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Laser speckle contrast imaging (LSCI) combines an excellent spatial and temporal resolution, with excellent reproducibility in humans. Recently, high-resolution LSCI (LSCI-HR), coupled or not with oximetry, have been marketed. They are promising approaches to assess wound healing, especially in rodents. However, their reproducibility and performance against a reference technique remain unknown.Healthy skin perfusion was evaluated at day 0 and repeated at day 2, using LSCI-HR, high-resolution LSCI with oximetry by reflectance spectrometry (LSCI-OX), compared with laser Doppler imaging (LDI) as a reference. In a second experiment, cutaneous perfusion was measured daily during 8 days after wounding at two different sites. The reproducibility of haemoglobin oxygenation with LSCI-OX was also assessed in the two experiments. Reproducibility was expressed as within-subject coefficients of variation (CV, in %).The inter-day reproducibility of healthy skin perfusion was better when assessed with LSCI-HR and LSCI-OX, compared to LDI (CVs between 12 and 17% and between 26 and 29%, respectively). Inter-site reproducibility of perfusion during wound healing was also better with LSCI-HR compared to LDI (CV = 12% and 23%, respectively). Finally, we observed a good, positive correlation between perfusion measured with LDI and LSCI-HR on the periulcer area (average r = 0.77 ± 0.24).Recently developed high-resolution LSCI devices provide good reproducibility to assess healthy and wounded skin perfusion in mice. However, the reproducibility of haemoglobin oxygenation is poor.

Objective There is no consensual definition of significant peripheral arterial disease of the upper limbs. Patients with end-stage renal disease are usually explored with Doppler ultrasound, which seems insufficient to characterize and quantify the arterial disease in this anatomic site. Candidates for haemodialysis access tend to be increasingly older and have polyvascular disease, and a better assessment of the vascular status of their upper limbs with finger systolic blood pressure is necessary. Photoplethysmography is simple and currently used in practice, but laser Doppler flowmetry may be more sensitive for low values. Our objective is to investigate additional information in the digit assessment over the ultrasound assessment of the upper limbs of patients awaiting haemodialysis and compare digital pressure values taken by photoplethysmography and laser Doppler. Methods All included patients with end-stage renal disease scheduled for haemodialysis access received a prospective evaluation of their upper limbs with a clinical examination of the hands, an arterial upper limb Doppler ultrasound, and finger systolic blood pressure using photoplethysmography and laser Doppler flowmetry. Significant upper limb arterial disease was defined by a finger systolic blood pressure below 60 mm Hg or a finger brachial pressure index below 0.7. Results Twenty-four patients were included in the study. In all, 41.7% of patients (n = 10) had parietal calcifications to the antebrachial arteries on Doppler ultrasound, 8.3% of patients (n = 2) had bilateral finger systolic blood pressure values below 60 mm Hg with laser Doppler flowmetry (but not confirmed with photoplethysmography), and 16.6% of patients (n = 4) had a finger brachial pressure index below 0.7 on both laser Doppler flowmetry and photoplethysmography. While there was an agreement between these two methods, higher values were recorded with photoplethysmography. The Pearson coefficient was 0.493 for the median of basal digital pressures in absolute values and 0.489 for finger brachial pressure index (p Conclusion Our study confirms the need to evaluate significant upper limb arterial disease in patients with end-stage renal disease not only with Doppler ultrasound but also with an evaluation of the finger systolic blood pressure. The correlation of the finger systolic blood pressure values using laser Doppler flowmetry and photoplethysmography was poor, which was probably due to an overestimation of the pressures with photoplethysmography. Despite the absence of a gold standard, we suggest that Laser Doppler flowmetry should be used rather than photoplethysmography to better characterize significant peripheral arterial disease of the upper limbs in patients with end-stage renal disease, particularly before creation of a new haemodialysis access. Protocol Record on clinical trial 38RC19.285.

Recent technical developments enable skin fluorescence to be quantified in vivo in humans. The present study aimed at determining whether flow mediated skin fluorescence was reproducible, sensitive to changes within an individual, and if it could differ between patients with coronary artery disease and healthy volunteers.First, forearm flow mediated skin fluorescence recorded during and after brachial artery occlusion was assessed following successive forearm occlusion periods (1, 2, 3 and 5min) and expressed as ischemic and hyperemic responses (as % of baseline). Secondly, 3min flow mediated skin fluorescence was assessed before and after 10min local cooling to 15°C. In a third protocol, the inter-day reproducibility of ischemic and hyperemic responses to 3min occlusion was tested at an interval of 7days, and compared between healthy controls and patients with coronary artery disease (CAD).In the first protocol, we observed a time dependent increase in the ischemic and hyperemic responses to occlusion. Next, we observed a lower hyperemic response after local cooling (9.8±4.2 versus 17.8±2.5% respectively, P0.001), while in contrast, the ischemic response was higher and exhibited greater variability (23±15 versus 11.8±6.4%; P=0.028). In the third protocol, the inter-day reproducibility of flow mediated skin fluorescence for a 3min occlusion period was excellent. The ischemic response was significantly lower in CAD patients than in healthy controls (6.7±4.8% vs 14.7±6.8% respectively, P0.001). Similarly, the hyperemic response was significantly decreased in the CAD group compared to healthy controls (11.6±3.6% vs 19.5±5.4% respectively, P0.001).We show that quantifying the ischemic and hyperemic flow mediated skin fluorescence is feasible, reproducible, sensitive to acute changes in skin blood flow, and distinguishes patients populations. However, more data are needed to evaluate the correlation with other methods or specific biochemical endothelial markers.

Objective In the present study we aimed to assess the reproducibility of skin microvascular reactivity while fast cooling locally with a custom-designed laser-Doppler flowmetry (LDF) probe. Methods Twenty-two healthy volunteers underwent local 15 °C cooling on the forearm during 5 (protocol 1, n = 12) or 30 min (protocol 2, n = 10). Skin blood flow was concomitantly assessed using LDF. Measurements were repeated after 30 min (protocol 1) or 7 days (protocols 1 and 2). Data were expressed as cutaneous vascular conductance (CVC) and percentage of baseline (%BL). Within subject coefficients of variation (CV) and intra-class correlation coefficients (ICC) were calculated. Results Immediate reproducibility of the 5-min cooling was very good, either expressed as CVC or %BL (CV were 8% and 18%; ICC were 0.85 and 0.78, respectively). However, the 30-min cooling was the most reproducible at 1 week, either as CVC or %BL (CV were 26% and 23%; ICC were 0.86 and 0.75, respectively). Local cooling was well tolerated by all volunteers. Conclusions We propose in the present work a reproducible 30-min LDF cooling test. Such a tool could be of great interest to assess microvascular reactivity to local cooling in diseases such as Raynaud's syndrome, and to further evaluate drugs for such diseases.

Objective Sodium nitroprusside (SNP) iontophoresis is a commonly used technique to assess non endothelium-dependent skin microvascular function in the forearm. However, the lack of data on the finger pad is a limitation when studying diseases affecting the digits (e.g. systemic sclerosis, SSc). We thus aimed to validate this technique in the finger pad compared to the forearm in SSc patients and healthy controls. Methods Six SSc patients and six controls were recruited. SNP and NaCl iontophoresis were performed on the finger pad and the forearm, with and without lidocaine/prilocaine. Cutaneous blood flow was simultaneously monitored using laser Doppler flowmetry. Results In all subjects, iontophoresis of SNP induced hyperemia in the forearm, which was not affected by pretreatment with lidocaine/prilocaine. In contrast, no increase in cutaneous vascular conductance was observed in the finger pad in any subject (apart from one patient with SSc). Conclusions The iontophoresis of SNP leads to a consistent, non axon reflex-dependent, increase in cutaneous vascular conductance in the forearm, both in patients with SSc and in healthy controls. On the finger pad however, such hyperemia was not consistent. As a consequence, other tools should be considered to assess non endothelium-dependent skin microvascular function in the finger pad.

One of the most important skin complications in systemic sclerosis (SSc) is digital ulceration. Local thermal hyperemia (LTH) in the skin is a biphasic response to local heating involving both neurovascular and endothelial responses. Since LTH is abnormal in SSc patients, we aimed at testing whether LTH could be a prognostic tool for the onset of digital ulcers.We prospectively enrolled 51 patients with SSc. Nailfold capillaroscopy and LTH were recorded at baseline, and patients were followed for 3 years.No patient with a LTH peak/plateau ratio ≥1 (n=19) developed digital ulcerations during the 3 year follow-up (100% negative predictive value), while 6 out of 32 patients with a LTH peak/plateau ratio1 at enrolment presented with finger pad ulcerations within 3 years (p=0.05). In contrast, when lidocaine/prilocaine was applied to the finger pad, no relationship between thermal hyperemia and digital ulcerations was observed.A LTH peak/plateau ratio on the finger pad greater than 1, which can easily be determined in routine clinical practice, could be used to reassure patients, whatever the subtype of SSc, about the low probability of future digital ulceration. However, the prognostic value of this parameter should be confirmed in a larger cohort.

Objectives Elderly patients are susceptible to skin ulcerations on the supramedial malleolar area of the leg. Our aim was, using local thermal hyperemia, to study microvascular function on the gaiter skin area of elderly, but otherwise healthy volunteers, because abnormal microvascular reactivity could contribute to ulcerations in this region. Methods Two groups of healthy volunteers were enrolled according to age, including 20 subjects aged from 18 to 30 years (young group) and 42 subjects aged from 60 to 86 years (older group). Local thermal hyperemia to 43 °C was performed for 1 h using heating circular probes and skin blood flow was recorded using Laser Doppler Imaging, with or without 2 h lidocaine/prilocaine cream application. Sodium nitroprusside iontophoresis was also performed. Results The initial local thermal hyperemia peak was lower in the older group (14.7 mV/mm Hg ± 6.9) compared to the young group (19.9 ± 7.2, P = 0.009). Lidocaine/prilocaine cream decreased the initial local thermal hyperemia peak and the late plateau for all groups. The local thermal hyperemia plateau and sodium nitroprusside iontophoresis corrected for skin resistance did not differ between older and younger subjects. Conclusions Physiological aging is associated with an altered initial axon reflex response to local heating in the supramedial malleolar skin. Further work is required to determine whether these changes are more pronounced in frail and dependent groups and whether they could explain the higher incidence of skin ulcerations in the supramedial malleolar skin associated with venous insufficiency and neuropathy.

Objective Laser Speckle Contrast Imaging (LSCI) can be used to assess real-time responses of skin microcirculation to pharmacological interventions. The main objective of this study was to determine whether intradermal or subdermal microdialysis fiber insertion, coupled with skin flux recording using LSCI, can be used to assess baseline cutaneous flux and the post-occlusive reactive hyperemic response. The microdialysis sites were compared to control area without microdialysis fibers. Methods One dermal and two subdermal microdialysis fibers were randomly inserted in the right forearm skin of six healthy volunteers. We performed consecutively tests of post-occlusive hyperemia, infusion of 29 mM sodium nitroprusside (SNP), local thermal hyperemia at 43 °C and a second 29 mM SNP infusion at the end of the experiment. Results Two hours after fiber insertion, cutaneous vascular conductances (CVC) at the subdermal fiber sites were not different from their respective control regions of interest, while at the dermal site CVC remained higher (0.48 +/− 0.15 versus 0.37 +/− 0.1 PU.mm Hg −1 , P = 0.003). The peak CVC and area under the curve observed during post-occlusive reactive hyperemia were similar at all fiber sites and their respective controls. We observed a similar increase in CVC using 29 mM SNP infusion, 40 min local heating at 43 °C, and their combination. Finally, physiological and pharmacological responses of the subdermal sites were reproducible in terms of amplitude, whether expressed as raw CVC or as %CVCmax. Conclusions We showed that studying skin microvascular physiological or pharmacological responses using inserted subdermal microdialysis fibers coupled with LSCI is feasible and reproducible, and provides two-dimensional information. This technique will be useful for future mechanistic studies of skin microcirculation.

Objective We tested the linearity between skin blood flux recorded with laser speckle contrast imaging (LSCI) and laser Doppler imaging (LDI), comparing different ways of expressing data. A secondary objective was to test within-subject variability of baseline flux with the two techniques. Methods We performed local heating at 36, 39, 42, and 44 °C on the forearm of healthy volunteers, and measured cutaneous blood flux with LDI and LSCI. Biological zero (BZ) was obtained by occluding the brachial artery. We expressed data as raw arbitrary perfusion units (APUs) and as a percentage increase from baseline (%BL), with and without subtracting BZ. Inter-site variability was expressed as a within subject coefficient of variation (CV). Results Twelve participants were enrolled. Inter-site variability at baseline was lower with LSCI (CV = 9.2%) than with LDI (CV = 20.7%). We observed an excellent correlation between both techniques when data were expressed as raw APUs or APU − BZ (R = 0.90; p R = 0.77, p R = 0.44, p = 0.003). Bland–Altman plots revealed a major proportional bias between the two techniques. Conclusion This study suggests that skin blood flux measured with LSCI is linearly related to the LDI signal over a wide range of perfusion. Subtracting BZ does not affect this linearity but introduces variability in baseline flux, thus decreasing the correlation when data are expressed as a function of baseline. Finally, systematic bias makes it impossible to assimilate arbitrary perfusion units provided by the two systems.

article i nfo Objective: We compared the inter-day reproducibility of post-occlusive reactive hyperemia (PORH) assessed by single-point laser Doppler flowmetry (LDF) and laser speckle contrast analysis (LSCI), and the reproducibility of local thermal hyperemia (LTH) assessed by LDF, laser Doppler imaging (LDI) and LSCI. We also tested whether skin blood flow assessment by LDF and by LSCI are correlated. Methods: Skin blood flow was evaluated during PORH and LTH using LDF, LDI (for LTH only) and LSCI on the forearms of healthy volunteers, at a 7 day interval. Data are expressed as cutaneous vascular conductance (CVC), as a function of baseline and scaled to the thermal plateau. Reproducibility is expressed as within subject coefficients of variation (CV, in %) and intra-class correlation coefficients (ICC). Results: Twenty-eight healthy participants were enrolled in this study. The reproducibility of the PORH peak CVC was better when assessed with LSCI compared to LDF (CV=8%; ICC=0.76 and CV=30%; ICC=0.54, respectively). Inter-day reproducibility of the LTH plateau was better when assessed with LSCI or LDI than LDF (CV=15%, ICC=0.66; CV=17%, ICC=0.51 and CV=42%, ICC=0.28 respectively). Finally, we observed significant correlation between simultaneous LDF and LSCI measurements of the PORH peak CVC (R=0.54; p=0.001). Conclusion: The recently developed LSCI technique showed very good inter-day reproducibility for assessing PORH and LTH. Moreover, we showed significant correlation between LSCI and single-point LDF for PORH. However, more data are needed to evaluate the linearity between the LSCI signal and skin blood flow.

Objective The primary objective of this study was to evaluate 1-week reproducibility of post-occlusive reactive hyperemia (PORH) and local thermal hyperemia (LTH) assessed by single-point laser-Doppler flowmetry (LDF) on different skin sites. We also evaluated spatial reproducibility of both tests on the forearm. Finally, we assessed the influence of mental stress and room temperature variations on PORH and LTH. Methods We performed PORH and LTH assessing skin blood flow on the forearm and on the finger pad with LDF. We repeated the sequence 1 week later. We also performed PORH and LTH during mental stress (Stroop test) and at room temperatures of 21 °C and 27 °C. Data were expressed as cutaneous vascular conductance (CVC), as a function of baseline and as a function of 44 °C vasodilation (%CVC 44 ). Reproducibility was expressed as within subject coefficients of variation (CV) and intra-class correlation coefficients (ICC). Results Fourteen Caucasian healthy volunteers were recruited. Median age was 25 (2.7) and 50% were female. Median body mass index was 21.2 (5). PORH was reproducible on the finger, whether expressed as raw CVC (CV = 25%; ICC = 0.56) or as %CVC 44 (CV = 24%; ICC = 0.60). However, PORH showed poor reproducibility on the forearm. In the same way, LTH was reproducible on the finger pad when expressed as CVC (CV = 17%; ICC = 0.81) but not on the forearm. Spatial reproducibility was poor on the forearm. Elevated room temperature (27 °C) affected PORH and LTH on the finger pad ( p Conclusion Single-point LDF is a reproducible technique to assess PORH and LTH on the finger pad when data are expressed as raw CVC or %CVC 44 . On the forearm, however, it shows great inter-day variability, probably due to spatial variability of capillary density. These results highlight the need for alternative techniques on the forearm.