Quantitative Assessment of Experimental Fracture Repair by Peripheral Computed Tomography

An experimental fracture model was used to assess bone mineral density at the fracture site by peripheral computed tomography and to compare the model with biomechanical, histological, and radiographic methods for the quantification of the fracture repair process. Transverse osteotomies in the mid-diaphysis of 28 tibia of sheep were externally fixed and mineral densities, cross-sectional areas, flexural rigidities, tissue composition, and projected callus area were calculated after 9 weeks of healing time. BMD measured by pQCT was strongly correlated with histologically determined percentages of mineralized tissue in the osteotomy gap (R ²= 0.71) and in the periosteal callus (R ²= 0.62). The percentage of mineralized tissue in the osteotomy gap was the best predictor of the flexural rigidity of the tibiae (R ²= 0.74). Because of high correlations with the histological findings, the volumetric BMD at the level of the osteotomy gap was also strongly correlated with the biomechanical findings (R ²= 0.70). Neither the cross-sectional area in pQCT nor the projected callus area in plane film radiography were positively correlated to the flexural rigidity of the tibiae. Quantitative computed tomography proved to be a successful estimator for the prediction of the mechanical stability of healing bones. The noninvasive procedure is a reliable tool for the quantification of the fracture repair process in experimental studies and may be useful for treatment decisions in particular clinical situations. Received: 2 May 1996 / Accepted: 24 June 1996     

Lung Cancer Screening: Use of Low-Dose Computed Tomography

IntroductionThe prognosis of lung cancer (LC) correlates directly with the stage of the disease at the time of diagnosis.Material and methodsWe performed low-dose CT (LDCT) in asymptomatic individuals ≥50 years old, smokers or former smokers of ≥10 pack-years, with no history of cancer. We followed an evaluation algorithm, according to the size and morphology of the nodules. The appropriate treatment for the LC diagnosis was given and patients were followed up for 5 years.ResultsWe studied 4951 individuals (65.4% males) with an average age of 56.89±5.26 years; 550 presented nodules. Of the 3891 nodules detected, 692 (19.57%) were considered positive, and 38 tumors (36 LC) were identified. In the annual follow-up, nodules were found in 224 subjects, 288 (7.91%) of which were positive (13 LC). In 80%, the study was performed with LDCT, and biopsy was indicated in 5.8% (baseline) and in 7.6% (annual) of the positive nodules. Prevalence was 0.89 and incidence was 0.1%. The sensitivity, specificity, PPV and NPV in the baseline study were 92.31, 89.54, 6.55 and 99.93%, respectively, and in the annual study, they were 76.92, 95.7, 4.52 and 99.94%, respectively. A total of 52 tumors were detected (49 LC), 25 (52.08%) in stage I. The 5-year overall survival rate for LC was 58.5% and cancer-specific survival was 67.1% (75.8% in surgical patients).ConclusionLDCT integrated into an elaborate nodule detection and evaluation program is a useful tool for diagnosing early-stage LC.     

Validation of Thoracic Quantitative Computed Tomography as a Method to Measure Bone Mineral Density

The purpose of this study was to measure precision of thoracic quantitative computed tomography (QCT) bone mineral density (BMD) and correlation to lumbar spine QCT bone density.We measured the reproducibility of thoracic QCT; two consecutive thoracic QCT scans of the T9, T10, and T11 vertebrae were performed on 95 subjects (49 females, 46 males; mean age, 62.5 years) undergoing coronary scanning. In order to correlate the thoracic to standard lumbar measurement, the subjects also underwent a lumbar QCT scan of the L1, L2, and L3 vertebrae as part of an abdominal aortic scanning study. The variation of thoracic BMD was assessed in different ethnic subgroups. Consecutive thoracic QCT measurements showed good agreement (r=0.98; RMS CV=5.78%). Thoracic bone density was significantly higher than lumbar bone density results (paired t-test, P=0.003), but the two methods correlated well (r=0.86). The regression equation for the relationship between lumbar (X) and thoracic (Y) QCT was Y=0.87X + 22.97. The standard error of estimate was 19.0 mg/cm3. Thoracic QCT from coronary calcium thoracic scans is able to measure BMD with rescan precision and regression errors that are small compared to the biologic variability in the population. Given the relatively small precision error and the reasonable correlation to lumbar BMD, an ancillary assessment of thoracic BMD in a cardiac scan is likely to be a useful assessment of bone mineral status in the general population.     

Finite Element Analysis of the Hip and Spine Based on Quantitative Computed Tomography

Quantitative computed tomography (QCT) provides three-dimensional information about bone geometry and the spatial distribution of bone mineral. Images obtained with QCT can be used to create finite element models, which offer the ability to analyze bone strength and the distribution of mechanical stress and physical deformation. This approach can be used to investigate different mechanical loading scenarios (stance and fall configurations at the hip, for example) and to estimate whole bone strength and the relative mechanical contributions of the cortical and trabecular bone compartments. Finite element analyses based on QCT images of the hip and spine have been used to provide important insights into the biomechanical effects of factors such as age, sex, bone loss, pharmaceuticals, and mechanical loading at sites of high clinical importance. Thus, this analysis approach has become an important tool in the study of the etiology and treatment of osteoporosis at the hip and spine.     

Peripheral Quantitative Computed Tomography of the Tibia: Pediatric Reference Values

Peripheral quantitative computed tomography (pQCT) has been used in a number of pediatric studies. Reference data for children are primarily limited to the radius. The purpose of this study was to establish normal reference ranges for pQCT measurements of the tibia for children. A cross-sectional sample of healthy, white, non-Hispanic children aged 5–18 years (n = 416; 197 boys) was measured at the distal tibia metaphysis and diaphysis by pQCT to assess trabecular and cortical bone, respectively. Differences were determined between and within genders by height for bone geometry, density, and strength. Height-specific normal ranges were calculated, and gender-specific centile curves were generated. A positive, linear relationship was found between tibia cortical bone geometry and strength parameters and height (r² ≥ 0.58, p < 0.001), with mean values greater for boys than girls (p ≤ 0.05). Trabecular volumetric bone mineral density values were relatively stable, but greater in boys than girls independent of height or age (p ≤ 0.01). The reference data for pQCT analyses of the tibia provide additional information on bone size, geometry, and strength in children. pQCT technology provides an additional tool for the evaluation of bone health in young subjects.     

Quantitative Computed Tomography Reveals the Effects of Race and Sex on Bone Size and Trabecular and Cortical Bone Density

To examine the effects of race and sex on bone density and geometry at specific sites within the proximal femur and lumbar spine, we used quantitative computed tomography to image 30 Caucasian American (CA) men, 25 African American (AA) men, 30 CA women, and 17 AA women aged 35–45 yr. Volumetric integral bone mineral density (BMD), trabecular BMD (tBMD), and cross sectional area were measured in the femoral neck, trochanter, total femur, and L1/L2 vertebrae. Volumetric cortical BMD (cBMD) was also measured in the femur regions of interest. Differences were ascertained using a multivariate regression model. Overall, AA subjects had denser bones than CA subjects, but there were no racial differences in bone size. Men had larger femoral necks but not larger vertebrae than women. The AA men had higher tBMD and cBMD in the femur than CA men, whereas AA women had higher femoral tBMD but not higher femoral cBMD than CA women. These data support the idea that higher hip fracture rates in women compared with men are associated with smaller bone size. Lower fracture rates in AA elderly compared with CA elderly are consistent with higher peak bone density, particularly in the trabecular compartment, and potentially lower rates of age-related bone loss rather than larger bone size.     

Recommendations for Thresholds for Cortical Bone Geometry and Density Measurement by Peripheral Quantitative Computed Tomography

Peripheral quantitative computed tomography (pQCT) is widely used for clinical and research purposes. For accurate determination of bone geometry (bone cross-sectional area, cortical thickness, and cortical area), volumetric bone mineral density (vBMD) and cortical bone mineral content (BMC), it is important to select the appropriate thresholds. A Stratec XCT-2000 scanner was used to compare current standard practice with new optimized thresholds. Currently, a single threshold of 710 mg/mL for the measurement of cortical vBMD and geometry is used. We hypothesised that this threshold may not be optimal and used the European Forearm Phantom (EFP) and patient data to test more appropriate thresholds. A single slice (1.2 mm width, 0.4 mm pixel size) was made at section 4 of the EFP (representing the diaphyseal portion of a long bone). The EFP has a known cortical thickness of 2.5 mm and, therefore, the correct threshold for geometry would be that which measures cortical thickness as 2.5 mm. Thresholds were altered at approximately the 50% value between soft tissue (60 mg/mL) and peak density (879 mg/mL), and cortical thickness versus threshold was plotted; the correct threshold for geometry was 460 mg/mL. By expressing this threshold as a percentage of the range of density values in the EFP ([460–60]/[879–60] = 49%) and then applying this percentage to in vivo data, the optimum threshold for geometry can be determined: ([1240−79] × 0.49) + 79 = 648 mg/mL. For cortical vBMD of in vivo bone measurements at the midshaft site of the radius, thresholds were varied around the peak value (1240 mg/mL), and the threshold was set to that which gave a cortical density of 1240 mg/mL; the threshold for cortical density was, therefore, 1200 mg/mL. A subset of radius scans from a population of young healthy females was analyzed using the new thresholds (648 mg/mL for bone geometry, 1200 mg/mL for cortical vBMD) versus the current threshold (710 mg/mL). For bone geometry, the mean difference between the analysis based on the new threshold and that based on the manufacturer-recommended threshold ranged between 2.1% and 14% (total area = 2.1%, cortical thickness = 14%, cortical area = 3.7%). Although there was a 10% difference between the analysis based on the new threshold and that based on the manufacturer-recommended threshold, this difference was not systematic. Thresholds will significantly affect results obtained from pQCT. The current threshold of 710 mg/mL is inadequate for accurate determination of bone geometry and cortical vBMD. New thresholds of 648 mg/mL for geometry and 1,200 mg/mL for cortical vBMD should be used.     

Cut-off Values Determined for Vertebral Fracture by Peripheral Quantitative Computed Tomography in Japanese Women

In spite of the benefits of bone mass measurement by dual-energy X-ray absorptiometry (DXA), the use of DXA has limitations. It is unable to assess a true bone density, and cannot discriminate between the trabecular and cortical bone compartments. Ultradistal radius bone density was measured using peripheral quantitative computed tomography (pQCT) to determine reference values for total bone density (BD), trabecular bone density (TBD), polar strength strain index (pSSI), total bone mineral content (BC), trabecular bone mineral content (TBC), cortical bone density (CBD), cortical bone mineral content (CBC) and polar cross-sectional moment of inertia (pCSMI) in the Japanese female population, and to ascertain the cut-off values of the measured indicators that could most efficiently discriminate osteoporotic subjects with vertebral fractures. A total of 5266 healthy Japanese women aged 20–89 years were included in this study to determine Japanese reference values. Additionally, 621 who had undergone radiographic examination of the thoracic and lumbar spine at the time of pQCT measurement were selected to determine the cut-off values of BD, TBD, pSSI and other indicators for vertebral fractures. All the healthy subjects were divided into 5 year age groups. The BD showed nonsignificant changes from the 20–24 year age group to the 45–49 year age group, and fell significantly thereafter. The TBD maintained a plateau until the 40–44 year group, which corresponds to the young adult mean (YAM) values of the lumbar spine, femoral neck and radius BMDs measured using DXA. The TBD decreased significantly thereafter. The pSSI did not change significantly from the 20–24 year age group to the 45–49 year age group, and decreased slightly in the 50–54 year age group and markedly after 55–59 years. The cut-off values for the discrimination of vertebral fractures were obtained by the calculation of sensitivities, specificities and the area under the curves obtained using age-adjusted receiver operating characteristics (ROC) analysis. Odds ratios and 95% confidence limits (CL) were calculated using age-adjusted logistic analysis. The cut-off values for vertebral fractures, the area under the ROC curves (AUC) and odds ratios were 270.1 mg/cm³ (−2.2 SD, 66.6% of YAM), 0.689 ± 0.025, 2.10 (1.63, 2.70) for BD, 104.8 mg/cm³ (−2.2 SD, 53.5% of YAM), 0.699 ± 0.023, 2.17 (1.69, 2.77) for TBD and 192.8 mm³ (−1.9 SD, 59.8% of YAM), 0.631 ± 0.028, 1.72 (1.34, 2.21) for pSSI, respectively. These findings suggest that ultradistal radius BMD measured using pQCT can be used to discriminate women with vertebral fractures. Received: 3 August 2000 / Accepted: 5 March 2001     

Threshold-Free Automatic Detection of Cortical Bone Geometry by Peripheral Quantitative Computed Tomography

An accurate assessment of bone strength is an important goal in clinical bone research. For appropriate information on bone strength, precise segmentation of actual cross-sectional bone geometry is needed. In this article, we introduce an automatic, simple, and fast approach for reliable segmentation of cortical bone cross-sectional area based on the outer boundary detection and subsequent shrinking (OBS) procedure. Using repeated in vivo peripheral quantitative computed tomography (pQCT) images of distal tibia from 25 subjects, we compared new segmentation results with those obtained from commonly applied simple density thresholds and from a recent advanced analysis based on distance regularized level set evolution (DRLSE). Manual segmentation of cortical bone done by 3 independent evaluators was considered a gold standard. The new approach showed nearly 50% less variation in error compared with threshold-based analysis in conjunction with a recently introduced statistical preprocessing method and agreed well with results obtained from manual segmentation. The DRLSE segmentation resulted consistently in ～15% mean overestimation of all geometrical traits with a similar variation of data as obtained from the OBS method. In conclusion, the OBS method improved assessment of all observed measures of cortical geometry and can enhance the cortical bone analysis of pQCT images in clinical research studies.