Laser Doppler Flowmetry Signals Research Articles

Tumor-Derived Exosomes Promote Tumor Growth Through Modulating Microvascular Hemodynamics in a Human Ovarian Cancer Xenograft Model.

Abnormal tumor vascular network contributes to aberrant blood perfusion and reduced oxygenation in tumors, which lead to poor efficacy of chemotherapy and radiotherapy. We aimed to explore the effects of the tumor-derived exosomes (TDEs) and C188-9 (a small molecule inhibitor of signal transducer and activator of transcription 3, STAT3) on tumor microvascular hemodynamics and determine which blood flow oscillations for various frequency intervals are responsible for these changes. Microvascular hemodynamics parameters were recorded using a PeriFlux 6000 EPOS system in tumor surface in a nude mouse subcutaneous xenograft model. Oscillations of laser Doppler flowmetry (LDF) signal were investigated by wavelet transform analysis. TDEs facilitated tumor growth at least partially was associated with increasing blood flow in smaller vessels with lower speed and decreasing the blood flow at larger vessels with higher speed. Lower oxyhemoglobin saturation (SO2) on tumor surface was aggravated by TDEs, and C188-9 treatment significantly alleviated this decrease. Wavelet transform spectral analysis revealed that TDEs increased the amplitude of oscillations in four frequency intervals related to endothelial (NO-dependent and -independent), myogenic and neurogenic activities, and C188-9 had no effect on this increase. TDEs facilitated tumor growth partially was associated with increasing blood flow in distributing vessels, reducing blood perfusion in larger vessels, and lowering SO2 on tumor surface. Enhanced vascular smooth muscle, endothelial and neurogenic activities occurred in tumor superficial zone.

Spectral changes in skin blood flow during pressure manipulations or sympathetic stimulation.

Skin blood flow is commonly determined by laser Doppler flowmetry (LDF). It has been suggested that pathophysiological conditions can be assessed by analysis of specific frequency domains of the LDF signals. We tested whether physiological stimuli that activate myogenic and neurogenic mechanisms would affect relevant portions of the laser Doppler spectrum. LDF sensors were placed on the right forearm of 14 healthy volunteers for myogenic (six females) and 13 for neurogenic challenge (five females). Myogenic responses were tested by positioning the arm ∼50° above/below heart level. Neurogenic responses were tested by immersing the left hand into an ice slurry with and without topical application of local anaesthetic. Short-time Fourier analyses were computed over the range of 0.06 to 0.15Hz for myogenic and 0.02 to 0.06Hz for neurogenic. No significant differences in spectral density were observed (P=0.40) in the myogenic range with arm above (7±54×10-4dB) and below heart (7±14×10-4dB). Neurogenic spectral density showed no significant increase from baseline to cold pressor test (0.0017±0.0013 and 0.0038±0.0039dB; P=0.087, effect size 0.47). After application of anaesthetic, neurogenic spectral density was unchanged between the baseline and cold pressor test (0.0014±0.0025 and 0.0006±0.0005dB; P=0.173). These results suggest that changes in the myogenic and neurogenic spectral density of LDF signals did not fully reflect the skin vascular function activated by pressure manipulation and sympathetic stimulation. Therefore, LDF myogenic and neurogenic spectral density data should be interpreted with caution.

Ice cooling challenge as a means to probe skin microvascular function

Skin microvasculature provides a window to study both systemic and local physiology. In vascular medicine, various challengers such reactive hyperemia, hypoxia or hyperoxia, and heat, have been used to study function and search for potential clinical biomarkers. A positive relationship between increased skin temperature and skin perfusion has been suggested, but skin cooling as a challenger has not been well explored. In the present study, the adaptive cardiovascular and hemodynamic impacts of single hand cooling were examined in a group of ten healthy women, 27.3±7.9 years old, of normal body mass index and ankle-brachial index, normotensive, non-smoking, and free from any medication and supplements. The study followed all principles of good clinical practice and ethics commission approval. After complete stabilization, a participant’s palm, randomly chosen, was placed in contact with a frozen surface covered by a plasticized cotton cloth. Blood perfusion was measured using a laser Doppler flowmetry (LDF) instrument, and temperature were continuously registered in both hands, before, during, and after (early and late recovery) the ice cooling challenge. Nominal values for blood perfusion and temperature were considered, as well as their wavelet transform (WT) components, translating endothelial [0.0095; 0.021] Hz, autonomic [0.021; 0.052] Hz, myogenic [0.052; 0.015] Hz, respiratory [0.15; 0.6] Hz, and cardiac [0.6; 2] Hz activities. No significant differences were observed between limbs regarding nominal LDF values for each experimental phase. Nonetheless, significant differences were observed for nominal temperature signals between limbs during the challenge (Wilcoxon’s signed rank test; p=0.047), and for early (p=0.028) and late (p=0.028) recovery phases. Significant differences were observed for ipsi- and contralateral LDF signals (Friedmann’s test, p<0.001, and p=0.012, respectively), and also for ipsi- and contralateral temperature signals (Friedmann’s test, p<0.001, and p=0.004, respectively). These contralateral responses have been previously described with other challengers applied only in the ipsilateral limb, whilst it is known that local cooling stimulates cutaneous thermoreceptors, sympathetic nerve activity and cutaneous vascular resistance. However, our findings also show that temperature may be more sensitive than LDF for studying the ice cooling challenge, and that the WT analysis approach can provide potential physiological interpretations. Nonetheless, a strong positive correlation (Spearman’s rs = 0.820, p<0.001) was observed between temperature and LDF signals overall for both limbs. In conclusion, this preliminary study suggests that this cooling challenger is effective to elicit vascular physiological changes in both limbs, indicating a putative centrally-mediated adaptive process that might be quantified by changes in cardiac and respiratory activities, as shown from WT analysis. Additionally, temperature signals and the use of WT analysis seem to provide more sensitive and explanatory insights than the use of LDF signals and nominal values alone. Suported by COFAC/ALIES. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Wireless Dynamic Light Scattering Sensors Detect Microvascular Changes Associated With Ageing and Diabetes.

This paper presents clinical results of wireless portable dynamic light scattering sensors that implement laser Doppler flowmetry signal processing. It has been verified that the technology can detect microvascular changes associated with diabetes and ageing in volunteers. Studies were conducted primarily on wrist skin. Wavelet continuous spectrum calculation was used to analyse the obtained time series of blood perfusion recordings with respect to the main physiological frequency ranges of vasomotions. In patients with type 2 diabetes, the area under the continuous wavelet spectrum in the endothelial, neurogenic, myogenic, and cardio frequency ranges showed significant diagnostic value for the identification of microvascular changes. Aside from spectral analysis, autocorrelation parameters were also calculated for microcirculatory blood flow oscillations. The groups of elderly volunteers and patients with type 2 diabetes, in comparison with the control group of younger healthy volunteers, showed a statistically significant decrease of the normalised autocorrelation function in time scales up to 10s. A set of identified parameters was used to test machine learning algorithms to classify the studied groups of young controls, elderly controls, and diabetic patients. Our conclusion describes and discusses the classification metrics that were found to be most effective.

Using Arterial Pulse and Laser Doppler Analyses to Discriminate between the Cardiovascular Effects of Different Running Levels.

Running can induce advantageous cardiovascular effects such as improved arterial stiffness and blood-supply perfusion. However, the differences between the vascular and blood-flow perfusion conditions under different levels of endurance-running performance remains unclear. The present study aimed to assess the vascular and blood-flow perfusion conditions among 3 groups (44 male volunteers) according to the time taken to run 3 km: Level 1, Level 2, and Level 3. The radial blood pressure waveform (BPW), finger photoplethygraphy (PPG), and skin-surface laser-Doppler flowmetry (LDF) signals of the subjects were measured. Frequency-domain analysis was applied to BPW and PPG signals; time- and frequency-domain analyses were applied to LDF signals. Pulse waveform and LDF indices differed significantly among the three groups. These could be used to evaluate the advantageous cardiovascular effects provided by long-term endurance-running training, such as vessel relaxation (pulse waveform indices), improvement in blood supply perfusion (LDF indices), and changes in cardiovascular regulation activities (pulse and LDF variability indices). Using the relative changes in pulse-effect indices, we achieved almost perfect discrimination between Level 3 and Level 2 (AUC = 0.878). Furthermore, the present pulse waveform analysis could also be used to discriminate between the Level-1 and Level-2 groups. The present findings contribute to the development of a noninvasive, easy-to-use, and objective evaluation technique for the cardiovascular benefits of prolonged endurance-running training.

Assessment of Blood Microcirculation Changes after COVID-19 Using Wearable Laser Doppler Flowmetry

The present work is focused on the study of changes in microcirculation parameters in patients who have undergone COVID-19 by means of wearable laser Doppler flowmetry (LDF) devices. The microcirculatory system is known to play a key role in the pathogenesis of COVID-19, and its disorders manifest themselves long after the patient has recovered. In the present work, microcirculatory changes were studied in dynamics on one patient for 10 days before his disease and 26 days after his recovery, and data from the group of patients undergoing rehabilitation after COVID-19 were compared with the data from a control group. A system consisting of several wearable laser Doppler flowmetry analysers was used for the studies. The patients were found to have reduced cutaneous perfusion and changes in the amplitude-frequency pattern of the LDF signal. The obtained data confirm that microcirculatory bed dysfunction is present in patients for a long period after the recovery from COVID-19.

Comparative view of reactive hyperemia perfusion changes in the upper-limb by laser Doppler flowmetry and optoacoustic tomography and meta-analysis

Laser Doppler flowmetry (LDF) is one of the most used technologies to access human in vivo blood perfusion. However, its single point measurement capacity in a depth that likely is lower than 1 mm, are major criticisms that limit its utility. New image-based techniques such as Optoacoustic Tomography (OAT) allow the non-invasive observation of larger tissue areas with greater spatial resolution. In this work, we compared synchronized LDF and OAT data during a Post-Occlusion Reactive Hyperemia (PORH) maneuver in the upper limb (occlusion of the brachial artery). Measurements were obtained in the volar forearm (OAT and LDF) and in the fingertip (LDF). All procedures respected the principles of good clinical practices for human research purposes. Results confirm that LDF and OAT signals are significantly correlated at the superficial plexus. LDF does not detect deeper vascular structures of the skin but, even so, it is still very useful to access perfusion in areas with higher capillary density such as the fingertip.

Diagnosis of Skin Vascular Complications Revealed by Time-Frequency Analysis and Laser Doppler Spectrum Decomposition.

Nowadays, photonics-based techniques are used extensively in various applications, including functional clinical diagnosis, progress monitoring in treatment, and provision of metrological control. In fact, in the frame of practical implementation of optical methods, such as laser Doppler flowmetry (LDF), the qualitative interpretation and quantitative assessment of the detected signal remains vital and urgently required. In the conventional LDF approach, the key measured parameters, index of microcirculation and perfusion rate, are proportional to an averaged concentration of red blood cells (RBC) and their average velocity within a diagnostic volume. These quantities compose mixed signals from different vascular beds with a range of blood flow velocities and are typically expressed in relative units. In the current paper we introduce a new signal processing approach for the decomposition of LDF power spectra in terms of ranging blood flow distribution by frequency series. The developed approach was validated in standard occlusion tests conducted on healthy volunteers, and applied to investigate the influence of local pressure rendered by a probe on the surface of the skin. Finally, in limited clinical trials, we demonstrate that the approach can significantly improve the diagnostic accuracy of detection of microvascular changes in the skin of the feet in patients with Diabetes Mellitus type 2, as well as age-specific changes. The results obtained show that the developed approach of LDF signal decomposition provides essential new information about blood flow and blood microcirculation and has great potential in the diagnosis of vascular complications associated with various diseases.

Oral Glucose Load and Human Cutaneous Microcirculation: An Insight into Flowmotion Assessed by Wavelet Transform.

Simple SummaryThere is increasing evidence to suggest that microcirculation becomes dysfunctional earlier than large blood vessels or the heart in several diseases. In diabetes mellitus, a disease characterized by chronic hyperglycemia, microvascular impairment is well-established; on the contrary, the effect of acute hyperglycemia in microcirculation remains unclarified. Our aim was to investigate the microvascular effect of an oral glucose load (OGL) using laser Doppler flowmetry (LDF) as a perfusion quantification technique, coupled with wavelet transform (WT) to perform a spectral decomposition of the LDF signal. On two distinct occasions (pre-load and post-load), sixteen healthy subjects drank either a standard glucose solution or water. Perfusion was assessed by LDF and WT while resting and during post-occlusive reactive hyperemia (PORH), evoked by a transient three-min occlusion of the brachial artery, in the forearm and the finger pulp. The OGL affected microcirculation in both sites compared to water, significantly blunting the PORH response in the forearm. The WT revealed significant differences in the cardiac and sympathetic components after OGL between the pre-load and post-load periods. These results suggest that an OGL induces a short-term subtle microvascular impairment, probably involving a modulation of the sympathetic nervous system.Microcirculation in vivo has been assessed using non-invasive technologies such as laser Doppler flowmetry (LDF). In contrast to chronic hyperglycemia, known to induce microvascular dysfunction, the effects of short-term elevations in blood glucose on microcirculation are controversial. We aimed to assess the impact of an oral glucose load (OGL) on the cutaneous microcirculation of healthy subjects, quantified by LDF and coupled with wavelet transform (WT) as an interpretation tool. On two separate occasions, sixteen subjects drank either a glucose solution (75 g in 250 mL water) or water (equal volume). LDF signals were obtained in two anatomical sites (forearm and finger pulp) before and after each load (pre-load and post-load, respectively), in resting conditions and during post-occlusive reactive hyperemia (PORH). The WT allowed decomposition of the LDF signals into their spectral components (cardiac, respiratory, myogenic, sympathetic, endothelial NO-dependent). The OGL blunted the PORH response in the forearm, which was not observed with the water load. Significant differences were found for the cardiac and sympathetic components in the glucose and water groups between the pre-load and post-load periods. These results suggest that an OGL induces a short-term subtle microvascular impairment, probably involving a modulation of the sympathetic nervous system.

MO640LASER DOPPLER FLOWMETRY IN STUDYING OF MICROVASCULAR DISORDERS IN PATIENTS WITH DIABETIC NEPHROPATHY

Abstract Background and Aims According to various research, vascular complications of type 2 diabetes mellitus are the main reason for patients' mortality. The most specific one, observed in patients with diabetes only, is diabetic microangiopathy, especially diabetic nephropathy. This complication accounts for more than 20% of cases of chronic kidney disease. So, the development of non-invasive methods for the diagnosis of vascular complications of type 2 diabetes mellitus is critically important. There is a perspective method for this problem - Laser Doppler flowmetry (LDF). It is currently used in the diagnosis of diabetic microangiopathy, but the limiting factor is the lack of a unified algorithmic approach to the data interpretation. This work aimed to analyze changes in the amplitude indicators of the low-frequency part of the LDF signal spectrum in patients with chronic kidney disease and type 2 diabetes and to identify their correlations with the glomerular filtration rate. Method The study included 42 patients (20 men and 22 women) with type 2 diabetes mellitus chronic kidney disease (stage C3-C4). The age of patients was 58-77 years (66 years on average). The duration of diabetes was more than 5 years (on average 7 years). All patients had diabetic nephropathy with a decrease in glomerular filtration rate, chronic kidney disease stage C3-C4. Laser Doppler flowmetry was done using the "LAZMA MC-1" system ("Lazma", Russia). Each patient had a 10-minute LDF registration. The sensor was placed on the skin of the rear of the foot. After recording the LDF curve, the special software has calculated amplitudes of endothelial, myogenic, neurogenic, respiratory, and pulse flux motions. Then we assessed the amplitude contribution of every frequency range to the total power of the local flux motion region. The next step was a correlation analysis with the estimated glomerular filtration rate. For statistical analysis, we used the GraphPad Prism 8 (GraphPad Software, USA). Results All examined patients had amplitude peaks in the neurogenic, myogenic, respiratory, and pulse ranges. There were no significant correlations between the glomerular filtration rate and the amplitudes of myogenic and neurogenic flux motions (p>0.05) (Fig. 1). However, there was a significant positive correlation between the contribution of myogenic flux motions to the low-frequency range and glomerular filtration rate (p<0.01), and a negative one – for the contribution of neurogenic flux motions (p<0.01) (Fig. 2). In six observations there was a tendency to a decrease in the contribution of endothelial flux motions as the glomerular filtration rate decreased. Conclusion The results of this study showed that laser Doppler flowmetry has the potential to diagnosis the nature of the dysfunction of individual microcirculation modulation mechanisms. In patients with chronic kidney disease of the C3-C4 stage decreasing the glomerular filtration rate correlated with decreasing the contribution of myogenic flux motions and increasing the contribution of neurogenic flux motions to the total power of the low-frequency part of the LDF signal amplitude-frequency spectrum. These changes can be explained within the framework of the existing understanding of the pathogenesis of diabetic microangiopathy, namely, damage to the smooth muscle layer of the wall of arterioles and venules with damage to myocyte pacemakers and changes of basal vascular tone pattern. It causes an increase in the role of neurogenic modulation of the micro-vascular bloodstream. These data can be an additional argument in favor of the further development of improving laser Doppler flowmetry using for the tasks of early (preclinical) non-invasive diagnosis of microvascular disorders in patients with type 2 diabetes mellitus, as well as for monitoring the effectiveness of the therapy. The reported study was funded by RFBR, project number 19-315-90080.

Synchronized research on endothelial dysfunction and microcirculation structure in dorsal skin of rats with type 2 diabetes mellitus.

The aim of this study was to explore changes in the microvascular tone as measured by laser Doppler flowmetry (LDF) and the microcirculation structure of the dorsal skin of rats with type 2 diabetes mellitus. The diabetic rat model was induced by a diet of high-sugar and high-lipid fodder combined with the injection of streptozotocin into the abdominal cavity. Depending on the interval between the development of diabetes and the experiments, the diabetic rats were subdivided into three groups. The evaluation of microvascular tone was based on the amplitude responses of the LDF signal fluctuations in the appropriate frequency range in the dorsal skin of the rats during a thermal test (at 42°C). The nitric oxide (NO) level in plasma was also used as a marker of endothelial dysfunction. Changes in the microcirculation structure in the diabetic rats were estimated by measuring the microvascular density in the choke vessels of the dorsal skin of the rats. The experimental results with respect to red blood cell (RBC)-related parameters showed decreased hematocrit and hemoglobin levels and increased standard deviation of the width of the RBC distribution in three diabetic rats. The increasing fluctuation amplitudes diminished in the endothelial frequency range in response to the thermal test and this was accompanied by abnormal NO levels in plasma of the diabetic groups as compared with healthy rats. A significant reduction in the microvascular density of the choke vessels of the dorsal skin was found only in the diabetic group at the most advanced stage of diabetes in this experiment. Thus, we suggest that endothelial dysfunction occurs in diabetic rats and changes in the microcirculation structure of the dorsal skin occur in a later stage of diabetes development. A. Photograph of measurement method by using a LDF probe and heating device in the dorsal skin of the rat. B. Dorsal skin LDF signals of a healthy rat during the thermal stimuli test. (a) Blood flow signal record for the test. Wavelet filtration of blood flow signal in (b) myogenic range, (c) neurogenic range, and (d) endothelial range.

Optical incoherent technique for noninvasive assessment of blood flow in tissues: Theoretical model and experimental study.

Laser noninvasive methods for assessment of a tissue blood flow (BF), for example, the Laser Doppler Flowmetry (LDF), are well-known today. However, in such methods, low-frequency fluctuations (LFFs) in the registered optical signal caused by blood volume changes inside a tissue have not been studied in details until now. The aim of this study is to investigate the LFFs formation and to justify the LFFs-based diagnostic technique for cutaneous BF assessment. LFFs are theoretically described and experimentally shown in the input LDF signal inside the frequency range 0 to 10 Hz. They are substantiated as the basis of the new diagnostic method, in which BF is defined as the magnitude of blood volume changes in a tissue per unit time. The hand-made prototype of the promising diagnostic tool with light emitted diodes is used to validate the technique in experiments in vivo on 16 healthy volunteers in comparison with the LDF method. Experimental results show a good similarity of the recorded BF for both coherent and incoherent method. The proposed technique makes it possible the creation of inexpensive diagnostic equipment for assessment of cutaneous BF without using lasers and coherent light, completely and functionally comparable to LDF devices.

Wearable Laser Doppler Flowmetry Sensor: A Feasibility Study with Smoker and Non-Smoker Volunteers.

Novel, non-invasive wearable laser Doppler flowmetry (LDF) devices measure real-time blood circulation of the left middle fingertip and the topside of the wrist of the left hand. The LDF signals are simultaneously recorded for fingertip and wrist. The amplitude of blood flow signals and wavelet analysis of the signal are used for the analysis of blood perfusion parameters. The aim of this pilot study is to validate the accuracy of blood circulation measurements recorded by one such non-invasive wearable LDF device for healthy young non-smokers and smokers. This study reveals a higher level of blood perfusion in the non-smoker group compared to the smoker group and vice-versa for the variation of pulse frequency. This result can be useful to assess the sensitivity of the wearable LDF sensor in determining the effect of nicotine for smokers as compared to non-smokers and also the blood microcirculation in smokers with different pathologies.

PULSE-WAVEFORM AND LASER-DOPPLER INDICES FOR IDENTIFYING COLORECTAL-CANCER PATIENTS

This study aimed to determine the effectiveness of using noninvasive arterial pulse-wave and laser-Doppler flowmetry (LDF) measurements to discriminate between colorectal-cancer (CC) patients and healthy control subjects. Radial-artery blood pressure waveform (BPW), finger photoplethysmography (PPG), and skin-surface LDF signals were measured noninvasively in 12 CC patients and 25 control subjects. Beat-to-beat, spectral, and variability analyses were applied to 20-minute-long recorded signals. Significant intergroup differences were found. In BPW, [Formula: see text]–[Formula: see text] amplitude indices were significantly larger while [Formula: see text]–[Formula: see text] phase-angle indices were significantly smaller in the CC patients than in the controls. The PPG and LDF variability indices were significantly larger and smaller, respectively, in CC patients. The relative energy contributions of the endothelial-, neural-, and myogenic-related frequency bands in LDF were significantly smaller in CC patients. The present findings indicate that pulse and LDF waveform analysis can be used to evaluate the arterial pulse-wave transmission condition, the responses of the blood-flow perfusion, and its regulatory activities in CC patients. There could be some similarities and differences in the present indices for different types of cancer. These findings could be utilized in the development of a rapid, noninvasive, and objective technique for evaluating the CC-induced blood-flow responses.

Synchronous Changes in Microcirculation Parameters of the Upper Limbs in Asymmetric Physical Loads

This is the first study on synchronous changes in microcirculation in the symmetrical organs of humans during asymmetric physical loads of the upper limbs. The study was conducted in healthy volunteers by the method of laser Doppler flowmetry (LDF). LDF signal transducers were fixed symmetrically on the lower parts of the right and left shoulders (3 cm above the elbow bend). Physical loads included the left or right arm swings in standing position for 1 min. Measurements were made in three states: (1) initial state, (2) immediately after physical activity, and (3) 5 min after loads. The changes in the mean perfusion value and the components of amplitude-frequency spectrum of blood flow fluctuations (myogenic, neurogenic, respiratory, and cardiac) were evaluated in both sides of the body. We observed the asymmetry of changes in microcirculation parameters after physical loads. It is shown that both left and right swings change the microcirculation parameters of both the left and right sides, and the changes on the left are more pronounced than on the right. A nonlinear relationship was observed between the changes in microcirculation parameters of symmetrical areas of paired organs and heart rate. Our data illustrate the specific regulation patterns of microcirculation blood flow in paired organs, which is associated with functional asymmetry. The physiological mechanisms of this asymmetry require further experimental and clinical research.

Minimizing the duration of laser Doppler flowmetry recordings while maintaining wavelet analysis quality: A methodological study

Recording oscillations in cutaneous blood perfusion using laser Doppler flowmetry (LDF) is of common use in clinical research, due, mainly, to its non-invasive nature. Detailed information about the vascular tone in different frequency bands and the related physiologic compartment can be inferred from wavelet analysis (WA) of an LDF signal. However, little is known about the minimal recording duration required to generate a proper representation of the frequency content of such signals. To address this question, the three lowest frequency bands (i.e. myogenic, neurogenic and endothelial) of the LDF wavelet power spectrum were studied to define the shortest recording duration needed to perform a quality WA. Sixty-five healthy participants were included for 20 min of basal LDF recording on forearm and dorsum of the foot. Recordings were short cut every minute and compared to the 20-min reference recording that is generally used in the literature.Our results indicate that minimum 10 min recordings are required for analysis of myogenic events, whatever the anatomical site. On the forearm, LDF recordings lengths should be at least 15 min and 10 min for the neurogenic and endothelial bands, respectively. On the foot, 13 min of LDF recording is required to assess neurogenic and endothelial bands.Depending on the aim of any given study involving healthy subjects, LDF recordings need to last at least 15 min on forearm and 13 min on the foot to maintain a quality WA on low-frequency bands.

Wavelet Analysis of Microcirculatory Flowmotion Reveals Cardiovascular Regulatory Mechanisms–Data from a Beta-Blocker

A variety of animal models exist for the study of cardiovascular function using many approaches from surgically induced ischemia to genetic manipulation. A murine physiological model was recently proposed for the non-invasive study of peripheral circulation and was strengthened by the wavelet transform analysis (WA) of laser Doppler flowmetry (LDF) signals. WA allows the extraction of cardiac, respiratory, sympathetic, endothelial, and myogenic components from the raw LDF signal. The present study was designed to evaluate the discernment capacity of the model through an analysis of the short-term effects of the well-known hypotensive cardiovascular drug, atenolol. Six male C57/BL6 mice (16 weeks old) were included in the study, with each animal serving as its own control. Following anesthesia with ketamine-xylazine, skin perfusions were continuously assessed in both hindlimbs by LDF during baseline and after two sequential atenolol administrations (2.5 and 5.0 mg/kg, as commonly prescribed). Expected atenolol-induced hypotension was present, associated with a significantly increased heart rate and peripheral perfusion with both dosages. Through the application of WA to the LDF signal, we could detail the mechanisms of the atenolol-induced peripheral perfusion modulation: an immediate amplitude decrease of the cardiac LDF spectrum with an amplitude increase of the sympathetic component (p < 0.05) and the endothelial and myogenic components (non-significant). These data suggested a regulatory crosstalk between the peripheral (baroreceptors) and the microcirculatory units, which ultimately resulted in hypotension, inotropic reduction, and tachycardia. In conclusion, WA offered insight that simply could not be seen with only the perfusion curve and, thus, was an effective tool to investigate this cardiovascular mechanism of regulation.

Stable laser-Doppler flow-motion patterns in the human cutaneous microcirculation: Implications for prospective geroscience studies.

Microvascular function has been assessed by determining the rhythmic oscillations in blood flow induced by the vasomotion of resistance vessels. Although laser-Doppler flowmetry (LDF) allows simple, non-invasive evaluation of this flow-motion in the cutaneous microcirculation, the temporal and spatial reproducibility of such assessments remains unclear.In the present study, we investigated cutaneous flow-motion in three consecutive years in eight skin regions using LDF in six healthy young volunteers. The characteristic flow-motion frequency was determined using fast-Fourier transformation. Additionally, in two years a more traditional measure of microvascular reactivity, postocclusive reactive hyperemia (PORH) was evoked in the forearm after transient brachial artery occlusion (1-2-3 min) induced by cuff inflation.Well-defined flow-motion was found in six regions showing significant differences in frequency: the highest flow-motion frequency was found in the frontal and temporal regions (8.0 ± 1.1 and 8.5 ± 1.0 cycles/min, cpm, respectively, mean ± SD) followed by the scapular, infraclavicular and coxal regions (7.5 ± 1.3; 6.7 ± 1.1 and 6.5 ± 1.2 cpm, respectively). The lowest, stable flow-motion was found in the posterior femoral region (5.5 ± 1.0 cpm), whereas flow-motion was detectable only sporadically in the limbs. The region-dependent flow-motion frequencies were very stable within individuals either between the body sides, or among the three measurements, only the infraclavicular region showed a small difference (114 ± 17%∗, % of value in 1st year; ∗P < 0.05). However, PORH indices differed after 2-3 min occlusions significantly in consecutive years.We report that flow-motion frequencies determined from LDF signals show both region-specificity and excellent intra-individual temporal and spatial reproducibility suggesting their usefulness for non-invasive follow-up of microvascular reactivity.

Effect of Aging and Carotid Atherosclerosis on Multifractality of Dental Pulp Blood Flow Oscillations

IntroductionAge-related changes of dental pulp tissue and atherosclerosis of carotid arteries as its feeding arteries could influence the functionality of pulpal circulation. The objective of our study was to evaluate the effect of aging (physiological process) and carotid bifurcation atherosclerosis (pathologic process) on the pulpal microcirculatory system using multifractal analysis of the laser Doppler flowmetry signal. MethodsThree groups of 10 subjects were enrolled in the study: the young group (healthy subjects, 20–25 years), the middle-aged group (healthy subjects, 50–60 years), and the clinical group (subjects with carotid bifurcation atherosclerosis, 50–60 years). Pulpal blood flow (PBF) signals recorded by laser Doppler flowmetry were assessed by multifractal analysis that estimates Hölder exponents of the signal. PBF levels, the average mean values, and the range of Hölder exponents were obtained. ResultsPBF levels were significantly higher in the young group compared with the middle-aged and clinical groups, and the difference between the middle-aged and clinical groups was not statistically significant. The range of the Hölder exponents was narrower in the middle-aged and clinical groups than in the young group and narrower in the clinical group than in the middle-aged group. The average mean value of Hölder exponents was significantly higher in the young group than in the middle-aged and clinical groups, whereas there was no significant difference between the middle-aged and clinical groups. ConclusionsOur study investigating the multifractality of the PBF signal showed that the aging process and carotid atherosclerosis could affect the complex structure of PBF oscillations and contribute to a better understanding of pulpal hemodynamics.

МЕТОД ОЦЕНКИ АДАПТИВНЫХ ИЗМЕНЕНИЙ В МИКРОЦИРКУЛЯТОРНО-ТКАНЕВЫХ СИСТЕМАХ ОРГАНИЗМА ЧЕЛОВЕКА

The work is aimed at developing a new approach to assessing adaptive changes in microcirculatory tissue systems when various loads are exerted on the body (sports or physiological stresses), based on the analysis of oscillations in microcirculatory blood flow and tissue oxygen saturation, measured by laser Doppler flowmetry (LDF) and tissue reflectance oximetry (TRO). The study involved eight healthy volunteers aged 21–49 years. Measurements were taken on the palmar surface of the middle finger of the right hand and the medial surface of the lower part of the forearm. The rhythmic oscillations of LDF and TRO were studied using wavelet analysis. Data analysis revealed resonant and synchronized oscillations in the LDF and TRO signals in the myogenic range as an adaptive change as a result of a reaction to physical activity and psychoemotional stress.