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Technical Developments |
1 From the BHF Cardiac MRI Unit (S.P., T.R.J., T.N.B., M.U.S.) and Department of Medical Physics (J.P.R.), Leeds General Infirmary, Great George St, Rm 170, D-floor, Jubilee Building, Leeds LS1 3EX, England. Received August 27, 2001; revision requested October 17; revision received December 10; accepted January 29, 2002. S.P. supported by a British Heart Foundation Junior Research Fellowship. Address correspondence to S.P. (e-mail: sven.plein@leedsth.nhs.uk).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMaterials and Methods ResultsDiscussionREFERENCES |
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© RSNA, 2002
Index terms: Coronary vessels, MR, 51.121412, 51.121413, 54.12144 • Heart, function, 51.12144 • Heart, perfusion, 51.12144 • Myocardium, MR, 511.12144
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMaterials and Methods ResultsDiscussionREFERENCES |
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Recent developments in MR imaging hardware and software have resulted in improved electrocardiographic triggering, better gradient performance, and faster acquisition sequences. These developments have led to substantial reductions in imaging times while preserving or improving image quality. By using these technical advances, we designed an MR imaging protocol for the comprehensive assessment of CAD that combines imaging of cardiac function, myocardial perfusion and viability, and coronary anatomy in one 1-hour imaging session. The purpose of this initial study was to evaluate the feasibility of this protocol in patients with CAD.
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Materials and Methods |
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TOPABSTRACTINTRODUCTIONMaterials and Methods ResultsDiscussionREFERENCES |
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MR Imaging Protocol
Studies were carried out with a 1.5-T MR imager (Gyroscan NT Intera CV; Philips Medical Systems, Best, the Netherlands) equipped with a Master gradient system (30 mT/m peak gradients and 150 m/T/sec slew rate) and a five-element cardiac phased-array coil. We used a vectorcardiographic method for electrocardiographic gating and triggering (16).
The MR imaging protocol has a theoretic total imaging time of 53 minutes and is summarized in Table 1. The pulse sequences in this protocol were chosen to minimize imaging times without unduly compromising image quality. The order of the images reflects our aim to separate the two perfusion images by a maximal time to allow washout of contrast agent after the first injection and to provide sufficient delay after the final injection for optimal MR imaging with delayed contrast enhancement. The protocol comprises acquisition of the following images.
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Image 2.—Breath-hold cine MR images in the two-chamber short-axis and four-chamber orientations (balanced fast field echo; 2.8/1.4; flip angle, 55°; partial Fourier acquisition; one signal acquired; field of view, 360 x 288 mm; matrix, 187 x 144; section thickness, 7 mm; electrocardiography triggered; 18 phases per cardiac cycle; one section per 5-second breath hold). The four-chamber image was acquired with 30 phases in an 8-second breath hold to allow assessment of the motion of the coronary arteries through the cardiac cycle. This information was used later in the protocol. The true left ventricular short axis was then planned on the basis of findings on the two- and four-chamber images.
Image 3.—A reference MR image to provide a three-dimensional (3D) coil sensitivity map (3D fast field echo; 8/0.51; flip angle, 7°; nine signals acquired; field of view, 530 x 530 mm; matrix, 32 x 26; two stacks of 50 coronal sections). These image data are required for reconstruction of data acquired in images 4 and 8.
Image 4.—A resting perfusion MR image obtained with a dynamic segmented k-space gradient-echo pulse sequence combined with a parallel data acquisition method (sensitivity encoding) (17). Four sections can be acquired every heartbeat up to a heart rate of 100 beats per minute (saturation-recovery T1-weighted turbo field echo; 3.1/1.6; flip angle, 15°; four short-axis sections acquired in sequential order from base to apex; saturation-recovery times of 42, 164, 287, and 410 msec, respectively; field of view, 350–450 mm as required to avoid image aliasing; acquisition matrix, 160 x 112 reconstructed to 256 x 256; one signal acquired; 8-mm section thickness; sensitivity encoding factor of 2). Data were acquired during 40 seconds, with 10 baseline images acquired in a first breath hold followed by two respiratory cycles and an additional breath hold. At the time of the second respiratory cycle, a bolus of gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany) was rapidly injected by hand into an antecubital vein at a dose of 0.05 mmol per kilogram of body weight followed by a flush of 10 mL of normal saline. During the contrast material washout phase, dynamic images were acquired during 1 minute with short breath holds at every eighth R-R interval.
Image 5.—A multisection cine data set that covers the left ventricle in 10–14 short-axis sections from apex to base and is obtained with a balanced fast field-echo sequence similar to that described for image 2 but with a matrix 192 x 163, section thickness of 6 mm, intersection gap of 4 mm, and two sections acquired during each 10–12-second breath hold.
Image 6.—A free-breathing navigator-gated transverse 3D segmented echo-planar turbo field-echo scout image for localization of the coronary arteries (16/4.9; flip angle, 40°; field of view, 350 x 245 mm; acquisition matrix, 192 x 256; section thickness, 4 mm with 2-mm overlap reconstructed to 50 2-mm-thick sections; partial Fourier acquisition; echo train length, 11; four acquisitions; four refocusing pulses; T2 preparation; fat suppression; and magnetization transfer). The navigator beam was placed perpendicular to the right hemidiaphragm, and real-time navigator gating was applied with an adaptive gating window (6-mm window for the outer 65% of k space, 2-mm window for the central 35% of k space) and a continuously updated mean gating window level.
Image 7.—A high-spatial-resolution 3D coronary MR angiogram of the right coronary artery (RCA). The course of the RCA was identified on image 6, and the imaging plane was planned with a three-point image planning tool by placing points at the origin, midpoint, and distal aspect of the vessel. Data acquisition was performed during free breathing with a 3D segmented k-space gradient-echo sequence (7/2.1; flip angle, 25°; T2 preparation prepulses (echo time, 50 msec); field of view, 400 x 300 mm; acquisition matrix, 512 x 288 reconstructed to 512 x 512; in-plane spatial resolution, 0.78 x 1.04 mm; eight contiguous 3-mm-thick sections interpolated during reconstruction to 16 1.5-mm-thick sections). Prospective navigator gating with an adaptive gating window was applied as in image 6 with real-time correction of the 3D volume position in the craniocaudal direction. We used the four-chamber balanced fast field-echo cine images acquired at a high temporal resolution to determine the period in the cardiac cycle with the least motion of the RCA. This period was used to determine the trigger delay and acquisition window for every patient individually. The acquisition window was in the range of 140–200 msec in all patients.
Image 8.—For administration of pharmacologic stress, patients were initially removed from the magnet bore, but they remained in the same position on the examination table. Adenosine was administered at a standard dose of 140 µg/kg/min for 5 minutes, and patients were monitored continuously (symptoms, blood pressure, heart rate, electrocardiogram) during the infusion. After 3 minutes of the infusion, patients were placed back in the magnet bore, and the second dynamic perfusion MR image was started. The sequence and image orientation were identical to those used at resting perfusion MR imaging except that the heart rate was adjusted as required. Immediately after completion of imaging, a bolus of 0.1 mmol/kg of contrast agent was injected to increase the total dose to 0.2 mmol/kg for MR imaging with delayed contrast enhancement.
Image 9.—A high-spatial-resolution 3D MR angiogram of the left coronary artery system obtained with the same sequence used to acquire image 7. The image orientation was planned with the three-point image planning tool by placing a point on the proximal left main stem (LMS) and the most distal aspects of the left anterior descending (LAD) and left circumflex (LCX) coronary arteries identified on the coronary scout image (image 6). The trigger delay and acquisition window were again determined individually on the basis of the 30-frame four-chamber cine acquisition.
Image 10.—An inversion-recovery segmented k-space gradient-echo (T1-weighted turbo field-echo) pulse sequence with a nonselective 180° prepulse for MR imaging with delayed contrast enhancement (7.5/3.8/200–250 [inversion time msec, which was adjusted for each patient to achieve optimal suppression of normal myocardium]; flip angle, 15°; trigger delay set according to the heart rate for data acquisition in middiastole; field of view, 300 x 300 mm; matrix, 256 x 256; 12 acquisitions; one section per breath hold). From six to eight short-axis sections were acquired to cover the left ventricle.
Image Analysis
Ventricular volume, wall motion, and perfusion data were analyzed off-line with a workstation (UltraSPARC 10; Sun Microsystems, Palo Alto, Calif) with commercially available analysis software (MASS, version 4.1; Medis, Leiden, the Netherlands). Coronary MR angiograms and MR images with delayed contrast enhancement were analyzed with a separate workstation equipped with commercial image postprocessing software (EasyVision, version 4.0; Philips Medical Systems). For measurements of wall motion, myocardial perfusion, and delayed contrast enhancement, the left ventricular short-axis sections were divided into anterior, lateral, inferior, and septal segments. The inferior segments were considered to represent the territory of the RCA; the lateral segments, the territory of the LCX coronary artery; and the anterior and septal segments, the territory of the LAD coronary artery.
All images were analyzed for the presence of imaging and motion artifacts in the area of interest. The image quality of each component of the MR image was graded as sufficient or insufficient for analysis on the basis of the presence or absence of artifacts.
Each part of the MR imaging protocol was analyzed separately with consensus of two observers (S.P., M.U.S.), who were blinded to the results of the other MR imaging components and the results of other clinical tests. For measurements of left ventricular volumes, endocardial contours were manually traced by one observer (S.P.) at end diastole and end systole on the short-axis cine data sets. Left ventricular end-diastolic volume (EDV) and left ventricular end-systolic volume (ESV) were computed with the modified Simpson rule and the ejection fraction (EF) determined as EF = [(EDV - ESV)/EDV] x 100%.
Segmental wall thickening was visually analyzed on the short-axis cine MR images, and the regional function of each segment (combined inward endocardial motion and systolic wall thickening) was graded as normal, hypokinetic, akinetic, or dyskinetic.
MR perfusion analysis was performed qualitatively by means of visual inspection of dynamic MR images in the cine mode. Rest and stress images were viewed side by side and compared section by section. Perfusion was characterized as normal or reduced for each segment. Reduced perfusion was reported if contrast material wash-in was delayed or if the signal intensity was noticeably lower than that in other parts of the myocardium. Fixed perfusion defects were reported if reduced perfusion was observed in a segment at rest and during stress. An inducible defect was reported if perfusion was rated as normal at rest but abnormal at stress. A combined fixed and inducible defect was reported if there was a mixture of both results in one segment.
MR images with delayed contrast enhancement were analyzed to assess the presence of hyperenhanced myocardial tissue in each segment. The maximal transmural extent of hyperenhancement for each segment was measured and expressed as a percentage of the wall thickness.
Coronary MR angiograms were analyzed by scrolling through the individual sections of the 3D data set. The LMS, LAD coronary artery, LCX coronary artery, and RCA were scored as normal or diseased. In diseased arteries, the presence of coronary artery stenoses was graded as mild (<50%), moderate (50%–70%), severe (70%–99%), or occluded (100%).
Conventional coronary angiograms were read independently by an experienced interventional cardiologist, who was blinded to the result of the MR imaging analysis. The grading system was the same as that used for the analysis of coronary MR angiograms.
Statistical Analysis
Means and SDs are given for all continuous data. For statistical analysis, the results of all four components of the MR imaging study were combined and compared with the conventional angiogram as the standard of reference for detection of CAD. The sensitivity and specificity of the combined MR analysis to depict significant CAD (moderate or severe) were determined for patients and individual coronary arteries. For the analysis of individual coronary arteries, the LMS was regarded as a separate vessel, with only the coronary MR angiograms used for comparison with conventional angiograms. Sensitivity was defined as the number of patients (arteries) with moderate or severe CAD with an abnormality on at least one component MR image. Specificity was the number of patients (arteries) with mild or no CAD on conventional angiograms with normal four-component MR images.
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Results |
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TOPABSTRACTINTRODUCTIONMaterials and Methods ResultsDiscussionREFERENCES |
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A summary of the results for all patients is displayed in Table 2. The Figure shows wall motion, perfusion, and MR images with delayed contrast enhancement and coronary MR angiograms acquired in patient 9.
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Perfusion
The perfusion MR images allowed qualitative analysis in all patients. In patient 8, the stress perfusion MR image was placed more basal than the rest perfusion MR image, and the comparison between rest and stress may have been unreliable. Normal resting perfusion could be demonstrated in four of the five patients without a history of MI. All four patients had inducible defects on stress perfusion MR images that matched the territories of significantly diseased coronary arteries. Patient 8, who did not have a history of MI, appeared to have fixed perfusion deficits in the anterior and inferior segments. All patients with previous MI had abnormalities on perfusion MR images, with fixed or inducible defects that matched occluded or severely diseased coronary vessels and akinetic or hypokinetic areas at wall motion analysis.
MR Imaging with Delayed Contrast Enhancement
Results at MR imaging with delayed contrast enhancement were normal in four of the patients without a history of MI, while patient 8 had a small transmural area of hyperenhancement in the inferior wall. This segment showed normal wall motion and a small fixed perfusion defect. At conventional angiography, the supplying coronary artery was severely diseased; this finding suggests that a small silent MI had occurred in the past. All five patients with a history of MI showed evidence of hyperenhancement with corresponding wall motion and perfusion abnormalities. All akinetic segments showed a complete transmural extent of hyperenhancement, while hypokinetic regions were either normal or showed only subendocardial hyperenhancement on MR images with delayed contrast enhancement.
Coronary MR Angiography
MR images of all but three coronary arteries were graded as sufficient for analysis. Patient 6 had an aberrant RCA that arose from the LAD coronary artery. MR imaging depicted the course of this vessel between the aorta and the pulmonary artery. Coronary MR angiograms correctly depicted 15 of 20 moderate or severe coronary artery stenoses, and 17 of the 20 arteries were correctly identified as normal.
Combined MR Imaging Analysis
When all components of the protocol were combined, MR images correctly depicted the presence of previous MI (five of five patients) or significant CAD (five of five patients) in all patients. Thus, the sensitivity and specificity of the combined analysis were both 100% (95% CI: 47.8%, 100%). On the basis of individual vessels, the analysis allowed localization of 19 of 20 moderate or severe lesions. Four false-positive results were reported in the 20 normal or mildly diseased vessels. Thus, the sensitivity of all components combined to depict moderate or severe stenosis in individual coronary arteries was 95% (95% CI: 75.1%, 99.9%) with a specificity of 80% (95% CI: 56.3%, 94.3%).
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Discussion |
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TOPABSTRACTINTRODUCTIONMaterials and Methods ResultsDiscussionREFERENCES |
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The four-component images in this protocol were each obtained to assess different pathologic effects of CAD and, thus, provide complementary information. Therefore, we considered the combined analysis as abnormal if any component image showed an abnormality. This diagnostic decision reduced the likelihood of false-negative results compared with the separate analysis of each component; the resulting sensitivity of our analysis was higher than those reported for single-component analysis (1–15). Despite the high sensitivity, the specificity in this study was acceptable even for analysis of individual vessels, and only four false-positive findings were reported. The high sensitivity may, in part, be the result of the high frequency of CAD in our patient cohort. On the other hand, the assignment of coronary artery territories was rigid, and individual variations were not considered; these methods may have adversely affected the accuracy of our analysis. A larger study of more patients will be required to fully assess the diagnostic accuracy with our protocol.
The protocol was completed in just longer than 1 hour in 10 nonselected patients. All patients tolerated the examination well with no adverse effects. Removal of patients from the magnet bore for administration of pharmacologic stress proved to be an effective way of ensuring patient compliance with this part of the protocol. The mean imaging time was 8 minutes longer than the expected theoretic imaging time. The longer time was the result of minor technical and patient-dependent problems, such as fold over and poor breath holding, that are to be expected in clinical practice. At the time this study was conducted, perfusion and coronary artery MR imaging required the use of prototype software with relatively long planning and image reconstruction times. With the commercial software available currently, the processing times for these images is shorter by as much as 2 minutes for each image, and the total imaging time may be shortened by an additional 8 minutes.
In our protocol, we aimed to provide short imaging times to allow the combination of several MR imaging components in one study while maintaining high image quality for each image. This goal is reflected in the order of the component images and the choice of sequences. We used a steady-state free precession sequence for all functional imaging. This technique offers considerably better signal-to-noise ratio and endocardial border definition than are offered with conventional gradient-echo sequences (18–20), in approximately half the imaging time (20). In our study, steady-state free precession sequences proved to be very robust and provided reproducibly high image quality in all patients. The presence of previous MI could be identified, and global left ventricular function, as a measure of surgical risk and patient prognosis, could be measured reliably. Breath holds for functional imaging were all less than 10 seconds and could be managed by all patients.
We obtained the perfusion MR images at the beginning and toward the end of the protocol to allow maximal clearance of contrast agent between the two injections. In the perfusion sequence, a parallel acquisition technique, sensitivity encoding (17,21) was used that allowed us to acquire four sections in every heartbeat. Multisection acquisition is vital to achieve high diagnostic accuracies in perfusion MR imaging, and high temporal resolution is required to allow accurate assessment of signal intensity slopes. Multisection coverage and acquisition in every heartbeat are difficult to achieve with conventional acquisition sequences. Therefore, the use of hybrid acquisition sequences has been suggested (8), but they can be limited by susceptibility and chemical shift artifacts. With sensitivity encoding, we were able to achieve multisection coverage with a conventional segmented k-space gradient-echo sequence that is inherently less susceptible to artifacts and, therefore, offers better image quality. Disadvantages of sensitivity encoding are that a reference image needs to be acquired that adds to the total imaging time of the protocol and that image planning is more time consuming because image aliasing must be avoided. Also, the signal-to-noise ratio in parallel acquisition is reduced by approximately the square root of the sensitivity-encoding factor.
Coronary artery MR angiography is at present arguably the least competitive of the MR imaging components in the assessment of CAD compared with the available reference standard, and substantial further developments are required to approach the spatial resolution and robustness of conventional angiography. Coronary MR angiography is also one of the most time-consuming cardiac MR imaging examinations. Therefore, the inclusion of coronary imaging in a condensed protocol such as this requires that compromises be made. The acquisition sequence used in this protocol is a modification of a sequence presented by Stuber et al (12) that has a similar spatial resolution but a substantially shorter imaging time. These improvements were achieved mainly by reducing the number of acquisitions, which resulted in a longer acquisition window. We used a pragmatic approach to minimize the effects of coronary artery motion during a longer acquisition window that is similar to a method recently described by Kim et al (22). We observed the time of minimal coronary motion individually in each patient on the 30-frame four-chamber cine acquisition and determined subject-specific acquisition windows. Findings in the work by Kim et al and an earlier study by Wang and colleagues (23) show that periods of minimal coronary motion vary between individuals and can be as long as 200 msec if the heart rate is less than 60 beats per minute. This variance allows the use of longer acquisition windows to shorten imaging times without unduly affecting image quality. In our study, nine of the 10 patients were being treated with beta-blocking medication, as are most patients with established or suspected CAD, and their mean heart rate was 54 beats per minute, which facilitated this approach to coronary imaging.
Other modifications of our coronary sequence were aimed to improve the efficiency of the respiratory navigator. Navigated acquisition may require long and unpredictable acquisition times caused by poor navigator efficiencies. To optimize the efficiency, we allowed continuous correction of the mean gating window position to adjust for diaphragmatic drift during the acquisition. We also used motion adaptive gating to acquire the central parts of k space in a narrow gating window (2 mm in our study) and the outer parts with a wider gating window (6 mm). Therefore, most of the data are acquired with a wide gating window, at higher navigator efficiency, but the important contrast information is acquired with a narrow gating window.
An alternative to our coronary sequence would be two-dimensional breath-hold techniques. However, 3D data sets offer better diagnostic information than do two-dimensional techniques because they provide a continuous data set and better signal-to-noise ratio. Furthermore, in a long total examination time, periods of free breathing provide important periods of rest for patients and improve their compliance with the procedure. The results of our approach are encouraging but should be validated against the previously published techniques.
MR imaging with delayed contrast enhancement for assessment of myocardial viability is rapidly gaining clinical recognition (9,10). The ability to depict nonviable tissue and its transmural extent make such imaging an extremely powerful and clinically relevant tool. Findings in a recent study have shown that dysfunctional myocardium with a high proportion of hyperenhancement is unlikely to recover function after revascularization (9). Findings in our study demonstrate that MR imaging with delayed contrast enhancement can easily be incorporated into a comprehensive MR imaging protocol, even if the contrast agent is administered in multiple separate injections to allow the acquisition of rest and stress perfusion data in the same session. The high clinical relevance of this test was confirmed in our patient population, where the extent of hyperenhancement correlated with the degree of myocardial dysfunction. In addition, MR images with delayed contrast enhancement depicted a small area of infarction in a patient with a normal electrocardiogram, normal wall motion, and no known history of MI.
To assess both inducible ischemia and viability in one imaging session, other groups have advocated the use of both dobutamine and adenosine stress in a combined protocol (24). We suggest that MR imaging with delayed contrast enhancement combined with adenosine perfusion MR imaging may be an easier, safer, and more practical alternative to obtain the same information.
A limitation of our study is that, with the exception of volumetric measurements, we analyzed all the image data qualitatively. Analysis time for all image components was less than 30 minutes per patient in this study. Although MR imaging allows semiquantitative or quantitative analysis, it is considerably more time consuming and, therefore, is of limited use in clinical practice. Furthermore, at present no standards have been agreed on for quantitative perfusion analysis. With the data acquired in this protocol, however, semiquantitative or quantitative analysis is feasible and will be the subject of future work.
In conclusion, this protocol, which allows acquisition of high-quality data for a comprehensive assessment of CAD, yields high diagnostic accuracy and can be completed in approximately 1 hour. We believe that the protocol now warrants evaluation in a wider patient population.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Author contributions: Guarantor of integrity of entire study, S.P.; study concepts, S.P., J.P.R., M.U.S., T.R.J.; study design, S.P., J.P.R., M.U.S.; literature research, S.P.; clinical studies, S.P., T.N.B., T.R.J.; data acquisition, T.R.J.; data analysis/interpretation, S.P., T.N.B.; statistical analysis, S.P.; manuscript preparation, all authors; manuscript definition of intellectual content and editing, S.P.; manuscript revision/review and final version approval, all authors.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMaterials and Methods ResultsDiscussionREFERENCES |
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