Synchronization between arterial blood pressure and cerebral oxyhaemoglobin concentration investigated by wavelet cross-correlation.

Wavelet cross-correlation (WCC) is used to analyse the relationship between low-frequency oscillations in near-infrared spectroscopy (NIRS) measured cerebral oxyhaemoglobin (O(2)Hb) and mean arterial blood pressure (MAP) in patients suffering from autonomic failure and age-matched controls. Statistically significant differences are found in the wavelet scale of maximum cross-correlation upon posture change in patients, but not in controls. We propose that WCC analysis of the relationship between O(2)Hb and MAP provides a useful method of investigating the dynamics of cerebral autoregulation using the spontaneous low-frequency oscillations that are typically observed in both variables without having to make the assumption of stationarity of the time series. It is suggested that for a short-duration clinical test previous transfer-function-based approaches to analyse this relationship may suffer due to the inherent nonstationarity of low-frequency oscillations that are observed in the resting brain.

Investigation of in vivo measurement of cerebral cytochrome-c-oxidase redox changes using near-infrared spectroscopy in patients with orthostatic hypotension.

We have previously used a continuous four-wavelength near-infrared spectrometer to measure changes in the cerebral concentrations of oxy-haemoglobin (Delta[HbO(2)] and deoxy-haemoglobin (Delta[HHb]) during head-up tilt in patients with primary autonomic failure. The measured changes in light attenuation also allow calculation of changes in the concentration of oxidized cytochrome-c-oxidase (Delta[(ox)CCO]), and this paper analyses the Delta[(ox)CCO] during the severe episodes of orthostatic hypotension produced by this experimental protocol. We studied 12 patients during a passive change in position from supine to a 60 degrees head-up tilt. The challenge caused a reduction in mean blood pressure of 59.93 (+/-26.12) mmHg (Mean (+/-SD), p < 0.0001), which was associated with a reduction in the total concentration of haemoglobin (Delta[HbT] = Delta[HbO(2)] + Delta[HHb]) of 5.02 (+/-3.81) microM (p < 0.0001) and a reduction in the haemoglobin difference concentration (Delta[Hb(diff)] = Delta[HbO(2)] - Delta[HHb]) of 14.4 (+/-6.73) microM (p < 0.0001). We observed a wide range of responses in Delta[(ox)CCO]. Six patients demonstrated a drop in Delta[(ox)CCO] (0.17 +/- 0.15 microM); four patients demonstrated no change (0.01 +/- 0.12 microM) and two patients showed an increase in Delta[(ox)CCO] (0.21 +/- 0.01 microM). Investigation of the association between the changes in concentrations of haemoglobin species and the Delta[(ox)CCO] for each patient show a range of relationships. This suggests that a simple mechanism for crosstalk, which might produce artefactual changes in [(ox)CCO], is not present between the haemoglobin and the (ox)CCO NIRS signals. Further investigation is required to determine the clinical significance of the changes in [(ox)CCO].

Comment on 'the use of the Henyey-Greenstein phase function in Monte Carlo simulations in biomedical optics'.

In this letter the authors highlight the presence of an error appearing in the discussion of the note 'The use of the Henyey-Greenstein phase function in Monte Carlo simulations in biomedical optics' previously published by them (Binzoni et al 2006 Phys. Med. Biol. 51 N313). In the light of this error, the discussion and conclusions in the original paper are revised in this letter and the role of the use of the phase functions in MC simulations, interpreted in probabilistic terms, is better clarified. The exact definition for the probability density function for the deflection angle, in the case of the Henyey-Greenstein model, is also given.

The use of the Henyey-Greenstein phase function in Monte Carlo simulations in biomedical optics.

Monte Carlo (MC) simulations are often at the heart of the testing procedure in biomedical optics. One of the critical points in MC simulations is to define the new photon direction after each scattering event. One of the most popular solutions is to use the Henyey-Greenstein phase function or some linear combinations of it. In this note, we demonstrate that randomly generating the angle defining the new direction of a photon after a collision, by means of the Henyey-Greenstein phase function, is not equivalent to generating the cosine of this angle, as is classically done. In practice, it is demonstrated that for a nearly isotropic medium (asymmetry parameter g approximately 0) this discrepancy is not large, however for an anisotropic medium as is typically found in vivo (e.g. g = 0.98) the two methods give completely different results.

Three dimensional optical imaging of blood volume and oxygenation in the neonatal brain.

Optical methods provide a means of monitoring cerebral oxygenation in newborn infants at risk of brain injury. A 32-channel optical imaging system has been developed with the aim of reconstructing three-dimensional images of regional blood volume and oxygenation. Full image data sets were acquired from 14 out of 24 infants studied; successful images have been reconstructed in 8 of these infants. Regional variations in cerebral blood volume and tissue oxygen saturation are present in healthy preterm infants. In an infant with a large unilateral intraventricular haemorrhage, a corresponding region of low oxygen saturation was detected. These results suggest that optical tomography may provide an appropriate technique for investigating regional cerebral haemodynamics and oxygenation at the cotside.

Anisotropic photon migration in human skeletal muscle.

It is demonstrated in the short head of the human biceps brachii of 16 healthy subjects (12 males and 4 females) that near infrared photon migration is anisotropic. The probability for a photon to travel along the direction of the muscle fibres is higher (approximately 0.4) than that of travelling along a perpendicular axis (approximately 0.3) while in the adipose tissue the probability is the same (approximately 0.33) in all directions. Considering that the muscle fibre orientation is different depending on the type of muscle considered, and that inside a given skeletal muscle the orientation may change, the present findings in part might explain the intrasubject variability observed in the physiological parameters measured by near infrared spectroscopy techniques. In other words, the observed regional differences might not only be physiological differences but also optical artefacts.

Absorption and scattering coefficient dependence of laser-Doppler flowmetry models for large tissue volumes.

Based on quasi-elastic scattering theory (and random walk on a lattice approach), a model of laser-Doppler flowmetry (LDF) has been derived which can be applied to measurements in large tissue volumes (e.g. when the interoptode distance is >30 mm). The model holds for a semi-infinite medium and takes into account the transport-corrected scattering coefficient and the absorption coefficient of the tissue, and the scattering coefficient of the red blood cells. The model holds for anisotropic scattering and for multiple scattering of the photons by the moving scatterers of finite size. In particular, it has also been possible to take into account the simultaneous presence of both Brownian and pure translational movements. An analytical and simplified version of the model has also been derived and its validity investigated, for the case of measurements in human skeletal muscle tissue. It is shown that at large optode spacing it is possible to use the simplified model, taking into account only a 'mean' light pathlength, to predict the blood flow related parameters. It is also demonstrated that the 'classical' blood volume parameter, derived from LDF instruments, may not represent the actual blood volume variations when the investigated tissue volume is large. The simplified model does not need knowledge of the tissue optical parameters and thus should allow the development of very simple and cost-effective LDF hardware.

Three-dimensional whole-head optical tomography of passive motor evoked responses in the neonate.

Optical tomography has been used to reconstruct three-dimensional images of the entire neonatal head during motor evoked responses. Data were successfully acquired during passive movement of each arm on four out of six infants examined, from which eight sets of bilateral images of hemodynamic parameters were reconstructed. Six out of the eight images showed the largest change in total hemoglobin in the region of the contralateral motor cortex. The mean distance between the peak response in the image and the estimated position of the contralateral motor cortex was 10.8 mm. These results suggest that optical tomography may provide an appropriate technique for non-invasive cot-side imaging of brain function.

Mapping human skeletal muscle perforator vessels using a quantum well infrared photodetector (QWIP) might explain the variability of NIRS and LDF measurements.

Near-infrared spectroscopy (NIRS) and laser Doppler flowmetry (LDF) have become the techniques of choice allowing the non-invasive study of local human skeletal muscle metabolism and blood perfusion on a small tissue volume (a few cm3). However, it has been shown that both NIRS and LDF measurements may show a large spatial variability depending on the position of the optodes over the investigated muscle. This variability may be due to local morphologic and/or metabolic characteristics of the muscle and makes the data interpretation and comparison difficult. In the present work, we use a third method to investigate this problem which permits fast, non-invasive mapping of the intramuscular vessel distribution in the human vastus latelralis muscle. This method uses an advanced, passive, infrared imaging sensor called a QWIP (quantum well infrared photodetector). We demonstrate, using a recovery-enhanced infrared imaging technique, that there is a significant presence of perforator vessels in the region of interest of approximately 30 x 18 cm (the number of vessels being: 14, 9, 8, 33, 17 and 18 for each subject, respectively). The presence of these vessels makes the skeletal muscle highly inhomogeneous, and may explain the observed NIRS and LDF spatial variability. We conclude that accurate comparison of the metabolic activity of two different muscle regions is not possible without reliable maps of vascular 'singularities' such as the perforator vessels, and that the QWIP-based imaging system is one method to obtain this information.

Translational and Brownian motion in laser-Doppler flowmetry of large tissue volumes.

This study reports the derivation of a precise mathematical relationship existing between the different p-moments of the power spectrum of the photoelectric current, obtained from a laser-Doppler flowmeter (LDF), and the red blood cell speed. The main purpose is that both the Brownian (defining the 'biological zero') and the translational movements are taken into account, clarifying in this way what the exact contribution of each parameter is to the LDF derived signals. The derivation of the equations is based on the quasi-elastic scattering theory and holds for multiple scattering (i.e. measurements in large tissue volumes and/or very high red blood cell concentration). The paper also discusses why experimentally there exists a range in which the relationship between the first moment of the power spectrum and the average red blood cells speed may be considered as 'linear' and what are the physiological determinants that can result in nonlinearity. A correct way to subtract the biological zero from the LDF data is also proposed. The findings should help in the design of improved LDF instruments and in the interpretation of experimental data.

A method for generating patient-specific finite element meshes for head modelling.

Finite element modelling of fields within the body, whether electrical or optical, requires knowledge of the geometry of the object being examined. It can be clinically impractical to obtain accurate surface information for individual patients, although a limited set of measurements such as the locations of sensors attached to the body, can be acquired more readily. In this paper, we describe how a generic surface taken from an adult head is warped to fit points measured on a neonatal head surface to provide a new, individual surface from which a finite element mesh was generated. Simulations show that data generated from this mesh and from the original neonatal head surface are similar to within experimental errors. However, data generated from a mesh of the best fit sphere were significantly different from data generated from the original neonatal head surface.

Linear single-step image reconstruction in the presence of nonscattering regions.

There is growing interest in the use of near-infrared spectroscopy for the noninvasive determination of the oxygenation level within biological tissue. Stemming from this application, there has been further research in using this technique for obtaining tomographic images of the neonatal head, with the view of determining the level of oxygenated and deoxygenated blood within the brain. Because of computational complexity, methods used for numerical modeling of photon transfer within tissue have usually been limited to the diffusion approximation of the Boltzmann transport equation. The diffusion approximation, however, is not valid in regions of low scatter, such as the cerebrospinal fluid. Methods have been proposed for dealing with nonscattering regions within diffusing materials through the use of a radiosity-diffusion model. Currently, this new model assumes prior knowledge of the void region; therefore it is instructive to examine the errors introduced in applying a simple diffusion-based reconstruction scheme in cases where a nonscattering region exists. We present reconstructed images, using linear algorithms, of models that contain a nonscattering region within a diffusing material. The forward data are calculated by using the radiosity-diffusion model, and the inverse problem is solved by using either the radiosity-diffusion model or the diffusion-only model. When using data from a model containing a clear layer and reconstructing with the correct model, one can reconstruct the anomaly, but the qualitative accuracy and the position of the reconstructed anomaly depend on the size and the position of the clear regions. If the inverse model has no information about the clear regions (i.e., it is a purely diffusing model), an anomaly can be reconstructed, but the resulting image has very poor qualitative accuracy and poor localization of the anomaly. The errors in quantitative and localization accuracies depend on the size and location of the clear regions.

Effect of graded hypoxia on the rat hepatic tissue oxygenation and energy metabolism monitored by near-infrared and 31P nuclear magnetic resonance spectroscopy.

Alteration in hepatic cellular adenosine triphosphate (ATP) levels has been shown to be a sensitive index for hypoxic damage. Hepatic ATP metabolism can be monitored by 31P nuclear magnetic resonance (NMR). Near-infrared spectroscopy (NIRS) can measure tissue oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), and cytochrome oxidase (Cyt Ox), which reflect ATP production. In this study, hepatic oxygenation parameters have been correlated with ATP metabolism under graded hypoxia. Sprague-Dawley rats underwent laparotomy for liver exposure. NIRS probes and an NMR coil were placed on the liver and the animal was positioned in the NMR magnet. Graded hypoxia was achieved by a stepwise reduction of the fraction of inspired oxygen (FiO2) from 15 to 4%. Recovery between the hypoxic periods was achieved using 30% oxygen. Hepatic tissue oxygenation parameters were measured continuously by NIRS; 31P-NMR spectra obtained at 1 min intervals from energy metabolites and intracellular pH were calculated. All the hypoxic grades produced an immediate reduction in HbO2 with a simultaneous increase in Hb. Cyt Ox was reduced significantly only with FiO2 of

Precise measurement of cerebral blood flow in newborn piglets from the bolus passage of indocyanine green.

Indocyanine green (ICG) is a near-infrared dye that has the potential to be used as a tracer for the minimally invasive measurement of cerebral blood flow (CBF). In order to examine the technique, the arterial and cerebral concentrations of ICG were measured in newborn piglets during the bolus passage of ICG at normocapnia and two levels of mild hypercapnia. The results were analysed by applying the Fick principle in both integral and differential forms using a linear regression technique to improve the precision of calculated values of CBF. It was found that the integral method, which has been used previously, is particularly sensitive to errors in the time registration between the arterial and tissue signals whereas the differential method is less so. In addition, the differential method allows the venous outflow to be calculated which gives further information on the state of the capillary bed. CBF was 39.7 +/- 4.6 ml 100 g(-1) min(-1) at an arterial carbon dioxide tension (PaCO2) of 33.0+/-2.2 mmHg and increased to 53.7+/-9.1 and 75.4+/-15.2 ml 100 g(-1) min(-1) at a PaCO2 of 42.1 +/- 2.6 and 54.2 +/- 3.1 mmHg respectively (mean +/- SD, n = 7). There was no significant change in cerebral metabolic rate for oxygen, validating the value of blood flow to an arbitrary scaling factor. When the inspired CO2 fraction was returned to zero, calculated CBF returned to baseline with a variation of 7% of the mean, indicating that this technique is highly precise.

Time resolved optical tomography of the human forearm.

A 32-channel time-resolved optical imaging instrument has been developed principally to study functional parameters of the new-born infant brain. As a prelude to studies on infants, the device and image reconstruction methodology have been evaluated on the adult human forearm. Cross-sectional images were generated using time-resolved measurements of transmitted light at two wavelengths. All data were acquired using a fully automated computer-controlled protocol. Images representing the internal scattering and absorbing properties of the arm are presented, as well as images that reveal physiological changes during a simple finger flexion exercise. The results presented in this paper represent the first simultaneous tomographic reconstruction of the internal scattering and absorbing properties of a clinical subject using purely temporal data, with additional co-registered difference images showing repeatable absorption changes at two wavelengths in response to exercise.

Assessment of hepatic ischaemia reperfusion injury by measuring intracellular tissue oxygenation using near infrared spectroscopy.

AIMS/BACKGROUND: Hepatic ischaemia/reperfusion (I/R) injury is a major cause of liver damage during liver surgery and transplantation. The relationship between the severity of I/R injury and the degree of intracellular hypoxia has not been investigated. METHODS: New Zealand white rabbits were used in 4 groups (n=6 each). At laparotomy, left lobe hepatic ischaemia was produced for 30, 45, or 60 min followed by 60 min reperfusion and compared with controls. Liver function, bile flow, and flow in the hepatic microcirculation (HM) were measured. Near infrared spectroscopy (NIRS) was used to monitor hepatic oxyhaemoglobin (HbO2), deoxyhaemoglobin (Hb), and cytochrome oxidase (Cyt Ox). RESULTS: I/R injury produced deranged liver function tests, reduced bile flow, and reduced flow in the microcirculation in comparison with controls. During ischaemia, HbO2 and Cyt Ox were significantly reduced in comparison with controls. After reperfusion, a biphasic change in tissue oxygenation was observed, with an initial increase in HbO2 and Cyt Ox followed by a progressive reduction. The reduction in tissue oxygenation with ischaemia and reperfusion paralleled the ischaemia time. After I/R, the changes in Cyt Ox (intracellular oxygenation) significantly correlated with the parameters of hepatocellular injury to a higher degree than HbO2 (extracellular oxygenation). CONCLUSION: This study shows the potential of monitoring the degree of I/R injury by measuring hepatic tissue intracellular oxygenation.

Three-dimensional time-resolved optical tomography of a conical breast phantom.

A 32-channel time-resolved imaging device for medical optical tomography has been employed to evaluate a scheme for imaging the human female breast. The fully automated instrument and the reconstruction procedure have been tested on a conical phantom with tissue-equivalent optical properties. The imaging protocol has been designed to obviate compression of the breast and the need for coupling fluids. Images are generated from experimental data with an iterative reconstruction algorithm that employs a three-dimensional (3D) finite-element diffusion-based forward model. Embedded regions with twice the background optical properties are revealed in separate 3D absorption and scattering images of the phantom. The implications for 3D time-resolved optical tomography of the breast are discussed.

Oxygen dependency and precision of cytochrome oxidase signal from full spectral NIRS of the piglet brain.

Oxidation changes of the copper A (Cu(A)) center of cytochrome oxidase in the brain were measured during brief anoxic swings at both normocapnia and hypercapnia (arterial PCO(2) approximately 55 mmHg). Hypercapnia increased total hemoglobin from 37.5 +/- 9.1 to 50.8 +/- 12.9 micromol/l (means +/- SD; n = 7), increased mean cerebral saturation (Smc(O(2))) from 65 +/- 4 to 77 +/- 3%, and oxidized Cu(A) by 0.43 +/- 0.23 micromol/l. During the onset of anoxia, there were no significant changes in the Cu(A) oxidation state until Smc(O(2)) had fallen to 43 +/- 5 and 21 +/- 6% at normocapnia and hypercapnia, respectively, and the maximum reduction during anoxia was not significantly different at hypercapnia (1.49 +/- 0.40 micromol/l) compared with normocapnia (1.53 +/- 0.44 micromol/l). Residuals of the least squares fitting algorithm used to convert near-infrared spectra to concentrations are presented and shown to be small compared with the component of attenuation attributed to the Cu(A) signal. From these observations, we conclude that there is minimal interference between the hemoglobin and Cu(A) signals in this model, the Cu(A) oxidation state is independent of cerebral oxygenation at normoxia, and the oxidation after hypercapnia is not the result of increased cerebral oxygenation.

Oxygen dependency of cerebral oxidative phosphorylation in newborn piglets.

Changes in hemoglobin oxygenation and oxidation state of the CuA centre of cytochrome oxidase were measured with full spectral near infrared spectroscopy simultaneously with phosphorus metabolites using nuclear magnetic resonance 31P spectroscopy at high time resolution (10 seconds) during transient anoxia (FiO2 = 0.0 for 105 seconds) in the newborn piglet brain. During the onset of anoxia, there was no change in either phosphocreatine (PCr) concentration or the oxidation state of the CuA centre of cytochrome oxidase until there was a substantial fall in cerebral hemoglobin oxygenation, at which point the CuA centre reduced simultaneously with the decline in PCr. At a later time during the anoxia, intracellular pH decreased rapidly, consistent with a fall in cerebral metabolic rate for O2 and reduced flux through the tricarboxylic acid cycle. The simultaneous reduction of CuA and decline in PCr can be explained in terms of the effects of the falling mitochondrial electrochemical potential. From these observations, it is concluded that, at normoxia, oxidative phosphorylation and the oxidation state of the components of the electron transport chain are independent of cerebral oxygenation and that the reduction in the CuA signal occurs when oxygen tension limits the capacity of oxidative phosphorylation to maintain the phosphorylation potential.