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Breast Lesion Detection and Characterization at Contrast-enhanced MR Mammography: Gadobenate Dimeglumine versus Gadopentetate Dimeglumine¹

¹ From the Department of Radiological Sciences, University of Rome "La Sapienza," Viale Regina Elena 324, 00161 Rome, Italy (F.P., C.C., R.O., F.V., F.F., A.N., R.P.); and Worldwide Medical Affairs, Bracco Imaging, Milan, Italy (M.A.K.). Received August 6, 2004; revision requested October 13; revision received November 13; accepted December 16. Address correspondence to F.P. (e-mail: federica.pediconi{at}uniroma1.it).

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
PURPOSE: To prospectively and intraindividually compare equivalent (0.1 mmol per kilogram of body weight) doses of gadobenate dimeglumine and gadopentetate dimeglumine for accuracy of detection and characterization of breast lesions at contrast material–enhanced magnetic resonance (MR) mammography.

MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. Twenty-six consecutive women (mean age, 47.8 years) suspected of having a breast tumor at mammography and sonography underwent two identical MR examinations at 1.5 T; examinations were separated by more than 48 hours but less than 72 hours. A T1-weighted three-dimensional gradient-echo sequence was used, and images were acquired before and at 0, 2, 4, 6, and 8 minutes after randomized injection of gadopentetate dimeglumine or gadobenate dimeglumine at an identical flow rate of 2 mL/sec. Separate and combined assessment of unenhanced, contrast-enhanced, and subtracted images was performed blindly by two readers in consensus. Accuracy for lesion detection was determined against a final diagnosis based on findings at conventional mammography, sonography, and surgery. Sensitivity, specificity, positive and negative predictive values, and overall accuracy for malignant lesion identification were determined against histologic results. Data were analyzed with the McNemar test, proportional odds models, and analysis of variance.

RESULTS: MR mammography with gadobenate dimeglumine depicted significantly (P = .003) more lesions (45 of 46) than did that with gadopentetate dimeglumine (36 of 46), and detected lesions were significantly (P < .001) more conspicuous with gadobenate dimeglumine. Confidence for characterization was significantly (P = .031) greater with gadobenate dimeglumine. Comparison of the contrast agents for their ability to help identify malignant lesions revealed significant (P = .02) superiority for gadobenate dimeglumine: Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy for malignant lesion identification were, respectively, 94.7%, 100%, 100%, 80.0%, and 95.6% with gadobenate dimeglumine and 76.3%, 100%, 100%, 47.1%, and 80.4% with gadopentetate dimeglumine. Quantitative evaluation of signal intensity–time curves revealed significantly (P < .001) greater lesion enhancement with gadobenate dimeglumine.

CONCLUSION: Detection of breast lesions and accurate identification of malignant lesions at MR imaging are significantly superior with gadobenate dimeglumine in comparison with gadopentetate dimeglumine.

© RSNA, 2005

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
Breast cancer is the second leading cause of cancer death among women in the developed world. It has been estimated that approximately 216 000 new cases of breast cancer will have been reported among women in the United States alone in 2004 and that more than 40 000 American women will have died of the disease during the year (1). The clinical emphasis is therefore on the early detection and diagnosis of breast cancer to enable successful treatment or surgical intervention before the primary tumor metastasizes.

Currently, conventional x-ray mammography and sonography are the techniques most widely used for the detection and localization of breast abnormalities. However, these techniques have limited sensitivity and specificity for the detection and diagnosis of breast lesions, particularly in patients with dense breast parenchyma or in patients with breast implants or postsurgical scars or deformity (2–5). As a possible alternative to these conventional techniques, contrast material–enhanced magnetic resonance (MR) mammography has emerged as a viable clinical tool for the detection, diagnosis, staging, and management of breast cancer (6–14). Advantageous attributes of MR imaging for diagnostic evaluation of breast cancer include high soft-tissue contrast; multiplanar sectioning, which permits the acquisition of contiguous thin sections that enable a full three-dimensional representation of one or both breasts; and the absence of ionizing radiation. However, whereas the sensitivity of contrast-enhanced MR mammography in the detection of breast cancer is generally high, the specificity for lesion characterization is typically only low to moderate (15–21). A principal limitation of contrast-enhanced MR mammography at present is its use in the detection and accurate characterization of small carcinomas with poor neoangiogenesis (9,22).

Results of a recent prospective multicenter study revealed a potential advantage for the high-relaxivity MR contrast agent gadobenate dimeglumine (MultiHance; Bracco Imaging, Milan, Italy) in comparison with the conventional contrast agent gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany) for contrast-enhanced MR mammography (23). Specifically, the results of this study demonstrated significant (P < .04) dose-related increases in global lesion detection in patients who were administered gadobenate dimeglumine and better lesion detection and higher sensitivity values for lesion characterization in patients who were administered 0.1 mmol of gadobenate dimeglumine per kilogram of body weight in comparison with patients administered 0.1 mmol/kg gadopentetate dimeglumine. Unfortunately, the findings for specificity in this study were compromised by a disproportionate distribution of malignant and nonmalignant lesions between the four randomized parallel dose groups.

The problems inherent to parallel group study designs are usually not encountered with intraindividual crossover study designs. Thus, the purpose of our study was to prospectively and intraindividually compare the use of equivalent 0.1 mmol/kg doses of gadobenate dimeglumine and gadopentetate dimeglumine for accuracy of depiction and characterization of breast lesions at contrast-enhanced MR mammography.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
The study was approved by the local ethics committee, and written informed consent was obtained from all patients. The study was performed independently of industry support, and all data and information deriving from and pertaining to the study was under the exclusive control of the investigating radiologists. Author M.A.K., an employee of Bracco Imaging, played no part in patient enrollment or examination and had no control over data and information submitted for publication.

Patients
A total of 26 consecutive women (mean age, 47.8 years ± 10.0 [standard deviation]; age range, 32–67 years) suspected of having breast cancer on the basis of conventional mammography and sonography conducted within 20 days of the study were prospectively enrolled between January 2002 and July 2003. Patients were excluded from the study if they were younger than 18 years of age, were pregnant or lactating, or had received any other contrast agent during the 48 hours before the contrast agent administration in our study; if they were undergoing radiation therapy, chemotherapy, or anticancer hormonal therapy before contrast agent administration; or if they had any medical condition or other circumstances that would substantially decrease the chances of obtaining reliable data. Patients with a history of hypersensitivity to gadolinium chelates or who had other contraindications to MR imaging were also excluded from the study.

Each enrolled patient underwent two contrast-enhanced MR mammography examinations; gadobenate dimeglumine was used as the MR contrast agent for one examination, and gadopentetate dimeglumine was used for the other. The order in which the contrast agents were administered was fully randomized: 13 patients (mean age, 48.0 years ± 9.5; age range, 32–65 years) were administered gadobenate dimeglumine as the first contrast agent and gadopentetate dimeglumine as the second (group A), and 13 patients (mean age, 47.7 years ± 10.9; age range, 34–67 years) were administered gadopentetate dimeglumine as the first contrast agent and gadobenate dimeglumine as the second (group B). One patient in group A was ultimately excluded from all evaluations of efficacy because of motion artifacts on the subtracted MR image set. Efficacy assessments were therefore performed for 12 patients in group A (mean age, 47.6 years ± 9.8; age range, 34–67 years).

Surgery or biopsy, with histologic evaluation of pathologic specimens, was performed in all patients between 24 hours and 1 month after completion of the second contrast-enhanced MR mammography examination. Pathologic specimens were obtained at core biopsy in five breasts, surgical biopsy in seven breasts, and lumpectomy or mastectomy in 17 breasts. Core biopsy was performed with use of imaging guidance (mammography, sonography, or MR imaging) in all cases for better visualization of the lesion. Needle localization for lumpectomy and surgical biopsy was similarly performed with imaging guidance (mammography, sonography, or MR imaging). For surgery and mastectomy, no imaging guidance was used. The five lesions in which core biopsy was performed comprised four cases of ductal carcinoma in situ (DCIS) and one case of lobular carcinoma in situ (LCIS). None of the breasts had associated radial scars, and all lesions were surgically excised within 1 month of diagnosis. The seven lesions for which surgical biopsy was performed comprised one case each of DCIS, LCIS, invasive ductal carcinoma (IDC), and mucinous carcinoma (MC), and three cases of radial scar in which no malignant foci were observed at histologic evaluation. Follow-up of lesions diagnosed as benign was performed with both mammography and MR imaging at intervals of 12–18 months after initial diagnosis. Conversely, for follow-up in breasts diagnosed as negative for lesions, routine mammography was performed after an interval of 18–24 months, depending on the age of the patient. For the purposes of this study, LCIS was considered a malignant lesion because it is usually a candidate for resection (24).

MR Imaging
Contrast-enhanced MR mammography was performed with a 1.5-T imager (Vision Plus; Siemens, Erlangen, Germany) by using a bilateral breast surface coil with the patient in the prone position. A transverse three-dimensional dynamic T1-weighted gradient-echo sequence was used, and images were acquired before contrast agent administration (unenhanced images) and at 0, 2, 4, 6, and 8 minutes after contrast agent administration (contrast-enhanced images). The imaging parameters were identical for both MR mammography examinations in each patient (repetition time msec/echo time msec, 8.1/4; flip angle, 30°; one signal acquired; rectangular field of view, 36 cm; and matrix, 396 x 512). The section thickness was 3 mm for each patient, and no intersection gap was used. The total acquisition time was no more than 120 seconds. No fat-suppression sequences were used; image subtraction was performed to eliminate the signal from fat.

For each examination, contrast agent administration was performed at an identical flow rate of 2 mL/sec (bolus) with a power injector (Spectris; Medrad, Indianola, Pa) by means of antecubital venous access. Each contrast agent was administered at a final dose of 0.1 mmol/kg and was followed by a 20-mL saline flush. Data acquisition started after contrast agent injection, at the end of the saline flush.

In all cases, the interval between the two MR examinations was more than 48 hours but less than 72 hours. A minimum interval of 48 hours between the two examinations was considered necessary to ensure complete elimination of the first contrast agent before administration of the second (25,26), while a maximum interval of 72 hours was considered appropriate to ensure full comparability of imaging findings from the two examinations.

Image Assessment
All images were evaluated by two observers (F.P. and R.O., 5 and 6 years of experience with contrast-enhanced MR mammogram interpretation, respectively) in consensus. The observers were unaware of all patient data (identity, medical history, clinical profile, results of comparative imaging procedures) and were fully blinded to the identity of the contrast agent administered. To minimize the possibility of memory playing a part in the evaluation, assessment of images from the second contrast-enhanced MR examination was performed at 2 weeks after the assessment of images from the first contrast-enhanced MR examination.

Assessment was performed in two separate reading sessions for each contrast-enhanced MR mammography examination. In the first session, evaluation of the unenhanced image sets from each examination was performed in randomized order. In the second session, evaluation of combined unenhanced, contrast-enhanced, and subtracted image sets was performed in randomized order, such as occurs typically in routine clinical practice. The subtracted images were acquired by subtracting the unenhanced images from the contrast-enhanced images on a pixel-by-pixel basis. Additional maximum intensity projection (MIP) reconstructions of subtracted images at 2 minutes after contrast agent administration were displayed on a separate workstation to facilitate improved lesion detection.

Images were evaluated first for technical quality by using a subjective "adequate or not adequate" criterion; if the observers considered an image set to be compromised because of motion artifacts, no further assessments were performed. The position of the lesions detected on each technically adequate image set was thereafter indicated on breast maps for later use in lesion matching. Lesion matching was performed by a third observer (F.V., 4 years of experience) who played no part in the initial assessment. The purpose was to match any lesions detected on images from the first contrast-enhanced MR examination with lesions detected on images from the second examination. The information indicated for each lesion included location (breast quadrant) and size. The imaging findings on each image set from each contrast-enhanced MR examination were subsequently evaluated against the reference standard (final diagnosis in each patient, which was formed on the basis of all available diagnostic information from imaging [conventional mammography and sonography] and surgery).

Qualitative Assessments
Lesion detection.—A preliminary evaluation was performed to compare gadobenate dimeglumine with gadopentetate dimeglumine in terms of the confidence for lesion detection on combined image sets, relative to unenhanced images alone, with the final diagnosis in each patient used as the reference standard. For this evaluation, the observers assigned a lesion detection score of 0 if they were uncertain whether a lesion was present, a score of 1 if they considered a lesion to be possibly or probably present, and a score of 2 if they considered a lesion to be definitely present. Lesions detected on contrast-enhanced MR mammograms that were subsequently shown not to be present at final diagnosis were considered to be false-positive lesions and were retrospectively assigned a score of –1 for the determination of confidence for lesion detection.

The accuracy for lesion detection at each contrast-enhanced MR mammography examination, relative to the final diagnosis, was determined both per lesion and per breast on the basis of the lesions indicated on the consensus assessment maps that were created during the evaluation of combined image sets. Lesions that were considered present at the final diagnosis but were not detected on contrast-enhanced MR mammograms were considered to be false-negative lesions. Lesions detected on contrast-enhanced MR mammograms that were not present at the final diagnosis were considered to be false-positive lesions. The sensitivity for lesion detection on a per lesion basis was determined by comparing, in terms of lesion size and location (breast quadrant), the lesions indicated on the assessment maps (considered true-positive lesions) with the lesions noted at the final diagnosis. Specificity was not calculated on a per lesion basis because it was not possible to designate a lesion as a true-negative lesion.

Both sensitivity and specificity could be calculated on a per breast basis. For this evaluation, a "true-positive breast" was one in which at least one lesion was present at both contrast-enhanced MR mammography and final diagnosis. Conversely, a "true-negative breast" was one in which no lesions were detected at either MR mammography or final diagnosis.

Lesion enhancement.—In addition to evaluation of lesion size, qualitative assessments were also performed for lesion conspicuity, margins, enhancement, pattern of enhancement, and type. These determinations were performed for all lesions detected on each image set by using predefined assessment scales as shown in Table 1.

Thereafter, the diagnostic accuracy for lesion characterization was performed on a per lesion and a per breast basis, relative to the histologic results available from biopsy or surgical specimens as the reference standard. The diagnostic accuracy for lesion characterization was determined in a manner similar to that described for lesion detection. On a per lesion basis, the sensitivity for characterization was defined as the proportion of histologically confirmed malignant lesions (true-positive lesions) that were correctly classified as malignant on the contrast-enhanced MR images, while the specificity for characterization was defined as the proportion of histologically confirmed nonmalignant lesions (true-negative lesions) that were correctly classified as nonmalignant on MR images. Additional calculations were performed to determine the positive and negative predictive values and overall accuracy for lesion characterization. On a per breast basis, the sensitivity for lesion characterization was defined as the proportion of breasts with at least one malignant lesion at histologic evaluation in which at least one malignant lesion was detected at MR mammography, while specificity was defined as the proportion of breasts with no malignant lesions at histologic evaluation in which there were no malignant lesions detected at MR mammography. Any lesions that were considered indeterminate at MR mammography were grouped with those lesions considered malignant (ie, true-positive lesions) for determinations of the accuracy for lesion characterization.

Quantitative Assessment
During the assessment of combined image sets, the two observers, working in consensus, also had the opportunity to place up to three regions of interest per lesion at each time point to permit the plotting of signal intensity (SI)-time curves. The most representative curve for each lesion was then described according to the SI rate (for which a rate of 1 is slow, a rate of 2 is intermediate, and a rate of 3 is fast) and the time course for SI enhancement (for which a score of 1 is a steady increase, a score of 2 is a plateau, and a score of 3 is washout).

Quantitative assessment of lesion enhancement was performed on the basis of the SI of the lesion on the unenhanced image (SI_pre) and the maximum SI of the lesion on the contrast-enhanced dynamic SI curve (SI_post), according to the following equation: percentage of lesion enhancement = [(SI_post – SI_pre)/SI_pre] · 100.

Regions of interest were also placed on areas of normal breast tissue and at positions outside the body to enable a determination of the SI noise. On the basis of the SI values at these regions of interest, values were determined for the lesion signal-to-noise ratio and contrast-to-noise ratio according to the following equations: lesion signal-to-noise ratio = (SI_post – SI_pre)/noise, and lesion-breast contrast-to-noise ratio = (SI_les – SI_br)/noise, where SI_les and SI_br are the postcontrast SI values determined at regions of interest on the lesion and breast, respectively.

Comparisons of the mean SI-time curves generated with use of gadobenate dimeglumine and gadopentetate dimeglumine were performed for the most common lesion types detected.

Statistical Analysis
All statistical analyses were performed by using SAS software (version 8.2; SAS Institute, Cary, NC), and P .05 was considered to indicate a significant difference. No correction for the multiplicity of statistical tests was performed, since the results showed consistency in terms of the difference between contrast agents.

The differences in score between gadobenate dimeglumine and gadopentetate dimeglumine in terms of the confidence for lesion detection and characterization and lesion conspicuity were tested by means of specific methods for analysis of categorical data in crossover designs (27). A subject-specific generalized linear mixed model was chosen, assuming proportional odds and a normal distribution for subject as the random effect. Fitting was performed by using the PROC NLMIXED command of the SAS program, with initial estimates obtained from a logistic regression model by using the PROC GENMOD command.

The confidence intervals for sensitivity, specificity, and positive and negative predictive values were calculated by using the exact binomial method. The comparative sensitivity (gadobenate dimeglumine vs gadopentetate dimeglumine) for the detection and characterization of lesions was tested by using the McNemar test (true-positive and false-negative lesions crossed by study agent).

Quantitative enhancement data were compared for the two contrast agents by means of analysis of variance for repeated measurements.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
A total of 46 lesions were detected at final diagnosis in the 25 evaluated patients, and all 46 lesions were assessed histologically. Thirty-eight lesions were confirmed to be malignant and comprised 19 IDC, 11 DCIS, three invasive lobular carcinoma (ILC), three LCIS, and two MC lesions. The remaining eight lesions were all confirmed to be benign and comprised three radial scars, three fibroadenomas, one case of ductal hyperplasia, and one case of lobular hyperplasia (Table 2).

Of the 46 lesions at final diagnosis, only 25 were detected on unenhanced MR images, and each of these 25 lesions was assigned a score of 1 (possibly or probably present). The remaining 21 lesions were not detected on unenhanced MR images and were retrospectively assigned a score of 0. On combined image sets obtained after administration of gadobenate dimeglumine, confidence scores of 0, 1, and 2 were assigned to one, 16, and 29 lesions, respectively, for a total score of 74. However, one of the lesions that was assigned a confidence score of 1 was subsequently shown to be false-positive and was reassigned a score of –1, for an adjusted total score of 72. This false-positive lesion was recorded in a breast that was later determined to contain four true-positive lesions (three IDCs and one ductal hyperplasia). On combined image sets obtained after administration of gadopentetate dimeglumine, confidence scores of 0, 1, and 2 were assigned to 18, 11, and 17 lesions, respectively, for a total score of 45. For both contrast agents, the overall confidence was improved on combined image sets compared with that on unenhanced images. Comparison of the scores for the combined image sets revealed significantly (P = .027, proportional odds model) greater confidence for lesion detection with gadobenate dimeglumine than with gadopentetate dimeglumine.

The order in which the contrast agents were administered did not influence the confidence scores: For patients in group A (gadobenate dimeglumine first, gadopentetate dimeglumine second) the confidence scores on gadobenate dimeglumine– and gadopentetate dimeglumine–enhanced images were 35 and 21, respectively, after adjustment for the false-positive lesion. For patients in group B (gadopentetate dimeglumine first, gadobenate dimeglumine second), the confidence scores on gadobenate dimeglumine– and gadopentetate dimeglumine–enhanced images were 37 and 24, respectively.

The total number of true-positive lesions detected on MR mammograms obtained with gadobenate dimeglumine and indicated on the assessment maps was 45, with one false-negative and one false-positive lesion. The false-negative lesion was a small (<1 cm) DCIS in a breast with two histologically confirmed DCIS lesions, while the false-positive lesion was the lesion that has already been described (Table 2). On the basis of these findings, the overall sensitivity for the detection of breast lesions on MR mammograms obtained with gadobenate dimeglumine was 97.8% (45 of 46 lesions; 95% confidence interval: 88.5%, 99.9%) on a per lesion basis. In contrast, the total number of lesions correctly identified on MR mammograms obtained with gadopentetate dimeglumine was 36, with 10 false-negative lesions and no false-positive lesions (Table 2). The overall sensitivity for the detection of breast lesions on MR mammograms obtained with gadopentetate dimeglumine was 78.3% (36 of 46 lesions; 95% confidence interval: 63.6%, 89.0%) on a per lesion basis. Comparison of the two contrast agents revealed a significantly (P = .003, McNemar test) superior sensitivity for breast lesion detection with gadobenate dimeglumine.

Of 50 breasts, there were 29 with confirmed lesions on MR mammograms obtained with gadobenate dimeglumine, with no false-positive or false-negative findings. In contrast, there were 27 breasts with confirmed lesions on MR mammograms obtained with gadopentetate dimeglumine, with no false-positive but two false-negative findings. The two breasts with false-negative findings were those in which solitary DCIS and IDC lesions were detected at final diagnosis based on results at mammography, sonography, and gadobenate dimeglumine–enhanced MR mammography. The sensitivity and specificity for lesion detection on a per breast basis are shown in Table 3.

View larger version (59K): [in this window] [in a new window] [Download PPT slide]   Figure 1a. Transverse MR images of a dynamic series in a 44-year-old patient with three histologically confirmed IDC lesions in the left breast. (a, b) Unenhanced T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) clearly reveal two lesions (arrow). (c–f) On unsubtracted T1-weighted gradient-echo images obtained with (c, e) 0.1 mmol/kg gadopentetate dimeglumine and (d, f) 0.1 mmol/kg gadobenate dimeglumine, contrast-enhanced lesions (arrow) are clearly visible. However, conspicuity is greater with gadobenate dimeglumine. (g) MIP reconstruction of subtracted images after gadopentetate dimeglumine administration reveals two lesions (arrow, arrowhead). (h) On the subtracted MIP reconstruction after gadobenate dimeglumine administration, these lesions (large arrow, arrowhead) and an additional small, histologically confirmed lesion (small arrow) are more clearly visible. (i, j) SI-time curves for (i) gadopentetate dimeglumine and (j) gadobenate dimeglumine demonstrate similar washout behavior, characteristic of a malignant lesion.

View larger version (55K): [in this window] [in a new window] [Download PPT slide]   Figure 1b. Transverse MR images of a dynamic series in a 44-year-old patient with three histologically confirmed IDC lesions in the left breast. (a, b) Unenhanced T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) clearly reveal two lesions (arrow). (c–f) On unsubtracted T1-weighted gradient-echo images obtained with (c, e) 0.1 mmol/kg gadopentetate dimeglumine and (d, f) 0.1 mmol/kg gadobenate dimeglumine, contrast-enhanced lesions (arrow) are clearly visible. However, conspicuity is greater with gadobenate dimeglumine. (g) MIP reconstruction of subtracted images after gadopentetate dimeglumine administration reveals two lesions (arrow, arrowhead). (h) On the subtracted MIP reconstruction after gadobenate dimeglumine administration, these lesions (large arrow, arrowhead) and an additional small, histologically confirmed lesion (small arrow) are more clearly visible. (i, j) SI-time curves for (i) gadopentetate dimeglumine and (j) gadobenate dimeglumine demonstrate similar washout behavior, characteristic of a malignant lesion.

View larger version (67K): [in this window] [in a new window] [Download PPT slide]   Figure 1c. Transverse MR images of a dynamic series in a 44-year-old patient with three histologically confirmed IDC lesions in the left breast. (a, b) Unenhanced T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) clearly reveal two lesions (arrow). (c–f) On unsubtracted T1-weighted gradient-echo images obtained with (c, e) 0.1 mmol/kg gadopentetate dimeglumine and (d, f) 0.1 mmol/kg gadobenate dimeglumine, contrast-enhanced lesions (arrow) are clearly visible. However, conspicuity is greater with gadobenate dimeglumine. (g) MIP reconstruction of subtracted images after gadopentetate dimeglumine administration reveals two lesions (arrow, arrowhead). (h) On the subtracted MIP reconstruction after gadobenate dimeglumine administration, these lesions (large arrow, arrowhead) and an additional small, histologically confirmed lesion (small arrow) are more clearly visible. (i, j) SI-time curves for (i) gadopentetate dimeglumine and (j) gadobenate dimeglumine demonstrate similar washout behavior, characteristic of a malignant lesion.

View larger version (60K): [in this window] [in a new window] [Download PPT slide]   Figure 1d. Transverse MR images of a dynamic series in a 44-year-old patient with three histologically confirmed IDC lesions in the left breast. (a, b) Unenhanced T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) clearly reveal two lesions (arrow). (c–f) On unsubtracted T1-weighted gradient-echo images obtained with (c, e) 0.1 mmol/kg gadopentetate dimeglumine and (d, f) 0.1 mmol/kg gadobenate dimeglumine, contrast-enhanced lesions (arrow) are clearly visible. However, conspicuity is greater with gadobenate dimeglumine. (g) MIP reconstruction of subtracted images after gadopentetate dimeglumine administration reveals two lesions (arrow, arrowhead). (h) On the subtracted MIP reconstruction after gadobenate dimeglumine administration, these lesions (large arrow, arrowhead) and an additional small, histologically confirmed lesion (small arrow) are more clearly visible. (i, j) SI-time curves for (i) gadopentetate dimeglumine and (j) gadobenate dimeglumine demonstrate similar washout behavior, characteristic of a malignant lesion.

View larger version (71K): [in this window] [in a new window] [Download PPT slide]   Figure 1e. Transverse MR images of a dynamic series in a 44-year-old patient with three histologically confirmed IDC lesions in the left breast. (a, b) Unenhanced T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) clearly reveal two lesions (arrow). (c–f) On unsubtracted T1-weighted gradient-echo images obtained with (c, e) 0.1 mmol/kg gadopentetate dimeglumine and (d, f) 0.1 mmol/kg gadobenate dimeglumine, contrast-enhanced lesions (arrow) are clearly visible. However, conspicuity is greater with gadobenate dimeglumine. (g) MIP reconstruction of subtracted images after gadopentetate dimeglumine administration reveals two lesions (arrow, arrowhead). (h) On the subtracted MIP reconstruction after gadobenate dimeglumine administration, these lesions (large arrow, arrowhead) and an additional small, histologically confirmed lesion (small arrow) are more clearly visible. (i, j) SI-time curves for (i) gadopentetate dimeglumine and (j) gadobenate dimeglumine demonstrate similar washout behavior, characteristic of a malignant lesion.

View larger version (66K): [in this window] [in a new window] [Download PPT slide]   Figure 1f. Transverse MR images of a dynamic series in a 44-year-old patient with three histologically confirmed IDC lesions in the left breast. (a, b) Unenhanced T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) clearly reveal two lesions (arrow). (c–f) On unsubtracted T1-weighted gradient-echo images obtained with (c, e) 0.1 mmol/kg gadopentetate dimeglumine and (d, f) 0.1 mmol/kg gadobenate dimeglumine, contrast-enhanced lesions (arrow) are clearly visible. However, conspicuity is greater with gadobenate dimeglumine. (g) MIP reconstruction of subtracted images after gadopentetate dimeglumine administration reveals two lesions (arrow, arrowhead). (h) On the subtracted MIP reconstruction after gadobenate dimeglumine administration, these lesions (large arrow, arrowhead) and an additional small, histologically confirmed lesion (small arrow) are more clearly visible. (i, j) SI-time curves for (i) gadopentetate dimeglumine and (j) gadobenate dimeglumine demonstrate similar washout behavior, characteristic of a malignant lesion.

View larger version (74K): [in this window] [in a new window] [Download PPT slide]   Figure 1g. Transverse MR images of a dynamic series in a 44-year-old patient with three histologically confirmed IDC lesions in the left breast. (a, b) Unenhanced T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) clearly reveal two lesions (arrow). (c–f) On unsubtracted T1-weighted gradient-echo images obtained with (c, e) 0.1 mmol/kg gadopentetate dimeglumine and (d, f) 0.1 mmol/kg gadobenate dimeglumine, contrast-enhanced lesions (arrow) are clearly visible. However, conspicuity is greater with gadobenate dimeglumine. (g) MIP reconstruction of subtracted images after gadopentetate dimeglumine administration reveals two lesions (arrow, arrowhead). (h) On the subtracted MIP reconstruction after gadobenate dimeglumine administration, these lesions (large arrow, arrowhead) and an additional small, histologically confirmed lesion (small arrow) are more clearly visible. (i, j) SI-time curves for (i) gadopentetate dimeglumine and (j) gadobenate dimeglumine demonstrate similar washout behavior, characteristic of a malignant lesion.

View larger version (69K): [in this window] [in a new window] [Download PPT slide]   Figure 1h. Transverse MR images of a dynamic series in a 44-year-old patient with three histologically confirmed IDC lesions in the left breast. (a, b) Unenhanced T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) clearly reveal two lesions (arrow). (c–f) On unsubtracted T1-weighted gradient-echo images obtained with (c, e) 0.1 mmol/kg gadopentetate dimeglumine and (d, f) 0.1 mmol/kg gadobenate dimeglumine, contrast-enhanced lesions (arrow) are clearly visible. However, conspicuity is greater with gadobenate dimeglumine. (g) MIP reconstruction of subtracted images after gadopentetate dimeglumine administration reveals two lesions (arrow, arrowhead). (h) On the subtracted MIP reconstruction after gadobenate dimeglumine administration, these lesions (large arrow, arrowhead) and an additional small, histologically confirmed lesion (small arrow) are more clearly visible. (i, j) SI-time curves for (i) gadopentetate dimeglumine and (j) gadobenate dimeglumine demonstrate similar washout behavior, characteristic of a malignant lesion.

View larger version (157K): [in this window] [in a new window] [Download PPT slide]   Figure 1i. Transverse MR images of a dynamic series in a 44-year-old patient with three histologically confirmed IDC lesions in the left breast. (a, b) Unenhanced T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) clearly reveal two lesions (arrow). (c–f) On unsubtracted T1-weighted gradient-echo images obtained with (c, e) 0.1 mmol/kg gadopentetate dimeglumine and (d, f) 0.1 mmol/kg gadobenate dimeglumine, contrast-enhanced lesions (arrow) are clearly visible. However, conspicuity is greater with gadobenate dimeglumine. (g) MIP reconstruction of subtracted images after gadopentetate dimeglumine administration reveals two lesions (arrow, arrowhead). (h) On the subtracted MIP reconstruction after gadobenate dimeglumine administration, these lesions (large arrow, arrowhead) and an additional small, histologically confirmed lesion (small arrow) are more clearly visible. (i, j) SI-time curves for (i) gadopentetate dimeglumine and (j) gadobenate dimeglumine demonstrate similar washout behavior, characteristic of a malignant lesion.

View larger version (105K): [in this window] [in a new window] [Download PPT slide]   Figure 1j. Transverse MR images of a dynamic series in a 44-year-old patient with three histologically confirmed IDC lesions in the left breast. (a, b) Unenhanced T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) clearly reveal two lesions (arrow). (c–f) On unsubtracted T1-weighted gradient-echo images obtained with (c, e) 0.1 mmol/kg gadopentetate dimeglumine and (d, f) 0.1 mmol/kg gadobenate dimeglumine, contrast-enhanced lesions (arrow) are clearly visible. However, conspicuity is greater with gadobenate dimeglumine. (g) MIP reconstruction of subtracted images after gadopentetate dimeglumine administration reveals two lesions (arrow, arrowhead). (h) On the subtracted MIP reconstruction after gadobenate dimeglumine administration, these lesions (large arrow, arrowhead) and an additional small, histologically confirmed lesion (small arrow) are more clearly visible. (i, j) SI-time curves for (i) gadopentetate dimeglumine and (j) gadobenate dimeglumine demonstrate similar washout behavior, characteristic of a malignant lesion.

View larger version (79K): [in this window] [in a new window] [Download PPT slide]   Figure 2a. Transverse MR images of a dynamic series in a 36-year-old patient with four histologically confirmed IDC lesions in the right breast. (a) Unenhanced T1-weighted gradient-echo image (8.1/4.0, 30° flip angle) does not clearly reveal presence of lesions. (b) MIP reconstruction of subtracted images obtained with 0.1 mmol/kg gadopentetate dimeglumine clearly reveals three lesions (arrows). (c) On subtracted MIP reconstruction obtained with 0.1 mmol/kg gadobenate dimeglumine, lesions are more conspicuous and more strongly enhanced. An additional small, histologically confirmed lesion (arrow), which is not seen on b, is clearly visible with gadobenate dimeglumine. (d, e) SI-time curves for (d) gadopentetate dimeglumine and (e) gadobenate dimeglumine reveal similar washout behavior, although the SI enhancement and conspicuity of the lesion are considerably greater with gadobenate dimeglumine.

View larger version (66K): [in this window] [in a new window] [Download PPT slide]   Figure 2b. Transverse MR images of a dynamic series in a 36-year-old patient with four histologically confirmed IDC lesions in the right breast. (a) Unenhanced T1-weighted gradient-echo image (8.1/4.0, 30° flip angle) does not clearly reveal presence of lesions. (b) MIP reconstruction of subtracted images obtained with 0.1 mmol/kg gadopentetate dimeglumine clearly reveals three lesions (arrows). (c) On subtracted MIP reconstruction obtained with 0.1 mmol/kg gadobenate dimeglumine, lesions are more conspicuous and more strongly enhanced. An additional small, histologically confirmed lesion (arrow), which is not seen on b, is clearly visible with gadobenate dimeglumine. (d, e) SI-time curves for (d) gadopentetate dimeglumine and (e) gadobenate dimeglumine reveal similar washout behavior, although the SI enhancement and conspicuity of the lesion are considerably greater with gadobenate dimeglumine.

View larger version (66K): [in this window] [in a new window] [Download PPT slide]   Figure 2c. Transverse MR images of a dynamic series in a 36-year-old patient with four histologically confirmed IDC lesions in the right breast. (a) Unenhanced T1-weighted gradient-echo image (8.1/4.0, 30° flip angle) does not clearly reveal presence of lesions. (b) MIP reconstruction of subtracted images obtained with 0.1 mmol/kg gadopentetate dimeglumine clearly reveals three lesions (arrows). (c) On subtracted MIP reconstruction obtained with 0.1 mmol/kg gadobenate dimeglumine, lesions are more conspicuous and more strongly enhanced. An additional small, histologically confirmed lesion (arrow), which is not seen on b, is clearly visible with gadobenate dimeglumine. (d, e) SI-time curves for (d) gadopentetate dimeglumine and (e) gadobenate dimeglumine reveal similar washout behavior, although the SI enhancement and conspicuity of the lesion are considerably greater with gadobenate dimeglumine.

View larger version (104K): [in this window] [in a new window] [Download PPT slide]   Figure 2d. Transverse MR images of a dynamic series in a 36-year-old patient with four histologically confirmed IDC lesions in the right breast. (a) Unenhanced T1-weighted gradient-echo image (8.1/4.0, 30° flip angle) does not clearly reveal presence of lesions. (b) MIP reconstruction of subtracted images obtained with 0.1 mmol/kg gadopentetate dimeglumine clearly reveals three lesions (arrows). (c) On subtracted MIP reconstruction obtained with 0.1 mmol/kg gadobenate dimeglumine, lesions are more conspicuous and more strongly enhanced. An additional small, histologically confirmed lesion (arrow), which is not seen on b, is clearly visible with gadobenate dimeglumine. (d, e) SI-time curves for (d) gadopentetate dimeglumine and (e) gadobenate dimeglumine reveal similar washout behavior, although the SI enhancement and conspicuity of the lesion are considerably greater with gadobenate dimeglumine.

View larger version (114K): [in this window] [in a new window] [Download PPT slide]   Figure 2e. Transverse MR images of a dynamic series in a 36-year-old patient with four histologically confirmed IDC lesions in the right breast. (a) Unenhanced T1-weighted gradient-echo image (8.1/4.0, 30° flip angle) does not clearly reveal presence of lesions. (b) MIP reconstruction of subtracted images obtained with 0.1 mmol/kg gadopentetate dimeglumine clearly reveals three lesions (arrows). (c) On subtracted MIP reconstruction obtained with 0.1 mmol/kg gadobenate dimeglumine, lesions are more conspicuous and more strongly enhanced. An additional small, histologically confirmed lesion (arrow), which is not seen on b, is clearly visible with gadobenate dimeglumine. (d, e) SI-time curves for (d) gadopentetate dimeglumine and (e) gadobenate dimeglumine reveal similar washout behavior, although the SI enhancement and conspicuity of the lesion are considerably greater with gadobenate dimeglumine.

Evaluation of lesion margins among true-positive lesions that were detected with both contrast agents revealed different classifications between evaluations with the two contrast agents for just seven of 36 lesions. The margins of one DCIS were described as irregular and/or ill defined on gadobenate dimeglumine–enhanced images but as lobulated on gadopentetate dimeglumine–enhanced images. One radial scar and one IDC were both described as having spiculated margins on images obtained after gadobenate dimeglumine administration but were described as having irregular and/or ill-defined margins on images obtained after gadopentetate dimeglumine administration. Conversely, another IDC was described as having spiculated margins on gadopentetate dimeglumine–enhanced images but had irregular and/or ill-defined margins on gadobenate dimeglumine–enhanced images. Finally, an MC and two fibroadenomas were all described as having smooth and/or well-defined margins after gadobenate dimeglumine administration but were described as having lobulated margins after gadopentetate dimeglumine administration.

The margins for the remaining 29 of 36 lesions were described similarly on images obtained after both gadobenate dimeglumine and gadopentetate dimeglumine administration: The IDC lesions were described as having irregular and/or ill-defined (n = 11) or spiculated (n = 3) margins, while the DCIS lesions were described as having irregular and/or ill-defined (n = 3), spiculated (n = 2), or smooth and/or well-defined margins. The MC and fibroadenoma found with use of each of the contrast agents were described as having smooth and/or well-defined margins, while both the ILC lesions and all three LCIS lesions were described as having lobulated margins. The two radial scars detected on images obtained with each contrast agent were described as having irregular and/or ill-defined margins.

In terms of enhancement patterns, the predominating classification for IDC was "rim enhancement" (n = 15) with each of the contrast agents. The enhancement pattern was described as ductlike for five of seven DCIS lesions and as rim enhancement for the remaining two lesions with use of each contrast agent. The MCs and fibroadenomas were all described as well circumscribed, round or oval, with homogeneous enhancement, while the radial scars were all described as demonstrating homogeneous enhancement with irregular contours. The two ILCs were described equally after both contrast agents as demonstrating either homogeneous enhancement with irregular contours or rim enhancement. Discrepant findings between images obtained with gadobenate dimeglumine and those obtained with gadopentetate dimeglumine were noted for two of three LCIS lesions only. Whereas one LCIS was described equally after each contrast agent as showing rim enhancement, one of the remaining lesions was described as being well circumscribed, round or oval, with homogeneous enhancement on gadobenate dimeglumine–enhanced images but was described as showing homogeneous enhancement with irregular contours on gadopentetate dimeglumine–enhanced images. The remaining LCIS lesion was described as well circumscribed, round or oval, with homogeneous enhancement after administration of gadopentetate dimeglumine but as showing homogeneous enhancement with irregular contours after administration of gadobenate dimeglumine.

Lesion characterization.—Despite minor differences in imaging findings for a few lesions, the overall confidence of the two observers for lesion characterization was largely unaltered after comparison of images obtained with gadobenate dimeglumine and images obtained with gadopentetate dimeglumine. The 25 lesions detected on unenhanced images were each assigned a confidence score of 1 (moderate confidence) when evaluation was based solely on unenhanced images. For 19 of these lesions, the confidence score was increased to 2 (high confidence) for both contrast-enhanced MR examinations on qualitative and quantitative evaluation of the combined image sets. The remaining six lesions comprised four lesions (two fibroadenomas, one LCIS, and one ILC) for which the confidence score was increased to 2 on gadobenate dimeglumine–enhanced images but remained at 1 on gadopentetate dimeglumine–enhanced images and two lesions (one small IDC and one small fibroadenoma) for which the confidence score remained at 1 on images obtained with both contrast agents.

The confidence scores for the 21 lesions not detected on unenhanced images included seven lesions for which the scores were increased to 1 after both contrast agents, one lesion for which the score was increased to 2 after both contrast agents, and three lesions (two DCIS and one IDC) for which the scores were increased to 2 with gadobenate dimeglumine but remained at 1 with gadopentetate dimeglumine. The nine lesions that were not detected on unenhanced images or on combined image sets with gadopentetate dimeglumine were each assigned a confidence score of 1 on the combined image sets with gadobenate dimeglumine. Finally, only one lesion (a small IDC) that was not detected on unenhanced images or on the combined image set with gadopentetate dimeglumine was assigned a score of 0 (low confidence) on the combined image set obtained with gadobenate dimeglumine.

The confidence for lesion characterization was not influenced by the order in which the contrast agents were administered: Among lesions that could be detected and characterized with both contrast agents, total confidence scores of 29 and 26 (for images obtained with gadobenate dimeglumine and gadopentetate dimeglumine, respectively) were recorded for patients in group A, and total confidence scores of 34 and 30 (for images obtained with gadobenate dimeglumine and gadopentetate dimeglumine, respectively) were recorded for patients in group B. The overall confidence level for combined image sets was improved for each contrast agent in comparison with that for unenhanced images. Comparison of combined image sets revealed greater confidence for lesion characterization with gadobenate dimeglumine than with gadopentetate dimeglumine for lesions detected with both contrast agents, although this difference was not significant (P = .09, proportional odds model).

Of the 46 lesions detected with gadobenate dimeglumine, 37 were characterized as malignant and nine were characterized as nonmalignant on the basis of quantitative and qualitative imaging findings. None were classified as indeterminate. One lesion that was classified as malignant on gadobenate dimeglumine–enhanced images was not present at final diagnosis. An additional two lesions were considered false-negative in terms of characterization: One was an MC that was erroneously classified as nonmalignant on gadobenate dimeglumine–enhanced MR images, and the other (a DCIS) was not detected on gadobenate dimeglumine–enhanced MR images but was detected and confirmed to be malignant at final diagnosis.

With use of gadopentetate dimeglumine, a total of 36 lesions were detected, of which 29 were correctly characterized as malignant (true-positive lesions) and seven were correctly characterized as nonmalignant (true-negative lesions). Again, no lesions were classified as indeterminate. However, 10 lesions that were present at final diagnosis were not detected on gadopentetate dimeglumine–enhanced images. Nine of these 10 lesions were characterized as malignant at final diagnosis and were therefore considered false-negative lesions on gadopentetate dimeglumine–enhanced MR mammograms. The remaining lesion was characterized as benign at final diagnosis and was therefore considered a true-negative lesion in regard to the identification of malignant lesions. The values for sensitivity, specificity, positive and negative predictive values, and overall accuracy for identification (detection and characterization) of malignant lesions, considering all histologically confirmed lesions present at final diagnosis, are shown in Table 4.

View larger version (69K): [in this window] [in a new window] [Download PPT slide]   Figure 3a. Transverse MR images of a dynamic series in a 65-year-old patient with two histologically confirmed DCIS lesions and one fibroadenoma in the right breast and three histologically confirmed IDC lesions and one case of ductal hyperplasia in the left breast. (a, b) T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) obtained with (a) 0.1 mmol/kg gadopentetate dimeglumine and (b) 0.1 mmol/kg gadobenate dimeglumine suggest presence of breast lesions (arrow), but fibrocystic disease makes accurate detection and characterization difficult. (c, d) MIP reconstructions of the subtracted images with (c) gadopentetate dimeglumine and (d) gadobenate dimeglumine more clearly reveal presence of lesions. On c, in the right breast, a fibroadenoma (straight arrow) and a DCIS (curved arrow) are seen, and in the left breast, two IDCs (arrows) are seen. On d, in the right breast, an additional small DCIS (arrowhead) can be seen together with the same fibroadenoma (straight arrow) and DCIS (curved arrow) as in c, and in the left breast, a third IDC (arrowhead) and a false-positive lesion (open arrow) are visible together with the two IDCs (filled arrows) seen in c. (e–h) SI-time curves for (e, g) gadopentetate dimeglumine and (f, h) gadobenate dimeglumine reveal enhancement patterns typical of DCIS (e and f) and fibroadenoma (g and h), but greater SI values are obtained with gadobenate dimeglumine.

View larger version (68K): [in this window] [in a new window] [Download PPT slide]   Figure 3b. Transverse MR images of a dynamic series in a 65-year-old patient with two histologically confirmed DCIS lesions and one fibroadenoma in the right breast and three histologically confirmed IDC lesions and one case of ductal hyperplasia in the left breast. (a, b) T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) obtained with (a) 0.1 mmol/kg gadopentetate dimeglumine and (b) 0.1 mmol/kg gadobenate dimeglumine suggest presence of breast lesions (arrow), but fibrocystic disease makes accurate detection and characterization difficult. (c, d) MIP reconstructions of the subtracted images with (c) gadopentetate dimeglumine and (d) gadobenate dimeglumine more clearly reveal presence of lesions. On c, in the right breast, a fibroadenoma (straight arrow) and a DCIS (curved arrow) are seen, and in the left breast, two IDCs (arrows) are seen. On d, in the right breast, an additional small DCIS (arrowhead) can be seen together with the same fibroadenoma (straight arrow) and DCIS (curved arrow) as in c, and in the left breast, a third IDC (arrowhead) and a false-positive lesion (open arrow) are visible together with the two IDCs (filled arrows) seen in c. (e–h) SI-time curves for (e, g) gadopentetate dimeglumine and (f, h) gadobenate dimeglumine reveal enhancement patterns typical of DCIS (e and f) and fibroadenoma (g and h), but greater SI values are obtained with gadobenate dimeglumine.

View larger version (56K): [in this window] [in a new window] [Download PPT slide]   Figure 3c. Transverse MR images of a dynamic series in a 65-year-old patient with two histologically confirmed DCIS lesions and one fibroadenoma in the right breast and three histologically confirmed IDC lesions and one case of ductal hyperplasia in the left breast. (a, b) T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) obtained with (a) 0.1 mmol/kg gadopentetate dimeglumine and (b) 0.1 mmol/kg gadobenate dimeglumine suggest presence of breast lesions (arrow), but fibrocystic disease makes accurate detection and characterization difficult. (c, d) MIP reconstructions of the subtracted images with (c) gadopentetate dimeglumine and (d) gadobenate dimeglumine more clearly reveal presence of lesions. On c, in the right breast, a fibroadenoma (straight arrow) and a DCIS (curved arrow) are seen, and in the left breast, two IDCs (arrows) are seen. On d, in the right breast, an additional small DCIS (arrowhead) can be seen together with the same fibroadenoma (straight arrow) and DCIS (curved arrow) as in c, and in the left breast, a third IDC (arrowhead) and a false-positive lesion (open arrow) are visible together with the two IDCs (filled arrows) seen in c. (e–h) SI-time curves for (e, g) gadopentetate dimeglumine and (f, h) gadobenate dimeglumine reveal enhancement patterns typical of DCIS (e and f) and fibroadenoma (g and h), but greater SI values are obtained with gadobenate dimeglumine.

View larger version (59K): [in this window] [in a new window] [Download PPT slide]   Figure 3d. Transverse MR images of a dynamic series in a 65-year-old patient with two histologically confirmed DCIS lesions and one fibroadenoma in the right breast and three histologically confirmed IDC lesions and one case of ductal hyperplasia in the left breast. (a, b) T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) obtained with (a) 0.1 mmol/kg gadopentetate dimeglumine and (b) 0.1 mmol/kg gadobenate dimeglumine suggest presence of breast lesions (arrow), but fibrocystic disease makes accurate detection and characterization difficult. (c, d) MIP reconstructions of the subtracted images with (c) gadopentetate dimeglumine and (d) gadobenate dimeglumine more clearly reveal presence of lesions. On c, in the right breast, a fibroadenoma (straight arrow) and a DCIS (curved arrow) are seen, and in the left breast, two IDCs (arrows) are seen. On d, in the right breast, an additional small DCIS (arrowhead) can be seen together with the same fibroadenoma (straight arrow) and DCIS (curved arrow) as in c, and in the left breast, a third IDC (arrowhead) and a false-positive lesion (open arrow) are visible together with the two IDCs (filled arrows) seen in c. (e–h) SI-time curves for (e, g) gadopentetate dimeglumine and (f, h) gadobenate dimeglumine reveal enhancement patterns typical of DCIS (e and f) and fibroadenoma (g and h), but greater SI values are obtained with gadobenate dimeglumine.

View larger version (166K): [in this window] [in a new window] [Download PPT slide]   Figure 3e. Transverse MR images of a dynamic series in a 65-year-old patient with two histologically confirmed DCIS lesions and one fibroadenoma in the right breast and three histologically confirmed IDC lesions and one case of ductal hyperplasia in the left breast. (a, b) T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) obtained with (a) 0.1 mmol/kg gadopentetate dimeglumine and (b) 0.1 mmol/kg gadobenate dimeglumine suggest presence of breast lesions (arrow), but fibrocystic disease makes accurate detection and characterization difficult. (c, d) MIP reconstructions of the subtracted images with (c) gadopentetate dimeglumine and (d) gadobenate dimeglumine more clearly reveal presence of lesions. On c, in the right breast, a fibroadenoma (straight arrow) and a DCIS (curved arrow) are seen, and in the left breast, two IDCs (arrows) are seen. On d, in the right breast, an additional small DCIS (arrowhead) can be seen together with the same fibroadenoma (straight arrow) and DCIS (curved arrow) as in c, and in the left breast, a third IDC (arrowhead) and a false-positive lesion (open arrow) are visible together with the two IDCs (filled arrows) seen in c. (e–h) SI-time curves for (e, g) gadopentetate dimeglumine and (f, h) gadobenate dimeglumine reveal enhancement patterns typical of DCIS (e and f) and fibroadenoma (g and h), but greater SI values are obtained with gadobenate dimeglumine.

View larger version (165K): [in this window] [in a new window] [Download PPT slide]   Figure 3f. Transverse MR images of a dynamic series in a 65-year-old patient with two histologically confirmed DCIS lesions and one fibroadenoma in the right breast and three histologically confirmed IDC lesions and one case of ductal hyperplasia in the left breast. (a, b) T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) obtained with (a) 0.1 mmol/kg gadopentetate dimeglumine and (b) 0.1 mmol/kg gadobenate dimeglumine suggest presence of breast lesions (arrow), but fibrocystic disease makes accurate detection and characterization difficult. (c, d) MIP reconstructions of the subtracted images with (c) gadopentetate dimeglumine and (d) gadobenate dimeglumine more clearly reveal presence of lesions. On c, in the right breast, a fibroadenoma (straight arrow) and a DCIS (curved arrow) are seen, and in the left breast, two IDCs (arrows) are seen. On d, in the right breast, an additional small DCIS (arrowhead) can be seen together with the same fibroadenoma (straight arrow) and DCIS (curved arrow) as in c, and in the left breast, a third IDC (arrowhead) and a false-positive lesion (open arrow) are visible together with the two IDCs (filled arrows) seen in c. (e–h) SI-time curves for (e, g) gadopentetate dimeglumine and (f, h) gadobenate dimeglumine reveal enhancement patterns typical of DCIS (e and f) and fibroadenoma (g and h), but greater SI values are obtained with gadobenate dimeglumine.

View larger version (173K): [in this window] [in a new window] [Download PPT slide]   Figure 3g. Transverse MR images of a dynamic series in a 65-year-old patient with two histologically confirmed DCIS lesions and one fibroadenoma in the right breast and three histologically confirmed IDC lesions and one case of ductal hyperplasia in the left breast. (a, b) T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) obtained with (a) 0.1 mmol/kg gadopentetate dimeglumine and (b) 0.1 mmol/kg gadobenate dimeglumine suggest presence of breast lesions (arrow), but fibrocystic disease makes accurate detection and characterization difficult. (c, d) MIP reconstructions of the subtracted images with (c) gadopentetate dimeglumine and (d) gadobenate dimeglumine more clearly reveal presence of lesions. On c, in the right breast, a fibroadenoma (straight arrow) and a DCIS (curved arrow) are seen, and in the left breast, two IDCs (arrows) are seen. On d, in the right breast, an additional small DCIS (arrowhead) can be seen together with the same fibroadenoma (straight arrow) and DCIS (curved arrow) as in c, and in the left breast, a third IDC (arrowhead) and a false-positive lesion (open arrow) are visible together with the two IDCs (filled arrows) seen in c. (e–h) SI-time curves for (e, g) gadopentetate dimeglumine and (f, h) gadobenate dimeglumine reveal enhancement patterns typical of DCIS (e and f) and fibroadenoma (g and h), but greater SI values are obtained with gadobenate dimeglumine.

View larger version (153K): [in this window] [in a new window] [Download PPT slide]   Figure 3h. Transverse MR images of a dynamic series in a 65-year-old patient with two histologically confirmed DCIS lesions and one fibroadenoma in the right breast and three histologically confirmed IDC lesions and one case of ductal hyperplasia in the left breast. (a, b) T1-weighted gradient-echo images (8.1/4.0, 30° flip angle) obtained with (a) 0.1 mmol/kg gadopentetate dimeglumine and (b) 0.1 mmol/kg gadobenate dimeglumine suggest presence of breast lesions (arrow), but fibrocystic disease makes accurate detection and characterization difficult. (c, d) MIP reconstructions of the subtracted images with (c) gadopentetate dimeglumine and (d) gadobenate dimeglumine more clearly reveal presence of lesions. On c, in the right breast, a fibroadenoma (straight arrow) and a DCIS (curved arrow) are seen, and in the left breast, two IDCs (arrows) are seen. On d, in the right breast, an additional small DCIS (arrowhead) can be seen together with the same fibroadenoma (straight arrow) and DCIS (curved arrow) as in c, and in the left breast, a third IDC (arrowhead) and a false-positive lesion (open arrow) are visible together with the two IDCs (filled arrows) seen in c. (e–h) SI-time curves for (e, g) gadopentetate dimeglumine and (f, h) gadobenate dimeglumine reveal enhancement patterns typical of DCIS (e and f) and fibroadenoma (g and h), but greater SI values are obtained with gadobenate dimeglumine.

View larger version (30K): [in this window] [in a new window] [Download PPT slide]   Figure 4. Mean percentage SI enhancement–time curves, signal-to-noise ratio (SNR)-time curves, and contrast-to-noise ratio (CNR)-time curves for 15 IDC lesions detected on both gadobenate dimeglumine (Gd-BOPTA)-enhanced and gadopentetate dimeglumine (Gd-DTPA)-enhanced MR mammograms. All values were consistently and significantly (P < .001) higher on gadobenate dimeglumine–enhanced images. Similarly higher values for gadobenate dimeglumine over gadopentetate dimeglumine were noted for all other lesions.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

The gadolinium-based contrast agents currently used for contrast-enhanced MR mammography have different structural and physicochemical properties, but all have similar in vivo T1 relaxivities between 4.3 and 5.0 L · mmol^–1 · sec^–1 (29,30). As a consequence, there is little if any difference between these contrast agents for routine MR imaging applications, when used at equivalent doses. Gadobenate dimeglumine differs from these conventional gadolinium-based contrast agents in that it possesses a twofold higher T1 relaxivity in vivo (9.7 L · mmol^–1 · sec^–1) because of weak and transient interactions of the gadolinium chelate with serum albumin (31). Results of numerous comparative studies with a variety of indications have shown that this increased T1 relaxivity translates into greater contrast enhancement, which is clinically advantageous for the improved detection, visualization, and delineation of lesions (32–38).

In a recent study (23), results of a large-scale interindividual comparison between gadobenate dimeglumine and gadopentetate dimeglumine in patients known to have or suspected of having breast cancer suggested that gadobenate dimeglumine may also have advantages for MR imaging of the breast. However, whereas results of this earlier study suggested that a dose of 0.1 mmol/kg gadobenate dimeglumine was superior to an equivalent dose of gadopentetate dimeglumine for the depiction of breast lesions, the study was compromised by disproportionate distributions of benign and malignant and solitary and multifocal lesions between the dose groups. Results of our intraindividual crossover comparison between gadobenate dimeglumine and gadopentetate dimeglumine in the same patients confirm all of the findings of the previous study (23) and support the conclusions of comparative studies for other indications in demonstrating the unequivocal superiority of gadobenate dimeglumine over gadopentetate dimeglumine. Specifically, results of our study reveal not only that gadobenate dimeglumine increases lesion contrast enhancement and therefore the conspicuity and confidence for characterization of lesions, but that it also significantly improves the detection of small (<5 mm) malignant foci in comparison with gadopentetate dimeglumine. This latter benefit can be considered a very important finding, given that the detection of very small malignant lesions with poor neoangiogenesis is considered one of the principal limitations to the routine use of contrast-enhanced MR mammography as a diagnostic imaging modality (9,22), particularly if, as proposed, contrast-enhanced MR mammography is to become a screening procedure for women with a high genetic risk of breast cancer (39–41).

Concerning the contrast enhancement of lesions, the superior performance obtained with gadobenate dimeglumine may be considered of value not only for the detection and preliminary staging of breast cancer but also for the evaluation of lesions prior to surgery (42) and for postsurgical follow-up of breasts (5,43). In this regard, an improved visualization of tumor margins and a clearer view of the degree of tumor infiltration would be advantageous for presurgical planning.

A major limitation of contrast-enhanced MR mammography as a routine diagnostic tool is a comparatively low specificity for the characterization of detected lesions (15–21). This is due in large part to the difficulty in distinguishing benign lesions from malignant lesions on the basis of morphologic features alone (8,15). Authors of one study (44) concluded that reproducible characterization of suspicious breast lesions is achievable by using combined assessment of the washout enhancement patterns and lesion margins. Generally, the SI-time curves of malignant lesions showed characteristic washout profiles, whereas the curves of benign lesions more frequently showed a steady increase or plateau profile. In our study, the SI-time curves acquired with gadobenate dimeglumine for the different lesion types were similar to those noted here and reported elsewhere for benign and malignant lesions depicted with gadopentetate dimeglumine. However, the greater contrast enhancement and improved lesion conspicuity obtained with gadobenate dimeglumine permitted improved definition of lesion margins and therefore improved confidence for lesion characterization. This may be particularly important in poorly vascularized lesions that show poor enhancement after the administration of gadopentetate dimeglumine.

Of note in the present study is that 100% specificity for lesion characterization was obtained with both contrast agents. Compared with results in other studies (15–21) and the observations from our routine clinical practice, a specificity value of 100% is clearly an overestimation, and in this case it reflects the comparatively limited total number of evaluated lesions, the high proportion of malignant lesions (38 of 46 lesions, 82.6%), and the low number of fibroadenomas (n = 3) in the overall lesion population. On the other hand, the fact that specificity values of 100% were obtained might be considered indicative of a continually improving performance with contrast-enhanced MR mammography compared with the situation a few years ago. With the advent of newer diagnostic procedures for the accurate differentiation of benign from malignant lesions (45), specificity values approaching 100% might not be an unrealistic expectation.

In summary, the results of the present study confirm the conclusions of a previous investigation (23) that the high T1 relaxivity of gadobenate dimeglumine compared with that of gadopentetate dimeglumine is beneficial for contrast-enhanced MR mammography. Although this study was limited in that only 25 patients and 46 histologically proved lesions were evaluated, the intraindividual crossover design of the investigation provides a clear indication of the superior contrast enhancement performance achievable with gadobenate dimeglumine. While it would be desirable to validate these findings prospectively in a larger patient population, it should be borne in mind that patients with confirmed breast malignancy are urgent candidates for surgery and are therefore less readily available for further investigation. On the other hand, further studies on the potential of gadobenate dimeglumine for contrast-enhanced MR mammography are clearly warranted.

	ACKNOWLEDGMENTS

 
We gratefully acknowledge Italo Nofroni, PhD, and Riccardo Spezia, MSc, for help with the statistical analysis of the data, and Massimiliano Danti, MD, for help with image processing.

	FOOTNOTES

 

Abbreviations: DCIS = ductal carcinoma in situ • IDC = invasive ductal carcinoma • LCIS = lobular carcinoma in situ • MC = mucinous carcinoma • MIP = maximum intensity projection • SI = signal intensity

See Materials and Methods for pertinent disclosures.

Author contributions: Guarantors of integrity of entire study, F.P., C.C., R.P.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, all authors; clinical and experimental studies, all authors; statistical analysis, all authors; and manuscript editing, all authors

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