Highest Achievable Resolution Research Articles

Sensitivity and specificity of Varian Halcyon's portal dosimetry for plan-specific pre-treatment QA.

Developed as a plan-specific pre-treatment QA tool, Varian portal dosimetry promises a fast, high-resolution, and integrated QA solution. In this study, the agreement between predicted fluence and measured cumulative portal dose was determined for the first 140 patient plans at our Halcyon linear accelerator. Furthermore, the capability of portal dosimetry to detect incorrect plan delivery was compared to that of a common QA phantom. Finally, tolerance criteria for verification of VMAT plan delivery with Varian portal dosimetry were derived. All patient plans and the corresponding verification plans were generated within the Eclipse treatment planning system. Four representative plans of different treatment sites (prostate, prostate with lymphatic drainage, rectum, and head & neck) were intentionally altered to model incorrect plan delivery. Investigated errors included both systematic and random errors. Gamma analysis was conducted on both portal dose (criteria γ2%/2mm , γ2%/1mm , and γ1%/1mm ) and ArcCHECK measurements (criteria γ3%/3mm , γ3%/2mm , and γ2%/2mm ) with a 10% low-dose threshold. Performance assessment of various acceptance criteria for plan-specific treatment QA utilized receiver operating characteristic (ROC) analysis. Predicted and acquired portal dosimetry fluences demonstrated a high agreement evident by average gamma passing rates for the clinical patient plans of 99.90%, 96.64%, and 91.87% for γ2%/2mm , γ2%/1mm , and γ1%/1mm , respectively. The ROC analysis demonstrated a very high capability of detecting erroneous plan delivery for portal dosimetry (area under curve (AUC)>0.98) and in this regard outperforms QA with the ArcCHECK phantom (AUC ≈ 0.82). With the suggested optimum decision thresholds excellent sensitivity and specificity is simultaneously possible. Owing to the high achievable spatial resolution, portal dosimetry at the Halcyon can reliably be deployed as plan-specific pre-treatment QA tool to screen for errors. It is recommended to support the fluence integrated portal dosimetry QA by independent phantom-based measurements of a random sample survey of treatment plans.

High-speed label-free multimode-fiber-based compressive imaging beyond the diffraction limit.

Glass fibers are miniature optical components that serve as ultra-narrow endoscopy probes. Ideally, one would want to perform imaging through a fiber at the highest achievable resolution and speed. State-of-the-art super-resolution techniques have shattered the diffraction limit, but more than twofold improvement requires fluorescent labeling and a long acquisition time. Moreover, it is challenging to implement super-resolution microscopy in a fiber format. Here we present fiber-based label-free video-rate imaging at more than 2-fold higher resolution than the diffraction limit. Our work paves the way to rapid, sub-wavelength endo-microscopy in unlabeled live specimens.

Optical Setup for Error Compensation in a Laser Triangulation System.

Absolute distance measurement is a field of research with a large variety of applications. Laser triangulation is a well-tested and developed technique using geometric relations to calculate the absolute distance to an object. The advantages of laser triangulation include its simple and cost-effective setup with yet a high achievable accuracy and resolution in short distances. A main problem of the technology is that even small changes of the optomechanical setup, e.g., due to thermal expansion, lead to significant measurement errors. Therefore, in this work, we introduce an optical setup containing only a beam splitter and a mirror, which splits the laser into a measurement beam and a reference beam. The reference beam can then be used to compensate for different error sources, such as laser beam dithering or shifts of the measurement setup due to the thermal expansion of the components. The effectiveness of this setup is proven by extensive simulations and measurements. The compensation setup improves the deviation in static measurements by up to 75%, whereas the measurement uncertainty at a distance of 1 m can be reduced to 85 μm. Consequently, this compensation setup can improve the accuracy of classical laser triangulation devices and make them more robust against changes in environmental conditions.

Transmission EBSD (t-EBSD) to determine grain and grain boundary properties on nanostructured superconductor samples

The knowledge of the properties of the grains and their grain boundaries is essential for the further optimization of sample performance of various high-Tc samples (YBa2Cu3Oy (YBCO), Bi-based cuprates, MgB2, iron-based materials). In these materials either the grains are of nanometer dimensions or the various additions of secondary phase(s) to improve the flux pinning are required to be of nanometer dimensions, so a high achievable resolution and better imaging properties are important to obtain reasonably high image quality of the recorded Kikuchi patterns to enable automated orientation mapping using the EBSD technique. Therefore, the newly developed transmission-EBSD (t-EBSD) technique is the method of choice to analyze the grain and the grain boundary properties in such nanostructured superconducting materials. Several results obtained on MgB2, melt-textured, infiltration-growth processed YBCO and electrospun Bi2Sr2CaCu2O8 nanowires are presented.

3D printing: an emerging tool for novel microfluidics and lab-on-a-chip applications

In the past few years, 3D printing technology has witnessed an explosive growth, penetrating various aspects of our lives. Current best-in-class 3D printers can fabricate micrometer scale objects, which has made fabrication of microfluidic devices possible. The highest achievable resolution is already at nanometer scale, which is continuing to drop. Since geometric complexity is not a concern for 3D printing, novel 3D microfluidics and lab-on-a-chip systems that are otherwise impossible to produce with traditional 2D microfabrication technology have started to emerge in recent years. In this review, we first introduce the basics of 3D printing technology for the microfluidic community and then summarize its emerging applications in creating novel microfluidic devices. We foresee widespread utilization of 3D printing for future developments in microfluidic engineering and lab-on-a-chip technology.

The Chromatin and Transcriptional Landscape of Native Saccharomyces cerevisiae Telomeres and Subtelomeric Domains.

Saccharomyces cerevisiae telomeres have been a paradigm for studying telomere position effects on gene expression. Telomere position effect was first described in yeast by its effect on the expression of reporter genes inserted adjacent to truncated telomeres. The reporter genes showed variable silencing that depended on the Sir2/3/4 complex. Later studies examining subtelomeric reporter genes inserted at natural telomeres hinted that telomere position effects were less pervasive than previously thought. Additionally, more recent data using the sensitive technology of chromatin immunoprecipitation and massively parallel sequencing (ChIP-Seq) revealed a discrete and noncontinuous pattern of coenrichment for all three Sir proteins at a few telomeres, calling the generality of these conclusions into question. Here we combined the ChIP-Seq of the Sir proteins with RNA sequencing (RNA-Seq) of messenger RNAs (mRNAs) in wild-type and in SIR2, SIR3, and SIR4 deletion mutants to characterize the chromatin and transcriptional landscape of all native S. cerevisiae telomeres at the highest achievable resolution. Most S. cerevisiae chromosomes had subtelomeric genes that were expressed, with only ∼6% of subtelomeric genes silenced in a SIR-dependent manner. In addition, we uncovered 29 genes with previously unknown cell-type-specific patterns of expression. These detailed data provided a comprehensive assessment of the chromatin and transcriptional landscape of the subtelomeric domains of a eukaryotic genome.

Large-area few-layered graphene film determination by multispectral imaging microscopy.

A multispectral imaging method for the rapid and accurate identification of few-layered graphene using optical images is proposed. Commonly rapid identification relies on optical interference effects which limits the choice of substrates and light sources. Our method is based on the comparison of spectral characteristics with principle components from a database which is populated by correlation of micro-Raman registration, spectral characteristics, and optical microscopy. Using this approach the thickness and extent of different graphene layers can be distinguished without the contribution of the optical interference effects and allows characterization of graphene on glass substrates. The high achievable resolution, easy implementation and large scale make this approach suitable for the in-line metrology of industrial graphene production.

Automatic post-picking using MAPPOS improves particle image detection from cryo-EM micrographs

Cryo-electron microscopy (cryo-EM) studies using single particle reconstruction are extensively used to reveal structural information on macromolecular complexes. Aiming at the highest achievable resolution, state of the art electron microscopes automatically acquire thousands of high-quality micrographs. Particles are detected on and boxed out from each micrograph using fully- or semi-automated approaches. However, the obtained particles still require laborious manual post-picking classification, which is one major bottleneck for single particle analysis of large datasets. We introduce MAPPOS, a supervised post-picking strategy for the classification of boxed particle images, as additional strategy adding to the already efficient automated particle picking routines. MAPPOS employs machine learning techniques to train a robust classifier from a small number of characteristic image features. In order to accurately quantify the performance of MAPPOS we used simulated particle and non-particle images. In addition, we verified our method by applying it to an experimental cryo-EM dataset and comparing the results to the manual classification of the same dataset. Comparisons between MAPPOS and manual post-picking classification by several human experts demonstrated that merely a few hundred sample images are sufficient for MAPPOS to classify an entire dataset with a human-like performance. MAPPOS was shown to greatly accelerate the throughput of large datasets by reducing the manual workload by orders of magnitude while maintaining a reliable identification of non-particle images.

Crustal structure of Guadeloupe islands and the Lesser Antilles arc from a new gravity and magnetic synthesis

Abstract Guadeloupe island (West French Indies) is one of the twenty islands that compose the Lesser Antilles arc, which results from the subduction of the Atlantic ocean plate beneath the Caribbean one. The island lies in a complex volcano-tectonic system and the need to understand its geological context has led to numerous on- and offshore geophysical investigations. This work presents a compilation and the processing of available, on-land, airborne and marine, gravity and magnetic data acquired during the last 40 years on Guadeloupe islands and at the scale of the Lesser Antilles arc. The overall dataset provides new Bouguer and reduced to the pole magnetic anomaly maps at the highest achievable resolution. Regionally, the main central negative gravity trend of the arc allows defining two subsident areas. The first one is parallel to the arc direction (~N160°E) to the north, whereas the second unexpected southern one is oriented parallel to oceanic ridges (N130°E). Along the Outer arc, the long wavelength positive anomaly is interpreted, at least along the Karukera spur, as an up-rise of the volcanic basement in agreement with the seismic studies. To the NE of Guadeloupe, the detailed analysis of the geophysical anomalies outlines a series of structural discontinuities consistent with the main bathymetric morphologies, and in continuity of the main fault systems already reported in this area. Based on geophysical evidences, this large scale deformation and faulting of the Outer arc presumably primarily affects the Atlantic subducting plate and secondarily deforms the upper Caribbean plate and the accretion prism, as evidenced in bathymetry as well as on the islands. At the scale of Guadeloupe island, combined gravity and magnetic modeling has been initiated based on existing interpretation of old seismic refraction profiles, with a general structure in three main layers. According to our geophysical anomalies, additional local structures are also modeled in agreement with geological observations: i) the gravity and magnetic signals confirm an up-rise of the volcanic basement below the limestone platforms outcropping on Grande-Terre island ; ii) the ancient volcanic complexes of Basse-Terre island are modeled with high density and reverse magnetized formations; iii) the recent volcanic centre is associated with formations consistent with the low measured density and the underlying hydrothermal system. The E-W models coherently image a NNW-SSE depression structure in half-graben beneath Basse-Terre island, its western scarp following the arc direction in agreement with bathymetric and seismic studies to the north of the island. The so-defined depressed area, and particularly its opening in half-graben toward the SW, is interpreted as the present-day front of deformation of the upper plate, associated with the recent volcanic activity on and around Guadeloupe. Based on this regional deformation model, perspectives are given for further integrated investigation of key targets to address the internal structure and evolution of the Lesser Antilles arc and Guadeloupe volcanic system.

Hyperpolarized C-13 studies of cancer metabolism in animal models. Hype or real?

The Warburg effect [1–3] is the tendency of many cancer types to metabolize glucose into lactate via glycolysis rather than oxidation in the TCA cycle. While fermentative glycolysis is highly inefficient in terms of ATP production (indeed, it yields only about 1/9 of the ATP that would be produced by the TCA cycle), it may confer a survival advantage on cancer cells, for instance by providing a source of carbon to support rapid proliferation [4]. The Warburg effect, and cancer metabolism more generally, may provide opportunities for novel therapeutic strategies that target specific metabolic pathways that cancer cells rely upon for survival and proliferation. Recently, there have been reports that indicate that cancer cells can survive on glutamine as a carbon source, even when glucose is removed from their growth medium [5,6]. Imaging tools for the study of metabolism include PET and MR spectroscopic imaging. Metabolic studies with PET make use of metabolites that have been isotopically labeled with e emitters such as C or N, or, alternatively, where one or more protons have been substituted with F. Over the past several decades F-18 PET using fluoro-deoxyglucose as the radiotracer has been widely adopted in oncological imaging. There have other radiotracers that have shown promise for imaging different metabolic alterations in tumors [7]. The advantages of PET include its high sensitivity (some metabolites can be detected at picomolar concentrations) and the relatively long half-lives of the radiotracers (10 minutes for N, 20 minutes for C, and 110 minutes for F). The disadvantages of PET include limitations on spatial resolution imposed by positron ranging (the highest achievable resolution is on the order of a few millimeters) and the inability of PET to distinguish between signal arising from the injected radiotracer and its metabolites. For the shorter-lived isotopes like C-11, there is the need for both a cyclotron and chemistry facilities for rapid synthesis of desired radiolabeled compounds.

Statistical resolution limits and the complexified Crame/spl acute/r-Rao bound

Array resolution limits and accuracy bounds on the multitude of signal parameters (e.g., azimuth, elevation, Doppler, range, cross-range, depth, frequency, chirp, polarization, amplitude, phase, etc.) estimated by array processing algorithms are essential tools in the evaluation of system performance. The case in which the complex amplitudes of the signals are unknown is of particular practical interest. A computationally efficient formulation of these bounds (from the perspective of derivations and analysis) is presented for the case of deterministic and unknown signal amplitudes. A new derivation is given using the unknown complex signal parameters and their complex conjugates. The new formula is readily applicable to obtaining either symbolic or numerical solutions to estimation bounds for a very wide class of problems encountered in adaptive sensor array processing. This formula is shown to yield several of the standard Crame/spl acute/r-Rao results for array processing, along with new results of fundamental interest. Specifically, a new closed-form expression for the statistical resolution limit of an aperture for any asymptotically unbiased superresolution algorithm (e.g., MUSIC, ESPRIT) is provided. The statistical resolution limit is defined as the source separation that equals its own Crame/spl acute/r-Rao bound, providing an algorithm-independent bound on the resolution of any high-resolution method. It is shown that the statistical resolution limit of an array or coherent integration window is about 1.2/spl middot/SNR/sup -1/4/ relative to the Fourier resolution limit of 2/spl pi//N radians (large number N of array elements). That is, the highest achievable resolution is proportional to the reciprocal of the fourth root of the signal-to-noise ratio (SNR), in contrast to the square-root (SNR/sup -1/2/) dependence of standard accuracy bounds. These theoretical results are consistent with previously published bounds for specific superresolution algorithms derived by other methods. It is also shown that the potential resolution improvement obtained by separating two collinear arrays (synthetic ultra-wideband), each with a fixed aperture B wavelengths by M wavelengths (assumed large), is approximately (M/B)/sup 1/2/, in contrast to the resolution improvement of M/B for a full aperture. Exact closed-form results for these problems with their asymptotic approximations are presented.

Factors Affecting the Production of Fast Transient Signals in Single Shot Laser Ablation Inductively Coupled Plasma Mass Spectrometry

Low sample consumption and high achievable spatial resolution combine to make laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) an attractive direct sampling technique for the analysis of solids. These desirable characteristics are best realized when the laser ablation system is operated in a single-shot fashion, in which each laser pulse produces a transient analyte signal. The temporal width of a single-shot LA analyte transient is inversely related to the best achievable signal-to-noise ratio (S/N). Thus, production of fast transient signals is an important consideration in single-shot LA analyses. In this study we explore the effects on transient pulse width of ablation-cell volume, the diameter and length of tubing used to connect the ablation cell to the ICP, and the composition and flow rate of ablation-cell sweep gas. Minimization of ablation-cell volume and the length and diameter of the transfer tube was found to dramatically decrease the peak widths of transient signals. However, use of helium gas to sweep analyte particles from the ablation cell was found to significantly reduce the effect of cell volume on transient width. Use of a cell volume of 0.70 cm3 and optimization of other instrumental parameters produced a transient sample pulse 85 ms in duration and limits of detection in the tens of femtograms range for single-shot laser-ablation events.

Lens-field axis alignment: a new objective lens alignment for high-resolution Electron Microscopy

Accurate alignment of an electron microscope is important when the highest achievable resolution is demanded. In a conventional alignment for high-resolution electron microscopy, the incident beam direction is aligned for the object point imaged at a viewing-screen center. It should be noted however that the object point corresponding to the viewing-screen center does not usually located on the magnetic-field axis of an objective lens due to lens misorientation and/or beam deflection caused by a leakage field around the objective lens. Then, the voltage-center and coma-free conditions cannot be satisfied simultaneously, even if a magnetic-field is rotationally symmetric. We implemented last year a proposed scheme to satisfy both coma-free and voltage-center conditions. This alignment scheme however requires a suitable deflector at the objective image plane.In this report, we summarize ordinary alignment procedures for high resolution electron microscopy and propose a new alignment procedure, which we call a lens-field axis alignment. Using this alignment we can satisfy the coma-free and voltage-center conditions simultaneously.