A novel smartphone scleral-image based tool for assessing jaundice in decompensated cirrhosis patients.

BACKGROUND AND AIM: Serum bilirubin is an established marker of liver disease. Reliable tools for non-invasive assessment of jaundice in cirrhosis patients, at risk of clinical decompensation, are highly desirable. While smartphone-based imaging has been described in neonatal jaundice, it has not been investigated in advanced cirrhosis patients. METHODS: We included 46 hospitalized patients with acute cirrhosis decompensation and jaundice. Scleral images using an Android smartphone were taken to derive "Scleral Color Values (SCV)," which were matched with same day serum bilirubin measurements. In 29 patients, repeat SCV and bilirubin measurements were performed over time. We analyzed the relationship of SCV and its dynamics with serum bilirubin, clinical scores, and patient outcomes. RESULTS: Of 46 patients, 26 (57%) had alcoholic hepatitis as the decompensation precipitant. Seven patients died during admission; a further 12 following hospital discharge. SCV had an excellent linear correlation with serum bilirubin (rho = 0.90, P < 0.001); changes in SCV and serum bilirubin across different time points, were also closely associated (rho = 0.77, P < 0.001). SCV correlated significantly with CLIF Consortium Acute Decompensation score (rho = 0.38, P < 0.001) and grade of Acute-on-Chronic Liver Failure (rho = 0.42, P = 0.039). SCV was higher in patients who died, however, not significantly (86.1 [IQR 83.0-89.7] vs 82.3 [IQR 78.5-83.3], P = 0.22). The associations of SCV with clinical parameters mirrored those of serum bilirubin. CONCLUSION: Smartphone-based assessment of jaundice shows excellent concordance with serum bilirubin and is associated with clinical parameters in acute cirrhosis decompensation. This approach offers promise for remote assessment of cirrhosis patients at-risk of decompensation, post hospital discharge.

Investigating the nasal cycle using unilateral peak nasal inspiratory flow and acoustic rhinometry minimal cross-sectional area measurements.

OBJECTIVE: To plot the nasal cycle using unilateral peak nasal inspiratory flow (UPNIF) and unilateral minimal cross-sectional area (UMCA) readings demonstrating a linear relationship in normal nasal function. Additionally, to determine how this changes in abnormal nasal function. DESIGN: A cross-sectional study measuring UPNIF and UMCA in controls demonstrating normal nasal function and in patients with nasal obstruction. SETTING: Royal National Throat Nose and Ear Hospital, London. PARTICIPANTS: A total of 39 participants, 26 controls and 13 patients, were recruited. Controls exhibited normal nasal function with SNOT-22 <5. Patients nasal obstruction symptoms secondary to inflammation or structural abnormality with SNOT-22 >9. MAIN OUTCOME MEASURES AND RESULTS: Airflow rates and resistance values were derived from UPNIF and UMCA measurements respectively based on Poiseuille's laws. Ratios between right and left UPNIF and UMCA values were taken to adjust for confounding factors. The relationship of 1/Resistance Ratio and Airflow Rate Ratio demonstrated a linear of direct proportionality of strong correlation and statistical significance (correlation coefficient = 0.76, P « 0.01). This suggests that data points from controls with a normal nasal cycle lie closely along the regressed line, whilst those lying significantly away were shown to belong to patients with nasal dysfunction. Olfactory dysfunction appears to be a sensitive discriminator in predicting this. CONCLUSION: This study demonstrates the directly proportional relationship of 1/Resistance Ratio and Airflow Rate Ratio in normal nasal function. Furthermore, nasal pathology can be predicted if data points lie significantly outside these normal limits. Further studies are needed to validate exact normal and abnormal thresholds.

Effect of blood transfusion on intestinal blood flow and oxygenation in extremely preterm infants during first week of life.

BACKGROUND: Extremely preterm infants receive frequent blood transfusions in the first week of life. The aim of this study was to measure the effect of blood transfusion on intestinal blood flow and oxygenation during the first week of life in extremely preterm infants. STUDY DESIGN AND METHODS: Superior mesenteric artery (SMA) peak systolic velocity (PSV) and diastolic velocities were measured 30 to 60 minutes before and after transfusion. Splanchnic tissue hemoglobin index (sTHI), splanchnic tissue oxygenation index (sTOI), and splanchnic fractional tissue oxygen extraction (sFTOE) were measured continuously from 15 to 20 minutes before to after transfusion along with vital variables. RESULTS: Twenty infants were studied (median gestational age, 26 weeks). Ten infants were partially fed (15-68 mL/kg/day). Heart rate and SaO2 remained unaltered; blood pressure increased significantly (p < 0.01) after transfusion. Mean SMA PSV (p = 0.63) and diastolic velocity (p = 0.65) remained unaltered. Mean pretransfusion SMA PSV was similar in partially fed (0.78 m/sec) compared to unfed infants (0.52 m/sec; p = 0.06) and the response to transfusion was not dissimilar. There was a significant increase in sTHI (mean difference, 32.3%; p < 0.01) and sTOI (14.6%; p = 0.03) and decrease in sFTOE (22.1%; p < 0.01) after transfusion. There was no significant difference in sTHI or sTOI between fed and unfed infants and their response to transfusion. CONCLUSIONS: Blood transfusion increased blood pressure and intestinal tissue oxygenation but did not alter blood flow velocities. Partial feeding had no impact on intestinal blood flow and tissue oxygenation changes.

Validation of a Hybrid Microwave-Optical Monitor to Investigate Thermal Provocation in the Microvasculature.

We have previously developed a hybrid microwave-optical system to monitor microvascular changes in response to thermal provocation in muscle. The hybrid probe is capable of inducing deep heat from the skin surface using mild microwaves (1-3 W) and raises the tissue temperature by a few degrees Celsius. This causes vasodilation and the subsequent increase in blood volume is detected by the hybrid probe using near infrared spectroscopy. The hybrid probe is also equipped with a skin cooling system which lowers the skin temperature while allowing microwaves to warm up deeper tissues. The hybrid system can be used to assess the condition of the vasculature in response to thermal stimulation. In this validation study, thermal imaging has been used to assess the temperature distribution on the surface of phantoms and human calf, following microwave warming. The results show that the hybrid system is capable of changing the skin temperature with a combination of microwave warming and skin cooling. It can also detect thermal responses in terms of changes of oxy/deoxy-hemoglobin concentrations.

Digital biomarkers from gaze tests for classification of central and peripheral lesions in acute vestibular syndrome.

Acute vestibular syndrome (AVS) is characterised by a sudden vertigo, gait instability, nausea and nystagmus. Accurate and rapid triage of patients with AVS to differentiate central (potentially sinister) from peripheral (usually benign) root causes is a challenge faced across emergency medicine settings. While there exist bedside exams which can reliably differentiate serious cases, they are underused due to clinicians' general unfamiliarity and low confidence interpreting results. Nystagmus is a fundamental part of AVS and can facilitate triaging, but identification of relevant characteristics requires expertise. This work presents two quantitative digital biomarkers from nystagmus analysis, which capture diagnostically-relevant information. The directionality biomarker evaluates changes in direction to differentiate spontaneous and gaze-evoked (direction-changing) nystagmus, while the intensity differential biomarker describes changes in intensity across eccentric gaze tests. In order to evaluate biomarkers, 24 sets of three gaze tests (left, right, and primary) are analysed. Both novel biomarkers were found to perform well, particularly directionality which was a perfect classifier. Generally, the biomarkers matched or eclipsed the performance of quantitative nystagmus features found in the literature. They also surpassed the performance of a support vector machine classifier trained on the same dataset, which achieved an accuracy of 75%. In conclusion, these biomarkers simplify the diagnostic process for non-specialist clinicians, bridging the gap between emergency care and specialist evaluation, ultimately benefiting patients with AVS.

Acousto-optic imaging of a color picture hidden behind a scattering layer.

An imaging technique has been developed to image a color picture hidden behind a 5 mm thick, highly scattering layer with low transmittance of 0.24%. Small vibrations (< 1 µm) were induced in the hidden picture, causing a time-varying speckle pattern on the scattering layer in the front, which is captured by a CCD camera and quantified as speckle contrast difference (SCD). With two lasers at 543 nm and 633 nm, the imaging system raster-scans the front of the scattering layer and the resulting SCD image reveals the color features of the hidden picture.

Classifying hidden colors behind an opaque layer with the acoustically modulated laser speckle contrast technique.

The acoustically modulated laser speckle contrast technique has been employed to quantify and classify 25 colors (made up by different percentages of the two base colors cyan and magenta) hidden behind a 5 mm thick opaque layer with 0.24% transmittance. The main components included two He-Ne lasers (543 and 633 nm), a consumer grade digital camera (Nikon 1 J1), focusing optics and a loudspeaker. The camera captured the laser speckle patterns with the sound on and off, respectively, from which the speckle contrast differences were calculated and used in a nearest neighbor classification algorithm. The classification accuracy was between 55% and 88% depending on the underlying reflectance of all the colors to be classified.

Development of a hybrid microwave-optical tissue oxygenation probe to measure thermal response in the deep tissue.

The design of a new non-invasive hybrid microwave-optical tissue oxygenation probe is presented, which consists of a microwave biocompatible antenna and an optical probe. The microwave antenna is capable of inducing localised heat in the deep tissue, causing tissue blood flow and therefore tissue oxygenation to change. These changes or thermal responses are measured by the optical probe using near-infrared spectroscopy. Thermal responses provide important information on thermoregulation in human tissue. The first prototype of the biocompatible antenna was developed and placed on the human calf for in vivo experiments. The measured results include oxy-, deoxy- and total haemoglobin concentration changes (ΔHbO2/ΔHHb/ΔHbT), tissue oxygenation index and the normalised tissue haemoglobin index for two human subjects. Both ΔHbO2 and ΔHbT show an increase during 5 min of microwave exposure. The thermal response, defined as the ratio of the increase in ΔHbT to the time duration, is 7.7 µM/s for subject 1 (fat thickness = 6.8 mm) and 18.9 µM/s for subject 2 (fat thickness = 5.0 mm), which may be influenced by the fat thicknesses. In both subjects, ΔHbO2 and ΔHbT continued to increase for approximately another 70 s after the microwave antenna was switched off.

Assessment of bilirubin levels in patients with cirrhosis via forehead, sclera and lower eyelid smartphone images.

One of the key biomarkers evaluating liver disease progression is an elevated bilirubin level. Here we apply smartphone imaging to non-invasive assessment of bilirubin in patients with cirrhosis. Image data was processed using two different approaches to remove variation introduced by ambient conditions and different imaging devices-a per-image calibration using a color chart in each image, and a two-step process using pairs of flash/ no-flash images to account for ambient light in combination with a one-time calibration. For the first time, results from the forehead, sclera (white of the eye) and lower eyelid were compared. The correlation coefficients between the total serum bilirubin and the predicted bilirubin via the forehead, sclera and lower eyelid were 0.79, 0.89 and 0.86 (all with p<0.001, n = 66), respectively. Given the simpler image capture for the sclera, the recommended imaging site for this patient cohort is the sclera.

Feasibility of smartphone colorimetry of the face as an anaemia screening tool for infants and young children in Ghana.

BACKGROUND: Anaemia affects approximately a quarter of the global population. When anaemia occurs during childhood, it can increase susceptibility to infectious diseases and impair cognitive development. This research uses smartphone-based colorimetry to develop a non-invasive technique for screening for anaemia in a previously understudied population of infants and young children in Ghana. METHODS: We propose a colorimetric algorithm for screening for anaemia which uses a novel combination of three regions of interest: the lower eyelid (palpebral conjunctiva), the sclera, and the mucosal membrane adjacent to the lower lip. These regions are chosen to have minimal skin pigmentation occluding the blood chromaticity. As part of the algorithm development, different methods were compared for (1) accounting for varying ambient lighting, and (2) choosing a chromaticity metric for each region of interest. In comparison to some prior work, no specialist hardware (such as a colour reference card) is required for image acquisition. RESULTS: Sixty-two patients under 4 years of age were recruited as a convenience clinical sample in Korle Bu Teaching Hospital, Ghana. Forty-three of these had quality images for all regions of interest. Using a naïve Bayes classifier, this method was capable of screening for anaemia (<11.0g/dL haemoglobin concentration) vs healthy blood haemoglobin concentration (≥11.0g/dL) with a sensitivity of 92.9% (95% CI 66.1% to 99.8%), a specificity of 89.7% (72.7% to 97.8%) when acting on unseen data, using only an affordable smartphone and no additional hardware. CONCLUSION: These results add to the body of evidence suggesting that smartphone colorimetry is likely to be a useful tool for making anaemia screening more widely available. However, there remains no consensus on the optimal method for image preprocessing or feature extraction, especially across diverse patient populations.

Development of a thermochromic lateral flow assay to improve sensitivity for dengue virus serotype 2 NS1 detection.

Dengue disease is a viral infection that has been widespread in tropical regions, such as Southeast Asia, South Asia and South America. A worldwide effort has been made over a few decades to halt the spread of the disease and reduce fatalities. Lateral flow assay (LFA), a paper-based technology, is used for dengue virus detection and identification because of its simplicity, low cost and fast response. However, the sensitivity of LFA is relatively low and is usually insufficient to meet the minimum requirement for early detection. In this study, we developed a colorimetric thermal sensing LFA format for the detection of dengue virus NS1 using recombinant dengue virus serotype 2 NS1 protein (DENV2-NS1) as a model antigen. Plasmonic gold nanoparticles, including gold nanospheres (AuNSPs) and gold nanorods (AuNRs), and magnetic nanoparticles (MNPs), namely iron oxide nanoparticles (IONPs) and zinc ferrite nanoparticles (ZFNPs), were studied for their thermal properties for sensing assays. AuNSPs with 12 nm diameter were chosen due to their great photothermal effect against light-emitting diodes (LEDs). In the thermal sensing assay, a thermochromic sheet is used as a temperature sensor transforming heat into a visible colour. In the typical LFA, the test line is visible at 6.25 ng mL-1 while our thermal sensing LFA offers a visual signal that can be observed at as low as 1.56 ng mL-1. The colorimetric thermal sensing LFA is capable of reducing the limit of detection (LOD) of DENV2-NS1 by 4 times compared to the typical visual readout. The colorimetric thermal sensing LFA can enhance the sensitivity of detection and deliver visuality to the user to translate without the need for an infrared (IR) camera. It has the potential to expand the utilities of LFA and satisfy early diagnostic applications.

Measuring the reflectance of hidden color objects with acoustically modulated laser speckle.

We demonstrate a technique to measure the reflectance of colored objects, including blue, green, and yellow, hidden behind an opaque slab based on acoustically modulated laser speckle. One colored paper at a time was placed behind a 1 cm thick opaque slab with an air gap of 5 mm. Small periodic movements (nanometer scale) at 200 Hz were induced in the colored paper. A coherent red He-Ne laser illuminated the front of the slab, producing acoustically modulated speckle patterns, which were captured by a CCD camera. The magnitude of the time-varying speckle intensity is indicative of the hidden colored paper's reflectance.

Warm-up effects on muscle oxygenation, metabolism and sprint cycling performance.

To investigate the effects of warm-up intensity on all-out sprint cycling performance, muscle oxygenation and metabolism, 8 trained male cyclists/triathletes undertook a 30-s sprint cycling test preceded by moderate, heavy or severe warm up and 10-min recovery. Muscle oxygenation was measured by near-infrared spectroscopy, with deoxyhaemoglobin ([HHb]) during the sprint analysed with monoexponential models with time delay. Aerobic, anaerobic-glycolytic and phosphocreatine energy provision to the sprint were estimated from oxygen uptake and lactate production. Immediately prior to the sprint, blood [lactate] was different for each warm up and higher than resting for the heavy and severe warm ups (mod. 0.94 ± 0.36, heavy 1.92 ± 0.64, severe 4.37 ± 0.93 mmol l(-1) P < 0.05), although muscle oxygenation was equally raised above rest. Mean power during the sprint was lower following severe compared to moderate warm up (mod. 672 ± 54, heavy 666 ± 56, severe 655 ± 59 W, P < 0.05). The [HHb] kinetics during the sprint were not different among conditions, although the time delay before [HHb] increased was shorter for severe versus moderate warm up (mod. 5.8 ± 0.6, heavy 5.6 ± 0.9, severe 5.2 ± 0.7 s, P < 0.05). The severe warm up was without effect on estimated aerobic metabolism, but increased estimated phosphocreatine hydrolysis, the latter unable to compensate for the reduction in estimated anaerobic-glycolytic metabolism. It appears that despite all warm ups equally increasing muscle oxygenation, and indicators of marginally faster oxygen utilisation at the start of exercise following a severe-intensity warm up, other energy sources may not be able to fully compensate for a reduced glycolytic rate in sprint exercise with potential detrimental effects on performance.

Regional cerebral and splanchnic tissue oxygen saturation in preterm infants - Longitudinal normative measurements.

BACKGROUND: To investigate regional splanchnic and cerebral tissue oxygen saturation in preterm infants <30 weeks gestation. METHODS: Cerebral (cTOI) and splanchnic (sTOI) Tissue Oxygenation Index were measured weekly in 5 min epochs for a total period of 60 min using NIRS (NIRO-300) for the first 8 weeks of life, in 48 appropriately grown preterm infants born at <30 weeks gestation. Infants who developed HPI and/or NEC (n = 12) and those that died (n = 1) were excluded from our main outcome measure of regional gut and cerebral tissue oxygenation in healthy preterm infants <30 weeks gestation. RESULTS: Median birthweight 789 g (460-1486), gestational age 25+6 weeks (23+0-29+1) and 51.4% female. 217 NIRS measurements were completed across the first 8 weeks of life. Mean weekly cTOI ranged from 56.8-65.4% and sTOI ranged from 36.7-46.0%. Mean cTOI was significantly higher than mean sTOI (p < 0.001) throughout the first 8 weeks of life. Mean cTOI decreased significantly with increasing postnatal age [-0.59% each week (-1.26% to -0.07%) p = 0.04]. None of the examined confounding factors had a significant effect. CONCLUSIONS: This is the first report of regional cerebral and splanchnic tissue oxygen saturation ranges during the first 8 weeks of life for preterm infants born at <30 weeks gestation.

Analysis of the changes in the oxidation of brain tissue cytochrome-c-oxidase in traumatic brain injury patients during hypercapnoea: a broadband NIRS study.

Using broadband near-infrared spectroscopy (NIRS) and cerebral microdialysis (MD),we investigated cerebral cellular metabolism and mitochondrial redox states, following hypercapnoea in 6 patients with traumatic brain injury (TBI). In all patients hypercapnoea increased intracranial pressure and cerebral blood flow velocity measured with transcranial Doppler. Despite the likely increase in cerebral oxygen delivery, we did not see an increase in the oxidation status of cytochrome-c-oxidase [oxCCO] in every patient. Analysis of the NIRS data demonstrated two patterns of the changes; Group A (n = 4) showed an increase in [oxCCO] of 0.34(± 0.34)µM and Group B (n = 2) a decrease of 0.40(± 0.41)µM. Although no obvious association was seen between the Δ[oxCCO] and the MD, measured changes in lactate and pyruvate concentrations. Further work using model informed data interpretation may be helpful in understanding the multimodal signals acquired in this heterogeneous patient group.

Effects of assuming constant optical scattering on haemoglobin concentration measurements using NIRS during a Valsalva manoeuvre.

Resolving for changes in concentration of tissue chromophores in the human adult brain with near-infrared spectroscopy has generally been based on the assumption that optical scattering and pathlength remain constant. We have used a novel hybrid optical spectrometer that combines multi-distance frequency and broadband systems to investigate the changes in scattering and pathlength during a Valsalva manoeuvre in 8 adult volunteers. Results show a significant increase in the reduced scattering coefficient of 17% at 790nm and 850nm in 4 volunteers during the peak of the Valsalva. However, these scattering changes do not appear to significantly affect the differential pathlength factor and the tissue haemoglobin concentration measurements.

The Nasal Obstruction Balance Index: A Novel Approach to Improving Correlation Between Unilateral Nasal Airway Measurements and Evaluating Nasal Airway Asymmetry.

OBJECTIVES/HYPOTHESIS: Demonstrate that the Nasal Obstruction Balance Index (NOBI) model fulfils the unmet need of improving unilateral correlation between subjective and objective nasal obstruction outcome measures and identifying the more obstructed side. Improve correlation between unilateral objective nasal airway measurements (nasal inspiratory peak flow [NIPF] and acoustic rhinometry [AR]) and subjective Visual Analogue Scale for nasal obstruction (VAS-NO) scores. Improve assessment of nasal airway asymmetry by evaluating unilateral measurements both before and after the application of nasal decongestant; which the patient could better understand. NOBI represents a ratio calculated by taking the difference between left and right nasal airway measurements and divided by the maximum unilateral measurement. It is based on Poiseuille's law and aims to reduce the confounding variables which challenge nasal airway measurement. STUDY DESIGN: Prospective cohort study. METHODS: Forty-three controls and 34 patients with nasal obstruction underwent both unilateral and bilateral NIPF, AR and VAS-NO measurements; these were repeated after the application of nasal decongestant. The NOBI values for unilateral NIPF, AR, and VAS-NO were calculated both before and after decongestant. RESULTS: The correlation between unilateral NIPF and AR measurements was enhanced considerably (r = 0.57, P < .01) when NOBI was applied. The NOBI metric significantly increased the correlation between unilateral NIPF, AR, and VAS-NO scores. Postdecongestant NOBI for NIPF and AR measurements correctly identified the more obstructed side in 82.4% and 94.1% of the deviated nasal septum (DNS) cases, respectively. CONCLUSION: The NOBI model provides a better correlation between unilateral subjective and objective measurements and identifies the more obstructed side. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2833-E2840, 2021.

A hybrid multi-distance phase and broadband spatially resolved spectrometer and algorithm for resolving absolute concentrations of chromophores in the near-infrared light spectrum.

For resolving absolute concentration of tissue chromophores in the human adult brain with near-infrared spectroscopy it is necessary to calculate the light scattering and absorption, at multiple wavelengths with some depth resolution. To achieve this we propose an instrumentation configuration that combines multi-distance frequency and broadband spectrometers to quantify chromophores in turbid media by using a hybrid spatially resolved algorithm. Preliminary results in solid phantoms as well as liquid dynamic homogeneous and inhomogeneous phantoms and in-vivo muscle measurements showed encouraging results.

Muscle oxygen saturation measured using "cyclic NIR signals" during exercise.

A new approach to measure muscle oxygen saturation (SmO(2)) using near infrared spectroscopy (NIRS) has been proposed in this paper. This approach exploits the cyclic NIRS signals seen during exercise which are often regarded as "movement artefacts". This new measure, which we term the "cyclic SmO(2)", has the potential to be less affected by the myoglobin which is traditionally believed to be indistinguishable from haemoglobin using NIRS techniques. The cyclic SmO(2) also has fewer assumptions than the conventional SmO(2) measured using time, phase and spatially resolved spectroscopy methods. In a cycling exercise study, NIRS measurements were made over the Vastus lateralis muscle of 11 subjects. In a light exercise protocol, the group mean of the conventional SmO(2) was 51.7 +/- 4.3% and that of the cyclic SmO(2) was 56.0 +/- 3.9%. It was immediately followed by a hard exercise protocol and the group mean of the conventional SmO(2) was reduced to 42.6 +/- 6.1% and that of the cyclic SmO(2) to 48.5 +/- 5.6%. The reduction agrees with the general expectation. The cyclic SmO(2) is a promising new measure of muscle oxygenation.