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Resolution limitations in intravascular ultrasound imaging.

Interest in the use of ultrasound to characterize the structure and composition of blood vessel walls has risen dramatically as a result of the development of intravascular ultrasonic imaging transducers mounted on the tips of small-diameter catheters. A study of the resolution of these transducers is needed to understand the limitations in the visualization of these structures. Theoretic and experimental studies of the resolution of the two principal designs of intravascular ultrasonic transducers, the mechanically scanned single element and the multielement circular array, were carried out. Comparisons of the two designs reveal that they have similar resolutions. However, the resolutions in two of the three dimensions are shown to decrease linearly with increasing radial distance. Significant errors in image interpretation, particularly in larger diameter vessels, will result if this variation in resolution is not accounted for.

Blood Vessels↗

Alcohol problem resolution in the severely mentally ill: a preliminary investigation.

Participants (N = 25) with a severe mental illness who were receiving mental health outpatient treatment at a state psychiatric hospital were interviewed regarding the resolution of their alcohol problem. Resolution was defined as abstinence or non-hazardous, consequence-free drinking for a minimum of 1 year. Participants were interviewed regarding their drinking history, life events, reasons for change and factors maintaining change. The results reveal that negative life events and weighing the pros and cons of drinking are more often associated with entry into treatment than positive life events and advice or warnings from others. In addition, resolution occurs with and without a history of alcohol-specific treatment and includes both abstinent and non-abstinent drinking outcomes. Although preliminary, these results are consistent with previous research investigating the resolution of alcohol problems in individuals with only a diagnosis of alcohol abuse or dependence. Unique to this population is the finding that control of psychological symptoms was identified as an important maintenance factor during the first 12 months following the resolution date. The limitations of the current study, as well as the implications of these findings for future research investigating processes of change in the severely mentally ill are discussed.

Adult↗

Time course of symptom resolution in patients with community-acquired pneumonia.

The majority of patients with community-acquired pneumonia are at low risk for short-term mortality or serious morbidity and are increasingly managed in the outpatient setting. Efforts to improve the quality of care for these patients will need to measure patient outcomes such as disease-specific symptom resolution. The aims of this study were to (1) develop a self-administered daily version of a symptom questionnaire for patients with pneumonia, (2) measure the reliability of this instrument, and (3) provide estimates for recovery rates based on symptom resolution in a cohort of low-risk patients with community-acquired pneumonia. This study was conducted as part of a prospective study of a new emergency department protocol for pneumonia at the Massachusetts General Hospital. Eligible study subjects included all adult patients with pneumonia presenting to the emergency department with a predicted low risk of short-term mortality. The main outcome measures were based on a new five item symptom questionnaire which rates the severity of cough, fatigue, dyspnea, myalgia, and fever. The questionnaires were self-administered on days 0-7, 14, 21 and 28 from the time of diagnosis of pneumonia. The symptom questions were also administered during patient interviews on days 0, 7, 14 and 28 in order to assess the questionnaire's reliability. Of the 166 eligible patients, 134 (81%) consented to participate in this study. The mean intra-class reliability coefficient of the symptom questionnaire was 0.75. The median times to resolution of individual symptoms ranged from 3 days for fever to 14 days for cough and fatigue. Thirty-five percent of patients had at least one symptom still present at the end of the 28-day study period. We found that a daily self-report questionnaire is a reliable measure of symptom resolution for patients with pneumonia. Full resolution of symptoms takes more than 28 days for a significant proportion of patients with pneumonia.

Adolescent↗

High-resolution electron cryomicroscopy of macromolecular assemblies.

Electron cryomicroscopy is a high-resolution imaging technique that is particularly appropriate for the structural determination of large macromolecular assemblies, which are difficult to study by X-ray crystallography or NMR spectroscopy. For some biological molecules that form two-dimensional crystals, the application of electron cryomicroscopy and image reconstruction can help elucidate structures at atomic resolution. In instances where crystals cannot be formed, atomic-resolution information can be obtained by combining high-resolution structures of individual components determined by X-ray crystallography or NMR with image-derived reconstructions at moderate resolution. This can provide unique and crucial information on the mechanisms of these complexes. Finally, image reconstructions can be used to augment X-ray studies by providing initial models that facilitate phasing of crystals of large macromolecular machines such as ribosomes and viruses.

Actin Cytoskeleton↗

High-resolution functional magnetic resonance imaging of the animal brain.

To fully understand brain function, one must look beyond the level of a single neuron. By elucidating the spatial properties of the columnar and laminar functional architectures, information regarding the neural processing in the brain can be gained. To map these fine functional structures noninvasively and repeatedly, functional magnetic resonance imaging (fMRI) can be employed. In this article the basic principles of fMRI are introduced, including specific hardware requirements and the equipment necessary for animal magnetic resonance research. Since fMRI measures a change in secondary hemodynamic responses induced by neural activity, it is critical to understand the principles and potential pitfalls of fMRI techniques. Thus, the underlying physics of conventional blood oxygenation, cerebral blood flow, and cerebral blood volume-based fMRI techniques are extensively discussed. Tissue-specific signal change is close to the site of neural activity, while signals from large vessels can be distant from the actual active site. Thus, methods to minimize large vessel contributions and to maximize tissue signals are described. The fundamental limitation of fMRI spatial resolution is the intrinsic hemodynamic response. Based on our high-resolution fMRI studies, the hemodynamic response is regulated at submillimeter functional domains and thus spatial resolution can be achieved to an order of 100 microm. Since hemodynamic responses are sluggish, it is difficult to obtain very high temporal resolution. By using an approach with multiple experiments with different stimulus conditions, temporal resolution can be improved on the order of 100 ms. With current fMRI technologies, submillimeter columnar- and laminar-specific specific functional images can be obtained from animal brains.

Animals↗

Use of frozen-hydrated axonemes to assess imaging parameters and resolution limits in cryoelectron tomography.

Using a 400-kV cryoelectron microscope, we have obtained tomographic reconstructions of frozen-hydrated sea urchin axonemes with 8-10-nm resolution, as assessed by detection of characteristic components including doublet microtubules, radial spokes, central sheath projections, and outer dynein arms. We did not detect the inner dynein arms or the microtubule lattice. The 1/(8 nm) and 1/(16 nm) layer lines are consistently present in power spectra of both projection images and tomographic reconstructions. Strength and detection of the layer lines are dependent upon total electron dose and defocus. Both layer lines are surprisingly resistant to electron doses of up to 11000 electrons/nm(2). We present a summary of resolution considerations in cryoelectron tomography and conclude that the fundamental limitation is the total electron dose required for statistical significance. The electron dose can be fractionated among the numerous angular views in a tomographic data set, but there is an unavoidable fourth-power dependence of total dose on target resolution. Since higher-resolution features are more beam-sensitive, this dose requirement places an ultimate limit on the resolution of individual tomographic reconstructions. Instrumental and computational strategies to circumvent this limitation are discussed.

Animals↗

Evaluation of in vivo total and regional air content and distribution in primate lungs with high-resolution CT.

RATIONALE AND OBJECTIVES: The authors sought to determine whether gray-scale quantitative information from high-resolution computed tomography (CT) could reliably yield estimates of lung air content and help determine changes in air content with lung inflation and deflation. MATERIALS AND METHODS: High-resolution CT images (n = 40) of lungs of two anesthetized monkeys were obtained after inflation with known air volumes. Percentage air content was calculated for each voxel, and lung volumes and patterns of air distribution were determined. RESULTS: When corrected for pressure and temperature, high-resolution CT-based volumes correlated closely with inflation volumes (r = .99; standard error = 3.4%). Patterns of regional change in air content demonstrated known patterns of ventilation. CONCLUSION: Although the high-spatial-frequency algorithm used in high-resolution CT enhances edges of structures and improves visualization of anatomic detail, gray-scale values from the same high-resolution CT data set remain a reliable index of regional lung attenuation.

Animals↗

Quantitative pulmonary imaging: spatial and temporal considerations in high-resolution CT.

RATIONALE AND OBJECTIVES: The authors performed this study to determine how scanner temporal resolution affects image quality in high-resolution computed tomography (CT)-based quantitative analysis of lung parenchyma. MATERIALS AND METHODS: A 37-kg, anesthetized white pig, in which 1.5-mm-diameter radiopaque markers were bronchoscopically implanted, was scanned supine with electron-beam CT and spiral CT scanners. Images were first acquired during apnea at functional residual capacity with electron-beam CT at a single level with multiple scan apertures. Without altering body posture, the animal was transported to the spiral CT scanner and scanned at the same lung volume and level. The animal was then euthanized and rescanned with spiral CT. All images were reconstructed with high-spatial-frequency algorithms resident on the respective scanners. RESULTS: High-resolution CT images of the live animal in the spiral scanner showed substantial cardiogenic motion artifacts for markers both near and distant from the heart. The matched postmortem images showed no motion artifacts. While line-pair phantom scans showed reduced spatial resolution of electron-beam CT compared with spiral CT scans, the electron-beam CT images of the markers in the live animal were free of artifacts, even with scan apertures of up to 700 msec. CONCLUSION: Motion artifacts may be accentuated by differences in high-resolution CT implementations. Applications such as lung parenchyma texture analysis, which regionally quantifies the subtle tissue density variations, will likely benefit from short scanning apertures.

Animals↗

Recognition of imagined hand movements with low resolution surface Laplacian and linear classifiers.

EEG-based Brain Computer Interfaces (BCIs) require on-line detection of mental states from spontaneous EEG signals. In this framework, it was suggested that EEG patterns can be better detected with EEG data transformed with Surface Laplacian computation (SL) than with the unprocessed raw potentials. However, accurate SL estimates require the use of many EEG electrodes, when local estimation methods are used. Since BCI devices have to use a limited number of electrodes for practical reasons, we investigated the performances of spline methods for SL estimates using a limited number of electrodes (low resolution SL). Recognition of mental activity was attempted on both raw and SL-transformed EEG data from five healthy people performing two mental tasks, namely imagined right and left hand movements. Linear classifiers were used including Signal Space Projection (SSP) and Fisher's linear discriminant. Results showed an acceptable average correlation between the waveforms obtained with the low resolution SL and these obtained with the SL computed from 26 electrodes (full resolution SL). More importantly, satisfactorily recognition scores for mental EEG-patterns were obtained with the low-resolution surface Laplacian transformation of the recorded potentials when compared with those obtained by using full resolution SL (82%). These results demonstrated also the utility of linear classifiers for the detection of mental patterns in the BCI field.

Biomedical Engineering↗

Sensitivity of transvenous defibrillation models to adaptive mesh density and resolution: the potential for interactive solution times.

The voltage gradients induced in ventricular myocardium by an electric shock have been shown to correlate to the probability of the shock producing a successful defibrillation. Finite element modeling is one method for computing these voltage gradients, although the meshing of complex biomedical domains is difficult on a patient-specific basis. We recently described an adaptive algorithm that automates the generation of finite element meshes for complex 3-D domains from bitmapped images. This article examines the sensitivity of the computed distribution of ventricular voltage gradients to the resolution of the images and to the adapted density of the mesh. The results allow us to establish an adaptation stopping criterion and a minimum input image resolution for modeling transvenous defibrillation. The sensitivity to adapted mesh density was analyzed by comparing voltage gradient histograms from successively finer meshes to histograms from a uniform mesh at the maximum possible density. Comparisons were made using the Kolmogorov-Smirnov test with the number of samples required to detect a 5% difference in the histograms at the 0.05 significance level. Adaptation to a global current density error estimate of 5% or less was required in order to achieve acceptance of the null hypothesis that the distributions were the same in all cases. Defibrillation efficacy, however, is predicted from the voltage gradient in the first quartile, and the results suggest that this region of the cumulative histogram converges faster during mesh adaptation than the histogram as a whole. We also compared histograms from models generated from successively finer input images. The histogram of each model was compared with the histogram obtained from the finest possible resolution. In all cases, the null hypothesis of no difference was accepted at resolutions of 2.3 x 2.3 x 3.0 mm. The average time required to build and adapt models to a 5% accuracy at the first quartile at this resolution was 1.8 min. on a common workstation. We believe that this demonstrates a potential for the eventual synthesis of finite element computations into interactive electrode placement tools on a subject-specific basis.

Algorithms↗

Calibration of trabecular bone structure measurements of in vivo three-dimensional peripheral quantitative computed tomography with 28-microm-resolution microcomputed tomography.

It has recently been shown that high-resolution computed tomography and magnetic resonance imaging have the potential to assess information about the microarchitecture of bone in a noninvasive way. However, due to the limited spatial resolution of the in vivo measurements, the individual trabeculae are not depicted with their true thickness. Nevertheless, the spacing of the structural elements allows the assessment of trabecular number. In a previous publication, the ridge number density (RND) was introduced as a measure for this structural index. It can be extracted from high-resolution three-dimensional (3D) images of patients and shows a reproducibility of 1.6%. In this work the Ridge extraction procedure is compared to and calibrated with microcomputed tomography (microCT) measurements. Three-dimensional measurements of 15 bone biopsies are made with a 28-microm-resolution microCT scanner as well as with a 165-microm-resolution peripheral quantitative computed tomography (pQCT) scanner. For the latter, the same settings are used as for patient examinations. The 15 pairs of measurements are analyzed and the resulting structural indices are compared. The results show that structural indices such as trabecular number, mean thickness, and mean separation can be determined from the 3D pQCT data with an r2 of between 0.81 and 0.96 if the microCT data are taken as the gold standard. The calibration equation found for the bone volume fraction has an intercept of 0.04 and a slope of 0.86 (r2 = 0.98), and trabecular number as the main additional structural index shows a nonsignificant intercept and a calibration slope of 0.91 with the microCT. The calibration procedure can be used directly for patient examinations. Applied to time-series measurements it may be of value for monitoring and quantifying microarchitectural changes due to therapy or aging.

Adult↗

High-resolution matrix-assisted laser desorption/ionization in a linear time-of-flight mass spectrometer.

A time-lag focusing method is developed for the improvement of mass resolution in a linear time-of-flight mass spectrometer for matrix-assisted laser desorption/ionization (MALDI). In this technique, the ions generated by the MALDI process are extracted by a pulsed voltage. A short time delay (280 ns) is inserted in between the laser desorption/ionization event and the ion extraction. The region between the repeller and extraction grid is field-free during the delay. The time-lag extraction allows the ions generated in the region between the repeller and the extraction grid to separate according to their velocity (energy). Application, to the repeller, of the appropriate pulse voltage provides the energy correction necessary to simultaneously detect all ions of the same mass/charge regardless of their initial energy, resulting in improved mass resolution. It is demonstrated that mass resolution in the range of 3000-6000 fwhm can be obtained. With this mass resolution, isotopically resolved mass spectra are observed for peptides with masses up to 3000 Da. For proteins, such as bovine insulin, cytochrome c, and apomyoglobin, resolution in the range of 800-1000 fwhm is observed with a mass measurement accuracy better than 0.01%.

Amino Acid Sequence↗

Improvement in the apparent mass resolution of oligonucleotides by using 12C/14N-enriched samples.

The apparent mass resolution of oligonucleotides in time-of-flight (TOF) mass spectrometers has been examined. In a reflectron TOF instrument, where the isotopic profile can be completely resolved, the apparent resolution matches the instrument's resolving power. In a linear TOF instrument, unresolved isotopic profiles limit the apparent resolution to much lower values than the actual instrument resolution. By using 12C/14N-enriched oligonucleotides, the apparent resolution can be improved significantly. The isotope enrichment method also enhances the signal-to-noise ratio.

Carbon Isotopes↗

HPLC and MALDI-TOF MS analysis of highly branched polystyrene: resolution enhancement by branching.

Temperature gradient interaction chromatography (TGIC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) were applied for the characterization of highly branched polystyrenes (PS) prepared by linking living polystyryl anions using 4-chlorodimethylsilylstyrene. Reversed-phase (RP)-TGIC showed an unexpectedly high resolution according to the number of branches despite significant overlap of the molecular weight as confirmed by MALDI-TOF MS. The enhancement of the resolution is ascribed to the contribution of the nonpolar groups in the branched PS: the dimethylsilyl groups in the branching unit as well as the sec-butyl initiator groups. As the number of branches increases, the number of nonpolar groups increases, which in turn increases the RP-TGIC retention synergistically with increasing molecular weight. In contrast, a poorer resolution was found in normal-phase-TGIC, in which the nonpolar groups reduce the retention. The resolution in RP-TGIC appears superior to that of liquid chromatography at the chromatographic critical condition (LCCC) of PS. It is seemingly due to the synergistic contribution of the incremental PS molecular weight to the functionality in the branched PS in RP-TGIC while only the functionality contributes to the separation in LCCC. This type of resolution enhancement could be utilized efficiently for the analysis of highly branched polymers such as dendrimers or hyperbranched polymers.

Chromatography, High Pressure Liquid↗

Chemical resolution of Pu+ from U+ and Am+ using a band-pass reaction cell inductively coupled plasma mass spectrometer.

Determination of the concentration and distribution of the Pu and Am isotopes is hindered by the isobaric overlaps between the elements themselves and U, generally requiring time-consuming chemical separation of the elements. A method is described in which chemical resolution of the elemental ions is obtained through ion-molecule reactions in a reaction cell of an ICPMS instrument. The reactions of "natural" U(+), (242)Pu(+), and (243)Am(+) with ethylene, carbon dioxide, and nitric oxide are reported. Since the net sensitivities to the isotopes of an element are similar, chemical resolution is inferred when one isobaric element reacts rapidly with a given gas and the isobar (or in this instance surrogate isotope) is unreactive or slowly reactive. Chemical resolution of the m/z 238 isotopes of U and Pu can be obtained using ethylene as a reaction gas, but little improvement in the resolution of the m/z 239 isobars is obtained. However, high efficiency of reaction of U(+) and UH(+) with CO(2), and nonreaction of Pu(+), allows the sub-ppt determination of (239)Pu, (240)Pu, and (242)Pu (single ppt for (238)Pu) in the presence of 7 orders of magnitude excess U matrix without prior chemical separation. Similarly, oxidation of Pu(+) by NO, and nonreaction of Am(+), permit chemical resolution of the isobars of Pu and Am over 2-3 orders of magnitude relative concentration. The method provides the potential for analysis of the actinides with reduced sample matrix separation.

Journal Article↗

Field-deployable, high-resolution, time-of-flight aerosol mass spectrometer.

The development of a new high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) is reported. The high-resolution capabilities of this instrument allow the direct separation of most ions from inorganic and organic species at the same nominal m/z, the quantification of several types of organic fragments (CxHy, CxHyOz, CxHyNp, CxHyOzNp), and the direct identification of organic nitrogen and organosulfur content. This real-time instrument is field-deployable, and its high time resolution (0.5 Hz has been demonstrated) makes it well-suited for studies in which time resolution is critical, such as aircraft studies. The instrument has two ion optical modes: a single-reflection configuration offers higher sensitivity and lower resolving power (up to approximately 2100 at m/z 200), and a two-reflectron configuration yields higher resolving power (up to approximately 4300 at m/z 200) with lower sensitivity. The instrument also allows the determination of the size distributions of all ions. One-minute detection limits for submicrometer aerosol are <0.04 microg m(-3) for all species in the high-sensitivity mode and <0.4 microg m(-3) in the high-resolution mode. Examples of ambient aerosol data are presented from the SOAR-1 study in Riverside, CA, in which the spectra of ambient organic species are dominated by CxHy and CxHyOz fragments, and different organic and inorganic fragments at the same nominal m/z show different size distributions. Data are also presented from the MIRAGE C-130 aircraft study near Mexico City, showing high correlation with independent measurements of surrogate aerosol mass concentration.

Journal Article↗

High-resolution mass spectrometry with a quadrupole operated in the fourth stability region

The properties of a quadrupole mass filter operated in the fourth stability region with Mathieu parameters (a,q) = (2 x 10(-3), 21.3) have been investigated experimentally and theoretically. A resolution at half-height (R1/2) of 13,900 has been obtained for 40 eV 39K+ ions formed by thermal ionization. With ion energies of 750 eV or more, a resolution at half-height of up to 5000 can be obtained. Extrapolation of resolution data obtained with ions of 40 eV-4800 eV energy shows that unit resolution should be possible for ions with energies of approximately 10 keV. For low-energy ions (e.g., 75 eV), the transmission of the quadrupole operated in the fourth region is many orders of magnitude less than that of a quadrupole operated in the first or second stability regions. Acceptance calculations show this is a result of the combination of a much lower acceptance and strongly defocusing fringing fields. However, for higher ion energies, the transmission with operation in the fourth region is found to be comparable to that of a quadrupole operated at the same resolution in the second region. The implications for inductively coupled plasma mass spectrometry are briefly discussed.

Journal Article↗

Dynamic thermodynamic resolution: control of enantioselectivity through diastereomeric equilibration.

A theoretical foundation, tools for recognition and control, and recent examples of a class of asymmetric transformation termed dynamic thermodynamic resolution are presented. Enantioselective reaction pathways that involve an induced diastereomeric equilibration to intermediates, which are configurationally stable on the time scale of a subsequent reaction, are illustrated. Dynamic thermodynamic resolution differs from the classic, well-documented pathways of kinetic resolution and dynamic kinetic resolution in that equilibration and resolution can be operative on one system in separate controllable steps. This approach offers a high level of flexibility and provides multiple opportunities for optimization of enantioselectivity.

Stereoisomerism↗