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Recently, 3-T magnetic resonance imaging (MRI) has been introduced for bone imaging. Through higher signal-to-noise ratios, as compared to 1.5-T MRI, it promises to be a more powerful tool for the assessment of cortical and trabecular bone measures. The goal of our study was to compare MRI-derived cortical and trabecular bone measures to quantitative computed tomography (QCT)-derived bone mineral density (BMD). Using 3-T MRI in 51 postmenopausal women, apparent (app.) measures of bone volume/total volume, trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular separation were derived at the distal radius, distal tibia and calcaneus. Cortical thickness (Ct.Th) was calculated at the distal radius and distal tibia. These measures were compared to QCT-derived BMD of the spine, hip and radius. Significant correlations ((*)P<.05; (**)P<.001; (***)P<.0001) were found between spine BMD- and MRI-derived Ct.Th (r(radius)=.55, (*)P<.05; r(tibia)=.67, (***)P<.0001) and app. Tb.N (r(radius)=.33, (*)P<.05; r(tibia)=.35, (*)P<.05) at the radius and tibia. Furthermore, within the first 10 mm at the radius, an inverse correlation for Ct.Th and app. BV/TV (r(6mm)=-.56, P<.001; r(10mm)=-.36, P<.05) and app. Tb.Th (r(6mm)=-.54, P<.001; r(10mm)=-.41, P<.05) was found., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The aim of this study was to compare structure measures obtained from high-resolution MR images of the calcaneus and the distal radius with bone mineral density (BMD) of the spine and hip in the prediction of osteoporotic spine fracture status. High-resolution MR images of the calcaneus and radius were obtained in 24 post-menopausal women with spine fractures and 22 age-matched controls. Imaging was performed at 1.5 T using a T1-weighted spin-echo sequence (slice thickness 1 mm, in-plane spatial resolution 195 x 195 microm(2)). Structure analysis was performed using parameters analogous to standard histomorphometry. Bone mineral density of the spine was obtained using quantitative CT and of the hip with dual-energy X-ray absorptiometry. Significant differences between both patient groups were obtained with BMD and all structure parameters ( p<0.05). Using receiver operating characteristic analysis to determine the diagnostic performance in differentiating both groups, the best results were found for BMD of the spine, one of the radial structure measures and a combination of the calcaneal structure measures. In this study BMD of the spine and structure measures of the distal radius were best suited to predict the osteoporotic fracture status of the spine. A combination of BMD and structure measures did not yield any additional information on fracture status.

Objective: To investigate whether recently developed in vivo high-resolution magnetic resonance-imaging and micro-finite element techniques can monitor changes in bone mechanical properties during long-term clinical trials aiming at evaluating the efficacy of new drugs for the treatment of osteoporosis., Design: Comparison of baseline and follow-up mechanical parameters calculated using micro-finite element analysis of the calcaneus for subjects participating in a study investigating the effect of idoxifene., Background: Contemporary measurements for the evaluation of bone mechanical properties, based on dual-energy X-ray absorptiometry measurements, are not very accurate and require large trial populations., Methods: A total of 56 postmenopausal subjects received either a placebo, 5 mg or 10 mg per day of idoxifene. Magnetic resonance-images of the calcaneus were made at baseline and after one year. Mechanical parameters of a trabecular volume of interest in the calcaneus were calculated using micro-finite element analysis., Results: Although there were no significant differences between the mean changes in the treated groups and the placebo group, there were significant changes from baseline within groups after one year of treatment. Significant changes, however, were found only for mechanical parameters and only in the treated groups., Conclusions: The present study is the first demonstration that longitudinal changes in bone mechanical properties due to trabecular micro-architectural changes may be quantified in long-term clinical studies. Since significant changes in mechanical parameters were obtained for the treated groups whereas no significant change in bone mass was found we conclude that the application of these techniques may increase the clinical significance of these trials., Relevance: A precise diagnosis of in vivo bone mechanical properties that accounts for (changes in) trabecular bone architecture is of particular importance for longitudinal clinical trials aiming at evaluating the efficacy of new drugs since it can lead to clinically relevant results from shorter follow-up intervals and may enable a reduction of the number of patients involved in the trial.

The authors have developed a system for the characterization of trabecular bone structure from high-resolution MR images. It features largely automated coil inhomogeneity correction, trabecular bone region segmentation, serial image registration, bone/marrow binarization, and structural calculation steps. The system addresses problems of efficiency and inter- and intraoperator variability inherent in previous analyses. The system is evaluated on repetitive scans of 8 volunteers for both two-dimensional (2D) apparent structure calculations and three-dimensional (3D) mechanical calculations using micro-finite element analysis. Coil correction methods based on a priori knowledge of the coil sensitivity and on low-pass filtering of the high-resolution mages are compared and found to perform similarly. Image alignment is found to cause small but significant changes in some structural parameters. Overall the automated system provides on the order of a 3-fold decrease in trained operator time over previous manual methods. Reproducibility is found to be dependent on image quality for most parameters. For 7 subjects with good image quality, reproducibility of 2-4% is found for 2D structural parameters, while 3D mechanical parameters vary by 4-9%, with percent standardized coefficients of variation in the ranges of 15-34% and 20-38% respectively.

Measurement of microstructural parameters of trabecular bone noninvasively in vivo is possible with high-resolution magnetic resonance (MR) imaging. These measurements may prove useful in the determination of bone strength and fracture risk, but must be related to other measures of bone properties. In this study in vivo MR imaging was used to derive trabecular bone structure measures and combined with micro-finite element analysis (microFE) to determine the effects of trabecular bone microarchitecture on bone mechanical properties in the distal radius. The subjects were studied in two groups: (I) postmenopausal women with normal bone mineral density (BMD) (n = 22, mean age 58 +/- 7 years) and (II) postmenopausal women with spine or femur BMD -1 SD to -2.5 SD below young normal (n = 37, mean age 62 +/- 11 years). MR images of the distal radius were obtained at 1.5 T, and measures such as apparent trabecular bone volume fraction (App BV/TV), spacing, number and thickness (App TbSp, TbN, TbTh) were derived in regions of interest extending from the joint line to the radial shaft. The high-resolution images were also used in a micro-finite element model to derive the directional Young's moduli (E1, E2 and E3), shear moduli (G12, G23 and G13) and anisotropy ratios such as E1/E3. BMD at the distal radius, lumbar spine and hip were assessed using dual-energy X-ray absorptiometry (DXA). Bone formation was assessed by serum osteocalcin and bone resorption by serum type I collagen C-terminal telopeptide breakdown products (serum CTX) and urinary CTX biochemical markers. The trabecular architecture displayed considerable anisotropy. Measures of BMD such as the ultradistal radial BMD were lower in the osteopenic group (p<0.01). Biochemical markers between the two groups were comparable in value and showed no significant difference between the two groups. App BV/TV, TbTh and TbN were higher, and App TbSp lower, in the normal group than the osteopenic group. All three directional measures of elastic and shear moduli were lower in the osteopenic group compared with the normal group. Anisotropy of trabecular bone microarchitecture, as measured by the ratios of the mean intercept length (MIL) values (MIL1/MIL3, etc.), and the anisotropy in elastic modulus (E1/E3, etc.), were greater in the osteopenic group compared with the normal group. The correlations between the measures of architecture and moduli are higher than those between elastic moduli and BMD. Stepwise multiple regression analysis showed that while App BV/TV is highly correlated with the mechanical properties, additional structural measures do contribute to the improved prediction of the mechanical measures. This study demonstrates the feasibility and potential of using MR imaging with microFE modeling in vivo in the study of osteoporosis.

Purpose: To use high-spatial-resolution magnetic resonance (MR) imaging to analyze the trabecular bone structure of the calcaneus in patients before and after heart transplantation and to compare this technique with bone mineral density (BMD) measurement in predicting therapy-induced bone loss and vertebral fracture status., Materials and Methods: High-spatial-resolution 1.5-T MR imaging of the calcaneus was performed in 40 men 11-120 months after heart transplantation, in 11 men before heart transplantation, and in 10 age-matched male volunteers. Sagittal and transverse T1-weighted spin-echo images with a voxel size of 0.195 x 0.195 x 1.000 mm were obtained, and structure measurements analogous to bone histomorphometric values were calculated. In addition, the BMD of the lumbar spine was determined in the transplant recipients pre- and postoperatively by using quantitative computed tomography, and vertebral fracture status was assessed., Results: Significant differences in structure and BMD measurements were found between patients before and after heart transplantation (P <. 05). In 17 (42%) of 40 transplant recipients, vertebral fractures were found. Although structure measurements were significantly different between patients with and those without fractures (P <.05), BMDs were not. Correlations between time after transplantation and some structure measurements were moderately significant (P <. 05), but such correlations with BMD measurements were not., Conclusion: MR imaging-derived structure measurements in the calcaneus are useful for monitoring bone changes after heart transplantation and assessing vertebral fracture status.

Conventional radiography and fractal analysis were used to quantify trabecular texture patterns in human femur specimens and these measures were used in conjunction with bone mineral density (BMD) to predict bone strength. Radiographs were obtained from 51 human femur specimens (25 male, 26 female). The radiographs were analyzed using three different fractal geometry based techniques, namely semi-variance, surface area and Fourier analysis. Maximum compressive strength (MCS) and shear stress (MSS) were determined with a material testing machine: BMD was measured using quantitative computed tomography (QCT). MCS and MSS both correlated significantly with BMD (MCS: R = 0.49-0.54; MSS: R = 0.69-0.72). Fractal dimension also correlated significantly with both biomechanical properties (MCS: R = 0.49-0.56; MSS: R = 0.47-0.54). Using multivariate regression analysis, the fractal dimension in addition to BMD improved correlations versus biomechanical properties. Both BMD and fractal dimension showed statistically significant correlation with bone strength. The fractal dimension provided additional information beyond BMD in correlating with biomechanical properties.

Trabecular bone structure and bone density contribute to the strength of bone and are potentially important in the study of osteoporosis. Fourier transforms of the textural patterns in radiographs of trabecular bone have previously been used for the measurement of trabecular bone structure in subjects, however, the relationship between these measures and biomechanical properties of bone have not previously been established. In this study radiographs were acquired of 28 cubic specimens of spinal trabecular bone along each of the three anatomic axes: cranio-caudal or superior-inferior (SI), medial-lateral (ML), and anterior-posterior (AP). The radiographs were digitized, background corrected, and uniformly aligned. The Fast Fourier transform (FFT) was performed on a region comprised solely of trabecular bone for each image. The zero (DC), first (FMO), and second moments (SMO) of the Fourier power spectrum and the fractal dimension (FD) as determined from the Fourier power spectrum were correlated with stereology measures, with bone mineral density (BMD) as well as with measured biomechanical properties [Young's elastic modulus (YM) and ultimate strength] of the cubes. The results show that the power spectra-based measures, when compared with structural parameters determined using 3D stereology, show good correlations with bone volume fraction, trabecular spacing, thickness, and number. These power spectral measures showed fair to good correlations with BMD and the biomechanical properties. Moreover, the correlations between the power spectral measures of trabecular structure and the BMD, YM, and stereology measures of structure depend on the orientation of the radiographic image. Specifically, these were significant differences in the measured biomechanical properties and the power spectral measures of the trabecular structure between the SI and ML and the SI and AP directions. In addition, depending on the spatial frequency range for analysis, the fractal dimension showed opposite trends with changes in BMD and biomechanical properties. Multivariate regression models showed the correlation coefficients increasing with the inclusion of some of the power spectral measures, suggesting that FFT-based texture analysis may play a potential role in studies of osteoporosis.

The measurement of bone microstructure as well as bone mineral density may improve the estimation of bone strength. Cubic specimens (N = 26, 12 mm X 12 mm X 12 mm) of human cadaver vertebrae were cut along three orthogonal anatomic orientations, i.e., superior-inferior (SI), medial-lateral (ML), and anterior-posterior (AP). Contact radiographs of the bone cubes along all three orientations were obtained and then digitized by a laser scanner with pixel size of 50 microns x 50 microns. The specimens were tested in compression along the 3 orthogonal orientations and the Young's modulus (YM) was calculated for each direction. Quantitative computed tomography (QCT) was used to obtain a measure of trabecular bone mineral density (BMD). Global gray level thresholding and local thresholding algorithms were used to extract the trabecular bone network. Apparent trabecular bone fraction (ABV/TV), mean intercept length (I.TH), mean intercept separation (I.SP), and number of nodes (N.ND) were measured from the extracted trabecular network. Fractal dimension (Fr.D) of the trabecular bone texture was also measured. Paired t-tests showed that the mean values of each texture parameter (except ABV/TV) and of YM along the SI direction were significantly different (p < 0.05) from those along the ML and AP direction. However, the mean values along the ML and AP directions were not significantly different. Multivariate regression of YM as a function of the texture parameters and BMD showed that without adjusting for the effect of BMD, YM was significantly explained by all the texture parameters (R2 = 0.2-0.6). When BMD was included in the regression, although the variations in YM of ML, AP, and SI orientations could be explained by BMD alone, some of the texture parameters did improve the overall prediction of the biomechanical properties, while, some parameters such as ABV/TV and Fr.D in the ML orientation showed a more significant overall effect in explaining mechanical strength than did BMD. In conclusion, trabecular texture parameters correlated significantly with BMD and YM. Trabecular texture parameters from projectional radiographs reflect the anisotropy of trabecular structure. Quantitative radiographic assessment of trabecular structure using fine-detail radiography can potentially improve the estimation of bone strength.

Purpose: Our goal was to use high resolution (HR) CT images combined with texture analysis to investigate the trabecular structure of human vertebral specimens and to compare these techniques with bone mineral density (BMD) in the prediction of bone strength., Method: HR CT images with a slice thickness of 1 mm were obtained of 28 bone cubes. Four different groups of texture analysis techniques were used to assess these images. In addition, quantitative CT (QCT) was performed and elastic modulus (EM) was determined biomechanically., Results: R2 between EM and BMD was 0.78 (p < 0.01). R2 values for EM versus most of the texture measures were also significant. Texture measures in addition to measures of BMD in a multivariate regression model significantly increased R2 up to 0.87., Conclusion: In an experimental setting, texture parameters calculated using HR CT images correlated significantly with EM. Combining texture measures with BMD improved the prediction of EM significantly.

Rationale and Objectives: The authors used direct magnification radiographs, combines with texture analysis, to investigate the trabecular structure of human vertebral specimens and compared these techniques with measurement of bone mineral density (BMD) by using quantitative computed tomography to predict bone strength., Methods: Direct magnification radiographs and BMD measurements were obtained from 38 motion segments from the thoracolumbar spines of 11 female human cadavers. Maximum compressive strength (MCS) was determined with a materials testing machine. Morphologic parameters, digital skeletons, and fractal dimension were obtained from the radiographs in three different regions of interest., Results: Correlations between BMD and MCS were statistically significant (r = .81, P < .01). With morphologic parameters, correlation coefficients of up to .64 (P < .01) were obtained. Use of multivariate regression analysis with one morphologic parameter (the width of the black pixels, or thicknessB) in addition to BMD improved correlations versus MCS (P < .01)., Conclusion: In an experimental setting, BMD showed statistically significant correlation with bone strength, whereas the structural parameters demonstrated only modest correlations. BMD together with one of these measures (thicknessB), however, showed the highest correlation.

High resolution magnetic resonance (MR) images of the distal radius were obtained at 1.5 Tesla in premenopausal normal, postmenopausal normal, and postmenopausal osteoporotic women. The image resolution was 156 microm in plane and 700 microm in the slice direction; the total imaging time was approximately 16 minutes. An intensity-based thresholding technique was used to segment the images into trabecular bone and marrow, respectively. Extensions of standard stereological techniques were used to derive measures of trabecular bone structure from these segmented images. The parameters calculated included apparent measures of trabecular bone volume fraction, trabecular thickness, trabecular spacing, and trabecular number. Fractal-based texture parameters, such as the box-counting dimension, were also derived. Trabecular bone mineral density (BMD) and cortical bone mineral content (BMC) were measured in the distal radius using peripheral quantitative computed tomography (pQCT). In a subset of patients, spinal trabecular BMD was measured using quantitative computed tomography (QCT). Correlations between the indices of trabecular bone structure measured from these high-resolution MR images, age, BMD, and osteoporotic fracture status were examined. Cortical BMC and trabecular BMD at the distal radius, spinal BMD, trabecular bone volume fraction, trabecular thickness, trabecular number, and fractal dimension all decreased with age. Trabecular spacing showed the greatest percentage change and increased with age. In addition, significant differences were evident in spinal BMD, radial trabecular BMD, trabecular bone volume fraction, trabecular spacing, and trabecular number between the postmenopausal nonfracture and the postmenopausal osteoporotic subjects. Trabecular spacing and trabecular number showed moderate correlation with radial trabecular BMD but correlated poorly with radial cortical BMC. High resolution MR imaging, a potentially useful tool for quantifying trabecular structure in vivo, may have applications for understanding and evaluating skeletal changes related to age and osteoporosis.

MR measurements of transverse relaxation time, T2*, in trabecular bone may provide both structural and density-related information for assessment of bone mineral status in osteoporosis. Using submillimeter scale glass phantoms as simplified models of trabecular bone, we have made a quantitative investigation of the dependence of T2* decay on modeled trabecular microstructure and MR image resolution. The experimental MR data are in excellent agreement with predictions from a computer simulation. Decreasing the modeled trabecular bone volume fraction, sigma, decreases the decay rate, as expected. However, if trabecular width and spacing are both increased without changing sigma, the decay rate is unchanged. The measured decay curves closely follow the predicted dependence on trabecular orientation. The decay rates are independent of image resolution, provided that the pixel dimensions are larger than the intertrabecular spacing. For smaller pixel sizes, the decay rate decreases with decreasing pixel size.

Purpose: To evaluate in vivo the relationship between magnetic resonance (MR) imaging relaxation time and bone mineral density (BMD) at the distal radius., Materials and Methods: The 1/T2* MR imaging relaxation rates and dual X-ray absorptiometry (DXA) measurements were evaluated in the trabecular bone of the distal 5 cm of the radius in 14 healthy premenopausal women and 11 healthy postmenopausal women and in 11 women with osteoporosis. Trabecular and total BMD were measured with peripheral quantitative computed tomography (CT)., Results: In healthy women, 1/T2* values and trabecular BMD at peripheral quantitative CT were significantly correlated but 1/T2* and total BMD were not. Statistically significant (P = .03) correlations between 1/T2* and DXA were found only in the most distal area covered with DXA. The 1/T2* values were more closely correlated with age and showed higher relative annual decreases (0.47%-0.81%) than peripheral quantitative CT (0.20%-0.59%) or DXA (0.10%-0.39%). Pre- and postmenopausal healthy subjects could be distinguished only with MR imaging, and postmenopausal healthy and osteoporotic subjects only with CT and DXA., Conclusion: MR imaging relaxation rates correlate well with trabecular BMD in vivo.

The contribution of trabecular bone structure to bone strength is of considerable interest in the study of osteoporosis and other disorders characterized by changes in the skeletal system. Magnetic resonance (MR) imaging of trabecular bone has emerged as a promising technique for assessing trabecular bone structure. In this in vitro study we compare the measures of trabecular structure obtained using MR imaging and higher-resolution X-ray tomographic microscopy (XTM) imaging of cubes from human distal radii. The XTM image resolution is similar to that obtained from histomorphometric sections (18 microns isotropic), while the MR images are obtained at a resolution comparable to that achievable in vivo (156 x 156 x 300 microns). Standard histomorphometric measures, such as trabecular bone area fraction (synonymous with BV/TV), trabecular width, trabecular spacing and trabecular number, texture-related measures and three-dimensional connectivity (first Betti number/volume) of the trabecular network have been derived from these images. The variation in these parameters as a function of resolution, and the relationship between the structural parameters, bone mineral density and the elastic modulus are also examined. In MR images, because the resolution is comparable to the trabecular dimensions, partial volume effects occur, which complicate the segmentation of the image into bone and marrow phases. Using a standardized thresholding criterion for all images we find that there is an overestimation of trabecular bone area fraction (approximately 3 times), trabecular width (approximately 3 times), fractal dimension (approximately 1.4 times) and first Betti number/ volume (approximately 10 times), and an underestimation of trabecular spacing (approximately 1.6 times) in the MR images compared with the 18-microns XTM images. However, even for a factor of 9 difference in spatial resolution, the differences in the morphological trabecular structure measures ranged from a factor of 1.4 to 3.0. We have found that trabecular width, area fraction, number, fractal dimension and Betti number/volume measured from the XTM and MR images increases, while trabecular spacing decreases, as the bone mineral density and elastic modulus increase. A preliminary bivariate analysis showed that in addition to bone mineral density alone, the Betti number, trabecular number and spacing contributed to the prediction of the elastic modulus. This preliminary study indicates that measures of trabecular bone structure using MR imaging may play a role in the study of osteoporosis.