Quantifying the Human Subchondral Trabecular Bone Microstructure in Osteoarthritis with Clinical CT.

Osteoarthritis (OA) is characterized by critical alterations of the subchondral bone microstructure, besides the well-known cartilaginous changes. Clinical computed tomography (CT) detection of quantitative 3D microstructural subchondral bone parameters is applied to monitor changes of subchondral bone structure in different stages of human OA and is compared with micro-CT, the gold standard. Determination by clinical CT (287 µm resolution) of key microstructural parameters in tibial plateaus with mild-to-moderate and severe OA reveals strong correlations to micro-CT (35 µm), high inter- and intraobserver reliability, and small relative differences. In vivo, normal, mild-to-moderate, and severe OA are compared with clinical CT (331 µm). All approaches detect characteristic expanded trabecular structure in severe OA and fundamental microstructural correlations with clinical OA stage. Multivariate analyses at various in vivo and ex vivo imaging resolutions always reliably separate mild-to-moderate from severe OA (except mild-to-moderate OA from normal), revealing a striking similarity between 287 µm clinical and 35 µm micro-CT. Thus, accurate structural measurements using clinical CT with a resolution near the trabecular dimensions are possible. Clinical CT offers an opportunity to quantitatively monitor subchondral bone microstructure in clinical and experimental settings as an advanced tool of investigating OA and other diseases affecting bone architecture.

Axial alignment is a critical regulator of knee osteoarthritis.

Although osteoarthritis (OA), a leading cause of disability, has been associated with joint malalignment, scientific translational evidence for this link is lacking. In a clinical case study, we provide evidence of osteochondral recovery upon unloading symptomatic isolated medial tibiofemoral knee OA associated with varus malalignment. By mapping response correlations at high resolution, we identify spatially complex degenerative changes in cartilage after overloading in a clinically relevant ovine model. We further report that unloading diminishes OA cartilage degeneration and alterations of critical parameters of the subchondral bone plate in a similar topographic fashion. Last, therapeutic unloading shifted the articular cartilage and subchondral bone phenotype to normal and restored several physiological correlations disturbed in neutral and varus OA, suggesting a protective effect on the integrity of the entire osteochondral unit. Collectively, these findings identify modifiable trajectories with considerable translational potential to reduce the burden of human OA.

Teaching medical anatomy: what is the role of imaging today?

PURPOSE: Medical anatomy instruction has been an important issue of debate for many years and imaging anatomy has become an increasingly important component in the field, the role of which has not yet been clearly defined. The aim of the paper was to assess the current deployment of medical imaging in the teaching of anatomy by means of a review of the literature. MATERIALS: A systematic search was performed using the electronic database PubMed, ScienceDirect and various publisher databases, with combinations of the relevant MeSH terms. A manual research was added. RESULTS: In most academic curricula, imaging anatomy has been integrated as a part of anatomical education, taught using a very wide variety of strategies. Considerable variation in the time allocation, content and delivery of medical imaging in teaching human anatomy was identified. Given this considerable variation, an objective assessment remains quite difficult. DISCUSSION: In most publications, students' perceptions regarding anatomical courses including imaging anatomy were investigated by means of questionnaires and, regardless of the method of teaching, it was globally concluded that imaging anatomy enhanced the quality and efficiency of instruction in human anatomy. More objective evaluation based on an increase in students' performance on course examinations or on specific tests performed before and after teaching sessions showed positive results in numerous cases, while mixed results were also indicated by other studies. CONCLUSION: A relative standardization could be useful in improving the teaching of imaging anatomy, to facilitate its assessment and reinforce its effectiveness.

Use of a Computed Tomography Based Approach to Validate Noninvasive Devices to Measure Rotational Knee Laxity.

The purpose of this study is to validate a noninvasive rotational knee laxity measuring device called "Rotameter P2" with an approach based on Computed Tomography (CT). This CT-approach using X-rays is hence invasive and can be regarded as a precise reference method that may also be applied to similar devices. An error due to imperfect femur fixation was observed but can be neglected for small torques. The most significant estimation error is due to the unavoidable soft tissues rotation and hence flexibility in the measurement chain. The error increases with the applied torque. The assessment showed that the rotational knee angle measured with the Rotameter is still overestimated because of thigh and femur displacement, soft tissues deformation, and measurement artefacts adding up to a maximum of 285% error at +15 Nm for the Internal Rotation of female volunteers. This may be questioned if such noninvasive devices for measuring the Tibia-Femoral Rotation (TFR) can help diagnosing knee pathologies and investigate ligament reconstructive surgery.

Expression of the yeast aquaporin Aqy2 affects cell surface properties under the control of osmoregulatory and morphogenic signalling pathways.

Aquaporins mediate rapid and selective water transport across biological membranes. The yeast Saccharomyces cerevisiae possesses two aquaporins, Aqy1 and Aqy2. Here, we show that Aqy2 is involved in controlling cell surface properties and that its expression is controlled by osmoregulatory and morphogenic signalling pathways. Deletion of AQY2 results in diminished fluffy colony morphology while overexpression of AQY2 causes strong agar invasion and adherence to plastic surfaces. Hyper-osmotic stress inhibits morphological developments including the above characteristics as well as AQY2 expression through the osmoregulatory Hog1 mitogen-activated protein kinase. Moreover, two pathways known to control morphological developments are involved in regulation of AQY2 expression: the protein kinase A pathway derepresses AQY2 expression through the Sfl1 repressor, and the filamentous growth Kss1 mitogen-activated protein kinase pathway represses AQY2 expression in a Kss1 activity-independent manner. The AQY2 expression pattern resembles in many ways that of MUC1/FLO11, which encodes a cell surface glycoprotein required for morphological developments. Our observations suggest a potential link between aquaporins and cell surface properties, and relate to the proposed role of mammalian aquaporins in tumour cell migration and invasion.

Quantitative dynamic contrast enhanced MRI of experimental synovitis in the rabbit knee: comparison of macromolecular blood pool agents vs. Gadolinium-DOTA.

The purpose of this study was to assess 2 Gd-based macromolecular intravascular contrast agents (P792, rapid clearance blood pool agent (rBPA) and P717, slow clearance blood pool agent (sBPA)) compared to Gd-DOTA (representative extracellular non specific agent) in MR imaging of knee rabbit experimental synovitis. Quantitative dynamic contrast enhanced MRI (qDCE-MRI) after intravascular injection of a low molecular weight contrast agent of 0.56 kDa (Gd-DOTA) and 2 high-molecular-weight contrast agents of 6.47 kDa (P792) and 52 kDa (P717) was performed in rabbits with carrageenan-induced synovitis of the right knee. P792 and P717 provided a progressive and persistent enhancement of arthritic synovial tissue while Gd-DOTA provided an early and rapidly declining enhancement with a concomitant diffusion in synovial fluid, thus limitating delineation of synovial pannus. P792 allowed acquisition of high-quality MR arthrograms, due to both a better diffusion in synovial pannus (vs. P717) and a concomitant restricted diffusion into the synovial fluid (vs. Gd-DOTA). In fact, experimental rabbit synovitis represent a specific entity that favors the T1 effect of high-molecular-weight agents, and especially rBPA P792, entrapped in synovial pannus, without diffusion in the synovial fluid. Due to this lack of arthrographic effect, P792 accumulation could be specifically sequentially analyzed by qDCE-MRI for detecting, characterizing and monitoring synovial vascular permeability changes during mono- or polysynovitis.

The Saccharomyces cerevisiae aquaporin Aqy1 is involved in sporulation.

Aquaporins mediate rapid selective water transport across biological membranes. Elucidation of their precise physiological roles promises important insight into cellular and organismal osmoregulation. The genome of the yeast Saccharomyces cerevisiae encodes two similar but differentially regulated aquaporins. Here, we show that expression of AQY1 is stimulated during sporulation and that the Aqy1 protein is detectable exclusively in spore membranes. When spores are rapidly frozen, those that lack Aqy1 survive better, providing for a functional test of active spore water channels. Under ambient conditions, lack of Aqy1 reduces spore fitness. Because this reduction is independent from germination conditions, Aqy1 may be important during spore formation rather than subsequent maintenance or germination. Indeed, it seems that Aqy1 is degraded after spores have been formed and during germination. Taken together, Aqy1 is developmentally controlled and may play a role in spore maturation, probably by allowing water outflow. Taken together, we demonstrate a functional role of an aquaporin in gametogenesis, as well as in the formation of durable structures such as spores, a role that may have wider biological and medical implications.

Imaging of diaphragmatic injury: a diagnostic challenge?

Diaphragmatic injuries occur in 0.8%-8% of patients after blunt trauma. Although the diagnosis may be obvious at standard chest radiography or computed tomography (CT) in most situations, some more subtle signs require careful analysis of CT images and examination with magnetic resonance (MR) imaging in some specific situations. Each method of imaging evaluation has advantages and pitfalls according to the type of diaphragmatic rupture. MR imaging with breath-hold acquisition permits good visualization of diaphragmatic abnormalities, but this technique cannot be performed in emergency situations. Because of a dramatic reduction in motion and beam-hardening artifacts and significant improvement of spatial resolution, especially along the z axis, helical CT and multisection CT allow better demonstration of the most subtle signs, such as a focal indentation of the liver or a right-sided collar sign. In addition, helical CT and multisection CT are useful tools in the evaluation of patients with multiple traumatic injuries.

Antigenic and functional properties of the human red blood cell urea transporter hUT-B1.

The Kidd (JK) blood group locus encodes the urea transporter hUT-B1, which is expressed on human red blood cells and other tissues. The common JK*A/JK*B blood group polymorphism is caused by a single nucleotide transition G838A changing Asp-280 to Asn-280 on the polypeptide, and transfection of erythroleukemic K562 cells with hUT-B1 cDNAs carrying either the G838 or the A838 nucleotide substitutions resulted in the isolation of stable clones that expressed the Jk(a) or Jk(b) antigens, respectively, thus providing the first direct demonstration that the hUT-B1 gene encodes the Kidd blood group antigens. In addition, immunochemical analysis of red blood cells demonstrated that hUT-B1 also exhibits ABO determinants attached to the single N-linked sugar chain at Asn-211. Moreover, immunoadsorption studies, using inside-out and right-side-out red cell membrane vesicles as competing antigen, demonstrated that the C- and N-terminal ends of hUT-B1 are oriented intracellularly. Mutagenesis and functional studies by expression in Xenopus oocytes revealed that both cysteines Cys-25 and Cys-30 (but not alone) are essential for plasma membrane addressing. Conversely, the transport function was not affected by the JK*A/JK*B polymorphism, C-terminal deletion (residues 360-389), or mutation of the extracellular N-glycosylation consensus site and remains poorly para-chloromercuribenzene sulfonate (pCMBS)-sensitive. However, transport studies by stopped flow light scattering using Jk-K562 transfectants demonstrated that the hUT-B1-mediated urea transport is pCMBS-sensitive in an erythroid context, as reported previously for the transporter of human red blood cells. Mutagenesis analysis also indicated that Cys-151 and Cys-236, at least alone, are not involved in pCMBS inhibition. Altogether, these antigenic, topologic, and functional properties might have implications into the physiology of hUT-B1 and other members of the urea transporter family.