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Whole-body MRI combined with a semiautomated hierarchical multispectral image analysis technique was evaluated as a method for detecting viable tumor tissue in a murine model of metastatic breast cancer (4T1 cell line). Whole-body apparent diffusion coefficient, T(2), and proton density maps were acquired in this study. The viable tumor tissue segmentation included three-stage k-means clustering of the parametric maps, morphologic operations, application of a size threshold, and reader discrimination of the segmented objects. The segmentation results were validated by histologic evaluation, and the detection accuracy of the technique was evaluated at three size thresholds (15, 100, and 500 voxels). The accuracy was 88.9% for a 500-voxel size threshold, and the area under receiver operating characteristic curve was 0.84. The regions of segmented viable tumor tissue within the primary tumors were found mostly on the periphery of the tumors in agreement with the histologic findings. The presented technique was found capable of detecting metastases and segmenting the viable tumor from necrotic regions within tumors found in this model. It offers a noninvasive, whole-body, viable tumor tissue detection method for preclinical and potentially clinical applications such as tumor screening and evaluating therapeutic efficacy.

The recent discovery of IL-17-producing CD4(+) Th subset significantly revised the Th1/Th2 dichotomy model proposed by Mosmann and Coffman almost two decades ago. Th17 cells are involved in the pathogenesis of many human autoimmune diseases. Th17 cells, their developmental pathways and their effector functions, therefore, provide novel therapeutic targets.

The role of angiogenesis during mechanically induced bone formation is incompletely understood. The relationship between the mechanical environment, angiogenesis, and bone formation was determined in a rat distraction osteogenesis model. Disruption of either the mechanical environment or endothelial cell proliferation blocked angiogenesis and bone formation. This study further defines the role of the mechanical environment and angiogenesis during distraction osteogenesis. Introduction: Whereas successful fracture repair requires a coordinated and complex transcriptional program that integrates mechanotransductive signaling, angiogenesis, and osteogenesis, the interdependence of these processes is not fully understood. In this study, we use a system of bony regeneration known as mandibular distraction osteogenesis (DO) in which a controlled mechanical stimulus promotes bone induction after an osteotomy and gradual separation of the osteotomy edges to examine the relationship between the mechanical environment, angiogenesis, and osteogenesis. Materials and Methods: Adult Sprague-Dawley rats were treated with gradual distraction, gradual distraction plus the angiogenic inhibitor TNP-470, or acute distraction (a model of failed bony regeneration). Animals were killed at the end of distraction (day 13) or at the end of consolidation (day 41) and examined with μCT, histology, and immunohistochemistry for angiogenesis and bone formation (n = 4 per time-point per group). An additional group of animals (n = 6 per time-point per group) was processed for microarray analysis at days 5, 9, 13, 21, and 41. Results and Conclusions: Either TNP-470 administration or disruption of the mechanical environment prevented normal osteogenesis and resulted in a fibrous nonunion. Subsequent analysis of the regenerate showed an absence of angiogenesis by gross histology and immunohistochemical localization of platelet endothelial cell adhesion molecule in the groups that failed to heal. Microarray analysis revealed distinct patterns of expression of genes associated with osteogenesis, angiogenesis, and hypoxia in each of the three groups. Our findings confirm the interdependence of the mechanical environment, angiogenesis, and osteogenesis during DO, and suggest that induction of proangiogenic genes and the proper mechanical environment are both necessary to support new vasculature for bone induction in DO.

The cover picture features the hallmark set of scales representing the balancing of opinions in our Viewpoint series, with the schematic cell indicating the focus of this issue's series, i.e. Th17 cells/IL-17. The schematic is taken from the article by Ouyang et al. (pp. 670–675) in which the therapeutic potential of drugs targeting the Th17 pathway for the treatment of autoimmune disease is considered.