Non-Invasive Measurement of Skin Microvascular Response during Pharmacological and Physiological Provocations

Abstract

Introduction: Microvascular changes in the skin due to pharmacological and physiological provocations can be used as a marker for vascular function. While laser Doppler flowmetry (LDF) has been used extensively for measurement of skin microvascular responses, Laser Speckle Contrast Imaging (LSCI) and Tissue Viability Imaging (TiVi) are novel imaging techniques. TiVi measures red blood cell concentration, while LDF and LSCI measure perfusion. Therefore, the aim of this study was to compare responses to provocations in the skin using these different techniques.

Method: Changes in skin microcirculation were measured in healthy subjects during (1) iontophoresis of sodium nitroprusside (SNP) and noradrenaline (NA), (2) local heating and (3) post-occlusive reactive hyperemia (PORH) using LDF, LSCI and TiVi.

Results: Iontophoresis of SNP increased perfusion (LSCI: baseline 40.9±6.2 PU; 10-min 100±25 PU; p<0.001) and RBC concentration (TiVi: baseline 119±18; 10-min 150±41 AU; p = 0.011). No change in perfusion (LSCI) was observed after iontophoresis of NA (baseline 38.0±4.4 PU; 10-min 38.9±5.0 PU; p = 0.64), while RBC concentration decreased (TiVi: baseline 59.6±11.8 AU; 10-min 54.4±13.3 AU; p = 0.021). Local heating increased perfusion (LDF: baseline 8.8±3.6 PU; max 112±55 PU; p<0.001, LSCI: baseline 50.8±8.0 PU; max 151±22 PU; p<0.001) and RBC concentration (TiVi: baseline 49.2±32.9 AU; max 99.3±28.3 AU; p<0.001). After 5 minutes of forearm occlusion with prior exsanguination, a decrease was seen in perfusion (LDF: p = 0.027; LSCI: p<0.001) and in RBC concentration (p = 0.045). Only LSCI showed a significant decrease in perfusion after 5 minutes of occlusion without prior exsanguination (p<0.001). Coefficients of variation were lower for LSCI and TiVi compared to LDF for most responses.

Conclusion: LSCI is more sensitive than TiVi for measuring microvascular changes during SNP-induced vasodilatation and forearm occlusion. TiVi is more sensitive to noradrenaline-induced vasoconstriction. LSCI and TiVi show lower inter-subject variability than LDF. These findings are important to consider when choosing measurement techniques for studying skin microvascular responses.

Conflict of interest statement

Competing Interests: FS has a role in the commercialization of the polarisation spectroscopy instrumentation. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Schematic diagram of the experimental setup.

The different skin sites used for measurement of microvascular responses to pharmacological and physiological provocations (see Table 2).

Fig 2. Iontophoresis of sodium nitroprusside and noradrenaline.

Skin microvascular response during iontophoresis of sodium nitroprusside (SNP) and noradrenaline (NA) as measured using laser Doppler flowmetry (LDF), Laser Speckle Contrast Imaging (LSCI) and Tissue Viability Imaging (TiVi). *** indicates significant change from baseline (p

Fig 3. Local heating.

Skin microvascular responses to 40 minutes of local heating as measured using laser Doppler flowmetry (LDF), Laser Speckle Contrast Imaging (LSCI) and Tissue Viability Imaging (TiVi). *** indicates significant change from baseline (p

Fig 4. Post-occlusive reactive hyperemia.

Skin microvascular responses to (I) occlusion with prior exsanguination, (II) PORH, (III) occlusion without prior exsanguination, (IV) PORH as measured using laser Doppler flowmetry (LDF), Laser Speckle Contrast Imaging (LSCI) and Tissue Viability Imaging (TiVi). * indicates significant change from baseline, p