Grid Of Spots Research Articles

Proton beam spot size and position measurements using a multi-strip ionization chamber

PurposeTo develop and characterize a large-area multi-strip ionization chamber (MSIC) for efficient measurement of proton beam spot size and position at a synchrotron-based proton therapy facility. Methods and MaterialsA 420 mm x 320 mm MSIC was designed with 240 vertical strips and 180 horizontal strips at 1.75 mm pitch. The MSIC was characterized by irradiating a grid of proton spots across 17 energies from 73.5 MeV to 235 MeV and comparing to simultaneous measurements made with a reference Gafchromic EBT3 film. Beam profiles, spot sizes, and positions were analyzed. Short term measurement stability and sensitivity were evaluated. ResultsExcellent agreement was demonstrated between the MSIC and EBT3 film for both spot size and position measurements. Spot sizes agreed within ± 0.18 mm for all energies tested. Measured beam spot positions agreed within ± 0.17 mm. The detector showed good short term measurement stability and low noise performance. ConclusionThe large-area MSIC enables efficient and accurate proton beam spot characterization across the clinical energy range. The results indicate the MSIC is suitable for pencil beam scanning proton therapy commissioning and quality assurance applications requiring fast spot size and position quantification.

Characterization of Functional Coatings on Cork Stoppers with Laser-Induced Breakdown Spectroscopy Imaging.

Evaluating the efficiency of surface treatments is a problem of paramount importance for the cork stopper industry. Generically, these treatments create coatings that aim to enhance the impermeability and lubrification of cork stoppers. Yet, current methods of surface analysis are typically time-consuming, destructive, have poor representativity or rely on indirect approaches. In this work, the use of a laser-induced breakdown spectroscopy (LIBS) imaging solution is explored for evaluating the presence of coating along the cylindrical surface and in depth. To test it, several cork stoppers with different shaped areas of untreated surface were analyzed by LIBS, making a rectangular grid of spots with multiple shots per spot, to try to identify the correspondent shape. Results show that this technique can detect the untreated area along with other features, such as leakage and holes, allowing for a high success rate of identification and for its performance at different depths, paving the way for future industry-grade quality control solutions with more complex surface analysis.

Toward areal chromatic confocal metrology

Chromatic confocal metrology suffers from a limitation in the number of measurement points that can be measured simultaneously in a single frame acquisition. We propose chromatic confocal areal metrology (ChromaCAM), in which the surface height for each point in a 2D grid of measurement spots, generated by a rectangular micro-lens array, is parallely analyzed through the utilization of a pinhole multiplexer unit, an analog optical analysis unit, and postprocessing algorithms. An experiment shows the viability of the simultaneous acquisition of multiple measurement points and the advantages over exisiting areal chromatic confocal approaches. Compared with conventional chromatic confocal metrology, the increase in the acquisition rate is significant and enables one-shot measurements.

Fast optical recording of neuronal activity by three-dimensional custom-access serial holography.

Optical recording of neuronal activity in three-dimensional (3D) brain circuits at cellular and millisecond resolution in vivo is essential for probing information flow in the brain. While random-access multiphoton microscopy permits fast optical access to neuronal targets in three dimensions, the method is challenged by motion artifacts when recording from behaving animals. Therefore, we developed three-dimensional custom-access serial holography (3D-CASH). Built on a fast acousto-optic light modulator, 3D-CASH performs serial sampling at 40 kHz from neurons at freely selectable 3D locations. Motion artifacts are eliminated by targeting each neuron with a size-optimized pattern of excitation light covering the cell body and its anticipated displacement field. Spike rates inferred from GCaMP6f recordings in visual cortex of awake mice tracked the phase of a moving bar stimulus with higher spike correlation between intra compared to interlaminar neuron pairs. 3D-CASH offers access to the millisecond correlation structure of in vivo neuronal activity in 3D microcircuits.

An adaptive spot placement method on Cartesian grid for pencil beam scanning proton therapy

Pencil beam scanning proton radiotherapy (RT) offers flexible proton spot placement near treatment targets for delivering tumoricidal radiation dose to tumor targets while sparing organs-at-risk. Currently the spot placement is mostly based on a non-adaptive sampling (NS) strategy on a Cartesian grid. However, the spot density or spacing during NS is a constant for the Cartesian grid that is independent of the geometry of tumor targets, and thus can be suboptimal in terms of plan quality (e.g. target dose conformality) and delivery efficiency (e.g. number of spots). This work develops an adaptive sampling (AS) spot placement method on the Cartesian grid that fully accounts for the geometry of tumor targets. Compared with NS, AS places (1) a relatively fine grid of spots at the boundary of tumor targets to account for the geometry of tumor targets and treatment uncertainties (setup and range uncertainty) for improving dose conformality, and (2) a relatively coarse grid of spots in the interior of tumor targets to reduce the number of spots for improving delivery efficiency and robustness to the minimum-minitor-unit (MMU) constraint. The results demonstrate that (1) AS achieved comparable plan quality with NS for regular MMU and substantially improved plan quality from NS for large MMU, using merely about 10% of spots from NS, where AS was derived from the same Cartesian grid as NS; (2) on the other hand, with similar number of spots, AS had better plan quality than NS consistently for regular and large MMU.

STARCH: copy number and clone inference from spatial transcriptomics data

Tumors are highly heterogeneous, consisting of cell populations with both transcriptional and genetic diversity. These diverse cell populations are spatially organized within a tumor, creating a distinct tumor microenvironment. A new technology called spatial transcriptomics can measure spatial patterns of gene expression within a tissue by sequencing RNA transcripts from a grid of spots, each containing a small number of cells. In tumor cells, these gene expression patterns represent the combined contribution of regulatory mechanisms, which alter the rate at which a gene is transcribed, and genetic diversity, particularly copy number aberrations (CNAs) which alter the number of copies of a gene in the genome. CNAs are common in tumors and often promote cancer growth through upregulation of oncogenes or downregulation of tumor-suppressor genes. We introduce a new method STARCH (spatial transcriptomics algorithm reconstructing copy-number heterogeneity) to infer CNAs from spatial transcriptomics data. STARCH overcomes challenges in inferring CNAs from RNA-sequencing data by leveraging the observation that cells located nearby in a tumor are likely to share similar CNAs. We find that STARCH outperforms existing methods for inferring CNAs from RNA-sequencing data without incorporating spatial information.

Phase Noise Robustness of a Coherent Spatially Parallel Optical Reservoir

Reservoir computing is a machine learning algorithm particularly adapted to process time-dependent signals. It can be easily implemented experimentally with good performance. However experimental implementations are subject to noise, which degrades performance. We develop strategies to mitigate the effects of noise. The specific system on which we illustrate our approaches—currently under development in our laboratory—is a coherent linear Fabry–Perot resonator in which neurons are encoded as a grid of spots on the input mirror plane. In this system, changes in the length of the resonator are the major source of noise and can be modeled as phase noise. This can in principle be partially solved by active stabilisation, but it is interesting to find other strategies to counter the effect of phase noise. We show that a completely unknown phase can be tolerated with only a small degradation of performance by using appropriate training and a readout layer architecture in which the output weights depend on the noisy parameter (the phase). Furthermore, the phase can be estimated by the reservoir itself, leading to an architecture in which the reservoir has two outputs, one of which (the phase estimation) is used to control the other. Our approach should find applications in many experimental implementations of reservoir computing.

Technical Note: Optimization of spot and trimmer position during dynamically collimated proton therapy.

To demonstrate a novel theoretical optimization design which considers beam spot and trimmer positioning in addition to beamlet weighting for dynamically collimated proton therapy (DCPT) treatments. Prior to this, the previous methods of plan optimization used to study this emerging technology relied upon an intuitive selection criterion to fix the trimmers blades for a uniform grid of beam spots before determining the individual beamlet weights. To evaluate the potential benefit from this new optimization design, a treatment planning optimization study was performed in order to compare the algorithm's functionality against the existing methods of plan optimization. A direct parameter optimization (DPO) method was developed to determine beam spot and trimmer positions cohesively with beamlet weighting for DCPT treatment plans. Gradients were numerically determined from applying small adjustments to the aforementioned parameters and quantifying the resulting impact on an objective function. This technique was compared to the conventional trimmer selection algorithm (TSA) which does not optimize spot position concurrently with trimmer position. Both planning methods were used to optimize a set of brain treatment plans, and the resulting dose distributions were compared with dose-volume histogram quantities in addition to target coverage, homogeneity, and conformity metrics. An overall improvement to the target conformity and healthy tissue sparing was achieved with DPO over TSA while maintaining an equivalent planning target volume (PTV) coverage index for the three brain patients evaluated in this study. On average, the conformity index improved by 5.5% when utilizing DPO. A similar improvement in reducing the dose to several organs at risk was also noted. Both the TSA and DPO planning methods can achieve highly conformal treatments with the dynamic collimation system (DCS) technology. However, an improvement in the target conformity and healthy tissue sparing was achieved by simultaneously optimizing beam spot position, trimmer location, and beamlet weights using DPO in comparison to the TSA technique.

A shortcut to marking 3D target curves on curved surface via a galvanometric laser scanner

Marking arbitrary three-dimensional (3D) target curves on given objects with curved surface is required in many industrial fields, such as fabric prepreg placement in composite material part fabrication, product assembly, surface painting for decoration, etc. A shortcut to the solution of this intractable problem is proposed by utilizing a galvanometric laser scanner (GLS) with the aid of a camera. Without using the existing tedious GLS calibration procedures, the proposed method directly establishes a mapping between the 3D coordinates of the laser spots on the object surface and the control voltages of the scanner. A single-hidden layer feedforward neural network (SLFN) is employed to model the mapping. By projecting a dense grid of laser spots on the object to be marked and simultaneously taking only one image, the SLFN model is trained in minutes via a linear solving mechanism. Experiments demonstrate that the trained SLFN model has a good generalization performance for marking 3D target curves. The 3D laser marking errors on experimental objects are less than 0.5 mm. The proposed method is especially suitable for on-site use and can be conveniently extended to multiple GLSs for marking large complex objects.

Surface localisation of laser photoelectron emission using Cu2O and Ag film structures

A laser electron source localised on a photocathode surface was developed on the basis of Ag and Cu2O thin films sequentially deposited by magnetron sputtering on a glass substrate. Photoemission of electrons under the action of the fourth (263 nm) harmonic of a femtosecond fibre laser was initiated from the surface of an Ag film deposited on the substrate surface. Photoelectron source localisation on the photocathode surface was provided by sputtering the Cu2O copper oxide film on its surface, which significantly (about 50 times) reduced the photoemission efficiency, and by subsequent removal of the copper oxide layer in the photoemission spot with a diameter of ∼15 μm by means of focused second-harmonic radiation of a femtosecond fibre laser. In conducting research on the photocathode surface, a grid of photoemission spots was formed, which greatly facilitated the laser beam alignment with the photoemission spot. A decrease in the noises of ultrafast transmission electron microscope, associated with spatial fluctuations of the laser beam initiating pulsed photoelectron emission from the microscope photocathode when using a localised electron source on the basis of a structure of thin Cu2O and Ag films, was experimentally demonstrated.

Discriminating prolonged, episodic or disturbed monazite age spectra: An example from the Kalak Nappe Complex, Arctic Norway

Monazite within a granite intruding the Kalak Nappe Complex (Norway) provides an informative example of a complex age spectrum in which U–Th–Pb data scatters for ˜300Ma along the Concordia curve. SIMS analyses yield 207Pb/235U ages (1σ) of 876±18 to 633±15Ma, and petrographically constrained age groupings suggest dates of 856±16Ma for oscillatory zoned cores, 761±32Ma for patchy domains, and 647±21Ma for rims. A grid of LA-ICPMS spots across a single grain resolve 207Pb/235U ages (1σ) of 884±23 to 564±14Ma, corroborating the spread in the SIMS dataset and highlighting its spatial relationship to BSE textures. Such Concordia patterns have led to diverse interpretations including prolonged growth or the influence of a variety of radiogenic-Pb mobility processes. In combination with U–Pb analyses, detailed chemical, EBSD, and Raman imaging are used to resolve the primary mechanism for this protracted age spread.The spread in monazite ages is not the result of deformation-induced radiogenic Pb loss because EBSD reveals that the grains are only weakly deformed and have no discernible microstructures. The age spread is not the result of thermally induced radiogenic Pb mobility either, as thermal diffusion time–temperature models fail to reproduce the observed age pattern, and even simplifications indicate diffusion domains that are vastly below the observed scale of dated domains. The age spread is not the result of metamictization as well-defined Raman peaks and the strong EBSPs indicate a well-ordered crystal structure. Younger monazite domains have smaller negative Eu/Eu* anomalies, elevated LaN/YbN ratios, and enhanced Th and U. The age distribution is primarily attributed to fluid-mediated element mass transfer driven by coupled substitution in the altered parts of monazite, consistent with the geochemical signatures in these domains. This process left the P–O framework of the original c. 850Ma magmatic crystal intact, as confirmed by EBSD, but variably purged of its radiogenic-Pb cargo, as demonstrated by spatial interpolation of LA-ICPMS U–Pb data. In some instances, removal of radiogenic Pb appears complete, consistent with the correlation between texturally-defined age domains and well-known tectonothermal events, as inferred from dated intrusive rocks in the region. These results indicate the susceptibility of monazite to fluid alteration, which allows even a single monazite grain to record several tectonothermal events and potentially chart much of an orogens history.

Laser-induced breakdown spectroscopy (LIBS) as a tool for in situ mapping and textural interpretation of lithium in pegmatite minerals

Laser-induced breakdown spectroscopy (LIBS) offers an efficient method for qualitative and semi-quantitative analysis of light elements ( Z < 10), including lithium. This relatively inexpensive analytical tool provides very rapid analysis with little sample damage, requiring minimal sample preparation. In principle, LIBS is a form of atomic emission spectroscopy, relying on characteristic spectra emitted from plasma generated by a high-energy laser pulse striking a sample (solid, liquid, or gas). In this study, LIBS mapping was applied to petrographically characterized samples of hydrothermally altered spodumene from the Neoarchaean Mt. Cattlin lithium pegmatite deposit. Spodumene (LiAlSi2O6) is the ore mineral in this deposit, but lithium is distributed in variety of minerals including primary micas and tourmaline, as well as in the alteration mineralogy of spodumene. Mapping was carried out using a grid of analysis spots of 125 μm diameter, spaced at 200 μm intervals, on a sample surface cut by a diamond saw blade without further preparation. Results from mapping of lithium in these samples effectively discriminated between spodumene, its alteration mineralogy, and matrix silicate minerals of the matrix. However, quantification of LIBS results using lithium-doped borosilicate glasses as standards was limited due to issues with the sensitivity of matrix matching of standards and self-absorption effects at Li2O values greater than ~2 wt%, especially at values greater than ~6 wt%. The results of this study testify to the effectiveness of LIBS as a mapping tool for light elements, which may be used as a complement to other mapping techniques. Mapping of lithium in pegmatite minerals has important applications in exploration, evaluation, and beneficiation of lithium pegmatite ore bodies.

SU-E-T-499: A Geant4/TOPAS Monte Carlo System for Validating Proton Therapy Treatment Plan Calculations at Mayo Clinic

Purpose: To build a Geant4‐based Monte Carlo (MC) dose verification system for proton therapy with a scanning nozzle. This system will be used routinely at the upcoming Mayo Clinic proton center for both research and verification of pencil beam dose calculations. Methods: Geant4 is a well‐verified MC toolkit that is applied extensively in many branches of physics, including medical physics. We implemented our dose verification system using TOPAS, a proton MC package that facilitates the use of Geant4. The system consists of: scripts that read in data from DICOM files and create TOPAS input parameter files; TOPAS geometry extensions to accommodate our scanning nozzle, and TOPAS code additions to input ‘parameterized’ phase space data for beam spots at the nozzle exit. Typically, a phase space file containing source events for a grid of beam spots covering the scanning area at the nozzle exit is about 500 Gb. To reduce the size of this file down to ∼30 Mb, we fit MC‐generated beam spot position and direction distributions to extract Twiss parameters. The beam energy distributions are fitted with skewed Gaussians. The phase space is then represented by a set of skewed Gaussian and Twiss parameters for each beam spot in the grid. Results: Using our MC dose calculation system, we show MC and pencil beam comparisons for: (1) water phantom, (2) prostate and (3) head and neck cases. Good agreement is obtained. To reach 2% statistical error on the MC dose calculations, a tumor 200 cm3 in volume would require around 1×107 protons. On a 100‐node cluster, such a calculation takes ∼1 hour to complete. Conclusion: A TOPAS‐based dose verification system for proton treatment plans has been built at Mayo Clinic. The typical computation time per plan is expected to be a few hours on a dedicated cluster. This work is supported by a grant from Varian Medical Systems.

Compression of periodic images for faster phase retrieval

In fringe analysis, or in projected grids for shape-from-shade, deviations from periodicity are used for finding phase changes. In another example, a Hartmann&#x2013;Shack sensor produces a deformed grid of spots on a camera. The gradients of the original wavefront are calculated from that image by centroiding the spots or by demodulating them. The computation time rises linearly with the number of pixels in the image. We introduce a method to reduce the size of the image without loss of accuracy prior to the calculation to reduce the total processing time. The compressed result is superior to an image measured with reduced resolution. Hence, higher accuracy and speed are obtained by oversampling the image and reducing it correctly prior to calculations. Compression or expansion coefficients are calculated through the requirement to maintain the integrity of the original phase data.

Adaptive optics implementation with a Fourier reconstructor

Adaptive optics takes its servo feedback error cue from a wavefront sensor. The common Hartmann-Shack spot grid that represents the wavefront slopes is usually analyzed by finding the spot centroids. In a novel application, we used the Fourier decomposition of a spot pattern to find deviations from grid regularity. This decomposition was performed either in the Fourier domain or in the image domain, as a demodulation of the grid of spots. We analyzed the system, built a control loop for it, and tested it thoroughly. This allowed us to close the loop on wavefront errors caused by turbulence in the optical system.

Systematic Peptide Array-based Delineation of the Differential β-Catenin Interaction with Tcf4, E-Cadherin, and Adenomatous Polyposis Coli

Nuclear accumulation of the complex between beta-catenin and proteins of the T-cell factor (Tcf) family is a hallmark of many cancers. Targeting this interaction for drug development is complicated by the fact that E-cadherin and adenomatous polyposis coli (APC) bind to overlapping sites on beta-catenin. Inhibiting their interactions might actually promote tumor growth. To identify selective beta-catenin binding hot spots of Tcf4, E-cadherin, and APC, array technology with peptides of up to 53 amino acids length was used. Interactions were monitored by a quantitative fluorescent readout, which was shown to represent a monitor of true equilibrium binding constants. We identified minimal binding motifs in the beta-catenin ligands and showed that most of the 15-mer and 20-mer repeats of APC did not interact, at least when non-phosphorylated, and defined a consensus binding motif also present in APC. We confirmed previously found hot spots and identified new ones. The method allowed us to locate a hydrophobic pocket that was relevant for the Tcf, but not the E-cadherin interaction, and would thus constitute an ideal drug target site.

Direct demodulation of Hartmann-Shack patterns.

Hartmann-Shack wave-front sensors produce a distorted grid of spots whose deviation from perfection is linear with the wave-front gradient. Usually, the centroid of each spot is calculated to provide that deviation, but it is also possible to perform the calculation by Fourier demodulation of the spot pattern [Opt. Commun. 215, 285, 2003]. We show that this demodulation can be performed directly on the grid, without reverting to Fourier transforms. Tracking the motion of each centroid individually is limited to well-defined spots with motions smaller than their pitch. In contrast, our method treats the image as a whole, is not limited to non-overlapping or sharp spots, and allows large spot motions. By replicating the array of spots slightly beyond the edge of the aperture, we reduce the chance for boundary phase dislocations in the reconstruction of the wave front. The method is especially suited to very large arrays.

DNA Microarrays and Animal Models of Learning and Memory

This chapter highlights the use of DNA microarray applied to dissect, and analyze the pathophysiology of learning and memory in the mammalian brain. Inhibitors of transcription or translation interfere with long-term memory (LTM) formation, indicating the requirement of de novo gene expression. A DNA microarray is a grid of DNA spots, called probes, each containing a unique DNA sequence. Microarray analysis results in large amounts of data that are difficult to interpret without computational methods. Cluster analysis is a commonly used method to investigate and interpret gene expression data sets. By grouping together, genes that have similar expression profiles, cluster analysis can be used for the extraction of regulatory motifs, inference of functional annotation, and classification of cell types or tissue samples. The chapter focuses on the use of DNA microarray technology to dissect, and analyze the pathophysiology of learning and memory in the mammalian brain, and present the experiments performed in different behavioral paradigms to study the physiology of learning and memory, and describe an animal model of cognition disorders.

Chapter 4 Techniques for Optimizing Microscopy and Analysis through Digital Image Processing

Publisher Summary This chapter describes the fundamentals of video microscopy and digital image processing to make best use of the powerful computerized techniques currently available. The use of digital image processors has greatly enhanced the utility of the optical microscope, permitting entire fields of study. By the end of this chapter, the structure of a digital imaging microscope as well as some of the fundamental techniques that improved the quantitative as well as qualitative aspects of the using light microscopy are discussed. Few examples are presented on the processes and the timing to apply digital imaging so as to extract the most useful information from one's samples. This chapter discusses the major components of the typical video microscopy system so that one is able to properly configure and utilize its features. Video cameras are the most common form of analog cameras used in biomedical science. Once an image from either a digital or analog camera has been received by the image processor and converted into a digital form (in the case of analog cameras) the images are fundamentally broken down into a finite grid of spots called “pixels,”

Relation between relative afferent pupillary defect and suprathreshold automated perimetry

The purpose of this study was to test for correlation between relative afferent pupillary defect (RAPD) and visual acuity, central differential light threshold and visual field defect measured by suprasthreshold automated grid perimetry. In 98 patients with optic neuropathies of different origin (inflammatory, ischemic, or compressive) in addition to a standard ophthalmological examination, static perimetry of the 30 degrees visual field with a dense grid of test spots, including measurement of the central differential light sensitivity, was done by means of the Tübingen Automated Perimeter. RAPD was tested using the swinging flashlight test quantified with neutral density filters. Visual acuity and central differential light sensitivity correlated only weakly with the RAPD. The visual field showed a better correlation (coeff. of corr. for all patients 0.58, for patients with optic neuritis 0.64. for patients with AION 0.53 and for patients with compressive neuropathies 0.84). One test spot not seen in perimetry corresponded to an RAPD of about 0.01 log-units. The results confirm those from previous studies obtained by threshold perimetry. The RAPD is a good parameter for the severity of an optic nerve lesion, especially of compressive origin.