Microarchitecture, but Not Bone Mechanical Properties, Is Rescued with Growth Hormone Treatment in a Mouse Model of Growth Hormone Deficiency

Growth hormone (GH) deficiency is related to an increased fracture risk although it is not clear if this is due to compromised bone quality or a small bone size. We investigated the relationship between bone macrostructure, microarchitecture and mechanical properties in a GH-deficient (GHD) mouse model undergoing GH treatment commencing at an early (prepubertal) or late (postpubertal) time point. Microcomputed tomography images of the femur and L4 vertebra were obtained to quantify macrostructure and vertebral trabecular microarchitecture, and mechanical properties were determined using finite element analyses. In the GHD animals, bone macrostructure was 25 to 43% smaller as compared to the GH-sufficient (GHS) controls (P < 0.001). GHD animals had 20% and 19% reductions in bone volume ratio (BV/TV) and trabecular thickness (Tb.Th), respectively. Whole bone mechanical properties of the GHD mice were lower at the femur and vertebra (67% and 45% resp.) than the GHS controls (P < 0.001). Both early and late GH treatment partially recovered the bone macrostructure (15 to 32 % smaller than GHS controls) and the whole bone mechanical properties (24 to 43% larger than GHD animals) although there remained a sustained 27–52% net deficit compared to normal mice (P < 0.05). Importantly, early treatment with GH led to a recovery of BV/TV and Tb.Th with a concomitant improvement of trabecular mechanical properties. Therefore, the results suggest that GH treatment should start early, and that measurements of microarchitecture should be considered in the management of GHD

A PRINCIPLE INVESTIGATION INTO THE FEASIBILITY OF USING MICROWAVE IMAGING TO MONITOR BONE HEALTH

INTRODUCTION Assessing bone health is of particular interest in age-associated disease and traumas such as osteoporosis, and fractures from extreme sports. Having tools that can safely and accurately assess bone health allows for the screening, diagnosis, and monitoring of disease or injury. The current gold standard for assessing bone health is high-resolution peripheral quantitative computed tomography (HR-pQCT) allowing direct three-dimensional (3D) visualization of bone. Recent evidence suggests microwave imaging can be a complementary medical imaging tool to HR-pQCT for dynamic assessment of full bone health [1]. Specifically, it was shown that microwave properties of cancellous bone are sensitive to physical changes in bone. However, this study was purely exploratory and provided no direct evidence for changes in dielectric properties with varying bone health. In this study, we aim to understand the interaction of electromagnetic waves with bone as a composite material, specifically the material anisotropy. Such information would be crucial to understanding how microwave measurements relate to the physical characteristics of the bone. METHODS Image data for the right and left tibia and radius of one female and two male subjects was acquired from HR-pQCT (XtremeCTII, Scanco Medical). The 3D image data was smoothed with a Gaussian filter (σ = 1.6) and segmented using histogram based segmentation. Cubes of edge length 82 voxels (5.002 mm) were extracted from the segmented images based on the bone center of geometry. The extracted cubes were imported into electromagnetic simulation software (SEMCAD X, Schmid &amp; Partner Engineering AG). A parallel plate waveguide filled with air was excited with a Gaussian pulse polarized in the z-axis (f0 = 6.5 GHz, BW = 11 GHz). The bone and marrow were assigned material properties from literature [2]. Resulting data was exported and processed using custom MATLAB scripts (R2013a, MathWorks). Three simulations were performed per image such that the electromagnetic wave was polarized in each of the three anatomical directions: anterior-posterior, medial-lateral, and proximal-distal. RESULTS The effective permittivity, ε’r, was calculated for each of the anatomical directions and plotted across the frequency range of the input signal. A representative plot for all images is shown in Figure 1. The effective permittivity for each orientation tend to vary around a common permittivity.DISCUSSION AND CONCLUSIONS The results presented here provide a rudimentary but novel insight into the anisotropic behaviour of bone at microwave frequencies. Furthermore, it presents a technique for 3D model acquisition and simulation of bone not yet present in literature. This technique will allow further exploration of the electromagnetic properties of bone such as a deeper insight into the anisotropic behaviour and development of a model for the effective medium of bone as a composite material. With such information, the microwave measurements of bone could be directly related to the bone’s physical properties. This would prove the potential of microwaves to assess bone health for disease or trauma and allow the development of in vivo imaging tools for assessing disease and trauma

The Nt=6N_t=6 equation of state for two flavor QCD

We improve the calculation of the equation of state for two flavor QCD by simulating on $N_t=6$ lattices at appropriate values of the couplings for the deconfinement/chiral symmetry restoration crossover. For $am_q=0.0125$ the energy density rises rapidly to approximately 1 ${\rm GeV/fm^3}$ just after the crossover($m_\pi/m_\rho\approx 0.4$ at this point). Comparing with our previous result for $N_t=4$~\cite{eos}, we find large finite $N_t$ corrections as expected from free field theory on finite lattices. We also provide formulae for extracting the speed of sound from the measured quantities.Comment: Contribution to Lattice 95 proceedings (combines talks presented by T. Blum and L. Karkkainen). LaTeX, 8 pages, uses espcrc2.sty, postscript figures include

Bone-GAN: Generation of virtual bone microstructure of high resolution peripheral quantitative computed tomography

Background:Data-driven development of medical biomarkers of bone requires a large amount of image data but physical measurements are generally too restricted in size and quality to perform a robust training. Purpose: This study aims to provide a reliable in silico method for the generation of realistic bone microstructure with defined microarchitectural properties. Synthetic bone samples may improve training of neural networks and serve for the development of new diagnostic parameters of bone architecture and mineralization. Methods: One hundred-fifty cadaveric lumbar vertebrae from 48 different male human spines were scanned with a high resolution peripheral quantitative CT. After prepocessing the scans, we extracted 10,795 purely spongeous bone patches, each with a side length of 32 voxels (5 mm) and isotropic voxel size of 164 m. We trained a volumetric generative adversarial network (GAN) in a progressive manner to create synthetic microstructural bone samples. We then added a style transfer technique to allow the generation of synthetic samples with defined microstructure and gestalt by simultaneously optimizing two entangled loss functions. Reliability testing was performed by comparing real and synthetic bone samples on 10 well-understood microstructural parameters. Results: The method was able to create synthetic bone samples with visual and quantitative properties that effectively matched with the real samples. The GAN contained a well-formed latent space allowing to smoothly morph bone samples by their microstructural parameters, visual appearance or both. Optimum performance has been obtained for bone samples with voxel size 32 × 32 × 32, but also samples of size 64 × 64 × 64 could be synthesized. Conclusions: Our two-step-approach combines a parameter-agnostic GAN with a parameter-specific style transfer technique. It allows to generate an unlimited anonymous database of microstructural bone samples with sufficient realism to be used for the development of new data-driven methods of bonebiomarkers. Particularly, the style transfer technique can generate datasets of bone samples with specific conditions to simulate certain bone pathologies.Este artículo se encuentra publicado en Medical Physics, (Junio 2023

The Lysyl Oxidase Inhibitor, β-Aminopropionitrile, Diminishes the Metastatic Colonization Potential of Circulating Breast Cancer Cells

Lysyl oxidase (LOX), an extracellular matrix remodeling enzyme, appears to have a role in promoting breast cancer cell motility and invasiveness. In addition, increased LOX expression has been correlated with decreases in both metastases-free, and overall survival in breast cancer patients. With this background, we studied the ability of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX, to regulate the metastatic colonization potential of the human breast cancer cell line, MDA-MB-231. BAPN was administered daily to mice starting either 1 day prior, on the same day as, or 7 days after intracardiac injection of luciferase expressing MDA-MB-231-Luc2 cells. Development of metastases was monitored by in vivo bioluminescence imaging, and tumor-induced osteolysis was assessed by micro-computed tomography (μCT). We found that BAPN administration was able to reduce the frequency of metastases. Thus, when BAPN treatment was initiated the day before, or on the same day as the intra-cardiac injection of tumor cells, the number of metastases was decreased by 44%, and 27%, and whole-body photon emission rates (reflective of total tumor burden) were diminished by 78%, and 45%, respectively. In contrast, BAPN had no effect on the growth of established metastases. Our findings suggest that LOX activity is required during extravasation and/or initial tissue colonization by circulating MDA-MB-231 cells, lending support to the idea that LOX inhibition might be useful in metastasis prevention

New fat free mass - fat mass model for use in physiological energy balance equations

<p>Abstract</p> <p>Background</p> <p>The Forbes equation relating fat-free mass (<it>FFM</it>) to fat mass (<it>FM</it>) has been used to predict longitudinal changes in <it>FFM </it>during weight change but has important limitations when paired with a one dimensional energy balance differential equation. Direct use of the Forbes model within a one dimensional energy balance differential equation requires calibration of a translate parameter for the specific population under study. Comparison of translates to a representative sample of the US population indicate that this parameter is a reflection of age, height, race and gender effects.</p> <p>Results</p> <p>We developed a class of fourth order polynomial equations relating <it>FFM </it>to <it>FM </it>that consider age, height, race and gender as covariates eliminating the need to calibrate a parameter to baseline subject data while providing meaningful individual estimates of <it>FFM</it>. Moreover, the intercepts of these polynomial equations are nonnegative and are consistent with observations of very low <it>FM </it>measured during a severe Somali famine. The models preserve the predictive power of the Forbes model for changes in body composition when compared to results from several longitudinal weight change studies.</p> <p>Conclusions</p> <p>The newly developed <it>FFM</it>-<it>FM </it>models provide new opportunities to compare individuals undergoing weight change to subjects in energy balance, analyze body composition for individual parameters, and predict body composition during weight change when pairing with energy balance differential equations.</p

The equation of state for two flavor QCD at N_t=6

We calculate the two flavor equation of state for QCD on lattices with lattice spacing a=(6T)^{-1} and find that cutoff effects are substantially reduced compared to an earlier study using a=(4T)^{-1}. However, it is likely that significant cutoff effects remain. We fit the lattice data to expected forms of the free energy density for a second order phase transition at zero-quark-mass, which allows us to extrapolate the equation of state to m_q=0 and to extract the speed of sound. We find that the equation of state depends weakly on the quark mass for small quark mass.Comment: 24 pages, latex, 11 postscipt figure

Casimir micro-sphere diclusters and three-body effects in fluids

Our previous article [Phys. Rev. Lett. 104, 060401 (2010)] predicted that Casimir forces induced by the material-dispersion properties of certain dielectrics can give rise to stable configurations of objects. This phenomenon was illustrated via a dicluster configuration of non-touching objects consisting of two spheres immersed in a fluid and suspended against gravity above a plate. Here, we examine these predictions from the perspective of a practical experiment and consider the influence of non-additive, three-body, and nonzero-temperature effects on the stability of the two spheres. We conclude that the presence of Brownian motion reduces the set of experimentally realizable silicon/teflon spherical diclusters to those consisting of layered micro-spheres, such as the hollow- core (spherical shells) considered here.Comment: 11 pages, 9 figure