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PubMed2004

Ultra-high resolution 3D NMR spectra from limited-size data sets.

The advantage of the filter diagonalization method (FDM) for analysis of triple-resonance NMR experiments is demonstrated by application to a 3D constant time (CT) HNCO experiment. With a 15N-,13C-labeled human ubiquitin sample (1.0 mM), high spectral resolution was obtained at 500 MHz in 25 min with only 6-8 increments in each of the CT dimensions. This data set size is about a factor of 50-100 smaller than typically required, yet FDM analysis results in a fully resolved spectrum with a sharp peak for each HNCO resonance. Unlike Fourier transform (FT) processing, in which spectral resolution in each dimension is inversely proportional to the acquisition time in this dimension, FDM is a true multi-dimensional method; the resolution in all dimensions is determined by the total information content of the entire signal. As the CT dimensions of the 3D HNCO signal have approximate time-reversal symmetry, they can each be doubled by combining the usual four hyper-complex data sets. This apparent quadrupling of the data is important to the success of the method. Thus, whenever raw sensitivity is not limiting, well-resolved n-dimensional spectra can now be obtained in a small fraction of the usual time. Alternatively, to maximize sensitivity, evolution periods of faster relaxing nuclei may be radically shortened, the total required resolution being obtained through chemical shift encoding of other, more slowly relaxing, spins. Improvements similar to those illustrated with a 3D HNCO spectrum are expected for other triple-resonance spectra, where CT evolution in the indirect dimensions is implemented.

Algorithms↗

PubMed2006

Resolution enhancement in 1D solid-state NMR spectra of spin-9/2 quadrupolar nuclei.

NMR is an insensitive spectroscopy, which often requires numerous accumulations, especially for 2D high-resolution methods (MQMAS and STMAS) for quadrupolar nuclei in solids. This may be a very important limitation for the case of insensitive nuclei, where a 1D spectrum with better resolution than the central-transition is then highly desirable. This problem has been addressed for the case of spin-5/2 nuclei by the Double-Quantum Filtered Satellite Transition Spectroscopy: DQF-SATRAS-ST(1). We extend this concept to the spin-9/2 nuclei with the SATRAS-ST(2) method. This method allows the observation of 1D spectra with a much better resolution than that observed in the isotropic projection of 2D MQ/ST(1)-MAS spectra. This enhanced resolution results from the much smaller homogeneous broadening that occurs on the SATRAS-ST(2) method as compared to MQ/ST(1)-MAS spectra. The main interest in this method is for well-crystallized samples.

Journal Article↗

PubMed2005

Postnatal spontaneous resolution of congenital cystic adenomatoid malformations.

PURPOSE: Although antenatal resolution of congenital cystic adenomatoid malformations (CCAMs) is well documented, complete spontaneous postnatal resolution is rare, its existence even questioned by some. METHODS: All cases of antenatally diagnosed CCAMs over 7 years were retrospectively reviewed. Inclusion criteria were the following: (1) antenatal diagnosis of CCAM, (2) persistence on postnatal imaging, and (3) subsequent spontaneous resolution on postnatal imaging. RESULTS: Of 56 antenatally diagnosed CCAMs, 2 patients were identified. Both had macrocystic lesions. In case 1, the CCAM that filled the hemithorax on antenatal ultrasound was smaller on postnatal chest radiograph and disappeared by age 37 months on computed tomography. Case 2 had significant reduction of the CCAM at birth (persistence of the lesion on initial radiographs and ultrasound was documented). By 5 months, the lesion was not evident on computed tomography. Neither case was associated with symptoms, polyhydramnios, hydrops, or other abnormalities. CONCLUSIONS: In patients with an antenatal diagnosis of CCAM, spontaneous resolution may occur postnatally in 4% of cases. Significant reduction in CCAM size may portend possible disappearance and therefore warrants an observational period before resection.

Age Factors↗

PubMedDate not supplied

Issues of resolution and polymorphism in single-particle reconstruction.

Three-dimensional reconstruction from electron microscopic (EM) images of isolated macromolecular complexes is being employed by many laboratories. This approach is extremely powerful and continues to improve in resolution. In the absence of stereochemical constraints that can be used to assess the quality of a reconstruction, as exist in X-ray crystallography, several other measures have typically been used. A very useful assessment of quality can be made in the comparison between the projections of the three-dimensional reconstruction and averages generated from classes of images. The main quantitative measure has been that of resolution statistics, typically based upon Fourier shell correlations. We show, using only simulated noise for images, that impressive resolution statistics are generated that can even extend the apparent resolution of the starting model. When truly independent reconstructions are generated starting from different initial models, however, such artefacts are not possible. We also show, using real images of DnaB rings, that in the presence of polymorphism artefactual reconstructions can be generated whose projections match class averages. These averages, however, are themselves artefactual as they involve heterogeneous images. The issues presented here need to be considered when single-particle EM reconstructions are evaluated.

Bacterial Proteins↗

PubMed2004

Automated most-probable loss tomography of thick selectively stained biological specimens with quantitative measurement of resolution improvement.

We describe the technique and application of energy filtering, automated most-probable loss (MPL) tomography to intermediate voltage electron microscopy (IVEM). We show that for thick, selectively stained biological specimens, this method produces a dramatic increase in resolution of the projections and the computed volumes versus standard unfiltered transmission electron microscopy (TEM) methods. This improvement in resolution is attributed to the reduction of chromatic aberration, which results from the large percentage of inelastic electron-scattering events for thick specimens. These improvements are particularly evident at the large tilt angles required to improve tomographic resolution in the z-direction. This method effectively increases the usable thickness of selectively stained samples that can be imaged at a given accelerating voltage by dramatically improving resolution versus unfiltered TEM and increasing signal-to-noise versus zero-loss imaging, thereby expanding the utility of the IVEM to deliver information from within specimens up to 3 microm thick.

Animals↗

PubMed2005

A resolution criterion for electron tomography based on cross-validation.

Despite much progress in electron tomography, quantitative assessment of resolution has remained a problematic issue. The criteria that are used in single particle analysis, based on gauging the consistency between density maps calculated from half data sets, are not directly applicable because of the uniqueness of a tomographic volume. Here, we propose two criteria based on a cross-validation approach. One, called FSC(e/o), is based on a Fourier shell correlation comparison between tomograms calculated from the even and odd members of a tilt series. The other, called noise-compensated leave-one-out (NLOO), is based on Fourier ring correlation comparisons between an original projection and the corresponding reprojection of the tomogram calculated from all the other projections, taking into account the differing noise statistics. Plotted as a function of tilt angle, they allow assessment of the angular dependence of resolution and quality control over the series of projections. Integrated over all projections, the results give a global figure for resolution. Tests on simulated tomograms established consistency between these criteria and the FSC(ref), a correlation coefficient calculated between a known reference structure and the corresponding portion of a tomogram containing that structure. The two criteria-FSC(e/o) and NLOO-are mutually consistent when residual noise is the major resolution-limiting factor. When the size of the tilt increment becomes a significant factor, NLOO provides a more reliable criterion, as expected, although it is computationally intensive. Applicable to entire tomograms or selected structures, NLOO has also been tested on experimental tomographic data.

Capsid↗

PubMed2004

Estimation of the effective and functional human cortical connectivity with structural equation modeling and directed transfer function applied to high-resolution EEG.

Different brain imaging devices are presently available to provide images of the human functional cortical activity, based on hemodynamic, metabolic or electromagnetic measurements. However, static images of brain regions activated during particular tasks do not convey the information of how these regions are interconnected. The concept of brain connectivity plays a central role in the neuroscience, and different definitions of connectivity, functional and effective, have been adopted in literature. While the functional connectivity is defined as the temporal coherence among the activities of different brain areas, the effective connectivity is defined as the simplest brain circuit that would produce the same temporal relationship as observed experimentally among cortical sites. The structural equation modeling (SEM) is the most used method to estimate effective connectivity in neuroscience, and its typical application is on data related to brain hemodynamic behavior tested by functional magnetic resonance imaging (fMRI), whereas the directed transfer function (DTF) method is a frequency-domain approach based on both a multivariate autoregressive (MVAR) modeling of time series and on the concept of Granger causality. This study presents advanced methods for the estimation of cortical connectivity by applying SEM and DTF on the cortical signals estimated from high-resolution electroencephalography (EEG) recordings, since these signals exhibit a higher spatial resolution than conventional cerebral electromagnetic measures. To estimate correctly the cortical signals, we used a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from individual MRI, a distributed source model and a regularized linear inverse source estimates of cortical current density. Before the application of SEM and DTF methodology to the cortical waveforms estimated from high-resolution EEG data, we performed a simulation study, in which different main factors (signal-to-noise ratio, SNR, and simulated cortical activity duration, LENGTH) were systematically manipulated in the generation of test signals, and the errors in the estimated connectivity were evaluated by the analysis of variance (ANOVA). The statistical analysis returned that during simulations, both SEM and DTF estimators were able to correctly estimate the imposed connectivity patterns under reasonable operative conditions, that is, when data exhibit an SNR of at least 3 and a LENGTH of at least 75 s of nonconsecutive EEG recordings at 64 Hz of sampling rate. Hence, effective and functional connectivity patterns of cortical activity can be effectively estimated under general conditions met in any practical EEG recordings, by combining high-resolution EEG techniques and linear inverse estimation with SEM or DTF methods. We conclude that the estimation of cortical connectivity can be performed not only with hemodynamic measurements, but also with EEG signals treated with advanced computational techniques.

Adult↗

PubMed2005

High-resolution ultrahigh-field MRI of stroke.

BACKGROUND: Ultrahigh-field MRI at 8 T offers unprecedented resolution for imaging brain structures and microvasculature. OBJECTIVE: The aim of this study is to apply high-resolution MRI for stroke imaging and to characterize findings at 1.5 and 8 T. METHODS: Seventeen subjects with minor ischemic infarcts were studied using T2-weighted gradient echo (GE) and rapid acquisition with relaxation enhancement (RARE) images at 8 T with resolution up to 200 microm. In 10 subjects, T1- and T2-weighted fast spin echo (FSE) and fluid-attenuated inversion recovery (FLAIR) images were also acquired at 1.5-T MRI. RESULTS: The 8-T images showed infarcts as sharply demarcated areas of high-signal intensity (n=21) and revealed more infarctions than 1.5-T images (n=14) (P<.003). The low-signal intensity areas that surrounded infarctions were suggestive of hemosiderin deposits. The 8-T characteristics of microvessels terminating within the infractions were distinct from normal vasculature. The 8-T images revealed an angioma at the site of a second stroke, not apparent on 1.5-T images. CONCLUSIONS: Ultrahigh-field MRI at 8 T is feasible for stroke imaging. The 8-T MRI visualized infarcts and microvasculature with high resolution, revealing infarcts and vascular pathologies that were not apparent at 1.5 T.

Adult↗

PubMed2006

The effects of single-trial averaging on the temporal resolution of functional MRI.

Computer simulations and event-related functional MRI (ER-fMRI) experiments were performed to investigate the effects of single-trial averaging and the corresponding contrast-to-noise ratio (CNR) on the minimal resolvable hemodynamic timing difference between brain areas. Three ER-fMRI sessions with temporally delayed (250, 500 and 1,000 ms) visual stimulations between two hemifields, each with 70 repeated single trials, were examined on two subjects. From the computer simulation, the temporal resolution improved as the CNR increased, which reached 500 and 100 ms for CNRs of 1.55 and 6.44, respectively. In the ER-fMRI experiments, the measured CNR increased as more single trials were averaged. The detectability of temporal differences was positively correlated (P<.05) with the CNR in all sessions for one subject but only in the 1,000-ms session for the other subject. Temporal resolution of 1,000 ms was achieved when more than 10 trials were averaged. The 500- and 250-ms delays might be differentiable when more than 20 trials were averaged, but the results were subject-dependent. This study demonstrated that the CNR could be significantly improved by single-trial averaging, which led to an improved temporal resolution of ER-fMRI. Temporal resolution in the range of hundreds of milliseconds was subject-dependent, which might be attributed to the intrinsic spatial variations in the timing of the blood oxygenation level-dependent (BOLD) response.

Adult↗

PubMed2006

Characterization of trabecular bone structure from high-resolution magnetic resonance images using fuzzy logic.

The purpose of this work was to apply fuzzy logic image processing techniques to characterize the trabecular bone structure with high-resolution magnetic resonance images. Fifteen ex vivo high-resolution magnetic resonance images of specimens of human radii at 1.5 T and 12 in vivo high-resolution magnetic resonance images of the calcanei of peri- and postmenopausal women at 3 T were obtained. Soft segmentation using fuzzy clustering was applied to MR data to obtain fuzzy bone volume fraction maps, which were then analyzed with three-dimensional (3D) fuzzy geometrical parameters and measures of fuzziness. Geometrical parameters included fuzzy perimeter and fuzzy compactness, while measures of fuzziness included linear index of fuzziness, quadratic index of fuzziness, logarithmic fuzzy entropy, and exponential fuzzy entropy. Fuzzy parameters were validated at 1.5 T with 3D structural parameters computed from microcomputed tomography images, which allow the observation of true trabecular bone structure and with apparent MR structural indexes at 1.5 T and 3 T. The validation was statistically performed with the Pearson correlation coefficient as well as with the Bland-Altman method. Bone volume fraction correlation values (r) were up to .99 (P<.001) with good agreements based on Bland-Altman analysis showing that fuzzy clustering is a valid technique to quantify this parameter. Measures of fuzziness also showed consistent correlations to trabecular number parameters (r>.85; P<.001) and good agreements based on Bland-Altman analysis, suggesting that the level of fuzziness in high-resolution magnetic resonance images could be related to the trabecular bone structure.

Aged↗

PubMed2006

Extensive heterogeneity in white matter intensity in high-resolution T2*-weighted MRI of the human brain at 7.0 T.

MRI at high magnetic field strength potentially allows for an increase in resolution and image contrast. The gains are particularly dramatic for T(2)(*)-weighted imaging, which is sensitive to susceptibility effects caused by a variety of sources, including deoxyhemoglobin, iron concentration, and tissue microstructure. On the other hand, the acquisition of high quality whole brain MRI at high field is hampered by the increased inhomogeneity in B(o) and B(1) fields. In this report, high-resolution gradient echo MRI was performed using an 8-channel detector to obtain T(2)(*)-weighted images over large brain areas. The high SNR achieved with the multi-channel array enabled T(2)(*)-weighted images of the brain with an unprecedented spatial resolution of up to 0.2 x 0.2 x 0.5 mm(3). This high resolution greatly facilitated the detection of microscopic susceptibility effects. In addition to the expected contrast between gray, white matter, cerebral spinal fluid, and veins, a large degree of heterogeneity in contrast was observed throughout the white matter of normal brain. The measured T(2)(*) values in white matter varied as much as 30% with some of the variation apparently correlating with the presence of large fiber bundles.

Adult↗

PubMed2007

Cognitive fatigue of executive processes: interaction between interference resolution tasks.

A resource depletion framework motivated a novel strategy for investigating whether the central executive is unitary or separable into relatively independent subprocesses. The idea that tasks with overlapping neural representations may involve similar executive components was also critical to our approach. Of particular interest were tasks requiring resolution of interference among competing representations. Within a single experimental session intensive training reduced the ability to resolve interference on a transfer task if the training task placed high demands on interference resolution. Negative transfer was absent when interference resolution was minimally required by the task, or when the training and transfer tasks did not rely on overlapping neural representations. These results suggest a nonunitary central executive composed of separable subcomponents, at least one of which mediates interference resolution. Our results are consistent with an executive control process specialized for the selection of task-relevant representations from competitors. The results also agree with the view that higher cognitive processes are resource limited and can be temporarily depleted.

Adolescent↗

PubMed2006

Ultrahigh-resolution optical coherence tomography in patients with decreased visual acuity after retinal detachment repair.

OBJECTIVE: To assess microstructural changes in the retina that may explain incomplete visual recovery after anatomically successful repair of rhegmatogenous retinal detachments (RD) using ultrahigh-resolution optical coherence tomography (UHR OCT). DESIGN: Retrospective observational case series. PARTICIPANTS: Seventeen patients with decreased visual acuity after RD repair. Twelve patients had macula-involving and 5 had macula-sparing RDs. METHODS: The UHR OCT prototype capable of approximately 3 mum axial resolution was developed for clinical use. The UHR OCT images through the center of the fovea in 17 patients with visual complaints after RD surgery were obtained. Patients were either postoperative patients from the New England Eye Center or tertiary referrals. Baseline visual acuity, preoperative lens status, location of retinal detachment, macular involvement, and postoperative visual acuity were recorded. MAIN OUTCOME MEASURES: The UHR OCT images after RD repair. RESULTS: The UHR OCT images were obtained 1 to 84 months (median, 5 months) postoperatively. The mean preoperative logarithm of the minimum angle of resolution (logMAR) visual acuity was 1.37 (Snellen equivalent, 20/390). The mean postoperative logMAR visual acuity was 0.48 (Snellen equivalent, 20/60). Anatomical abnormalities that were detected included distortion of the photoreceptor inner/outer segments (IS/OS) junction in 14 of 17 patients (82%), epiretinal membranes in 10 of 17 patients (59%), residual subretinal fluid in 3 of 17 patients (18%), and cystoid macular edema in 2 of 17 patients (12%). Of the 5 patients with preoperative macula-on detachments, 4 had distortion of the outer retina after RD repair. CONCLUSIONS: The higher resolution of UHR OCT facilitates imaging of the IS/OS junction. Therefore, UHR OCT is able to confirm prior histopathologic findings that damage to photoreceptor outer segments may occur as a consequence of retinal detachment. This may explain poor postoperative visual acuity in eyes with anatomically successful repair.

Adult↗

PubMed2006

High-resolution retinal imaging of cone-rod dystrophy.

PURPOSE: This study examines a patient with cone-rod dystrophy using high-resolution adaptive optics retinal imaging. Conventional ophthalmoscopes provide limited resolution due to their inability to overcome the eye's optical aberrations. In contrast, adaptive optics ophthalmoscopes correct these aberrations to provide noninvasive high-resolution views of the living retina. To date, adaptive optics ophthalmoscopy has been used mainly to examine the normal retina. Here we use adaptive optics ophthalmoscopy to image cone-rod dystrophy in vivo and compare these results with standard clinical tests. DESIGN: Observational case report. METHODS: High-resolution retinal images of a patient with cone-rod dystrophy were obtained with the University of Rochester adaptive optics flood-illuminated ophthalmoscope and the adaptive optics scanning laser ophthalmoscope located at the University of Houston and compared with standard clinical tests, including fundus photography, Goldmann visual fields, fluorescein angiography, optical coherence tomography, electroretinography, and multifocal electroretinography. MAIN OUTCOME MEASURES: Direct measurement of cone density and diameter and comparison of adaptive optics images with standard clinical imaging and functional tests. RESULTS: Adaptive optics images were acquired at multiple retinal locations throughout a clinically detected bull's-eye lesion. Within the atrophic regions, we observed large areas devoid of wave-guiding cones. In contrast, regions that appeared relatively spared by clinical examination contained a completely tiled cone mosaic. However, in these areas the cones were abnormally large, resulting in a 6.6-fold reduction from the normal peak cone density (patient peak density: 30 100 cones/mm2, normal peak density: 199 200 cones/mm2). Multifocal electroretinography confirmed a 5.5-fold reduction in amplitude of the central peak (10.8 nanovolts/degree2 vs. 59.8 nanovolts/degree2). CONCLUSIONS: Adaptive optics ophthalmoscopy is a noninvasive technique to observe a patient's retinal pathology directly at a cellular level. It can provide a quantitative measurement of photoreceptor loss in retinal disease.

Adult↗

PubMed2006

Knowledge-based real-space explorations for low-resolution structure determination.

The accurate and effective interpretation of low-resolution data in X-ray crystallography is becoming increasingly important as structural initiatives turn toward large multiprotein complexes. Substantial challenges remain due to the poor information content and ambiguity in the interpretation of electron density maps at low resolution. Here, we describe a semiautomated procedure that employs a restraint-based conformational search algorithm, RAPPER, to produce a starting model for the structure determination of ligase interacting factor 1 in complex with a fragment of DNA ligase IV at low resolution. The combined use of experimental data and a priori knowledge of protein structure enabled us not only to generate an all-atom model but also to reaffirm the inferred sequence registry. This approach provides a means to extract quickly from experimental data useful information that would otherwise be discarded and to take into account the uncertainty in the interpretation--an overriding issue for low-resolution data.

Algorithms↗

PubMed2007

Identification of secondary structure elements in intermediate-resolution density maps.

An increasing number of structural studies of large macromolecular complexes, both in X-ray crystallography and cryo-electron microscopy, have resulted in intermediate-resolution (5-10 A) density maps. Despite being limited in resolution, significant structural and functional information may be extractable from these maps. To aid in the analysis and annotation of these complexes, we have developed SSEhunter, a tool for the quantitative detection of alpha helices and beta sheets. Based on density skeletonization, local geometry calculations, and a template-based search, SSEhunter has been tested and validated on a variety of simulated and authentic subnanometer-resolution density maps. The result is a robust, user-friendly approach that allows users to quickly visualize, assess, and annotate intermediate-resolution density maps. Beyond secondary structure element identification, the skeletonization algorithm in SSEhunter provides secondary structure topology, which is potentially useful in leading to structural models of individual molecular components directly from the density.

Computational Biology↗

PubMed2006

EFTEM spectrum imaging at high-energy resolution.

This paper deals with the application of high-energy resolution EFTEM image series and the corrections needed for reliable data interpretation. The detail of spectral information gained from an image series is largely determined by the intrinsic energy resolution. In this work we show that energy resolution values of as low as 0.8 eV in spectra extracted from EFTEM image series can be obtained with a small energy-selecting slit. At this resolution level aberrations of the energy filter, in particular the non-isochromaticity, can no longer be neglected. We show that the four most prominent factors for EFTEM image series data correction--spatial drift, non-isochromaticity, energy drift and image distortion--must not be treated independently but have to be corrected in unison. We present an efficient algorithm for this correction, and demonstrate the applied correction for the case of a GaN/AlN multilayer sample.

Journal Article↗

PubMed2004

Theoretical derivation of SNR, CNR and spatial resolution for a local adaptive strain estimator for elastography.

Conventional techniques in elastography estimate the axial strain as the gradient of the displacement (time-delay) estimates obtained using cross-correlation of pre- and temporally stretched postcompression radiofrequency (RF) A-line segments. The use of a constant stretch factor for stretching the postcompression A-line is not adequate in the presence of heterogeneous targets that are commonly encountered. This led to the development of several adaptive strain estimation techniques in elastography. Yet, a theoretical framework for the image quality of adaptive strain estimation has not been established. In this work, we develop theoretical expressions for the image quality [measured in terms of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and spatial resolution] of elastograms obtained using an adaptive strain estimator developed by Alam et al. (1998). We show a linear trade-off between the SNR and axial resolution of the strain elastogram with respect to the window length used for strain estimation. The CNR shows a quadratic tradeoff with the axial resolution with respect to the window length. The SNR, CNR and axial resolution are shown to improve with the ultrasonic bandwidth.

Algorithms↗