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High resolution SE-I SEM study of enamel crystal morphology.

Until recently high resolution TEM was the only imaging mode capable of probing the atomic lattice structure of crystals composing tooth enamel. Studies designed to determine the polyhedral shape of normal enamel crystals and initiation of carious lesions in enamel crystals were hampered and limited by interpretation of two-dimensional TEM images from thin section and freeze fracture replica specimens lacking depth of field. The newly developed SE-I signal mode for SEM (SE-I/SE-II ratio) can produce images of enamel crystals approaching beam diameter dimensions (0.7-2.0 nm), rivaling the resolution of the TEM technique and generating topographic contrasts for three dimensional imaging at very high magnification (approximately 1,000,000X). Ultrathin chromium (Cr) films generate enriched high resolution SE-I contrasts of enamel crystal surfaces and when imaged using an immersion lens field emission SEM operated at high voltage (20-30 KeV) produce unsurpassed topographic contrasts. Since the grain size of Cr is below the resolution of any SEM and is ultrathin (approximately 1 nm), then SE-I images can provide a more accurate representation of enamel crystal structure than TEM methodologies. Our SE-I SEM observations of normal human enamel crystals reveal fractured spicules which contain angled flat surfaces delineated by a prominent 2 nm wide SE-I edge brightness contrast. Although microscopic observations often show crystals which are hexagonal in cross-section, in both SEM and TEM many other growth habits, including rectangular or irregular crystals (30-40 nm in width) which contain "notches," are also observed. More detailed morphological studies are therefore required to determine the most likely habit planes and their relevance to the function of the enamel crystals.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromium↗

Determination of conditions for optimum resolution of a high angle thin window energy dispersive spectrometer.

The energy resolution of an energy dispersive spectrometer (EDS) equipped with an ultrathin window (UTW) and mounted at a high take-off angle (72 degrees) on a transmission electron microscope has been studied under a variety of operating conditions. The spectrometer resolution is close to that specified by the manufacturer, up to count rates of 400 cps. Above 400 cps the resolution deteriorates rapidly, and the MCA dead time and zero width increase. Above 10 keV, the height of the background is much greater than expected for bremsstrahlung and shows the shape which has previously been attributed to backscattered electron flux into the detector. It is postulated that the deterioration in resolution with count rate is caused by backscattered electrons reaching the detector through the UTW.

Electron Probe Microanalysis↗

Nanoanalysis by a high-resolution energy filtering transmission electron microscope.

An energy-filtering transmission electron microscope with 300 kV acceleration voltage was developed and the spatial resolution of elemental distribution images was improved. Observing oxygen monolayers in Al(11)O(3)N(9), it was shown that the actual resolution attained is up to 0.5 nm. Surface plasmon loss images of silver particles were taken with a resolution of better than 0.4 nm. Furthermore, the sensitivity is sufficiently high to distinguish indium content differences of 2.5 atomic percent in In(x)Al(1-x)As. This performance is good enough to analyze elemental distribution with atomic-level resolution. Furthermore, since analysis with the energy-filtering microscope is easy and practical, nanoanalysis may come into wide use not only in academic fields but also in industry.

Journal Article↗

High-resolution crystallography and drug design.

Ultra-high-resolution X-ray crystallography of macromolecules (i.e. resolution better than 0.8 Angstroms) is a rising field that promises to provide new insight into the structure-function relationships of biomacromolecules. The picture emerging from macromolecular structures at this resolution is far more complex than previously understood, requiring for its study improved tools for structure refinement, analysis and annotation. Some of these problems were highlighted during the recent High Resolution Drug Design Meeting (Bischenberg-Strasbourg, France, 13-16 May 2004). We will review here some of the results and discussions that took place during that meeting and elaborate on the trends and challenges ahead in this emerging new field of research.

Animals↗

Combined time-resolved and high-spatial-resolution 3D MRA using an extended adaptive acquisition.

PURPOSE: To combine the benefits of time-resolved dynamic imaging and single elliptical centric acquisitions in a reasonable scan time. MATERIALS AND METHODS: A time series of images with moderate spatial resolution was acquired using the 3D Time-Resolved Imaging of Contrast KineticS (3D TRICKS) technique with elliptical centric encoding during contrast arrival. Following venous opacification, a complete large centrically encoded k-space volume was acquired. The high-spatial-frequency portions of this volume were combined with a 3D TRICKS time frame to form a high-resolution image. An additional single image is formed by suppressing background and signal averaging all acquired data, including post-venous low-spatial-frequency data. For this image, 2D temporal correlation analysis is used to suppress low-spatial-frequency vein contributions. Arrival time and spatial correlations are used to suppress background. RESULTS: The 3D TRICKS time frame may be selected to ensure a combined high-resolution image that has optimal central k-space sampling for any vascular region. The single image formed by signal averaging all acquired data has increased contrast-to-noise (CNR) and signal-to-noise (SNR) ratios. CONCLUSION: The advantages of time-resolved and high-spatial-resolution imaging were combined using an extended dual-phase acquisition. Some SNR and CNR gain was achieved by signal averaging. This process is facilitated by background and vein suppression.

Animals↗

Utilizing SENSE to achieve lower station sub-millimeter isotropic resolution and minimal venous enhancement in peripheral MR angiography.

PURPOSE: To use the parallel imaging technique, sensitivity encoding (SENSE), to increase spatial resolution and decrease venous contamination in peripheral magnetic resonance angiography (MRA). MATERIALS AND METHODS: Moving table, single-bolus peripheral contrast-enhanced (CE) -MRA was performed on nine patients. Manual table movement combined with SENSE in the upper station allowed for more rapid overall scan coverage such that acquisition of the lower station began 34 seconds after aortic contrast arrival. True sub- millimeter isotropic resolution was achieved in the lower station. RESULTS: Diagnostic MR angiograms of all three stations were obtained in all nine patients. Venous enhancement did not confound interpretation in any case. Sub-millimeter lower station resolution provided excellent vascular detail. CONCLUSION: Decreased delay time between upper and lower station acquisition in single bolus peripheral MR angiograms, now possible using parallel imaging techniques, combined with lower station sub-millimeter resolution may decrease venous contamination and increase overall interpretability, thus increasing clinical acceptance of peripheral MRA.

Humans↗

A targeted contrast agent for magnetic resonance imaging of thrombus: implications of spatial resolution.

A preparation of ultra-small superparamagnetic iron oxide (USPIO) particles coupled to an RGD peptide (RGD-USPIO) was investigated as an MR contrast agent, targeted to activated platelets, in both ex vivo and in vivo thrombus models. Thrombus visualization ex vivo was compared using RGD-USPIO and a non-targeted UPSIO. The influence of thrombus visualization on thrombus exposure time to RGD-USPIO (ex vivo) and on the spatial resolution of the MR image (ex vivo and in vivo) was assessed. RGD-USPIO resulted in better thrombus visualization than non-targeted USPIO ex vivo, and maximum enhancement was achieved after approximately one hour exposure time of the thrombus to RGD-USPIO. The ability to visualize the clots was highly dependent on the spatial resolution of the image. In vivo, an in-plane resolution of less than 0.2 x 0.2 mm(2) was required for good clot visualization after contrast enhancement. It is concluded that the achievable resolution and sensitivity is a potential limitation to the usefulness of active vascular targeting in MRI.

Animals↗

Effect of windowing and zero-filled reconstruction of MRI data on spatial resolution and acquisition strategy.

Standard, MR spin-warp sampling strategies acquire data on a rectangular k-space grid. That method samples data from the "corners" of k-space, i.e., data that lie in a region of k-space outside of an ellipse just inscribed in the rectangular boundary. Illustrative calculations demonstrate that the data in the corners of k-space contribute to the useful resolution only if an interpolation method such as a zero-filled reconstruction is used. The consequences of this finding on data acquisition and data windowing strategies are discussed. A further implication of this result is that the spatial resolution of images reconstructed with zero-filling (but without radial windowing) is expected to display angular dependence, even when the phase- and frequency-encoded resolutions are identical. This hypothesis is experimentally verified with a slit geometry phantom. It is also observed that images reconstructed without zero-filling do not display the angular dependence of spatial resolution predicted solely by the maximal k-space extent of the raw data. The implications of these results for 3D contrast-enhanced angiographic acquisitions with elliptical centric view ordering are explored with simulations.

Filtration↗

A segment-interleaved motion-compensated acquisition in the steady state (SIMCAST) technique for high resolution imaging of the inner ear.

MRI, with ever-increasing spatial resolution, recently has depicted progressively more anatomic details of the inner ear and is playing an important role in the diagnostic evaluation of patients with sensorineural hearing loss. We present a three-dimensional (3D) segment-interleaved, motion-compensated acquisition in steady state (SIMCAST) sequence that allows further increase in spatial resolution in reasonable scan times minimizing artifacts due to susceptibility and motion. The sequence uses gradient moment nulling over TR and segmented interleaved acquisition of multiple data sets with different radiofrequency (RF) phase-cycling schemes. Combination of data from multiple acquisitions by averaging and maximum intensity projection were compared. Images of phantoms and in vivo inner ears were obtained with both full and fractional echoes and compared with other high resolution techniques such as three-dimensional gradient-echo and two-dimensional (2D) and three-dimensional fast spin-echo (FSE) sequences. The new sequence achieves improved signal-to-noise ratio (SNR) and spatial resolution resulting in improved depiction of inner ear structures.

Adult↗

High-resolution real-time spiral MRI for guiding vascular interventions in a rabbit model at 1.5 T.

PURPOSE: To study the feasibility of a combined high spatial and temporal resolution real-time spiral MRI sequence for guiding coronary-sized vascular interventions. MATERIALS AND METHODS: Eight New Zealand White rabbits (four normal and four with a surgically-created stenosis in the abdominal aorta) were studied. A real-time interactive spiral MRI sequence combining 1.1 x 1.1 mm(2) in-plane resolution and 189-msec total image acquisition time was used to image all phases of an interventional procedure (i.e., guidewire placement, balloon angioplasty, and stenting) in the rabbit aorta using coronary-sized devices on a 1.5 T MRI system. RESULTS: Real-time spiral MRI identified all rabbit aortic stenoses and provided high-temporal-resolution visualization of guide-wires crossing the stenoses in all animals. Angioplasty balloon dilatation and deployment of coronary-sized copper stents in the rabbit aorta were also successfully imaged by real-time spiral MRI. CONCLUSION: Combining high spatial and temporal resolution with spiral MRI allows real-time MR-guided vascular intervention using coronary-sized devices in a rabbit model. This is a promising approach for guiding coronary interventions.

Animals↗

High-resolution, time-resolved MRA provides superior definition of lower-extremity arterial segments compared to 2D time-of-flight imaging.

PURPOSE: To evaluate a novel time-resolved contrast-enhanced (CE) projection reconstruction (PR) magnetic resonance angiography (MRA) method for identifying potential bypass graft target vessels in patients with Class II-IV peripheral vascular disease. MATERIALS AND METHODS: Twenty patients (M:F = 15:5, mean age = 58 years, range = 48-83 years), were recruited from routine MRA referrals. All imaging was performed on a 1.5 T MRI system with fast gradients (Signa LX; GE Healthcare, Waukesha, WI). Images were acquired with a novel technique that combined undersampled PR with a time-resolved acquisition to yield an MRA method with high temporal and spatial resolution. The method is called PR hyper time-resolved imaging of contrast kinetics (PR-hyperTRICKS). Quantitative and qualitative analyses were used to compare two-dimensional (2D) time-of-flight (TOF) and PR-hyperTRICKS in 13 arterial segments per lower extremity. Statistical analysis was performed with the Wilcoxon signed-rank test. RESULTS: Fifteen percent (77/517) of the vessels were scored as missing or nondiagnostic with 2D TOF, but were scored as diagnostic with PR-hyperTRICKS. Image quality was superior with PR-hyperTRICKS vs. 2D TOF (on a four-point scale, mean rank = 3.3 +/- 1.2 vs. 2.9 +/- 1.2, P < 0.0001). PR-hyperTRICKS produced images with high contrast-to-noise ratios (CNR) and high spatial and temporal resolution. 2D TOF images were of inferior quality due to moderate spatial resolution, inferior CNR, greater flow-related artifacts, and absence of temporal resolution. CONCLUSION: PR-hyperTRICKS provides superior preoperative assessment of lower limb ischemia compared to 2D TOF.

Aged↗

High-sensitivity quantitation of cabergoline and pergolide using a triple-quadrupole mass spectrometer with enhanced mass-resolution capabilities.

Quantitative analysis of pharmaceuticals with low systemic plasma levels requires the utmost in sensitivity and selectivity from the analytical method used. A recently introduced triple-quadrupole mass spectrometer with unique enhanced mass-resolution capability was evaluated in the analysis of two such drugs, cabergoline and pergolide, in plasma. Liquid chromatographic/electrospray ionization selected reaction monitoring determination of cabergoline in plasma at unit mass-resolution demonstrated improved sensitivity (50 fg on-column), coupled with suitable accuracy and precision over a broad linear dynamic range covering five orders of magnitude (50 fg to 5 ng on-column). Liquid chromatographic/atmospheric pressure chemical ionization selective reaction monitoring determination of pergolide in plasma also attained a high level of sensitivity (500 fg on-column) at unit mass-resolution, with accuracy and precision values well within pharmaceutical industry standards. Again, a linear dynamic range covering five orders of magnitude (500 fg to 50 ng on-column) was achieved for the assay. Utility of the enhanced mass-resolution feature of the triple-quadrupole mass spectrometer in the determination of pergolide resulted in an improvement in analyte sensitivity (250 fg on-column) and linear dynamic range (250 fg to 50 ng on-column).

Animals↗

Use of tert-butylbenzoylated tartardiamide chiral stationary phase for the enantiomeric resolution of acidic compounds by nano-liquid chromatography.

Several racemic acidic compounds of pharmaceutical and environmental interest have been separated into their enantiomers by nano-liquid chromatography (nano-LC) employing a tert-butylbenzoylated tartardiamide chiral stationary phase (CHI-TBB). CHI-TBB was packed into a fused silica capillary of 100 microm id and retained by two frits made with a heated wire; detection was on-column at a window (about 0.5 cm) prepared by removing the polyimide layer. The normal phase mode was selected for eluting the studied acidic compounds and therefore n-hexane/2-propanol/acetic acid (89/10/1, v/v/v) was used as mobile phase. Working at a flow rate of 220 nL/min a good resolution was obtained for mecoprop, dichlorprop, diclofop, fenoxaprop (herbicides) and for DF 1738Y, DF 1770Y, DF 2008Y (drugs under evaluation). In order to optimize the chiral resolution we modified the polarity of the mobile phase by adding several polar additives such as ethyl acetate, dichloromethane, tert-butyl methyl ether. Better results were obtained for some herbicides on working with 2-propanol/CH2Cl2/n-hexane/acetic acid (8/4/87/1, v/v/v/v). The influence of the capillary temperature on chiral resolution was studied for two herbicides with different chemical structures, namely mecoprop and haloxyfop in the temperature range between 10 and 40 degrees C and with n-hexane/2-propanol/1% acetic acid (89/10/1, v/v/v) as the mobile phase. Linear correlation of ln k vs 1/T and In alpha vs 1/ T was observed; deltaH degrees values were negative, demonstrating that retention of analytes was an exothermic process. A decrease in resolution was observed with rising temperature, showing that enantioresolution was mainly influenced by selectivity factors.

Anti-Inflammatory Agents, Non-Steroidal↗

k-space filtering in 2D gradient-echo breath-hold hyperpolarized 3He MRI: spatial resolution and signal-to-noise ratio considerations.

In this work some of the factors that can influence the signal-to-noise ratio (SNR) and spatial resolution in MR images of inhaled hyperpolarized gases are systematically addressed. In particular, the effects of RF depletion of longitudinal polarization and image gradient diffusion dephasing were assessed in terms of their contribution to a k-space filter. By means of theoretical simulations and a novel method of experimental validation using a variable transverse magnetization of the 1H signal, systematic quantitative and qualitative investigations of the effects of k-space filtering intrinsic to imaging of hyperpolarized gas were made. A 2D gradient-echo image is considered for a range of flip angles with centric, sequential, and half-Fourier Cartesian phase-encoding strategies, and the results are assessed in terms of SNR and spatial resolution in the reconstructed images. Centric phase encoding was found to give the best SNR at higher flip angles, with a trade-off in spatial resolution compared to sequential phase encoding. A half-Fourier approach potentially offers increased SNR through the use of higher flip angles without compromising the spatial resolution, which is comparable to that achieved with sequential encoding.

Fourier Analysis↗

Mapping at glomerular resolution: fMRI of rat olfactory bulb.

The rat olfactory bulb contains approximately 2000 functional units called glomeruli which are used to recognize specific characteristics of odorants. Activity localization of individual glomerulae ( approximately 0.002 microL) has important consequences for understanding mechanisms in olfactory information encoding. High-resolution functional MRI (fMRI) data from the rat olfactory bulb are presented using the blood oxygenation level dependent (BOLD) method at 7 T. Either individual or clusters of fMRI voxels suggestive of activity in the olfactory nerve and glomerular layers were reproducibly detected with repeated 2-min exposures of iso-amyl acetate at spatial resolution of 0.001-0.003 microL. The importance of glomerular clustering for olfaction and the implications of BOLD mapping with even higher spatial resolution (i.e., <<0.001 microL voxels) are discussed. High-resolution in vivo mapping of the rat olfactory bulb with fMRI at high magnetic field promises to provide novel data for understanding olfaction.

Animals↗

Multishot partial-k-space EPI for high-resolution fMRI demonstrated in a rat whisker barrel stimulation model at 3T.

A multishot partial-k-space EPI technique is presented and validated by fMRI at high spatial resolution. High-resolution phase maps corrected by phase-encoded reference scans have less off-resonance effects. Phantom studies demonstrate that this method can substantially improve partial-k-space EPI image formation. BOLD fMRI at submillimeter spatial resolution (156 x 156 x 2000 microm(3), 0.049 microl) was achieved in a rat whisker barrel stimulation model using this technique. The study included eight rats, five of which were administered an intravascular contrast agent (monocrystalline iron oxide nanocolloid (MION)) after the BOLD experiments. In two rats the highest BOLD responses were in the deep layers (IV-VI), and in six rats the highest responses were on the surface and in the deep cortical layers. Most of the pixels that exhibited high BOLD responses had high blood volume weightings. The benefits of this technique are expected to increase for high-resolution fMRI at higher magnetic fields, where T(2) (*) is shorter.

Animals↗

Dynamic imaging with multiple resolutions along phase-encode and slice-select dimensions.

An implementation is reported of an imaging method to obtain MUltiple Resolutions along Phase-encode and Slice-select dimensions (MURPS), which enables dynamic imaging of focal changes using a graded, multiresolution approach. MURPS allows one to trade spatial resolution in part of the volume for improved temporal resolution in dynamic imaging applications. A unique method of Hadamard slice encoding is used, enabling the varying of the phase encode and slice resolution while maintaining a constant effective TR throughout the entire 3-D volume. MURPS was implemented using a gradient-recalled echo sequence, and its utility was demonstrated for MR temperature monitoring. In this preliminary work, it has been shown that changes throughout a large volume can be effectively monitored in times that would normally only permit dynamic imaging in one or a very few slices.

Body Temperature↗

Simultaneous acquisition of multiple resolution images for dynamic contrast enhanced imaging of the breast.

An imaging technique is described that allows the reconstruction of a series of images at high temporal rates, while simultaneously providing images at high spatial resolution. The method allows one to arbitrarily choose from among several combinations of temporal/spatial resolutions during postprocessing. This flexibility is accomplished by strategically interleaving multiple undersampled projection reconstruction datasets (or subapertures), in which each set can be used to reconstruct a high temporal resolution image. Images with increasingly higher spatial resolutions can subsequently be formed by combining two or more subaperture datasets. The technique is demonstrated in vivo to assess the kinetics of contrast enhancement and to visualize the architectural features of suspicious breast lesions.

Aged↗