Computational modeling of chemotactic signaling and aggregation of microglia around implantation site during deep brain stimulation

It is well established that prolonged electrical stimulation of brain tissue causes massive release of ATP in the extracellular space. The released ATP and the products of its hydrolysis, such as ADP and adenosine, become the main elements mediating chemotactic sensitivity and motility of microglial cells via subsequent activation of P2Y_2,12 as well as A3A and A2A adenosine receptors. The size of the sheath around the electrode formed by the microglial cells is an important criterion for the optimization of the parameters of electrical current delivered to brain tissue. Here, we study a purinergic signaling pathway underlying the chemotactic motion of microglia towards the implanted electrode during deep brain stimulation. We present a computational model describing formation of a stable aggregate around the implantation site due to the joint chemo-attractive action of ATP and ADP together with a mixed influence of extracellular adenosine. The model was built in accordance with the classical Keller-Segel approach and includes an equation for the cells’ density as well as equations describing the hydrolysis of extracellular ATP via successive reaction steps ATP →ADP →AMP →adenosine. The results of our modeling allowed us to reveal the dependence of the width of the encapsulating layer around the electrode on the amount of ATP released due to permanent electrical stimulation. The dependences of the aggregates’ size on the parameter governing the nonlinearity of interaction between extracellular adenosine and adenosine receptors are also analyzed.     

Imaging cortical electrical stimulation in vivo: fast intrinsic optical signal versus voltage-sensitive dyes

We applied high-temporal-resolution optical imaging utilizing both the fast intrinsic optical signal (fIOS) and voltage-sensitive dyes (VSDs) to observe the spatiotemporal characteristics of rat somatosensory cortex during electrical stimulation. We find that changes in both the fIOS and VSD signals occur rapidly (<30 ms) after the stimulus is applied, suggesting that both membrane depolarization and transmembrane ion movement occur shortly after the stimulus, preceding the more gradual physiological changes in oxygen consumption revealed by the slower component of the intrinsic optical signal. We find that the VSD signal spreads through a much larger area of cortex than the fIOS.     

In vivo optical neural recording using fiber-based surface plasmon resonance

We propose an intrinsic optical method for in vivo neural recording using optic fiber-based surface plasmon resonance (SPR) phenomena. The fiber-based SPR method is electrical artifact free, labeling free, and feasible for a portable system compared with conventional in vivo neural recording systems. We simultaneously detected SPR signals and electrical neural activity from the rat somatosensory cortex evoked by electrical stimulation on the forepaw. Pharmacological analysis using a voltage-gated sodium channel blocker confirmed the neural origins of the optical signals. This fiber-based SPR system promises the enhanced ability to record in vivo neural activity for the investigation of neurons and their networks.     

The effect of artifacts on dependence measurement in fMRI

The study of effective connectivity by means of neuroimaging depends on the measurement of similarity between activity patterns at different locations in the brain, without necessarily presupposing a particular model for this dependence. When these interactions are measured using functional magnetic resonance imaging (fMRI) techniques, however, imaging and physiological artifacts create patterns of dependence that may be unrelated to cortical activity. We demonstrate some of these effects through the measurement of short-range dependencies present in fMRI scans of the primary visual cortex (V1) in the anaesthetized macaque monkey. High-field (4.7 T) fMRI scans were conducted to measure responses based on the blood oxygen level-dependent contrast mechanism, during periods of no sensory stimulation and of visual stimulation with rotating polar-transformed checkerboard gratings. Dependence between the haemodynamic activity at different spatial locations (i.e., different voxels) was measured using correlation, mutual information and functional covariance. Particular attention was paid to understanding the sources of spurious dependence that may be observed during such investigations. Two main effects were detected: (a) short-range correlations introduced by the process of image reconstruction and (b) perturbations in the haemodynamic response caused by breathing. The image reconstruction artifacts were shown to create an artificially high short-range dependence in the readout direction of the scan, and the breathing artifacts caused enhanced short-range dependence in both the readout and phase-encode directions. Additional dependence in the phase-encode direction due to image-ghosting is also possible but will not be discussed in this report, as it can be alleviated by fine adjustment of preemphasis (elimination of eddy currents). A technique is described for removing breathing artifacts, and the effect of breathing on the apparent dependence between voxels is illustrated. The correlation of haemodynamic activity with the stimulus was found to be affected by breathing, although this effect can be neutralised by averaging the haemodynamic responses over many repetitions of the stimulus. Nonetheless, patterns of dependent activity between voxels may be lost in this averaging process, which makes the removal of breathing artifacts necessary if statistical dependence and the study of effective connectivity is the primary aim of an investigation.     

Estimation of the scattering coefficients of turbid media using angle-resolved optical frequency-domain imaging

Noninvasive measurements of the scattering coefficients of optically turbid media using angle-resolved optical frequency-domain imaging (OFDI) are demonstrated. It is shown that, by incoherently averaging OFDI reflectance signals acquired at different backscattering angles, speckle noise is reduced, allowing scattering coefficients to be extracted from a single A-line with much higher accuracy than with measurements from conventional OFDI and optical coherence tomography systems. Modeling speckle as a random phasor sum, the relationship between the measurement accuracy and the number of compounded angles is derived. The sensitivity analysis is validated with measurements from a tissue phantom.     

Near-field scanning optical microscopy local luminescence studies of rhodamine dye

This article presents results of near-field scanning optical microscope measurement of local luminescence of rhodamine 3B intercalated in montmorillonite samples. We focus on how local topography affects both the excitation and luminescence signals and resulting optical artifacts. The Finite Difference in Time Domain method (FDTD) is used to model the electromagnetic field distribution of the full tip-sample geometry including far-field radiation. Even complex problems like localized luminescence can be simulated computationally using FDTD and these simulations can be used to separate the luminescence signal from topographic artifacts.     

产生暗归零码光标记信号的新方案

在对预编码、调制和编码过程进行改进的基础上,提出了一种利用一个双臂马赫-曾德尔铌酸锂调制器和一个电信号时延器产生可调占空比和消光比的光暗脉冲归零码二进制信号的新方案。实验证明这种信号能用传统的二进制强度调制-直接检测系统的接收机进行检测。实验得到了在调节电信号时延器时速率为2.5 Gbit/s的光暗脉冲归零码二进制信号的频谱变化规律,以及占空比分别为0.25,0.35,0.60和0.80时光暗脉冲归零码二进制信号的误码率和眼图。此外,利用该方案产生的光暗脉冲归零码二进制信号可以作为标记在光标记交换网络中得到应用。     

Simultaneous fluorometry and phosphorometry of Langendorff perfused rat heart: ex vivo animal studies

Fluorescence imaging of intrinsic fluorophores of tissue is a powerful method to assess metabolic changes at the cellular and intracellular levels. At the same time, exogenous phosphorescent probes can be used to accurately measure intravascular tissue oxygenation. Heart failure is the leading cause of death in America. A rat heart can potentially model the human heart to study failures or other abnormalities optically. We report simultaneous fluorescence and phosphorescence measurements performed on a rat heart. We have used two different optical systems to acquire fluorescence signals of flavoprotein and nicotinamide adenine dinucleotide--the two intrinsic fluorophores of mitochondria--and the phosphorescence signal of an intravascular oxygen probe to extract intracellular and intravascular metabolism loads, respectively.     

Neural stimulation with optical radiation

This paper reviews the existing research on infrared neural stimulation, a means of artificially stimulating neurons that has been proposed as an alternative to electrical stimulation. Infrared neural stimulation (INS) is defined as the direct induction of an evoked potential in response to a transient targeted deposition of optical energy. The foremost advantage of using optical radiation for neural stimulation is its spatial resolution. Exogenously applied or trans‐genetically synthesized fluorophores are not used to achieve stimulation. Here, current work on INS is presented for motor nerves, sensory nerves, central nervous system, and in vitro preparations. A discussion follows addressing the mechanism of INS and its potential use in neuroprostheses. A brief review of neural depolarization involving other optical methods is also presented. Topics covered include optical stimulation concurrent with electrical stimulation, optical stimulation using exogenous fluorophores, and optical stimulation by transgenic induction of light‐gated ion channels.     

Optical measurement of neural activity using surface plasmon resonance

We demonstrate that surface plasmon resonance (SPR) is applicable to the optical detection of neural signals. A low-noise SPR sensor was developed as a label- and artifact-free method for the extracellular recording of neural activity. The optical responses obtained from a rat sciatic nerve were highly correlated with simultaneously recorded electrical responses. Additional studies with stimulation intensity and lidocaine further confirmed that the optically measured signals originated from neural activities.     

Stimulated photon echo with temporal data coding in the Hopfield-Little regime

A model of an optical neural network with associative memory using stimulated photon echo (SPE) with temporal data coding is presented. The electrical field’s calculation of the SPE signals is carried out for case of multiple influences on the resonant medium by optical pulses. A computer model of an optical echo processor with associative retrieval of information is elaborated.     

Influence of the source bandwidth on the observation of microwave photon echoes

The fluctuations of the source frequency are shown to be responsible of an extra damping of the optical precession and of the photon echoes observed in the experiments involving many shots and an averaging of the detected signals. Assuming a phase diffusing model and various profiles for the frequency power spectrum, the r.m.s. accumulated phase error is calculated and two asymptotic behaviours are pointed out according to the relative values of the sequence duration and of the frequency correlation time. The calculation is well supported by a photon echo experiment at a 3-mm wavelength.     

Display of spatial coherence

The mutual-intensity function plays a major role in characterizing quasi-monochromatic, partially coherent optical signals. We demonstrate an optical system for displaying the mutual intensity of a one-dimensional input beam. The experimental system is based on the fact that the mutual intensity of a signal can be expressed as the ensemble averaging of a cross-correlation operation between two related optical signals. The setup consists of a Sagnac interferometer followed by an optoelectronic joint transform correlator. Experimental results demonstrate the capabilities of the mutual-intensity analyzer.     

Fast imaging for magnetic resonance electrical impedance tomography

In magnetic resonance electrical impedance tomography (MREIT), currents are injected into an object, the resulting magnetic flux density is measured using MRI, and the conductivity distribution reconstructed using these MRI data. The relatively long acquisition times of conventional MREIT methods limit the signal averaging rate and are susceptible to motion artifacts. In this study, we reconstructed the conductivity distribution of an agarose gel phantom from data acquired in under a minute using a single-shot, spin echo, echo planar imaging (SS-SEPI) pulse sequence. The results demonstrate that SS-SEPI can be used for MREIT data acquisition.     

Optical Vector Network Analyzer with an Improved Dynamic Range Based on a Polarization Multiplexing Electro-Optic Modulator

We present a new method to achieve an optical vector network analyzer(OVNA) based on a polarization multiplexing electro-optic modulator(PM-EOM) without an optical bandpass filter. Optical single sideband(OSSB)modulated signals with a tunable optical carrier-sideband ratio(OCSR) are obtained at the output of the PMEOM. The OCSR can be flexibly tuned by controlling bias voltages of the PM-EOM. The dynamic range of the OVNA is expanded by taking the improvement of the OCSR into account. The transmission response of an optical device under test(ODUT) is measured based on one-to-one mapping from optical domain to electrical domain. By optimizing the OCSR of the OSSB modulated signals, the dynamic range of the OVNA can be effectively improved with 3.7 dB. An analytical model is derived to describe the transfer function of the ODUT.The magnitude and phase responses of a fiber Bragg grating are characterized with a large dynamic range.     

A “three colour channel” system to synthesize complex point spread functions

In this paper a “hybrid” system is introduced, which consists of an incoherent optical system and an electronic system, In the optical processor the temporal as well as the spatial frequencies of the input image are manipulated. A CTV camera transposes the light distribution at the output of the optical system into three electrical signals. These electrical signals are modulated and combined to one signal, which will be fed into a visual display, showing a fringe pattern, whose brightness is proportional to the magnitude of the desired (complex) image.     

Functional optical coherence tomography for detecting neural activity through scattering changes

We have demonstrated functional optical coherence tomography (fOCT) for neural imaging by detecting scattering changes during the propagation of action potentials through neural tissue. OCT images of nerve fibers from the abdominal ganglion of the sea slug Aplysia californica were taken before, during, and after electrical stimulation. Images acquired during stimulation showed localized reversible increases in scattering compared with those acquired before stimulation. Motion-mode OCT images of nerve fibers showed transient scattering changes from spontaneous action potentials. These results demonstrate that OCT is sensitive to the optical changes in electrically active nerve fibers.     

An investigation into the role of the optical detection set-up in the recording of cardiac optical mapping signals: A Monte Carlo simulation study

Photon scattering is known to distort the fluorescence signals recorded from optically mapped cardiac tissue. However, the contribution of the parameters which define the optical detection set-up has not been assessed. In this study, Monte Carlo (MC) simulations of photon scattering within ventricular tissue are combined with a detailed model of a tandem-lens optical detection apparatus to characterise (i) the spatial origin upon emission of photons recorded in voltage-sensitive fluorescence measurements of cardiac electrical activity (using the fluorescent dye di-4-ANEPPS) and how this affects signal distortion, and (ii) the role the detector characteristics could play in modulating signal distortion during uniform illumination and photon emission from tissue depth. Results show that, for the particular excitation/emission wavelengths considered (488 nm and 669 nm, respectively), the dimensions of the scattering volume during uniform illumination extend around 3 times further in the surface recording plane than in depth. As a result, fluorescence recordings during electrical propagation are more distorted when transmembrane potential levels differ predominantly in the surface plane than in depth. In addition, MC simulation results show that the spatial accuracy of the fluorescence signal is significantly limited due to photon scattering, with only a small fraction of the recorded signal intensity originating from tissue beneath the pixel (approximately 11% for a 0.25×0.25 mm pixel). Increasing pixel size increases this fraction, however, it also results in an increase in the scattering volume dimensions, thus reducing the spatial resolution of the optical system, and increasing signal distortion. MC simulations also demonstrate that photon scattering in cardiac tissue limits the ability of optical detection system tuning in accurately locating fluorescent emission from depth. Specifically, our results prove that the focal plane depth that yields maximum signal intensity provides an underestimation of the emission depth. In conclusion, our study demonstrates the potential of MC simulations of photon scattering in guiding the design of optical mapping set-ups to optimise performance under diverse experimental conditions.     

Ultrafast electrical signal generation,propagation and detection

Short-pulse optical sources have allowed the study of ultrafast electrical phenomena in the circuits and devices which will become future electronic systems. In this paper techniques for the generation, propagation and detection of electrical signals in the femtosecond regime are presented.     

Distortions in multiple-pulse solid state NMR imaging: gradient decoupling, time-sequenced second averaging, and over-sampling

Three approaches to reducing image artifacts are described that are specific to multiple-pulse line-narrowing methods of NMR imaging. Gradient decoupling avoids excess line broadening from off-resonance gradient phase evolution by restricting the gradient to selected windows in which the gradient Hamiltonian commutes with the toggling frame state, and where the averaged Hamiltonian between gradient pulses is either cyclic or anti-cyclic. This forces the residual averaged dipolar Hamiltonian to be independent of the gradient evolution. Time-sequenced second averaging addresses the on-resonance broadening, where residual error terms dominate the spin dynamics (a lack of second averaging), by adding a second coherent averaging that retains part of the modulation associated with off-resonance terms, and thus smoothes out the line-narrowing efficiency with spatial offset. Over-sampling is useful to increase both the resolution and sensitivity of an image, but it introduces a sampling modulation that produces sidebands. These are eliminated by a series of prepulses in a fashion reminiscent of CYCLOPS phase cycling.