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Keywords:

  • osteoporosis;
  • fracture;
  • CT;
  • microstructure

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. References

We applied MDCT for in vivo evaluation of the microarchitecture of human vertebrae. Microstructure parameters, such as structure model index, Euler's number, and bone volume fraction, revealed higher relative risk for prevalent vertebral fracture than did BMD obtained by DXA. Thus, microstructure analysis by MDCT, together with simultaneously obtained volumetric BMD values, is useful for clinical assessment of fracture risk.

Introduction: BMD measurement by DXA alone has limitations in predicting fracture, and methods for clinical assessment of bone quality, such as microstructure, are awaited. This study was undertaken to examine the applicability of multidetector row CT (MDCT) for in vivo evaluation of trabecular microstructure.

Materials and Methods: Optimal conditions for MDCT scanning were determined at a spatial resolution of 250 × 250 × 500 μm, using μCT data of excised human vertebra specimens as a reference. We analyzed the trabecular microstructure of the vertebrae of 82 postmenopausal women (55-76 years old), including 39 women with and 43 without a recent vertebral fracture.

Results: Microstructure indices obtained by MDCT scanning revealed higher relative risk for prevalent vertebral fracture (OR: 16.0 for structure model index, 13.6 for bone volume fraction, and 13.1 for Euler's number) than did spinal BMD obtained by DXA (OR: 4.8). MDCT could also provide volumetric BMD data, which had higher diagnostic value (OR: 12.7) than did DXA.

Conclusion: Vertebral microarchitecture can be visualized by MDCT, and microstructure parameters obtained by MDCT, together with volumetric BMD, provided better diagnostic performance for assessing fracture risk than DXA measurement.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. References

BMD MEASUREMENTS ARE widely used for the diagnosis of osteoporosis and for the evaluation of the efficacy of treatment for this disease. However, BMD measurements alone have limitations in predicting fracture. In fact, a recent study indicates that 82% of postmenopausal women with fracture had BMD measurements in the osteopenic, not osteoporotic, range. (1) In addition, there is accumulating evidence that only a small fraction of the reduction in fracture with therapy can be accounted for by the increase in BMD. (2) These results suggest that factors other than BMD, such as bone structure and turnover rate of bone remodeling, contribute to bone fragility. (3)

μCT enables us to evaluate, at an ultra-high resolution, the microstructure of bone samples without destroying them, but it cannot be used in vivo. Studies by high-resolution CT, using different texture analysis methods as well as thresholding techniques, have reported results on its use. (4–6) However, the in-plane spatial resolution of conventional high-resolution CT is only 400 × 400 μm, and this conventional CT only gives information on the characteristic texture of a structure, such as rough versus smooth, homogeneous versus heterogeneous, or high versus low orientation of trabecular distribution. The reason for this is that the trabecular structure is subjected to partial-volume effects. Spiral CT has a higher resolution than conventional CT; however, it is subjected to scan-axis partial volume effects. Multidetector row CT (MDCT) is a new technique that has a substantially higher spatial resolution than standard spiral CT (i.e., it provides an in-plane spatial resolution of 250 μm and a minimum slice thickness of 500 μm) and thus promises to improve the assessment of trabecular bone structure.

This study was undertaken to apply MDCT for 3D imaging of the trabecular microarchitecture of human vertebrae and to evaluate the use of the microstructure parameters obtained by MDCT for the assessment of fracture risk in postmenopausal women.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. References

Specimen study

Specimens

Five formalin-fixed specimens of vertebrae of female cadavers (62-83 years of age at the time of death) were obtained from Tokyo Metropolitan Institute of Gerontology and Geriatrics Hospital. These vertebrae were used to define the appropriate scanning milli-ampere second value within clinically available values that revealed trabecular microstructure with a low signal-to-noise ratio. To compare the MDCT images with those obtained by μCT, we mounted the excised vertebral specimens on a sample holder of 40 mm diameter filled with an 8% gelatinous solution containing 88% protein, 1% mineral, and 11% water to keep the specimens steady. Specimens that contained air on CT images were excluded. The study protocol was approved by the ethical committee of Tokyo Metropolitan Institute of Gerontology and Geriatrics.

Imaging by μCT

μCT scanning was performed ex vivo on excised human vertebrae to validate MDCT images and data. A μCT apparatus (μCT40) and its analysis software were purchased from SCANCO Medical (Basserdorf, Switzerland). (7) Details of an earlier model (μCT20) were described previously. (8) The process was piloted by an Alpha DS10 workstation (Compaq Computer Corp.), and an open VMS system in a cluster configuration was used to perform 3D analysis. Each specimen was positioned as so to permit scanning of 600 slices with 40-μm increments with a spatial resolution of ∼40 μm.

Imaging by MDCT

After μCT scanning, bone specimens in the holder were placed in a 20-cm thickness water-equivalent solid phantom (Standard Grade Solid Water Gammex 457; GAMMEX RMI) and scanned by MDCT. Axial CT images with a collimation of 0.5 mm, a table feed of 2 mm, and a reconstruction index of 0.3 mm were obtained with a MDCT system having four detectors (SOMATOM plus 4 Volume Zoom; Siemens, Erlangen, Germany). An ultra-high spatial resolution kernel was applied (head, filter H 70 very sharp). CT scanning of excised vertebra was performed with the following scanning conditions: field of view (FOV) of 100 mm and pixel matrix of 512 × 512, leading to a maximal spatial resolution of ∼250 × 250 × 500 μm3.

We first determined optimal conditions for MDCT scanning by using excised human vertebrae and compared the MDCT data with those obtained by μCT as a reference. Figure 1 shows images of an excised human vertebra obtained by μCT (Fig. 1A, with the volume of interest shown by a square), high-resolution CT images obtained by MDCT at 200, 250, and 300 mAs (Fig. 1B), their binarized images (Fig. 1C), and reconstructed 3D images (Fig. 1D). Scanning at 350 mAs was not performed because of overload of X-ray tube use for clinical cases. Measurements were repeated at the same position five times, and precision of repeated measurements was 2.35 ± 0.56% for bone volume/total volume (BV/TV), 2.21 ± 2.91% for trabecular number (Tb.N), 3,17 ± 3.28% for trabecular thickness (Tb.Th), 3.62 ± 1.29% for trabecular separation (Tb.Sp), 7.45 ± 1.26% for Euler's number, 4,08 ± 1.48% for structural model index (SMI), and 4.21 ± 1.42% for fractal dimension (n = 3 each).

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Figure FIG. 1.. Visualization of spinal microstructure by MDCT scanning. Representative images of excised human vertebrae by (A) μCT image (volume of interest delimited by the square) and (B-D) MDCT images are shown. MDCT images were obtained under different conditions at 200, 250, and 300 mA; each CT image was analyzed at different threshold values (1120, 1200, and 1280). (B) Original 2D MDCT images at 200, 250, and 300 mA. (C) Binarized 2D CT images at 200, 250, and 300 mAs. (D) 3D CT images at 200, 250, and 300 mAs. The binarized and 3D images were prepared by using a threshold value of 1200. The linear correlations (r) and statistical significances (p) between apparent BV/TV measured by μCT and MDCT at 200, 250, and 300 mAs are also shown at the right.20

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Structure analysis

Both MDCT image data and μCT data were transferred to a workstation (Precision 360; Dell), and structural indices were calculated using a 3D image analysis system (TRI/3D-BON; RATOC System Engineering Co., Tokyo, Japan). To compare the parameters between μCT images and MDCT images, we defined the volume of interest (VOI) in μCT images first, and then adjusted it for MDCT images with reference to the VOI in μCT images. Grayscale images were segmented by using a median filter to remove noise with a fixed threshold to extract mineralized bone components. We used a standardized method of image thresholding based on the density histogram of a selected region of interest (ROI) to ensure consistency in the image thresholding across all subjects studied. Isolated small particles in the marrow space and isolated small holes in bone were removed by using a cluster-labeling algorithm.

Trabecular microstructure parameters were calculated in 3D as follows: bone volume (BV) was calculated using tetrahedrons corresponding to the enclosed volume of the triangulated surface. Total tissue volume (TV) was the entire volume of analysis, and apparent trabecular bone volume fraction (app BV/TV) was calculated from these values. Apparent trabecular thickness (app Tb.Th) was determined according to the method described by Hildebrand and Ruggsegger. (9) Apparent trabecular number (app Tb.N) and apparent trabecular separation (app Tb.Sp) were estimated based on the plate model. (10)

In addition to the computation of metric parameters, nonmetric parameters were calculated to obtain the 3D nature of the trabecular bone samples. Fractal dimensions of trabecular bone were measured as a representative of complexity using the box-counting method(11) that was developed in 3D. Connectivity was calculated by using the Euler method of Odgaard and Gundersen (Euler's number). (12) Degree of anisotropy (DA) was determined from the ratio between the maximal and minimal radii of the mean intercept length (MIL) ellipsoid. (13)

The interactive analysis time, including data examination, ROI definition, and image segmentation, was ∼10 minutes for each type of data.

Biomechanical study

Specimens and microstructure analysis

Four femoral head specimens were obtained during surgery for femoral neck fracture at Nagasaki Rosai Hospital (2 men, 70 and 78 years of age; 2 women, 83 and 85 years of age). Surrounding soft tissues were removed, and 10-mm3 specimens were prepared and stored at −20°C before use. The study protocol was approved by the ethical committee of Nagasaki Rosai Hospital.

These specimens were placed in an acrylic tank containing physiological saline solution and scanned by MDCT. Scanning direction was adjusted to the direction of loading in the biomechanical test. The scanning condition was the same as in the cadaver specimen study described above. Microstructure parameters were obtained for all of the specimens by the same procedure described above.

Determination of bone strength by compression test

Specimens were placed centrally on the compression testing fixture, which is able to hold the specimen stably in the cylinder and load only compressive direction without rotation or bending, and was attached to the materials-testing machine (Instron model 5582). A compression force was applied in a cranio-caudal direction using the fixture at a nominal deformation rate of 0.5 mm/minute and a sampling rate of 20 Hz. Crosshead displacement was recorded as specimen deformation. A load-deformation curve was displayed with a monitoring recorder linked to the tester in each specimen. The ultimate load (kgf) was obtained directly from the load-deformation curve.

Patient study

Patients

Spinal microarchitecture was examined in 82 postmenopausal women (55-76 years old, 65.3 ± 4.8 years) with MDCT scanning. Microstructure parameters were compared between 39 women who experienced their first spinal fracture during the previous 6 months (age: 66.2 ± 3.8 years old) and 43 women without fracture (age: 64.4 ± 5.5 years old) to assess the correlation between these parameters and fracture. Spinal fracture was defined according to the criteria proposed by Genant et al. (14) (i.e., vertebral deformity was considered as a fracture when at least a 20% reduction in anterior, middle, and/or posterior height and a 10% reduction in area were observed). Individuals who had had an osteoporotic fracture 6 months or more before the study were excluded, because bone structure would have been altered by the fracture. None of the postmenopausal women had received drugs affecting bone mass or bone metabolism within 6 months before the study. Nagasaki University ethics committee approved the protocol, and all subjects (i.e., fracture cases and controls) gave their informed consent.

BMD measurements

BMD of the lumbar spine (L2-L4) in antero-posterior (AP) projection was determined using DXA, and fractured vertebrae were excluded from the analysis. The obtained values were expressed as units of grams per centimeter squared for the projected area. Expert-EL (Lunar Corp., Madison, WI, USA) was used to measure the BMD of the lumbar spine. The CV (short-term precision) for L2-L4 was 1.1%.

To obtain volumetric BMD data by QCT, we scanned the patients simultaneously with MDCT using a bone mineral reference phantom (B-MAS2000; KYOTOKAGAKU Co., Kyoto, Japan) containing calibration objects with equivalent densities of 0, 50, 100, 150, and 200 mg/cm3 calcium hydroxyapatite. Reconstructed stacked 3D volume data of the vertebral body with reference phantom were used for the determination of volumetric BMD. VOI was defined in the same region for microstructure measurement of the reconstructed vertebral CT image.

Imaging by MDCT and structure analysis

The whole third lumbar spine including both endplates was scanned by MDCT, as shown in Fig. 2A. Patients were in the supine position for horizontal scanning of the vertebral body. The vertebral body was scanned under the appropriate X-ray condition, which was determined in the ex vivo cadaver study as described above. For the analysis of microstructure, the size of the VOI of 65 × 65 pixels in plane was defined (Fig. 2B); the total number of slices varied according to the size of the vertebral body. The VOI was defined manually within the internal part of the cancellous bone to avoid the cortex, the basivertebral foramen, and both endplates. The midline of the VOI in the x-axis in the axial image was in the center of the vertebral body, and the frontal edge on both sides of the VOI was just behind the cortex. The average number of slices was 43.8 ± 5.3 (range, 28–52 slices).

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Figure FIG. 2.. ROI for analysis of trabecular microstructure by MDCT. (A) The whole third lumbar spine including both endplates was scanned by MDCT. (B) The volume of interest (VOI) of 65 × 65 pixels in plane was defined in the anterior part of the spongiosa (delimited by the square) to avoid cortex and the basivertebral foramen.20

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The procedure for structure analysis was the same as that for the cadaver specimen study described above. Samples from three patients were scanned five times on different days, using manually defined VOI; the precision was confirmed by the same operator. Precision of measurements of microstructure parameters was 0.67% for fractal dimension, 0.84% for Tb.Th, 1.13% for SMI, 2.04% for DA, 6.57% for Tb.N, 7.13% for BV/TV, 7.36% for Tb.Sp, and 12.30% for Euler's number.

Statistical analysis

Data analysis was performed with the software statistical package for Social Science, SPSS (SPSS, Chicago, IL, USA). Mean and SD of microstructure parameters and BMD were calculated for the postmenopausal women with or without fracture. The significance of differences between the two groups was calculated by ANOVA and posthoc test (Fisher's protected least significant difference {PLSD}), at the 95% significance level. Correlations of microstructure parameters or BMD with age or body weight of the subjects and correlations between microstructure parameters and BMD were assessed using linear regression analysis. Area under the curve (AUC) in receiver operator characteristic (ROC) analysis was generated to determine the diagnostic efficacy for detection of fracture cases. Additionally, the ORs per SD were calculated by logistic regression analysis to provide an estimate for the discriminatory capability of each variable for spinal fracture, as a single parameter or in combination with DXA or QCT value.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. References

Specimen study

Optimal conditions for MDCT scanning

To determine the optimal conditions for MDCT scanning, we obtained vertebral specimens from cadavers and scanned them by both μCT (Fig. 1A) and MDCT (Figs. 1B-1D). Microstructure parameters were calculated at threshold values of 1120, 1200, and 1280 to binarize bone CT images. These values of threshold were numbers on a scale from 0 to 4290 according to linear attenuation, which has no units. As shown in Fig. 1 (right), at all three threshold levels, BV/TV obtained by μCT revealed the highest correlation with app BV/TV by MDCT at 300 mAs (r = 0.979, p < 0.005 at a threshold value of 1200).

When scanned at 0.5 mm thickness, 71-mm scan length, 0.8 feed/rotation, and 120 kVp, weighted CT dose indices (CTDIw) were 46.3 mGy for 200 mAs, 59.1 mGy for 250 mAs, and 77.1 mGy for 300 mAs.

Correlation between microstructure parameters and biomechanical properties

To examine whether microstructure parameters correlate with biomechanical properties, another set of four specimens were obtained from the femoral head at surgery and subjected to compression test after scanning by μCT and MDCT. As shown in Fig. 3, microstructure parameters obtained by MDCT revealed a high correlation with ultimate load (kgf); a significant correlation with the ultimate load was obtained for app BV/TV (p < 0.05), SMI (p < 0.05), and app Th.N (p < 0.05).

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Figure FIG. 3.. Correlation between microstructure parameters and bone strength. Ten-millimeter cubic specimens were obtained from the femoral head of four individuals and scanned by μCT and MDCT. Structure analysis was performed as described in the Materials and Methods section. The specimens were subjected to biomechanical test, and the ultimate load was obtained from the load-deformation curve. Shown are significant correlations between microstructure parameters obtained by MDCT and bone strength. p values are shown for each parameter.20

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Patient study

Association of microstructure parameters with prevalent spinal fracture

To examine the use of trabecular microarchitecture information obtained by MDCT scanning for the assessment of fracture, we compared the microstructure parameters derived from MDCT images between 43 women without fracture (age: 64.4 ± 5.5 years old) and 39 women with a recent spinal fracture (age: 66.2 ± 3.8 years old). As shown in Table 1, there was no significant difference in age, age at menopause, body height (BH), or body weight (BW) between these two groups of women.

Table Table 1.. Comparison of Vertebral Microstructural Parameters Between Two Groups Without and With Fracture
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Figures 4A-4F show representative 2D (Figs. 4A and 4B), its binarized 2D (Figs. 4C and 4D), and 3D (Figs. 4E and 4F) MDCT images of the third lumbar vertebra of a 62-year-old woman without vertebral fracture (Figs. 4A, 4C, and 4E) and those of a women of the same age with a fracture in the thoracic spine (Figs. 4B, 4D, and 4F).

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Figure FIG. 4.. Representative 2D and 3D MDCT images of the third lumbar spine. (A and B) 2D and (E and F) 3D MDCT images of the third lumbar spine were obtained from (A and E) a 62-year-old woman without vertebral fracture and (B and F) a woman of the same age with a vertebral fracture in her thoracic spine. (C and D) Binarized images are also shown.20

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Table 1 summarizes the results of microstructure parameters, as well as areal (by DXA) and volumetric (by MDCT) BMD values in the two groups of women. Areal BMD by DXA was significantly lower in postmenopausal women with a fracture than in those without one (0.836 ± 0.191 versus 0.925 ± 0.161 g/cm2, p < 0.05). Among the microstructure indices obtained by MDCT, app BV/TV, app Tb.N, app Tb.Th, and fractal dimension were significantly lower; whereas app Tb.Sp, SMI, Euler's number, and DA were significantly higher in women with a fracture than in those without a fracture (Table 1). Volumetric BMD determined by MDCT was also significantly lower in postmenopausal women with a fracture (72.0 ± 18.5 versus 103.9 ± 23.5 mg/cm3, p < 0.0001).

Table 2 shows the correlation of microstructure parameters with BMD values obtained by DXA and QCT. Most microstructure parameters were more highly correlated with volumetric BMD by QCT than with areal BMD by DXA.

Table Table 2.. Correlations Between Microstructural Parameters and BMD
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ROC analysis was performed to determine the diagnostic value of microstructure parameters with respect to fracture (Table 3). The highest AUC value was obtained for SMI (0.928), which was significantly higher than that for areal BMD by DXA (0.647) or volumetric BMD by MDCT (0.870). AUC values of Euler's number (0.857) and app Tb.Sp (0.818) were similar to that value of volumetric BMD, and significantly exceeded that of areal BMD by DXA. The ORs for the association of SMI (16.0), app BV/TV (13.6), Euler's number (13.1), app Tb.Sp (7.4), fractal dimension (7.4), app Tb.N (6.6), and app Tb.Th (5.5) with fracture were higher than the OR for that of areal BMD by DXA with it (4.8); the ORs for SMI, app BV/TV, and Euler's number exceeded that ratio of volumetric BMD (12.7). Multivariate regression analysis showed significant correlations of SMI (R2 = 0.329, p < 0.0001) and Tb.Th (R2 = 0.154, p < 0.005), as well as volumetric BMD (R2 = 0.159, p < 0.005), with fracture (Table 4). Combining areal or volumetric BMD data with some microstructural parameters further increased R2 values compared with BMD alone (Table 4).

Table Table 3.. ROC Analysis and ORs of Microstructural Parameters for Their Association with Spinal Fracture
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Table Table 4.. Correlation of Microstructure Parameters and BMD with Fracture
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Table 5 shows the correlations of spinal microarchitecture or BMD with age and BW. Most microstructure parameters and volumetric BMD by MDCT correlated with age, especially SMI, Euler's number, and app BV/TV, whereas areal BMD values by DXA showed a moderate correlation with both age and BW.

Table Table 5.. Correlations of Microstructural Parameters by MDCT With Age or Body Weight
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DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. References

The purpose of this study was to evaluate the diagnostic value of in vivo analysis of spinal trabecular microstructure, focusing on its association with prevalent spinal fracture. Compared with postmenopausal women without a spinal fracture, those with one had a smaller trabecular bone fraction (app BV/TV: 36.1 versus 26.2) in association with fewer trabeculae (app Tb.N: 0.97 versus 0.78), more rodlike structure (SMI: 1.87 versus 2.70), and lower connectivity (Euler's number: −1037 versus −457). The ORs of microstructure parameters, such as SMI, Euler's number, and app BV/TV, for association with prevalent fracture were much higher than that ratio for association of areal BMD by DXA with it. SMI and Euler's number, which represent nonmetric features of trabecular structure, would seem to be more useful than metric parameters such as app Tb.N, app Tb.Th, or app Tb.Sp. It is an advantage of the MDCT scanning system that, in addition to assessing these 3D microstructure parameters, volumetric BMD values can be obtained at the same time by using a reference phantom; these values correlate highly with the presence of fracture.

In vivo analysis of trabecular microstructure has been studied using conventional radiography, high-resolution CT, and high-resolution MRI. Conventional radiography has a spatial resolution of up to 40 μm; however, it delivers projectional images of the trabecular structure. Conventional high-resolution CT with spatial resolution of 400 μm shows only structural texture, because the trabecular structure is subjected to partial-volume effects. With the use of high-resolution CT in vivo, analysis of trabecular structure such as connectivity from a skeletonized representation of the trabecular network, (4) parameters derived from run-length encoding, (6) and number or area of holes in trabecular structure(15) have been reported. Their images had a slice thickness of 1.5 mm and the FOV was reduced to yield an image matrix with a pixel size of 0.31 mm. A good relationship between texture parameters calculated from high-resolution CT images and biomechanical properties has also been reported. (5) However, this spatial resolution only provides characteristics of trabecular structure, and 2D image has limited reproducibility among follow-up examinations.

With the recent advances in MRI hardware and software, it has become possible to obtain higher resolution MR images of trabecular bone(16–22) with in-plane resolutions as high as 150 μm and slice thicknesses of 280 μm in vivo. (23) MRI has an advantage of nonionization, and trabecular microstructure obtained in vivo by using high-resolution MR has been shown to be useful in predicting prevalent spinal fractures. Structural parameters of the distal radius with a 3D spin-echo sequence (voxel size of 137 × 137 × 500 μm3) in 36 female patients were reported to provide a better index than the BMD of the distal radius. (24) 3D gradient-echo sequence (voxel size of 156 × 156 × 500 μm3) could discriminate between groups with and without a recent hip fracture. (21) A disadvantage of high-resolution MRI in vivo, however, is the relatively long acquisition time of up to 10 ± 20 minutes. A small FOV is required to obtain a high signal-to-noise ratio in the fast gradients with optimized coils. Because of these prerequisites and motion artifacts in the axial skeleton, application of high-resolution MRI is currently limited to peripheral sites such as phalanges, calcaneus, and distal radius. (19, 20, 25–27) Vertebral fracture is the most common osteoporotic fracture, and the presence of fracture indicates a greater risk for future fracture, independently of BMD. (28) The direct assessment of vertebral microstructure, as reported here, can be expected to provide greater sensitivity for assessing the risk of spinal fracture.

To our knowledge, there has been no report on in vivo analysis of microstructure by MDCT. Several specimen studies showed the capability to depict microstructure by MDCT in comparison with contact radiography(16) or μCT. (17) Although MDCT is the only available technique to analyze vertebral microstructure in vivo, high radiation exposure cannot be avoided. The radiation dose for DXA is small (0.08 ± 4.6 mSv). Fan beam DXA with increased resolution requires an increased radiation dose (6.7 ± 31 mSv), but this dose is smaller than that for QCT (25 ± 360 mSv). (29) In a study comparing radiation doses between single-detector row CT and MDCT, a 28% higher radiation dose was needed within the scanned volume for the latter at a constant noise level. (30) In this study, we evaluated the image quality of trabecular microstructure as a function of radiation exposure dose by using excised human vertebrae. Within the limits of clinically available radiation sets, MDCT at 300 mAs provided the best image quality and showed the highest correlation with the μCT data. As the reference level for CT examination of the abdomen (CTDIw) of adult patients is 35 mGy (according to European Commission 1999), the CTDIw for our current MDCT scanning at 300 mAs was 77.1 mGy. This radiation dose would be acceptable for a once-a-year study on postmenopausal women. On further advancement of the technology, a reduction in the radiation dose and higher resolution with a higher signal-to-noise ratio would be expected to make this method an even more useful diagnostic tool. In fact, the CTDIw for a new 16-detector row CT apparatus is 19.7 mGy, and advanced CT technology is expected to provide higher-resolution CT images. In the future, finite element analysis (FEA) may also be applied to 3D MDCT data for assessment of biomechanical properties, (31, 32) and together this combination should provide a powerful tool for early evaluation of fracture risk.

In conclusion, 3D imaging of trabecular microstructure can be performed by using clinical MDCT at a high spatial resolution, and microstructure parameters derived from these images, especially those related to the shape of trabecular structures and connectivity, are more useful than spinal DXA for the assessment of fracture risk.

Acknowledgements

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. References

The authors thank Tomoko Nakata and Takako Shimogama (Division of Radiology, Nagasaki University Hospital) and Jun Kono (Department of Radiology, Nagasaki Saiseikai Hospital) for CT scanning and analysis of trabecular structure. This work was supported in part by the Program for Promotion of Fundamental Studies in Health Science from Pharmaceuticals and Medical Device Agency (Pmda) of Japan (MF-14 to MI) and by a Health and Labour Sciences Research Grant (Comprehensive Research on Aging and Health) from the Ministry of Health, Labour and Welfare of Japan (to MI and HO).

References

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. References
  • 1
    Siris ES, Chen Y-T, Abbott TA, Barrett-Connor E, Miller PD, Wehren LE, Berger MC 2004 Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Intern Med 164:11081112.
  • 2
    Riggs BL, Melton LJ 2002 Bone turnover matters: The raloxifene treatment paradox of dramatic decreases in vertebral fractures without commensurate increases in bone density. J Bone Miner Res 17:1114.
  • 3
    Seeman E 2002 Pathogenesis of bone fragility in women and men. Lancet 359:18411850.
  • 4
    Chevalier F, Laval-Jeantet A, Laval-Jeantet M, Bergot C 1992 CT image analysis of the vertebral trabecular network in vivo. Calcif Tissue Int 51:813.
  • 5
    Link TM, Majumdar S, Lin J, Augat P, Gould R, Newitt D, Ouyang X, Lang T, Mathur A, Genant HK 1998 Assessment of trabecular structure using high-resolution CT images and texture analysis. J Comput Assist Tomogr 22:1524.
  • 6
    Ito M, Ohki M, Hayashi K, Yamada M, Uetani M, Nakamura T 1995 Trabecular texture analysis of CT images in the relationship with spinal fracture. Radiology 194:5559.
  • 7
    Ruegsegger P, Koller B, Mueller R 1996 A microtomographic system for the non-destructive evaluation of bone architecture. Calcif Tissue Int 58:2429.
  • 8
    Mueller R, Hahn M, Vogel M, Delling G, Ruegsegger P 1996 Morphometric analysis of non-invasively assessed bone biopsies: Comparison of high-resolution computed tomography and histologic sections. Bone 18:215220.
  • 9
    Hildebrand T, Ruegsegger P 1997 A new method for the model-independent assessment of thickness in three-dimensional images. J Microsc 185:6775.
  • 10
    Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR 1987 Bone histomorphometry: Standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2:595610.
  • 11
    Fazzalari NL, Parkinson IH 1996 Fractal dimension and architecture of trabecular bone. J Pathol 178:100105.
  • 12
    Odgaard A, Gundersen HJ 1993 Quantification of connectivity in cancellous bone, with special emphasis on 3-D reconstructions. Bone 14:173182.
  • 13
    Harrigan TP, Mann RW 1984 Characterization of microstructural anisotropy in orthotropic materials using a second rank tensor. J Mater Sci 19:761767.
  • 14
    Genant HK, Wu CY, vanKuijk C, Nevitt M 1994 Vertebral fracture assessment using a semi-quantitative technique. J Bone Miner Res 8:11371148.
  • 15
    Gordon CL, Lang TF, Augat LP, Genant HK 1998 Image-based assessment of spinal trabecular bone structure from high-resolution CT images. Osteoporos Int 8:317.
  • 16
    Link TM, Vieth V, Stehling C, Lotter A, Beer A, Newitt D, Majumdar S 2003 High-resolution MRI vs multislice spiral CT: Which technique depicts the trabecular bone structure best? Eur Radiol 13:663.
  • 17
    Issever AS, Vieth V, Lotter A, Meier N, Laib A, Newitt D, Majumdar S, Link TM 2002 Local differences in the trabecular bone structure of the proximal femur depicted with high-spatial-resolution MR imaging and multisection CT. Acad Radiol 9:1395.
  • 18
    Gordon CL, Webber CE, Christoforou N, Nahmias C 1997 In vivo assessment of trabecular bone structure at the distal radius from high-resolution magnetic resonance images. Med Phys 24:585593.
  • 19
    Majumdar S, Genant HK, Grampp S, Newitt DC, Truong V-H, Lin JC, Mathur A 1997 Correlation of trabecular bone structure with age, bone mineral density and osteoporotic status: In vivo studies in the distal radius using high resolution magnetic resonance imaging. J Bone Miner Res 12:111118.
  • 20
    Link TM, Majumdar S, Augat P, Lin JC, Newitt D, Lu Y, Lane NE, Genant HK 1998 In vivo high resolution MRI of the calcaneus: Differences in trabecular structure in osteoporosis patients. J Bone Miner Res 13:11751182.
  • 21
    Majumdar S, Link TM, Augat P, Lin JC, Newitt D, Lane NE, Genant HK 1999 Trabecular bone architecture in the distal radius using magnetic resonance imaging in subjects with fractures of the proximal femur. Osteoporos Int 10:231239.
  • 22
    Majumdar S, Kothari M, Augat P, Newitt DC, Link TM, Lin JC, Lang T, Lu Y, Genant HK 1998 High-resolution magnetic resonance imaging: Three-dimensional trabecular bone architecture and biomechanical properties. Bone 22:445454.
  • 23
    Majumdar S, Newitt D, Mathur A, Osman D, Gies A, Chiu E, Lotz J, Kinney J, Genant H 1996 Magnetic resonance imaging of trabecular bone structure in the distal radius: Relationship with X-ray tomographic microscopy and biomechanics. Osteoporos Int 6:376385.
  • 24
    Wehrli F, Hwang S, Ma J, Song H, Ford J, Haddad J 1998 Cancellous bone volume and structure in the forearm: Noninvasive assessment with MR microimaging and image processing. Radiology 206:347357.
  • 25
    Lin J, Amling M, Newitt D, Selby K, Delling G, Genant H, Majumdar S 1996 Heterogeneity of trabecular bone structure in the calcaneus using high resolution magnetic resonance imaging (MRI). Osteoporos Int 8:1624.
  • 26
    Link T, Majumdar S, Lin J, Newitt D, Augat P, Ouyang X, Mathur A, Genant H 1998 A comparative study of trabecular bone properties in the spine and femur using high resolution MRI and CT. J Bone Miner Res 13:122132.
  • 27
    Kuehn B, Stampa B, Heller M, Glueer C 1997 In vivo assessment of trabecular bone structure of the human phalanges using high resolution magnetic resonance imaging. Osteoporos Int 7:291.
  • 28
    Ross PD, Genant HK, Davis JW, Miller PD, Wasnich RD 1993 Predicting vertebral fracture incidence from prevalent fractures and bone density among non-black, osteoporotic women. Osteoporos Int 3:120126.
  • 29
    Njeh CF, Fuerst T, Hans D, Blake GM, Genant HK 1999 Radiation exposure in bone mineral density assessment. Appl Radiat Isot 50:215.
  • 30
    Thornton FJ, Paulson EK, Yoshizumi TT, Frush DP, Nelson RC 2003 Single versus multi-detector row CT: Comparison of radiation doses and dose profiles. Acad Radiol 10:379.
  • 31
    Van Rietbergen B, Weinans H, Huiskes R, Odgaard A 1995 A new method to determine trabecular bone elastic properties and loading using micromechanical finite-element models. J Biomech 28:6981.
  • 32
    Ito M, Nishida A, Koga A, Ikeda S, Shiraishi A, Uetani M, Hayashi K, Nakamura T 2002 Contribution of trabecular and cortical components to the mechanical properties of bone and their regulating parameters. Bone 31:351358.