Multi-site Photoplethysmography Research Articles

Deep learning classification of systemic sclerosis from multi-site photoplethysmography signals.

Introduction: A pilot study assessing a novel approach to identify patients with Systemic Sclerosis (SSc) using deep learning analysis of multi-site photoplethysmography (PPG) waveforms ("DL-PPG"). Methods: PPG recordings having baseline, unilateral arm pressure cuff occlusion and reactive hyperaemia flush phases from 6 body sites were studied in 51 Controls and 20 SSc patients. RGB scalogram images were obtained from the PPG, using the continuous wavelet transform (CWT). 2 different pre-trained convolutional neural networks (CNNs, namely, GoogLeNet and EfficientNetB0) were trained to classify the SSc and Control groups, evaluating their performance using 10-fold stratified cross validation (CV). Their classification performance (i.e., accuracy, sensitivity, and specificity, with 95% confidence intervals) was also compared to traditional machine learning (ML), i.e., Linear Discriminant Analysis (LDA) and K-Nearest Neighbour (KNN). Results: On a participant basis DL-PPG accuracy, sensitivity and specificity for GoogLeNet were 83.1 (72.3-90.9), 75.0 (50.9-91.3) and 86.3 (73.7-94.3)% respectively, and for EfficientNetB0 were 87.3 (77.2-94.0), 80.0 (56.3-94.3) and 90.1 (78.6-96.7)%. The corresponding results for ML classification using LDA were 66.2 (53.9-77.0), 65.0 (40.8-84.6) and 66.7 (52.1-79.2)% respectively, and for KNN were 76.1 (64.5-85.4), 40.0 (19.1-63.9), and 90.2 (78.6-96.7)% respectively. Discussion: This study shows the potential of DL-PPG classification using CNNs to detect SSc. EfficientNetB0 gave an overall improved performance compared to GoogLeNet, with both CNNs performing better than the traditional ML methods tested. Our automatic AI approach, using transfer learning, could offer significant benefits for SSc diagnostics in a variety of clinical settings where low-cost portable and easy-to-use diagnostics can be beneficial.

Prospective Assessment of the Diagnostic Accuracy of Multi-site Photoplethysmography Pulse Measurements for Diagnosis of Peripheral Artery Disease in Primary Care.

Peripheral arterial disease (PAD) is associated with cerebral and coronary artery disease. Symptomatic PAD affects about 5% of people over 55years; many more have asymptomatic PAD. Early detection enables modification of arterial disease risk factors. Diagnostically, assessment of symptoms or signs can be unreliable; ankle brachial pressure index (ABPI) testing is time-consuming and few healthcare professionals are properly trained. This study assessed the diagnostic accuracy of multi-site photoplethysmography (MPPG), an alternative non-invasive test for PAD, in primary care. PAD patients identified from general practice registers were age- and sex-matched with controls. Participants were assessed using MPPG, ABPI and duplex ultrasound (DUS). Outcome measures were sensitivity and specificity of MPPG and ABPI (relative to DUS) and concordance. MPPG test results were available in 249 of 298 eligible participants from 16 practices between May 2015 and November 2016. DUS detected PAD in 101/249 (40.6%). MPPG sensitivity was 79.8% (95% confidence interval [CI] 69.9-87.6%), with specificity 71.9% (95% CI 63.7-79.2%). ABPI sensitivity was 80.2% (95% CI 70.8-87.6%), with specificity 88.6% (95% CI 82-93.5%). With comparable sensitivity to ABPI, MPPG is quick, automated and simpler to do than ABPI; it offers the potential for rapid and accessible PAD assessments in primary care.

Validation of a Standardised Duplex Ultrasound Classification System for the Reporting and Grading of Peripheral Arterial Disease

Duplex ultrasound (DUS), a non-invasive means of arterial mapping, allows for the reliable diagnosis of peripheral arterial disease (PAD). One of the authors (C.P.O.), developed a standardised DUS based scoring system, devised for rapid detection and reporting of PAD. The purpose of this study was to validate this system, and to determine the diagnostic performance both overall and per disease severity. In total, 250 participants were recruited, based on diagnosis of (n= 125) or absence of PAD (n= 125) from general practice registers. Right and left legs per subject were handled as independent readings, determining actual PAD status via ankle brachial pressure index (ABPI) < 0.9, and then further grading disease severity using suggested ABPI ranges. Data were excluded if no corresponding ABPI value was obtained per DUS determination or if the ABPI reading was > 1.4, owing to the risk of false negatives due to incompressible vessels. Diagnostic sensitivity and specificity were obtained overall, and per severity classification. Furthermore, inter-rater agreement between ABPI and DUS determined PAD severity was determined by linear weighted Cohen's kappa. The sensitivity and specificity in the detection of disease overall was 81.0% (95% confidence interval [CI] 73.4 - 87.2) and 86.3% (95% CI 82.3 - 89.8), respectively. From mild to severe PAD, sensitivity increased from 71.1% (95% CI 55.7 - 83.6) to 89.3% (95% CI 71.8 - 97.7). Furthermore, a Cohen's kappa value of 0.63 (95% CI 0.57 - 0.69) was obtained, indicating moderate agreement between the two diagnostic methods. The findings of this study validate the diagnostic performance of the standardised DUS scoring system, as well as its capacity to grade severity of disease, offering a potential tool for the identification of PAD in community/research settings following initial screening methods. Confirmatory work could include a comparison of DUS determined disease with gold standard methods of non-invasive angiography, and novel tools such as toe flex near infrared spectroscopy and multisite photoplethysmography.

Validation of a new device for photoplethysmographic measurement of multi-site arterial pulse wave velocity

Pulse wave velocity (PWV) is commonly used for assessing arterial stiffness and it is a useful and accurate cardiovascular mortality predictor. Currently, many techniques and devices for PWV measurement are known, but they are usually expensive and require operator experience. One possible solution for PWV measurement is photoplethysmography (PPG), which is convenient, inexpensive and provides continuous PWV results. The aim of this paper is validation of a new device for PPG sensor-based measurement of multi-site arterial PWV using a SphygmoCor XCEL (as the reference device) according to the recommendations of the Artery Society Guidelines (ASG). In this study, 108 subjects (56 men and 52 women, 20–91 years in 3 required age groups) were enrolled. The multi-site PWV was simultaneous measured by 7 PPG sensors commonly used in pulse oximetry in clinical settings. These sensors were placed on the forehead, and right and left earlobes, fingers and toes. Pulse transit time (PTT) was measured offline as the difference of time delay between two onsets of the pulse wave determined by the intersecting tangent method. The PWV was calculated by dividing the distance between PPG sensors by PTT. During PPG signals measurement, reference carotid to femoral PWV (cfPWV) was performed with a SphygmoCor XCEL system. The Pearson correlation coefficient (r) between the obtained PWV results was calculated. The Bland-Altman method was used to establish the level of agreement between the two devices. Mean difference (md) and standard deviation (SD) were also calculated. The multi-site PWV was highly correlated with accuracy at the ASG-defined level of “Acceptable” (md < 1.0 m/s and SD ≤ 1.5 m/s) with cfPWV: forehead - right toe (r = 0.75, md = 0.20, SD = 0.97), forehead - left toe (r = 0.79, md = 0.18, SD = 0.91), right ear - right toe (r = 0.79, md = 0.11, SD = 0.96), left ear - left toe (r = 0.75, md = 0.43, SD = 0.99), right ear - left toe (r = 0.78, md = 0.40, SD = 0.93), left ear - right toe (r = 0.78, md = 0.11, SD = 0.96), right finger - right toe (r = 0.66, md = 0.95, SD = 1.29), left finger - left toe (r = 0.67, md = 0.68, SD = 1.35). This study showed that PWV measured with the multi-site PPG system, in relation to the obtained numerical values, correlated very well with that measured using the commonly known applanation tonometry method. However, it should be noted, that the measured PWV concerns the central and muscular part of the arterial tree while the cfPWV is only for the central one. The best results were obtained when the proximal PPG sensor was placed on the head (ear or forehead) and the distal PPG sensor on the toe. PPG sensors can be placed in many sites at the same time, which provides greater freedom of their configuration. Multi-site photoplethysmography is an alternative method for PWV measurement and creates new possibilities for the diagnostics of cardiovascular diseases.

The use of multi-site photoplethysmography (PPG) as a screening tool for coronary arterial disease and atherosclerosis

Objective. We present the design and validation of a non-invasive smart-phone based screening tool for atherosclerosis and coronary arterial disease (CAD), which is the leading cause of mortality worldwide. Approach. We designed a three-channel photoplethysmography (PPG) device that connects to a smart phone application for measuring pulse transit time (PTT) and pulse wave velocity (PWV) using PPG probes that are simultaneously clipped onto to the ear, index finger, and big toe, respectively. Validation was performed through a clinical study with 100 participants (age 20 to 77) at a research hospital in Nagpur, India. Study subjects were stratified by age and divided into three groups corresponding to the disease severity: CAD, hypertensive (‘Pre-CAD’), and Healthy. Main results. PWV measurements derived from the Ear-Toe probe measurements yielded the best performance, with median PWV values increasing monotonically as a function of disease severity and age, as follows: 14.2 m s−1 for the older-patient CAD group, 12.2 m s−1 for the younger-patient CAD group, 11.6 m s−1 for the older-patient Pre-CAD group, 10.2 m s−1 for the younger-patient Pre-CAD group, 9.7 m s−1 for the older healthy controls, and 8.4 m s−1 for the younger healthy controls. Using just two simple features, the PTT and patient height, we demonstrate a machine learning prediction model for CAD with a median accuracy of 0.83 (AUC). Significance. This work demonstrates the ability to predict atherosclerosis and CAD using a single simple physiological measurement with a multi-site PPG tool that is electrically powered by a mobile phone and does not require any electrocardiogram reference. Furthermore, this method only requires a single anthropometric measurement, which is the patient’s height.

Age-related changes in pulse risetime measured by multi-site photoplethysmography

Objective: It is accepted that changes in the peripheral pulse waveform characteristics occur with ageing. Pulse risetime is one important feature which has clinical value. However, it is unclear how it varies across the full age spectrum from child to senior and for different peripheral measurement sites. The objectives of this study were to determine the association between age and pulse risetime characteristics over an 8-decade age range at the ears, fingers, and toes, and to consider effects arising from differences in systolic blood pressure (SBP), height and heart rate. Approach: Multi-site photoplethysmography (MPPG) pulse waveforms were recorded non-invasively from the right and left ears, fingers, and toes of 304 normal healthy human subjects (range 6–87 years; 156 male and 148 female). SBP, height, and heart rate were also measured. Multi-site PPG pulse risetimes, and their site differences, were determined. Main results: Univariate regression analysis showed positive correlations with risetime for age (ears, fingers and toes: + 0.8, + 1.9, and + 1.1 ms/year, respectively), SBP (+0.5, + 1.3, and + 0.9 ms/mmHg) and height (+0.5, + 1.2, and + 1.0 ms/cm), but with a clear inverse association with heart rate (−1.8, − 2.5, and − 1.6 ms min) (P < 0.0001). No significant differences between male and female subjects were found for pulse risetime. Significance: Normative multi-site PPG risetime characteristics have been defined in over 300 subjects and are shown to increase with age linearly up to the 8th decade. In contrast, we have shown that heart rate has a clear inverse relationship with risetime for all measurement sites.

Multi-Site Photoplethysmographic and Electrocardiographic System for Arterial Stiffness and Cardiovascular Status Assessment.

The development and validation of a system for multi-site photoplethysmography (PPG) and electrocardiography (ECG) is presented. The system could acquire signals from 8 PPG probes and 10 ECG leads. Each PPG probe was constituted of a light-emitting diode (LED) source at a wavelength of 940 nm and a silicon photomultiplier (SiPM) detector, located in a back-reflection recording configuration. In order to ensure proper optode-to-skin coupling, the probe was equipped with insufflating cuffs. The high number of PPG probes allowed us to simultaneously acquire signals from multiple body locations. The ECG provided a reference for single-pulse PPG evaluation and averaging, allowing the extraction of indices of cardiovascular status with a high signal-to-noise ratio. Firstly, the system was characterized on optical phantoms. Furthermore, in vivo validation was performed by estimating the brachial-ankle pulse wave velocity (baPWV), a metric associated with cardiovascular status. The validation was performed on healthy volunteers to assess the baPWV intra- and extra-operator repeatability and its association with age. Finally, the baPWV, evaluated via the developed instrumentation, was compared to that estimated with a commercial system used in clinical practice (Enverdis Vascular Explorer). The validation demonstrated the system’s reliability and its effectiveness in assessing the cardiovascular status in arterial ageing.

Comparing Ankle-Brachial Pressure Index with Photoplethysmography for the Diagnosis of Peripheral Arterial Disease: A Qualitative Study

Introduction - Few studies have investigated in-depth the experiences of patients and clinicians with the ankle-brachial pressure index (ABPI). Despite known issues with inter-observer reliability ABPI is widely used in clinical practice to diagnose peripheral arterial disease (PAD). This study set out to identify, describe and understand experiences using ABPI in primary care, in the context of a trial comparing ABPI with a novel diagnostic device for PAD, multi-site photoplethysmography (MPPG). Methods - Patients were recruited to a clinical trial comparing ABPI and MPPG in the diagnosis of PAD within UK primary care. A researcher (JS) observed practice nurse use of ABPI and MPPG with 51 patients (n=29 cases, n=22 controls) across 9 general practices. 12 nurses and 27 patients (n=17 cases and n=10 controls) were later interviewed. Data was analysed thematically using NVivo 11 as a data management tool. Results - Most participants stated a preference for MPPG. Reasons included: (1) patients reported or displayed signs of discomfort with ABPI, especially during compression of the lower leg (2) nurses considered MPPG easier to use, and ABPI required higher levels of confidence and dexterity (3) MPPG was quicker to use and to take readings, and (4) MPPG recordings were perceived to be less subjective. Several patients struggled to identify a preference between MPPG and ABPI, even where discomfort was present. These patients expected tests for diagnosing medical conditions to be uncomfortable or time-consuming. When a foot pulse was not obtainable or difficult to obtain during ABPI, this caused anxiety amongst patients. An additional theme was identified relating to patients’ reasons for participation in the study. For many, participation was partly to help others, but also a desire to obtain a diagnosis or further information about existing symptoms. This was reflected in observational data; patients wanted further information about the test results as they were in progress. Conclusion - This is one of the first studies to use qualitative methods (observation and interviews) to explore and understand experiences of using devices for PAD diagnosis in primary care. Whilst ABPI is a non-invasive and routine procedure it is associated with a number of drawbacks in practice. Nurses require considerable dexterity to employ the test effectively, and some patients experience discomfort and/or anxiety. In contrast MPPG was deemed to be easier and quicker to use, and was perceived to be less subjective. Work is also underway in the clinical trial to assess MPPG diagnostic test accuracy and with the patient and clinician preference findings of this qualitative research the technique is showing great promise for use in primary care.

Nurses' and patients' experiences and preferences of the ankle-brachial pressure index and multi-site photoplethysmography for the diagnosis of peripheral arterial disease: A qualitative study.

Peripheral arterial disease is a global health problem, affecting around 20% of people aged over 60 years. Whilst ankle-brachial pressure index (ABPI) is regularly used for diagnosis, it has a number of limitations, which have presented a need for alternative methods of diagnosis. Multi-site photoplethysmography (MPPG) is one such method, but evidence of acceptability of both methods is lacking. This study aims to describe and compare preferences and experiences amongst nurses and patients of ABPI and MPPG use in primary care. We used qualitative research methods in the context of a clinical diagnostic study comparing ABPI with MPPG. Use of ABPI and MPPG by 13 nurses were observed with 51 patients across general practice surgeries in North-East England in 2015/16. Follow-up semi-structured interviews were conducted with 12 nurses and 27 patients. Data were thematically analysed. Two major themes were identified: (1) device preferences; (2) test discomfort and anxiety. There was a compelling preference for MPPG due to ease of use, speed of the test, patient comfort, and perceived device accuracy/objectivity. However some patients struggled to identify a preference, describing ambivalence to medical testing. ABPI was deemed uncomfortable and painful, particularly when the blood pressure cuff was inflated at the lower limbs. There was also evidence of anxiety amongst patients when their foot pulses were not identified using ABPI. Whilst ABPI is a non-invasive and routine procedure it was associated with a number of drawbacks in clinical practice. Nurses required considerable dexterity to employ the test, and it resulted in anxiety amongst some patients. Conversely, MPPG was deemed to be easier and quicker to use, and perceived to be less subjective. Should diagnostic accuracy and cost be comparable to ABPI, then the findings of this study suggest MPPG would be preferable to ABPI for patients as well as nurses.

Multi-Site Photoplethysmography Technology for Blood Pressure Assessment: Challenges and Recommendations.

Hypertension is one of the most prevalent diseases and is often called the “silent killer” because there are usually no early symptoms. Hypertension is also associated with multiple morbidities, including chronic kidney disease and cardiovascular disease. Early detection and intervention are therefore important. The current routine method for diagnosing hypertension is done using a sphygmomanometer, which can only provide intermittent blood pressure readings and can be confounded by various factors, such as white coat hypertension, time of day, exercise, or stress. Consequently, there is an increasing need for a non-invasive, cuff-less, and continuous blood pressure monitoring device. Multi-site photoplethysmography (PPG) is a promising new technology that can measure a range of features of the pulse, including the pulse transit time of the arterial pulse wave, which can be used to continuously estimate arterial blood pressure. This is achieved by detecting the pulse wave at one body site location and measuring the time it takes for it to reach a second, distal location. The purpose of this review is to analyze the current research in multi-site PPG for blood pressure assessment and provide recommendations to guide future research. In a systematic search of the literature from January 2010 to January 2019, we found 13 papers that proposed novel methods using various two-channel PPG systems and signal processing techniques to acquire blood pressure using multi-site PPG that offered promising results. However, we also found a general lack of validation in terms of sample size and diversity of populations.

Quantifying the Delays Between Multi-Site Photoplethysmography Pulse and Electrocardiogram R-R Interval Changes Under Slow-Paced Breathing.

Objective: Objective assessment of autonomic function is important, including the investigation of slow-paced breathing to induce associated periodic changes in the cardiovascular system – such as blood pressure and heart rate. However, pulse changes across a range of peripheral body sites have seldom been explored with this challenge. The primary aim of this pilot study was to utilize multi-site photoplethysmography (MPPG) technology to quantify the phase delays, i.e., correlation lags, between changes in heart rate and changes in key pulse features with slow-paced breathing (0.1 Hz).Methods: Waveforms were collected simultaneously from the right and left ear lobes, thumbs, and great toes of 18 healthy adult subjects. Cross correlation lags between reference beat-to-beat changes in electrocardiogram (ECG) R-R wave interval and changes in pulse arrival time (foot of pulse; PATf) and also for pulse amplitude (foot-to-peak; AMP) were determined.Results: Relative to R-R changes, the median ear, thumb, and toe PATf correlation lags were 3.4, 2.9, and 2.1 beats, respectively; contrasting to AMP with 5.7, 6.0, and 6.9 beats, respectively. These PATf correlation lags in beats were significantly lower than for the AMP measure. Segmental differences between sites and timing measure variability have also been quantified.Conclusion: This pilot study has indicated bilateral similarity plus segmental differences for relative delays in PPG pulse timing and amplitude measures relative to R-R interval changes with paced breathing. These correlation and variability data are now available for comparison with cardiovascular patient groups to support development of autonomic function assessment techniques.

Data-driven assessment of cardiovascular ageing through multisite photoplethysmography and electrocardiography

The cardiovascular system is designed to distribute a steady flow through its elastic properties. With ageing, fatigue and fracture of elastin lamellae cause a loss of elasticity defined arterial stiffness. Arterial stiffness causes changes of the pulse wave propagation through the arterial tree, which volumetric counterpart can be assessed non-invasively through photoplethysmography (PPG). PPG may be employed in combination with electrocardiography (ECG). It is here reported an implementation of analysis of multisite PPG and single lead ECG relying on Deep Convolutional Neural Networks (DCNNs). DCNNs generate peculiar filters allowing for data-driven automated selection of the features of interest. The ability of a DCNN to predict subject's age from PPG (left and right brachial, radial and tibial arteries plus fingers) and ECG (Lead I) in a healthy male population (age range: 20–70 years) was investigated. A performance in age prediction of 7 years of root mean square error was obtained, which was superior to other feature-based procedures. The accuracy in age prediction of the machinery in the healthy population may serve for the generation of age-matched normal ranges for the identification of outliers suggesting cardiovascular diseases manifesting as fastened cardiovascular ageing which is recognized as a risk factor for ischemic diseases.

Innovative Multi-Site Photoplethysmography Analysis for Quantifying Pulse Amplitude and Timing Variability Characteristics in Peripheral Arterial Disease.

Photoplethysmography (PPG) is a simple-to-perform vascular optics measurement technique that can detect blood volume changes in the microvascular bed of tissue. Beat-to-beat analysis of the PPG waveform enables the study of the variability of pulse features, such as the amplitude and the pulse arrival time (PAT), and when quantified in the time and frequency domains, has considerable potential to shed light on perfusion changes associated with peripheral arterial disease (PAD). In this pilot study, innovative multi-site bilateral finger and toe PPG recordings from 43 healthy control subjects and 31 PAD subjects were compared (recordings each at least five minutes, collected in a warm temperature-controlled room). Beat-to-beat normalized amplitude variability and PAT variability were then quantified in the time-domain using two simple statistical measures and in the frequency-domain bilaterally using magnitude squared coherence (MSC). Significantly reduced normalized amplitude variability (healthy control 0.0384 (interquartile range 0.0217–0.0744) vs. PAD 0.0160 (0.0080–0.0338) (p < 0.0001)) and significantly increased PAT variability (healthy control 0.0063 (0.0052–0.0086) vs. PAD 0.0093 (0.0078–0.0144) (p < 0.0001)) was demonstrated for the toe site in PAD using the time-domain analysis. Frequency-domain analysis demonstrated significantly lower MSC values across a range of frequency bands for PAD patients. These changes suggest a loss of right-to-left body side coherence and cardiovascular control in PAD. This study has also demonstrated the feasibility of using these measurement and analysis methods in studies investigating multi-site PPG variability for a wide range of cardiac and vascular patient groups.

Innovative multi-site photoplethysmography measurement and analysis demonstrating increased arterial stiffness in paediatric heart transplant recipients

Objective: It has been documented that heart transplantation in children is often complicated by arterial hypertension and increased arterial stiffness. We use innovative multi-site photoplethysmography (MPPG) pulse measurement and analysis technology to assess changes in arterial stiffness in paediatric heart transplant recipients (HTRs) in comparison with healthy control (HC) children. Approach: A group of 20 HTRs (median age 13.5 years, eight male) were compared to an overall age- and gender-matched group of 161 HCs (median age 11.6 years, 74 male). Peripheral pulse was recorded bilaterally using MPPG at the ear lobe, index finger and great toe sites, along with an electrocardiogram cardiac timing reference. Segmental pulse arrival times between peripheral sites (finger–ear, PATf–e; toe–finger, PATt–f; and toe–ear PATt–e) were calculated as arterial stiffness measures, and differences between subject groups were tested using multivariate analysis. Normalised ear, finger and toe pulse shapes were also studied and compared between groups. Main results: After correction for heart rate and diastolic and mean arterial blood pressures, the HTR group was found to have significantly lower segmental PATt–e and PATt–f measurements, with median values of 150 ms versus 172 ms in the HC group (p = 0.02), and 104 ms versus 118 ms in the HC group (p = 0.01), respectively, consistent with increased arterial stiffness in the patient group. The normalised ear, finger and toe sites showed only a mild elongation in each pulse rise time for the transplant group. Significance: This study shows that innovative and easy-to-do MPPG gives further evidence for increased arterial stiffness in children who have undergone successful cardiac transplantation.

Novel photoplethysmography cardiovascular assessments in patients with Raynaud's phenomenon and systemic sclerosis: a pilot study

Multisite photoplethysmography (PPG) cardiovascular assessments can evaluate endothelial, peripheral autonomic and arterial dysfunction. The aim of this pilot study was to investigate the potential clinical utility of the technology in assessing patients with SSc and primary RP (PRP). Multisite PPG pulse measurements, a reference ankle brachial pressure index (ABPI) and a full clinical assessment were undertaken for three subject groups: SSc, PRP and controls. Endothelial and autonomic function and arterial disease measures were obtained using pulse wave analysis. Nineteen SSc, 19 PRP and 23 control subjects were assessed and compared. Endothelial function was significantly impaired in SSc (P < 0.02), but with no difference between controls and PRP. Receiver operating characteristic-based classification accuracy was 81% (sensitivity 90%, specificity 74%) for separating SSc from controls and 82% (sensitivity 84%, specificity 79%) for separating SSc from PRP. SSc patients with digital ulcers had significantly lower endothelial function compared with those without ulcers (P < 0.05). Autonomic dysfunction was suggested in both SSc and PRP and was most exaggerated in patients with diffuse SSc. All groups had overall normal ABPI and arterial stiffness timing measures. Bilateral timing differences at the toes, which represents peripheral occlusive arterial disease, did show increased asymmetry in SSc (P < 0.02). Multisite PPG pulse technology showed potential diagnostic ability. By using measures of endothelial function, it differentiated SSc from control and PRP subjects with an accuracy of at least 81%. Objective pulse-derived measures of autonomic function and arterial disease in SSc have also been reported in this pilot study.

Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis–a new potential diagnostic biomarker

Autonomic nervous system dysfunction is frequently reported in chronic fatigue syndrome (CFS) with orthostatic intolerance, a common symptom that can be objectively assessed. The frequent finding of autonomic dysfunction and symptoms on standing has the potential to provide a diagnostic biomarker in chronic fatigue. In this study we explored the clinical value of non-invasive optical multi-site photoplethysmography (PPG) technology to assess cardiovascular responses to standing. Multi-site PPG pulses were collected from tissue pads of the ears, fingers and toes of 14 patients with CFS and 14 age-matched sedentary subjects using a measurement protocol of a 10 min baseline (subject supine) followed by 3 min of tilting on a tilt table (head-up to 70°). Percentage change in pulse timing (pulse transit time, PTTf) and pulse amplitude (AMP) at each site were calculated using beat-to-beat pulse wave analysis. A significant reduction in the overall pulse timing response to controlled standing was found for the CFS group (using summed absolute percentage change in PTTf for ear, finger and toe sites, median change of 26% for CFS and 37% for control with p = 0.002). There were no significant differences between subject groups for the AMP measure at any site. Changes in AMP with tilt were, however, weakly significantly and negatively correlated with fatigue severity (p < 0.05). Receiver operating characteristic (ROC) analysis of timing measures produced an area under the curve of 0.81. Experimental linear discriminant classification analysis comparing both timing and amplitude measures produced an overall diagnostic accuracy of 82%. Pulse wave abnormalities have been observed in CFS and represent a potential objective measure to help differentiate between CFS patients and healthy controls.

Microvascular optical assessment confirms the presence of peripheral autonomic dysfunction in primary biliary cirrhosis

Autonomic dysfunction (AD) is a significant problem in primary biliary cirrhosis (PBC) and is equally present in early disease stages. Currently, AD in PBC is considered to be central in origin. The aim of this study was to examine peripheral mechanisms in the pathogenesis of AD in PBC using novel microvascular optical assessments for this patient group. Twenty-four early stage PBC patients and 24 age-matched controls attended for two microvascular optical-based measurement techniques. Firstly, the regulation of microvascular blood volume to the periphery was assessed using multisite photoplethysmography (PPG) by examining the degree of correlation between the right and left sides of the body, with reduced correlation consistent with peripheral AD. Secondly, the peripheral vasomotor reflex response to standing was dynamically tested using laser Doppler flowmetry to quantify the degree of autonomic tone in peripheral vasoconstriction. PBC patients had a significantly reduced right to left side blood volume multisite PPG correlation compared with controls when corrected for age, body mass index, heart rate and systolic blood pressure [impaired synchronization between pulse wave amplitude between right and left fingers and right and left ears (both P<0.05)]. The veno-arteriolar reflex on standing in PBC patients was significantly lower than for the controls, consistent with poorer autonomic tone for vasoconstriction in PBC (P<0.01). This study provides evidence for the presence of peripheral autonomic nervous system involvement in PBC. Prospective studies are now warranted to determine the full clinical potential of microvascular optical assessment in PBC.

Similarity in bilateral photoplethysmographic peripheral pulse wavecharacteristics at the ears, thumbs and toes

The characteristics of the photoplethysmography (PPG) pulse signal are body sitespecific, with pulses from the various peripheral sites showing differences inpulse transit time, strength and shape, and variation of each over time. The aimof this study was to determine the similarity in the right-left pulsecharacteristics for a group of normal subjects with pulses obtainedsimultaneously from six peripheral sites (ears, thumbs and big toes). A multi-site photoplethysmography pulse measurement and analysis system is described andcomprised six sets of pulse probes and amplifiers, arranged and electronicallymatched in pairs for the right and left side comparisons. Two sets of data werecollected: firstly a set of validation data to test the electronic matching ofright-left channels, and secondly a set of physiological data for pulses from40 normal subjects. The right-to-left side similarity in pulse waveform shape atthe three segmental levels (ears, thumbs and toes) was assessed using two typesof analysis: root mean square error (RMSE) providing a measure of differences,and cross correlation analysis providing a measure of the degree of similarity.Very low levels of RMSE and correlation coefficients close to unity wereobtained for the system validation data, demonstrating good right-left channelmatching. The RMSE was an order of magnitude lower than that calculated for thenormative physiological data, where median RMSE levels were between 0.053 and0.060 relative to a peak-to-peak pulse amplitude of unity. The mediancorrelation coefficients were greater than 0.98 for all three segmental levelsstudied, with the maximum values approaching those of the validation data. Wehave shown that pulses from the right and left sides of normal subjects arehighly correlated at each segmental level. We have obtained a normative range ofpulse data, with which specific (vascular) patient groups can be compared.