A pilot clinical study to estimate intracranial pressure utilising cerebral photoplethysmograms in traumatic brain injury patients.

PURPOSE: In this research, a non-invasive intracranial pressure (nICP) optical sensor was developed and evaluated in a clinical pilot study. The technology relied on infrared light to probe brain tissue, using photodetectors to capture backscattered light modulated by vascular pulsations within the brain's vascular tissue. The underlying hypothesis was that changes in extramural arterial pressure could affect the morphology of recorded optical signals (photoplethysmograms, or PPGs), and analysing these signals with a custom algorithm could enable the non-invasive calculation of intracranial pressure (nICP). METHODS: This pilot study was the first to evaluate the nICP probe alongside invasive ICP monitoring as a gold standard. nICP monitoring occurred in 40 patients undergoing invasive ICP monitoring, with data randomly split for machine learning. Quality PPG signals were extracted and analysed for time-based features. The study employed Bland-Altman analysis and ROC curve calculations to assess nICP accuracy compared to invasive ICP data. RESULTS: Successful acquisition of cerebral PPG signals from traumatic brain injury (TBI) patients allowed for the development of a bagging tree model to estimate nICP non-invasively. The nICP estimation exhibited 95% limits of agreement of 3.8 mmHg with minimal bias and a correlation of 0.8254 with invasive ICP monitoring. ROC curve analysis showed strong diagnostic capability with 80% sensitivity and 89% specificity. CONCLUSION: The clinical evaluation of this innovative optical nICP sensor revealed its ability to estimate ICP non-invasively with acceptable and clinically useful accuracy. This breakthrough opens the door to further technological refinement and larger-scale clinical studies in the future. TRIAL REGISTRATION: NCT05632302, 11th November 2022, retrospectively registered.

Energy-Efficient PPG-Based Respiratory Rate Estimation Using Spiking Neural Networks.

Respiratory rate (RR) is a vital indicator for assessing the bodily functions and health status of patients. RR is a prominent parameter in the field of biomedical signal processing and is strongly associated with other vital signs such as blood pressure, heart rate, and heart rate variability. Various physiological signals, such as photoplethysmogram (PPG) signals, are used to extract respiratory information. RR is also estimated by detecting peak patterns and cycles in the signals through signal processing and deep-learning approaches. In this study, we propose an end-to-end RR estimation approach based on a third-generation artificial neural network model-spiking neural network. The proposed model employs PPG segments as inputs, and directly converts them into sequential spike events. This design aims to reduce information loss during the conversion of the input data into spike events. In addition, we use feedback-based integrate-and-fire neurons as the activation functions, which effectively transmit temporal information. The network is evaluated using the BIDMC respiratory dataset with three different window sizes (16, 32, and 64 s). The proposed model achieves mean absolute errors of 1.37 ± 0.04, 1.23 ± 0.03, and 1.15 ± 0.07 for the 16, 32, and 64 s window sizes, respectively. Furthermore, it demonstrates superior energy efficiency compared with other deep learning models. This study demonstrates the potential of the spiking neural networks for RR monitoring, offering a novel approach for RR estimation from the PPG signal.

Optical determination of lithium therapeutic levels in micro-volumes of interstitial fluid.

BACKGROUND: Long-term management of bipolar disorder (BD), characterized by mood fluctuating between episodes of mania and depression, involves the regular taking of lithium preparations as the most reliable mood stabilizer for bipolar patients. However, despite its effectiveness in preventing and reducing mood swings and suicidality, lithium has a very narrow therapeutic index and it is crucial to carefully monitor lithium plasma levels as concentrations >1.2 mmol/L are potentially toxic and can be fatal. Current methods of lithium therapeutic monitoring involve frequent blood tests, which have several drawbacks related to the invasiveness of the technique, comfort, cost and reliability. Dermal interstitial fluid (ISF) is an accessible and information-rich biofluid, and correlations have been found between blood and ISF levels of lithium medication. METHODS: In the current study, we sought to investigate the optical determination of lithium therapeutic concentrations in samples of ISF extracted from porcine skin utilizing a microneedle-based approach. Monitoring of lithium levels in porcine ISF was achieved by employing a spectrophotometric method based on the reaction between the chromogenic agent Quinizarin and lithium. RESULTS: The resulting spectra show spectral variations which relate to lithium concentrations of lithium in samples of porcine ISF with a coefficient of determination (R2 ) of 0.9. This study has demonstrated successfully that therapeutic levels of lithium in micro-volumes of porcine ISF can be measured with a high level of accuracy utilizing spectroscopic techniques. CONCLUSIONS: The results support the future development of a miniaturized and minimally-invasive device for lithium monitoring in bipolar patients.

Near-Infrared Spectroscopy (NIRS) in Traumatic Brain Injury (TBI).

Traumatic brain injury (TBI) occurs when a sudden trauma causes damage to the brain. TBI can result when the head suddenly and violently impacts an object or when an object pierces the skull and enters brain tissue. Secondary injuries after traumatic brain injury (TBI) can lead to impairments on cerebral oxygenation and autoregulation. Considering that secondary brain injuries often take place within the first hours after the trauma, noninvasive monitoring might be helpful in providing early information on the brain's condition. Near-infrared spectroscopy (NIRS) is an emerging noninvasive monitoring modality based on chromophore absorption of infrared light with the capability of monitoring perfusion of the brain. This review investigates the main applications of NIRS in TBI monitoring and presents a thorough revision of those applications on oxygenation and autoregulation monitoring. Databases such as PubMed, EMBASE, Web of Science, Scopus, and Cochrane library were utilized in identifying 72 publications spanning between 1977 and 2020 which were directly relevant to this review. The majority of the evidence found used NIRS for diagnosis applications, especially in oxygenation and autoregulation monitoring (59%). It was not surprising that nearly all the patients were male adults with severe trauma who were monitored mostly with continue wave NIRS or spatially resolved spectroscopy NIRS and an invasive monitoring device. In general, a high proportion of the assessed papers have concluded that NIRS could be a potential noninvasive technique for assessing TBI, despite the various methodological and technological limitations of NIRS.

Design and Analysis of a Continuous and Non-Invasive Multi-Wavelength Optical Sensor for Measurement of Dermal Water Content.

Dermal water content is an important biophysical parameter in preserving skin integrity and preventing skin damage. Traditional electrical-based and open-chamber evaporimeters have several well-known limitations. In particular, such devices are costly, sizeable, and only provide arbitrary outputs. They also do not permit continuous and non-invasive monitoring of dermal water content, which can be beneficial for various consumer, clinical, and cosmetic purposes. We report here on the design and development of a digital multi-wavelength optical sensor that performs continuous and non-invasive measurement of dermal water content. In silico investigation on porcine skin was carried out using the Monte Carlo modeling strategy to evaluate the feasibility and characterize the sensor. Subsequently, an in vitro experiment was carried out to evaluate the performance of the sensor and benchmark its accuracy against a high-end, broad band spectrophotometer. Reference measurements were made against gravimetric analysis. The results demonstrate that the developed sensor can deliver accurate, continuous, and non-invasive measurement of skin hydration through measurement of dermal water content. Remarkably, the novel design of the sensor exceeded the performance of the high-end spectrophotometer due to the important denoising effects of temporal averaging. The authors believe, in addition to wellbeing and skin health monitoring, the designed sensor can particularly facilitate disease management in patients presenting diabetes mellitus, hypothyroidism, malnutrition, and atopic dermatitis.

Comparison of Dual Beam Dispersive and FTNIR Spectroscopy for Lactate Detection.

Near Infrared (800-2500 nm) spectroscopy has been extensively used in biomedical applications, as it offers rapid, in vivo, bed-side monitoring of important haemodynamic parameters, which is especially important in critical care settings. However, the choice of NIR spectrometer needs to be investigated for biomedical applications, as both the dual beam dispersive spectrophotomer and the FTNIR spectrometer have their own advantages and disadvantages. In this study, predictive analysis of lactate concentrations in whole blood were undertaken using multivariate techniques on spectra obtained from the two spectrometer types simultaneously and results were compared. Results showed significant improvement in predicting analyte concentration when analysis was performed on full range spectral data. This is in comparison to analysis of limited spectral regions or lactate signature peaks, which yielded poorer prediction models. Furthermore, for the same region, FTNIR showed 10% better predictive capability than the dual beam dispersive NIR spectrometer.

Novel Polydimethylsiloxane (PDMS) Pulsatile Vascular Tissue Phantoms for the In-Vitro Investigation of Light Tissue Interaction in Photoplethysmography.

Currently there exists little knowledge or work in phantoms for the in-vitro evaluation of photoplethysmography (PPG), and its' relationship with vascular mechanics. Such phantoms are needed to provide robust, basic scientific knowledge, which will underpin the current efforts in developing new PPG technologies for measuring or estimating blood pressure, blood flow and arterial stiffness, to name but a few. This work describes the design, fabrication and evaluation of finger tissue-simulating pulsatile phantoms with integrated custom vessels. A novel technique has been developed to produce custom polydimethylsiloxane (PDMS) vessels by a continuous dip-coating process. This process can accommodate the production of different sized vessel diameters (1400-2500 µm) and wall thicknesses (56-80 µm). These vessels were embedded into a mould with a solution of PDMS and India ink surrounding them. A pulsatile pump experimental rig was set up to test the phantoms, where flow rate (1-12 L·min-1), heart rate (40-120 bpm), and total resistance (0-100% resistance clamps) could be controlled on demand. The resulting flow profiles approximates human blood flow, and the detected contact PPG signal (red and infrared) from the phantom closely resembles the morphology of in-vivo PPG waveforms with signal-to-noise ratios of 38.16 and 40.59 dB, for the red and infrared wavelengths, respectively. The progress made by this phantom development will help in obtaining new knowledge in the behaviour of PPG's under differing flow conditions, optical tissue properties and differing vessel stiffness.

Identification and Quantitative Determination of Lactate Using Optical Spectroscopy-Towards a Noninvasive Tool for Early Recognition of Sepsis.

Uninterrupted monitoring of serum lactate levels is a prerequisite in the critical care of patients prone to sepsis, cardiogenic shock, cardiac arrest, or severe lung disease. Yet there exists no device to continuously measure blood lactate in clinical practice. Optical spectroscopy together with multivariate analysis is proposed as a viable noninvasive tool for estimation of lactate in blood. As an initial step towards this goal, we inspected the plausibility of predicting the concentration of sodium lactate (NaLac) from the UV/visible, near-infrared (NIR), and mid-infrared (MIR) spectra of 37 isotonic phosphate-buffered saline (PBS) samples containing NaLac ranging from 0 to 20 mmol/L. UV/visible (300-800 nm) and NIR (800-2600 nm) spectra of PBS samples were collected using the PerkinElmer Lambda 1050 dual-beam spectrophotometer, while MIR (4000-500 cm-1) spectra were collected using the Spectrum two FTIR spectrometer. Absorption bands in the spectra of all three regions were identified and functional groups were assigned. The concentration of lactate in samples was predicted using the Partial Least-Squares (PLS) regression analysis and leave-one-out cross-validation. The regression analysis showed a correlation coefficient (R2) of 0.926, 0.977, and 0.992 for UV/visible, NIR, and MIR spectra, respectively, between the predicted and reference samples. The RMSECV of UV/visible, NIR, and MIR spectra was 1.59, 0.89, and 0.49 mmol/L, respectively. The results indicate that optical spectroscopy together with multivariate models can achieve a superior technique in assessing lactate concentrations.

Investigations into the Effects of pH on Quantitative Measurements of Lactate in Biological Media Using ATR-FTIR Spectroscopy.

Quantification of lactate/lactic acid in critical care environments is essential as lactate serves as an important biochemical marker for the adequacy of the haemodynamic circulation in shock and of cell respiration at the onset of sepsis/septic shock. Hence, in this study, ATR-FTIR was explored as a potential tool for lactate measurement, as the current techniques depend on sample preparation and fails to provide rapid response. Moreover, the effects of pH on PBS samples (7.4, 7, 6.5 and 6) and change in solution conditions (PBS to whole blood) on spectral features were also investigated. A total 189 spectra from five sets of lactate containing media were obtained. Results suggests that lactate could be measured with more than 90% accuracy in the wavenumber range of 1500-600 cm-1. The findings of this study further suggest that there exist no effects of change in pH or media, when estimating lactate concentration changes in this range of the Mid-IR spectral region.

Monte Carlo Analysis of Optical Interactions in Reflectance and Transmittance Finger Photoplethysmography.

Photoplethysmography (PPG) is a non-invasive photometric technique that measures the volume changes in arterial blood. Recent studies have reported limitations in developing and optimising PPG-based sensing technologies due to unavailability of the fundamental information such as PPG-pathlength and penetration depth in a certain region of interest (ROI) in the human body. In this paper, a robust computational model of a dual wavelength PPG system was developed using Monte Carlo technique. A three-dimensional heterogeneous volume of a specific ROI (i.e., human finger) was exposed at the red (660 nm) and infrared (940 nm) wavelengths in the reflectance and transmittance modalities of PPG. The optical interactions with the individual pulsatile and non-pulsatile tissue-components were demonstrated and the optical parameters (e.g., pathlength, penetration depth, absorbance, reflectance and transmittance) were investigated. Results optimised the source-detector separation for a reflectance finger-PPG sensor. The analysis with the recorded absorbance, reflectance and transmittance confirmed the maximum and minimum impact of the dermis and bone tissue-layers, respectively, in the formation of a PPG signal. The results presented in the paper provide the necessary information to develop PPG-based transcutaneous sensors and to understand the origin of the ac and dc components of the PPG signal.

Dual pO2/pCO2 fibre optic sensing film.

A fibre optic multi-sensor has been developed for biomedical sensing applications using a tip coating solution sensitive to both oxygen and carbon dioxide. An oxygen sensitive phosphorescence quenching complex based on platinum octaethylporphyrin (PtOEP) was combined with a carbon dioxide sensitive phosphorescence compound based on 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS). When excited by blue light (470 nm), the resultant coating had two fluorescent peaks at 515 nm (green) and 645 nm (red) which responded to partial pressure of CO2 and O2 respectively. The sensor was tested in vitro and shown to be able to measure CO2 and O2 simultaneously and in real time, with calibration constants of 0.0384 kPa-1 and 0.309 kPa-1 respectively. The O2 sensitive peak received some overlap from the 515 nm peak (0.38% of peak intensity) as well as some cross-sensitivity (maximum, 5.1 kPa pCO2 gave a measurement equivalent to 0.43 kPa of O2, a ratio of 0.08 : 1). However, these effects can be subtracted from measurements and no significant cross-sensitivity or overlap was seen in CO2 measurements from O2. This novel compound presents great potential for use in medical sensors and we expect it to be important to a wide range of future applications.

Review of Protocols Used in Ultrasound Thrombolysis.

OBJECTIVES: This paper focuses on the review of protocols used in thrombolysis studies with ultrasound. MATERIALS AND METHODS: Data from peer-review articles were acquired. RESULTS: The protocols of several published reports are summarized in 3 tables (in vitro, in vivo, and clinical), providing detailed information concerning clot model, thrombolytic drug, treatment mode, sonication parameters, evaluation method, thrombolysis outcome, side effects, and conclusions. CONCLUSIONS: The aim of this review was to give an overview of the different protocols used so far in the field of sonothrombolysis and investigate the impact of several aspects involved on sonothrombolysis outcome.

Fiber-optic fluorescence-quenching oxygen partial pressure sensor using platinum octaethylporphyrin.

The development and bench testing of a fiber-optic oxygen sensor is described. The sensor is designed for measurement of tissue oxygen levels in the mucosa of the digestive tract. The materials and construction are optimized for insertion through the mouth for measurement in the lower esophagus. An oxygen-sensitive fluorescence-quenching film was applied as a solution of platinum octaethylporphyrin (PtOEP) poly(ethyl methacrylate) (PEMA) and dichloromethane and dip coated onto the distal tip of the fiber. The sensor was tested by comparing relative fluorescence when immersed in liquid water at 37°C, at a range of partial pressures (0-101 kPa). Maximum relative fluorescence at most oxygen concentrations was seen when the PtOEP concentration was 0.1 g.L-1, four layers of coating solution were applied, and a fiber core radius of 600 µm was selected, giving a Stern-Volmer constant of 0.129 kPa-1. The performance of the sensor is suitable for many in vivo applications, particularly mucosal measurements. It has sufficient sensitivity, is sterilizable, and is sufficiently flexible and robust for insertion via the mouth without damage to the probe or risk of harm to the patient.

Investigation of peripheral photoplethysmographic morphology changes induced during a hand-elevation study.

A hand-elevation study was carried out in the laboratory in order to alter peripheral blood flow with the aim of increasing understanding of factors affecting the morphology of peripheral photoplethysmographic signals. Photoplethysmographic (PPG) signals were recorded from twenty healthy volunteer subjects during a hand-elevation study in which the right hand was raised and lowered relative to heart level, while the left hand remained static. Red and infrared (IR) PPG signals were obtained from the right and left index fingers using a custom-made PPG processing system. PPG features were identified using a feature-detection algorithm based on the first derivative of the PPG signal. The systolic PPG amplitude, the reflection index, crest time, pulse width at half height, and delta T were calculated from 20 s IR PPG signals from three positions of the right hand with respect to heart level (-50, 0, +50 cm) in 19 volunteers. PPG features were found to change with hand elevation. On lowering the hand to 50 cm below heart level, ac systolic PPG amplitudes from the finger decreased by 68.32 %, while raising the arm increased the systolic amplitude by 69.99 %. These changes in amplitude were attributed to changes in hydrostatic pressure and the veno-arterial reflex. Other morphological variables, such as crest time, were found to be statistically significantly different across hand positions, indicating increased vascular resistance on arm elevation than on dependency. It was hypothesized that these morphological PPG changes were influenced by changes in downstream venous resistance, rather than arterial, or arteriolar, resistance. Changes in hand position relative to heart level can significantly affect the morphology of the peripheral ac PPG waveform. These alterations are due to a combination of physical effects and physiological responses to changes in hand position, which alter vascular resistance. Care should be taken when interpreting morphological data derived from PPG signals and methods should be standardized to take these effects into account.

Developing technologies to assess vascular ageing: a roadmap from VascAgeNet.

Vascular ageing is the deterioration of arterial structure and function which occurs naturally with age, and which can be accelerated with disease. Measurements of vascular ageing are emerging as markers of cardiovascular risk, with potential applications in disease diagnosis and prognosis, and for guiding treatments. However, vascular ageing is not yet routinely assessed in clinical practice. A key step towards this is the development of technologies to assess vascular ageing. In this Roadmap, experts discuss several aspects of this process, including: measurement technologies; the development pipeline; clinical applications; and future research directions. The Roadmap summarises the state of the art, outlines the major challenges to overcome, and identifies potential future research directions to address these challenges.

Direct pulse oximetry within the esophagus, on the surface of abdominal viscera, and on free flaps.

BACKGROUND: Pulse oximetry is a noninvasive photometric technique that provides information about arterial blood oxygen saturation (SpO2) and heart rate and has widespread clinical applications. This is accomplished via peripheral pulse oximetry probes mainly attached to the finger, toe, or earlobe. The direct application of pulse oximetry to an organ, such as the esophagus, liver, bowel, stomach or free flap, might provide an indication of how well perfused an organ or a free flap is. Also, the placement of a pulse oximetry probe at a more central site, such as the esophagus, might be more reliable at a time when conventional peripheral pulse oximetry fails. METHODS: The focus of this article is the development and in vivo applications of new custom-made photoplethysmographic (PPG) and pulse oximetry optical and fiberoptic probes and instrumentation in an effort to investigate their suitability for the estimation of arterial blood oxygen saturation at different organs and tissues. The article will cover examples of application areas including real-time PPG and SpO2 monitoring for the esophagus and solid organs, including free flaps, using custom-made probes. RESULTS: Clinical studies have successfully demonstrated the feasibility of acquiring PPGs and estimating arterial blood oxygen saturation values from a variety of organs and tissues. CONCLUSIONS: The technological developments and the measurements presented in this work pave the way to a new era of pulse oximetry where direct and continuous monitoring of blood oxygen saturation of internal organs and tissues (esophagus, bowel, liver, stomach, free flaps) could be possible.

A review of the effect of skin pigmentation on pulse oximeter accuracy.

Objective. Pulse oximetry is a non-invasive optical technique used to measure arterial oxygen saturation (SpO2) in a variety of clinical settings and scenarios. Despite being one the most significant technological advances in health monitoring over the last few decades, there have been reports on its various limitations. Recently due to the Covid-19 pandemic, questions about pulse oximeter technology and its accuracy when used in people with different skin pigmentation have resurfaced, and are to be addressed.Approach. This review presents an introduction to the technique of pulse oximetry including its basic principle of operation, technology, and limitations, with a more in depth focus on skin pigmentation. Relevant literature relating to the performance and accuracy of pulse oximeters in populations with different skin pigmentation are evaluated.Main Results. The majority of the evidence suggests that the accuracy of pulse oximetry differs in subjects of different skin pigmentations to a level that requires particular attention, with decreased accuracy in patients with dark skin.Significance. Some recommendations, both from the literature and contributions from the authors, suggest how future work could address these inaccuracies to potentially improve clinical outcomes. These include the objective quantification of skin pigmentation to replace currently used qualitative methods, and computational modelling for predicting calibration algorithms based on skin colour.

Non-invasive monitoring of intracranial pressure changes: healthy volunteers study.

Objective: This research aims to evaluate the possible association between pulsatile near infrared spectroscopic waveform features and induced changes in intracranial pressure in healthy volunteers. Methods: An optical intracranial pressure sensor was attached to the forehead of 16 healthy volunteers. Pulsatile near infrared spectroscopic signals were acquired from the forehead during body position changes and Valsalva manoeuvers. Features were extracted from the pulsatile signals and analyses were carried out to investigate the presence of statistical differences in the features when intracranial pressure changes were induced. Classification models were developed utilizing the features extracted from the pulsatile near-infrared spectroscopic signals to classify between different body positions and Valsalva manoeuvre. Results: The presence of significant differences in the majority of the analyzed features (p < 0.05) indicates the technique's ability to distinguish between variations in intracranial pressure. Furthermore, the disparities observed in the optical signal features captured by the proximal and distal photodetectors support the hypothesis that alterations in back-scattered light directly correspond to brain-related changes. Further research is required to subtract distal and proximal signals and construct predictive models employing a gold standard measurement for non-invasive, continuous monitoring of intracranial pressure. Conclusion: The study investigated the use of pulsatile near infrared spectroscopic signals to detect changes in intracranial pressure in healthy volunteers. The results revealed significant differences in the features extracted from these signals, demonstrating a correlation with ICP changes induced by positional changes and Valsalva manoeuvre. Classification models were capable of identifying changes in ICP using features from optical signals from the brain, with a sensitivity ranging from 63.07% to 80% and specificity ranging from 60.23% to 70% respectively. These findings underscored the potential of these features to effectively identify alterations in ICP. Significance: The study's results demonstrate the feasibility of using features extracted from optical signals from the brain to detect changes in ICP induced by positional changes and Valsalva manoeuvre in healthy volunteers. This represents a first step towards the non-invasive monitoring of intracranial pressure.

Evaluation of electrical and optical plethysmography sensors for noninvasive monitoring of hemoglobin concentration.

Completely noninvasive monitoring of hemoglobin concentration has not yet been fully realized in the clinical setting. This study investigates the viability of measuring hemoglobin concentration noninvasively by evaluating the performance of two types of sensor using a tissue phantom perfused with a blood substitute. An electrical sensor designed to measure blood volume changes during the cardiac cycle was used together with an infrared optical sensor for detection of erythrocyte-bound hemoglobin. Both sensors demonstrated sensitivity to changes in pulse volume (plethysmography). The electrical sensor produced a signal referred to as capacitance plethysmograph (CPG) a quantity which was invariant to the concentration of an infrared absorbing dye present in the blood substitute. The optical sensor signal (photoplethysmograph) increased in amplitude with increasing absorber concentration. The ratio PPG:CPG is invariant to pulse pressure. This quantity is discussed as a possible index of in vivo hemoglobin concentration.

Effects of using different algorithms and fiducial points for the detection of interbeat intervals, and different sampling rates on the assessment of pulse rate variability from photoplethysmography.

OBJECTIVE: Pulse Rate Variability (PRV) has been widely used as a surrogate of Heart Rate Variability (HRV). However, there are several technical aspects that may affect the extraction of PRV information from pulse wave signals such as the photoplethysmogram (PPG). The aim of this study was to evaluate the effects of changing the algorithm and fiducial points used for determining inter-beat intervals (IBIs), as well as the PPG sampling rate, from simulated PPG signals with known PRV content. METHODS: PPG signals were simulated using a proposed model, in which PRV information can be modelled. Two independent experiments were performed. First, 5 IBIs detection algorithms and 8 fiducial points were used for assessing PRV information from the simulated PPG signals, and time-domain and Poincaré plot indices were extracted and compared to the expected values according to the simulated PRV. The best combination of algorithms and fiducial points were determined for each index, using factorial designs. Then, using one of the best combinations, PPG signals were simulated with varying sampling rates. PRV indices were extracted and compared to the expected values using Student t-tests or Mann-Whitney U-tests. RESULTS: From the first experiment, it was observed that AVNN and SD2 indices behaved similarly, and there was no significant influence of the fiducial points used. For other indices, there were several combinations that behaved similarly well, mostly based on the detection of the valleys of the PPG signal. There were differences according to the quality of the PPG signal. From the second experiment, it was observed that, for all indices but SDNN, the higher the sampling rate the better. AVNN and SD2 showed no statistical differences even at the lowest evaluated sampling rate (32 Hz), while RMSSD, pNN50, S, SD1 and SD1/SD2 showed good performance at sampling rates as low as 128 Hz. CONCLUSION: The best combination of IBIs detection algorithms and fiducial points differs according to the application, but those based on the detection of the valleys of the PPG signal tend to show a better performance. The sampling rate of PPG signals for PRV analysis could be lowered to around 128 Hz, although it could be further lowered according to the application. SIGNIFICANCE: The standardisation of PRV analysis could increase the reliability of this signal and allow for the comparison of results obtained from different studies. The obtained results allow for a first approach to establish guidelines for two important aspects in PRV analysis from PPG signals, i.e. the way the IBIs are segmented from PPG signals, and the sampling rate that should be used for these analyses. Moreover, a model for simulating PPG signals with PRV information has been proposed, which allows for the establishing of these guidelines while controlling for other variables, such as the quality of the PPG signal.