Artificial intelligence-assisted quantification and assessment of whole slide images for pediatric kidney disease diagnosis.

MOTIVATION: Pediatric kidney disease is a widespread, progressive condition that severely impacts growth and development of children. Chronic kidney disease is often more insidious in children than in adults, usually requiring a renal biopsy for diagnosis. Biopsy evaluation requires copious examination by trained pathologists, which can be tedious and prone to human error. In this study, we propose an artificial intelligence (AI) method to assist pathologists in accurate segmentation and classification of pediatric kidney structures, named as AI-based Pediatric Kidney Diagnosis (APKD). RESULTS: We collected 2935 pediatric patients diagnosed with kidney disease for the development of APKD. The dataset comprised 93 932 histological structures annotated manually by three skilled nephropathologists. APKD scored an average accuracy of 94% for each kidney structure category, including 99% in the glomerulus. We found strong correlation between the model and manual detection in detected glomeruli (Spearman correlation coefficient r = 0.98, P < .001; intraclass correlation coefficient ICC = 0.98, 95% CI = 0.96-0.98). Compared to manual detection, APKD was approximately 5.5 times faster in segmenting glomeruli. Finally, we show how the pathological features extracted by APKD can identify focal abnormalities of the glomerular capillary wall to aid in the early diagnosis of pediatric kidney disease. AVAILABILITY AND IMPLEMENTATION: https://github.com/ChunyueFeng/Kidney-DataSet.

A novel pipeline for computerized mouse spermatogenesis staging.

MOTIVATION: Differentiating 12 stages of the mouse seminiferous epithelial cycle is vital towards understanding the dynamic spermatogenesis process. However, it is challenging since two adjacent spermatogenic stages are morphologically similar. Distinguishing Stages I-III from Stages IV-V is important for histologists to understand sperm development in wildtype mice and spermatogenic defects in infertile mice. To achieve this, we propose a novel pipeline for computerized spermatogenesis staging (CSS). RESULTS: The CSS pipeline comprises four parts: (i) A seminiferous tubule segmentation model is developed to extract every single tubule; (ii) A multi-scale learning (MSL) model is developed to integrate local and global information of a seminiferous tubule to distinguish Stages I-V from Stages VI-XII; (iii) a multi-task learning (MTL) model is developed to segment the multiple testicular cells for Stages I-V without an exhaustive requirement for manual annotation; (iv) A set of 204D image-derived features is developed to discriminate Stages I-III from Stages IV-V by capturing cell-level and image-level representation. Experimental results suggest that the proposed MSL and MTL models outperform classic single-scale and single-task models when manual annotation is limited. In addition, the proposed image-derived features are discriminative between Stages I-III and Stages IV-V. In conclusion, the CSS pipeline can not only provide histologists with a solution to facilitate quantitative analysis for spermatogenesis stage identification but also help them to uncover novel computerized image-derived biomarkers. AVAILABILITY AND IMPLEMENTATION: https://github.com/jydada/CSS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Automatic DNA replication tract measurement to assess replication and repair dynamics at the single-molecule level.

MOTIVATION: DNA fibre assay has a potential application in genomic medicine, cancer and stem cell research at the single-molecule level. A major challenge for the clinical and research implementation of DNA fibre assays is the slow speed in which manual analysis takes place as it limits the clinical actionability. While automatic detection of DNA fibres speeds up this process considerably, current publicly available software have limited features in terms of their user interface for manual correction of results, which in turn limit their accuracy and ability to account for atypical structures that may be important in diagnosis or investigative studies. We recognize that core improvements can be made to the GUI to allow for direct interaction with automatic results to preserve accuracy as well as enhance the versatility of automatic DNA fibre detection for use in variety of situations. RESULTS: To address the unmet needs of diverse DNA fibre analysis investigations, we propose DNA Stranding, an open-source software that is able to perform accurate fibre length quantification (13.22% mean relative error) and fibre pattern recognition (R > 0.93) with up to six fibre patterns supported. With the graphical interface, we developed, user can conduct semi-automatic analyses which benefits from the advantages of both automatic and manual processes to improve workflow efficiency without compromising accuracy. AVAILABILITY AND IMPLEMENTATION: The software package is available at https://github.com/lgole/DNAStranding. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A comprehensive AI model development framework for consistent Gleason grading.

BACKGROUND: Artificial Intelligence(AI)-based solutions for Gleason grading hold promise for pathologists, while image quality inconsistency, continuous data integration needs, and limited generalizability hinder their adoption and scalability. METHODS: We present a comprehensive digital pathology workflow for AI-assisted Gleason grading. It incorporates A!MagQC (image quality control), A!HistoClouds (cloud-based annotation), Pathologist-AI Interaction (PAI) for continuous model improvement, Trained on Akoya-scanned images only, the model utilizes color augmentation and image appearance migration to address scanner variations. We evaluate it on Whole Slide Images (WSI) from another five scanners and conduct validations with pathologists to assess AI efficacy and PAI. RESULTS: Our model achieves an average F1 score of 0.80 on annotations and 0.71 Quadratic Weighted Kappa on WSIs for Akoya-scanned images. Applying our generalization solution increases the average F1 score for Gleason pattern detection from 0.73 to 0.88 on images from other scanners. The model accelerates Gleason scoring time by 43% while maintaining accuracy. Additionally, PAI improve annotation efficiency by 2.5 times and led to further improvements in model performance. CONCLUSIONS: This pipeline represents a notable advancement in AI-assisted Gleason grading for improved consistency, accuracy, and efficiency. Unlike previous methods limited by scanner specificity, our model achieves outstanding performance across diverse scanners. This improvement paves the way for its seamless integration into clinical workflows.

Gleason grading is a well-accepted diagnostic standard to assess the severity of prostate cancer in patients' tissue samples, based on how abnormal the cells in their prostate tumor look under a microscope. This process can be complex and time-consuming. We explore how artificial intelligence (AI) can help pathologists perform Gleason grading more efficiently and consistently. We build an AI-based system which automatically checks image quality, standardizes the appearance of images from different equipment, learns from pathologists' feedback, and constantly improves model performance. Testing shows that our approach achieves consistent results across different equipment and improves efficiency of the grading process. With further testing and implementation in the clinic, our approach could potentially improve prostate cancer diagnosis and management.

Fatigue performance analysis of strength-graded zirconia polycrystals for monolithic three-unit implant-supported prostheses.

The aim of this study was to evaluate the fatigue behavior of strength-graded zirconia polycrystals used as monolithic three-unit implant-supported prosthesis; complementarily, crystalline phase and micromorphology were also assessed. Fixed prostheses with 3 elements supported by 2 implants were confectioned, as follows: Group 3Y/5Y - monolithic structures of a graded 3Y-TZP/5Y-TZP zirconia (IPS e.max® ZirCAD PRIME); Group 4Y/5Y - monolithic structures of a graded 4Y-TZP/5Y-TZP zirconia (IPS e.max® ZirCAD MT Multi); Group Bilayer - framework of a 3Y-TZP zirconia (Zenostar T) veneered with porcelain (IPS e.max Ceram). The samples were tested for fatigue performance with step-stress analysis. The fatigue failure load (FFL), the number of cycles required until failure (CFF), and the survival rates in each cycle were recorded. The Weibull module was calculated and the fractography analyzed. The crystalline structural content via Micro-Raman spectroscopy and the crystalline grain size via Scanning Electron microscopy were also assessed for graded structures. Group 3Y/5Y showed the highest FFL, CFF, probability of survival, and reliability (based on Weibull modulus). Group 4Y/5Y showed significantly superior FFL and probability of survival than group bilayer. Fractographic analysis revealed catastrophic flaws in the monolithic structure and cohesive fracture of porcelain in bilayer prostheses, all originating from the occlusal contact point. The graded zirconia presented small grain size (≤0.61 µm), with the smallest values at the cervical region. The main composition of graded zirconia was of grains at tetragonal phase. The strength-graded monolithic zirconia, especially the 3Y-TZP/5Y-TZP, showed to be promising for use as monolithic three-unit implant-supported prosthesis.

Quantitative image-based collagen structural features predict the reversibility of hepatitis C virus-induced liver fibrosis post antiviral therapies.

The novel targeted therapeutics for hepatitis C virus (HCV) in last decade solved most of the clinical needs for this disease. However, despite antiviral therapies resulting in sustained virologic response (SVR), a challenge remains where the stage of liver fibrosis in some patients remains unchanged or even worsens, with a higher risk of cirrhosis, known as the irreversible group. In this study, we provided novel tissue level collagen structural insight into early prediction of irreversible cases via image based computational analysis with a paired data cohort (of pre- and post-SVR) following direct-acting-antiviral (DAA)-based treatment. Two Photon Excitation and Second Harmonic Generation microscopy was used to image paired biopsies from 57 HCV patients and a fully automated digital collagen profiling platform was developed. In total, 41 digital image-based features were profiled where four key features were discovered to be strongly associated with fibrosis reversibility. The data was validated for prognostic value by prototyping predictive models based on two selected features: Collagen Area Ratio and Collagen Fiber Straightness. We concluded that collagen aggregation pattern and collagen thickness are strong indicators of liver fibrosis reversibility. These findings provide the potential implications of collagen structural features from DAA-based treatment and paves the way for a more comprehensive early prediction of reversibility using pre-SVR biopsy samples to enhance timely medical interventions and therapeutic strategies. Our findings on DAA-based treatment further contribute to the understanding of underline governing mechanism and knowledge base of structural morphology in which the future non-invasive prediction solution can be built upon.