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1. Deep learning extended depth-of-field microscope for fast and slide-free histology

   https://doi.org/10.1073/pnas.2013571117  

   Jin, Lingbo; Tang, Yubo; Wu, Yicheng; Coole, Jackson B.; Tan, Melody T.; Zhao, Xuan; Badaoui, Hawraa; Robinson, Jacob T.; Williams, Michelle D.; Gillenwater, Ann M.; et al (December 2020, Proceedings of the National Academy of Sciences)

   null (Ed.)

   Microscopic evaluation of resected tissue plays a central role in the surgical management of cancer. Because optical microscopes have a limited depth-of-field (DOF), resected tissue is either frozen or preserved with chemical fixatives, sliced into thin sections placed on microscope slides, stained, and imaged to determine whether surgical margins are free of tumor cells—a costly and time- and labor-intensive procedure. Here, we introduce a deep-learning extended DOF (DeepDOF) microscope to quickly image large areas of freshly resected tissue to provide histologic-quality images of surgical margins without physical sectioning. The DeepDOF microscope consists of a conventional fluorescence microscope with the simple addition of an inexpensive (less than $10) phase mask inserted in the pupil plane to encode the light field and enhance the depth-invariance of the point-spread function. When used with a jointly optimized image-reconstruction algorithm, diffraction-limited optical performance to resolve subcellular features can be maintained while significantly extending the DOF (200 µm). Data from resected oral surgical specimens show that the DeepDOF microscope can consistently visualize nuclear morphology and other important diagnostic features across highly irregular resected tissue surfaces without serial refocusing. With the capability to quickly scan intact samples with subcellular detail, the DeepDOF microscope can improve tissue sampling during intraoperative tumor-margin assessment, while offering an affordable tool to provide histological information from resected tissue specimens in resource-limited settings. 

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2. High-rate emphasized DeepLabV3Plus for Semantic Segmentation of Breast Cancer-related Hematoxylin and Eosin-stained Images

   https://doi.org/10.1109/EMBC53108.2024.10782325  

   Lee, Sanghoon; Zhao, Yanjun; Choi, Wookjin (July 2024, IEEE)

   Deep learning algorithms have been successfully adopted to extract meaningful information from digital images, yet many of them have been untapped in the semantic image segmentation of histopathology images. In this paper, we propose a deep convolutional neural network model that strengthens Atrous separable convolutions with a high rate within spatial pyramid pooling for histopathology image segmentation. A well-known model called DeepLabV3Plus was used for the encoder and decoder process. ResNet50 was adopted for the encoder block of the model which provides us the advantage of attenuating the problem of the increased depth of the network by using skip connections. Three Atrous separable convolutions with higher rates were added to the existing Atrous separable convolutions. We conducted a performance evaluation on three tissue types: tumor, tumor-infiltrating lymphocytes, and stroma for comparing the proposed model with the eight state-of-the-art deep learning models: DeepLabV3, DeepLabV3Plus, LinkNet, MANet, PAN, PSPnet, UNet, and UNet++. The performance results show that the proposed model outperforms the eight models on mIOU (0.8058/0.7792) and FSCR (0.8525/0.8328) for both tumor and tumor-infiltrating lymphocytes. 

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3. Deep learning-enabled virtual histological staining of biological samples

   https://doi.org/10.1038/s41377-023-01104-7  

   Bai, Bijie; Yang, Xilin; Li, Yuzhu; Zhang, Yijie; Pillar, Nir; Ozcan, Aydogan (March 2023, Light: Science & Applications)

   Abstract Histological staining is the gold standard for tissue examination in clinical pathology and life-science research, which visualizes the tissue and cellular structures using chromatic dyes or fluorescence labels to aid the microscopic assessment of tissue. However, the current histological staining workflow requires tedious sample preparation steps, specialized laboratory infrastructure, and trained histotechnologists, making it expensive, time-consuming, and not accessible in resource-limited settings. Deep learning techniques created new opportunities to revolutionize staining methods by digitally generating histological stains using trained neural networks, providing rapid, cost-effective, and accurate alternatives to standard chemical staining methods. These techniques, broadly referred to asvirtual staining, were extensively explored by multiple research groups and demonstrated to be successful in generating various types of histological stains from label-free microscopic images of unstained samples; similar approaches were also used for transforming images of an already stained tissue sample into another type of stain, performing virtual stain-to-stain transformations. In this Review, we provide a comprehensive overview of the recent research advances in deep learning-enabled virtual histological staining techniques. The basic concepts and the typical workflow of virtual staining are introduced, followed by a discussion of representative works and their technical innovations. We also share our perspectives on the future of this emerging field, aiming to inspire readers from diverse scientific fields to further expand the scope of deep learning-enabled virtual histological staining techniques and their applications. 

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4. Dynamic predictions of postoperative complications from explainable, uncertainty-aware, and multi-task deep neural networks

   https://doi.org/10.1038/s41598-023-27418-5  

   Shickel, Benjamin; Loftus, Tyler J.; Ruppert, Matthew; Upchurch, Gilbert R.; Ozrazgat-Baslanti, Tezcan; Rashidi, Parisa; Bihorac, Azra (December 2023, Scientific Reports)

   Abstract Accurate prediction of postoperative complications can inform shared decisions regarding prognosis, preoperative risk-reduction, and postoperative resource use. We hypothesized that multi-task deep learning models would outperform conventional machine learning models in predicting postoperative complications, and that integrating high-resolution intraoperative physiological time series would result in more granular and personalized health representations that would improve prognostication compared to preoperative predictions. In a longitudinal cohort study of 56,242 patients undergoing 67,481 inpatient surgical procedures at a university medical center, we compared deep learning models with random forests and XGBoost for predicting nine common postoperative complications using preoperative, intraoperative, and perioperative patient data. Our study indicated several significant results across experimental settings that suggest the utility of deep learning for capturing more precise representations of patient health for augmented surgical decision support. Multi-task learning improved efficiency by reducing computational resources without compromising predictive performance. Integrated gradients interpretability mechanisms identified potentially modifiable risk factors for each complication. Monte Carlo dropout methods provided a quantitative measure of prediction uncertainty that has the potential to enhance clinical trust. Multi-task learning, interpretability mechanisms, and uncertainty metrics demonstrated potential to facilitate effective clinical implementation. 

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5. Artifact-free whole-slide imaging with structured illumination microscopy and Bayesian image reconstruction

   https://doi.org/10.1093/gigascience/giaa035  

   Johnson, Karl A; Hagen, Guy M (April 2020, GigaScience)

   Abstract Background Structured illumination microscopy (SIM) is a method that can be used to image biological samples and can achieve both optical sectioning and super-resolution effects. Optimization of the imaging set-up and data-processing methods results in high-quality images without artifacts due to mosaicking or due to the use of SIM methods. Reconstruction methods based on Bayesian estimation can be used to produce images with a resolution beyond that dictated by the optical system. Findings Five complete datasets are presented including large panoramic SIM images of human tissues in pathophysiological conditions. Cancers of the prostate, skin, ovary, and breast, as well as tuberculosis of the lung, were imaged using SIM. The samples are available commercially and are standard histological preparations stained with hematoxylin-eosin. Conclusion The use of fluorescence microscopy is increasing in histopathology. There is a need for methods that reduce artifacts caused by the use of image-stitching methods or optical sectioning methods such as SIM. Stitched SIM images produce results that may be useful for intraoperative histology. Releasing high-quality, full-slide images and related data will aid researchers in furthering the field of fluorescent histopathology. 

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