Laser Doppler Fluxmeter Research Articles

Screening for Peripheral Artery Disease Using an Automated Four-Limb Blood Pressure Monitor Equipped with Toe-Brachial Index Measurement.

Toe-brachial index (TBI) measurement helps to detect peripheral artery disease (PAD) in patients with incompressible ankle arteries due to medial arterial calcification, which is most frequently associated with diabetes. We aimed to evaluate how an automated four-limb blood pressure monitor equipped with TBI measurement could contribute to PAD screening. In 117 patients (mean age 63.2 ± 12.8 years), ankle-brachial index (ABI) measurement was performed using the Doppler-method and the MESI mTablet. TBI was obtained via photoplethysmography (MESI mTablet, SysToe) and a laser Doppler fluxmeter (PeriFlux 5000). Lower limb PAD lesions were evaluated based on vascular imaging. A significant correlation was found between Doppler and MESI ankle-brachial index values (r = 0.672), which was stronger in non-diabetic (r = 0.744) than in diabetic (r = 0.562) patients. At an ABI cut-off of 0.9, Doppler (AUC = 0.888) showed a sensitivity/specificity of 67.1%/97.4%, MESI (AUC 0.891) exhibited a sensitivity/specificity of 57.0%/100%; at a cut-off of 1.0, MESI demonstrated a sensitivity/specificity of 74.7%/94.8%. The TBI values measured using the three devices did not differ significantly (p = 0.33). At a TBI cut-off of 0.7, MESI (AUC = 0.909) revealed a sensitivity/specificity of 92.1%/67.5%. Combining MESI ABI and TBI measurements recognised 92.4% of PAD limbs. Using an ABI cut-off level of 1.0 and sequential TBI measurement increases the sensitivity of the device in detecting PAD. The precise interpretation of the obtained results requires some expertise.

Oscillometric measurement of the ankle-brachial index and the estimated carotid-femoral pulse wave velocity improves the sensitivity of an automated device in screening peripheral artery disease.

To overcome the time and personnel constraints of the Doppler method, automated, four-limb blood pressure monitors were recently developed. Their additional functions, such as measuring the estimated carotid-femoral pulse wave velocity (ecfPWV), have been, thus far, less studied. We aimed to compare the sensitivity and specificity of different ankle-brachial index (ABI), toe-brachial index (TBI), and ecfPWV measurement methodologies to evaluate their contribution to peripheral artery disease (PAD) screening. Among 230 patients (mean age 64 ± 14 years), ABI measurements were performed using a Doppler device and a manual sphygmomanometer. The Doppler ABI was calculated by taking the higher, while the modified Doppler ABI by taking the lower systolic blood pressure of the two ankle arteries as the numerator, and the higher systolic blood pressure of both brachial arteries as the denominator. The automated ABI measurement was carried out using an automatic BOSO ABI-system 100 PWV device, which also measured ecfPWV. TBI was obtained using a laser Doppler fluxmeter (Periflux 5000) and a photoplethysmographic device (SysToe). To assess atherosclerotic and definitive PAD lesions, vascular imaging techniques were used, including ultrasound in 160, digital subtraction angiography in 66, and CT angiography in four cases. ROC analysis exhibited a sensitivity/specificity of 70.6%/98.1% for the Doppler ABI (area under the curve, AUC = 0.873), 84.0%/94.4% for the modified Doppler ABI (AUC = 0.923), and 61.5%/97.8% for the BOSO ABI (AUC = 0.882) at a cutoff of 0.9. Raising the cutoff to 1.0 increased the sensitivity of BOSO to 80.7%, with the specificity decreasing to 79.1%. The ecfPWV measurement (AUC = 0.896) demonstrated a 63.2%/100% sensitivity/specificity in predicting atherosclerotic lesions at a cutoff of 10 m/s. Combining BOSO ABI and ecfPWV measurements recognized 89.5% of all PAD limbs. The combined BOSO ABI and ecfPWV measurements may help select patients requiring further non-invasive diagnostic evaluation for PAD. The user-friendly feasibility may make it suitable for screening large populations.

Can we boost screening for peripheral arterial disease?

Abstract Despite the high prevalence of peripheral artery disease (PAD), the diagnosis is often delayed. The delayed diagnosis is due in part to comorbidities which can mask PAD symptoms, and in large part to the low use of conventional diagnostic tools. For PAD diagnostics, the guidelines recommend Doppler-based ankle-brachial index (ABI). The method is time consuming and requires skills. The toe pressure measurement which helps to eliminate the falsely elevated ankle pressures due to mediasclerosis is an almost neglected method for screening. In recent years, automatic, oscillometric four-limb blood pressure monitors have become available that provide data within minutes. We aimed to compare an automatic four limb blood pressure monitor with devices regularly used in our department. Methods Blood pressure was measured in 92 individuals (mean age 65±14 years) using a Doppler device (Hadeco) and a conventional manual sphygmomanometer on all four limbs, as well as an automatic, four-limb pressure monitor (BOSO ABI system-100 PWV) which also measured pulse wave velocity (PWV). Toe pressure was measured with a laser Doppler fluxmeter (Periflux 5000) and a photophlethysmography based toe pressure monitor (Systoe). Patients without known PAD but with at least one abnormal test result underwent a vascular imaging including ultrasound, CT or digital subtraction angiography. Among the 92 individuals there were patients with confirmed PAD, persons at high or very high cardiovascular risk, patients with non-ischaemic cardial diseases and healthy volunteers. Results ABI values of the posterior tibial artery at the corresponding side measured by Doppler and BOSO showed a strong correlation with each other (Pearson's r: 0.8 and 0.7), while the Doppler ABI values of the dorsal pedal artery showed a moderate or weak correlation with BOSO ABI values (r: 0.63 and 0.27). The toe pressure measured by laser Doppler and Systoe did not differ significantly. The ROC curve analysis of the Periflux TBI values supported 0.6 as a cut-off level (91.6% sensitivity, 84% specificity). Of the 52 individuals with high or very high cardiovascular risk, 15 with Doppler, 12 with BOSO and 29 with Periflux could be considered as abnormal, the vascular imaging confirmed PAD in 12 of them. Doppler ABI was abnormal in 96%, BOSO ABI in 69%, BOSO ABI combined with PWV in 92%, Periflux and Systoe toe brachial index (TBI) in 100–100% in 72 limbs with confirmed PAD. In control subjects, ABI, TBI, and PWV were normal; in subjects with high or very high risk, PWV was 58% abnormal, in confirmed PAD, 85%. All patients with abnormal PWV showed atherosclerotic lesions by the vascular imaging. Summary For detection of PAD, the measurement of TBI had the highest sensitivity. PAD screening of a large population may be possible using automatic four limb blood pressure monitors. By combining with additional features (e.g. PWV) the detection ratio can be improved to the level of the Doppler ABI method. Funding Acknowledgement Type of funding sources: None.

Comparison of Effects of Vitamin E and Wen-jing-tang (Unkei-to), An Herbal Medicine, on Peripheral Blood Flow in Post-menopausal Women with Chilly Sensation in the Lower Extremities: A Randomized Prospective Study

We examined the association between blood flow and chilly sensation in the lower extremities, comparing the changes in blood flow induced by the vitamin E and herbal therapy (Wen-jing-tang) in perimenopausal women with chilly sensation. One hundred sixty-one perimenopausal women aged 42-61 years (mean: 50.4 +/- 3.8 years) with chilly sensation in the lower extremities participated in the study. The participants were randomized for treatment with Wen-jing-tang or a vitamin E preparation containing 600 mg tocopherol nictinate per day for 8 weeks. Blood flow measurement was performed by laser Doppler fluxmetry to determine tissue under the jaw, in the middle finger, and in the third toe. Wen-jing-tang significantly increased the peripheral blood flow in the skin surface in the tiptoe (12.8 +/- 8.8, p = 0.0068) from basal levels (6.0 +/- 5.1), although no significant change was observed in the blood flow in fingertip or under the jaw during treatment. The rate of increase of blood flow in the skin surface of in the lower extremities was significantly higher in the Wen-jing-tang treating group (116.4 +/- 46.5%) than in the vitamin E group (39.8 +/- 21.3%) (p < 0.0001). When the effects of herbal treatment and vitamin E treatment were compared in the subjects with baseline upper extremity blood flow above the mean + 1.5 SD, mean blood flow through the upper extremities was found to have been significantly decreased after Wen-jing-tang treatment (from 57.7 +/- 4.8 to 43.1 +/- 4.2, p = 0.0277), whereas it remained unchanged after treatment with vitamin E. Classical monographs described Wen-jing-tang as being particularly useful in curing chilly sensation in lower extremities. The present study using a laser Doppler fluxmeter demonstrated that treatment with this herbal medicine significantly increased blood flow through the periphery of lower extremities in patients with chilly sensation. It also showed that this herbal medicine suppresses excessive blood flow through the upper half of the body and thus stimulates restoration of physiological distribution of blood flow throughout the entire body.

Laser doppler fluxmetry and the larynx

Problem: The study has three aims: (1) to determine whether a laser Doppler flux meter is a reliable and reproducible measure of laryngeal blood flux. (2) to determine whether blood flux, as measured, correlates with microvessel density as a less invasive, reliable method of quantifying angiogenesis. (3) to measure the effect of sequential division of nerves and vessels on laryngeal blood flow using the aforementioned specially designed laser Doppler probe. Methods: Using a laser Doppler monitor we measured the response to a known vasoconstrictor in the animal experiments. Reproducibility was tested and LDF readings obtained were compared to conventionally obtained quantification of microvessel density. Patients undergoing laryngectomies had continuous LDF measurements and the effect of sequential division of nerves and vessels was assessed. Results: In an animal model we demonstrated that the laser Doppler flux meter was capable of detecting change when one was expected ( P = 0.01). We also demonstrated good reproducibility of laser Doppler measurements in laryngeal mucosa both in the human and animal models (correlation coefficients of 0.956 and 0.947, respectively; with P = 0.01). Division of the superior laryngeal nerve caused a marked drop in ipsilateral laryngeal blood flux. Laser Doppler fluxmetry did not correlate with micro-vessel density as measured conventionally using immuno-histochemistry. Conclusion: Laser Doppler fluxmetry is a reliable and reproducible method of estimating blood flux in the larynx. We were able to show that division of the superior laryngeal nerve causes a significant fall in mucosal blood flux and therefore should be preserved whenever possible. However, it would seem that blood flux and microvessel density were not directly comparable parameters. Significance: It would appear from our study that LDF cannot be directly used to quantify angiogenesis. An improved understanding of laryngeal innervation and blood supply will contribute to the complex knowledge base that underpins the future of laryngeal transplantation. Support: This study was made possible by funds kindly donated from the estate of the late Thomas Green Esquire, and managed by the Medway Head and Neck Cancer Research Fund.

Laser Doppler flux-metry as an experimental tool in laryngology.

Angiogenesis is a cascade-like mechanism, essential for the progression of solid tumours. Quantifying microvessel density is considered the gold standard for measuring baseline angiogenesis and indeed "the response to intervention". Applying immunohistochemical techniques to biopsies conventionally does this; however, it would be very helpful to have a less invasive, reliable method of quantifying blood flux, and hence angiogenesis. The aim of the study was to validate the use of a laser Doppler flux meter as an experimental tool in laryngology. The principle and technique of laser Doppler flux-metry is described. A validation study designed to estimate the reproducibility and ability to measure change was performed in the human larynx and in an animal model. Statistical advice was sought and analysis was performed using SPSS software. Our experiments show good reproducibility of laser Doppler measurements in the human and animal model (correlation coefficient 0.956 and 0.947, respectively, P=0.01). We have also shown that the laser Doppler flux meter is capable of detecting change when it is expected ( P<0.01). Utilising a standardised technique, laser Doppler flux-metry appears to be a reliable and reproducible method of estimating blood flux in the larynx.

Laser Doppler flux-metry in laryngeal squamous cell carcinoma.

Tumour angiogenesis has recently attracted a great deal of attention as a critical part of oncogenesis and a necessary prerequisite for a malignant phenotype. Novel antiangiogenic therapy for solid tumours including laryngeal cancer is entering clinical trials. Quantifying microvessel density is considered the gold standard for measuring baseline angiogenesis and indeed 'the response to intervention'. We hypothesize that laser Doppler flux-metry could provide a non-invasive reliable method of quantifying blood flux within tumours. The aims were to determine whether a laser Doppler flux meter could be used as a reliable and reproducible method of estimating blood flux in the human larynx and to establish baseline Doppler flux recordings for the human larynx. The method used was a validation study in patients with laryngeal squamous cell cancer and normal controls. Statistical analysis was performed using SPSS software. We have demonstrated good reproducibility of laser Doppler measurements in human laryngeal mucosa (correlation coefficient 0.956 @P = 0.01). We have also derived arbitrary means of laser Doppler flux-metry in normal laryngeal mucosa and in squamous cell carcinoma of the larynx. Comparisons between normal and tumour laser Doppler flux-metry (LDF) readings showed no significant difference. We suggest that Laser Doppler flux-metry is a potentially useful tool with which to study blood flow in the larynx and propose arbitrary LDF levels for the normal and diseased human larynx.

A modular device to measure the effects of plantar foot pressure on the microcirculation of the heel

Background: Past research has concentrated on foot function and plantar foot pressure, with many devices developed for this purpose. However, little is known of how cutaneous blood flow compensates for ambulatory repetitive circulatory insults and how ulceration occurs. Objectives: To develop a system to measure the effects of plantar foot pressure on cutaneous blood flow in the supine and semi-weight bearing positions. Method: A system was developed that integrated a laser Doppler fluxmeter with a pressure probe, allowing plantar foot pressure and skin blood flow to be recorded simultaneously. The system was tested using four volunteers (28±8.6 years). Results: A significant difference existed between baseline laser Doppler flowmetry (LDF) in the supine and semi-weight bearing positions ( P=0.023). Differences between both positions also existed in the reduction in LDF levels following application of pressure ( P=0.015), the maximum hyperaemic response ( P=0.034) and time taken to reach maximum hyperaemic response ( P=0.019). Conclusion: The device has shown that with current technology it is now possible not only to investigate plantar foot pressure but also how it affects skin blood flow, which in some cases can lead to ulceration. The effect of plantar foot pressure on cutaneous blood flow differs depending on whether the subject is supine or semi-weight bearing. Thus, to understand the effects of plantar foot pressure on skin blood flow future researchers must ensure that subjects are in an upright position when recording.

Elastotic degenerative change and yellowish discolouration in photoaged skin.

One clinical sign of photodamage is a sallow discolouration of the skin, and solar elastotic degenerative change in the upper dermis may cause this change. We have attempted to quantify these phenomena and relate them to each other and to age. Twenty-seven healthy volunteers (age 18 to 61 years) were recruited. We examined the back of the hand of photodamaged individuals and the inner upper arm to demonstrate changes due to ageing. Each site was assessed for cutaneous blood flux using a laser Doppler fluxmeter (PF4000, Perimed UK), and for melanin pigmentation using a Melanin Index meter (Dermotronics Ltd, Cardiff, UK). Skin colour was measured using a diode array spectrophotometer (MCPD-1000, Photal, Japan), which computes CIE coordinates L*, a*, b*. Biopsies from each site were obtained from 13 of the subjects and were processed and stained with Gomori's aldehyde fuchsin. The percentage area of elastic staining material in the dermis was measured using image analysis. Sections were measured in four bands of 200 micron depth, and four fields were measured per band. Neither melanin content nor skin blood flux correlated with age for either skin site. Percentage area of elastosis correlated with age on the exposed site from the uppermost 600 microns of the dermis, (<200 micron depth, r=0.74, P<0.01, 200<depth<400, r=0.57, P<0.05; 400<depth<600, r=0.57, P<0.05). No correlation was found on the unexposed inner upper arm site. On the back of hand site, a linear relationship was found between a parameter derived from the L*, a*, b* coordinates of (b*-5a*) and both age (r=0.904, P<0.001) and percentage area of elastosis of the uppermost 200 microns of dermis (r=0.74, P<0.01). This was not seen for the inner upper arm site. On exposed sites, the coefficient (b*-5a*) correlates with solar elastosis and these both correlate with age, which is related to exposure. This data confirms that solar elastosis accounts for the yellowish discolouration of sun damaged skin, and suggests that the coefficient b*-5a* could be used for the non-invasive quantification of solar elastosis.

Regional variations in skin perfusion and skin thickness may contribute to varying efficacy of topical, local anaesthetics in neonates.

The national Swedish screening programme for inborn errors of metabolism includes blood sampling from all neonates. Heel lancing has hitherto been the method of choice for these screening tests. Studies have recently been done to find out whether the use of EMLA can alleviate pain caused by heel lancing. EMLA had little, if any effect when applied to the heel of full term babies. Similar results were reported concerning preterm infants. Other authors have found that differences in skin thickness or in skin blood perfusion may influence the effect of EMLA. The aim of this study was to establish whether differences in skin thickness or in skin blood perfusion were present in three regions: the forehead, the dorsum of the hand and the heel. Ten healthy full term neonates were included in the study on skin perfusion. Measurements were made with a laser Doppler flux meter. Twenty-seven healthy full term neonates were included for measurements of skin thickness using a high frequency B-mode ultrasonic meter. The heel skin perfusion was two to three times higher than the skin perfusion at the dorsum of the hand and at the forehead but there was no significant difference when comparing skin thickness of the heel with the dorsum of the hand and the forehead. A rapid clearance of a topically applied local anaesthetic, due to high cutaneous blood flow, may explain why EMLA seems to be of little value when it is applied to the neonatal heel.

Calcitonin gene-related peptide increases microcirculation after mechanically induced ischemia in an experimental island flap.

Vasoconstriction, as a result of mechanical manipulation of blood vessels during microsurgery, may produce a decrease in blood supply and endanger flap viability. A study was undertaken to determine the effects of the topical vasodilator calcitonin gene-related peptide on the microcirculation of flaps after mechanically induced ischemia. A neurovascular island flap based on the superficial epigastric vessels was raised in 42 rats. Blood cell flux in the flap was recorded continuously with a laser Doppler flux meter. The feeding artery was pinched to induce vasospasm, and different concentrations of calcitonin gene-related peptide (10(-7), 10(-8), 10(-9), 10(-10) mol) or a control of sodium chloride 0.9% was applied topically to relieve the ischemia. Results showed that calcitonin gene-related peptide at a concentration of 10(-7) mol significantly shortened the time to reach 50% of the original blood cell flux values (270 +/- 123 seconds) and significantly increased the number of flaps in which the blood cell flux values were restored to prestress levels within 30 minutes. The data support the conclusion that, in this model, topical calcitonin gene-related peptide at the concentration of 10(-7) mol was effective in promoting recovery of the microcirculation after mechanically induced ischemia, without the adverse effects associated with other commonly used vasodilators.

Effect of Compression Stockings on the Skin Microcirculation in Chronic Venous Insufficiency

Objective: To use a single fibre laser Doppler fluxmeter to assess the microcirculatory effects of compression stockings. Design: Controlled study comprising patient and control groups. Setting: Department of Surgery, University College London Medical School, London, UK. Patients and participants: Ten patients with lipodermatosclerosis caused by chronic venous insufficiency and 10 control subjects. Interventions: Measurements were made from the liposclerotic skin of patients and 8 cm above the medial malleolus in controls. Laser Doppler flux (LDF), blood ce velocity (BCV) and concentration of moving blood cells (CMBC) were recorded with the subject lying supine. A class II graduated compression stocking was applied to the leg and laser Doppler recordings were repeated. The protocol was repeated with the subject sitting. Main outcome measures: The effects of a compression stocking on LDF, BCV and CMBC in the horizontal and sitting positions were measured. Results: In patients in the supine position, the compression stocking resulted in a 28% median increase in LDF ( p = 0.03), with a corresponding 29% median increase in BCV. There was no significant change in CMBC. In the sitting position, the compression stocking caused a 105% median increase in LDF ( p &lt; 0.01) due to a corresponding 89% median increase in BCV ( p = 0.01); there was only 25% median increase in CMBC. The effects of compression in controls were similar to those in patients. Conclusion: Compression stockings may be effective in the treatment of chronic venous insufficiency by increasing the microcirculatory flow velocity.

Correlation between peripheral vascular resistance and time to peak flow during reactive hyperaemia

Earlier studies have proposed that the time to reach peak hyperaemic flux recorded with laser Doppler (tp) is a simple and accurate method of evaluating ischaemic limbs and possibly a method of estimating the peripheral vascular resistance (PR). The aim of this study was to investigate the relationship between the tp and changes in limb vascular resistance caused by arterial stenosis. Forty postocclusive hyperaemia tests with arterial stenoses of different pressure gradients were performed in four pigs. A laser Doppler fluxmeter was used to record postocclusive hyperaemia in the skin of one hind limb. A specially designed tourniquet was used for the arterial occlusion. Proximal and distal to the occlusion level a snare was used to form different grades of stenosis. The PR (mmHg.ml-1.min-1) was either estimated by infusion of a known blood volume into the tested limb over a given time period with simultaneous measurement of pressure or calculated on the basis of measurements of limb blood flow and blood pressure gradients. The tp was closely related to total limb vascular resistance assessed by the blood infusion method (r = 0.83, p < 0.0003) and to the resistance calculated from volume blood flow and intraarterial pressures (r = 0.86, p < 0.0001). This study suggests that the tp accurately reflects limb vascular resistance in an experimental model. Thus tp may be used as a quantitative indicator of overall blood flow impairment, and should be evaluated in patients with lower-limb atherosclerosis.

Level of arterial obstruction in patients with peripheral arterial occlusive disease (PAOD) determined by laser Doppler fluxmetry

To evaluate the laser Doppler fluxmeter as a non-invasive screening method to determine the level of peripheral arterial occlusive disease (PAOD) in the lower limb. Open study of the veno-arterial reflex (VAR) during a shift in body position using a laser Doppler fluxmeter at five probe positions distal to the knee, compared with the occlusion level determined by arteriography and segmental plethysmography. 50 legs comprising 10 normal controls, 20 legs with suprainguinal obstructions (10 claudication and 10 critical ischaemia) and 20 legs with infrainguinal obstructions (10 claudication and 10 critical ischaemia). Controls had normal VAR (mean flux reductions of 38% during dependency) at all probe positions. Legs with infrainguinal disease had normal reflexes proximally but significantly disturbed reflexes distally, whereas suprainguinal disease showed alterations at all sites. Claudicants had diminished flux reduction (mean 12%) whilst those with critical ischaemia increased the flux (mean 32%). This simple, non-invasive technique may be of use in determining the level of obstruction in PAOD.

Reactive hyperemia in term neonates and adults—A laser Doppler fluxmetry study of skin microcirculation

The reactivities of neonatal and adult microcirculation have been studied and compared. The cutaneous reactive hyperemia after 1 and 4 min of arterial occlusion (AO) was measured with a laser-Doppler fluxmeter in 21 healthy neonates and 10 adults. Local skin temperature, mean arterial blood pressure (MAP), and skin prick hematocrit were also determined at the same time. The magnitude of neonatal reactive hyperemia was approximately one-third that of the adult response regardless of the duration of AO. In both groups, with age-specific regressions, the hyperemic blood flow response after 4 min of AO developed more slowly in subjects with low MAP and was of low magnitude in subjects with high hematocrit values. In response to a prolongation of AO, from 1 to 4 min, the magnitude and duration of hyperemia increased significantly and similarly in both neonates and adults. We conclude that compared to adults neonates have a less pronounced ability to increase skin microcirculation in response to local ischemia. The normally low blood pressure and high hematocrit in newborn infants contribute further to this conclusion.