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1
Department of Radiology, University Hospital Nijmegen, Geert Grooteplein 10,
P. O. Box 9101, 6500 HB Nijmegen, the Netherlands
2
Department of Internal Medicine, University Hospital Nijmegen, 6500 HB
Nijmegen, the Netherlands
3
Present address: Department of Radiology, Slingeland Ziekenhuis,
Kruisbergseweg 25, 7009 BL Doetinchem, the Netherlands
Received July 2, 1999;
accepted after revision August 30, 1999.
Address correspondence to M. B. J. M. Korst.
Abstract
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SUBJECTS AND METHODS. Thirty-eight patients suspected of having renal artery stenosis underwent MR angiography and intraarterial digital subtraction angiography, which was the method of reference. Three-dimensional gradient-echo MR subtraction angiography (TR/TE, 5.8/1.8 msec) was performed on a 1.5-T imager using a phased array body coil. Before imaging, a separate timing bolus sequence was used, administering 1.0 ml of contrast agent. Gadopentetate dimeglumine (15 ml) was injected using an MR power injector. Two observers, who were unaware of each other's interpretation and of MR findings, assessed digital subtraction angiography. Likewise, two other observers assessed MR angiography.
RESULTS. Digital subtraction angiography depicted 75 main and 17 accessory renal arteries (n = 92). All main renal arteries and 13 accessory renal arteries were identified on MR angiography. Compared with digital subtraction angiography, MR imaging correctly classified 57 of 66 arteries without a hemodynamically significant stenosis (0-49%), 22 of 22 arteries as significantly stenotic (50-99%), and four of four occluded arteries; five stenoses were overestimated. There was one false-positive finding of an accessory renal artery on MR angiography that was identified retrospectively on digital subtraction angiography. Interobserver agreement was high. Sensitivity and specificity for grading significant stenosis were 100% and 85%, respectively.
CONCLUSION. Contrast-enhanced MR angiography, using ±0.1 mmol/kg of gadolinium, is an accurate method in the assessment of renal artery stenosis and accessory renal arteries.
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MR Imaging Technique
In all patients, MR imaging was performed with a 1.5-T imager (Magnetom
Vision; Siemens, Erlangen, Germany) using a phased array body coil. The arms
of the patients were placed alongside the abdomen. Initially, a sequence was
used to determine the transit time of the contrast bolus from the time of
injection until its arrival at the level of the perirenal aorta, using the
following parameters: TR/TE, 5.8/2.4 msec; flip angle, 10°; one 10-mm
slice in the transverse plane; and 60 acquisitions during 60 sec. During this
sequence, patients were allowed to breath normally. With an MR-compatible
power injector (Spectris MR Injector; Medrad, Pittsburgh, PA), a bolus of 1.0
ml of gadopentetate dimeglumine (Magnevist, 0.5 mmol/ml; Schering, Berlin,
Germany) was administered, followed by a saline flush of 15 ml, at a rate of
2.5 ml/sec IV via a 20-gauge catheter inserted in an antecubital vein. Using
the software package (MR angiography software package; Siemens) of the MR
imager, we determined the time of arrival of the contrast agent in the
perirenal aorta by generating a signal intensity-versus-time curve.
After the timing bolus sequence, two identical breath-hold three-dimensional gradient-echo sequences were performed in the coronal plane, one before and one during contrast injection. In all patients the following parameters were used: TR/TE, 5.8/1.8 msec; flip angle, 30°; field of view, 400 mm; slab thickness, 70 mm; 24 partitions; 160-224 x 512 matrix; and time of acquisition, 24 sec or less. No slice interpolation was used.
For timing of acquisition we used the formula T-delay = T-transit - 1/4 T-acq, where T-delay = time of starting acquisition after beginning of contrast injection, T-transit = time of test bolus arriving in perirenal aorta, and T-acq = acquisition time of sequence. Approximately 0.1 mmol/kg body weight of gadolinium was injected at the same rate as the timing bolus (2.5 ml/sec), also followed by a 15-ml saline flush. In all patients, 15 ml or less of gadopentetate dimeglumine was administered, including the timing bolus of 1 ml.
Digital Subtraction Angiography Technique
Intraarterial digital subtraction angiography was performed with a digital
subtraction unit (Polytron 1000; Siemens). A transfemorally inserted 5-French
pigtail catheter was positioned to ensure placement of the side holes at the
level of the origin of the renal arteries. After IV administration of 20 mg of
butyl bromide scopolamine (Buscopan; Boehringer-Ingelheim, Mannheim, Germany)
or 0.5-1.0 mg of glucagon hydrochloride (GlucaGen 1 IE; Novo Nordisk,
Bagsvaerd, Denmark), a bolus injection of 1:1 diluted 20 ml of iohexol
(Omnipaque 350 mg I/ml; Nycomed, Oslo, Norway) was injected intraarterially. A
standard 10° left anterior oblique projection was used in most patients.
If necessary, additional views (anteroposterior or oblique) were obtained or
selective catheterization was performed.
Image Analysis
Digital subtraction angiography images were assessed by two independent
observers who were unaware of MR angiography findings and of each other's
interpretations. Subsequently, consensus was achieved for final interpretation
in all cases. Likewise, two other observers independently interpreted the MR
angiograms. The images were assessed for renal artery stenosis and accessory
renal arteries. The intrarenal arteries were not assessed because the renal
artery was truncated at the hilum in most patients because of the limited slab
thickness. Each renal artery was analyzed for the presence of stenosis, which
was graded on the basis of the most severe reduction of arterial diameter
compared with an uninvolved renal artery segment proximal or distal to the
stenosis. A renal artery was graded as normal (grade 0), mildly stenotic
(1-49%, grade 1), moderately stenotic (50-75%, grade 2), severely stenotic
(75-99%, grade 3), or occluded (100%, grade 4). A stenosis of 50% or more was
considered hemodynamically significant. To obtain subtracted source images of
MR angiography, the unenhanced images were subtracted from the enhanced
images. For analysis of MR angiography, subtracted source images and
maximum-intensity-projection images were printed on hard copy. If necessary,
additional multiplanar reformation imaging or targeted (subvolume) maximum
intensity projection was performed using the console of the MR imager or a
workstation (Sienet 1000; Siemens).
Statistical Analysis
Sensitivity, specificity, and predictive values of MR angiography as a
diagnostic test for renal artery stenosis were calculated using digital
subtraction angiography as the method of reference. Because stenoses of 50% or
more were considered hemodynamically significant, grades 0 and 1 stenoses were
regarded as negative tests for renal artery stenosis and grades 2, 3, and 4 as
positive tests for renal artery stenosis. The parameters were calculated for
the patient group: a patient was positive for the disease if a unilateral or
bilateral renal artery stenosis was present. Cohen's kappa (
) analysis
was used to test for agreement beyond that of chance between the two observers
of MR angiography and of digital subtraction angiography (determination of
poor [=0.00], slight [=0.01-0.20], fair [=0.21-0.40],
moderate [=0.41-0.60], substantial [=0.61-0.80], and almost
perfect [=0.81-1.00] agreement). Kappa value was calculated with
respect to the classification of the different grades of stenosis (grades 0-4)
and with respect to the presence (grades 2, 3, or 4) or absence (grades 0 and
1) of significant stenosis.
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In 38 patients, 75 main renal arteries and 17 accessory renal arteries were identified on digital subtraction angiography (one patient had undergone nephrectomy before the study). MR angiography correctly identified all 75 main renal arteries and 13 accessory renal arteries (Fig. 2). Three of the missed accessory renal arteries (all without stenosis) were identified on MR angiography in retrospect only (Fig. 3A,3B) and were considered false-negative findings. The remaining fourth accessory renal artery, identified on digital subtraction angiography, was classified as an early division of the main renal artery on MR angiography; reevaluation of the digital subtraction angiogram confirmed this finding. MR angiography prospectively revealed another accessory renal artery (with a stenosis of 75-99%); reevaluation of the digital subtraction angiogram confirmed these findings (Fig. 4A,4B). In both cases, the digital subtraction angiography images were of moderate quality but were considered diagnostic. The depiction of these two latter vessels on MR angiography were considered false-negative and false-positive findings, respectively, because digital subtraction angiography was used as the method of reference.
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Ninety-three arteries (in 38 patients) were evaluated for stenosis. The consensus grading of stenosis revealed by contrast-enhanced MR angiography and by intraarterial digital subtraction angiography is presented in Table 2, including the false-positive (n = 1) and false-negative (n = 4) findings already described. As shown in Table 2, slight differences in interpretation of stenosis occurred between grades 0 and 1 and between grades 2 and 3; we noted both over- and underestimation of stenosis on MR angiography within the subgroups ranging from 0% to 50% and ranging from 50% to 99% (Figs. 5A,5B and 6A,6B). If grades 0 and 1 were considered to represent a nonsignificant stenosis and both grades 2 and 3 a hemodynamically significant stenosis, five arteries were judged to have a significant stenosis on MR angiography but were not stenotic on digital subtraction angiography. All occluded arteries were correctly classified on MR angiography.
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The sensitivity and specificity for the detection of significant stenosis
and occlusion in the 38 patients were 100% and 85.0%, respectively. The
positive and negative predictive values were 85.7% and 100%, respectively.
Agreement between the two observers of digital subtraction angiography and MR
angiography in the classification of all grades of stenosis (grades 0-4) was
substantial: = 0.73 on digital subtraction angiography and =
0.70 on MR angiography. The interobserver agreement for the presence or
absence of significant stenosis was almost perfect: =0.90 on digital
subtraction angiography and =0.91 on MR angiography.
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All MR angiograms were considered technically sufficient for analysis; no study had to be repeated. Adequate timing of the bolus is essential; previous studies showed optimal results if an MR power injector and timing bolus were used [21, 22, 28, 29]. In this study, the transit time varied widely (10-30 sec); this is in accordance with the findings of previous studies [21, 22, 28]. We consider exact measurement of transit time essential for an optimal examination, and this is even more important if a standard dose of ±0.1 mmol/kg at an injection rate of 2.5 ml/sec is used, as in our series. The use of an MR power injector has been described as superior to hand injection; the optimal injection rate for abdominal vessels was reported to be approximately 2 ml/sec [22, 29]. We used a separate timing bolus sequence because the software package of our imager does not allow automated detection of contrast agent and synchronization of the data acquisition in one sequence [30, 31]. In one patient, we could not determine the transit time; by using an estimated transit time, a satisfactory study was generated.
In this series, a phased array body coil was used, which increases signal- and contrast-to-noise ratios if compared with a body coil. However, this coil can limit the field of view and also has the drawback of signal inhomogeneity in the direct vicinity of the coil [32, 33]. To our knowledge, no studies have compared a body coil with a phased array coil in performing MR angiography. It was assumed that the use of phased array coil would improve imaging, but future comparative studies will be needed to determine if such a coil should be preferred.
In this study, 75 main and 17 accessory renal arteries were detected on digital subtraction angiography. MR angiography correctly identified all main and 13 accessory renal arteries. Three accessory arteries (false-negative findings) were not detected on MR angiography. After reevaluation, these accessory renal arteries could be identified. We think that the tortuosity and the relatively small caliber of these particular arteries and the limited spatial resolution of MR angiography caused the difficulty in recognizing these arteries on maximum-intensity-projection, source, and multiplanar reformatted images. A learning curve is definitely present in detecting small accessory arteries on MR angiography. Despite these false-negative findings, we think that identification of accessory renal arteries can be sufficient on MR angiography. Previous studies identified a various number of accessory renal arteries, comparing contrast-enhanced MR angiography and digital subtraction angiography: Steffens et al. [16] identified six of nine accessory renal arteries (in 50 patients), Hany et al. [10] 10 of 11 (in 39 patients), De Cobelli et al. [13] 17 of 18 (in 55 patients), and Bakker et al. [12] 21 of 22 (in 44 patients).
One accessory renal artery was identified as an early division of the main renal artery on MR angiography, and this finding was confirmed after reanalysis of the digital subtraction angiogram. Another accessory renal artery was identified on MR angiography; again, in retrospect only, this artery was identified on digital subtraction angiography. Because digital subtraction angiography was used as the method of reference, these two arteries were classified as false-negative and false-positive findings, respectively. However, because the MR angiography findings were confirmed after reanalysis of digital subtraction angiograms, it raises the question whether digital subtraction angiography is an indisputable method of reference.
MR angiography findings incorrectly suggested a significant stenosis in
five renal arteries, rendering a specificity of 85.0%. However, negative
predictive value and sensitivity were 100%; the values of these parameters are
comparable to those in previous studies, which report a sensitivity and
specificity ranging from 93% to 100% and from 90% to 98%, respectively
[10,
12,13,14,
16,17,18].
The use of ±0.1 mmol/kg of body weight of contrast agent proved to be
sufficient in this study, confirming earlier studies
[13,
16,
18,
34]. In a recent study by Lee
et al. [34] and an earlier
study by Earls et al. [22], a
similar technique for performing contrast-enhanced MR angiography was
described, using a timing bolus sequence and an MR power injector. This
technique generated reliable and diagnostic studies; however, the results were
not correlated with angiography in most cases
[34]. Because of its high
sensitivity, MR angiography can be used reliably to exclude renal artery
stenosis and to serve as a useful screening method for renal artery stenosis.
Using a single dose of contrast agent will make MR angiography more
cost-effective as a screening method. A recent study showed that the dose of
±0.1 mmol/kg could also be sufficient when imaging with a 1.0-T system
[19]. The high interobserver
agreement expressed in the kappa values (=0.91 for significant
stenosis) indicates that contrast-enhanced MR angiography can result in
unequivocal grading of stenosis. This is in accordance with a recent study by
Gilfeather et al. [35] showing
a marginal difference in the interobserver variability of MR angiography and
digital subtraction angiography.
In conclusion, MR angiography using ±0.1 mmol/kg of gadolinium, a phased array body coil, subtraction technique, timing bolus, and MR power injector, is a safe and accurate screening method for renal artery stenosis and accessory renal arteries.
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