4-D nanoSCOPE · Advancing osteoporosis medicine by observing bone microstructure and remodelling using a four-dimensional nanoscope

Due to Europe's ageing society, there has been a dramatic increase in the occurrence of osteoporosis (OP) and related diseases. Sufferers have an impaired quality of life, and there is a considerable cost to society associated with the consequent loss of productivity and injuries. The current understanding of this disease needs to be revolutionized, but study has been hampered by a lack of means to properly characterize bone structure, remodeling dynamics and vascular activity. This project, 4D nanoSCOPE, will develop tools and techniques to permit time-resolved imaging and characterization of bone in three spatial dimensions (both in vitro and in vivo), thereby permitting monitoring of bone remodeling and revolutionizing the understanding of bone morphology and its function.To advance the field, in vivo high-resolution studies of living bone are essential, but existing techniques are not capable of this. By combining state-of-the art image processing software with innovative 'precision learning' software methods to compensate for artefacts (due e.g. to the subject breathing or twitching), and innovative X-ray microscope hardware which together will greatly speed up image acquisition (aim is a factor of 100), the project will enable in vivo X-ray microscopy studies of small animals (mice) for the first time. The time series of three-dimensional X-ray images will be complemented by correlative microscopy and spectroscopy techniques (with new software) to thoroughly characterize (serial) bone sections ex vivo.The resulting three-dimensional datasets combining structure, chemical composition, transport velocities and local strength will be used by the PIs and international collaborators to study the dynamics of bone microstructure. This will be the first time that this has been possible in living creatures, enabling an assessment of the effects on bone of age, hormones, inflammation and treatment.