Characterization of the mid-coronal plane method for measurement of radiographic change in knee joint space width across different levels of image parallax.

OBJECTIVE: Radiographic measurement of the change in knee joint space width (ΔJSW) is often affected by image parallax, which causes an apparent exaggeration of JSW due to projectional differences. This issue with parallax (quantified by intermargin distance) can in part be addressed with a novel mid-coronal plane (MCP) measurement method. The objectives of the study were to determine 1) accuracy and 2) reproducibility of the MCP method, and 3) compare the MCP method to that used in the Osteoarthritis Initiative (OAI) for different categories of parallax. METHODS: Posteroanterior radiographs (n = 70) with known JSW were digitally reconstructed from CT images of cadaver knees and used to determine the accuracy of ΔJSW using the MCP method for parallax categories of None, Mild/Moderate, and Severe. Reproducibility was determined from pairs of clinical radiographs selected from the OAI (n = 170). The MCP method was also compared to the OAI methodology. Both reproducibility and agreement were characterized by Bland-Altman analysis and intraclass correlation coefficients (ICC). RESULTS: The MCP method was accurate to 0.11 mm in cases with no parallax, and 0.18 mm across all categories of parallax for medial and lateral compartments. Reproducibility of the MCP method was graded "excellent" (ICC 0.98, 95% CI [0.98, 0.99]). The MCP results agreed very well with the OAI (ICC 0.92, 95% CI [0.89, 0.94]), with mean absolute differences between methods increasing with increasing parallax. CONCLUSION: The MCP method is an accurate, reproducible alternative to the OAI method for multi-center clinical trials where subject and X-ray beam positioning may be variable.

Quantitative imaging of proteoglycan in cartilage using a gadolinium probe and microCT.

OBJECTIVE: Micro-computed tomography (microCT) imaging has the potential to allow the three-dimensional (3D) visualization of cartilage morphology. However, cartilage intensity on a microCT image is weak because cartilage does not strongly attenuate X-rays. This work was designed to demonstrate that exposure of cartilage to charged gadolinium compounds modifies the intensity to allow an improved visualization of cartilage morphology and the determination of proteoglycan content. DESIGN: Trypsin was used to deplete proteoglycan in bovine nasal cartilage disks. Disks were then exposed to Gd(3+), gadopentetate (Gd-DTPA(2-)), or gadoteridol (Gd-HP-DO3A), and imaged with microCT. The intensities of the disks were measured from the images and compared to the actual proteoglycan content determined with a dimethylmethylene blue assay. RESULTS: Treatment of naïve disks with 200 mM Gd(3+) for 24h at room temperature produced a 2.8-fold increase in intensity on microCT images. Similar treatment with 200 mM Gd-DTPA(2-) produced a 1.4-fold increase. After 2h of trypsin treatment at room temperature, the intensities of cartilage disks exposed to 20 0mM Gd(3+) decreased by 12%. Conversely, the intensities of trypsin-treated disks exposed to 200 mM Gd-DPTA(2-) increased by 15%. Trypsin treatment caused a 4% increase in the intensities of disks exposed to neutral Gd-HP-DO3A. The correlation between proteoglycan content and the microCT intensity of cartilage treated with Gd(3+) was very good (r(2)=0.81). CONCLUSIONS: Gadolinium and microCT allow an improved 3D visualization of cartilage and quantification of its proteoglycan content.

Magnetic resonance imaging of denervation-induced muscle atrophy: effects of clenbuterol in the rat.

We show that magnetic resonance imaging (MRI) can be used to quantify the amount of muscle in the lower legs of adult rats and to noninvasively monitor the onset and progression of denervation-induced atrophy. Muscle cross-sectional areas determined from 2D gradient-echo MR images allow longitudinal quantification of the protective effects of a beta(2)-adrenergic agonist clenbuterol. We also show that the estimation of clenbuterol's efficacy is improved by computation of the muscle volume. Rapid animal throughput and the ability to accurately estimate efficacy make MRI an attractive technology for studying skeletal muscle atrophy and hypertrophy, allowing the evaluation of potential therapies in longitudinal studies.

Three-dimensional microimaging (MRmicroI and microCT), finite element modeling, and rapid prototyping provide unique insights into bone architecture in osteoporosis.

With the proportion of elderly people increasing in many countries, osteoporosis has become a growing public health problem, with rising medical, social, and economic consequences. It is well recognized that a combination of low bone mass and the deterioration of the trabecular architecture underlies osteoporotic fractures. A comprehensive understanding of the relationships between bone mass, the three-dimensional (3D) architecture of bone and bone function is fundamental to the study of new and existing therapies for osteoporosis. Detailed analysis of 3D trabecular architecture, using high-resolution digital imaging techniques such as magnetic resonance microimaging (MRmicroI), micro-computed tomography (microCT), and direct image analysis, has become feasible only recently. Rapid prototyping technology is used to replicate the complex trabecular architecture on a macroscopic scale for visual or biomechanical analysis. Further, a complete set of 3D image data provides a basis for finite element modeling (FEM) to predict mechanical properties. The goal of this paper is to describe how we can integrate three-dimensional microimaging and image analysis techniques for quantitation of trabecular bone architecture, FEM for virtual biomechanics, and rapid prototyping for enhanced visualization. The integration of these techniques provide us with an unique ability to investigate the role of bone architecture in osteoporotic fractures and to support the development of new therapies.

Evaluation of changes in trabecular bone architecture and mechanical properties of minipig vertebrae by three-dimensional magnetic resonance microimaging and finite element modeling.

The study objective was to analyze the three-dimensional (3D) trabecular architecture and mechanical properties in vertebral specimens of young and mature Sinclair minipigs to assess the relative contribution of architecture to bone strength. We used 3D magnetic resonance microimaging (MRmicroI) and direct image analysis to evaluate a set of standard structural measurements and new architectural descriptors of trabecular bone in biopsy specimens from L2, L3, and L4 vertebrae (n = 16 in each group) from young (mean age, 1.2 years) and mature (mean age, 4.8 years) minipigs. The measurements included bone volume/tissue volume (BV/TV), marrow star volume (Ma.St.V), connectivity density (ConnD), and two new parameters, percent platelike trabeculae (% plate) and percent bone in the load direction (% boneLD). The % plate, calculated from surface curvature, allowed the delineation of plates from rods. The % boneLD quantified the percentage of bone oriented along the long axis of the vertebral body. We showed that 3D MRmicroI can detect the subtle changes in trabecular architecture between the two age groups. ConnD, star volume, % plate, % boneLD, and BV/TV were found to be more effective than the model-based, derived indices (trabecular thickness [Tb.Th], trabecular separation [Tb.Sp], and trabecular number [Tb.N]) in differentiating the structural changes. BV/TV, % plate, and % boneLD significantly increased (p < 0.05) in all three vertebral sites of the mature minipigs. The significant decrease in ConnD and star volume in the mature vertebra was consistent with the concurrent increase of platelike trabecular bone (p < 0.05). Overall, ConnD, star volume, % plate, and % boneLD provided a coherent picture of the architectural changes between the two age groups. Apparent modulus and maximum stress were determined experimentally on biopsy specimens from L2 vertebrae (n = 16). When apparent modulus was predicted using 3D MRmicroI data sets as input for finite element modeling (FEM), the results were similar to the experimentally determined apparent modulus (p = 0.12). Both methods were then used to compare the young and the mature animals; the experimental and predicted apparent modulus were significantly higher for the mature group (p = 0.003 and 0.012, respectively). The experimental maximum stress in the vertebra of the mature animals was twice as high as that for the young animals (p = 0.006). Bone quantity (BV/TV or bone mineral content [BMC]) alone could explain approximately 74-85% of the total variability in stress and modulus. The inclusion of either ConnD or % boneLD with BV/TV in a multiple regression analysis significantly improved the predictability of maximum stress, indicating that architecture makes additional contributions to compressive strength in normal minipig vertebra.

Bone architecture and image synthesis.

3-D bone architecture can now be measured by micro-computer tomography or micro-magnetic resonance imaging. The principles of the micro-computer technique is reviewed and new architectural parameters can be computed. In addition, the method allows the contruction of polymer models by stereolithography, a method that can be used to perform repetitive mechanical studies on the same bone sample. These non destructive methods are interesting in the pre-clinical studies on bone diseases and in the investigation of animal trials on new pharmacological compounds active on bone.

Motion suppression improves quantification of rat liver volume in vivo by magnetic resonance imaging.

In response to the presence of certain compounds, rat liver weight can increase. Under the assumption that the liver density does not change, the liver volume will increase as well. To develop the capability to monitor this process noninvasively over time, we used liver volumes determined from MR images to estimate the in vivo liver volumes and weights of normal rats. We acquired multislice, spin-echo images from 18 rats using several protocols for suppression of motion artifacts. We found that volumes determined from data obtained using a combination of gradient moment nulling and respiratory gating, or a combination of signal averaging and "retarded" (after the pi pulse) phase-encoding, produced the most accurate estimates of in vivo liver volume and weight.

Stroboscopic nuclear magnetic resonance microscopy of arterial blood flow.

NMR microscopy was used to obtain transverse flow profiles of arterial blood flow in the rat carotid artery at 33 microns resolution. The images were gated to the EKG and correspond to identified regions of diastole. The profiles show that flow is laminar during this part of the heart cycle. These results provide the first direct view of blood flow profiles in arteries of submillimeter diameter and suggest that animals as small as juvenile rodents will serve as valuable models for hemodynamic studies. Extensions to flow during systole, stenoses, and flow in the vicinity of the carotid bifurcation are discussed.

Stroboscopic NMR microscopy of the carotid artery.

The non-invasive measurement of vascular dynamics and elasticity is critical in understanding haemodynamic conditions of cardiovascular diseases such as hypertension and atherosclerosis. Although there are numerous invasive and in vitro techniques for such measurements, until now non-invasive methods have been limited. We have now obtained stroboscopic NMR images of the carotid arteries of 80-g rats. The change in the cross-sectional area of arteries of diameter approximately 600-800 microns was correlated with the change in absolute blood pressure. These are the first microimages of a dynamic system and enable the direct visualization of compliance, the non-invasive measurement of Young's modulus, the direct determination of the local effects of vasoconstrictors and vasodilators and the mapping of the entire cardiac cycle.