arXiv subjects

Roarke Horstmeyer

Publications and source records attributed to Roarke Horstmeyer.

At least 19 recordsLinked to original sources

arXiv2025

Towards a mobile quantitative phase imaging microscope with smartphone phase-detection sensors

Quantitative phase imaging (QPI) enables visualization and quantitative extraction of the optical phase information of transparent samples. However, conventional QPI techniques typically rely on multi-frame acquisition or complex interferometric optics. In this work, we introduce Quad-Pixel Phase Gradient Imaging ($QP^{2}GI$), a single-shot quantitative phase imaging method based on a commercial quad-pixel phase detection autofocus (PDAF) sensor, where each microlens on the sensor covers a $2\times2$ pixel group. The phase gradients of the sample induce focal spot displacements under each microlens, which lead to intensity imbalances among the four pixels. By deriving the phase gradients of the sample from these imbalances, $QP^{2}GI$ reconstructs quantitative phase maps of the sample from a single exposure. We establish a light-propagation model to describe this process and evaluate its performance in a customized microscopic system. Experiments demonstrate that quantitative phase maps of microbeads and biological specimens can be reconstructed from a single acquisition, while low-coherence illumination improves robustness by suppressing coherence-related noise. These results reveal the potential of quad-pixel PDAF sensors as cost-effective platforms for single-frame QPI.

physics.optics↗

arXiv2025

Wide-Field Reflective Imaging with an Epi-Illumination Multi-Camera Array Microscope

We present an epi-illumination multi-camera array microscope (epi-MCAM) designed for wide-field reflective imaging of non-transparent samples. The epi-MCAM contains 24 tightly packed and synchronized epi-illumination microscope units, arranged in a $4 \times 6$ planar array at 18 mm spacing. Each unit contains a unique CMOS image sensor (13 megapixels each), an objective and tube lens pair, and a beamsplitter and epi-illumination light path. An epi-MCAM capture cycle produces a stitched image covering $72 \times 108~\mathrm{mm}^2$ at a micrometer scale resolution down to 2.46 $μ$m. To image samples exceeding this native field of view, we translate the entire array across the sample surface to enable high-resolution coverage of large objects. We demonstrate the system's ability to image both flat and three-dimensionally structured reflective samples, such as semiconductor wafers and printed circuit boards, which highlight the epi-MCAM's strong potential within industrial inspection applications.

physics.optics↗

arXiv2025

Curvature-adaptive gigapixel microscopy at submicron resolution and centimeter scale

Large-area microscopy with submicron resolution is limited by tradeoffs between field of view (FOV), resolution, and imaging speed. Samples are rarely flat across centimeter-scale FOV, which often requires existing solutions to use mechanical scanning to ensure focused capture at reduced throughput. Here, we present PANORAMA, a single-shot, re-imaging microscope that achieves seamless, gigapixel imaging over a 16.3$\times$18.8 $\text{mm}^2$ FOV at 0.84 um resolution without mechanical scanning. By using a telecentric photolithography lens, a large-aperture tube lens, and a flat micro-camera array with adaptive per-camera focus control, PANORAMA maintains submicron focus across flat, curved or uneven samples that span centimeters. This approach improves imaging throughput and adaptability, enabling gigapixel multi-modal microscopy of large flat and non-flat samples in one shot, thus broadening its applications in biomedical and materials imaging.

physics.optics↗

arXiv2025

Large-scale compressive microscopy via diffractive multiplexing across a sensor array

Microscopes face a trade-off between spatial resolution, field-of-view, and frame rate -- improving one of these properties typically requires sacrificing the others, due to the limited spatiotemporal throughput of the sensor. To overcome this, we propose a new microscope that achieves snapshot gigapixel-scale imaging with a sensor array and a diffractive optical element (DOE). We improve the spatiotemporal throughput in two ways. First, we capture data with an array of 48 sensors resulting in 48x more pixels than a single sensor. Second, we use point spread function (PSF) engineering and compressive sensing algorithms to fill in the missing information from the gaps surrounding the individual sensors in the array, further increasing the spatiotemporal throughput of the system by an additional >5.4x. The array of sensors is modeled as a single large-format "super-sensor," with erasures corresponding to the gaps between the individual sensors. The array is placed at the output of a (nearly) 4f imaging system, and we design a DOE for the Fourier plane that generates a distributed PSF that encodes information from the entire super-sensor area, including the gaps. We then computationally recover the large-scale image, assuming the object is sparse in some domain. Our calibration-free microscope can achieve ~3 μm resolution over >5.2 cm^2 FOVs at up to 120 fps, culminating in a total spatiotemporal throughput of 25.2 billion pixels per second. We demonstrate the versatility of our microscope in two different modes: structural imaging via darkfield contrast and functional fluorescence imaging of calcium dynamics across dozens of freely moving C. elegans simultaneously.

physics.optics↗

arXiv2025

Detecting immune cells with label-free two-photon autofluorescence and deep learning

Label-free imaging has gained broad interest because of its potential to omit elaborate staining procedures which is especially relevant for in vivo use. Label-free multiphoton microscopy (MPM), for instance, exploits two-photon excitation of natural autofluorescence (AF) from native, metabolic proteins, making it ideal for in vivo endomicroscopy. Deep learning (DL) models have been widely used in other optical imaging technologies to predict specific target annotations and thereby digitally augment the specificity of these label-free images. However, this computational specificity has only rarely been implemented for MPM. In this work, we used a data set of label-free MPM images from a series of different immune cell types (5,075 individual cells for binary classification in mixed samples and 3,424 cells for a multi-class classification task) and trained a convolutional neural network (CNN) to classify cell types based on this label-free AF as input. A low-complexity squeezeNet architecture was able to achieve reliable immune cell classification results (0.89 ROC-AUC, 0.95 PR-AUC, for binary classification in mixed samples; 0.689 F1 score, 0.697 precision, 0.748 recall, and 0.683 MCC for six-class classification in isolated samples). Perturbation tests confirmed that the model is not confused by extracellular environment and that both input AF channels (NADH and FAD) are about equally important to the classification. In the future, such predictive DL models could directly detect specific immune cells in unstained images and thus, computationally improve the specificity of label-free MPM which would have great potential for in vivo endomicroscopy.

cs.LG↗

arXiv2024

Recording dynamic facial micro-expressions with a multi-focus camera array

We present an approach of utilizing a multi-camera array system for capturing dynamic high-resolution videos of the human face, with improved imaging performance as compared to traditional single-camera configurations. Employing an array of 54 individual high-resolution cameras, each with its own 13 megapixel sensor (709 megapixels total), we uniquely focus each camera to a different plane across the curved surface of the human face in order to capture dynamic facial expressions. Post-processing methods then stitch together each synchronized set of 54 images into a composite video frame. Our multi-focus strategy overcomes the resolution and depth-of-field (DOF) limitations for capturing macroscopically curved surfaces such as the human face, while maintaining high lateral resolution. Specifically we demonstrate how our setup achieves a generally uniform lateral resolution of 26.75 +/- 8.8 micrometer across a composite DOF of ~43mm that covers the entire face (85 cm^2 + FOV). Compared to a single-focus configuration this is almost a 10-fold increase in effective DOF. We believe that our new approach for multi-focus camera array video sets the stage for future video capture of a variety of dynamic and macroscopically curved surfaces at microscopic resolution.

physics.optics↗

arXiv2024

Rapid 3D imaging at cellular resolution for digital cytopathology with a multi-camera array scanner (MCAS)

Optical microscopy has long been the standard method for diagnosis in cytopathology. Whole slide scanners can image and digitize large sample areas automatically, but are slow, expensive and therefore not widely available. Clinical diagnosis of cytology specimens is especially challenging since these samples are both spread over large areas and thick, which requires 3D capture. Here, we introduce a new parallelized microscope for scanning thick specimens across extremely wide fields-of-view (54x72 mm^2) at 1.2 and 0.6 μm resolutions, accompanied by machine learning software to rapidly assess these 16 gigapixel scans. This Multi-Camera Array Scanner (MCAS) comprises 48 micro-cameras closely arranged to simultaneously image different areas. By capturing 624 megapixels per snapshot, the MCAS is significantly faster than most conventional whole slide scanners. We used this system to digitize entire cytology samples (scanning three entire slides in 3D in just several minutes) and demonstrate two machine learning techniques to assist pathologists: first, an adenocarcinoma detection model in lung specimens (0.73 recall); second, a slide-level classification model of lung smears (0.969 AUC).

physics.optics↗

arXiv2024

Beneath the Surface: Revealing Deep-Tissue Blood Flow in Human Subjects with Massively Parallelized Diffuse Correlation Spectroscopy

Diffuse Correlation Spectroscopy (DCS) allows the label-free investigation of microvascular dynamics deep within living tissue. However, common implementations of DCS are currently limited to measurement depths of $\sim 1-1.5cm$, which can limit the accuracy of cerebral hemodynamics measurement. Here we present massively parallelized DCS (pDCS) using novel single photon avalanche detector (SPAD) arrays with up to 500x500 individual channels. The new SPAD array technology can boost the signal-to-noise ratio by a factor of up to 500 compared to single-pixel DCS, or by more than 15-fold compared to the most recent state-of-the-art pDCS demonstrations. Our results demonstrate the first in vivo use of this massively parallelized DCS system to measure cerebral blood flow changes at $\sim 2cm$ depth in human adults. We compared different modes of operation and applied a dual detection strategy, where a secondary SPAD array is used to simultaneously assess the superficial blood flow as a built-in reference measurement. While the blood flow in the superficial scalp tissue showed no significant change during cognitive activation, the deep pDCS measurement showed a statistically significant increase in the derived blood flow index of 8-12% when compared to the control rest state.

physics.med-ph↗

arXiv2024

A comprehensive overview of diffuse correlation spectroscopy: theoretical framework, recent advances in hardware, analysis, and applications

Diffuse correlation spectroscopy (DCS) is a powerful tool for assessing microvascular hemodynamic in deep tissues. Recent advances in sensors, lasers, and deep learning have further boosted the development of new DCS methods. However, newcomers might feel overwhelmed, not only by the already complex DCS theoretical framework but also by the broad range of component options and system architectures. To facilitate new entry into this exciting field, we present a comprehensive review of DCS hardware architectures (continuous-wave, frequency-domain, and time-domain) and summarize corresponding theoretical models. Further, we discuss new applications of highly integrated silicon single-photon avalanche diode (SPAD) sensors in DCS, compare SPADs with existing sensors, and review other components (lasers, fibers, and correlators), as well as new data analysis tools, including deep learning. Potential applications in medical diagnosis are discussed, and an outlook for the future directions is provided, to offer effective guidance to embark on DCS research.

physics.ins-det↗

arXiv2023

Computational 3D topographic microscopy from terabytes of data per sample

We present a large-scale computational 3D topographic microscope that enables 6-gigapixel profilometric 3D imaging at micron-scale resolution across $>$110 cm$^2$ areas over multi-millimeter axial ranges. Our computational microscope, termed STARCAM (Scanning Topographic All-in-focus Reconstruction with a Computational Array Microscope), features a parallelized, 54-camera architecture with 3-axis translation to capture, for each sample of interest, a multi-dimensional, 2.1-terabyte (TB) dataset, consisting of a total of 224,640 9.4-megapixel images. We developed a self-supervised neural network-based algorithm for 3D reconstruction and stitching that jointly estimates an all-in-focus photometric composite and 3D height map across the entire field of view, using multi-view stereo information and image sharpness as a focal metric. The memory-efficient, compressed differentiable representation offered by the neural network effectively enables joint participation of the entire multi-TB dataset during the reconstruction process. To demonstrate the broad utility of our new computational microscope, we applied STARCAM to a variety of decimeter-scale objects, with applications ranging from cultural heritage to industrial inspection.

physics.optics↗

arXiv2023

Tensorial tomographic Fourier Ptychography with applications to muscle tissue imaging

We report Tensorial tomographic Fourier Ptychography (ToFu), a new non-scanning label-free tomographic microscopy method for simultaneous imaging of quantitative phase and anisotropic specimen information in 3D. Built upon Fourier Ptychography, a quantitative phase imaging technique, ToFu additionally highlights the vectorial nature of light. The imaging setup consists of a standard microscope equipped with an LED matrix, a polarization generator, and a polarization-sensitive camera. Permittivity tensors of anisotropic samples are computationally recovered from polarized intensity measurements across three dimensions. We demonstrate ToFu's efficiency through volumetric reconstructions of refractive index, birefringence, and orientation for various validation samples, as well as tissue samples from muscle fibers and diseased heart tissue. Our reconstructions of muscle fibers resolve their 3D fine-filament structure and yield consistent morphological measurements compared to gold-standard second harmonic generation scanning confocal microscope images found in the literature. Additionally, we demonstrate reconstructions of a heart tissue sample that carries important polarization information for detecting cardiac amyloidosis.

physics.optics↗

arXiv2023

Digital staining in optical microscopy using deep learning -- a review

Until recently, conventional biochemical staining had the undisputed status as well-established benchmark for most biomedical problems related to clinical diagnostics, fundamental research and biotechnology. Despite this role as gold-standard, staining protocols face several challenges, such as a need for extensive, manual processing of samples, substantial time delays, altered tissue homeostasis, limited choice of contrast agents for a given sample, 2D imaging instead of 3D tomography and many more. Label-free optical technologies, on the other hand, do not rely on exogenous and artificial markers, by exploiting intrinsic optical contrast mechanisms, where the specificity is typically less obvious to the human observer. Over the past few years, digital staining has emerged as a promising concept to use modern deep learning for the translation from optical contrast to established biochemical contrast of actual stainings. In this review article, we provide an in-depth analysis of the current state-of-the-art in this field, suggest methods of good practice, identify pitfalls and challenges and postulate promising advances towards potential future implementations and applications.

eess.IV↗

arXiv2023

Imaging across multiple spatial scales with the multi-camera array microscope

This article experimentally examines different configurations of a novel multi-camera array microscope (MCAM) imaging technology. The MCAM is based upon a densely packed array of "micro-cameras" to jointly image across a large field-of-view at high resolution. Each micro-camera within the array images a unique area of a sample of interest, and then all acquired data with 54 micro-cameras are digitally combined into composite frames, whose total pixel counts significantly exceed the pixel counts of standard microscope systems. We present results from three unique MCAM configurations for different use cases. First, we demonstrate a configuration that simultaneously images and estimates the 3D object depth across a 100 x 135 mm^2 field-of-view (FOV) at approximately 20 um resolution, which results in 0.15 gigapixels (GP) per snapshot. Second, we demonstrate an MCAM configuration that records video across a continuous 83 x 123 mm^2 FOV with two-fold increased resolution (0.48 GP per frame). Finally, we report a third high-resolution configuration (2 um resolution) that can rapidly produce 9.8 GP composites of large histopathology specimens.

eess.IV↗

arXiv2023

Parallelized computational 3D video microscopy of freely moving organisms at multiple gigapixels per second

To study the behavior of freely moving model organisms such as zebrafish (Danio rerio) and fruit flies (Drosophila) across multiple spatial scales, it would be ideal to use a light microscope that can resolve 3D information over a wide field of view (FOV) at high speed and high spatial resolution. However, it is challenging to design an optical instrument to achieve all of these properties simultaneously. Existing techniques for large-FOV microscopic imaging and for 3D image measurement typically require many sequential image snapshots, thus compromising speed and throughput. Here, we present 3D-RAPID, a computational microscope based on a synchronized array of 54 cameras that can capture high-speed 3D topographic videos over a 135-cm^2 area, achieving up to 230 frames per second at throughputs exceeding 5 gigapixels (GPs) per second. 3D-RAPID features a 3D reconstruction algorithm that, for each synchronized temporal snapshot, simultaneously fuses all 54 images seamlessly into a globally-consistent composite that includes a coregistered 3D height map. The self-supervised 3D reconstruction algorithm itself trains a spatiotemporally-compressed convolutional neural network (CNN) that maps raw photometric images to 3D topography, using stereo overlap redundancy and ray-propagation physics as the only supervision mechanism. As a result, our end-to-end 3D reconstruction algorithm is robust to generalization errors and scales to arbitrarily long videos from arbitrarily sized camera arrays. The scalable hardware and software design of 3D-RAPID addresses a longstanding problem in the field of behavioral imaging, enabling parallelized 3D observation of large collections of freely moving organisms at high spatiotemporal throughputs, which we demonstrate in ants (Pogonomyrmex barbatus), fruit flies, and zebrafish larvae.

physics.optics↗

arXiv2022

Large-scale single-photon imaging

Benefiting from its single-photon sensitivity, single-photon avalanche diode (SPAD) array has been widely applied in various fields such as fluorescence lifetime imaging and quantum computing. However, large-scale high-fidelity single-photon imaging remains a big challenge, due to the complex hardware manufacture craft and heavy noise disturbance of SPAD arrays. In this work, we introduce deep learning into SPAD, enabling super-resolution single-photon imaging over an order of magnitude, with significant enhancement of bit depth and imaging quality. We first studied the complex photon flow model of SPAD electronics to accurately characterize multiple physical noise sources, and collected a real SPAD image dataset (64 $\times$ 32 pixels, 90 scenes, 10 different bit depth, 3 different illumination flux, 2790 images in total) to calibrate noise model parameters. With this real-world physical noise model, we for the first time synthesized a large-scale realistic single-photon image dataset (image pairs of 5 different resolutions with maximum megapixels, 17250 scenes, 10 different bit depth, 3 different illumination flux, 2.6 million images in total) for subsequent network training. To tackle the severe super-resolution challenge of SPAD inputs with low bit depth, low resolution, and heavy noise, we further built a deep transformer network with a content-adaptive self-attention mechanism and gated fusion modules, which can dig global contextual features to remove multi-source noise and extract full-frequency details. We applied the technique on a series of experiments including macroscopic and microscopic imaging, microfluidic inspection, and Fourier ptychography. The experiments validate the technique's state-of-the-art super-resolution SPAD imaging performance, with more than 5 dB superiority on PSNR compared to the existing methods.

physics.optics↗

arXiv2022

Tensorial tomographic differential phase-contrast microscopy

We report Tensorial Tomographic Differential Phase-Contrast microscopy (T2DPC), a quantitative label-free tomographic imaging method for simultaneous measurement of phase and anisotropy. T2DPC extends differential phase-contrast microscopy, a quantitative phase imaging technique, to highlight the vectorial nature of light. The method solves for permittivity tensor of anisotropic samples from intensity measurements acquired with a standard microscope equipped with an LED matrix, a circular polarizer, and a polarization-sensitive camera. We demonstrate accurate volumetric reconstructions of refractive index, birefringence, and orientation for various validation samples, and show that the reconstructed polarization structures of a biological specimen are predictive of pathology.

physics.optics↗

arXiv2022

Multi-modal imaging using a cascaded microscope design

We present a new Multimodal Fiber Array Snapshot Technique (M-FAST), based on an array of 96 compact cameras placed behind a primary objective lens and a fiber bundle array. which is capable of large-area, high-resolution, multi-channel video acquisition. The proposed design provides two key improvements to prior cascaded imaging system approaches: a novel optical arrangement that accommodates the use of planar camera arrays, and the new ability to acquire multi-modal image data acquisition. M-FAST is a multi-modal, scalable imaging system that can acquire snapshot dual-channel fluorescence images as well as d phase contrast measurements over a large 8x10mm^2 FOV at 2.2um full-pitch resolution.

physics.optics↗

arXiv2022

Imaging dynamics beneath turbid media via parallelized single-photon detection

Noninvasive optical imaging through dynamic scattering media has numerous important biomedical applications but still remains a challenging task. While standard diffuse imaging methods measure optical absorption or fluorescent emission, it is also well-established that the temporal correlation of scattered coherent light diffuses through tissue much like optical intensity. Few works to date, however, have aimed to experimentally measure and process such temporal correlation data to demonstrate deep-tissue video reconstruction of decorrelation dynamics. In this work, we utilize a single-photon avalanche diode (SPAD) array camera to simultaneously monitor the temporal dynamics of speckle fluctuations at the single-photon level from 12 different phantom tissue surface locations delivered via a customized fiber bundle array. We then apply a deep neural network to convert the acquired single-photon measurements into video of scattering dynamics beneath rapidly decorrelating tissue phantoms. We demonstrate the ability to reconstruct images of transient (0.1-0.4s) dynamic events occurring up to 8 mm beneath a decorrelating tissue phantom with millimeter-scale resolution, and highlight how our model can flexibly extend to monitor flow speed within buried phantom vessels.

physics.optics↗