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Small-angle x-ray scattering (SAXS) imaging can differentiate tissue types based on their nanoscale molecular structure. However, characterization of the coherent scattering cross-section profile of relevant tissues is needed to optimally design SAXS imaging techniques for a variety of biomedical applications. Reported measured nervous tissue x-ray scattering cross sections under a synchrotron source have had limited agreement. We report a set of x-ray cross-section measurements obtained from planar SAXS imaging of 1 mm thick mouse brain (APP/PS1 wild-type) coronal slices using an 8 keV laboratory x-ray source. Two characteristic peaks were found at 0.96 and 1.60 nm−1 attributed to myelin. The peak intensities varied by location in the slice. We found that regions of gray matter, white matter, and corpus callosum could be segmented by their increasing intensities of myelin peaks respectively. Measured small-angle x-ray scattering cross sections were then used to define brain tissue scattering properties in a GPU-accelerated Monte Carlo simulation of SAXS computed tomography (CT) using a higher monochromatic x-ray energy (20 keV) to study design trade-offs for noninvasive in vivo SAXS imaging on a small-animal head including radiation dose, signal-to-noise ratio (SNR), and the effect of skull presence on the previous two metrics. Simulation results show the estimated total dose to the mouse head for a single SAXS-CT slice was 149.4 mGy. The pixel SNR was approximately 30.8 for white matter material whether or not a skull was present. In this early-stage proof-of-principle work, we have demonstrated our brain cross-section data and simulation tools can be used to assess optimal instrument parameters for dedicated small-animal SAXS-CT prototypes. [ABSTRACT FROM AUTHOR]

Osteocytes are the most abundant cell in the bone, and have multiple functions including mechanosensing and regulation of bone remodeling activities. Since osteocytes are embedded in the bone matrix, their inaccessibility makes in vivo studies problematic. Therefore, a non-invasive technique with high spatial resolution is desired. The purpose of this study is to investigate the use of third harmonic generation (THG) microscopy as a noninvasive technique for high-resolution imaging of the lacunar-canalicular network (LCN) in live mice. By performing THG imaging in combination with two- and three-photon fluorescence microscopy, we show that THG signal is produced from the bone-interstitial fluid boundary of the lacuna, while the interstitial fluid-osteocyte cell boundary shows a weaker THG signal. Canaliculi are also readily visualized by THG imaging, with canaliculi oriented at small angles relative to the optical axis exhibiting stronger signal intensity compared to those oriented perpendicular to the optical axis (parallel to the image plane). By measuring forward- versus epi-detected THG signals in thinned versus thick bone samples ex vivo, we found that the epi-collected THG from the LCN of intact bone contains a superposition of backward-directed and backscattered forward-THG. As an example of a biological application, THG was used as a label-free imaging technique to study structural variations in the LCN of live mice deficient in both histone deacetylase 4 and 5 (HDAC4, HDAC5). Three-dimensional analyses were performed and revealed statistically significant differences between the HDAC4/5 double knockout and wild type mice in the number of osteocytes per volume and the number of canaliculi per lacunar surface area. These changes in osteocyte density and dendritic projections occurred without differences in lacunar size. This study demonstrates that THG microscopy imaging of the LCN in live mice enables quantitative analysis of osteocytes in animal models without the use of dyes or physical sectioning. [ABSTRACT FROM AUTHOR]

Osteocyte apoptosis is the first reaction to estrogen depletion, thereby stimulating osteoclastic bone resorption resulting in bone loss. We investigated the effects of two different risedronate (RIS) doses (high and low) on osteocyte apoptosis, osteoclast activity and bone loss in ovariectomized rats. Forty rats with ovariectomy (OVX) and sham ovariectomy (SHAM) were divided into 4 groups: 1) SHAM rats treated with saline (SHAM); 2) OVX rats treated with saline (OVX); 3) OVX rats treated with low-dose RIS (OVX-LR, 0.08 μg/kg/day); 4) OVX rats treated with high-dose RIS (OVX-HR, 0.8 μg/kg/day). All animals were sacrificed 90 days after surgery for the examinations of osteocyte apoptosis by caspase-3 staining, osteoclast activity by TRAP staining and bone volume by micro-CT scanning in lumbar vertebral cancellous bone. Both low and high dose RIS significantly reduced caspase-3 positive osteocytes, empty lacunae and TRAP positive osteoclasts in OVX rats. Although the difference in caspase-3 positive osteocytes was not significant between the OVX-LR and OVX-HR groups, numerically these cells were significantly more prevalent in OVX-HR (not OVX-LR) group than in SHAM group. TRAP positive osteoclasts were significantly higher in OVX-LR group than in SHAM or OVX-HR group. There was no significant difference in bone volume among the OVX-LR, OVX-HR and SHAM groups, but lower in OVX group alone. However, significant increase in trabecular thickness only occurred in OVX-LR group. We conclude that both low and high dose RIS significantly inhibit osteocyte apoptosis and osteoclast activity in OVX rats, but the low-dose RIS has weaker effect on osteoclast activity. However, low-dose RIS preserves cancellous bone mass and microarchitecture as well as high-dose RIS after estrogen depletion. [ABSTRACT FROM AUTHOR]

In a world where millions of people are dependent on batteries to provide them with convenient and portable energy, battery recycling is of the utmost importance. In this paper, we developed a new method to sort 18650 Lithium-ion batteries in large quantities and in real time for harvesting used cells with enough capacity for battery reuse. Internal resistance and capacity tests were conducted as a basis for comparison with a novel degradation-based method based on X-ray radiographic scanning and digital image contrast computation. The test results indicate that the sorting accuracy of the test cells is about 79% and the execution time of our algorithm is at a level of 200 milliseconds, making our method a potential real-time solution for reusing the remaining capacity in good used cells. [ABSTRACT FROM AUTHOR]

Small animal studies have demonstrated significant high-dose recombinant parathyroid hormone1-34 (rPTH1-34) effects on intercalary allograft healing. Towards a human adjuvant therapy to decrease non-unions, we evaluated rPTH1-34 safety and efficacy in a clinically relevant canine femoral allograft model. Adult female mongrel hounds (n = 20) received a 5cm mid-diaphyseal osteotomy reconstructed with a plated allograft, and were randomized to: 1) Placebo (n = 5; daily saline), 2) Continuous rPTH1-34 (n = 7; 5 μg/kg/day s.c. from day 1–55 post-op), or 3) Delayed rPTH1-34 (n = 8; 5 μg/kg/day s.c. from day 14–28 post-op). Safety was assessed by physical behavior and blood calcium monitoring. Cone beam CT (CB-CT) was performed on days 14, 28 and 56 post-op to assess 2D cortical healing, 3D bone volume, and Union Ratio. Biomechanical testing and dynamic histomorphometry were also performed. The high drug dose was poorly tolerated, as most dogs receiving rPTH1-34 had to be given intravenous saline, and one dog died from hypercalcemia. Continuous rPTH1-34 significantly increased 2D healing and callus volumes at 4-weeks versus Placebo, and sustained the significant increase in cortical union at 8-week (p<0.05). These rPTH1-34 effects were confirmed by histomorphometry, revealing significant increases in mineral apposition rates (MAR) on host bone and graft-host junctions (p<0.05). Delayed rPTH1-34 significantly increased callus volume and MAR at 8 weeks (p<0.05). Although no biomechanical differences were observed, as expected for early healing, the results demonstrated that 2D RUST scoring significantly correlated with torsional biomechanics (p<0.01). In conclusion, 8-weeks of intermittent high-dose rPTH1-34 treatment significantly increases callus formation and accelerates bony union of intercalary massive allografts in a clinically relevant canine model, but with serious side-effects from hypercalcemia. [ABSTRACT FROM AUTHOR]

Disease-mediated mosquitoes have been receiving much attention, as the World Health Organization recently declared the Zika virus a global public health emergency. Mosquitoes transmit pathogens that cause various tropical diseases including malaria, dengue fever and yellow fever as well as Zika virus. The vector efficiency of mosquitoes depends on their blood-feeding characteristics and the mechanics of their blood-sucking pump system, but only a few studies have attempted to investigate these key issues. In this study, we demonstrate the rapid and gluttonous liquid-feeding characteristics of Ae. albopictus which transmits Zika virus can be explained by similar proportion of two blood-sucking pumps and accelerated liquid intake driven by fast expanding of pumps. Our results provide insight into the vector efficiency of Ae. albopictus in terms of feeding velocity, pumping frequency, liquid-intake rate, and wall shear stress. [ABSTRACT FROM AUTHOR]

Objective: Various methods for radiation-dose calculation have been investigated over previous decades, focusing on the use of magnetic resonance imaging (MRI) only. The bulk-density-assignment method based on manual segmentation has exhibited promising results compared to dose-calculation with computed tomography (CT). However, this method cannot be easily implemented in clinical practice due to its time-consuming nature. Therefore, we investigated an automatic anatomy segmentation method with the intention of providing the proper methodology to evaluate synthetic CT images for a radiation-dose calculation based on MR images. Methods: CT images of 20 brain cancer patients were selected, and their MR images including T1-weighted, T2-weighted, and PETRA were retrospectively collected. Eight anatomies of the patients, such as the body, air, eyeball, lens, cavity, ventricle, brainstem, and bone, were segmented for bulk-density-assigned CT image (BCT) generation. In addition, water-equivalent CT images (WCT) with only two anatomies—body and air—were generated for a comparison with BCT. Histogram comparison and gamma analysis were performed by comparison with the original CT images, after the evaluation of automatic segmentation performance with the dice similarity coefficient (DSC), false negative dice (FND) coefficient, and false positive dice (FPD) coefficient. Results: The highest DSC value was 99.34 for air segmentation, and the lowest DSC value was 73.50 for bone segmentation. For lens segmentation, relatively high FND and FPD values were measured. The cavity and bone were measured as over-segmented anatomies having higher FPD values than FND. The measured histogram comparison results of BCT were better than those of WCT in all cases. In gamma analysis, the averaged improvement of BCT compared to WCT was measured. All the measured results of BCT were better than those of WCT. Therefore, the results of this study show that the introduced methods, such as histogram comparison and gamma analysis, are valid for the evaluation of the synthetic CT generation from MR images. Conclusions: The image similarity results showed that BCT has superior results compared to WCT for all measurements performed in this study. Consequently, more accurate radiation treatment for the intracranial regions can be expected when the proper image similarity evaluation introduced in this study is performed. [ABSTRACT FROM AUTHOR]

Purified myelin membranes (PMMs) are the starting material for biochemical analyses such as the isolation of detergent-insoluble glycosphingolipid-rich domains (DIGs), which are believed to be representatives of functional lipid rafts. The normal DIGs isolation protocol involves the extraction of lipids under moderate cooling. Here, we thus address the influence of cooling on the structure of PMMs and its sub-fractions. Thermodynamic and structural aspects of periodic, multilamellar PMMs are examined between 4°C and 45°C and in various biologically relevant aqueous solutions. The phase behavior is investigated by small-angle X-ray scattering (SAXS) and differential scanning calorimetry (DSC). Complementary neutron diffraction (ND) experiments with solid-supported myelin multilayers confirm that the phase behavior is unaffected by planar confinement. SAXS and ND consistently show that multilamellar PMMs in pure water become heterogeneous when cooled by more than 10–15°C below physiological temperature, as during the DIGs isolation procedure. The heterogeneous state of PMMs is stabilized in physiological solution, where phase coexistence persists up to near the physiological temperature. This result supports the general view that membranes under physiological conditions are close to critical points for phase separation. In presence of elevated Ca2+ concentrations (> 10 mM), phase coexistence is found even far above physiological temperatures. The relative fractions of the two phases, and thus presumably also their compositions, are found to vary with temperature. Depending on the conditions, an “expanded” phase with larger lamellar period or a “compacted” phase with smaller lamellar period coexists with the native phase. Both expanded and compacted periods are also observed in DIGs under the respective conditions. The observed subtle temperature-dependence of the phase behavior of PMMs suggests that the composition of DIGs is sensitive to the details of the isolation protocol. [ABSTRACT FROM AUTHOR]

Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on the impact of osteoporosis on peri-implant bone (re)modeling, which is ultimately responsible for the long term stability of the bone-implant system. Here, we inserted an implant in a mouse model mimicking estrogen deficiency-induced bone loss and we monitored with longitudinal in vivo micro-computed tomography the spatio-temporal changes in bone (re)modeling and architecture, considering the separate contributions of trabecular, endocortical and periosteal surfaces. Specifically, 12 week-old C57BL/6J mice underwent OVX/SHM surgery; 9 weeks after we inserted special metal-ceramics implants into the 6th caudal vertebra and we measured bone response with in vivo micro-CT weekly for the following 6 weeks. Our results indicated that ovariectomized mice showed a reduced ability to increase the thickness of the cortical shell close to the implant because of impaired peri-implant bone formation, especially at the periosteal surface. Moreover, we observed that healthy mice had a significantly higher loss of trabecular bone far from the implant than estrogen depleted animals. Such behavior suggests that, in healthy mice, the substantial increase in peri-implant bone formation which rapidly thickened the cortex to secure the implant may raise bone resorption elsewhere and, specifically, in the trabecular network of the same bone but far from the implant. Considering the already deteriorated bone structure of estrogen depleted mice, further bone loss seemed to be hindered. The obtained knowledge on the dynamic response of diseased bone following implant insertion should provide useful guidelines to develop advanced treatments for osteoporotic fracture fixation based on local and selective manipulation of bone turnover in the peri-implant region. [ABSTRACT FROM AUTHOR]

Propagation-based phase-contrast computed micro-tomography (PPCT) dominates the non-destructive, three-dimensional inner-structure measurement in synchrotron-based biomedical research due to its simple experimental setup. To quantitatively visualize tiny density variations in soft tissues and organs closely related to early pathological morphology, an experimental study of synchrotron-based X-ray PPCT combined with generalized phase and attenuation duality (PAD) phase retrieval was implemented with the hepatic echinococcosis (HE) infection rat model at different stages. We quantitatively analyzed and evaluated the different pathological characterizations of hepatic echinococcosis during the development of this disease via our PAD-based PPCT and especially provided evidence that hepatic alveolar echinococcosis invades the liver tissue and spreads through blood flow systems with abundant blood supply in the early stage. Additionally, the infiltration of tiny vesicles in HE lesions can be clearly observed by our PAD-PPCT technique due to the striking contrast-to-noise ratio (CNR) and mass density resolution, which cannot be found by the medical imaging techniques, such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound, in hospitals. The results demonstrated that our PAD-PPCT technique has a great potential for indicating the subtle structural information of pathological changes in soft biomedical specimens, especially helpful for the research of early micro-morphology of diseases. [ABSTRACT FROM AUTHOR]

BRIL (bone-restricted IFITM-like), is a short transmembrane protein expressed almost exclusively in osteoblasts. Although much is known about its bone-restricted gene expression pattern and protein biochemical and topological features, little information is available for BRIL physiological function. Two autosomal dominant forms of osteogenesis imperfecta (OI) are caused by distinct, but recurrent mutations in the BRIL gene. Yet, the underlying mechanisms by which those mutations lead to OI are still poorly understood. A previous report indicated that BRIL knockout (KO) mice had bone deformities, shortened long bones, and reproductive problems. Here we generated and systematically analyzed the skeletal phenotype of a new global Bril KO/LacZ knockin mouse model. KO mice reproduced and thrived normally up to 12 month of age. The skeletal phenotype of KO and WT littermates was assessed at embryonic (E13.5 to E18.5) and postnatal (2 days, 3 weeks, 3 months and 8 months) time-points. Embryos from E13.5 through to E18.5 showed significant X-Gal staining in all skeletal elements without any apparent patterning anomalies. Although bone deformities were never observed at any postnatal ages, minor and transient differences were noted in terms of bone length and static uCT parameters, but not systematically across all ages and genders. These changes, however, were not accompanied by significant alteration in bone material properties as assessed by a 3-point bending test. In addition, no changes were detected in circulating serum markers of bone turnover (P1NP, CTX-I, and osteocalcin). Gene expression monitoring also revealed no major impact of the loss of BRIL. Further, when mice were challenged with a surgically-induced fracture in tibia, bones repaired equally well in the KO mice as compared to WT. Finally, we showed that BRIL C-terminus is not a bona fide binding site for calcium. In conclusion, our in depth analysis suggest that skeletal patterning, bone mass accrual and remodeling in mice proceeded independent of BRIL. [ABSTRACT FROM AUTHOR]

Phase-contrast x-ray computed tomography (PCCT) is currently investigated as an interesting extension of conventional CT, providing high soft-tissue contrast even if examining weakly absorbing specimen. Until now, the potential for dose reduction was thought to be limited compared to attenuation CT, since meaningful phase retrieval fails for scans with very low photon counts when using the conventional phase retrieval method via phase stepping. In this work, we examine the statistical behaviour of the reverse projection method, an alternative phase retrieval approach and compare the results to the conventional phase retrieval technique. We investigate the noise levels in the projections as well as the image quality and quantitative accuracy of the reconstructed tomographic volumes. The results of our study show that this method performs better in a low-dose scenario than the conventional phase retrieval approach, resulting in lower noise levels, enhanced image quality and more accurate quantitative values. Overall, we demonstrate that the lower statistical limit of the phase stepping procedure as proposed by recent literature does not apply to this alternative phase retrieval technique. However, further development is necessary to overcome experimental challenges posed by this method which would enable mainstream or even clinical application of PCCT. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we investigated the correlation between fracture classification and secondary screw penetration. Methods: We retrospectively identified 189 patients with displaced proximal humeral fractures treated by ORIF at our hospital between June 2006 and June 2013. All fractures were classified radiographically before surgery and follow-up for least 2 years after surgery was recommended. At each follow-up, radiographs were taken in three orthogonal views to evaluate secondary screw penetration. Results: The study population consisted of 189 patients. Of these, 70 were male and 119 female, with a mean age of 59.1 years; the mean follow-up time was 28.5 months. Secondary screw penetration occurred in 26 patients. The risk of developing secondary screw penetration was 11.3-fold higher in four-part fractures than two-part fractures (P < 0.05), 8.6-fold higher for type C fractures than type A fractures (P < 0.05) and 11.0-fold higher for medial hinge disruption group than intact medial hinge group fractures (P < 0.05). However there was no difference between three-part fractures and two-part fractures (P = 0.374), and between type B and type A fractures (P = 0.195). Age, gender, time to surgery and the number of screw in humeral head had no influence on the secondary screw penetration rate (P > 0.05). Conclusions: Patients with four-part fractures, type C fractures and medial hinges disruption are vulnerable to secondary screw penetration. This allows additional precautions to be instituted and measures to be taken as needed. [ABSTRACT FROM AUTHOR]

Background The aim of this study is to propose a new method to quantify radioactivity with PET/CT imaging in mandibular extension in head and neck squamous cell carcinoma (HNSCC), using innovative software, and to compare results with microscopic surgical specimens. Patients and methods This prospective study enrolled 15 patients who underwent 18 F-NaF and 18 F-FDG PET/CT. We compared the delineations of bone invasions obtained with 18 F-NaF PET/CT and 18 F-FDG PET/CT with the results of histopathological analysis of mandibular resections (from right and left bone borders). A method for visualization and quantification of PET images was developed. Results For all patients, a significant difference ( p = 0.032 for right limits and p = 0.011 for left limits) was observed between 18 F-FDG PET/CT imaging and histopathology results, and no significant difference ( p = 0.88 for right limits and p = 0.55 for left limits) was observed between 18 F-NaF PET/CT imaging and histopathology results. The right limits were less than 10 mm in 93% of patients, and the left limits were less than 10 mm in 86% of patients. Conclusions The dedicated software enabled the objective delineation of radioactivity within the bone. We can confirm that 18 F-NaF is a precise and specific bone marker for the assessment of intraosseous mandibular extensions of head and neck cancers. Clinical question/level of evidence Therapeutic, III. [ABSTRACT FROM AUTHOR]

Objectives: The diagnosis of ossification of the posterior longitudinal ligament (OPLL) on magnetic resonance imaging (MRI) is challenging. The purpose of this study is to evaluate the usefulness of the multiecho fast field echo (mFFE) MRI in the detection of ossification of the posterior longitudinal ligament and dural ossification (DO) of the cervical spine. Methods: Sixty-three patients who underwent MRI with mFFE and CT for cervical spine were retrospectively evaluated. The presence of OPLL and DO on MR images was assessed by two independent readers. The sensitivity, specificity, and accuracy of MRI for detecting OPLL and DO were determined using CT as a reference standard. Image contrast ratios were obtained between the OPLL and perilesional structures on each sequence. Results: There were 31 patients with OPLL and 13 DO lesions. The mean sensitivity, specificity, and accuracy of both readers were 94%, 81%, 88% for OPLL and 92%, 81%, 86% for DO, respectively. The contrast ratios for OPLL and intervertebral disc, spinal cord and cerebrospinal fluid were significantly superior on mFFE images, whereas those for OPLL and bone marrow were significantly inferior on mFFE images than those of T1-and T2-weighted images (p ≤ 0.016). Conclusions: MRI with mFFE may be sufficient for the assessment of OPLL and DO, with good contrasts between OPLL and intervertebral disc, spinal cord, and cerebrospinal fluid. [ABSTRACT FROM AUTHOR]

Bone's microporosity plays important roles in bone biology and bone mechanical quality. In this study, we explored the accuracy and reproducibility of nondestructive desktop μCT for 3D visualization and subsequent morphometric analysis of mouse cortical bone microporosity including the vascular canal network and osteocyte lacunae. The accuracy of measurements was evaluated in five murine fibula using confocal laser scanning microscopy (CLSM) in conjunction with Fluorescein isothiocyanate (FITC) staining as the reference method. The reproducibility of μCT-derived cortical bone microstructural indices was examined in 10 fibulae of C57Bl/6J male mice at a nominal resolution of 700 nanometer. Three repeated measurements were made on different days. An excellent correlation between μCT and CLSM was observed for both mean lacuna volume (r = 0.98, p = 0.002) and for mean lacuna orientation (r = 0.93, p = 0.02). Whereas the two techniques showed no significant differences for these parameters, the mean lacuna sphericity acquired from μCT was significantly higher than CLSM (p = 0.01). Reproducibility was high, with precision errors (PE) of 1.57–4.69% for lacuna parameters, and of 1.01–9.45% for vascular canal parameters. Intraclass correlation coefficient (ICC) showed a high reliability of the measurements, ranging from 0.998–1.000 for cortical parameters, 0.973–0.999 for vascular canal parameters and 0.755–0.991 for lacuna parameters. In conclusion, desktop μCT is a valuable tool to quantify the 3D characteristics of bone vascular canals as well as lacunae which can be applied to intact murine bones with high accuracy and reproducibility. Thus, μCT might be an important tool to improve our understanding of the physiological and biomechanical significance of these cannular and lacunar structure in cortical bone. [ABSTRACT FROM AUTHOR]

Objective: Cartilage and subchondral bone form a functional unit. Here, we aimed to examine the effect of meniscus coverage on the characteristics of this unit in knees of older individuals. Methods: We assessed the hyaline cartilage, subchondral cortical plate (SCP), and subchondral trabecular bone in areas covered or uncovered by the meniscus from normal cadaver knees (without degeneration). Bone cores harvested from the medial tibial plateau at locations uncovered (central), partially covered (posterior), and completely covered (peripheral) by the meniscus were imaged by micro-CT. The following were measured on images: cartilage volume (Cart.Vol, mm3) and thickness (Cart.Th, mm); SCP thickness (SCP.Th, μm) and porosity (SCP.Por, %); bone volume to total volume fraction (BV/TV, %); trabecular thickness (Tb.Th, μm), spacing (Tb.Sp, μm), and number (Tb.N, 1/mm); structure model index (SMI); trabecular pattern factor (Tb.Pf); and degree of anisotropy (DA). Results: Among the 28 specimens studied (18 females) from individuals with mean age 82.8±10.2 years, cartilage and SCP were thicker at the central site uncovered by the meniscus than the posterior and peripheral sites, and Cart.Vol was greater. SCP.Por was highest in posterior samples. In the upper 1–5 mm of subchondral bone, central samples were characterized by higher values for BV/TV, Tb.N, Tb.Th, and connectivity (Tb.Pf), a more plate-like trabecular structure and lower anisotropy than with other samples. Deeper down, at 6–10 mm, the differences were slightly higher for Tb.Th centrally, DA peripherally and SMI posteriorly. Conclusions: The coverage or not by meniscus in the knee of older individuals is significantly associated with Cart.Th, SCP.Th, SCP.Por and trabecular microarchitectural parameters in the most superficial 5 mm and to a lesser extent the deepest area of subchondral trabecular bone. These results suggest an effect of differences in local loading conditions. In subchondral bone uncovered by the meniscus, the trabecular architecture resembles that of highly loaded areas. [ABSTRACT FROM AUTHOR]

A growing number of studies have investigated combination treatment as an approach to treat bone disease. The goal of this study was to investigate the combination of alendronate and raloxifene with a particular focus on mechanical properties. To achieve this goal we utilized a large animal model, the beagle dog, used previously by our laboratory to study both alendronate and raloxifene monotherapies. Forty-eight skeletally mature female beagles (1–2 years old) received daily oral treatment: saline vehicle (VEH), alendronate (ALN), raloxifene (RAL) or both ALN and RAL. After 6 and 12 months of treatment, all animals underwent assessment of bone material properties using in vivo reference point indentation (RPI) and skeletal hydration using ultra-short echo magnetic resonance imaging (UTE-MRI). End point measures include imaging, histomorphometry, and mechanical properties. Bone formation rate was significantly lower in iliac crest trabecular bone of animals treated with ALN (-71%) and ALN+RAL (-81%) compared to VEH. In vivo assessment of properties by RPI yielded minimal differences between groups while UTE-MRI showed a RAL and RAL+ALN treatment regimens resulted in significantly higher bound water compared to VEH (+23 and +18%, respectively). There was no significant difference among groups for DXA- or CT-based measures lumbar vertebra, or femoral diaphysis. Ribs of RAL-treated animals were smaller and less dense compared to VEH and although mechanical properties were lower the material-level properties were equivalent to normal. In conclusion, we present a suite of data in a beagle dog model treated for one year with clinically-relevant doses of alendronate and raloxifene monotherapies or combination treatment with both agents. Despite the expected effects on bone remodeling, our study did not find the expected benefit of ALN to BMD or structural mechanical properties, and thus the viability of the combination therapy remains unclear. [ABSTRACT FROM AUTHOR]

For accurate analysis of bone formation and resorption during fracture healing, correct registration of follow-up onto baseline image is required. A per-fragment approach could improve alignment compared to standard registration based on the whole fractured region. In this exploratory study, we tested the effect of fragment size and displacement on a per-fragment registration, and compared the results of this per-fragment registration to the results of the standard registration in two stable fractures and one unstable fracture. To test the effect of fragment size and displacement, high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of three unfractured radii were divided into subvolumes. Different displacements in x-, y, or z-direction or rotations around each axis were applied, and each subvolume was registered onto the initial volume to realign it. Next, registration of follow-up onto baseline scan was performed in two stable and one unstable fracture. After coarsely aligning the follow-up onto the baseline scan, a more accurate registration was performed of the whole fracture, i.e. the standard registration, and of each fracture fragment separately, i.e. per-fragment registration. Alignment was checked using overlay images showing baseline, follow-up and overlap between these scans, and by comparing correlation coefficients between the standard and per-fragment registration. Generally, subvolumes as small as 300 mm3 that were displaced up to 0.82 mm in x- or y-, or up to 1.64 mm in z-direction could be realigned correctly. For the fragments of all fractures, correlation coefficients were higher after per-fragment registration compared to standard registration. Most improvement was found in the unstable fracture and one fragment of the unstable fracture did not align correctly. This exploratory study showed that image registration of individual subvolumes, such as fracture fragments, is feasible in both stable and unstable fractures, and leads to better alignment of these fragments compared to an approach that is based on registration using the whole fractured region. This result is promising for additional analysis of bone formation and resorption in HR-pQCT studies on fracture healing. [ABSTRACT FROM AUTHOR]

X-ray tomography is a powerful tool giving access to the morphology of biofilms, in 3D porous media, at the mesoscale. Due to the high water content of biofilms, the attenuation coefficient of biofilms and water are very close, hindering the distinction between biofilms and water without the use of contrast agents. Until now, the use of contrast agents such as barium sulfate, silver-coated micro-particles or 1-chloronaphtalene added to the liquid phase allowed imaging the biofilm 3D morphology. However, these contrast agents are not passive and potentially interact with the biofilm when injected into the sample. Here, we use a natural inorganic compound, namely iron sulfate, as a contrast agent progressively bounded in dilute or colloidal form into the EPS matrix during biofilm growth. By combining a very long source-to-detector distance on a X-ray laboratory source with a Lorentzian filter implemented prior to tomographic reconstruction, we substantially increase the contrast between the biofilm and the surrounding liquid, which allows revealing the 3D biofilm morphology. A comparison of this new method with the method proposed by Davit et al (Davit et al., 2011), which uses barium sulfate as a contrast agent to mark the liquid phase was performed. Quantitative evaluations between the methods revealed substantial differences for the volumetric fractions obtained from both methods. Namely, contrast agent—biofilm interactions (e.g. biofilm detachment) occurring during barium sulfate injection caused a reduction of the biofilm volumetric fraction of more than 50% and displacement of biofilm patches elsewhere in the column. Two key advantages of the newly proposed method are that passive addition of iron sulfate maintains the integrity of the biofilm prior to imaging, and that the biofilm itself is marked by the contrast agent, rather than the liquid phase as in other available methods. The iron sulfate method presented can be applied to understand biofilm development and bioclogging mechanisms in porous materials and the obtained biofilm morphology could be an ideal basis for 3D numerical calculations of hydrodynamic conditions to investigate biofilm-flow coupling. [ABSTRACT FROM AUTHOR]

Objective: In adults, obesity has been associated with several health outcomes including increased bone density. Our objective was to evaluate the association between percent body fat and fat mass with bone mineral density (BMD) in a nationally representative population of children and adolescents. Study design: A total of 8,348 participants 8–18 years of age from the National Health and Nutrition Examination Survey (NHANES) 1999–2006 had whole body DXA scans performed. We conducted linear regressions to examine the relationship between percent body fat and fat mass with outcome variables of total body, pelvic and lumbar spine areal BMD (aBMD), controlling for lean body mass and assessing for gender and race/ethnicity interactions. Results: We found evidence of gender and race/ethnicity interactions with percent body fat and total fat mass for the different BMD areas. Generally, there were decreases in total body aBMD (p<0.001) and lumbar spine aBMD (p<0.001) with increasing percent body fat and total fat mass, with less consistent patterns for pelvic aBMD. Conclusion: Our findings of regional differences in the relationship of adiposity to aBMD in children and adolescents with significant interactions by gender and race/ethnicity emphasizes the need for further investigations to understand the impact of adiposity on bone health outcomes. [ABSTRACT FROM AUTHOR]

The estimation of local and structural mechanical properties of bones with micro Finite Element (microFE) models based on Micro Computed Tomography images depends on the quality bone geometry is captured, reconstructed and modelled. The aim of this study was to validate microFE models predictions of local displacements for vertebral bodies and to evaluate the effect of the elastic tissue modulus on model’s predictions of axial forces. Four porcine thoracic vertebrae were axially compressed in situ, in a step-wise fashion and scanned at approximately 39μm resolution in preloaded and loaded conditions. A global digital volume correlation (DVC) approach was used to compute the full-field displacements. Homogeneous, isotropic and linear elastic microFE models were generated with boundary conditions assigned from the interpolated displacement field measured from the DVC. Measured and predicted local displacements were compared for the cortical and trabecular compartments in the middle of the specimens. Models were run with two different tissue moduli defined from microindentation data (12.0GPa) and a back-calculation procedure (4.6GPa). The predicted sum of axial reaction forces was compared to the experimental values for each specimen. MicroFE models predicted more than 87% of the variation in the displacement measurements (R2 = 0.87–0.99). However, model predictions of axial forces were largely overestimated (80–369%) for a tissue modulus of 12.0GPa, whereas differences in the range 10–80% were found for a back-calculated tissue modulus. The specimen with the lowest density showed a large number of elements strained beyond yield and the highest predictive errors. This study shows that the simplest microFE models can accurately predict quantitatively the local displacements and qualitatively the strain distribution within the vertebral body, independently from the considered bone types. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the population’s awareness about the radiation exposure associated with five specific imaging tests, and their preference regarding three different formats for receiving the information before undergoing an imaging test. Methods: A quantitative and qualitative evaluation through a survey and focal groups including general population from two health departments in Spain. The sampling was carried out in stages (according to health department size) and stratified by age and sex, to get a representative sample. We randomly selected the participants from these stages to be contacted by telephone by a trained nurse. Oral informed consent was obtained. Results: Of 602 participants in the quantitative survey, 418 (70.3%) stated that they were aware of the risk associated with radiation. While the majority of these 418 participants knew that x-rays involve radiation (85.4%), fewer were aware that CT (42%) and mammography (38%) also involve radiation, and a substantial proportion believed, incorrectly, that MRI (38%) and ultrasound (18.4%) expose patients to radiation. The population preference was to receive the information using both oral and written formats, accompanied by a table showing the equivalence of the radiation associated with the imaging test to either a number of chest X-rays and exposure number of days of background radiation. Discussion: The general population does not receive enough information regarding radiation exposure and the associated risks related to imaging tests. Initiatives should be designed to reinforce the patient’s awareness when ordering a diagnostic imaging test. [ABSTRACT FROM AUTHOR]

Background and objectives: In dialysis patients, there is an increasing evidence that altered bone metabolism is associated with cardiovascular calcifications. The main objective of this study was to analyse, in hemodialysis patients, the relationships between bone turnover, mineralization and volume, evaluated in bone biopsies, with a plain X-ray vascular calcification score. Design, setting, participants and measurements: In a cross-sectional study, bone biopsies and evaluation of vascular calcifications were performed in fifty hemodialysis patients. Cancellous bone volume, mineralized bone volume, osteoid volume, activation frequency, bone formation rate/bone surface, osteoid thickness and mineralization lag time were determined by histomorphometry. Vascular calcifications were assessed by the simple vascular calcification score (SVCS) in plain X-Ray of pelvis and hands and, for comparison, by the Agatston score in Multi-Slice Computed Tomography (MSCT). Results: SVCS≥3 was present in 20 patients (40%). Low and high bone turnover were present in 54% and 38% of patients, respectively. Low bone volume was present in 20% of patients. In multivariable analysis, higher age (p = 0.015) and longer hemodialysis duration (p = 0.017) were associated with SVCS≥3. Contrary to cancellous bone volume, the addition to this model of mineralized bone volume (OR = 0.863; 95%CI: 0.766, 0.971; p = 0.015), improved the performance of the model. For each increase of 1% in mineralized bone volume there was a 13.7% decrease in the odds of having SVCS≥3 (p = 0.015). An Agatston score>400 was observed in 80% of the patients with a SVCS≥3 versus 4% of patients with a SVCS<3, (p<0.001). Conclusion: Higher mineralized bone volume was associated with a lower plain X-ray vascular calcification. This study corroborates the hypothesis of the existence of a link between bone and vessel and reinforces the clinical utility of this simple and inexpensive vascular calcification score in dialysis patients. [ABSTRACT FROM AUTHOR]

Background: Professional dancers are at risk of developing low bone mineral density (BMD). However, whether low BMD phenotypes already exist in pre-vocational dance students is relatively unknown. Aim: To cross-sectionally assess bone mass parameters in female dance students selected for professional dance training (first year vocational dance students) in relation to aged- and sex-matched controls. Methods: 34 female selected for professional dance training (10.9yrs ±0.7) and 30 controls (11.1yrs ±0.5) were examined. Anthropometry, pubertal development (Tanner) and dietary data (3-day food diary) were recorded. BMD and bone mineral content (BMC) at forearm, femur neck (FN) and lumbar spine (LS) were assessed using Dual-Energy X-Ray Absorptiometry. Volumetric densities were estimated by calculating bone mineral apparent density (BMAD). Results: Dancers were mainly at Tanner pubertal stage I (vs. stage IV in controls, p<0.001), and demonstrated significantly lower body weight (p<0.001) and height (p<0.01) than controls. Calorie intake was not different between groups, but calcium intake was significantly greater in dancers (p<0.05). Dancers revealed a significantly lower BMC and BMD values at all anatomical sites (p<0.001), and significantly lower BMAD values at the LS and FN (p<0.001). When adjusted for covariates (body weight, height, pubertal development and calcium intake), dance students continued to display a significantly lower BMD and BMAD at the FN (p<0.05; p<0.001) at the forearm (p<0.01). Conclusion: Before undergoing professional dance training, first year vocational dance students demonstrated inferior bone mass compared to controls. Longitudinal models are required to assess how bone health-status changes with time throughout professional training. [ABSTRACT FROM AUTHOR]

Introduction: Omeprazole (OP) is one the proton pump inhibitor (PPI) agents, and available over the counter in generic formulations. Epidemiological investigations have been confirmed a relationship between long term use of PPI agents and bone metabolism. Bone scintigraphy is commonly used for analysing the bone metabolism in clinical practice. This study was conducted to assess the effect of omeprazole on the sensitivity of bone imaging to distinguish simulated closed fracture in the rat's foot. Methods: A total number of 32 adult, male NMRI were chosen. The animals were divided into two principle groups equally for four and eight weeks experiment. Each group was equally divided into four groups. These subgroups included the standard or control rats (4W S and 8W S) not receiving omeprazole and the others that received 25 (4W OP 25 and 8W OP 25), 50 (4W OP 50 and 8W OP 50), 100 (4W OP 100 and 8W OP 100) mg/kg of the drug. Reproducible closed fracture was created in the rat's foot after 4 and 8 weeks of experiments. Radioisotope studies have been undertaken. Results: All closed fractures created in the feet of animals were visualized by images. The radiotracer uptake ratio at affected foot (target) versus contralateral healthy foot (non-target) was not influenced by omeprazole in the different animal groups. The quantitative investigation indicated that biodistribution of radiotracer was not affected by omeprazole in the other parts of the skeleton. Conclusion: Radioisotope imaging by 99mTc-MDP is sensitive modality to identify the occult fracture and is not affected by omeprazole. [ABSTRACT FROM AUTHOR]

One consequence of demographic change is the increasing demand for biocompatible materials for use in implants and prostheses. This is accompanied by a growing number of experimental animals because the interactions between new biomaterials and its host tissue have to be investigated. To evaluate novel materials and engineered tissues the use of non-destructive imaging modalities have been identified as a strategic priority. This provides the opportunity for studying interactions repeatedly with individual animals, along with the advantages of reduced biological variability and decreased number of laboratory animals. However, histological techniques are still the golden standard in preclinical biomaterial research. The present article demonstrates a detailed method comparison between histology and magnetic resonance imaging. This includes the presentation of their image qualities as well as the detailed statistical analysis for assessing agreement between quantitative measures. Exemplarily, the bony ingrowth of tissue engineered bone substitutes for treatment of a cleft-like maxillary bone defect has been evaluated. By using a graphical concordance analysis the mean difference between MRI results and histomorphometrical measures has been examined. The analysis revealed a slightly but significant bias in the case of the bone volume and a clearly significant deviation for the remaining defect width But the study although showed a considerable effect of the analyzed section position to the quantitative result. It could be proven, that the bias of the data sets was less originated due to the imaging modalities, but mainly on the evaluation of different slice positions. The article demonstrated that method comparisons not always need the use of an independent animal study, additionally. [ABSTRACT FROM AUTHOR]

Objective: This study presents national surveys of patient exposure from nuclear medicine (NM) diagnostic procedures in 2010 and 2015 in the Republic of Croatia. Methods: The survey was performed according to the European Commission Dose DataMed (DDM) project methodology. 28 most frequent NM diagnostic procedures were identified. Data about frequencies of procedures and average administered activities of radioisotopes used in those procedures were collected. Average administered activities were converted to effective doses according to the dose conversion coefficients. Then the collective effective dose to the population and an effective dose per capita were calculated based on the number of the most frequent NM diagnostic procedures and the average effective dose per procedure. Results: In 2010, 41200 NM diagnostic procedures led to 146.7 manSv collective effective dose to the population and in 2015, 42000 NM diagnostic procedures led to 146.8 manSv collective effective dose to the population. The frequencies of NM diagnostic procedures were 9.7 and 9.8 annually per 1000 population with 34.1 μSv and 34.2 μSv effective dose per capita for 2010 and 2015, respectively. The main contributors to the annual collective dose from NM in Croatia are examinations of the bone, heart, thyroid and PET/CT tumour diagnostic. Average administered activities have not changed considerably from 2010 to 2015. Nevertheless, within the frequency of some of the procedures, significant changes were found in five-year period. Conclusions: Frequencies, average administered activities and collective effective dose to the population from NM diagnostic procedures in Croatia are comparable to the values reported by other European surveys. Changes were found between 2010 and 2015 and we intend to perform this study periodically to identify possible trends, but also to raise awareness about the potential dose optimization. [ABSTRACT FROM AUTHOR]

Exploring the effect of non-impact and impact sports is particular relevant to understand the interaction between skeletal muscle and bone health during growth. The current study aimed to compare total and regional bone and soft-tissue composition, in parallel to measurements of blood lipid and inflammatory profiles between adolescent athletes and non-athletes. Anthropometry, biological maturity, dual energy X-ray absorptiometry (DXA) scans, training load and lipid and inflammatory profiles were assessed in a cross-sectional sample of 53 male adolescents (20 non-athletes, 15 swimmers and 18 basketball players) aged 12–19 years. Multiple comparisons between groups were performed using analysis of variance, covariance and magnitude effects (ES-r and Cohen’s d). The comparisons of controls with other groups were very large for high-sensitivity C-reactive protein (d range: 2.17–2.92). The differences between sports disciplines, regarding tissue outputs obtained from DXA scan were moderate for all variables except fat tissue (d = 0.4). It was possible to determine small differences (ES-r = 0.17) between controls and swimmers for bone area at the lower limbs (13.0%). In parallel, between swimmers and basketball players, the gradient of the differences was small (ES-r range: 0.15–0.23) for bone mineral content (24.6%), bone area (11.3%) and bone mineral density (11.1%) at the lower limbs, favoring the basketball players. These observations highlight that youth male athletes presented better blood and soft tissues profiles with respect to controls. Furthermore, sport-specific differences emerged for the lower limbs, with basketball players presenting higher bone mineral content, area and density than swimmers. [ABSTRACT FROM AUTHOR]

Design: Observational cross-sectional study. The current study aims to yield normative data: i.e., the physiological standard for 30 selected quantitative 3D parameters that accurately capture and describe a full-skeleton, upright-standing attitude. Specific and exclusive consideration was given to three distinct categories: postural, spine morphology and pelvic parameters. To capture such 3D parameters, the authors selected a non-ionising 3D opto-electronic stereo-photogrammetric approach. This required the identification and measurement of 27 body landmarks, each specifically tagged with a skin marker. As subjects for the measurement of these parameters, a cohort of 124 asymptomatic young adult volunteers was recruited. All parameters were identified and measured within this group. Postural and spine morphology data have been compared between genders. In this regard, only five statistically significant differences were found: pelvis width, pelvis torsion, the “lumbar” lordosis angle value, the lumbar curve length, and the T12-L5 anatomically-bound lumbar angle value. The “thoracic” kyphosis mean angle value was the same in both sexes and, even if, derived from skin markers placed on spinous processes it resulted in perfect agreement with the X-ray based literature. As regards lordosis, a direct comparison was more difficult because methods proposed in the literature differ as to the number and position of vertebrae under consideration, and their related angle values. However, when the L1 superior–L5 inferior end plate Cobb angle was considered, these results aligned strongly with the existing literature. Asymmetry was a standard postural-spinal feature for both sexes. Each subject presented some degree of leg length discrepancy (LLD) with μ = 9.37mm. This was associated with four factors: unbalanced posture and/or underfoot loads, spinal curvature in the frontal plane, and pelvis torsion. This led to the additional study of the effect of LLD equalisation influence on upright posture, relying on a sub-sample of 100 subjects (51 males, 49 females). As a result of the equalisation, about 82% of this sub-sample showed improvement in standing posture, mainly in the frontal plane; while in the sagittal plane less than 1/3 of the sub-sample showed evidence of change in spinal angles. A significant variation was found in relation to pelvis torsion: 46% of subjects showed improvement, 49% worsening. The method described in study presents several advantages: non-invasive aspect; relatively short time for a complete postural evaluation with many clinically useful 3D and 2D anatomical/biomechanical/clinical parameters; analysis of real neutral unconstrained upright standing posture. [ABSTRACT FROM AUTHOR]

We propose a novel metal artifact reduction (MAR) algorithm for CT images that completes a corrupted sinogram along the metal trace region. When metal implants are located inside a field of view, they create a barrier to the transmitted X-ray beam due to the high attenuation of metals, which significantly degrades the image quality. To fill in the metal trace region efficiently, the proposed algorithm uses multiple prior images with residual error compensation in sinogram space. Multiple prior images are generated by applying a recursive active contour (RAC) segmentation algorithm to the pre-corrected image acquired by MAR with linear interpolation, where the number of prior image is controlled by RAC depending on the object complexity. A sinogram basis is then acquired by forward projection of the prior images. The metal trace region of the original sinogram is replaced by the linearly combined sinogram of the prior images. Then, the additional correction in the metal trace region is performed to compensate the residual errors occurred by non-ideal data acquisition condition. The performance of the proposed MAR algorithm is compared with MAR with linear interpolation and the normalized MAR algorithm using simulated and experimental data. The results show that the proposed algorithm outperforms other MAR algorithms, especially when the object is complex with multiple bone objects. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate if the new Discovery Molecular Insights (DMI) PET/CT scanner provides equivalent results compared to the standard of care PET/CT scanners (GE Discovery 600 or GE Discovery 690) used in our clinic and to explore any possible differences in semi-quantitative measurements. Methods: The local Institutional Review Board approved the protocol and written informed consent was obtained from each patient. Between September and November 2016, 50 patients underwent a single 18F-FDG injection and two scans: the clinical standard PET/CT followed immediately by the DMI PET/CT scan. We measured SUVmax and SUVmean of different background organs and up to four lesions per patient from data acquired using both scanners. Results: DMI PET/CT identified all the 107 lesions detected by standard PET/CT scanners, as well as additional 37 areas of focal increased 18F-FDG uptake. The SUVmax values for all 107 lesions ranged 1.2 to 14.6 (mean ± SD: 2.8 ± 2.8), higher on DMI PET/CT compared with standard of care PET/CT. The mean lesion:aortic arch SUVmax ratio and mean lesion:liver SUVmax ratio were 0.2–15.2 (mean ± SD: 3.2 ± 2.6) and 0.2–8.5 (mean ± SD: 1.9 ± 1.4) respectively, higher on DMI PET/CT than standard PET/CT. These differences were statistically significant (P value < 0.0001) and not correlated to the delay in acquisition of DMI PET data (P < 0.0001). Conclusions: Our study shows high performance of the new DMI PET/CT scanner. This may have a significant role in diagnosing and staging disease, as well as for assessing and monitoring responses to therapies. [ABSTRACT FROM AUTHOR]

Ultrasound (US) imaging of an infant's hip joint is widely used for early detection of developmental dysplasia of the hip. In current US-based diagnosis of developmental dysplasia of the hip, trained clinicians acquire US images and, if they judge them to be adequate (i.e., to contain relevant hip joint structures), analyze them manually to extract clinically useful dysplasia metrics. However, both the scan adequacy classification and dysplasia metrics extraction steps exhibit significant variability within and between both clinicians and institutions, which can result in significant over- and undertreatment rates. To reduce the subjectivity resulting from this variability, we propose a computational image analysis technique that automatically identifies adequate images and subsequently extracts dysplasia metrics from these 2-D US images. Our automatic method uses local phase symmetry-based image measures to robustly identify intensity-invariant geometric features of bone/cartilage boundaries from the US images. Using the extracted geometric features, we trained a random forest classifier to classify images as adequate or inadequate, and in the adequate images we used a subset of the geometric features to calculate key dysplasia metrics. We validated our method on a data set of 693 US scans collected from 35 infants. Our approach produces excellent agreement with clinician adequacy classifications (area under the receiver operating characteristic curve = 0.985) and in reducing variability in the measured developmental dysplasia of the hip metrics (p < 0.05). The automatically computed dysplasia metrics appear to be slightly biased toward higher Graf categories than the manually estimated metrics, which could potentially reduce missed early diagnoses. [ABSTRACT FROM AUTHOR]

Hip Osteoarthritis (OA) is a common disease among the middle-aged and elderly people. Conventionally, hip OA is diagnosed by manually assessing X-ray images. This study took the hip joint as the object of observation and explored the diagnostic value of deep learning in hip osteoarthritis. A deep convolutional neural network (CNN) was trained and tested on 420 hip X-ray images to automatically diagnose hip OA. This CNN model achieved a balance of high sensitivity of 95.0% and high specificity of 90.7%, as well as an accuracy of 92.8% compared to the chief physicians. The CNN model performance is comparable to an attending physician with 10 years of experience. The results of this study indicate that deep learning has promising potential in the field of intelligent medical image diagnosis practice. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the setup discrepancy between BrainLAB 6 degree-of-freedom (6D) ExacTrac and cone-beam computed tomography (CBCT) used with the imaging guidance system Novalis Tx for intracranial stereotactic radiosurgery. We included 107 consecutive patients for whom white stereotactic head frame masks (R408; Clarity Medical Products, Newark, OH) were used to fix the head during intracranial stereotactic radiosurgery, between August 2012 and July 2016. The patients were immobilized in the same state for both the verification image using 6D ExacTrac and online 3D CBCT. In addition, after radiation treatment, registration between the computed tomography simulation images and the CBCT images was performed with offline 6D fusion in an offline review. The root-mean-square of the difference in the translational dimensions between the ExacTrac system and CBCT was <1.01 mm for online matching and <1.10 mm for offline matching. Furthermore, the root-mean-square of the difference in the rotational dimensions between the ExacTrac system and the CBCT were <0.82° for online matching and <0.95° for offline matching. It was concluded that while the discrepancies in residual setup errors between the ExacTrac 6D X-ray and the CBCT were minor, they should not be ignored. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop a flexible and free image processing and analysis solution, based on the Public Domain ImageJ platform, for the segmentation and analysis of complex biological plant root systems in soil from x-ray tomography 3D images. Contrasting root architectures from wheat, barley and chickpea root systems were grown in soil and scanned using a high resolution micro-tomography system. A macro (Root1) was developed that reliably identified with good to high accuracy complex root systems (10% overestimation for chickpea, 1% underestimation for wheat, 8% underestimation for barley) and provided analysis of root length and angle. In-built flexibility allowed the user interaction to (a) amend any aspect of the macro to account for specific user preferences, and (b) take account of computational limitations of the platform. The platform is free, flexible and accurate in analysing root system metrics. [ABSTRACT FROM AUTHOR]

Introduction: Osteochondral allograft (OCA) transplantation is generally effective for treating large cartilage lesions. Cleansing OCA subchondral bone to remove donor marrow elements is typically performed with pulsed lavage. However, the effects of clinical and experimental parameters on OCA marrow removal by pulsed lavage are unknown. The aim of the current study was to determine the effects on marrow cleansing in human osteochondral cores (OCs) of (1) lavage duration, (2) lavage flow intensity, and (3) OC sample type and storage condition. Methods: OCs were harvested from human femoral condyles and prepared to a clinical geometry (cylinder, diameter = 20 mm). The OCs were from discarded remnants of llograft tissues (OC) or osteoarthritis patients undergoing otal Knee Replacement (OC). The experimental groups subjected to standard flow lavage for 45 seconds (430 mL of fluid) and 120 seconds (1,150 mL) were (1) OCT/FROZEN (stored at -80°C), (2) OCT/FRESH (stored at 4°C), and (3) OCA/FRESH. The OCA/FRESH group was subsequently lavaged at high flow for 45 seconds (660 mL) and 120 seconds (1,750 mL). Marrow cleansing was assessed grossly and by micro-computed tomography (μCT). Results: Gross and μCT images indicated that marrow cleansing progressed from the OC base toward the cartilage. Empty marrow volume fraction (EMa.V/Ma.V) increased between 0, 45, and 120 seconds of standard flow lavage, and varied between groups, being higher after FROZEN storage (86–92% after 45–120 seconds) than FRESH storage of either OCT or OCA samples (36% and 55% after 45 and 120 seconds, respectively). With a subsequent 120 seconds of high flow lavage, EMa.V/Ma.V of OCA/FRESH samples increased from 61% to 78%. Conclusions: The spatial and temporal pattern of marrow space clearance was consistent with gradual fluid-induced extrusion of marrow components. Pulsed lavage of OCAs with consistent time and flow intensity will help standardize marrow cleansing and may improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Core decompression is an efficient treatment for early stage ischemic necrosis of the femoral head. In conventional procedures, the pre-operative X-ray only shows one plane of the ischemic area, which often results in inaccurate drilling. This paper introduces a new method that uses computer-assisted technology and rapid prototyping to enhance drilling accuracy during core decompression surgeries and presents a validation study of cadaveric tests. Methods: Twelve cadaveric human femurs were used to simulate early-stage ischemic necrosis. The core decompression target at the anterolateral femoral head was simulated using an embedded glass ball (target). Three positioning Kirschner wires were drilled into the top and bottom of the large rotor. The specimen was then subjected to computed tomography (CT). A CT image of the specimen was imported into the Mimics software to construct a three-dimensional model including the target. The best core decompression channel was then designed using the 3D model. A navigational template for the specimen was designed using the Pro/E software and manufactured by rapid prototyping technology to guide the drilling channel. The specimen-specific navigation template was installed on the specimen using positioning Kirschner wires. Drilling was performed using a guide needle through the guiding hole on the templates. The distance between the end point of the guide needle and the target was measured to validate the patient-specific surgical accuracy. Results: The average distance between the tip of the guide needle drilled through the guiding template and the target was 1.92±0.071 mm. Conclusions: Core decompression using a computer-rapid prototyping template is a reliable and accurate technique that could provide a new method of precision decompression for early-stage ischemic necrosis. [ABSTRACT FROM AUTHOR]

Background: Age-related chronic diseases are prevalent in HIV-infected persons in the antiretroviral therapy (ART) era. Bone mineral density (BMD) loss and emphysema have separately been shown to occur at a younger age and with lesser risk exposure in HIV-infected compared to HIV-uninfected individuals. In non-HIV infected smokers, emphysema has been shown to independently predict low BMD. We hypothesized that emphysema would independently associate with thoracic vertebral bone attenuation, a surrogate for bone mineral density, in HIV-infected individuals. Methods: Clinical, pulmonary function, and radiographic data were analyzed for 164 individuals from the University of Pittsburgh’s HIV Lung Research Center cohort. Chest CT scans were used to quantify emphysema and compute Hounsfield Unit (HU) attenuation of the 4th, 7th, and 10th thoracic vertebrae. The association between mean HU attenuation values across the three vertebrae and radiographic emphysema, age, sex, body mass index (BMI), steroid use, viral load, CD4 count, and forced expiratory volume in the first second (FEV1) was assessed by univariate and multivariate analyses. Results: In univariate analysis, mean HU attenuation decreased with increasing age (p<0.001), pack years (p = 0.047), and percent emphysema (p<0.001). In a multivariable model, including pack years, age, sex, ART and steroid use, greater emphysema was independently associated with this surrogate marker of BMD in HIV-infected individuals (p = 0.034). Conclusions: The association of emphysema with thoracic bone attenuation in HIV-infected individuals is consistent with previous reports in non-HIV infected smokers. These findings suggest that emphysema should be considered a potential marker of osteoporosis risk in HIV-infected individuals. [ABSTRACT FROM AUTHOR]

Objectives: To introduce a fully-automated algorithm for the detection of small cortical interruptions (≥0.246mm in diameter) on high resolution peripheral quantitative computed tomography (HR-pQCT) images, and to investigate the additional value of manual correction of the automatically obtained contours (semi-automated procedure). Methods: Ten metacarpophalangeal joints from seven patients with rheumatoid arthritis (RA) and three healthy controls were imaged with HR-pQCT. The images were evaluated by an algorithm according to the fully- and semi-automated procedure for the number and surface of interruptions per joint. Reliability between the fully- and semi-automated procedure and between two independent operators was tested using intra-class correlation coefficient (ICC) and the proportion of matching interruptions. Validity of single interruptions detected was tested by comparing it to visual scoring, as gold standard. The positive predictive value (PPV) and sensitivity were calculated. Results: The median number of interruptions per joint was 14 (range 2 to 59) and did not significantly differ between the fully- and semi-automated procedure (p = 0.37). The median interruption surface per joint was significantly higher with the fully- vs. semi-automated procedure (respectively, 8.6mm2 vs. 5.8mm2 and 6.1mm2, p = 0.01). Reliability was almost perfect between the fully- and semi-automated procedure for both the number and surface of interruptions (ICC≥0.95) and the proportion of matching interruptions was high (≥76%). Also the inter-operator reliability was almost perfect (ICC≥0.97, proportion of matching interruptions 92%). The PPV ranged from 27.6% to 29.9%, and sensitivity from 69.7% to 76.3%. Most interruptions detected with the algorithm, did show an interruption on a 2D grayscale image. However, this interruption did not meet the criteria of an interruption with visual scoring. Conclusion: The algorithm for HR-pQCT images detects cortical interruptions, and its interruption surface. Reliability and validity was comparable for the fully- and semi-automated procedures. However, we advise the use of the semi-automated procedure to assure quality. The algorithm is a promising tool for a sensitive and objective assessment of cortical interruptions in finger joints assessed by HR-pQCT. [ABSTRACT FROM AUTHOR]

There is growing evidence that body shape and regional body composition are strong indicators of metabolic health. The purpose of this study was to develop statistical models that accurately describe holistic body shape, thickness, and leanness. We hypothesized that there are unique body shape features that are predictive of mortality beyond standard clinical measures. We developed algorithms to process whole-body dual-energy X-ray absorptiometry (DXA) scans into body thickness and leanness images. We performed statistical appearance modeling (SAM) and principal component analysis (PCA) to efficiently encode the variance of body shape, leanness, and thickness across sample of 400 older Americans from the Health ABC study. The sample included 200 cases and 200 controls based on 6-year mortality status, matched on sex, race and BMI. The final model contained 52 points outlining the torso, upper arms, thighs, and bony landmarks. Correlation analyses were performed on the PCA parameters to identify body shape features that vary across groups and with metabolic risk. Stepwise logistic regression was performed to identify sex and race, and predict mortality risk as a function of body shape parameters. These parameters are novel body composition features that uniquely identify body phenotypes of different groups and predict mortality risk. Three parameters from a SAM of body leanness and thickness accurately identified sex (training AUC = 0.99) and six accurately identified race (training AUC = 0.91) in the sample dataset. Three parameters from a SAM of only body thickness predicted mortality (training AUC = 0.66, validation AUC = 0.62). Further study is warranted to identify specific shape/composition features that predict other health outcomes. [ABSTRACT FROM AUTHOR]

Nanoscale studies of bone provide key indicators to evidence subtle structural changes that may occur in the biomedical, forensic and archaeological contexts. One specific problem encountered in all those disciplines, for which the identification of nanostructural cues could prove useful, is to properly monitor the effect of heating on bone tissue. In particular, the mechanisms at work at the onset of heating are still relatively unclear. Using a multiscale approach combining Raman microspectroscopy, transmission electron microscopy (TEM), synchrotron quantitative scanning small-angle X-ray scattering imaging (qsSAXSI) and polarized light (PL) microscopy, we investigate the ultrastructure of cortical bovine bone heated at temperatures < 300°C, from the molecular to the macroscopic scale. We show that, despite limited changes in crystal structure, the mineral nanoparticles increase in thickness and become strongly disorganized upon heating. Furthermore, while the nanostructure in distinct anatomical quadrants appears to be statistically different, our results demonstrate this stems from the tissue histology, i.e. from the high degree of heterogeneity of the microstructure induced by the complex cellular processes involved in bone tissue formation. From this study, we conclude that the analysis of bone samples based on the structure and organization of the mineral nanocrystals requires performing measurements at the histological level, which is an advantageous feature of qsSAXSI. This is a critical aspect that extends to a much broader range of questions relating to nanoscale investigations of bone, which could also be extended to other classes of nanostructured heterogeneous materials. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the usefulness of cone-beam computed tomography with automated bone subtraction (CBCT-ABS) in the preoperative embolization of hypervascular tumors located in the pelvic bone. Materials and methods: This retrospective study included 26 patients with pelvic bone tumors who underwent preoperative embolization between January 2014 and October 2016. A CBCT-ABS scan was taken in a total of 17 patients (CBCT-ABS group), and only a series of digital subtraction angiographies (DSAs) was taken in the remaining 9 patients (DSA group). The percent devascularization, number of angiographic runs, total dose-area product (DAP), fluoroscopy time, interventional procedure time, operative time, and estimated blood loss were compared between the two groups using Mann-Whitney test. Results: The percent devascularization, interventional procedure time, fluoroscopy time, operative time, and estimated blood loss were not statistically different between the two groups (p > 0.05). On the other hand, the number of angiographic runs in the CBCT-ABS group was significantly lower than that in the DSA group (p = 0.029). The total DAP of the CBCT-ABS group (mean, 17700.7 μGym2) was higher than that of the DSA group (mean, 8939.4 μGym2) (p = 0.002). Conclusions: The use of CBCT-ABS during the preoperative embolization of pelvic bone tumors significantly reduces the number of angiographic runs at the cost of an increased radiation dose. [ABSTRACT FROM AUTHOR]

Object: To compare the clinical efficacy of titanium mesh cages and autogenous iliac bone graft to restore vertebral height through posterior approach in patients with thoracic and lumbar spinal tuberculosis. Method: 59 patients with spinal tuberculosis underwent interbody fusion and internal fixation through posterior approach in our department from January 2011 to December 2013. In group A, 34 patients obtained titanium mesh for the reconstruction of vertebral height, among them 25 patients (group A1) suffered from single-segment spinal tuberculosis, and 9 patients, (group A2) had multi-segment spinal tuberculosis. In group B, 25 patients got autogenous iliac bone graft to restore vertebral height, including 24 patients with single-segment spinal tuberculosis (group B1), and 1 patient with multi-segment spinal tuberculosis (group B2). The clinical efficacy was evaluated based on average operation time, blood loss, hospital stays, hospitalization expenses, visual analog scale (VAS), Oswestry Disability Index (ODI), erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), neurological function recovery, bony fusion, intervertebral height, Cobb angle and postoperative complications. Results: Final follow-up time was an average of 35.5 months ranging from 15 to 56 months. All patients were completely cured and obtained solid bone fusion. The bony fusion time was 9.4±6.1 months in group A1, 10.2±2.7 months in group A2 and 8.7±3.6 months in group B1. There were no significant difference among three groups (P>0.05). The Cobb correction and restoration of intervertebral height significantly improved compared with those in preoperation, but without significant difference among three groups (P>0.05). The loss of angular correction and intervertebral height in group A1 were found to be less than those in group B1 (P<0.05), but with no significant difference between group A1 and group A2, and between group A2 and group B1 (P>0.05). Patients in group B1 got the most loss of angular correction and intervertebral height. In addition, neurological function was revealed to be significantly improved after surgery. There were significant differences of VAS, ODI, ESR and CRP between preoperation and postoperation at the final follow-up time (P<0.05), with no significant difference among three groups (P>0.05). No statistically significant difference was found when analyzing blood loss, hospital stays, hospitalization expenses, and corrective cost among three groups (P>0.05). Complications included cerebrospinal fluid leakage (2 cases in group A1 and group A2), sinus formation (3 cases in group A1, group A2 and group B1), and intervertebral infection (1 case in group B1), but no implant failure or donor site complications was found in any patient. Conclusions: Titanium mesh cages could obtain good clinical efficacy comparable to autogenous iliac bone graft when treating single-segment spinal tuberculosis, and may be better than autogenous iliac bone graft for treating multi-segment spinal tuberculosis. [ABSTRACT FROM AUTHOR]

Teriparatide [human parathyroid hormone (1–34)], which exerts an anabolic effect on bone, is used for the treatment of osteoporosis in patients who are at a high risk for fracture. That the once-daily administration of teriparatide causes an increase in cortical porosity in animal models and clinical studies has been a matter of concern. However, it is not well documented that the frequency of administration and/or the total dose of teriparatide affect the cortical porosity. The present study developed 4 teriparatide regimens [20 μg/kg/day (D20), 40 μg/kg/day (D40), 140 μg/kg/week (W140) and 280 μg/kg/week (W280)] in the rabbit as a model animal with a well-developed Haversian system and osteons. The total weekly doses were equivalent in the low-dose groups (D20 and W140) and in the high-dose groups (D40 and W280). After the short-term (1 month) administration of TPDT, micro-CT, histomorphometry and three-dimensional second harmonic generation (3D-SHG) imaging to visualize the bone collagen demonstrated that daily regimens but not weekly regimens were associated with the significant development of cortical porosity and endosteal naïve bone formation by marrow fibrosis. We concomitantly monitored the pharmacokinetics of the plasma teriparatide levels as well as the temporal changes in markers of bone formation and resorption. The analyses in the present study suggested that the daily repeated administration of teriparatide causes more deleterious changes in the cortical microarchitecture than the less frequent administration of higher doses. The findings of the present study may have some implications for use of teriparatide in clinical treatment. [ABSTRACT FROM AUTHOR]

Structural analysis of biological membranes is important for understanding cell and sub-cellular organelle function as well as their interaction with the surrounding environment. Imaging of whole cells in three dimension at high spatial resolution remains a significant challenge, particularly for thick cells. Cryo-transmission soft X-ray microscopy (cryo-TXM) has recently gained popularity to image, in 3D, intact thick cells (∼10μm) with details of sub-cellular architecture and organization in near-native state. This paper reports a new tool to segment and quantify structural changes of biological membranes in 3D from cryo-TXM images by tracking an initial 2D contour along the third axis of the microscope, through a multi-scale ridge detection followed by an active contours-based model, with a subsequent refinement along the other two axes. A quantitative metric that assesses the grayscale profiles perpendicular to the membrane surfaces is introduced and shown to be linearly related to the membrane thickness. Our methodology has been validated on synthetic phantoms using realistic microscope properties and structure dimensions, as well as on real cryo-TXM data. Results demonstrate the validity of our algorithms for cryo-TXM data analysis. [ABSTRACT FROM AUTHOR]

Objective: The literature shows that bone mineral density (BMD) and the geometric architecture of trabecular bone in the femur may be affected by inadequate dietary intake of Mg. In this study, we used microcomputed tomography (micro-CT) to characterize and quantify the impact of a low-Mg diet on femoral trabecular bones in mice. Materials and methods: Four-week-old C57BL/6J male mice were randomly assigned to 2 groups and supplied either a normal or low-Mg diet for 8weeks. Samples of plasma and urine were collected for biochemical analysis, and femur tissues were removed for micro-CT imaging. In addition to considering standard parameters, we regarded trabecular bone as a cylindrical rod and used computational algorithms for a technical assessment of the morphological characteristics of the bones. BMD (mg-HA/cm3) was obtained using a standard phantom. Results: We observed a decline in the total tissue volume, bone volume, percent bone volume, fractal dimension, number of trabecular segments, number of connecting nodes, bone mineral content (mg-HA), and BMD, as well as an increase in the structural model index and surface-area-to-volume ratio in low-Mg mice. Subsequently, we examined the distributions of the trabecular segment length and radius, and a series of specific local maximums were identified. The biochemical analysis revealed a 43% (96%) decrease in Mg and a 40% (71%) decrease in Ca in plasma (urine excretion). Conclusions: This technical assessment performed using micro-CT revealed a lower population of femoral trabecular bones and a decrease in BMD at the distal metaphysis in the low-Mg mice. Examining the distributions of the length and radius of trabecular segments showed that the average length and radius of the trabecular segments in low-Mg mice are similar to those in normal mice. [ABSTRACT FROM AUTHOR]

In the adult skeleton, cells of the immune system interact with those of the skeleton during all phases of bone repair to influence the outcome. Mast cells are immune cells best known for their pathologic role in allergy, and may be involved in chronic inflammatory and fibrotic disorders. Potential roles for mast cells in tissue homeostasis, vascularization and repair remain enigmatic. Previous studies in combined mast cell- and Kit-deficient KitW-sh/W-sh mice (KitW-sh) implicated mast cells in bone repair but KitW-sh mice suffer from additional Kit-dependent hematopoietic and non- hematopoietic deficiencies that could have confounded the outcome. The goal of the current study was to compare bone repair in normal wild type (WT) and Cpa3Cre/+ mice, which lack mast cells in the absence of any other hematopoietic or non- hematopoietic deficiencies. Repair of a femoral window defect was characterized using micro CT imaging and histological analyses from the early inflammatory phase, through soft and hard callus formation, and finally the remodeling phase. The data indicate 1) mast cells appear in healing bone of WT mice but not Cpa3Cre/+ mice, beginning 14 days after surgery; 2) re-vascularization of repair tissue and deposition of mineralized bone was delayed and dis-organised in Cpa3Cre/+ mice compared with WT mice; 3) the defects in Cpa3Cre/+ mice were associated with little change in anabolic activity and biphasic alterations in osteoclast and macrophage activity. The outcome at 56 days postoperative was complete bridging of the defect in most WT mice and fibrous mal-union in most Cpa3Cre/+ mice. The results indicate that mast cells promote bone healing, possibly by recruiting vascular endothelial cells during the inflammatory phase and coordinating anabolic and catabolic activity during tissue remodeling. Taken together the data indicate that mast cells have a positive impact on bone repair. [ABSTRACT FROM AUTHOR]

Mice are extensively used for experimental bone-healing studies. However, there are few established nondestructive in vivo techniques for longitudinal fracture-healing analysis in mice, including in vivo micro-computed tomography (μCT) and radiography. Importantly, none of the established methods can discriminate between non-mineralized fibrous tissue and cartilage in the soft fracture callus. Therefore, the objective was to establish high-resolution in vivo magnetic resonance imaging (MRI) for the longitudinal assessment of soft callus formation during bone healing in mice. C57BL/6J mice received a femur osteotomy stabilized using an external fixator and were randomly assigned to five groups. Group 1 mice were scanned three times longitudinally during fracture healing using an optimized MRI scanning protocol to establish an algorithm to characterize the different fracture-callus tissues. Mice of groups 2–4 were scanned once on day 10, 14 or 21, respectively, euthanized after scanning and their femurs subjected to ex vivo μCT and histomorphometric analysis to compare the data assessed by MRI with μCT and histology. Control group 5 mice were not scanned. After 28 days, mice of groups 1 and 5 were euthanized and the fracture-healing outcome was evaluated by bending-test, μCT and histology to determine whether the repeated anesthesia, handling and the MRI measurements themselves influenced fracture healing. The callus-tissue values determined by MRI were mostly comparable to those obtained by μCT and histomorphometric analysis. However, at time points characterized by small relative bone or cartilage areas, MRI measurements were weakly comparable to histomorphometric data, possibly due to the inferior spatial resolution. Importantly, at the early and intermediate phases of healing, cartilage and fibrous-tissue values obtained by MRI were highly accurate. Furthermore, repeated anesthesia, handling and MRI scans did not impact bone healing. Therefore, we demonstrated the feasibility of high-resolution in vivo MRI for longitudinal assessment of soft callus formation during murine endochondral fracture healing. [ABSTRACT FROM AUTHOR]

Objective: The degradation of articular cartilage, which characterises osteoarthritis (OA), is usually paired with excessive bone remodelling, including subchondral bone sclerosis, cysts, and osteophyte formation. Experimental models of OA are widely used to investigate pathogenesis, yet few validated methodologies for assessing periarticular bone morphology exist and quantitative measurements are limited by manual segmentation of micro-CT scans. The aim of this work was to chart the temporal changes in periarticular bone in murine OA by novel, automated micro-CT methods. Methods: OA was induced by destabilisation of the medial meniscus (DMM) in 10-week old male mice and disease assessed cross-sectionally from 1- to 20-weeks post-surgery. A novel approach was developed to automatically segment subchondral bone compartments into plate and trabecular bone in micro-CT scans of tibial epiphyses. Osteophyte volume, as assessed by shape differences using 3D image registration, and by measuring total epiphyseal volume was performed. Results: Significant linear and volumetric structural modifications in subchondral bone compartments and osteophytes were measured from 4-weeks post-surgery and showed progressive changes at all time points; by 20 weeks, medial subchondral bone plate thickness increased by 160±19.5 μm and the medial osteophyte grew by 0.124±0.028 μm3. Excellent agreement was found when automated measurements were compared with manual assessments. Conclusion: Our automated methods for assessing bone changes in murine periarticular bone are rapid, quantitative, and highly accurate, and promise to be a useful tool in future preclinical studies of OA progression and treatment. The current approaches were developed specifically for cross-sectional micro-CT studies but could be applied to longitudinal studies. [ABSTRACT FROM AUTHOR]