Matthias Kohl-Bareis

A Hybrid Multi-Distance Phase and Broadband Spatially Resolved Spectrometer and Algorithm for Resolving Absolute Concentrations of Chromophores in the Near-Infrared Light Spectrum

For resolving absolute concentration of tissue chromophores in the human adult brain with near-infrared spectroscopy it is necessary to calculate the light scattering and absorption, at multiple wavelengths with some depth resolution. To achieve this we propose an instrumentation configuration that combines multi-distance frequency and broadband spectrometers to quantify chromophores in turbid media by using a hybrid spatially resolved algorithm. Preliminary results in solid phantoms as well as liquid dynamic homogeneous and inhomogeneous phantoms and in-vivo muscle measurements showed encouraging results.

Algorithms for Muscle Oxygenation Monitoring corrected for Adipose Tissue Thickness

The measurement of skeletal muscle oxygenation by NIRS methods is obstructed by the subcutaneous adipose tissue which might vary between < 1 mm to more than 12 mm in thickness. A new algorithm is developed to minimize the large scattering effect of this lipid layer on the calculation of muscle haemoglobin / myoglobin concentrations. First, we demonstrate by comparison with ultrasound imaging that the optical lipid signal peaking at 930 nm is a good predictor of the adipose tissue thickness (ATT). Second, the algorithm is based on measurements of the wavelength dependence of the slope &Dgr;A/&Dgr;&rgr; of attenuation A with respect to source detector distance &rgr; and Monte Carlo simulations which estimate the muscle absorption coefficient based on this slope and the additional information of the ATT. Third, we illustrate the influence of the wavelength dependent transport scattering coefficient of the new algorithm by using the solution of the diffusion equation for a two-layered turbid medium. This method is tested on experimental data measured on the vastus lateralis muscle of volunteers during an incremental cycling exercise under normal and hypoxic conditions (corresponding to 0, 2000 and 4000 m altitude). The experimental setup uses broad band detection between 700 and 1000 nm at six source-detector distances. We demonstrate that the description of the experimental data as judged by the residual spectrum is significantly improved and the calculated changes in oxygen saturation are markedly different when the ATT correction is included.

Device for simultaneous positron emission tomography, laser speckle imaging and RGB reflectometry: Validation and application to cortical spreading depression and brain ischemia in rats

Brain function critically relies on the supply with energy substrates (oxygen and glucose) via blood flow. Alterations in energy demand as during neuronal activation induce dynamic changes in substrate fluxes and blood flow. To study the complex system that regulates cerebral metabolism requires the combination of methods for the simultaneous assessment of multiple parameters. We developed a multimodal imaging device to combine positron emission tomography (PET) with laser speckle imaging (LSI) and RGB reflectometry (RGBR). Depending on the radiotracer, PET provides 3-dimensional quantitative information of specific molecular processes, while LSI and RGBR measure cerebral blood flow (CBF) and hemoglobin oxygenation at high temporal and spatial resolution. We first tested the functional capability of each modality within our system and showed that interference between the modalities is negligible. We then cross-calibrated the system by simultaneously measuring absolute CBF using (15)O-H2O PET (CBF(PET)) and the inverse correlation time (ICT), the LSI surrogate for CBF. ICT and CBF(PET) correlated in multiple measurements in individuals as well as across different animals (R(2)=0.87, n=44 measurements) indicating that ICT can be used for absolute quantitative assessment of CBF. To demonstrate the potential of the combined system, we applied it to cortical spreading depression (CSD), a wave of transient cellular depolarization that served here as a model system for neurovascular and neurometabolic coupling. We analyzed time courses of hemoglobin oxygenation and CBF alterations coupled to CSD, and simultaneously measured regional uptake of (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) used as a radiotracer for regional glucose metabolism, in response to a single CSD and to a cluster of CSD waves. With this unique combination, we characterized the changes in cerebral metabolic rate of oxygen (CMRO2) in real-time and showed a correlation between (18)F-FDG uptake and the number of CSD waves that passed the local tissue. Finally, we examined CSD spontaneously occurring during focal ischemia also referred to as peri-infarct depolarization (PID). In the vicinity of the ischemic territory, we observed PIDs that were characterized by reduced CMRO2 and increased oxygen extraction fraction (OEF), indicating a limitation of oxygen supply. Simultaneously measured PET showed an increased (18)F-FDG uptake in these regions. Our combined system proved to be a novel tool for the simultaneous study of dynamic spatiotemporal alterations of cortical blood flow, oxygen metabolism and glucose consumption under normal and pathologic conditions.

Effects of Assuming Constant Optical Scattering on Haemoglobin Concentration Measurements Using NIRS during a Valsalva Manoeuvre

Resolving for changes in concentration of tissue chromophores in the human adult brain with near-infrared spectroscopy has generally been based on the assumption that optical scattering and pathlength remain constant. We have used a novel hybrid optical spectrometer that combines multi-distance frequency and broadband systems to investigate the changes in scattering and pathlength during a Valsalva manoeuvre in 8 adult volunteers. Results show a significant increase in the reduced scattering coefficient of 17% at 790nm and 850nm in 4 volunteers during the peak of the Valsalva. However, these scattering changes do not appear to significantly affect the differential pathlength factor and the tissue haemoglobin concentration measurements.

Muscle oxygenation during exercise under hypoxic conditions assessed by spatially resolved broadband NIR spectroscopy

Near-infrared spectroscopy (NIRS) is used for the non-invasive measurement of muscle oxygenation during an incremental cycle test in healthy volunteers. A broad band spatially resolved system is used that allows the reliability of current algorithms to be inspected with the main emphasis on tissue oxygen saturation (SO2) and oxygenated and deoxygenated haemoglobin concentrations. Physiological conditions were modulated by changing oxygen supply from normal (21 % O2 in inspired air) to conditions corresponding to 2000 and 4000 m altitude above sea level (15.4 and 11.9 % O2). Under these hypoxic conditions the decrease in SO2 with increased exercise power is highly correlated with the oxygen content of the inspired air. There is a clear correlation with physiological parameters (heart rate, pulse oxymetry, blood gas, lactate, spirometric data). Skin oxygenation parameters are compared to those of muscle.

Cerebral oxygenation monitoring during cardiac bypass surgery in infants with broad band spatially resolved spectroscopy

Neurological impairments following cardio-pulmonary bypass (CPB) during open heart surgery can result from microembolism and ischaemia. Here we present results from monitoring cerebral haemodynamics during CPB with near infrared spatially resolved broadband spectroscopy. In particular, the study has the objective (a) to monitor oxy- and deoxy-hemoglobin concentrations (oxy-Hb, deoxy-Hb) and their changes as well as oxygen saturation during CPB surgery and (b) to develop and test algorithms for the calculation of these parameters from broad band spectroscopy. For this purpose a detection system was developed based on an especially designed lens imaging spectrograph with optimised sensitivity of recorded reflectance spectra for wavelengths between 600 and 1000 nm. The high f/#-number of 1:1.2 of the system results in about a factor of 10 higher light throughput combined with a lower astigmatism and crosstalk between channels when compared with a commercial mirror spectrometers (f/# = 1:4). For both hemispheres two independent channels each with three source-detector distances (&rgr; = 25 . 35 mm) were used resulting in six spectra. The broad band approach allows to investigate the influence of the wavelength range on the calculated haemoglobin concentrations and their changes and oxygen saturation when the attenuation A(&lgr;) and its slope &Dgr;A(&lgr;)/&Dgr;&rgr; are evaluated. Furthermore, the different depth sensitivities of these measurement parameters are estimated from Monte Carlo simulations and exploited for an optimization of the cerebral signals. It is demonstrated that the system does record cerebral oxygenation parameters during CPB in infants. In particular, the correlation of haemoglobin concentrations with blood supply (flow, pressure) by the heart-lung machine and the significant decreases in oxygen saturation during cardiac arrest is discussed.

Spectroscopic measurement of Adipose Tissue Thickness and comparison with Ultrasound Imaging

Near-infrared spectroscopy (NIRS) is widely applied for applications monitoring skeletal muscle oxygenation. However, this method is obstructed by the subcutaneous adipose tissue thickness (ATT) which might vary between < 1 mm to more than 12 mm. Though diffuse optical imaging can be applied to measure ATT, the objective here is to get this measure from spectroscopic data of a single source-detector distance. For the measurement of the optical lipid signal we used a broad band spatially resolved system (SRS), which is based on measurements of the wavelength dependence of the attenuation A for source detector distances &rgr; between 29 mm and 39 mm. Ultrasound images served as an anatomical reference of the lipid layer. The measurements were taken on 5 different muscle groups of 20 healthy volunteers, each for left and right limbs, e.g. vastus medialis, vastus lateralis and gastrocnemius muscle on the leg and ventral forearm muscles and biceps brachii muscle on the arm. Different analysis strategies were tested for the best calculation of ATT. There is a good non-linear correlation between optical lipid signal and ultrasound data, with an overall error in ATT prediction of about 0.5 mm. This finding is supported experimentally by additional MRI measurements as well as a multi-layer Monte Carlo (MC) model. Based on this data of the ATT thickness, a newly developed algorithm which exploits the wavelength dependence of the slope in attenuation with respect to source-detector distance and MC simulation for these parameters as a function of absorption and scattering coefficients delivers a considerably better fit of reflectance spectra when fitting haemoglobin concentrations. Implications for the monitoring of muscle oxygen saturation are discussed.

Tissue oxygenation during exercise measured with NIRS: a quality control study

We assess the data quality of calculated tissue oxygen saturation (SO2) and haemoglobin concentrations recorded on muscle during an incremental cycling protocol in healthy volunteers. The protocol was repeated three times at the same day and a fourth time at a different day to estimate the reproducibility of the method. A novel broad-band, spatially resolved spectrometer (SRS) system was employed which allowed us to compare SRS-based oxygenation parameters with modified Lambert-Beer (MLB) data. We found that the inter-subject variation in SO2 (standard deviation about 6 %) is considerably larger than the reproducibility (about 1.5 %) both for same day and different day tests. When changes in SO2 during the cycling test were considered the reproducibility is better than 1 %. Time courses of SRS-based haemoglobin parameters are different from MLB-data with higher reproducibility for SRS. The magnitudes of the haemoglobin changes were found to be considerably larger for the SRS method. Furthermore, the broad band approach was tested against a four-wavelength analysis with the differences found to be negligible.

Muscle Oxygenation During Running Assessed by Broad Band NIRS

We used spatially resolved near-infrared spectroscopy (SRS-NIRS) to assess calf and thigh muscle oxygenation during running on a motor-driven treadmill. Two protocols were used: An incremental speed protocol was performed in 5-min stages, while a pacing paradigm modulated the step frequency (2.3xa0Hz [SLow]; 3.3xa0Hz [SHigh]) during a constant velocity for 2xa0min each. A SRS-NIRS broadband system was used to measure total haemoglobin concentration and oxygen saturation (SO2). An accelerometer was placed on the hip joints to measure limb acceleration through the experiment. The data showed that the calf desaturated to a significantly lower level than the thigh. During the pacing protocol, SO2 was significantly different between the high and low step frequencies. Additionally, physiological data as measured by spirometry were different between the SLow vs. SHigh pacing trials. Significant differences in VO2 at the same workload (speed) indicate alterations in mechanical efficiency. These data suggest that SRS broadband NIRS can be used to discern small changes in muscle oxygenation, making this device useful for metabolic exercise studies in addition to spirometry and movement monitoring by accelerometers.

Wavelength selection for the improvement of the signal to noise ratio for imaging of haemoglobin oxygenation with RGB reflectometry

We demonstrate the optimisation of wavelengths for the imaging of cortical haemoglobin oxygenation with broadband RGB reflectometry. Wavelengths were chosen in order to minimise the likely crosstalk and optimise the signal-to-noise ratio by simulating effects of different combinations of wavelengths on the condition number of the resulting extinction coefficient matrices. The results obtained were evaluated experimentally for four combinations of commercially available LED combinations and compared with data from the literature.