Validation of HR-pQCT against micro-CT for morphometric and biomechanical analyses: A review

High-resolution peripheral quantitative computed-tomography (HR-pQCT) has the potential to become a powerful clinical assessment and diagnostic tool. Given the recent improvements in image resolution, from 82 to 61 μm, this technology may be used to accurately quantify in vivo bone microarchitecture, a key biomarker of degenerative bone diseases. However, computational methods to assess bone microarchitecture were developed for micro computed tomography (micro-CT), a higher-resolution technology only available for ex vivo studies, and validation of these computational analysis techniques against the gold-standard micro-CT has been inconsistent and incomplete. Herein, we review methods for segmentation of bone compartments and microstructure, quantification of bone morphology, and estimation of mechanical strength using finite-element analysis, highlighting the need throughout for improved standardization across the field. Studies have relied on homogenous datasets for validation, which does not allow for robust comparisons between methods. Consequently, the adaptation and validation of novel segmentation approaches has been slow to non-existent, with most studies still using the manufacturer's segmentation for morphometric analysis despite the existence of better performing alternative approaches. The promising accuracy of HR-pQCT for capturing morphometric indices is overshadowed by considerable variability in outcomes between studies. For finite element analysis (FEA) methods, the use of disparate material models and FEA tools has led to a fragmented ability to assess mechanical bone strength with HR-pQCT. Further, the scarcity of studies comparing 62 μm HR-pQCT to the gold standard micro-CT leaves the validation of this imaging modality incomplete. This review revealed that without standardization, the capabilities of HR-pQCT cannot be adequately assessed. The need for a public, extendable, heterogeneous dataset of HR-pQCT and corresponding gold-standard micro-CT images, which would allow HR-pQCT users to benchmark existing and novel methods and select optimal methods depending on the scientific question and data at hand, is now evident. With more recent advancements in HR-pQCT, the community must learn from its past and provide properly validated technologies to ensure that HR-pQCT can truly provide value in patient diagnosis and care.