DOT-NIRS-University College London-Delpy 1999-1988

Use of mitochondrial inhibitors to demonstrate that cytochrome oxidase near-infrared spectroscopy can measure mitochondrial dysfunction noninvasively in the brain.

Cooper CE, Cope M, Springett R, Amess PN, Penrice J, Tyszczuk L, Punwani S, Ordidge R, Wyatt J, Delpy DT.

Department of Biological Sciences, University of Essex, Colchester, UK.

The use of near-infrared spectroscopy to measure noninvasively changes in the redox state of cerebral cytochrome oxidase in vivo is controversial. We therefore tested these measurements using a multiwavelength detector in the neonatal pig brain. Exchange transfusion with perfluorocarbons revealed that the spectrum of cytochrome oxidase in the near-infrared was identical in the neonatal pig, the adult rat, and in the purified enzyme. Under normoxic conditions, the neonatal pig brain contained 15 micromol/L deoxyhemoglobin, 29 micromol/L oxyhemoglobin, and 1.2 micromol/L oxidized cytochrome oxidase. The mitochondrial inhibitor cyanide was used to determine whether redox changes in cytochrome oxidase could be detected in the presence of the larger cerebral hemoglobin concentration. Addition of cyanide induced full reduction of cytochrome oxidase in both blooded and bloodless animals. In the blooded animals, subsequent anoxia caused large changes in hemoglobin oxygenation and concentration but did not affect the cytochrome oxidase near-infrared signal. Simultaneous blood oxygenation level-dependent magnetic resonance imaging measurements showed a good correlation with near-infrared measurements of deoxyhemoglobin concentration. Possible interference in the near-infrared measurements from light scattering changes was discounted by simultaneous measurements of the optical pathlength using the cerebral water absorbance as a standard chromophore. We conclude that, under these conditions, near-infrared spectroscopy can accurately measure changes in the cerebral cytochrome oxidase redox state.

Publication Types:

PMID: 9886352 [PubMed – indexed for MEDLINE]

Experimental and theoretical comparison of NIR spectroscopy measurements of cerebral hemoglobin changes.

Firbank M, Elwell CE, Cooper CE, Delpy DT.

Department of Medical Physics and Bioengineering, University College London, London WC1E 6JA, United Kingdom CO4 3SQ.

Two near-infrared spectroscopy (NIRS) methods are available for measuring changes (Delta) in total cerebral hemoglobin concentration (CHC): 1) a continuous measurement of the changes in total hemoglobin concentration (Delta[Hb]tot) and 2) the difference between two absolute measurements of CHC, each derived from a small, controlled change in inspired O2 fraction. This paper investigates the internal consistency of these two methods by using an experimental and theoretical comparison. NIRS was used to measure [Hb]tot in five newborn piglets before and after a change in arterial PCO2. Delta[Hb]tot demonstrated a low coefficient of variation of 2.8 +/- 2.8 (SD) % which allowed changes in CO2-cerebral blood volume reactivity to be clearly discriminated. However, a high coefficient of variation of 22.8 +/- 3.5% on the DeltaCHC measurements obscured any CO2 reactivity changes. A theoretical analysis demonstrates the effects of optical pathlength, background absorption, scatter, and blood vessel diameter on both methods. For more accurate monitoring of CHC, individual measurements of optical pathlength and more accurate pulse oximetry are required.

Publication Types:

PMID: 9804599 [PubMed – indexed for MEDLINE]

A theoretical study of the signal contribution of regions of the adult head to near-infrared spectroscopy studies of visual evoked responses.

Firbank M, Okada E, Delpy DT.

University Department of Radiology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.

Near-infrared (NIR) spectroscopy has been used in studies of the cerebral hemodynamic response to visual processing. In this paper, we present theoretical results from finite element and Monte Carlo modeling in order to help understand the contribution to the NIR signal from different parts of the head. The results from the models show that at the typical optode spacings used in these studies, an infrared spectroscopy measurement of intensity is sensitive to the outer 1-2 mm of the cortical gray matter and the partial optical path length in the gray matter is approximately 10 mm, compared with a total optical path length of 400 mm. When the NIR measurement is of change in mean photon arrival time (or phase shift), the signal comes from the upper 2-4 mm of the cortical surface and there is an increased lateral spread of the contributing tissue. We predict that for a 4-cm separation of input and detection optodes at 800 nm, a 1 microM change in hemoglobin concentration in the cortex corresponds to an attenuation change of approximately 0.001 OD (optical density) or 1 ps mean time change. Movement of the brain caused by this increase in volume will cause an absorption change of approximately half this magnitude, but does not affect the photon arrival time at 4-cm spacing. A discrepancy between the predicted and the experimentally measured intensities may support the supposition that the NIR signal is actually very sensitive to changes occurring in the pial cerebral vessels lying on the brain surface.

Publication Types:

PMID: 9698577 [PubMed – indexed for MEDLINE]

The relationship of oxygen delivery to absolute haemoglobin oxygenation and mitochondrial cytochrome oxidase redox state in the adult brain: a near-infrared spectroscopy study.

Cooper CE, Delpy DT, Nemoto EM.

Department of Biological Sciences, Central Campus, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK.

Near-infrared spectroscopy was used to determine the effect of changes in the rate of oxygen delivery to the adult rat brain on the absolute concentrations of oxyhaemoglobin, deoxyhaemoglobin and the redox state of the CuA centre in mitochondrial cytochrome oxidase. The cytochrome oxidase detection algorithm was determined to be robust to large changes in haemoglobin oxygenation and concentration. By assuming complete haemoglobin deoxygenation and CuA reduction following mechanical ventilation on 100% N2O, the absolute concentration of oxyhaemoglobin (35 microM), deoxyhaemoglobin (27 microM) and the redox state of CuA (82% oxidized) were calculated in the normal adult brain. The mean arterial blood pressure was decreased by exsanguination. When the pressure reached 100 mmHg, haemoglobin oxygenation started to fall, but the total haemoglobin concentration and oxidized CuA levels only fell when cerebral blood volume autoregulation mechanisms failed at 50 mmHg. Haemoglobin oxygenation fell linearly with decreases in the rate of oxygen delivery to the brain, but the oxidized CuA concentration did not start to fall until this rate was 50% of normal. The results suggest that the brain maintains more than adequate oxygen delivery to mitochondria and that near-infrared spectroscopy may be a good measure of oxygen insufficiency in vivo.

Publication Types:

PMID: 9620863 [PubMed – indexed for MEDLINE]

PMCID: PMC1219521

In vivo measurements of the wavelength dependence of tissue-scattering coefficients between 760 and 900 nm measured with time-resolved spectroscopy.

Matcher SJ, Cope M, Delpy DT.

We present in vivo values for the optical transport coefficients (mu(a), mu(s)?) of the adult human forearm, calf, and head from 760 to 900 nm measured with time-resolved spectroscopy. The accuracy of the method is tested with tissue-simulating phantoms. We obtain mu(s)?(lambda) approximately 1.1 – (5.1 x 10(-4) lambda) mm(-1) (forearm), 1.6 – (8.9 x 10(-4) lambda) mm(-1) (calf), and 1.45 – (6.5 x 10(-4) lambda) mm(-1) (head), where lambda is measured in nanometers. At 800 nm we obtain mu(a) = 0.023 +/- 0.004 mm(-1) (forearm), 0.017 +/- 0.005 mm(-1) (calf), and 0.016 +/- 0.001 mm(-1) (head). Our values differ substantially from published in vitro data. In particular, our transport coefficients for the adult head are substantially lower than previously reported values for adult human cerebral matter and pig skull cortical bone measured in vitro.

PMID: 18250686 [PubMed – in process]

Theoretical and experimental investigation of near-infrared light propagation in a model of the adult head.

Okada E, Firbank M, Schweiger M, Arridge SR, Cope M, Delpy DT.

Near-infrared light propagation in various models of the adult head is analyzed by both time-of-flight measurements and mathematical prediction. The models consist of three- or four-layered slabs, the latter incorporating a clear cerebrospinal fluid (CSF) layer. The most sophisticated model also incorporates slots that imitate sulci on the brain surface. For each model, the experimentally measured mean optical path length as a function of source-detector spacing agrees well with predictions from either a Monte Carlo model or a finite-element method based on diffusion theory or a hybrid radiosity-diffusion theory. Light propagation in the adult head is shown to be highly affected by the presence of the clear CSF layer, and both the optical path length and the spatial sensitivity profile of the models with a CSF layer are quite different from those without the CSF layer. However, the geometry of the sulci and the boundary between the gray and the white matter have little effect on the detected light distribution.

PMID: 18250644 [PubMed – in process]

The effect of scalp ischaemia on measurement of cerebral blood volume by near-infrared spectroscopy.

Owen-Reece H, Elwell CE, Wyatt JS, Delpy DT.

Department of Anaesthesia, National Hospital for Neurology and Neurosurgery, London, UK.

Near-infrared spectroscopy (NIRS) is a noninvasive method of quantifying changes in cerebral haemodynamics from changes in the absorption of near-infrared light by oxyhaemoglobin and deoxyhaemoglobin. Measurement of neonatal cerebral blood volume (CBV) by NIRS was described in 1990 but it has been suggested that, in adults, scalp and skull blood content contribute a significant amount to the cerebral haemodynamic variables quantifiable by NIRS. To investigate this, CBV was measured in nine adult subjects, in the frontal region of the head, before and after inflating a pneumatic tourniquet proximal to the measurement site. Because a change in scalp blood content could potentially alter the pathlength of light passing through the head and hence affect the measured CBV, the optical pathlength factor was therefore also measured before and after tourniquet inflation. Blood flow occlusion was confirmed by laser Doppler velocimetry. The results showed that tourniquet inflation had no effect on the estimated value of CBV or the differential pathlength factor. We conclude that, provided the distance between light entry and exit on the surface of the scalp is sufficiently large, changes in scalp blood flow have no effect on NIRS measurement of cerebral haemodynamics.

Publication Types:

PMID: 8953626 [PubMed – indexed for MEDLINE]

Comment on:

Near-infrared spectroscopy and cerebral hemodynamics.

Owen-Reece H, Smith M, Elwell CE, Goldstone JC, Delpy DT.

Publication Types:

PMID: 8706504 [PubMed – indexed for MEDLINE]

Near-infrared spectroscopy: theory and applications.

Wahr JA, Tremper KK, Samra S, Delpy DT.

Department of Anesthesiology, University of Michigan, Ann Arbor, USA.

In conclusion, NIRS appears to offer both a new monitoring modality and new information about cerebral oxygenation. Technical problems in the application of this technology persist, most notably determination of pathlength and the volume of tissue interrogated. Those familiar with the history of pulse oximetry will recall that although Millikan developed an ear oximeter in 1947, it was not until Aoyagi combined recognition of the pulse signal with spectroscopy in the 1970s that oximetry was transformed into a clinically applicable monitor. In much the same way, NIRS may find the same tremendous usefulness as a noninvasive monitor of cerebral oxygen utilization, pending resolution of the remaining technical problems.

Publication Types:

PMID: 8725427 [PubMed – indexed for MEDLINE]

The finite element method for the propagation of light in scattering media: boundary and source conditions.

Schweiger M, Arridge SR, Hiraoka M, Delpy DT.

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

This paper extends our work on applying the Finite Element Method (FEM) to the propagation of light in tissue. We address herein the topics of boundary conditions and source specification for this method. We demonstrate that a variety of boundary conditions stipulated on the Radiative Transfer Equation can be implemented in a FEM approach, as well as the specification of a light source by a Neumann condition rather than an isotropic point source. We compare results for a number of different combinations of boundary and source conditions under FEM, as well as the corresponding cases in a Monte Carlo model.

Publication Types:

PMID: 8587533 [PubMed – indexed for MEDLINE]

Performance comparison of several published tissue near-infrared spectroscopy algorithms.

Matcher SJ, Elwell CE, Cooper CE, Cope M, Delpy DT.

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

We have collected multiwavelength near-infrared (NIR) attenuation spectra on human forearm muscle, the adult rat head, and newborn piglet head to compare the changes in chromophore concentration derived from these data using published algorithms from four groups. We find differences between the results from the algorithms on each data set, particularly in their estimation of cytochrome oxidase (cyt-aa3) redox changes. We also find some differences when applying the same algorithm to the three data sets, suggesting possible difficulties in transferring algorithms between different physiological systems (e.g., Kurth, C. D., Steven, J. M., Benaron, D., and Chance, B. (1993) J. Clin. Monit. 9, 163-170). We have also compared the algorithms using simulated data generated using measured hemoglobin absorption spectra and a diffusion model for light transport in tissue. We find that while the algorithms from three groups are in broad agreement, that published by Piantadosi (Piantadosi, C. A. (1993) Methods Toxicol. 2, 107-126) produces significantly different results for cyt-aa3 and HbO2. Either the hemoglobin spectra used to produce the simulated data are inaccurate or the modeling is incorrect, or this algorithm is erroneous.

Publication Types:

PMID: 7668392 [PubMed – indexed for MEDLINE]

The spatial resolution performance of a time-resolved optical imaging system using temporal extrapolation.

Hebden JC, Hall DJ, Delpy DT.

Department of Medical Physics, University College London, England.

Optical imaging methods are being explored as a potential means of screening for breast cancer. Previous investigations of time-resolved imaging techniques have suggested that due to the lack of photons with sufficiently small pathlengths, the spatial resolution achievable through a human breast would be unlikely to be better than a centimeter. Experimental results presented here indicate, however, that higher resolution may be achieved by extrapolating the measured temporal distribution of transmitted photons. This is performed using a least-squares fit between data and an analytic model of photon transport. The spatial resolution of a time-resolved imaging system was evaluated by measuring the edge response produced by an opaque mask embedded in the center of a 51-mm-thick, very highly scattering medium. The limiting spatial resolution was improved from about 13 mm to about 5 mm.

Publication Types:

PMID: 7565351 [PubMed – indexed for MEDLINE]

Measurement of the optical properties of the skull in the wavelength range 650-950 nm.

Firbank M, Hiraoka M, Essenpreis M, Delpy DT.

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

The optical properties of samples of bone from pig skull have been measured over the wavelength range 650-950 nm. The scattering phase function was measured on thin samples of the bone using a goniometer, and a value for the mean cosine g, of the scattering angle, was calculated. The scattering and absorption coefficients, mu s and mu a were then determined from measurements of diffuse reflectance and transmittance made with a pair of integrating spheres, by a step-wise search through a table of diffuse reflectance and transmittance versus mu a and mu s generated by a Monte Carlo model incorporating the measured scattering phase function. Values for g measured on six samples varied from 0.925 +/- 0.014 at 650 nm to 0.945 +/- 0.013 at 950 nm. Corresponding values for mu a and mu s measured on 18 samples were mu a = 0.04 +/- 0.002 mm-1, mu s = 35 +/- 0.7 mm-1 at 650 nm to mu a = 0.05 +/- 0.002 mm-1, mu s = 24 +/- 0.6 mm-1 at 950 nm.

Publication Types:

PMID: 8488176 [PubMed – indexed for MEDLINE]

Wavelength dependence of the differential pathlength factor and the log slope in time-resolved tissue spectroscopy.

Essenpreis M, Cope M, Elwell CE, Arridge SR, van der Zee P, Delpy DT.

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

Publication Types:

PMID: 8362674 [PubMed – indexed for MEDLINE]


Estimation of optical pathlength through tissue from direct time of flight measurement.

Delpy DT, Cope M, van der Zee P, Arridge S, Wray S, Wyatt J.

Department of Medical Physics, University College London, UK.

Quantitation of near infrared spectroscopic data in a scattering medium such as tissue requires knowledge of the optical pathlength in the medium. This can now be estimated directly from the time of flight of picosecond length light pulses. Monte Carlo modelling of light pulses in tissue has shown that the mean value of the time dispersed light pulse correlates with the pathlength used in quantitative spectroscopic calculations. This result has been verified in a phantom material. Time of flight measurements of pathlength across the rat head give a pathlength of 5.3 +/- 0.3 times the head diameter.

Publication Types:

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