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Yuzhu Li

Yuzhu Li contributes to research discovery and scholarly infrastructure.

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Published work

6 published item(s)

preprint2026arXiv

Continuous quantification of viral plaque dynamics using ultra-large-area label-free imaging enables rapid antiviral susceptibility testing

The plaque reduction assay (PRA) remains the gold standard for antiviral susceptibility testing, evaluating drug potency by measuring reductions in plaque-forming units (PFUs). However, the traditional PRA is time-consuming, labor-intensive, prone to manual counting errors, and offers limited scalability. Moreover, its reliance on destructive fixation and chemical staining reduces the assay to a static, endpoint observation, obscuring the dynamic, time-resolved kinetics of dose-dependent viral inhibition. Here, we introduce a label-free, time-resolved PRA platform that transforms the conventional assay into a continuous, high-dimensional measurement of viral infection dynamics. Our system integrates a compact lens-free imaging setup with a custom-designed ultra-large-area (100 cm^2) thin-film transistor (TFT) image sensor and deep learning-based algorithms to autonomously quantify PFU dynamics within an incubator. Validated using herpes simplex virus type-1 (HSV-1) treated with acyclovir, the platform matched chemically-stained ground truth measurements with zero false positives while accelerating readout by ~26 hours. Crucially, our system revealed that increasing drug concentrations induce temporally distinct delays and suppress new PFU formation, enabling conclusive drug efficacy evaluations within ~60 hours post-infection. This scalable, label-free framework redefines antiviral susceptibility testing as a rapid, time-resolved and information-rich measurement framework, providing a generalizable platform for virology research, high-throughput drug screening, and clinical diagnostics.

preprint2026arXiv

Principle-Guided Supervision for Interpretable Uncertainty in Medical Image Segmentation

Uncertainty quantification complements model predictions by characterizing their reliability, which is essential for high-stakes decision making such as medical image segmentation. However, most existing methods reduce uncertainty to a scalar confidence estimate, leaving its spatial distribution semantically underconstrained. In this work, we focus on uncertainty interpretability, namely, whether estimated uncertainty behaves in a human-understandable manner with respect to sources of ambiguity. We identify three perception-aligned principles requiring the spatial distribution of uncertainty to reflect: (1) image contrast between structures, (2) severity of image corruption, and (3) geometric complexity in anatomical structures. Accordingly, we develop a principle-guided uncertainty supervision framework (PriUS) based on evidential learning, in which the corresponding supervision objectives are explicitly enforced during training. We further introduce quantitative metrics to measure the consistency between predicted uncertainty and image attributes that induce ambiguity. Experiments on ACDC, ISIC, and WHS datasets showed that, compared with state-of-the-art methods, PriUS produced more consistent uncertainty estimates while maintaining competitive segmentation performance.

preprint2025arXiv

Deep learning-enabled virtual multiplexed immunostaining of label-free tissue for vascular invasion assessment

Immunohistochemistry (IHC) has transformed clinical pathology by enabling the visualization of specific proteins within tissue sections. However, traditional IHC requires one tissue section per stain, exhibits section-to-section variability, and incurs high costs and laborious staining procedures. While multiplexed IHC (mIHC) techniques enable simultaneous staining with multiple antibodies on a single slide, they are more tedious to perform and are currently unavailable in routine pathology laboratories. Here, we present a deep learning-based virtual multiplexed immunostaining framework to simultaneously generate ERG and PanCK, in addition to H&E virtual staining, enabling accurate localization and interpretation of vascular invasion in thyroid cancers. This virtual mIHC technique is based on the autofluorescence microscopy images of label-free tissue sections, and its output images closely match the histochemical staining counterparts (ERG, PanCK and H&E) of the same tissue sections. Blind evaluation by board-certified pathologists demonstrated that virtual mIHC staining achieved high concordance with the histochemical staining results, accurately highlighting epithelial cells and endothelial cells. Virtual mIHC conducted on the same tissue section also allowed the identification and localization of small vessel invasion. This multiplexed virtual IHC approach can significantly improve diagnostic accuracy and efficiency in the histopathological evaluation of vascular invasion, potentially eliminating the need for traditional staining protocols and mitigating issues related to tissue loss and heterogeneity.

preprint2022arXiv

Deep Learning-enabled Detection and Classification of Bacterial Colonies using a Thin Film Transistor (TFT) Image Sensor

Early detection and identification of pathogenic bacteria such as Escherichia coli (E. coli) is an essential task for public health. The conventional culture-based methods for bacterial colony detection usually take >24 hours to get the final read-out. Here, we demonstrate a bacterial colony-forming-unit (CFU) detection system exploiting a thin-film-transistor (TFT)-based image sensor array that saves ~12 hours compared to the Environmental Protection Agency (EPA)-approved methods. To demonstrate the efficacy of this CFU detection system, a lensfree imaging modality was built using the TFT image sensor with a sample field-of-view of ~10 cm^2. Time-lapse images of bacterial colonies cultured on chromogenic agar plates were automatically collected at 5-minute intervals. Two deep neural networks were used to detect and count the growing colonies and identify their species. When blindly tested with 265 colonies of E. coli and other coliform bacteria (i.e., Citrobacter and Klebsiella pneumoniae), our system reached an average CFU detection rate of 97.3% at 9 hours of incubation and an average recovery rate of 91.6% at ~12 hours. This TFT-based sensor can be applied to various microbiological detection methods. Due to the large scalability, ultra-large field-of-view, and low cost of the TFT-based image sensors, this platform can be integrated with each agar plate to be tested and disposed of after the automated CFU count. The imaging field-of-view of this platform can be cost-effectively increased to >100 cm^2 to provide a massive throughput for CFU detection using, e.g., roll-to-roll manufacturing of TFTs as used in the flexible display industry.

preprint2022arXiv

Virtual stain transfer in histology via cascaded deep neural networks

Pathological diagnosis relies on the visual inspection of histologically stained thin tissue specimens, where different types of stains are applied to bring contrast to and highlight various desired histological features. However, the destructive histochemical staining procedures are usually irreversible, making it very difficult to obtain multiple stains on the same tissue section. Here, we demonstrate a virtual stain transfer framework via a cascaded deep neural network (C-DNN) to digitally transform hematoxylin and eosin (H&E) stained tissue images into other types of histological stains. Unlike a single neural network structure which only takes one stain type as input to digitally output images of another stain type, C-DNN first uses virtual staining to transform autofluorescence microscopy images into H&E and then performs stain transfer from H&E to the domain of the other stain in a cascaded manner. This cascaded structure in the training phase allows the model to directly exploit histochemically stained image data on both H&E and the target special stain of interest. This advantage alleviates the challenge of paired data acquisition and improves the image quality and color accuracy of the virtual stain transfer from H&E to another stain. We validated the superior performance of this C-DNN approach using kidney needle core biopsy tissue sections and successfully transferred the H&E-stained tissue images into virtual PAS (periodic acid-Schiff) stain. This method provides high-quality virtual images of special stains using existing, histochemically stained slides and creates new opportunities in digital pathology by performing highly accurate stain-to-stain transformations.

preprint2021arXiv

Label-free virtual HER2 immunohistochemical staining of breast tissue using deep learning

The immunohistochemical (IHC) staining of the human epidermal growth factor receptor 2 (HER2) biomarker is widely practiced in breast tissue analysis, preclinical studies and diagnostic decisions, guiding cancer treatment and investigation of pathogenesis. HER2 staining demands laborious tissue treatment and chemical processing performed by a histotechnologist, which typically takes one day to prepare in a laboratory, increasing analysis time and associated costs. Here, we describe a deep learning-based virtual HER2 IHC staining method using a conditional generative adversarial network that is trained to rapidly transform autofluorescence microscopic images of unlabeled/label-free breast tissue sections into bright-field equivalent microscopic images, matching the standard HER2 IHC staining that is chemically performed on the same tissue sections. The efficacy of this virtual HER2 staining framework was demonstrated by quantitative analysis, in which three board-certified breast pathologists blindly graded the HER2 scores of virtually stained and immunohistochemically stained HER2 whole slide images (WSIs) to reveal that the HER2 scores determined by inspecting virtual IHC images are as accurate as their immunohistochemically stained counterparts. A second quantitative blinded study performed by the same diagnosticians further revealed that the virtually stained HER2 images exhibit a comparable staining quality in the level of nuclear detail, membrane clearness, and absence of staining artifacts with respect to their immunohistochemically stained counterparts. This virtual HER2 staining framework bypasses the costly, laborious, and time-consuming IHC staining procedures in laboratory, and can be extended to other types of biomarkers to accelerate the IHC tissue staining used in life sciences and biomedical workflow.