@article {3377, title = {Novel inter-hemispheric white matter connectivity in the BTBR mouse model of autism.}, journal = {Brain Res}, volume = {1513}, year = {2013}, month = {06/2013}, pages = {26-33}, abstract = {Alterations in the volume, density, connectivity and functional activation of white matter tracts are reported in some individuals with autism and may contribute to their abnormal behaviors. The BTBR (BTBR T+tf/J) inbred strain of mouse, is used to model facets of autism because they develop low social behaviors, stereotypical and immune changes similar to those found in people with autism. Previously, it was thought a total absence of corpus callosal interhemispheric connective tissues in the BTBR mice may underlie their abnormal behaviors. However, postnatal lesions of the corpus callosum do not precipitate social behavioral problems in other strains of mice suggesting a flaw in this theory. In this study we used digital pathological methods to compare subcortical white matter connective tracts in the BTBR strain of mice with those found in the C57Bl/6 mouse and those reported in a standardized mouse brain atlas. We report, for the first time, a novel connective subcortical interhemispheric bridge of tissue in the posterior, but not anterior, cerebrum of the BTBR mouse. These novel connective tissues are comprised of myelinated fibers, with reduced myelin basic protein levels (MBP) compared to levels in the C57Bl/6 mouse. We used electrophysiological analysis and found increased inter-hemispheric connectivity in the posterior hemispheres of the BTBR strain compared with the anterior hemispheres. The conduction velocity was slower than that reported in normal mice. This study shows there is novel abnormal interhemispheric connectivity in the BTBR strain of mice, which may contribute to their behavioral abnormalities.}, keywords = {Analysis of Variance, Animals, Autistic Disorder, Brain, Corpus Callosum, Disease Models, Animal, Electroencephalography, Enzyme-Linked Immunosorbent Assay, Female, Functional Laterality, Image Processing, Computer-Assisted, Male, Mice, Mice, Inbred C57BL, Mice, Neurologic Mutants, Microtubule-Associated Proteins, Myelin Basic Protein, Nerve Fibers, Myelinated, Neuroimaging, Spectrum Analysis}, issn = {1872-6240}, doi = {10.1016/j.brainres.2013.04.001}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23570707}, author = {Miller, V M and Disha Gupta and Neu, N and Cotroneo, A and Chadwick B. Boulay and Seegal, R F} } @article {2194, title = {Brain-computer interfacing based on cognitive control.}, journal = {Ann Neurol}, volume = {67}, year = {2010}, month = {06/2010}, pages = {809-16}, abstract = {

OBJECTIVE:\ 

Brain-computer interfaces (BCIs) translate deliberate intentions and associated changes in brain activity into action, thereby offering patients with severe paralysis an alternative means of communication with and control over their environment. Such systems are not available yet, partly due to the high performance standard that is required. A major challenge in the development of implantable BCIs is to identify cortical regions and related functions that an individual can reliably and consciously manipulate. Research predominantly focuses on the sensorimotor cortex, which can be activated by imagining motor actions. However, because this region may not provide an optimal solution to all patients, other neuronal networks need to be examined. Therefore, we investigated whether the cognitive control network can be used for BCI purposes. We also determined the feasibility of using functional magnetic resonance imaging (fMRI) for noninvasive localization of the cognitive control network.

METHODS:\ 

Three patients with intractable epilepsy, who were temporarily implanted with subdural grid electrodes for diagnostic purposes, attempted to gain BCI control using the electrocorticographic (ECoG) signal of the left dorsolateral prefrontal cortex (DLPFC).

RESULTS:\ 

All subjects quickly gained accurate BCI control by modulation of gamma-power of the left DLPFC. Prelocalization of the relevant region was performed with fMRI and was confirmed using the ECoG signals obtained during mental calculation localizer tasks.

INTERPRETATION:\ 

The results indicate that the cognitive control network is a suitable source of signals for BCI applications. They also demonstrate the feasibility of translating understanding about cognitive networks derived from functional neuroimaging into clinical applications.

}, keywords = {Cognition, Computers, Electrodes, Electroencephalography, Epilepsy, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Neuropsychological Tests, Oxygen, Prefrontal Cortex, Psychomotor Performance, Spectrum Analysis, Time Factors, User-Computer Interface}, issn = {1531-8249}, doi = {10.1002/ana.21985}, url = {http://www.ncbi.nlm.nih.gov/pubmed/20517943}, author = {Vansteensel, Mariska J and Hermes, Dora and Aarnoutse, Erik J and Bleichner, Martin G and Gerwin Schalk and van Rijen, Peter C and Leijten, Frans S S and Ramsey, Nick F} } @article {2110, title = {Determination of signal-to-noise ratios and spectral SNRs in cryo-EM low-dose imaging of molecules.}, journal = {J Struct Biol}, volume = {166}, year = {2009}, month = {05/2009}, pages = {126-32}, abstract = {

Attempts to develop efficient classification approaches to the problem of heterogeneity in single-particle reconstruction of macromolecules require phantom data with realistic noise models. We have estimated the signal-to-noise ratios and spectral signal-to-noise ratios for three steps in the electron microscopic image formation from data obtained experimentally. An important result is that structural noise, i.e., the irreproducible component of the object prior to image formation, is substantial, and of the same order of magnitude as the reproducible signal. Based on this result, the noise modeling for testing new classification techniques can be improved.

}, keywords = {Cryoelectron Microscopy, Image Processing, Computer-Assisted}, issn = {1095-8657}, doi = {10.1016/j.jsb.2009.02.012}, url = {http://www.ncbi.nlm.nih.gov/pubmed/19269332}, author = {Baxter, Bill and Grassucci, Robert A and Gao, Haixiao and Frank, Joachim} } @article {2114, title = {Exploration of parameters in cryo-EM leading to an improved density map of the E. coli ribosome.}, journal = {J Struct Biol}, volume = {164}, year = {2008}, month = {10/2008}, pages = {24-32}, abstract = {

A number of image processing parameters in the 3D reconstruction of a ribosome complex from a cryo-EM data set were varied to test their effects on the final resolution. The parameters examined were pixel size, window size, and mode of Fourier amplitude enhancement at high spatial frequencies. In addition, the strategy of switching from large to small pixel size during angular refinement was explored. The relationship between resolution (in Fourier space) and the number of particles was observed to follow a lin-log dependence, a relationship that appears to hold for other data, as well. By optimizing the above parameters, and using a lin-log extrapolation to the full data set in the estimation of resolution from half-sets, we obtained a 3D map from 131,599 ribosome particles at 6.7A resolution (FSC=0.5).

}, keywords = {Cryoelectron Microscopy, Escherichia coli, Image Enhancement, Image Processing, Computer-Assisted, Ribosomes}, issn = {1095-8657}, doi = {10.1016/j.jsb.2008.05.007}, url = {http://www.ncbi.nlm.nih.gov/pubmed/18606549}, author = {LeBarron, Jamie and Grassucci, Robert A and Shaikh, Tanvir R and Baxter, Bill and Sengupta, Jayati and Frank, Joachim} } @article {2113, title = {Particle-verification for single-particle, reference-based reconstruction using multivariate data analysis and classification.}, journal = {J Struct Biol}, volume = {164}, year = {2008}, month = {10/2008}, pages = {41-8}, abstract = {

As collection of electron microscopy data for single-particle reconstruction becomes more efficient, due to electronic image capture, one of the principal limiting steps in a reconstruction remains particle-verification, which is especially costly in terms of user input. Recently, some algorithms have been developed to window particles automatically, but the resulting particle sets typically need to be verified manually. Here we describe a procedure to speed up verification of windowed particles using multivariate data analysis and classification. In this procedure, the particle set is subjected to multi-reference alignment before the verification. The aligned particles are first binned according to orientation and are binned further by K-means classification. Rather than selection of particles individually, an entire class of particles can be selected, with an option to remove outliers. Since particles in the same class present the same view, distinction between good and bad images becomes more straightforward. We have also developed a graphical interface, written in Python/Tkinter, to facilitate this implementation of particle-verification. For the demonstration of the particle-verification scheme presented here, electron micrographs of ribosomes are used.

}, keywords = {Algorithms, Artificial Intelligence, Classification, Image Enhancement, Image Processing, Computer-Assisted, Microscopy, Electron, Multivariate Analysis, Ribosomes}, issn = {1095-8657}, doi = {10.1016/j.jsb.2008.06.006}, url = {http://www.ncbi.nlm.nih.gov/pubmed/18619547}, author = {Shaikh, Tanvir R and Trujillo, Ramon and LeBarron, Jamie and Baxter, Bill and Frank, Joachim} } @article {2112, title = {SPIDER image processing for single-particle reconstruction of biological macromolecules from electron micrographs.}, journal = {Nat Protoc}, volume = {3}, year = {2008}, month = {10/2008}, pages = {1941-74}, abstract = {

This protocol describes the reconstruction of biological molecules from the electron micrographs of single particles. Computation here is performed using the image-processing software SPIDER and can be managed using a graphical user interface, termed the SPIDER Reconstruction Engine. Two approaches are described to obtain an initial reconstruction: random-conical tilt and common lines. Once an existing model is available, reference-based alignment can be used, a procedure that can be iterated. Also described is supervised classification, a method to look for homogeneous subsets when multiple known conformations of the molecule may coexist.

}, keywords = {Image Processing, Computer-Assisted, Microscopy, Electron, Models, Molecular, Molecular Structure, Software, User-Computer Interface}, issn = {1750-2799}, doi = {10.1038/nprot.2008.156}, url = {http://www.ncbi.nlm.nih.gov/pubmed/19180078}, author = {Shaikh, Tanvir R and Gao, Haixiao and Baxter, Bill and Asturias, Francisco J and Boisset, Nicolas and Leith, ArDean and Frank, Joachim} } @article {2109, title = {SPIRE: the SPIDER reconstruction engine.}, journal = {J Struct Biol}, volume = {157}, year = {2007}, month = {01/2007}, pages = {56-63}, abstract = {

SPIRE is a Python program written to modernize the user interaction with SPIDER, the image processing system for electron microscopical reconstruction projects. SPIRE provides a graphical user interface (GUI) to SPIDER for executing batch files of SPIDER commands. It also lets users quickly view the status of a project by showing the last batch files that were run, as well as the data files that were generated. SPIRE handles the flexibility of the SPIDER programming environment through configuration files: XML-tagged documents that describe the batch files, directory trees, and presentation of the GUI for a given type of reconstruction project. It also provides the capability to connect to a laboratory database, for downloading parameters required by batch files at the start of a project, and uploading reconstruction results at the end of a project.

}, keywords = {Computational Biology, Image Processing, Computer-Assisted, Software, Software Design}, issn = {1047-8477}, doi = {10.1016/j.jsb.2006.07.019}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17055743}, author = {Baxter, Bill and Leith, ArDean and Frank, Joachim} } @article {2115, title = {Particle picking by segmentation: a comparative study with SPIDER-based manual particle picking.}, journal = {J Struct Biol}, volume = {152}, year = {2005}, month = {12/2005}, pages = {211-20}, abstract = {

Boxing hundreds of thousands of particles in low-dose electron micrographs is one of the major bottle-necks in advancing toward achieving atomic resolution reconstructions of biological macromolecules. We have shown that a combination of pre-processing operations and segmentation can be used as an effective, automatic tool for identifying and boxing single-particle images. This paper provides a brief description of how this method has been applied to a large data set of micrographs of ice-embedded ribosomes, including a comparative analysis of the efficiency of the method. Some results on processing micrographs of tripeptidyl peptidase II particles are also shown. In both cases, we have achieved our goal of selecting at least 80\% of the particles that an expert would select with less than 10\% false positives.

}, keywords = {Algorithms, Aminopeptidases, Cryoelectron Microscopy, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Internet, Particle Size, Ribosomes, Serine Endopeptidases, Software, Software Validation}, issn = {1047-8477}, doi = {10.1016/j.jsb.2005.09.007}, url = {http://www.ncbi.nlm.nih.gov/pubmed/16330229}, author = {Adiga, Umesh and Baxter, Bill and Hall, Richard J and Rockel, Beate and Rath, Bimal K and Frank, Joachim and Glaeser, Robert M} } @article {2116, title = {A binary segmentation approach for boxing ribosome particles in cryo EM micrographs.}, journal = {J Struct Biol}, volume = {145}, year = {2004}, month = {01/2004}, pages = {142-51}, abstract = {

Three-dimensional reconstruction of ribosome particles from electron micrographs requires selection of many single-particle images. Roughly 100,000 particles are required to achieve approximately 10 A resolution. Manual selection of particles, by visual observation of the micrographs on a\ computer\ screen, is recognized as a bottleneck in automated single-particle reconstruction. This paper describes an efficient approach for automated boxing of ribosome particles in micrographs. Use of a fast, anisotropic non-linear reaction-diffusion method to pre-process micrographs and rank-leveling to enhance the contrast between particles and the background, followed by binary and morphological segmentation constitute the core of this technique. Modifying the shape of the particles to facilitate segmentation of individual particles within clusters and boxing the isolated particles is successfully attempted. Tests on a limited number of micrographs have shown that over 80\% success is achieved in automatic particle picking.

}, keywords = {Algorithms, Anisotropy, Automatic Data Processing, Cryoelectron Microscopy, Image Enhancement, Image Processing, Computer-Assisted, Particle Size, Pattern Recognition, Automated, Ribosomes, Software Design}, issn = {1047-8477}, doi = {10.1016/j.jsb.2003.10.026}, url = {http://www.ncbi.nlm.nih.gov/pubmed/15065681}, author = {Adiga, Umesh and Malladi, Ravi and Baxter, Bill and Glaeser, Robert M} } @article {2120, title = {Optical mapping of drug-induced polymorphic arrhythmias and torsade de pointes in the isolated rabbit heart.}, journal = {J Am Coll Cardiol}, volume = {29}, year = {1997}, month = {03/1997}, pages = {831-42}, abstract = {

OBJECTIVES:\ 

This study sought to 1) test the hypothesis that in the setting of bradycardia and drug-induced action potential prolongation, multiple foci of early afterdepolarizations (EADs) result in beat to beat changes in the origin and direction of the excitation wave front and are responsible for polymorphic arrhythmias; and 2) determine whether EADs may initiate nonstationary reentry, giving rise to the typical torsade de pointes (TDP) pattern.

BACKGROUND:\ 

In the past, it has been difficult to associate EADs or reentry with the undulating electrocardiographic (ECG) patterns of TDP.

METHODS:\ 

A voltage-sensitive dye was used for high resolution\ videoimaging\ of electrical waves on the\ epicardial\ and endocardial\ surface\ of the Langendorff-perfused\ rabbitheart. ECG and monophasic action potentials from the right septal region were also recorded. Bradycardia was induced by ablation of the atrioventricular node.

RESULTS:\ 

Perfusion of low potassium chloride Tyrode solution plus quinidine led to prolongation of the action potential and the QT interval. Eventually, EADs and triggered activity ensued, giving rise to intermittent episodes of polymorphic arrhythmia. In one experiment, triggered activity was followed by a long episode of vortex-like reentry with an ECG pattern characteristic of TDP. However, in most experiments, focal activity of varying origins and propagation patterns was observed. Triggered responses also showed varying degrees of local block. Similar results were obtained with E-4031. Burst pacing both at control conditions and in the presence of quinidine consistently led to vortex-like reentry whose ECG pattern resembled TDP. However, the cycle length of the arrhythmia with quinidine was longer than that for control ([mean +/- SEM] 194 +/- 12 vs. 132 +/- 8 ms, p \< 0.03).

CONCLUSIONS:\ 

Drug-induced polymorphic ventricular arrhythmias may result from beat to beat changes in wave propagation patterns initiated by EADs or EAD-induced nonstationary reentrant activity. In contrast, burst pacing-induced polymorphic tachycardia in the presence or absence of drugs is the result of nonstationary reentrant activity.

}, keywords = {Action Potentials, Animals, Anti-Arrhythmia Agents, Arrhythmias, Cardiac, Electrocardiography, Heart, Heart Conduction System, Image Processing, Computer-Assisted, Models, Cardiovascular, Organ Culture Techniques, Perfusion, Piperidines, Pyridines, Quinidine, Rabbits, Torsades de Pointes}, issn = {0735-1097}, doi = {10.1016/S0735-1097(96)00588-8}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9091531}, author = {Asano, Y and Davidenko, J M and Baxter, Bill and Gray, R A and Jalife, J} } @article {2118, title = {Technical features of a CCD video camera system to record cardiac fluorescence data.}, journal = {Ann Biomed Eng}, volume = {25}, year = {1997}, month = {07/1997}, pages = {713-25}, abstract = {

A charge-coupled device (CCD) camera was used to acquire movies of transmembrane activity from thin slices of sheep ventricular\ epicardial\ muscle stained with a voltage-sensitive dye. Compared with photodiodes, CCDs have high spatial resolution, but low temporal resolution. Spatial resolution in our system ranged from 0.04 to 0.14 mm/pixel; the acquisition rate was 60, 120, or 240 frames/sec. Propagating waves were readily visualized after subtraction of a background image. The optical signal had an amplitude of 1 to 6 gray levels, with signal-to-noise ratios between 1.5 and 4.4. Because CCD cameras integrate light over the frame interval, moving objects, including propagating waves, are blurred in the resulting movies. A computer model of such an integrating\ imaging\ system was developed to study the effects of blur, noise, filtering, and quantization on the ability to measure conduction velocity and action potential duration (APD). The model indicated that blurring, filtering, and quantization do not affect the ability to localize wave fronts in the optical data (i.e., no systematic error in determining spatial position), but noise does increase the uncertainty of the measurements. The model also showed that the low frame rates of the CCD camera introduced a systematic error in the calculation of APD: for cutoff levels \> 50\%, the APD was erroneously long. Both noise and quantization increased the uncertainty in the APD measurements. The optical measures of conduction velocity were not significantly different from those measured simultaneously with microelectrodes. Optical APDs, however, were longer than the electrically recorded APDs. This APD error could be reduced by using the 50\% cutoff level and the fastest frame rate possible.

}, keywords = {Action Potentials, Algorithms, Animals, Body Surface Potential Mapping, Calibration, Computer Simulation, Electric Conductivity, Fluorescent Dyes, Image Processing, Computer-Assisted, Models, Cardiovascular, Sheep, Ventricular Function, Video Recording}, issn = {0090-6964}, doi = {10.1007/BF02684848}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9236983}, author = {Baxter, Bill and Davidenko, J M and Loew, L M and Wuskell, J P and Jalife, J} } @article {2124, title = {Nonstationary vortexlike reentrant activity as a mechanism of polymorphic ventricular tachycardia in the isolated rabbit heart.}, journal = {Circulation}, volume = {91}, year = {1995}, month = {05/1995 }, pages = {2454-69}, abstract = {

BACKGROUND:\ 

Ventricular tachycardia may result from vortexlike reentrant excitation of the myocardium. Our general hypothesis is that in the structurally normal heart, these arrhythmias are the result of one or two nonstationary three-dimensional electrical scroll waves activating the heart muscle at very high frequencies.

METHODS AND RESULTS:\ 

We used a combination of high-resolution video imaging, electrocardiography, and image processing in the isolated rabbit heart, together with mathematical modeling. We characterized the dynamics of changes in transmembrane potential patterns on the epicardial surface of the ventricles using optical mapping. Image processing techniques were used to identify the surface manifestation of the reentrant organizing centers, and the location of these centers was used to determine the movement of the reentrant pathway. We also used numerical simulations incorporating Fitzhugh-Nagumo kinetics and realistic heart geometry to study how stationary and nonstationary scroll waves are manifest on the epicardial surface and in the simulated ECG. We present epicardial surface manifestations (reentrant spiral waves) and ECG patterns of nonstationary reentrant activity that are consistent with those generated by scroll waves established at the right and left ventricles. We identified the organizing centers of the reentrant circuits on the epicardial surface during polymorphic tachycardia, and these centers moved during the episodes. In addition, the arrhythmias that showed the greatest movement of the reentrant centers displayed the largest changes in QRS morphology. The numerical simulations showed that stationary scroll waves give rise to monomorphic ECG signals, but nonstationary meandering scroll waves give rise to undulating ECGs characteristic of torsade de pointes.

CONCLUSIONS:\ 

Polymorphic ventricular tachycardia in the healthy, isolated rabbit heart is the result of either a single or paired ("figure-of-eight") nonstationary scroll waves. The extent of the scroll wave movement corresponds to the degree of polymorphism in the ECG. These results are consistent with our numerical simulations that showed monomorphic ECG patterns of activity for stationary scroll waves but polymorphic patterns for scroll waves that were nonstationary.

}, keywords = {Animals, Electrocardiography, Heart, Image Processing, Computer-Assisted, Models, Cardiovascular, Perfusion, Rabbits, Tachycardia, Ventricular}, issn = {0009-7322}, doi = {10.1161/01.CIR.91.9.2454}, url = {http://www.ncbi.nlm.nih.gov/pubmed/7729033}, author = {Gray, R A and Jalife, J and Panfilov, A and Baxter, Bill and Cabo, C and Davidenko, J M and Pertsov, A V} }