Tomography micro-CT Research Articles

A mouse model of progressive lung fibrosis with cutaneous involvement induced by a combination of oropharyngeal and osmotic minipump bleomycin delivery.

Systemic sclerosis (SSc) with interstitial lung disease (SSc-ILD) lacks curative pharmacological treatments, thus necessitating effective animal models for candidate drug discovery. Existing bleomycin (BLM)-induced SSc-ILD mouse models feature spatially limited pulmonary fibrosis, spontaneously resolving after 28 days. Here, we present an alternative BLM administration approach in female C57BL/6 mice, combining oropharyngeal aspiration (OA) and subcutaneous mini-pump delivery (pump) of BLM to induce a sustained and more persistent fibrosis, while retaining stable skin fibrosis. A dose-finding study was performed with BLM administered as 10 µg (OA) +80 mg/kg (pump) (10 + 80), 10 + 100, and 15 + 100. Forty-two days after OA, micro-computed tomography (micro-CT) imaging and histomorphometric analyses showed that the 10 + 100 and 15 + 100 treatments induced significant alterations in lung micro-CT-derived readouts, Ashcroft score, and more severe fibrosis grades compared with saline controls. In addition, a marked reduction in hypodermal thickness was observed in the 15 + 100 group. A time-course characterization of the BLM 15 + 100 treatment at days 28, 35, and 42, including longitudinal micro-CT imaging, revealed progressing alterations in lung parameters. Lung histology highlighted a sustained fibrosis accompanied by a reduction in hypodermis thickness throughout the explored time-window, with a time-dependent increase in fibrotic biomarkers detected by immunofluorescence analysis. BLM-induced alterations were partly mitigated by Nintedanib treatment. Our optimized BLM delivery approach leads to extensive and persistent lung fibrotic lesions coupled with cutaneous fibrotic alterations: it thus represents a significant advance compared with current preclinical models of BLM-induced SSc-ILD.NEW & NOTEWORTHY This study introduces an innovative approach to enhance the overall performance of the mouse bleomycin (BLM)-induced model for systemic sclerosis with interstitial lung disease (SSc-ILD). By combining oropharyngeal aspiration and subcutaneous mini-pump delivery of BLM, our improved model leads to sustained lung fibrosis and stable skin fibrosis in female C57BL/6 mice. The optimized 15 + 100 treatment results in extensive and persistent lung fibrotic lesions and thus represents a significant improvement over existing preclinical models of BLM-induced SSc-ILD.

An optimized CT-dense agent perfusion and micro-CT imaging protocol for chick embryo developmental stages

Compared to classical techniques of morphological analysis, micro-CT (μ-CT) has become an effective approach allowing rapid screening of morphological changes. In the present work, we aimed to provide an optimized micro-CT dense agent perfusion protocol and μ-CT guidelines for different stages of chick embryo cardiogenesis. Our study was conducted over a period of 10 embryonic days (Hamburger-Hamilton HH36) in chick embryo hearts. During the perfusion of the micro-CT dense agent at different developmental stages (HH19, HH24, HH27, HH29, HH31, HH34, HH35, and HH36), we demonstrated that durations and volumes of the injected contrast agent gradually increased with the heart developmental stages contrary to the flow rate that was unchanged during the whole experiment. Analysis of the CT imaging confirmed the efficiency of the optimized parameters of the heart perfusion.

A novel reservoir classification method for sandstone reservoir evaluation using multi-scale digital rock method

The formulation of an effective development plan, optimizing exploitation efficiency, relies heavily on accurate reservoir characterization. However, existing reservoir classification methodologies, which rely on macroscopic geological observations and well-logging data, have limitations in data availability and fail to capture micro-scale pore structure characteristics accurately. The emerging technology of digital rock, widely employed in the petroleum industry, also faces challenges in accurately capturing reservoir heterogeneity due to its single-scale nature and limited application for reservoir classification. To overcome these challenges, this study presents an innovative reservoir classification approach based on the multi-scale digital rock method. This approach integrates qualitative assessment of micro-CT images for particle contact relationships and pore types with quantitative evaluation of multi-scale characteristic parameters, obtained from micro-CT and scanning electron microscopy (SEM) images. The proposed classification method demonstrates excellent agreement with the prioritization of development and production data for offshore sandstone reservoirs. By establishing a robust evaluation methodology, this classification method facilitates exploration potential assessment and development strategy optimization within the field.

Absence of E2f1 Negates Pro-osteogenic Impacts of p21 Absence.

Loss of p21 leads to increased bone formation post-injury; however, the mechanism(s) by which this occurs remains undetermined. E2f1 is downstream of p21 and as a transcription factor can act directly on gene expression; yet it is unknown if E2f1 plays a role in the osteogenic effects observed when p21 is differentially regulated. In this study we aimed to investigate the interplay between p21 and E2f1 and determine if the pro-regenerative osteogenic effects observed with the loss of p21 are E2f1 dependent. To accomplish this, we employed knockout p21 and E2f1 mice and additionally generated a p21/E2f1 double knockout. These mice underwent burr-hole injuries to their proximal tibiae and healing was assessed over 7days via microCT imaging. We found that p21 and E2f1 play distinct roles in bone regeneration where the loss of p21 increased trabecular bone formation and loss of E2f1 increased cortical bone formation, yet loss of E2f1 led to poorer bone repair overall. Furthermore, when E2f1 was absent, either individually or simultaneously with p21, there was a dramatic decrease of the number of osteoblasts, osteoclasts, and chondrocytes at the site of injury compared to p21-/- and C57BL/6 mice. Together, these results suggest that E2f1 regulates the cell populations required for bone repair and has a distinct role in bone formation/repair compared to p21-/-E2f1-/-. These results highlight the possibility of cell cycle and/or p21/E2f1 being potential druggable targets that could be leveraged in clinical therapies to improve bone healing in pathologies such as osteoporosis.

Paeoniflorin mitigates MMP-12 inflammation in silicosis via Yang-Yin-Qing-Fei Decoction in murine models

BackgroundSilicosis presents a significant clinical challenges and economic burdens, with Traditional Chinese Medicine (TCM) emerging as a potential therapeutic avenue. However, the precise effects and mechanisms of TCM in treating silicosis remain uncertain and subject to debate. ObjectiveThe study aims to elucidate the therapeutic role and mechanisms of the Yang-Yin-Qing-Fei Decoction (YYQFD) and its key component, paeoniflorin, in silicosis using a murine model. MethodsSilicotic mice were treated with YYQFD, pirfenidone (PFD), or paeoniflorin. RAW264.7 cells and mouse lung fibroblasts (MLF) were stimulated with silica, matrix metalloproteinase-12 (MMP-12), or TGF-β1, followed by treatment with paeoniflorin, PFD, or relevant inhibitors. YYQFD constituents were characterized using High-Performance Liquid Chromatography (HPLC). Lung fibrosis severity was assessed via histopathological examination, micro-CT imaging, lung functions, and Western blot analysis. Transcriptome sequencing and bioinformatics analysis were employed to delineate the gene expression profile and target genes modulated by YYQFD in silicosis. ResultsTreatment with YYQFD ameliorated silica-induced lung fibrosis. Transcriptome sequencing identified MMP-12 as a potential common target of YYQFD and PFD. Additionally, a potential pro-inflammatory role of MMP-12, regulated by silica-induced TLR4 signaling pathways, was revealed. Paeoniflorin, one of the most distinctive compounds in YYQFD, attenuated silica-induced MMP-12 increase and its derived inflammatory factors in macrophages through a direct binding effect. Notably, paeoniflorin treatment exerted anti-fibrotic effects by inhibiting MMP-12-derived inflammatory factors and TGF-β1-induced myofibroblast differentiation in silica-exposed mice. ConclusionsThis study underscores paeoniflorin as one of the most principal bioactive compounds in YYQFD, highlighting its capacity to attenuate lung inflammation driven by macrophage-derived MMP-12 and reduce lung fibrosis both in vivo and in vitro.

Automatic reconstruction of closely packed fabric composite RVEs using yarn-level micro-CT images processed by convolutional neural networks (CNNs) and based on physical characteristics

Micro-CT scanning is an advanced technique to reconstruct inner architectures for RVEs of fabric composites. Currently, however, there exist few automatic approaches to separate closely packed yarns in the micro-CT images with economical resolution that can only identify yarns but not individual fibers. To tackle this issue, an innovative method has been developed in this work to identify cross-section area of the yarns via deep-learning-based image segmentation, and then reconstruct 3D geometry model of the composites containing local fiber orientations. The image segmentation was achieved through semantic segmentation by U-Net with validation accuracy of 87 % counted by mIOU and object detection by YOLO v8 with validation accuracy of 99.5 % counted by mAP50. Micro-CT slices with different morphological characteristics were divided into three groups via a ResNet50-based image classification network and selected in ratio to form the training datasets for U-Net and YOLO v8 with high representativity and efficiency. Extraction of individual cross-sections of weft and warp yarns were conducted only using the micro-CT scanning from one angle of view to reduce scanning cost and yarn-to-yarn penetration error. An algorithm considering physical constraints of the yarns was also completed to estimate local fiber orientations with maximum error of 18.065°, nearly 50 % smaller than the existing method.

Monoliths for gas storage manufactured with precision pore engineering using 3D-printed templates

A fast, customizable, and systematic route for producing activated carbon monoliths for gas storage with low interparticle porosity (9 % to 24 %) containing tailored macro channels is disclosed. The production uses a three-dimensional (3D)-printed polymeric lattice, rich in oxygen, as a sacrificial template. Its interstitial voids are filled with a phenolic resin that is carbonized and activated at 1173 K under carbon dioxide (CO2). Sequential pyrolysis occurs via thermal treatment with the 3D-printed lattice removed first, rendering macro channels with the same shape as the template in accurately placed positions. Resulting in adsorbents with interparticle porosities ranging from 10 % to 23 %, calculated from X-ray micro-computed tomography (micro-CT) images. The axial resolution of these macro channels was similar to the SLA printing layer thickness used of 100 µm. Making it the best resolution attained to date in fabricating monoliths via a 3D-printed sacrificial templating method. Breakthrough experiments indicated healthy macro channel connectivity due to the reduced mass transfer zone. Moreover, excellent mechanical integrity was displayed, with a monolith withstanding 900 N before excessive fracturing occurred despite the presence of macro channels. Therefore, this method emphasizes its use for gas storage applications by enabling the adsorbent material to efficiently utilize the volumetric space while allowing a fast rate of adsorption over the entire structure.

Single image multi-scale enhancement for rock Micro-CT super-resolution using residual U-Net

Micro-CT, also known as X-ray micro-computed tomography, has emerged as the primary instrument for pore-scale properties study in geological materials. Several studies have used deep learning to achieve super-resolution reconstruction in order to balance the trade-off between resolution of CT images and field of view. Nevertheless, most existing methods only work with single-scale CT scans, ignoring the possibility of using multi-scale image features for image reconstruction. In this study, we proposed a super-resolution approach via multi-scale fusion using residual U-Net for rock micro-CT image reconstruction (MS-ResUnet). The residual U-Net provides an encoder-decoder structure. In each encoder layer, several residual sequential blocks and improved residual blocks are used. The decoder is composed of convolutional ReLU residual blocks and residual chained pooling blocks. During the encoding-decoding method, information transfers between neighboring multi-resolution images are fused, resulting in richer rock characteristic information. Qualitative and quantitative comparisons of sandstone, carbonate, and coal CT images demonstrate that our proposed algorithm surpasses existing approaches. Our model accurately reconstructed the intricate details of pores in carbonate and sandstone, as well as clearly visible coal cracks.

Root and canal morphology of the maxillary first molar: A micro-computed tomography-focused observation of literature with illustrative cases. Part 2: Internal root morphology

The complexity of root canal morphology can influence cleaning and shaping of the root canal system and, ultimately, treatment outcomes. Undiscovered root canal morphology can greatly reduce the prognosis of endodontic treatment due to the preservation of offending organisms and their by products. The maxillary first molar has been identified as one of the most challenging teeth to treat endodontically due to its complex internal anatomy, the presence of additional and accessory canals and intricate root canal configurations. This paper is the second of two that provide a micro computed tomography (micro-CT)-focused overview of available literature on various aspects of the root and canal morphology of the maxillary first permanent molar. The aim of this paper is to provide an overview of relevant aspects of the internal root morphology in different populations. The content is supported by illustrative micro-CT images and clinical cases or images.

Pore-to-field scale modeling of residual gas trapping in tight carbonate underground gas reservoirs

The deep saline aquifer and depleted gas reservoirs are suitable candidates for CO2 storage. The estimation of residual gas and corresponding flowing behavior are major parameters for successful CO2 trapping in geological formations. In this article the residual gas trapping phenomenon in pore scale has been studied using Micro-CT images. In macro scale, the results of imbibition experiments on core plug samples have been considered to determine residual gas saturation (RGS) and the corresponding water relative permeability. In the field scale, pressure transient data in water leg has been used to determine the water relative permeability at RGS in a tight carbonate reservoir in Middle East. In the proposed workflow, an artificial intelligence approach is applied to determine absolute permeability profile. Then, a numerical dynamic single well model is built to calculate the water relative permeability. The comparison of core and pressure transient data shows that the absolute permeability and water relative permeability from core imbibition test are significantly overestimated while the results of gas-water simulation in pore scale confirmed the real field transient data. The proposed method can be used by industrial reservoir simulator to define rock/fluid interaction parameters in simulation of CO2 storage in depleted underground gas reservoirs.

Effect of EDTA with porous balloon on calcified lesion: An atherosclerotic cadaver study.

Ethylene diamine tetra-acetic acid (EDTA) is a chelating agent used to dissolve calcium deposits but evidence in decalcifying atherosclerotic lesions is limited. We assessed the feasibility and efficacy of EDTA delivered via porous balloon to target calcified lesions in cadaveric below-the-knee (BTK) arteries. Using porcine carotid arteries, EDTA concentration was measured in the arterial wall and outside the artery at the 0-, 0.5-, 4-, and 24-h circulation after the injection through a porous balloon. In cadaver BTK samples, the proximal and distal anterior tibial artery (ATA) and distal posterior tibial artery (PTA) were studied. EDTA-2Na/H2O or EDTA-3Na/H2O were administrated using a porous balloon, then circulated for 6 h for EDTA-3Na/H2O and 24 h for EDTA-2Na/H2O and EDTA-3Na/H2O. Micro-CT imaging of the artery segments before and after the circulation and cross-sectional analyses were performed to evaluate calcium burden. In the porcine carotid study, EDTA was delivered through a porous balloon present in the arterial wall and was retained there for 24 h. In BTK arteries, cross-sectional analyses of micro-CT revealed a significant decrease in the calcium area in the distal ATA segment under 24-h circulation with EDTA-2Na/H2O and in the distal ATA segment under 24-h circulation with EDTA-3Na/H2O. The proximal ATA segment under 6-h circulation with EDTA-3Na/H2O showed no significant change in any parameters of calcium CONCLUSION: EDTA-3Na/H2O or EDTA-2Na/H2O with longer circulation times resulted in greater calcium reduction in atherosclerotic lesion. EDTA may have a potential therapeutic option for the treatment of atherosclerotic calcified lesions.

Micro-CT and histological examination of accessory canals in 34 equine cheek teeth.

Accessory canals and apical deltas have been extensively studied in human dentistry. Their clinical role as a difficult to clean reservoir for bacteria during endodontic treatments has been well described. Many papers describe in detail the pulp anatomy of equine dentition but little attention has been given to their apical ramifications. The goal of this paper is to describe the presence and anatomy of these accessory canals and apical deltas in healthy equine cheek teeth and discuss their possible relevance in the light of equine endodontics. To accomplish this, 15 maxillary and 19 mandibular healthy cheek teeth were collected ranging from Triadan 06 s to 11 s with eruption ages from 4 to 9 years. Their root anatomy was documented in detail based on micro computed tomography images. A subset of 3 teeth also underwent histological examination. Accessory canals were found in all but two teeth examined. Up to 44 accessory canals per tooth have been found with locations ranging from the root furcation down to the apex of the root and with highly variable diameters. Apical deltas in different stages of development were found in 84% of the roots. The presence of accessory canals identified on microCT images could be confirmed using histological examination although some of them were obliterated by reparative dentin. Accessory canals can be found in most equine cheek teeth and add complexity to their endodontic anatomy. This could have important implications for their treatment in case of pulp pathology. In humans, failure to remove bacterial biofilm from such canals has been associated with failure of endodontic treatment. Research on diseased equine teeth is required to gain a better understanding of their clinical relevance in horses.

Plastic Fruit Stickers in Industrial Composting─Surface and Structural Alterations Revealed by Electron Microscopy and Computed Tomography.

Often large quantities of plastics are found in compost, with price look-up stickers being a major but little-explored component in the contamination path. Stickers glued to fruit or vegetable peels usually remain attached to the organic material despite sorting processes in the composting plant. Here, we investigated the effects of industrial composting on the structural alterations of these stickers. Commercial polypropylene (PP) stickers on banana peels were added to a typical organic material mixture for processing in an industrial composting plant and successfully resampled after a prerotting (11 days) and main rotting step (25 days). Afterward, both composted and original stickers were analyzed for surface and structural changes via scanning electron microscopy, Fourier-transform infrared spectroscopy, and micro- and nano-X-ray computed tomography (CT) combined with deep learning approaches. The composting resulted in substantial surface changes and degradation in the form of microbial colonization, deformation, and occurrence of cracks in all stickers. Their pore volumes increased from 16.7% in the original sticker to 26.3% at the end of the compost process. In a similar way, the carbonyl index of the stickers increased. Micro-CT images additionally revealed structural changes in the form of large adhesions that penetrated the surface of the sticker. These changes were accompanied by delamination after 25 days of composting, thus overall hinting at the degradation of the stickers and the subsequent formation of smaller microplastic pieces.

Evaluation of component interface quality in 3D micro-CT images of metallurgical coke

Metallurgical coke is a crucial component in the production of steel worldwide. It is a porous composite material, created by conversion of metallurgical coal in a coke oven. A key property of metallurgical coke is its strength, and there is evidence that poor interface quality between the two key components of coke can have deleterious effect on coke strength. Here we create small samples of coke and image them using high resolution 3D micro-CT, with pixel size of approximately \(8\,\mu\)m. We use a Gabor filter, combined with morphology techniques to isolate the different components in the samples. We then develop a measure, called excess porosity to quantify the quality of the interfaces between components. This measure enables us to highlight problem interactions between components.

Volume X-Ray Micro-Computed Tomography Analysis of the Early Cephalized Central Nervous System in a Marine Flatworm, Stylochoplana pusilla.

Platyhelminthes are a phylum of simple bilaterian invertebrates with prototypic body systems. Compared with non-bilaterians such as cnidarians, the bilaterians are likely to exhibit integrated free-moving behaviors, which require a concentrated nervous system "brain" rather than the distributed nervous system of radiatans. Marine flatworms have an early cephalized 'central' nervous system compared not only with non-bilaterians but also with parasitic flatworms or freshwater planarians. In this study, we used the marine flatworm Stylochoplana pusilla as an excellent model organism in Platyhelminthes because of the early cephalized central nervous system. Here, we investigated the three-dimensional structures of the flatworm central nervous system by the use of X-ray micro-computed tomography (micro-CT) in a synchrotron radiation facility. We found that the obtained tomographic images were sufficient to discriminate some characteristic structures of the nervous system, including nerve cords around the cephalic ganglion, mushroom body-like structures, and putative optic nerves forming an optic commissure-like structure. Through the micro-CT imaging, we could obtain undistorted serial section images, permitting us to visualize precise spatial relationships of neuronal subpopulations and nerve tracts. 3-D micro-CT is very effective in the volume analysis of the nervous system at the cellular level; the methodology is straightforward and could be applied to many other non-model organisms.

Ice-Core Micro-CT Image Segmentation with Dual Stream Spectrum Deconvolution Neural Network and Gaussian Mixture Model

Polar ice sheets, or ice cores, are among the most well-known natural archives that might provide crucial historical details about our planet's previous environment. An important factor in establishing the fundamental characteristics of ice, likes pore close-off, albedo, melt events, is the ice-core microstructure. To engulf these complications Ice-Core Micro-CT Image Segmentation with Dual Stream Spectrum Deconvolution Neural Network and Gaussian Mixture Model (ICMCTS-WSOA-DSSDNN-GMM)is proposed. Initially, micro scale CT images are collect from Alfred Wegener Institute ice-core storage as input. Then,data’s are given to pre-processing. In pre-processing, it enhance image brightness, remove salt pepper noise, crop outer ring (carbon fiber casing) to have only ice particles in image utilizing Federated Neural Collaborative Filtering (FNCF).The pre-processing output is given to segmentation. Here, micro scale CT image is utilized for segmenting high-resolution scans using Gaussian Mixture Model (GMM). After that, the segmented images are given to Dual Stream Spectrum Deconvolution Neural Network optimized with Water Strider Optimization Algorithm for classifying micro scale CT images as sintered snow, compacted firn and bubbly ice. The proposed ICMCTS-WSOA-DSSDNN-GMM method is executed in python. The performance of ICMCTS-WSOA-DSSDNN-GMM approach attains 16.24%, 17.90% and 27.7% high accuracy, 14.04%, 25.51% and 19.31% higher precision and 14.36%, 12.65%, 14.51% higher recall analyzed with existing techniques likes Ice-Core Micro-CT Image Segmentation With Deep Learning and Gaussian Mixture Method (ICMCTS-U-net-GMM), Computer Aided Detection of COVID 19 from CT Images Depend on Gaussian Mixture Method with Kernel Support Vector Machines Classifer (ICMCTS-KNN-GMM) and the Gmmseg: Gaussian mixture based generative semantic segmentation methods(ICMCTS-FCN-GMM) respectively.

The impact of crystal phase transition on the hardness and structure of kidney stones

Calcium oxalate kidney stones, the most prevalent type of kidney stones, undergo a multi-step process of crystal nucleation, growth, aggregation, and secondary transition. The secondary transition has been rather overlooked, and thus, the effects on the disease and the underlying mechanism remain unclear. Here, we show, by periodic micro-CT images of human kidney stones in an ex vivo incubation experiment, that the growth of porous aggregates of calcium oxalate dihydrate (COD) crystals triggers the hardening of the kidney stones that causes difficulty in lithotripsy of kidney stone disease in the secondary transition. This hardening was caused by the internal nucleation and growth of precise calcium oxalate monohydrate (COM) crystals from isolated urine in which the calcium oxalate concentrations decreased by the growth of COD in closed grain boundaries of COD aggregate kidney stones. Reducing the calcium oxalate concentrations in urine is regarded as a typical approach for avoiding the recurrence. However, our results revealed that the decrease of the concentrations in closed microenvironments conversely promotes the transition of the COD aggregates into hard COM aggregates. We anticipate that the suppression of the secondary transition has the potential to manage the deterioration of kidney stone disease.

Comparative Evaluation of Volume and Homogeneity of Obturation with Four Different Obturation Systems Using Micro-Computed Tomography: An In vitro Study.

To evaluate and compare volume and homogeneity of the three different root canal obturation systems. Single-rooted premolar (n = 24) teeth samples were selected, and crowns were removed for standardization. Four groups are divided randomly as (n = 6), namely: For group I (single-cone gutta-percha obturation), group II (Beefill 2 in 1 obturation), group III (GuttaCore obturation), group IV (GuttaFlow bioseal obturation) and the root canal were subjected to prepare till X3 (protaper next) and subjected to micro-CT imaging. After completion of obturation, the image was taken by using micro-CT imaging. This is to evaluate the volume of filled obturation material in the canal space and the voided area sections, viz. the apical, middle, coronal, and third sections. Group III (GuttaCore obturation) showed the least significant mean of the difference in relation to the volume of the canal obturation (81.148). The least mean significant difference in area of voids in the canal region for apical (0.00133), middle (0.00233), and coronal thirds (0.00533). The most statistically significant difference is in the apical and middle thirds root canal space. All the experimental groups showed significant differences in volume and voids in the obturation at three different levels, and the GuttaCore obturation systems occupied more of the volume with less voids in the prepared root canal space.

Modeling of 3D-printed composite filaments using X-ray computer tomography images segmented by neural networks

This study introduces a novel semi-analytical two-scale approach to model 3D-printed composite filament where both fibers and voids are present. The proposed approach utilizes micro computer tomography (micro-CT) images to visualize fibers and voids. Then, a novel segmentation process based on neural network algorithms (specifically the YOLO v7 algorithm) is employed to segment the distinct fiber and void phases. The volume fractions and the geometries of the phases are then used in the first scale (the micro-scale) of the approach and the effective elastic properties of internal regions of the filament are obtained using the Mori–Tanaka effective field method. These regions are then joined together to form the second scale (the macro-scale), for which the elastic properties are evaluated using the finite element method. The two-scale approach is applied for 3D-printed nylon reinforced with continuous carbon fibers and the predictions of the elastic properties are compared to tensile tests conducted on the single filament. A great agreement is observed for Young’s modulus along the fiber direction of the single printed filament.

Effects of LP533401 on vascular and bone calcification in hyperlipidemic mice

Peripheral serotonin levels are associated with cardiovascular disease risk. We previously found that serum serotonin levels are higher in hyperlipidemic mice than wild-type mice. Evidence also suggests that serotonin regulates biomineralization, in that serotonin treatment augments TNF-a-induced matrix calcification of aortic valve interstitial cells and that a selective inhibitor of peripheral serotonin, LP533401, rescues bone loss induced by ovariectomy in mice. Thus, in the present study, we examined the effects of LP533401 on both skeletal bone mineral density (BMD) and aortic calcification in both young and older hyperlipidemic mice susceptible to calcific atherosclerosis and bone loss. By serial in vivo microCT imaging, we assessed BMD and aortic calcification of Apoe−/− mice fed an atherogenic (high cholesterol) diet alone or mixed with LP533401. Results show that in the young mice, LP533401 blunted skeletal bone loss in lumbar vertebrae but not in femurs. LP533401 also blunted the initial development of aortic calcification but not its progression. Echocardiographic analysis showed that LP533401 blunted both hyperlipidemia-induced cardiac hypertrophy and left ventricular dysfunction. In the older mice, LP533401 increased the BMD of lumbar vertebrae but not of femurs. The aortic calcification progressed in both controls and LP533401-treated mice, but, at post-treatment, LP533401-treated mice had significantly less aortic calcification than the controls. These findings suggest that LP533401 mitigates adverse effects of hyperlipidemia on skeletal and vascular tissues in site- and stage-dependent manners.