This PDF file contains the front matter associated with SPIE Proceedings Volume 11237 including the Title Page, Copyright information, Table of Contents, Introduction, and Conference Committee listing.

We present a lightweight TD-NIRS system, two-wavelength, one detection channel that can be battery operated and worn as a backpack for freely-moving cerebral and muscle hemodynamic monitoring. Oxy- and deoxy-genated hemoglobin absolute concentration can be retrieved in real time even in outdoor measurements thanks to the rugged feature of the device.

Near-Infrared Spectroscopy (NIRS) is a non-invasive technique, extensively used to monitor the hemodynamic variations in cerebral neuronal tissues. For cerebral NIRS, the back-scattering probe is more prevailing, in which an incident beam is diffused, and only a slight fraction of the source optical energy reaches the light detectors. Multiplexing in the time domain is the conventional method used to distinguish the optical density of each NIR source at the receiver site. Even though time-multiplexing is straightforward and convenient, the ambient light can significantly contaminate the NIR beams during the sampling-path from the source to the detector. In this work, we present a novel method based on frequency division multiplexing (FDM) to overcome the interference of ambient light even without an external optical filter. The method proposes to modulate the NIR source intensities by using specific carrier frequencies distinct from the dominant frequency components of ambient light intensity. By modulating the intensity of each NIR source, and applying them at their specific frequency channels, the receiver is capable of distinguishing the received optical signals based on their frequency channel. Because the frequency channels are adjusted at distinct dominant frequency components of the ambient intensity, the latter ambient noise can be filtered out instantly. The method has been implemented by using electronic circuit design and evaluated both by numerical simulation and experimental measurements. The signal to noise ratio (SNR) has been improved at least by 45dB.

We developed a wearable system for wireless monitoring of oxygenation of deep tissues such as liver and lung during exercise. It is also useful where subcutaneous fat thickness is high. Our system utilizes Continuous Wave Near Infrared Spectroscopy (CW NIRS) with source-detector distances from 10mm to 60mm. This allows us to observe tissues at various depths. To mitigate the interference of the overlaying tissue layers such as skin, fat and muscle, we developed a multi-layer Monte Carlo model for photon diffusion. Flexible structure of our device helps achieve better skin contact and expand its usability to most body parts.

Objective assessment of olfactory function has diagnostic and legal value. We have designed an odor detection task in which the subject reported the conscious sensing of an odorant via a button press while the hemodynamic activity from the forehead was monitored using a 4-channel fNIRS system. The task consisted of intermingled odor and non-odor trials. We recorded from 17 subjects and each of them underwent 60 trials. The time domain analysis of the raw data showed that the hemodynamic activity was statistically different between the odor and non-odor trials especially for oxyhemoglobin in far channels. In order to single out the odor-induced hemodynamic response from that of motor activity, finger tapping was considered as a control condition for odor detection. Pairwise correlation indicated that motor activity had a short lasting influence on hemodynamic response while the hemodynamic response to different odors were highly correlated over time. In conclusion, we believe that fNIRS monitoring of hemodynamic response could be potentially used for objective assessment of odor detection in cases that subjective report is unreliable.

Electroencephalography (EEG) and cerebral near-infrared spectroscopy (NIRS) are both well-known monitoring methods to quantify cerebral neurophysiology and hemodynamics states of the brain. A stable regulatory system operates to guarantee sufficient spatial and temporal distribution of energy substrates for ongoing neuronal activity. Most EEG signals are associated with the neural activity of an enormous number of neurons that are interconnected and firing concurrently. The conventional EEG bandwidth is 0.16Hz to 70Hz. In this study, the EEG recording bandwidth is extended in low frequency (0.016Hz to 70Hz) by using a novel EEG amplifier. We aimed to investigate the low-frequency EEG and brain tissue deoxygenation by using novel multi-modal measurements. We used combined NIRS and EEG measurements for estimating the electrophysiological activity and hemodynamic changes in the adult human forehead during a hypoxic breathing condition. For the experiment, an altitude simulation kit was used to restrict the concentration of oxygen in the air that was inhaled by the subjects. The hypoxic breathing conditions led to variations in CO2 concentration (pCO2). Prolong (low-frequency) EEG signal shift, accompanied by an increase of deoxygenated hemoglobin during simulated hypoxic breathing were observed in this experiment.

Simultaneous prefrontal activation and heart rate variability can be collected in healthy adults to examine their relationship using functional near-infrared spectroscopy (fNIRS) and electrocardiogram (ECG). The present study replicates previous findings in functional magnetic resonance imaging (fMRI) using fNIRS, which creates the potential for simultaneous ambulatory measurement of neural and cardiovascular variables. Collecting such measures during physical activity will assess questions regarding a potential cardiovascular-linked mechanism for exercise-induced neural plasticity in future studies.

The development of portable functional Near-Infrared Spectroscopy (fNIRS) systems has been widely investigated for neurology (TBI/Epilepsy/Stroke) and psychiatry (ADD/Dementia) research and holds great opportunity for neurological injury prevention and rehabilitation in athletes and military personnel. However, widespread adoption of fNIRS has been precluded by systems’ weight, complexity, and cost. With focus on affordability, portability (weighs <150g), and comfort, our group has developed a 16-channel fNIRS headband with an accompanying phone application. Our wear-and-go design would help athletes and military personnel to easily provide fNIRS data during routine activities and facilitate big-data research to identify novel biomarkers related to neurological injury.

We investigated the effects of hypoxia on neurophysiological parameters during rest and moderate intensity exercise to understand cerebral metabolism. 31 male (age= 31±13 yr, height= 177±5 cm, mass= 79±9 kg) and 4 female (age= 25±7 yr, height= 169±7 cm, mass= 60±5kg) participants were recruited. Near-infrared spectroscope (NIRS) was placed over the right prefrontal cortex to measure relative changes in oxy (HbO₂), deoxy (HHb), total (tHb) and hemoglobin difference (HbDiff). Participants rested in a supine position for 30-minutes, followed by a 2-minute washout period before beginning a 10-second squat-stand (0.05 Hz) maneuver for 5 minutes. Thereafter participants repeated the supine and squat-stand protocol in a normobaric environmental chamber (14.8% oxygen; ~2750m). The difference from the last 5 minutes of supine rest was compared to the first 5 minutes in both conditions. The difference between the supine rest vs. squat-stand was compared in both conditions. NIRS standard deviation (SD) was compared during the 30-minutes of supine rest vs. the 5 minutes of squat-stand. A Wilcoxon signed-rank test was use to compare paired samples. Results showed a significant decrease in HbO₂, tHb and HbDiff, a significant increase in HHb at the end of the supine rest in hypoxia vs. normoxia, and an increase in SD of all parameters in hypoxia. For squat-stand, there was a significant decrease in HbDiff and a significant increase in HHb in hypoxia, with a significant increase in SD of all parameters in hypoxia. These results suggest altered cerebral metabolism at altitudes about 2750m during rest and exercise.

Brown/beige adipose tissue (BAT) is expected to contribute to protecting lifestyle-related diseases. The purpose of this study was to examine if near-infrared time-resolved spectroscopy (NIR_TRS) is capable of distinguishing BAT from muscle and white adipose tissue (WAT). We analyzed the optical characteristics of tissues in the supraclavicular region, where BAT deposits can be located, and deltoid and abdominal regions in 36 participants (16 men and 20 women) who were apparently healthy individuals, with a median age of 44.5 years, in winter and summer. They also had a median body fat percentage of 28.3% and a deltoid and abdominal adipose tissue thickness of 0.85 cm and 1.71 cm, respectively. The total hemoglobin concentration [total-Hb] and the reduced scattering coefficient (μs′) were determined using nearinfrared time-resolved spectroscopy (NIRTRS) with a 3 cm optode separation for supraclavicular and deltoid regions and a 2 cm optode separation for abdominal region. The results regarding data collected in winter were the following: deltoid (μ_s' = 9.6 [9.1, 10.4] cm^-1 , [total-Hb] = 114.9 [107.0, 127.7] μM); abdominal (μ_s' = 9.0 [7.9, 10.1] cm^-1 , [total-Hb] = 11.2 [8.0, 16.0] μM); and supraclavicular (μ_s' = 7.9 [7.2, 8.7] cm^-1 , [total-Hb] = 60.7 [48.9, 74.7] μM)) in winter. Some data are overlapped between groups of muscle and BAT. These results indicated that [total-Hb] and μs′ show region-specific characteristics. We conclude that using [total-Hb] - μs′ relationship determined by NIR_TRS is a useful strategy to distinguish BAT from other tissues in a simple, rapid, and non-invasive manner.

This study investigated the effects of normobaric hypoxia on mechanical cardiac function during resting and short-term moderate intensity exercise. The cardiac contraction force and ventricular twist of eleven healthy male participants (24±5 years, 176±3cm, 76±9kg) were assessed using seismocardiography (SCG). The SCG was placed superficially to the sternum, 1 cm above the Xiphoid process. An isometric squat-stand maneuver performed at 0.05 Hz for 5 minutes was used as the exercise stimulus. Participants began by resting supine for 30-minutes under normobaric normoxia (712mmHg, 577m, 19.8% oxygen), followed by the squat-stand maneuver. Participants repeated the supine and squat-stand maneuver in a normobaric hypoxic (712mmHg, ~2750m, 14.8% oxygen) environmental simulation chamber. SCG was measured for 30 seconds at the end of normoxic rest (T1), end of normoxic squat-stands (T2), end of hypoxic rest (T3), and end of hypoxic squat-stands (T4). An average of 5 cardiac beats from the SCG were analyzed to determine contraction force and ventricular twist (milligravity, mG). No significant differences were found under resting conditions between T1 and T3 (13±2, 15±3 mG). Furthermore, no significant differences were found comparing squat-stands between normoxia (T2, 35±6 mG) and hypoxia (T4, 45±9 mG), although there were trends showing an increase in contraction force during hypoxia (p=0.2). Ventricular twist mechanics showed similar responses. These results suggest that acute shortduration normobaric hypoxia had no significant effect on the contractility and ventricular twist mechanics of the heart after a moderate-intensity squat-stand exercise. This shows that mechanical cardiac function can be assessed using SCG.

We investigated the effects of acute hypoxia on heart rate variability (HRV) parameters during supine rest and moderate-intensity exercise. 27 male (age= 28±11 yr, height= 177±6 cm, mass= 79±9 kg) and 4 female (age= 25±7 yr, height= 169±7 cm, mass= 60±5kg) participants were recruited. Participants rested for 30 minutes in a supine position, after which 5 minutes of isometric squat-stands (0.05 Hz) were performed. This was performed under both normoxic and hypoxic (14.8% oxygen; ~2750m) conditions. Within subject comparisons were made between the last 5 minutes of each supine portion, and between the squat-stand maneuvers at normoxia vs. hypoxia. Depending on normality distribution, a Wilcoxon signed-rank test or a paired sample t-test was used with alpha set at p<0.05. Significant differences in %LF (48±18 vs 56±16), %HF (44±19 vs 35±18), LF/HF ratio (1.8±2 vs 2.3±1), NN₅₀ beats (104±61 vs 82±70), pNN₅₀ (36±22 vs 27±24), SD1 (50±31 vs 42±30), SD2 (101±55 vs 90±46), SD2/SD1 ratio (2.4±1 vs 2.7±1), and % determinism (97±2 vs 98±1) were seen between normoxia and hypoxia, respectively. Significant differences in NN₅₀ (92±26 vs 81±30), pNN₅₀ (21±6 vs 17±7), SD2 (188±60 vs 177±56) and sample entropy (0.3±0.2 vs 0.2±0.1) were also seen during squat-stands between normoxia and hypoxia, respectively. These results suggest changes in physiology and HRV parameters during exposure to acute hypoxia. This research has implications for autonomic function and its influence on cardiac control at altitude.

A novel contemporary approach of integrating micro-electronics into flexible wearable e-textile for muscle physiology detection is presented here. Textile sensor array is used for camera-less, real-time, and continuous monitoring of muscle activations and movements. The functionality is amplified with an aid of near infrared spectroscopy (NIRS) sensors to monitor the metabolism during the movement. This multi-modal sensing wearable e-textile has a huge potential to integrate and commercialize futuristic health monitoring wearables.

This study investigated the influence of moderate-intensity exercise (EX; 20 min cycling exercise, 60% heart rate reserve) on executive function (EF) and prefrontal cortex (PFC) hemodynamics, compared to control (CON; 20 min seated, listening to statistics audio recording). EF tests were Go/NoGo, Task Switching, and Reading Span. Near-infrared spectroscopy (NIRS) measured total hemoglobin concentration (tHb). Compared to CON, right PFC tHb was elevated from baseline at 0 and 15 min post-EX during Go/NoGO and Task Switching, and at 0 min post-EX during Reading Span. In both EX and CON, tHb was unchanged during “rest” between EF tests.

A shortened approach to measure mitochondrial capacity using Near-Infrared Spectroscopy (NIRS) was evaluated. Comparisons were made between 6-occlusion versus 22-occlusion protocols in two data sets (bicep, forearm). A third data set evaluated four serial 6-occlusion tests. The rate constants were not different between 22-cuff and 6-cuff for bicep (p=0.56) and forearm (p=0.76). The correlations were R2=0.9 for the bicep and R2=0.93 for the forearm. Mitochondrial capacity was not different between the four tests (P>0.05). The 6-Cuff analysis provided the same results in less time. There were no order effects for the rate constants for repeated 6-cuff tests of mitochondrial capacity.

We investigated central fatigue during maximal exercise (EXmax) after 12×20-min respiratory muscle endurance training (eRMT) sessions over 4 weeks using cerebral near-infrared spectroscopy (NIRS; left, right prefrontal cortices: LPFC, RPFC); and self-reported effort perceptions (RPE). Healthy participants improved eRMT performance with no spirometry changes. Pre-eRMT, EXmax oxygenated (O2Hb), deoxygenated (HHb), and total (tHb) hemoglobin increases were larger in LPFC than RPFC. Post-eRMT, EXmax O2Hb, HHb, and tHb increases were smaller in LPFC than RPFC. Post-eRMT EXmax RPE were smaller. eRMT-induced LPFC-to-RPFC hemodynamic shifts during EXmax may facilitate decreased RPE.

The aims of this study were to clarify the influences of fat layer thickness (FLT) and aerobic capacity on optical property dynamics during exercise by using near-infrared time-resolved spectroscopy (NIRTRS) in humans. Endurance-trained men and healthy control men with various FLT performed a ramp incremental cycling exercise test until exhaustion. Absorption coefficient, reduced scattering coefficient, and mean optical pathlength in the vastus lateralis were continuously monitored by three-wavelength (763, 801 and 836 nm) NIRTRS. Our results have demonstrated that FLT and aerobic capacity affect the optical property dynamics during exercise and that the effects may differ depending on the wavelength.

This pilot study investigated hemodynamics in bone and muscle of the same leg during resistance exercise, using near-infrared spectroscopy (NIRS). Total (tHb) and oxygenated (O2Hb) hemoglobin increased in bone but decreased in muscle. Absolute peak tHb and O2Hb changes in bone were much smaller than absolute antipeak changes in muscle. Bone tHb and O2Hb reached an initial peak quickly and then decreased progressively; muscle tHb and O2Hb decreased initially and then plateaued. Bone perfusion changes during exercise appear independent of metabolism, suggesting that bone hemodynamics measured using NIRS during resistance training are driven by blood vessel compression and release.

The effect of fatigue on the hemodynamic responses of active skeletal muscle has yet to be fully understood due to the limited evaluation techniques of deep tissues hemodynamics. We adopted diffuse correlation spectroscopy (DCS), a promising optical imaging technique of tissue blood flow velocity, to determine fatigue-related changes in blood flow and vascular conductance of active muscle. Hemodynamic and electrophysiological responses of the flexor digitorum superficialis were continuously monitored by DCS and electromyogram (EMG) from the non-dominant forearm of youngadult participants (n=12). Systemic blood pressure was monitored from the other side of upper arm every minute. Participants performed 2 minutes of dynamic handgrip exercise (with a duty cycle of 2-s contraction and 2-s relaxation) with the load of 10% or 30% of maximal voluntary contraction (MVC) twice. To induce muscle fatigue, static handgrip (40% MVC for 2 minutes) was performed between the two sessions of dynamic handgrip exercise. Induction of fatigue was confirmed by significant decreases of EMG mean frequency in both load conditions. Muscle fatigue induced significant increase of active muscle blood flow and mean blood pressure in both load conditions. Vascular conductance of active muscle showed tendency of (10% MVC) or significant (30% MVC) increase after fatigue induction. These results suggest the enhanced vasodilatation along with fatigue in active muscles, possibly derived by accumulated metabolic and vasodilator substances. Our results demonstrate the possible application of DCS to detect and evaluate the fatigue effect of active skeletal muscle.

Introduction: By elevating intramuscular pressure and increasing muscle oxygen consumption, a sustained contraction of a limb muscle can compromise muscle metabolic status and function. In this study, we aimed to investigate the effect of isometric forearm muscle contractions at different intensities and isotonic contractions on muscle oxygenation dynamics using near-infrared spectroscopy (NIRS). Methods: The maximum voluntary contraction (MVC) force of forearm flexor muscles in the dominant arm was measured in ten healthy adult volunteers. A NIRS sensor was placed and fixed over the common flexor muscles of the forearm to monitor muscle rSO₂. A reflectance pulse oximeter sensor was placed over the common extensor muscles, and a tourniquet cuff was placed loosely around the upper arm on the same side. Following a three-minute baseline measurement, each subject was instructed to perform a series of 30-second sustained isometric flexor muscle contractions at 10%, 30% and 50% MVC using a handgrip dynamometer. A 30-second isotonic muscle contraction followed by a 30-second episode of tourniquet-induced ischemia completed the experiment. Three minutes of recovery time were allowed after each episode. Results: Similar patterns of rSO₂ changes were seen in all subjects during episodes of isometric contractions (30% MVC and 50% MVC), isotonic contractions, and ischemia. Isometric muscle contraction at 50% MVC induced the lowest level of muscle rSO₂ (-16% ± 2.7%, p<0.0001). Conclusions: Isometric muscle contraction at 50% MVC induces a higher level of muscle hypoxia, in comparison to isotonic muscle contraction and limb muscle ischemia. Sustained isometric muscle contraction can compromise muscle oxygenation dynamics, which may expedite muscle fatigue and dysfunction.

Using portable near-infrared spectroscopy (NIRS), we characterized lower limb spastic vs. non-spastic muscle hemodynamic responses to the Modified Ashworth Scale (MAS; functional spasticity scale) and passive ankle range-of-motion (ROM) tests. This 12-wk observational study in an out-patient spasticity clinic had baseline, ~6-wk, and ~12-wk time points. Within-individual (contralateral control) and between-group (patient vs. control) measurements were compared. Spastic hemodynamic responses to MAS and ROM assessments were irregular and highly variable. Non-spastic hemodynamic changes followed three clear, repeatable patterns. NIRS may be useful in developing a hemodynamic/metabolic spasticity index.

Mitochondrial oxidative phosphorylation, which modulates resynthesis of PCr, depends in part on the availability of O₂ for the mitochondria in working muscle. Particularly during intense exercise, the induced lower O₂ availability due to hypoxic condition by inadequate blood flow affects mitochondrial oxidative phosphorylation. However, there are few studies which have reported the relationship between mitochondrial stimuli and oxygen diffusion rate from capillary to mitochondria in skeletal muscle (muscle rDO₂) during varying-workload exercise including under severe acidosis conditions in humans. The purpose of this study was to investigate the relationship between muscle PCr, rDO₂, and muscle deoxygenation in humans during incremental dynamic exercise. Twelve healthy, nonsmoking male subjects participated in this study. The subjects performed incremental dynamic handgrip exercise until exhaustion. Muscle PCr during exercise was evaluated using 31-phosphorus magnetic resonance spectroscopy. Muscle deoxygenation level was monitored using near-infrared spectroscopy, and muscle rDO₂ was determined by the rate of muscle deoxygenation during temporary arterial occlusion immediately after the end of each exercise stage. Muscle PCr level subsequently decreased with higher workloads, and muscle rDO₂ above 10%MVC significantly increased from the resting, and was constant with higher workloads. Muscle deoxygenation level was also significantly greater above 10%MVC, and gradually increased with higher workloads. These results suggest that muscle rDO₂ is limited at higher workloads, although mitochondrial stimuli are increased. The constant muscle rDO₂ with higher workloads may be caused by reduced O₂ gradient from capillary to mitochondria.

We investigated blood flow response for reactive hyperemia test in type1 diabetic and control rats using diffuse correlation spectroscopy (DCS). The baseline blood flow, peak amplitude and time to peak blood flow responses after releasing from ischemia were significantly decreased after induction of hyperglycemic state in diabetic rats. Furthermore, the baseline blood flow and the peak amplitude were significantly decreased from 1st week to 10th week in diabetic rats, suggesting the progress of vascular dysfunction caused by sustained glycemic stress. This research showed a potential of DCS to diagnose vascular function in diabetes that was altered by acute and chronic hyperglycemic stress.

Background: Worldwide >2.3 billion individuals are affected by bladder disease. The current evaluative test is invasive, associated with complications and often declined. Non-invasive evaluation of bladder hemodynamics using continuouswave near-infrared spectroscopy (NIRS) is an established technique. Recently, fNIRS was shown to detect activity in the brain regions previously identified by fMRI to relate to bladder sensation and control of voiding. We now report a system for simultaneous wireless fNIRS measurements of bladder and brain. Method: Two dual-wavelength (760/850 nm) fNIRS systems were used in parallel. A 23-channel array (35 mm interoptode distance) housed in a neoprene cap was positioned over the bilateral frontal cortex, and a 4-channel grid of 4 emitters and 1 detector taped to the skin over the bladder. Natural bladder filling to capacity and spontaneous voiding were monitored in two volunteer subjects. Proprietary software (Oxysoft v3.2.56) linked the devices, and generated video and graphical displays of changes in oxygenated, de-oxygenated, and total hemoglobin from raw optical data recorded at 50 Hz. Results: Simultaneous brain and bladder data were captured in both subjects. Localized brain activity was evident on video as topographical colorimetric changes indicative of increases in oxyhemoglobin concentration in areas previously linked via fMRI to bladder sensation and function; signal intensity varied in relation to phases of voiding. In the bladder detrusor muscle oxyhemoglobin increased prior to permission to void; changes during uroflow differed between the symptomatic and asymptomatic subjects. Conclusion: Simultaneous wireless fNIRS of brain and bladder is feasible, and offers new physiological dimensions for evaluating bladder control and function.