Guoan Zheng

Lucas Kreiss, Shaowei Jiang, Xiang Li et al. · pku

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.

Shaowei Jiang, Kaikai Guo, Jun Liao et al.

Fourier ptychography is a recently developed imaging approach for large field-of-view and high-resolution microscopy. Here we model the Fourier ptychographic forward imaging process using a convolution neural network (CNN) and recover the complex object information in the network training process. In this approach, the input of the network is the point spread function in the spatial domain or the coherent transfer function in the Fourier domain. The object is treated as 2D learnable weights of a convolution or a multiplication layer. The output of the network is modeled as the loss function we aim to minimize. The batch size of the network corresponds to the number of captured low-resolution images in one forward / backward pass. We use a popular open-source machine learning library, TensorFlow, for setting up the network and conducting the optimization process. We analyze the performance of different learning rates, different solvers, and different batch sizes. It is shown that a large batch size with the Adam optimizer achieves the best performance in general. To accelerate the phase retrieval process, we also discuss a strategy to implement Fourier-magnitude projection using a multiplication neural network model. Since convolution and multiplication are the two most-common operations in imaging modeling, the reported approach may provide a new perspective to examine many coherent and incoherent systems. As a demonstration, we discuss the extensions of the reported networks for modeling single-pixel imaging and structured illumination microscopy (SIM). 4-frame resolution doubling is demonstrated using a neural network for SIM. We have made our implementation code open-source for the broad research community.

Cheng Jiang, Jun Liao, Pei Dong et al.

Artificial Intelligence (AI)-powered pathology is a revolutionary step in the world of digital pathology and shows great promise to increase both diagnosis accuracy and efficiency. However, defocus and motion blur can obscure tissue or cell characteristics hence compromising AI algorithms'accuracy and robustness in analyzing the images. In this paper, we demonstrate a deep-learning-based approach that can alleviate the defocus and motion blur of a microscopic image and output a sharper and cleaner image with retrieved fine details without prior knowledge of the blur type, blur extent and pathological stain. In this approach, a deep learning classifier is first trained to identify the image blur type. Then, two encoder-decoder networks are trained and used alone or in combination to deblur the input image. It is an end-to-end approach and introduces no corrugated artifacts as traditional blind deconvolution methods do. We test our approach on different types of pathology specimens and demonstrate great performance on image blur correction and the subsequent improvement on the diagnosis outcome of AI algorithms.

Shaowei Jiang, Jun Liao, Zichao Bian et al.

Structured illumination has been widely used for optical sectioning and 3D surface recovery. In a typical implementation, multiple images under non-uniform pattern illumination are used to recover a single object section. Axial scanning of the sample or the objective lens is needed for acquiring the 3D volumetric data. Here we demonstrate the use of axially-shifted pattern illumination (asPI) for virtual volumetric confocal imaging without axial scanning. In the reported approach, we project illumination patterns at a tilted angle with respect to the detection optics. As such, the illumination patterns shift laterally at different z sections and the sample information at different z-sections can be recovered based on the captured 2D images. We demonstrate the reported approach for virtual confocal imaging through a diffusing layer and underwater 3D imaging through diluted milk. We show that we can acquire the entire confocal volume in ~1s with a throughput of 420 megapixels per second. Our approach may provide new insights for developing confocal light ranging and detection systems in degraded visual environments.

Jun Liao, Yutong Jiang, Zichao Bian et al.

Whole slide imaging (WSI) has recently been cleared for primary diagnosis in the US. A critical challenge of WSI is to perform accurate focusing in high speed. Traditional systems create a focus map prior to scanning. For each focus point on the map, sample needs to be static in the x-y plane and axial scanning is needed to maximize the contrast. Here we report a novel focus map surveying method for WSI. The reported method requires no axial scanning, no additional camera and lens, works for stained and transparent samples, and allows continuous sample motion in the surveying process. It can be used for both brightfield and fluorescence WSI. By using a 20X, 0.75 NA objective lens, we demonstrate a mean focusing error of ~0.08 microns in the static mode and ~0.17 microns in the continuous motion mode. The reported method may provide a turnkey solution for most existing WSI systems for its simplicity, robustness, accuracy, and high-speed. It may also standardize the imaging performance of WSI systems for digital pathology and find other applications in high-content microscopy such as DNA sequencing and time-lapse live-cell imaging.