Vahid Entezari

Contrast Enhanced Computed Tomography can predict the glycosaminoglycan content and biomechanical properties of articular cartilage

OBJECTIVE An early hallmark of osteoarthritis (OA) is the progressive loss of glycosaminoglycans (GAGs), the extracellular matrix (ECM) component of articular cartilage that confers it with compressive stiffness. Our aim in this work is to establish the feasibility of using Contrast Enhanced Computed Tomography (CECT) with an anionic iodinated contrast agent - Cysto Conray II - as a minimally invasive tool to measure the changes in the GAG content as well as the compressive stiffness of articular cartilage. METHODS The GAG content of mated osteochondral plugs excised from bovine patello-femoral joints was progressively degraded using chondroitinase ABC. The mated plugs were then immersed in an anionic, tri-iodinated contrast agent, imaged using peripheral quantitative computed tomography (pQCT), subjected to an unconfined compressive stress relaxation test and the GAG content measured using 1,9-dimethylmethylene blue (DMMB) assay. Partial correlation analysis was performed to compare the variation in X-ray attenuation measured by pQCT to the variation in GAG content and in equilibrium compressive modulus. RESULTS The X-ray attenuation of cartilage exposed to an anionic, tri-iodinated, contrast agent measured by quantitative computed tomography (QCT) accounted for 83% of the variation in GAG content (r(2)=0.83, P<0.0001) and 93% of the variation in the equilibrium compressive modulus (r(2)=0.93, P<0.0001). CONCLUSION Using a mated osteochondral plug model to evaluate the biochemical composition and biomechanical properties of cartilage, this study demonstrates the interrelationships between X-ray attenuation, GAG content, and equilibrium compressive modulus, and that CECT can be used to monitor and quantify changes in the GAG content and biomechanical properties of articular cartilage.

Cationic contrast agents improve quantification of glycosaminoglycan (GAG) content by contrast enhanced CT imaging of cartilage

Minimally invasive and non‐destructive methods to quantify glycosaminoglycans (GAGs) in articular cartilage extracellular matrix are of significant interest for the biochemical analysis of cartilage and diagnosis and tracking of osteoarthritis in vivo. Here, we report the use of cationic iodinated contrast agents in comparison to conventional anionic contrast agents for the quantitative monitoring of GAG concentrations with peripheral quantitative computed tomography. Using an ex vivo bovine osteochondral plug model, the cationic contrast agents were evaluated for their ability to distribute into articular cartilage and generate a positive relationship with GAG content. The cationic agents resulted in much higher equilibrium X‐ray attenuations in cartilage extracellular matrix (ECM) than anionic agents. Experiments with samples subjected to enzymatic GAG degradation demonstrated that the cationic agents were up to five times more sensitive (p = 0.0001) to changes in GAG content and had a 24% higher correlation (p = 0.002) compared to the anionic agent (R2 = 0.86, p < 0.0001 compared with R2 = 0.62, p = 0.004). The natural inhomogeneous distribution of GAGs in the ECM could clearly be identified in undegraded samples.

Compressive axial mechanical properties of rat bone as functions of bone volume fraction, apparent density and micro-CT based mineral density

Mechanical testing has been regarded as the gold standard to investigate the effects of pathologies on the structure-function properties of the skeleton. With recent advances in computing power of personal computers, virtual alternatives to mechanical testing are gaining acceptance and use. We have previously introduced such a technique called structural rigidity analysis to assess mechanical strength of skeletal tissue with defects. The application of this technique is predicated upon the use of relationships defining the strength of bone as a function of its density for a given loading mode. We are to apply this technique in rat models to assess their compressive skeletal response subjected to a host of biological and pharmaceutical stimulations. Therefore, the aim of this study is to derive a relationship expressing axial compressive mechanical properties of rat cortical and cancellous bone as a function of equivalent bone mineral density, bone volume fraction or apparent density over a range of normal and pathologic bones. We used bones from normal, ovariectomized and partially nephrectomized animals. All specimens underwent micro-computed tomographic imaging to assess bone morphometric and densitometric indices and uniaxial compression to failure. We obtained univariate relationships describing 71-78% of the mechanical properties of rat cortical and cancellous bone based on equivalent mineral density, bone volume fraction or apparent density over a wide range of density and common skeletal pathologies. The relationships reported in this study can be used in the structural rigidity analysis introduced by the authors to provide a non-invasive method to assess the compressive strength of bones affected by pathology and/or treatment options.

Noninvasive Prediction of Fracture Risk in Patients with Metastatic Cancer to the Spine

Purpose: Skeletal metastases affect up to 85% of breast cancer patients by the time of their death. This prospective in vivo study evaluated the diagnostic performance of computed tomography–based structural rigidity analysis (CTRA) to predict vertebral fracture risk in breast cancer patients with skeletal metastasis and in comparison with the current standard of care. Experimental Design: Torso CT scans of 94 women with vertebral metastatic breast cancer were obtained as part of routine screening for lung and liver metastases. The load-bearing capacity (LBC) and axial (EA) and bending (EI) rigidities of vertebrae T8 to L5 were calculated from CT images. The LBC was normalized by patient body mass index (BMI) to account for height and mass variations. Vertebral fracture risk was also calculated using the current radiographic-based criteria based on lesion size and location. The actual occurrence of a new vertebral fracture was assessed radiographically over the ensuing 4 months. Results: Eleven vertebral fractures occurred in 10 patients. The structural parameters EA, EI, LBC, and LBC/BMI were all 100% sensitive and 55%, 53%, 44%, and 70% specific to predict fracture risk, respectively. Although radiographic criteria correctly predicted all fracture cases (100% sensitive), only 48 of the 236 spinal segments that did not have a fracture were correctly predicted not to fracture (20% specific). Conclusions: CTRA, using CT scans as part of routine screening for lung and liver metastasis, is shown to be as sensitive as, and significantly more specific than, the current radiographic criteria for predicting vertebral fracture in breast cancer patients with skeletal metastasis. (Clin Cancer Res 2009;15(24):7676–83)

Contrast-enhanced CT with a High-Affinity Cationic Contrast Agent for Imaging ex Vivo Bovine, Intact ex Vivo Rabbit, and in Vivo Rabbit Cartilage

PURPOSE To quantify the affinity of a cationic computed tomography (CT) contrast agent (CA(4+)) and that of an anionic contrast agent (ioxaglate) to glycosaminoglycans (GAGs) in ex vivo cartilage tissue explants and to characterize the in vivo diffusion kinetics of CA(4+) and ioxaglate in a rabbit model. MATERIALS AND METHODS All in vivo procedures were approved by the institutional animal care and use committee. The affinities of ioxaglate and CA(4+) to GAGs in cartilage (six bovine osteochondral plugs) were quantified by means of a modified binding assay using micro-CT after plug equilibration in serial dilutions of each agent. The contrast agents were administered intraarticularly to the knee joints of five New Zealand white rabbits to determine the in vivo diffusion kinetics and cartilage tissue imaging capabilities. Kinetics of diffusion into the femoral groove cartilage and relative contrast agent uptake into bovine plugs were characterized by means of nonlinear mixed-effects models. Diffusion time constants (τ) were compared by using a Student t test. RESULTS The uptake of CA(4+) in cartilage was consistently over 100% of the reservoir concentration, whereas it was only 59% for ioxaglate. In vivo, the contrast material-enhanced cartilage reached a steady CT attenuation for both CA(4+) and ioxaglate, with τ values of 13.8 and 6.5 minutes, respectively (P = .04). The cartilage was easily distinguishable from the surrounding tissues for CA(4+) (12 mg of iodine per milliliter); comparatively, the anionic contrast agent provided less favorable imaging results, even when a higher concentration was used (80 mg of iodine per milliliter). CONCLUSION The affinity of the cationic contrast agent CA(4+) to GAGs enables high-quality imaging and segmentation of ex vivo bovine and rabbit cartilage, as well as in vivo rabbit cartilage. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112246/-/DC1.

Effect of mechanical convection on the partitioning of an anionic iodinated contrast agent in intact patellar cartilage

To determine if mechanical convection accelerates partitioning of an anionic contrast agent into cartilage while maintaining its ability to reflect the glycosaminoglycan (GAG) content in contrast‐enhanced computed tomography (CECT) of cartilage. Bovine patellae (N = 4) were immersed in iothalamate and serially imaged over 24 h of passive diffusion at 34°C. Following saline washing for 14 h, each patella was serially imaged over 2.5 h of mechanical convection by cyclic compressive loading (120N, 1 Hz) while immersed in iothalamate at 34°C. After similar saline washing, each patella was sectioned into 15 blocks (n = 60) and contrast concentration per time point as well as GAG content were determined for each cartilage block. Mechanical convection produced 70.6%, 34.4%, and 16.4% higher contrast concentration at 30, 60, and 90 min, respectively, compared to passive diffusion (p < 0.001) and boosted initial contrast flux 330%. The correlation between contrast concentration and GAG content was significant at all time points and correlation coefficients improved with time, reaching R2 = 0.60 after 180 min of passive diffusion and 22.5 min of mechanical convection. Mechanical convection significantly accelerated partitioning of a contrast agent into healthy cartilage while maintaining strong correlations with GAG content, providing an evidence‐based rationale for adopting walking regimens in CECT imaging protocols.

An improved method to assess torsional properties of rodent long bones

Torsion is an important testing modality commonly used to calculate structural properties of long bones. However, the effects of size and geometry must be excluded from the overall structural response in order to compare material properties of bones of different size, age and species. We have developed a new method to analyze torsional properties of bones using actual cross-sectional information and length-wise geometrical variations obtained by micro-computed topographic (microCT) imaging. The proposed method was first validated by manufacturing three rat femurs through rapid prototyping using a plastic with known material properties. The observed variations in calculated torsional shear modulus of the hollow elliptical model of mid-shaft cross-section (Ekeland et al.), multi-prismatic model of five true cross-sections (Levenston et al.) and multi-slice model presented in this study were 96%, -7% and 6% from the actual properties of the plastic, respectively. Subsequently, we used this method to derive relationships expressing torsional properties of rat cortical bone as a function of muCT-based bone volume fraction or apparent density over a range of normal and pathologic bone densities. Results indicate that a regression model of shear modulus or shear strength and bone volume fraction or apparent density described at least 81% of the variation in torsional properties of normal and pathologic bones. Coupled with the structural rigidity analysis technique introduced by the authors, the relationships reported here can provide a non-invasive tool to assess fracture risk in bones affected by pathologies and/or treatment options.

The effect of simulated scapular winging on glenohumeral joint translations.

HYPOTHESIS In this study, we aim to test whether scapular winging results in a significant change in glenohumeral translation in the initial phase of the throwing motion. METHODS Six shoulders underwent an abbreviated throwing motion (ATM) from late cocking to the end of acceleration by use of a validated robotic system. The intact specimens were tested to establish a baseline. The position of the scapula was then affected to simulate scapular winging by placing a cylindrical wedge under the inferior angle of the scapula, and the ATM was performed again. For both conditions, the average glenohumeral translations and scapular rotations were plotted over time to calculate the area under the curve, as a representative of the overall glenohumeral translations and scapular rotations observed during the ATM. RESULTS Throughout the motion, the winged scapulae showed, on average, 7.7° more upward rotation, 1.6° more internal rotation, and 5.3° more anterior tipping as compared with the baseline. The scapular position relative to the hanging arm was significantly different between the baseline and scapular winging conditions in all arm positions, except for maximal external rotation and the neutral position. Comparing the area under the curve at baseline and with scapular winging indicated that scapular winging significantly increased anterior translation of the glenohumeral joint whereas translation in the superior/inferior and medial/lateral directions did not result in a change in translation. DISCUSSION These results may suggest a more important role of abnormalities in scapular position in predisposing throwing athletes to shoulder injuries of the anterior capsulolabral structures and consecutive glenohumeral instability.

Substitutes of structural and non-structural autologous bone grafts in hindfoot arthrodeses and osteotomies: a systematic review.

BackgroundStructural and non-structural substitutes of autologous bone grafts are frequently used in hindfoot arthrodeses and osteotomies. However, their efficacy is unclear.The primary goal of this systematic review was to compare autologous bone grafts with structural and non-structural substitutes regarding the odds of union in hindfoot arthrodeses and osteotomies.MethodsThe Medline and EMBASE and Cochrane databases were searched for relevant randomized and non-randomized prospective studies as well as retrospective comparative chart reviews.Results10 studies which comprised 928 hindfoot arthrodeses and osteotomies met the inclusion criteria for this systematic review. The quality of the retrieved studies was low due to small samples sizes and confounding variables. The pooled random effect odds for union were 12.8 (95% CI 12.7 to 12.9) for structural allografts, 5.7 (95% CI 5.5 to 6.0) for cortical autologous grafts, 7.3 (95% CI 6.0 to 8.6) for cancellous allografts and 6.0 (95% CI 5.7 to 6.4) for cancellous autologous grafts. In individual studies, the odds of union in hindfoot arthrodeses achieved with cancellous autologous grafts was similar to those achieved with demineralised bone matrix or platelet derived growth factor augmented ceramic granules.ConclusionOur results suggest an equivalent incorporation of structural allografts as compared to autologous grafts in hindfoot arthrodeses and osteotomies. There is a need for prospective randomized trials to further clarify the role of substitutes of autologous bone grafts in hindfoot surgery.

Design and manufacture of a novel system to simulate the biomechanics of basic and pitching shoulder motion

Objectives Cadaveric models of the shoulder evaluate discrete motion segments using the glenohumeral joint in isolation over a defined trajectory. The aim of this study was to design, manufacture and validate a robotic system to accurately create three-dimensional movement of the upper body and capture it using high-speed motion cameras. Methods In particular, we intended to use the robotic system to simulate the normal throwing motion in an intact cadaver. The robotic system consists of a lower frame (to move the torso) and an upper frame (to move an arm) using seven actuators. The actuators accurately reproduced planned trajectories. The marker setup used for motion capture was able to determine the six degrees of freedom of all involved joints during the planned motion of the end effector. Results The testing system demonstrated high precision and accuracy based on the expected versus observed displacements of individual axes. The maximum coefficient of variation for displacement of unloaded axes was less than 0.5% for all axes. The expected and observed actual displacements had a high level of correlation with coefficients of determination of 1.0 for all axes. Conclusions Given that this system can accurately simulate and track simple and complex motion, there is a new opportunity to study kinematics of the shoulder under normal and pathological conditions in a cadaveric shoulder model.