Monitoring the effects of dexamethasone treatment by MRI using in vivo iron oxide nanoparticle-labeled macrophages.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic disease causing recurring inflammatory joint attacks. These attacks are characterized by macrophage infiltration contributing to joint destruction. Studies have shown that RA treatment efficacy is correlated to synovial macrophage number. The aim of this study was to experimentally validate the use of in vivo superparamagnetic iron oxide nanoparticle (SPION) labeled macrophages to evaluate RA treatment by MRI. METHODS: The evolution of macrophages was monitored with and without dexamethasone (Dexa) treatment in rats. Two doses of 3 and 1 mg/kg Dexa were administered two and five days following induction of antigen induced arthritis. SPIONs (7 mg Fe/rat) were injected intravenously and the knees were imaged in vivo on days 6, 10 and 13. The MR images were scored for three parameters: SPION signal intensity, SPION distribution pattern and synovial oedema. Using 3D semi-automated software, the MR SPION signal was quantified. The efficacy of SPIONs and gadolinium chelate (Gd), an MR contrast agent, in illustrating treatment effects were compared. Those results were confirmed through histological measurements of number and area of macrophages and nanoparticle clusters using CD68 immunostaining and Prussian blue staining respectively. RESULTS: Results show that the pattern and the intensity of SPION-labeled macrophages on MRI were altered by Dexa treatment. While the Dexa group had a uniform elliptical line surrounding an oedema pocket, the untreated group showed a diffused SPION distribution on day 6 post-induction. Dexa reduced the intensity of SPION signal 50-60% on days 10 and 13 compared to controls (P = 0.00008 and 0.002 respectively). Similar results were found when the signal was measured by the 3D tool. On day 13, the persisting low grade arthritis progression could not be demonstrated by Gd. Analysis of knee samples by Prussian blue and CD68 immunostaining confirmed in vivo SPION uptake by macrophages. Furthermore, CD68 immunostaining revealed that Dexa treatment significantly decreased the area and number of synovial macrophages. Prussian blue quantification corresponded to the macrophage measurements and both were in agreement with the MRI findings. CONCLUSIONS: We have demonstrated the feasibility of MRI tracking of in vivo SPION-labeled macrophages to assess RA treatment effects.

Improving bone strength prediction in human proximal femur specimens through geometrical characterization of trabecular bone microarchitecture and support vector regression.

We investigate the use of different trabecular bone descriptors and advanced machine learning tech niques to complement standard bone mineral density (BMD) measures derived from dual-energy x-ray absorptiometry (DXA) for improving clinical assessment of osteoporotic fracture risk. For this purpose, volumes of interest were extracted from the head, neck, and trochanter of 146 ex vivo proximal femur specimens on multidetector computer tomography. The trabecular bone captured was characterized with (1) statistical moments of the BMD distribution, (2) geometrical features derived from the scaling index method (SIM), and (3) morphometric parameters, such as bone fraction, trabecular thickness, etc. Feature sets comprising DXA BMD and such supplemental features were used to predict the failure load (FL) of the specimens, previously determined through biomechanical testing, with multiregression and support vector regression. Prediction performance was measured by the root mean square error (RMSE); correlation with measured FL was evaluated using the coefficient of determination R2. The best prediction performance was achieved by a combination of DXA BMD and SIM-derived geometric features derived from the femoral head (RMSE: 0.869 ± 0.121, R2: 0.68 ± 0.079), which was significantly better than DXA BMD alone (RMSE: 0.948 ± 0.119, R2: 0.61 ± 0.101) (p < 10-4). For multivariate feature sets, SVR outperformed multiregression (p < 0.05). These results suggest that supplementing standard DXA BMD measurements with sophisticated femoral trabecular bone characterization and supervised learning techniques can significantly improve biomechanical strength prediction in proximal femur specimens.

Effect of exercise intervention on thigh muscle volume and anatomical cross-sectional areas--quantitative assessment using MRI.

The objective of this study was to evaluate the location-specific magnitudes of an exercise intervention on thigh muscle volume and anatomical cross-sectional area, using MRI. Forty one untrained women participated in strength, endurance, or autogenic training for 12 weeks. Axial MR images of the thigh were acquired before and after the intervention, using a T1-weighted turbo-spin-echo sequence (10 mm sections, 0.78 mm in-plane resolution). The extensor, flexor, adductor, and sartorius muscles were segmented between the femoral neck and the rectus femoris tendon. Muscle volumes were determined, and anatomical cross-sectional areas were derived from 3D reconstructions at 10% (proximal-to-distal) intervals. With strength training, the volume of the extensors (+3.1%), flexors (+3.5%), and adductors (+3.9%) increased significantly (P < 0.05) between baseline and follow-up, and with endurance training, the volume of the extensor (+3.7%) and sartorius (+5.1%) increased significantly (P < 0.05). No relevant or statistically significant change was observed with autogenic training. The greatest standardized response means were observed for the anatomical cross-sectional area in the proximal aspect (10-30%) of the thigh and generally exceeded those for muscle volumes. The study shows that MRI can be used to monitor location-specific effects of exercise intervention on muscle cross-sectional areas, with the proximal aspect of the thigh muscles being most responsive.

Trabecular bone structure obtained from multislice spiral computed tomography of the calcaneus predicts osteoporotic vertebral deformities.

PURPOSE: To compare multislice computed tomography (MSCT)-derived parameters of the trabecular bone structure of the calcaneus with bone mineral density (BMD) in their ability to differentiate between donors with and without osteoporotic fractures of the spine and to optimize CT scan protocols. METHODS: Forty-two postmortem calcanei (81.2 +/- 10 years) were imaged with a 16-detector row MSCT system using 4 different scan protocols varying spatial resolution (12-24 lp/cm) and radiation dose. Structural parameters of trabecular bone were derived from these images, and BMDs of the calcanei were determined using dual x-ray absorptiometry. Vertebral deformities of the spine were radiographically classified using the Spinal Fracture Index. Diagnostic performance in differentiation between donors with and without vertebral fractures was assessed using receiver operating characteristic (ROC) analysis. RESULTS: There were significant case-control differences for many of the structural parameters measured (P < 0.05). The highest ROC values were found for apparent trabecular thickness using the high-resolution and high-dose protocols. Statistically significant correlations were found between most structure parameters and BMD (up to r = 0.85, P < 0.01). CONCLUSION: Structural parameters of trabecular bone as obtained from high-resolution MSCT images of the calcaneus can be used to differentiate between donors with and without osteoporotic vertebral fractures, using a high-resolution and high-dose CT protocol.