The Value of Quality-Assured Magnetic Resonance Imaging of the Breast for the Early Detection of Breast Cancer in Asymptomatic Women.

PURPOSE: The aim of this study was to evaluate the exclusive performance of quality-assured high-resolution breast magnetic resonance imaging (MRI) for early detection of breast cancer in a population of asymptomatic women. MATERIALS AND METHODS: A total of 1189 MRI examinations performed in 789 asymptomatic women (mean age, 51.1 years) were evaluated. All examinations were performed using open bilateral surface coil, dedicated compression device, and high spatial resolution (matrix, 512 × 512). Digital mammography was available for all participants. Assessment included density types, artifact level, and Breast Imaging Reporting and Data System classification. Evaluation was performed by 2 readers. In addition, a computer-assisted diagnosis (CAD) system was used for image assessment. RESULTS: Breast MRI showed density types I and II in 87.6% and artifacts categories III and IV in 3.1%. Study included 32 carcinomas (8 ductal carcinoma in situ, 24 invasive tumors). Both readers detected 29 of 32 correctly (sensitivity 90.6%). The variation between the readers was low (reader 1: specificity, 94.4% and positive predictive value (PPV), 25.7%; reader 2: specificity, 97.6% and PPV, 34.1%). Sensitivity of CAD was 62.5% (specificity, 84.4%; PPV, 5.2%). Digital mammography detected 13 of 32 carcinomas (sensitivity, 56.3%; specificity, 98.4%; PPV, 32.1%). CONCLUSIONS: The exclusive use of quality-assured breast MRI allows the early detection of breast cancer with a high sensitivity and specificity. The CAD analysis of MRI does not give additional information but shows results comparable with digital mammography.

Short first-pass MRI of the breast.

To reduce examination time and costs, a new concept for MRI of the breast is presented. This short first-pass MRI takes 4-5 minutes and could be applied to approximately three-quarters of all women.

Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells.

Normal bone marrow (BM) contains T cells whose function and origin are poorly understood. We observed that CD8+ T cells in BM consist chiefly of CCR7+ L-selectin+ central memory cells (TCMs). Adoptively transferred TCMs accumulated more efficiently in the BM than naive and effector T cells. Intravital microscopy (IVM) showed that TCMs roll efficiently in BM microvessels via L-, P-, and E-selectin, whereas firm arrest required the VCAM-1/alpha4beta1 pathway. alpha4beta1 integrin activation did not depend on pertussis toxin (PTX)-sensitive Galphai proteins but was reduced by anti-CXCL12. In contrast, TCM diapedesis did not require CXCL12 but was blocked by PTX. After extravasation, TCMs displayed agile movement within BM cavities, remained viable, and mounted potent antigen-specific recall responses for at least two months. Thus, the BM functions as a major reservoir for TCMs by providing specific recruitment signals that act in sequence to mediate the constitutive recruitment of TCMs from the blood.

Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis.

Invasive tumor dissemination in vitro and in vivo involves the proteolytic degradation of ECM barriers. This process, however, is only incompletely attenuated by protease inhibitor-based treatment, suggesting the existence of migratory compensation strategies. In three-dimensional collagen matrices, spindle-shaped proteolytically potent HT-1080 fibrosarcoma and MDA-MB-231 carcinoma cells exhibited a constitutive mesenchymal-type movement including the coclustering of beta 1 integrins and MT1-matrix metalloproteinase (MMP) at fiber bindings sites and the generation of tube-like proteolytic degradation tracks. Near-total inhibition of MMPs, serine proteases, cathepsins, and other proteases, however, induced a conversion toward spherical morphology at near undiminished migration rates. Sustained protease-independent migration resulted from a flexible amoeba-like shape change, i.e., propulsive squeezing through preexisting matrix gaps and formation of constriction rings in the absence of matrix degradation, concomitant loss of clustered beta 1 integrins and MT1-MMP from fiber binding sites, and a diffuse cortical distribution of the actin cytoskeleton. Acquisition of protease-independent amoeboid dissemination was confirmed for HT-1080 cells injected into the mouse dermis monitored by intravital multiphoton microscopy. In conclusion, the transition from proteolytic mesenchymal toward nonproteolytic amoeboid movement highlights a supramolecular plasticity mechanism in cell migration and further represents a putative escape mechanism in tumor cell dissemination after abrogation of pericellular proteolysis.