Archive for the 'DOT' Category

IOP publish. highlights of 2008

http://www.iop.org/EJ/journal/-page=extra.highlights2008/0031-9155

Diffuse optical tomography, pubmed sept2005-sept2008

Diffuse optical tomography of pain and tactile stimulation: activation in cortical sensory and emotional systems.

Becerra L, Harris W, Joseph D, Huppert T, Boas DA, Borsook D.

P.A.I.N. Group McLean Hospital, Massachusetts General Hospital, Harvard Medical School, USA. lbecerra@mclean.harvard.edu

Using diffuse optical tomography (DOT), we detected activation in the somatosensory cortex and frontal brain areas following tactile (brush) and noxious heat stimulation. Healthy volunteers received stimulation to the dorsum of the right hand. In the somatosensory cortex area, tactile stimulation produced a robust, contralateral to the stimulus, hemodynamic response with a weaker activation on the ipsilateral side. For the same region, noxious thermal stimuli produced bilateral activation of similar intensity that had a prolonged activation with a double peak similar to results that have been reported with functional MRI. Bilateral activation was observed in the frontal areas, oxyhemoglobin changes were positive for brush stimulation while they were initially negative (contralateral) for heat stimulation. These results suggest that based on the temporal and spatial characteristics of the response in the sensory cortex, it is possible to discern painful from mechanical stimulation using DOT. Such ability might have potential applications in a clinical setting in which pain needs to be assessed objectively (e.g., analgesic efficacy, pain responses during surgery).


Quantitative diffuse optical tomography for small animals using an ultrafast gated image intensifier.

Patwardhan SV, Culver JP.

Washington University School of Medicine, Department of Radiology, Mallinckrodt Institute of Radiology, St. Louis, Missouri 63110, USA.

The quantitative accuracy of fluorescence and bioluminescence imaging of small animals can be improved by knowledge of the in situ optical properties of each animal. Obtaining in situ optical property maps is challenging, however, due to short propagation distances, requirements for high dynamic range, and the need for dense spatial, temporal, and spectral sampling. Using an ultrafast gated image intensifier and a pulsed laser source, we have developed a small animal diffuse optical tomography system with multiple synthetic modulation frequencies up to >1 GHz. We show that amplitude and phase measurements with useful contrast-to-noise ratios can be obtained for modulation frequencies over the range of approximately 250 to 1250 MHz. Experiments with tissue simulating phantoms demonstrate the feasibility of reconstructing the absorption and scattering optical properties in a small animal imaging system.


Time-resolved diffuse optical tomography and its application to in vitro and in vivo imaging.

Zhao H, Gao F, Tanikawa Y, Yamada Y.

Tianjin University, State Key Laboratory of Precision Measuring Technology and Instruments, Tianjin 3000072, China. huijuanzhao@tju.edu.cn

This work reviews our research during the past several years on time-resolved (TR) near-infrared diffuse optical tomography (DOT). Following an introduction of the measuring modes, two proposed schemes of image reconstruction in TR-DOT are described: one utilizes the full TR data, and the other, referred to as the modified generalized pulse spectrum technique (GPST), uses the featured data extracted from the TR measurement. The performances of the two algorithms in quantitativeness and spatial resolution are comparatively investigated with 2-D simulated data. TR-DOT images are then presented for phantom experiments, which are obtained by using a 16-channel time-correlated single photon counting system, and the factors affecting the quantification of the reconstruction are discussed. Finally, in vitro and in vivo imaging examples are illustrated for validating the capibility of TR-DOT to provide not only the anatomical but also the physiological information of the objects.

Publication Types:

PMID: 18163810 [PubMed – indexed for MEDLINE]


Multispectral diffuse optical tomography with absorption and scattering spectral constraints.

Li C, Grobmyer SR, Chen L, Zhang Q, Fajardo LL, Jiang H.

J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611-6131, USA.

We present a new method to simultaneously reconstruct the images of oxyhemoglobin, deoxyhemoglobin, and water concentrations, as well as the volume fraction images of the scattering particles using continuous wave multispectral diffuse optical tomography with the absorption and scattering spectral prior constraints. In this method, the nonlinear relationship between the reduced scattering coefficient and the volume fraction and the size of the particles is linearized, allowing direct reconstruction of the volume fraction of scattering particles in tissues. The method is validated by a series of numerical simulations, phantom experiments, and in vivo clinical experiments. The initial clinical results indicate that the volume fraction of scattering particles in a malignant tumor is higher than that in a benign tumor.

Publication Types:

PMID: 18059661 [PubMed – indexed for MEDLINE]


Optimization of optode arrangements for diffuse optical tomography: A singular-value analysis.

Culver JP, Ntziachristos V, Holboke MJ, Yodh AG.

We develope a method to optimize the resolution of diffuse optical tomographic instruments. Singular-value analysis of the tomographic weight matrix associated with specific data types, geometries, and optode arrangements is shown to provide a measure of image resolution. We achieve optimization of device configuration by monitoring the resolution measure described. We introduce this idea and demonstrate its utility by optimizing the spatial sampling interval and field-of-view parameters in the parallel-plane transmission geometry employed for diffuse optical breast imaging. We also compare resolution in transmission and remission geometries.

PMID: 18040425 [PubMed – in process]


Fast analytical approximation for arbitrary geometries in diffuse optical tomography.

Ripoll J, Nieto-Vesperinas M, Weissleder R, Ntziachristos V.

Diffuse optical tomography is a novel imaging technique that resolves and quantifies the optical properties of objects buried in turbid media. Typically, numerical solutions of the diffusion equation are employed to construct the tomographic problem when media of complex geometries are investigated. Numerical methods offer implementation simplicity but also significant computation burden, especially when large three-dimensional reconstructions are involved. We present an alternative method of performing tomography of diffuse media of arbitrary geometries by means of an analytical approach, the Kirchhoff approximation. We show that the method is extremely efficient in computation times and consider its potential as a real-time three-dimensional imaging tool.

PMID: 18007854 [PubMed – in process]


Noncontact optical imaging in mice with full angular coverage and automatic surface extraction.

Meyer H, Garofalakis A, Zacharakis G, Psycharakis S, Mamalaki C, Kioussis D, Economou EN, Ntziachristos V, Ripoll J.

Institute of Electronic Structure and Laser, Foundation for Research and Technology-Hellas, Heraklion Crete, Greece. heimeyer@iesl.forth.gr

During the past decade, optical imaging combined with tomographic approaches has proved its potential in offering quantitative three-dimensional spatial maps of chromophore or fluorophore concentration in vivo. Due to its direct application in biology and biomedicine, diffuse optical tomography (DOT) and its fluorescence counterpart, fluorescence molecular tomography (FMT), have benefited from an increase in devoted research and new experimental and theoretical developments, giving rise to a new imaging modality. The most recent advances in FMT and DOT are based on the capability of collecting large data sets by using CCDs as detectors, and on the ability to include multiple projections through recently developed noncontact approaches. For these to be implemented, we have developed an imaging setup that enables three-dimensional imaging of arbitrary shapes in fluorescence or absorption mode that is appropriate for small animal imaging. This is achieved by implementing a noncontact approach both for sources and detectors and coregistering surface geometry measurements using the same CCD camera. A thresholded shadowgrammetry approach is applied to the geometry measurements to retrieve the surface mesh. We present the evaluation of the system and method in recovering three-dimensional surfaces from phantom data and live mice. The approach is used to map the measured in vivo fluorescence data onto the tissue surface by making use of the free-space propagation equations, as well as to reconstruct fluorescence concentrations inside highly scattering tissuelike phantom samples. Finally, the potential use of this setup for in vivo small animal imaging and its impact on biomedical research is discussed.


Diffuse optical tomography system to image brain activation with improved spatial resolution and validation with functional magnetic resonance imaging.

Joseph DK, Huppert TJ, Franceschini MA, Boas DA.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, MA 02129, USA. danny@nmr.mgh.harvard.edu

Although most current diffuse optical brain imaging systems use only nearest- neighbor measurement geometry, the spatial resolution and quantitative accuracy of the imaging can be improved through the collection of overlapping sets of measurements. A continuous-wave diffuse optical imaging system that combines frequency encoding with time-division multiplexing to facilitate overlapping measurements of brain activation is described. Phantom measurements to confirm the expected improvement in spatial resolution and quantitative accuracy are presented. Experimental results showing the application of this instrument for imaging human brain activation are also presented. The observed improvement in spatial resolution is confirmed by functional magnetic resonance imaging.

Publication Types:

PMID: 17068557 [PubMed – indexed for MEDLINE]


Diffuse photon propagation in multilayered geometries.

Sikora J, Zacharopoulos A, Douiri A, Schweiger M, Horesh L, Arridge SR, Ripoll J.

Institute of the Theory of Electrical Engineering, Measurement and Information Systems, Warsaw University of Technology, Koszykowa 75, 00-661 Warsaw, Poland.

Diffuse optical tomography (DOT) is an emerging functional medical imaging modality which aims to recover the optical properties of biological tissue. The forward problem of the light propagation of DOT can be modelled in the frequency domain as a diffusion equation with Robin boundary conditions. In the case of multilayered geometries with piecewise constant parameters, the forward problem is equivalent to a set of coupled Helmholtz equations. In this paper, we present solutions for the multilayered diffuse light propagation for a three-layer concentric sphere model using a series expansion method and for a general layered geometry using the boundary element method (BEM). Results are presented comparing these solutions to an independent Monte Carlo model, and for an example three layered head model.

Publication Types:

PMID: 16424578 [PubMed – indexed for MEDLINE]


Dynamic physiological modeling for functional diffuse optical tomography.

Diamond SG, Huppert TJ, Kolehmainen V, Franceschini MA, Kaipio JP, Arridge SR, Boas DA.

Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA 02129, USA. sdiamond@nmr.harvard.edu

Diffuse optical tomography (DOT) is a noninvasive imaging technology that is sensitive to local concentration changes in oxy- and deoxyhemoglobin. When applied to functional neuroimaging, DOT measures hemodynamics in the scalp and brain that reflect competing metabolic demands and cardiovascular dynamics. The diffuse nature of near-infrared photon migration in tissue and the multitude of physiological systems that affect hemodynamics motivate the use of anatomical and physiological models to improve estimates of the functional hemodynamic response. In this paper, we present a linear state-space model for DOT analysis that models the physiological fluctuations present in the data with either static or dynamic estimation. We demonstrate the approach by using auxiliary measurements of blood pressure variability and heart rate variability as inputs to model the background physiology in DOT data. We evaluate the improvements accorded by modeling this physiology on ten human subjects with simulated functional hemodynamic responses added to the baseline physiology. Adding physiological modeling with a static estimator significantly improved estimates of the simulated functional response, and further significant improvements were achieved with a dynamic Kalman filter estimator (paired t tests, n=10, P<0.05). These results suggest that physiological modeling can improve DOT analysis. The further improvement with the Kalman filter encourages continued research into dynamic linear modeling of the physiology present in DOT. Cardiovascular dynamics also affect the blood-oxygen-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI). This state-space approach to DOT analysis could be extended to BOLD fMRI analysis, multimodal studies and real-time analysis.

PMID: 16242967 [PubMed – indexed for MEDLINE]


Evidence that cerebral blood volume can provide brain activation maps with better spatial resolution than deoxygenated hemoglobin.

Culver JP, Siegel AM, Franceschini MA, Mandeville JB, Boas DA.

Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4525 Scott Avenue, St. Louis, MO 63110, USA. culverj@wustl.edu

With the aim of evaluating the relative performance of hemodynamic contrasts for mapping brain activity, the spatio-temporal response of oxy-, deoxy-, and total-hemoglobin concentrations were imaged with diffuse optical tomography during electrical stimulation of the rat somatosensory cortex. For both 6-s and 30-s stimulus durations, total hemoglobin images provided smaller activation areas than oxy- or deoxy-hemoglobin images. In addition, analysis of regions of interest near the sagittal sinus vein show significantly greater contrast in both oxy- and deoxy-relative to total hemoglobin, suggesting that oximetric contrasts have larger draining vein contributions compared to total hemoglobin contrasts under the given stimulus conditions. These results indicate that total hemoglobin and cerebral blood volume may have advantages as hemodynamic mapping contrasts, particularly for large amplitude, longer duration stimulus paradigms.

Publication Types:

PMID: 16084112 [PubMed – indexed for MEDLINE]


Diffuse optical tomography with a priori anatomical information.

Guven M, Yazici B, Intes X, Chance B.

Electrical, Computer, and Systems Engineering Department, Rensselaer Polytechnic Institute, Troy, NY, USA.

Diffuse optical tomography (DOT) poses a typical ill-posed inverse problem with a limited number of measurements and inherently low spatial resolution. In this paper, we propose a hierarchical Bayesian approach to improve spatial resolution and quantitative accuracy by using a priori information provided by a secondary high resolution anatomical imaging modality, such as magnetic resonance (MR) or x-ray. In such a dual imaging approach, while the correlation between optical and anatomical images may be high, it is not perfect. For example, a tumour may be present in the optical image, but may not be discernable in the anatomical image. The proposed hierarchical Bayesian approach allows incorporation of partial a priori knowledge about the noise and unknown optical image models, thereby capturing the function-anatomy correlation effectively. We present a computationally efficient iterative algorithm to simultaneously estimate the optical image and the unknown a priori model parameters. Extensive numerical simulations demonstrate that the proposed method avoids undesirable bias towards anatomical prior information and leads to significantly improved spatial resolution and quantitative accuracy.

Publication Types:

PMID: 15930606 [PubMed – indexed for MEDLINE]


Optical tomographic imaging of small animals.

Hielscher AH.

Department of Biomedical Engineering, Columbia University, ET351 Mudd Building, 500 West 120th Street, MC8904, New York, NY 10027, USA. ahh20004@columbia.edu

Diffuse optical tomography is emerging as a viable new biomedical imaging modality. Using visible and near-infrared light this technique can probe the absorption and scattering properties of biological tissues. The main applications are currently in brain, breast, limb and joint imaging; however, optical tomographic imaging of small animals is attracting increasing attention. This interest is fuelled by recent advances in the transgenic manipulation of small animals that has led to many models of human disease. In addition, an ever increasing number of optically reactive biochemical markers has become available, which allow diseases to be detected at the molecular level long before macroscopic symptoms appear. The past three years have seen an array of novel technological developments that have led to the first optical tomographic studies of small animals in the areas of cerebral ischemia and cancer.

Publication Types:

PMID: 15722019 [PubMed – indexed for MEDLINE]


Improved quantification of small objects in near-infrared diffuse optical tomography.

Srinivasan S, Pogue BW, Dehghani H, Jiang S, Song X, Paulsen KD.

Dartmouth College, Thayer School of Engineering, Hanover, NH 03755, USA. Subha@dartmouth.edu

Diffuse optical tomography allows quantification of hemoglobin, oxygen saturation, and water in tissue, and the fidelity in this quantification is dependent on the accuracy of optical properties determined during image reconstruction. In this study, a three-step algorithm is proposed and validated that uses the standard Newton minimization with Levenberg-Marquardt regularization as the first step. The second step is a modification to the existing algorithm using a two-parameter regularization to allow lower damping in a region of interest as compared to background. This second stage allows the recovery of the actual size of an inclusion. A region-based reconstruction is the final third step, which uses the estimated size and position information from step 2 to yield quantitatively accurate average values for the optical parameters. The algorithm is tested on simulated and experimental data and is found to be insensitive to object contrast and position. The percentage error between the true and the average recovered value for the absorption coefficient in test images is reduced from 47 to 27% for a 10-mm inclusion, from 38 to 13% for a 15-mm anomaly, and from 28 to 5.5% for a 20-mm heterogeneity. Simulated data with absorbing and scattering heterogeneities of 15 mm diam located in different positions show recovery with less than 15% error in absorption and 6% error in reduced scattering coefficients. The algorithm is successfully applied to clinical data from a subject with a breast abnormality to yield quantitatively increased absorption coefficients, which enhances the contrast to 3.8 compared to 1.23 previously. Copyright 2004 Society of Photo-Optical Instrumentation Engineers.

Publication Types:

PMID: 15568936 [PubMed – indexed for MEDLINE]


Fiber optic in vivo imaging in the mammalian nervous system.

Mehta AD, Jung JC, Flusberg BA, Schnitzer MJ.

Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.

The compact size, mechanical flexibility, and growing functionality of optical fiber and fiber optic devices are enabling several new modalities for imaging the mammalian nervous system in vivo. Fluorescence microendoscopy is a minimally invasive fiber modality that provides cellular resolution in deep brain areas. Diffuse optical tomography is a non-invasive modality that uses assemblies of fiber optic emitters and detectors on the cranium for volumetric imaging of brain activation. Optical coherence tomography is a sensitive interferometric imaging technique that can be implemented in a variety of fiber based formats and that might allow intrinsic optical detection of brain activity at a high resolution. Miniaturized fiber optic microscopy permits cellular level imaging in the brains of behaving animals. Together, these modalities will enable new uses of imaging in the intact nervous system for both research and clinical applications.

Publication Types:

PMID: 15464896 [PubMed – indexed for MEDLINE]


Three-dimensional optical tomographic brain imaging in small animals, part 1: hypercapnia.

Bluestone AY, Stewart M, Lasker J, Abdoulaev GS, Hielscher AH.

Columbia University, Departments of Biomedical Engineering and Radiology, New York, New York 10027, USA.

In this study, we explore the potential of diffuse optical tomography for brain oximetry. While several groups have already reported on the sensitivity of optical measurements to changes in oxyhemoglobin, deoxyhemoglobin, and blood volume, these studies were often limited to single source-detector geometries or topographic maps, where signals obtained from within the brain are projected onto 2-D surface maps. In this two-part study, we report on our efforts toward developing a volumetric optical imaging system that allows one to spatially resolve 3-D hemodynamic effects in rat brains. In part 1, we describe the instrumentation, optical probe design, and the model-based iterative image reconstruction algorithm employed in this work. Consideration of how a priori anatomical knowledge can be incorporated in the reconstruction process is presented. This system is then used to monitor global hemodynamic changes that occur in the brain under various degrees of hypercapnia. The physiologic cerebral response to hypercapnia is well known and therefore allows an initial performance assessment of the imaging system. As expected, we observe global changes in blood volume and oxygenation, which vary linearly as a function of the concentration of the inspired carbon dioxide. Furthermore, experiments are designed to determine the sensitivity of the reconstructions of only 1 mm to inaccurate probe positioning. We determine that shifts can significantly influence the reconstructions. In part 2 we focus on more local hemodynamic changes that occur during unilateral carotid occlusion performed at lower-than-normal systemic blood pressure. In this case, the occlusion leads to a predominantly monohemispherically localized effect, which is well described in the literature. Having explored the system with a well-characterized physiologic effect, we investigate and discuss the complex compensatory cerebrovascular hemodynamics that occur at normotensive blood pressure. Overall, these studies demonstrate the potential and limitations of our diffuse optical imager for visualizing global and focal hemodynamic phenomenon three dimensionally in the brains of small animals. (c) 2004 Society of Photo-Optical Instrumentation Engineers.

Publication Types:

PMID: 15447026 [PubMed – indexed for MEDLINE]

initial dip

One page.

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Dynamics and nonlinearities of the BOLD response at very short stimulus durations.

Yeşilyurt B, Uğurbil K, Uludağ K.

Max-Planck-Institute for Biological Cybernetics, High-Field Magnetic Resonance Center, 72076 Tübingen, Germany.

In designing a functional imaging experiment or analyzing data, it is typically assumed that task duration and hemodynamic response are linearly related to each other. However, numerous human and animal studies have previously reported a deviation from linearity for short stimulus durations (<4 s). Here, we investigated nonlinearities of blood-oxygenation-level-dependent (BOLD) signals following visual stimulation of 5 to 1000 ms duration at two different luminance levels in human subjects. It was found that (a) a BOLD response to stimulus durations as short as 5 ms can be reliably detected; this stimulus duration is shorter than employed in any previous study investigating BOLD signal time courses; (b) the responses are more nonlinear than in any other previous study: the BOLD response to 1000 ms stimulation is only twice as large as the BOLD response to 5 ms stimulation although 200 times more photons were projected onto the retina; (c) the degree of nonlinearity depends on stimulus intensity; that is, nonlinearities have to be characterized not only by stimulus duration but also by stimulus features like luminance. These findings are especially of most practical importance in rapid event-related functional magnetic resonance imaging (fMRI) experimental designs. In addition, an ‘initial dip’ response – thought to be generated by a rapid increase in cerebral metabolic rate of oxygen metabolism (CMRO(2)) relative to cerebral blood flow – was observed and shown to colocalize well with the positive BOLD response. Highly intense stimulation, better tolerated by human subjects for short stimulus durations, causes early CMRO(2) increase, and thus, the experimental design utilized in this study is better for detecting the initial dip than standard fMRI designs. These results and those from other groups suggest that short stimulation combined with appropriate experimental designs allows neuronal events and interactions to be examined by BOLD signal analysis, despite its slow evolution.

PMID: 18479876 [PubMed – as supplied by publisher]


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Transient and sustained BOLD responses to sustained visual stimulation.

Uludağ K.

Max-Planck-Institute for Biological Cybernetics, High-Field Magnetic Resonance Center, 72076 Tübingen, Germany.

Examining the transients of the blood-oxygenation-level-dependent (BOLD) signal using functional magnetic resonance imaging is a tool to probe basic brain physiology. In addition to the so-called initial dip and poststimulus undershoot of the BOLD signal, occasionally, overshoot at the beginning and at the end of stimulation and stimulus onset and offset (‘phasic’) responses are observed. Hemifield visual stimulation was used in human subjects to study the latter transients. As expected, sustained (‘tonic’) stimulus-correlated contralateral activation in the visual cortex and LGN was observed. Interestingly, bilateral phasic responses were observed, which only partly overlapped with the tonic network and which would have been missed using a standard analysis. A biomechanical model of the BOLD signal (‘balloon model’) indicated that, in addition to phasic neuronal activity, vascular uncoupling can also give rise to phasic BOLD signals. Thus, additional physiological information (i.e., cerebral blood flow) and examination of spatial distribution of the activity might help to assess the BOLD signal transients correctly. In the current study, although vascular uncoupled responses cannot be ruled out as an explanation of the observed phasic BOLD network, the spatial distribution argues that sustained hemifield visual stimulation evokes both bilateral phasic and contralateral sustained neuronal responses. As a consequence, in rapid event-related experimental designs, both the phasic and tonic networks cannot be separated, possibly confounding the interpretation of BOLD signal data. Furthermore, a combination of phasic and tonic responses in the same region of interest might also mimic a BOLD response typically observed in adaptation experiments.

PMID: 18479869 [PubMed – as supplied by publisher]


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Independent components of the haemodynamic response in intrinsic optical imaging.

Schiessl I, Wang W, McLoughlin N.

Faculty of Life Sciences, University of Manchester, Manchester, M60 1QD, UK. i.schiessl@manchester.ac.uk

Functional brain imaging methods are prone to contamination from global vascular artefacts. A variety of methods have been proposed to help segment functional from non-specific changes. Here we quantify the improvement in the signal to noise ratio (SNR) of functional maps, derived from intrinsic optical imaging studies of macaque visual cortex, through the application of Extended Spatial Decorrelation (ESD). The resulting independent component maps and their corresponding time courses reveal for the first time a fast vascular component in the haemodynamic response. ESD is a blind source separation algorithm that utilises spatial statistical features in brain images to separate the recorded mixed sources into independent components. We have investigated differential and single condition experiments using a variety of visual stimuli. To calculate the improvement of the SNR in decibel (dB) we back project separated components onto the original single trial data and analyse the corresponding Fourier spectrum. The application of ESD improved SNR in the functional brain maps from 0.52 to 16.88 dB on differential imaging data and from 1.69 to 12.83 dB in the case of single condition experiments. Analysing the independent components further we found that they can separate different functional compartments of the cortical vasculature. Some of the components, classified as arterial through slit spectroscopy, revealed a strong fast response to the stimulus onset/offset starting approximately 0.2 s after the change of the stimulus and reaching a peak after approximately 0.4 s. This fast haemodynamic response raises new questions concerning the spatial specificity of the so-called « initial dip ».

Publication Types:

PMID: 17959391 [PubMed – indexed for MEDLINE]


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Temporal profiles and 2-dimensional oxy-, deoxy-, and total-hemoglobin somatosensory maps in rat versus mouse cortex.

Prakash N, Biag JD, Sheth SA, Mitsuyama S, Theriot J, Ramachandra C, Toga AW.

University of California, Los Angeles, David Geffen School of Medicine, Department of Neurology, Laboratory of Neuro Imaging, Los Angeles, CA 90095, USA. neal.prakash@gmail.com

BACKGROUND: Mechanisms of neurovascular coupling-the relationship between neuronal chemoelectrical activity and compensatory metabolic and hemodynamic changes-appear to be preserved across species from rats to humans despite differences in scale. However, previous work suggests that the highly cellular dense mouse somatosensory cortex has different functional hemodynamic changes compared to other species. METHODS: We developed novel hardware and software for 2-dimensional optical spectroscopy (2DOS). Optical changes at four simultaneously recorded wavelengths were measured in both rat and mouse primary somatosensory cortex (S1) evoked by forepaw stimulation to create four spectral maps. The spectral maps were converted to maps of deoxy-, oxy-, and total-hemoglobin (HbR, HbO, and HbT) concentration changes using the modified Beer-Lambert law and phantom HbR and HbO absorption spectra. RESULTS:: Functional hemodynamics were different in mouse versus rat neocortex. On average, hemodynamics were as expected in rat primary somatosensory cortex (S1): the fractional change in the log of HbT concentration increased monophasically 2 s after stimulus, whereas HbO changes mirrored HbR changes, with HbO showing a small initial dip at 0.5 s followed by a large increase 3.0 s post stimulus. In contrast, mouse S1 showed a novel type of stimulus-evoked hemodynamic response, with prolonged, concurrent, monophasic increases in HbR and HbT and a parallel decrease in HbO that all peaked 3.5-4.5 s post stimulus onset. For rats, at any given time point, the average size and shape of HbO and HbR forepaw maps were the same, whereas surface veins distorted the shape of the HbT map. For mice, HbO, HbR, and HbT forepaw maps were generally the same size and shape at any post-stimulus time point. CONCLUSIONS: 2DOS using image splitting optics is feasible across species for brain mapping and quantifying the map topography of cortical hemodynamics. These results suggest that during physiologic stimulation, different species and/or cortical architecture may give rise to different hemodynamic changes during neurovascular coupling.

Publication Types:

PMID: 17574868 [PubMed – indexed for MEDLINE]

PMCID: PMC2227950


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A coherent neurobiological framework for functional neuroimaging provided by a model integrating compartmentalized energy metabolism.

Aubert A, Pellerin L, Magistretti PJ, Costalat R.

Département de Physiologie, Université de Lausanne, 1005 Lausanne, Switzerland.

Functional neuroimaging has undergone spectacular developments in recent years. Paradoxically, its neurobiological bases have remained elusive, resulting in an intense debate around the cellular mechanisms taking place upon activation that could contribute to the signals measured. Taking advantage of a modeling approach, we propose here a coherent neurobiological framework that not only explains several in vitro and in vivo observations but also provides a physiological basis to interpret imaging signals. First, based on a model of compartmentalized energy metabolism, we show that complex kinetics of NADH changes observed in vitro can be accounted for by distinct metabolic responses in two cell populations reminiscent of neurons and astrocytes. Second, extended application of the model to an in vivo situation allowed us to reproduce the evolution of intraparenchymal oxygen levels upon activation as measured experimentally without substantially altering the initial parameter values. Finally, applying the same model to functional neuroimaging in humans, we were able to determine that the early negative component of the blood oxygenation level-dependent response recorded with functional MRI, known as the initial dip, critically depends on the oxidative response of neurons, whereas the late aspects of the signal correspond to a combination of responses from cell types with two distinct metabolic profiles that could be neurons and astrocytes. In summary, our results, obtained with such a modeling approach, support the concept that both neuronal and glial metabolic responses form essential components of neuroimaging signals.

Publication Types:

PMID: 17360498 [PubMed – indexed for MEDLINE]

PMCID: PMC1820730


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Intrinsic optical signal imaging of neocortical seizures: the ‘epileptic dip’.

Bahar S, Suh M, Zhao M, Schwartz TH.

Department of Neurological Surgery, Weill-Cornell Medical College, New York Presbyterian Hospital, New York, New York, USA. bahars@umsl.edu

Focal neocortical seizures, induced by injection of 4-aminopyridine, were imaged in the rat neocortex using the intrinsic optical signal, with incident light at various wavelengths. We observed focal, reproducible and prolonged reflectance drops following seizure onset, regardless of wavelength, in the ictal onset zone. A persistent drop in light reflectance with incident orange light, which corresponds to a decrease in oxygenated hemoglobin, was observed. We describe this phenomenon as an ‘epileptic dip’ as it is reminiscent of the ‘initial dip’ observed using the intrinsic optical signal, and also with blood oxygen level-dependent functional magnetic resonance imaging, after normal sensory processing, although with much longer duration. This persistent ictal ischemia was confirmed by direct measurement of tissue oxygenation using oxygen-sensitive electrodes.

Publication Types:

PMID: 16543814 [PubMed – indexed for MEDLINE]


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Brain lactate kinetics: Modeling evidence for neuronal lactate uptake upon activation.

Aubert A, Costalat R, Magistretti PJ, Pellerin L.

Département de Physiologie, Université de Lausanne, 1005 Lausanne, Switzerland.

A critical issue in brain energy metabolism is whether lactate produced within the brain by astrocytes is taken up and metabolized by neurons upon activation. Although there is ample evidence that neurons can efficiently use lactate as an energy substrate, at least in vitro, few experimental data exist to indicate that it is indeed the case in vivo. To address this question, we used a modeling approach to determine which mechanisms are necessary to explain typical brain lactate kinetics observed upon activation. On the basis of a previously validated model that takes into account the compartmentalization of energy metabolism, we developed a mathematical model of brain lactate kinetics, which was applied to published data describing the changes in extracellular lactate levels upon activation. Results show that the initial dip in the extracellular lactate concentration observed at the onset of stimulation can only be satisfactorily explained by a rapid uptake within an intraparenchymal cellular compartment. In contrast, neither blood flow increase, nor extracellular pH variation can be major causes of the lactate initial dip, whereas tissue lactate diffusion only tends to reduce its amplitude. The kinetic properties of monocarboxylate transporter isoforms strongly suggest that neurons represent the most likely compartment for activation-induced lactate uptake and that neuronal lactate utilization occurring early after activation onset is responsible for the initial dip in brain lactate levels observed in both animals and humans.

Publication Types:

PMID: 16260743 [PubMed – indexed for MEDLINE]

PMCID: PMC1297516


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Interaction between tissue oxygen tension and NADH imaging during synaptic stimulation and hypoxia in rat hippocampal slices.

Foster KA, Beaver CJ, Turner DA.

Research and Surgery Services, Durham Veterans Affairs Medical Center, Durham, NC 27710, USA. fosterka@duke.edu

Oxygen and NADH are essential components in the production of ATP in the CNS. This study examined the dynamic interaction between tissue oxygen tension (pO(2)) and NADH imaging changes within hippocampal tissue slices, during metabolic stresses including hypoxia and synaptic activation. The initiation of abrupt hypoxia (from 95% O(2) to 95% N(2)) caused a rapid decrease in pO(2), onset of hypoxic spreading depression (hsd; at 6.7+/-1.3 mm Hg; n=15), and a monophasic increase in NADH. Provided that reoxygenation was prompt, synaptic responses, pO(2) and NADH levels returned to baseline following hsd. Longer hypoxia caused irreversible neuronal dysfunction, an increase in pO(2) beyond baseline (due to decreased tissue demand), and hyperoxidation of NADH (10+/-2% decrease below baseline; n=7). Synaptic activation in ambient 95% O(2) caused a decrease or ‘initial dip’ in pO(2) and a biphasic NADH response (oxidation followed by reduction). The oxidizing phase of the NADH response was mitochondrial as it was synchronous with the ‘initial’ dip in pO(2). Following slow graded reductions in ambient oxygen levels to 8%, four of seven slices developed hsd following synaptic stimulation. The hypoxic threshold for graded oxygen reductions occurred at 7.9+/-5.8 mm Hg O(2) (n=7). Our hypoxic threshold range (6.7-7.9 mm Hg O(2) from abrupt and graded oxygen reduction, respectively) correlates well with reported in vivo values of <12 mm Hg O(2). The major findings of this study include: 1) determination of the critical physiological threshold of pO(2) (based upon hsd), which is a marker of imminent neuronal death if oxygen is not rapidly restored; 2) NADH hyperoxidation and an increase in pO(2) beyond baseline levels following longer periods of hypoxia; and 3) the occurrence of a pO(2) ‘dip’ during synaptic stimulation, which correlates with the early oxidizing phase of the biphasic NADH response.

Publication Types:

PMID: 15837126 [PubMed – indexed for MEDLINE]


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Modeling the hemodynamic response to brain activation.

Buxton RB, Uludağ K, Dubowitz DJ, Liu TT.

Department of Radiology, 0677, and Center for Functional MRI, University of California-San Diego, La Jolla, CA 92093-0677, USA. rbuxton@ecsd.edu

Neural activity in the brain is accompanied by changes in cerebral blood flow (CBF) and blood oxygenation that are detectable with functional magnetic resonance imaging (fMRI) techniques. In this paper, recent mathematical models of this hemodynamic response are reviewed and integrated. Models are described for: (1) the blood oxygenation level dependent (BOLD) signal as a function of changes in cerebral oxygen extraction fraction (E) and cerebral blood volume (CBV); (2) the balloon model, proposed to describe the transient dynamics of CBV and deoxy-hemoglobin (Hb) and how they affect the BOLD signal; (3) neurovascular coupling, relating the responses in CBF and cerebral metabolic rate of oxygen (CMRO(2)) to the neural activity response; and (4) a simple model for the temporal nonlinearity of the neural response itself. These models are integrated into a mathematical framework describing the steps linking a stimulus to the measured BOLD and CBF responses. Experimental results examining transient features of the BOLD response (post-stimulus undershoot and initial dip), nonlinearities of the hemodynamic response, and the role of the physiologic baseline state in altering the BOLD signal are discussed in the context of the proposed models. Quantitative modeling of the hemodynamic response, when combined with experimental data measuring both the BOLD and CBF responses, makes possible a more specific and quantitative assessment of brain physiology than is possible with standard BOLD imaging alone. This approach has the potential to enhance numerous studies of brain function in development, health, and disease.

Publication Types:

PMID: 15501093 [PubMed – indexed for MEDLINE]


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Coupling of changes in cerebral blood flow with neural activity: what must initially dip must come back up.

Ances BM.

Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA. beau.ances@uphs.upenn.edu

Activation flow coupling, increases in neuronal activity leading to changes in cerebral blood flow (CBF), is the basis of many neuroimaging methods. An early rise in deoxygenation, the « initial dip, » occurs before changes in CBF and cerebral blood volume (CBV) and may provide a better spatial localizer of early neuronal activity compared with subsequent increases in CBF. Imaging modality, anesthetic, degree of oxygenation, and species can influence the magnitude of this initial dip. The observed initial dip may reflect a depletion of mitochondrial oxygen (O(2)) buffers caused by increased neuronal activity. Changes in CBF mediated by nitric oxide (NO) or other metabolites and not caused by a lack of O(2) or energy depletion most likely lead to an increased delivery of capillary O(2) in an attempt to maintain intracellular O(2) buffers.

Publication Types:

PMID: 14688611 [PubMed – indexed for MEDLINE]

Stereology is not tomography

Stereology (from Greek stereos = solid) was originally defined as `the spatial interpretation of sections’. It is an interdisciplinary field that is largely concerned with the three-dimensional interpretation of planar sections of materials or tissues. It provides practical techniques for extracting quantitative information about a three-dimensional material from measurements made on two-dimensional planar sections of the material. See the Examples below. Stereology is an important and efficient tool in many applications of microscopy (such as petrography, materials science, and biosciences including histology, bone and neuroanatomy). Stereology is a developing science with many important innovations being developed mainly in Europe. New innovations such as the proportionator continue to make important improvements in the efficiency of stereological procedures.

In addition to two-dimensional plane sections, stereology also applies to three-dimensional slabs (e.g. 3D microscope images), one-dimensional probes (e.g. needle biopsy), projected images, and other kinds of `sampling’. It is especially useful when the sample has a lower spatial dimension than the original material. Hence, stereology is often defined as the science of estimating higher dimensional information from lower dimensional samples.

Stereology is based on fundamental principles of geometry (e.g. Cavalieri’s principle) and statistics (mainly survey sampling inference). It is a completely different approach from computed tomography.
Classical applications of stereology include:

* calculating the volume fraction of quartz in a rock by measuring the area fraction of quartz on a typical polished plane section of rock (« Delesse principle »);
* calculating the surface area of pores per unit volume in a ceramic, by measuring the length of profiles of pore boundary per unit area on a typical plane section of the ceramic (multiplied by 4 / π);
* calculating the total length of ca

Stereology is not tomography

Stereology is a completely different enterprise from computed tomography or for DOT. A computed tomography algorithm effectively reconstructs the complete internal three-dimensional geometry of an object, given a complete set of all plane sections through it (or equivalent X-ray data). On the contrary, stereological techniques require only a few `representative’ plane sections, and statistically extrapolate from them to the three-dimensional material.

Stereology exploits the fact that some 3-D quantities can be determined without 3-D reconstruction: for example, the 3-D volume of any object can be determined from the 2-D areas of its plane sections, without reconstructing the object. (This means that stereology only works for certain quantities like volume, and not for other quantities).

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. ccooper@essex.ac.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:

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]

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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