Bone metastases radiographically appear as regions with high (i.e. blastic metastases) or low (i.e. lytic metastases) bone mineral density. The clinical assessment of metastatic features is based on computed tomography (CT) but it is still unclear if the actual size of the metastases can be accurately detected from the CT images and if the microstructure in regions surrounding the metastases is altered (Nägele et al., 2004, Calc Tiss Int). This study aims to evaluate (i) the capability of the CT in evaluating the metastases size and (ii) if metastases affect the bone microstructure around them. Ten spine segments consisted of a vertebra with lytic or mixed metastases and an adjacent control (radiologically healthy) were obtained through an ethically approved donation program. The specimens were scanned with a clinical CT (AquilionOne, Toshiba: slice thickness:1mm, in-plane resolution:0.45mm) to assess clinical metastatic features and a micro-CT (VivaCT80, Scanco, isotropic voxel size:0.039mm) to evaluate the detailed microstructure. The volume of the metastases was measured from both CT and micro-CT images (Palanca et al., 2021, Bone) and compared with a linear regression. The microstructural alteration around the metastases was evaluated in the volume of interest (VOI) defined in the micro-CT images as the volume of the vertebral body excluding the metastases. Three 3D microstructural parameters were calculated in the VOI (CTAn, Bruker SkyScan): Bone Volume Fraction (BV/TV), Trabecular Thickness (Tb.Th.), Trabecular Spacing (Tb.Sp.). Medians of each parameter were compared (Kruskal-Wallis, p=0.05). One specimen was excluded as it was not possible to define the size of the metastases in the CT scans. A strong correlation between the volume obtained from the CT and micro-CT images was found (R2=0.91, Slope=0.97, Intercept=2.55, RMSE=5.7%, MaxError=13.12%). The differences in BV/TV, Tb.Th. and Tb.Sp. among vertebrae with lytic and mixed metastases and control vertebrae were not statistically significant (p-value>0.6). Similar median values of BV/TV were found in vertebrae with lytic (13.2±2.4%) and mixed (12.8±9.8%) metastases, and in controls (13.0±10.1%). The median Tb.Th. was 176±18 ∓m, 179±43 ∓m and 167±91 ∓m in vertebrae with lytic and mixed metastases and control vertebrae, respectively. The median Tb. Sp. was 846±26 ∓m, 849±286 ∓m and 880±116 ∓m in vertebrae with lytic and mixed metastases and control vertebrae, respectively. In conclusion, the size of vertebral metastases can be accurately assess using CT images. The 3D microstructural parameters measured were comparable with those reported in the literature for healthy vertebrae (Nägele et al., 2004, Calc Tiss Int, Sone et al., 2004, Bone) and showed how the microstructure of the bone tissue surrounding the lesion is not altered by the metastases.
Current therapies for osteoporosis are limited to generalised antiresorptive or anabolic interventions, which do not target specific regions to improve skeletal health. Moreover, the adaptive changes of separate and combined pharmacological and biomechanical treatments in the ovariectomised (OVX) mouse tibia has not been studied yet. Therefore, this study combines micro- computed tomography (micro-CT) imaging and computational modelling to evaluate the efficacies of treatments in reducing bone loss. In vivo micro-CT (10.4µm/voxel) images of the right tibiae of N=18 female OVX C57BL/6 mice were acquired at weeks 14, 16, 18, 20 and 22 of age for 3 groups: mechanical loading (ML), parathyroid hormone (PTH) or combined therapies (PTHML). All mice received either injection of PTH (100μg/kg/day, 5days/week) or vehicle from week 18. The right tibiae were mechanically loaded in vivo at week 19 and 21 with a 12N peak load, 40 cycles/day and 3 days/week. Bone adaptation was quantified through spatial changes in bone mineral density (BMD) and strain distribution was obtained from micro-CT-based finite element models.Abstract
Objectives
Methodology
Subject-specific finite element models (FEMs) allow for a variety of biomechanical conditions to be tested in a highly repeatable manner. Accuracy of FEMs is improved by mapping density using quantitative computed tomography (QCT) and choosing a constitutive relationship relating density and mechanical properties of bone. Although QCT-derived FEMs have become common practice in contemporary computational studies of whole bones, many density-modulus relationships used at the whole bone level were derived using mechanical loading of small trabecular or cortical bone cores. These cores were mechanically loaded to derive an apparent modulus, which is related to each core's mean apparent or ash density. This study used these relationships and either elemental or nodal material mapping strategies to elucidate optimal methods for scapular QCT-FEMs. Six cadaveric scapulae (3 male; 3 female; mean age: 68±10 years) were loaded within a micro-CT in a custom CT-compatible hexapod robot Pre- and post-loaded scans were acquired (spatial resolution = 33.5 µm) and DVC was used to quantify experimental full-field displacements (BoneDVC, Insigneo) (Figure 1).. Experimental reaction forces applied to the scapulae were measured using a 6-DOF load cell. FEMs were derived from corresponding QCT scans of each cadaver bone. These models were mapped with one of fifteen density-modulus relationships and elemental or nodal material mapping strategies. DVC-derived BCs were imposed on the QCT-FEMs using local displacement measurements obtained from the DVC algorithm. Comparisons between the empirical and computational models were performed using resultant reaction loads and full-field displacements (Figure 2).Introduction
Methods
DVC is a novel full-field and contactless measurement technique for calculating displacements and strains inside bones (Grassi and Isaksson 2015) through the comparison of 3D reconstructions (CT, micro-CT, MRI, etc.) from unloaded and loaded samples. Recent in zero-strain tests to estimate the measurement precision by applying a known state of strain (Palanca, Tozzi et al. 2015) suggested that DVC is suitable to identify regions where bone tissue is yielded (i.e. subjected to high strains). Conversely to reliably measure strain in the physiological range a severe compromise with spatial resolution is necessary (Dall'Ara, Barber et al. 2014, Palanca, Tozzi et al. 2015). In order to use DVC to explore the relationship between the local physiological strain and bone microarchitecture, an error lower than 200 microstrain (an order of magnitude lower than the mean strain) and a spatial resolution of the strain measurement lower than 100 μm is required. The aim of this work is to define if, and to what extend, high-quality images obtained by synchrotron radiation micro computed tomography (SR-μCT) improve the precision of a global DVC approach. Cylindrical specimens of cortical and trabecular bone were extracted from a fresh bovine femur and embedded in acrylic resin. Both samples were scanned twice without any repositioning (‘repeated scantest’) at beamline l13–2 of Diamond Light Source (Oxford, UK). 4000 projections of 53 ms exposure were collected via fly-scanning with a CdWO4scintillator-coupled pco.edge 5.5 detector with 4× magnification and an effective pixel size of 1.6μm. Strains were evaluated using a global DVC approach (ShIRT-FE) in two cubic volumes of interest (VOI) of 1,000 voxels in side length, for each specimen, exploring a DVC spatial resolution from 16 to 498 μm. The precision of measurements was evaluated extracting a similar indicator to (Liu and Morgan 2007). Precision improved with decreasing spatial resolution, confirming a trend similar to that obtained with ‘laboratory source’ μCT on similar specimens (Palanca, Tozzi et al. 2015). To obtain a precision of better than 200 microstrains the cortical and trabecular samples required spatial resolutions of 41 and 80 μm respectively. Comparing these results to those of previous studies, where similar specimens were scanned with ‘laboratory source’ μCT (effective voxel size of the order of ten μm) the errors were vastly reduced (approximately one order of magnitude). In fact, in order to obtain a precision of better than 200 microstrain, spatial resolutions of 550 (cortical) and 480 (trabecular) μm were needed (Dall'Ara, Barber et al. 2014). This work showed that using high-quality tomograms obtained by synchrotron radiation μCT decreases the measurement uncertainties of a global DVC approach with respect to those obtained with laboratory source μCT. DVC could therefore be used with μCT data to evaluate displacement and strain in the physiological range with remarkable spatial resolution.
