Hemodynamic Changes Associated with Lateralized Periodic Discharges: A Near-Infrared Spectroscopy and Continuous EEG Study.

BACKGROUND: Lateral periodic discharges (LPDs) have been recognized as a common electroencephalographic (EEG) pattern in critically ill patients. However, management decisions in these patients are still a challenge for clinicians. This study investigates hemodynamic changes associated with LPDs and evaluates if this pattern is likely to represent an ictal, interictal, or ictal-interictal continuum phenomenon via non-invasive near infra-red spectroscopy (NIRS) with concurrent with continuous EEG. METHODS: Seventeen patients admitted to the intensive care unit with LPDs on continuous electroencephalogram (EEG) were included. Participants engaged in NIRS recording-with scalp probes on right and left frontal regions simultaneously. Associations between LPDs laterality, primary frequency, NIRS a of cerebral oxygen saturation (SO2), total hemoglobin concentration (tHb), oxygenated hemoglobin concentration (O2Hb), de-oxygenated hemoglobin concentration (HHb), and variables in participant medical history were studied. RESULTS: Hemispheres with LPDs showed higher overall SO2 when compared to non-LPDs hemispheres (57% vs 52%, p = 0.03). Additionally, mildly increased tHb, O2Hb, and mildly decreased HHb concentrations were detected in the hemisphere showing LPDs, but changes were not statistically significant. A higher primary frequency of LPDs was associated with lower cerebral SO2 (Pearson correlation r = - 0.55, p = 0.022) and O2Hb (Pearson correlation r = - 0.52, p = 0.033). In patients with seizure during their EEG recording (64.7%), lower tHb (28.2 µmol/L vs 37.8 µmol/L, p = 0.049) and O2Hb (15.5 µmol/L vs 24.2 µmol/L, p = 0.033) were recorded in the LPDs hemisphere. CONCLUSIONS: This study demonstrates an increased cerebral SO2 in the hemisphere with LPDs, and decreased SO2 and O2Hb when the frequency of LPDs increases. The findings indicate that LPDs increase oxygen demand on the ipsilateral hemisphere. We infer that a threshold of LPDs frequency might exit, when the cerebral oxygen demand begins to supersede the ability of delivery, and saturation decreases.

Noninvasive determination of brain tissue oxygenation during sleep in obstructive sleep apnea: a near-infrared spectroscopic approach.

STUDY OBJECTIVES: Recurrent apneas and hypoxemia during sleep in obstructive sleep apnea (OSA) are associated with profound changes in cerebral blood flow to the extent that cerebral autoregulation may be insufficient to protect the brain. Since the brain is sensitive to hypoxia, the cerebrovascular morbidity seen in OSA could be due to chronic, cumulative effects of intermittent hypoxia. Near-infrared spectroscopy (NIRS) has the potential to noninvasively monitor brain tissue oxygen saturation (SO2), and changes in concentration of oxyhemoglobin [O2Hb], deoxyhemoglobin [HHb] and total hemoglobin [tHb] with real-time resolution. We hypothesized that brain tissue oxygenation would be worse during sleep in OSA relative to controls and sought to determine the practical use of NIRS in the sleep laboratory. DESIGN: We evaluated changes in brain tissue oxygenation using NIRS during overnight polysomnography. SETTING: Studies were conducted at University of Illinois, Chicago and Carle Hospital, Urbana, Illinois. PATIENTS: Nineteen subjects with OSA and 14 healthy controls underwent continuous NIRS monitoring during polysomnography. MEASUREMENTS AND RESULTS: We observed significantly lower indexes of brain tissue oxygenation (SO2: 57.1 +/- 4.9 vs. 61.5 +/- 6.1), [O2Hb]: 22.8 +/- 7.7 vs. 31.5 +/- 9.1, and [tHb]: 38.6 +/- 11.2 vs. 48.6 +/- 11.4 micromol/L) in OSA than controls (all P < 0.05). However, multivariate analysis showed that the differences might be due to age disparity between the two groups. CONCLUSIONS: NIRS is an effective tool to evaluate brain tissue oxygenation in OSA. It provides valuable data in OSA assessment and has the potential to bridge current knowledge gap in OSA.

Noninvasive determination of the optical properties of adult brain: near-infrared spectroscopy approach.

The basic parameters for physiological measurements provided by near-infrared spectroscopy are the local absorption and scattering coefficients. For the adult human head, they have been difficult to measure noninvasively because of the layered structure of the head. The results of measurements of absorption and reduced scattering coefficients through the forehead on 30 adult volunteers using a multidistance frequency domain method are reported. The optode separation distance ranged from 10 to 80 mm and measurements were recorded at 758 and 830 nm. The measured absorption and reduced scattering coefficients of the forehead were used to evaluate the hemoglobin content in the scalp and brain as well as cerebral oxygen saturation. We found that cerebral oxygenation was relatively narrowly distributed within the subject group (the standard deviation was about 3% for scalp and 6% for brain, respectively), whereas hemoglobin concentrations had a relatively broader distribution. We found that as the optode distance increased, the absorption coefficients increased and the scattering coefficients decreased, retrieving the optical values of scalp and brain for shorter and longer optode distances, respectively. We present the transition curves of the absorption and reduced scattering coefficients as functions of the optode distance. In order to verify the values for each layer, a comparison between the experimental data and a prediction based on the two-layer model of the adult head was carried out. The thicknesses of scalp and skull for the two-layer model were obtained by magnetic resonance imaging of a subject's head. The optical parameters obtained from the two-layer model agreed very well with those measured by the multidistance method.

Detection of the fast neuronal signal on the motor cortex using functional frequency domain near infrared spectroscopy.

Using non-invasive near infrared spectroscopy fast changes in the range of ms in the optical properties of neurons during brain activity have been described. Since the signal is small, the system to detect it has to be highly noise optimized. We used a frequency-domain tissue oximeter, whose laser diodes were modulated at 110 MHz and the amplitude (AC), mean intensity (DC) and phase (phi) of the modulated optical signal was measured at 96 Hz sample rate. In two volunteers, 36 and 37 years old, the probe consisting of 4 crossed source detector pairs was placed above the motor cortex (C3 position), contralateral to the hand performing the tapping exercise. The tapping frequency was set at 2.5 times the heart rate of the subject to avoid the influence of harmonics on the signal. An electronic device recorded the tapping movement. Control-data were obtained from a solid medium of approximately the same optical properties as the human head. To reduce physiological noise the arterial pulsatility was removed using an adaptive filter, the data was detrended by a high pass filter and a cross correlation function between the optical data and the tapping signal was calculated. The instrumental noise of the control data was very low (AC mean 0.0015% +/- SD 0.00092%, DC 0.00037% +/- 0.00023% and phi 0.00083 degrees +/- 0.00042 degrees). On the head the noise level was AC 0.0042% +/- 0.0031%, DC 0.0021% +/- 0.0012% and phi 0.0020 degrees +/- 0.0017 degrees. In 14 DC, 5 AC and 0 phi out of 30 locations a fast signal was detected, which was higher (p<0.001) than the noise level. This signal disappeared during non-tapping periods. With the signal to noise ratio that we have achieved single subject measurements become feasible.

Mapping of hemodynamics on the human calf with near infrared spectroscopy and the influence of the adipose tissue thickness.

We investigated the influence of the adipose tissue thickness (ATT) on near-infrared spectroscopy (NIRS) measurements of the absorption coefficient (mu a), the reduced scattering coefficient (mu s') and changes in concentrations of oxyhemoglobin ([O2Hb]) and deoxyhemoglobin ([HHb]). We used a frequency domain spectrometer and a special probe to generate maps of these parameters on the human calf during venous occlusion. For ATT below 6 mm mu a remained constant, whereas for ATT between 6 and 14 mm mu a decreased quickly and became almost constant again for ATT larger than 14 mm. Mu s' was not significantly altered by the ATT but the values showed a high variability between subjects. We found significantly different changes in both the [O2Hb] and the [HHb] between the proximal and distal locations of measurement. Although ATT influences the recovery of the optical properties of the underlying tissue, these differences depending on the location cannot be sufficiently explained by the ATT for the following reasons. The ATT varied little within one subject (mean difference 0.88 +/- 1.80 mm). The inter-subject variability was 5 times higher. For a given ATT within one subject we observed different values for changes in [O2Hb] and [HHb] depending on the measurement location. Moreover for a smaller ATT the difference between the values of delta[O2Hb] and delta[HHb] proximal versus distal were more distinct. The thinner the overlying tissue (ATT) the higher is the proportion of muscle tissue in the probed tissue volume. Therefore these differences are most likely coming from the muscle tissue rather than the ATT. This indicates that although the ATT has an evident influence on the measurement of optical parameters and hemodynamics and should therefore be recognized when performing NIRS measurements, other factors will have to be considered as well.

Absolute frequency-domain pulse oximetry of the brain: methodology and measurements.

A new method to non-invasively measure the absolute tissue oxygen saturation (SO2) and arterial oxygen saturation (fdSaO2) by frequency-domain spectroscopy is described. This method is based on the quantitative measurement of the tissue absorption spectrum, which is used to determine global SO2. From the amplitude of absorption changes caused by arterial pulsation oscillations, in the range of 633-841 nm, the fdSaO2 can be calculated. During deoxygenation (air/N2 mixture) experiments, we measured the fdSaO2 and SO2 on the forehead of three healthy volunteers and compared them to the arterial oxygen saturation measured by conventional pulse oximetry (poSaO2) on the finger. fdSaO2 and poSaO2 agree very well (mean difference: -1.2 +/- 2.6%). Changes in SO2 were systematically smaller than in fdSaO2 or poSaO2 probably due to autoregulation. The measurements with 4 and 8 wavelengths had comparable quality.

Age-correlated changes in cerebral hemodynamics assessed by near-infrared spectroscopy.

Cerebral hemodynamic responses due to normal aging may interfere with hormonal changes, drug therapy, diseases, life style, and other factors. Age-correlated alterations in cerebral vasculature and autoregulatory mechanisms are the subject of interest in many studies. Near-infrared spectroscopy (NIRS) is widely used for monitoring cerebral hemodynamics and oxygenation changes at the level of small vessels. We believe that the compensatory ability of cerebral arterioles under hypoxic conditions and the dilatatory ability of cerebral vessels due to vasomotion may decline with normal aging. To test this hypothesis we used frequency-domain NIRS to measure changes in cerebral tissue oxygenation and oxy- and deoxy-hemoglobin concentrations caused by hypoxia during breath holding. We also assessed cerebral vasomotion during profound relaxation. Thirty seven healthy volunteers, 12 females and 25 males, ranging from 22 to 56 years of age (mean age 35 +/- 11 years) participated in the study. We observed age-correlated changes in the cerebral hemodynamics of normal subjects: diminished cerebral hemodynamic response to hypoxia due to breath holding in middle-aged subjects (38-56 years) and reduced amplitude of cerebral hemodynamic changes due to vasomotion during rest. Snoring related changes in cerebral hemodynamics did not allow us to observe the effect of age in a group of snorers. The prolonged supine position influenced measured changes due to hypoxia. In this investigation NIRS methodology allowed detection of age-correlated changes in cerebral oxygenation and hemodynamics. Other variables, such as snoring or posture impacted the observations in our group of healthy volunteers.

Correlation of functional and resting state connectivity of cerebral oxy-, deoxy-, and total hemoglobin concentration changes measured by near-infrared spectrophotometry.

The aim is to study cerebral vascular functional connectivity during motor tasks and resting state using multichannel frequency-domain near-infrared spectrophotometry. Maps of 5.7 × 10.8 cm size displaying changes in cerebral oxyhemoglobin (O(2)Hb), deoxyhemoglobin (HHb), and total hemoglobin (tHb) concentrations were measured in the motor cortex in 12 subjects (mean age of 28.8±12.7 yrs) during resting state and during two palm squeezing tasks with different timing. For each condition, phase plane plots, cross correlation functions, and connectivity indices were generated for O(2)Hb, HHb, and tHb. The amplitude of the concentration changes in O(2)Hb and HHb depends on the age of the subject. We found large regions of connectivity, which were similar for resting state and task conditions. This means the spatial relationships during resting state, when changes in O(2)Hb, HHb, and tHb corresponded to spontaneous oscillations, were correlated to the spatial patterns during the activation tasks, when changes in O(2)Hb, HHb, and tHb concentration were related to the alternation of stimulation and rest. Thus, the vascular functional connectivity was also present during resting state. The findings suggest that the vascular response to functional activation may be a nonlinear synchronization phenomenon and that resting state processes are more important than previously expected.

Regional differences of hemodynamics and oxygenation in the human calf muscle detected with near-infrared spectrophotometry.

PURPOSE: Measurements in muscle tissue are often performed at a selected single location over the muscle of interest. The hypothesis is that the values obtained reflect the status within the entire muscle or muscle group. This, however, may not be the case. The study was performed to investigate whether this hypothesis is true for hemodynamics and oxygenation in the healthy human calf muscle at rest. MATERIALS AND METHODS: Hemoglobin flow, blood flow, oxygen consumption, and venous hemoglobin oxygen saturation were mapped at 22 locations in 30 legs of 15 healthy subjects (nine women, six men aged 26-37 years) simultaneously by using frequency-domain near-infrared spectrophotometry with a specially designed probe during venous occlusion. RESULTS: For all parameters, spatial heterogeneity was found between subjects and within individual legs. All parameters were highly significantly different when comparing proximal and distal regions. Differences were also found between medial and lateral regions. The global mean values (+/-standard deviation) over all measurements were as follows: hemoglobin flow, 1.27 micromol per 100 mL/min +/- 0.88; blood flow, 0.56 mL per 100 g/min +/- 0.38; oxygen consumption, 0.016 mL per 100 g/min +/- 0.011; and venous oxygen saturation, 77.6% +/- 5.9. The thickness of the overlying adipose tissue had an influence on the measurements and must be considered. CONCLUSION: Highly significant spatial heterogeneity of hemodynamics and oxygenation was found in the healthy human calf muscle.

Fast cerebral functional signal in the 100-ms range detected in the visual cortex by frequency-domain near-infrared spectrophotometry.

Brain activity is associated with physiological changes, which alter the optical properties of the tissue in the near-infrared part of the spectrum. Two major types of optical signals following functional brain activation can be distinguished: a slow signal due to hemodynamic changes and a fast signal, which is directly related to neuronal activity. The fast signal is small and therefore difficult to detect. We used a specially noise-optimized frequency-domain near-infrared spectrometer with a pi-sensor, which was expected to be particularly sensitive to deeper tissue layers, to investigate the human visual cortex during visual stimulation generated by a checkerboard. We were able to detect significant fast signals in single light bundles, but not in pi-signals. The fast signals were mostly collocated with strong slow hemodynamic signals, but showed a higher degree of localization than the latter. The latencies of 40 +/- 16 ms of the fast signals were similar between locations. Our results also indicate that the brain responds differently to a single and double (forth and back) reversal of the checkerboard, with a stronger reaction upon the double reversal.

Different time evolution of oxyhemoglobin and deoxyhemoglobin concentration changes in the visual and motor cortices during functional stimulation: a near-infrared spectroscopy study.

Neurovascular coupling is the generic term for changes in cerebral metabolic rate of oxygen (CMRO(2)), cerebral blood flow, and cerebral blood volume related to brain activity. The goal of this paper is to better understand the effects of neurovascular coupling in the visual and motor cortices using frequency-domain near-infrared spectroscopy. Maps of concentration changes in oxyhemoglobin [O(2)Hb], deoxyhemoglobin [HHb], and total hemoglobin of the visual and motor cortices were generated during stimulation using a reversing checkerboard screen and palm-squeezing, respectively. Seven healthy volunteers of 18-37 years of age were included. In the visual cortex the patterns of [O(2)Hb] and [HHb] were strongly linearly correlated (r(2) > 0.8 in 13 of a total of 24 locations). In 20 locations the change in [O(2)Hb] was larger than 0.25 microM. The mean slope of the linear regression between [O(2)Hb] and [HHb] was -3.93 +/- 0.31 (SE). The patterns of the [O(2)Hb] and [HHb] traces over the motor cortex looked different. The [O(2)Hb] reached its maximum change a few seconds before the [HHb] reached its minimum. This was confirmed by the linear regression analysis (r(2) > 0.8 in none of 40 locations). In 20 locations the change in [O(2)Hb] was larger than 0.25 microM. The mean slope of the regression line was -1.76 +/- 0.20, which is significantly higher than that in the motor cortex (P < 0.0000001). Patterns of [O(2)Hb] and [HHb] differ among cortex areas. This implies that the regulation of perfusion in the visual cortex is different from that in the motor cortex. There is evidence that the CMRO(2) increases substantially in the visual cortex, while this is not the case for the motor cortex.

Functional frequency-domain near-infrared spectroscopy detects fast neuronal signal in the motor cortex.

Millisecond changes in the optical properties of the human brain during stimulation were detected in five volunteers using noninvasive frequency-domain near-infrared spectroscopy. During a motor stimulation task we found highly significant signals, which were directly related to neuronal activity and exhibited much more localized patterns than the slow hemodynamic signals that are also detected by the near-infrared method. We considerably reduced the noise in the instrumental system and improved data analysis algorithms. With the achieved signal-to-noise ratio, single subject measurements were feasible without the requirement of particularly strong stimuli and within a reasonable period of measurement of 5 min at a mean signal-to-noise ratio of 3.6. The advantage of this noninvasive technique with respect to electrical recording is that it is able to detect neuronal activity with the relatively high spatial resolution of 8 mm.

Localized irregularities in hemoglobin flow and oxygenation in calf muscle in patients with peripheral vascular disease detected with near-infrared spectrophotometry.

PURPOSE: Near-infrared spectrophotometry is used to measure flow, concentration, and oxygenation of hemoglobin in arterioles, capillaries, and venules several centimeters deep in tissue. The purpose of this study was to investigate the distribution of flow, concentration, and oxygenation of hemoglobin in calf muscle in patients with documented peripheral arterial occlusive disease (PVD), patients with risk factors for PVD,and healthy younger subjects at rest. METHOD: With a frequency-domain near-infrared spectrophotometer and a specially designed probe, we generated maps at 22 locations simultaneously of hemoglobin flow, concentration, and oxygenation, with the venous occlusion method. Eight legs of 7 patients with diagnosed PVD (PVD group), 10 legs of 8 patients with normal ankle-brachial index but with risk factors for PVD (RF group), and 16 legs of 8 healthy subjects (H group) were studied. RESULTS: Global mean values were significantly (P <.05) different between the three groups for oxygen consumption (PVD group, 0.027 +/- 0.009 mL/100 g/min; RF group, 0.038 +/- 0.017 mL/100 g/min; H group, 0.022 +/- 0.020 mL/100 g/min), venous oxygen saturation (PVD, 59.7% +/- 15.4%; RF, 69.6% +/- 10.5%; H, 80.8% +/- 4.5%), and, at 60 s of venous occlusion, concentration changes in oxyhemoglobin (PVD, 4.48 +/- 3.25 micromol/L; RF, 8.44 +/- 2.33 micromol/L; H, 6.85 +/- 4.57 micromol/L), deoxyhemoglobin (PVD, 3.60 +/- 0.73 micromol/L; RF, 4.39 +/- 1.30 micromol/L; H, 2.36 +/- 1.79 micromol/L), and total hemoglobin (PVD, 8.07 +/- 3.83 micromol/L; RF, 12.83 +/- 2.75 micromol/L; H, 9.21 +/- 6.34 micromol/L). No significant difference was found between the three groups for hemoglobin flow (PVD, 0.92 +/- 0.69 micromol/100 mL/min; RF, 1.68 +/- 0.50 micromol/100 mL/min; H, 1.44 +/- 1.17 micromol/100 mL/min) and blood flow (PVD, 0.45 +/- 0.28 mL/100 g/min; RF, 0.77 +/- 0.21 mL/100 g/min; H, 0.62 +/- 0.50 mL/100 g/min). All parameters featured a distribution dependent on location. CONCLUSION: Mean value for venous oxygen saturation was higher in healthy subjects compared to patients with documented PVD. In patients with PVD, areas of lower oxygenation were clearly discernible. At distal locations of calf muscle, significant correlations between reduced hemoglobin flow, venous oxygen saturation, oxyhemoglobin, and total hemoglobin and reduced ankle-brachial index were found. Maps revealed localized irregularities in oxyhemoglobin, total hemoglobin, and venous oxygen saturation in patients with PVD. Near-infrared spectrophotometry is a noninvasive bedside technique that can enable determination of blood flow and oxygenation in tissue and may provide a method for evaluating patients with PVD.