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Abstract QCT is commonly employed in research studies and clinical trials to measure BMD at the proximal femur. In this study we compared two analysis software options, QCTPro CTXA and MIAF-Femur, using CT scans of the semi-anthropometric European Proximal Femur Phantom (EPFP) and in vivo data from 130 Chinese elderly men and women aged 60–80 years. Integral (Int), cortical (Cort) and trabecular (Trab) vBMD, volume, and BMC of the neck (FN), trochanter (TR), inter-trochanter (IT), and total hip (TH) VOIs were compared. Accuracy was determined in the 5 mm wide central portion of the femoral neck of the EPFP. Nominal values were: cross-sectional area (CSA) 4.9 cm2, cortical thickness (C.Th) 2 mm, CortBMD 723 mg/cm3 and TrabBMD 100 mg/cm3. In MIAF the so-called peeled trabecular VOI was analyzed, which excludes subcortical bone to avoid partial volume artefacts at the endocortical border that artificially increase TrabBMD. For CTXA uncorrected, so called raw cortical values were used for the analysis. QCTPro and MIAF phantom results were: CSA 5.9 cm2 versus 5.1 cm2; C.Th 1.68 mm versus 1.92 mm; CortBMD 578 mg/cm3 versus 569 mg/cm3; and TrabBMD 154 mg/cm3 versus 104 mg/cm3. In vivo correlations (R2) of integral and trabecular bone parameters ranged from 0.63 to 0.96. Bland–Altman analysis for TH and FN TrabBMD showed that lower mean values were associated with higher differences, which means that TrabBMD differences between MIAF and CTXA are larger for osteoporotic than for normal patients, which can be largely explained by the inclusion of subcortical BMD in the trabecular VOI analyzed by CTXA in combination with fixed thresholds used to separate cortical from trabecular bone compartments. Correlations between CTXA corrected CortBMD and MIAF were negative, whereas raw data correlated positively with MIAF measurements for all VOIs questioning the validity of the CTXA corrections. The EPFP results demonstrated higher MIAF accuracy of cortical thickness and TrabBMD. Integral and trabecular bone parameters were highly correlated between CTXA and MIAF. Partial volume artefacts at the endocortical border artificially increased trabecular BMD by CTXA, especially for osteoporosis patients. With respect to volumetric cortical measurements with CTXA, the use raw data is recommended, because corrected data cause a negative correlation with MIAF CortBMD. Highlights • The primary use of CTXA should be limited to the analysis of areal BMD, which provides DXA equivalent hip T-scores. • Integral BMD values of the total hip obtained by CTXA agree well with those obtained from a MIAF analysis. • Trabecular and cortical BMD values strongly depend on the thresholds used in the CTXA analysis. • The use of CTXA corrected cortical data is strongly discouraged. • The study results underscore the need of standardization of analysis VOIs and cortical segmentation algorithms. [ABSTRACT FROM AUTHOR]

Motivation: Cortical bone is an important contributor to bone strength and is pivotal to understand the etiology of osteoporotic fractures and the specific mechanisms of antiosteoporotic treatment regimen. 3D computed tomography (CT) can be used to measure cortical thickness, density, and mass in the proximal femur, lumbar vertebrae, and distal forearm. However, the spatial resolution of clinical whole body CT scanners is limited by radiation exposure; partial volume artefacts severely impair the accurate assessment of cortical parameters, in particular in locations where the cortex is thin such as in the lumbar vertebral bodies or in the femoral neck. Method: Model-based deconvolution approaches recover the cortical thickness by numerically deconvolving the image along 1D profiles using an estimated scanner point spread function (PSF) and a hypothesized uniform cortical bone mineral density (reference density). In this work we provide a new essentially analytical unique solution to the model-based cortex recovery problem using few characteristics of the measured profile and thus eliminate the non-linear optimization step for deconvolution. Also, the proposed approach allows to get rid of the PSF in the model and reduces sensitivity to errors in the reference density. Additionally, run-time and memory effective computation of cortical thickness was achieved with the help of a lookup table. Results: The method accuracy and robustness was validated and compared to that of a deconvolution approach recently proposed for cortical bone and of the 50% relative threshold technique: in a simulated environment with noise and various error levels in the reference density and using CT acquisitions of the European Forearm Phantom (EFP II), a modification of a widely used anthropomorphic standard of cortical and trabecular bone compartments that was scanned with various scan protocols. Conclusion: Results of simulations and of phantom data analysis verified the following properties of the new method: 1) Robustness against errors in the reference density. 2) Excellent accuracy on ground truth data with various noise levels. 3) Very fast computation using a lookup table. [ABSTRACT FROM AUTHOR]

Many studies use threshold-based techniques to assess in vivo the muscle, bone and adipose tissue distribution of the legs using computed tomography (CT) imaging. More advanced techniques divide the legs into subcutaneous adipose tissue (SAT), anatomical muscle (muscle tissue and adipocytes within the muscle border) and intra- and perimuscular adipose tissue. In addition, a so-called muscle density directly derived from the CT-values is often measured. We introduce a new integrated approach to quantify the muscle-lipid system (MLS) using quantitative CT in patients with sarcopenia or osteoporosis. The analysis targets the thigh as many CT studies of the hip do not include entire legs The framework consists of an anatomic coordinate system, allowing delineation of reproducible volumes of interest, a robust semi-automatic 3D segmentation of the fascia and a comprehensive method to quantify of the muscle and lipid distribution within the fascia. CT density-dependent features are calibrated using subject-specific internal CT values of the SAT and external CT values of an in scan calibration phantom. Robustness of the framework with respect to operator interaction, image noise and calibration was evaluated. Specifically, the impact of inter- and intra-operator reanalysis precision and addition of Gaussian noise to simulate lower radiation exposure on muscle and AT volumes, muscle density and 3D texture features quantifying MLS within the fascia, were analyzed. Existing data of 25 subjects (age: 75.6 ± 8.7) with porous and low-contrast muscle structures were included in the analysis. Intra- and inter-operator reanalysis precision errors were below 1% and mostly comparable to 1% of cohort variation of the corresponding features. Doubling the noise changed most 3D texture features by up to 15% of the cohort variation but did not affect density and volume measurements. The application of the novel technique is easy with acceptable processing time. It can thus be employed for a comprehensive quantification of the muscle-lipid system enabling radiomics approaches to musculoskeletal disorders. [ABSTRACT FROM AUTHOR]

The aim of this study was the registration of digitized thin 2D sections of mouse vertebrae and tibiae used for histomorphometry of trabecular bone structure into 3D micro computed tomography (μCT) datasets of the samples from which the sections were prepared. Intensity-based and segmentation-based registrations (SegRegs) of 2D sections and 3D μCT datasets were applied. As the 2D sections were deformed during their preparation, affine registration for the vertebrae was used instead of rigid registration. Tibiae sections were additionally cut on the distal end, which subsequently undergone more deformation so that elastic registration was necessary. The Jaccard distance was used as registration quality measure. The quality of intensity-based registrations and SegRegs was practically equal, although precision errors of the elastic registration of segmentation masks in tibiae were lower, while those in vertebrae were lower for the intensity-based registration. Results of SegReg significantly depended on the segmentation of the μCT datasets. Accuracy errors were reduced from approximately 64% to 42% when applying affine instead of rigid transformations for the vertebrae and from about 43% to 24% when using B-spline instead of rigid transformations for the tibiae. Accuracy errors can also be caused by the difference in spatial resolution between the thin sections (pixel size: 7.25 μm) and the μCT data (voxel size: 15 μm). In the vertebrae, average deformations amounted to a 6.7% shortening along the direction of sectioning and a 4% extension along the perpendicular direction corresponding to 0.13–0.17 mm. Maximum offsets in the mouse tibiae were 0.16 mm on average. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis is an important pathophysiological process of chronic inflammation, especially in inflammatory arthritis. Quantitative measurement of changes in vascularization may improve the diagnosis and monitoring of arthritis. The aim of this work is the development of a 3D imaging and analysis framework for quantification of vascularization in experimental arthritis. Methods: High-resolution micro-computed tomography (μCT) was used to scan knee joints of arthritic human tumor necrosis factor transgenic (hTNFtg) mice and non-arthritic wild-type controls previously perfused with lead-containing contrast agent Microfil MV-122. Vessel segmentation was performed by combination of intensity-based (local adaptive thresholding) and form-based (multi-scale method) segmentation techniques. Four anatomically defined concentric spherical shells centered in the knee joint were used as analysis volumes of interest. Vessel density, density distribution as well as vessel thickness, surface, spacing and number were measured. Simulated digital vessel tree models were used for validation of the algorithms. Results: High-resolution μCT allows the quantitative assessment of the vascular tree in the knee joint during arthritis. Segmentation and analysis were highly automated but occasionally required manual corrections of the vessel segmentation close to the bone surfaces. Vascularization was significantly increased in arthritic hTNFtg mice compared to wild type controls. Precision errors for the morphologic parameters were smaller than 3% and 6% for intra- and interoperator analysis, respectively. Accuracy errors for vessel thickness were around 20% for vessels larger than twice the resolution of the scanner. Conclusions: Arthritis-induced changes of the vascular tree, including detailed and quantitative description of the number of vessel branches, length of vessel segments and the bifurcation angle, can be detected by contrastenhanced high-resolution μCT. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis is an important pathophysiological process of chronic inflammation, especially in inflammatory arthritis. Quantitative measurement of changes in vascularization may improve the diagnosis and monitoring of arthritis. The aim of this work is the development of a 3D imaging and analysis framework for quantification of vascularization in experimental arthritis.Methods: High-resolution micro-computed tomography (μCT) was used to scan knee joints of arthritic human tumor necrosis factor transgenic (hTNFtg) mice and non-arthritic wild-type controls previously perfused with lead-containing contrast agent Microfil MV-122. Vessel segmentation was performed by combination of intensity-based (local adaptive thresholding) and form-based (multi-scale method) segmentation techniques. Four anatomically defined concentric spherical shells centered in the knee joint were used as analysis volumes of interest. Vessel density, density distribution as well as vessel thickness, surface, spacing and number were measured. Simulated digital vessel tree models were used for validation of the algorithms.Results: High-resolution μCT allows the quantitative assessment of the vascular tree in the knee joint during arthritis. Segmentation and analysis were highly automated but occasionally required manual corrections of the vessel segmentation close to the bone surfaces. Vascularization was significantly increased in arthritic hTNFtg mice compared to wild type controls. Precision errors for the morphologic parameters were smaller than 3% and 6% for intra- and interoperator analysis, respectively. Accuracy errors for vessel thickness were around 20% for vessels larger than twice the resolution of the scanner.Conclusions: Arthritis-induced changes of the vascular tree, including detailed and quantitative description of the number of vessel branches, length of vessel segments and the bifurcation angle, can be detected by contrast-enhanced high-resolution μCT. [ABSTRACT FROM AUTHOR]

Quantitative computer tomography (QCT)-based finite element (FE) models of vertebral body provide better prediction of vertebral strength than dual energy X-ray absorptiometry. However, most models were validated against compression of vertebral bodies with endplates embedded in polymethylmethal-crylate (PMMA). Yet, loading being as important as bone density, the absence of intervertebral disc (IVD) affects the strength. Accordingly, the aim was to assess the strength predictions of the classic FE models (vertebral body embedded) against the in vitro and in silico strengths of vertebral bodies loaded via IVDs. High resolution peripheral QCT (HR-pQCT) were performed on 13 segments (T11/T12/L1). T11 and L1 were augmented with PMMA and the samples were tested under a 4° wedge compression until failure of T12. Specimen-specific model was generated for each T12 from the HR-pQCT data. Two FE sets were created: FE-PMMA refers to the classical vertebral body embedded model under axial compression; FE-IVD to their loading via hyperelastic IVD model under the wedge compression as conducted experimentally. Results showed that FE-PMMA models overestimated the experimental strength and their strength prediction was satisfactory considering the different experimental set-up. On the other hand, the FE-IVD models did not prove significantly better (Exp/FE-PMMA: R=0.68; Exp/FE-IVD: R2=0.71, p=0.84). In conclusion, FE-PMMA correlates well with in vitro strength of human vertebral bodies loaded via real IVDs and FE-IVD with hyperelastic IVDs do not significantly improve this correlation. Therefore, it seems not worth adding the IVDs to vertebral body models until fully validated patient-specific IVD models become available. [ABSTRACT FROM AUTHOR]

Objective. To develop a precise three-dimensional (3D) segmentation technique for bone erosions in high-resolution peripheral quantitative CT (HR-pQCT) datasets to measure their volume, surface area and shape parameters. Assessment of bone erosions in patients with RA is important for diagnosis and evaluation of treatment efficacy. HR-pQCT allows quantifying periarticular bone loss in arthritis.Methods. HR-pQCT scans with a spatial resolution of about 120 µm of the second to fourth metacarpophalangeal joints were acquired in patients with RA. Erosions were identified by placing a seed point in each of them. After applying 3D segmentation, the volume, surface area and sphericity of erosions were calculated. Results were compared with an approximation method using manual measurements. Intra- and interoperator precision analysis was performed for both the 3D segmentation and the manual technique.Results. Forty-three erosions were assessed in 18 datasets. Intra- and interoperator precisions (RMSCV/RMSSD) for erosion volume were 5.66%/0.49 mm3 and 7.76%/0.76 mm3, respectively. The correlation between manual measurements and their simulation using segmentation volumes was r = 0.87. Precision errors for the manual method were 15.39% and 0.36 mm3, respectively.Conclusion. We developed a new precise 3D segmentation technique for quantification of bone erosions in HR-pQCT datasets that correlates to the volume, shape and surface area of the erosion. The technique allows fast and effective measurement of the erosion size and could therefore be helpful for rapid and quantitative assessment of erosion size. [ABSTRACT FROM PUBLISHER]

Denosumab reduced the incidence of new fractures in postmenopausal women with osteoporosis by 68% at the spine and 40% at the hip over 36 months compared with placebo in the FREEDOM study. This efficacy was supported by improvements from baseline in vertebral (18.2%) strength in axial compression and femoral (8.6%) strength in sideways fall configuration at 36 months, estimated in Newtons by an established voxel-based finite element (FE) methodology. Since FE analyses rely on the choice of meshes, material properties, and boundary conditions, the aim of this study was to independently confirm and compare the effects of denosumab on vertebral and femoral strength during the FREEDOM trial using an alternative smooth FE methodology. Unlike the previous FE study, effects on femoral strength in physiological stance configuration were also examined. QCT data for the proximal femur and two lumbar vertebrae were analyzed by smooth FE methodology at baseline, 12, 24, and 36 months for 51 treated (denosumab) and 47 control (placebo) subjects. QCT images were segmented and converted into smooth FE models to compute bone strength. L1 and L2 vertebral bodies were virtually loaded in axial compression and the proximal femora in both fall and stance configurations. Denosumab increased vertebral body strength by 10.8%, 14.0%, and 17.4% from baseline at 12, 24, and 36 months, respectively ( p < 0.0001). Denosumab also increased femoral strength in the fall configuration by 4.3%, 5.1%, and 7.2% from baseline at 12, 24, and 36 months, respectively ( p < 0.0001). Similar improvements were observed in the stance configuration with increases of 4.2%, 5.2%, and 5.2% from baseline ( p ≤ 0.0007). Differences between the increasing strengths with denosumab and the decreasing strengths with placebo were significant starting at 12 months (vertebral and femoral fall) or 24 months (femoral stance). Using an alternative smooth FE methodology, we confirmed the significant improvements in vertebral body and proximal femur strength previously observed with denosumab. Estimated increases in strength with denosumab and decreases with placebo were highly consistent between both FE techniques. [ABSTRACT FROM AUTHOR]

Objective. To monitor size and shape changes of bone erosions and changes in BMD in the vicinity of the erosion and in the periarticular trabecular compartment of patients with RA using high-resolution peripheral quantitative CT (HR-pQCT) imaging and to compare an automated three-dimensional (3D) image processing technique with manual measurements of erosion width and depth. Methods. The shape of 40 bone erosions and composition of bone around the erosions were analysed in the MCP joints of 22 RA patients both manually and by semi-automated 3D image processing at two different time points. Periosteal segmentation was performed using volume growing and morphological operations. Image registration was applied for transfer of baseline segmentations to follow-up datasets. Results. Eight erosions decreased in size, 6 increased and 28 remained stable. Increasing erosions were more spherical and smaller at baseline compared with decreasing or stable erosions. BMD in the vicinity of shrinking erosions increased, while it decreased next to expanding erosions. There was moderate agreement in the determination of erosion volume between semi-automated and manual measurements, but agreement was poor when assessing changes in volume over time. Conclusion. Longitudinal changes in erosion size and shape and of BMD in the vicinity of an erosion can be measured. BMD changes are associated with progression and regression of erosions. However, the semi-automated and manual approaches did not classify longitudinal changes of erosion volume in the same way. Further research is necessary to define the nature of these differences. [ABSTRACT FROM AUTHOR]