Archive pour 10 juillet 2008

initial dip

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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.

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 ».

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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.

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.

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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.

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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.

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.

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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.

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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.

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.

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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.

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.

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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.

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.

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PMID: 14688611 [PubMed – indexed for MEDLINE]

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A9CAD is a general purpose 2-dimensional freeware CAD program. It supports industry standard DWG/DXF drawing formats. With A9CAD you can draw shapes such as line, rectangle, circle, poly-line, text and dimension; performing drawing modifications like move, scale, rotate, explode, trim, fillet and mirror; edit color, fill mode, line type and line width; change entity attributes via properties window; manage drawing styles and settings; and configure drawing environments. (15.6MB)

HOMEPAGE | | DOWNLOAD addded Nov 26 ’04


Power System Simulator is graphical editor for power system modelling. Application implements element connections in natural way. After solving, power flow results are shown on the same graph. It also shows actual active power flows which are represented with arrows on power lines. (614KB)

DOWNLOAD added Jan 20 ’05


AutoCAD® converter from SolidWorks Corporation. No need to upgrade to the next version of AutoCAD® software. Open and edit any DWG file using any version of AutoCAD. (3.6MB)

HOMEPAGE | | DOWNLOAD added Jun 22 ’05


Google SketchUp is an easy-to-learn 3D modeling program whose few simple tools enable you to create 3D models of houses, sheds, decks, home additions, woodworking projects, even space ships. You can add details, textures and glass to your models, design with dimensional accuracy, and place your finished models in Google Earth, share them with others by posting them to the 3D Warehouse, or print hard copies. (19MB)

HOMEPAGE | | DOWNLOAD added Jul 9 ’06


Anim8or is a 3D computer animation program that is designed to allow straightforward creation of animations. You interactively create and edit objects, figures, and scenes directly on the computers screen. The basic interface is similar to most 3D animation and CAD programs. (671KB)

HOMEPAGE | | DOWNLOAD added Aug 1 ’06


Solid Edge 2D Drafting includes a wealth of tools designed to ease the transition of 2D AutoCAD users updating to Solid Edge, including import wizards, WYSIWYG of imported files (matching of AutoCAD fonts and color schemes) and many other capabilities that make it a compelling application for AutoCAD 2D users looking for more value and productivity from their 2D CAD seats. (239MB)

HOMEPAGE added Sep 11 ’06


A simple creation tool for floor plans, 3D models and interrior design concepts. (37.8MB)

HOMEPAGE | | DOWNLOAD added Dec 7 ’06


DevConv, the DXF, DXB, DWG converter. DevConv is a stand-alone tool, AutoCad is not required. Supports all new versions of DWG/DXF/DXB files (R9 to R2006/2007 formats). (3.1MB)

HOMEPAGE | | DOWNLOAD added Dec 14 ’06


A free download from the CoCreate product family – CoCreate Modeling Personal Edition, a 3D CAD system you can use for assemblies with up to 60 parts. Download a FREE version and see how liberating an explicit, geometry-based 3D CAD system can be. (83MB)

HOMEPAGE updated Apr 5 ’08


Shape your ideas in just a few minutes with EasyCAD Iris, the room visualization software to design your wall tile and flooring patterns without prior knowledge of computer graphics. (1.4MB)

HOMEPAGE | | DOWNLOAD added Jul 12 ’07


Live DXF2BMP is free software that converts CAD generated drawing to raster image; drawings can be generated by any CAD program that support DXF format such as AutoCAD®. (1.6MB)

HOMEPAGE | | DOWNLOAD added Sep 18 ’07


« CNC Live » is a brand new vision for CNC software; we tried in this program to make CNC processing easy, simple, affordable and time effective. « CNC Live » takes a BMP « bitmap » image or a DXF « Drawing Exchange Format » drawing as an input, generate working path, simulates and executes it. « CNC Live » is the ideal CNC software for plasma and oxy fuel cutting, milling, routing, profiling, pocketing, drilling and PCB developing and drilling. (6.1MB)

HOMEPAGE | | DOWNLOAD added Oct 7 ’07


Reads and writes AutoCAD® DWG files from 2.5 to 2008, has industry standard AutoCAD Commands, has AutoCAD® Menu, Script, Font Compatibility. Free for non-commercial use. (85MB)

HOMEPAGE | | DOWNLOAD added Dec 6 ’07


General purpose CAD program. (5MB)

HOMEPAGE | | DOWNLOAD added Mar 28 ’08


AutoCAD functionality for free personal use only. DWG 2008 DXF read and write. Similar icons, commands and interface. IntelliCAD AutoLISP interpreter, temporary point snap (like oSnap), layers, blocks. Hatch, block and xref editing. 3D shading and rendering options. Optional approx. 10000 Symbols ALE library. Free for personal use. (92MB)

HOMEPAGE | | DOWNLOAD added May 21 ’08


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