Mechanical Testing of Artificial Vessels and Tissues for Photoplethysmography Phantoms.

Various studies have looked at the efficiency of artificial vessel and tissue networks in the study of photoplethysmography (PPG) in an effort to better understand the origin of various morphological features present in the signal. Whilst there are all reasonable attempts made to replicate geometrical features such as vessel depth, vessel wall thickness and diameter etc., not many studies have attempted to replicate the mechanical properties such as vessel elasticity and tissue compressibility. This study reports two methods for tissue mechanical testing for the analysis of vessel elasticity and tissue compressibility. A two-part polydimethylsiloxane (PDMS) was used as a base material for both tissue and vessel construction, and the properties altered by changing the curing component ratio. Tissue compression properties were investigated using an industrially calibrated materials testing device using the protocol from the ASTM 0575-91 testing method. Vessel elasticity was investigated using a custom method and apparatus to report vessel diameter and length change simultaneously. Tissue compressive properties proved reasonably easy to replicate through catalyst alteration, however the vessel elasticity properties were found to be higher than expected at all reasonable catalyst ratios. The property of hyper-elasticity was observed in the artificial vessels though, leading to the conclusion that alternative material recipes or construction methods may be needed to correctly replicate the expected mechanical characteristics. Clinical Relevance- The latest generation of health monitoring devices, especially those that are wearable and used widely by individuals wishing to monitor their health daily are becoming smarter and more sophisticated in their functionality. The majority of such devices use photoplethysmography (PPG) as their primary monitoring technique. Being able to replicate the PPG in a phantom allows the continued study and development of devices, and to improve their functionality without the continued need for extensive user-testing.

Monte Carlo Characterization of Short-Wave Infrared Optical Wavelengths for Biosensing Applications.

Short-wave infrared (SWIR) spectroscopy has shown great promise in probing the composition of biological tissues. Currently there exists an enormous drive amongst researchers to design and develop SWIR-based optical sensors that can predict the concentration of various biomarkers non-invasively. However, there is limited knowledge regarding the interaction of SWIR light with vascular tissue, especially in terms of parameters like the optimal source-detector separation, light penetration depth, optical pathlength, etc., all of which are essential components in designing optical sensors. With the aim to determine these parameters, Monte Carlo simulations were carried out to examine the interaction of SWIR light with vascular skin. SWIR photons were found to penetrated only 1.3 mm into the hypodermal fat layer. The highest optical pathlength and penetration depths were seen at 1mm source-detector separation, and the lowest being 0.7mm. Although the optical pathlength varied significantly with increasing source-detector separation at SWIR wavelengths, penetration depth remained constant. This may explain why collecting optical spectra from depth of tissue at SWIR wavelengths is more challenging than collecting optical spectra from near-infrared wavelengths, where both the optical pathlength and penetration depth change rapidly with source-detector separation.

In-vivo quantification of lactate using Near Infrared reflectance spectroscopy.

Elevated lactate levels in blood (hyperlactatemia) are indications of hypoperfusion or sepsis in critical care conditions. Quantification and monitoring of this important marker is performed using intermittent blood sampling, which fails to provide a complete scenario to aid clinicians in diagnosis. The feasibility of Near Infrared (NIR) Spectroscopy as an alternative to state-of-the-art techniques in critical care environments for non-invasive and continuous monitoring of lactate has previously been established. Nevertheless, the challenge lies in translating this research from bench to bedside monitoring. For this reason, a pilot investigation was carried out with a portable NIR spectrometer, where spectra in the range of 900-1300 nm were collected from 8 healthy human volunteers undertaking a high intensity incremental exercise protocol for lactate monitoring. This paper reports on the measurement set-up, spectra acquisition and analysis of diffuse NIR reflectance spectra of varying concentrations of lactate. The results obtained by 2D correlation analysis and linear regression are promising and show that the wavelengths 923 nm, 1047 nm, 1142 nm, 1233 nm, 1280 nm and 1330 nm are significant for lactate concentration determination in the NIR region. This provides the necessary confidence for using NIR sensor technology for lactate detection in critical care.

An empirical investigation of deviations from the Beer-Lambert law in optical estimation of lactate.

The linear relationship between optical absorbance and the concentration of analytes-as postulated by the Beer-Lambert law-is one of the fundamental assumptions that much of the optical spectroscopy literature is explicitly or implicitly based upon. The common use of linear regression models such as principal component regression and partial least squares exemplifies how the linearity assumption is upheld in practical applications. However, the literature also establishes that deviations from the Beer-Lambert law can be expected when (a) the light source is far from monochromatic, (b) the concentrations of analytes are very high and (c) the medium is highly scattering. The lack of a quantitative understanding of when such nonlinearities can become predominant, along with the mainstream use of nonlinear machine learning models in different fields, have given rise to the use of methods such as random forests, support vector regression, and neural networks in spectroscopic applications. This raises the question that, given the small number of samples and the high number of variables in many spectroscopic datasets, are nonlinear effects significant enough to justify the additional model complexity? In the present study, we empirically investigate this question in relation to lactate, an important biomarker. Particularly, to analyze the effects of scattering matrices, three datasets were generated by varying the concentration of lactate in phosphate buffer solution, human serum, and sheep blood. Additionally, the fourth dataset pertained to invivo, transcutaneous spectra obtained from healthy volunteers in an exercise study. Linear and nonlinear models were fitted to each dataset and measures of model performance were compared to attest the assumption of linearity. To isolate the effects of high concentrations, the phosphate buffer solution dataset was augmented with six samples with very high concentrations of lactate between (100-600 mmol/L). Subsequently, three partly overlapping datasets were extracted with lactate concentrations varying between 0-11, 0-20 and 0-600 mmol/L. Similarly, the performance of linear and nonlinear models were compared in each dataset. This analysis did not provide any evidence of substantial nonlinearities due high concentrations. However, the results suggest that nonlinearities may be present in scattering media, justifying the use of complex, nonlinear models.

The efficacy of support vector machines in modelling deviations from the Beer-Lambert law for optical measurement of lactate.

Lactate is an important biomarker with a significant diagnostic and prognostic ability in relation to life-threatening conditions and diseases such as sepsis, diabetes, cancer, pulmonary and kidney diseases, to name a few. The gold standard method for the measurement of lactate relies on blood sampling, which due to its invasive nature, limits the ability of clinicians in frequent monitoring of patients' lactate levels. Evidence suggests that the optical measurement of lactate holds promise as an alternative to blood sampling. However, achieving this aim requires better understanding of the optical behavior of lactate. The present study investigates the potential deviations of absorbance from the Beer-Lambert law in high concentrations of lactate. To this end, a number of nonlinear models namely support vector machines with quadratic, cubic and quartic kernels and radial basis function kernel are compared with the linear principal component regression and linear support vector machine. Interestingly, it is shown that even in extremely high concentrations of lactate (600 mmol/L) in a phosphate buffer solution, the linear models surpass the performance of the other models.

Near Infrared and Aquaphotomic analysis of water absorption in lactate containing media.

Increased concentrations of lactate levels in blood are often seen in patients with life-threatening cellular hypoperfusion or infections. State-of-the-art techniques used in clinical practice for measuring serum lactate concentrations rely on intermittent blood sampling and do not permit continuous monitoring of this all important parameter in critical care environments.In recent years, Near Infrared (NIR) Spectroscopy has been established as a possible alternative to existing methods that can mitigate these constraints and be used for non-invasive continuous monitoring of lactate. Nevertheless, the dominant absorption of -OH overtone bands of water in the NIR presents a challenge and complicates the accurate detection of other absorbers such as lactate. For this reason, comprehensive analysis of the -OH overtone bands with systematic lactate concentration changes is essential. This paper reports on the analysis of NIR spectra of two aqueous systems of varying concentrations of lactate in saline and whole blood using the principles of Aquaphotomics.The results show distinctive conformational and structural differences in lactate-water binding, which arise due to the molecular interactions of bonds present in respective solvents.

In vitro quantification of lactate in Phosphate Buffer Saline (PBS) samples.

Continuous measurement of lactate levels in the blood is a prerequisite in intensive care patients who are susceptible to sepsis due to their suppressed immune system and increased metabolic demand. Currently, there exists no noninvasive tool for continuous measurement of lactate in clinical practice. The current mode of measurement is based on arterial blood gas analyzers which require sampling of arterial blood. In this work, we propose the use of Near Infra-Red (NIR) spectroscopy together with multivariate models as a means to non-invasively predict the concentration of lactate in the blood. As the first step towards this objective, we examined the possibility of accurately predicting concentrations of sodium lactate (NaLac) from the NIR spectra of 37 isotonic phosphate buffer saline (PBS) samples containing NaLac ranging from 0 to 20 mmol/L. NIR spectra of PBS samples were collected using the Lambda 1050 dual beam spectrometer over a spectral range of 800 - 2600 nm with a quartz cell of 1 mm optical path. Estimates and calibration of the lactate concentration with the NIR spectra were made using Partial Least-Squares (PLS) regression analysis and leave-one-out cross-validation on filtered spectra. The regression analysis showed a correlation coefficient of 0.977 and a standard error of 0.89 mmol/L between the predicted and prepared samples. The results suggest that NIR spectroscopy together with multivariate models can be a valuable tool for non-invasive assessment of blood lactate concentrations.

Comparison of a Genetic Algorithm Variable Selection and Interval Partial Least Squares for quantitative analysis of lactate in PBS.

Blood lactate is an important biomarker that has been linked to morbidity and mortality of critically ill patients, acute ischemic stroke, septic shock, lung injuries, insulin resistance in diabetic patients, and cancer. Currently, the clinical measurement of blood lactate is done by collecting intermittent blood samples. Therefore, noninvasive, optical measurement of this significant biomarker would lead to a big leap in healthcare. This study, presents a quantitative analysis of the optical properties of lactate. The benefits of wavelength selection for the development of accurate, robust, and interpretable predictive models have been highlighted in the literature. Additionally, there is an obvious, time- and cost-saving benefit to focusing on narrower segments of the electromagnetic spectrum in practical applications. To this end, a dataset consisting of 47 spectra of Na-lactate and Phosphate Buffer Solution (PBS) was produced using a Fourier transform infrared spectrometer, and subsequently, a comparative study of the application of a genetic algorithm-based wavelength selection and two interval selection methods was carried out. The high accuracy of predictions using the developed models underlines the potential for optical measurement of lactate. Moreover, an interesting finding is the emergence of local features in the proposed genetic algorithm, while, unlike the investigated interval selection methods, no explicit constraints on the locality of features was imposed. Finally, the proposed genetic algorithm suggests the formation of α-hydroxy-esters methyl lactate in the solutions while the other investigated methods fail to indicate this.

Near Infrared Spectrometric Investigations on the behaviour of Lactate.

In patients with life-threatening illnesses, the metabolic production and disposal of lactate are impaired, which leads to a build-up of blood lactate. In critical care units, the changes in lactate levels are measured through intermittent, invasive, blood sampling and in vitro assay. Continuous monitoring is lacking, yet such monitoring could allow early assessment of severity and prognosis to guide therapy. Currently, there is no routine means to measure lactate levels continuously, particularly non-invasively. The motivation of this study was to understand the interaction of lactate with light in the Near Infra Red (NIR) region of the electromagnetic spectrum. This was to create an opportunity to explore the possibility of a non-invasive sensing technology to monitor lactate continuously.In vitro studies were performed using solution samples with varying concentration levels of sodium lactate in isotonic Phosphate Buffer Solution (PBS) at constant pH (7.4). These samples were prepared using stoichiometric solution compositions and spectra for each sample were taken using a state-of-the-art spectrometer in the NIR region. The spectra were then analysed qualitatively by 2D correlation analysis, which identified the regions of interest. Further analysis of these regions using linear regression at four randomly selected wavelengths showed bathochromic shifts, which, moreover, showed systematic variation correlating with lactate concentration.

In vivo investigation of ear canal pulse oximetry during hypothermia.

Pulse oximeters rely on the technique of photoplethysmography (PPG) to estimate arterial oxygen saturation (SpO[Formula: see text]). In conditions of poor peripheral perfusion such as hypotension, hypothermia, and vasoconstriction, the PPG signals detected are often weak and noisy, or in some cases unobtainable. Hence, pulse oximeters produce erroneous SpO[Formula: see text] readings in these circumstances. The problem arises as most commercial pulse oximeter probes are designed to be attached to peripheral sites such as the finger or toe, which are easily affected by vasoconstriction. In order to overcome this problem, the ear canal was investigated as an alternative site for measuring reliable SpO[Formula: see text] on the hypothesis that blood flow to this central site is preferentially preserved. A novel miniature ear canal PPG sensor was developed along with a state of the art PPG processing unit to investigate PPG measurements from the bottom surface of the ear canal. An in vivo study was carried out in 15 healthy volunteers to validate the developed technology. In this comparative study, red and infrared PPGs were acquired from the ear canal and the finger of the volunteers, whilst they were undergoing artificially induced hypothermia by means of cold exposure (10 [Formula: see text]C). Normalised Pulse Amplitude (NPA) and SpO[Formula: see text] was calculated from the PPG signals acquired from the ear canal and the finger. Good quality baseline PPG signals with high signal-to-noise ratio were obtained from both the PPG sensors. During cold exposure, significant differences were observed in the NPA of the finger PPGs. The mean NPA of the red and infrared PPGs from the finger have dropped by >80%. Contrary to the finger, the mean NPA of red and infrared ear canal PPGs had dropped only by 0.2 and 13% respectively. The SpO[Formula: see text]s estimated from the finger sensor have dropped below 90% in five volunteers (failure) by the end of the cold exposure. The ear canal sensor, on the other hand, had only failed in one volunteer. These results strongly suggest that the ear canal may be used as a suitable alternative site for monitoring PPGs and arterial blood oxygen saturation at times were peripheral perfusion is compromised.

Investigation of photoplethysmography, laser doppler flowmetry and near infrared spectroscopy during induced thermal stress.

Continuous assessment of blood flow, blood volume, and blood and tissue oxygenation are of vital importance in critically ill patients. Photoplethysmography (PPG), Pulse Oximetry (PO), Laser Doppler Flowmetry (LDF) and Near Infrared Spectroscopy (NIRS) are amongst the most widely used techniques to monitor such perfusion parameters. In this study, we investigated the feasibility of using dual-wavelength PPG signals on providing comparable information as LDF and NIRS, besides arterial oxygen saturation (SpO2) as measured by pulse oximetry. All three techniques were investigated on six healthy volunteers during whole-body cold exposure. PPG and LDF sensors were attached on the finger and hand respectively, while NIRS was positioned above the left forearm. Measurements at room temperature (24°C) were followed and preceded by a cold exposure (10°C). The results showed that changes in pulsatile PPG amplitudes and hemoglobin concentration estimated from finger PPG signals indicate strong similarities with gold-standard LDF and NIRS measurements.

Investigation of photoplethysmography and arterial blood oxygen saturation from the ear-canal and the finger under conditions of artificially induced hypothermia.

Pulse oximeters relay on the technique of photoplethysmography (PPG) to estimate arterial oxygen saturation (SpO2). In conditions of poor peripheral perfusion such as hypotension, hypothermia, and vasoconstriction, pulse oximeters become inaccurate or provide no reading. This is due to the poor quality of the PPG signals detected at that instance. In order to overcome this problem, the ear canal has been proposed as a alternative measurement site for measuring reliable SpO2. Hence, an ear canal PPG sensor was developed along with a PPG processing system. The performance of the sensor was evaluated by measuring the red and infrared PPGs and SpO2 from 10 healthy volunteers undergoing artificially induced hypothermia. The results from the ear canal sensor were compared with simultaneously acquired results from the finger. Hypothermia was induced by exposing the volunteers to cold temperatures of 10 ± 1°C. The results acquired suggest that the ear canal pulse oximeter endures more in estimating SpO2 values accurately when compared with the more common finger pulse oximeter.

The human ear canal: investigation of its suitability for monitoring photoplethysmographs and arterial oxygen saturation.

For the last two decades, pulse oximetry has been used as a standard procedure for monitoring arterial oxygen saturation (SpO2). However, SpO2 measurements made from extremities such as the finger, ear lobe and toes become susceptible to inaccuracies when peripheral perfusion is compromised. To overcome these limitations, the external auditory canal has been proposed as an alternative monitoring site for estimating SpO2, on the hypothesis that this central site will be better perfused. Therefore, a dual wavelength optoelectronic probe along with a processing system was developed to investigate the suitability of measuring photoplethysmographic (PPG) signals and SpO2 in the human auditory canal. A pilot study was carried out in 15 healthy volunteers to validate the feasibility of measuring PPGs and SpO2 from the ear canal (EC), and comparative studies were performed by acquiring the same signals from the left index finger (LIF) and the right index finger (RIF) in conditions of induced peripheral vasoconstriction (right hand immersion in ice water). Good quality baseline PPG signals with high signal-to-noise ratio were obtained from the EC, the LIF and the RIF sensors. During the ice water immersion, significant differences in the amplitude of the red and infrared PPG signals were observed from the RIF and the LIF sensors. The average drop in amplitude of red and infrared PPG signals from the RIF was 52.7% and 58.3%. Similarly, the LIF PPG signal amplitudes have reduced by 47.52% and 46.8% respectively. In contrast, no significant changes were seen in the red and infrared EC PPG amplitude measurements, which changed by +2.5% and -1.2% respectively. The RIF and LIF pulse oximeters have failed to estimate accurate SpO2 in seven and four volunteers respectively, while the EC pulse oximeter has only failed in one volunteer. These results suggest that the EC may be a suitable site for reliable monitoring of PPGs and SpO2s even in the presence of peripheral vasoconstriction.

Investigation of Pulse Transit Times utilizing multisite reflectance photoplethysmography under conditions of artificially induced peripheral vasoconstriction.

Pulse Transit Time (PTT) is the time it takes for an arterial pulsation to travel from the heart to a peripheral site. In recent times, PTT has been advocated as a marker for assessing increased vascular resistance. However, the reliability of PTT as a marker for cardiovascular risks and its inverse relation to beat-to-beat blood pressure is still being investigated. In order to validate the technique as a reliable marker of vascular resistance, PTT measurements were made using photoplethysmographic (PPG) signals obtained from multiple measurement sites in 12 healthy volunteers undergoing right hand immersion in ice water for 30 secs. PTT measurements were made from the ear canal (EC), the left (LIF) and right index fingers (RIF) using custom made photoplethysmographic probes. Activation of the sympathetic nervous system during the ice water immersion caused an increase in vascular resistance, which is associated with an increase in mean arterial pressure and a decrease in PTT in all measurement sites. However, the change in PTT was much larger in the RIF when compared to the LIF and the EC. This demonstrates the cerebral flow autoregulation and the profound peripheral vasoconstriction seen in the right hand. After the ice immersion period, the mean PTT measured from the EC returned to baseline, whereas the LIF PTT exceeded baseline values. This is due to the local vasodilation resulted from the activation of a thermoregulation mechanism.

Devepopment of an optical probe to investigate the suitability of measuring photoplethysmographs and blood oxygen saturation from the human auditory canal.

Pulse oximetry has become a standard for patient monitoring in the operating room, and the finger is the most common site used for monitoring blood oxygen saturation (SpO2). However, SpO2 measurements made from extremities such as the finger, ear lobe and toes become susceptible to inaccuracies, when patients become hypothermic, hypovolemic and vasoconstrictive. This is due to the week arterial pulsations detected in these conditions. To overcome this limitation, the external auditory canal has been proposed as an alternative monitoring site for estimating SpO2, on the hypothesis that this central site will be better perfused. A dual wavelength optoelectronic sensor along with a processing system was developed to investigate the suitability of measuring photoplethysmographic (PPG) signals and SpO2 values in the human auditory canal. A pilot study was conducted on 12 healthy volunteers to validate the developed sensor. The red and infrared PPG signals obtained from all the volunteers were of very good quality. The SpO2 values recorded from the ear canal were compared with simultaneously acquired data from a commercial finger pulse oximeter. The results show good correlation between the commercial pulse oximeter and the custom made ear canal sensor (r(2) = 0.825).