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The feasibility of assessing the parameters of cerebral hemodynamics without skull trepanation using imaging photoplethysmography with illumination in the near-infrared spectrum range was demonstrated for the first time. The results were obtained when studying changes in blood flow in the rat brain in response to short-term respiratory failure (apnea test). Translation of the results into clinical practice will be useful for the development of a method for non-invasive assessment of cerebral blood flow in patients with cerebrovascular diseases.

Compared to the conventional finger photoplethysmography (PPG) sensor that is widely used in clinical practice to assess arterial blood oxygen saturation and heart rate, an imaging PPG (IPPG) system can remotely provide multiple contactless measurements across large areas of the body to give valuable vascular and cardiovascular information. The IPPG technique is noncontact and can be a low cost and easy to use tool for medical diagnostics as well as in biological-medical research of the cardiovascular system. The technology and optical modeling relating to this technique continue to be developed, but already IPPG can provide potentially useful information for investigating a number of clinical and physiological conditions. In this chapter, we will overview a range of different IPPG applications, particularly beyond the standard PPG assessment of pulse oximetry, and the monitoring of heart and respiratory rates. These applications include the intraoperative monitoring of cerebral microcirculation, the visualization of skin capillary function across the body, assessing the circulatory-system reactivity in response to functional testing, evaluating the functional reserve of cerebral and musculocutaneous vessels, instrumental identification of scleroderma, and the contactless assessment of endothelial function.

Purpose. Comprehensive study of autonomic regulation assessed during follow-up could provide new detailed information about the risks stratification for hypertensive patients. Therefore, we investigated the associations of these indices with death, stroke, and revascularization during the follow-up observation of 55 patients. Methods. All patients were with target organ damage, and 27 of them had associated clinical conditions (ACC). Mean age of patients with and without ACC was 62.6 ± 4.2 and 51.9 ± 9.9 (mean ± SD) years, respectively. Follow-up was from 66 to 95 months. At entry, autonomic regulation was assessed by the tilt test, Valsalva maneuver, hand-grip test, and cold-stress vasoconstriction. Hemodynamic parameters were measured by continuous blood pressure monitoring, occlusion plethysmography, and electrocardiography. Re-examination of patients was carried out by questioning and physical and laboratory examination. Results. We found that fatal outcomes were associated with a lower Valsalva index (1.34 ± 0.16 vs. 1.69 ± 0.37, P<0.05) and depressed cold vasoconstriction (0.20 ± 0.02 vs. 0.39 ± 0.16%, P<0.05) but with higher peripheral resistance (1.36 ± 0.19 vs. 0.89 ± 0.25, P<0.001) and respiratory-range blood pressure variability (BPV) (18.2 ± 14.2 vs. 6.2 ± 4.2 mmHg, P<0.001). Higher total-range BPV (103 ± 51 vs. 65 ± 45 mmHg, P<0.05) in patients who had a stroke was observed. Initial diastolic orthostatic hypertension (6.6 ± 10.8 vs. 0.4 ± 6.3 mmHg, P<0.05) and lower Valsalva index (1.36 ± 0.11 vs. 1.82 ± 0.37, P<0.05) in patients who suffered a new ACC were important findings as well. Conclusions. This study shows that such autonomic regulation indices as Valsalva index, blood pressure dynamics in the tilt test, cold-stress vasomotor reactivity, and BPV are important for prognosis of hypertension course.

Assessment of the cerebral blood-flow-reserve in patients with cerebrovascular diseases is extremely important in terms of making prognosis, determining treatment tactics, and controlling the revascularization outcome in the case of reconstructive interventions on the brain vessels. However, there is no easy-to-use, contactless method for either assessing the functional reserve of the cortical vascular network or intraoperative monitoring of surgical intervention. Our study aims to demonstrate feasibility of green-light imaging photoplethysmography (iPPG) to estimate cerebrovascular functional reserve in animal model of craniosurgical intervention. Custom-made iPPG system was exploited to visualize intracranial vessels in anesthetized Wistar rats (n = 15). Video frames of rat’s cortex were recorded concurrently with systemic blood pressure, end-tidal CO2, and electrocardiogram. We found that injection of dorzolamide (carbonic-anhydrase inhibitor) significantly increased the blood-pulsations amplitude in all animals by 35 ± 19% (p 2 by 32 ± 7% (p

Objective: Instrumental identification of proximal scleroderma, which is necessary for the early diagnosis of systemic sclerosis (SSD), has not yet been developed. The aim of this study was to assess the potential diagnostic value of the imaging photoplethysmography (IPPG) method in patients with SSD. Approach: The study enrolled 19 patients with SSD and 21 healthy subjects matched by age and sex with the patients. Spatial distribution of capillary-blood-flow parameters and their dynamics was estimated in the facial area of patients and subjects. In the IPPG system, a 40 s video of the subject's face illuminated by green polarized light was recorded with a monochrome digital camera in synchronization with the electrocardiogram. Experimental data were processed using custom software allowing assessment of an arrival time of the blood pressure wave (PAT), an amplitude of pulsatile component (APC) of the photoplethysmographic (PPG) waveform, and their variability. Main results: Our study has revealed a significant increase in PAT variability in patients with SSD compared to the control group: 52 ± 47 ms vs 24 ± 13 ms (P =0.01). Similarly, the variability of the PPG-pulse shape was larger in patients with SSD: 0.13 ± 0.07% vs 0.09 ± 0.02% (P < 0.001). In addition, patients with scleroderma showed a significantly greater degree of asymmetry of the APC parameter than the control group: 17.7 ± 9.7 vs 7.9 ± 5.0 (P < 0.001). At the same time, no correlation was found between the PPG waveform parameters and either the form or duration of the disease. Also, no relationship between the characteristics of the PPG waveform and the modified Rodnan skin score was found. Significance: Novel instrumental markers found in our pilot study showed that the IPPG method can be used for diagnosing SSD in the early stages of the disease.

The laws governing blood pressure and heart rate coupling contain significant information about underlying physiological mechanisms of cardiovascular response to both internal and external stresses. Detailed investigation of these mechanisms requires a better understanding of the short-term physiological dynamics observed during orthostatic tilt test. Revealing characteristic profiles of tilt test responses could be essential for a variety of applications ranging from basic physiological studies to the differential diagnostics in patients with orthostatic disorders suffering from spontaneous syncope episodes of unknown etiology. Six different indicators of blood pressure versus heart rate coupling during both the entire tilt test procedure as well as its supine and orthostatic phases have been considered in this study. Empirical classification patterns indicate that several considered indices exhibit significant discrepancies between the test phases as well as between the patients and normal subjects involved in the study.

Assessment of the cerebral blood-flow-reserve in patients with cerebrovascular diseases is extremely important in terms of making prognosis, determining treatment tactics, and controlling the revascularization outcome in the case of reconstructive interventions on the brain vessels. However, there is no easy-to-use, contactless method for either assessing the functional reserve of the cortical vascular network or intraoperative monitoring of surgical intervention. Our study aims to demonstrate feasibility of green-light imaging photoplethysmography (iPPG) to estimate cerebrovascular functional reserve in animal model of craniosurgical intervention. Custom-made iPPG system was exploited to visualize intracranial vessels in anesthetized Wistar rats (n = 15). Video frames of rat's cortex were recorded concurrently with systemic blood pressure, end-tidal CO

The velocity of the pulse wave (PWV) propagating through the vascular tree is an essential parameter for diagnostic the state of the cardiovascular system especially when it is measured in the pool of carotid arteries. In this research, we showed for the first time that the time of the blood-pressure-wave propagation from the heart to the face is a function of the body position. Significant asymmetry and asynchronicity of blood pulsations in the facial area were found in a recumbent position. Parameters of blood pulsations were measured by an advanced camera-based photoplethysmography system in 73 apparently healthy subjects. Most likely, observed changes of the blood-pulsation parameters are caused by variations of the arterial blood pressure due to hydrostatic pressure changes, and secondary reaction of blood vessels in response to these variations. Demonstrated feasibility of PWV measurements in the pool of carotid arteries provides considerable advantages over other technologies. Moreover, possibilities of the method to estimate physiological regulation of the peripheral blood flow (particularly, as a response to the gravitational changes) have been demonstrated. The proposed concept allows development of non-invasive medical equipment capable of solving a wide range of scientific and practical problems related to vascular physiology.

Six different metrics of mutual coupling of simultaneously registered signals representing blood pressure and pulse interval dynamics have been considered. Stress test responses represented by the reaction of the recorded signals to the external input by tilting the body into the upright position have been studied. Additionally, to the conventional metrics like the joint signal coherence Coher and the sensitivity of the pulse intervals response to the blood pressure changes baroreflex sensitivity (BRS), also alternative indicators like the synchronization coefficient Sync and the time delay stability estimate TDS representing the temporal fractions of the analyzed signal records exhibiting rather synchronous dynamics have been determined. In contrast to BRS, that characterizes the intensity of the pulse intervals response to the blood pressure changes during observed feedback responses, both Sync and TDS likely indicate how often such responses are being activated in the first place. The results indicate that in most cases BRS is typically reciprocal to both Sync and TDS suggesting that low intensity of the feedback responses characterized by low BRS is rather compensated by their more frequent activation indicated by higher Sync and TDS. The proposed additional indicators could be complementary for the differential diagnostics of blood pressure regulation efficacy and also lead to a deeper insight into the involved concomitant factors this way also aiming at the improvement of the mathematical models representing the underlying feedback control mechanisms.

We suggest a complementary indicator of the blood pressure – heart rate feedback regulation based on their synchronization pattern assessed by Hilbert transform. We determine the synchronization coefficient Sync as the fraction of time fragments where the standard deviation of the differences between instantaneous phases of blood pressure and pulse intervals are below a certain threshold. While BRS characterizes the intensity of the pulse intervals response to the blood pressure changes during observed feedback responses, the Sync likely indicates how often such responses are activated in the first place. Data from 95 tilt test records indicate that in both healthy subjects and patients with moderate autonomic dysfunction BRS and Sync are typically reciprocal suggesting that low intensity of the feedback responses characterized by low BRS is rather compensated by their more frequent activation indicated by higher Sync. In contrast, in diabetes patients with autonomic neuropathy BRS and Sync are positively correlated likely indicating the breakdown of this compensation in some of the diabetic patients. Therefore we suggest that Sync could be used as an additional indicator of the blood pressure – heart rate feedback regulation activity that is complementary to the widely used baroreflex sensitivity (BRS).

Background The non-invasive biomarkers of migraine can help to develop the personalized medication of this disorder. In testing of the antimigraine drugs the capsaicin-induced skin redness with activated TRPV1 receptors in sensory neurons associated with the release of the migraine mediator CGRP has already been widely used. Methods Fourteen migraine patients (mean age 34.6 ± 10.2 years) and 14 healthy volunteers (mean age 29.9 ± 9.7 years) participated in the experiment. A new arrangement of imaging photoplethysmography recently developed by us was used here to discover novel sensitive parameters of dermal blood flow during capsaicin applications in migraine patients. Results Blood pulsation amplitude (BPA) observed as optical-intensity waveform varying synchronously with heartbeat was used for detailed exploration of microcirculatory perfusion induced by capsicum patch application. The BPA signals, once having appeared after certain latent period, were progressively rising until being saturated. Capsaicin-induced high BPA areas were distributed unevenly under the patch, forming “hot spots.” Interestingly the hot spots were much more variable in migraine patients than in the control group. In contrast to BPA, a slow component of waveforms related to the skin redness changed significantly less than BPA highlighting the latter parameter as the potential sensitive biomarker of capsaicin-induced activation of the blood flow. Thus, in migraine patients, there is a non-uniform (both in space and in time) reaction to capsaicin, resulting in highly variable openings of skin capillaries. Conclusion BPA dynamics measured by imaging photoplethysmography could serve as a novel sensitive non-invasive biomarker of migraine-associated changes in microcirculation.

Photoplethysmography (PPG) devices are widely used in clinical practice but the origin of PPG signal is still under debating. The classical theory assumes that the PPG waveform stems from variations of blood volume in pulsating arteries. In this research we analysed high-speed video recordings of capillaries in a fingernail bed. It was found that speed of erythrocytes in capillaries has pronounced modulation in time, which follows variations of instantaneous blood pressure in arteries. However, the mean speed significantly differs even for neighbour capillaries whereas change of the speed occurs in phase for the most of capillaries. Moreover, the light intensity remitted from the papillary dermis is also modulated at the heartbeat frequency displaying significant correlation with waveforms of the RBC speed. Obtained results can hardly be explained by the classical theory of PPG signal formation. Shallow penetrating visible light acquires modulation of erythrocytes density in the capillary bed without interacting with deeper situated pulsating arteries. Therefore, the capillary bed could serve as a distributed sensor for monitor the status of deep vessels. Better understanding of the photoplethysmography basis will result in a wider range of applications of this fast growing technology in both medical and research practice.

Velocity of the pulse wave propagation through the vascular system is an important diagnostic marker for various diseases such as hypertension, diabetes, and peripheral atherosclerosis. In this paper, the technique of measuring the pulse-wave propagation time to different parts of the body by means of non-contact optical method, which uses conventional video recording of a studied body's part illuminated by incoherent green light, is discussed. It allows us to measure spatial distribution of the pulse transit time from the heart to the human face with high spatial and temporal resolution. The algorithm of the video data processing is based on the recently proposed model of light interaction with human tissue. According to this model, the light intensity modulation at the heartbeat frequency arises from mechanical compression/decompression of the inter-capillary tissue caused by changes of the transmural arterial pressure. To support the new model of light interaction with living tissue we show several experimental observations. Mapping the pulse transit time opens new possibilities for visualization of the pulse wave propagation in different parts of the body in various physiological states and disease. Accurate measurements of the pulse wave parameters increases capability to assess local microcirculation regulation, which is very important for development of new efficient systems of early diagnosis of various diseases.

Context Migraine mechanisms remain largely uncovered for various reasons including a very high complexity of the neurophysiological mechanisms implicated in this disorder and a plethora of endogenous biologically active compounds involved in the pathological process. The functional role of parasympathetic innervation of meninges and cholinergic mechanisms of migraine are among little explored issues despite multiple evidence indirectly indicating the role of acetylcholine (ACh) and its analogues in migraine and other types of headache. In the current short review, we discuss morphological, functional, and clinical issues related to the role of ACh and its analogues such as carbachol and nicotine in this most common neurological disorder. Evidence acquisition In the present work, studies published from 1953 to 2016 were investigated. Literature was searched with following keywords: acetylcholine (ACh), carbachol, nicotine, parasympathetic, mast cells, vasoactive intestinal polypeptide (VIP), and pituitary adenylate cyclase-activating polypeptide (PACAP). Results Parasympathetic fibers originated from SPG and trigeminal nerves can interact at the level of meninges which is considered to be the origin site of migraine pain. Here, in dura mater, ACh, VIP, and PACAP released by parasympathetic afferents can both affect mast cells provoking its degranulation and additional release of neurotransmitters, or they can directly affect trigeminal nerves inducing nociception. Conclusions In summary, cholinergic mechanisms in migraine and other types of headache remain little elucidated and future studies should clarify the role of parasympathetic nerves and molecular mechanisms of cholinergic modulation within the nociceptive system.

Evaluation of skin microcirculation allows for the assessment of functional states for neuroendocrine and endothelial regulation. We present a novel method to visualize skin microvessels in any area of the body, which is in contrast to classical capillaroscopy, in which the application areas are limited to the nailfold and retina capillaries. The technique is based on microscopic video-image analysis. It exploits a specific feature of irregularity of red-blood-cells motion. Feasibility of the method is demonstrated by mapping the skin capillaries in the forearm and face of 11 healthy volunteers. The proposed method is promising for the quantitative assessment of cutaneous microcirculation in a wide range of diseases and functional states.

Recent studies indicate that migraine is associated with increased risk of cardiovascular diseases. However, links between autonomic cardiovascular regulation, arterial hypertension (AH) and migraine are still little explored. In this study, we evaluated autonomic regulation in migraine patients with and without hypertension. We studied 104 patients with migraine, aged 34±10 y, including 28 with and 76 without hypertension (M+AH and M-AH groups, respectively). The control group consisted of 88 healthy volunteers matched by age and sex. The autonomic regulation of circulation was examined with the tilt-table test, deep-breathing and Valsalva Maneuver, handgrip test, cold-stress induced vasoconstriction, arterial baroreflex, and blood pressure variability measurements. We found that migraine patients with concomitant hypertension demonstrated reduced arterial baroreflex, whereas other parameters of cardiac autonomic regulation were unchanged. In contrast, most indicators of vasomotor reactivity (blood pressure response to the hand-grip, Valsalva maneuver and cold vasoconstriction) were enhanced in migraine patients with no significant differences between migraine patients with and without hypertension. Patients from both M+AH and M-AH groups more commonly had a family history of cardiovascular disorders. Our data revealed increased vasomotor reactivity in migraine patients, with or without concomitant hypertension. This was associated with the family history of cardiovascular diseases.

We studied the mutual dynamics of systolic blood pressure and pulse intervals. We used two approaches to estimate their stability, based either of phase difference analysis or on time delay stability analysis. In the first approach, we determined the intervals where the time delay of the maximum of the absolute value of the cross-correlation function of two analyzed processes remains stable. In the second approach, we focused on the average correlation time of the phase differences of two processes as a measure of their time delay stability. The first method takes into account only the linear interaction of the processes while the second method represents more sophisticated mechanisms of their interaction. Our results indicate that moderate correlation between the stability coefficients obtained by two different approaches can be obtained. We have also shown that the stability coefficients differ significantly in healthy volunteers and in diabetic patients. We suggest that these stability measures might appear useful as complementary indicators of the efficacy of short-term blood pressure regulation.

We studied the dynamics of blood pressure and heart rate fluctuations during a head-up tilt testing in 127 patients and healthy individuals. To assess the regulation efficiency, in addition to the conventionally measured baroreflex sensitivity BRS, we also studied the stochastic phase synchronization coefficient Sync between short-term variations of the blood pressure and the heart rate estimated by Hilbert transform. We observed either negative or insignificant correlations between BRS and Sync in healthy subjects as well as in patients with moderate autonomic disorders. We attribute this effect to the partial compensation of the reduced BRS by a more frequent activation of the feedback mechanism indicated by a higher Sync value. In contrast, in diabetes patients with confirmed autonomic neuropathy BRS and Sync exhibited pronounced positive correlation (C = 0.82; p < 0.01) that likely indicates the breakdown of this compensation mechanism.

Laser Doppler Flowmetry and Laser Speckle Contrast Imaging are applied usually for assessment of parameters of the cutaneous blood flow during thermoregulation. Alternatively, this work explores the feasibility of blood pulsation imaging under incoherent green illumination for measuring the response of human body on local thermal impact. The proposed technique allows assessment of the cutaneous blood flow changes during thermoregulation simultaneously in different areas of the body. The preliminary experiments show that the blood pulsation amplitude (BPA) is sufficiently reliable index, which could characterize the relative change of the cutaneous blood flow similarly to the parameter measured with the Laser Doppler Flowmetry technique. It is shown that BPA grows up proportionally to the skin temperature increase in the preliminary cooled finger, whilst it is in the steady state in another finger having the constant temperature. The rate of BPA increase is individual characteristic of a subject, which could serve as a parameter of the subject’s vasomotor reactivity on the temperature changes. High quality of visualized distribution of blood pulsations, good repeatability of the BPA, and revealed dependencies of its response on the skin-temperature change offer the prospect for development new system of studying microcirculation.

Video-based system allows measurements not only the heart rate and its variability but also the time delay of blood pulsations in the facial area. We found that the delay is different in right and left cheeks for subjects in the recumbent position.

Article, Background The autonomous cardiovascular control can contribute to progression of migraine. However, current data on cardiovascular reactivity in migraine, especially severe forms, are essentially contradictory. The main aim of this study was to compare the autonomous regulation of circulation in patients with episodic and chronic migraine and healthy subjects. Methods Seventy three migraine patients (mean age 35 ± 10) including episodic migraine (51 patients, 4–14 headache days/months) and chronic migraine (22 patients, ≥15 headache days/month) along with age-match control (71 healthy voluntaries) were examined. The autonomic regulation of circulation was examined with the tilt-table test, a deep breathing and Valsalva Maneuver, handgrip test, cold-stress vasoconstriction, arterial baroreflex and blood pressure variability. Results The changes in heart rate induced by deep breathing, Valsalva Maneuver, and blood pressure in tilt-table test in patients with migraine did not differ from the control group. In contrast, the values of cold-stress-vasoconstriction forearm blood-flow reactivity (p, published version, peerReviewed

Vasomotor reactivity, which is important to estimate neurogenic regulation of blood vessels in patients with different pathologies, is still assessed by occlusion plethysmography using sensors contacting the limbs. Recently we proposed a contactless approach for measuring blood flow changes during venous occlusion using imaging photoplethysmography [Kamshilin et al., Sci. Rep. 7, 464 201728352083]. In this work, the response of the vascular system on the occlusion was studied simultaneously by contact air-plethysmography system and remote optical system under illumination by incoherent polarized green light. A high correlation (r > 0.93) between the waveforms measured by both system was observed. Moreover, we found that the response of the optical system on the venous occlusion is uniform at the whole area of the forearm. The new optical technique is more convenient for assessment of the blood flow dynamics because it can be used for measurements in any part of the body. Method of imaging photoplethysmography is very promising for use in equipment intended for evaluation of neurogenic mechanisms of regulation of vascular blood flow.

The feedback regulation of blood pressure and heart rate is an important indicator of human autonomic function. Here we suggest a method to evaluate its efficacy by detecting the epochs of synchronization and by determining their quantitative characteristics from the beat-to-beat data records. We assess the phases of both processes using Gilbert Transform and analyze the phase differences. By applying the proposed method to the tilt test records from different groups of patients as well as healthy individuals we obtained a significant difference (p < 0.05) in the values of the synchronization coefficient. Our method is particularly useful for the data analysis under non-stationary conditions.