Search

Vanishing bone metastasis (pseudopathological vertebral body enhancement) is a pitfall in the interpretation of contrast-enhanced computed tomography (CT) scans of patients with thoracic vein obstruction, mainly in the superior vena cava and brachiocephalic veins, typically being related to thrombosis due to malignant tumors. On the basis of the CT findings, pseudopathological vertebral body enhancement can be misdiagnosed as sclerotic bone metastasis, leading to unnecessary treatment. Although not rare, pseudopathological vertebral body enhancement is usually underdiagnosed by radiologists. The aim of this study is to review the pathophysiology of this phenomenon, illustrating the most common collateral venous pathways in thoracic vein obstruction and making the correlation with the CT findings. Resumo Vanishing bone metastasis é um pitfall na tomografia computadorizada (TC) com contraste em pacientes com obstrução das veias torácicas, principalmente das veias cava superior e braquiocefálica, geralmente ocasionada por tumores malignos. Na TC, aparece como um realce pseudopatológico do corpo vertebral e pode ser erroneamente interpretado como metástase óssea esclerótica, levando a tratamento desnecessário. Embora não seja raro, esse achado geralmente é subdiagnosticado pelos radiologistas. O objetivo deste estudo é revisar a fisiopatologia desse fenômeno, ilustrando as vias venosas colaterais mais comuns na obstrução da veia torácica e correlacionar com os achados da TC.

Vanishing bone metastasis (pseudopathological vertebral body enhancement) is a pitfall in the interpretation of contrast-enhanced computed tomography (CT) scans of patients with thoracic vein obstruction, mainly in the superior vena cava and brachiocephalic veins, typically being related to thrombosis due to malignant tumors. On the basis of the CT findings, pseudopathological vertebral body enhancement can be misdiagnosed as sclerotic bone metastasis, leading to unnecessary treatment. Although not rare, pseudopathological vertebral body enhancement is usually underdiagnosed by radiologists. The aim of this study is to review the pathophysiology of this phenomenon, illustrating the most common collateral venous pathways in thoracic vein obstruction and making the correlation with the CT findings.

Biominerals typically have complex hierarchical structures traversing many length scales. This makes their structural characterization complicated, since it requires 3D techniques that can probe full specimens at down to nanometer-resolution, a combination that is difficult – if not impossible – to achieve simultaneously. One challenging example is bone, a mineralized tissue with a highly complex architecture that is replete with a network of cells. X-ray computed tomography techniques enable multiscale structural characterization through the combination of various equipment and emerge as promising tools for characterizing biominerals. Using bone as an example, we discuss how combining different X-ray imaging instruments allow characterizing bone structures from the nano- to the organ-scale. In particular, we compare and contrast human and rodent bone, emphasize the importance of the osteocyte lacuno-canalicular network in bone, and finally illustrate how combining synchrotron X-ray imaging with laboratory instrumentation for computed tomography is especially helpful for multiscale characterization of biominerals.

International audience; OBJECTIVES:Interleukin (IL)-38 is a newly characterised cytokine that belongs to the IL-1 family. This cytokine is expressed in the rheumatoid arthritis (RA) synovial tissue and IL-38 deficient mice have exacerbated arthritis. Here, we analysed the effect of IL-38 overexpression in the joints of arthritic mice, in human macrophages and synovial fibroblasts in vitro.METHODS:Articular injections of an adeno-associated virus (AAV) 2/8 encoding IL-38 were performed in collagen-induced arthritis (CIA), K/BxN serum transfer-induced arthritis (STIA) and antigen-induced arthritis (AIA) in mice. The effect of IL-38 overexpression was evaluated through clinical scores, immunohistochemistry, microCT, Luminex and RT-qPCR analysis. THP-1 macrophages were transduced with a lentiviral vector to overexpress IL-38.RESULTS:Clinical inflammatory scores were significantly decreased after AAV IL-38 injection in joints of mice with CIA and STIA, but not AIA. This decrease was accompanied by reduced macrophage infiltration and a decreased expression of Th17 cytokines (IL-17, IL-23, IL-22) and TNFα. However, IL-38 overexpression had no effect on cartilage or bone destruction. In vitro, the THP-1 monocytic cell line expressed less IL-6, TNFα and IL-23 after IL-38 overexpression. Conditioned media from these cells, containing released IL-38, also exert an anti-inflammatory effect on human primary macrophages and synovial fibroblasts from patients with RA.CONCLUSIONS:This study shows for the first time that IL-38 overexpression attenuates the severity of experimental arthritis. IL-38 may exert its anti-inflammatory effects by decreasing the production of proinflammatory cytokines by macrophages and synovial fibroblasts. This effect can lead to the development of novel treatment strategies in arthritis.

Magnetic resonance imaging (MRI)-guided attenuation correction (AC) of positron emission tomography (PET) data and/or radiation therapy (RT) treatment planning is challenged by the lack of a direct link between MRI voxel intensities and electron density. Therefore, even if this is not a trivial task, a pseudo-computed tomography (CT) image must be predicted from MRI alone. In this work, we propose a two-step (segmentation and fusion) atlas-based algorithm focusing on bone tissue identification to create a pseudo-CT image from conventional MRI sequences and evaluate its performance against the conventional MRI segmentation technique and a recently proposed multi-atlas approach. The clinical studies consisted of pelvic CT, PET and MRI scans of 12 patients with loco-regionally advanced rectal disease. In the first step, bone segmentation of the target image is optimized through local weighted atlas voting. The obtained bone map is then used to assess the quality of deformed atlases to perform voxel-wise weighted atlas fusion. To evaluate the performance of the method, a leave-one-out cross-validation (LOOCV) scheme was devised to find optimal parameters for the model. Geometric evaluation of the produced pseudo-CT images and quantitative analysis of the accuracy of PET AC were performed. Moreover, a dosimetric evaluation of volumetric modulated arc therapy photon treatment plans calculated using the different pseudo-CT images was carried out and compared to those produced using CT images serving as references. The pseudo-CT images produced using the proposed method exhibit bone identification accuracy of 0.89 based on the Dice similarity metric compared to 0.75 achieved by the other atlas-based method. The superior bone extraction resulted in a mean standard uptake value bias of -1.5 +/- 5.0% (mean +/- SD) in bony structures compared to -19.9 +/- 11.8% and -8.1 +/- 8.2% achieved by MRI segmentation-based (water-only) and atlas-guided AC. Dosimetric evaluation using dose volume histograms and the average difference between minimum/maximum absorbed doses revealed a mean error of less than 1% for the both target volumes and organs at risk. Two-dimensional (2D) gamma analysis of the isocenter dose distributions at 1%/1 mm criterion revealed pass rates of 91.40 +/- 7.56%, 96.00 +/- 4.11% and 97.67 +/- 3.6% for MRI segmentation, atlas-guided and the proposed methods, respectively. The proposed method generates accurate pseudo-CT images from conventional Dixon MRI sequences with improved bone extraction accuracy. The approach is promising for potential use in PET AC and MRI-only or hybrid PET/MRI-guided RT treatment planning.

Accessory bones, variants, and coalitions are not uncommon at the hand-wrist region. They are often overlooked because they are usually asymptomatic and found incidentally on imaging. However, they may sometimes present as a (painful) swelling or mimic a (sequel of a) fracture. Other symptoms may be attributed to impingement and exercise-related pain. Thorough knowledge of the anatomy, systematic imaging analysis, and the awareness of their existence are the clues to a correct identification. Plain radiography and magnetic resonance imaging (MRI) play a pivotal role in the correct diagnosis. In general, signal intensity on MRI is similar to the normal bony structures. However, concomitant bone marrow edema may indicate the presence of impingement. Therefore, MRI sequences with fat suppression should be included in case of symptomatic findings. This article provides a kaleidoscopic overview of some of the prevalent bony anomalies of the hand-wrist region and their potential pathogenic nature.

Major hallmarks of osteoarthritis (OA) are cartilage degeneration, inflammation and osteophyte formation. COX-2 inhibitors counteract inflammation-related pain, but their prolonged oral use entails the risk for side effects. Local and prolonged administration in biocompatible and degradable drug delivery biomaterials could offer an efficient and safe treatment for the long-term management of OA symptoms. Therefore, we evaluated the disease-modifying effects and the optimal dose of polyesteramide microspheres delivering the COX-2 inhibitor celecoxib in a rat OA model. Four weeks after OA induction by anterior cruciate ligament transection and partial medial meniscectomy, 8-week-old female rats (n = 6/group) were injected intra-articular with celecoxib-loaded microspheres at three dosages (0.03, 0.23 or 0.39 mg). Unloaded microspheres served as control. During the 16-week follow-up, static weight bearing and plasma celecoxib concentrations were monitored. Post-mortem, micro-computed tomography and knee joint histology determined progression of synovitis, osteophyte formation, subchondral bone changes, and cartilage integrity. Systemic celecoxib levels were below the detection limit 6 days upon delivery. Systemic and local adverse effects were absent. Local delivery of celecoxib reduced the formation of osteophytes, subchondral sclerosis, bone cysts and calcified loose bodies, and reduced synovial inflammation, while cartilage histology was unaffected. Even though the effects on pain could not be evualated directly in the current model, our results suggest the application of celecoxib-loaded microspheres holds promise as novel, safe and effective treatment for inflammation and pain in OA.

A 39-year-old man presented with severe bone pain in the tibiae and forearms in the wake of a poststreptococcal sepsis complicated with pneumonia and erysipelas 4 months earlier. Bone scintigraphy was indicative of periostitis of the tibia, ulna, and radius bilaterally, and in combination with the increased inflammatory parameters and dysproteinemia, the diagnosis of Goldbloom syndrome was made. Goldbloom syndrome is an idiopathic periosteal hyperostosis associated with dysproteinemia and elevated inflammatory parameters. Although it has only been described in children/adolescents, this case illustrates that, in the specific clinical and biochemical setting, it should also be considered in adults. ispartof: CLINICAL NUCLEAR MEDICINE vol:43 issue:10 pages:E366-E367 ispartof: location:United States status: published

International audience; The exhumation of Danish astronomer Tycho Brahe (1546-1601) was performed in 2010 to verify speculative views on the cause of his death. Previous analyses of skeletal and hair remains recovered from his grave refuted the presumption that he died from poisoning. These studies also outlined the possibility that he actually died from an acute illness, echoing the rather vague and inaccurate testimony of some historical records. We performed a detailed paleopathological analysis of Tycho Brahe's skeletal remains, along with a reconstruction of his diet based on carbon and nitrogen stable isotopes analysis and an estimate of his physical status (relative body fat) based on medullar and cortical dimensions of the femo-ral shaft. The astronomer's remains exhibit bone changes indicative of diffuse idiopathic skeletal hyperostosis (DISH). The study further allows us to classify him as obese (100% reliability according to our decision tree designed from Danish males), and points out his rich diet (high input of animal protein and/or marine resources) and high social status. Comorbidi-ties of DISH and obesity are reviewed, and their influence on health status is discussed. We further consider some conditions associated with metabolic syndrome as possible causes of Tycho Brahe's final symptoms (urinary retention, renal failure and coma), including diabetes, alcoholic ketoacidosis and benign prostatic hypertrophy. Although a definite and specific diagnosis cannot be established, our study points to today's civilization diseases often associated with DISH and metabolic syndrome as the possible cause of death of Tycho Brahe.

Meloxicam, a preferential COX-2 inhibitor, is a commonly used nSAID in pigs. Besides having potential side effects on the gastrointestinal tract, this type of drug might potentially affect osteogenesis and chondrogenesis, processes relevant to growing pigs. Therefore, the effects of long-term meloxicam treatment on growing pigs were studied. Twelve piglets (n=6 receiving daily meloxicam 0.4 mg/kg orally from 48 until 110 days of age; n=6 receiving only applesauce (vehicle control)) were subjected to visual and objective gait analysis by pressure plate measurements at several time points. Following euthanasia a complete postmortem examination was performed and samples of the talus and distal tibia, including the distal physis, were collected. Trabecular bone microarchitecture was analysed by microCT scanning, bone stiffness by compression testing and growth plate morphology using light microscopy. Animals were not lame and gait patterns did not differ between the groups. Pathological examination revealed no lesions compatible with known side effects of nSAIDs. Trabecular bone microarchitecture and growth plate morphology did not differ between the two groups. The findings of this in vivo study reduce concerns regarding the long-term use of meloxicam in young, growing piglets.

Background Little is known about the effects of adrenal steroids on skeletal maturation and bone mass acquisition in healthy prepubertal boys. Objective To study whether adrenal-derived steroids within the physiological range are associated with skeletal maturation, areal and volumetric bone mineral density (aBMD and vBMD) and bone geometry in healthy prepubertal and early pubertal boys. Methods 98 healthy prepubertal and early pubertal boys (aged 6-14 y) were studied cross-sectionally. Androstenedione (A) and estrone (E1) were determined by liquid chromatography tandem mass spectrometry and DHEAS was determined by immunoassay. Whole body and lumbar spine aBMD and bone area were determined by dual-energy X-ray absorptiometry. Trabecular (distal site) and cortical (proximal site) vBMD and bone geometry were assessed at the non-dominant forearm and leg using peripheral QCT. Skeletal age was determined by X-ray of the left hand. Results Adrenal-derived steroids (DHEAS, A and E1) are positively associated with bone age in prepubertal and early pubertal children, independently of age. There are no associations between the adrenal-derived steroids and the studied parameters of bone size (lumbar spine and whole body bone area, trabecular or cortical area at the radius or tibia, periosteal circumference and cortical thickness at the radius or tibia) or BMD (aBMD or vBMD). Conclusion In healthy prepubertal and early pubertal boys, serum adrenal-derived steroid levels, are associated with skeletal maturation, independently of age, but not with bone size or (v)BMD. Our data suggest that adrenal derived steroids are not implicated in the accretion of bone mass before puberty in boys.

Osteopenia and osteoporosis predominately occur in the fully grown skeleton. However, it is unknown whether disuse osteopenia in skeletally mature, but growing, mice resembles that of fully grown mice. Twenty-four 16-week-old (young) and eighteen 44-week-old (aged) female C57BL/6J mice were investigated. Twelve young and nine aged mice were injected with botulinum toxin in one hind limb; the remaining mice served as controls. The mice were euthanized after 3 weeks of disuse. The femora were scanned by micro-computed tomography (µCT) and bone strength was determined by mechanically testing the femoral mid-diaphysis and neck. At the distal femoral metaphysis, the loss of trabecular bone volume fraction (BV/TV) differed between the young and aged mice. However, at the distal femoral epiphysis, no age-dependent differences were observed. Thinning of the trabeculae was not affected by the age of the mice at either the distal femoral metaphysis or the epiphysis. Furthermore, the aged mice lost more bone strength at the femoral mid-diaphysis, but not at the femoral neck, compared to the young mice. In general, the bone loss induced by botulinum toxin did not differ substantially between young and aged mice. Therefore, the loss of bone in young mice resembles that of aged mice, even though they are not fully grown.

Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) is a noninvasive thermal technique that enables rapid heating of a specific area in the human body. Its clinical relevance has been proven for the treatments of soft tissue tumors, like uterine fibroids, and for the treatments of solid tumors in bone. In MR-HIFU treatment, MR-thermometry is used to monitor the temperature evolution in soft tissue. However, this technique is currently unavailable for bone tissue. Computer models can play a key role in the accurate prediction and monitoring of temperature. Here, we present a computer ray tracing model that calculates the heat production density in the focal region. This model accounts for both the propagation of shear waves and the interference between longitudinal and shear waves. The model was first compared with a finite element approach which solves the Helmholtz equation in soft tissue and the frequency-domain wave equation in bone. To obtain the temperature evolution in the focal region, the heat equation was solved using the heat production density generated by the raytracer as a heat source. Then, we investigated the role of the interaction between shear and longitudinal waves in terms of dissipated power and temperature output. The results of our model were in agreement with the results obtained by solving the Helmholtz equation and the frequency-domain wave equation, both in soft tissue and bone. Our results suggest that it is imperative to include both shear waves and their interference with longitudinal waves in the model when simulating high intensity focused ultrasound propagation in solids. In fact, when modeling HIFU treatments, omitting the interference between shear and longitudinal waves leads to an over-estimation of the temperature increase in the tissues.

The primary goal of this cross-sectional in vivo study was to assess peripheral bone microarchitecture, bone strength, and bone remodeling in adult type 1 diabetes (T1D) patients with and without diabetic microvascular disease (MVD+ and MVD-, respectively) and to compare them with age-, gender-, and height-matched healthy control subjects (CoMVD+ and CoMVD-, respectively). The secondary goal was to assess differences in MVD- and MVD+ patients. Fifty-five patients with T1DM (MVD+ group: n = 29) were recruited from the Funen Diabetes Database. Dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultradistal radius and tibia, and biochemical markers of bone turnover were performed in all participants. There were no significant differences in HR-pQCT parameters between MVD- and CoMVD- subjects. In contrast, MVD+ patients had larger total and trabecular bone areas (p = 0.04 and p = 0.02, respectively), lower total, trabecular, and cortical volumetric bone mineral density (vBMD) (p < 0.01, p < 0.04, and p < 0.02, respectively), and thinner cortex (p = 0.03) at the radius, and lower total and trabecular vBMD (p = 0.01 and p = 0.02, respectively) at the tibia in comparison to CoMVD+. MVD+ patients also exhibited lower total and trabecular vBMD (radius p = 0.01, tibia p < 0.01), trabecular thickness (radius p = 0.01), estimated bone strength, and greater trabecular separation (radius p = 0.01, tibia p < 0.01) and network inhomogeneity (radius p = 0.01, tibia p < 0.01) in comparison to MVD- patients. These differences remained significant after adjustment for age, body mass index, gender, disease duration, and glycemic control (average glycated hemoglobin over the previous 3 years). Although biochemical markers of bone turnover were significantly lower in MVD+ and MVD- groups in comparison to controls, they were similar between the MVD+ and MVD- groups. The results of our study suggest that the presence of MVD was associated with deficits in cortical and trabecular bone vBMD and microarchitecture that could partly explain the excess skeletal fragility observed in these patients.

Van den Ende-Gupta Syndrome (VDEGS) is an autosomal recessive disorder characterized by blepharophimosis, distinctive nose, hypoplastic maxilla, and skeletal abnormalities. Using homozygosity mapping in four VDEGS patients from three consanguineous families, Anastacio et al. [Anastacio et al. (2010); Am J Hum Genet 87:553-559] identified homozygous mutations in SCARF2, located at 22q11.2. Bedeschi et al. [2010] described a VDEGS patient with sclerocornea and cataracts with compound heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2 mutation. Because sclerocornea had been described in DiGeorge-velo-cardio-facial syndrome but not in VDEGS, they suggested that the ocular abnormalities were caused by the 22q11.2 microdeletion. We report on a 23-year-old male who presented with bilateral sclerocornea and the VDGEGS phenotype who was subsequently found to be homozygous for a 17 bp deletion in exon 4 of SCARF2. The occurrence of bilateral sclerocornea in our patient together with that of Bedeschi et al., suggests that the full VDEGS phenotype may include sclerocornea resulting from homozygosity or compound heterozygosity for loss of function variants in SCARF2. © 2014 Wiley Periodicals, Inc. ispartof: American Journal of Medical Genetics A vol:164 issue:5 pages:1170-1174 ispartof: location:United States status: published

An ideal novel treatment for bone defects should provide regeneration without autologous or allogenous grafting, exogenous cells, growth factors, or biomaterials while ensuring spatial and temporal control as well as safety. Therefore, a novel osteoinductive nonviral in vivo gene therapy approach using sonoporation was investigated in ectopic and orthotopic models. Constitutive or regulated, doxycycline-inducible, bone morphogenetic protein 2 and 7 coexpression plasmids were repeatedly applied for 5 days. Ectopic and orthotopic gene transfer efficacy was monitored by coapplication of a luciferase plasmid and bioluminescence imaging. Orthotopic plasmid DNA distribution was investigated using a novel plasmid-labeling method. Luciferase imaging demonstrated an increased trend (61% vs. 100%) of gene transfer efficacy, and micro-computed tomography evaluation showed significantly enhanced frequency of ectopic bone formation for sonoporation compared with passive gene delivery (46% vs. 100%) dependent on applied ultrasound power. Bone formation by the inducible system (83%) was stringently controlled by doxycycline in vivo, and no ectopic bone formation was observed without induction or with passive gene transfer without sonoporation. Orthotopic evaluation in a rat femur segmental defect model demonstrated an increased trend of gene transfer efficacy using sonoporation. Investigation of DNA distribution demonstrated extensive binding of plasmid DNA to bone tissue. Sonoporated animals displayed a potentially increased union rate (33%) without extensive callus formation or heterotopic ossification. We conclude that sonoporation of BMP2/7 coexpression plasmids is a feasible, minimally invasive method for osteoinduction and that improvement of bone regeneration by sonoporative gene delivery is superior to passive gene delivery.

International audience; In this paper we present a new population-based implant design methodology, which advances the state-of-the-art approaches by combining shape and bone quality information into the design strategy. The method enhances the mechanical stability of the fixation and reduces the intra-operative in-plane bending which might impede the functionality of the locking mechanism. The method is presented for the case of mandibular locking fixation plates, where the mandibular angle and the bone quality at screw locations are taken into account. Using computational anatomy techniques, the method automatically derives, from a set of computed tomography images, the mandibular angle and the bone thickness and intensity values at the path of every screw. An optimisation strategy is then used to optimise the two parameters of plate angle and screw position. Results for the new design are presented along with a comparison with a commercially available mandibular locking fixation plate. A statistically highly significant improvement was observed. Our experiments allowed us to conclude that an angle of 126 degrees and a screw separation of 8 mm is a more suitable design than the standard 120 degrees and 9 mm.

Purpose: The outcome of a detailed assessment of various strategies for atlas-based whole-body bone segmentation from magnetic resonance imaging (MRI) was exploited to select the optimal parameters and setting, with the aim of proposing a novel one-registration multi-atlas (ORMA) pseudo-CT generation approach. Methods: The proposed approach consists of only one online registration between the target and reference images, regardless of the number of atlas images (N), while for the remaining atlas images, the pre-computed transformation matrices to the reference image are used to align them to the target image. The performance characteristics of the proposed method were evaluated and compared with conventional atlas-based attenuation map generation strategies (direct registration of the entire atlas images followed by voxel-wise weighting (VWW) and arithmetic averaging atlas fusion). To this end, four different positron emission tomography (PET) attenuation maps were generated via arithmetic averaging and VWW scheme using both direct registration and ORMA approaches as well as the 3-class attenuation map obtained from the Philips Ingenuity TF PET/MRI scanner commonly used in the clinical setting. The evaluation was performed based on the accuracy of extracted whole-body bones by the different attenuation maps and by quantitative analysis of resulting PET images compared to CT-based attenuation-corrected PET images serving as reference. Results: The comparison of validation metrics regarding the accuracy of extracted bone using the different techniques demonstrated the superiority of the VWW atlas fusion algorithm achieving a Dice similarity measure of 0.82 ± 0.04 compared to arithmetic averaging atlas fusion (0.60 ± 0.02), which uses conventional direct registration. Application of the ORMA approach modestly compromised the accuracy, yielding a Dice similarity measure of 0.76 ± 0.05 for ORMA-VWW and 0.55 ± 0.03 for ORMA-averaging. The results of quantitative PET analysis followed the same trend with less significant differences in terms of SUV bias, whereas massive improvements were observed compared to PET images corrected for attenuation using the 3-class attenuation map. The maximum absolute bias achieved by VWW and VWW-ORMA methods was 06.4 ± 5.5 in the lung and 07.9 ± 4.8 in the bone, respectively. Conclusions: The proposed algorithm is capable of generating decent attenuation maps. The quantitative analysis revealed a good correlation between PET images corrected for attenuation using the proposed pseudo-CT generation approach and the corresponding CT images. The computational time is reduced by a factor of 1/N at the expense of a modest decrease in quantitative accuracy, thus allowing us to achieve a reasonable compromise between computing time and quantitative performance.