(Radiology. 2001;219:545-550.)
© RSNA, 2001
Comparison of Single-Shot Fast Spin-Echo and Conventional Spin-Echo Sequences for MR Imaging of the Heart: Initial Experience1
Olivier B. Vignaux, MD,
Joelle Augui, MD,
Joel Coste, MD, PhD,
Christophe Argaud, MSc,
Patrick Le Roux, MSc,
Pierre G. Carlier, MD, PhD,
Denis Duboc, MD, PhD and
Paul Legmann, MD
1 From the Departments of Radiology (O.B.V., J.A., P.L.), Biostatistics (J.C.), and Cardiology (D.D.), Université René Descartes, Hôpital Cochin, 27 rue du Fg Saint Jacques, 75679 Paris Cedex 14, France; Service Hospitalier Frederic Joliot, Orsay, France (P.G.C.); and GE Medical Systems, Buc, France (C.A., P.L.R.). Received June 27, 2000; revision requested August 7; revision received September 14; accepted October 11. Address correspondence to O.B.V. (e-mail: olivier.vignaux@cch.ap-hop-paris.fr).
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ABSTRACT
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A conventional T1-weighted spin-echo (SE) magnetic resonance (MR) imaging sequence was compared with breath-hold and non–breath-hold half- Fourier single-shot fast SE MR sequences with black-blood preparation and high spatial resolution for imaging of various cardiac diseases. The optimized single-shot fast SE sequence provided better or equal image quality in less time. Breath-hold and non–breath-hold single-shot fast SE sequences may replace the conventional T1-weighted SE sequence for first-line cardiac MR imaging.
Index terms: Heart, diseases, 51.1935, 51.22, 51.31, 51.32, 51.824, 51.848 • Heart, MR, 51.121411, 51.121412, 51.121415, 51.121416 • Magnetic resonance (MR), rapid imaging, 51.121411, 51.121412, 51.121415, 51.121416 • Magnetic resonance (MR), technology, 51.121411, 51.121412, 51.121415, 51.121416
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INTRODUCTION
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In cardiac imaging, probably more than in any other area of magnetic resonance (MR) imaging, the technical challenge is to achieve the best possible compromise between the opposing constraints of very short acquisition time, high signal-to-noise ratio, high spatial resolution, and clinical applicability. Spin-echo (SE) acquisition is the mainstay for morphologic evaluation of the heart because of its high contrast resolution and reduced sensitivity to magnetic induction field (B0) imperfections, but it has limited temporal resolution. To minimize respiratory and other motion-related artifacts, multiple signals are acquired, and this further lengthens imaging times. Shorter acquisition times can be achieved with fast (or turbo) SE pulse sequences, which can replace conventional SE pulse sequences for many applications, including imaging of the chest and the heart (1,2).
A faster single-shot fast SE technique has been proposed for cardiac imaging (3,4). In this sequence, a long echo train is coupled with half-Fourier reconstruction so that all data required to form the image of a single section can be acquired in less than 500 msec (5). With the single-shot technique, the center of k space is acquired in a short time compared with the time required for most physiologic motion, and, thus, motion blurring is reduced. Recent study results have shown that this single-shot fast SE technique can replace the electrocardiogram (ECG) triggered fast SE sequence for evaluation of thoracic aortic disease (6). In cardiac imaging, because the long echo trains required, coupled with the relatively short T2, are sources of myocardial blurring, this sequence is usually used as a "super scout view" to provide a quick transverse, coronal, or sagittal imaging plane survey.
However, Le Roux et al (7) demonstrated the possibility of achieving less blurring and higher spatial resolution with this single-shot technique by applying spatial presaturation slabs on each side of the field of view. The field of view can thereby be reduced in the phase-encoding direction without back-folding artifacts (ie, outer volume suppression). Furthermore, T2 weighting could be reduced with a center-to-outer half k-space sampling, so an intermediate-weighted image was obtained.
Our preliminary clinical experience suggested that this intermediate-weighted single-shot fast SE sequence with high spatial resolution and black-blood preparation could offer a very fast and attractive alternative to the conventional T1-weighted SE sequence for first-line MR morphologic studies of the heart. Accordingly, the purpose of our study was to retrospectively compare breath-hold and non–breath-hold high-spatial-resolution, black-blood, single-shot fast SE MR imaging with conventional T1-weighted SE MR imaging in patients referred for evaluation of various cardiac diseases.
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Materials and Methods
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Patient Population
From April to September 1999, 25 patients (17 men, eight women; mean age, 37 years; age range, 21–62 years) were referred for MR heart examinations. Indications included cardiac tumors (n = 3), suspected arrhythmogenic right ventricular dysplasia (n = 16), cardiac sarcoidosis (n = 3), Still syndrome with suspected cardiac involvement (n = 1), and constrictive pericarditis (n = 2). The study was approved by the institutional review board, and informed consent was obtained for all subjects. All patients underwent surface ECG and echocardiography. Four patients underwent myocardial scintigraphy, and 12 underwent cardiac angiography. The diagnosis of arrhythmogenic right ventricular dysplasia was based on documented ventricular tachycardias; ECG abnormalities (ie, repolarization abnormalities in the right precordial leads); and localized or diffuse abnormalities of right ventricular contraction, as shown at echocardiography or right ventricular angiography, in the absence of any other identifiable structural heart or pulmonary disease.
Imaging
The single-shot fast SE sequence (SSFSE; GE Medical Systems, Milwaukee, Wis) is illustrated in Figure 1. Black-blood contrast was enhanced by using a nonselective pulse that inverts blood in the body, followed by a selective pulse that restores magnetization in the section (8,9). This double inversion for blood suppression was applied before the start of the half-Fourier single-shot fast SE readout. The inversion time is the time between this double inversion and the application of the 90° excitation pulse. If the inversion time was chosen so that blood spins were passing the null point of the T1 recovery curve when the 90° pulse was applied (Fig 1, point A), then the blood had no signal intensity. We used an inversion time of 600 msec, and two ECG periods were allowed between section acquisition to allow inverted blood to recover.
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Figure 1. Timing diagram of the single-shot fast SE sequence. The acquisition is triggered by the ECG wave, at which spins are inverted by means of a nonselective 180° pulse. Immediately afterward, spins within the imaging section are returned to their equilibrium position by means of a selection-selective 180° pulse. After a delay (ie, inversion time), which is chosen such that the recovering blood magnetization is passing through zero, the half-Fourier acquisition is started. A = null point of T1 recovery curve when 90° pulse applied, RF = radio frequency.
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Optimized presaturation slabs, with quadratic phase pulses generated by the Shinnar-Le Roux algorithm, were used to reduce the field of view in the phase-encoding direction without introducing back-folding artifacts (7). For a millimetric spatial resolution, an echo train length of only 40 is required. With 4.5-msec echo spacing, the total imaging time is 180 msec. Because the data at the center of the k space define the image contrast, T2 weighting can be reduced if the order of the phase-encoding steps is altered so the center of the k space can be sampled earlier in the echo train. Thus, a center-to-outer half k-space sampling was used so an intermediate-weighted image could be obtained. The specific absorption rate was minimized by decreasing the refocusing pulse angle (170°) and using optimized presaturation pulses.
All patients underwent imaging with a 1.5-T imager (Signa LX; GE Medical Systems), capable of a maximum gradient of 23 mT/m and a 190-µsec rise time, with a torso phased-array coil. Three ECG electrodes were placed dorsally on the patient’s skin close to the position of the heart. The trigger delay was minimal for the conventional SE acquisition and 610 msec for the single-shot fast SE acquisition. After the patient was positioned headfirst in a supine position in the center of the magnet, three-dimensional gradient-echo scout images were acquired. Transverse multisection single-shot fast SE acquisitions were performed during suspended respiration at end inspiration. Subsequently, the patient was instructed to breath freely, and the same transverse single-shot fast SE and T1-weighted conventional SE acquisitions were then performed without breath holding. Superior-to-inferior spatial presaturation bands were used with the conventional SE sequence. The main parameters of the pulse sequences are shown in Table 1. Additional gradient-echo (ie, FASTCARD; GE Medical Systems) sequences were performed in some cases to evaluate cardiac function.
Image Analysis
Film hard-copy images without any pulse sequence information were obtained, and the quality of the transverse images acquired with the two sequences were compared retrospectively side by side by two radiologists (O.B.V., J.A.). One of the two radiologists (O.B.V.) had been involved in some of the clinical interpretations, and the other had not. The two readers, who were blinded with regard to the clinical diagnoses, independently evaluated the sets of images for the following criteria: (a) delineation of endocardium and visualization of intracavitary structures (ie, intracavitary muscular bands, valves), (b) delineation of pericardium, (c) absence of intracavitary and extracardiac ghost artifacts, (d) overall image quality, and (e) conspicuity of abnormality. Abnormalities were cardiac tumor identified at echocardiography, right ventricular intramyocardial increased signal intensity suggestive of fatty infiltration and focal or diffuse thinning of the right ventricular wall in suspected arrhythmogenic right ventricular dysplasia, abnormal myocardial signal intensity and/or myocardial nodule in sarcoidosis and Still syndrome with suspected cardiac involvement, and pericardial thickening in constrictive pericarditis.
A six-point rating scale was used, with 5 as the highest grade and 0 as the lowest: A score of 5 indicated optimal delineation of endocardium and visualization of intracavitary structures; 4, very high delineation and visualization; 3, high delineation and visualization; 2, moderate delineation and visualization; 1, low delineation and visualization; and 0, very low delineation and visualization. For delineation of the pericardium, 5 indicated optimal (ie, delineation in all regions); 4, very good; 3, good; 2, moderate; 1, low; and 0, very low. For intracavitary and extracardiac ghost artifacts, 5 indicated none; 4, very few; 3, few; 2, many intracavitary or extracardiac ghost artifacts; 1, many intracavitary and extracardiac ghost artifacts; and 0, not interpretable. For overall image quality, 5 indicated optimal; 4, very high; 3, high; 2, moderate; 1, low; and 0, very low. For conspicuity of abnormality, 5 indicated very high; 4, high; 3, moderate; 2, low; 1, very low; and 0, no abnormality shown.
Consensus reading was not used for discordant grades, and all data were averaged for each parameter. Despite elimination of sequence information from the images, the radiologists were able to recognize the sequences, because the half-Fourier single-shot fast SE images were often distinguishable from the conventional SE images owing to differences in contrast.
Statistical Analyses
Nonparametric statistical methods (ie, Wilcoxon pairwise signed rank tests) were used to compare modality performance based on the ordinal-scaled criteria—that is, endocardium delineation and intracavitary visualization structure, pericardium delineation, absence of intracavitary and extracardiac ghost artifacts, overall image quality, and abnormality conspicuity. Two-tailed P values were used, and values less than .05 were considered to indicate statistical significance. The computations were performed by using the SAS package (SAS/STAT user’s guide, version 6. Cary, NC: SAS Institute, 1990).
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Results
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Conventional T1-weighted SE MR Imaging
The mean scores of the conventional T1-weighted SE sequence for all criteria are shown in Table 2. Regarding abnormality conspicuity at MR imaging, 17 of the 25 patients had abnormalities, and eight had normal findings. Abnormalities included cardiac tumors in three patients, right ventricular intramyocardial fatty infiltration consistent with arrhythmogenic right ventricular dysplasia in 10 patients, systemic sarcoidosis and septal myocardial nodule in two patients, and pericardial thickening suggestive of constrictive pericarditis in two patients.
Breath-hold and Non–Breath-hold Single-Shot Fast SE MR Imaging
The mean scores of the breath-hold and non–breath-hold single-shot fast SE sequences for all criteria also are shown in Table 2. Seven patients had normal MR findings, and 18 had abnormalities, including the three patients with cardiac tumors and both patients with constrictive pericarditis at T1-weighted spin-echo imaging. Right ventricular intramyocardial foci of increased signal intensity due to fatty infiltration were visualized in all 10 patients with right ventricular fatty infiltration at T1-weighted MR imaging (Fig 2). Moreover, focal or diffuse contraction abnormalities were observed at additional gradient-echo sequences of the right ventricle in seven of the 10 patients with fatty infiltration. Six patients, including two of the three patients without contraction abnormalities, also had focal or diffuse right ventricular wall thinning at both single-shot fast SE and conventional SE MR imaging. Among the patients with cardiac sarcoidosis, increased intramyocardial signal intensity due to a septal sarcoid was more pronounced at single-shot fast SE than at conventional T1-weighted MR imaging in two patients and was seen at only single-shot fast SE MR imaging in one patient (Fig 3).
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Figure 2a. Transverse (a) conventional ECG-triggered SE (echo time, 30 msec; trigger delay, 450 msec; acquisition time, 5 minutes 12 seconds), (b) ECG-triggered breath-hold single-shot fast SE (effective echo time, 26 msec; trigger delay, 610 msec; acquisition time, 22 seconds), and (c) non-breath-hold single-shot fast SE (effective echo time, 26 msec; trigger delay, 610 msec; acquisition time, 22 seconds) MR images obtained at a similar level in a 28-year-old patient with arrhythmogenic right ventricular dysplasia. Foci of increased signal intensity in the right ventricular free wall due to fatty replacement (arrow) are seen at all three sequences. The clarity of the chambers is higher on the single-shot fast SE images owing to blood suppression.
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Figure 2b. Transverse (a) conventional ECG-triggered SE (echo time, 30 msec; trigger delay, 450 msec; acquisition time, 5 minutes 12 seconds), (b) ECG-triggered breath-hold single-shot fast SE (effective echo time, 26 msec; trigger delay, 610 msec; acquisition time, 22 seconds), and (c) non-breath-hold single-shot fast SE (effective echo time, 26 msec; trigger delay, 610 msec; acquisition time, 22 seconds) MR images obtained at a similar level in a 28-year-old patient with arrhythmogenic right ventricular dysplasia. Foci of increased signal intensity in the right ventricular free wall due to fatty replacement (arrow) are seen at all three sequences. The clarity of the chambers is higher on the single-shot fast SE images owing to blood suppression.
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Figure 2c. Transverse (a) conventional ECG-triggered SE (echo time, 30 msec; trigger delay, 450 msec; acquisition time, 5 minutes 12 seconds), (b) ECG-triggered breath-hold single-shot fast SE (effective echo time, 26 msec; trigger delay, 610 msec; acquisition time, 22 seconds), and (c) non-breath-hold single-shot fast SE (effective echo time, 26 msec; trigger delay, 610 msec; acquisition time, 22 seconds) MR images obtained at a similar level in a 28-year-old patient with arrhythmogenic right ventricular dysplasia. Foci of increased signal intensity in the right ventricular free wall due to fatty replacement (arrow) are seen at all three sequences. The clarity of the chambers is higher on the single-shot fast SE images owing to blood suppression.
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Figure 3a. Transverse (a) conventional nonenhanced ECG-triggered SE (echo time, 30 msec; trigger delay, 390 msec; acquisition time, 5 minutes 27 seconds), (b) breath-hold single-shot fast SE (effective echo time, 26 msec; trigger delay, 610 msec; acquisition time, 24 seconds), (c) non-breath-hold single-shot fast SE (effective echo time, 26 msec; trigger delay, 610 msec; acquisition time, 24 seconds), and (d) contrast material-enhanced T1-weighted conventional SE with fat suppression (echo time, 30 msec; acquisition time, 6 minutes 14 seconds) MR images obtained at a similar level in a 35-year-old patient with cardiac sarcoidosis. In a, no lesion is depicted. In b, nodular subtle increased signal intensity (arrow) in the septal wall due to a septal sarcoid is seen. In c, respiratory ghost artifacts are higher and result in lower lesion (arrow) conspicuity. In d, the nodular sarcoid (arrow) in the septal wall is depicted.
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Figure 3b. Transverse (a) conventional nonenhanced ECG-triggered SE (echo time, 30 msec; trigger delay, 390 msec; acquisition time, 5 minutes 27 seconds), (b) breath-hold single-shot fast SE (effective echo time, 26 msec; trigger delay, 610 msec; acquisition time, 24 seconds), (c) non-breath-hold single-shot fast SE (effective echo time, 26 msec; trigger delay, 610 msec; acquisition time, 24 seconds), and (d) contrast material-enhanced T1-weighted conventional SE with fat suppression (echo time, 30 msec; acquisition time, 6 minutes 14 seconds) MR images obtained at a similar level in a 35-year-old patient with cardiac sarcoidosis. In a, no lesion is depicted. In b, nodular subtle increased signal intensity (arrow) in the septal wall due to a septal sarcoid is seen. In c, respiratory ghost artifacts are higher and result in lower lesion (arrow) conspicuity. In d, the nodular sarcoid (arrow) in the septal wall is depicted.
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Figure 3c. Transverse (a) conventional nonenhanced ECG-triggered SE (echo time, 30 msec; trigger delay, 390 msec; acquisition time, 5 minutes 27 seconds), (b) breath-hold single-shot fast SE (effective echo time, 26 msec; trigger delay, 610 msec; acquisition time, 24 seconds), (c) non-breath-hold single-shot fast SE (effective echo time, 26 msec; trigger delay, 610 msec; acquisition time, 24 seconds), and (d) contrast material-enhanced T1-weighted conventional SE with fat suppression (echo time, 30 msec; acquisition time, 6 minutes 14 seconds) MR images obtained at a similar level in a 35-year-old patient with cardiac sarcoidosis. In a, no lesion is depicted. In b, nodular subtle increased signal intensity (arrow) in the septal wall due to a septal sarcoid is seen. In c, respiratory ghost artifacts are higher and result in lower lesion (arrow) conspicuity. In d, the nodular sarcoid (arrow) in the septal wall is depicted.
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Figure 3d. Transverse (a) conventional nonenhanced ECG-triggered SE (echo time, 30 msec; trigger delay, 390 msec; acquisition time, 5 minutes 27 seconds), (b) breath-hold single-shot fast SE (effective echo time, 26 msec; trigger delay, 610 msec; acquisition time, 24 seconds), (c) non-breath-hold single-shot fast SE (effective echo time, 26 msec; trigger delay, 610 msec; acquisition time, 24 seconds), and (d) contrast material-enhanced T1-weighted conventional SE with fat suppression (echo time, 30 msec; acquisition time, 6 minutes 14 seconds) MR images obtained at a similar level in a 35-year-old patient with cardiac sarcoidosis. In a, no lesion is depicted. In b, nodular subtle increased signal intensity (arrow) in the septal wall due to a septal sarcoid is seen. In c, respiratory ghost artifacts are higher and result in lower lesion (arrow) conspicuity. In d, the nodular sarcoid (arrow) in the septal wall is depicted.
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Statistical Analyses
Compared with the conventional SE sequence, the breath-hold single-shot fast SE sequence scored higher for all evaluated judgment criteria (Table 2). Differences in endocardium delineation and intracavitary structure visualization (P < .05), absence of ghost artifacts (P < .001), and overall image quality (P < .01) reached statistical significance. Differences in pericardium delineation and abnormality conspicuity were not significantly different.
When the conventional SE sequence and non–breath-hold single-shot fast SE sequence were compared, the mean scores of the conventional sequence were higher for absence of ghost artifacts and abnormality conspicuity, equal for overall image quality, and lower for delineation of endocardium and visualization of intracavitary structures and for pericardium delineation. With all parameters, these differences were not statistically significant.
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Discussion
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Morphologic imaging of the heart has improved with use of single-shot fast SE imaging techniques, which allow multisection examination of the entire heart in a short breath hold. The half-Fourier single-shot fast SE sequence has been modified for cardiac imaging, which requires three main features: a short acquisition window for constraining the motion artifacts to acceptable levels, high spatial resolution, and good myocardial edge definition with reduced myocardial blurring.
Le Roux et al (7) presented a solution for achieving a short acquisition window, with good spatial resolution and less myocardial blurring: They reduced the field of view in the phase-encoding direction to limit the phase-encoding steps and applied two optimized presaturation slabs with quadratic phase pulses generated by the Shinnar-Leroux algorithm out of the field of view to avoid back-folding artifacts. For a millimetric spatial resolution, and by using half-Fourier acquisition, an echo train length of only 40 is required. This short echo train length, in conjunction with an effective echo time of approximately 30 msec, theoretically resulted in reduced image blurring. In addition, the myocardial edge definition was improved by using a blood-suppressed preparation method (8,9).
Our study findings demonstrated that this half-Fourier black-blood single-shot fast SE sequence with high spatial resolution provided an accurate and time-efficient method for morphologic studies of the heart and could be performed without breath holding. The half-Fourier black-blood single-shot fast SE sequence enabled sufficient anatomic coverage of the entire heart in a single breath hold, and mean acquisition times were substantially shorter compared with those for conventional SE imaging (mean time, 23 vs 327 seconds). Thus, the acquisition time was reduced by a factor of approximately 15. Reduced imaging times allowed decreased respiratory motion artifacts and time for multiplanar assessment, when clinically relevant.
The described single-shot fast SE sequence is therefore useful for cardiac anatomic studies, such as those of congenital heart diseases and cardiac tumors, and for evaluation of the pericardium. In our study, pericardial thickening was seen in both patients with constrictive pericarditis. In addition to evaluating cardiac morphology, the half-Fourier single-shot fast SE sequence seems to be useful for assessing right ventricular dysplasia, because fatty intramyocardial infiltration appears as loci of increased signal intensity on these fast-sequence images. In our study, foci of increased signal intensity due to fatty infiltration were visualized at single-shot fast SE imaging in all 10 patients with right ventricular fatty infiltration at conventional T1-weighted MR imaging.
Furthermore, the difference in contrast between the single-shot fast SE and conventional T1-weighted SE sequences may be pertinent in myocarditis, because the contrast at T2-weighted imaging may render the inflammation more conspicuous (10,11). In our study, both single-shot fast SE sequences outperformed the conventional SE sequence for detection of myocardial signal abnormalities in the patients with cardiac sarcoidosis. The single-shot fast SE sequences may be useful in other settings, such as acute infarction with areas of myocardial ischemia seen as loci of increased intensity, reflective of myocardial edema and tissue necrosis (12).
Black-blood fast SE pulse sequences result also in substantial time savings (1,2). However, acquisition times are still longer (typically 2–4 minutes) than those for the half-Fourier single-shot fast SE sequence. Furthermore, these sequences still require the acquisition of multiple signals to reduce motion artifacts, and they often cause the same disturbing motion artifacts as those seen with conventional SE techniques (13). Turbo fast low-angle shot acquisition with a black-blood preparation pulse is a single-shot T1-weighted acquisition that also is very fast and free of motion artifacts. Nevertheless, the gradient-echo technique is more sensitive to BO imperfections and has limited contrast resolution compared with the SE technique.
Our study had limitations, including the inability to prevent readers from distinguishing the single-shot fast SE images from the conventional SE images and the use of subjective grading criteria. Respiratory gating, which may improve image quality, was not used with the conventional SE sequence. On the other hand, the signal-to-noise ratio could have been maximized for the single-shot technique possibly by using 7-mm-thick sections with no intersection gap.
The trigger delay was different between the sequences, because multisection conventional SE acquisitions provide images of different positions. Each image was acquired during a different cardiac phase—some during systole and others during diastole. With the single-shot fast SE sequence, all data acquisitions were gated in diastole (610-msec trigger delay for all sections), and this improved image quality because diastolic acquisition minimized cardiac motion artifacts. A disadvantage of the black-blood preparation pulse used with the single-shot fast SE sequence, however, was that slowly flowing blood near the myocardium could be incompletely suppressed and appear hyperintense. However, the thickness of the selective 180° pulse could be modified to minimize this, so this artifact did not adversely affect the quality of the single-shot fast SE images.
In conclusion, breath-hold and non–breath-hold high-spatial-resolution single-shot fast SE sequences, which are very robust with regard to motion artifacts and black-blood contrast, not only provide super scout views for a quick imaging plane survey, but they have good potential as very fast clinical protocols for morphologic studies of the heart. High-spatial-resolution, black-blood, single-shot fast SE MR imaging may replace conventional T1-weighted SE MR imaging for first-line routine cardiac MR examinations, even when long breath holding is impossible, and thereby reduce the acquisition time by a factor of approximately 15.
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FOOTNOTES
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Abbreviations: ECG = electrocardiogram,
SE = spin echo
Author contributions: Guarantors of integrity of entire study, O.B.V., J.A., P.L.; study concepts and design, O.B.V., J.A., P.L., D.D.; literature research, O.B.V., J.A., P.L., D.D.; clinical studies, O.B.V., J.A., D.D.; data acquisition, O.B.V., C.A., P.L.R, P.G.C.; data analysis, O.B.V., J.A., P.L.; statistical analysis, O.B.V., J.C.; manuscript preparation, O.B.V., J.A.; definition of intellectual content, O.B.V., J.A., P.L., D.D.; manuscript editing, O.B.V., J.A.; manuscript review, all authors; manuscript final version approval, D.D., P.L.
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Right Ventricular MR Abnormalities in Myotonic Dystrophy and Relationship with Intracardiac Electrophysiologic Test Findings: Initial Results
Radiology,
July 1, 2002;
224(1):
231 - 235.
[Abstract]
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ABSTRACT
INTRODUCTION
