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We aim to develop a deep-learning-based method for automatic proximal femur segmentation in quantitative computed tomography (QCT) images. We proposed a spatial transformation V-Net (ST-V-Net), which contains a V-Net and a spatial transform network (STN) to extract the proximal femur from QCT images. The STN incorporates a shape prior into the segmentation network as a constraint and guidance for model training, which improves model performance and accelerates model convergence. Meanwhile, a multi-stage training strategy is adopted to fine-tune the weights of the ST-V-Net. We performed experiments using a QCT dataset which included 397 QCT subjects. During the experiments for the entire cohort and then for male and female subjects separately, 90% of the subjects were used in ten-fold stratified cross-validation for training and the rest of the subjects were used to evaluate the performance of models. In the entire cohort, the proposed model achieved a Dice similarity coefficient (DSC) of 0.9888, a sensitivity of 0.9966 and a specificity of 0.9988. Compared with V-Net, the Hausdorff distance was reduced from 9.144 to 5.917 mm, and the average surface distance was reduced from 0.012 to 0.009 mm using the proposed ST-V-Net. Quantitative evaluation demonstrated excellent performance of the proposed ST-V-Net for automatic proximal femur segmentation in QCT images. In addition, the proposed ST-V-Net sheds light on incorporating shape prior to segmentation to further improve the model performance.

Concerns raised at a 2010 Bone Summit held for National Aeronautics and Space Administration Johnson Space Center led experts in finite element (FE) modeling for hip fracture prediction to propose including hip load capacity in the standards for astronaut skeletal health. The current standards for bone are based upon areal bone mineral density (aBMD) measurements by dual X-ray absorptiometry (DXA) and an adaptation of aBMD cut-points for fragility fractures. Task Group members recommended (i) a minimum permissible outcome limit (POL) for post-mission hip bone load capacity, (ii) use of FE hip load capacity to further screen applicants to astronaut corps, (iii) a minimum pre-flight standard for a second long-duration mission, and (iv) a method for assessing which post-mission physical activities might increase an astronaut's risk for fracture after return. QCT-FE models of eight astronaut were analyzed using nonlinear single-limb stance (NLS) and posterolateral fall (NLF) loading configurations. QCT data from the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort and the Rochester Epidemiology Project were analyzed using identical modeling procedures. The 75th percentile of NLS hip load capacity for fractured elderly males of the AGES cohort (9537N) was selected as a post-mission POL. The NLF model, in combination with a Probabilistic Risk Assessment tool, was used to assess the likelihood of exceeding the hip load capacity during post-flight activities. There was no recommendation to replace the current DXA-based standards. However, FE estimation of hip load capacity appeared more meaningful for younger, physically active astronauts and was recommended to supplement aBMD cut-points.

Fractures of the proximal femur are the most devastating outcome of osteoporosis. It is generally understood that age-related changes in hip structure confer increased risk, but there have been few explicit comparisons of such changes in healthy subjects to those with hip fracture. In this study, we used quantitative computed tomography and tensor-based morphometry (TBM) to identify three-dimensional internal structural patterns of the proximal femur associated with age and with incident hip fracture. A population-based cohort of 349 women representing a broad age range (21-97years) was included in this study, along with a cohort of 222 older women (mean age 79±7years) with (n=74) and without (n=148) incident hip fracture. Images were spatially normalized to a standardized space, and age- and fracture-specific morphometric features were identified based on statistical maps of shape features described as local changes of bone volume. Morphometric features were visualized as maps of local contractions and expansions, and significance was displayed as Student's t-test statistical maps. Significant age-related changes included local expansions of regions low in volumetric bone mineral density (vBMD) and local contractions of regions high in vBMD. Some significant fracture-related features resembled an accentuated aging process, including local expansion of the superior aspect of the trabecular bone compartment in the femoral neck, with contraction of the adjoining cortical bone. However, other features were observed only in the comparison of hip fracture subjects with age-matched controls including focal contractions of the cortical bone at the superior aspect of the femoral neck, the lateral cortical bone just inferior to the greater trochanter, and the anterior intertrochanteric region. Results of this study support the idea that the spatial distribution of morphometric features is relevant to age-related changes in bone and independent to fracture risk. In women, the identification by TBM of fracture-specific morphometric alterations of the proximal femur, in conjunction with vBMD and clinical risk factors, may improve hip fracture prediction.

Hip fracture risk rises exponentially with age, but there is little knowledge about how fracture-related alterations in hip structure differ from those of aging. We employed computed tomography (CT) imaging to visualize the three-dimensional (3D) spatial distribution of bone mineral density (BMD) in the hip in relation to age and incident hip fracture. We used intersubject image registration to integrate 3D hip CT images into a statistical atlas comprising women aged 21 to 97 years (n = 349) and a group of women with (n = 74) and without (n = 148) incident hip fracture 4 to 7 years after their imaging session. Voxel-based morphometry was used to generate Student's t test statistical maps from the atlas, which indicated regions that were significantly associated with age or with incident hip fracture. Scaling factors derived from intersubject image registration were employed as measures of bone size. BMD comparisons of young, middle-aged, and older American women showed preservation of load-bearing cortical and trabecular structures with aging, whereas extensive bone loss was observed in other trabecular and cortical regions. In contrast, comparisons of older Icelandic fracture women with age-matched controls showed that hip fracture was associated with a global cortical bone deficit, including both the superior cortical margin and the load-bearing inferior cortex. Bone size comparisons showed larger dimensions in older compared to younger American women and in older Icelandic fracture women compared to controls. The results indicate that older Icelandic women who sustain incident hip fracture have a structural phenotype that cannot be described as an accelerated pattern of normal age-related loss. The fracture-related cortical deficit noted in this study may provide a biomarker of increased hip fracture risk that may be translatable to dual-energy X-ray absorptiometry (DXA) and other clinical images.

Because they are not reliably discriminated by areal bone mineral density (aBMD) measurements, it is unclear whether minimal vertebral deformities represent early osteoporotic fractures. To address this, we compared 90 postmenopausal women with no deformity (controls) with 142 women with one or more semiquantitative grade 1 (mild) deformities and 51 women with any grade 2-3 (moderate/severe) deformities. aBMD was measured by dual-energy X-ray absorptiometry (DXA), lumbar spine volumetric bone mineral density (vBMD) and geometry by quantitative computed tomography (QCT), bone microstructure by high-resolution peripheral QCT at the radius (HRpQCT), and vertebral compressive strength and load-to-strength ratio by finite-element analysis (FEA) of lumbar spine QCT images. Compared with controls, women with grade 1 deformities had significantly worse values for many bone density, structure, and strength parameters, although deficits all were much worse for the women with grade 2-3 deformities. Likewise, these skeletal parameters were more strongly associated with moderate to severe than with mild deformities by age-adjusted logistic regression. Nonetheless, grade 1 vertebral deformities were significantly associated with four of the five main variable categories assessed: bone density (lumbar spine vBMD), bone geometry (vertebral apparent cortical thickness), bone strength (overall vertebral compressive strength by FEA), and load-to-strength ratio (45-degree forward bending ÷ vertebral compressive strength). Thus significantly impaired bone density, structure, and strength compared with controls indicate that many grade 1 deformities do represent early osteoporotic fractures, with corresponding implications for clinical decision making.

Although age-related variations in areal bone mineral density (aBMD) and the prevalence of osteoporosis have been well characterized, there is a paucity of data on femoral strength in the population. Addressing this issue, we used finite-element analysis of quantitative computed tomographic scans to assess femoral strength in an age-stratified cohort of 362 women and 317 men, aged 21 to 89 years, randomly sampled from the population of Rochester, MN, and compared femoral strength with femoral neck aBMD. Percent reductions over adulthood were much greater for femoral strength (55% in women, 39% in men) than for femoral neck aBMD (26% in women, 21% in men), an effect that was accentuated in women. Notable declines in strength started in the mid-40s for women and one decade later for men. At advanced age, most of the strength deficit for women compared with men was a result of this decade-earlier onset of strength loss for women, this factor being more important than sex-related differences in peak bone strength and annual rates of bone loss. For both sexes, the prevalence of "low femoral strength" (

The development of many systemic autoimmune diseases, including systemic lupus erythematosus, is associated with overactivation of the type I interferon (IFN) pathway, lymphopenia and increased follicular helper T (Tfh)‐cell differentiation. However, the cellular and molecular mechanisms underlying these immunological perturbations remain incompletely understood. Here, we show that the mechanistic target of rapamycin complex 2 (mTORC2) promotes Tfh differentiation and disrupts Treg homeostasis. Inactivation of mTORC2 in total T cells, but not in Tregs, greatly ameliorated the immunopathology in a systemic autoimmunity mouse model. This was associated with reduced Tfh differentiation, B‐cell activation, and reduced T‐cell glucose metabolism. Finally, we show that type I IFN can synergize with TCR ligation to activate mTORC2 in T cells, which partially contributes to T‐cell lymphopenia. These data indicate that mTORC2 may act as downstream of type I IFN, TCR and costimulatory receptor ICOS, to promote glucose metabolism, Tfh differentiation, and T‐cell lymphopenia, but not to suppress Treg function in systemic autoimmunity. Our results suggest that mTORC2 might be a rational target for systemic autoimmunity treatment. [ABSTRACT FROM AUTHOR]