Full Field Laser Perfusion Imaging and Post Occlusive Reactive Hyperaemia in the Skin Microcirculation: A Biomarker of Cardiovascular Disease Risk?
The full field laser perfusion imager (FLPI) is a new, non-invasive device which can measure dynamic changes in blood flow of the skin microcirculation. Endothelial dysfunction is the earliest detectable functional indicator of cardiovascular disease (CVD), contributing to the development of atherosclerosis. Assessment of endothelial function provides a powerful method to identify patients at risk of developing CVD before the appearance of clinical symptoms. FLPI in combination with post occlusive reactive hyperaemia (PORH) has the potential to become an important tool for the assessment of skin microvascular function and dysfunction. The aims of this project were to firstly develop a test of PORH (following 5 minutes of arterial occlusion) using FLPI and secondly to compare this test with the EndoPAT device, the only food and drug administration (FDA) validated assessment. FLPI was used to assess the reproducibility of changes in forearm skin blood flow following PORH using different protocols to find the optimal settings for repeated measures (cuff position, measurement site and skin temperature). The most reproducible PORH results were found with an upper arm blood pressure cuff and a distal measurement site at the forearm. An upper arm cuff and a proximal measurement site at the forearm was second and a lower arm cuff and a distal measurement site the least reproducible (Variance n=10: 8%; n=10 17%; n=5 31%, respectively). Skin heating was introduced to the PORH protocol to see how this affected the reproducibility of the test. Forearm skin heating to 35°C prior to and during PORH did not improve reproducibility of the test (n=10; Variance 41% vs. 8% without heating). The results from the developmental phase of the study indicate that the most reproducible method of PORH to use with FLPI is with an upper arm blood pressure cuff and a distal measurement site without heating of the forearm skin. The most reproducible PORH protocol was then applied to two groups of healthy volunteers (G1 n=15: 18-30 years; G2 n=15: 40-70 years) to investigate the effect of age on endothelial function and to compare with the EndoPAT device, an alternative method of endothelial function assessment. No significant differences were noted between G1 and G2 for the PORH response measured by FLPI (G1 228±74% vs. G2 230±86%) however a significant negative correlation was found between PORH response and age in G2 (r=-0.599; p<0.05). Significant differences in endothelial function were observed between G1 and G2 by EndoPAT (G1 2.68±0.6units vs. G2 2.28±0.6units, p<0.05). The PORH test also detected significant differences between males and females (M 202.1±63.5% vs. F 256.9±85.8%, p<0.05), across all study volunteers, which were undetected by EndoPAT. PORH coupled with FLPI has the potential to become a useful biomarker of skin microvascular endothelial function. FLPI was able to detect changes in endothelial function between males and females and within an older healthy population. Further work is needed to evaluate this method in patients with varying levels of disease.
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