Objective. Bone strength depends on both mineral content and bone structure. The aim of this in vitro study was to develop a method for quantitative assessment of trabecular bone structure by applying three-dimensional image processing to data acquired with multi-slice and cone-beam computed tomography using micro-computed tomography as reference.Material and Methods. 15 bone samples from the radius were examined. After segmentation, quantitative measures of bone volume, trabecular thickness, trabecular separation, trabecular number, trabecular nodes and trabecular termini were obtained.Results. Both clinical machines overestimated bone volume and trabecular thickness and underestimated trabecular nodes and number but cone-beam CT to a lesser extent. Parameters obtained from cone beam CT were strongly correlated to µCT, with correlation coefficients between 0.93 and 0.98 for all parameters except trabecular termini.Conclusions. The high correlation between cone-beam CT and micro-CT suggest the possibility to quantify and monitor changes of trabecular bone microarchitecture in vivo using cone beam CT. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems CorporationResponse to Reviewers (without author information) Revision NoteThis document gives a point-by-point response to the comments made by the Reviewers. Most of these comments have led to changes in the manuscript. In order to facilitate the task for the Editor and the Reviewers, the changes are marked with Reviewer 1 or Reviewer 2 with the following subtitles. Comment:Response:Changes:Proposed changes from the Reviewers in italics.In this document we have noted Page XX and Line XX, were to find the changes in the manuscript. Comment about weakness in the study:Weaknesses: Small sample population may affect study power. Unfortunately no a priori power analysis has been performed; it may be worth to include it (post-hoc). Response:We agree that for planning the current study it might have been wise to perform power calculations. With the high correlation coefficients obtained for CBCT (0.73 and above), post-hoc power calculations yield power estimates of at least 95% for all studied parameters (exact distribution, onetailed test, alpha=0.05). However in this study, we think that the relevant research question is not whether there is a positive correlation, but how strong the (expected) correlation is. This is the main reason for including confidence intervals rather than p values in Table 3. In accordance with this, we find it less relevant to include power calculation post hoc. Reviewer 1 Comment 1: It may be worth to include "Cone Beam Computed Tomography" in the title. CBCT is presently a topic of interest and it may appeal to the readers, focusing their attention on this paper, especially due to the study conclusion Response:We agree with the reviewer and CBCT is now included in the title Changes:The new title is:Trabecular bone structure parameters from 3D image processing of clinical multi-slice and cone-beam computed tomography data...

Objectives: The aim of this study was to evaluate how imaging parameters at clinical dental CBCT affect the accuracy in quantifying trabecular bone structures, contrast-to-noise ratio (CNR) and radiation dose. Methods: 15 radius samples were examined using CBCT (Accuitomo FPD; J. Morita Mfg., Kyoto, Japan). Nine imaging protocols were used, differing in current, voltage, rotation degree, voxel size, imaging area and rotation time. Radiation doses were measured using a kerma area product-meter. After segmentation, six bone structure parameters and CNRs were quantified. Micro-CT (mCT) images with an isotropic resolution of 20 mm were used as a gold standard. Results: Structure parameters obtained by CBCT were strongly correlated to those by mCT, with correlation coefficients .0.90 for all studied parameters. Bone volume and trabecular thickness were not affected by changes in imaging parameters. Increased tube current from 5 to 8 mA, decreased isotropic voxel size from 125 to 80 mm and decreased rotation angle from 360°to 180°affected correlations for trabecular termini negatively. Decreasing rotation degree also weakened correlations for trabecular separation and trabecular number at 80 mm voxel size. Changes in the rotation degree and tube current affected CNR significantly. The radiation dose varied between 269 and 1153 mGy cm 2 . Conclusions: Trabecular bone structure can be accurately quantified by clinical dental CBCT in vitro, and the obtained structure parameters are strongly related to those obtained by mCT. A fair CNR and strong correlations can be obtained with a low radiation dose, indicating the possibility for monitoring trabecular bone structure also in vivo.

Stiffness and shear moduli of human trabecular bone may be analyzed in vivo by finite element (FE) analysis from image data obtained by clinical imaging equipment such as high resolution peripheral quantitative computed tomography (HR-pQCT). In clinical practice today, this is done in the peripheral skeleton like the wrist and heel. In this cadaveric bone study, fourteen bone specimens from the wrist were imaged by two dental cone beam computed tomography (CBCT) devices and one HR-pQCT device as well as by dual energy X-ray absorptiometry (DXA). Histomorphometric measurements from micro-CT data were used as gold standard. The image processing was done with an in-house developed code based on the automated region growing (ARG) algorithm. Evaluation of how well stiffness (Young’s modulus E3) and minimum shear modulus from the 12, 13, or 23 could be predicted from the CBCT and HR-pQCT imaging data was studied and compared to FE analysis from the micro-CT imaging data. Strong correlations were found between the clinical machines and micro-CT regarding trabecular bone structure parameters, such as bone volume over total volume, trabecular thickness, trabecular number and trabecular nodes (varying from 0.79 to 0.96). The two CBCT devices as well as the HR-pQCT showed the ability to predict stiffness and shear, with adjusted R2-values between 0.78 and 0.92, based on data derived through our in-house developed code based on the ARG algorithm. These findings indicate that clinically used CBCT may be a feasible method for clinical studies of bone structure and mechanical properties in future osteoporosis research.

Osteoporosis, characterized by reduced bone mineral density and micro-architectural degeneration, significantly enhances fracture-risk. There are several viable methods for trabecular bone micro-imaging, which widely vary in terms of technology, reconstruction principle, spatial resolution, and acquisition time. We have performed an excised cadaveric bone specimen study to evaluate different CT-imaging modalities for trabecular bone microstructural analysis. Excised cadaveric bone specimens from the distal radius were scanned using micro-CT and four in vivo CT imaging modalities: HR-pQCT, dental CBCT, wholebody MDCT, and extremity CBCT. A new algorithm was developed to optimize soft thresholding parameters for individual in vivo CT modalities for computing quantitative bone volume fraction maps. Finally, agreement of trabecular bone micro-structural measures, derived from different in vivo CT imaging, with reference measures from micro-CT imaging was examined. Observed values of most trabecular measures, including trabecular bone volume, network area, transverse and plate-rod micro-structure, thickness, and spacing, for in vivo CT modalities were higher than their micro-CT-based reference values. In general, HR-pQCT-based trabecular bone measures were closer to their reference values as compared to other in vivo CT modalities. Despite large differences in observed values of measures among modalities, high linear correlation (r Î [0.94 0.99]) was found between micro-CT and in vivo CT-derived measures of trabecular bone volume, transverse and plate micro-structural volume, and network area. All HR-pQCT-derived trabecular measures, except the erosion index, showed high correlation (r Î [0.91 0.99]). The plate-width measure showed a higher correlation (r Î [0.72 0.91]) among in vivo and micro-CT modalities than its counterpart binary plate-rod characterization-based measure erosion index (r Î [0.65 0.81]). Although a strong correlation was observed between micro-structural measures from in vivo and micro-CT imaging, large shifts in their values for in vivo modalities warrant proper scanner calibration prior to adopting in multi-site and longitudinal studies.

Background As bone microstructure is known to impact bone strength, the aim of this in vitro study was to evaluate if the emerging photon-counting detector computed tomography (PCD-CT) technique may be used for measurements of trabecular bone structures like thickness, separation, nodes, spacing and bone volume fraction. Methods Fourteen cubic sections of human radius were scanned with two multislice CT devices, one PCD-CT and one energy-integrating detector CT (EID-CT), using micro-CT as a reference standard. The protocols for PCD-CT and EID-CT were those recommended for inner- and middle-ear structures, although at higher mAs values: PCD-CT at 450 mAs and EID-CT at 600 (dose equivalent to PCD-CT) and 1000 mAs. Average measurements of the five bone parameters as well as dispersion measurements of thickness, separation and spacing were calculated using a three-dimensional automated region growing (ARG) algorithm. Spearman correlations with micro-CT were computed. Results Correlations with micro-CT, for PCD-CT and EID-CT, ranged from 0.64 to 0.98 for all parameters except for dispersion of thickness, which did not show a significant correlation (p = 0.078 to 0.892). PCD-CT had seven of the eight parameters with correlations ρ > 0.7 and three ρ > 0.9. The dose-equivalent EID-CT instead had four parameters with correlations ρ > 0.7 and only one ρ > 0.9. Conclusions In this in vitro study of radius specimens, strong correlations were found between trabecular bone structure parameters computed from PCD-CT data when compared to micro-CT. This suggests that PCD-CT might be useful for analysing bone microstructure in the peripheral human skeleton.