Tanja Karen

Hemodynamic response to visual stimulation in newborn infants using functional near-infrared spectroscopy

Brain activity is associated with physiological changes, which alter the optical properties of tissue. These changes can be detected by near‐infrared spectroscopy (NIRS). Aim of the study was to determine changes in cerebral oxygenation in response to stimulation in the visual cortex in newborn infants during spontaneous sleep in the first days of life. We used an in‐house developed multichannel NIRS imaging instrument, the MCP‐II, to measure changes in concentration of oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb) in specific brain areas. In 10 out of 15 subjects, a significant increase in O2Hb and/or a significant decrease in HHb were found in one or more channels over the occipital cortex. During stimulation, O2Hb increased by a mean of 0.98 μmol/l, HHb decreased by a mean 0.17 μmol/l, and total‐Hb increased by a mean of 0.81 μmol/l. The hemodynamic response to visual stimulation in the occipital cortex in newborn infants is similar to adults. The increase in O2Hb and the simultaneous decrease in HHb during stimulation suggest an increase in cerebral blood flow (CBF) that overcompensates for the increased oxygen consumption (CMRO2) in the activated cortical area. Hum Brain Mapp, 2008.

Near infrared spectroscopy to study the brain: an overview

This paper gives an overview of principles, technologies, and applications using near infrared spectrometry and imaging (NIRS and NIRI) to study brain function. The physical background is reviewed and technologies and their properties are discussed. Advantages and limitations of NIRI are described. The basic functional signals obtained by NIRI, the neuronal and the hemodynamic signal are described and in particular publications about the former are reviewed. Applications in adults and neonates are reviewed, too.

Inhaled Corticosteroids for Bronchopulmonary Dysplasia: A Meta-analysis.

CONTEXT: Bronchopulmonary dysplasia (BPD) in preterm infants remains a major health burden despite many therapeutic interventions. Inhaled corticosteroids (IC) may be a safe and effective therapy. OBJECTIVE: To assess the safety and efficacy of IC for prevention or treatment of BPD or death in preterm infants. DATA SOURCES: PubMed, the Cochrane Library, Embase, and CINAHL from their inception until November 2015 together with other relevant sources. STUDY SELECTION: Randomized controlled trials of ICs versus placebo for either prevention or treatment of BPD. DATA EXTRACTION: This meta-analysis used a random-effects model with assessment of quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Thirty-eight trials were identified, and 16 met inclusion criteria. ICs were associated with a significant reduction in death or BPD at 36 weeks’ postmenstrual age (risk ratio [RR] = 0.86, 95% confidence interval [CI] 0.75 to 0.99, I2 = 0%, P = .03; 6 trials, n = 1285). BPD was significantly reduced (RR = 0.77, 95% CI 0.65 to 0.91, I2 = 0%, 7 trials, n = 1168), although there was no effect on death (RR = 0.97, 95% CI 0.42 to 2.2, I2 = 50%, 7 trials, n = 1270). No difference was found for death or BPD at 28 days’ postnatal age. The use of systemic steroids was significantly reduced in treated infants (13 trials, n = 1537, RR = 0.87, 95% CI 0.76 to 0.98 I2 = 3%,). No significant differences were found in neonatal morbidities and other adverse events. LIMITATIONS: Long-term follow-up data are awaited from a recent large randomized controlled trial. CONCLUSIONS: Very preterm infants appear to benefit from ICs with reduced risk for BPD and no effect on death, other morbidities, or adverse events. Data on long-term respiratory, growth, and developmental outcomes are eagerly awaited.

Quantifying the effect of adipose tissue in muscle oximetry by near infrared spectroscopy

Change of muscle tissue oxygen saturation (StO2), due to exercise, measured by near infrared spectroscopy (NIRS) is known to be lower for subjects with higher adipose tissue thickness. This is most likely not physiological but caused by the superficial fat and adipose tissue. In this paper we assessed, in vitro, the influence of adipose tissue thickness on muscle StO2, measured by NIRS oximeters. We measured StO2 of a liquid phantom by 3 continuous wave (CW) oximeters (Sensmart Model X-100 Universal Oximetry System, INVOS 5100C, and OxyPrem v1.3), as well as a frequency-domain oximeter, OxiplexTS, through superficial layers with 4 different thicknesses. Later, we employed the results to calibrate OxyPrem v1.3 for adipose tissue thickness in-vivo.

Comparison of tissue oximeters on a liquid phantom with adjustable optical properties: an extension

Cerebral near-infrared spectroscopy (NIRS) oximetry may help clinicians to improve patient treatment. However, the application of NIRS oximeters is increasingly causing confusion to the users due to the inconsistency of tissue oxygen haemoglobin saturation (StO2) readings provided by different oximeters. To establish a comparability of oximeters, in our study we performed simultaneous measurements on the liquid phantom mimicking properties of neonatal heads and compared the tested device to a reference NIRS oximeter (OxiplexTS). We evaluated the NIRS oximeters FORE-SIGHT, NIRO and SenSmart, and reproduced previous results with the INVOS and OxyPrem v1.3 oximeters. In general, linear relationships of the StO2 values with respect to the reference were obtained. Device specific hypoxic and hyperoxic thresholds (as used in the SafeBoosC study, www.safeboosc.eu) and a table allowing for conversion of StO2 values are provided.

Hemoglobin spectra affect measurement of tissue oxygen saturation

Tissue oxygen saturation (StO2) is a valuable clinical parameter e.g. for intensive care applications or monitoring during surgery. Studies showed that near-infrared spectroscopy (NIRS) based tissue oximeters of different brands give systematically different readings of StO2. Usually these readings are linearly correlated and therefore StO2 readings from one instrument can easily be converted to those of another instrument. However, it is interesting to understand why there is this difference. One reason may be that different brands employ different spectra of hemoglobin. The aim here was to investigate how these different absorption spectra of hemoglobin affect the StO2 readings. Therefore, we performed changes in StO2 in a phantom experiment with real human hemoglobin at three different concentrations (26.5, 45 and 70 μM): desaturation by yeast consuming the oxygen and re-saturation by bubbling oxygen gas. The partial pressure of O2 in the liquid changed from at least 10 kPa to ~0 kPa and ISS OxiplexTS, a frequency-domain NIRS instrument, was used to monitor changes of StO2. When we employed two different absorption spectra for hemoglobin, StO2 values were comparable in the normal physiological range. However, particularly at high and low StO2 values, a difference of >6% between these two spectra were noticed. Such a difference of >6% is substantial and relevant for medical applications. This may partly explain why different brands of NIRS instruments provide different StO2 readings. The hemoglobin spectra are therefore a factor to be considered for future developments and applications of NIRS oximeters.

Optical properties of mice's stool in 550 to 1000 nm wavelength range

The aim of this work was to measure optical properties of stool of mice to provide this relevant wavelength-dependent behavior for optical imaging modalities such as fluorescent molecular tomography and near-infrared optical tomography. BALB/c nude female mice were studied and optical properties of the stool were determined by employing the inverse adding-doubling approach. The animals were kept on chlorophyll-free diet. Nine stool samples were measured. The wavelength-dependent behavior of absorption and scattering in 550 to 1000 nm range is presented. The reduced scattering spectrum is fitted to the Mie scattering approximation in the near-infrared (NIR) wavelength range and to the Mie + Rayleigh approximation in visible/NIR range with the fitting coefficients presented. The study revealed that the absorption spectrum of stool can lead to crosstalk with the spectrum of hemoglobin in the NIR range.

In vivo precision assessment of a near-infrared spectroscopy-based tissue oximeter (OxyPrem v1.3) in neonates considering systemic hemodynamic fluctuations

Abstract. The aim was to determine the precision of a noninvasive near-infrared spectroscopy (NIRS)-based tissue oximeter (OxyPrem v1.3). Using a linear mixed-effects model, we quantified the variability for cerebral tissue oxygenation (StO2) measurements in 35 preterm neonates to be 2.64%, a value that meets the often-articulated clinicians’ demand for a precise tissue oxygenation measurement. We showed that the variability of StO2 values measured was dominated by spontaneous systemic hemodynamic fluctuations during the measurement, meaning that precision of the instrument was actually even better. Based on simultaneous and continuous measurements of peripheral arterial oxygenation and cerebral StO2 with a second sensor, we were able to determine and quantify the physiological instability precisely. We presented different methods and analyses aiming at reducing this systematic physiological error of in vivo precision assessments. Using these methods, we estimated the precision of the OxyPrem tissue oximeter to be   ≤  1.85  %  . With our study, we deliver relevant information to establish highly precise cerebral oxygenation measurements with NIRS-based oximetry, facilitating the further development toward a substantially improved diagnosis and treatment of patients with respect to brain oxygenation.

193 Apnea of Prematurity: Association with Neurodevelopmental Outcome?

Background: Idiopathic apnea of prematurity is a very common problem in preterm infants that may require pharmacologic or respiratory intervention and delay hospital discharge. Several authors have shown that apneas, especially associated with hypoxemia and/or bradycardia, decrease cerebral blood flow which may induce brain injury.Aim: To investigate the association of apnea in preterm infants with subsequent neurodevelopmental outcome when compared with matched controls without apnea.Methods: 28 infants < 32 gestational weeks and / or < 1500g birth weight with recurrent apnea (> 3 per 24 hours) were matched with 28 infants the same gestational age without apnea. All infants were assessed at 24 months corrected for prematurity (Bayley II and neurological examination).Results: Gender distribution, mean gestational age, birth weight, days of mechanical ventilation, CPAP and days of oxygen were similar in both groups. The average length of hospital stay was longer in patients with apnea. There was no significant difference between the mean MDI and/or PDI of infants with apnea when compared with those of infants without apnea.Conclusion: Power analysis with alpha=0.05 and beta=0.2 reveals that the sample size of 56 suffices to exclude a possible difference of more than 11 points within the Bayley II scales (equivalent to 0.75 of a standard deviation of 15) when comparing infants with apnea to controls.Background: Idiopathic apnea of prematurity is a very common problem in preterm infants that may require pharmacologic or respiratory intervention and delay hospital discharge. Several authors have shown that apneas, especially associated with hypoxemia and/or bradycardia, decrease cerebral blood flow which may induce brain injury.Aim: To investigate the association of apnea in preterm infants with subsequent neurodevelopmental outcome when compared with matched controls without apnea.Methods: 28 infants < 32 gestational weeks and / or < 1500g birth weight with recurrent apnea (> 3 per 24 hours) were matched with 28 infants the same gestational age without apnea. All infants were assessed at 24 months corrected for prematurity (Bayley II and neurological examination).Results: Gender distribution, mean gestational age, birth weight, days of mechanical ventilation, CPAP and days of oxygen were similar in both groups. The average length of hospital stay was longer in patients with apnea. There was no significant difference between the mean MDI and/or PDI of infants with apnea when compared with those of infants without apnea.Conclusion: Power analysis with alpha=0.05 and beta=0.2 reveals that the sample size of 56 suffices to exclude a possible difference of more than 11 points within the Bayley II scales (equivalent to 0.75 of a standard deviation of 15) when comparing infants with apnea to controls.

258 Investigation of the Hemodynamic Response to Flash Visual Stimulation in Neonates Using Near Infrared Spectroscopy

Background/Aims: Near-infrared spectroscopy (NIRS) is used to study the hemodynamic response to visual stimulation in sleeping neonates. The specific aims of this study were to determine whether a response in the visual cortex can be detected in term neonates during the first days of life and, if so, to determine the direction and magnitude of changes in deoxyhemoglobin (HHb) during stimulation.Methods: Ten healthy, term neonates, aged 2 to 14 d, were subjected to binocular visual stimulation using red lights, flashing at a frequency of 0.5 or 1 Hz. Lights were directed towards each eye at a distance of approximately 5 cm. Stimulation periods of 20 s were alternated with rest periods of approximately 20 s. An in-house developed NIRS imaging instrument, the MCP-II, measured localized changes in concentrations of oxyhemoglobin (O2Hb) and HHb. The NIRS sensor contains 4 light sources and 4 photodetectors covering an area of 2.5 by 3.75 cm with 10 different light paths at 100 Hz. The centre of the sensor was positioned 1 cm above the inion.Results: The concentrations of O2Hb and HHb during the last 10 s of the stimulation period were compared to the concentrations during the 10 s preceding stimulation. In 6 out of 10 subjects, a significant (p< 0.01) increase in O2Hb and/or a significant decrease in HHb was observed in one or more locations. During stimulation, O2Hb increased by a mean of 1.3 micromol/l, HHb decreased by a mean 0.5 micromol/l, and total Hb increased by a mean of 0.9 micromol/l.Conclusions: Our results show that a hemodynamic response to visual stimulation, similar to that observed in adults, can be measured in sleeping neonates. The increase in O2Hb and simultaneous decrease in HHb during stimulation suggest an increase in cerebral blood flow that overcompensates for the increased oxygen consumption in the activated cortical area.