Multicenter precision of cortical and trabecular bone quality measures assessed by high-resolution peripheral quantitative computed tomography

Abstract

High-resolution peripheral quantitative computed tomography (HR-pQCT) has recently been introduced as a clinical research tool for in vivo assessment of bone quality. The utility of this technology to address important skeletal health questions requires translation to standardized multicenter data pools. Our goal was to evaluate the feasibility of pooling data in multicenter HR-pQCT imaging trials. Reproducibility imaging experiments were performed using structure and composition-realistic phantoms constructed from cadaveric radii. Single-center precision was determined by repeat scanning over short-term (<72 hours), intermediate-term (3-5 months), and long-term intervals (28 months). Multicenter precision was determined by imaging the phantoms at nine different HR-pQCT centers. Least significant change (LSC) and root mean squared coefficient of variation (RMSCV) for each interval and across centers was calculated for bone density, geometry, microstructure, and biomechanical parameters. Single-center short-term RMSCVs were <1% for all parameters except cortical thickness (Ct.Th) (1.1%), spatial variability in cortical thickness (Ct.Th.SD) (2.6%), standard deviation of trabecular separation (Tb.Sp.SD) (1.8%), and porosity measures (6% to 8%). Intermediate-term RMSCVs were generally not statistically different from short-term values. Long-term variability was significantly greater for all density measures (0.7% to 2.0%; p < 0.05 versus short-term) and several structure measures: cortical thickness (Ct.Th) (3.4%; p < 0.01 versus short-term), cortical porosity (Ct.Po) (15.4%; p < 0.01 versus short-term), and trabecular thickness (Tb.Th) (2.2%; p < 0.01 versus short-term). Multicenter RMSCVs were also significantly higher than short-term values: 2% to 4% for density and micro-finite element analysis (µFE) measures (p < 0.0001), 2.6% to 5.3% for morphometric measures (p < 0.001), whereas Ct.Po was 16.2% (p < 0.001). In the absence of subject motion, multicenter precision errors for HR-pQCT parameters were generally less than 5%. Phantom-based multicenter precision was comparable to previously reported in in vivo single-center precision errors, although this was approximately two to five times worse than ex vivo short-term precision. The data generated from this study will contribute to the future design and validation of standardized procedures that are broadly translatable to multicenter study designs.

Figure 1

The UCSF Extremity Bone Structure (EBS) phantom is shown in a photograph (A). Each phantom consists of a 7-cm diameter cylinder of soft-tissue equivalent polymer resin. Each cylinder contains five 1-cm thick cadaveric bone embedments (B), sectioned from the distal radius at a location corresponding to the standard location for an in vivo HR-pQCT exam (9.0-mm proximal to mid-point of the distal endplate). The phantom uses custom brackets for standardized mounting on the scanner gantry. A representative image for one bone section is shown on the right (C).

Figure 2

The noise performance of each imaging system was assessed in a single phantom designed for routine density calibration and daily quality control. The signal to noise ratio (SNR) was calculated as the ratio of the mean attenuation of the high-density cylinder (µ, green region) to the standard deviation of the attenuation in the tissue-equivalent background (σ_µ, red region).

Figure 3

The resolution performance of each imaging system was measured by estimating the point spread function (PSF) from images of a custom wire phantom (A). The phantom consisted of five 25-µm tungsten wires oriented parallel to the long axis of an 8-cm cylinder of tissue-equivalent polymer resin. One wire was located at the center, while the other four were located 3-cm from the center at 90° intervals. From the reconstructed image of the wire cross-sections (B), the PSF is estimated and then the resolution is calculated from the spatial frequency corresponding to 10% of the MTF (C).

Figure 4

The noise and spatial resolution of the individual HR-pQCT systems from the nine imaging centers participating in this study is presented in bar graph form. Above (A) the noise performance is characterized by a simple SNR measurement in the standard QC density phantom with error bars indicating the standard deviation of SNR for three repeat scans. Below (B), the spatial resolution is estimated to be the spatial frequency corresponding to the 10%-height of the modulation transfer function (MTF).

Figure 5

HR-pQCT images of the UCSF EBS Phantom from three different imaging centers that represent the median SNR and resolution performance (site E, top), a high-resolution, high noise system (site B, middle), and a low resolution, low noise system (site G, bottom). For each image the mean SNR and spatial resolution (10% MTF) at the center of the FOV are indicated.

Figure 6

On top (A–D) are summary bar graphs of the reproducibility of select HR-pQCT measures expressed as RMSCV [%] over short- (<72 hours), intermediate- (3–5 months), and long-term (28 months) for single centers (black, dark grey, light grey, respectively) compared to the multi-center reproducibility of nine different systems (white). On the bottom (E–H) are line graphs illustrating the stability of select HR-pQCT measures monitored at a single site over the course of 28 months. All values were normalized to the baseline for visualization purposes.

Figure 7

The comparability of individual imaging systems is illustrated in this figure for the standard density (A), geometric (B), microstructural (C), and biomechanical (D) parameters. For each parameter the value measured for each 1-cm bone section was normalized to the mean value of that section across all nine systems. These graphs represent the mean normalized value for each parameter at a given center.