Enrichment methods to detect bone marrow micrometastases in breast carcinoma patients: clinical relevance

INTRODUCTION: Improving technologies for the detection and purification of bone marrow (BM) micrometastatic cells in breast cancer patients should lead to earlier prognosis of the risk of relapse and should make it possible to design more appropriate therapies. The technique used has to overcome the challenges resulting from the small number of target cells (one per million hematopoietic cells) and the heterogeneous expression of micrometastatic cell markers. In the present study, we have assessed the clinical relevance of current methods aimed at detecting rare disseminated carcinoma cells. METHODS: BM aspirates from 32 carcinoma patients were screened for the presence of micrometastatic cells positive for epithelial cell adhesion molecule and positive for cytokeratins, using optimized immunodetection methods. A comparison with data obtained for 46 control BM aspirates and a correlation with the clinical status of patients were performed. RESULTS: We developed a sensitive and efficient immunomagnetic protocol for the enrichment of BM micrometastases. This method was used to divide 32 breast carcinoma patients into three categories according to their epithelial cell adhesion molecule status. These categories were highly correlated with the recently revised American Joint Committee on Cancer staging system for breast cancer, demonstrating the clinical relevance of this simple and reliable immunomagnetic technique. We also evaluated immunocytochemical detection of cytokeratin-positive cells and cytomorphological parameters. Immunocytochemistry-based methods for the detection of BM micrometastases did not provide any information about the clinical status of patients, but helped to refine the immunomagnetic data by confirming the presence of micrometastases in some cases. We also tested a new density gradient centrifugation system, able to enrich the tumor fraction of BM specimens by twofold to threefold as compared with standard Ficoll methods. CONCLUSION: These improved methods for the detection of micrometastatic cells in patient BM should help clinicians to predict the clinical status of breast cancer patients at the time of surgery or treatment

Validation of Equilibrated Warping-image registration with mechanical regularization-on 3D ultrasound images

International audienceImage registration plays a very important role in quantifying cardiac motion from medical images, which has significant implications in the diagnosis of cardiac diseases and the development of personalized cardiac computational models. Many approaches have been proposed to solve the image registration problem; however, due to the intrinsic ill-posedness of the image registration problem, all these registration techniques , regardless of their variabilities, require some sort of regularization. An efficient regularization approach was recently proposed based on the equilibrium gap principle, named equilibrated warping. Compared to previous work, it has been formulated at the continuous level within the finite strain hyperelasticity framework and solved using the finite element method. Regularizing the image registration problem using this principle is advantageous as it produces a realistic solution that is close to that of an hyperelastic body in equilibrium with arbitrary boundary tractions, but no body load. The equilibrated warping method has already been extensively validated on both tagged and untagged magnetic resonance images. In this paper, we provide full validation of the method on 3D ultrasound images, based on the 2011 MICCAI Motion Tracking Challenge data