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Renal Time-resolved MR Angiography: Quantitative Comparison of Gadobenate Dimeglumine and Gadopentetate Dimeglumine with Different Doses¹

¹ From the Department of Diagnostic Radiology, University Hospital of Regensburg, Franz-Josef-Strauss-Allee 11, D-93042 Regensburg, Germany. Received November 27, 2000; revision requested January 3, 2001; revision received February 15; accepted February 26. Address correspondence to M.V. (e-mail: markus.voelk@klinik.uni-regensburg.de).

	ABSTRACT

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PURPOSE: Results with different doses of gadobenate dimeglumine and gadopentetate dimeglumine were compared at magnetic resonance (MR) angiography of the renal arteries. The signal-to-noise ratio (SNR) was evaluated as a quantitative measure of image quality.

MATERIALS AND METHODS: Sixty consecutive patients (age range, 24–81 years; mean age, 65 years) underwent intraarterial digital subtraction angiography (DSA) and contrast material–enhanced time-resolved MR angiography. DSA was the standard of reference. Fifteen patients received gadopentetate dimeglumine at doses of 0.2 or 0.1 mmol per kilogram of body weight. Fifteen patients received gadobenate dimeglumine at doses of 0.05 or 0.1 mmol/kg. The SNR was calculated in the aorta and both main renal arteries. The number and degree of stenoses of the renal arteries and accessory vessels were evaluated by four observers.

RESULTS: SNRs with gadobenate dimeglumine at a dose of 0.1 mmol/kg were significantly superior to those with gadopentetate dimeglumine at a dose of 0.1 mmol/kg. Differences were not statistically significant between the SNRs in the other groups. Eleven (85%) of 13 hemodynamically significant renal artery stenoses were detected correctly with MR angiography as were 22 (85%) of 26 accessory renal arteries.

CONCLUSION: SNRs with gadobenate dimeglumine were higher than those with gadopentetate dimeglumine, but in most cases the differences in SNRs were not statistically significant.

Index terms: Contrast media, comparative studies, 961.12942 • Magnetic resonance (MR), vascular studies, 961.12942 • Renal arteries, MR, 961.12942 • Renal arteries, stenosis or obstruction, 961.122, 961.12942, 961.721

	INTRODUCTION

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Results of studies with gadolinium complexes as paramagnetic contrast agents were reported in the early 1980s (1,2). These contrast media allowed applications such as contrast material–enhanced magnetic resonance (MR) angiography (3–5). Gadobenate dimeglumine (MultiHance; Bracco, Milan, Italy) is a contrast material with a contrast mechanism that is based on weak protein binding in body fluid; the weak binding should result in signal intensities from the vasculature that are higher than those obtained with gadopentetate dimeglumine (Magnevist; Berlex Laboratories, Wayne, NJ) (6,7). In a preliminary study to compare results with gadobenate dimeglumine to those with gadopentetate dimeglumine at MR angiography, gadobenate dimeglumine produced a 29% higher vascular peak enhancement with longer duration than that produced with gadopentetate dimeglumine at the same dose and flow rate (8).

The purpose of this study was to compare results with different doses of gadobenate dimeglumine and gadopentetate dimeglumine at MR angiography of the renal arteries. The signal-to-noise ratio (SNR) was evaluated as a quantitative measure of image quality.

	MATERIALS AND METHODS

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Patients
This clinical study was approved by the ethics committee of our faculty. Written informed consent was obtained from all patients before the procedures.

From April through September 2000, 60 consecutive patients (21 women, 39 men; age range, 24–81 years; mean age, 65 years ± 12.2 (SD); mean body weight, 75 kg ± 12.8; weight range, 52–107 kg) suspected of having a renal artery stenosis underwent intraarterial digital subtraction angiography (DSA) and time-resolved contrast-enhanced MR angiography of the renal arteries.

The 60 patients were randomly assigned to one of four dose groups: 15 patients, gadopentetate dimeglumine 0.2 mmol per kilogram of body weight; 15 patients, gadopentetate dimeglumine 0.1 mmol/kg; 15 patients, gadobenate dimeglumine 0.1 mmol/kg; 15 patients, gadobenate dimeglumine 0.05 mmol/kg.

Gadopentetate dimeglumine 0.2 mmol/ kg and gadobenate dimeglumine 0.1 mmol/kg are the standard doses recommended for MR angiography. In addition, the potential benefit of a 50% dose reduction was investigated. The basic clinical data for the dose groups are presented in Table 1.

MR Imaging Technique
MR angiography was performed with a 1.5-T superconducting MR imager (Magnetom Symphony; Siemens Medical Systems, Iselin, NJ). A four-element phased-array body coil was used in all patients. A true fast imaging with steady precession sequence (repetition time msec/echo time msec of 5.98/3.0, 70° flip angle, 19 sections acquired, section thickness of 8 mm, field of view of 320 mm [rectangular, 6/8], matrix of 256 x 153) in coronal and sagittal orientations was used to acquire a localization image. The coronal MR angiography slab was placed parallel to the abdominal aorta and covered the main aortic branches and the aortic bifurcation.

The parameters of the dynamic three-dimensional T1-weighted MR angiography sequence (spoiled gradient-echo fast low-angle shot, or FLASH) were as follows: 4.0/1.65; flip angle, 25°; receiver bandwidth, 488 Hz/pixel; field of view, 300 mm (rectangular, 7/8); acquisition matrix, 143 x 256; coronal slab, 72 mm thick (48 partitions); and imaging time, 30 seconds for three dynamic images. The k-space asymmetry was 48% in the readout direction, 37% in the direction of line phase encoding, and 50% in the direction of partition phase encoding. Partition thickness was 1.5 mm after k-space interpolation by means of zero filling in the direction of partition encoding. The in-plane spatial resolution of 1.84 x 1.17 mm led to a voxel volume of 3.2 mm³.

A nonenhanced study was acquired as a reference image before the contrast agent was administered. The nonenhanced study was acquired during an inspiration breath hold; no other special instructions were made to make the kidney position identical for the pre- and postcontrast studies. Bolus transit time was not measured. Fifteen seconds after initiation of the intravenous bolus injection of gadobenate dimeglumine or gadopentetate dimeglumine followed with 25 mL of saline, with an injection rate of 2.5 mL/sec, MR angiography was performed in a 30-second inspiration breath hold, which allowed acquisition of three consecutive measurements. The bolus of intravenous contrast agent was injected with a power injector (Spectris; Medrad, Pittsburgh, Pa) through an 18-gauge catheter placed in a peripheral arm vein, such as in the antecubital fossa. A central catheter was not used in any patient.

After the nonenhanced measurements were subtracted, a maximum intensity projection algorithm was applied to all MR angiograms by using the commercially available software on the MR imaging system (Magnetom Symphony software, NUMARIS 3.5, version VA13E; Siemens Medical Systems). Maximum intensity projection images were reconstructed in steps of 9° (range, 180°). No subvolume maximum intensity projection images were obtained to optimize each vessel, and no unwanted background tissue signal intensity was removed before maximum intensity projection reconstruction.

Image Analysis
The SNR was calculated separately, on the basis of signal intensities, for the abdominal aorta and right and left renal arteries. Signal intensities on MR images were evaluated by one investigator (M.V.) by using regions of interest. The region of interest was 0.5 cm² in the abdominal aorta and was 0.1 cm² in the right and left renal arteries. The region-of-interest measurements of the renal arteries were obtained in the proximal third of these vessels. Noise was measured in the right psoas muscle, owing to the lack of free air in the slab. This anatomic structure was chosen because its signal intensity is the most homogeneous of the objects in the slab. Noise was defined as the SD of the signal intensity in this region of interest. The region of interest in the psoas muscle was 1 cm².

Four experienced radiologists (M.S., M.L., J.S., J.L.) assessed both DSA images and MR angiograms independently for the degree of stenosis of the main renal arteries; the right and left renal arteries were analyzed separately. A caliper marked in tenths of a millimeter was used to measure the vessel diameters. To classify the degree of stenosis on DSA images, we used an approach similar to that of Hany et al (10), who regarded stenoses of 50% or more as hemodynamically significant. Stenoses were grouped into the following categories: no stenosis, 0%; mild stenosis, 1%–29%; moderate stenosis, 30%–49%; significant stenosis, 50%–99%; and occlusion, 100% stenosis. Only the main renal arteries proximal to the first segmental branch were evaluated with regard to stenoses.

In addition, the degree of stenosis of accessory renal arteries was classified as significant (diameter reduction, 50%) or nonsignificant (diameter reduction, <50%). When the observers evaluated DSA images or MR angiograms, they were blinded to the results with the other modality and to the kind and dose of contrast material. The observers were also blinded to the clinical history and to each other’s interpretation. To prevent bias, images were presented in a random order. Image analysis was based on hard copies of original MR angiograms, maximum intensity projection images, and DSA images.

Statistical Analysis
Statistical analysis was performed with software (EXCEL, Microsoft, Redmond, Wash; SPSS for Windows version 7.0, SPSS, Chicago, Ill). The Wilcoxon signed-rank test was applied for each pairwise comparison of gadopentetate dimeglumine versus gadobenate dimeglumine. Differences with a P value less than .05 were considered statistically significant.

	RESULTS

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The mean values and SDs of the SNRs are listed in Table 2. In a comparison of the mean values in the gadobenate dimeglumine groups with those in the gadopentetate dimeglumine groups, the following relative differences in the SNR were found: (a) Gadobenate dimeglumine 0.05 mmol/kg versus gadopentetate dimeglumine 0.1 mmol/kg: aorta, 5.7%; right renal artery, 6.9%; left renal artery, 11.1%. (b) Gadobenate dimeglumine 0.05 mmol/kg versus gadopentetate dimeglumine 0.2 mmol/kg: aorta, 1.4%; right renal artery, -7.3%; left renal artery, -2.4%. (c) Gadobenate dimeglumine 0.1 mmol/ kg versus gadopentetate dimeglumine 0.1 mmol/kg: aorta, 18.1% (P < .05); right renal artery, 17.5% (P < .05); left renal artery, 20.3% (P < .05). (d) Gadobenate dimeglumine 0.1 mmol/kg versus gadopentetate dimeglumine 0.2 mmol/kg: aorta, 20.3%; right renal artery, 4.4%; left renal artery, 8.1%. (e) Gadobenate dimeglumine 0.05 mmol/kg (Fig 1a) versus gadobenate dimeglumine 0.1 mmol/kg (Fig 1b): aorta, -13.2%; right renal artery, -11.4%; left renal artery, -10.3%. (f) Gadopentetate dimeglumine 0.1 mmol/kg (Fig 2a) versus gadopentetate dimeglumine 0.2 mmol/kg (Fig 2b): aorta, -4.3%; right renal artery, -13.8%; left renal artery, -13.2%.

View larger version (114K): [in this window] [in a new window] [Download PPT slide]   Figure 1a. Coronal three-dimensional time-resolved MR angiograms (4.0/1.65 with 25° flip angle) of the renal arteries in anteroposterior maximum intensity projection images. Differences in SNR were not significant between the two dose groups. (a) First image obtained after power injection of gadobenate dimeglumine 0.05 mmol/kg followed with saline reveals a lower right accessory renal artery (arrow) that was correctly detected and graded (no stenosis) by all four observers. (b) First image obtained after power injection of gadobenate dimeglumine 0.1 mmol/kg followed with saline. No stenosis was detected.

View larger version (123K): [in this window] [in a new window] [Download PPT slide]   Figure 1b. Coronal three-dimensional time-resolved MR angiograms (4.0/1.65 with 25° flip angle) of the renal arteries in anteroposterior maximum intensity projection images. Differences in SNR were not significant between the two dose groups. (a) First image obtained after power injection of gadobenate dimeglumine 0.05 mmol/kg followed with saline reveals a lower right accessory renal artery (arrow) that was correctly detected and graded (no stenosis) by all four observers. (b) First image obtained after power injection of gadobenate dimeglumine 0.1 mmol/kg followed with saline. No stenosis was detected.

View larger version (137K): [in this window] [in a new window] [Download PPT slide]   Figure 2a. Coronal three-dimensional time-resolved MR angiograms (4.0/1.65 with 25° flip angle) of the renal arteries in anteroposterior maximum intensity projection images. Differences in SNR were not significant between the two dose groups. (a) First image obtained after power injection of gadopentetate dimeglumine 0.1 mmol/kg followed with saline reveals hemodynamically nonsignificant stenosis of the left renal artery (right arrow) that was detected and graded correctly by all four observers. The hemodynamically significant stenosis of the right renal artery (left arrow) was detected and graded correctly by all four observers. (b) First image obtained after power injection of gadopentetate dimeglumine 0.2 mmol/kg followed with saline. No stenosis was detected.

View larger version (127K): [in this window] [in a new window] [Download PPT slide]   Figure 2b. Coronal three-dimensional time-resolved MR angiograms (4.0/1.65 with 25° flip angle) of the renal arteries in anteroposterior maximum intensity projection images. Differences in SNR were not significant between the two dose groups. (a) First image obtained after power injection of gadopentetate dimeglumine 0.1 mmol/kg followed with saline reveals hemodynamically nonsignificant stenosis of the left renal artery (right arrow) that was detected and graded correctly by all four observers. The hemodynamically significant stenosis of the right renal artery (left arrow) was detected and graded correctly by all four observers. (b) First image obtained after power injection of gadopentetate dimeglumine 0.2 mmol/kg followed with saline. No stenosis was detected.

One hundred nineteen renal arteries in 60 patients were evaluated with respect to degree of stenosis. None of the renal arteries were occluded. One patient had undergone right-sided nephrectomy. Fifty-nine renal arteries were normal (0% stenosis) at MR angiography and DSA. Thirty-two renal arteries showed mild stenosis (1%–29%), and 15 showed moderate stenosis (30%–49%). Thirteen renal arteries showed a hemodynamically significant (50%) stenosis at DSA; 11 (85%) were correctly depicted at MR angiography. No branch artery stenosis was detected at either DSA or MR angiography. Four (8%) of 47 hemodynamically nonsignificant stenoses were overestimated at MR angiography. There were no differences concerning the contrast agent or dose. Sensitivity and specificity were not calculated owing to the small number of stenoses in each dose group.

Twenty-two (85%) of 26 accessory renal arteries were depicted at MR angiography. Two accessory renal arteries were not depicted in either contrast agent group (n = 4). Intraarterial angiography depicted three stenoses of accessory renal arteries, which were also detected at MR angiography. All three stenoses were graded as significant (>50%) by all observers at both DSA and MR angiography. The remaining accessory vessels were normal at intraarterial angiography (n = 23) and MR angiography (n = 19).

	DISCUSSION

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Overall SNRs were higher with gadobenate dimeglumine than with gadopentetate dimeglumine in renal time-resolved MR angiography, but most of the differences in SNRs were not statistically significant.

In a comparison of the SNR with gadobenate dimeglumine 0.1 mmol/kg to that with gadopentetate dimeglumine 0.1 mmol/ kg, gadobenate dimeglumine was significantly superior to gadopentetate dimeglumine. This result is confirmed in a phase I study to measure the maximum signal intensity in the abdominal aorta (11). Owing to the nearly twofold relaxivity with gadobenate dimeglumine compared with that of gadopentetate dimeglumine at the same dose (7), increased SNR can be expected with the former. In addition, the pharmacokinetics of gadobenate dimeglumine that result from its protein-binding properties cause a higher and wider maximum signal intensity and a higher steady state.

In a comparison of all other dose groups, no other SNRs were significantly different. In a comparison of gadobenate dimeglumine 0.05 mmol/kg with gadopentetate dimeglumine 0.1 mmol/kg, differences were not expected to be significant because of the twofold difference in dose. The higher concentration of gadopentetate dimeglumine compared with the concentration of gadobenate dimeglumine compensated for its lower relaxivity. As expected, SNR with gadobenate dimeglumine was 2.4%–7.3% lower than that with gadopentetate dimeglumine, but the difference was not significant.

SNRs for gadobenate dimeglumine in both concentrations were not significantly different. This result is explained by the saturation kinetics of gadobenate dimeglumine at these doses. Findings in a phase II study (12) demonstrate that there is almost no increase in diagnostic information in the abdominal aorta and its major branches when the dose of 0.05 mmol/kg of gadobenate dimeglumine is doubled. Findings in the current study indicated a saturation pattern at approximately 0.1 mmol/kg with a diagnostic range from 0.05 to 0.15 mmol/kg.

In contrast to the findings of Hany et al (13), we found no statistically significant differences in SNR with gadopentetate dimeglumine 0.1 or 0.2 mmol/kg. Hany et al mentioned that it is likely that improvements in MR imaging technique, including time-resolved three-dimensional MR angiography, will permit further reductions in the minimum dose of contrast agent required. A flip angle of 40° was used in the study by Hany et al. A flip angle of 25° was used in the time-resolved three-dimensional MR angiography technique in our study, and it might have resulted in a higher dependency on the T1 shortening effect of MR contrast agents.

Injection of smaller volumes of a contrast agent (ie, 20 mL instead of 40 mL) with a constant injection rate of 2.5 mL/sec may improve bolus geometry. This is a potential advantage with gadobenate dimeglumine.

The detection rate of accessory renal arteries and their stenoses in our study is almost similar to those reported in the literature (10,14,15). A limitation of this study was the small number of renal artery stenoses in each of the four dose groups; thus, a statistical evaluation is not useful, and a statement concerning the diagnostic performance is not possible.

Findings in the literature (12,13) indicate that gadobenate dimeglumine 0.1 mmol/kg and gadopentetate dimeglumine 0.2 mmol/kg may be considered the doses recommended for MR angiography. In our study with time-resolved three-dimensional MR angiography, differences were not significant with a 50% reduced dose compared with a full dose of either contrast agent.

	FOOTNOTES

 
Abbreviations: DSA = digital subtraction angiography, SNR = signal-to-noise ratio

Author contributions: Guarantor of integrity of entire study, M.V.; study concepts, M.V., M.S., J.L.; study design, M.V., M.S.; literature research, M.V., M.S.; clinical studies, M.V.; data acquisition, M.V.; data analysis/ interpretation, M.V., M.S., M.L., J.S., C.M.; statistical analysis, M.V., M.S.; manuscript definition of intellectual content, M.V., M.S.; manuscript preparation and editing, M.V.; manuscript revision/review, M.S., J.L.; manuscript final version approval, S.F.

	REFERENCES

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