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(Radiology. 1999;210:566-572.)
© RSNA, 1999

Technical Developments

Coronary Arteries: MR Angiography with Fast Contrast-enhanced Three-dimensional Breath-hold Imaging—Initial Experience

Winfried Kessler, MD1, Gerhard Laub, PhD2, Stephan Achenbach, MD1, Dieter Ropers, MD1, Werner Moshage, MD1 and Werner G. Daniel, MD1

1 Department of Internal Medicine II, University of Erlangen-Nürnberg, Östliche Stadtmauerstrasse 29, 91054 Erlangen, Germany (W.K., S.A., D.R., W.M., W.G.D.)
2 Siemens Medical Engineering, Erlangen, Germany (G.L.).


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Gadolinium-enhanced, three-dimensional, breath-hold magnetic resonance (MR) coronary angiography was performed in two healthy volunteers and 11 patients suspected or known to have coronary artery disease. MR angiograms were compared with those obtained with retrospective respiratory gating. Of 52 main coronary arteries, 47 could be visualized with the breath-hold technique and 49 with the gating technique. Signal-to-noise and contrast-to-noise ratios were significantly higher with the breath-hold technique. Overall image quality was slightly lower with breath-hold imaging. With either technique, three of five significant coronary stenoses were correctly identified.

Index terms: Coronary vessels, MR, 54.12142, 54.12143 • Magnetic resonance (MR), vascular studies, 54.121416, 54.12142


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Since the early 1990s, magnetic resonance (MR) angiography has been emerging as a noninvasive method for coronary artery imaging (1–6). So far, most clinical studies have been performed with either two-dimensional breath-hold techniques (7–11) or, more recently, with three-dimensional (3D) approaches based on respiratory gating (12–16). In these studies, the overall sensitivities for detection of hemodynamically significant coronary artery stenoses with at least 50% diameter reduction ranged between 0% and 90% for the two-dimensional (7–11) and 38% and 83% for the 3D (12,14,15) techniques. Each of these techniques has specific limitations. The two-dimensional technique, which is based on the acquisition of multiple parallel or oblique sections, requires 30–60 repeated breath holds for a comprehensive investigation of the major coronary arteries (17), which may be strenuous for patients with impaired cardiac or respiratory function. In addition, misregistration of contiguous sections may occur if the diaphragmatic position cannot be exactly reproduced (18). In contrast, respiratory-gated 3D techniques permit the acquisition of truly contiguous sections, but they require long imaging times and image degradation may occur due to inconsistent breathing patterns and patient movement (19). In addition, vessel-to-background contrast is low due to in-plane and through-plane saturation effects.

Regarding these technical limitations, a major step forward would be to image the coronary arteries by acquiring a 3D data set within one breath hold. This has previously been attempted by using echo-planar imaging (20,21), but it has not yet gained clinical relevance since echo-planar imagers are not widely available and image quality is impaired because of low signal-to-noise ratio and spatial resolution (13). Herein, we present the initial results of a fast contrast material–enhanced 3D breath-hold technique for imaging the coronary arteries. All MR angiograms were compared with those obtained with a conventional 3D respiratory-gated technique.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Two healthy volunteers and 11 patients suspected or known to have coronary artery disease underwent MR imaging. The mean age was 49 years (range, 31–63 years). All subjects were in stable sinus rhythm. In six patients, conventional contrast-enhanced angiography of the coronary arteries was performed within 3 days after MR imaging according to standard techniques. All subjects were examined in the supine position on a 1.5-T whole-body imager with gradient overdrive (Vision; Siemens, Erlangen, Germany). The maximum gradient strength was 25 mT/m with a gradient rise time of 12 µsec/mT/m, corresponding to a maximum slew rate of 80 mT/m/msec. A circular polarized body array coil was used for signal reception to increase signal-to-noise ratio. Data acquisition was electrocardiographically triggered and timed to middle diastole. First, 3D MR coronary angiography was performed by using retrospective respiratory gating. In a second step, MR angiograms were obtained with the new fast contrast-enhanced breath-hold technique. All images were acquired in transaxial orientation starting craniad to the presumed origin of the left main coronary artery. Positioning of the imaging slab was guided by use of coronal spin-echo scout images. Nitroglycerin (0.8 mg) was administered sublingually to the subjects before MR angiography to achieve coronary vasodilatation. The study was conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all subjects before the investigation.

Breath-Hold MR Imaging
Breath-hold imaging was performed in inspiration by using a fast 3D gradient-echo sequence (repetition time msec/echo time msec = 3.4/0.9 with flip angle of 20°) during contrast material injection. A 64-mm-thick volume with transaxial orientation was divided into 16 contiguous 4-mm-thick partitions. With use of zero filling, the data were interpolated to 32 2-mm-thick partitions. Depending on the size of the heart, the imaging slab covered the proximal and eventually the middle segments of the coronary arteries (Fig 1). With a field of view of 300 x 300 mm and a matrix of 140 x 256, the spatial resolution was 2.1 x 1.2 x 2 mm. The k-space trajectory is shown in Figure 2. One-half of k space in the phase-encoding direction (70 lines) was acquired within each heartbeat. Phase encoding started in the center of k space after a fat-saturation pulse to suppress signal from perivascular tissue. Each partition was acquired over two subsequent heartbeats with a diastolic acquisition window of 70 x 3.4 msec = 238 msec. With 16 partitions, 32 heartbeats were required to acquire the complete 3D data set. An additional presaturation pulse after the fat-saturation pulse covering the anterior chest wall was used to avoid wraparound effects.



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  		Figure 1. Schematic of positioning of the imaging slab for 3D breath-hold imaging. With a craniocaudal extension of 64 mm, usually the proximal and middle segments of the left anterior descending (straight arrow) and left circumflex (arrowhead) coronary arteries and the proximal segment of the right coronary artery (curved arrow) are covered.

 


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  		Figure 2. Schematic of k-space trajectory with use of a 3D gradient-echo sequence for contrast-enhanced breath-hold MR coronary angiography. Each • and {bigcirc} represents a one-dimensional readout period of 256 data points. The measured data (•) consist of Ny = 140 lines and Nz = 16 partitions. By using zero filling ({bigcirc}), 32 partitions are reconstructed. Asymmetric encoding is used to increase the spatial resolution in the section-select direction. Every heartbeat, one-half of the line loop is acquired with the first data point starting at the center of k space. ECG = electrocardiographic gating, FS = fat-saturation pulse, SP = saturation pulse, TD = trigger delay.

 
A total of 20 mL of gadopentetate dimeglumine (Magnevist, 0.5 mol/L; Schering, Berlin, Germany) was injected manually into a cubital vein over 20 seconds according to the individual transit time followed by bolus injection of a 10-mL saline solution flush. The contrast agent transit time was determined individually with a test bolus by using a turbo fast low-angle shot (FLASH) sequence (sequential single-section acquisition; 5.8/2.4; flip angle, 15°; one signal acquired; section thickness, 8 mm; field of view, 350 x 350 mm; matrix, 128 x 256; imaging time per section, 742 msec). The sequence provided 30 longitudinal images of the thoracic aorta in 1-second intervals and was started after a rapid bolus injection of 2 mL of gadopentetate dimeglumine and an 8-mL saline solution flush (Fig 3a). From these images, a signal intensity curve of the ascending aorta was obtained (Fig 3b). The transit time was determined as time to peak enhancement. The delay between contrast agent injection and onset of image acquisition was then calculated to ensure temporal coincidence of image acquisition with steady contrast material concentration within the coronary arteries as proposed by Prince et al (22): imaging delay = transit time + (injection time/2) - (expected imaging time/2).



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  		Figure 3a. (a) Spin-echo turbo FLASH MR image shows contrast enhancement of the left atrium (LA) and the aorta after administration of gadopentetate dimeglumine. A region of interest for signal intensity measurement is placed over the ascending aorta ({bigcirc}1). (b) Relative signal intensity (Rel SI) in the ascending aorta over time after contrast agent administration. The contrast material transit time is determined on the basis of the maximum (Max) of the curve.

 


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  		Figure 3b. (a) Spin-echo turbo FLASH MR image shows contrast enhancement of the left atrium (LA) and the aorta after administration of gadopentetate dimeglumine. A region of interest for signal intensity measurement is placed over the ascending aorta ({bigcirc}1). (b) Relative signal intensity (Rel SI) in the ascending aorta over time after contrast agent administration. The contrast material transit time is determined on the basis of the maximum (Max) of the curve.

 
Respiratory-gated MR Imaging
Respiratory gating was performed by using the navigator-echo technique reported by Li et al (13). With this technique, only image data that were acquired during an almost identical respiratory phase were retrospectively processed for image reconstruction. A navigator echo was used to monitor the diaphragmatic position. Five acquisitions, starting during middle diastole, were used to cover the whole respiratory cycle; 24 kz phase-encoding steps were obtained per cardiac cycle. Retrospectively, the most frequently detected diaphragmatic position, which usually was seen at end expiration, was selected as the gating center. By using a narrow acceptance range of ±1 mm of the gating center, 20%–40% of k space was covered. The remaining k space was filled with acquisitions next to the gating center. One or two overlapping imaging slabs containing 24 contiguous sections each were obtained by using a non–velocity-compensated 3D gradient-echo sequence (7.4/2.7) with fat saturation. An incremental flip angle series of 20°–90° was applied to compensate for saturation effects. The field of view was 225 x 300 mm, the matrix 192 x 256, and the section thickness 2 mm, resulting in a spatial resolution of 1.17 x 1.17 x 2 mm. Depending on the patient's heart rate, the acquisition time for one imaging slab was 10–15 minutes.

Image Analysis
Images obtained by using the two different MR techniques were analyzed by two independent observers (W.K., D.R.). To quantify image quality, signal-to-noise and contrast-to-noise ratios were determined for the transaxial sections. To achieve this, the relative signal intensities were measured within small regions of interest that were positioned over the proximal segments of the visualized coronary arteries, the perivascular tissue, and artifact-free space anterior to the chest wall (Fig 4). The signal-to-noise ratio was defined as the signal intensity within the vessel lumen divided by the SD of artifact-free noise. The contrast-to-noise ratio was calculated by dividing the difference between the signal intensity in the vessel lumen and that of the perivascular connective tissue by the SD of artifact-free noise. In addition, the mean vessel lengths of the visualized coronary arteries were determined after curvilinear multiplanar image reconstruction by means of commercially available software (NUMARIS; Siemens) (14,15). With this technique, secondary images are created in a curved imaging plane that is fitted to the tortuous course of the vessel through the volume data set. After data reformatting, the respective coronary artery is visualized in a straightened monoplanar projection image. If a coronary artery was not visualized at all, although it was covered by the imaging volume, a value of 0 mm was used for the calculation. If the vessel was located outside the imaging volume, it was excluded from analysis.



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  		Figure 4. Transaxial MR image obtained with contrast-enhanced 3D breath-hold imaging. {bigcirc} indicates the regions of interest used for signal intensity measurements of the coronary arteries (left main coronary artery, 1) and perivascular tissue (2). The arrow indicates the left anterior descending coronary artery. AO = aorta, PA = pulmonary artery.

 
For qualitative image analysis of the original transaxial images, the following scoring scale was used: 0, no vessels seen; 1, poor vessel visibility with considerable blurring; 2, fair vessel visibility with moderate blurring; 3, moderate vessel visibility with little blurring; and 4, good vessel visibility with no or almost no blurring.

To compare the ability of the two MR imaging protocols to visualize significant coronary artery stenoses in six patients suspected of having coronary artery disease, stenosis assessment was performed. In contrast to the other five patients, conventional contrast-enhanced angiography was performed in these patients after the MR investigation, thus permitting stenosis evaluation in a blinded manner. According to findings in previous studies (7–12,14,15), a segmental signal intensity reduction or signal intensity loss on the MR angiogram was considered representative of a hemodynamically significant coronary artery stenosis with a diameter reduction of at least 50%. The left main coronary artery and the proximal and middle segments of the left anterior descending, left circumflex, and right coronary arteries were assessed separately. In case of disagreement between the two observers, the images were reviewed again and a final assessment was made in consensus. The results were compared with findings on the coronary angiograms obtained after cardiac catheterization.

Statistical Analysis
Differences in signal-to-noise and contrast-to-noise ratios and image quality ratings between contrast-enhanced breath-hold and respiratory-gated images were compared by using the Student t test. For calculation, the mean values of the two independent analyses were used. A P value less than .05 was considered statistically significant. All values are expressed as the mean ± SD.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
By using contrast-enhanced 3D breath-hold MR angiography, 47 of 52 (90%) major coronary arteries could be visualized. In three cases, the right coronary artery was located outside the imaging volume. In two cases, visualization of the left circumflex coronary artery was prevented by impaired image quality or because of total vessel occlusion already shown at contrast-enhanced angiography before the MR investigation. An example of a left main, left anterior descending, and right coronary artery after curvilinear multiplanar reconstruction is shown in Figure 5. With the respiratory-gated technique, 49 of 52 (94%) coronary arteries were visible. Not visible were the occluded left circumflex and two right coronary arteries that were located outside the imaging volume. The mean lengths of the different coronary arteries as determined with the two MR techniques were almost identical (Table). The Table also shows the signal-to-noise and contrast-to-noise ratios for each imaging technique; both ratios were significantly higher for the MR images obtained with the breath-hold technique (P < .01 and P < .05, respectively). However, the overall image quality, expressed with the image quality ratings, was lower with the breath-hold technique than with the respiratory-gated technique although the difference did not reach statistical significance (2.5 ± 1.1 vs 2.9 ± 0.7).



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  		Figure 5. Curvilinear multiplanar reconstruction MR image of the right coronary artery (arrow) and the left main and left anterior descending coronary arteries (arrowhead) was obtained in a healthy volunteer, with contrast-enhanced 3D breath-hold imaging.

 

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  		Imaging Data for Coronary Arteries Depicted at MR Angiography in 13 Subjects
 
Figure 6 shows two corresponding curvilinear multiplanar reconstruction images of a left anterior descending coronary artery obtained with each technique. In the six patients who underwent MR imaging before cardiac catheterization, contrast-enhanced angiography revealed five stenoses of at least 50% diameter reduction in the proximal or middle vessel segments. Four of the stenoses were located in the left anterior descending coronary artery (two in the proximal segment and two in the middle segment) and one in the left circumflex coronary artery (proximal segment). Three of five stenoses were correctly identified with the breath-hold technique, as well as with the respiratory-gated technique (Table).



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  		Figure 6a. (a) Curvilinear multiplanar reconstruction 3D breath-hold and (b) respiratory-gated MR images in a healthy volunteer depict a left anterior descending coronary artery (arrow) without significant stenosis.

 


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  		Figure 6b. (a) Curvilinear multiplanar reconstruction 3D breath-hold and (b) respiratory-gated MR images in a healthy volunteer depict a left anterior descending coronary artery (arrow) without significant stenosis.

 
An example of a severe proximal stenosis of a left anterior descending coronary artery documented at breath-hold imaging and the corresponding contrast-enhanced angiogram is shown in Figure 7.



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  		Figure 7a. (a) Curvilinear multiplanar reconstruction 3D breath-hold MR image and (b) corresponding conventional contrast-enhanced angiogram in the right anterior oblique projection depict a severe proximal stenosis (arrow) of the left anterior descending coronary artery.

 


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  		Figure 7b. (a) Curvilinear multiplanar reconstruction 3D breath-hold MR image and (b) corresponding conventional contrast-enhanced angiogram in the right anterior oblique projection depict a severe proximal stenosis (arrow) of the left anterior descending coronary artery.

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
MR angiography of the coronary arteries has advanced rapidly during the past few years owing to major improvements in imaging techniques (2–7,23,24). However, consistent visualization of the coronary artery tree with diagnostic image quality remains challenging. Initial results of overall sensitivity and specificity of 90% and 92%, respectively, for detecting significant coronary artery stenoses with two-dimensional breath-hold imaging (5,7) could not be reproduced in subsequent studies (8–11). Use of new respiratory-gated 3D techniques (12,13,24,25) can help address many of the problems inherent in the two-dimensional breath-hold techniques. Use of these 3D techniques permits acquisition of nearly isotropic data sets with high signal-to-noise ratio suitable for continuous visualization of coronary vessels in curvilinear multiplanar or 3D reconstruction images (14–16).

Misregistration of contiguous sections, one of the major drawbacks of two-dimensional breath-hold imaging (18), is avoided. In addition, elimination of the repeated strenuous breath holds makes this technique applicable to a wider range of patients. However, until now, findings in clinical studies have failed to show superiority of respiratory-gated 3D MR coronary angiography compared with breath-hold two-dimensional techniques in detecting significant coronary artery stenoses (12, 14,15). One reason is that respiratory gating is susceptible to inconsistent breathing patterns that may lead to impairment of image quality (15,19). In addition, with conventional retrospective respiratory gating, relatively long imaging times of approximately 30 minutes are required for the acquisition of a complete volumetric data set owing to the need for multiple oversampling of image data. This, of course, increases the likelihood of patient movement leading to image degradation and vessel blurring. Prospective respiratory gating with correction of image position may overcome this problem, since, with this technique, total imaging time can be reduced by using wider gating windows (25). To our knowledge, however, the clinical value of this method has not yet been evaluated.

In this study, we implemented a contrast-enhanced fast gradient-echo technique for imaging of the coronary arteries that combines the advantages of 3D data acquisition and short imaging within one breath hold. Until now, comparable contrast-enhanced techniques have been used successfully for imaging of the thoracic and abdominal aorta; visceral, pulmonary, and renal arteries; and aortocoronary bypass grafts (26–29). In our study, 47 (90%) of 52 main coronary arteries could be visualized. These results are almost identical to those with the respiratory-gated technique that we used for comparison. Here, visualization of 49 (94%) coronary arteries was possible. This difference was due to the fact that in two cases the corresponding coronary artery (right coronary artery) was located outside the imaging volume. The mean lengths of the visualized vessels also compared favorably between both methods and are consistent with results in other two-dimensional and 3D MR studies, except for the right coronary artery (5,6,8,11,12,24). Here, we found distinctly lower values, but this is due to the fact that the vessel was often not completely covered by the imaging slab. This problem has already been reported in a study comprising a larger number of subjects and should be overcome by acquiring an additional imaging slab in a more caudal position (15). Alternatively, two oblique imaging volumes can be oriented along the long axis of the left main or left anterior descending and the right or left circumflex coronary arteries. Use of this technique permits visualization of long vessel segments on a single section, and projection angiograms made up of contiguous sections may be obtained (30).

Our 3D breath-hold images demonstrated significantly higher signal-to-noise and contrast-to-noise ratios than did our respiratory-gated images. This can be explained by the T1-shortening effect of gadopentetate dimeglumine, which was administered intravenously to minimize blood saturation effects associated with the short repetition time of 3.4 msec. High vessel signal intensities were obtained in all subjects, which indicates correct timing of contrast agent arrival in the coronary vessels during image acquisition. The formula used for timing of the contrast material arrival was initially proposed for use with longer imaging protocols with linear k-space acquisitions. This was to ensure temporal coincidence of sampling of the central parts of k space, which predominantly contribute to image contrast, with the center of the steady-state phase of intravascular contrast material concentration (22). By using this timing scheme, absence of contrast material at the beginning and end of image data acquisition occurs if the imaging time is much longer than the contrast material injection time and this may lead to image degradation. This effect, however, is not expected to be very pronounced in our study, since the imaging time was only approximately 9 seconds longer than the injection time for gadopentetate dimeglumine. In addition, when image data acquisition started, a certain concentration of contrast material was already reached within the coronary arteries, since the contrast agent transit time used for calculation was determined on the basis of the maximum and not the onset of the up slope in the signal intensity curves. Furthermore, the presence of the contrast agent within specific vessel areas is always longer than the actual injection time, thus covering also the final parts of data acquisition.

The attempt to quantify image analysis on the basis of signal-to-noise and contrast-to-noise ratios resulted in statistical superiority of the breath-hold technique. Qualitative image analysis, however, demonstrated a slightly better visibility of the coronary vessels with use of the respiratory-gated technique. Several reasons might be responsible for this controversial result. First, the spatial resolution of the breath-hold images was distinctly lower (2.1 x 1.2 x 2 mm vs 1.17 x 1.17 x 2 mm). Second, the diastolic time window of data acquisition is 175 msec with the respiratory-gated technique and 238 msec with the breath-hold technique. The latter method, therefore, is more susceptible to motion effects of the coronary arteries. In addition, the inability of patients to hold their breath until the end of the measurement might have further contributed to image blurring in some of the cases.

In this study, three of five hemodynamically significant coronary stenoses could be detected with each MR technique. Of course, this small number does not allow us to draw any final conclusions about the clinical usefulness of the methods. The results, however, show the feasibility of stenosis assessment with the breath-hold technique. Future angiographically guided studies with larger numbers of patients are needed to show the ultimate clinical value of the method.

In conclusion, contrast-enhanced, 3D, breath-hold MR angiography is a promising rapid MR technique for visualization of the coronary arteries and may be useful in assessing hemodynamically significant coronary artery stenoses. Although the currently used technique could not demonstrate a superiority of image quality compared to that with the respiratory-gated technique, the method presents a major improvement, since volumetric data sets suitable for MR coronary angiograms in secondary image reconstructions can be obtained within a minimum acquisition time. The major limitations of this particular implementation are related to the length of the diastolic data acquisition and spatial resolution. Further improvements in image quality can be expected in the near future with use of stronger gradient systems. Single MR laboratories have already shown gradient systems with up to 34 mT/m and a slew rate of 150 mT/m/msec (31). On the basis of these data, the acquisition time could be cut by a factor of 2. Alternatively, a noticeable increase in spatial resolution could be achieved. Considering these further technical developments, 3D contrast-enhanced breath-hold imaging may become an efficient tool in the diagnosis and management of coronary artery disease.


   Footnotes
 
Address reprint requests to W.K.

Abbreviations: FLASH = fast low-angle shot 3D = three-dimensional

Author contributions: Guarantors of integrity of entire study, W.K., G.L., W.G.D.; study concepts, W.K., G.L., S.A.; study design, all authors; definition of intellectual content, W.K., S.A., D.R.; literature research, W.K., D.R.; clinical studies, W.K., S.A., D.R., W.M. W.G.D.; data acquisition, all authors; data analysis, W.K., S.A., D.R., W.M., W.G.D.; statistical analysis, W.K., S.A., D.R.; manuscript preparation, W.K., G.L., S.A.; manuscript editing, W.K., D.R.; manuscript review, W.K., G.L., S.A., W.M., W.G.D.

Received January 30, 1998; revision requested April 7, 1998; revision received June 19, 1998; accepted August 20, 1998.
   References
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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