Multisite longitudinal calibration of HR-pQCT scanners and precision in osteogenesis imperfecta

For high-resolution peripheral quantitative computed tomography (HR-pQCT) to be used in longitudinal multi-center studies to assess disease and treatment effects, data must be aggregated across multiple timepoints and scanners. This requires an understanding of the factors contributing to scanner precision, and multi-scanner cross-calibration procedures, especially for clinical populations with severe phenotypes, like osteogenesis imperfecta (OI).

To address this, we first evaluated single- and multi-center short- and long-term precision errors of standard HR-pQCT parameters. Two imaging phantoms were circulated among 13 sites (7 XtremeCT and 6 XtremeCT2) and scanned in triplicate at 3 timepoints/site. Additionally, duplicate in vivo radial and tibial scans were acquired in 29 individuals with OI. Secondly, we investigated subject- and scanner-related factors that contribute to precision errors using regression analysis. Thirdly, we proposed a reference site selection criterion for multisite cross-calibration and demonstrated the external validity of phantom-based calibrations.

Our results show excellent short-term single-site precision in both phantoms (CV % < 0.5%) and in density, microarchitecture and finite element parameters of OI participants (CV % = 0.75 to 1.2%). In vivo reproducibility significantly improved with (i) cross sectional area image registration versus no registration and (ii) scans with no motion artifacts. While reproducibility was similar across OI subtypes and anatomical sites, XtremeCT2 scanners achieved ~2.5% better precision than XtremeCT for trabecular parameters. Finally, we demonstrate that multisite longitudinal precision errors resulting from inconsistencies between scanners can be partially corrected through scanner cross-calibration.

This study is the first to assess long-term reproducibility and cross-calibration in a study using first and second generation HR-pQCT scanners. The results presented in this context provide timely guidelines for future use of this powerful clinical imaging modality in multi-center longitudinal clinical trials.