Deoxyhemoglobin Concentration Research Articles

Relationship Between Age and Cerebral Hemodynamic Response to Breath Holding: A Functional Near-Infrared Spectroscopy Study.

Cerebrovascular reactivity (CVR) is routinely measured as a predictor of stroke in people with a high risk of ischemic attack. Neuroimaging techniques such as emission tomography, magnetic resonance imaging, and transcranial doppler are frequently used to measure CVR even though each technique has its limitations. Functional near-infrared spectroscopy (fNIRS), also based on the principle of neurovascular coupling, is relatively inexpensive, portable, and allows for the quantification of oxy- and deoxy-hemoglobin concentration changes at a high temporal resolution. This study examines the relationship between age and CVR using fNIRS in 45 young healthy adult participants aged 18-41years (6 females, 26.64 ± 5.49years) performing a simple breath holding task. Eighteen of the 45 participants were scanned again after a week to evaluate the feasibility of fNIRS in reliably measuring CVR. Results indicate (a) a negative relationship between age and hemodynamic measures of breath holding task in the sensorimotor cortex of 45 individuals and (b) widespread positive coactivation within medial sensorimotor regions and between medial sensorimotor regions with supplementary motor area and prefrontal cortex during breath holding with increasing age. The intraclass correlation coefficient (ICC) indicated only a low to fair/good reliability of the breath hold hemodynamic measures from sensorimotor and prefrontal cortices. However, the average hemodynamic response to breath holding from the two sessions were found to be temporally and spatially in correspondence. Future improvements in the sensitivity and reliability of fNIRS metrics could facilitate fNIRS-based assessment of cerebrovascular function as a potential clinical tool.

Predicting Student Performance Using Machine Learning in fNIRS Data.

Increasing student involvement in classes has always been a challenge for teachers and school managers. In online learning, some interactivity mechanisms like quizzes are increasingly used to engage students during classes and tasks. However, there is a high demand for tools that evaluate the efficiency of these mechanisms. In order to distinguish between high and low levels of engagement in tasks, it is possible to monitor brain activity through functional near-infrared spectroscopy (fNIRS). The main advantages of this technique are portability, low cost, and a comfortable way for students to concentrate and perform their tasks. This setup provides more natural conditions for the experiments if compared to the other acquisition tools. In this study, we investigated levels of task involvement through the identification of correct and wrong answers of typical quizzes used in virtual environments. We collected data from the prefrontal cortex region (PFC) of 18 students while watching a video lecture. This data was modeled with supervised learning algorithms. We used random forests and penalized logistic regression to classify correct answers as a function of oxyhemoglobin and deoxyhemoglobin concentration. These models identify which regions best predict student performance. The random forest and penalized logistic regression (GLMNET with LASSO) obtained, respectively, 0.67 and 0.65 area of the ROC curve. Both models indicate that channels F4-F6 and AF3-AFz are the most relevant for the prediction. The statistical significance of these models was confirmed through cross-validation (leave-one-subject-out) and a permutation test. This methodology can be useful to better understand the teaching and learning processes in a video lecture and also provide improvements in the methodologies used in order to better adapt the presentation content.

Critical Thinking Analysis Using Functional Near-Infrared Spectroscopy (fNIRS)

Critical thinking which is also known as creative thinking, is a fundamental skill needed to solve any problems in our life. The behaviour of critical thinking involves reviewing the results of the application of decisions made and implementing change where possible. It also happens when someone aims to achieve the best possible outcomes in any situation. It plays an important role in innovation, development, and health. Hence, knowing someone’s critical thinking behaviour is essential to improve one’s ability. However, to have good critical thinking skill is very challenging without understanding its features and biological behaviour. To understand the critical thinking behaviour based on cognitive function and neural activities, the psychological research methods and principles from neuroscience are necessary. Thus, this study aims to analyse critical thinking behaviour in the human brain by looking on the Hemodynamic Response Function (HRF). The instrument used in this study is a functional Near-Infrared Spectroscopy (fNIRS) device, called Wearable Optical Topography (WOT-100) with 16 channels where it measured the HRF of oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbR) concentration and Platform Optical Topographic Analysis Tools (POTATo) developed by HITACHI performed the pre-processing of raw data. Experimental results show that the mean concentration of HbO measured for High Scores (HS) group at right and left PFC were slightly difference with concentration value of 17.6945mol/μm and 17.3514mol/μm while for Low Scores (LS) group shows the mean concentration of HbO at left PFC was higher than right PFC with concentration value of 25.0353mol/μm and 14.2499mol/µm respectively. Hence, these results show that the LS group tend to use their left PFC during task given due to laborious decision-making process happen influences by time duration subjects answering the tasks. Therefore, these results suggest an imperative role for individual differences in their neural activation. The outcome of this study highlights the significance of individual differences and their cognitive preference and potentials in performance of functional tasks such as attention, creativity, imagery, decision making and working memory that leads to critical thinking behaviour.

Tracking Brain Development From Neonates to the Elderly by Hemoglobin Phase Measurement Using Functional Near-Infrared Spectroscopy.

The biological and neurological processes during the lifespan are dynamic with significant alterations associated with different stages of life. The phase and coupling of oxy-hemoglobin (Δ[HbO]) and deoxy-hemoglobin concentration changes (Δ[Hb]) measured by functional near-infrared spectroscopy (fNIRS) are shown to characterize the neurovascular and metabolic development of infants. However, the changes in phase and coupling across the human lifespan remain mostly unknown. Here, fNIRS measurements of Δ[HbO] and Δ[Hb] conducted at two sites on different age populations (from newborns to elderly) were combined. Firstly, we assessed the influence of random noise on the calculation of the phase difference and phase-locking index (PLI) in fNIRS measurement. The results showed that the phase difference is close to π as the noise intensity approaches -8 dB, and the coupling strength (i.e., PLI) presents a u-shape curve as the noise increase. Secondly, phase difference and PLI in the frequency range 0.01-0.10 Hz were calculated after denoising. It showed that the phase difference increases from newborns to 3-4-month-olds babies. This phase difference persists throughout adulthood until finally being disrupted in the old age. The children's PLI is the highest, followed by that of adults. These two groups' PLI are significantly higher than those of infants and the elderly (p < 0.001). Lastly, a hemodynamic model was used to explain the observations and found close associations with cerebral autoregulation and speed of blood flow. These results demonstrate that the phase-related parameters measured by fNIRS can be used to study the brain and assess brain health throughout the lifespan.

Changes in Diffuse Optical Tomography Images During Early Stages of Neoadjuvant Chemotherapy Correlate with Tumor Response in Different Breast Cancer Subtypes.

This study's primary objective was to evaluate the changes in optically derived parameters acquired with a diffuse optical tomography breast imaging system (DOTBIS) in the tumor volume of patients with breast carcinoma receiving neoadjuvant chemotherapy (NAC). In this analysis of 105 patients with stage II-III breast cancer, normalized mean values of total hemoglobin ([Formula: see text]), oxyhemoglobin ([Formula: see text]), deoxy-hemoglobin concentration ([Formula: see text]), water, and oxygen saturation ([Formula: see text]) percentages were collected at different timepoints during NAC and compared with baseline measurements. This report compared changes in these optical biomarkers measured in patients who did not achieve a pathologic complete response (non-pCR) and those with a pCR. Differences regarding molecular subtypes were included for hormone receptor-positive and HER2-negative, HER2-positive, and triple-negative breast cancer. At baseline, [Formula: see text] was higher for pCR tumors (3.97 ± 2.29) compared with non-pCR tumors (3.00 ± 1.72; P = 0.031). At the earliest imaging point after starting therapy, the mean change of [Formula: see text] compared with baseline ([Formula: see text]) was statistically significantly higher in non-pCR (1.23 ± 0.67) than in those with a pCR (0.87 ± 0.61; P < 0.0005), and significantly correlated to residual cancer burden classification (r = 0.448; P < 0.0005). [Formula: see text] combined with HER2 status was proposed as a two-predictor logistic model, with AUC = 0.891; P < 0.0005; and 95% confidence interval, 0.812-0.969. This study demonstrates that DOTBIS measured features change over time according to tumor pCR status and may predict early in the NAC treatment course whether a patient is responding to NAC.

A Drowsiness Reduction Strategy Utilizing Visual Stimulation With Different Colors of Light: An fNIRS Study

Drowsiness during driving is a severe problem that must be addressed to improve road safety. Numerous counter-measures have been proposed to resolve this issue like adaptive environmental settings (temperature, sound, and light). The objective of this study was to accurately predict the effects of exposure to different colors of light on human drowsiness by using functional near-infrared spectroscopy and other physical measurements (heart rate and eye closure). We targeted two regions of the brain (visual and pre-frontal cortices). Twenty-three healthy subjects were investigated to evaluate all variables related to the awakening state, and twenty-one healthy subjects were also examined in the drowsy state evaluation. Eventually, the ten most suitable subjects were exposed to red, green, and blue lights under drowsy conditions, according to the experimental paradigm. Dim light was maintained in the experimental premises before and after colored light exposure to limit the results to those produced only in response to the desired stimuli. Eye closure, heart rate, and changes in oxy and deoxy hemoglobin concentrations were measured to characterize the condition (awake/drowsy) of the subject. A support vector machine classifier was used to identify the classification accuracy of awake and drowsy states. In conclusion, exposure to blue light triggered the activation of oxy hemoglobin in targeted brain regions; however, deoxy hemoglobin was not significantly affected by exposure to any of the colored lights. Noticeably, our study revealed that blue light exposure is more effective at reducing drowsiness than exposure to red and green lights.

Effect of Prolonged Pressure on Hemodynamics of Sacral Tissues Assessed by Diffuse Optical Imaging: A Pilot Study.

Pressure injuries (PIs) are wounds resulting from prolonged pressure exerting on the skin and underlying tissues over bony prominences (e.g., lower back, heels, shoulders) in bed-bound patients and wheelchair users. Minimizing pressure has long been considered the most effective preventative method, and current guidelines require visual skin inspection and repositioning every two hours. However, these strategies are often applied deficiently and do not adequately prevent PIs from becoming penetrating wounds. Recent studies attribute the development of PIs to cell deformation, inflammatory, and ischemic damages that cumulatively propagate from the microscale (death of few cells) to the macroscale (tissue necrosis) within one to several hours. Although the nature of the PI pathogenesis is complex and multifactorial, measuring tissue alterations in real-time may elucidate the origination mechanism and ultimately allow detecting PIs at the earliest stage. In this pilot study, we evaluated the ability of diffuse optical imaging (DOI) to assess hemodynamic changes resulting from prolonged pressure on the sacral tissues in five healthy volunteers laying immobile in a supine position for 2hours. A thin, body-conforming optical imaging probe encompassing 256 optodes arranged in a regularly spaced grid over a 160×160 mm area was used to construct DOI volumetric images representing changes of oxyhemoglobin (HbO2) and deoxyhemoglobin (HHb) concentration from a zeroed baseline. After 2hours of continuous body weight pressure, hemodynamic images in all subjects were substantially dissimilar from their individual baseline. We also found that hemodynamic similarity computed pairwise across subjects exhibited a high value and limited variability around the mean, thus denoting a consistent level of image similarity across subjects. These preliminary results indicate that prolonged pressure causes distinctive hemodynamic patterns that can be effectively investigated with DOI and that monitoring functional changes over time holds potential for clarifying the development mechanisms of PIs.

Analysis Protocols for MRI Mapping of the Blood Oxygenation-Sensitive Parameters T2* and T2 in the Kidney.

Renal hypoxia is generally accepted as a key pathophysiologic event in acute kidney injury of various origins and has also been suggested to play a role in the development of chronic kidney disease. Here we describe step-by-step data analysis protocols for MRI monitoring of renal oxygenation in rodents via the deoxyhemoglobin concentration sensitive MR parameters T2* and T2-a contrast mechanism known as the blood oxygenation level dependent (BOLD) effect.This chapter describes how to use the analysis tools provided by vendors of animal and clinical MR systems, as well as how to develop an analysis software. Aspects covered are: data quality checks, data exclusion, model fitting, fitting algorithm, starting values, effects of multiecho imaging, and result validation.This chapter is based upon work from the PARENCHIMA COST Action, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by two separate chapters describing the basic concept and data analysis.

Prefrontal cortex activation during working memory task in schizophrenia: A fNIRS study.

Neurocognitive cognitive deficits including working memory (WM) impairment is a key component of schizophrenia (SCZ). Though a prefrontal cortex (PFC) abnormality is recognised to contribute to WM impairment, the exact nature of its neurobiological basis in SCZ is not well established. Functional near infra-red spectroscopy (fNIRS) is an emerging low-cost neuroimaging tool to study neuro-hemodynamics. In this background, we examined the hemodynamic activity during a WM task in schizophrenia using fNIRS. fNIRS was acquired during computerised N-back (zero-, one- & two-back) task in 15 SCZ patients and compared with 22 healthy controls. Performance in N-back test were calculated using signal detection theory alongside the mean reaction times. Concentration and latencies of oxy-, deoxy-, and totalhaemoglobin, and oxygen saturation were computed from 8*8 optodes positioned over bilateral PFC. SCZ performed poorly as measured by most of the WM parameters (p < 0.05). Lesser deoxyhemoglobin concentration (two > zero, at right BA10, p = 0.006) was noted in the right frontopolar cortex in SCZ surviving multiple-comparison correction. In addition, olanzapine equivalent doses correlated negatively with right frontopolar cortex activation (two > zero back, BA10, ρ = 0.70, p = 0.004) and better performance in two back (false alarm rate, ρ = 0.61, p = 0.015). A delayed but compensatory hyperactivation of right frontopolar cortex noted in SCZ may underlie the WM deficit in SCZ. Future studies are recommended to replicate the role of right frontopolar cortex in WM using larger samples and systematically explore the effect of antipsychotics on them.

Direct mapping from diffuse reflectance to chromophore concentrations in multi-fx spatial frequency domain imaging (SFDI) with a deep residual network (DRN).

Spatial frequency domain imaging (SFDI) is an emerging technology that enables label-free, non-contact, and wide-field mapping of tissue chromophore contents, such as oxy- and deoxy-hemoglobin concentrations. It has been shown that the use of more than two spatial frequencies (multi-fx ) can vastly improve measurement accuracy and reduce chromophore estimation uncertainties, but real-time multi-fx SFDI for chromophore monitoring has been limited in practice due to the slow speed of available chromophore inversion algorithms. Existing inversion algorithms have to first convert the multi-fx diffuse reflectance to optical absorptions, and then solve a set of linear equations to estimate chromophore concentrations. In this work, we present a deep learning framework, noted as a deep residual network (DRN), that is able to directly map from diffuse reflectance to chromophore concentrations. The proposed DRN is over 10x faster than the state-of-the-art method for chromophore inversion and enables 25x improvement on the frame rate for in vivo real-time oxygenation mapping. The proposed deep learning model will help enable real-time and highly accurate chromophore monitoring with multi-fx SFDI.

Prefrontal Cortex Hemodynamics During Exercise in Older Adults With Motoric Cognitive Risk Syndrome

The motoric cognitive risk syndrome (MCR) is a recently described pre-dementia syndrome in older adults characterized by slow gait coupled with subjective cognitive complaints. While previous studies have demonstrated the benefits of exercise on cerebral hemodynamics in healthy older adults, to date, no study has characterized the effects of exercise on these parameters among more vulnerable older persons with MCR. To address this knowledge gap, we investigated how the brain area responsible for high-order cognitive function (i.e., prefrontal cortex) is affected during acute cycling exercise in 19 older adults with MCR (Age (mean ± SD): 73.7 ± 7.1 years; BMI: 32.1 ± 5.5 kg/m2; gait speed: 0.55 ± 0.1 m/s; Modified Mini-Mental score: 91.8 ± 6.8; 74% female). Participants performed an incremental submaximal cycling test and we used functional near-infrared spectroscopy to assess changes in concentrations of Oxyhemoglobin (O2Hb), Deoxyhemoglobin (dHb) and total hemoglobin (Hbt) during exercise. Results showed that participants cycled for 4.9 ± 0.5 minutes, achieved a submaximal load of 54.7 ± 17.3 watts, a peak exercise heart rate of 95.7 ± 14.7 beats/min and a rate of perceived exertion (13.8 ± 2.0). Compared to baseline, there was an increase of 97.3 % in the O2Hb, 86 % on the Hbt and an 87.9 decrease of dHb while exercising. Our findings suggest that acute exercise at light through moderate intensity increases prefrontal cortex oxygenation in older adults with MCR. Additional studies are also warranted to characterize the effects of chronic exercise on cerebral hemodynamics in at-risk older adults.

Assessing Dynamic Cerebral Autoregulation in Patients with Sickle Cell Disease Using Near-Infrared Spectroscopy and Paced Breathing

Introduction. Sickle cell disease (SCD) is caused by hemoglobin S polymerization leading to vaso-occlusion, small vessel disease, and reduced tissue oxygen saturation. Noninvasive assessments and screening of small vessel disease and decreased oxygen saturation in select organs, like the brain, are poorly developed. Cerebral autoregulation, a mechanism that ensures cerebral blood flow (CBF) remains constant with changes in mean arterial pressure, is impaired with and is a marker of small vessel disease. Frequency-domain near-infrared spectroscopy (FD-NIRS) can be used as a noninvasive technique to measure cerebral autoregulation by recording cerebral microvascular changes in hemoglobin concentration that are related to cerebral blood flow. Transfer function analysis is a method to noninvasively quantify the relationship between measured physiologic signals, and can be used to estimate cerebral autoregulation. In this study, we hypothesized patients with SCD have impaired cerebral autoregulation and reduced tissue oxygen saturation, which we evaluated via FD-NIRS with transfer function analysis, as compared to healthy controls. Methods. All patients provided informed consent under an IRB protocol approved by the University of Pittsburgh and Carnegie Mellon University. Patients with SCD (n = 11) and healthy, race-matched controls (n =14) were enrolled. All participants sat upright in a chair with probes of a commercial multi-distance FD-NIRS apparatus applied to their forehead in a dark room (Fig. 1A). We used paced breathing to dynamically induce controlled changes in the microvascular tone at 0.1, 0.125, and 0.1667 Hz, spanning normal to more challenging breathing rates, with a visual metronome guiding each paced breathing session (Fig.1.B). To validate each breathing pace, we recorded the participants' respiratory rate via a belt placed around their chest, and their mean arterial pressure through a finger and arm cuff attached to a beat-to-beat finger plethysmographer (Fig.1.A). We used the modified Beer-Lambert law to calculate changes in oxy-hemoglobin (O), deoxy-hemoglobin (D), and total hemoglobin (T) concentrations. Data was bandpass-filtered around the paced breathing frequencies, and the Hilbert transform was applied to calculate the amplitude ratios, |D|/|O|, and phase latency, Arg(D)−Arg(O). The tissue oxygen saturation of hemoglobin, StO2 (mean ±SD), was computed based on an average baseline of two minutes. Results. Arg(D)−Arg(O) and |D|/|O| are shown for controls and patients at all paced breathing frequencies (Fig.1C-D) from the largest source-detector distance. A non-zero phase lag between D and O within both groups indicates influences of cerebral blood volume (CBV) and CBF changes. The phase differences of D and O are therefore related to cerebral autoregulation. We found a greater phase difference (mean range: -320° to -340°) in patients with SCD compared to controls (mean range: -200° to -240°), indicating the presence of vascular obstruction and impaired cerebral autoregulation. Higher amplitude ratios |D|/|O| may indicate slower blood transmit times. We found that patients with SCD had increased amplitude ratios for hemodynamic oscillations at lower paced breathing frequencies compared to healthy controls (Fig. 1D). Finally, we found a significantly reduced cerebral tissue oxygen saturation in patients with SCD (63.1 % ± 7.8 %) in comparison with controls (65.9 % ± 4.9 %, p&amp;lt;0.05, Fig.1E). Discussion. We provide preliminary evidence that FD-NIRS can be used to assess cerebral autoregulation in SCD. Our results confirm and extend those of a prior study by Reinhard et al, 2003, by using the phase latency, Arg(D)−Arg(O), and the amplitude ratios, |D|/|O|, to assess autoregulation. In addition, we detected a noticeable reduction in oxygen saturation in patients with SCD as compared to healthy controls. Further studies may extend our findings to additional frequencies in a larger sample size to more comprehensively assess the impact of mean arterial pressure on autoregulation. Noninvasive measurement of cerebral autoregulation and brain oxygenation in SCD by FD-NIRS may represent a novel biomarker of cerebral vasculopathy in SCD and may help monitor changes in cerebral oxygenation, particularly during treatment with drugs that modulate the hemoglobin oxygen affinity, such as the recently FDA-approved voxelotor. Figure 1 Disclosures No relevant conflicts of interest to declare.

Role of prefrontal cortex during Sudoku task: fNIRS study.

BackgroundSudoku is a popular cognitively stimulating leisure-time activity. Many studies have been directed toward finding an algorithm to solve Sudoku, but the investigation of the neural substrates involved in Sudoku has been challenging.MethodsSudoku task was divided into two steps to understand the differential function of the prefrontal cortex (PFC) while applying heuristic rules. PFC activity was recorded at 16 optode locations using functional near infrared spectroscopy. Classical two-way analysis of variance as well as general linear model-based approach was used to analyze the data from 28 noise-free recordings obtained from right-handed participants.Results Post hoc analysis showed a significant increase in oxyhemoglobin concentrations and decrease in deoxyhemoglobin concentrations at all 16 optode locations during step 1 (3 × 3 subgrids) and step 2 (easy level 9 × 9 Sudoku) when compared with the rest (p < 0.0001). Contrasting the step 2 – step 1 revealed that medial regions of PFC were preferentially activated.ConclusionBoth the medial and lateral regions of PFC are activated during Sudoku task. However, the medial regions of PFC play a differential role, especially when we consider searching and selecting the heuristic rules. Thus, Sudoku may be used for cognitive remediation training in neuropsychiatric disorders involving PFC.

Noninvasive Monitoring of Deep Tissue Oxygenation in Buried Flaps by Time-Resolved Near-Infrared Spectroscopy in Pigs.

Flap monitoring in reconstructive surgery is particularly important because flap failure is a dramatic event for the patient and for the medical team. Noninvasive deep tissue oxygenation monitoring is a challenge. The aim of this experimental study was to assess the performance of time-resolved near-infrared spectroscopy compared with continuous-wave near-infrared spectroscopy and with invasive oxygen partial pressure measurement in pigs. Thirty fasciocutaneous flaps based on the superficial epigastric inferior pedicle were harvested and buried under the transcutaneous dorsal muscle (approximately 1 cm thick). An optical probe was placed on the skin above each buried flap. For each pig, two buried flaps were performed, one submitted to arterial occlusion and one to venous occlusion. Oxyhemoglobin and deoxyhemoglobin concentrations were observed for over 40 minutes before clamping, almost 20 minutes during clamping and during a period of release of approximately 20 minutes. Variations in time-resolved near-infrared spectroscopy were compared to the oxygen partial pressure and continuous-wave near-infrared spectroscopy variations. All vascular events were detected by the time-resolved near-infrared spectroscopy. During arterial clamping, oxyhemoglobin decreased rapidly, whereas deoxyhemoglobin increased moderately. The divergence of oxyhemoglobin and deoxyhemoglobin curves indicated arterial occlusion. During venous clamping, deoxyhemoglobin increased, whereas oxyhemoglobin increased briefly then remained stable or decreased moderately. The initial increases in the oxyhemoglobin and deoxyhemoglobin curves indicated venous occlusion. Oxygen partial pressure failed to detect vascular events in three cases. Continuous-wave near-infrared spectroscopy could not clearly identify vascular occlusions. Thus, the authors demonstrated the relevance of time-resolved near-infrared spectroscopy to buried flap monitoring. Time-resolved near-infrared spectroscopy could differentiate between arterial occlusion and venous occlusion.

Caffeine enhances BOLD responses to electrical whisker pad stimulation in rats during alpha‐chloralose anaesthesia

By reducing the cerebral blood flow and thereby increasing the resting deoxyhaemoglobin concentration, many human studies have shown that caffeine has a beneficial effect on enhancing the magnitude of blood-oxygenation-level-dependent (BOLD) responses. However, the effect of caffeine on BOLD responses in animals under anaesthesia has not been demonstrated. In this study, we aimed to determine the effect of systemic caffeine administration on BOLD responses in rats under alpha-chloralose. By applying electric whisker pad stimulation to male Sprague-Dawley rats, we performed fMRI measurements before and after the caffeine injection (40mg/kg, n=7) or an equivalent volume of saline (n=6) at 7T. To understand the potential perturbation of animal physiology during stimulation, arterial blood pressure was measured in a separate group of animals (n=3) outside the scanner. Caffeine significantly decreased baseline BOLD signals (p=.05) due to the increased deoxyhaemoglobin level. Both BOLD responses and t-values in the primary somatosensory cortex were significantly increased (both p<.05). The blood pressure changed insignificantly (p>.05). No significant differences in BOLD responses and t-values were observed in the control condition of saline injection (both p>.05). These findings suggested that, although the cerebral activity was lower under alpha-chloralose anaesthesia, the higher level of deoxygemoglobin at the baseline under the caffeinated condition can benefit the magnitude of BOLD responses in rats. These findings suggest that animal models might serve as potential platforms for further caffeine-related fMRI research studies.

INTRATRACHEAL SALINE BOLUS INCREASES SURVIVABILITY IN RABBITS EXPOSED TO LETHAL DOSE OF INHALED HYDROGEN SULFIDE

SESSION TITLE: Pharmacotherapeutics Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Hydrogen Sulfide (H2S) is a highly toxic, flammable, and colorless gas. In addition to industrial accident risks, H2S has been identified as a potential terrorist chemical and military threat agent for use in mass-casualty events, with no effective antidotes. In this study, we investigate the effects of a small volume of intratracheal (IT) slow-drip saline versus IT fast bolus saline treatment to prolong survival in H2S exposure in an animal model for potential treatments during mass-casualty crises. METHODS: The effects of IT saline in H2S exposure were tested on 49 New Zealand white male rabbits. Animals were anesthetized and intubated, but not ventilated. H2S gas (2000 ppm) was delivered along with a 1.5% isoflurane in air mixture (2.25 liters/min)for 30 minutes.Three groups were compared: no saline into endotracheal tube control(n=16), IT slow saline drip (n=17) and fast IT saline bolus group (n=16). Animals in IT slow drip saline group received 3cc of saline in 3 minutes, while fast saline bolus group animals received it in less than 20 seconds. Both treatment groups were compared to the control group. Systemic blood pressure and heart rate were continuously monitored.The changes in tissue oxy and deoxy hemoglobin concentrations were measured non-invasively over the brain region using continuous wave near infrared spectroscopy. Animals were deemed survivors at 60 minutes from the start of toxic exposure. Animals were sacrificed when systolic blood pressure dropped below 20 mmHg. RESULTS: The average weight for all animals(n=49) in this study was 3.88 ± 0.35 kg, mean ± SD. The survival rate of the fast saline, slow saline, and the control groups were 56.25%, and,23.53%, and 25%.Log-rank (Mantel-Cox) test showed that the survivability in the treatment groups and control groups are significantly different (p=0.0417). Slow saline group versus fast saline group difference was also significant (p=0.0140). The slow saline group compared to control group results were not different (p=0.7031). CONCLUSIONS: The rapid administration of a small volume of saline bolus given via IT route was effective in prolonging survival in lethal H2S exposure when given rapidly. These findings appear likely due to the rapid bolus stimulating cough and breathing responses in apneic animals, in contrast to the slow dripping of a similar amount of saline.While the stimulation of breathing leads to inhalation of more H2S in this model, improvement in hypoxemia in these animals appears to be of greater importance than the risk of additional H2S exposure.Thus, we propose that the hypoxemia from H2S-induced respiratory depression is a major contributor to mortality compared to the metabolic inhibition of cytochromes from H2S in this scenario. CLINICAL IMPLICATIONS: This has potential implications for the treatment victims of H2S exposure who cannot be removed from the exposure site as this commonly occurs in mass-casualty events. DISCLOSURES: No relevant relationships by vikhyat bebarta, source=Web Response No relevant relationships by Gerry Boss, source=Web Response No relevant relationships by Matthew Brenner, source=Web Response No relevant relationships by Tanya Burney, source=Web Response No relevant relationships by Adriano Chan, source=Web Response No relevant relationships by Melina Doosty, source=Web Response No relevant relationships by Philippe Haouzi, source=Web Response No relevant relationships by Tara Hendry-Hofer, source=Web Response No relevant relationships by Jangwoen Lee, source=Web Response No relevant relationships by Sari Mahon, source=Web Response No relevant relationships by David Mukai, source=Web Response No relevant relationships by George Philipopoulos, source=Web Response

Inter-Session Reliability of Functional Near-Infrared Spectroscopy at the Prefrontal Cortex While Walking in Multiple Sclerosis.

Many established technologies are limited in analyzing the executive functions in motion, especially while walking. Functional near-infrared spectroscopy (fNIRS) fills this gap. The aim of the study is to investigate the inter-session reliability (ISR) of fNIRS-derived parameters at the prefrontal cortex while walking in people with multiple sclerosis (MS) and healthy control (HC) individuals. Twenty people with MS/HC individuals walked a 12 m track back and forth over 6 min. The primary outcomes were the absolute and relative reliability of the mean, slope coefficient (SC), and area under the curve (A) of the oxy-/deoxyhemoglobin concentrations (HbO/HbR) in the Brodmann areas (BA) 9/46/10. The SC and the A of HbO exhibited a fair ISR in BA10 in people with MS. For the mean and A of the HbR, almost all areas observed revealed a fair ISR. Overall, the ISR was better for HbR than HbO. A fair to excellent ISR was found for most BA of the prefrontal cortex in HC individuals. In total, the ISR of the analyzed fNIRS-derived parameters was limited. To improve the ISR, confounders such as fatigue and mind wandering should be minimized. When reporting the ISR, the focus should be on the mean/A rather than SC.

Use of photoacoustic imaging for monitoring vascular disrupting cancer treatments.

Vascular disrupting agents disrupt tumor vessels, blocking the nutritional and oxygen supply tumors need to thrive. This is achieved by damaging the endothelium lining of blood vessels, resulting in red blood cells (RBCs) entering the tumor parenchyma. RBCs present in the extracellular matrix are exposed to external stressors resulting in biochemical and physiological changes. The detection of these changes can be used to monitor the efficacy of cancer treatments. Spectroscopic photoacoustic (PA) imaging is an ideal candidate for probing RBCs due to their high optical absorption relative to surrounding tissue. The goal of this work is to use PA imaging to monitor the efficacy of the vascular disrupting agent 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) through quantitative analysis. Then, 4T1 breast cancer cells were injected subcutaneously into the left hind leg of eight BALB/c mice. After 10 days, half of the mice were treated with 15 mg/kg of DMXAA and the other half were injected with saline. All mice were imaged using the VevoLAZR X PA system before treatment, 24 and 72 hours after treatment. The imaging was done at six wavelengths and linear spectral unmixing was applied to the PA images to quantify three forms of hemoglobin (oxy, deoxy and met-hemoglobin). After imaging, tumors were histologically processed and H&E and TUNEL staining were used to detect the tissue damage induced by the DMXAA treatment. The total hemoglobin concentration remained unchanged after treatment for the saline treated mice. For DMXAA treated mice, a 10% increase of deoxyhemoglobin concentration was detected 24 hours after treatment and a 22.6% decrease in total hemoglobin concentration was observed by 72 hours. A decrease in the PA spectral slope parameters was measured 24 hours after treatment. This suggests that DMXAA induces vascular damage, causing red blood cells to extravasate. Furthermore, H&E staining of the tumor showed areas of bleeding with erythrocyte deposition. These observations are further supported by the increase in TUNEL staining in DMXAA treated tumors, revealing increased cell death due to vascular disruption. This study demonstrates the capability of PA imaging to monitor tumor vessel disruption by the vascular disrupting agent DMXAA.

Asymmetrical cortical vein sign predicts early neurological deterioration in acute ischemic stroke patients with severe intracranial arterial stenosis or occlusion

BackgroundSusceptibility weighted imaging (SWI) provides an approximate assessment of tissue perfusion and shows prominent hypointense cortical veins in the ischemic territory because of the increased concentration of deoxyhemoglobin. We aimed to evaluate whether asymmetrical prominent cortical vein sign (APCVS) on SWI can predict early neurological deterioration (END) in acute ischemic stroke patients with severe intracranial arterial stenosis or occlusion (SIASO).MethodsOne hundred and nine acute ischemic stroke patients with SIASO who underwent SWI were retrospectively recruited. END was defined as an increase in the National Institutes of Health Stroke Scale score ≧2 points despite standard treatment in the first 72 h after admission. The APCVS was defined as more and/or large vessels with greater signal loss than those in the opposite hemisphere on SWI.ResultsThirty out of the 109 (27.5%) patients developed END. Sixty (55.0%) patients presented with APCVS on SWI. APCVS occurred in 24 (80%) patients with END, whereas it only occurred in 36 (45.6%) patients without END (P = 0.001). Patients with APCVS were more likely to have END (40.0%, vs. 12.2%, P = 0.001) than those without END. Multivariate logistic regression indicated that APCVS (OR = 4.349, 95% C.I. = 1.580–11.970, P = 0.004) was a significant predictor of END in acute ischemic stroke patients with SIASO, adjusted for previous stroke history and acute infarct volume.ConclusionsIn acute ischemic stroke patients with SIASO, the APCVS might be a useful neuroimaging marker for predicting END, which suggests the importance of evaluation of perfusion status.

Tissue oxygenation in peripheral muscles and functional capacity in cystic fibrosis: a cross-sectional study.

What is the central question of this study? How do peripheral muscle tissue oxygenation and physical conditioning levels of children and adolescents with cystic fibrosis compare to demographically matched controls? What is the main finding and its importance? Children and adolescents with cystic fibrosis consumed more oxygen, more quickly and exhibited slower recovery, demonstrating that there may have been deficiencies in oxygen supply related to both oxygen uptake and oxygen transport. Cystic fibrosis affects skeletal muscle performance and functional capacity. However, it is currently unclear how peripheral muscle behaviour is affected, especially in children and adolescents. To examine this, we compared tissue oxygenation of children and adolescents with cystic fibrosis against healthy volunteers. We also evaluated the functional capacity of participants via the modified shuttle test (MST) and assessed for associations between performance and near-infrared spectroscopy. A total of 124 participants enrolled. Participants were divided into either the cystic fibrosis group (CFG) or the healthy group (HG). Statistical comparisons between groups were evaluated with the Mann-Whitney U test and associations with functional capacity were evaluated using Spearman's correlation coefficient. CFG volunteers scored lower on the MST compared to the HG. They walked shorter distances (P=0.001) with less efficiency because they performed the tests with a less efficient walking economy (P=0.001) and a greater deoxyhaemoglobin concentration (P=0.001). Further, they experienced reduced tissue oxygen saturation (P=0.037) faster than the HG. As a result, they presented lower respiratory (P=0.001) and lower heart (P=0.001) rate values at the end of the MST, with a longer post-test heart rate recovery time (P=0.005). There was a significant association between deoxygenation time and functional capacity. The CFG consumed more oxygen, more quickly, with a slower recovery, reflecting impairments in the dynamics of muscle oxygen extraction. The results suggest differences in functional capacity and haemodynamic recovery in children and adolescents with cystic fibrosis.