Towards single-shot coherent imaging via overlap-free ptychography

Ptychographic imaging at synchrotron and XFEL sources requires dense overlapping scans, limiting throughput and increasing dose. Extending coherent diffractive imaging to overlap-free operation on extended samples remains an open problem. Here, we extend PtychoPINN (O. Hoidn \emph{et al.}, \emph{Scientific Reports} \textbf{13}, 22789, 2023) to deliver \emph{overlap-free, single-shot} reconstructions in a Fresnel coherent diffraction imaging (CDI) geometry while also accelerating conventional multi-shot ptychography. The framework couples a differentiable forward model of coherent scattering with a Poisson photon-counting likelihood; real-space overlap enters as a tunable parameter via coordinate-based grouping rather than a hard requirement. On synthetic benchmarks, reconstructions remain accurate at low counts ($\sim\!10^4$ photons/frame), and overlap-free single-shot reconstruction with an experimental probe reaches amplitude structural similarity (SSIM) 0.904, compared with 0.968 for overlap-constrained reconstruction. Against a data-saturated supervised model with the same backbone (16,384 training images), PtychoPINN achieves higher SSIM with only 1,024 images and generalizes to unseen illumination profiles. Per-graphics processing unit (GPU) throughput is approximately $40\times$ that of least-squares maximum-likelihood (LSQ-ML) reconstruction at matched $128\times128$ resolution. These results, validated on experimental data from the Advanced Photon Source and the Linac Coherent Light Source, unify single-exposure Fresnel CDI and overlapped ptychography within one framework, supporting dose-efficient, high-throughput imaging at modern light sources.

Domain Knowledge Guided Bayesian Optimization For Autonomous Alignment Of Complex Scientific Instruments

Bayesian Optimization (BO) is a powerful tool for optimizing complex non-linear systems. However, its performance degrades in high-dimensional problems with tightly coupled parameters and highly asymmetric objective landscapes, where rewards are sparse. In such needle-in-a-haystack scenarios, even advanced methods like trust-region BO (TurBO) often lead to unsatisfactory results. We propose a domain knowledge guided Bayesian Optimization approach, which leverages physical insight to fundamentally simplify the search problem by transforming coordinates to decouple input features and align the active subspaces with the primary search axes. We demonstrate this approach's efficacy on a challenging 12-dimensional, 6-crystal Split-and-Delay optical system, where conventional approaches, including standard BO, TuRBO and multi-objective BO, consistently led to unsatisfactory results. When combined with an reverse annealing exploration strategy, this approach reliably converges to the global optimum. The coordinate transformation itself is the key to this success, significantly accelerating the search by aligning input co-ordinate axes with the problem's active subspaces. As increasingly complex scientific instruments, from large telescopes to new spectrometers at X-ray Free Electron Lasers are deployed, the demand for robust high-dimensional optimization grows. Our results demonstrate a generalizable paradigm: leveraging physical insight to transform high-dimensional, coupled optimization problems into simpler representations can enable rapid and robust automated tuning for consistent high performance while still retaining current optimization algorithms.

A Start To End Machine Learning Approach To Maximize Scientific Throughput From The LCLS-II-HE

With the increasing brightness of Light sources, including the Diffraction-Limited brightness upgrade of APS and the high-repetition-rate upgrade of LCLS, the proposed experiments therein are becoming increasingly complex. For instance, experiments at LCLS-II-HE will require the X-ray beam to be within a fraction of a micron in diameter, with pointing stability of a few nanoradians, at the end of a kilometer-long electron accelerator, a hundred-meter-long undulator section, and tens of meters long X-ray optics. This enhancement of brightness will increase the data production rate to rival the largest data generators in the world. Without real-time active feedback control and an optimized pipeline to transform measurements to scientific information and insights, researchers will drown in a deluge of mostly useless data, and fail to extract the highly sophisticated insights that the recent brightness upgrades promise. In this article, we outline the strategy we are developing at SLAC to implement Machine Learning driven optimization, automation and real-time knowledge extraction from the electron-injector at the start of the electron accelerator, to the multidimensional X-ray optical systems, and till the experimental endstations and the high readout rate, multi-megapixel detectors at LCLS to deliver the design performance to the users. This is illustrated via examples from Accelerator, Optics and End User applications.

Generalizing Stochastic Smoothing for Differentiation and Gradient Estimation

We deal with the problem of gradient estimation for stochastic differentiable relaxations of algorithms, operators, simulators, and other non-differentiable functions. Stochastic smoothing conventionally perturbs the input of a non-differentiable function with a differentiable density distribution with full support, smoothing it and enabling gradient estimation. Our theory starts at first principles to derive stochastic smoothing with reduced assumptions, without requiring a differentiable density nor full support, and we present a general framework for relaxation and gradient estimation of non-differentiable black-box functions $f:\mathbb{R}^n\to\mathbb{R}^m$. We develop variance reduction for gradient estimation from 3 orthogonal perspectives. Empirically, we benchmark 6 distributions and up to 24 variance reduction strategies for differentiable sorting and ranking, differentiable shortest-paths on graphs, differentiable rendering for pose estimation, as well as differentiable cryo-ET simulations.

Uncertainty Quantification via Stable Distribution Propagation

We propose a new approach for propagating stable probability distributions through neural networks. Our method is based on local linearization, which we show to be an optimal approximation in terms of total variation distance for the ReLU non-linearity. This allows propagating Gaussian and Cauchy input uncertainties through neural networks to quantify their output uncertainties. To demonstrate the utility of propagating distributions, we apply the proposed method to predicting calibrated confidence intervals and selective prediction on out-of-distribution data. The results demonstrate a broad applicability of propagating distributions and show the advantages of our method over other approaches such as moment matching.