Asian Cardiovasc Thorac Ann 2006;14:387-393
© 2006 Asia Publishing EXchange Ltd
Evaluation of the Spatial Resolution with 1.5-4 Tesla in a Stenosis Model
Thomas Wittlinger, MD,
Ivo Martinovic, MD1,
Anton Moritz, MD,
Sandro Romanzetti, MD2
Department of Thoracic and Cardiovascular Surgery, University Hospital, Frankfurt, Germany
1 Department of Heart Surgery, University Hospital, Marburg, Germany
2 Institute of Medicine, Research Center Jülich, Jülich, Germany
For reprint information contact: Thomas Wittlinger, MD Tel: 49 63 018 3315 Fax: 49 67 326 5370 Email: thomaswittlinger{at}t-online.de, Department of Thoracic and Cardiovascular Surgery, University Hospital, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
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ABSTRACT
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Since it was first described in the early 1990s, magnetic resonance coronary angiography has evolved into a promising noninvasive modality for imaging the coronary arteries. The aim of this study was to evaluate the detection accuracy and spatial resolution of vascular stenosis in contrast-enhanced 3-dimensional magnetic resonance angiography on a flow phantom. The examinations were performed with 1.5, 3, and 4 T whole-body imaging systems. For imaging at 4 T, we used a gradient-echo-multi-slice sequence. The system was flushed with gadopentetate dimeglumine contrast medium at flow rates of 40 and 60 mL·min–1. The accurate detection of in vitro stenoses was possible in segments of 0.4 mm in diameter at 4 T. The best results were obtained at a flow velocity of 40 mL·min–1 and a contrast medium concentration of 0.2 mmol·L–1. Contrast-enhanced high-field 3-dimensional magnetic resonance imaging provided a highly accurate evaluation of the degree of stenosis in this model. Exact evaluation of vessel diameters < 0.4 mm was not possible, even with 4 T. In vivo studies are necessary to overcome the current limitations in the visualization of small distal vessel segments.
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INTRODUCTION
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Cardiovascular disease remains the leading cause of death in the western world. Among recently developed noninvasive approaches to visualization of the coronary arteries, magnetic resonance coronary angiography (MRCA) offers particular advantages over other techniques such as multi-detector computed tomography and electron-beam computed tomography.1 The current limitations of MRCA include a suboptimal signal-to-noise ratio (SNR), which limits spatial resolution. The ability to visualize and assess more distal or branching vessels is desirable, and quantitative grading of coronary artery stenoses is the ultimate goal. The SNR is directly related to the strength of the magnetic field. Improved SNR can be expected from higher-strength magnets; 3.0 Tesla (T) and 4.0 T systems have recently been approved for clinical use.1 Imaging at 4 T yields an approximately 2.5-fold increase in SNR over imaging at 1.5 T.2 This improved image quality can increase the in-plane resolution to a vessel diameter of < 1 mm. The stronger magnetic field gives rise to numerous impediments including increased susceptibility to artefacts, reduced T2* and increased T1 radiofrequency field distortions.2–4 General sequence design and efficient myocardial motion suppression is decreased in high-field magnetic resonance imaging (MRI). Recent improvements in 3 and 4 T hardware (vector electrocardiogram), short-bore magnets, dedicated surface coils, and the adaptation of cardiac-specific software and 2-dimensional selective real-time navigators have made it possible to implement MRCA methodology with whole-body 3 and 4 T scanners.5–7 The extension of nonsignificant risk status to clinical fields up to 8 T by the US Food and Drug Administration in 2003 facilitated further growth of this technology. In addition to the effects of a static magnetic field, the effects of radiofrequency and gradient fields have to be considered.1 Several studies have demonstrated no significant changes in vital signs in subjects exposed to field strengths up to 8 T.8 The aim of this study was to evaluate the spatial resolution of MRCA on a dedicated coronary stenosis model at 1.5, 3.0, and 4.0 T. The influence of contrast medium concentration and flow velocity on the spatial resolution was also examined.
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MATERIALS AND METHODS
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For evaluation of stenosis, glass tube in vitro vessel models with defined diameters were used. Glass tubes were embedded in a 3 x 4 cm Plexiglas block. The details are given in Table 1
and Figure 1. The models with stenosis all had a pre- and poststenotic internal diameter of 2.8 mm, with the stenosed segments having diameters between 0.3 and 2.5 mm, corresponding to stenoses of 10.7% to 89.3%. The lengths of the stenoses were 3–10 mm (Table 1). The diameters of the non-stenosed phantoms ranged from 0.3 to 5.5 mm. The length of the pre- and poststenotic areas were different, in order to simulate stenosis morphology seen in coronary angiography.
For imaging, 10% hydroxyethyl starch (HAES, Fresenius Kabi, Dusseldorf, Germany) with susceptibility characteristics and properties similar to those of blood was used. This fluid shows almost equivalent osmolarity and viscosity to human blood. The contrast medium was gadopentetate dimeglumine (Magnevist; Schering AG, Berlin, Germany). To determine the influence of contrast medium concentration on spatial resolution, the models were perfused with Magnevist at 0.1, 0.2, and 0.3 mmol·L–1. The phantom was placed in a water bath in the isocenter of the magnet. Measurements were performed first in the z-axis and additionally at 45° and 90°. The study was carried out with stationary contrast medium and a defined flow rate. Flow rates of 40 and 60 mL·min–1 with constant flow were used, which correspond to average intracoronary flow rates described in the literature, and also to those determined in our own patient studies.7 Continuous flow rates were produced by means of a pump (Lauda thermostat type GPS 1517; Dr K Wobsa GmbH, Lauda-Königshofen, Germany) that was set up outside the MRI area, to avoid ferromagnetic effects, and connected to the phantom with a long supply line. The flow rates set at the pump had been tested in a previous study using an electromagnetic flowmeter (Carolina Medical Electronics, Inc., King, NC, USA). The phantom was placed in a water bath with the supply line, to simulate the environment of the human thorax.
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IMAGING AT 1.5 T
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In vitro MRI was performed on a whole-body 1.5 T Intera scanner (Philips Medical Systems, Best, The Netherlands) with a gradient of 30 mT and a slew rate of 150 T·m–1·sec–1. A multisegment quadrature T/R head coil was used for signal acquisition, and a T1 fast-field-echo gradient-echo-sequence was used for imaging (echo time minimum, flip angle 25°, matrix 512 x 512, field of view 30 cm, slice thickness 1 mm).
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IMAGING AT 3 T
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The in vitro models were examined with a 3 T MRI scanner (Signa 3 T, GE Medical Systems, Milwaukee, WI, USA) with a gradient of 40 mT and a rise time of 268 msec. The gradient amplitude was 69 mT·m–1 and the gradient slew rate was 259 T·m–1·sec–1. A multisegment quadrature T/R head coil was used for signal acquisition. The MRI was performed with 3D gradient-echo-sequences (fast spoiled gradient echo) with echo time set to minimum, a flip angle of 25°, matrix of 512 x 512, field of view 30 cm, and a slice thickness of 1 mm. The repetition times were 0.9 msec minimal and 2.9 msec maximal.
To improve spatial resolution, we performed measurements with the number of excitations (NEX) = 0.5, 1, and 2. NEX = 0.5 represents a half Fourier transformation of the k space, whereby only slightly more than half of the lines of the k space are selected, and the rest of the image is reconstructed from these data. NEX = 1 represents the standard transformation of the entire k space. For NEX = 2, two averages are taken, which makes it possible for an increase of approximately 40% to be achieved in the SNR.7
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IMAGING AT 4 T
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The Varian 4T Research System (Varian GmbH NMR System, Darmstadt, Germany) installed at the Institute of Medicine of the Research Center Jülich is a state-of-the-art MR scanner based on a 4 T active shielded superconducting magnet produced by Oxford Magnet Technology (OMT, Oxford, UK). The system also comprises high-stability shims and Siemens Sonata gradients, which are capable of a maximum gradient field amplitude of 40 mT·m–1 and 200 µsec rise time. The main properties of a gradient system are: the maximum gradient amplitude, which determines the highest attainable resolution; and the rise time, which is the time needed to reach the maximum gradient amplitude from the ground state. The 4 T MRI scanner is equipped with the Siemens Sonata gradient system. This system, which also features active shielded coils for better performance, is the most powerful system for specialized applications such as functional MRI, anatomical imaging, and real-time cardiac imaging. The Sonata gradient system delivers a 40 mT·m–1 maximum gradient amplitude on the 3 axes simultaneously, with tailored gradient waveforms, and provides an extremely short rise time of 200 µsec. In clinical terms, these characteristics translate into sub-millimeter spatial resolution and short repetition and echo times so that in applications such as real-time cardiac imaging, images are recorded at high speed and at the optimal resolution (Figure 2). The MRI was performed with an echo time of 5 msec, repetition time of 20 msec, flip angle of 5°, matrix of 256 x 256, field of view 100 x 100 mm, and slice thickness of 0.5 mm. In this study, we used a 16 cm quadrature birdcage coil to receive the MR signal.
Image analyses were performed on the 3D data with a Varian Unity Inova system (Varian, Inc., Palo Alto, CA, USA). The image data were reformed in a multiplanar fashion as described previously.9 Determination of the internal diameters was carried out at the workstation on the basis of the different measurements and with the help of a signal intensity profile, using the technique described by Hoogeveen. The reliability of the method was calculated using sensitivity and specificity tables. The concordance correlation was determined using the method of Lin.10 This is +1 when there is perfect concordance. The 95% confidence levels for sensitivity and specificity were calculated following an approximation according to Geigy scientific tables. At the 95% confidence level, the p value (McNemar’s test) and Cohen’s kappa showed a correlation between the experimental and reference groups as well as among members of the experimental groups. The results of the flow measurements were assessed using the t test, and a value of p < 0.05 was considered to be statistically significant. All calculations were carried out using SAS/Stat version 8.2 (SAS Institute, Cary, NC, USA).
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RESULTS
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At 1.5 T, vessel stenosis with a minimum diameter of 0.91 mm can be evaluated, but MRI overestimates the actual diameters (Table 2). The best results were obtained at a flow rate of 40 mL·min–1; however, the differences between results obtained at the two flow velocities were not significant. Determination of the length of stenosis was possible only in vessels with a diameter of at least 1.5 mm, because vessels smaller than 1 mm in diameter exhibited very short stenoses (3–5 mm).
With 3 T MRI, vessel stenosis with a minimum diameter of 0.6 mm could be evaluated. Magnetic resonance imaging slightly overestimates the actual diameters (Table 2
). The best results were obtained at a flow rate of 40 mL·min–1 at NEX 2. The flow rate or contrast medium concentration had no statistically significant influence on the accuracy of correlation to NEX. In the clinical situation, however, lower resolutions can be expected due to the limitations of the intrinsic periodic movements of the heart and the extrinsic respiratory movements that are superimposed over the cardiac movements. Both movement components amount to 1–2 cm, which is more than 30 times the resolution and approximately 5 to 10 times the size of coronary diameters. In a further step, longitudinal imaging of the stenotic segments was investigated. This showed that exact longitudinal imaging is problematic, especially in vessel segments with diameters < 1 mm; in addition, mean variations of 0.58 mm were observed. The values for the variations in intra-stenotic length measurements (Figure 3) are primarily due to high-grade stenoses of 79%–90%. The high-grade stenoses in our model were less than 5 mm in length (Table 1), which are difficult to image, and this results in a substantial measurement error. With stenoses of < 70%, corresponding to vessel diameters of > 1 mm, the variation in measurement was only 0.28 mm. At 3.0 T, the limits of exact evaluation were reached with vessels of 1 mm diameter and short stenoses of up to 5 mm in length.
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Figure 3. Variations in magnetic resonance imaging (MRI) measurements of stenosis in the reference sample at 1.5, 3, and 4 T.
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With the newly developed 4 T high-field scanner, vessel stenoses with a minimum diameter of 0.4 mm could be evaluated. Imaging of vessels with a diameter < 0.4 mm was not possible. Magnetic resonance imaging slightly overestimated the actual diameters (Tables 2 and 3). The best results were obtained at a flow rate of 40 mL·min–1 (Table 4). Correlation with the relevant standard was higher at 40 mL·min–1. In the 4 T study, the best results were obtained with a mean of 64 averages, which made it possible to evaluate vessels of 0.4 mm diameter, but also increased the measurement time by a factor of 2. The best results were obtained with a contrast medium concentration of 0.2 mmol·L–1, but a statistical correlation could not be verified. The longitudinal imaging of stenotic vessel areas was also investigated. This revealed that exact longitudinal imaging is problematic, especially in vessel segments with diameters < 1 mm; a mean variation of 0.58 mm was observed. The values for the variations in intra-stenotic length measurements shown in Figure 3 are primarily due to high-grade stenoses of 79%–90%. Since these are short narrow sections of 3–5 mm (Table 1), which are difficult to image, a substantial measurement error arises. With stenoses of < 74%, corresponding to vessel diameters of > 0.72 mm, the variation in measurement amounted to only 0.22 mm. In comparison to 1.5 T and 3 T, the spatial resolution at 4 T was significantly higher ( p < 0.005). Examples of the images at 1.5, 3, and 4 T can be seen in Figures 4 and 5.
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Figure 4. Example of a 0.8 mm vessel at 3 T. The degree and the length of stenosis are clearly visible.
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Figure 5. Example of a vessel with 0.8 mm diameter at 1.5 and 4 T. With 4 T (upper image), the degree and the length of the stenosis are clearly visible. Evaluation with 1.5 T (lower image) is impossible due to the low spatial resolution.
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DISCUSSION
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Using currently available 3 T and 4 T scanner hardware, software, and sequences, we demonstrated that in vitro 3-dimensional coronary MRI with a high SNR and an enhanced spatial resolution is feasible. To date, only one group has investigated the possibility of in vivo 3 T MRA of the coronary arteries. A clear improvement in coronary imaging, with respect to longitudinal imaging, was achieved.11 Furthermore, an improvement was possible in SNR and contrast-to-noise ratio compared with the corresponding sequence at 1.5 T.7 The sharpness of the coronary vessels was comparable at both field strengths (vessel sharpness 24%–49% vs. 46% ± 10%). With these results, it is necessary to take into account the fact that the tests at 3 T were carried out on healthy volunteers; the method might not be easily transferred to measurements in patients.11,12 No studies are available yet on the use of high-field equipment with strengths greater than 3 T in patients with coronary artery disease.
Only one study, published in 2001, concerned the effect of field strength on SNR, which increased 2.0-fold at 3 T and 2.5-fold at 4 T, compared to 1.5 T.2,13 This improvement can be used to increase in-plane resolution and reduce layer thickness and the time needed for the test.2 Our own data showed a clear improvement in imaging of stenosis morphology at 4 T. Compared to MRCA at 1.5 and 3 T, a higher spatial resolution was possible as well as more precise evaluation of the intra-stenotic vessel segments (Figure 4). Using a conventional MR scanner at 1.5 T, the achievable resolution is approximately 0.91 mm. This can be improved to 0.60 mm at 3 T and to 0.4 mm at 4 T. At 3 T, the best SNR was obtained with the NEX = 2 method and this had no effect on the resolution. In the 4 T MRI test, the best results were regularly obtained with a mean of 64 averages; this made it possible to evaluate vessels of 0.4 mm diameter, but the measurement time also increased by a factor of 2. This played no role in the in vitro tests, but the shorter measurement with high-field scanners will prove to be a critical parameter in clinical use. The flow rate had no significant influence on the results.
The spatial resolution of the MR method is also dependent on the length of the stenosis. Currently, the limit for short stenoses of 3–4 mm in length is 0.5–0.6 mm, compared to 0.4 mm for long stenoses of 7–11 mm. This is also reflected in the measurement error, which is clearly higher for vessels < 0.6 mm than for vessels > 0.72 mm for which it amounts to 0.22 mm. It is precisely for high-grade short stenoses that the advantage of high-field MRI becomes apparent, as these cannot be adequately imaged with a conventional scanner at up to 1.5 T. The best results were obtained at a contrast medium concentration of 0.2 mmol·L–1, a higher or lower concentration did not improve the results in this study. This represents a limitation of these in vitro data, as the concentration of contrast medium in coronary vessels is too brief if using the available contrast media. The use of blood-pool contrast media in the future holds a promise of improved results. It must be noted that in these in vitro studies, 3-dimensional cardiac and respiratory movements were not taken into account in the test results.
There is a substantial difference in signal between 1.5 T and 4 T in the dephasing experienced by the spins as a result of inhomogeneities in the magnetic field. On account of the more than doubling of field strength per time unit, the dephasing is also intensified. Thus, the effective relaxation time, T2*, which in addition to T2 includes the effects of inhomogeneities in the magnetic field, is clearly shorter than that at 1.5 T. This increases the influence of susceptibility artifacts. This can, however, be partially decreased by an increase in spatial resolution or by the selection of thinner layers, but at the expense of a reduced SNR. Compared to 1.5 T, the increased sensitivity to inhomogeneities in the magnetic field leads to a reduction in signal intensity for gradient sequences at the same echo time. Susceptibility effects are especially problematic during echoplanar imaging because the effective transverse relaxation time is clearly shorter than at 1.5 T. Furthermore, the substantially higher dephasing due to field inhomogeneities leads to an increase in extinction and distortion effects. This effect can be reduced by a reduction in the number of Fourier lines taken up by the echo train, which can, for example, be effected through segmentation of the k space or by parallel imaging. The present study investigated only the in vitro use of 4 T MRCA; an evaluation of its possible greater significance in the clinical situation was not the aim of the tests. As the use of a higher field strength showed an improvement in spatial resolution, comparative investigations at 1.5 and 4 T should be carried out with regard to clinical use.
The clear increase in SNR at 3 T raises the possibility that fine anatomical details such as the chordae tendineae and mitral valve leaflets will be recognizable in the future; hence, an increase in the range of indications seems to be possible.14 Further improvements in data acquisition can be achieved by steady-state free precession technology.15 There is no cause for concern about effects on vital signs or any danger to patients. In a study that used field strengths up to 8 T on healthy volunteers, Chakeres and colleagues8 were able to observe only a slight increase of 3.6 mm Hg in systolic blood pressure. From a practical viewpoint, a cost-benefit analysis will have to show whether the disadvantages of a long scan period and the time-consuming pre- and post-processing of data with MRI technology will be of less concern than the substantial dose of radiation delivered to the patient with multi-detector computed tomography. Due to the potential of high resolution of 0.4 mm, it can be expected that it will be possible to image the distal vessel segments that so far have been excluded from MRI technology. Whether high-field MRCA will also be able to identify short high-grade stenoses in distal segments is uncertain. In the near future, this will certainly remain within the domain of cardiac catheterization, while MRCA appears to be eminently suitable for risk evaluation and the planning of interventional procedures. A further possible indication is peripheral MRI angiography, as resolution in the area of the lower leg arteries is clearly better at 3 T than at 1.5 T.9
The results of this study show that MRCA at 4 T is possible and that a substantial improvement in results can be expected. So far, the small number of available 4 T MRI scanners has prevented widespread use. Further improvements to the hardware and a better depth adaptation of the sequences are necessary. In this study, only the feasibility in an in vitro model was tested; the value of 4 T MRI in the detection of coronary artery disease remains to be defined. Further evaluation on a native vessel model to confirm the improved spatial resolution and SNR is necessary. If the initial encouraging results are confirmed, studies in healthy volunteers and patients with coronary artery disease will be possible, and a substantial advance is anticipated for high-field MRCA.
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REFERENCES
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ABSTRACT
INTRODUCTION
