Surface deformation-based analysis was used to assess local shape variations in the hippocampi and caudate nuclei of children with fetal alcohol spectrum disorders. High-resolution structural magnetic resonance imaging images were acquired for 31 children (19 controls and 12 children diagnosed with fetal alcohol syndrome/partial FAS). Hippocampi and caudate nuclei were manually segmented, and surface meshes were reconstructed. An iterative closest point algorithm was used to register the template of one control subject to all other shapes in order to capture the true geometry of the shape with a fixed number of landmark points. A point distribution model was used to quantify the shape variations in terms of a change in co-ordinate positions. Using the localized Hotelling T(2) method, regions of significant shape variations between the control and exposed subjects were identified and mapped onto the mean shapes. Binary masks of hippocampi and caudate nuclei were generated from the segmented volumes of each brain. These were used to compute the volumes and for further statistical analysis. The Mann-Whitney test was performed to predict volume differences between the groups. Although the exposed and control subjects did not differ significantly in their volumes, the shape analysis showed the hippocampus to be more deformed at the head and tail regions in the alcohol-exposed children. Between-group differences in caudate nucleus morphology were dispersed across the tail and head regions. Correlation analysis showed associations between the degree of compression and the level of alcohol exposure. These findings demonstrate that shape analysis using three-dimensional surface measures is sensitive to fetal alcohol exposure and provides additional information than volumetric measures alone.

A majority of breast cancers (BC) are age-related and we seek to determine what cellular and molecular changes occur in breast tissue with age that make women more susceptible to cancer initiation. Immune-epithelial cell interactions are important during mammary gland development and the immune system plays an important role in BC progression. The composition of human immune cell populations is known to change in peripheral blood with age and in breast tissue during BC progression. Less is known about changes in immune populations in normal breast tissue and how their interactions with mammary epithelia change with age. We quantified densities of T cells, B cells, and macrophage subsets in pathologically normal breast tissue from 122 different women who ranged in age from 24 to 74 years old. Donor-matched peripheral blood from a subset of 20 donors was analyzed by flow cytometry. Tissue immune cell densities and localizations relative to the epithelium were quantified in situ with machine learning-based image analyses of multiplex immunohistochemistry-stained tissue sections. In situ results were corroborated with flow cytometry analyses of peri-epithelial immune cells from primary breast tissue preparations and transcriptome analyses of public data from bulk tissue reduction mammoplasties. Proportions of immune cell subsets in breast tissue and donor-matched peripheral blood were not correlated. Density (cells/mm2) of T and B lymphocytes in situ decreased with age. T cells and macrophages preferentially localized near or within epithelial bilayers, rather than the intralobular stroma. M2 macrophage density was higher than M1 macrophage density and this difference was due to higher density of M2 in the intralobular stroma. Transcriptional signature analyses suggested age-dependent decline in adaptive immune cell populations and functions and increased innate immune cell activity. T cells and macrophages are so intimately associated with the epithelia that they are embedded within the bilayer, suggesting an important role for immune-epithelial cell interactions. Age-associated decreased T cell density in peri-epithelial regions, and increased M2 macrophage density in intralobular stroma suggests the emergence of a tissue microenvironment that is simultaneously immune-senescent and immunosuppressive with age.

Background Consistent localization of cerebellar cortex in a standard coordinate system is important for functional studies and detection of anatomical alterations in studies of morphometry. To date, no pediatric cerebellar atlas is available. New method The probabilistic Cape Town Pediatric Cerebellar Atlas (CAPCA18) was constructed in the age-appropriate National Institute of Health Pediatric Database asymmetric template space using manual tracings of 16 cerebellar compartments in 18 healthy children (9–13 years) from Cape Town, South Africa. The individual atlases of the training subjects were also used to implement multi atlas label fusion using multi atlas majority voting (MAMV) and multi atlas generative model (MAGM) approaches. Segmentation accuracy in 14 test subjects was compared for each method to ‘gold standard’ manual tracings. Results Spatial overlap between manual tracings and CAPCA18 automated segmentation was 73% or higher for all lobules in both hemispheres, except VIIb and X. Automated segmentation using MAGM yielded the best segmentation accuracy over all lobules (mean Dice Similarity Coefficient 0.76; range 0.55–0.91). Comparison with existing methods In all lobules, spatial overlap of CAPCA18 segmentations with manual tracings was similar or higher than those obtained with SUIT (spatially unbiased infra-tentorial template), providing additional evidence of the benefits of an age appropriate atlas. MAGM segmentation accuracy was comparable to values reported recently by Park et al. (2014) in adults (across all lobules mean DSC = 0.73, range 0.40–0.89). Conclusions CAPCA18 and the associated multi atlases of the training subjects yield improved segmentation of cerebellar structures in children.

<p>High CDK7 mRNA expression is associated with poor prognosis in TNBC transcriptomic datasets</p>

<p>Supplementary Figure Legends</p>