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Guizar-Sicairos, Manuel

Publications and source records attributed to Guizar-Sicairos, Manuel.

Accelerated deep self-supervised ptycho-laminography for three-dimensional nanoscale imaging of integrated circuits

Three-dimensional inspection of nanostructures such as integrated circuits is important for security and reliability assurance. Two scanning operations are required: ptychographic to recover the complex transmissivity of the specimen, and rotation of the specimen to acquire multiple projections covering the 3D spatial frequency domain. Two types of rotational scanning are possible: tomographic and laminographic. For flat, extended samples, for which the full 180° coverage is not possible, the latter is preferable because it provides better coverage of the 3D spatial frequency domain compared to limited-angle tomography. It is also because the amount of attenuation through the sample is approximately the same for all projections. However, both techniques are time consuming because of extensive acquisition and computation time. Here, we demonstrate the acceleration of ptycho-laminographic reconstruction of integrated circuits with 16 times fewer angular samples and 4.67 times faster computation by using a physics-regularized deep self-supervised learning architecture. We check the fidelity of our reconstruction against a densely sampled reconstruction that uses full scanning and no learning. As already reported elsewhere [ Opt. Express 28 , 12872 ( 2020 ) OPEXFF 1094-4087 10.1364/OE.379200 ], we observe improvement of reconstruction quality even over the densely sampled reconstruction, due to the ability of the self-supervised learning kernel to fill the missing cone.

47 OTHER INSTRUMENTATION↗

Imaging crossing fibers in mouse, pig, monkey, and human brain using small-angle X-ray scattering

Myelinated axons (nerve fibers) efficiently transmit signals throughout the brain via action potentials. Multiple methods that are sensitive to axon orientations, from microscopy to magnetic resonance imaging, aim to reconstruct the brain's structural connectome. As billions of nerve fibers traverse the brain with various possible geometries at each point, resolving fiber crossings is necessary to generate accurate structural connectivity maps. However, doing so with specificity is a challenging task because signals originating from oriented fibers can be influenced by brain (micro)structures unrelated to myelinated axons. X-ray scattering can specifically probe myelinated axons due to the periodicity of the myelin sheath, which yields distinct peaks in the scattering pattern. Here, in this work, we show that small-angle X-ray scattering (SAXS) can be used to detect myelinated, axon-specific fiber crossings. We first demonstrate the capability using strips of human corpus callosum to create artificial double- and triple-crossing fiber geometries, and we then apply the method in mouse, pig, vervet monkey, and human brains. We compare results to polarized light imaging (3D-PLI), tracer experiments, and to outputs from diffusion MRI that sometimes fails to detect crossings. Given its specificity, capability of 3-dimensional sampling and high resolution, SAXS could serve as a ground truth for validating fiber orientations derived using diffusion MRI as well as microscopy-based methods.

59 BASIC BIOLOGICAL SCIENCES↗

Electron ptychography achieves atomic-resolution limits set by lattice vibrations

Transmission electron microscopes use electrons with wavelengths of a few picometers, potentially capable of imaging individual atoms in solids at a resolution ultimately set by the intrinsic size of an atom. However, owing to lens aberrations and multiple scattering of electrons in the sample, the image resolution is reduced by a factor of 3 to 10. By inversely solving the multiple scattering problem and overcoming the electron-probe aberrations using electron ptychography, we demonstrate an instrumental blurring of less than 20 picometers and a linear phase response in thick samples. The measured widths of atomic columns are limited by thermal fluctuations of the atoms. As a result, our method is also capable of locating embedded atomic dopant atoms in all three dimensions with subnanometer precision from only a single projection measurement.

42 ENGINEERING↗

Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue

Myelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelin’s nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the method’s sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures.

36 MATERIALS SCIENCE↗

PtychoShelves , a versatile high-level framework for high-performance analysis of ptychographic data

Over the past decade, ptychography has been proven to be a robust tool for non-destructive high-resolution quantitative electron, X-ray and optical microscopy. It allows for quantitative reconstruction of the specimen's transmissivity, as well as recovery of the illuminating wavefront. Additionally, various algorithms have been developed to account for systematic errors and improved convergence. With fast ptychographic microscopes and more advanced algorithms, both the complexity of the reconstruction task and the data volume increase significantly. PtychoShelves is a software package which combines high-level modularity for easy and fast changes to the data-processing pipeline, and high-performance computing on CPUs and GPUs.

97 MATHEMATICS AND COMPUTING↗