Measurement Of Cutaneous Blood Flow Research Articles

David O. Warner, M.D., Recipient of the 2022 Excellence in Research Award

David O. Warner, M.D., Recipient of the 2022 Excellence in Research Award

Effects of insulin analogs as an add-on to metformin on cutaneous microcirculation in type 2 diabetic patients

BackgroundA single insulin injection was shown to improve microcirculatory blood flow. Our aim was to examine the effects of 4weeks of insulin therapy by three randomly assigned insulin analog regimens (Detemir, Aspart, and their combination) on cutaneous blood flow (CBF) and microcirculatory endothelial function as an add-on to metformin in type 2 diabetic patients poorly controlled on oral antidiabetic treatment. MethodsFourty-two type 2 diabetic patients with no history of cardiovascular disease in secondary failure to oral antidiabetic agents had CBF measurements before and after acetylcholine (Ach) iontophoretic administration. CBF measurements were performed at fasting and after a standardized breakfast during the post-prandial period. Before randomization (Visit 1, V1) during the tests, participants took only metformin. The same tests were repeated after 4weeks of insulin treatment (Visit 2, V2). ResultsThirty-four patients had good quality recordings for both visits. During V1, CBF and CBF response to Ach increased in the post-prandial period. After 4weeks of insulin treatment, metabolic parameters improved. Compared to V1, CBF at fasting did not increase at V2 but there was an improvement in endothelial function at fasting after Ach iontophoresis, without difference across insulin regimens. Oxidative stress markers were not modified, and E-selectin and vascular cell adhesion molecule 1 levels decreased after insulin treatment, without differences between insulin groups. ConclusionsA strategy of improving glycemic control for 4weeks with insulin analogs improves microcirculatory endothelial reactivity and reduces endothelial biomarkers at fasting, whatever the insulin regimen used. Insulin therapy associated to metformin is able to improve fasting microvascular endothelial function even before complete metabolic control.

The measurement of cutaneous blood flow in healthy volunteers subjected to physical exercise with ultrasound Doppler imaging and laser Doppler flowmetry.

We aimed to evaluate hemodynamic parameters in the cutaneous microcirculation during recovery to graded dynamic exercise performed on a cycloergometer by using two distinctive methods: high-frequency ultrasound Doppler flowmetry (UDF) and laser Doppler fluxmetry (LDF). Regarding UDF, the medium linear blood flow velocity (Vam) was estimated, expressed in absolute units (cm/s) whereas blood flow assessed by LDF was registered in arbitrary perfusion units (PU). We compared the corresponding perfusion values obtained by UDF and LDF, respectively, every 20 s during recovery period to physical exercise. Three types of microvascular blood flow dynamics were recorded: blood flow with an occasional paroxysm, a pulsatile blood flow pattern, and a shunting-type blood flow pattern. In the first type, the reaction time of registration and the direction of changes of UDF and LDF values coincided in 77.7%, exhibiting high correlation (r = 0.77; p≤0.001). In the second type, the direction of changes of UDF and LDF showed 85.0% similarity and a moderate correlation (r = 0.66; p = 0.0015), whereas in the third type, there was also a moderate correlation (r = 0.53, p = 0.0024). Our pilot experiments have shown that UDF could be regarded as a comparable substitutional method to LDF for studying skin microcirculation.

RTOG, CTCAE and WHO criteria for acute radiation dermatitis correlate with cutaneous blood flow measurements

BackgroundVarious clinician-assessed scoring criteria have been used to grade acute radiation dermatitis. However, it is not known whether these scoring criteria correlate with changes in objective skin biophysical parameters and patient-reported symptoms following radiotherapy. We seek to correlate three different clinician-assessed scoring criteria with skin biophysical changes and patient-reported symptoms in breast cancer patients undergoing radiotherapy. MethodsA prospective cohort study was performed in a university hospital medical center. The severity of acute radiation dermatitis in 101 breast cancer patients was graded using the RTOG, CTCAE and WHO clinical scoring criteria. We also measured various skin biophysical parameters (skin blood flow, pigmentation, hydration, and pH) by non-invasive techniques before and after radiotherapy. Patient-reported breast symptoms (pain, itching, local heat, and tightness) were evaluated using a questionnaire. ResultsThe three different clinician-assessed scoring criteria correlated most strongly with changes in cutaneous blood flow following radiotherapy for breast cancer (correlation coefficient 0.70 for RTOG, 0.68 for CTCAE, and 0.50 for WHO). All three scoring criteria also showed moderate correlation with changes in skin pigmentation (correlation coefficients 0.4–0.5), but showed no significant correlation with skin hydration or pH (correlation coefficients <0.2). The scoring criteria correlated poorly with patient-reported breast symptoms (correlation coefficients <0.3). ConclusionsThe three clinician-assessed scoring criteria (especially the RTOG and CTCAE criteria) show strong correlation with cutaneous blood flow measurements, but correlate less well with other skin biophysical parameters and patient-reported symptoms.

Assessment of Skin Microvascular Function and Dysfunction With Laser Speckle Contrast Imaging

In recent years, skin microcirculation has been considered an easily accessible and potentially representative vascular bed to evaluate and understand the mechanisms of microvascular function and dysfunction.1–3 Vascular dysfunction (including impaired endothelium-dependent vasodilation) induced by different pathologies is evident in the cutaneous circulation.4–7 It has been suggested that the skin microcirculation may mirror generalized systemic vascular dysfunction in magnitude and underlying mechanisms.1 Furthermore, minimally invasive skin-specific methodologies using laser systems make the cutaneous circulation a useful translational model for investigating mechanisms of skin physiology and skin pathophysiology induced either by skin disease itself or by other diseases such as vascular, rheumatologic, and pneumologic. To date, the skin has been used as a circulation model to investigate vascular mechanisms in a variety of diseased states, including hypercholesterolemia,8 Alzheimer disease,9 carpal tunnel syndrome,10 schizophrenia,11 hypertension,6 renal disease,12 type 2 diabetes,13 peripheral vascular disease,14 atherosclerotic coronary artery disease,2 heart failure,15 systemic sclerosis,16 obesity,17 primary aging,18,19 and sleep apnea.20 Assessment of skin microvascular function can be done by both invasive and noninvasive techniques. Among noninvasive techniques, laser systems are mainly used.21 The recent development of the laser speckle contrast imaging (LSCI) technique for monitoring skin microvascular function enables its use as a surrogate end point in clinical trials. LSCI allows for noncontact, real-time, and noninvasive monitoring of cutaneous blood flow changes.22,23 Recent evidence has shown that the LSCI technique dramatically reduces the variability of clinical measurements compared with laser Doppler flowmetry (LDF), making the technique a fascinating tool to facilitate microvascular studies in clinical routine.23,24 In this review, we describe …

Increasing the “region of interest” and “time of interest”, both reduce the variability of blood flow measurements using laser speckle contrast imaging

Objective Both spatial variability and temporal variability of skin blood flow are high. Laser speckle contrast imagers (LSCI) allow non-contact, real-time recording of cutaneous blood flow on large skin surfaces. Thereafter, the observer can define different sizes for the region of interest (ROI) in the images to decrease spatial variability and different durations over which the blood flow values are averaged (time of interest, TOI) to decrease temporal variability. We aimed to evaluate the impact of the choices of ROI and TOI on the analysis of rest blood flow and post occlusive reactive hyperemia (PORH). Methods Cutaneous blood flow (CBF) was assessed at rest and during PORH. Three different sizes of ROI (1 mm 2, 10 mm 2 and 100 mm 2), and three different TOI (CBF averaged over 1 s, 15 s, and 30 s for rest, and over 1 s, 5 s and 10 s for PORH peak) were evaluated. Inter-subjects and intra-subjects coefficient of variations (inter-CV and intra-CV) were studied. Results The inter-subject variability of CBF is about 25% at rest and is moderately improved when the size of the ROI increases (inter-CV = 31%, for 1 s and 1 mm 2 versus inter-CV = 23%, for 15 s and 100 mm 2). However, increasing the TOI does not improve the results. The variability of the PORH peak is lower with an inter-CV varying between 11.4% (10 s and 100 mm 2) and 21.6% (5 s and 1 mm 2). The lowest intra-CV for the CBF at rest was 7.3% (TOI of 15 s on a ROI of 100 mm 2) and was 3.1% for the PORH peak (TOI of 10 s on a ROI of 100 mm 2). Conclusion We suggest that a size of ROI larger than 10 mm 2 and a TOI longer than 1 s are required to reduce the variability of CBF measurements both at rest and during PORH peak evaluations at the forearm level. Many technical aspects such as comparison of laser speckle contrast imaging and laser Doppler imaging or the effect of skin to head distance on recorded values with LCSI are required to improve future studies using this fascinating clinical tool.

Sympathetic sudomotor neural function in amyotrophic lateral sclerosis

In patients with amyotrophic lateral sclerosis (ALS), sudomotor and vasomotor function have been considered to be impaired based on sympathetic skin response (SSR) or cutaneous blood flow measurements. We evaluated sympathetic sudomotor and vasoconstrictive neural function in ALS. We simultaneously recorded SSR, skin blood flow, and skin sympathetic nerve activity (SSNA) by microneurography in 20 patients with sporadic ALS and 20 healthy controls. Resting frequency of SSNA was significantly higher in ALS patients than in controls (p <0.05), but the increase of SSNA associated with mental arithmetic was smaller in ALS patients than controls (p <0.05). ALS patients also exhibited slight prolongation of SSNA reflex latencies compared with controls (p <0.05). In conclusion, sympathetic hyperactivity was observed in relation to sudomotor and vasoconstrictive skin responses. Since SSNA reflex latencies reflect central sympathetic function, the central autonomic pathways may be slightly impaired in patients with ALS.

Perineural capsaicin treatment attenuates reactive hyperaemia in the rat skin

The neural mechanisms of reactive cutaneous hyperaemia were studied by using a novel experimental approach: the simultaneous measurement of cutaneous blood flow by laser-Doppler flowmetry in adjacent innervated and chemodenervated skin regions of the rat hindpaw served by the same artery. Transient occlusion of the femoral artery (0.5–6 min) resulted in reactive hyperaemia that was greatly reduced in the chemodenervated region. After 3 min arterial occlusion, peak cutaneous blood flow was 109±13% vs. 53±7%* (% change from baseline, n=11, * P<0.05), and the total hyperaemic response was 110±21 vs. 52±12* (arbitrary perfusion units) in intact vs. chemodenervated skin regions, respectively. The findings provide clear evidence for the involvement of peptidergic capsaicin-sensitive afferent nerves in the mechanism of reactive cutaneous hyperaemia.

Thoracic sympatholysis with epidural blockade assessed by quantitative measurement of cutaneous blood flow.

Quantifying sympathetic activity is difficult. Direct measurement is possible and superior to indirect techniques, but nerves to internal organs are not accessible in humans. Recently, we validated a quantitative technique for measurement of cutaneous blood flow using heat as an indicator. The aim of the study was to investigate whether sympatholysis during thoracic epidural blockade (TEA) may be documented by changes in regional cutaneous blood flow. A secondary aim was to assess whether, during TEA, local heating itself enhances regional blood flow. Six patients scheduled for elective coronary artery bypass grafting (CABG) were studied. An epidural catheter was inserted at the T2-3 interspace. Measurements were performed with an electrode, which can measure the local temperature of the skin. The probe is covered with a thermostatically controlled cap to avoid a thermic gradient to air. As a result of the cap, a change in temperature of the central disc depends almost solely on the blood flow in the underlying tissue. Regional cutaneous blood flow rates were measured before and after epidural anesthesia with and without local heating. All patients had a sensory blockade covering at least T1-5. Cutaneous blood flow increased in all six patients after blockade (13.6 ml/min/100 g, range 10.6-14.6 vs. 18.4 ml/min/100 g, range 13.9-24.5; P<0.05). Local heating did not further enhance blood flow. High TEA is associated with a uniform increase in thoracic cutaneous blood flow, and is suggestive of regional sympatholysis. Quantitative measurements of skin blood flow appear promising for documenting regional sympatholysis during TEA.

An ipsilateral superdrainaged transverse rectus abdominis myocutaneous flap for breast reconstruction.

A conventional single pedicled TRAM (transverse rectus abdominis myocutaneous) flap is a musculocutaneous flap widely used for breast reconstruction. However, complications such as partial flap necrosis, fat necrosis, and fatty induration may occur as a result of unstable blood flow circulation to the flap. One major factor is venous congestion in the flap. In an effort to obtain more stable TRAM flap blood circulation, we anastomosed the ipsilateral deep inferior epigastric vein of a pedicled TRAM flap to the thoracodorsal vein. This procedure provides superdrainage by means of enhanced venous perfusion. This flap with superdrainage augmentation is referred to as a superdrainaged TRAM flap (12 patients). Changes in cutaneous blood flow were also assessed by measurement of cutaneous blood flow in zone IV using a laser blood flow meter (8 patients). The patients who underwent breast reconstructive surgery using this technique showed no evidence of postoperative complications such as flap necrosis, fat necrosis, or fatty induration. Satisfactory results were obtained during breast reconstruction in patients who had previously undergone a radical mastectomy with resultant large areas of tissue defects. In addition, the two patient groups, 12 patients with superdrainaged TRAM flap and 20 patients with single pedicled TRAM flap, were compared to assess differences in complications. The incidence of partial flap necrosis, fat necrosis, and fatty induration was lower among patients with superdrainaged flap than those with single pedicled flap.

Diagnosis of acute localized irradiation lesions: review of the French experimental experience.

In the last 50 years several radiation accidents occurred in which industrial radiographers and others suffered severe radiation injuries from inadvertent contact with radiation sources. Such accidents involving acute localized injuries are characterized by a severe initial reaction progressing through erythema to skin necrosis with a spontaneous resolution of the lesion over a 2-mo period for the lower doses. However, the early symptoms observed on the skin give no indication as to the in-depth pathology, and cutaneous and muscular radionecrosis started generally from early epithelial, microvascular, and vascular lesions and from delayed muscular and connective tissue lesions. In a case of acute localized irradiation, different biophysical techniques are able to give real responses in biological dosimetry. More numerous are the methods, especially imaging methods, that make it possible for the clinician to evaluate the extent of the early injuries and to manage the medical intervention. We have developed animal experimental models of acute localized irradiation: overexposure to the gamma rays of a 192Ir industrial radiographic collimated source (in the pig and the rabbit) and overexposure to the beta rays of a 90Sr-90Y collimated source (in the pig). In these experimental models, most of the imaging techniques used in clinical practice, as infra-red thermography, microwave thermography, cutaneous and tissular vascular scintigraphy (beta or gamma emitters), cutaneous blood flow measurements by cutaneous laser Doppler, x ray computed tomography, nuclear magnetic resonance imaging, and skin topography, were correlated with clinical evaluation and histopathological observations, after high doses of gamma or beta irradiations ranging from 4 to 340 Gy at the skin surface. All these techniques are not for isolated use and the present review indicates that their combination is necessary to give an improved diagnostic and prognostic picture of early and late delayed radiation damage to the skin and subcutaneous tissues.

Mapping of the human body skin with laser Doppler flowmetry.

The purpose of this study was to evaluate cutaneous blood flow in the human body to better establish normal flow ranges and to determine whether the location, side of the body, sex, and age affect the flow range at seven different sites. From March 1993 to February 1994 a Periflux system 4001 laser Doppler flowmeter was used to measure the cutaneous microflow circulation of 1,680 selected points in 120 volunteers. The mean normal cutaneous blood flow of 120 volunteers was between 4 and 9 perfusion units (PU) except in the head, neck, hand, and foot. Mean cutaneous blood flow measurements were as follows: the upper arm, 6.6 +/- 1.20 PU (mean +/- SE); the forearm, 6.7 +/- 1.95 PU; the thorax, 7.1 +/- 1.72 PU; the flank, 6.3 +/- 1.23 PU; the abdomen, 5.3 +/- 1.79 PU; the thigh, 4.8 +/- 1.34 PU; the lower leg, 4.6 +/- 1.39 PU (p < 0.05). The blood flow of the thorax was highest and was 54% higher than the lower leg. The group of teenagers had the highest cutaneous blood flow, with an average value of 6.9 +/- 0.62 PU. The group of subjects in their sixties proved to have the lowest cutaneous blood flow-32% less than the teenagers. Gender differences were not noted. There were no significant differences in blood flow in regard to the side of the body.

WS062 Standardization of skin colour and cutaneous blood flow measurements

WS062 Standardization of skin colour and cutaneous blood flow measurements

Axon Reflex Vasodilatation in Human Skin Measured by a Laser Doppler Technique.

This study was designed to investigate whether or not an objective method to measure a blood flow value by laser Doppler technique is possible to study the mechanism of an axon reflex vasodilatation elicited by i.d. injection of histamine or substance P into human skin. The probe of laser Doppler flowmeter was placed 10 mm apart from the injection site in the ventral forearm. The blood flow increased after the i.d. injection of histamine, substance P, but not after injection of Ringer solution. Penetration by the hypodermic needle produced an increase in the blood flow, but this increase was masked by the injection of the Ringer solution. The histamine- or substance P-induced blood flow increase was dose-dependent in both duration and intensity. Pretreatment with diphenhydramine ointment or xylocaine jelly 1 h prior to i.d. injection of histamine or substance P significantly attenuated the blood flow increase elicited by either vasoactive substance. Pretreatment of the skin with capsaicin (1% alcoholic solution) for 2 or 3 days markedly reduced the histamine- or substance P-induced blood flow increase. These results show that the measurement of cutaneous blood flow by laser Doppler flowmeter is useful in studying the mechanism of vasoactive substances-induced axon reflex vasodilatation.

Colorimetric quantification of erythema-a comparison of two colorimeters (Lange Micro Color and Minolta Chroma Meter CR-200) with a clinical scoring scheme and laser-Doppler flowmetry

Erythema elicited by the local irritant sodium lauryl sulphate was studied in comparison with unexposed skin. Colour coordinates of the CIE system were recorded using two commercially available colorimeters. With both colorimeters a positive movement of the alpha-axis (toward red, P less than 0.001) and a negative movement on the L-axis (toward dark, P less than 0.01) were registered. Technical and in-vivo experimentation showed the two pieces of equipment to be accurate. However, a simple conversion factor cannot be established. Both pieces of equipment correlated positively with clinical scoring of erythema and with measurement of cutaneous blood flow by laser-Doppler flowmetry. In conclusion, the two colorimeters appeared comparable. Colorimetry by the CIE system, which takes into account the non-linear colour perception of the human eye, was found useful with potential value in both experimental and clinical dermatology. The techniques appeared suitable for routine testing.

Skin reactions to irritants assessed by non‐invasive bioengineering methods

Pathophysiological components of irritant contact dermatitis caused by 3 chemically-different irritants were investigated. 20 healthy volunteers were patch tested with sodium lauryl sulphate, nonanoic acid and hydrochloric acid on the flexor side of the upper arm. The skin response was evaluated after 24, 48 and 96 h by visual scoring and measured by the following bioengineering methods: transepidermal water loss measurement, electrical conductance for measurement of skin hydration, laser Doppler flowmetry for measurement of cutaneous blood flow and 20 MHz ultrasound A-scan for measurement of skin thickness. In spite of homogeneous inflammatory responses, significant differences in the severity of the injury to the skin barrier function caused by the different irritants were found. Also significant differences between irritants were found in the time course of development of maximum irritant reactions. Bioengineering methods indicating inflammatory responses (measurement of blood flow and skin thickness) were helpful in quantifying the irritant response in general, while bioengineering methods indicating epidermal damage (measurement of TEWL and electrical conductance) were helpful in classifying the individual irritants.

Measurement of cutaneous blood flow by clearance of hydrogen gas generated by electrolysis.

In an attempt to assess the reliability of a method for measurement of local blood flow-namely, the clearance of electrochemically generated hydrogen gas-a series of experiments were conducted using the skin and skin flap in rats and rabbits. The results showed high accuracy in obtained values, good reproducibility in the repeated measurements, and consistency with the values obtained by the hydrogen gas inhalation method. Histological examination revealed only minimal damage to the tissue resulting from the measurement. Using this method, blood flow was measured at different sites on the flap in rats. The critical point of blood flow as measured by this method was thoroughly consistent with the dye distance as well as with the survival length. No injurious effects of the measurement procedure on flap survival were noticed. The present study suggests a wide potential application of this method in plastic surgery because of its high reliability and because no radioactivity is involved.

Patch Test Responses Evaluated by Cutaneous Blood Flow Measurements

We measured the cutaneous blood flow in positive standard patch test reactions by use of the laser-Doppler technique. The results were compared with conventional visual readings to develop a quantitative method. Compared with the basal blood flow in negative or nontested sites, the blood flow was significantly increased about fivefold in the doubtful reactions (?+), and about tenfold in both weak (1+) and strong (2+) positive reactions. The blood flows in the 1+ and 2+ reactions did not differ significantly from each other. No 3+ positive reactions were measured. We conclude that this method might be used to separate negative, doubtful, and positive reactions, whereas weak and strong positive reactions have to be differentiated by other means.

Patch test responses evaluated by cutaneous blood flow measurements

Patch test responses evaluated by cutaneous blood flow measurements

Evaluation of Cutaneous Blood Flow Responses by 133Xenon Washout and a Laser-Doppler Flowmeter

A new method for noninvasive measurement of cutaneous blood flow is laser-Doppler flowmetry. The technique is based on the fact that laser light is back-scattered from the moving red blood cells, with Doppler-shifted frequencies; these impulses lead to photodetectors and are converted to flow signals. In this work we used a new system with a low noise level. Comparison was made between this technique and the atraumatic epicutaneous 133Xenon technique for measurement of cutaneous blood flow during reactive hyperemia and orthostatic pressure changes. The laser-Doppler flowmeter seems to measure blood flow in capillaries as well as in arteriovenous anastomoses, while the 133Xe method probably measures only capillary flow. A calibration of the laser-Doppler method against the 133Xe method would appear to be impossible in skin areas where arteriovenous anastomoses are present. The changes in blood flow during reactive hyperemia, orthostatic pressure changes, and venous stasis were found to be parallel as measured by the two methods in skin areas without shunt vessels. The laser-Doppler flowmeter would appear to be a useful supplement to the 133Xe washout method in cutaneous vascular physiology, but it is important to keep in mind that different parameters may be measured.