DOT- Imperial College London- Delpy 2008/06–2005/06

Measuring circulating blood volume in newborn infants using pulse dye densitometry and indocyanine green.

Aladangady N, Leung T, Costeloe K, Delpy D.

Department of Child Health, Homerton University Hospital/Bart’s and the London School of Medicine and Dentistry, London, UK.

Background: Circulating blood volume (BV) is an important, but often unconsidered, variable in newborn infants undergoing intensive care. The data on validation and repeatability of BV measurement are limited. Aim: To validate and test the repeatability of measuring BV in newborn infants using indocyanine green (ICG) and pulse dye densitometry (PDD). Methods: Validation- Paired measurements of BV were made using the fetal hemoglobin (HbF) dilution and the PDD method. Repeatability- The BV was measured twice at an interval of 30-40 min in a second group of infants. Results: Validation- Data from three of 13 infants studied were excluded because of probe dislodgement or ICG injection error. The median (range) birth weight of the 10 infants whose data were analyzed was 1032 g (740-2384 g) and seven (70%) were receiving either mechanical ventilation or nasal CPAP. The median BV measured by HbF dilution was 66.2 ml.kg(-1) (43.7-81.0 ml.kg(-1)) and by the PDD method was 68.9 ml.kg(-1) (49.3-101.0 ml.kg(-1)). The mean difference was 5.92 ml.kg(-1) (sd 17.33 ml.kg(-1)). Repeatability- Twelve infants were studied and three excluded because of probe dislodgement/motion artifact or ICG injection error. The median weight of the nine infants whose data were analyzed was 1208 g (795-2600 g). The median (range) BV1 and BV2 were 70.5 ml.kg(-1) (53.1-160 ml.kg(-1)) and 87.5 ml.kg(-1) (38.0-248.0 ml.kg(-1)), respectively. Mean difference of the two BV estimates (BV1-BV2) was -24.6 ml.kg(-1) (sd 33.3 ml.kg(-1)) and coefficient of repeatability was 66.5 ml.kg(-1). Conclusion: Pulse dye densitometry can be used to measure BV in the newborn infant at the cotside but the repeatability measurements suggest that its use is limited.

PMID: 18544143 [PubMed – as supplied by publisher]


Changes in prefrontal cortical behaviour depend upon familiarity on a bimanual co-ordination task: an fNIRS study.

Leff DR, Elwell CE, Orihuela-Espina F, Atallah L, Delpy DT, Darzi AW, Yang GZ.

Royal Wolfson Image Computing Laboratory and Department of Biosurgery and Surgical Technology, Imperial College London, UK.

To investigate neurocognitive mechanisms associated with task-related expertise development, this paper investigates serial changes in prefrontal activation patterns using functional near infrared spectroscopy (fNIRS). We evaluate cortical function in 62 healthy subjects with varying experience during serial evaluations of a knot-tying task. All tasks were performed bimanually and self paced, with fixed episodes of motor rest for five repetitions. Improvements in technical skill were evaluated using dexterity indices to quantify time, total movements and pathlength required to complete trials. Significant improvements in technical skills were observed in novices between the 2nd and 3rd trials, associated with increasing task familiarity. In trained subjects, minimal fluctuation in task-related oxyhaemoglobin (HbO(2)) and deoxyhaemoglobin (HHb) changes were observed in association with more stable task performance. In contrast, two significant transitions in prefrontal haemodynamic change were observed in novices. Greater task-related increases in HbO(2) and decreases in HHb were identified on the second trial compared to the first. Relative decreases in HbO(2) and increases in HHb change were observed between the third and fourth, and fourth and fifth trials respectively. These data suggest that prefrontal processing across five knot-tying trials is influenced by the level of experience on a task. Modifications in prefrontal activation appear to confer technical performance adaptation in novices.

PMID: 17964187 [PubMed – indexed for MEDLINE]


Measurement of frontal lobe functional activation and related systemic effects: a near-infrared spectroscopy investigation.

Tachtsidis I, Leung TS, Devoto L, Delpy DT, Elwell CE.

Medical Physics and Bioengineering, University College London, Malet Place Engineering Building, Gower Street, London WC1E 6BT. iliastac@medphys.ucl.ac.uk

Near-infrared spectroscopy (NIRS) has been used to measure changes in cerebral oxy- and deoxy- haemoglobin (delta[HbO2], delta[HHb]) in response to functional activation. It has been previously reported that during functional activation of the motor cortex heart rate increases. The aim of this study was to investigate systemic changes during functional activation of the frontal cortex. The responses to anagram presentations with varying difficulty (4-Letters and 7-Letters) over a 6 minute period were recorded. A Hamamatsu NIRO 200 NIRS system recorded delta[HbO2] and delta[HHb] using the modified Beer Lambert law (MBL) and tissue oxygenation index (TOI) employing spatial resolved spectroscopy (SRS) over the left and right frontal hemisphere. Mean blood pressure (MBP) and heart rate (HR) were measured continuously. Nine young healthy volunteers (mean age 23) were included in the analysis. Significant task related changes were observed in both the NIRS and systemic signals during the anagram solving with increases in [HbO2] and [HHb] accompanied by changes in MBP and HR. The [HbO2] and [HHb] signals measured over the frontal region were found to have a varying association with the MBP signal across different volunteers. The effect of these systemic changes on measured NIRS signals must be considered

Publication Types:

PMID: 18290351 [PubMed – indexed for MEDLINE]


Measurement of cerebral tissue oxygenation in young healthy volunteers during acetazolamide provocation: a transcranial Doppler and near-infrared spectroscopy investigation.

Tachtsidis I, Tisdall M, Delpy DT, Smith M, Elwell CE.

Medical Physics and Bioengineering, University College London, Malet Place Engineering Building, Gower Street, London WCIE 6BT. iliastac@medphys.ucl.ac.uk

Recent advances in near-infrared spectroscopy (NIRS) allow measurements of absolute tissue oxygen saturation (TOI) using spatially resolved spectroscopy (SRS), while enabling better depth sensitivity. However concerns remain regarding the relative contribution of the extracranial circulation to the cerebral NIRS TOI signal. In this study we investigated this during a period of selective rise in cerebral blood flow (CBF) produced by the administration of acetazolamide (ACZ) in 10 healthy volunteers. A two channel spectrometer (NIRO 300, Hamamatsu Photonics KK) was used to measure absolute cerebral TOI over the frontal cortex using the SRS technique using an optode spacing of 5 cm and 1.5 cm for channel 1 and 2 respectively. After ACZ administration we were able to observe a significant increase in the velocity of middle cerebral artery (V(mca), measured with the transcranial Doppler (TCD)) which was accompanied by an increase in TOI as monitored by the NIRO 300 with an optode spacing of 5 cm but not with an optode spacing of 1.5 cm. Furthermore a direct relationship was seen between the V(mca) and the TOI measured at 5 cm optode spacing. This work suggests that using this commercial NIRS instrument with an optode spacing of 5 cm one is able to detect the intracranial changes.

Publication Types:

PMID: 18290350 [PubMed – indexed for MEDLINE]


Cerebral tissue oxygen saturation calculated using low frequency haemoglobin oscillations measured by near infrared spectroscopy in adult ventilated patients.

Leung TS, Tisdall MM, Tachtsidis I, Smith M, Delpy DT, Elwell CE.

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

Oxy- (HbO2) and deoxy- (HHb) haemoglobin signals measured by near infrared (NIR) spectroscopy over the human frontal lobes frequently contain respiratory and low frequency oscillations (LFOs). It has been suggested previously that venous oxygen saturation (SvO2) can be calculated from these respiratory oscillations. In this paper, we investigated the use of a Fourier transform based algorithm to calculate an oxygen saturation measure known as S(osc)O2 which may be a close estimate of the underlying SvO2. S(osc)O2 was calculated using three different frequency ranges, (1) respiratory oscillations only, (2) LFOs only, and (3) both respiratory oscillations and LFOs. At each frequency range S(osc)O2 was calculated using either (1) the modified Beer-Lambert law (MBL) or (2) spatially resolved spectroscopy (SRS). In total six different measurements of S(osc)O2 were investigated here. Experiments were performed in six adult ventilated patients with traumatic brain injury. The patients’ inspired oxygen fraction (FiO2) was raised in two hyperoxic phases. The calculated S(osc)O2 values were compared with other cerebral oxygenation measures including an intraparenchymal catheter based brain tissue oxygen tension (PbrO2) and the NIR based tissue oxygenation index (TOI). It was found that the S(osc)O2 calculated using the combined respiratory and LFO frequency range and the SRS method resulted in the highest detection rates of hyperoxic changes. This measure of S(osc)O2 may provide a viable, continuous, non invasive, bedside measure of cerebral venous oxygen saturation.

Publication Types:

PMID: 18290334 [PubMed – indexed for MEDLINE]


Investigation of frontal cortex, motor cortex and systemic haemodynamic changes during anagram solving.

Tachtsidis I, Leung TS, Tisdall MM, Devendra P, Smith M, Delpy DT, Elwell CE.

Department of Medical Physics and Bioengineering, Malet Place Engineering Building, Gower Street, University College London, London, UK WC1E 6BT.

We have previously reported changes in the concentrations of oxy-(delta[HbO2]) deoxy- (delta[HHb]) and total haemoglobin (delta[HbT] = delta[HbO2] + delta[HHb]) measured using near infrared spectroscopy (NIRS) over the frontal cortex (FC) during an anagram solving task. These changes were associated with a significant increase in both mean blood pressure (MBP) and heart rate (HR). The aim of this study was to investigate whether the changes in MBP previously recorded during an anagram solving task produces associated changes in scalp blood flow (flux) measured by laser Doppler and whether any changes are seen in NIRS haemodynamic measurements over a control region of the brain (motor cortex: MC). During the 4-Letter anagram task significant changes were observed in the delta[HbO2], delta[HHb] and delta[HbT] in both the frontal and motor cortex (n = 11, FC p < 0.01, MC p < 0.01). These changes were accompanied by significant changes in both MBP (n = 11, p < 0.01) and scalp flux (n = 9, p = 0.01). During the 7-Letter anagram task significant changes were observed in the delta[HbO2] and delta[HbT] (n = 11, FC p < 0.01, MC p < 0.01), which were accompanied by significant changes in both MBP (n = 11, p = 0.05) and flux (n = 9, p = 0.05). The task-related changes seen in MBP and flux in this study appear to contribute to the changes in the NIRS signals over both the activated and control regions of the cortex.

Publication Types:

PMID: 18290310 [PubMed – indexed for MEDLINE]


Functional optical signal analysis: a software tool for near-infrared spectroscopy data processing incorporating statistical parametric mapping.

Koh PH, Glaser DE, Flandin G, Kiebel S, Butterworth B, Maki A, Delpy DT, Elwell CE.

University College London, Department of Medical Physics and Bioengineering, Biomedical Optics Research Laboratory, Gower Street, London WC1E 6BT United Kingdom. pkoha.medphys.ucl.ac.uk

Optical topography (OT) relies on the near infrared spectroscopy (NIRS) technique to provide noninvasively a spatial map of functional brain activity. OT has advantages over conventional fMRI in terms of its simple approach to measuring the hemodynamic response, its ability to distinguish between changes in oxy- and deoxy-hemoglobin and the range of human participants that can be readily investigated. We offer a new software tool, functional optical signal analysis (fOSA), for analyzing the spatially resolved optical signals that provides statistical inference capabilities about the distribution of brain activity in space and time and by experimental condition. It does this by mapping the signal into a standard functional neuroimaging analysis software, statistical parametric mapping (SPM), and forms, in effect, a new SPM toolbox specifically designed for NIRS in an OT configuration. The validity of the program has been tested using synthetic data, and its applicability is demonstrated with experimental data.

Publication Types:

PMID: 18163826 [PubMed – indexed for MEDLINE]


Pioneers in biomedical optics: special section honoring professor Frans F. Jobsis of Duke University.

Delpy DT, Ferrari M, Piantadosi CA, Tamura M.

Publication Types:

Personal Name as Subject:

PMID: 18163804 [PubMed – indexed for MEDLINE]


Theoretical investigation of measuring cerebral blood flow in the adult human head using bolus Indocyanine Green injection and near-infrared spectroscopy.

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

Department of Medical Physics, University College London, London, UK. tsl@medphys.ucl.ac.uk

To investigate the accuracy of measuring cerebral blood flow (CBF) using a bolus injection of Indocyanine Green (ICG) detected by near-infrared spectroscopy in adult human heads, simulations were performed using a two-layered model representing the extracerebral and intracerebral layers. Modeled optical data were converted into tissue ICG concentration using either the one-detector modified Beer-Lambert law (MBLL) method, or the two-detector partial path-length (PPL) method. The CBFs were estimated using deconvolution and blood flow index techniques. Using the MBLL method, the CBFs were significantly underestimated but the PPL method improved their accuracy and robustness, especially when used as relative measures. The dispersion of the arterial input function also affected the CBF estimates.

Publication Types:

PMID: 17356602 [PubMed – indexed for MEDLINE]


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

Tachtsidis I, Tisdall M, Leung TS, Cooper CE, Delpy DT, Smith M, Elwell CE.

Department of Medical Physics and Bioengineering, Malet Place Engineering Building, University College London, Gower Street, London, UK. iliastac@medphys.ucl.ac.uk

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].

Publication Types:

PMID: 17237591 [PubMed – indexed for MEDLINE]


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

Rowley AB, Payne SJ, Tachtsidis I, Ebden MJ, Whiteley JP, Gavaghan DJ, Tarassenko L, Smith M, Elwell CE, Delpy DT.

Department of Engineering Science, University of Oxford, Oxford, UK. abr@robots.ox.ac.uk

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.

Publication Types:

PMID: 17237588 [PubMed – indexed for MEDLINE]


Quantitative spatially resolved measurement of tissue chromophore concentrations using photoacoustic spectroscopy: application to the measurement of blood oxygenation and haemoglobin concentration.

Laufer J, Delpy D, Elwell C, Beard P.

Department of Medical Physics & Bioengineering, University College London, Malet Place Engineering Building, London WC1E 6BT, UK.

A new approach based on pulsed photoacoustic spectroscopy for non-invasively quantifying tissue chromophore concentrations with high spatial resolution has been developed. The technique is applicable to the quantification of tissue chromophores such as oxyhaemoglobin (HbO(2)) and deoxyhaemoglobin (HHb) for the measurement of physiological parameters such as blood oxygen saturation (SO(2)) and total haemoglobin concentration. It can also be used to quantify the local accumulation of targeted contrast agents used in photoacoustic molecular imaging. The technique employs a model-based inversion scheme to recover the chromophore concentrations from photoacoustic measurements. This comprises a numerical forward model of the detected time-dependent photoacoustic signal that incorporates a multiwavelength diffusion-based finite element light propagation model to describe the light transport and a time-domain acoustic model to describe the generation, propagation and detection of the photoacoustic wave. The forward model is then inverted by iteratively fitting it to measurements of photoacoustic signals acquired at different wavelengths to recover the chromophore concentrations. To validate this approach, photoacoustic signals were generated in a tissue phantom using nanosecond laser pulses between 740 nm and 1040 nm. The tissue phantom comprised a suspension of intralipid, blood and a near-infrared dye in which three tubes were immersed. Blood at physiological haemoglobin concentrations and oxygen saturation levels ranging from 2% to 100% was circulated through the tubes. The signal amplitude from different temporal sections of the detected photoacoustic waveforms was plotted as a function of wavelength and the forward model fitted to these data to recover the concentrations of HbO(2) and HHb, total haemoglobin concentration and SO(2). The performance was found to compare favourably to that of a laboratory CO-oximeter with measurement resolutions of +/-3.8 g l(-1) (+/-58 microM) and +/-4.4 g l(-1) (+/-68 microM) for the HbO(2) and HHb concentrations respectively and +/-4% for SO(2) with an accuracy in the latter in the range -6%-+7%.

PMID: 17183133 [PubMed – indexed for MEDLINE]


Comment on:

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

Binzoni T, Leung TS, Gandjbakhche AH, Rüfenacht D, Delpy DT.

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.

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

Austin T, Gibson AP, Branco G, Yusof RM, Arridge SR, Meek JH, Wyatt JS, Delpy DT, Hebden JC.

Department of Paediatrics and Child Health, University College London, UK. topunaustin@doctors.org.uk

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.

Publication Types:

PMID: 16644237 [PubMed – indexed for MEDLINE]


Optimal determination of detector placement in cerebral NIR spectroscopy of neonates using chemometric techniques.

Leung TS, Elwell CE, Delpy DT.

This paper investigates the optimal placement of NIRS optodes in order to maximise the detection of haemoglobin changes in cortical grey matter resulting from an evoked response in neonates. The analysis is based upon predictions of optical signal at the surface of the head, using a Finite Element based model of light diffusion in tissue. Using the generated intensity data, the combination of optode positions, which maximise the signal from cortical grey matter whilst minimising that from surface tissue or cerebral white matter, is determined using a Chemometric statistical analysis. The neonatal head is modelled as a 2 dimensional circle with 3 layers corresponding to the skin/scalp, and grey and white matter. A wide range of absorption coefficients for each layer is simulated, based upon physiologically reasonable values for parameters. Surface intensity at 10 different optode positions have been generated for a total of 31,250 combinations of these variables for the 3 layers. It was found that with 3 optodes at 5, 15, and 50 mm apart from the source, the smallest root-mean-square error between the estimated and modelled values can be obtained. Increasing the number of optodes further does not improve the performance.

Publication Types:

PMID: 16594128 [PubMed – indexed for MEDLINE]


Anisotropic photon migration in human skeletal muscle.

Binzoni T, Courvoisier C, Giust R, Tribillon G, Gharbi T, Hebden JC, Leung TS, Roux J, Delpy DT.

Département de Neurosciences Fondamentales, University of Geneva, Switzerland. Tiziano.Binzoni@medecine.unige.ch

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.

PMID: 16481676 [PubMed – indexed for MEDLINE]


Measurement of the absolute optical properties and cerebral blood volume of the adult human head with hybrid differential and spatially resolved spectroscopy.

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

Department of Medical Physics & Bioengineering, University College London, Gower Street, London WC1E 6BT, UK.

A hybrid differential and spatially resolved spectroscopy (SRS) technique has been developed to measure absolute absorption coefficient (mu(a)), reduced scattering coefficient (mu'(s)) and cerebral blood volume (CBV) in the adult human head. A spectrometer with both differential and SRS capabilities has been used to carry out measurements in 12 subjects. Two versions of the calculation have been considered using the hybrid technique, with one considering water as a chromophore as well as oxy- and deoxy-haemoglobin, and one ignoring water. The CBV has also been measured using a previously described technique based on changing the arterial saturation (SaO(2)) measured separately by a pulse oximeter, resulting in mean +/- SD CBV(a) (intra-individual coefficient of variation) = 2.22 +/- 1.06 ml/100 g (29.9%). (The superscript on CBV indicates the different calculation basis.) Using the hybrid technique with water ignored, CBV(0) = 3.18 +/- 0.73 ml/100 g (10.0%), mu(0)(a)(813 nm) = 0.010 +/- 0.003 mm(-1) and mu'(0)(s)(813 nm) = 1.19 +/- 0.55 mm(-1) (data quoted at 813 nm). With water considered, CBV(w) = 3.05 +/- 0.77 ml/100 g (10.5%), mu(w)(a)(813 nm) = 0.010 +/- 0.003 mm(-1) and mu'(w)(s)(813 nm) = 1.28 +/- 0.56 mm(-1). The mean biases between CBV(0)/CBV(w), CBV(0)/CBV(a) and CBV(w)/CBV(a) are 0.14 +/- 0.09, 0.79 +/- 1.22 and 0.65 +/- 1.24 ml/100 g. The mean biases between mu(0)(a)(813 nm)/mu(w)(a)(813 nm) and mu'(0)(s)(813 nm)/mu'(w)(s)(813 nm) are (5.9 +/- 10.0) x 10(-4) mm(-1) and -0.084 +/- 0.266 mm(-1), respectively. The method we describe extends the functionality of the current SRS instrumentation.

Publication Types:

PMID: 16424590 [PubMed – indexed for MEDLINE]


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

Binzoni T, Leung TS, Rüfenacht D, Delpy DT.

Département de Neurosciences Fondamentales, Faculty of Medicine, University of Geneva, Switzerland. Tiziano.Binzoni@medecine.unige.ch

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.

Publication Types:

PMID: 16394341 [PubMed – indexed for MEDLINE]


Estimation of cerebral oxy- and deoxy-haemoglobin concentration changes in a layered adult head model using near-infrared spectroscopy and multivariate statistical analysis.

Leung TS, Elwell CE, Delpy DT.

Department of Medical Physics and Bioengineering, Malet Place Engineering Building, University College London, Gower Street, London WC1E 6BT, UK.

The non-invasive measurement of cerebral oxy- (DeltaHbO(br)2) and deoxy-haemoglobin (DeltaHHb(br)) changes using near-infrared spectroscopy instruments is often affected by the absorption in the extracerebral layer. We have exploited the multivariate calibration (partial least squares, PLS) method to minimize the errors for a range of blood volume, oxygen saturation and extracerebral layer thicknesses. The changes in the mean time of flight of photons (Delta tau) and attenuation (DeltaA) on the surface of a 3D adult head model were simulated using a finite-element method based on the diffusion equation. The PLS was then performed to identify the optimal number of detectors, their positions and weightings, to optimize the estimation of DeltaHbO(br)2 and DeltaHHb(br). We define the ‘nominal accuracy’ as the accuracy of estimating DeltaHbO(br)2 and DeltaHHb(br) over a nominal range of extracerebral layer thicknesses and ‘robustness’ as the accuracy beyond the nominal range. The results showed that for one or two detectors, Delta tau performed better than DeltaA while using them together gave the best performance. When more detectors were used, the performances of using Delta tau, DeltaA or both together became comparable, showing that a larger number of detectors can compensate for the performance of a simple DeltaA measurement despite this measurement having a relatively lower sensitivity to intracerebral absorption changes.

Publication Types:

PMID: 16333155 [PubMed – indexed for MEDLINE]


Time-resolved optical mammography using a liquid coupled interface.

Yates TD, Hebden JC, Gibson AP, Enfield L, Everdell NL, Arridge SR, Delpy DT.

University College London, Department of Medical Physics & Bioengineering, London WC1E 6BT, United Kingdom.

A method has been devised for generating three-dimensional optical images of the breast using a 32-channel time-resolved system and a liquid-coupled interface. The breast is placed in a hemispherical cup surrounded by sources and detectors, and the remaining space is filled with a fluid with tissue-like optical properties. This approach has three significant benefits. First, cups can accommodate a large range of breast sizes, enabling the entire volume of the breast to be sampled. Second, the coupling of the source and detector optics at the surface is constant and independent of the subject, enabling intensity measurements to be employed in the image reconstruction. Third, the external geometry of the reconstructed volume is known exactly. Images of isolated targets with contrasting absorbing and scattering properties have been acquired, and the performance of the system has been evaluated in terms of the contrast, spatial resolution, and localization accuracy. These parameters were strongly dependent on the location of the targets within the imaged volume. Preliminary images of a healthy human subject are also presented, which reveal subtle heterogeneity, particularly in the distribution of scatter. The ability to detect an absorbing target adjacent to the breast is also demonstrated.

Publication Types:

PMID: 16292971 [PubMed – indexed for MEDLINE]


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

Gibson AP, Austin T, Everdell NL, Schweiger M, Arridge SR, Meek JH, Wyatt JS, Delpy DT, Hebden JC.

Department of Medical Physics and Bioengineering, University College London, Malet Place Engineering Building, London WC1E 6BT, UK. agibson@medphys.ucl.ac.uk

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.

Publication Types:

PMID: 16246586 [PubMed – indexed for MEDLINE]


In vitro measurements of absolute blood oxygen saturation using pulsed near-infrared photoacoustic spectroscopy: accuracy and resolution.

Laufer J, Elwell C, Delpy D, Beard P.

Department of Medical Physics and Bioengineering, University College London, Malet Place Engineering Building, London WC1E 6BT, UK.

Pulsed photoacoustic spectroscopy was used to measure blood oxygen saturation in vitro. An optical parametric oscillator laser system provided nanosecond excitation pulses over the wavelength range 740-1040 nm which were used to generate photoacoustic signals in a cuvette through which a saline suspension of red blood cells was circulated. The signal amplitude and the effective attenuation coefficient were extracted from the photoacoustic signals as a function of wavelength to provide photoacoustic spectra of the blood. From these, the relative concentrations of oxy- and deoxyhaemoglobin, and therefore blood oxygen saturation (SO2), were determined using forward models of the absorbed energy distribution based on diffusion theory. A standard linear model of the dependence of absorbance on the concentration of chromophores was also used to calculate the blood oxygen saturation from the signal amplitude spectra. The diffusion approximation model was shown to produce the highest accuracy in blood SO2. The photoacoustically determined oxygen saturation was found to have an accuracy of +/-4% SO2 for signal amplitude data and +/-2.5% SO2 for effective attenuation spectra. The smallest change in oxygen saturation that can be measured using this technique was +/-1% SO2.

Publication Types:

PMID: 16148401 [PubMed – indexed for MEDLINE]


Linear and nonlinear reconstruction for optical tomography of phantoms with nonscattering regions.

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

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

Most research in optical imaging incorrectly assumes that light transport in nonscattering regions in the head may be modeled by use of the diffusion approximation. The effect of this assumption is examined in a series of experiments on tissue-equivalent phantoms. Images from cylindrical and head-shaped phantoms with and without clear regions [simulating the cerebrospinal fluid (CSF) filled ventricles] and a clear layer (simulating the CSF layer surrounding the brain) are reconstructed with linear and nonlinear reconstruction techniques. The results suggest that absorbing and scattering perturbations can be identified reliably with nonlinear reconstruction methods when the clear regions are also present in the reference data but that the quality of the image degrades considerably if the reference data does not contain these features. Linear reconstruction performs similarly to nonlinear reconstruction, provided the clear regions are present in the reference data, but otherwise linear reconstruction fails. This study supports the use of linear reconstruction for dynamic imaging but suggests that, in all cases, image quality is likely to improve if the clear regions are modeled correctly.

Publication Types:

PMID: 16004037 [PubMed – indexed for MEDLINE]


A physiological model of cerebral blood flow control.

Banaji M, Tachtsidis I, Delpy D, Baigent S.

Department of Medical Physics and Bioengineering, University College London, Gower Street, London WC1E 6BT, UK. m.banaji@ucl.ac.uk

The construction of a computational model of the human brain circulation is described. We combine an existing model of the biophysics of the circulatory system, a basic model of brain metabolic biochemistry, and a model of the functioning of vascular smooth muscle (VSM) into a single model. This represents a first attempt to understand how the numerous different feedback pathways by which cerebral blood flow is controlled interact with each other. The present work comprises the following: Descriptions of the physiology underlying the model; general comments on the processes by which this physiology is translated into mathematics; comments on parameter setting; and some simulation results. The simulations presented are preliminary, but show qualitative agreement between model behaviour and experimental results.

Publication Types:

PMID: 15854674 [PubMed – indexed for MEDLINE]

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