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At least 595 records · Page 33Linked to original sources

PubMed2002

Time-resolved, undersampled projection reconstruction imaging for high-resolution CE-MRA of the distal runoff vessels.

Imaging of the blood vessels below the knee using contrast-enhanced (CE) MRI is challenging due to the need to coordinate image acquisition and arrival of the contrast in the targeted vessels. Time-resolved acquisitions have been successful in consistently capturing images of the arterial phase of the bolus of contrast agent in the distal extremities. Although time-resolved exams are robust in this respect, higher spatial resolution for the depiction of tight stenoses and the small vessels in the lower leg is desirable. A modification to a high-spatial-resolution T(1)-weighted pulse sequence (projection reconstruction-time resolved imaging of contrast kinetics (PR-TRICKS)) that improves the through-plane spatial resolution by a factor of 2 and maintains a high frame rate is presented. The undersampled PR-TRICKS pulse sequence has been modified to double the spatial resolution in the slice direction by acquiring high-spatial-frequency slice data only after first pass of the bolus of contrast agent. The acquisition reported in the present work (PR-hyperTRICKS) has been used to image healthy volunteers and patients with known vascular disease. The temporal resolution was found to be beneficial in capturing arterial phase images in the presence of asymmetric filling of vessels.

Contrast Media↗

PubMed2002

High-resolution, spin-echo BOLD, and CBF fMRI at 4 and 7 T.

With growing interest in noninvasive mapping of columnar organization and other small functional structures in the brain, achieving high spatial resolution and specificity in fMRI is of critical importance. We implemented a simple method for BOLD and perfusion fMRI with high spatial resolution and specificity. Increased spatial resolution was achieved by selectively exciting a slab of interest along the phase-encoding direction for EPI, resulting in a reduced FOV and number of phase-encoding steps. Improved spatial specificity was achieved by using SE EPI acquisition at high fields, where it is predominantly sensitive to signal changes in the microvasculature. Robust SE BOLD and perfusion fMRI were obtained with a nominal in-plane resolution up to 0.5 x 0.5 mm(2) at 7 and 4 Tesla, and were highly reproducible under repeated measures. This methodology enables high-resolution and high-specificity studies of functional topography in the millimeter to submillimeter spatial scales of the human brain.

Adult↗

PubMed2002

Variable-density adaptive imaging for high-resolution coronary artery MRI.

Variable-density (VD) spiral k-space acquisitions are used to acquire high-resolution (0.78 mm), motion-compensated images of the coronary arteries. Unlike conventional methods, information for motion compensation is obtained directly from the coronary anatomy itself. Specifically, periods of minimal coronary distortion are identified by applying the correlation coefficient template matching algorithm to real-time images generated from the inner, high-density portions of the VD spirals. Combining the data associated with these images together, high-resolution, motion-compensated coronary images are generated. Because coronary motion is visualized directly, the need for cardiac-triggering, breath-holding, and navigator echoes is eliminated. The motion compensation capability of the technique is determined by the inner-spiral spatial and temporal resolution. Results indicate that the best performance is achieved using inner-spiral images with high spatial resolution (1.6-2.9 mm), even though temporal resolution (four to six independent frames per second) suffers as a result. Image quality within the template region in healthy volunteers was found to be comparable to that achieved with cardiac-triggered breath-hold scans, although extended acquisition times of around 5 min were needed to overcome reduced SNR efficiency.

Algorithms↗

PubMed2003

High-resolution assessment of blood flow in murine RIF-1 tumors by monitoring uptake of H(2)(17)O with proton T(1rho)-weighted imaging.

Perfusion parameters, such as blood flow, are critical properties of tumors related to angiogenesis, drug delivery, radiosensitivity, bioenergetic status, and steady state levels of metabolites, such as lactate, that have been proposed as indices of tumor response to therapy. The existing MR methods for measuring tumor blood flow (TBF) have limitations related to sensitivity, spatial resolution, or dependence on other physiological properties such as vascular permeability. To address many of these difficulties, this study introduces the use of an (17)O-enriched tracer in conjunction with high-resolution, indirect MRI to measure TBF. To demonstrate the advantages of this technique, relative TBF was measured in subcutaneous RIF-1 tumors in C3H mice by monitoring the uptake of H(2) (17)O with a resolution of 0.16 x 0.31 x 3 mm in 13 sec. At this resolution, tumor heterogeneity with respect to blood flow is clearly visible. Measurement of the tracer arterial input function, which is necessary for determination of absolute blood flow, may be facilitated with improved temporal resolution.

Animals↗

PubMed2004

High temporal and spatial resolution 4D MRA using spiral data sampling and sliding window reconstruction.

Contrast-enhanced magnetic resonance angiography (CE-MRA) requires high spatial resolution to demonstrate detailed vasculature and high temporal resolution to capture the contrast bolus. Sparse bright voxels in MRA permit substantial undersampling in MRI data acquisition, allowing simultaneous high temporal and spatial resolution. We developed a time-resolved 3D MRA technique using the efficient spiral sampling trajectory, and performed off-resonance corrections using inhomogeneity field maps. View sharing and sliding window reconstruction were utilized to generate high temporal resolution. High-resolution 3D angiograms were generated at 1-2 s per frame, with a 5-8 ml gadolinium dose, in patients with vascular disease.

Arteriosclerosis↗

PubMed2005

Effects of breathing and cardiac motion on spatial resolution in the microscopic imaging of rodents.

One can acquire high-resolution pulmonary and cardiac images in live rodents with MR microscopy by synchronizing the image acquisition to the breathing cycle across multiple breaths, and gating to the cardiac cycle. The precision with which one can synchronize image acquisition to the motion defines the ultimate resolution limit that can be attained in such studies. The present work was performed to evaluate how reliably the pulmonary and cardiac structures return to the same position from breath to breath and beat to beat across the prolonged period required for MR microscopy. Radiopaque beads were surgically glued to the abdominal surface of the diaphragm and on the cardiac ventricles of anesthetized, mechanically ventilated rats. We evaluated the range of motion for the beads (relative to a reference vertebral bead) using digital microradiography with two specific biological gating methods: 1) ventilation synchronous acquisition, and 2) both ventilation synchronous and cardiac-gated acquisitions. The standard deviation (SD) of the displacement was < or =100 microm, which is comparable to the resolution limit for in vivo MRI imposed by signal-to-noise ratio (SNR) constraints. With careful control of motion, its impact on resolution can be limited. This work provides the first quantitative measure of the motion-imposed resolution limits for in vivo imaging.

Animals↗

PubMed2006

Undersampled elliptical centric view-order for improved spatial resolution in contrast-enhanced MR angiography.

Although contrast-enhanced MR angiography (CE-MRA) has been successfully developed into a routine clinical imaging technique, there is still need for improved spatial resolution in a given acquisition time. Undersampled projection reconstruction (PR) techniques maintain spatial resolution with reduced scan times, and the elliptical centric (EC) view order provides high quality arterial phase images without venous contamination. In this work, we present a hybrid elliptical centric-projection reconstruction (EC-PR) technique to provide spatial resolution improvement over standard EC in a given time. The k-space sampling was performed by undersampling the periphery of the k(Y)-k(Z) phase encoding plane of an EC view order in a PR like manner. The sampled views were maintained on a rectilinear grid, and thus reconstructed by standard 3DFT. The non-sampled views were compensated either by zero-filling or performing a 2D homodyne reconstruction. Compared to a fully sampled k-space, the EC-PR sequence acquired in the same scan time provides a resolution improvement of about two, as shown by point spread function analysis and phantom experiments. The hypothesis that EC-PR provides improved resolution while retaining diagnostically adequate SNR was tested in 11 CE-MRA studies of the popliteal and carotid arteries and shown to be true (P < 0.03).

Carotid Arteries↗

PubMed2006

Navigator gated high temporal resolution tissue phase mapping of myocardial motion.

Data acquisition for phase contrast velocity mapping of myocardial motion is typically based on multiple breath-held 2D measurements with limited acquisition duration and consequently relatively poor temporal resolution. In order to overcome the limitations of breath-hold acquisitions, an improved navigator-guided technique was implemented based on 2 navigator signals within each cardiac cycle in combination with paired acceptance and rejection criteria of successive navigator signals. Respiratory gated phase contrast measurements with 3-directional velocity encoding were performed in 12 healthy volunteers in basal, midventricular, and apical locations of the left ventricle during free breathing with a temporal resolution of 13.8 ms. Results were compared to standard breath-hold measurements with a temporal resolution of 69 ms. Data from the high temporal resolution study revealed details in left ventricular motion patterns that were previously not seen in phase contrast measurements and are only known from echocardiography. The proposed navigator gated technique for high temporal resolution velocity mapping is, therefore, highly promising for the detection of local and global motion abnormalities in patients with disturbed left ventricular performance, such as diastolic dysfunction.

Adult↗

PubMed2003

Determination of amplicon boundaries at 20q13.2 in tissue samples of human gastric adenocarcinomas by high-resolution microarray comparative genomic hybridization.

Comparative genomic hybridization (CGH) of gastric adenocarcinomas frequently shows gains and amplifications of chromosome 20. However, the underlying genetic lesion is unknown and conventional CGH results do not allow specification of the target region. In order to investigate this chromosomal aberration with a higher resolution and sensitivity, microarray-based CGH was performed with both scanning and high-resolution arrays of chromosome 20 in a series of 27 gastric adenocarcinomas. Locus-specific fragments of genomic DNA from bacterial artificial chromosome (BAC) clones were spotted as microarrays. A scanning array contained a set of 27 BAC clones covering chromosome 20q. A high-resolution array contained 27 overlapping BAC clones at 20q13.2. This high-resolution array was used to narrow down the amplicon at 20q13.2 in tumours showing amplification of this chromosomal region with the scanning array. Positive copy number changes on chromosome 20q were detected in 12 of 27 cases (44%). These changes included gain of the whole arm of chromosome 20q in 8 of 27 (30%) cases, amplification restricted to 20q12.1 in one case, and amplifications restricted to 20q13 in three cases (11%). The three tumours showing amplification restricted to 20q13 were analysed further using the high-resolution array. In one tumour, the whole contig was amplified at a constant level. One of the other two tumours had a clear proximal breakpoint, while the other tumour had a clear distal breakpoint within the 20q13.2 region. The proximal and the distal breakpoint were approximately 800 kb apart. In the present study, an amplicon at 20q13.2 has been narrowed down to 800 kb which is likely to harbour one or more putative oncogenes relevant to gastric carcinogenesis, for which ZNF217 and CYP24 are good candidates.

Adenocarcinoma↗

PubMed1992

Optimizing signal and mass resolution for matrix-assisted laser desorption utilizing a linear time-of-flight mass spectrometer.

Results are presented for various instrumental configurations employed for matrix-assisted laser desorption mass spectrometry. Mass resolution is determined for a linear time-of-flight mass spectrometer for various lengths of the field-free region. A wire ion guide is utilized and is shown to improve ion transport efficiencies for longer field-free regions. It is also determined experimentally that a modest mass resolution increase is often obtained in configurations employing the wire ion guide when compared to the mass resolution obtained with the same geometry without the wire ion guide. Optimal applied potentials are determined for the wire ion guide. No mass dependence on the optimal applied potential (-100 V) for the wire ion guide is observed for samples of equine myoglobin (MW 16,951.5 Da) and a bacterial protease (MW 27,228.4 Da). The optimal applied voltage was also found to be identical (-100 V) for the singly through quadruply charged molecular ion species of rabbit gamma globulin (MW approximately 150,000 Da). It is shown that a 2 m flight tube with a wire ion guide provides better signal-to-noise mass spectra than a 1 m flight tube without the wire ion guide and can more than double the mass resolution obtainable. Utilization of a 4 m flight tube gives minimal mass resolution enhancement at the expense of signal-to-noise.

Animals↗

PubMed2006

Enhanced mass resolution method development, validation and assay application to support preclinical studies of a new drug candidate.

A very highly sensitive and highly selective liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method was developed to evaluate and quantify a new drug candidate in different biological matrices. Following a simple plasma protein precipitation using acetonitrile, the post-treatment samples were analyzed on a C18 column interfaced with a new generation of triple-quadrupole mass spectrometer. The recently introduced triple-quadrupole mass spectrometer, the TSQ Quantum Ultra, with enhanced mass-resolution capability, demonstrated improved sensitivity (0.05 ng/mL), coupled with suitable accuracy and precision, over a broad linear dynamic range (0.05-1000 ng/mL). A comparison of the assay performance data (dynamic range, calibration curve equation, precision and accuracy) of the enhanced resolution method against a unit resolution method under optimized conditions showed the performance improvement of the enhanced mass resolution method for bioanalytical high-throughput applications. The enhanced mass resolution method herein described was successfully applied to the evaluation of the pharmacokinetic profile of a new drug candidate in rat, rabbit and dog plasma samples.

Animals↗

PubMed2005

Unexpected intrauterine death following resolution of hydrops fetalis after betamethasone treatment in a fetus with a large cystic adenomatoid malformation of the lung.

Without intervention, the development of hydrops fetalis secondary to cystic adenomatoid malformation of the lung (CAML) implies a 100% mortality rate. Conversely, four CAML cases with in-utero resolution of hydrops fetalis after prenatal betamethasone therapy with good clinical outcome have been reported in the literature. The mechanism is speculated to be the effect of corticosteroid in improving lung maturation. Here we present another CAML case with resolution of hydrops fetalis after prenatal betamethasone therapy but which was followed by later intrauterine death. We speculate that the resolution of the CAML lesion itself may be more important in determining the clinical outcome than the resolution of hydrops. The association between prenatal betamethasone therapy and resolution of hydrops may be related to a different mechanism other than improvement of lung maturation.

Adult↗

PubMed1994

Crystal structure of toxin II from the scorpion Androctonus australis Hector refined at 1.3 A resolution.

The crystal structure of toxin II from the scorpion Androctonus australis Hector has been refined at 1.3 A resolution using restrained least-squares methods. The final R-factor is 0.148 for the 13,619 reflections between 7.0 A and 1.3 A resolution with F > 2.5 sigma (F) and the bond length standard deviation from ideality is 0.017 A. Although minor changes have been introduced relative to the model previously refined at 1.8 A resolution, the use of higher-resolution data has allowed the modelling of some discrete disorder. Thus, three residues (including a disulphide bridge) have been built with multiple conformations. Occupancies were refined for the 106 solvent molecules included in the model, nine of them with explicit multiple sites. There is well-defined electron density for some of the protein hydrogen atoms in the final difference Fourier map. A detailed description of the toxin structure is presented, along with a comparison with the high-resolution structure of the related variant-3 scorpion toxin.

Amino Acid Sequence↗

PubMed1998

Self-organizing neural networks bridge the biomolecular resolution gap.

Topology-representing neural networks are employed to generate pseudo-atomic structures of large-scale protein assemblies by combining high-resolution data with volumetric data at lower resolution. As an application example, actin monomers and structural subdomains are located in a three-dimensional (3D) image reconstruction from electron micrographs. To test the reliability of the method, the resolution of the atomic model of an actin polymer is lowered to a level typically encountered in electron microscopic reconstructions. The atomic model is restored with a precision nine times the nominal resolution of the corresponding low-resolution density. The presented self-organizing computing method may be used as an information-processing tool for the synthesis of structural data from a variety of biophysical sources.

Actins↗

PubMed2000

Resolution of tethered antiparallel and parallel holliday junctions by the Flp site-specific recombinase.

Members of the integrase family site-specific recombinases (also called the tyrosine family) bring about recombination in two steps by exchanging pairs of single strands at a time. The product of the first exchange reaction is a four-way DNA junction, the Holliday intermediate. The conformational dynamics by which the recombination complex "isomerizes" from the Holliday-forming to the Holliday-resolving mode are not well understood. Experiments with the lambda Int and Escherichia coli XerC/XerD systems imply that the strand configurations at the branch point of the protein-free junction dictate the resolution mode in the protein-bound junction. We have examined the question of strand bias during resolution for the Flp system by using a series of synthetic Holliday junctions that are conformationally constrained by local sequences or by strand tethering. We have not observed a strong resolution bias in favor of the strands designed to assume the "crossed" configuration within the unbound junction. The resolution patterns with antiparallel junctions in a variety of substrate contexts reveal either parity in strand choice, or only modest disparity. On the other hand, the highly biased resolutions observed in the case of tethered parallel junctions can be explained by the non-equivalence in protein occupancy of the DNA arms of these substrates and/or inefficient conversion of cleavage events to recombinants at the tethered ends.

Base Sequence↗

PubMed2000

The ultrahigh resolution crystal structure of ribonuclease A containing an isoaspartyl residue: hydration and sterochemical analysis.

Crystals of the deamidated form of bovine pancreatic ribonuclease which contains an isoaspartyl residue in position 67 diffract to 0. 87 A at 100 K. We have refined the crystallographic model using anisotropic displacement parameters for all atoms to a conventional crystallographic residual R=0.101 for all observed reflections in the resolution range 61.0-0.87 A. The ratio observations/parameters is 7.2 for the final model. This structure represents one of the highest resolution protein structures to date and interestingly, it is the only example containing more than one molecule in the asymmetric unit with a resolution better than 1.0 A. The non-crystallographic symmetry has been used as a validation check of the geometrical parameters and it has allowed an estimate for an upper limit of errors associated with this high resolution model. In the present structure it was possible to obtain a more accurate picture of the active site whose electron density was not clearly interpretable in the previous 1.9 A resolution structure. In particular, the P1 site is alternatively occupied either by a sulphate anion or by a water molecule network. Most of hydrogen atoms were visible in the electron density maps, including those involved in C(alpha)-H(alpha).O interactions. Analysis of protein-solvent interactions has revealed the occurrence of an extensive cluster of water molecules, predominantly arranged in pentagonal fused rings and surrounding hydrophobic moiety of side-chains. Finally, in spite of the limited sample of residues, we have detected a clear dependence of backbone N-C(alpha)-C angle on residue conformation. This correlation can be fruitfully used as a valuable tool in protein structure validation.

Amides↗

PubMed2001

The 1.85 A resolution crystal structures of tissue factor in complex with humanized Fab D3h44 and of free humanized Fab D3h44: revisiting the solvation of antigen combining sites.

The outstanding importance of the antigen-antibody recognition process for the survival and defence strategy of higher organisms is in sharp contrast to the limited high resolution structural data available on antibody-antigen pairs with antigenic proteins. The limitation is the most severe for structural data not restricted to the antigen-antibody complex but extending to the uncomplexed antigen and antibody. We report the crystal structure of the complex between tissue factor (TF) and the humanized Fab fragment D3h44 at a resolution of 1.85 A together with the structure of uncomplexed D3h44 at the same resolution. In conjunction with the previously reported 1.7 A crystal structure of uncomplexed TF, a unique opportunity is generated to explore details of the recognition process. The TF.D3h44 interface is characterised by a high number of polar interactions, including as may as 46 solvent molecules. Conformational changes upon complex formation are very small and almost exclusively limited to the reorientation of side-chains. The binding epitope is in complete agreement with earlier mutagenesis experiments. A revaluation of two other antibody-antigen pairs reported at similar resolutions, shows that all these complexes are very similar with respect to the solvation of the interface, the number of solvent positions conserved in the uncomplexed and complexed proteins and the number of water molecules expelled from the surface and replaced by hydrophilic atoms from the binding partner upon complex formation. A strategy is proposed on how to exploit this high resolution structural data to guide the affinity maturation of humanised antibodies.

Amino Acid Sequence↗

PubMed2001

Improving resolution in fast rotating-frame experiments.

The rapid rotating-frame technique allows significant reduction in data-acquisition time compared with the two-dimensional method by stroboscopic observation of the nuclear magnetization during its evolution in the rotating frame. A onefold reduction in the dimensionality of the original rotating-frame experiment is achieved by using a train of strong radiofrequency pulses separated by short acquisition windows. The penalty for shortening experimental time is a reduction in spectral resolution compared with the two-dimensional method due to relaxation of transverse magnetization components during the observation windows. A variant of the rapid-rotating frame technique for improving spectral resolution based on undersampling and self-phase encoding is presented. An M-fold resolution improvement requires M experiments, thus, making possible a tradeoff between spectral resolution and experimental time. The technique was applied for spatial localization of quadrupole nuclei in powder solids, and resolution improvement is demonstrated on one- and two-dimensional NQR images.

Journal Article↗