DOT-NIRS-University College London Delpy 2004-2000

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

Binzoni T, Leung T, Delpy DT, Fauci MA, Rüfenacht D.

Department of Radiology, Faculty of Medicine, University of Geneva, Switzerland. Tiziano.Binzoni@medecine.unige.ch

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.

Publication Types:

PMID: 15272688 [PubMed – indexed for MEDLINE]


Spectral characteristics of spontaneous oscillations in cerebral haemodynamics are posture dependent.

Tachtsidis I, Elwell CE, Lee CW, Leung TS, Smith M, Delpy DT.

Department of Medical Physics & Bioengineering, University College London, London WC1E 6JA, UK. iliastac@medphys.ucl.ac.uk

Publication Types:

PMID: 15174599 [PubMed – indexed for MEDLINE]


Measurement of the optical properties of the adult human head with spatially resolved spectroscopy and changes of posture.

Leung TS, Elwell CE, Tachtsidis I, Henty JR, Delpy DT.

Department of Medical Physics & Bioengineering, University College London, London WC1E 6JA, UK. tsl@medphys.ucl.ac.uk

Publication Types:

PMID: 15174596 [PubMed – indexed for MEDLINE]


Investigation of cerebral haemodynamics by near-infrared spectroscopy in young healthy volunteers reveals posture-dependent spontaneous oscillations.

Tachtsidis I, Elwell CE, Leung TS, Lee CW, Smith M, Delpy DT.

Department of Medical Physics and Bioengineering, University College London, London WC1E 6JA, UK. iliastac@medphys.ucl.ac.uk

Autonomic reflexes enable the cardiovascular system to respond to gravitational displacement of blood during changes in posture. Spontaneous oscillations present in the cerebral and systemic circulation of healthy subjects have demonstrated a regulatory role. This study assessed the dynamic responses of the cerebral and systemic circulation upon standing up and the posture dependence of spontaneous oscillations. In ten young healthy volunteers, blood pressure and cerebral haemodynamics were continuously monitored non-invasively using the Portapres and near-infrared spectroscopy (NIRS), respectively. Oscillatory changes in the cerebral NIRS signals and the diastolic blood pressure (DBP) signal have been identified by the fast Fourier analysis. Blood pressure increased during standing and returned to basal level when volunteers sat on a chair. The mean value of cerebral tissue oxygen index (TOI) as measured by NIRS did not demonstrate any significant changes. Oscillatory changes in DBP, oxyhaemoglobin concentration [O2Hb] and TOI showed a significant increase when subjects were standing. Investigation of the low frequency component (approximately 0.1 Hz) of these fluctuations revealed posture dependence associated with activation of autonomic reflexes. Systemic and cerebral changes appeared to preserve adequate blood flow and cerebral perfusion during standing in healthy volunteers. Oscillatory changes in [O2Hb] and TOI, which may be related to the degree of cerebral sympathetic stimulation, are posture dependent in healthy subjects.

Publication Types:

PMID: 15132309 [PubMed – indexed for MEDLINE]


Monitoring cytochrome redox changes in the mitochondria of intact cells using multi-wavelength visible light spectroscopy.

Hollis VS, Palacios-Callender M, Springett RJ, Delpy DT, Moncada S.

Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London, WC1E 6AE, UK.

We have developed an optical system based on visible light spectroscopy for the continuous study of changes in the redox states of mitochondrial cytochromes in intact mammalian cells. Cells are suspended in a closed incubation chamber in which oxygen and nitric oxide (NO) concentrations can be monitored during respiration. Simultaneously the cells are illuminated with a broad-band tungsten-halogen light source. Emergent light in the visible region (from 490-650 nm) is detected using a spectrophotometer and charge-coupled device camera system. Intensity spectra are then converted into changes in optical attenuation from a ‘steady-state’ baseline. The oxidised-minus-reduced absorption spectra of the mitochondrial cytochromes are fitted to the attenuation spectra using a multi-wavelength least-squares algorithm. Thus, the system can measure changes in the redox states of the cytochromes during cellular respiration. Here we describe this novel methodology and demonstrate its validity by monitoring the action of known respiratory chain inhibitors, including the endogenous signalling molecule NO, on cytochrome redox states in human leukocytes.

Publication Types:

PMID: 14670609 [PubMed – indexed for MEDLINE]


The oxygen dependency of cerebral oxidative metabolism in the newborn piglet studied with 31P NMRS and NIRS.

Springett RJ, Wylezinska M, Cady EB, Hollis V, Cope M, Delpy DT.

Department of Radiology, Dartmouth College, Hanover, New Hampshire, USA.

Mean cerebral saturation and changes in the oxidation state of the CuA centre of cytochrome oxidase were measured by near infra-red spectroscopy simultaneously with phosphorous metabolites and intracellular pH measured using 31P NMR spectroscopy during transient anoxia (inspired oxygen fraction = 0.0 for 105 seconds) in the newborn piglet brain. By collecting high quality 31P spectra every 10 seconds, it was possible to resolve the delay between the onset of anoxia and the fall in PCr and to show that the CuA centre of cytochrome oxidase reduced simultaneously with the fall in PCr. From these observations it is concluded that, at normoxia, oxygen tension at the mitochondrial level is substantially above a critical value at which oxidative metabolism becomes oxygen dependent.

Publication Types:

PMID: 14562751 [PubMed – indexed for MEDLINE]


Near-infrared light propagation in an adult head model. II. Effect of superficial tissue thickness on the sensitivity of the near-infrared spectroscopy signal.

Okada E, Delpy DT.

Department of Electronics and Electrical Engineering, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan. okada@elec.keio.ac.jp

It is important for near-infrared spectroscopy (NIRS) and imaging to estimate the sensitivity of the detected signal to the change in hemoglobin that results from brain activation and the volume of tissue interrogated for a specific source-detector fiber spacing. In this study light propagation in adult head models is predicted by Monte Carlo simulation to investigate the effect of the superficial tissue thickness on the partial optical path length in the brain and on the spatial sensitivity profile. In the case of source-detector spacing of 30 mm, the partial optical path length depends mainly on the depth of the inner skull surface whereas the spatial sensitivity profile is significantly affected by the thickness of the cerebrospinal fluid layer. The mean optical path length that can be measured by time-resolved experiments increases when the skull thickness increases whereas the partial mean optical path length in the brain decreases when the skull thickness increases. These results indicate that it is not appropriate to use the mean optical path length as an alternative to the partial optical path length to compensate the NIRS signal for the difference in sensitivity caused by variation of the superficial tissue thickness.

Publication Types:

PMID: 12790440 [PubMed – indexed for MEDLINE]


Near-infrared light propagation in an adult head model. I. Modeling of low-level scattering in the cerebrospinal fluid layer.

Okada E, Delpy DT.

Department of Electronics and Electrical Engineering, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan. okada@elec.keio.ac.jp

Adequate modeling of light propagation in a human head is important for quantitative near-infrared spectroscopy and optical imaging. The presence of a nonscattering cerebrospinal fluid (CSF) that surrounds the brain has been previously shown to have a strong effect on light propagation in the head. However, in reality, a small amount of scattering is caused by the arachnoid trabeculae in the CSF layer. In this study, light propagation in an adult head model with discrete scatterers distributed within the CSF layer has been predicted by Monte Carlo simulation to investigate the effect of the small amount of scattering caused by the arachnoid trabeculae in the CSF layer. This low scattering in the CSF layer is found to have little effect on the mean optical path length, a parameter that can be directly measured by a time-resolved experiment. However, the partial optical path length in brain tissue that relates the sensitivity of the detected signal to absorption changes in the brain is strongly affected by the presence of scattering within the CSF layer. The sensitivity of the near-infrared signal to hemoglobin changes induced by brain activation is improved by the effect of a low-scattering CSF layer.

Publication Types:

PMID: 12790439 [PubMed – indexed for MEDLINE]


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

Gibson AP, Riley J, Schweiger M, Hebden JC, Arridge SR, Delpy DT.

Department of Medical Physics and Bioengineering, University College London, UK.

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.

Publication Types:

PMID: 12630743 [PubMed – indexed for MEDLINE]


Simultaneous measurement of cerebral tissue oxygenation over the adult frontal and motor cortex during rest and functional activation.

Leung TS, Elwell CE, Henty JR, Delpy DT.

Department of Medical Physics & Bioengineering, University College London, London, WC1E 6JA, UK.

Publication Types:

PMID: 12580459 [PubMed – indexed for MEDLINE]


Three-dimensional optical tomography of the premature infant brain.

Hebden JC, Gibson A, Yusof RM, Everdell N, Hillman EM, Delpy DT, Arridge SR, Austin T, Meek JH, Wyatt JS.

Department of Medical Physics & Bioengineering, University College London, 11-20 Capper Street, London WC1E 6JA, UK.

For the first time, three-dimensional images of the newborn infant brain have been generated using measurements of transmitted light. A 32-channel time-resolved imaging system was employed, and data were acquired using custom-made helmets which couple source fibres and detector bundles to the infant head. Images have been reconstructed using measurements of mean flight time relative to those acquired on a homogeneous reference phantom, and using a head-shaped 3D finite-element-based forward model with an external boundary constrained to match the measured positions of the sources and detectors. Results are presented for a premature infant with a cerebral haemorrhage predominantly located within the left ventricle. Images representing the distribution of absorption at 780 nm and 815 nm reveal an asymmetry consistent with the haemorrhage, and corresponding maps of blood volume and fractional oxygen saturation are generally within expected physiological values.

Publication Types:

PMID: 12502040 [PubMed – indexed for MEDLINE]


Quantitative near infrared spectroscopy measurement of cerebral hemodynamics in newborn piglets.

Brown DW, Picot PA, Naeini JG, Springett R, Delpy DT, Lee TY.

Imaging Division, Lawson Health Research Institute, London, Ontario, Canada, N6A 4V2.

Severely premature infants are often at increased risk of cerebral hemorrhage and/or ischemic injury caused by immature autoregulatory control of blood flow to the brain. If blood flow is too high, the infant is at risk of hemorrhage, whereas too little blood flow can result in ischemic injury. The development of a noninvasive, bedside means of measuring cerebral hemodynamics would greatly facilitate both diagnosis and monitoring of afflicted individuals. It is to this end that we have developed a near infrared spectroscopy (NIRS) system that allows for quantitative, bedside measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). The technique requires an i.v. injection of the near infrared chromophore indocyanine green. Six newborn piglets, median age of 18 h (range 6-54 h), median weight of 1.75 kg (range 1.5-2.1 kg), were studied. Measurements of CBF, CBV, and MTT were made at normocapnia, hypocapnia, and hypercapnia to test the technique over a range of hemodynamic conditions. The accuracy of our new approach has been determined by direct comparison with measurements made using a previously validated computed tomography technique. Paired t tests showed no significant difference between computed tomography and NIRS measurements of CBF, CBV, and MTT, and mean biases between the two methods were -2.05 mL x min(-1) x 100 g(-1), -0.18 mL x 100 g(-1), and 0.43 s, respectively. The precision of NIRS CBF, CBV, and MTT measurements, as determined by repeated-measures ANOVA, was 9.71%, 13.05%, and 7.57%, respectively.

Publication Types:

PMID: 11978878 [PubMed – indexed for MEDLINE]


Nitric oxide does not inhibit cerebral cytochrome oxidase in vivo or in the reactive hyperemic phase after brief anoxia in the adult rat.

De Visscher G, Springett R, Delpy DT, Van Reempts J, Borgers M, van Rossem K.

Department of Neuropathology, Discovery Research, Janssen Research Foundation, Turnhoutseweg 30, B-2340 Beerse, Belgium. gdvissch@janbe.jnj.com

In this study, near-infrared spectroscopy was applied to examine whether cytochrome oxidase in the rat brain is inhibited by nitric oxide in vivo. During normoxia, intravenous N(G)-nitro-L-arginine methyl ester (L-NAME) administration significantly decreased the cerebral saturation of hemoglobin with oxygen but did not alter the cytochrome oxidase redox state. Anoxia significantly reduced the cytochrome oxidase. The time course of the recovery of the redox state during reoxygenation was not altered by L-NAME. The results suggest that in adult rats, cytochrome oxidase is not inhibited by nitric oxide, either in physiologic conditions or during reoxygenation after a brief anoxic period.

PMID: 11973423 [PubMed – indexed for MEDLINE]


Local temperature changes and human skeletal muscle metabolism.

Binzoni T, Delpy D.

Departments of Radiology and Physiology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

The aim of this review is to describe the effects induced by local temperature changes on human skeletal muscle metabolism. More specifically, we will consider the influence of temperature on the mechanical properties of muscle contraction, on aerobic metabolism, anaerobic metabolism and on the Lohmann reaction. The text has been voluntarily organized on the basis of a simple bioenergetic model describing the different energy fluxes appearing in the muscle system. This approach should better highlight some of the points that still need to be investigated. Although it was not always possible to restrict the discussion to human muscle, the references report mainly data obtained directly on humans or on isolated human fibres. A short comment on skeletal muscle temperature measurement techniques, on humans, is also included.

Publication Types:

PMID: 11499164 [PubMed – indexed for MEDLINE]


Time resolved optical tomography of the human forearm.

Hillman EM, Hebden JC, Schweiger M, Dehghani H, Schmidt FE, Delpy DT, Arridge SR.

Department of Medical Physics and Bioengineering, University College London, UK.

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.

Publication Types:

PMID: 11324955 [PubMed – indexed for MEDLINE]


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

Springett R, Newman J, Cope M, Delpy DT.

Department of Medical Physics and Bioengineering, University College London, London WC1E 6JA, United Kingdom. rspringett@medphys.ucl.ac.uk

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.

Publication Types:

PMID: 11045954 [PubMed – indexed for MEDLINE]


Optical tomography in the presence of void regions

Dehghani H, Arridge SR, Schweiger M, Delpy DT.

Department of Medical Physics and Bioengineering, University College London, United Kingdom.

There is a 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 the use of this technique for obtaining tomographic images of the neonatal head, with the view of determining the levels of oxygenated and deoxygenated blood within the brain. Owing to 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 location; therefore it is instructive to examine the errors introduced in applying a simple diffusion-based reconstruction scheme in cases in which there exists a nonscattering region. We present reconstructed images of objects that contain a nonscattering region within a diffusive material. Here the forward data is calculated with the radiosity-diffusion model, and the inverse problem is solved with either the radiosity-diffusion model or the diffusion-only model. The reconstructed images show that even in the presence of only a thin nonscattering layer, a diffusion-only reconstruction will fail. When a radiosity-diffusion model is used for image reconstruction, together with a priori information about the position of the nonscattering region, the quality of the reconstructed image is considerably improved. The accuracy of the reconstructed images depends largely on the position of the anomaly with respect to the nonscattering region as well as the thickness of the nonscattering region.

PMID: 10975376 [PubMed – as supplied by publisher]

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