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Background and Objectives: Due to the development of methods for analyzing signals of autonomous blood circulation control, cardiovascular system disorders can be diagnosed today in the early stages. It is promising to use specialized devices for personalized diagnosis of the cardiovascular system and monitoring its state. Research on autonomous blood circulation control systems is a complex problem both from the point of view of physiology and radiophysics. Its solution requires the development of methods and specialized devices for the analysis and registration of signals from the cardiovascular system. Therefore the object of research is the development of a photoplethysmogram sensor with a digital communication channel with a band of 0.05-30 Hz, recording the signals from the autonomous blood circulation monitoring system. Materials and Methods: To compare the level of noise and nonlinear distortions in the center of the frequency range of interest to us (at a frequency of 0.1 Hz), the power spectra of the signals were analyzed, and the coherence function was also calculated. Results: a prototype of a device for recording and analyzing a photoplethysmogram signal was developed and implemented, which makes it possible to register the signals from the circuits of autonomous blood circulation regulation. A comparative analysis of the developed device with a serial analog sensor was carried out, which demonstrated the advantages of the developed device. Conclusion: The developed broadband digital sensor can be used in wearable devices to diagnose the functional state of the cardiovascular system based on the analysis of synchronization between the circuits of autonomous regulation of blood circulation.

Background ― Effective treatment of melanoma is only possible during the early stages of the disease. However, current techniques of cancer diagnostics are not sensitive enough to be reliable during the early stages. Photoacoustic cytometry provides a very perspective method for early diagnostics, which, in principle, can detect even a single melanoma circulating melanoma cell. However, the photoacoustic monitoring system needs to be paired with an effective automated algorithm, which will detect acoustic responses from melanoma cells among normal blood cells. Objective ― The study aims to compare the currently adopted algorithm for the detection of circulating melanoma cells based on a calculation of the standard deviation of the acoustic responses with the new model-based algorithm. Methods ― We tested and compared two different methods of automated detection of melanoma acoustic responses. The first approach was based on a calculation of the deviation of the acoustic responses. The second approach was based on the subtraction of the ensemble average normal acoustic response from melanoma acoustic responses. The resulting differential signals contained positive spikes, which were detected. Results ― The model-based approach demonstrated better sensitivity and specificity when detecting circulating melanoma cells in comparison to the approach based on the calculation of standard deviation of the acoustic responses. Conclusions ― Obtained results suggest that the model-based approach is a more reliable basis for an automated algorithm for the detection of circulating melanoma cells. The model-based approach has an additional advantage of being simpler to calculate and requires less computational power to run in real-time.

The work aims to carry out a comparative analysis of the spectral indices of the photoplethysmogram signals and RR-intervals of healthy volunteers, patients with COVID-19, as well as patients with COVID-19 and chronic arterial hypertension of 1-2 degrees. The study included 45 records of pairs of electrocardiogram and photoplethysmogram signals. Each sample included 15 pairs of 20-minute experimental signals. The study revealed an increase in the integrated power of the low-frequency (LF) band over the integrated power of the high-frequency (HF) band in the photoplethysmogram signals in patients with COVID-19, burdened with hypertension. In the signals of the RR-intervals, the largest values of the ratio of the LF to HF indices are associated with patients without cardiovascular diseases. In turn, this may be an indicator of the different effects of viral infection and arterial hypertension on the loops of autonomic control of heart rate and vascular tone.

This study aims to investigate the strength of synchronization between the autonomic control loops of the cardiovascular system (CVS) in patients with COronaVIrus Disease 2019 (COVID-19). Methods — We calculated the total percent of phase synchronization index (S index) between the loops of autonomic control of heart rate and vascular tone in two sample groups: healthy individuals and COVID-19 patients. Results — The group-average value of the S index in COVID-19 patients is lower comparing to healthy individuals, the Mann-Whitney U-test confirmed that the differences are statistically significant. Conclusion — Obtained results suggest that the decreased value of the S index reflects the presence of a viral disease, and the S index is a promising basis for non-invasive screening diagnostics of viral diseases, particularly of COVID-19.

This work aims to analyze the coupling between autonomic control loops of blood circulation in patients with Covid-19. In this work, we assessed the degree of coupling between the mechanisms of autonomic control using noninvasive signals of the cardiovascular system - RR-intervals signals and photoplethysmogram signals. Statistical evaluation of the study results using the methods of phase synchronization analysis did not reveal significant differences between the VDPSOH RI SDWLHQWV ZLWK ɋRYLG-19 and healthy subjects of the corresponding age group.

this study presents the results of the spectral analysis of the photoplethysmographic signals obtained from the healthy subjects and the patients with early pre-clinical stages of arterial hypertension, coronary artery disease, and aortic valve stenosis patients. The normalized power density of the low-frequency (LF%) oscillations is significantly higher in the cardiovascular patients, while the normalized power density of the high-frequency (HF%) oscillations and the LF/HF ratio are significantly lower in comparison to the healthy subjects. Aging had no significant effect on the spectral indexes. It was shown that the spectral analysis of the photoplethysmographic signals can be used to diagnose the dysfunction of the autonomic control even at early pre-clinical stages of cardiovascular diseases.

This study examines missing value imputation in the Russian Acute Coronary Syndrome Registry (RusACSR) and assessment of the probability of predicting mortality. Linear methods with the most probable or average value were used for imputation. The prediction problem was solved using the k-nearest neighbors method. This work reveals that the imputation method, despite their simplicity, increases the probability of prediction of mortality by 6%.

The goal of our study was to investigate gender-related specificities of photoplethysmogram (PPG) spectral assessment dynamics in healthy individuals during the passive tilt test. Material and Methods — The study involved 38 men (33±7 years old) and 15 women (27±8 years old). The PPG signal was recorded for 10 minutes in the horizontal and vertical positions of the human body (passive tilt test). The following spectral parameters of PPG were calculated: HF%, LF%, and LF/HF. Results — In the horizontal body position, men had significantly higher values of the LF% index. In the course of the passive tilt test, an increase in HF% was observed by almost 1.5 times in men and by more than 5 times in women. Significant differences in the values of vegetative indicators were achieved: in women, HF% values exceeded those in men, while LF% values were noticeably lower. Conclusion — Men displayed signs (assessed by LF%) of augmented sympathetic activity, relative to women, at all stages of their passive tilt test. During the transition from the horizontal to the vertical position, a significant increase in respiratory influences (assessed by HF%) on PPG signal components was established, which was more pronounced in women.

The purpose of this work is to study the interaction between the autonomic regulatory loops of blood circulation from long time series. Methods ― We simultaneously recorded four-hour signals of electrocardiogram and photoplethysmogram from the ear and finger of ten healthy adults. We determined the intervals of phase synchronization of the studied regulatory loops and analyzed the dependence of their length on the recording time. The deviations of the total percentage of phase synchronization (index S) from its mean value were estimated in moving non-overlapping windows. Results ― For studied signals we found no significant correlation between the length of synchronization epoch and the time of its beginning. A sharp increase in the deviation of the index S from its mean was shown at the end of the experiment. Conclusion ― The increase in the deviation from the mean at the end of our records is most likely associated more with psychosomatic influences than with hormonal regulation or immobilization stress.

Objective: In this work, the development of the features of an autonomic system of blood circulatory regulation from the period of late prematurity to full-term infants is investigated using the example of signals of the photoplethysmogram of blood vessels, electrocardiogram, and respiration. The previous works of foreign and domestic authors show that interdependency between physiological rhythms emerges early in development. Much attention was paid to the study of cardiorespiratory coupling and his development in newborns, nevertheless, there are still many questions in this area. In this study, in addition to studying the standard low-frequency cardiorespiratory effect, we studied the relationships between the low-frequency components of the autonomic regulation of heart rate (using an electrocardiogram) and the tone of the arterial vessels (using photoplethysmogram of blood vessels).Approach: The goal of the work is to estimate the dynamics of the development of the coupling of the autonomic regulatory circuits of the cardiovascular system and respiratory system. In this paper, special attention is paid to the study of phase synchronization of these processes, as well as to the interaction of frequency components. We studied the coherence between heart rate variability, photoplethysmograms of blood vessels, and respiration signals of newborns with a gestational age of 30 weeks to 40 weeks.Main results: No significant changes in the measure of the estimation of phase synchronization with increases in the gestational age of the infant were found. The reason may be a notable change in the degree of connectedness of the studied systems after birth. There was also an assumption about the presence of changes in the direction of connectedness, but not in its strength.Significance: This study carries a fundamental interest - an understanding of the higher risk for negative results at the end of a premature population. Moreover, the continuation of work in this direction may allow creating a tool for the development of early markers of impaired autonomic regulation of the functions of the cardiovascular system and respiration in young children.

Background ― The treatment of the cancer, especially in more aggressive metastatic forms is more effective at early disease stage. However, existing diagnostic techniques are not sensitive enough for early cancer detection. An alternative, perspective diagnostic approach can be based on photoacoustic (PA) method of irradiation of cancer cells in biotissue, blood and lymph by laser pulses. The fast thermal expansion of heated zones into cells associated with intrinsic or artificial PA contrast agents leads to generation of acoustic waves detected with ultrasound transducers. In particular, melanoma cells with melanin as a PA marker are darker than normal red blood cells and, therefore, produce greater acoustic responses. This technique can theoretically detect even a single cancer cell in the tissue and blood background; however, a robust algorithm of automated response detection is yet to be developed. Objective ― The main aim is to develop the approach for data pre-analysis that can improve the sensitivity and noise resistance of the automated in individual cancer cell detection algorithm, based on estimation of the amplitude of the acoustic responses. Methods ― Acoustic responses were obtained from a round polyurethane tube with human blood, or solution of the mouse melanoma cells in 10 mol/L concentration. In control experiments the laser was blocked by an opaque film. Many (up to 1000) acoustic responses were obtained from normal blood cells and pigmented cancer cells. Spectral analysis of the acoustic responses was used to find the spectral ranges that provide valuable diagnostic information with the sufficient signal-to-noise ratio. Results ― It was estimated that relevant diagnostics information in the acoustic responses is limited to the 0-12 MHz frequency band. Application of the 8th order low-pass Butterwort filter with 12 MHz cut-off frequency improved the signal-to-noise ratio from 21.14±10.39 to 110.81±56.94 for the cancer-related responses, and from 1.04±0.1 to 2.23±0.33 for the normal blood responses. Conclusions ― Adoption of low-pass filtering during the pre-analysis of acoustic responses results in better sensitivity of automated cancer cells detection algorithm.

We studied the properties of low-frequency (LF) heart rate variability (HRV) and photoplethysmographic waveform variability (PPGV) and their interaction under conditions where the hemodynamic connection between them is obviously absent, as well as the LF regulation of PPGV in the absence of heart function. The parameters of HRV and finger PPGV were evaluated in 10 patients during cardiac surgery under cardiopulmonary bypass (on-pump cardiac surgery) with or without cardioplegia. The following spectral indices of PPGV and HRV were ertimated: the total spectral power (TP), the high-frequency (HF) and the LF ranges of TP in percents (HF% and LF%), and the LF/HF ratio. We assessed also the index S of synchronization between the LF oscillations in finger photoplethysmogram (PPG) and heart rate (HR) signals. The analysis of directional couplings was carried out using the methods of phase dynamics modeling. It is shown that the mechanisms leading to the occurrence of oscillations in the LF range of PPGV are independent of the mechanisms causing oscillations in the LF range of HRV. At the same time, the both above-mentioned LF oscillations retain their activity under conditions of artificial blood circulation and cardioplegia (the latter case applies only to LF oscillations in PPG). In artificial blood circulation, there was a coupling from the LF oscillations in PPG to those in HR, whereas the coupling in the opposite direction was absent. The coupling from the LF oscillations in PPG to those in HR has probably a neurogenic nature, whereas the opposite coupling has a hemodynamic nature (due to cardiac output).

Introduction: The main problem in analyzing low-frequency components of biological processes is conducting specialized experiments with long-term signal recording. However, the information about the system behavior on long scales can make an invaluable contribution to understanding the nature of the interaction between separate elements of the system. Purpose: Analyzing the features of the dynamics of the proposed quantitative index which characterizes the degree of phase synchronization of complex non-stationary biological systems (contours of autonomic regulation of the cardiovascular system) on time scales about tens and hundreds of characteristic oscillation periods (hundreds of seconds) using long experimental records. Results: During the experiments, we obtained simultaneous registration of two-hour signals from 23 healthy subjects: cardiointervalogram and photoplethysmogram vessels. The dynamics of the total percentage of phase synchronization (S index) of 0.1 Hz oscillations in the PPG and CIG was estimated in sliding windows. Similarly, we investigated the powers of so-called low-frequency (LF, 0.1 Hz) and high-frequency (HF, > 0.1 Hz) components of the spectrum of the original signals. The features of the interaction between the studied indices were evaluated using correlation analysis methods. We have found that the S index dynamics shows signs of its oscillatory nature with a characteristic oscillation period about 1000 s. The interaction between LF and HF oscillations in the autonomic circulatory regulation is of a complex nonlinear character. We have also identified signs of oscillations with a period about 1000 s in the dependencies of the total percentage of the phase synchronization of 0.1 Hz contours in circulatory regulation. A structural model of the interaction between circulatory regulatory contours is formed which explains the observed effects. Practical relevance: Obtaining fundamental knowledge about the interaction and regulation of the cardiovascular system elements will allow us to improve the methods we are developing for the diagnostics and therapy of pathological disturbances in the cardiovascular system.

In this paper, we studied the features of the autonomic regulatory system of the heart rate and the tone of the arteries in newborns. During the experiment, we obtained 15 records of synchronous electrocardiograms and photoplethysmograms of newborns. A spectral analysis was conducted, the results of which revealed a number of features, including the presence of an LF peak at a lower frequency than is common in adult subjects. Based on these results, we have chosen new parameters to assess the degree of synchronization of the autonomic regulatory contours of the blood circulation in newborns, which contribute to the greater significance of the results.

We proposed a method of experimental observation of the Arnold tongues in the study of the synchronization of the contours of autonomic regulation of the heart rate with a characteristic frequency of about 0.1 Hz and respiration. The formulation of a special active experiment made it possible to determine the boundaries of synchronization tongues in 3 subjects. The method allows noninvasive research. The basic idea is to influence the contours of heart rate regulation with a respiratory signal, which has respiratory frequency varying linearly about 0.1 Hz according to the sound signal generated by a special device. The amplitude of the breath is changed by the subjects at the command of the researcher. The study is important for understanding the features of complex multichannel systems of biological nature and their mathematical modeling.

The paper is devoted to diagnostics of phase synchronization of the autonomic regulatory contours of blood circulation according to experimental data. Using the method of diagnostics of phase synchronization intervals of the cardiovascular system regulation processes we studied the statistical properties of quantitative estimates of synchronization, where special attention is paid to the choice of the length of the experimental signals.

Objective ― The purpose of this paper is to study statistical and dynamic properties of the low-frequency (LF) oscillation synchronization in the heart rate variability (HRV) and the finger photoplethysmographic waveform variability (PPGV) in time. Material and Methods ― Our study included 42 healthy men aged 19-21 years. The HRV and the finger PPGV were simultaneously recorded in all subjects during 7,200 seconds at rest. We extracted the LF oscillations in the HRV and the PPGV. To estimate this synchronization we used the method we suggested earlier. Index S was calculated as the relative time of synchronization between the considered LF oscillations. Results ― The sequence of the synchronization intervals between the LF oscillations behaves as a weakly correlated random process, demonstrating the 1/f distribution. However, the distribution of the index S, estimated even for 10-minute records, is close to normal. The results of estimating the S value from realizations of increasing length indicate that S tends to a fixed value with the increase of time series length. Conclusion ― For practical studies we recommend using the experimental records of ECG and PPG with the length of 10 minutes or more, which will provide a standard deviation of the S estimate less than 10%.

We compare the spectral indices of photoplethysmogram variability (PPGV) estimated using photoplethysmograms recorded from the earlobe and the middle fingers of the right and left hand and analyze their correlation with similar indices of heart rate variability (HRV) in 30 healthy subjects (26 men) aged 27 (25, 29) years (median with inter-quartile ranges) at rest and under the head-up tilt test. The following spectral indices of PPGV and HRV were compared: mean heart rate (HR), total spectral power (TP), high-frequency (HF) and low-frequency (LF) ranges of TP in percents (HF% and LF%), LF/HF ratio, and spectral coherence. We assess also the index S of synchronization between the LF oscillations in HRV and PPGV. The constancy of blood pressure (BP) and moderate increase of HR under the tilt test indicate the presence of fast processes of cardiovascular adaptation with the increase of the sympathetic activity in studied healthy subjects. The impact of respiration on the PPGV spectrum (accessed by HF%) is less than on the HRV spectrum. It is shown that the proportion of sympathetic vascular activity (accessed by LF%) is constant in the PPGV of three analyzed PPGs during the tilt test. The PPGV for the ear PPG was less vulnerable to breathing influence accessed by HF% (independently from body position) than for PPGs from fingers. We reveal the increase of index S under the tilt test indicating the activation of interaction between the heart and distal vessels. The PPGV spectra for finger PPGs from different hands are highly coherent, but differ substantially from the PPGV spectrum for the ear PPG. We conclude that joint analysis of frequency components of PPGV (for the earlobe and finger PPGs of both hands) and HRV and assessment of their synchronization provide additional information about cardiovascular autonomic control.