR imaging is possible under stress conditions and allows accurate detection of wall-motion abnormalities.

© RSNA, 2002

Index terms: Coronary vessels, diseases, 54.76 • Coronary vessels, stenosis or obstruction, 54.76 • Heart, MR, 51.121412, 51.121416, 51.12144, 51.12149 • Magnetic resonance (MR), comparative studies, 51.121416, 51.121419 • Magnetic resonance (MR), motion studies, 51.12144


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Noninvasive detection of coronary arterial disease (CAD) is a major challenge. With exercise echocardiography (ECG), only limited information about the localization and extent of CAD can be obtained, and sensitivity and specificity are low (1). At the time this article was written, dobutamine hydrochloride–induced stress ECG was one of the most widely used methods for detecting myocardial ischemia on the basis of visualization of wall-motion abnormalities (WMAs). However, this technique is limited by moderate image quality in 10%–15% of all examinations (2,3), although recent improvements in ECG techniques, such as harmonic imaging, might improve image quality (4,5), and the need for acoustic windows, which are defined by the anatomy of the patient.

Magnetic resonance (MR) imaging of the heart is highly accurate and reproducible for determining left ventricular volumes, function, and muscle mass with use of spin-echo (6–9), gradient-echo, or echo-planar breath-hold MR imaging, with low interstudy variability (10–16). It has been shown that dobutamine hydrochloride stress MR imaging is superior to dobutamine hydrochloride stress ECG for noninvasive detection of CAD, especially in patients with moderate ECG image quality (ie, myocardial motion detectable in >=13 segments, but no clear endocardial border) (17–19). However, even with turbo techniques, several limitations of MR imaging when compared with ECG remain because of image acquisition during several heartbeats. Image acquisition requires approximately 10–16 seconds and an additional 3–4 seconds for image reconstruction, which prohibits display and analysis or adaption of image planes in real time. This limitation has been regarded as a potential safety problem of MR imaging during stress testing (20). In addition, image quality is reduced by cardiac arrhythmias or breathing motion and is thus performed during breath holding.

The development of high-performance gradient systems and optimized hybrid sequences that combine turbo gradient-echo and echo-planar MR imaging makes acquisition of complete cardiac images in real time possible (21,22). This technique has several advantages when compared with conventional acquisition techniques because the complete data set is acquired during a single measurement interval and not during several heartbeats. Breath holding is not necessary to preserve image quality and, although ECG monitoring is important for the patient’s safety, it is no longer required to trigger imaging.

In combination with interactive planning tools, real-time planning and adaption of imaging planes can be performed (23). However, in contrast with conventional MR imaging techniques, spatial resolution is reduced and a high number of echo-planar imaging readouts are used to reach adequate temporal resolution, which may lead to image distortion and reduce accuracy.

It has been reported that real-time image quality is sufficient for assessment of left ventricular function and may be superior to that obtained at ECG (23). Close correlation of real-time and conventional MR imaging for determining left ventricular volumes has been found (22). If real-time imaging were sufficiently accurate to depict new WMAs, it could be used to monitor or even to examine patients during stress examinations.

The aim of the current study was to determine the accuracy of real-time MR imaging when compared with conventional echo-planar MR imaging for detecting WMAs at rest and during dobutamine hydrochloride stress.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients
The study was approved by the institutional review committee of Humboldt University in Berlin. Patients who were scheduled to undergo coronary angiography, were known to have CAD, and had previously undergone percutaneous transluminal coronary angioplasty (with or without stent implantation) or bypass surgery consecutively underwent screening for study inclusion. For safety reasons, patients were excluded from the study if one or more of the following criteria were met: myocardial infarction in the past 4 weeks, unstable angina pectoris, known left main coronary arterial stenosis, New York Heart Association class III heart failure, class II valvular disease, dilated or obstructive cardiomyopathy, ejection fraction of less than 20%, blood pressure higher than 220/110 mm Hg, or claustrophobia. Twenty-five consecutive patients were included after written informed consent was obtained, depending on the availability of the MR imager. At the time of imaging, two patients were excluded from the study because of previously unknown claustrophobia. In an additional patient, technical problems prohibited MR imaging, which resulted in a study population of 22 patients. The characteristics of the study group are listed in Table 1.


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  		TABLE 1. Patient Characteristics

 
Stress Testing Protocol
Dobutamine hydrochloride (Dobutamine 280 mg/50 mL; Fresenius Deutschland, Bad Homburg, Germany) was infused intravenously over 3 minutes per dose at doses of 10, 20, 30, and 40 µg per kilogram of body weight per minute and was stopped at whatever dose was being administered when 85% of the age-predicted heart rate was reached. The highest dose, however, was continued and supplemented with 0.25-mg fractions of atropinsulfate (Atropine 0.5 mg/mL; Braun Melsungen, Melsungen, Germany) (maximal dose, 1 mg), administered intravenously as a slow bolus, if less than 85% of the age-predicted heart rate was achieved with the maximum dose of dobutamine hydrochloride and if stress test findings were negative. Esmolol hydrochloride ([5 mg/kg intravenously as a slow bolus] Brevibloc 100 mg/10 mL; Baxter Deutschland, Unterschleissheim, Germany) and glyceroltrinitrat (0.4 mg Nitrolingual spray; G. Pohl-Boskamp, Hohenlockstedt, Germany) were administered after the test when clinically indicated. Stress testing was discontinued at patient request or when the following occurred: new WMAs (detected by means of echo-planar images displayed later at the next stress level), chest discomfort indicative of progressive or severe angina, dyspnea, systolic blood pressure decrease of more than 40 mm Hg, arterial hypertension (blood pressure >= 240/120 mm Hg), severe arrhythmia, or other serious adverse effects. ECG rhythm, blood pressure, and symptoms were monitored continuously.

MR Imaging
Patients were examined in the supine position by using a 1.5-T whole-body MR imager (Gyroscan ACS-NT; Philips Medical Systems, Best, the Netherlands) with research software (Cardiac Patch CPR6) and rapid-gradient systems (21 mT/m amplitude, 100 mT/m/sec slew rate). A dedicated five-element phased-array cardiac coil placed around the thorax of the patient was used for image acquisition. A small field of view was used to decrease acquisition time. Only the two anterior segments of the coil were applied for data acquisition to avoid aliasing with the small fields of view.

After two rapid surveys to determine the axis of the left ventricle, three short-axis sections were obtained by using as a reference standard a segmented k-space echo-planar imaging sequence routinely used at our institution for stress MR imaging. Images were acquired during end-expiratory breath holds of approximately 12–16 heartbeats for each section (24). The details of the sequence are shown in Table 2. Image acquisition was then repeated with use of a real-time technique, with identical section positions.


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  		TABLE 2. MR Imaging Parameters

 
The real-time sequence consists of a hybrid segmented k-space turbo gradient-echo echo-planar imaging sequence (21–23), with a repetition time msec/echo time msec of 16.5/6.8, a temporal resolution of 62 msec (16 images per second) and a spatial resolution of 2.2 x 4.4 mm (Table 2). Thirty consecutive images were acquired to cover at least two complete cardiac cycles. Zero filling was applied to better use the information contained in the raw data (k space) and to reduce partial volume effects and edge-detection artifacts. To ensure similar conditions and geometry when compared with the reference technique, real-time imaging was also performed during end expiration and with R-wave ECG triggering of acquisition of the first image at end-diastole, even though this was not required to preserve image quality. The imaging time for real-time multisection acquisition of short-axis views was a maximum of 6 seconds. To keep the duration of dobutamine hydrochloride infusion as short as possible, real-time images of identical geometry were obtained with the patient at rest, at a dose of 20 µg, and at the maximum dobutamine hydrochloride and atropine sulfate doses. Image acquisition started approximately 1 minute after the beginning of administration of a stress level dose. During an examination, echo-planar images of the middle short-axis section were displayed at the next dobutamine hydrochloride stress level for rapid review of new onsets of WMAs. Because of hardware restrictions, real-time images were reconstructed later. Echo-planar images were acquired at every stress level. The total time for an examination with use of both MR imaging techniques was 30–40 minutes. No postprocessing was performed; images were, however, analyzed later.

Qualitative MR Image Analysis
All images were displayed as continuous cine loops and assessed visually. Image quality, endocardial movement, and systolic wall thickening, which were used to compare images obtained at rest and at medium and peak stress, were evaluated independently off line by two experienced cardiologists (S.S., E.N.) (with 3 years of experience each) who were blinded to results obtained with any other technique. In cases of discrepancy, consensus was reached by means of joint image review. Image quality was assessed as diagnostic or nondiagnostic. It was considered diagnostic if all 16 segments could be visualized and interpreted with regard to wall motion.

Similar to the procedure used at routine stress ECG, the left ventricular myocardium was divided into 16 segments. Each of the 16 segments was individually assessed for wall motion at rest, during increasing dobutamine hydrochloride stress levels (for real-time imaging only at 20 µg) and at maximum stress. Segmental wall motion was graded as normal or abnormal. Similar to the procedure for stress ECG, segmental wall motion was subjectively considered abnormal if hypokinesia (reduction of endocardial motion and systolic wall thickening), akinesia (absence of endocardial motion and systolic wall thickening), or dyskinesia (paradoxic wall motion) was observed. Every segment was assigned to the perfusion territory of a specific coronary artery, as suggested by the American Society of Echocardiography (25) (Fig 1). Results were determined for perfusion territories. Results of ischemia detection were determined for each patient. Results for each patient were considered positive and indicative of myocardial ischemia in a perfusion territory if new or worsening WMAs in one or more segments developed during dobutamine hydrochloride stress or if WMAs observed at rest that improved during low-dose stress deteriorated during peak stress.



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  		Figure 1. Diagram shows a segment model of the left ventricle: Short-axis view of the basal, middle, and apical left ventricular myocardium. The myocardium is divided into 16 segments that are assigned to perfusion territories of the coronary arteries (25,26). LAD = left anterior descending coronary artery, LCX = left circumflex coronary artery, and RCA = right coronary artery.

 
Angiography
Biplanar coronary angiography was performed after dobutamine hydrochloride stress MR imaging in all patients. Coronary arterial stenoses were imaged in multiple projections, minimizing overlapping of side branches and foreshortening of relevant coronary arterial stenoses.

Coronary angiograms were interpreted by the examiner and reviewed by the clinical conference chairman and, in cases of discrepancy, reviewed with a third reviewer (E.F.). Quantitative coronary angiography was performed in cases of doubt, when visual results could not clearly be assigned to a stenosis of 25%, 50%, or 75% or greater (Quansad Quantitative Coronary Angiography postprocessing equipment; Arri, Munich, Germany). All three reviewers were experienced cardiologists (5–20 years experience) blinded to the results of noninvasive testing. Significant CAD was defined as an area reduction greater than 75% with respect to prestenotic segment areas in at least one major epicardial coronary artery or a major branch of one of these vessel distributions or coronary arterial bypass graft.

Data Analysis
Sensitivity was calculated by using the following formula: Sensitivity = true-positive finding/(true-positive finding + false-negative finding); specificity = true-negative finding/(false-positive finding + true-negative finding).

As a measurement of agreement, Cohen {kappa} coefficients were calculated. The {kappa} coefficient equals 1 when there is complete agreement of two methods. When the observed agreement exceeds chance agreement, {kappa} is positive, with its magnitude reflecting strength of agreement. A value greater than 0.7 was considered satisfactory.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
In all patients, the age-predicted heart rate was reached during dobutamine hydrochloride stress, with a mean dose of 39.00 ± 4.30 µg/kg/m plus 0.31 mg ± 0.27 atropine (Table 1). No major adverse effects of dobutamine hydrochloride were observed. Image quality was diagnostic for echo-planar and real-time imaging: Image quality was sufficient for qualitative analysis of wall motion with use of both techniques in all patients.

The numbers of perfusion territories with WMAs detected with echo-planar and real-time imaging at rest and maximum dobutamine hydrochloride stress are shown in Table 3. With performance of the Cohen {kappa} test, values of 0.97 for the diagnosis of WMAs at rest and of 0.94 at maximum dobutamine hydrochloride stress were obtained for real-time imaging, when compared with echo-planar imaging.


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  		TABLE 3. Perfusion Territories with WMAs Detected with Echo-planar and Real-Time Imaging at Rest and Maximum Dobutamine Stress

 
With real-time imaging, new or worsening WMAs or a biphasic response to dobutamine hydrochloride, either of which was indicative of ischemia, was found in 96% (22 of 23) of all positive results with use of the standard technique (Cohen {kappa} test, 0.97). No perfusion territory without WMAs imaged with use of the conventional technique was considered abnormal at real-time imaging (Table 4). An example of new-onset hypokinesia during stress detected with use of both imaging techniques is shown in Figure 2.


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  		TABLE 4. Real-Time versus Echo-Planar Imaging: Perfusion Territories Indicative of Ischemia

 


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  		Figure 2. End-diastolic (ED) and end-systolic (ES) short-axis views obtained at the basal level by using echo-planar (EPI) and real-time MR imaging at rest and dobutamine hydrochloride stress (40 µg/kg with 0.5 mg atropinsulfate): At rest, wall motion is normal, whereas during dobutamine hydrochloride stress, a new onset of hypokinesia (arrows) in the basal-septal segment is detected with both imaging techniques.

 
In 16 patients, significant coronary arterial stenosis was detected with angiography. A sensitivity of 88% (14 of 16 patients) and a specificity of 83% (five of six patients) for diagnosing ischemia with echo-planar imaging and of 81% (13 of 16 patients) and 83% (five of six patients), respectively, with real-time MR imaging, when compared with coronary angiography, was found (Fig 3, Table 5).



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  		Figure 3. Graph shows the sensitivity and specificity of real-time and echo-planar imaging (EPI) for the diagnosis of ischemia, when compared with angiography. Detection of ischemia with real-time MR imaging is similar to that with standard echo-planar MR imaging.

 

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  		TABLE 5. MR Imaging versus Angiography: Demonstration of Coronary Arterial Stenosis with Ischemia

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
Real-time MR image acquisition is similar to echo-planar imaging for detecting WMAs in patients known to have CAD. Real-time imaging is possible during high-dose dobutamine hydrochloride MR imaging. Image quality and contrast between blood and myocardium are sufficient to adequately assess wall motion and detect WMAs at rest or during pharmacologic stress.

In contrast with conventional MR imaging techniques, such as echo-planar or turbo gradient-echo imaging, ECG triggering is not necessary to preserve image quality, and high-quality images can be obtained even in patients with arrhythmia. Patients with atrial fibrillation, frequent premature heartbeats, or sinus arrhythmia (27) may have moderately reduced MR image quality. With real-time imaging, image quality is independent of these pitfalls, as the complete data set is acquired in real time (65 msec). In addition, breath holding is not necessary to preserve image quality.

A potential advantage is the ability to image the entire heart in 12–16 seconds, which may further improve diagnostic accuracy when compared with conventional MR imaging techniques that allow acquisition of only a limited number of views (eg, five) per stress level at current imaging speeds.

In addition, real-time image acquisition may allow stress during ergometric exercise, which is regarded as the more physiologic stress test, with a better safety profile (28).

A limitation of the study protocol was acquisition of real-time images at only two stress levels (20 µg/kg and maximum dobutamine hydrochloride dose). This was due to patient safety considerations, since pharmacologic stress had to be kept to a minimum. These two stress levels were chosen to visualize wall motion at rest, at maximum inotropy without ischemia, and at maximum stress. Increasing contraction of segments during low-dose dobutamine hydrochloride stress or decreasing contraction during high-dose dobutamine hydrochloride stress may have been missed in some cases.

The patient population included in the current study was small and inhomogeneous; almost all patients had previously had a myocardial infarction, and most had undergone revascularization procedures, including coronary arterial bypass. Angiography was considered the reference standard for predicting ischemia, followed by impaired myocardial function in the current study, although coronary arterial patency or stenosis is not always accurately predictive of function. Patients with previous infarction who subsequently undergo angioplasty might have restoration of normal flow in the vessel but might still have impaired myocardial function in the perfusion territory as a result of scar tissue formation. In this specific patient population, results of real-time imaging were similar to those of echo-planar imaging, and a sensitivity of 81% and a specificity of 83% were found at comparison with angiography. Previous studies (19) in which high-dose dobutamine hydrochloride stress MR imaging was performed have been restricted to patients suspected of having CAD. Thus, the diagnostic accuracy of the current study cannot be compared with previous results and is expected to be lower. The value of real-time imaging as a screening test in patients suspected of having CAD remains to be determined in a future study.

Because of the high prevalence of patients who have multiple-vessel disease and have previously undergone coronary angioplasty or bypass surgery, defined assignment of segments to stenosed arteries was considered not useful for comparison of real-time and conventional MR imaging with coronary angiography.

Currently, some technical limitations need to be considered. The major limitation was the low spatial resolution (2.2 x 4.4 for the real-time technique vs 1.3 x 2.6 mm) with the echo-planar imaging technique. Zero filling was used to better apply the information contained in the raw data (k space) and to reduce partial volume effects and edge-detection artifacts (29,30). With this method, voxel size improved to 1.1 x 2.2 mm. This spatial resolution is probably not sufficient for detecting viable myocardium, since a dobutamine hydrochloride–induced increase in 2-mm or greater wall thickening is regarded as a diagnostic criterion for viability (31). However, for visual detection of WMAs, spatial resolution was sufficient, probably because of the eye’s ability to interpret motion patterns rather than thickness alone.

At rest, the temporal resolution of 62 msec used in the current study is just sufficient to acquire end-diastolic and end-systolic images at isovolumetric phases, since end-systole lasts approximately 50–80 msec, with a longer isovolumetric phase at end-diastole. During dobutamine hydrochloride stress, however, the isovolumetric phase is shortened and may be missed with the temporal resolution used in the current study. Acquiring several heartbeats for each section overcomes this problem, since different phases of the cardiac cycle are sampled in different heartbeats; thus, the chance of acquiring an image during maximum contraction is increased. These two limitations, low spatial and temporal resolution, may explain the small differences observed between echo-planar and real-time imaging.

The human eye is excellent at assessing abnormalities of complex motion patterns. However, limitations of visual interpretation of wall motion are well known. For example, changes in short-duration myocardial motion may be missed visually, even when an imaging modality with sufficient temporal resolution is used for data acquisition (32). Therefore, quantitative analysis of regional wall motion and WMAs would be helpful. Accurate determination of timing of regional motion events and regional myocardial wall thickening and thinning, as well as velocity and direction of myocardial motion in real time, is a future goal (33). In the current setting, with suboptimal spatial and temporal resolution on the real-time MR images, quantitative analysis of WMAs was not considered useful.

A third technical limitation of the study was that, although images were acquired in real time, reconstruction had to be performed offline because of hardware restrictions at the time of the study. Patients could not be monitored online for new onset of WMAs. Instead, monitoring was performed conventionally at imaging pauses, such as at the beginning of the next dobutamine hydrochloride stress level. However, at least in some patients, it was not possible to review the 16 segments without increasing the stress level duration to more than 3 minutes. Current patient monitoring is therefore suboptimal, since no sufficient image data is available during imaging. If this information were available, a stress test might be stopped earlier, since new WMAs are criteria for stopping the test. Thus, real-time imaging did not enable better monitoring of the patients in the current study, since only offline reconstruction was available and the value of real-time techniques was not known during the study. In the future, however, real-time images could be acquired continuously because of the latest hardware solutions, which already allow real-time reconstruction and interactive imaging (23) and could therefore increase patient safety.

Two strategies may be used with real-time imaging for stress MR imaging examinations. The first strategy, which can be applied at present, is continuous visualization of cardiac motion in real time to monitor the patient and rapidly detect signs of ischemia. High-spatial-resolution breath-hold imaging would be performed at 3-minute intervals for diagnosis. The second strategy is real-time imaging for diagnosing ischemia with use of pharmacologic or ergometric stress.

In conclusion, real-time MR imaging allows accurate detection of WMAs; therefore, it can be used for online analysis of wall motion with pharmacologic stress to reduce imaging time and improve patient safety and may allow use of physical stress. Because no data averaging or ECG triggering of several heartbeats is needed to use the real-time technique, it may be possible to perform imaging in patients who have atrial fibrillation or frequent premature heartbeats without loss of image quality. Real-time imaging may be an important addition to breath-hold MR imaging when hardware and software improvements allowing real-time image reconstruction become widely available.


   FOOTNOTES
 
Abbreviations: CAD = coronary arterial disease, ECG = echocardiography, WMA = wall-motion abnormality

Author contributions: Guarantors of integrity of entire study, S.S., E.N.; study concepts and design, S.S., E.N.; literature research, S.S.; clinical and experimental studies, S.S.; data acquisition, S.S., C.K., I.P., H.L., A.B., B.S.; data analysis/interpretation, S.S., E.N.; statistical analysis, S.S., E.N.; manuscript preparation, S.S; manuscript definition of intellectual content, S.S., E.N.; manuscript editing, S.S.; manuscript revision/review and final version approval, E.N., E.F.


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 MATERIALS AND METHODS
RESULTS
 DISCUSSION
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