Repositioning error in longitudinal high-resolution peripheral-quantitative computed tomography (HR-pQCT) imaging can lead to different bone volumes being assessed over time. To identify the same bone volumes at each time point, image registration is used. While crosssectional area image registration corrects axial misalignment, 3D registration additionally corrects rotations. Other registration methods involving matched angle analysis (MA) or boundary transformations (3D-TB) can be used to limit interpolation error in 3D-registering micro-finite-element data. We investigated the effect of different image registration methods on short-term in vivo precision in adults with osteogenesis imperfecta, a collagen-related genetic disorder resulting in low bone mass, impaired quality, and increased fragility. The radii and tibiae of 29 participants were imaged twice on the same day with full repositioning. We compared the precision error of different image registration methods for density, microstructural, and micro-finite-element outcomes with data stratified based on anatomical site, motion status, and scanner generation. Regardless of the stratification, we found that image registration improved precision for total and trabecular bone mineral densities, trabecular and cortical bone mineral contents, area measurements, trabecular bone volume fraction, separation, and heterogeneity, as well as cortical thickness and perimeter. 3D registration marginally outperformed cross-sectional area registration for some outcomes, such as trabecular bone volume fraction and separation. Similarly, precision of micro-finite-element outcomes was improved after image registration, with 3D-TB and MA methods providing greatest improvements. Our regression model confirmed the beneficial effect of image registration on HR-pQCT precision errors, whereas motion had a detrimental effect on precision even after image registration. Collectively, our results indicate that 3D registration is recommended for longitudinal HR-pQCT imaging in adults with osteogenesis imperfecta. Since our precision errors are similar to those of healthy adults, these results can likely be extended to other populations, although future studies are needed to confirm this.
High‐resolution peripheral quantitative computed tomography (HR‐pQCT) imaging, together with computational finite element analysis (FEA), offers an attractive, noninvasive tool to quantify bone strength development in pediatric studies. Evidence of annual changes and errors in repeated HR‐pQCT measures is limited, and time intervals required to reliably capture changes in children's bone strength or microarchitecture have not yet been defined. Our objectives were: (1) to quantify annual changes in bone strength and microarchitectural properties; (2) to define precision errors for pediatric bone strength outcomes; (3) to characterize annual changes in contrast to pediatric precision errors; and (4) to estimate monitoring time intervals (MTIs) required to reliably characterize bone development at the distal radius and tibia. We obtained distal radius (7% of ulnar length) and tibia (8%) bone properties using HR‐pQCT and FEA from 38 follow‐up study participants (21 girls) at baseline (mean age 10.6 years, SD 1.7 years) and after 1 year; and from 32 precision study participants (16 girls) at baseline (mean age 11.3 years, SD 1.6 years) and after 1 week. We characterized mean annual changes (paired t tests) contrasted to pediatric precision errors (CV%RMS) and estimated MTIs. Annual increases in bone strength, total area, cortical thickness, and density ranged between 3.0% and 25.3% and 2.4% and 15.6% at the distal radius and tibia, respectively. Precision errors for all bone strength outcomes were ≤6.8% and ≤5.1% at the distal radius and tibia, respectively, and appeared lower than annual gains in bone strength at both sites. Cortical porosity decreased 19.6% at the distal radius and 6.6% at the distal tibia; these changes exceeded respective precision errors, indicating cortical bone consolidation. MTIs ranged between 0.5 years and infinity at the distal radius and 0.5 and 5.9 years at the distal tibia. Estimated MTIs suggest that pediatric bone strength, cortical bone density, and porosity development can be reliably monitored with annual measurements. © 2019 American Society for Bone and Mineral Research.
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