Contactless photoplethysmography for assessment of small fiber neuropathy.

Chronic pain is a prevalent condition affecting approximately one-fifth of the global population, with significant impacts on quality of life and work productivity. Small fiber neuropathies are a common cause of chronic pain, and current diagnostic methods rely on subjective self-assessment or invasive skin biopsies, highlighting the need for objective noninvasive assessment methods. The study aims to develop a modular prototype of a contactless photoplethysmography system with three spectral bands (420, 540, and 800 nm) and evaluate its potential for assessing peripheral neuropathy patients via a skin topical heating test and spectral analyses of cutaneous flowmotions. The foot topical skin heating test was conducted on thirty volunteers, including fifteen healthy subjects and fifteen neuropathic patients. Four cutaneous nerve fiber characterizing parameters were evaluated at different wavelengths, including vasomotor response trend, flare area, flare intensity index, and the spectral power of cutaneous flowmotions. The results show that neuropathic patients had significantly lower vasomotor response (50%), flare area (63%), flare intensity index (19%), and neurogenic component (54%) of cutaneous flowmotions compared to the control group, independent of photoplethysmography spectral band. An absolute value of perfusion was 20%-30% higher in the 420 nm band. Imaging photoplethysmography shows potential as a cost-effective alternative for objective and non-invasive assessment of neuropathic patients, but further research is needed to enhance photoplethysmography signal quality and establish diagnostic criteria.

Multimodal Approach of Optical Coherence Tomography and Raman Spectroscopy Can Improve Differentiating Benign and Malignant Skin Tumors in Animal Patients.

As in humans, cancer is one of the leading causes of companion animal mortality. Up to 30% of all canine and feline neoplasms appear on the skin or directly under it. There are only a few available studies that have investigated pet tumors by biophotonics techniques. In this study, we acquired 1115 optical coherence tomography (OCT) images of canine and feline skin, lipomas, soft tissue sarcomas, and mast cell tumors ex vivo, which were subsequently used for automated machine vision analysis. The OCT images were analyzed using a scanning window with a size of 53 × 53 µm. The distributions of the standard deviation, mean, range, and coefficient of variation values were acquired for each image. These distributions were characterized by their mean, standard deviation, and median values, resulting in 12 parameters in total. Additionally, 1002 Raman spectral measurements were made on the same samples, and features were generated by integrating the intensity of the most prominent peaks. Linear discriminant analysis (LDA) was used for sample classification, and sensitivities/specificities were acquired by leave-one-out cross-validation. Three datasets were analyzed-OCT, Raman, and combined. The combined OCT and Raman data enabled the best sample differentiation with the sensitivities of 0.968, 1, and 0.939 and specificities of 0.956, 1, and 0.977 for skin, lipomas, and malignant tumors, respectively. Based on these results, we concluded that the proposed multimodal approach, combining Raman and OCT data, can accurately distinguish between malignant and benign tissues.

Microvascular blood flow changes of the abductor pollicis brevis muscle during sustained static exercise.

A practical assessment of the general health and microvascular function of the palm muscle, abductor pollicis brevis (APB), is important for the diagnosis of different conditions. In this study, we have developed a protocol and a probe to study microvascular blood flow using near-infrared diffuse correlation spectroscopy (DCS) in APB during and after thumb abduction at 55% of maximum voluntary contraction (MVC). Near-infrared time resolved spectroscopy (TRS) was also used to characterize the baseline optical and hemodynamic properties. Thirteen (n=13) subjects were enrolled and subdivided in low MVC (N=6, MVC<2.3 kg) and high MVC (N=7, MVC≥2.3 kg) groups. After ruling out significant changes in the systemic physiology that influence the muscle hemodynamics, we have observed that the high MVC group showed a 56% and 36% decrease in the blood flow during exercise, with respect to baseline, in the long and short source-detector (SD) separations (p=0.031 for both). No statistical differences were shown for the low MVC group (p=1 for short and p=0.15 for long SD). These results suggest that the mechanical occlusion, due to increased intramuscular pressure, exceeded the vasodilation elicited by the higher metabolic demand. Also, blood flow changes during thumb contraction negatively correlated (R=-0.7, p<0.01) with the absolute force applied by each subject. Furthermore, after the exercise, muscular blood flow increased significantly immediately after thumb contractions in both high and low MVC groups, with respect to the recorded values during the exercise (p=0.031). An increase of 251% (200%) was found for the long (short) SD in the low MVC group. The high MVC groups showed a significant 90% increase in blood flow only after 80 s from the start of the protocol. For both low and high MVC groups, blood flow recovered to baseline values within 160 s from starting the exercise. In conclusion, DCS allows the study of the response of a small muscle to static exercise and can be potentially used in multiple clinical conditions scenarios for assessing microvascular health.

Remote Photoplethysmography for Evaluation of Cutaneous Sensory Nerve Fiber Function.

About 2% of the world's population suffers from small nerve fiber dysfunction, neuropathy, which can result in severe pain. This condition is caused by damage to the small nerve fibers and its assessment is challenging, due to the lack of simple and objective diagnostic techniques. The present study aimed to develop a contactless photoplethysmography system using simple instrumentation, for objective and non-invasive assessment of small cutaneous sensory nerve fiber function. The approach is based on the use of contactless photoplethysmography for the characterization of skin flowmotions and topical heating evoked vasomotor responses. The feasibility of the technique was evaluated on volunteers (n = 14) using skin topical anesthesia, which is able to produce temporary alterations of cutaneous nerve fibers function. In the treated skin region in comparison to intact skin: neurogenic and endothelial component of flowmotions decreased by ~61% and 41%, the local heating evoked flare area decreased by ~44%, vasomotor response trend peak and nadir were substantially reduced. The results indicate for the potential of the remote photoplethysmography in the assessment of the cutaneous nerve fiber function. It is believed that in the future this technique could be used in the clinics as an affordable alternative to laser Doppler imaging technique.

Relationship of mottling score, skin microcirculatory perfusion indices and biomarkers of endothelial dysfunction in patients with septic shock: an observational study.

BACKGROUND: In patients with septic shock, the skin is often chosen for the evaluation of peripheral perfusion and oxygenation. Changes in skin microcirculatory vessel oxygen saturation and relative hemoglobin concentration can be described using a mottling score or captured with hyperspectral imaging. However, the effectiveness of the mottling score in assessing microcirculation remains to be shown. We hypothesize that the mottling score in patients with septic shock is related to skin microcirculatory perfusion indices quantified by hyperspectral imaging, biomarkers that reflect endothelium activation and damage, and clinical outcome. METHODS: Hyperspectral imaging of the knee area was performed in 95 intensive care patients with septic shock enrolled in a single-center observational study to obtain relative oxy/deoxyhemoglobin concentration values and construct anatomical maps of skin microcirculatory saturation. The blood was sampled to obtain concentrations of thrombomodulin, plasminogen activator inhibitor-1 (PAI-1), soluble intercellular adhesion molecule-1 (ICAM-1), soluble vascular cell adhesion molecule-1 (VCAM-1), angiopoietin-2, and syndecan-1. The spectrophotometrically obtained skin microvascular perfusion indices were compared to the mottling score and biomarker concentration. The association between mottling score, skin microcirculatory perfusion indices, and 28-day mortality was also analyzed. RESULTS: Microcirculatory oxygen saturation was significantly lower and total hemoglobin concentration was significantly higher in patients with a mottling score of 2 compared to those with a score of 0 (p = 0.02), with no difference between other scores. We found an association between microcirculatory oxygen saturation and PAI-1 levels (rho = - 0.3; p = 0.007). Increased mottling score and decreased microcirculatory oxygen saturation were predictive of 28-day mortality (mottling score 2 vs 0: OR 15.31, 95% CI 4.12-68.11; microcirculatory oxygen saturation: OR 0.90, 95% CI 0.85-0.95). Endothelial biomarkers did not increase the predictive value of skin microcirculatory perfusion indices. CONCLUSIONS: Higher mottling scores are associated with lower microcirculatory oxygen saturation but with significant overlap between scores. Microcirculatory oxygen saturation is a quantitative measure of peripheral oxygenation and is more specific than the mottling score in predicting 28-day mortality.

Multimodal Device for Real-Time Monitoring of Skin Oxygen Saturation and Microcirculation Function.

The present study introduces a recently developed compact hybrid device for real-time monitoring of skin oxygen saturation and temperature distribution. The prototype involves a snapshot hyperspectral camera, multi-wavelength illuminator, thermal camera, and built-in computer with custom-developed software. To validate this device in-vivo we performed upper arm vascular occlusion on eight healthy volunteers. Palm skin oxygen saturation maps were analyzed in real-time using k-means segmentation algorithm and two-layer optical diffuse model. The prototype system demonstrated a satisfying performance of skin hyperspectral measurements in the spectral range of 507-625 nm. The results confirmed the reliability of the proposed system for in-vivo assessment of skin hemoglobin saturation with oxygen and microcirculation.

Imaging photoplethysmography for clinical assessment of cutaneous microcirculation at two different depths.

The feasibility of bispectral imaging photoplethysmography (iPPG) system for clinical assessment of cutaneous microcirculation at two different depths is proposed. The iPPG system has been developed and evaluated for in vivo conditions during various tests: (1) topical application of vasodilatory liniment on the skin, (2) skin local heating, (3) arterial occlusion, and (4) regional anesthesia. The device has been validated by the measurements of a laser Doppler imager (LDI) as a reference. The hardware comprises four bispectral light sources (530 and 810 nm) for uniform illumination of skin, video camera, and the control unit for triggering of the system. The PPG signals were calculated and the changes of perfusion index (PI) were obtained during the tests. The results showed convincing correlations for PI obtained by iPPG530 nm and LDI at (1) topical liniment (r = 0.98) and (2) heating (r = 0.98) tests. The topical liniment and local heating tests revealed good selectivity of the system for superficial microcirculation monitoring. It is confirmed that the iPPG system could be used for assessment of cutaneous perfusion at two different depths, morphologically and functionally different vascular networks, and thus utilized in clinics as a cost-effective alternative to the LDI.

Two-stage multi-Gaussian fitting of conduit artery photoplethysmography waveform during induced unilateral hemodynamic events.

Photoplethysmography (PPG) is an optical technique with high diagnostic potential, yet clinical applications remain underdeveloped. Standardization of signal recording and quantification of waveform are essential prerequisites for broader clinical use. The aim of this study was to utilize a two-stage multi-Gaussian fitting technique in order to examine the parameters of conduit artery PPG waveform recorded during increasing the unilateral regional vascular resistance (RVR). This study was conducted on 14 young and healthy volunteers; various external compressions (ECs) were performed by inflating a tight cuff at 0, 40, 80, and 200 mmHg, while registering femoral PPG (wavelength 880 nm), diameter, blood flow linear velocity (vascular ultrasound), and the arterial pressure (Finapres) during the states of the baseline, partial, and total arterial occlusion, and resultant reactive hyperemia. An increase of the EC elevated the arterial stiffness (AS) and the unilateral distal RVR, and caused a shift of the fitted multi-Gaussian parameters: a decreased delay between reflected and traverse wave components and an increased ratio of their amplitudes. It was concluded that two-stage multi-Gaussian waveform quantification demonstrates an approach potentially extending the use of arterial site PPG in the assessment of diagnostically useful markers e.g., the RVR and the AS.

Effect of probe contact pressure on the photoplethysmographic assessment of conduit artery stiffness.

Currently, photoplethysmography (PPG) is a frequently studied optical blood pulsation detection technique among biophotonic and biomedical researchers due to the fact that it shows high potential for estimating the arterial stiffness (AS). The extraction of diagnostically useful information requires standardized measurement procedure with good repeatability. However, the effects of a crucially important factor-the optimal contact pressure (CP) of the probe-are often ignored. Also, CP values are not reported to evaluate those effects. It is hypothesized that AS estimated from PPG pulse wave 2nd derivative parameter b/a is strongly inconsistent when recorded at nonoptimal probe CP. Our pilot study confirmed this during in vivo PPG recordings from conduit artery sites on five healthy subjects at variable probe CP (0 to 15 kPa) by using 880 nm reflectance type sensor, force transducer, and PPG alternating current (AC) signal pulse area derived optimal CP criterion. The b/a values, calculated from PPG with variable CP, showed variation >300 percent. In contrast, at the optimal CP, the b/a showed high repeatability (coefficient of variability <5 percent). The effect has been explained with exponential pulse pressure-volume relationship model which indicates the optimal CP range.

Finger and ear photoplethysmogram waveform analysis by fitting with Gaussians.

Analysis of the contour of the blood volume pulse (VP) has become important because it contains much information about cardiovascular activity. Traditionally, pulse contour analysis requires first or higher derivatives to be calculated. This paper describes a novel algorithm for analysing simultaneously measured ear and finger photoplethysmography (PPG) signals. The algorithm separates the systolic wave and the diastolic wave of the VP and fits each of them with the sum of two Gaussian functions. The VP was obtained from PPG signals taken from 40 healthy subjects at each heartbeat cycle. From the evaluated VP, time values of the direct wave and three reflected waves were calculated, as well as the augmentation index (AI) and the reflection index (RI). The evaluated parameters were compared with those that were obtained by the derivative method, and it was demonstrated that the new method can be used to analyze VP waveforms.