Brain hypoxia, neurocognitive impairment, and quality of life in people post-COVID-19.

OBJECTIVE: Systemic hypoxia occurs in COVID-19 infection; however, it is unknown if cerebral hypoxia occurs in convalescent individuals. We have evidence from other conditions associated with central nervous system inflammation that hypoxia may occur in the brain. If so, hypoxia could reduce the quality of life and brain function. This study was undertaken to assess if brain hypoxia occurs in individuals after recovery from acute COVID-19 infection and if this hypoxia is associated with neurocognitive impairment and reduced quality of life. METHODS: Using frequency-domain near-infrared spectroscopy (fdNIRS), we measured cerebral tissue oxygen saturation (StO2) (a measure of hypoxia) in participants who had contracted COVID-19 at least 8 weeks prior to the study visit and healthy controls. We also conducted neuropsychological assessments and health-related quality of life assessments, fatigue, and depression. RESULTS: Fifty-six percent of the post-COVID-19 participants self-reported having persistent symptoms (from a list of 18), with the most reported symptom being fatigue and brain fog. There was a gradation in the decrease of oxyhemoglobin between controls, and normoxic and hypoxic post-COVID-19 groups (31.7 ± 8.3 µM, 27.8 ± 7.0 µM and 21.1 ± 7.2 µM, respectively, p = 0.028, p = 0.005, and p = 0.081). We detected that 24% of convalescent individuals' post-COVID-19 infection had reduced StO2 in the brain and that this relates to reduced neurological function and quality of life. INTERPRETATION: We believe that the hypoxia reported here will have health consequences for these individuals, and this is reflected in the correlation of hypoxia with greater symptomology. With the fdNIRS technology, combined with neuropsychological assessment, we may be able to identify individuals at risk of hypoxia-related symptomology and target individuals that are likely to respond to treatments aimed at improving cerebral oxygenation.

Classification of Respiratory Syncytial Virus and Sendai Virus Using Portable Near-Infrared Spectroscopy and Chemometrics

There is evidence that it may be possible to detect viruses and viral infection optically using techniques such as Raman and infrared (IR) spectroscopy and hence open the possibility of rapid identification of infected patients. However, high-resolution Raman and IR spectroscopy instruments are laboratory-based and require skilled operators. The use of low-cost portable or field-deployable instruments employing similar optical approaches would be highly advantageous. In this work, we use chemometrics applied to low-resolution near-IR (NIR) reflectance/absorbance spectra to investigate the potential for simple low-cost virus detection suitable for widespread societal deployment. We present the combination of near-IR spectroscopy (NIRS) and chemometrics to distinguish two respiratory viruses, respiratory syncytial virus (RSV), the principal cause of severe lower respiratory tract infections in infants worldwide, and Sendai virus (SeV), a prototypic paramyxovirus. Using a low-cost and portable spectrometer, three sets of RSV and SeV spectra, dispersed in phosphate-buffered saline (PBS) medium or Dulbecco's modified eagle medium (DMEM), were collected in long- and short-term experiments. The spectra were preprocessed and analyzed by partial least-squares discriminant analysis (PLS-DA) for virus type and concentration classification. Moreover, the virus type/concentration separability was visualized in a low-dimensional space through data projection. The highest virus-type classification accuracy obtained in PBS and DMEM is 85.8% and 99.7%, respectively. The results demonstrate the feasibility of using portable NIR spectroscopy as a valuable tool for rapid, on- site, and low-cost virus prescreening for RSV and SeV with the further possibility of extending this to other respiratory viruses such as SARS-CoV-2.

Altered tissue oxygenation in patients with post COVID-19 syndrome.

BACKGROUND: Post COVID-19 syndrome (PCS) is a complex condition with partly substantial impact on patients' social and professional life and overall life quality. Currently, the underlying cause(s) of PCS are unknown. Since PCS-specific symptoms could be associated with systemic alterations in tissue oxygen supply, we aimed to investigate changes in tissue oxygenation in patients with PCS. METHODS: A case-control study including 30 PCS patients (66.6 % males, 48.6 ± 11.2 years, mean time after (first) acute infection: 324 days), 16 cardiologic patients (CVD) (65.5 % males, 56.7 ± 6.3 years) and 11 young healthy controls (55 % males, 28.5 ± 7.4 years) was conducted. Near infrared spectroscopy (NIRS) was used to assess changes in tissue oxygenation during an arterial occlusion protocol on the non-dominant forearm (brachioradialis, 760/850 nm, 5 Hz). The protocol included 10-min rest, a 2-min baseline measurement followed by a 3-min ischemic period (upper-arm cuff, 50 mmHg above resting systolic blood pressure) and a 3-min reoxygenation period. PCS patients were grouped by presence of arterial hypertension and elevated BMI to assess the impact of risk factors. RESULTS: No differences in mean tissue oxygenation in the pre-occlusion phase existed between groups (p ≥ 0.566). During ischemia, comparisons of linear regressions slopes revealed slower oxygen desaturation for PCS patients (-0.064 %/s) compared to CVD patients (-0.08 %/s) and healthy subjects (-0.145 %/s) (p < 0.001). After cuff release, slowest speed for reoxygenation was detected in PCS patients at 0.84 %/s compared to CVD patients (1.04 %/s) and healthy controls (CG: 2.07 %/s) (p < 0.001). The differences between PCS patients and CVD patients during ischemia remained significant also after correction for risk factors. Analyses of complications during acute infection, persistence of PCS symptoms (time after acute infection), or PCS severity (number of lead symptoms) as confounding factors did not reveal a significant effect. CONCLUSIONS: This study provides evidence that the rate of tissue oxygen consumption is persistently altered in PCS and that PCS patients show an even slower decline in tissue oxygenation during occlusion than CVD patients. Our observations may at least partly explain PCS-specific symptoms such as physical impairment and fatigue.

Initial five and ten-minute regional cerebral oxygen saturation as a predictor of the futility of resuscitation for out-of-hospital cardiac arrest

This study aimed to investigate the usefulness of cerebral regional oxygen saturation (rSO2) during the initial 5 and 10 minutes of cardiopulmonary resuscitation (CPR) compared with an initial rSO2 and mean rSO2 during entire CPR to predict the futility of resuscitation for patients without of-hospital-cardiac arrest (OHCA). This was a prospective study involving 52 adult patients presenting in OHCA and whose cerebral rSO2 values were measured until either CPR was terminated or sustained return of spontaneous circulation (ROSC) was achieved. Receiver operating characteristics analyses were used to evaluate which time and type of measurement is better to predict non-ROSC. The area under the curve (AUC) of each rSO2 value according to measurement time (overall, initial 5 minutes and 10 minutes) were the highest value of 0.743, 0.724, and 0.739, mean values of 0.724, 0.677 and 0.701 and rSO2 (Changes in values of regional cerebral oxygen) value of 0.722, 0.734 and 0.724, respectively, while all of the initial values had a poor AUC (<0.7) and also were not statistically significant. The optimal cut-off value of each rSO2 values during overall, initial 5 minutes and 10 minutes were the highest value of 26% (sensitivity, 53.9% specificity, 92.3%), 24% (sensitivity, 56.4% specificity, 92.3%), and 30% (sensitivity, 61.5% specificity, 84.6%), mean value of 15.2%, 15.3% and 16%, respectively. None of the patients with a persistent rSO2 <=18% during the overall period achieved ROSC. Initial 5 minutes and 10 minutes cerebral rSO2 values an out-of-hospital-cardiac arrest (OHCA) are a better predictor in deciding the futility of CPR, compared to initial and overall measurements.Copyright © 2023 The Author(s). Published by MRE Press.

Dynamic matching of oxygen uptake kinetics and muscle deoxygenation in post-COVID-19

Recent studies showed that post-COVID-19 patients with reduced pulmonary oxygen uptake (VO2p) kinetics, exhibited a lower peripheral oxygen extraction [lower C(a-v) O2 /Ca O2 ] rather than a central cardiac limitation (supernormal predicted exercisepeak cardiac output), opening further questions of what is impacting VO dynamics. We proposed to investigate the dynamic matching of VO2p , increase of heart rate (HR) and muscle deoxygenation (deoxy[Hb + Mb]) at the onset of heavy-exercise in post-COVID-19 patients. We expected to find a slowness of VO unrelated to circulatory impairment. 12 patients (90 days after onset of symptoms) were compared to 10 healthy controls. The VO rate of change, deoxy[Hb + Mb] in vastus lateralis (by near infrared spectroscopy) and HR were analyzed during a constant work-rate exercise test up to limit of tolerance (~70%peak work-rate). Post-COVID-19 patients had significantly slower VO2p kinetics than controls (Tau-VO2p 52+/-9 vs 40+/-11 seconds(s);p=0,001 and MRT-VO 70+/-12 vs 51+/-10 s;p<0,001). In contrast, t1/2 -HR was faster in patients (65+/-28 vs 85+/-20 s, p=0,04). Not only deoxy[Hb + Mb] dynamics were not accelerated compared to controls, suggesting normal muscle microvascular O2 delivery, but significantly slower (MRT-deoxy[Hb + Mb] 25+/-7 vs 20+/-2 s;p=0,02)(Figure 1). In conclusion, a sluggish on-exercise VO2p in these patients seems unrelated to central and peripheral circulatory adjustments. .

Regional Oxygenation in Neonates with Anemia.

Purpose. Assessment of regional oxygenation in neonates with anemic syndrome and after its correction. Materials and methods. The study included 76 neonates. Depending on the fact of the presence or absence of anemia, which required its correction, all included in the study infants were divided into 2 groups: with anemia - 8 patients and without it - 68 patients. Multiregional monitoring of tissue oxygenation was performed with the help of INVOS 5100C cerebral/somatic oximeter (Covidien, Medtronic, USA). Results and discussion. In comparison with infants with anemia, the comparison group had higher level of minimal cerebral oxygenation (73 [66;80] versus 56 [39;70], p=0.0447), and lower cFTOE values (0.17 [0.11;0.23] versus 0.35 [0,30;0,48], p=0,0021). It was also found that a newborn with RDS and cFTOE> 0.22 is 3.5 times more likely to have anemia, which requires PRBC transfusion. Correction of anemia was accompanied by the increase of hemoglobin level by 51 [36;56] g/l and hematocrit - by 16 [15;17] %. Moreover, only crSO2 and cFTOE showed the differences before and after transfusion: crSO2 before - 60 [55;69] and after - 65 [61;71], p=0.0156;cFTOE before - 0.40 [0.30;0.45] and after 0.34 [0.27;0.38], p=0.0078. Conclusion. Monitoring of regional oxygenation in neonates can be used for early diagnosis of oxygen imbalance in tissues on the background of development of anemia, and assessment of the effectiveness of its correction as well.Copyright © 2020, Professionalnye Izdaniya. All rights reserved.

Daily Amplitude of Cerebral Regional Oxygen Saturation as a Criterion of Effectiveness of Intensive Care in Neonates with Respiratory Disorders.

Purpose. To determine non-invasive criteria of intensive care efficiency in neonates with respiratory disorders. Materials and methods. The study included 78 newborns with gestational age of 37 [34;39] weeks and clinical and laboratory markers of respiratory disorder. During the early neonatal period in addition to the standard monitoring of vital signs in all patients, we evaluated an abdominal and cerebral oxygenation using the INVOS 5100C cerebral/somatic oximeter (Covidien, Medtronic, USA). On the base of the time taken to reach cardiopulmonary stability (no need of any hemodynamic support and the presence of effective spontaneous breathing or switch to non-invasive mechanical ventilation), all patients were divided into three groups: 1st (25 patients) - 4 days of life, 2nd (31 patients) - 7 days of life, 3rd (22 patients) - more than 7 days. Results. Significant differences between the values at the beginning of intensive care and the time taken to reach cardiopulmonary stability were obtained only for daily amplitude of cerebral regional oxygen saturation - DELTAcrSO2 (15 [9;19] versus 6 [5;9], p1-4 =0.0049 in the first group and 12 [8;19] versus 8 [5;15], p1-7 =0.0156 in the second one);DELTAcrSO2 level in the groups was the following: 8 [5;15] in the 1st group, 11 [8;14] in the 2nd group, and the 3rd - 13 [9;22], respectively, p<0.0001. Significant positive correlations (p<0.0001) were noted between the NIRS parameters and traditional clinical status markers. Conclusion. Daily amplitude of cerebral regional oxygen saturation could serve as a tool for assessment of intensive care (respiratory and hemodynamic) efficiency in neonates with respiratory disorders.Copyright © 2020, Professionalnye Izdaniya. All rights reserved.

Reduced brain activity and functional connectivity during creative idea generation in individuals with smartphone addiction.

Since the COVID-19 outbreak, the frequency of smartphone use has surged, which has caused an increase in smartphone addiction among individuals. Smartphone addiction can impair various cognitive abilities. However, to date, the impact of smartphone addiction on creative cognition remains unclear. The current functional near-infrared spectroscopy (fNIRS) study compared neural differences between smartphone addiction tendency (SAT) and healthy control (HC) individuals during creative idea generation. In particular, by manipulating a key component of creative cognition, that is, overcoming semantic constraints, we explored whether SAT individuals could overcome semantic constraints. Both the SAT and HC groups completed the alternate uses task (AUT) in semantic constraint and unconstraint conditions. The results indicated that the prefrontal cortex (PFC) and temporal region were less active during AUT in the SAT group than in the HC group. In the SAT group, the PFC was less active under constraint than unconstraint conditions. Moreover, both task-related and resting-state functional connectivity analyses indicated weaker coupling between PFC and temporal region in the SAT than in the HC group. Furthermore, left DLPFC mediated the effect of smartphone addiction on creative performance. These findings provide unprecedented neuroimaging evidence on the negative impact of smartphone addiction on creative cognition.

fNIRS neuroimaging in olfactory research: A systematic literature review.

There are a number of key features which make olfaction difficult to study; subjective processes of odor detection, discrimination and identification, and individualistic odor hedonic perception and associated odor memories. In this systematic review we explore the role functional near-infrared spectroscopy (fNIRS) has played in understanding olfactory perception in humans. fNIRS is an optical neuroimaging technique able to measure changes in brain hemodynamics and oxygenation related to neural electrical activity. Adhering to PRISMA guidelines, results of this search found that generally the majority of studies involving healthy adult subjects observed increased activity in response to odors. Other population types were also observed, such as infants, individuals with autism, attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), mild cognitive impairment (MCI) and dysosmia. fNIRS coverage heavily favored the prefrontal cortex, temporal and parietal regions. This review finds that odor induced cortical activation is dependent on multiple factors, such as odorant type, gender and population type. This review also finds that there is room for improvement in areas such as participant diversity, use of wearable fNIRS systems, physiological monitoring and multi-distance channels.

Monitoring the quality of ethanol-based hand sanitizers by low-cost near-infrared spectroscopy.

The use of near-infrared spectroscopy (NIRS) based on a low-cost portable instrument for monitoring the quality of the three major formulations of ethanol-based hand sanitizers used for prevention against CoVID-19 disease is described. The quality of the sanitizers was evaluated using two approaches. In the first, a qualitative method was developed to identify gross non-conformities, using NIR spectral data compression by principal components analysis and projection of the spectrum of the tested sample in the principal component space delimited by samples of sanitizers prepared in the laboratory. In the second, a quantitative method was designed to determine the active substance (ethanol) employing multivariate regression based on partial least squares. The results demonstrate that the first approach can be used to detect non-conformities in the sanitizer composition, mostly associated with incorrect ethanol content. The second explores the use of NIRS for determination of the ethanol content in the three formulations aiming the quality control of the sanitizer manufacturing process. The ethanol content can be determined with an absolute root mean square error of prediction (RMSEP) equal to 0.68% (m/m), 0.83% (m/m) and 1.0% (v/v) for the three formulations evaluated. The RMSEP was estimated as 1.3% (m/m) for the commercial products. The measurement protocol takes approximately 1 min and requires only about 120 µL of a sample. Besides, NIRS was employed to compare the rate of volatilization of the ethanol in the different formulations, an important parameter concerning the efficacy of ethanol-based sanitizers.

Evaluating the Endothelial Impairments in COVID-19 Patients Using Near-Infrared Spectroscopy: the HEMOCOVID-19 trial

HEMOCOVID-19 is a multi-center trial aiming to assess the microvascular and endothelial health of severe COVID-19 patients in the intensive care using near-infrared spectroscopy. Here, we present the preliminary results, showing that peripheral microcirculatory alterations are associated with the severity of acute respiratory distress syndrome. © 2022 The Author(s).

Near-Infrared Spectroscopy as a Potential COVID-19 Early Detection Method: A Review and Future Perspective.

The coronavirus disease 2019 (COVID-19) pandemic is a worldwide health anxiety. The rapid dispersion of the infection globally results in unparalleled economic, social, and health impacts. The pathogen that causes COVID-19 is known as a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A fast and low-cost diagnosis method for COVID-19 disease can play an important role in controlling its proliferation. Near-infrared spectroscopy (NIRS) is a quick, non-destructive, non-invasive, and inexpensive technique for profiling the chemical and physical structures of a wide range of samples. Furthermore, the NIRS has the advantage of incorporating the internet of things (IoT) application for the effective control and treatment of the disease. In recent years, a significant advancement in instrumentation and spectral analysis methods has resulted in a remarkable impact on the NIRS applications, especially in the medical discipline. To date, NIRS has been applied as a technique for detecting various viruses including zika (ZIKV), chikungunya (CHIKV), influenza, hepatitis C, dengue (DENV), and human immunodeficiency (HIV). This review aims to outline some historical and contemporary applications of NIRS in virology and its merit as a novel diagnostic technique for SARS-CoV-2.

Performance and reproducibility assessment across multiple time-domain near-infrared spectroscopy device replicas

Reproducibility between different replicas of the same device is an important aspect in the biomedical research field. Multiple replicas of a dual-wavelength, single-channel “NIRSBOX” device have been assembled and characterized. In this work, we present their full performance assessment. Characterization is focused on measurement accuracy, reproducibility, and reliability, following well-defined and widely adopted procedures to assess the quality of diffuse-optics instruments. The results of the performance assessment procedures are promising, demonstrating highly reproducible performances over different time-domain near-infrared spectroscopy devices, a feature of paramount importance when it comes to comparing results from different instruments, e.g. in multicenter studies. © 2022 SPIE

Application of Near-infrared Spectroscopy and Multivariate Methods for the Estimation of Isopropyl Alcohol Content in Hand Sanitizer Formulation

To address the need of alcohol-based hand sanitizers during COVID-19, U.S. FDA has issued a guidance for the preparation of hand sanitizers that recommends 80% v/v ethanol or 75%v/v isopropyl alcohol (IPA) along with other ingredients. The aim of this study was to develop a new method to estimate IPA content in hand sanitizers by using Near-infrared (NIR) spectroscopy with a multivariate chemo-metric approach. Calibration samples containing 10-90% of IPA were used for model development. NIR data was mathematically pretreated with multiple scattering correction before development of partial least squares (PLSR) and principal component regressions (PCR) model. Both models showed good linearity over the selected range of IPA content with high R2 (>0.993), low root mean squared error (<2.163), minimum difference between standard errors between calibration and validation models (0.0009). The proposed NIR with multivariate methods provide rapid analysis of IPA content in the hand sanitizer.

Rapid Classification of Respiratory Syncytial Virus and Sendai Virus by a Low-cost and Portable Near-infrared Spectrometer

In this work, we present the combination of near-infrared spectroscopy and chemometrics to distinguish respiratory syncytial virus (RSV) and Sendai virus (SeV), the first study of its kind. Using a low-cost and portable spectrometer, a total of 440 virus spectra were collected over four separate sessions. The spectra were pre-processed by normalisation and baseline removal, and variable elimination was conducted based on the standard deviation. Partial least squares discrimination analysis was used to model the relationship between the spectra and the virus categories, resulting in the accuracy of 0.825 and 0.855 for validation and prediction, respectively. Since the portable spectrometer has simple operation and can provide analytical results in real time, it can be used as a viable tool for rapid, on-site and low-cost virus screening for RSV, SeV and possibly other similar viruses such as SARS-CoV-2.

Regional pulmonary oxygen saturations immediately after birth.

BACKGROUND: Partial oxygen saturation (SpO2) increases within minutes during transition from the intrauterine to extrauterine life. This study aims to determine the postnatal course of pulmonary regional oxygen saturation (rSO2) measured by Near-Infrared Spectroscopy (NIRS). METHODS: We conducted an observational study at the delivery room in infants above 35 weeks of gestation who did not need resuscitation and did not develop respiratory distress. Preductal pulse oximetry (Covidien NellcorTM) and right pulmonary apex oxygen saturation (raSO2) and basal oxygen saturation (rbSO2) (Covidien INVOSTM) were measured, starting from the postnatal third minute of life, until the 15th minute. The correlations between SpO2 and pulmonary rSO2 were analyzed. RESULTS: Of the 110 infants included in the study, 87 were term and 23 were late preterms. The gestational age and birth weight were 38.5 ± 1.36 weeks and 3285 ± 508 g, respectively. Median (5th-95th percentile) raSO2 and rbSO2 were 79% (58-95%) and 78% (46-95%) at the third minute, respectively. The rSO2 values measured from both sides increased and reached a steady-state around postnatal 9 min, similar to SpO2 values. The pulmonary NIRS values were significantly higher for babies born by C-Section compared to babies born by vaginal delivery (p < 0.05). CONCLUSION: We found that rSO2 measurements increased within minutes in the postnatal period in late preterm and term babies without respiratory distress and reached a plateau at the postnatal 9th minute. The normal values obtained from this preliminary study may be used to predict the prognosis of cases with respiratory distress.

Evaluating a new generation of wearable high-density diffuse optical tomography technology via retinotopic mapping of the adult visual cortex.

Significance: High-density diffuse optical tomography (HD-DOT) has been shown to approach the resolution and localization accuracy of blood oxygen level dependent-functional magnetic resonance imaging in the adult brain by exploiting densely spaced, overlapping samples of the probed tissue volume, but the technique has to date required large and cumbersome optical fiber arrays. Aim: To evaluate a wearable HD-DOT system that provides a comparable sampling density to large, fiber-based HD-DOT systems, but with vastly improved ergonomics. Approach: We investigated the performance of this system by replicating a series of classic visual stimulation paradigms, carried out in one highly sampled participant during 15 sessions to assess imaging performance and repeatability. Results: Hemodynamic response functions and cortical activation maps replicate the results obtained with larger fiber-based systems. Our results demonstrate focal activations in both oxyhemoglobin and deoxyhemoglobin with a high degree of repeatability observed across all sessions. A comparison with a simulated low-density array explicitly demonstrates the improvements in spatial localization, resolution, repeatability, and image contrast that can be obtained with this high-density technology. Conclusions: The system offers the possibility for minimally constrained, spatially resolved functional imaging of the human brain in almost any environment and holds particular promise in enabling neuroscience applications outside of the laboratory setting. It also opens up new opportunities to investigate populations unsuited to traditional imaging technologies.

Performance assessment of commercial continuous-wave near-infrared spectroscopy devices for the international HEMOCOVID-19 clinical trial

HEMOCOVID-19 project spans four countries and eight hospitals to evaluate the microvascular and endothelial health of severe COVID-19 patients using near-infrared spectroscopy (NIRS) of the forearm muscle. In order to implement the project, we have developed protocols and tested ten commercial continuous-wave NIRS devices of the same model (PortaMon, Artinis, NL). They were characterized and compared for intra-And inter-device, inter-And intra-operator and temporal variability in solid phantoms and in vivo. © COPYRIGHT SPIE. Downloading of the is permitted for personal use only.

HEMOCOVID-19 Study: An International Clinical Study to Evaluate Microvascular and Endothelial Impairments in Severe COVID-19 Patients Using Near-Infrared Spectroscopy

We present the HEMOCOVID-19 study spanning four countries and eight hospitals where near-infrared spectroscopy is utilized to evaluate microvascular and endothelial health of severe COVID-19 patients at the intensive care. © 2021 SPIE. All rights reserved.