Understanding the rules of life

Bioscience for an integrated understanding of health

Category: CASE Studentships

Combining high‐resolution 3D imaging of bone microstructure with single‐photon emission computerised tomography (SPECT) to assess bone vascular metabolism with age

Primary Supervisor

Dr Claire Clarkin – University of Southampton

Co-Supervisor(s)

Dr Philipp Schneider – University of Southampton
Dr Philip Marsden – Unitive Design and Analysis

Summary

Today, the role of the vasculature in skeletal ageing remains poorly understood as the calcified nature of skeletal tissue has made it challenging to visualise the blood vessels and how they may become altered in disease.

For study of the bone vasculature high‐resolution X‐ray computed tomography (CT) has been invaluable to our group for visualising the intracortical micro‐porosity including blood vessel canals. However, interpretation of these canals has been somewhat limited as X‐ray CT does not reveal the soft tissue vasculature within the calcified bone matrix. Also, the use of X‐ray contrast agents can result in disjointed vascular components in the CT data sets. A less invasive and accessible imaging method is still to be found for elucidation of intracortical bone vascular function. New imaging techniques based on ionising radiation are available for medical diagnosis and research purposes, which may provide a solution here. These include Positron Emission Tomography
(PET) or Single Photon Emission CT (SPECT), which are non‐destructive, non‐invasive 3D imaging techniques that can image through the mineralised bone tissue.

It has been reported that circulating pro‐angiogenic vascular endothelial growth factor (VEGF) levels are linked to bone loss with age. Using a transgenic model we have found that genetic deletion of VEGF resulted in severely porous bone in vivo which is more severe in males. These findings reveal that regulation of the bone vasculature appears sexually dimorphic and reduced VEGF with age may impact male and female bone quality differently.

The aim of this PhD is to better interrogate the bone vascular phenotype in both sexes using this ageing mouse model and developing dual imaging techniques combining SPECT imaging (Phil Marsden, Unitive Design and Analysis) with μCT (University of Southampton), to address this question and determine ex vivo measurements of bone vascular function and metabolism.