Continuous-wave NIRS Device Research Articles

Performance Assessment of a Commercial Continuous-Wave Near-Infrared Spectroscopy Tissue Oximeter for Suitability for Use in an International, Multi-Center Clinical Trial.

Despite the wide range of clinical and research applications, the reliability of the absolute oxygenation measurements of continuous wave near-infrared spectroscopy sensors is often questioned, partially due to issues of standardization. In this study, we have compared the performances of 13 units of a continuous wave near-infrared spectroscopy device (PortaMon, Artinis Medical Systems, NL) to test their suitability for being used in the HEMOCOVID-19 clinical trial in 10 medical centers around the world. Detailed phantom and in vivo tests were employed to measure the precision and reproducibility of measurements of local blood oxygen saturation and total hemoglobin concentration under different conditions: for different devices used, different operators, for probe repositioning over the same location, and over time (hours/days/months). We have detected systematic differences between devices when measuring phantoms (inter-device variability, <4%), which were larger than the intra-device variability (<1%). This intrinsic variability is in addition to the variability during in vivo measurements on the forearm muscle resulting from errors in probe positioning and intrinsic physiological noise (<9%), which was also larger than the inter-device differences (<3%) during the same test. Lastly, we have tested the reproducibility of the protocol of the HEMOCOVID-19 clinical trial; that is, forearm muscle oxygenation monitoring during vascular occlusion tests over days. Overall, our conclusion is that these devices can be used in multi-center trials but care must be taken to characterize, follow-up, and statistically account for inter-device variability.

Comparison of frequency-domain and continuous-wave near-infrared spectroscopy devices during the immediate transition

BackgroundNon-invasive monitoring of cerebral tissue oxygen saturation (rcSO2) during transition is of growing interest. Different near-infrared spectroscopy (NIRS) techniques have been developed to measure rcSO2. We compared rcSO2 values during the immediate transition in preterm neonates measured with frequency-domain NIRS (FD-NIRS) with those measured with continuous-wave NIRS (CW-NIRS) devices in prospective observational studies.MethodsWe compared rcSO2 values measured with an FD-NIRS device during the first 15 min after birth in neonates with a gestational age ≥ 30 weeks but < 37 weeks born at the Erasmus MC- Sophia Children’s Hospital, Rotterdam, the Netherlands, with similar values measured with a CW-NIRS device in neonates born at the Medical University of Graz, Austria. Mixed models were used to adjust for repeated rcSO2 measurements, with fixed effects for time (non-linear), device, respiratory support and the interaction of device and respiratory support with time. Additionally, parameters such as total haemoglobin concentration and oxygenated and deoxygenated haemoglobin concentrations measured by FD-NIRS were analysed.ResultsThirty-eight FD-NIRS measurements were compared with 58 CW-NIRS measurements. The FD-NIRS rcSO2 values were consistently higher than the CW-NIRS rcSO2 values in the first 12 min, irrespective of respiratory support. After adjustment for respiratory support, the time-dependent trend in rcSO2 differed significantly between techniques (p < 0.01).ConclusionAs cerebral saturation measured with the FD-NIRS device differed significantly from that measured with the CW-NIRS device, differences in absolute values need to be interpreted with care. Although FD-NIRS devices have technical advantages over CW-NIRS devices, FD-NIRS devices may overestimate true cerebral oxygenation and their benefits might not outweigh the usability of the more clinically viable CW-NIRS devices.

Moderate-Intensity Aerobic Exercise Restores Appetite and Prefrontal Brain Activity to Images of Food Among Persons Dependent on Methamphetamine: A Functional Near-Infrared Spectroscopy Study.

The brain prefrontal control system is critical to successful recovery from substance use disorders, and the prefrontal cortex (PFC) regulates striatal reward-related processes. Substance-dependent individuals exhibit an increased response to drug rewards and decreased response to natural, nondrug rewards. Short-term aerobic exercise can ameliorate craving and inhibitory deficits in methamphetamine users, but the effect of exercise on food reward is unknown. This study used functional near-infrared spectroscopy (fNIRS) to measure the effects of moderate- and high-intensity short-term aerobic exercise on prefrontal activity related to food images and recorded the subjective feelings of appetite in methamphetamine-dependent users. In total, 56 men who met the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for methamphetamine dependence, with a mean (SD) body mass index of 24.7 (3.5) kg/m2 and age of 30.2 (5.1) years, were randomly assigned to one of two exercise groups: moderate intensity (n = 28; 65%–75% of maximum heart rate) and high intensity (n = 28; 76%–85% of heart rate maximum). Each group also performed a resting control session for 35 min 1 week before or after the exercise, in a counterbalanced order. Mean oxygenated hemoglobin concentration changes in the PFC when viewing visual food cues were assessed by fNIRS, and subjective feelings of appetite were self-rated using visual analog scales after moderate- or high-intensity aerobic exercise and after the resting control session. A continuous-wave NIRS device was used to obtain functional data: eight sources and seven detectors were placed on the scalp covering the PFC, resulting in 20 channels per participant. We found that moderate-intensity aerobic exercise significantly increased both, the activation of the left orbitofrontal cortex (OFC) to images of high-calorie food (P = 0.02) and subjective sensations of hunger (F(1,54) = 7.16, P = 0.01). To our knowledge, this study provides the first evidence that moderate-intensity aerobic exercise increases OFC activity associated with high-calorie food images and stimulates appetite in methamphetamine-dependent individuals. These changes suggest that exercise may reestablish the food reward pathway hijacked by drugs and restore sensitivity to natural rewards. This evidence may contribute to the development of specific exercise programs for populations with methamphetamine dependence.

Delta-9-tetrahydrocannabinol intoxication is associated with increased prefrontal activation as assessed with functional near-infrared spectroscopy: A report of a potential biomarker of intoxication

The primary psychoactive compound in cannabis, Δ9-tetrahydrocannabinol (THC), binds to cannabinoid receptors (CB1) present in high concentrations in the prefrontal cortex (PFC). It is unknown whether the PFC hemodynamic response changes with THC intoxication. We conducted the first double-blind, placebo-controlled, cross-over study of the effect of THC intoxication on functional near infrared spectroscopy (fNIRS) measures of PFC activation. Fifty-four adult, regular (at least weekly) cannabis users received a single oral dose of synthetic THC (dronabinol; 5–50 mg, dose individually tailored to produce intoxication) and identical placebo on two visits at least one week apart. fNIRS recordings were obtained during a working memory task (N-Back) at three timepoints: before THC/placebo, at 100 min (when peak effects were expected), and at 200 min after THC/placebo administration. Functional data were collected using a continuous-wave NIRS device, with 8 sources and 7 detectors arrayed over the forehead, resulting in 20 channels covering PFC regions. Participants also completed frequent heart rate measures and subjective ratings of intoxication. Approximately half of participants reported significant intoxication. Intoxication ratings were not correlated with dose of THC. Increases in heart rate significantly correlated with intoxication ratings after THC dosing. Results indicated that 100 min after THC administration, oxygenated hemoglobin (HbO) response significantly increased from pre-dose HbO levels throughout the PFC in participants who reported significant intoxication. Changes in HbO response significantly correlated with self-reported intoxication at 100 min after THC administration. Among those who reported intoxication, HbO response decreased at 200 min after THC, when intoxication had largely resolved, compared to the peak THC time point. This study demonstrates that THC intoxication causes increased PFC activity, and fNIRS of the PFC can measure this effect. Increased neural activation in PFC represents a potential biomarker for cannabis intoxication.

Muscle deoxygenation kinetics in cycling time trial

Background: Concentration changes of oxygenated and deoxygenated haemoglobin (O2Hb and HHb) measured by near infrared spectroscopy (NIRS) provides information about oxygen delivery and extraction at the muscular level. The kinetic response of HHb reflects the adjustment of the oxidative metabolism in skeletal muscle and could therefore be related to exercise tolerance. While most studies used laboratory cycling to investigate the kinetic responses, the effect of cycling time trials in field conditions remains to be shown. Therefore, the aim of this study was to investigate changes in HHb during maximal effort cycling time trials in field conditions. Methods: Thirteen trained cyclists and triathletes (N=13; mean ± SD: age 32 ± 7 years; body mass 74.6 ± 7.4 kg; stature 182 ± 5 cm; maximum oxygen uptake 67.9 ± 3.0 mL·min-1·kg-1; maximal power output 406 ± 39 W), completed 3 cycling time trials lasting 10, 4 and 1 min on a flat road, interspersed by a 30 min recovery period after each trial. Relative changes in HHb were recorded on the right vastus lateralis muscle with a portable continuous-wave NIRS device. Second-by-second data normalised to 100% of the response were used to resolve the amplitude, the time delay and the time constant by nonlinear regression. A repeated measure ANOVA was used to compare the parameter estimates across the time trial durations. Results: The mean power output during the 10-, 4- and 1- minute cycling time trials was 352 ± 45, 385 ± 49 and 525 ± 73 W, respectively (p=0.001). No significant differences were observed for cadence during the 10- vs. 1-minute cycling time trials (p=0.264), however significant differences were observed between 4- vs. 1-minute (p=0.05) The parameter estimates of the kinetic response were significantly affected by time trial duration. The amplitude for 10- vs. 1- minute (78.20 ± 8.42 vs. 89.16 ± 6.82; p = 0.022) as well as for 4- vs. 1-minute (74.99 ± 6.12 vs. 89.16 ± 6.82; p = 0.006) cycling time trial duration showed significant differences. Moreover, significant effects can be reported for the 10- vs. 1-minute time delay parameter (9.54 ± 2.07 s vs. 3.65 ± 1.71s; p = 0.001). Mean response time also demonstrated significant differences for 10- vs. 1-minute cycling time trials (13.45 ± 2.39 s vs. 6.85 ± 1.90 s; p = 0.001). No significant differences were reported for the time constant among the different cycling time trial durations (p>0.05). Discussion: These findings support that the physiological response to high intensity exercise during multiple cycling time trial durations could be monitored by alterations in muscle deoxygenation kinetic parameters. Furthermore, these results imply that changes at the microvascular level are time dependent when exposed to maximal exhaustion. However further research is recommended to support these findings of muscle deoxygenation kinetics during cycling time trial in field conditions.

Muscle deoxygenation during moderate- and severe-intensity cycling in youth elite-cyclists

Background: Near-infrared spectroscopy (NIRS) is a well-established technique to measure tissue oxygenation and haemodynamics during exercise. While muscle oxygen consumption is derived by measuring concentration changes of oxygenated and deoxygenated haemoglobin and myoglobin (O 2 Hb and HHb), total haemoglobin (tHb = O 2 Hb + HHb) reflect blood volume and perfusion. In particular, the change in HHb is considered a proxy for oxygen extraction at the muscle level during exercise and arterial occlusion, where the rate of reoxygenation has been used as a measure of mitochondrial function (Ryan et al, 2012: Journal of Applied Physiology, 113, 175-183). NIRS-derived signals therefore reflect the dynamic balance between oxygen delivery and utilisation and may be important measures to monitor training induced adaptations of aerobic function in skeletal muscle. However, current literature is scarce regarding reliability measures, especially in young athletes, which needs to be established to interpret changes with confidence. Purpose: To assess the test-retest reliability of HHb-changes during moderate- and severe- intensity cycling, and during arterial occlusion in youth elite-cyclists. Methods: Fifteen cyclist (mean ± SD: age 13.5 ± 1.8 y; stature 163.2 ± 12.2 cm; body mass 51.3 ± 12.4 kg; O 2max 62.1 ± 4.2 mL . min -1. kg -1 ) completed two 6-min rest-to-work transitions (T) from baseline (BL: 60 W) to moderate- (90% of the first ventilatory threshold [VT1]: 120 ± 26 W) and to severe- (50% between VT and maximum power [Delta50]: 204 ± 43 W) intensity cycling. The transitions were interspersed by 8 min BL cycling. After Delta50 cycling, an occlusion was applied on the proximal thigh at a pressure of 300 mmHG until a levelling-off of the HHb signal was observed (3-5 min). The protocol was repeated after a passive rest of 1 h. Changes in HHb were measured on the belly of the right vastus lateralis muscle with a portable continuous-wave NIRS device at a sampling rate of 5 Hz (PortaMon, Artinis). Second-per-second data, were corrected for blood volume changes and normalised to the full functional range measured during the occlusion (0-100%). HHb changes (%) were calculated from BL to the maximum of VT1 (I”BL-VT1) and from BL to the maximum of Delta50 (I”BL-Delta50). In addition, the reoxygenation after occlusion was assessed with the slope of linear regression analysis (% . s -1 ). A typical example of the HHb signal is shown in Figure 1. Absolute and relative reliability was calculated with Bland-Altman statistics ± 95% limits of agreement and the coefficient of variation (CV; %), respectively. Paired t-tests were used for comparisons. Results: The I”BL-VT1 was 20.5 ± 11.7 and 21.6 ± 12.3% during T1 and T2, respectively (p = 0.079). The bias was 1.1 ± 2.3 % (95% LoA: -5.6 – 3.3) and the CV 10.1% (7.3 – 16.4). The I”BL-Delta50 were 58.1 ± 9.6 (T1) and 56.5 ± 9.3% (T2) (p = 0.133) and the bias and CV were 1.6 ± 3.9% (-6.0 – 9.3) and 5.4% (3.9 – 8.6), respectively. The reoxygenation slopes were 7.2 ± 2.0 (T1) and 7.6 ± 2.1 % . s -1 (T2) (p = 0.053) with a bias and CV of 0.4 ± 0.7 % . s -1 (-1.8 – 1.0) and 7.0% (5.1 – 11.2), respectively. Discussion: The present study quantified reliability for NIRS-derived changes in HHb during cycling at moderate and severe intensity as well as for reoxygenation after occlusion. The provided levels of 5.4% for severe-intensity cycling and 7.0% for the reoxygenation slope, are well below the level of 10% considered as acceptable for a measurement, and the level of 10.1% for moderate-intensity cycling is only marginally higher. The reliability data established, provide limits within which training induced adaptations may be interpreted with confidence. Longitudinal studies in young athletes could potentially benefit from these findings since the magnitude of changes in NIRS variables is probably greater than the reported measurement error.

Using Functional Near-Infrared Spectroscopy to Measure Effects of Delta 9-Tetrahydrocannabinol on Prefrontal Activity and Working Memory in Cannabis Users.

Intoxication from cannabis impairs cognitive performance, in part due to the effects of Δ9-tetrahydrocannabinol (THC, the primary psychoactive compound in cannabis) on prefrontal cortex (PFC) function. However, a relationship between impairment in cognitive functioning with THC administration and THC-induced change in hemodynamic response has not been demonstrated. We explored the feasibility of using functional near-infrared spectroscopy (fNIRS) to examine the functional changes of the human PFC associated with cannabis intoxication and cognitive impairment. Eighteen adult regular cannabis users (final sample, n = 13) performed a working memory task (n-back) during fNIRS recordings, before and after receiving a single dose of oral synthetic THC (dronabinol; 20–50 mg). Functional data were collected using a continuous-wave NIRS device, in which 8 Sources and 7 detectors were placed on the forehead, resulting in 20 channels covering PFC regions. Physiological changes and subjective intoxication measures were collected. We found a significant increase in the oxygenated hemoglobin (HbO) concentration after THC administration in several channels on the PFC during both the high working memory load (2-back) and the low working memory load (0-back) condition. The increased HbO response was accompanied by a trend toward an increased number of omission errors after THC administration. The current study suggests that cannabis intoxication is associated with increases in hemodynamic blood flow to the PFC, and that this increase can be detected with fNIRS.

Exercise capacity and oxygen recovery half times of skeletal muscle in patients with fibromyalgia

It is known that increased muscle fatigability and exercise intolerance is a major symptom of fibromyalgia (FM) [1]. Although many models have been proposed, the patho-physiology of exercise intolerance in FM remains unclear. Up to now, muscle fatigue and exercise tolerance can be explained by numerous central and peripheral mechanisms [1]; however, the exact patho-physiological role of the microvascular involvement in FM is still unclear. As a peripheral mechanism, there are few reports on abnormalities of the microcirculation in patients with fibromyalgia. Continuous wave near-infrared spectroscopy (NIRS) technology is based on the fact that light in the wavelength range 650–950 nm is weakly absorbed by tissues and signal intensity changed mainly due to hemoglobin. Since light passing through the large vessels is mostly absorbed, light that reaches the detector comes mainly from small blood vessels (arterioles, capillaries and venules) [2]. Thus, it gives dynamic balance information between oxygen supply and consumption of skeletal muscles. The objective of the present study was to evaluate association with exercise intolerance and oxygen recovery half times of skeletal muscle in patients with FM. Thirty-three female subjects (18 consecutive female patients with FM), aged between 21 and 36 years, were investigated. All subjects were fully informed of any risks and discomforts associated with the experiments before giving their informed written consent to participate with ethical approved. All have taken examination by near-infrared spectroscopy and cardiopulmonary exercise testing. In the experiment protocol, brachial ischemia was used for detecting muscular oxygen kinetics by NIRS method before cardiopulmonary exercise testing. A continuous wave NIRS device was used (Niroxcope 201, Biophotonics Lab) and the probe containing multiple source-detectors was placed on the subjects’ lower half of left forearm and arterial blood flow is restricted by placing a tourniquet on the upper arm at a pressure of 250 mmHg after a 5 min baseline measurement, and then post-ischemic measurement was taken. In both rest and post-ischemic traces, change of difference of oxyhemoglobin and deoxyhemoglobin concentrations between minimum point and maximum point was taken as the full range and time to reach half of the 95% of the full range was calculated as half-time value (t1/2) [2]. Then, all participants underwent a standard Bruce multistage maximal treadmill protocol with metabolic measurements. All exercise testings were discontinued due to fatigue. Peak oxygen conM. Dinler AE C. Aksoy AE A. Oncel AE E. Berker Department of Physical Medicine and Rehabilitation, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey