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[Anatomy and pathology of the retrobulbar space in MRI using a high-resolution surface coil].

Because of its high soft tissue resolution and its lack of radiation hazard, MRI is considered a valuable method in the diagnosis of orbital disease. Insufficient spatial resolution was considered the main drawback of orbital MRI. Another problem was the chemical shift artifact caused by shifting of the signal of fat and water. To optimize image quality, a high-resolution coil with a small diameter was constructed. Twenty patients with intraorbital changes were examined with MRI. We used a special surface coil with a diameter of 4 cm. For optimal image quality we modified the bandwidth and other parameters of the sequences. For comparison additional measurements were performed in 13 patients with the standard surface coil (diameter 11 cm) and/or the head coil. The best results were obtained with a middle bandwidth (78 Hz); the chemical shift was reduced significantly. Little motion artifacts are visible in every examination caused by involuntary eye movements, which led to evaluation limitations in 3 cases. Compared to the examination with normal coils, the detection of details was much better. In 3 cases small changes were only found with the high-resolution orbital coil. With the high-resolution surface coil it is possible to examine the orbit. It is like looking through a magnifying glass. Using an optimized bandwidth, both the signal-to-noise and the chemical shift are acceptable. The new orbital coil is especially useful for the detection of small orbital lesions.

Adolescent↗

Nonstationary scatter subtraction-restoration in high-resolution PET.

UNLABELLED: Although removal of object scatter has been shown to improve both contrast and quantitation accuracy, subtraction of detector scatter leads to marginal contrast enhancement and negligible resolution recovery at the expense of reduced sensitivity and increased statistical noise. Since detector scatter has correct information about radioactivity but slightly erroneous information about source location, we suggest that this component should be restored to preserve sensitivity and improve resolution. METHODS: A scatter correction model that consecutively removes object scatter and restores detector scatter is proposed. The scatter components are processed in the spatial domain using nonstationary scatter kernels. The detector scatter restoration kernel is obtained by piecewise inversion in the Fourier space. The model was tested using line source and hot spot phantom measurements. RESULTS: Object scatter subtraction increased contrast substantively with no effect on resolution. Detector scatter restoration recovered resolution almost completely with modest contrast enhancement in small lesions. Spillover effects were reduced to less than 5% for hot spots > or = 3 x FWHM, at the expense of moderate noise amplification. CONCLUSION: While subtraction of object scatter is necessary for contrast enhancement and quantitation accuracy, restoration of detector scatter preserves sensitivity and improves quantitation accuracy by reducing spillover effects in high-resolution PET.

Image Enhancement↗

A randomized controlled trial of antibiotics on symptom resolution in patients presenting to their general practitioner with a sore throat.

BACKGROUND: Sore throat is a common symptom presented to general practitioners (GPs), and there remains controversy about the appropriate use of antibiotics. AIM: To compare, in a randomized controlled trial, the effectiveness of penicillin, cefixime and placebo on symptom resolution in patients presenting with a sore throat in general practice. METHOD: Twenty-two GPs in Avon recruited 154 patients, aged 16-60 years, presenting to their GP with a sore throat, and for whom the GP would normally prescribe an antibiotic. Patients were randomized to one of three groups: penicillin V 250 mg four times a day; cefixime 200 mg daily; and placebo. Each was prescribed for five days. The main outcome measures were a diary of symptom resolution over seven days and eradication of group A beta-haemolytic streptococcus (GABHS). RESULTS: Of the 103 (67%) patients who completed symptom diaries, 40 were allocated to receive penicillin, 29 cefixime and 34 placebo. In the analysis including all patients, symptom resolution was greater by day 3 in the cefixime group than in the placebo group. Penicillin did not improve symptom resolution by day 3 compared with placebo, and cefixime was not statistically significantly different from penicillin. There were significant differences in the proportion of patients using analgesia at day 3, with the proportion being lowest in the cefixime group. The results for the subgroup of patients without GABHS were similar to those for all patients; in particular, the only statistically significant difference was between cefixime and placebo. Although numbers were too small for statistical significance, among patients with GABHS the effects of penicillin and cefixime were similarly raised in relation to placebo. CONCLUSION: Compared with placebo, cefixime can improve the rate of resolution of symptoms in patients with a sore throat who are selected for antibiotic treatment by their GP. The unexpected finding that cefixime was of benefit compared with placebo for patients without GABHS suggests that bacteria other than GABHS may be important in the pathogenesis of sore throat.

Adolescent↗

Narrowband UV-B produces superior clinical and histopathological resolution of moderate-to-severe psoriasis in patients compared with broadband UV-B.

OBJECTIVE: To compare the therapeutic effectiveness of daily exposure to narrowband (NB) UV-B vs broadband (BB) UV-B with and without tar. DESIGN: Half-body exposures to NB UV-B or BB UV-B were given daily for 4 weeks in this comparative treatment study. Narrowband UV-B was delivered from TL-01 fluorescent bulbs and BB UV-B from conventional bulbs in the same phototherapy cabinet. Narrowband UV-B was compared using a paired treatment approach to BB UV-B above the waist and to BB UV-B with tar (Goeckerman treatment) below the waist. SETTING: General clinical research center of a university hospital inpatient unit. PATIENTS: Twenty-two patients with moderate-to-severe plaque-type psoriasis completed the study. MAIN OUTCOME MEASURES: Clinical efficacy was measured weekly using psoriasis severity scoring. Therapeutic outcomes after 4 weeks were compared in paired biopsy samples from treated lesions using objective histopathological measures (quantitative reduction in epidermal acanthosis and keratin 16 expression). RESULTS: Clinical resolution of psoriasis was achieved on 86% of paired sites treated with NB UV-B vs 73% treated with BB UV-B. Histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 88% of lesions treated with NB UV-B vs 59% treated with BB UV-B. Epidermal acanthosis was reduced more completely by NB UV-B treatment. Clinical resolution of psoriatic lesions occurred more rapidly following NB UV-B treatment, with some patients achieving complete resolution after 2 to 3 weeks of treatment. CONCLUSIONS: Narrowband UV-B offers a significant therapeutic advantage over BB UV-B in the treatment of psoriasis, with faster clearing and more complete disease resolution. The erythema response to NB UV-B treatment was significantly more intense and persistent compared with BB UV-B. Considerably more necrotic keratinocytes were observed in histopathological sections of skin treated with NB UV-B after a single 2.0-minimum erythema dose exposure. Treatment should be coupled with obligate minimum erythema dose testing to NB UV-B and close clinical observation during dose increases.

Adolescent↗

Calculation of electric fields and currents induced in a millimeter-resolution human model at 60 Hz using the FDTD method.

The finite-difference time-domain (FDTD) method has previously been used to calculate induced currents in anatomically based models of the human body at frequencies ranging from 20 to 915 MHz and resolutions down to about 1.25 cm. Calculations at lower frequencies and higher resolutions have been precluded by the huge number of time steps that would be needed in these simulations. This paper describes a method used to overcome this problem and efficiently calculate induced currents in an MRI-based, 6-mm-resolution model of the human under a high-voltage transmission line. This model is significantly higher resolution than the 1.31-cm-resolution model previously used; therefore, it can be used to pinpoint locations of peak current densities in the body. Proposed safety guidelines would allow external electric fields of 10 kV/m and 25 kV/m for exposure to 60 Hz fields of the general public and workers, respectively. For this external electric field exposure of 10 kV/m, local induced current densities as high as 20 mA/m2 are found in the head and trunk with even higher values (above 150 mA/m2) in the legs. These currents are considerably higher than the 4 or even 10 mA/m2 that have been suggested in the various safety guidelines, thus indicating an inconsistency in the proposed guidelines. In addition, several ratios of E/H typical of power line exposures were examined, and it was found that the vertical electric field couples strongly to the body, whereas the horizontal magnetic field does not.

Computer Simulation↗

Overcoming Artificial Structures in Resolution-Enhanced Hi-C Data by Signal Decomposition and Multi-Scale Attention.

Computational enhancement is an important strategy for inferring high-resolution features from genome-wide chromosome conformation capture (Hi-C) data, which typically have limited resolution. Deep learning has been highly successful in this task but we show that it creates prevalent artificial structures in the enhanced data due to the need to divide the large contact matrix into small patches. In addition, previous deep learning methods largely focus on local patterns, which cannot fully capture the complexity of Hi-C data. Here we propose Smooth, High-resolution, and Accurate Reconstruction of Patterns (SHARP) for enhancing Hi-C data. It uses the novel approach of decomposing the data into three types of signals, due to one-dimensional proximity, contiguous domains, and other fine structures, respectively, and applies deep learning only to the third type of signals, such that enhancement of the first two is unaffected by the patches. For the deep learning part, SHARP uses both local and global attention mechanisms to capture multi-scale contextual information. We compare SHARP with state-of-the-art methods extensively, including application to data from new samples and another species, and show that SHARP has superior performance in terms of resolution enhancement accuracy, avoiding creation of artificial structures, identifying significant interactions, and enrichment in chromatin states.

Hi‐C↗

High-resolution imaging of the middle ear with optical coherence tomography: a feasibility study.

BACKGROUND: Optical coherence tomography (OCT) is a new medical imaging technology that generates cross-sectional images of tissue microstructure with micron-scale resolution. Optical coherence tomography is analogous to ultrasound, measuring the intensity of infrared light rather than acoustical waves. OBJECTIVE: To demonstrate the feasibility of using OCT for ultra-high-resolution imaging of the middle ear via ex vivo imaging studies of human tissue. DESIGN: Images of the tympanic membrane and middle ear were acquired ex vivo, through the ear canal, without perforating the tympanic membrane. MATERIALS: Four excised intact temporal bones and the auditory apparatus were harvested from cadavers and imaged fresh, without previous fixation. RESULTS: The resulting images were compared with the gross sample and verified the ability of OCT to delineate relevant structures, such as the tympanic membrane and its sublayers, and the middle ear ossicles, nerves, and tendons at higher resolutions than possible with standard clinical imaging technologies. CONCLUSION: The ability of OCT to produce high-resolution images of tissue structure, without contact and in real time, as well as its ability to be integrated with endoscopes, suggests that this technology could become a useful modality for the diagnosis and management of a range of clinical middle ear abnormalities.

Ear, Middle↗

Reflection contrast microscopy for high resolution detection of (3)H-estradiol in ultrathin sections of human stratum corneum.

A single autoradiographical method for light and electron microscopy (LM and EM) is presented. Human skin, containing (3)H-estradiol ((3)H-E2) after an in vitro permeation experiment, was processed via a non-extractive tissue preparation protocol, comprising cryo-fixation, freeze-drying, osmium tetroxide vapor fixation, and Spurr resin embedding. Semithin sections were processed for LM autoradiography, while ultrathin sections were processed both for high-resolution LM and EM autoradiography. The autoradiographs were visualized by bright-field microscopy (BFM), reflection contrast microscopy (RCM), and transmission electron microscopy to evaluate the potentials of RCM visualization in high-resolution LM autoradiography. RCM visualization of ultrathin vs. semithin resin sections showed an improved stratum corneum morphology. Histological staining was superfluous. The localization of (3)H-E2 in human stratum corneum using high-resolution LM autoradiography and RCM was as accurate as with high-resolution EM autoradiography.

Autoradiography↗

Low-resolution docking: prediction of complexes for underdetermined structures.

One of the most fundamental questions concerning ligand-receptor interaction is whether such a process of intermolecular association is generally determined by local structural elements of the participating molecules, or whether there are also large-scale motifs in molecule structures that facilitate complex formation. From the point of view of practical docking computations, the elaborate character of local structural details in ligand-receptor interaction creates a large number of false-positive matches, which interfere with determination of the best fit. Another significant obstacle in protein docking is the problem of structural data inaccuracy (poor structure resolution, conformational changes upon complex formation, etc.). Our study [Vakser (1995) Protein Eng., 8, 371-377], based on ultralow (approximately 7 A resolution) representation of molecular structures, allowes to average all high-resolution structural details, and still predict most of the structural features of the ligand-receptor complex. The approach dramatically improves the signal-to-noise ratio in determination of the best fit, and moves the structure inaccuracy tolerance to the range of the macrostructure. In the present paper, we describe a further validation of the main principles of this approach and a detailed analysis of the low-resolution docking results. This includes clustering of ligand positions around the receptor molecule and cross-validation of ligands and receptors from different complexes. We also discuss the important implications of the approach to the multiple-minima problem and a possible role of different structural elements in the recognition mechanism.

Animals↗

Slit-scan flow cytometry for consistent high resolution DNA analysis of X- and Y-chromosome bearing sperm.

This paper describes the application of slit-scan flow cytometry for accurate DNA analysis of X- and Y-chromosome bearing sperm. The introduction of the slit-scanning technique was initiated to improve the consistency in resolution of the X and Y population from donor to donor. An optimal resolution is essential for high purity sorting of X and Y sperm, as the difference in DNA content is small (3-4%) in most mammals. This difference is the discriminatory parameter for the flow cytometric sorting of the two populations. Our approach was to focus on the role of the sperm tail in the detection process. Slit-scan flow cytometric analysis allows the whole sperm to be spatially analyzed along the direction of flow. Sperm were stained with Dansyl Lysine, a UV excitable fluorescent membrane dye, which stained the head, midpiece, and principal piece. Analysis of these stained sperm showed that there was no difference between the relative number of sperm that travel headfirst or tailfirst through the detection zone of the flow cytometer. The influence of sperm with coiled tails on DNA analysis was also investigated. The proportion of sperm with coiled tails influences semen quality. The standard X-Y separation procedure uses Hoechst 33342, which stains all intact sperm, both living and dead. Propidium iodide was added to discriminate the dead sperm population. Slit-scan analysis showed that measurement of a sample containing a high proportion of living sperm with coiled tails results in an inferior DNA histogram and reduced X-Y resolution. Sperm with coiled tails can result in a lower detected fluorescence intensity, but the reason for this is unclear. Slit-scan flow cytometry allows exclusion of sperm with coiled tails from the analysis, resulting in a restoration of high resolution of X- and Y-chromosome bearing sperm populations.

Animals↗

High-resolution cytometry of FISH dots in interphase cell nuclei.

BACKGROUND: Flow cytometry (FCM) and laser scanning cytometry (LSCM) provide indispensable tools for measuring large number of cells with low resolution. Confocal microscopy, on the other hand, is used for measuring small number of cells with high resolution. In this paper, we present a reasonable compromise between the two extremes. METHODS: We have developed a completely automated, high-resolution system (high-resolution cytometer, HRCM) capable of analyzing microscope slides with FISH-stained interphase nuclei in two dimensions as well as in three dimensions using a fully motorized epi-fluorescence microscope and a cooled digital CCD camera fully controlled by a high-performance computer which performs both acquisition and related on-line image analysis. The images of different dyes are acquired sequentially using highly specific filters and superimposed in computer memory. For each nucleus and each hybridization dot, user-selected attributes (such as position, size, intensity, etc.) are computed off-line using another processor or computer connected with a network. RESULTS: Using HRCM, it is possible to analyze multi-color preparations including UV-excited dyes as well as repeatedly hybridized preparations reacquiring individual nuclei. The speed of the acquisition and analysis is about 50 nuclei per minute in two dimensions and 1 nucleus per minute in three dimensions, but depends on the density of nuclei on the slide; the precision of the lateral and axial measurements is approximately 100 nm. CONCLUSIONS: Thus, using overnight acquisition, quantities comparable to those of FCM or LSCM measurements can be analyzed with an accuracy comparable to confocal microscopy. HRCM is suitable for a number of clinical and scientific tasks: routine diagnostics, follow-up of therapy, studies of chromatin structure, and many other different aspects of cell research.

Cell Nucleus↗

Resolution of racemic carboxylic acids via the lipase-catalyzed irreversible transesterification of vinyl esters.

The lipase-catalyzed irreversible transesterification procedure using vinyl esters was applied to the resolution of racemic 2-phenoxypropanoic acids. Aspergillus niger lipase showed high enantioselectivities and reasonable reaction rates. The enantioselectivity was found to be affected profoundly by several variables, e.g., the alcohol as nucleophile, the organic solvent used, and the reaction temperature. A gram-scale resolution of (RS)-2-phenoxypropanoic acid was achieved after optimization of the reaction conditions. Then this irreversible transesterification procedure was applied to the resolution of some related 2-substituted carboxylic acids. Thus, racemic 2-methoxy-2-phenylacetic acid was resolved via the A. niger lipase-catalyzed transesterification of the corresponding vinyl ester. 2-Phenylpropanoic acid and 2-phenylbutanoic acid were resolved using Pseudomonas sp. lipase. A gram-scale resolution of 2-phenylbutanoic acid was achieved by this procedure coupled with the porcine liver esterase-catalyzed hydrolysis of the resulting methyl ester.

Carboxylic Acids↗

Direct chromatographic resolution and isolation of the four stereoisomers of meta-hydroxyphenylpropanolamine.

Methods for the direct chiral chromatographic separation of the four stereoisomers of meta-hydroxyphenylpropanolamine (MHPA) on an analytical and preparative scale are described. Separations were carried out on a Crownpak CR (+) chiral column with 113 mM aqueous perchloric acid as the mobile phase. Baseline resolution of the more retained (+)-stereoisomers (1S configuration) and partial resolution of the less retained (-)-stereoisomers (1R configuration) were obtained under these chromatographic conditions. Removal of the bulk of the (1R,2S)-stereoisomer (metaraminol) from the initial crude mixture by fractional crystallization as the (+)-bitartarate salt substantially improved the peak resolution factors (Rs) of the remaining three stereoisomers. Semipreparative chromatographic resolution of the latter isomeric mixture provided milligram quantities of each stereoisomer in >97% enantiomeric excess. Subsequent recrystallization of their bitartarate or fumarate salts gave enantiomeric purities >99%.

Chromatography, Ion Exchange↗

Pseudo-continuous arterial spin labeling technique for measuring CBF dynamics with high temporal resolution.

Cerebral blood flow (CBF) can be measured noninvasively with nuclear magnetic resonance (NMR) by using arterial water as an endogenous perfusion tracer. However, the arterial spin labeling (ASL) techniques suffer from poor temporal resolution due to the need to wait for the exchange of labeled arterial spins with tissue spins to produce contrast. In this work, a new ASL technique is introduced, which allows the measurement of CBF dynamics with high temporal and spatial resolution. This novel method was used in rats to determine the dynamics of CBF changes elicited by somatosensory stimulation with a temporal resolution of 108 ms. The onset time of the CBF response was 0.6 +/- 0.4 sec (mean +/- SD) after onset of stimulation (n = 10). The peak response was observed 4.4 +/- 3.7 sec (mean +/- SD) after stimulation began. These results are in excellent agreement with previous data obtained with invasive techniques, such as laser-Doppler flowmetry and hydrogen clearance, and suggest the appropriateness of this novel technique to probe CBF dynamics in functional and pathological studies with high temporal and spatial resolution. Magn Reson Med 42:425-429, 1999.

Animals↗

Unlimited increase in the resolution of DNA ladders.

Fractionation of DNA ladders by gel electrophoresis is limited by the progressive compressing of the long DNA end of a ladder. Improvement in the resolution of this DNA is achieved by use of the following two-step electrophoresis. Initially, the DNA ladder is fractionated by conventional constant field agarose gel electrophoresis. Subsequently, gel electrophoresis is performed in the reverse direction by pulsing the electrical field (PFGE). A newly developed type of pulsing is used, which causes inversion of a double-stranded DNA ladder: the distance migrated increases as the length of the DNA molecule increases. Thus, the resolution of DNA bands continues to increase during the PFGE. These two stages of electrophoresis are serially repeated. Eventually, both the short and the long DNA ends of the ladder migrate out of the gel while a selected region of the ladder undergoes progressive increase in resolution during back-and-forth migration. Improved resolution of DNA bands is achieved, without a known limit.

Chemical Fractionation↗

Image quality assessment in contemporary interventional cardiology laboratories: spatial and low-contrast video resolution.

Two measures of fluoroscopic image quality-high-contrast video spatial resolution and low-contrast video resolution-were assessed in 64 interventional cardiology catheterization laboratories. The results of high-contrast spatial resolution testing indicate variable levels of performance with median values of 1.5, 2.0, and 2.5 line pairs/mm at the three levels of magnification. The results of the low-contrast video resolution testing indicate clinically relevant limitations in performance. This was particularly true when testing was performed in a dynamic mode under simulated large patient conditions. Under these conditions, 50% of systems failed to detect a wire of diameter 0.017". In addition, limited system dynamic range was identified in a substantial fraction of laboratories and may contribute to these important variations in performance. Taken together, these findings serve to characterize overall system performance in the current era of interventional cardiology and reaffirm the continued need for image quality assessment programs.

Cardiac Catheterization↗

Separation of basic drug enantiomers by capillary electrophoresis using ovoglycoprotein as a chiral selector: comparison of chiral resolution ability of ovoglycoprotein and completely deglycosylated ovoglycoprotein.

Separations of basic drug enantiomers by capillary electrophoresis (CE) using ovoglycoprotein (OGCHI) as a chiral selector are described. The effects of running buffer pH and 2-propanol content on the migration times and resolution of basic drug enantiomers were examined using a linear polyacrylamide-coated capillary. High resolution of basic drug enantiomers was attained using a mixture of 50 mM sodium phosphate buffer (pH 4.5-6.0) and 2-propanol (5-30%) including 50 microM OGCHI. It was found that ionic and hydrophobic interactions could work for the recognition of basic drug enantiomers. Further, we compared the chiral resolution ability of OGCHI with that of completely deglycosylated OGCHI (cd-OGCHI) using them as chiral selectors in CE. OGCHI showed higher resolution for basic drug enantiomers tested than cd-OGCHI. The results suggest that the chiral recognition site(s) for OGCHI exists on the protein domain of OGCHI.

Buffers↗

Resolution in capillary electrophoresis with nonaqueous methanol as solvent: theoretical prediction and experimental confirmation.

The resolution of the analytes was predicted from their known pKa* values and actual mobilities in nonaqueous methanolic solutions according to theory taking longitudinal diffusion as the only cause for peak dispersion. This leads to an equation of the resolution as a function of the pH*, as both selectivity and efficiency are dependent on the pH of the buffer. The experimentally obtained resolution values were in acceptable agreement with the predicted theoretical ones in most cases. This was demonstrated for substituted benzoic acids as analytes. The pKa* values needed for the calculation of the resolution were derived from the pH* dependence of the effective mobility. The pH* scale in methanol was based on conventional pKa* values of acetic acid and chloroacetic acid taken from the literature.

Benzoates↗