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MDCT of the Breast

¹ Department of Radiological Sciences, University La Sapienza of Rome-Policlinico Umberto I, Via Regina Elena, 324, 00161 Rome, Italy.
² Department of Surgical Sciences, University La Sapienza of Rome-Policlinico Umberto I, Rome, Italy.

Received September 12, 2007; accepted after revision December 12, 2007.

 
Address correspondence to A. Perrone.

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Abstract

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OBJECTIVE. The purpose of this study was to evaluate retrospectively the accuracy of low-dose MDCT in the differentiation of breast lesions suspected on mammography and sonography.

MATERIALS AND METHODS. MDCT was performed on 61 patients with mammographic or sonographic findings suggestive of breast cancer who could not undergo MR mammography. For each lesion, morphologic features, attenuation, and time-attenuation curve pattern were evaluated. The 1-minute cut point of attenuation was analyzed on the images. CT findings were compared with histopathologic results, which were the reference standard.

RESULTS. Forty-seven of 61 patients underwent surgery, and the pathologic findings revealed 27 malignant and 20 benign lesions. With CT 25 of 27 malignant lesions and all 20 benign lesions were diagnosed correctly. CT had a sensitivity of 92.6%, specificity of 100%, positive predictive value of 100%, negative predictive value of 90.9%, and accuracy of 95.74%. The cutoff attenuation value, which had the best validity for differentiating malignant and benign lesions, was calculated to be 90 H on the 1-minute images.

CONCLUSION. Our results confirm and strengthen the importance of all imaging parameters and not one in particular. Dynamic MDCT can be used in the evaluation of selected patients with suspected breast tumors.

Keywords: breast cancer • enhancement effects • MDCT • morphologic features

Introduction

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The diagnosis of breast cancer requires sensitive and specific examinations to detect the lesion and avoid surgical intervention in benign lesions. Moreover, therapeutic planning requires accurate preoperative evaluation of tumor extent and detection of multicentric and multifocal lesions. MR mammography has been reported to be a valid technique for diagnosis, especially in cases in which findings on mammography or sonography are equivocal, and therapeutic planning [1-3].

Some patients cannot undergo MRI owing to contraindications or conditions that limit its execution, such as anxiety and claustrophobia. Among the options for these patients are positron emission mammography and dedicated breast MRI. Positron emission mammography is used in the diagnosis of malignant neoplasms of the breast. The technique combines the quantitative capabilities of whole-body PET with millimeter resolution. It can be used to image the earliest and smallest in situ forms of breast cancer, substantially improving sensitivity in detection of small breast tumors because of its high resolution of approximately 1-2 mm. This technique is promising but involves exposure to radiation [4]. Dedicated breast MRI is a fully integrated MRI system designed specifically for breast imaging. The risk of claustrophobia is less than with conventional MRI, full coverage of both breasts can be achieved, the chest wall and axillae can be depicted in a single image, and image contrast and resolution are not compromised. Moreover, the breast MRI apparatus includes a fully integrated biopsy system with which core biopsy and vacuum-assisted biopsy can be performed. Positron emission mammography and breast MRI, however, are not widely available and are the most expensive breast imaging techniques. MDCT has become commercially available, suggesting that this technique may be used in breast imaging [5-9]. The purpose of our study was to evaluate retrospectively the accuracy of low-dose MDCT in the differentiation of breast lesions suspected on mammography or sonography.

Materials and Methods

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Patients
The institutional review board approved our study. From March 2002 to February 2006, 61 patients (mean age, 55 years; range, 41-76 years) with suspicious findings on mammography or sonography were referred to our department to undergo dynamic breast MDCT. Twenty patients could not undergo the previously recommended MR mammography because of obesity (one patient) or claustrophobia (29 patients). Forty-one patients were already known to be unable to undergo MRI (six patients with a pacemaker, seven with an incompatible prosthesis, 10 with severe obesity, 12 with claustrophobia, four with severe dyspnea, two with clips). Informed consent was obtained from each patient.

View larger version (144K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A —58-year-old woman with phyllodes tumor in left breast. Dynamic MDCT scans at baseline (A) and 1 minute after contrast administration (B) show large, regular lesion with early and intense enhancement in most of breast.

View larger version (141K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B —58-year-old woman with phyllodes tumor in left breast. Dynamic MDCT scans at baseline (A) and 1 minute after contrast administration (B) show large, regular lesion with early and intense enhancement in most of breast.

View larger version (129K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A —46-year-old woman with nonspecific inflammatory tissue in right breast. Dynamic MDCT scans at baseline (A) and 1 minute after contrast administration (B) show thickened homogeneous tissue beneath nipple, which exhibited strong enhancement.

View larger version (148K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B —46-year-old woman with nonspecific inflammatory tissue in right breast. Dynamic MDCT scans at baseline (A) and 1 minute after contrast administration (B) show thickened homogeneous tissue beneath nipple, which exhibited strong enhancement.

For acquisition before and 1 minute after IV administration of a nonionic contrast agent (iomeprol, Iomeron 350, Bracco) at a flow of 2-3 mL/s, all patients were scanned from the level of the axilla to the lower edge of the breast during a breath-hold. Acquisitions 3 and 8 minutes after contrast administration were limited to the portion of the breast containing the lesion previously identified. Only in cases in which multiple lesions were evident 1 minute after contrast administration was acquisition extended to the entire breast, also in the late phases. For optimal evaluation of the extent of a lesion, maximum-intensity-projection and multiplanar reformation images in the sagittal and coronal planes were made from the volume data set with 1-mm thickness, 1-mm reconstruction increment, and a standard soft-tissue kernel (B30).

Two experienced radiologists independently analyzed the images obtained for all patients; interpretation discrepancies were resolved by consensus. The following parameters were evaluated: morphologic features of the lesion, particularly margins and size; attenuation of the sus pected nodules in a region of interest (0.5-1 cm²) in the most contrast-enhanced part of the lesion; time-attenuation curve pattern for each lesion (percentage and absolute values) categorized according to the Kuhl system [10] (type 1, progressive, sustained and increasing enhance ment; type 2, plateau, rapid growth 1 minute after contrast administration and stable in late enhancement; type 3, washout, rapid growth 1 minute after contrast administration and abrupt decline in attenuation); a cutoff point of CT attenuation on the images 1 minute after contrast administration for differentiation of malignant and benign lesions.

MDCT results were compared with histopathologic findings for patients who had undergone surgery. Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated. Statistical analysis was performed with the paired Student's t test, and the results were considered significant at p < 0.005.

Results

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Forty-seven of 61 patients underwent surgery, and the pathologic findings revealed 27 malignant lesions (19 invasive ductal carcinomas, six ductal carcinomas in situ, and two invasive lobular carcinomas) and 20 benign lesions (six fibroadenomas, two benign phyllodes tumors [Figs. 1A and 1B], 11 fibrocystic disease, and one case of aspecific inflammatory tissue [Figs. 2A and 2B]). Multifocal disease was diagnosed in four patients with invasive ductal carcinoma. Multicentric disease was present in one patient with invasive lobular carcinoma and in another with invasive ductal carcinoma. Fourteen patients did not undergo surgery because CT did not depict malignant lesions. In 12 of the 14 cases, no suspected lesion was detected; in the other two cases, the morphologic features and enhancement pattern showed benign characteristics. CT results were confirmed with fine-needle aspiration cytologic examination (nine patients) or needle core biopsy (five patients). These patients had normal findings on sonographic and mammographic follow-up a mean of 24 months (range, 18-48 months) after treatment.

View larger version (74K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3A —72-year-old woman with ductal carcinoma in situ in left breast approximately 2.5 cm behind nipple. Dynamic MDCT images obtained 1 (A) and 8 (B) minutes after contrast administration show very small ( 4 mm) smooth lesion with homogeneous enhancement; time-attenuation curve was washout type.

View larger version (57K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3B —72-year-old woman with ductal carcinoma in situ in left breast approximately 2.5 cm behind nipple. Dynamic MDCT images obtained 1 (A) and 8 (B) minutes after contrast administration show very small ( 4 mm) smooth lesion with homogeneous enhancement; time-attenuation curve was washout type.

View larger version (6K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4 —Graph shows time-attenuation curve of absolute values for benign versus malignant lesions.

View larger version (7K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5 —Graph shows time-attenuation curve of percentage values for benign versus malignant lesions.

As for the morphologic features of the 39 lesions detected on CT, among 27 nodules with an irregular or spiculated shape, 22 were malignant lesions and five were benign. Of the 12 lesions with smooth margins, three were histologically malignant and nine were benign. The widest diameter of the lesions ranged from 0.2 cm (ductal carcinoma in situ) to 6.5 cm (phyllodes tumor) with a mean value of approximately 1.3 cm. Nineteen of these lesions had a diameter less than 1 cm (mean diameter, 0.6 cm) (Figs. 3A and 3B). In the evaluation of the time-attenuation curve patterns (Figs. 4 and 5), the 25 malignant lesions detected on CT had a washout pattern (16 cases) (Figs. 6A, 6B, 6C and 6D) or a plateau pattern (nine cases). All of the benign lesions had a persistent and progressive pattern (Figs. 7A, 7B, 7C and 7D).

View larger version (83K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 6A —52-year-old woman with invasive ductal carcinoma in left breast. Dynamic MDCT images at baseline (A) and 1 minute (B) after contrast administration depict irregular lesion with homogeneous enhancement; evaluation of time-attenuation curve showed washout pattern.

View larger version (100K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 6B —52-year-old woman with invasive ductal carcinoma in left breast. Dynamic MDCT images at baseline (A) and 1 minute (B) after contrast administration depict irregular lesion with homogeneous enhancement; evaluation of time-attenuation curve showed washout pattern.

View larger version (115K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 6C —52-year-old woman with invasive ductal carcinoma in left breast. Coronal and sagittal multiplanar reconstructions 1 minute after contrast administration show lesion in A and B located in upper left quadrant of breast, approximately 2 cm behind nipple.

View larger version (70K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 6D —52-year-old woman with invasive ductal carcinoma in left breast. Coronal and sagittal multiplanar reconstructions 1 minute after contrast administration show lesion in A and B located in upper left quadrant of breast, approximately 2 cm behind nipple.

View larger version (82K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7A —50-year-old woman with fibroadenoma in right breast. Dynamic MDCT scans show lesion with smooth margins and sustained and increasing enhancement (A, baseline; B, at 1 minute after contrast administration; C, at 3 minutes; D, at 8 minutes) in upper outer quadrant of breast.

View larger version (99K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7B —50-year-old woman with fibroadenoma in right breast. Dynamic MDCT scans show lesion with smooth margins and sustained and increasing enhancement (A, baseline; B, at 1 minute after contrast administration; C, at 3 minutes; D, at 8 minutes) in upper outer quadrant of breast.

View larger version (67K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7C —50-year-old woman with fibroadenoma in right breast. Dynamic MDCT scans show lesion with smooth margins and sustained and increasing enhancement (A, baseline; B, at 1 minute after contrast administration; C, at 3 minutes; D, at 8 minutes) in upper outer quadrant of breast.

View larger version (91K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7D —50-year-old woman with fibroadenoma in right breast. Dynamic MDCT scans show lesion with smooth margins and sustained and increasing enhancement (A, baseline; B, at 1 minute after contrast administration; C, at 3 minutes; D, at 8 minutes) in upper outer quadrant of breast.

Statistical analysis with the Student's t test did not reveal a significant difference between malignant and benign lesions (t = 0.0098, p < 0.005) under basal conditions, and there was overlap between the two types of lesions (Fig. 8). The difference became significant after the first and third minutes (t = 8.1 and 9.8, p < 0.005) (Figs. 9 and 10). Images at the eighth minute after contrast administration revealed an overlap between the two groups (t = 0.066, not significant; p < 0.005) (Fig. 11). Nevertheless, the curve pattern between the third and eighth minutes and the attenuation difference in the two phases indicated the different courses of these nodules. Malignant lesions had a mean decrease of 14% (minimum, 0%; maximum, 46%), whereas benign lesions had a mean increase of 21% (minimum, 6%; maximum, 35%). This difference in pattern was statistically significant (t = 3.63, p < 0.005). The cutoff of attenuation values (the last parameter) that best differentiated malignant and benign lesions was calculated to be 90 H on the 1-minute images, which allowed correct diagnosis of all the benign lesions (specificity, 100%) and all but one of the malignant lesions (Figs. 12A, 12B, 12C and 12D).

View larger version (8K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 8 —Graph shows distribution of attenuation values under basal conditions for malignant (light gray) versus benign (dark gray) lesion groups.

View larger version (9K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9 —Graph shows distribution of attenuation values 1 minute after contrast administration for malignant (light gray) versus benign (dark gray) lesion groups.

View larger version (9K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 10 —Graph shows distribution of attenuation values 3 minutes after contrast administration for malignant (light gray) versus benign (dark gray) lesion groups.

View larger version (10K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 11 —Graph shows distribution of attenuation values 8 minutes after contrast administration for malignant (light gray) versus benign (dark gray) lesion groups.

View larger version (87K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 12A —54-year-old woman with invasive ductal carcinoma in upper inner quadrant of right breast. Dynamic MDCT images at baseline (A) and 1 (B), 3 (C), and 8 (D) minutes after contrast administration depict spiculated lesion with low enhancement 1 minute after contrast administration. Lesion was only one in study with value less than 90 H 1 minute after contrast administration; evaluation of time-attenuation curve, however, showed washout pattern.

View larger version (87K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 12B —54-year-old woman with invasive ductal carcinoma in upper inner quadrant of right breast. Dynamic MDCT images at baseline (A) and 1 (B), 3 (C), and 8 (D) minutes after contrast administration depict spiculated lesion with low enhancement 1 minute after contrast administration. Lesion was only one in study with value less than 90 H 1 minute after contrast administration; evaluation of time-attenuation curve, however, showed washout pattern.

View larger version (98K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 12C —54-year-old woman with invasive ductal carcinoma in upper inner quadrant of right breast. Dynamic MDCT images at baseline (A) and 1 (B), 3 (C), and 8 (D) minutes after contrast administration depict spiculated lesion with low enhancement 1 minute after contrast administration. Lesion was only one in study with value less than 90 H 1 minute after contrast administration; evaluation of time-attenuation curve, however, showed washout pattern.

View larger version (87K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 12D —54-year-old woman with invasive ductal carcinoma in upper inner quadrant of right breast. Dynamic MDCT images at baseline (A) and 1 (B), 3 (C), and 8 (D) minutes after contrast administration depict spiculated lesion with low enhancement 1 minute after contrast administration. Lesion was only one in study with value less than 90 H 1 minute after contrast administration; evaluation of time-attenuation curve, however, showed washout pattern.

Discussion

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CT, usually used for the staging and follow-up of breast cancer, has been proposed [5, 11-14] as an alternative to dynamic MRI in the detection of neoplastic lesions and in the evaluation of extension of the lesions for planning of accurate breast-conserving therapy. Even if MRI findings often settle diagnostic doubt about a lesion after mammography or sonography owing to the depiction of morphologic features and the acquisition of a time-attenuation curve pattern, there are absolute and relative contraindications to MRI, such as presence of a pacemaker or clips, claustrophobia, and severe dyspnea due to heart disease. In our department, breast CT is reserved for these special cases because of the disadvantages of radiation exposure at CT [10, 15]. This exposure to radiation can be minimized with automatic device-modulating dose delivery (patient care dose) [16].

According to our experience, at a value of 60-70 mAs it is possible to obtain good image quality with a total radiation dose of 18.24 mGy for a 4-MDCT scanner and 16.40 mGy for a 64-MDCT scanner when acquisition is extended to the entire breast in the late phases. When the study is limited to the region of interest at the third and eighth minutes after contrast administration, the radiation dose is approximately 13.6 mGy for 4-MDCT and 12.3 mGy for 64-MDCT. These doses are approximately three times that of conventional mammography in two projections per breast.

Compared with MRI, the advantage of dynamic CT mammography is a shorter acquisition time. A complete study can be performed in one breath-hold with good spatial and contrast resolution due to the strong contrast enhancement of the surrounding fat tissue. One of the most important advantages of MDCT, particularly 64-MDCT, is thin collimation, which improves multiplanar and 3D reconstructions. Moreover, preoperative CT can be performed with the patient in the supine position. Use of this position facilitates simultaneous localization of the lesion and evaluation of its extent and examination of the skin and chest wall, the lymph nodes of both axillae, and the internal mammary and supraclavicular chains of lymph nodes [5, 6, 17]. Uematsu et al. [5] reported that tumor extent correlates significantly with measurements on 3D reconstructions. Therefore 3D CT can be considered an accurate preoperative imaging technique for candidates for breast-conserving surgery. We did not assess disease extent for preoperative planning.

A further application of breast CT concerns the possibility of CT-guided breast biopsy or preoperative guidance on lesions detected on CT or MRI [8, 9]. One report [18] describes the possibility of CT-guided core needle biopsy as a method for replacing needle localization and surgical biopsy of a group of breast lesions hidden on mammograms and sonograms or visible only on MRI but MRI-guided biopsy is not feasible. Compared with surgical biopsy, CT biopsy is less invasive, less expensive, and quicker to perform. Compared with MRI-guided biopsy, CT-guided biopsy does not require use of a breast coil, allowing direct access to the lesion.

Our purpose was to show the accuracy of 4- or 64-MDCT in examining all of the parameters studied in previous reports, such as morphologic features, enhancement features, and time-attenuation curves [5, 19, 20]. As for the morphologic features of a lesion, it is known that spiculated or irregular margins are predictive of the presence of malignancy, whereas regular or smooth margins often are indicators of benign nodules [2]. In our study, 22 of 27 malignant lesions had an irregular or spiculated shape, whereas nine of 12 histologically benign lesions had regular or polycyclic margins. Considering only the morphologic parameter (irregular margins indicate malignancy, regular margins indicate benignity), we correctly diagnosed as malignant 22 of 27 lesions and as benign nine of 12 lesions (sensitivity, 88%; specificity, 64%; positive predictive value, 81%; negative predictive value, 75%; accuracy, 79%).

Because the physiologic basis of detection of breast cancer with CT or MRI is to visualize the increased vessel attenuation and vessel permeability brought about by angiogenic activity of malignant and benign lesions, contrast administration is indispensable for breast CT. In our study, for differentiation of benign from malignant lesions, sensitivity and specificity increased at a cutoff attenuation value of 90 H 1 minute after contrast administration. This threshold allowed us to diagnose correctly all benign and all malignant lesions, except for a lesion that manifested with high attenuation ( 54 H) under basal conditions and low attenuation ( 75 H) with contrast enhancement. Miyake et al. [19] indicated a cutoff value of 60 H 30 seconds after injection of contrast medium. Using this value, we correctly diagnosed all of the malignant lesions with a sensitivity of 100% but with substantial reduction in specificity (64.2%).

Strong enhancement on 1-minute images is caused by the neoangiogenesis typical of malignant lesions [21, 22]. Although sensitivity for invasive cancer is very high, sensitivity for carcinoma in situ is lower because of lack of vascularity and the consequent inconsistent angiogenic activity of preinvasive cancer that translates into an inconsistent enhancement pattern. This fact can explain our two cases of false-negative findings (histological carcinoma in situ), in which no lesion was evident because of the weak enhancement in a breast containing large amounts of glandular tissue [21, 23, 24]. Therefore, in cases of carcinoma in situ, mammography and MDCT can be considered complementary. The former can depict microcalcifications, and the latter can help in detection of carcinoma in situ mammographically hidden owing to the absence of microcalcifications. For this reason, it is important to consider the dynamic features of a lesion.

The information about breast lesions acquired with dynamic contrast-enhanced MDCT is similar to that from dynamic MRI. Kuhl and Schild [21] evaluated the time-attenuation curve patterns of breast lesions and categorized them as type 1 (progressive, sustained and increasing enhancement), type 2 (plateau, rapid growth 1 minute after contrast administration and stable in late enhancement), and type 3 (washout, rapid growth 1 minute after contrast administration and abrupt decline in attenuation). The type 1 pattern often is considered to indicate a benign lesion, and the type 2 and 3 patterns suggest malignant lesions.

Results in this series showed that the densitometric course of a lesion between the third and the eighth minutes after contrast administration is important. Calculating the densitometric difference of the two lesion groups, we noticed a reduction of approximately 14% for the malignant lesions and mild increase of 21% for the benign lesions, but this difference was not statistically significant. Only results of the time-attenuation curve analysis combined with the irregular morphologic features of the lesion allowed us to make a correct diagnosis in the only case of low densitometric growth found 1 minute after contrast administration. The curve was the washout type.

In our study, all benign lesions had progressive enhancement up to the eighth minute after contrast administration. Even though they had early and intense enhancement, the two phyllodes tumors were considered benign lesions because they had regular margins and exhibited progressive and late enhancement. In 22 patients, CT depicted neither focal lesions nor areas characterized as having marked enhancement. As a consequence, no region of interest was placed. However, eight of these patients underwent surgery because of mammographic or sonographic findings. Histopathologic diagnosis revealed two carcinomas in situ and six cases of fibrocystic disease.

Compared with previous reports about CT and MRI of the breast, our study confirmed that CT has better specificity but lesser ability to depict malignant masses [11, 20, 23-27]. Furthermore, both CT and MRI are more sensitive than mammography and sonography in the detection of multicentric or multifocal lesions, which is important for correct surgical planning [1-3]. In our series, two cases of multifocal disease and four cases of multicentric disease were diagnosed.

In a study of dynamic MDCT of breast tumors, Inoue et al. [20] concluded that reliable findings for breast cancer are the presence of irregular shape and spiculated margins and that the time-attenuation curve pattern should be considered an unreliable predictor. Contrarily, we found that the morphologic features of a lesion evaluated under basal conditions did not have high enough accuracy for differentiation of malignant from benign lesions. Our results therefore confirm and strengthen the importance of all parameters. Enhancement pattern especially suggests the usefulness of dynamic MDCT of breasts for differentiating benign from malignant lesions in patients with suspected breast tumors.

Findings in a few previous reports and in our study of MDCT in the characterization of breast lesions suggest that it may be feasible to use MDCT for selected patients. MDCT can be used when mammographic and sonographic findings are equivocal in the absence of a clinically palpable lesion and in cases of suspicious lesions, especially in patients who refuse biopsy or for whom MRI is contraindicated. Further studies are needed to determine the accuracy of MDCT in preoperative staging, assessment of the extent of disease, and detection of multifocal and multicentric lesions in patients with a presumed solitary malignant tumor. These findings are crucial to undertaking correct management.

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