Prefrontal oxygenation is quantified with time-resolved near-infrared spectroscopy: effect of sex on baseline oxygenation and the response during exercise.

With the use of time-resolved near-infrared spectroscopy that enables quantitative analysis of optical properties and oxygenation in cerebral tissues and thereby subject-to-subject comparisons in the variables, this study examined the influence of sex on baseline optical properties and oxygenation in the prefrontal cortex (PFC) and the responses during cycling exercise. Absolute levels of oxygenated- and deoxygenated-hemoglobin concentration (Oxy-Hb and Deoxy-Hb) in bilateral PFC were measured at rest and during unilateral cycling at low and moderate intensity in young participants (8 women and 10 men). Unilateral cycling was utilized to evaluate no lateralization of the prefrontal oxygenation responses during exercise. Baseline optical properties of bilateral PFC, defined optical path length and reduced scattering coefficient, and their responses during cycling were not different between the sexes. Baseline absolute Oxy-Hb of bilateral PFC was significantly lower in women (37 ± 3 µM) than in men (47 ± 7 µM), whereas absolute Deoxy-Hb revealed no sex-related difference. The absolute Oxy-Hb levels in bilateral PFC during low- and moderate-intensity cycling were also lower in women. However, no sex difference was observed when using changes against the baseline levels to normalize baseline differences. No laterality-related differences were observed in the changes in prefrontal Oxy-Hb and Deoxy-Hb during unilateral cycling. Ascertaining no sex-related difference in optical properties of the PFC, the current findings suggest that baseline absolute level of oxygenation in the PFC is lower in women than in men, likely due to lower oxygen supply rather than higher oxygen utilization, and that prefrontal oxygenation responds similarly during exercise independently of sex.

Dissociation between exercise intensity thresholds: mechanistic insights from supine exercise.

This study tested the hypothesis that the respiratory compensation point (RCP) and breakpoint in deoxygenated [heme] [deoxy[heme]BP, assessed via near-infrared spectroscopy (NIRS)] during ramp incremental exercise would occur at the same metabolic rate in the upright (U) and supine (S) body positions. Eleven healthy men completed ramp incremental exercise tests in U and S. Gas exchange was measured breath-by-breath and time-resolved-NIRS was used to measure deoxy[heme] in the vastus lateralis (VL) and rectus femoris (RF). RCP (S: 2.56 ± 0.39, U: 2.86 ± 0.40 L·min-1, P = 0.02) differed from deoxy[heme]BP in the VL in U (3.10 ± 0.44 L·min-1, P = 0.002), but was not different in S in the VL (2.70 ± 0.50 L·min-1, P = 0.15). RCP was not different from the deoxy[heme]BP in the RF for either position (S: 2.34 ± 0.48 L·min-1, U: 2.76 ± 0.53 L·min-1, P > 0.05). However, the deoxy[heme]BP differed between muscles in both positions (P < 0.05), and changes in deoxy[heme]BP did not relate to ΔRCP between positions (VL: r = 0.55, P = 0.080, RF: r = 0.26, P = 0.44). The deoxy[heme]BP was consistently preceded by a breakpoint in total[heme], and was, in turn, itself preceded by a breakpoint in muscle surface electromyography (EMG). RCP and the deoxy[heme]BP can be dissociated across muscles and different body positions and, therefore, do not represent the same underlying physiological phenomenon. The deoxy[heme]BP may, however, be mechanistically related to breakpoints in total[heme] and muscle activity.

Relationship Between Cognitive Dysfunction and Systemic Metabolic Disorders in Elderly: Dementia Might be a Systematic Disease.

Vascular cognitive impairment (VCI) plays an important role in dementia in elderly people, and refers to the contribution of vascular pathology to the entire spectrum of cognitive disorders, ranging from mild cognitive impairment to severe dementia, as well as the pathological spectrum, from 'pure' Alzheimer disease through degrees of vascular comorbidity to 'pure' vascular dementia. In the present study, we investigated the relationship between cognitive dysfunction and systemic metabolic disorders, by employing deep learning (DL). We studied 202 patients (73.4 ± 13.0 years), 94.6% of whom were undergoing treatment for lifestyle diseases, and 68.8% of whom had a history of cerebrovascular disorder. We evaluated cognitive dysfunction by performing a Mini Mental State Examination (MMSE). We performed general blood examination, including Complete Blood Count and Basic Metabolic Panel, and measured cerebral blood oxygenation in the prefrontal cortex (PFC) using time-resolved near infrared spectroscopy (TNIRS). We then used deep neural networks to assess the MMSE scores of the subjects based on the TNIRS parameters and the blood examination data, independently. Next, we compared predicted MMSE scores based on the TNIRS and the blood examination. There was a significant positive correlation between the TNIRS parameters and the blood examination data (r = 0.6, p < 0.01). These observations suggest that cognitive dysfunction in patients with VCI may be caused by combinations of systemic metabolic disorders such as energy and oxygen metabolisms and cerebral circulatory disturbance due to arteriosclerosis resulting from lifestyle-related diseases.

Characterization of melt-quenched and milled amorphous solids of gatifloxacin.

The objectives of this study were to characterize and investigate the differences in amorphous states of gatifloxacin. We prepared two types of gatifloxacin amorphous solids coded as M and MQ using milling and melt-quenching methods, respectively. The amorphous solids were characterized via X-ray diffraction (XRD), nonisothermal differential scanning calorimetry (DSC) and time-resolved near-infrared (NIR) spectroscopy. Both the solids displayed halo XRD patterns, the characteristic of amorphous solids; however, in the non-isothermal DSC profiles, these amorphous solids were distinguished by their crystallization and melting temperatures. The Kissinger-Akahira-Sunose plots of non-isothermal crystallization temperatures at various heating rates indicated a lower activation energy of crystallization for the amorphous solid M than that of MQ. These results support the differentiation between two amorphous states with different physical and chemical properties.

Assessing changes in regional cerebral hemodynamics in adults with a high-density full-head coverage time-resolved near-infrared spectroscopy device.

Significance: Cerebral oximeters have the potential to detect abnormal cerebral blood oxygenation to allow for early intervention. However, current commercial systems have two major limitations: (1) spatial coverage of only the frontal region, assuming that surgery-related hemodynamic effects are global and (2) susceptibility to extracerebral signal contamination inherent to continuous-wave near-infrared spectroscopy (NIRS). Aim: This work aimed to assess the feasibility of a high-density, time-resolved (tr) NIRS device (Kernel Flow) to monitor regional oxygenation changes across the cerebral cortex during surgery. Approach: The Flow system was assessed using two protocols. First, digital carotid compression was applied to healthy volunteers to cause a rapid oxygenation decrease across the ipsilateral hemisphere without affecting the contralateral side. Next, the system was used on patients undergoing shoulder surgery to provide continuous monitoring of cerebral oxygenation. In both protocols, the improved depth sensitivity of trNIRS was investigated by applying moment analysis. A dynamic wavelet filtering approach was also developed to remove observed temperature-induced signal drifts. Results: In the first protocol (28±5 years; five females, five males), hair significantly impacted regional sensitivity; however, the enhanced depth sensitivity of trNIRS was able to separate brain and scalp responses in the frontal region. Regional sensitivity was improved in the clinical study given the age-related reduction in hair density of the patients (65±15 years; 14 females, 13 males). In five patients who received phenylephrine to treat hypotension, different scalp and brain oxygenation responses were apparent, although no regional differences were observed. Conclusions: The Kernel Flow has promise as an intraoperative neuromonitoring device. Although regional sensitivity was affected by hair color and density, enhanced depth sensitivity of trNIRS was able to resolve differences in scalp and brain oxygenation responses in both protocols.

Precision of time-resolved near-infrared spectroscopy-based measurements of cerebral oxygenation in preterm infants.

Significance: Time-resolved near-infrared spectroscopy (t-NIRS) is a new technology; at the moment, data on its precision in preterm infants are rare. Aim: Therefore, the aim of this study was to analyze the precision of t-NIRS-based measurements of the cerebral oxygenation in preterm infants. Approach: In 70 neonates [age: 4.7 ± 2.0 days, sex (f/m): 33/37], cerebral oxygenation ( t - rSO 2 ) was measured with an optode placed over the left frontotemporal lobe on the head, measurement duration was 1 min, and a reapplication was done for four further times (five applications). Results: Overall mean for t - rSO 2 values was 62.2 % ± 4.1 % . We found a within-patient variation for t - rSO 2 of 2.6%. Furthermore, 95% of all observed values were within a range of ± 5 % from the mean when looking on several reapplications and ± 2 % when looking within one application. Most of the variation in t - rSO 2 (60.4%) contributed to differences between patients. The remaining 39.6% of the variation was due to measurement errors and real changes of the measured signal within the neonates. Conclusions: Since within-patient variation of t - rSO 2 measures were below a clinical meaningful threshold of 5%, the measurement can be denoted as precise.

Machine Learning-Based Assessment of Cognitive Impairment Using Time-Resolved Near-Infrared Spectroscopy and Basic Blood Test.

We have demonstrated that machine learning allows us to predict cognitive function in aged people using near-infrared spectroscopy (NIRS) data or basic blood test data. However, the following points are not yet clear: first, whether there are differences in prediction accuracy between NIRS and blood test data; second, whether there are differences in prediction accuracy for cognitive function in linear models and non-linear models; and third, whether there are changes in prediction accuracy when both NIRS and blood test data are added to the input layer. We used a linear regression model (LR) for the linear model and random forest (RF) and deep neural network (DNN) for the non-linear model. We studied 250 participants (mean age = 73.3 ± 12.6 years) and assessed cognitive function using the Mini Mental State Examination (MMSE) (mean MMSE scores = 22.9 ± 6.1). We used time-resolved NIRS (TNIRS) to measure absolute concentrations of hemoglobin and optical pathlength at rest in the bilateral prefrontal cortices. A basic blood test was performed on the same day. We compared predicted MMSE scores and grand truth MMSE scores; prediction accuracies were evaluated using mean absolute error (MAE) and mean absolute percentage error (MAPE). We found that (1) the DNN-based prediction using TNIRS data exhibited lower MAE and MAPE compared with those using blood test data, (2) the difference in MAPE between TNIRS and blood test data was only 0.3%, (3) adding TNIRS data to the blood test data of the input layer only improved MAPE by 1.0% compared to the use of blood test data alone, whereas the use of the blood test data alone exhibited the prediction accuracy with 81.8% sensitivity and 91.3% specificity (N = 202, repeated five-fold cross validation). Given these findings and the benefits of using blood test data (low cost and large-scale screening possible), we concluded that the DNN model using blood test data is still the most suitable for mass screening.

Impact of supine exercise on muscle deoxygenation kinetics heterogeneity: mechanistic insights into slow pulmonary oxygen uptake dynamics.

Oxygen uptake (V̇o2) kinetics are slowed in the supine (S) position purportedly due to impaired muscle O2 delivery ([Formula: see text]); however, these conclusions are predicated on single-site measurements in superficial muscle using continuous-wave near-infrared spectroscopy (NIRS). This study aimed to determine the impact of body position [i.e., upright (U) versus S] on deep and superficial muscle deoxygenation (deoxy[heme]) using time-resolved (TR-) NIRS, and how these relate to slowed pulmonary V̇o2 kinetics. Seventeen healthy men completed constant power tests during 1) S heavy-intensity exercise and 2) U exercise at the same absolute work rate, with a subset of 10 completing additional tests at the same relative work rate as S. Pulmonary V̇o2 was measured breath-by-breath and, deoxy- and total[heme] were resolved via TR-NIRS in the superficial and deep vastus lateralis and superficial rectus femoris. The fundamental phase V̇o2 time constant was increased during S compared with U (S: 36 ± 10 vs. U: 27 ± 8 s; P < 0.001). The deoxy[heme] amplitude (S: 25-28 vs. U: 13-18 µM; P < 0.05) and total[heme] amplitude (S: 17-20 vs. U: 9-16 µM; P < 0.05) were greater in S compared with U and were consistent for the same absolute (above data) and relative work rates (n = 10, all P < 0.05). The greater deoxy- and total[heme] amplitudes in S vs. U supports that reduced perfusive [Formula: see text] in S, even within deep muscle, necessitated a greater reliance on fractional O2 extraction and diffusive [Formula: see text]. The slower V̇o2 kinetics in S versus U demonstrates that, ultimately, these adjustments were insufficient to prevent impairments in whole body oxidative metabolism.NEW & NOTEWORTHY We show that supine exercise causes a greater degree of muscle deoxygenation in both deep and superficial muscle and increases the spatial heterogeneity of muscle deoxygenation. Therefore, this study suggests that any O2 delivery gradient toward deep versus superficial muscle is insufficient to mitigate impairments in oxidative function in response to reduced whole muscle O2 delivery. More heterogeneous muscle deoxygenation is associated with slower V̇o2 kinetics.

Quantification of joint blood flow by dynamic contrast-enhanced near-infrared spectroscopy: application to monitoring disease activity in a rat model of rheumatoid arthritis.

Significance: Current guidelines for rheumatoid arthritis (RA) management recommend early treatment with disease modifying antirheumatic drugs (DMARDs). However, DMARD treatment fails in 30% of patients and current monitoring methods can only detect failure after 3 to 6 months of therapy. Aim: We investigated whether joint blood flow (BF), quantified using dynamic contrast-enhanced time-resolved near-infrared spectroscopy, can monitor disease activity and treatment response in a rat model of RA. Approach: Ankle joint BF was measured every 5 days in eight rats with adjuvant-induced arthritis (AIA) and four healthy controls. Arthritis was allowed to progress for 20 days before rats with AIA were treated with a DMARD once every 5 days until day 40. Results: Time and group had separate significant main effects on joint BF; however, there was no significant interaction between time and group despite a notable difference in average joint BF on day 5. Comparison of individual blood flow measures between rats with AIA and control group animals did not reveal a clear response to treatment. Conclusions: Joint BF time courses could not distinguish between rats with AIA and study controls. Heterogeneous disease response and low temporal frequency of BF measurements may have been important study limitations.

BabyLux device: a diffuse optical system integrating diffuse correlation spectroscopy and time-resolved near-infrared spectroscopy for the neuromonitoring of the premature newborn brain.

The BabyLux device is a hybrid diffuse optical neuromonitor that has been developed and built to be employed in neonatal intensive care unit for the noninvasive, cot-side monitoring of microvascular cerebral blood flow and blood oxygenation. It integrates time-resolved near-infrared and diffuse correlation spectroscopies in a user-friendly device as a prototype for a future medical grade device. We present a thorough characterization of the device performance using test measurements in laboratory settings. Tests on solid phantoms report an accuracy of optical property estimation of about 10%, which is expected when using the photon diffusion equation as the model. The measurement of the optical and dynamic properties is stable during several hours of measurements within 3% of the average value. In addition, these measurements are repeatable between different days of measurement, showing a maximal variation of 5% in the optical properties and 8% for the particle diffusion coefficient on a liquid phantom. The variability over test/retest evaluation is < 3 % . The integration of the two modalities is robust and without any cross talk between the two. We also perform in vivo measurements on the adult forearm during arterial cuff occlusion to show that the device can measure a wide range of tissue hemodynamic parameters. We suggest that this platform can form the basis of the next-generation neonatal neuromonitors to be developed for extensive, multicenter clinical testing.

Concurrent measurement of cerebral hemodynamics and electroencephalography during transcranial direct current stimulation.

Transcranial direct current stimulation (tDCS) is currently being used for research and treatment of some neurological and neuropsychiatric disorders, as well as for improvement of cognitive functions. In order to better understand cerebral response to the stimulation and to redefine protocols and dosage, its effects must be monitored. To this end, we have used functional diffuse correlation spectroscopy (fDCS) and time-resolved functional near-infrared spectroscopy (TR-fNIRS) together with electroencephalography (EEG) during and after stimulation of the frontal cortex. Twenty subjects participated in two sessions of stimulation with two different polarity montages and twelve also underwent a sham session. Cerebral blood flow and oxyhemoglobin concentration increased during and after active stimulation in the region under the stimulation electrode while deoxyhemoglobin concentration decreased. The EEG spectrum displayed statistically significant power changes across different stimulation sessions in delta (2 to 4 Hz), theta (4 to 8 Hz), and beta (12 to 18 Hz) bands. Results suggest that fDCS and TR-fNIRS can be employed as neuromonitors of the effects of transcranial electrical stimulation and can be used together with EEG.

The effect of dietary nitrate supplementation on the spatial heterogeneity of quadriceps deoxygenation during heavy-intensity cycling.

This study investigated the influence of dietary inorganic nitrate (NO3-) supplementation on pulmonary O2 uptake (V˙O2) and muscle deoxyhemoglobin/myoglobin (i.e. deoxy [Hb + Mb]) kinetics during submaximal cycling exercise. In a randomized, placebo-controlled, cross-over study, eight healthy and physically active male subjects completed two step cycle tests at a work rate equivalent to 50% of the difference between the gas exchange threshold and peak V˙O2 over separate 4-day supplementation periods with NO3--rich (BR; providing 8.4 mmol NO3-∙day-1) and NO3--depleted (placebo; PLA) beetroot juice. Pulmonary V˙O2 was measured breath-by-breath and time-resolved near-infrared spectroscopy was utilized to quantify absolute deoxy [Hb + Mb] and total [Hb + Mb] within the rectus femoris, vastus lateralis, and vastus medialis There were no significant differences (P > 0.05) in the primary deoxy [Hb + Mb] mean response time or amplitude between the PLA and BR trials at each muscle site. BR significantly increased the mean (three-site) end-exercise deoxy [Hb + Mb] (PLA: 91 ± 9 vs. BR: 95 ± 12 µmol/L, P < 0.05), with a tendency to increase the mean (three-site) area under the curve for total [Hb + Mb] responses (PLA: 3650 ± 1188 vs. BR: 4467 ± 1315 µmol/L sec-1, P = 0.08). The V˙O2 slow component reduction after BR supplementation (PLA: 0.27 ± 0.07 vs. BR: 0.23 ± 0.08 L min-1, P = 0.07) correlated inversely with the mean increases in deoxy [Hb + Mb] and total [Hb + Mb] across the three muscle regions (r2 = 0.62 and 0.66, P < 0.05). Dietary NO3- supplementation increased O2 diffusive conductance across locomotor muscles in association with improved V˙O2 dynamics during heavy-intensity cycling transitions.

Changes in whole tissue heme concentration dissociates muscle deoxygenation from muscle oxygen extraction during passive head-up tilt.

Skeletal muscle deoxygenated hemoglobin and myoglobin concentration ([HHb]), assessed by near-infrared spectroscopy (NIRS), is commonly used as a surrogate of regional O2 extraction (reflecting the O2 delivery-to-consumption ratio, Q̇/V̇o2). However, [HHb] change (Δ[HHb]) is also influenced by capillary-venous heme concentration, and/or small blood vessel volume (reflected in total heme; [THb]). We tested the hypotheses that Δ[HHb] is associated with O2 extraction, and insensitive to [THb], over a wide range of Q̇/V̇o2 elicited by passive head-up tilt (HUT; 10-min, 15° increments, between -10° and 75°). Steady-state common femoral artery blood flow (FBF) was measured by echo-Doppler, and time-resolved NIRS measured [HHb] and [THb] of vastus lateralis (VL) and gastrocnemius (GS) in 13 men. EMG confirmed muscles were inactive. During HUT in VL [HHb] increased linearly (57 ± 10 to 101 ± 16 µM; P < 0.05 above 15°) and was associated (r(2) ∼ 0.80) with the reduction in FBF (618 ± 75 ml/min at 0° to 268 ± 52 ml/min at 75°; P < 0.05 above 30°) and the increase in [THb] (228 ± 30 vs. 252 ± 32 µM; P < 0.05 above 15°). GS response was qualitatively similar to VL. However, there was wide variation within and among individuals, such that the overall limits of agreement between Δ[HHb] and ΔFBF ranged from -35 to +19% across both muscles. Neither knowledge of tissue O2 saturation nor vascular compliance could appropriately account for the Δ[HHb]-ΔFBF dissociation. Thus, under passive tilt, [HHb] is influenced by Q̇/V̇o2, as well as microvascular hematocrit and/or tissue blood vessel volume, complicating its use as a noninvasive surrogate for muscle microvascular O2 extraction.

Muscle deoxygenation in the quadriceps during ramp incremental cycling: Deep vs. superficial heterogeneity.

Muscle deoxygenation (i.e., deoxy[Hb + Mb]) during exercise assesses the matching of oxygen delivery (Q̇O2) to oxygen utilization (V̇O2). Until now limitations in near-infrared spectroscopy (NIRS) technology did not permit discrimination of deoxy[Hb + Mb] between superficial and deep muscles. In humans, the deep quadriceps is more highly vascularized and oxidative than the superficial quadriceps. Using high-power time-resolved NIRS, we tested the hypothesis that deoxygenation of the deep quadriceps would be less than in superficial muscle during incremental cycling exercise in eight males. Pulmonary V̇O2 was measured and muscle deoxy[Hb + Mb] was determined in the superficial vastus lateralis (VL), vastus medialis (VM), and rectus femoris (RF-s) and the deep rectus femoris (RF-d). deoxy[Hb + Mb] in RF-d was significantly less than VL at 70% (67.2 ± 7.0 vs. 75.5 ± 10.7 µM) and 80% (71.4 ± 11.0 vs. 79.0 ± 15.4 µM) of peak work rate (WR(peak)), but greater than VL and VM at WR(peak) (87.7 ± 32.5 vs. 76.6 ± 17.5 and 75.1 ± 19.9 µM). RF-s was intermediate at WR(peak) (82.6 ± 18.7 µM). Total hemoglobin and myoglobin concentration and tissue oxygen saturation were significantly greater in RF-d than RF-s throughout exercise. The slope of deoxy[Hb + Mb] increase (proportional to Q̇O2/V̇O2) in VL and VM slowed markedly above 70% WR(peak), whereas it became greater in RF-d. This divergent deoxygenation pattern may be due to a greater population of slow-twitch muscle fibers in the RF-d muscle and the differential recruitment profiles and vascular and metabolic control properties of specific fiber populations within superficial and deeper muscle regions.

Non-invasive monitoring of brain temperature by near-infrared spectroscopy.

Optical techniques are promising methods for measuring tissue temperature noninvasively due to the transparency of tissue to near infrared-light and the temperature dependent light-absorbing properties of endogenous absorbers, particularly water. Besides being noninvasive, the instruments are compact and portable, permitting bedside monitoring.

Effect of stimulation by foliage plant display images on prefrontal cortex activity: a comparison with stimulation using actual foliage plants.

BACKGROUND AND PURPOSE: Natural scenes like forests and flowers evoke neurophysiological responses that can suppress anxiety and relieve stress. We examined whether images of natural objects can elicit neural responses similar to those evoked by real objects by comparing the activation of the prefrontal cortex during presentation of real foliage plants with a projected image of the same foliage plants. METHODS: Oxy-hemoglobin concentrations in the prefrontal cortex were measured using time-resolved near-infrared spectroscopy while the subjects viewed the real plants or a projected image of the same plants. RESULTS: Compared with a projected image of foliage plants, viewing the actual foliage plants significantly increased oxy-hemoglobin concentrations in the prefrontal cortex. However, using the modified semantic differential method, subjective emotional response ratings ("comfortable vs. uncomfortable" and "relaxed vs. awakening") were similar for both stimuli. CONCLUSIONS: The frontal cortex responded differently to presentation of actual plants compared with images of these plants even when the subjective emotional response was similar. These results may help explain the physical and mental health benefits of urban, domestic, and workplace foliage.