The use of near infrared spectroscopy (NIRS) to measure vascular haemodynamics in human bone tissue in vivo

Rationale: Poor cardiovascular health is associated with reduced bone strength and increased risk of fragility fracture. However, direct measurement of intraosseous vascular health is difficult due to the density and mineral content of bone. The aim of this PhD project was to investigate the feasibility of near infrared spectroscopy (NIRS) for the investigation of vascular haemodynamics in human bone in vivo. NIRS provides inexpensive, non-invasive, safe, and real time data on changes in oxygenated and deoxygenated haemoglobin concentration at superficial anatomical sites. NIRS utilises a source optode of near infrared (NIR) light and detector optode that obtains representative data of the interactions of NIR photons with tissue. Method: A systematic review was performed identifying the current existing applications of NIRS (and similar technologies) for measuring human bone tissue in vivo. This review informed the development of an arterial occlusion protocol for obtaining haemodynamic measurements of the proximal tibia and lateral calf, including assessment of the protocol’s reliability. For thirty-six participants, NIRS results were also compared to alternative tests of bone haemodynamics involving dynamic contrast enhanced MRI (DCE-MRI), and measures of general bone health based on dual x-ray absorptiometry testing and blood markers of bone metabolism. Results: This thesis presents novel data demonstrating NIRS can obtain acceptably reliable markers of haemodynamics at the proximal tibia in vivo, comparable with reliability assessments of alternative modalities measuring intraosseous haemodynamics, and the use of NIRS for measuring muscle. Novel associations have been demonstrated between haemodynamic markers measured with NIRS and DCE-MRI, giving confidence NIRS truly represents bone haemodynamics. Increased NIRS markers of oxygen extraction during occlusion, and greater post-ischaemic vascular response to occlusion, were both associated with greater bone mineral density. Conclusion: As a feasibility study, this PhD project has demonstrated the potential for NIRS to contribute to research around the potential pathophysiological role of vascular dysfunction within bone tissue, but also the limitations and need for further development of NIRS technology.