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Rapid analysis of non-uniformly sampled pulsed field gradient data for velocity estimation.

Bretthorst's recent generalization of the Lomb-Scargle periodogram shows that a sufficient statistic for frequency estimation from non-uniformly, but simultaneously sampled quadrature data is equivalent to the FFT of those data with the missing samples replaced by zeros. We have applied this concept to the rapid analysis of pulsed field gradient MRI data which have been non-uniformly sampled in the velocity encoding wave vector q. For a small number of q samples, it is more computationally efficient to calculate the periodogram directly rather than using the FFT algorithm with a large number of zeros. The algorithm we have implemented for finding the peak of the generalized periodogram is simple and robust; it involves repeated apodization and grid searching of the periodogram until the desired velocity resolution is achieved. The final estimate is refined by quadratic interpolation. We have tested the method for fully developed Poiseuille flow of a Newtonian fluid and have demonstrated substantial improvement in the precision of velocity measurement achievable in a fixed acquisition time with non-uniform sampling. The method is readily extendible to multidimensional data. Analysis of a 256 by 256 pixel image with 8 q samples and an effective velocity resolution of better than 1/680 of the Nyquist range requires approximately 1 minute computation time on a 400 MHz SUN Ultrasparc II processor.

Blood Flow Velocity↗

Quantifying the variability of a complex motor task specifically studying the gait of dyskinetic CP children.

Lately, more and more interest has been directed towards the variability of complex motor tasks and its diagnostic value in motion disorders. However, there is no standardized way of quantifying variability of motion. In this respect, the purpose of this study is to explore the usefulness of variability computations derived from three-dimensional (3D) motion trajectories. A mathematical and computational algorithm was defined to first extract and overlay the 3D data for the trajectories. As an example for the application, the trajectories of the ankle marker representing the motion during swing were chosen. The method was used to determine the variability during swing for CP children with and without dyskinesia (n=31). A group of healthy adult normals served as control (n=8). The results were validated against the visual rating of swing variability by experienced clinical observers. The calculated values were superior to the previously used pelvic span/ankle spread ratio. The proposed method of quantifying the variability of a complex, repetitive motor task proved to be valid and useful. It has no limitation with regard to reprocessing previously collected data, or as to which equipment is used to gather the 3D coordinates during the motion.

Algorithms↗

An investigation of the imaging characteristics of the Y2O2S:Eu3+ phosphor for application in X-ray detectors of digital mammography.

Y2O2S:Eu laboratory prepared screens were evaluated as mammographic image receptors and were compared to similarly prepared screens of Gd2O2S:Tb and Y2O2S:Tb phosphor materials, often used in X-ray imaging detectors. The evaluation was performed by determining the Modulation Transfer Function (MTF) and the spatial frequency dependent Detective Quantum Efficiency (DQE). Y2O2S:Eu exhibited higher DQE values at low frequencies and given its good spectral matching with digital optical detectors, it may be appropriate for use in X-ray digital mammography.

Europium↗

Dynamic changes in the cerebral metabolic rate of O2 and oxygen extraction ratio in event-related functional MRI.

Dynamic changes in the cerebral metabolic rate of oxygen (CMRO(2)) and oxygen extraction ratio (OER) in an event-related functional MRI (ER-fMRI) were measured in this study. Six subjects participated in this study at a magnetic field of 1.9 T. Cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) changes were acquired during the brief visual stimulation, and the corresponding changes in CMRO(2) and OER were then determined. The results showed that the maximum relative changes in CMRO(2) and OER were about 10.36 +/- 0.85 and -6.54 +/- 0.55%, respectively, while the maximum changes in CBF and BOLD were approximately 17.35 +/- 1.37 and 1.03 +/- 0.06%, respectively. The CBF, CMRO(2), and OER changes reach their maximum approximately 1 s earlier than the BOLD signal change (4.15 +/- 0.21, 4.16 +/- 0.21, and 4.17 +/- 0.21 s vs 5.12 +/- 0.24 s after stimulation, P < 0.05).

Arousal↗

Estimation of FMRI response delays.

We present an efficient algorithm using the Hilbert Transform for estimating the delay of the BOLD response to neuronal stimulation. With minimal additional computations, the algorithm estimates parameters generated in the widely used cross-correlation method and simplifies the interpolation required to estimate the response delay from the cross-correlation function. We examined errors in the Hilbert-based delay estimate associated with the use of DFT on short-duration discrete signals and proposed a method for minimizing these errors. Furthermore, we compared the delay estimates obtained with the Hilbert method to those obtained using the onset of the BOLD response. The Hilbert method resulted in less variance in the delay estimate despite the potential for higher variability in the latter part of the BOLD response. This improved delay estimate was attributed to the reduced sensitivity of the Hilbert method to noise contamination compared to the onset method.

Algorithms↗

Optimized EPI for fMRI studies of the orbitofrontal cortex.

A common problem in gradient-echo echo planar imaging (EPI) is the occurrence of image distortions and signal losses caused by susceptibility gradients near air/tissue interfaces. Since EPI is frequently used for functional magnetic resonance imaging experiments based on the blood oxygenation level-dependent effect, functional studies of certain brain regions affected by susceptibility gradients, such as the temporal lobes and the orbitofrontal cortex, may be compromised. In this work a method for signal recovery in certain regions of the orbitofrontal cortex is presented. The influence of in-plane susceptibility gradients is reduced by optimization of the imaging slice orientation. Through-plane susceptibility gradients are partly compensated by means of a moderate preparation gradient pulse similar to z-shimming. In contrast to several other techniques proposed in the literature for reducing susceptibility effects, this method does not compromise the temporal resolution and is therefore applicable to event-related studies.

Algorithms↗

The elusive concept of brain connectivity.

Neurons and neural populations do not function as islands onto themselves. Rather, they interact with other such elements through their afferent and efferent connections in an orchestrated manner so as to enable different sensorimotor and cognitive tasks to be performed. The concept of functional connectivity and the allied notion of effective connectivity were introduced to designate the functional strengths of such interactions. Functional neuroimaging methods, especially PET and fMRI, have been used extensively to evaluate the functional connectivity between different brain regions. After providing a brief historical review of these notions of brain connectivity, I argue that the conceptual formulations of functional and effective connectivity are far from clear. Specifically, the terms functional and effective connectivity are applied to quantities computed on types of functional imaging data (e.g., PET, fMRI, EEG) that vary in spatial, temporal, and other features, using different definitions (even for data of the same modality) and employing different computational algorithms. Until it is understood what each definition means in terms of an underlying neural substrate, comparisons of functional and/or effective connectivity across studies may appear inconsistent and should be performed with great caution.

Brain↗

Multitracer: a Java-based tool for anatomic delineation of grayscale volumetric images.

A Java-based tool for delineating anatomic boundaries in 8- and 16- bit grayscale volumetric images is described. Modern features implemented by the tool include the ability to simultaneously view the current cursor position and the previously delineated boundaries on three orthogonal planes, the ability to magnify images during delineation using high-quality interpolation, the ability to encode and save boundaries with subvoxel resolution, and the ability to utilize coregistered images interchangeably during delineation. Additional features facilitate use of the tool in a multiuser, multiplatform environment and provide support for the documentation of anatomic delineation protocols. In addition to providing direct estimates of structure volumes, areas, and lengths, the tool allows contoured boundaries to be exported for more sophisticated analyses. The tool also provides support for manual editing of image volumes to remove confounding structures and for manual correction of image volumes that have been inaccurately edited. In addition to its research utility, the tool also has potential value in education, allowing students to interact with volumetric data and structural boundaries in three dimensions.

Artifacts↗

Influence of fMRI data sampling on the temporal characterization of the hemodynamic response.

Experimental and modeling studies were used to estimate the effect of different sampling rates (repetition times, TR) and different sampling positions on the estimates of the temporal properties of the hemodynamic response function (HRF) derived from fMRI studies. Data were acquired at a TR of 250 ms and then subjected to various degrees of undersampling. Using a gaussian fitting function it is demonstrated that the accuracy of HRF peak time determination decreases with lower sampling rate (higher TR). The decrease in accuracy amounts to about 50 ms per second of TR increase. In addition, temporal shifts of the HRF peak time are found when reducing the influence of the more variable descending part of HRF curve by using a temporal cut-off after HRF peak time. The shift scales with TR, amounts up to 100 ms for a TR of 1500 ms and a cut-off of 3-4 s and depends on the sampling position. The use of the full HRF function does not lead to a shift but increases the influence of potential confounding factors as large veins and poststimulus undershoot. Since both accuracy and potential shifts of HRF peak determination scale with TR, it is important that temporal fMRI studies are carried out with high sampling rates.

Arousal↗

Conformational analysis of thiopeptides: free energy calculations on the effects of thio-substitutions on the conformational distributions of alanine dipeptides.

When the oxygen atom in a peptide bond is replaced by a sulfur atom, the restriction in the available conformational space and the ability of thioamides to confer resistance to enzymatic degradation renders thioamides as potentially useful building blocks for drug design and protein engineering. The solvation free energy differences between conformers of the same dipeptide can be high. Yet, previous conformational studies, basing on the (phi, psi) conformational energy maps of thio-substituted dipeptides, neglected both explicit water interactions and free energy considerations. In this paper, the (phi, psi) conformational free energy maps are obtained by single umbrella sampling in an explicit water environment for both alanine dipeptide and the corresponding thioamide derivatives. The phi and psi angles for the minima in the relative energy maps calculated with dielectric of 80 are similar to the corresponding phi and psi angles in the relative free energy maps for both Ac-Ala-NHMe (Ac: acetyl; Ala: alanine) and Act-Alat-NHMe (Act: thio-acetyl; Alat: thio-alanine). However, some large differences between the relative energy and relative free energy of major minima indicate that the consideration of free energy is important in determination of the relative occupancy of particular minima. Free energy maps for both Ac-Ala-NHMe and Act-Alat-NHMe show that thio-substitution favors conformations where phi < 0 because of the deeper beta and alphaR minima. The changes in the position and relative stability of minima were explained in terms of the destabilization of the regions near phi = -120, 0 and 120, psi = 60, -60, 180, which correspond to the increased steric hindrance due to the bulkier sulfur atom.

Alanine↗

Development and validation of the computerized clinician administered post-traumatic stress disorder scale-1-revised.

A computer administered version of the clinician administered post-traumatic stress disorder (PTSD) scale-1 was developed to assess PTSD in subjects presenting with psychological symptoms following exposure to a traumatic event. Both forms were administered to 40 subjects who met the Diagnostic and Statistical Manual, third edition, revised (DSM-III-R) criteria for exposure to a significantly traumatic stressor. Inter-observer reliability was demonstrated with a kappa statistic of 0.90. The computer version had a sensitivity of 0.95 and a specificity 0.95. A correlation of 0.95 was found between the two versions and the mean score difference was non-significant. The computer form demonstrated adequate internal reliability and test-retest reliability. Overall results suggest the computer version is a valid and reliable measure of PTSD.

Adolescent↗

Simulation of the filtering role of habituation to stimuli.

In the context of a medium-term study designed to integrate the simulation of different types and processes of learning-such as classical, operant, and some cognitive types--one must start with other more elementary ones that are facilitators of the more complex types and processes. Of special interest is habituation, owing to the filtering out of irrelevant stimuli, which means that the simulated agent does not have to respond to them. This paper presents two difference functions constructed to computationally simulate the characteristics that define habituation. The behavior of these functions is described, as are differences arising from stimulus intensity and interstimulus intervals. Results are compared with existing empirical data.

Animals↗

Numerically solving physiological models based on a polynomial approach.

Much research effort has been directed in different physiological contexts towards describing realistic behaviors with differential equations. One observes obviously that more state-variables give the model more accuracy. Unfortunately, the computational cost involved is higher. A new algorithm is presented for simulating a model described by a system of differential equations in which efficiency may not be altered by its size. In order to do this, the method is based on a polynomial description of the state-variables' evolution and on a computation distributed control. Evaluations and results performed with classical models like Fitzhugh Nagumo or Hodgkin Huxley, allow validation of the method and exhibits its potential to decrease the computational costs.

Algorithms↗

Testing differences between nested covariance structure models: Power analysis and null hypotheses.

For comparing nested covariance structure models, the standard procedure is the likelihood ratio test of the difference in fit, where the null hypothesis is that the models fit identically in the population. A procedure for determining statistical power of this test is presented where effect size is based on a specified difference in overall fit of the models. A modification of the standard null hypothesis of zero difference in fit is proposed allowing for testing an interval hypothesis that the difference in fit between models is small, rather than zero. These developments are combined yielding a procedure for estimating power of a test of a null hypothesis of small difference in fit versus an alternative hypothesis of larger difference.

Analysis of Variance↗

Computational design and experimental validation of oligonucleotide-sensing allosteric ribozymes.

Allosteric RNAs operate as molecular switches that alter folding and function in response to ligand binding. A common type of natural allosteric RNAs is the riboswitch; designer RNAs with similar properties can be created by RNA engineering. We describe a computational approach for designing allosteric ribozymes triggered by binding oligonucleotides. Four universal types of RNA switches possessing AND, OR, YES and NOT Boolean logic functions were created in modular form, which allows ligand specificity to be changed without altering the catalytic core of the ribozyme. All computationally designed allosteric ribozymes were synthesized and experimentally tested in vitro. Engineered ribozymes exhibit >1,000-fold activation, demonstrate precise ligand specificity and function in molecular circuits in which the self-cleavage product of one RNA triggers the action of a second. This engineering approach provides a rapid and inexpensive way to create allosteric RNAs for constructing complex molecular circuits, nucleic acid detection systems and gene control elements.

Allosteric Site↗

[I: Box whisker plots--Flexible alternative to "MSE Plots"].

Data description for continuous parameters is sometimes only based on means and standard deviations of measurement series, graphical representation only concentrates on corresponding "MSE plots", which provide means and standard deviations or even only mean squared errors. However, this strategy is only correct for normally distributed data. Outliers may seriously bias mean and standard deviations and may therefore lead to wrong clinical conclusions. The present paper suggests the use of medians and quartiles, which - just like their graphical pendant, the nonparametric "box whisker plot" - can be applied much more flexibly.

Bias↗

[MR-based volumetric analysis of small tumor volumes: accuracy of phantom examinations of simulated eye tumors].

PURPOSE: The determination of tumor volume in ocular tumors is very important for the planning and success of radiation therapy. This study uses an animal model to evaluate the accuracy of MR-based volumetry of ocular tumors. MATERIALS AND METHODS: In a total of 25 porcine eyes obtained from the slaughterhouse, ocular tumors were produced by injecting a mixture of hand creme and Gd-DTPA under ophthalmoscopic guidance. The injected volume varied between 0.05 ml and 2.7 ml. The eyes were examined with a 1.5 Tesla scanner and a 4 cm circular surface coil especially developed for ocular MRI. After data transfer to a separate workstation, volumetric analysis was carried out by three independent radiologists using semiautomated software. The determined volume was compared with the injected volume. RESULTS: Of the 25 prepared porcine eyes, 23 were suitable for volumetric analysis. The injection of the mixture of hand creme and Gd-DTPA produced two different types of tumors. Ophthalmoscopically, 14 ellipsoid and 9 lobulated to mushroom-shaped tumors were found and confirmed by MRI. Minor deviation was found between injected volume and volume calculated by MRI, with a correlation coefficient of 0.96. CONCLUSION: Using appropriate technique, MRI is capable of determining small tumor volumes with high accuracy in an animal model. Minor differences can be expected when transferring the results to clinical studies.

Animals↗

Head and body center of gravity control strategies: adaptations following vestibular rehabilitation.

OBJECTIVE: We present for the first time evidence that vestibulopathy impairs coordination of the head with the body center of gravity (CG) during free speed gait over ground. Vestibulopathic individuals demonstrate uncoordinated movement and gait due, at least in part, to impaired head stability and visual fixation. Vestibular rehabilitation increases speed and stability during gait and stair climbing, although the underlying mechanisms are poorly understood. MATERIAL AND METHODS: To determine whether these locomotor improvements are due to reorganized coordination of the head with whole body CG, three-dimensional kinematics were obtained from 10 vestibulopathic individuals before and after vestibular rehabilitation and from 10 matched healthy control subjects during unconstrained, paced and in-place gait. Head control patterns were characterized using both qualitative pattern analysis and quantification of coherence between head and body CG displacements. RESULTS: Patterns of head-CG coordination differ between normal and vestibulopathic individuals in all three directions of head rotation--pitch, roll and yaw--before rehabilitation. Following vestibular rehabilitation, subjects with vestibulopathy demonstrate more normal patterns in pitch and improvements toward normal in roll and yaw. CONCLUSION: These data strongly suggest that compensatory mechanisms, obtained during vestibular rehabilitation, mediate head-CG coordination.

Adaptation, Physiological↗