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Development of a flexible Erlang mixture model for survival analysis is introduced. The model for the survival density is built from a structured mixture of Erlang densities, mixing on the integer shape parameter with a common scale parameter. The mixture weights are constructed through increments of a distribution function on the positive real line, which is assigned a Dirichlet process prior. The model has a relatively simple structure, balancing flexibility with efficient posterior computation. Moreover, it implies a mixture representation for the hazard function that involves time-dependent mixture weights, thus offering a general approach to hazard estimation. Extension of the model is made to accommodate survival responses corresponding to multiple experimental groups, using a dependent Dirichlet process prior for the group-specific distributions that define the mixture weights. Model properties, prior specification, and posterior simulation are discussed, and the methodology is illustrated with synthetic and real data examples. 

Imaging through scattering is a pervasive and difficult problem in many biological applications. The high background and the exponentially attenuated target signals due to scattering fundamentally limits the imaging depth of fluorescence microscopy. Light-field systems are favorable for high-speed volumetric imaging, but the 2D-to-3D reconstruction is fundamentally ill-posed, and scattering exacerbates the condition of the inverse problem. Here, we develop a scattering simulator that models low-contrast target signals buried in heterogeneous strong background. We then train a deep neural network solely on synthetic data to descatter and reconstruct a 3D volume from a single-shot light-field measurement with low signal-to-background ratio (SBR). We apply this network to our previously developed computational miniature mesoscope and demonstrate the robustness of our deep learning algorithm on scattering phantoms with different scattering conditions. The network can robustly reconstruct emitters in 3D with a 2D measurement of SBR as low as 1.05 and as deep as a scattering length. We analyze fundamental tradeoffs based on network design factors and out-of-distribution data that affect the deep learning model’s generalizability to real experimental data. Broadly, we believe that our simulator-based deep learning approach can be applied to a wide range of imaging through scattering techniques where experimental paired training data is lacking.

 

We use specially designed plasmonic photodetectors to develop a new method for image differentiation that can produce edge-enhanced images without external optical elements and under incoherent illumination, unlike traditional optical spatial filters. 

Photonics provides a promising approach for image processing by spatial filtering, with the advantage of faster speeds and lower power consumption compared to electronic digital solutions. However, traditional optical spatial filters suffer from bulky form factors that limit their portability. Here we present a new approach based on pixel arrays of plasmonic directional image sensors, designed to selectively detect light incident along a small, geometrically tunable set of directions. The resulting imaging systems can function as optical spatial filters without any external filtering elements, leading to extreme size miniaturization. Furthermore, they offer the distinct capability to perform multiple filtering operations at the same time, through the use of sensor arrays partitioned into blocks of adjacent pixels with different angular responses. To establish the image processing capabilities of these devices, we present a rigorous theoretical model of their filter transfer function under both coherent and incoherent illumination. Next, we use the measured angle-resolved responsivity of prototype devices to demonstrate two examples of relevant functionalities: (1) the visualization of otherwise invisible phase objects and (2) spatial differentiation with incoherent light. These results are significant for a multitude of imaging applications ranging from microscopy in biomedicine to object recognition for computer vision.

 

Acousto-optic imaging (AOI) enables optical-contrast imaging deep inside scattering samples via localized ultrasound-modulation of scattered light. While AOI allows optical investigations at depths, its imaging resolution is inherently limited by the ultrasound wavelength, prohibiting microscopic investigations. Here, we propose a computational imaging approach that allows optical diffraction-limited imaging using a conventional AOI system. We achieve this by extracting diffraction-limited imaging information from speckle correlations in the conventionally detected ultrasound-modulated scattered-light fields. Specifically, we identify that since “memory-effect” speckle correlations allow estimation of the Fourier magnitude of the field inside the ultrasound focus, scanning the ultrasound focus enables robust diffraction-limited reconstruction of extended objects using ptychography (i.e., we exploit the ultrasound focus as the scanned spatial-gate probe required for ptychographic phase retrieval). Moreover, we exploit the short speckle decorrelation-time in dynamic media, which is usually considered a hurdle for wavefront-shaping- based approaches, for improved ptychographic reconstruction. We experimentally demonstrate noninvasive imaging of targets that extend well beyond the memory-effect range, with a 40-times resolution improvement over conventional AOI.

 

Angle-sensitive plasmonic photodetectors that can perform optical-domain spatial filtering operations are developed. The edge enhancement capabilities of these devices are demonstrated via computational imaging simulations based on their measured angular response.

 

Intensity Diffraction Tomography (IDT) is a new computational microscopy technique providing quantitative, volumetric, large field-of-view (FOV) phase imaging of biological samples. This approach uses computationally efficient inverse scattering models to recover 3D phase volumes of weakly scattering objects from intensity measurements taken under diverse illumination at a single focal plane. IDT is easily implemented in a standard microscope equipped with an LED array source and requires no exogenous contrast agents, making the technology widely accessible for biological research.Here, we discuss model and learning-based approaches for complex 3D object recovery with IDT. We present two model-based computational illumination strategies, multiplexed IDT (mIDT) [1] and annular IDT (aIDT) [2], that achieve high-throughput quantitative 3D object phase recovery at hardware-limited 4Hz and 10Hz volume rates, respectively. We illustrate these techniques on living epithelial buccal cells and Caenorhabditis elegans worms. For strong scattering object recovery with IDT, we present an uncertainty quantification framework for assessing the reliability of deep learning-based phase recovery methods [3]. This framework provides per-pixel evaluation of a neural network predictions confidence level, allowing for efficient and reliable complex object recovery. This uncertainty learning framework is widely applicable for reliable deep learning-based biomedical imaging techniques and shows significant potential for IDT. 

Coherent imaging through scatter is a challenging task. Both model-based and data-driven approaches have been explored to solve the inverse scattering problem. In our previous work, we have shown that a deep learning approach can make high-quality and highly generalizable predictions through unseen diffusers. Here, we propose a new deep neural network model that is agnostic to a broader class of perturbations including scatterer change, displacements, and system defocus up to 10× depth of field. In addition, we develop a new analysis framework for interpreting the mechanism of our deep learning model and visualizing its generalizability based on an unsupervised dimension reduction technique. We show that our model can unmix the scattering-specific information and extract the object-specific information and achieve generalization under different scattering conditions. Our work paves the way to arobustandinterpretabledeep learning approach to imaging through scattering media.

 

Traditional imaging cytometry uses fluorescence markers to identify specific structures but is limited in throughput by the labeling process. We develop a label-free technique that alleviates the physical staining and provides multiplexed readouts via a deep learning–augmented digital labeling method. We leverage the rich structural information and superior sensitivity in reflectance microscopy and show that digital labeling predicts accurate subcellular features after training on immunofluorescence images. We demonstrate up to three times improvement in the prediction accuracy over the state of the art. Beyond fluorescence prediction, we demonstrate that single cell–level structural phenotypes of cell cycles are correctly reproduced by the digital multiplexed images, including Golgi twins, Golgi haze during mitosis, and DNA synthesis. We further show that the multiplexed readouts enable accurate multiparametric single-cell profiling across a large cell population. Our method can markedly improve the throughput for imaging cytometry toward applications for phenotyping, pathology, and high-content screening.