This PhD project offers a unique interdisciplinary life sciences experience at the interface of medicine, biomedical imaging and computational engineering, with the aim to better understand life influences on bone quality in children and tweenagers. You will work closely together with colleagues across Bioengineering in the Faculty of Engineering and Physical Sciences (https://www.feps.soton.ac.uk), μ-VIS X-ray Imaging Centre (www.muvis.org) and the MRC Lifecourse Epidemiology Unit (LEU) (www.mrc.soton.ac.uk) in Southampton.
Risk of osteoporosis, a condition in older age which leads to broken bones with minimal trauma, starts to accrue from before birth. Maternal factors during pregnancy such as vitamin D insufficiency are associated with reduced offspring bone mineral density (BMD), which is assessed by 2D dual-energy X-ray absorptiometry (DXA), which is often blind to the deteriorated 3D bone structure, which can lead to decreased bone strength and increased fracture risk. New high-resolution peripheral quantitative computed tomography (HRpQCT) permit a step change in non-invasive in vivo 3D bone assessment capability.
Such image-based 3D bone structural measures from HRpQCT have been shown to predict incident fractures in adulthood, independently of the standard BMD measures from clinical 2D DXA, while the relevant 3D bone structural determinants in childhood are unknown. At the MRC LEU at University Hospital Southampton HRpQCT scans are being undertaken on children at 6-8 years old who were born into the MAVIDOS trial (https://www.mrc.soton.ac.uk/web2/cohorts/mavidos-maternal-vitamin-d-osteoporosis-study). BMD assessment using DXA has suggested a positive effect on offspring bone mass. HRpQCT scans, at 11-13 years old, are also being undertaken on children born to the Southampton Women’s Survey (www.mrc.soton.ac.uk/sws).
The student will first investigate in MAVIDOS whether and to what extent maternal vitamin D supplementation in pregnancy leads to altered bone quality, and thus to decreased bone strength in the offspring. Secondly, in the Southampton Women’s Survey, the student will study associations between exposure to maternal and postnatal diet, growth, puberty, and bone quality and strength at 11-13 years. The study aims are:
- Implement standardised and (semi-)automated workflow for HRpQCT data for (i) segmentation and (ii) quantification of bone structure
- Establish fully automated finite element analysis (FEA) framework for HRpQCT data.
- Visualise and analyse the link between bone structure/material properties and bone mechanics.
- Investigate links between maternal vitamin D supplementation and offspring bone microarchitecture and strength, with further analysis of effect modifiers such as key genetic loci and maternal/childhood environmental exposures.
The findings from this interdisciplinary project will yield novel information on the effect of intrauterine vitamin D exposure on the subsequent development of bone quality and biomechanical strength. Analysis of genetic and environmental effect modifiers will allow approaches to be stratified to individuals. The project findings will thus directly inform population approaches to pregnancy and early childhood health.
An undergraduate degree (minimum UK 2:1 honours degree).