Relationship between Mammographic Density and Age in the United Arab Emirates Population.

OBJECTIVE: Higher breast density is a strong, independent risk factor for breast cancer. Breast density varies by age, ethnicity, and geographic area although dense breast tissue has been associated with younger age and premenopausal status. The relationship between breast density and age in women in the United Arab Emirates (UAE) has not been determined. This study evaluated breast density in the UAE population and its relationship with age. METHODS: Women participating in the national cancer screening program from August 2015 to May 2018 who underwent screening mammography were included. Breast parenchymal density was classified according to the American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BI-RADS) from category a (almost entirely fatty) through d (extremely dense). Subjects were divided into six age groups, and the association between age and breast density was evaluated. RESULTS: Of the 4911 women included, 1604 (32.7%), 2149 (43.8%), 1055 (21.5%), and 103 (2.1%) were classified as having categories a-d breast density, respectively. A significant negative correlation was observed between age and breast density category (p < 0.001). Women of mean age 44 ± 7 years had the highest breast density, whereas those of mean age 56 ± 14 years had the lowest breast density. Comparisons of Emirati women with Lebanese and Western women showed that breast density was lower in Emirati women than in the other populations. CONCLUSIONS: To our knowledge, this is the first study to evaluate the relationship between mammographic breast density and age in UAE women. As in other populations, age was inversely related to breast density, but the proportion of Emirati women with dense breasts was lower than in other populations. Because this study lacked demographic, clinical, and histopathological data, further evaluation is required.

IL-6-mediated cross-talk between human preadipocytes and ductal carcinoma in situ in breast cancer progression.

BACKGROUND: The function of preadipocytes in the progression of early stage breast cancer has not been fully elucidated at the molecular level. To delineate the role of preadipocytes in breast cancer progression, we investigated the cross-talk between human breast ductal carcinoma in situ (DCIS) cells and preadipocytes with both an in vitro culture and xenograft tumor model. METHODS: GFP or RFP was transduced into human DCIS cell line MCF10DCIS.com cells or preadipocytes using lentivirus. Cell sorter was used to separate pure, viable populations of GFP- or RFP-transduced cells. Cell viability and proliferation was assessed by crystal violet assays and cell migration and invasion capability was assayed by the transwell strategy. Gene and protein levels were measured by western blot, RT-PCR and immunostaining. Adipokines and cytokines were quantified using ELISA. Human tumor xenografts in a nude mice model were used. Ultrasound imaging of tumors was performed to evaluate the therapeutic potential of a IL-6 neutralizing antibody. RESULTS: In the co-culture system with the MCF10DCIS.com and preadipocytes, MCF10DCIS.com proliferation, migration and invasion were enhanced by preadipocytes. Preadipocytes exhibited in an increased IL-6 secretion and cancer-associated fibroblast markers expression, FSP1 and α-SMC in co-culture with MCF10DCIS.com or in MCF10DCIS.com conditioned media, whereas the adipocyte differentiation capacity was suppressed by co-culture with MCF10DCIS.com. A neutralizing antibody of IL-6 or IL-6R suppressed the promotion of MCF10DCIS.com proliferation and migration by co-culture with preadipocytes. In the xenograft tumor model, the tumor growth of MCF10DCIS.com was enhanced by the co-injection of preadipocytes, and the administration of IL-6 neutralizing antibodies resulted in potent effects on tumor inhibition. CONCLUSIONS: Our findings suggest that IL-6-mediated cross-talk between preadipocytes and breast DCIS cells can promote the progression of early stage breast cancer. Therefore, blocking IL-6 signaling might be a potential therapeutic strategy for breast DCIS characterized by pathological IL-6 overproduction.

Different Biological Action of Oleic Acid in ALDHhigh and ALDHlow Subpopulations Separated from Ductal Carcinoma In Situ of Breast Cancer.

The mechanisms underlying breast cancer progression of ductal carcinoma in situ (DCIS) associated with fatty acids are largely unknown. In the present study, we compared the action of oleic acid (OA) on two human DCIS cell lines, MCF10DCIS.COM (ER/PR/HER2-negative) and SUM225 (HER2 overexpressed). OA led to a significant increase in proliferation, migration, lipid accumulation and the expression of lipogenic proteins, such as SREBP-1, FAS and ACC-1, in MCF10DCIS.COM cells but not SUM225 cells. The ALDHhigh subpopulation analyzed by the ALDEFLUOR assay was approximately 39.2±5.3% of MCF10DCIS.COM cells but was small (3.11±0.9%) in SUM225 cells. We further investigated the different biological action of OA in the distinct ALDHlow and ALDHhigh subpopulations of MCF10DCIS.COM cells. OA led to an increase in the expression of ALDH1A1, ALDH1A2 and ALDH1A3 in MCF10DCIS.COM cells. SREBP-1 and ACC-1 were highly expressed in ALDHhigh cells relative to ALDHlow cells, whereas FAS was higher in ALDHlow cells. In the presence of OA, ALDHhigh cells were more likely to proliferate and migrate and displayed significantly high levels of SREBP-1 and FAS and strong phosphorylation of FAK and AKT relative to ALDHlow cells. This study suggests that OA could be a critical risk factor to promote the proliferation and migration of ALDHhigh cells in DCIS, leading to breast cancer progression.

In vivo Tracking of Dendritic Cell using MRI Reporter Gene, Ferritin.

The noninvasive imaging of dendritic cells (DCs) migrated into lymph nodes (LNs) can provide helpful information on designing DCs-based immunotherapeutic strategies. This study is to investigate the influence of transduction of human ferritin heavy chain (FTH) and green fluorescence protein (GFP) genes on inherent properties of DCs, and the feasibility of FTH as a magnetic resonance imaging (MRI) reporter gene to track DCs migration into LNs. FTH-DCs were established by the introduction of FTH and GFP genes into the DC cell line (DC2.4) using lentivirus. The changes in the rate of MRI signal decay (R2*) resulting from FTH transduction were analyzed in cell phantoms as well as popliteal LN of mice after subcutaneous injection of those cells into hind limb foot pad by using a multiple gradient echo sequence on a 9.4 T MR scanner. The transduction of FTH and GFP did not influence the proliferation and migration abilities of DCs. The expression of co-stimulatory molecules (CD40, CD80 and CD86) in FTH-DCs was similar to that of DCs. FTH-DCs exhibited increased iron storage capacity, and displayed a significantly higher transverse relaxation rate (R2*) as compared to DCs in phantom. LNs with FTH-DCs exhibited negative contrast, leading to a high R2* in both in vivo and ex vivo T2*-weighted images compared to DCs. On histological analysis FTH-DCs migrated to the subcapsular sinus and the T cell zone of LN, where they highly expressed CD25 to bind and stimulate T cells. Our study addresses the feasibility of FTH as an MRI reporter gene to track DCs migration into LNs without alteration of their inherent properties. This study suggests that FTH-based MRI could be a useful technique to longitudinally monitor DCs and evaluate the therapeutic efficacy of DC-based vaccines.

Ultrasound screening of contralateral breast after surgery for breast cancer.

OBJECTIVE: To determine whether supplemental screening ultrasound (US) to mammography could improve cancer detection rate of the contralateral breast in patients with a personal history of breast cancer and dense breasts. MATERIALS AND METHODS: During a one-year study period, 1314 screening patients with a personal history of breast cancer and dense breasts simultaneously underwent mammography and breast US. BI-RADS categories were given for mammography or US-detected lesions in the contralateral breast. The reference standard was histology and/or 1-year imaging follow-up, and the cancer rate according to BI-RADS categories and cancer detection rate and positive biopsy rate according to detection modality were analyzed. RESULTS: Of 1314 patients, 84 patients (6.4%) were categorized as category 3 with one interval cancer and one cancer which was upgraded to category 4A after 6-month follow-up US (2.5% cancer rate, 95% CIs 1.5-9.1%). Fifteen patients (1.1%) had category 4A or 4B lesions in the contralateral breast. Four lesions were detected on mammography (two lesions were also visible on US) and 11 lesions were detected on US and 5 cancers were confirmed (33.3%, 95% CIs 15.0-58.5%). Six patients (0.5%) had category 4C lesions, 2 detected on mammography and 4 on US and 4 cancers were confirmed (66.7%, 95% CIs 29.6-90.8%). No lesions were categorized as category 5 in the contralateral breast. Cancer detection rate by mammography was 3.3 per 1000 patients and that by US was 5.0 per 1000 patients, therefore overall cancer detection rate by mammography plus US was 8.3 per 1000 patients. Positive biopsy rate of mammography-detected lesions was 66.7% (4 of 6) and that of US-detected lesions was 40.0% (6 of 15). CONCLUSION: US can be helpful to detect mammographically occult breast cancer in the contralateral breast with high positive biopsy rate and low category 3 rate in patients with a previous history of breast cancer and dense breasts.

Automated breast ultrasound system (ABUS): reproducibility of mass localization, size measurement, and characterization on serial examinations.

BACKGROUND: Automated breast ultrasound (ABUS) is gaining popularity for breast cancer detection and diagnosis with its high reproducibility. Consistent recognition of breast lesions on serial exams is critical, and high reproducibility for lesion characterization is expected with ABUS, but not well reported. PURPOSE: To retrospectively evaluate the reproducibility of ABUS for mass localization, size measurement, and characterization. MATERIAL AND METHODS: Bilateral whole breast US images were obtained twice using a commercially available ABUS within a mean interval of 1.3 days. In total, 24 patients were imaged before biopsy or surgery. There were 24 breast cancers and nine benign diagnoses. Two breast radiologists reviewed every paired three-dimensional dataset with regard to lesion visibility, reproducibility of documented location (clockface location, distance from nipple, and lesion depth), size of the lesions, and similarity for lesion characteristics. Lesion similarity was classified as being identical, similar, or different by consensus reading using the SomoVu workstation. Intraclass correlation coefficients (ICCs) and the Bland-Altman method were used to determine the amount of agreement between assessments of lesion location and size. RESULTS: Among 33 breast lesions, 31 lesions were depicted in both serial examinations. ICCs for the displayed lesion location (clock face location, distance from nipple), and the individual size of detected lesions were 0.994, 0.926, and 0.980, indicating excellent reliability. However, the ICC for lesion depth from the skin was 0.342 showing low reliability. For lesion similarity, 16 cancers and five benign lesions were classified as being identical, and six cancers and two benign lesions were classified as being similar. Two benign lesions were assessed to have different lesion characteristics and final assessment categories. CONCLUSION: The ABUS provided reproducible images for mass localization, size measurement, and characterization, which may be useful for follow-up studies.

A population-based tissue probability map-driven level set method for fully automated mammographic density estimations.

PURPOSE: A major challenge when distinguishing glandular tissues on mammograms, especially for area-based estimations, lies in determining a boundary on a hazy transition zone from adipose to glandular tissues. This stems from the nature of mammography, which is a projection of superimposed tissues consisting of different structures. In this paper, the authors present a novel segmentation scheme which incorporates the learned prior knowledge of experts into a level set framework for fully automated mammographic density estimations. METHODS: The authors modeled the learned knowledge as a population-based tissue probability map (PTPM) that was designed to capture the classification of experts' visual systems. The PTPM was constructed using an image database of a selected population consisting of 297 cases. Three mammogram experts extracted regions for dense and fatty tissues on digital mammograms, which was an independent subset used to create a tissue probability map for each ROI based on its local statistics. This tissue class probability was taken as a prior in the Bayesian formulation and was incorporated into a level set framework as an additional term to control the evolution and followed the energy surface designed to reflect experts' knowledge as well as the regional statistics inside and outside of the evolving contour. RESULTS: A subset of 100 digital mammograms, which was not used in constructing the PTPM, was used to validate the performance. The energy was minimized when the initial contour reached the boundary of the dense and fatty tissues, as defined by experts. The correlation coefficient between mammographic density measurements made by experts and measurements by the proposed method was 0.93, while that with the conventional level set was 0.47. CONCLUSIONS: The proposed method showed a marked improvement over the conventional level set method in terms of accuracy and reliability. This result suggests that the proposed method successfully incorporated the learned knowledge of the experts' visual systems and has potential to be used as an automated and quantitative tool for estimations of mammographic breast density levels.

Practice guideline for the performance of breast ultrasound elastography.

Ultrasound (US) elastography is a valuable imaging technique for tissue characterization. Two main types of elastography, strain and shear-wave, are commonly used to image breast tissue. The use of elastography is expected to increase, particularly with the increased use of US for breast screening. Recently, the US elastographic features of breast masses have been incorporated into the 2nd edition of the Breast Imaging Reporting and Data System (BI-RADS) US lexicon as associated findings. This review suggests practical guidelines for breast US elastography in consensus with the Korean Breast Elastography Study Group, which was formed in August 2013 to perform a multicenter prospective study on the use of elastography for US breast screening. This article is focused on the role of elastography in combination with B-mode US for the evaluation of breast masses. Practical tips for adequate data acquisition and the interpretation of elastography results are also presented.

Association of tumour stiffness on sonoelastography with axillary nodal status in T1 breast carcinoma patients.

OBJECTIVES: To evaluate whether tumour stiffness on sonoelastography is associated with axillary nodal metastasis in T1 breast carcinoma patients. METHODS: Between May 2006 and December 2010, 200 consecutive women (mean age, 51.6; range, 27 - 81 years) who underwent B-mode ultrasound (US), sonoelastography, and curative surgery with axillary nodal evaluation for clinically node negative T1 breast carcinomas (mean invasive tumour size, 12.4; range, 3 - 20 mm at pathology) were identified. The association between the elasticity score of the tumour and histopathological axillary nodal status was evaluated using a logistic regression model after controlling for imaging and clinicopathological variables of the tumour. RESULTS: The overall incidence of axillary nodal metastasis was 15.5 % (31 of 200). Axillary nodal metastasis was significantly more frequent in tumours with elasticity scores ≥4 than in tumours with elasticity scores <4 (21.7 % vs. 4.2 %; P < 0.001). At multivariate analysis, an elasticity score ≥4 [odds ratio (OR), 6.95; P = 0.004], US size >10 mm (OR, 5.98; P = 0.022), and lymphovascular invasion (OR, 10.68; P < 0.001) of tumours were independently associated with axillary nodal metastasis. CONCLUSIONS: Tumour stiffness on sonoelastography is independently associated with axillary nodal metastasis in T1 breast carcinoma patients. KEY POINTS: • Prediction of axillary nodal status using imaging techniques is valuable. • High ultrasound elasticity scores of T1 tumours were associated with axillary metastasis • Node-positive T1 tumours frequently had elasticity scores 4 or 5. • Sonoelastography might render axillary surgery unnecessary in T1 breast carcinoma patients.

Stiffness of tumours measured by shear-wave elastography correlated with subtypes of breast cancer.

OBJECTIVE: To evaluate the correlation between stiffness values obtained by shear-wave elastography (SWE) and breast cancer subtypes. METHODS: This was an institutional review board-approved retrospective study with a waiver of informed consent. The stiffness of 337 invasive breast cancers in 337 women was evaluated by SWE and mean stiffness values (kPa) and qualitative colour scores (1-5) of tumours were obtained. The results were analysed according to BI-RADS category, tumour size, grade and tumour subtype (triple-negative [TN], human epidermal growth factor receptor 2 [HER2]-positive, and oestrogen receptor [ER]-positive) using a multiple linear regression analysis. RESULTS: The mean stiffness values and colour scores were: 146.8 kPa ± 57.0 and 4.1 ± 1.1; 165.8 kPa ± 48.5 and 4.6 ± 0.7 for TN tumours (n = 64), 160.3 kPa ± 56.2 and 4.3 ± 1.0 for HER2-positive tumours (n = 55) and 136.9 kPa ± 57.2 and 4.0 ± 1.1 for ER-positive tumours (n = 218; P < 0.0001). All three breast cancers classified as BI-RADS category 3 on B-mode ultrasound were TN subtype. A multiple linear regression analysis revealed that tumour size, histological grade and tumour subtype were independent factors that influenced the stiffness values. CONCLUSION: High stiffness values correlated with aggressive subtypes of breast cancer. KEY POINTS: • Shear-wave elastography is increasingly used to measure the stiffness of breast tumours. • Triple-negative and HER2-positive tumours showed greater stiffness than ER-positive tumours. • All breast cancers classified as BI-RADS 3 on B-mode ultrasound were triple-negative subtype. • Tumour size, histological grade and subtype were independent factors influencing SWE stiffness.

Ultrasonographic assessment of breast density.

Ultrasonographic (US) assessment of breast density has the potential to provide a nonionizing method. This study was to prospectively evaluate intermodality and interobserver agreements for assessment of breast density between US and mammography. Institutional review board approval was obtained. Forty-one women (mean 52.1 years; range 25-72 years) with variable breast density consented to participate. Eight radiologists blinded to mammographic information performed breast US for all participants and assessed each breast density using four categories based on the proportion of the breast occupied by the fibroglandular tissue. All participants underwent full-field digital mammography and mammographic density was independently assessed by eight radiologists 2 weeks after US using the breast imaging reporting and data system (BI-RADS) 4-category system. Intermodality agreements between US and mammographic assessments and interobserver agreements among radiologists were assessed using kappa statistics (к) and intraclass correlation coefficients (ICCs). There was substantial intermodality agreement between the US and mammographic assessments of breast density (к = 0.65 and ICC = 0.80), and 68 % (222/328) of the assessments had exact agreement. When categories were dichotomized into fatty (categories 1 and 2) and dense (categories 3 and 4), 86 % (282/328) of the assessments had exact agreement (к = 0.71). The interobserver agreement for the US assessments of breast density was substantial (average к = 0.63, ICC = 0.82) and not significantly different from that for the mammographic assessments (average к = 0.74, ICC = 0.85) (P = 0.701). US and mammography demonstrated substantial intermodality and interobserver agreement for assessment of breast density.

Survival outcomes of breast cancer patients who receive neoadjuvant chemotherapy: association with dynamic contrast-enhanced MR imaging with computer-aided evaluation.

PURPOSE: To retrospectively evaluate whether dynamic contrast agent-enhanced (DCE) magnetic resonance (MR) imaging parameters assessed by a computer-aided evaluation program are associated with recurrence-free and overall survival in breast cancer patients who received neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: This study was institutional review board approved and informed consent was waived. Between January 2007 and December 2009, 187 consecutive women (mean age, 46.6 years; range, 24-78 years) who had undergone NAC, DCE MR imaging before and after NAC, and surgery for invasive breast cancers (mean size, 5.0 cm; range, 2.0-14.8 cm on surgical histologic analysis) were identified. The tumor size, volume, and kinetic parameters (persistent, plateau, or washout components) were measured with a computer-aided evaluation program on DCE MR images before and after NAC, and their percentage changes were calculated. The Cox proportional hazards model was used to determine the association between DCE MR imaging parameters and recurrence-free survival and overall survival after controlling for clinical-pathologic variables. RESULTS: There were 50 events, including 38 recurrences (29 distant, six local, and three both) and 12 deaths, at a mean follow-up of 47.4 months. At multivariate analysis, a smaller reduction in tumor volume (recurrence-free survival hazard ratio, 5.75; 95% confidence interval: 1.14, 8.64; and overall survival hazard ratio, 2.12; 95% confidence interval: 1.08, 5.69) and a smaller reduction in washout component (recurrence-free survival hazard ratio, 1.15; 95% CI: 1.06, 1.55; and overall survival hazard ratio, 1.26; 95% confidence interval: 1.03, 1.52) after NAC were independent significant variables for worse recurrence-free survival and overall survival. CONCLUSION: Smaller reduction in tumor volume and a smaller reduction in washout component on DCE MR images assessed with computer-aided evaluation after NAC were independent parameters of worse recurrence-free survival and overall survival in breast cancer patients who received NAC.

Intraductal mass on breast ultrasound: final outcomes and predictors of malignancy.

OBJECTIVE: The purpose of this study was to retrospectively investigate the final outcomes of intraductal masses on breast ultrasound and determine the clinical and radiologic variables associated with malignancy. MATERIALS AND METHODS: A database search (2006-2008) was performed to find patients who had an intraductal mass on breast ultrasound. Histopathologic or ultrasound follow-up (> 24 months) data were available from 147 women (mean age, 49.8 years) with 163 intraductal masses. Clinical and radiologic variables (age, symptom, personal and family history, lesion size, and distance from the nipple) and pathologic results were collected. Ultrasound features of the intraductal masses were reviewed by two radiologists in consensus and classified into three morphologic types: mass incompletely filling the duct, mass completely filling the duct, and mass extending outside the duct. Involvement of a branch duct was also analyzed. Associations between variables and final outcomes were analyzed using chi-square tests and Student t tests. RESULTS: Thirteen (8%) of the 163 intraductal masses were malignant (10 ductal carcinomas in situ and three invasive ductal carcinomas). Malignancy was significantly associated with symptoms (p = 0.008) and personal history of breast cancer (p < 0.007). Malignant intraductal masses were larger than benign intraductal masses (1.4 cm vs 0.9 cm, p = 0.02). Malignant intraductal masses tended to fill the duct more completely or extend outside the duct (p < 0.001), and they more frequently involved the branch duct (p < 0.001) than did the benign intraductal masses. CONCLUSION: Our study showed that 8% of intraductal masses are malignant. Symptoms, personal history, lesion size, and ultrasound features can be possible predictors of malignancy.

Differentiation of benign from malignant solid breast masses: comparison of two-dimensional and three-dimensional shear-wave elastography.

OBJECTIVES: To prospectively compare the diagnostic performances of two-dimensional (2D) and three-dimensional (3D) shear-wave elastography (SWE) for differentiating benign from malignant breast masses. METHODS: B-mode ultrasound and SWE were performed for 134 consecutive women with 144 breast masses before biopsy. Quantitative elasticity values (maximum and mean elasticity in the stiffest portion of mass, Emax and Emean; lesion-to-fat elasticity ratio, Erat) were measured with both 2D and 3D SWE. The area under the receiver operating characteristic curve (AUC), sensitivity and specificity of B-mode, 2D, 3D SWE and combined data of B-mode and SWE were compared. RESULTS: Sixty-seven of the 144 breast masses (47 %) were malignant. Overall, higher elasticity values of 3D SWE than 2D SWE were noted for both benign and malignant masses. The AUC for 2D and 3D SWE were not significantly different: Emean, 0.938 vs 0.928; Emax, 0.939 vs 0.930; Erat, 0.907 vs 0.871. Either 2D or 3D SWE significantly improved the specificity of B-mode ultrasound from 29.9 % (23 of 77) up to 71.4 % (55 of 77) and 63.6 % (49 of 77) without a significant change in sensitivity. CONCLUSION: Two-dimensional and 3D SWE performed equally in distinguishing benign from malignant masses and both techniques improved the specificity of B-mode ultrasound.

Outcome of breast lesions detected at screening ultrasonography.

OBJECTIVE: To assess the final outcome of breast lesions detected during screening ultrasonography (US) and categorized by BI-RADS final assessment. MATERIALS AND METHODS: During a 1-year period, 3817 consecutive asymptomatic women with negative findings at both clinical breast examinations and mammography underwent bilateral whole breast US and BI-RADS categories were provided for US-detected breast lesions. The reference standard was a combination of histology and US follow-up (≥12 months), and the final outcomes of 1192 US-detected lesions were analyzed. RESULTS: Of 904 category 2 lesions, 890 remained stable for 12-60 months. Biopsies of 14 lesions revealed no malignancies (NPV=100%). Of 247 category 3 lesions, 232 remained stable for 12-60 months. Biopsies of 15 lesions revealed 2 malignancies, which were diagnosed within 6 months of the index examination and were node negative (NPV=99.2%). Of 41 category 4 lesions, biopsies of 38 lesions revealed 5 malignancies (PPV=12.2%), and 3 remained stable for 37-51 months. No US-detected lesion was classified as category 5. CONCLUSION: The rates of malignancy for US-detected BI-RADS categories 2, 3, and 4 lesions were 0%, 0.8%, and 12.2%, respectively. The final assessment of US BI-RADS categorization showed it to be an appropriate predictor of malignancy for screening US-detected breast lesions.

Computer-aided detection system performance on current and previous digital mammograms in patients with contralateral metachronous breast cancer.

BACKGROUND: The computer-aided detection (CAD) system is widely used for screening mammography. The performance of the CAD system for contralateral breast cancer has not been reported for women with a history of breast cancer. PURPOSE: To retrospectively evaluate the performance of a CAD system on current and previous mammograms in patients with contralateral metachronous breast cancer. MATERIAL AND METHODS: During a 3-year period, 4945 postoperative patients had follow-up examinations, from whom we selected 55 women with contralateral breast cancers. Among them, 38 had visible malignant signs on the current mammograms. We analyzed the sensitivity and false-positive marks of the system on the current and previous mammograms according to lesion type and breast density. RESULTS: The total visible lesion components on the current mammograms included 27 masses and 14 calcifications in 38 patients. The case-based sensitivity for all lesion types was 63.2% (24/38) with false-positive marks of 0.71 per patient. The lesion-based sensitivity for masses and calcifications was 59.3% (16/27) and 71.4% (10/14), respectively. The lesion-based sensitivity for masses in fatty and dense breasts was 68.8% (11/16) and 45.5% (5/11), respectively. The lesion-based sensitivity for calcifications in fatty and dense breasts was 100.0% (3/3) and 63.6% (7/11), respectively. The total visible lesion components on the previous mammograms included 13 masses and three calcifications in 16 patients, and the sensitivity for all lesion types was 31.3% (5/16) with false-positive marks of 0.81 per patient. On these mammograms, the sensitivity for masses and calcifications was 30.8% (4/13) and 33.3% (1/3), respectively. The sensitivity in fatty and dense breasts was 28.6% (2/7) and 33.3% (3/9), respectively. CONCLUSION: In the women with a history of breast cancer, the sensitivity of the CAD system in visible contralateral breast cancer was lower than in most previous reports using the same CAD system probably due to the relatively small size, subtlety of the lesion findings, and dense parenchymal pattern.

Evaluation of tumor extent in breast cancer patients using real-time MR navigated ultrasound: preliminary study.

OBJECTIVES: To evaluate the accuracy of real-time MR navigated ultrasound (MRnav US) for tumor extent measurements in breast cancer and to investigate variables influencing the accuracy of MRnav US in comparison with US alone. METHODS: Fifty-three patients with 60 malignancies underwent preoperative breast MRI and US with or without MRI navigation. Maximum lesion sizes based on MRnav US and US alone were measured, and their relationship with the pathology was analyzed considering the differences in the clinicopathologic variables of the patients. RESULTS: Among 60 breast cancers, mean lesion size at initial breast US without MRI navigation and at MRI-navigated US was 19 mm and 24 mm, respectively, compared with 28 mm on the histopathology. Overall, the tumor size estimated with MRnav US was more strongly correlated with the histologic tumor size than with US alone. Accurate measurements by MRnav US were significantly more frequent in the lesions that were presented as a mass type on MRI. In addition, the accurate measurement of mass extent was improved with MRnav US in patients who had non-mass type lesions on MRI and who had undergone neoadjuvant systemic chemotherapy when compared with US alone. CONCLUSION: MRnav US was more accurate for tumor extent estimation than US alone, and specific clinicopathologic variables can affect the accuracy of MRnav US.

Magnetic resonance enhancement pattern and diagnostic accuracy of gadofluorine M in a rabbit VX2 tumor model: Comparison with gadopentetate dimeglumine.

OBJECTIVE: The purpose of this study was to evaluate the enhancement pattern and the diagnostic accuracy of gadofluorine M in comparison with gadopentetate dimeglumine in a rabbit VX2 tumor model. MATERIALS AND METHODS: Thirteen rabbits with experimentally induced VX2 carcinomas in the thighs underwent sequential T1-weighted enhancement MR imaging using a 3.0T MR imager, first with gadopentetate dimeglumine, and then 24 (n=4) or 4h (n=9) later with gadofluorine M. In 4 rabbits with 13 tumors, the time-percentage enhancement (PE; i.e., percentage of signal intensity increase) curve was obtained for up to 24h for each contrast agent. In 9 rabbits with 49 tumors (random numbers of VX2 tumors were inoculated at random sites in the thigh), 3 readers unaware of the histopathologic results interpreted the MR images and determined the number and conspicuity level of the detected tumors. The reference standard was the histopathology of the specimen. RESULTS: The time-to-peak PE for gadopentetate dimeglumine was 1min and gadopentetate dimeglumine showed a rapid washout pattern. The time-to-peak PE for gadofluorine M was 30min and gadofluorine M showed a plateau enhancement pattern for up to 24h. The peak PE of gadofluorine M was approximately twice that of the same dose of gadopentetate dimeglumine (108.2±14.8 vs. 51.5±24.0). The sensitivities for detecting VX2 tumors by 3 readers were 89.8% (44/49), 85.7% (42/49), and 95.9% (47/49) for gadopentetate dimeglumine-enhanced MR imaging, and 87.8% (43/49), 89.8% (44/49), and 89.8% (44/49) for gadofluorine M-enhanced MR imaging. No significant differences in the sensitivities existed between the two contrast agents for any reader. However, the conspicuity level of tumors was superior with gadofluorine M-enhanced MR imaging for two readers and similar for the other reader. CONCLUSION: Gadofluorine M showed strong and plateau enhancement of tumors for up to 24h. In the reader study, gadofluorine M showed better conspicuity for VX2 tumors than gadopentetate dimeglumine, but had a similar sensitivity.

Detection of prostaglandin E2-induced dendritic cell migration into the lymph nodes of mice using a 1.5 T clinical MR scanner.

The control of dendritic cell (DC) migration into lymph nodes (LNs) is important for the development of more effective DC-based immunotherapies. This study was undertaken to evaluate, dynamically and noninvasively, prostaglandin E2 (PGE2)-enhanced migration of DCs using a 1.5 T clinical MR scanner. DC2.4 cells were labeled with superparamagnetic iron oxide (SPIO), a clinically approved MRI contrast agent. DCs were stimulated with tumor necrosis factor-α and interferon-γ in the presence or absence of PGE2. Before and after subcutaneous injection of labeled DCs into the hind leg footpads of mice, MRI detailing the extent of DC migration into popliteal LNs was performed using a 1.5 T clinical MR scanner. SPIO labeling did not influence the viability, endocytic activity, migratory ability and/or co-stimulatory molecule expression of DCs. PGE2 enhanced significantly chemokine receptor-7 expression and the migration of DCs (p < 0.05). After subcutaneous injection of DCs, there were decreases in MR signal intensity in popliteal LNs at 24 h post-injection; in PGE2-treated cells, the MR signal intensity was significantly lower (decrease of 86.6 ± 2.5%) than in PGE2-untreated cells (decrease of 70.0 ± 4.2%) (p < 0.05). Histological analyses with the conventionally used Prussian blue stain demonstrated that the PGE2-treated DCs migrated more deeply into the center of LNs. PGE2-enhanced migration of SPIO-labeled DCs into LNs can be detected using a 1.5 T clinical MR scanner. Our results suggest that in vivo MRI of DC migration is a useful imaging method to predict DC therapy with a high rate of efficacy and to improve DC-based immunotherapy, thereby reducing costs compared with current treatments in clinical trials.

Clinical application of shear wave elastography (SWE) in the diagnosis of benign and malignant breast diseases.

Shear wave elastography (SWE) is an emerging technique which can obtain quantitative elasticity values in breast disease. We therefore evaluated the diagnostic performance of SWE for the differentiation of breast masses compared with conventional ultrasound (US). Conventional US and SWE were performed by three experienced radiologists for 158 consecutive women who had been scheduled for US-guided core biopsy or surgical excision in 182 breast masses (89 malignancies and 93 benign; mean size, 1.76 cm). For each lesion, quantitative elasticity was measured in terms of the Young's modulus (in kilopascals, kPa) with SWE, and BI-RADS final categories were assessed with conventional US. The mean elasticity values were significantly higher in malignant masses (153.3 kPa ± 58.1) than in benign masses (46.1 kPa ± 42.9), (P < 0.0001). The average mean elasticity values of invasive ductal (157.5 ± 57.07) or invasive lobular (169.5 ± 61.06) carcinomas were higher than those of ductal carcinoma in situ (117.8 kPa ± 54.72). The average mean value was 49.58 ± 43.51 for fibroadenoma, 35.3 ± 31.2 for fibrocystic changes, 69.5 ± 63.2 for intraductal papilloma, and 149.5 ± 132.4 for adenosis or stromal fibrosis. The optimal cut-off value, yielding the maximal sum of sensitivity and specificity, was 80.17 kPa, and the sensitivity and specificity of SWE were 88.8% (79 of 89) and 84.9% (79 of 93). The area under the ROC curve (Az value) was 0.898 for conventional US, 0.932 for SWE, and 0.982 for combined data. In conclusion, there were significant differences in the elasticity values of benign and malignant masses as well as invasive and intraductal cancers with SWE. Our results suggest that SWE has the potential to aid in the differentiation of benign and malignant breast lesions.