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PubMed2000

Near-infrared study of fluctuations in cerebral hemodynamics during rest and motor stimulation: temporal analysis and spatial mapping.

We have noninvasively studied the motor cortex hemodynamics in human subjects under rest and motor stimulation conditions using a multichannel near-infrared tissue spectrometer. Our instrument measures optical maps of the cerebral cortex at two wavelengths (758 and 830 nm), with an acquisition time of 160 ms per map. We obtained optical maps of oxy- and deoxy-hemoglobin concentration changes in terms of amplitudes of folding average, power spectrum and coherence at the stimulation repetition frequency, and the phase synchronization index. Under periodic motor stimulation conditions, we observed coherence and frequency or phase synchronization of the local hemodynamic changes with stimulation. Our main findings are the following: (1) The amplitude of the hemodynamic response to the motor stimulation is comparable to the amplitude of the fluctuations at rest. (2) The spatial patterns of the oxy- and deoxy-hemoglobin responses to the stimulation are different. (3) The hemodynamic response to stimulation shows a spatial localization and a level of phase synchronization with the motor stimulation that depends on the stimulation period.

Adult↗
PubMed2005

Optical measurements reveal nature of intercellular coupling across ventricular wall.

Previously, we showed that intercellular uncoupling through gap junctions is an important mechanism for maintaining transmural heterogeneities of repolarization that are responsible for ventricular arrhythmias in disease states such as heart failure. However, rotational anisotropy between transmural muscle layers also may influence coupling. To determine the effect of rotational anisotropy on transmural coupling, we developed a numerical three-dimensional model of passive cardiac tissue in which rotational anisotropy was varied in a controlled fashion. Simulations of optical mapping demonstrated that spatial averaging produced a voltage decay in space best fit by a single decaying exponential compared with the theoretically predicted decay. As fiber orientation varied by 90 degrees with respect to the transmural surface, the effective transmural space constant (lambda(TM)) changed by only 0.31% in simulations. In contrast, reducing intercellular conductivity by 24% decreased lambda(TM) by 7.7%. In the canine wedge preparation (n = 5), lambda measured by optical mapping of the epicardial and subepicardial surface was similar transverse (lambda(TV) = 0.73 +/- 0.10 mm) and transmural (lambda(TM) = 0.70 +/- 0.08 mm) to subepicardial fibers. We confirmed previous findings that lambda(TM) in subepicardial layers was significantly reduced by 14 +/- 2% compared with deeper layers of myocardium, providing evidence for transmural uncoupling in the epicardial-midmyocardial interface. These data establish the theoretical and experimental basis for measuring intercellular coupling between muscle layers spanning the ventricular wall with optical mapping techniques. Furthermore, this study demonstrates that transmural uncoupling at the epicardial-midmyocardial interface may be attributable to heterogeneous expression of cardiac gap junctions and not rotational anisotropy.

Action Potentials↗
PubMed2005

Use of translucent indium tin oxide to measure stimulatory effects of a passive conductor during field stimulation of rabbit hearts.

Biomathematical models and experiments have indicated that passive extracellular conductors influence field stimulation. Because metallic conductors prevent optical mapping under the conductor, we have evaluated a passive translucent indium tin oxide (ITO) thin-film conductor to allow mapping of transmembrane potential (V(m)) and stimulatory current under the conductor. A 1-cm ITO disk was patterned photolithographically and positioned between 0.3-cm(2) mesh shock electrodes on the ventricular epicardium of isolated perfused rabbit hearts stained with 4-{2-[6-(dibutylamino)-2-naphthylenal]ethenyl}-1-(3-sulfopropyl)-, hydroxide, inner salt (di-4-ANEPPS). For a 1-A, 10-ms shock during the action potential plateau, optical maps from fluorescence collected using emission ratiometry (excitation at 488 nm and emissions at 510-570 and >590 nm) indicated that the disk altered V(m) by as much as the height of an action potential. DeltaV(m) became more positive near the edge of the disk, where the ITO conductance gradient was parallel to applied current, and more negative near the opposite edge, where the gradient was not parallel to current. For diastolic shocks, the disk expedited membrane excitation at the sites of positive DeltaV(m) in the heart and in a cardiac model with realistic ITO disk surface and interfacial conductances. Optical maps of ITO transmittance and the model indicated that the disk introduced anodal and cathodal stimulatory current at opposite edges of the disk. Thus ITO allows study of the stimulatory effects of a passive conductor in an electric field.

Animals↗
PubMed2002

Demonstration of electrical and anatomic connections between Marshall bundles and left atrium in dogs: implications on the generation of P waves on surface electrocardiogram.

INTRODUCTION: The muscle bundles within the ligament of Marshall (LOM) are electrically active. The importance of these muscle bundles (Marshall bundle [MB]) to atrial activation and the generation of the ECG P wave is unclear. METHODS AND RESULTS: We used optical mapping techniques to study epicardial activation patterns in isolated perfused left atrium in four dogs. In another seven dogs, P waves were studied before and after in vivo radiofrequency (RF) ablation of the connection between coronary sinus (CS) and the LOM. Computerized mapping was performed before and after RF ablation. Optical mapping studies showed that CS pacing resulted in broad wavefronts propagating from the middle and distal LOM directly to the adjacent left atrium (LA). Serial sections showed direct connection between MB and LA near the orifice of the left superior pulmonary vein in two dogs. In vivo studies showed that MB potentials were recorded in three dogs. After ablation, the duration of P waves remained unchanged. In the other four dogs, MB potentials were not recorded. Computerized mapping showed that LA wavefronts propagated to the MB region via LA-MB connection and then excited the CS. After ablation, the activation of CS muscle sleeves is delayed, and P wave duration increased from 65.3 +/- 14.9 msec to 70.5 +/- 17.2 msec (P = 0.025). CONCLUSION: In about half of the normal dogs, MB provides an electrical conduit between LA free wall and CS. Severing MB alters the atrial activation and lengthens the P wave. MB contributes to generation of the P wave on surface ECG.

Animals↗
PubMed2004

Optical tomographic mapping of cerebral haemodynamics by means of time-domain detection: methodology and phantom validation.

One of the primary applications of diffuse optical imaging is to localize and quantify the changes in the cerebral oxygenation during functional brain activation. Up to now, data from an optical imager are simply presented as a two-dimensional (2D) topographic map using the modified Beer-Lambert law that assumes homogeneous optical properties beneath each optode. Due to the highly heterogeneous nature of the optical properties in the brain, the assumption is evidently invalid, leading to both low spatial resolution and inaccurate quantification in the assessment of haemodynamic changes. To cope with these difficulties, we propose a nonlinear tomographic image reconstruction algorithm for a two-layered slab geometry that uses time-resolved reflected light. The algorithm is based on the previously developed generalized pulse spectrum technique, and implemented within a semi-three-dimensional (3D) framework to conform to the topographic visualization and to reduce computational load. We demonstrate the advantages of the algorithm in quantifying simulated changes in haemoglobin concentrations and investigate its robustness to the uncertainties in the cortical structure and optical properties, as well as the effects of random noises on image quality. The methodology is also validated by experiments using a solid layered phantom.

Algorithms↗
PubMed1996

Dominant optic atrophy mapped to chromosome 3q region. II. Clinical and epidemiological aspects.

Sixty-two patients from three large Danish families with autosomal dominant optic atrophy were clinically examined, and retrospective follow-up was made on 30 patients. We found great inter-and intrafamiliar variation in visual acuity and visual decline. One hundred and seventy-five chromosomal markers were analyzed in 118 family members. Linkage was demonstrated between the disease gene (OPA1) and the microsatellite markers D3S1314, D3S1262, D3S1265 and D3S1601, with the highest Lod score to D3S1601 Z=11.75. All markers are located on chromosome 3q in the telomeric area, the most probable location for the OPA1 gene being D3S1601-OPA1-D3S1265. Using data from the Danish Family Register of Hereditary Eye Diseases, the minimum prevalence rate was estimated to 1:12.301, making DOA the most common hereditary optic atrophy.

Adolescent↗
PubMed2003

Transient up-regulation of retinal EphA3 and EphA5, but not ephrin-A2, coincides with re-establishment of a topographic map during optic nerve regeneration in goldfish.

Eph tyrosine kinase receptors and their ligands, the ephrins, play a key role in the establishment of retinotectal topography during development. Tectal up-regulation of ephrin-A2 in goldfish, coincident with the reestablishment of a retinotectal map, suggests a similar role during optic nerve regeneration. Here we report a complementary study of EphA3, EphA5 and ephrin-A2 expression in the retina. EphA3 and EphA5 are transiently up-regulated as ascending naso-temporal gradients, whereas ephrin-A2 remains uniform. The expression profiles differ from those in developing chick and mouse, suggesting that different combinations of retinal Eph receptors and ligands can generate topographic guidance information.

Amacrine Cells↗
PubMed2005

A novel locus for X-linked recessive CMT with deafness and optic neuropathy maps to Xq21.32-q24.

The authors describe a Korean family with X-linked recessive Charcot-Marie-Tooth disease (CMT) having deafness and optic neuropathy. An X chromosome-wide linkage analysis identified a 15.2-cM candidate region flanked by DXS990 and DXS8067 on Xq21.32-q24 with the maximum lod score at DXS8077 (3.62, theta = 0.00). This locus does not overlap previously identified four loci for X-linked CMT, and the authors propose it as CMTX5.

Adolescent↗
PubMed2001

Mapping action potentials and calcium transients simultaneously from the intact heart.

Intracellular calcium handling plays an important role in cardiac electrophysiology. Using two fluorescent indicators, we developed an optical mapping system that is capable of measuring calcium transients and action potentials at 256 recording sites simultaneously from the intact guinea pig heart. On the basis of in vitro measurements of dye excitation and emission spectra, excitation and emission filters at 515 +/- 5 and >695 nm, respectively, were used to measure action potentials with di-4-ANEPPS, and excitation and emission filters at 365 +/- 25 and 485 +/- 5 nm, respectively, were used to measure calcium transients with indo 1. The percent error due to spectral overlap was small when action potentials were measured (1.7 +/- 1.0%, n = 3) and negligible when calcium transients were measured (0%, n = 3). Recordings of calcium transients, action potentials, and isochrone maps of depolarization time and the time of calcium transient onset indicated negligible error due to fluorescence emission overlap. These data demonstrate that the error due to spectral overlap of indo 1 and di-4-ANEPPS is sufficiently small, such that optical mapping techniques can be used to measure calcium transients and action potentials simultaneously in the intact heart.

Action Potentials↗
PubMed1991

Inverse perspective mapping simplifies optical flow computation and obstacle detection.

We present a scheme for obstacle detection from optical flow which is based on strategies of biological information processing. Optical flow is established by a local "voting" (non-maximum suppression) over the outputs of correlation-type motion detectors similar to those found in the fly visual system. The computational theory of obstacle detection is discussed in terms of space-variances of the motion field. An efficient mechanism for the detection of disturbances in the expected motion field is based on "inverse perspective mapping", i.e., a coordinate transform or retinotopic mapping applied to the image. It turns out that besides obstacle detection, inverse perspective mapping has additional advantages for regularizing optical flow algorithms. Psychophysical evidence for body-scaled obstacle detection and related neurophysiological results are discussed.

Algorithms↗
PubMed2006

What can we learn from the optically recorded epicardial action potential?

Optical mapping using voltage-sensitive fluorescent dyes has become a major tool for studying excitation propagation in the heart. Computational and experimental studies have indicated that the optical upstroke morphology reflects the orientation of the subsurface excitation front. In a recent whole heart computational study performed by Bishop et al. (Bishop, M. J., B. Rodriguez, J. Eason, J. P. Whiteley, N. Trayanova, and D. J. Gavaghan. 2006. Synthesis of voltage-sensitive optical signals: application to panoramic optical mapping. Biophys. J. 90:2938-2945), an example was provided of two different directions of propagation having nevertheless very similar epicardial optical upstrokes. The goal of this comment is to clarify the interpretation of optical upstroke morphologies and reconcile the results obtained by Bishop et al. with previous computational and experimental studies.

Action Potentials↗
PubMed2006

The effect of cryoinjury on ventricular tachycardia in the swine right ventricle.

This study was performed to assess the influence of the cryoinjury on the dynamics of wavefronts and to determine whether they can convert ventricular fibrillation (VF) to ventricular tachycardia (VT) in fibrillating right ventricular (RV) of swines using an optical mapping system. A cryoinjury with a diameter of 12 mm was created on the epicardium of perfused RV of swines (n = 6) and optical mapping were taken from baseline until 10 minutes after the cryoinjury. Out of 35 cryoinjuries, the images were possible to be interpreted in 32. The optical action potential could not be observed in either the cryoinjury or peri-injury sites at 1 and 3 minutes, was observed in only the cryoinjury site at 5 minutes, and recovered in both sites at 10 minutes. The cycle length of the tachycardia was 135.9 +/- 23.6 msec at baseline, 176.2 +/- 79.3 msec at 1 minute, 187.6 +/- 97.9 msec at 3 minutes, 185.5 +/- 19.2 msec at 5 minutes, and 152.1 +/- 64.1 msec at 10 minutes. The cycle lengths at 1, 3, and 5 minutes after the cryoinjury were significantly more prolonged than that at baseline (p = 0.001, p = 0.006, p = 0.016). After the cryoinjury, the VF changed to VT in 9 (28.0%), and terminated in 2 (6.3%). These changes were observed mainly within 5 minutes after cryoinjury. The cryoinjury had anti-fibrillatory effects on the tissue with VF. This phenomenon was related to a decreasing mass and stabilizing wavefronts.

Animals↗
PubMed2005

Mechanisms of superiority of ascending ramp waveforms: new insights into mechanisms of shock-induced vulnerability and defibrillation.

Monophasic ascending ramp (AR) and descending ramp (DR) waveforms are known to have significantly different defibrillation thresholds. We hypothesized that this difference arises due to differences in mechanisms of arrhythmia induction for the two waveforms. Rabbit hearts (n = 10) were Langendorff perfused, and AR and DR waveforms (7, 20, and 40 ms) were randomly delivered from two line electrodes placed 10 mm apart on the anterior ventricular epicardium. We optically mapped cellular responses to shocks of various strengths (5, 10, and 20 V/cm) and coupling intervals (CIs; 120, 180, and 300 ms). Optical mapping revealed that maximum virtual electrode polarization (VEP) was reached at significantly different times for AR and DR of the same duration (P < 0.05) for all tested CIs. As a result, VEP for AR were stronger than for DR at the end of the shock. Postshock break excitation resulting from AR generated faster propagation and typically could not form reentry. In contrast, partially dissipated VEP resulting from DR generated slower propagation; the wavefront was able to propagate into deexcited tissue and thus formed a shock-induced reentry circuit. Therefore, for the same delivered energy, AR was less proarrhythmic compared with DR. An active bidomain model was used to confirm the electrophysiological results. The VEP hypothesis explains differences in vulnerability associated with monophasic AR and DR waveforms and, by extension, the superior defibrillation efficacy of the AR waveform compared with the DR waveform.

Animals↗
PubMed1980

Egomotion and relative depth map from optical flow.

When an observer moves in a 3D world, optical flow fields are generated on his retina. We argue that such an observer can in principle compute the parameters of his egomotion, and following this, the relative depth map of the stationary environment solely from the instantaneous positional velocity fields (IPVF). Moreover, we argue that in the stationary world, this analysis can be done locally, and is not dependent on global properties of the optical flow under the imposed ocnstraints (smoothness of the egomotion path, rigidity of objects, temporal continuity of perception). To investigate the method, and to analyze its performance, a computer model has been constructed whch simulates an observer moving through a 3D world of stationary rectangular planes at different depths and orientations. The results suggest that the method offers a reasonable and computationally feasible means of extracting information about egomotion and surface layout from optical flows, under certain circumstances. We discuss some issues related to extending the analysis to the case of a rigid world of moving objects, and some issues related to the status of information extractable from optical flows with respect to other sources of information.

Computers↗
PubMed2005

Optical action potential upstroke morphology reveals near-surface transmural propagation direction.

The analysis of surface-activation patterns and measurements of conduction velocity in ventricular myocardium is complicated by the fact that the electrical wavefront has a complex 3D shape and can approach the heart surface at various angles. Recent theoretical studies suggest that the optical upstroke is sensitive to the subsurface orientation of the wavefront. Our goal here was to (1) establish the quantitative relationship between optical upstroke morphology and subsurface wavefront orientation using computer modeling and (2) test theoretical predictions experimentally in isolated coronary-perfused swine right ventricular preparations. We show in numerical simulations that by suitable placement of linear epicardial stimulating electrodes, the angle phi of wavefronts with respect to the heart surface can be controlled. Using this method, we developed theoretical predictions of the optical upstroke shape dependence on phi. We determined that the level VF* at which the rate of rise of the optical upstroke reaches the maximum linearly depends on phi. A similar relationship was found in simulations with epicardial point stimulation. The optical mapping data were in good agreement with theory. Plane waves propagating parallel to myocardial fibers produced upstrokes with VF*<0.5, consistent with theoretical predictions for phi>0. Similarly, we obtained good agreement with theory for plane waves propagating in a direction perpendicular to fibers (VF*>0.5 when phi<0). Finally, during epicardial point stimulation, we discovered characteristic saddle-shaped VF* maps that were in excellent agreement with theoretically predicted changes in phi during wavefront expansion. Our findings should allow for improved interpretation of the results of optical mapping of intact heart preparations.

Action Potentials↗
PubMed1993

Current source density profiles of optical recording maps: a new approach to the analysis of spatio-temporal neural activity patterns.

Spatio-temporal spreading of activity in the CA1 region of the rat hippocampal slice was studied by two experimental approaches. At identical locations in the tissue we measured both the extracellular field potential distribution with microelectrode recordings and the intracellular potential distribution by optical recording, using voltage-sensitive fluorescent dyes. Current source density analysis (CSD) was applied to the extracellular field potential distributions (eCSD) to enhance the spatial resolution. In order to obtain an analogous improvement for the optical recordings, we developed a new CSD transformation, which calculates the locations of the transmembrane current generators from the intracellular potential distributions (iCSD). Compared to the underlying fluorescence maps, the new iCSD profiles exhibit a considerable improvement in spatial resolution. Results can be directly interpreted in terms of physiological membrane processes, such as postsynaptic potentials and action potentials. The iCSD profiles show a surprisingly good correspondence with the classical eCSD profiles both qualitatively and quantitatively, the only difference being that cell body activity is reduced in amplitude. Thus, this new optical CSD analysis paves the way for a quantitative interpretation, rather than the hitherto predominantly qualitative interpretation of spatio-temporal activity profiles from optical recording measurements.

Action Potentials↗
PubMed2001

Patterns of wave break during ventricular fibrillation in isolated swine right ventricle.

Several different patterns of wave break have been described by mapping of the tissue surface during fibrillation. However, it is not clear whether these surface patterns are caused by multiple distinct mechanisms or by a single mechanism. To determine the mechanism by which wave breaks are generated during ventricular fibrillation, we conducted optical mapping studies and single cell transmembrane potential recording in six isolated swine right ventricles (RV). Among 763 episodes of wave break (0.75 times x s(-1) x cm(-2)), optical maps showed three patterns: 80% due to a wave front encountering the refractory wave back of another wave, 11.5% due to wave fronts passing perpendicular to each other, and 8.5% due to a new (target) wave arising just beyond the refractory tail of a previous wave. Computer simulations of scroll waves in three-dimensional tissue showed that these surface patterns could be attributed to two fundamental mechanisms: head-tail interactions and filament break. We conclude that during sustained ventricular fibrillation in swine RV, surface patterns of wave break are produced by two fundamental mechanisms: head-tail interaction between waves and filament break.

Action Potentials↗
PubMed2006

Effects of gap geometry on conduction through discontinuous radiofrequency lesions.

BACKGROUND: Gaps of sufficient cross-sectional dimensions within linear radiofrequency (RF) lesions may allow conduction through the lesion. The purpose of this study was to examine the effects of different gap geometries on conduction through discontinuous RF lesions. METHODS AND RESULTS: Radiofrequency lesions were created in isolated, perfused rabbit right ventricular (RV) free wall preparations to produce gaps with 3 different lesion geometries: straight, bifurcated, and angled (n=10 each group). Angled preparations contained 2 right angles within the conduction path. Optical mapping was used to assess bidirectional conduction through the myocardium before and after gap formation during pacing at 1000-, 400-, and 200-ms cycle lengths. Histological analysis was performed on each preparation after optical mapping. After lesion formation, 9 of 10 straight gap preparations and 1 of 10 angled gap preparations demonstrated bidirectional conduction (P<0.001) at all cycle lengths. Nine of 10 bifurcated gap preparations demonstrated bidirectional conduction and 1 demonstrated unidirectional conduction at all cycle lengths. Two bifurcated gap preparations showed rate-dependent unidirectional 2:1 conduction. All unidirectional and rate-dependent block occurred during impulse propagation in the direction of diverging arms of the bifurcation. The occurrence of bidirectional conduction in the gaps was associated with the gap geometry (P<0.0001). Histological analysis confirmed the continuity of viable myocardium transmurally throughout the length of the gap in each preparation. The sites of conduction block were demonstrated to be just after the first angle in the conduction path for angled gaps and at the branch point of a bifurcated gap. The predominant myofiber orientation was changed relative to the conduction path at angulations of the gaps. Flecainide (0.1 micromol/L) produced bidirectional conduction block in straight and bifurcated gap preparations with bidirectional conduction at baseline. CONCLUSIONS: Conduction through discontinuities in RF lesions is associated with gap geometry. Complex gap geometry may allow for unidirectional and/or rate-dependent block. Gaps within RF lesions are susceptible to pharmacological blockade.

Animals↗