Upscaling ofIn VivoHR-pQCT Images Enables Accurate Simulations of Human Microstructural Bone Adaptation

In silicotrials of treatments in a virtual physiological human (VPH) would revolutionize research in the biomedical field. Hallmarks of bone disease and treatments can already be simulated in pre-clinical models and inex vivodata of humans using microstructural bone adaptation simulations. The increasing availability ofin vivohigh resolution peripheral quantitative computed tomography (HR-pQCT) images provides novel opportunities to validate and ultimately utilize microstructural bone adaptation simulations to improve our understanding of bone diseases and move towardsin silicoVPH decision support systems for clinicians.In the present study, we investigated if microstructural bone adaptation simulations ofin vivohuman HR-pQCT images yielded accurate results. Since high-resolution ground truth images cannot be obtainedin vivo, we applied anex vivoapproach to study resolution dependence and the effect of upscaling on morphometric accuracy. To address simulation initialisation issues, we developed an input regularisation approach to reduce initialisation shocks observed in microstructural bone adaptation simulations and evaluated upscaling as a way to improve the accuracy of model inputs. Finally, we compared ourex vivoresults to simulations run onin vivoimages to investigate whetherin vivoimage artefacts further affect simulation outcomes.