Novel Method to Assess Endothelial Function via Monitoring of Perfusion Response to Local Heating by Imaging Photoplethysmography.

Endothelial dysfunction is one of the most important markers of the risk of cardiovascular complications. This study is aimed to demonstrate the feasibility of imaging photoplethysmography to assess microcirculation response to local heating in order to develop a novel technology for assessing endothelial function. As a measure of vasodilation, we used the relative dynamics of the pulsatile component of the photoplethysmographic waveform, which was assessed in a large area of the outer surface of the middle third of the subject's forearm. The perfusion response was evaluated in six healthy volunteers during a test with local skin heating up to 40-42 °C and subsequent relaxation. The proposed method is featured by accurate control of the parameters affecting the microcirculation during the prolonged study. It was found that in response to local hyperthermia, a multiple increase in the pulsation component, which has a biphasic character, was observed. The amplitude of the first phase of the perfusion reaction depends on both the initial skin temperature and the difference between the basal and heating temperatures. The proposed method allows the assessment of a reproducible perfusion increase in response to hyperthermia developed due to humoral factors associated with the endothelium, thus allowing detection of its dysfunction.

Advantages of imaging photoplethysmography for migraine modeling: new optical markers of trigemino-vascular activation in rats.

BACKGROUND: Existent animal models of migraine are not without drawbacks and limitations. The aim of our study was to evaluate imaging photoplethysmography (PPG) as a method of assessing intracranial blood flow in rats and its changes in response to electrical stimulation of dural trigeminal afferents. METHODS: Experiments were carried out with 32 anesthetized adult male Wistar rats. Trigeminovascular system (TVS) was activated by means of electrical stimulation of dural afferents through a closed cranial window (CCW). Parameters of meningeal blood flow were monitored using a PPG imaging system under green illumination with synchronous recording of an electrocardiogram (ECG) and systemic arterial blood pressure (ABP). Two indicators related to blood-flow parameters were assessed: intrinsic optical signals (OIS) and the amplitude of pulsatile component (APC) of the PPG waveform. Moreover, we carried out pharmacological validation of these indicators by determining their sensitivity to anti-migraine drugs: valproic acid and sumatriptan. For statistical analysis the non-parametric tests with post-hoc Bonferroni correction was used. RESULTS: Significant increase of both APC and OIS was observed due to CCW electrical stimulation. Compared to saline (n = 11), intravenous administration of both the sumatriptan (n = 11) and valproate (n = 10) by using a cumulative infusion regimen (three steps performed 30 min apart) lead to significant inhibitory effect on the APC response to the stimulation. In contrast, intravenous infusion of any substance or saline did not affect the OIS response to the stimulation. It was found that infusion of either sumatriptan or valproate did not affect the response of ABP or heart rate to the stimulation. CONCLUSIONS: Imaging PPG can be used in an animal migraine model as a method for contactless assessment of intracranial blood flow. We have identified two new markers of TVS activation, one of which (APC) was pharmacologically confirmed to be associated with migraine. Monitoring of changes in APC caused by CCW electrical stimulation (controlling efficiency of stimulation by OIS) can be considered as a new way to assess the peripheral mechanism of action of anti-migraine interventions.

Novel capsaicin-induced parameters of microcirculation in migraine patients revealed by imaging photoplethysmography.

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.

Duality in response of intracranial vessels to nitroglycerin revealed in rats by imaging photoplethysmography.

Among numerous approaches to the study of migraine, the nitroglycerin (NTG) model occupies a prominent place, but there is relatively insufficient information about how NTG affects intracranial vessels. In this study we aim to assess the effects of NTG on blood-flow parameters in meningeal vessels measured by imaging photoplethysmography (iPPG) in animal experiments. An amplitude of the pulsatile component (APC) of iPPG waveform was assessed before and within 2.5 h after the NTG administration in saline (n = 13) or sumatriptan (n = 12) pretreatment anesthetized rats in conditions of a closed cranial window. In animals of both groups, NTG caused a steady decrease in blood pressure. In 7 rats of the saline group, NTG resulted in progressive increase in APC, whereas decrease in APC was observed in other 6 rats. In all animals in the sumatriptan group, NTG administration was accompanied exclusively by an increase in APC. Diametrically opposite changes in APC due to NTG indicate a dual effect of this drug on meningeal vasomotor activity. Sumatriptan acts as a synergist of the NTG vasodilating action. The results we obtained contribute to understanding the interaction of vasoactive drugs in the study of the headache pathophysiology and methods of its therapy.

Study of cerebrovascular reactivity to hypercapnia by imaging photoplethysmography to develop a method for intraoperative assessment of the brain functional reserve.

Intraoperative assessment of cerebrovascular reactivity is a relevant problem of neurosurgery. To assess the functional reserve of cerebral blood flow, we suggest using imaging photoplethysmography for measuring changes in cortical perfusion caused by CO2 inhalation. Feasibility of the technique was demonstrated in three groups of anesthetized rats (n=21) with opened and closed cranial windows. Our study for the first time revealed that the hemodynamic response to hypercapnia strongly depends on the cranial state. However, it was shown that regardless of the direction of changes in local and systemic hemodynamics, the ratio of normalized changes in arterial blood pressure and cortical perfusion could be used as a measure of the cerebrovascular functional reserve.

Animal model of assessing cerebrovascular functional reserve by imaging photoplethysmography.

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 < 0.001). Such an increase negatively correlated with significant decrease in end-tidal CO2 by 32 ± 7% (p < 0.001). It is noteworthy that the dorzolamide injection did not lead to significant changes in systemic blood pressure. Concluding, pulsations amplitude is a marker of the vascular tone that can be used to evaluate the functional cerebrovascular reserve. Imaging PPG is a simple and convenient method to assess cerebral blood flow, including during various neurosurgical interventions.

Novel instrumental markers of proximal scleroderma provided by imaging photoplethysmography.

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.

Contactless Assessment of Cerebral Autoregulation by Photoplethysmographic Imaging at Green Illumination.

Accurate and practical assessment of the brain circulation is needed to adequately estimate the viability of cerebral blood flow regulatory mechanisms in various physiological conditions. The objective of our study was to examine feasibility of the contactless green-light imaging photoplethysmography (PPG) for assessing cerebral autoregulation by revealing the dynamic relationships between cortical microcirculation assessed by PPG and changes in systemic blood pressure caused by visceral and somatic peripheral stimuli. In anesthetized male Wistar rats, the PPG video images of the open parietal cortex (either with unimpaired or dissected dura mater), electrocardiogram, and systemic arterial blood pressure (ABP) in the femoral artery were continuously recorded before, during and after visceral (colorectal distension) or somatic (tail squeezing) stimulation. In the vast majority of experiments with intact and removed dura mater, both spontaneous and peripheral stimulation-evoked changes in ABP negatively correlated with the accompanying alterations in the amplitude of pulsatile PPG component (APC), i.e., an increase of ABP resulted in a decrease of APC and vice versa. The most pronounced ABP and APC alterations were induced by noxious stimuli. Visceral painful stimulation in all cases caused short-term hypotension with simultaneous increase in cortical APC, whereas somatic noxious stimuli in 8 of 21 trials produced hypertensive effect with decreased APC. Animals with pressure 50-70 mmHg possessed higher negative cerebrovascular response rate of ABP-APC gradients than rats with either lower or higher pressure. Severe hypotension reversed the negative ratio to positive one, which was especially evident under visceral pain stimulation. Amplitude of the pulsatile PPG component probably reflects the regulation of vascular tone of cerebral cortex in response to systemic blood pressure fluctuations. When combined with different kinds of peripheral stimuli, the technique is capable for evaluation of normal and elucidation of impaired cerebrovascular system reactivity to particular physiological events, for example pain. The reported contactless PPG monitoring of cortical circulatory dynamics during neurosurgical interventions in combination with recordings of changes in other physiological parameters, such as systemic blood pressure and ECG, has the appealing potential to monitor viability of the cortex vessels and determine the state of patient's cerebrovascular autoregulation.

Alterations of blood pulsations parameters in carotid basin due to body position change.

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.

Video capillaroscopy clarifies mechanism of the photoplethysmographic waveform appearance.

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.

Influence of polarization filtration on the information readout from pulsating blood vessels.

Imaging photoplethysmography (IPPG) is a recently developed technique for noncontact assessment of cardiovascular function. However, its wide use is limited by low signal-to-noise ratio due to motion artifacts. The aim of this work is to estimate the polarization-filtration impact on discriminating artifacts in IPPG measurements. Experiments were carried out in-vivo by almost simultaneous illumination of subject's palm with polarized and non-polarized light during video recording of 41 subjects. It was found that the light-polarization filtration efficiently reduces motion artifacts compared to the non-polarized illumination while the pulsation amplitude measured at the heartbeat frequency remains unaffected. The polarization filtration improves reliability of IPPG system in non-contact monitoring of subject's heart rate and its variability.

Accurate measurement of the pulse wave delay with imaging photoplethysmography.

Assessment of the cardiovascular parameters using noncontact video-based or imaging photoplethysmography (IPPG) is usually considered as inaccurate because of strong influence of motion artefacts. To optimize this technique we performed a simultaneous recording of electrocardiogram and video frames of the face for 36 healthy volunteers. We found that signal disturbances originate mainly from the stochastically enhanced dichroic notch caused by endogenous cardiovascular mechanisms, with smaller contribution of the motion artefacts. Our properly designed algorithm allowed us to increase accuracy of the pulse-transit-time measurement and visualize propagation of the pulse wave in the facial region. Thus, the accurate measurement of the pulse wave parameters with this technique suggests a sensitive approach to assess local regulation of microcirculation in various physiological and pathological states.