Investigating non-invasive laser imaging and oxidative biomarkers as an indicator of microvascular function in peripheral artery disease

Endothelial dysfunction is prevalent in obese and elderly individual and in patients who have diabetes. It is a major contributor to peripheral artery disease (PAD) which is characterised by impaired blood flow in peripheral tissues.  In the most severe form, PAD leads to critical limb ischaemia (CLI), where impaired blood flow results in a reduction in oxygenation and nutrition of peripheral tissues results in claudication or resting pain, ulcers, gangrene and in the worst-case scenario, amputation.  The current diagnosis of critical limb ischaemia uses limb pressure in combination with a clinical observation such as resting pain, foot ulcer or gangrene. Diabetes-induced neuropathy exacerbates CLI as the lack of sensation masks one of the key diagnostic factors, resting pain.  In cases of ulcers and gangrene transcutaneous tissue oxygenation (TcPO2) is used to identify the potential of healing in patients with diabetes. Endothelial function can be assessed non-invasively using a Laser Doppler technique measuring dermal microcirculation and may be an earlier predictor of severity.  Yet, currently, the technology is not readily used to assist clinical decisions made in surgery, largely because the technology has employed single point measurements that lack spatial resolution or laser imaging which can lack temporal resolution.  A new technique allows simultaneous measurement of perfusion and oxygenation (pO2) in real time (moorO2Flo).   

The overall aim of this project is to explore the feasibility of use of laser Doppler/laser Speckle contrast imaging to aid clinical assessment and limb viability in patients with critical limb ischaemia and link with biomarkers of inflammation and oxidative stress. 

Project will validate cutting edge laser technology to assess if dermal microvascular function can provide improved clinical information pre or post operation.  Determine whether Laser imaging of microvascular function can influence intra-op decisions for successful vascular/endovascular reconstruction.  Link clinical assessment with biomarkers of plasma endothelial function including inflammation (interleukins), oxidative stress (Nox, Nrf2), endothelial activation (endothelin-1) and endothelial dysfunction (eNOS).

This translational project will enable the student to conduct imaging and thermal flare assessment in humans, investigate molecular biomarkers, and validate technology for new clinical practice.