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Determining cell identities in imaging sequences is an important yet challenging task. The conventional method for cell identification is via cell tracking, which is complex and can be time-consuming. In this study, we propose an innovative approach to cell identification during early $\textit{C. elegans}$ embryogenesis using machine learning. Cell identification during $\textit{C. elegans}$ embryogenesis would provide insights into neural development with implications for higher organisms including humans. We employed random forest, MLP, and LSTM models, and tested cell classification accuracy on 3D time-lapse confocal datasets spanning the first 4 hours of embryogenesis. By leveraging a small number of spatial-temporal features of individual cells, including cell trajectory and cell fate information, our models achieve an accuracy of over 91%, even with limited data. We also determine the most important feature contributions and can interpret these features in the context of biological knowledge. Our research demonstrates the success of predicting cell identities in time-lapse imaging sequences directly from simple spatio-temporal features.

Phase diversity is a widefield aberration correction method that uses multiple images to estimate the phase aberration at the pupil plane of an imaging system by solving an optimization problem. This estimated aberration can then be used to deconvolve the aberrated image or to reacquire it with aberration corrections applied to a deformable mirror. The optimization problem for aberration estimation has been formulated for both Gaussian and Poisson noise models but the Poisson model has never been studied in microscopy nor compared with the Gaussian model. Here, the Gaussian- and Poisson-based estimation algorithms are implemented and compared for widefield microscopy in simulation. The Poisson algorithm is found to match or outperform the Gaussian algorithm in a variety of situations, and converges in a similar or decreased amount of time. The Gaussian algorithm does perform better in low-light regimes when image noise is dominated by additive Gaussian noise. The Poisson algorithm is also found to be more robust to the effects of spatially variant aberration and phase noise. Finally, the relative advantages of re-acquisition with aberration correction and deconvolution with aberrated point spread functions are compared., Comment: 13 pages, 9 figures

Two major challenges in time-of-flight positron emission tomography (TOF-PET) are low spatial resolution and high radioactive dose to the patient, both of which result from limitations in detection technology rather than fundamental physics. A new type of TOF-PET detector employing low-atomic number (low-Z) scintillation media and large-area, high-resolution photodetectors to record Compton scattering locations in the detector has been proposed as a promising alternative, but the minimum technical requirements for such a system have not yet been established. Here we present a simulation study evaluating the potential of a proposed low-Z detection medium, linear alkylbenzene (LAB) doped with a switchable molecular recorder, for next-generation TOF-PET detection. We developed a custom Monte Carlo simulation of full-body TOF-PET using the TOPAS Geant4 software package. By quantifying contributions and tradeoffs for energy, spatial, and timing resolution of the detector, we show that at reasonable combination of specifications, our likelihood-based identification of pairs of first interaction locations in the simulated detector identifies 87.1% of pairs with zero or negligible error, and correctly rejects 90% of all in-patient scatters. The same specifications give TOF-PET sensitivity of ~66.7% and PSF width 4.6 mm with clear contrast. A detector with these specifications provides a clear image of a brain phantom simulated at less than 1% of a standard radiotracer dose., Comment: 25 pages, 9 figures

The pyramids of the Giza plateau have fascinated visitors since ancient times and are the last of the Seven Wonders of the ancient world still standing. It has been half a century since Luiz Alvarez and his team used cosmic-ray muon imaging to look for hidden chambers in Khafres Pyramid. Advances in instrumentation for High-Energy Physics (HEP) allowed a new survey, ScanPyramids, to make important new discoveries at the Great Pyramid (Khufu) utilizing the same basic technique that the Alvarez team used, but now with modern instrumentation. The Exploring the Great Pyramid Mission plans to field a very-large muon telescope system that will be transformational with respect to the field of cosmic-ray muon imaging. We plan to field a telescope system that has upwards of 100 times the sensitivity of the equipment that has recently been used at the Great Pyramid, will image muons from nearly all angles and will, for the first time, produce a true tomographic image of such a large structure.

Clusters of similar or dissimilar objects are encountered in many fields. Frequently used approaches treat the central object of each cluster as latent. Yet, often objects of one or more types cluster around objects of another type. Such arrangements are common in biomedical images of cells, in which nearby cell types likely interact. Quantifying spatial relationships may elucidate biological mechanisms. Parent-offspring statistical frameworks can be usefully applied even when central objects (parents) differ from peripheral ones (offspring). We propose the novel multivariate cluster point process (MCPP) to quantify multi-object (e.g., multi-cellular) arrangements. Unlike commonly used approaches, the MCPP exploits locations of the central parent object in clusters. It accounts for possibly multilayered, multivariate clustering. The model formulation requires specification of which object types function as cluster centers and which reside peripherally. If such information is unknown, the relative roles of object types may be explored by comparing fit of different models via the deviance information criterion (DIC). In simulated data, we compared DIC of a series of models; the MCPP correctly identified simulated relationships. It also produced more accurate and precise parameter estimates than the classical univariate Neyman-Scott process model. We also used the MCPP to quantify proposed configurations and explore new ones in human dental plaque biofilm image data. MCPP models quantified simultaneous clustering of Streptococcus and Porphyromonas around Corynebacterium and of Pasteurellaceae around Streptococcus and successfully captured hypothesized structures for all taxa. Further exploration suggested the presence of clustering between Fusobacterium and Leptotrichia, a previously unreported relationship.

We propose PET scanners using low atomic number media that undergo a persistent local change of state along the paths of the Compton recoil electrons. Measurement of the individual scattering locations and angles, deposited energies, and recoil electron directions allows using the kinematical constraints of the 2-body Compton scattering process to perform a statistical time-ordering of the scatterings, with a high probability of precisely identifying where the gamma first interacted in the detector. In these cases the Line-of-Response is measured with high resolution, determined by the underlying physics processes and not the detector segmentation. There are multiple such media that act through different mechanisms. As an example in which the change of state is quantum-mechanical through a change in molecular configuration, rather than thermodynamic, as in a bubble chamber, we present simulations of a two-state photoswitchable organic dye, a `Switchillator', that is activated to a fluorescent-capable state by the ionization of the recoil electrons. The activated state is persistent, and can be optically excited multiple times to image individual activated molecules. Energy resolution is provided by counting the activated molecules. Location along the LOR is implemented by large-area time-of-flight MCP-PMT photodetectors with single photon time resolution in the tens of ps and sub-mm spatial resolution. Simulations indicate a large reduction of dose.

We investigate rotational diffusion of fluorescent molecules in angular potential wells, the excitation and subsequent emissions from these diffusing molecules, and the imaging of these emissions with high-NA aplanatic optical microscopes. Although dipole emissions only transmit six low-frequency angular components, we show that angular structured illumination can alias higher frequency angular components into the passband of the imaging system. We show that the number of measurable angular components is limited by the relationships between three time scales: the rotational diffusion time, the fluorescence decay time, and the acquisition time. We demonstrate our model by simulating a numerical phantom in the limits of fast angular diffusion, slow angular diffusion, and weak potentials., Comment: 22 pages, 5 figures

We investigate the properties of a single-view fluorescence microscope in a 4$f$ geometry when imaging fluorescent dipoles without using the monopole or scalar approximations. We show that this imaging system has a spatio-angular band limit, and we exploit the band limit to perform efficient simulations. Notably, we show that information about the out-of-plane orientation of ensembles of in-focus fluorophores is recorded by paraxial fluorescence microscopes. Additionally, we show that the monopole approximation may cause biased estimates of fluorophore concentrations, but these biases are small when the sample contains either many randomly oriented fluorophores in each resolvable volume or unconstrained rotating fluorophores., Comment: 21 pages, 12 figures. Portions of this work previously appeared as arXiv:1812.07093, which was split during refereeing

We introduce the basic elements of a spatio-angular theory of fluorescence microscopy, providing a unified framework for analyzing systems that image single fluorescent dipoles and ensembles of overlapping dipoles that label biological molecules. We model an aplanatic microscope imaging an ensemble of in-focus fluorescent dipoles as a linear Hilbert-space operator, and we show that the operator takes a particularly convenient form when expressed in a basis of complex exponentials and spherical harmonics$-$a form we call the dipole spatio-angular transfer function. We discuss the implications of our analysis for all quantitative fluorescence microscopy studies and lay out a path towards a complete theory., Comment: 14 pages, 4 figures

We explore the use of the recently proposed "total nuclear variation" (TNV) as a regularizer for reconstructing multi-channel, spectral CT images. This convex penalty is a natural extension of the total variation (TV) to vector-valued images and has the advantage of encouraging common edge locations and a shared gradient direction among image channels. We show how it can be incorporated into a general, data-constrained reconstruction framework and derive update equations based on the first-order, primal-dual algorithm of Chambolle and Pock. Early simulation studies based on the numerical XCAT phantom indicate that the inter-channel coupling introduced by the TNV leads to better preservation of image features at high levels of regularization, compared to independent, channel-by-channel TV reconstructions., Comment: Submitted to Physics in Medicine and Biology

We integrate a small and portable medical x-ray device with mechanical testing equipment to enable in-situ, non-invasive measurements of a granular material's response to mechanical loading. We employ an orthopedic C-arm as the x-ray source and detector to image samples mounted in the materials tester. We discuss the design of a custom rotation stage, which allows for sample rotation and tomographic reconstruction under applied compressive stress. We then discuss the calibration of the system for 3d computed tomography, as well as the subsequent image reconstruction process. Using this system to reconstruct packings of 3d-printed particles, we resolve packing features with 0.52 mm resolution in a (60 mm)$^3$ field of view. By analyzing the performance bounds of the system, we demonstrate that the reconstructions exhibit only moderate noise., Comment: 10 pages, 8 figures