Model-Agnostic Binary Patch Grouping for Bone Marrow Whole Slide Image Representation.

Histopathology is the reference standard for pathology diagnosis, and has evolved with the digitization of glass slides [ie, whole slide images (WSIs)]. While trained histopathologists are able to diagnose diseases by examining WSIs visually, this process is time consuming and prone to variability. To address these issues, artificial intelligence models are being developed to generate slide-level representations of WSIs, summarizing the entire slide as a single vector. This enables various computational pathology applications, including interslide search, multimodal training, and slide-level classification. Achieving expressive and robust slide-level representations hinges on patch feature extraction and aggregation steps. This study proposed an additional binary patch grouping (BPG) step, a plugin that can be integrated into various slide-level representation pipelines, to enhance the quality of slide-level representation in bone marrow histopathology. BPG excludes patches with less clinical relevance through minimal interaction with the pathologist; a one-time human intervention for the entire process. This study further investigated domain-general versus domain-specific feature extraction models based on convolution and attention and examined two different feature aggregation methods, with and without BPG, showing BPG's generalizability. The results showed that using BPG boosts the performance of WSI retrieval (mean average precision at 10) by 4% and improves WSI classification (weighted-F1) by 5% compared to not using BPG. Additionally, domain-general large models and parameterized pooling produced the best-quality slide-level representations.

Whole slide image representation in bone marrow cytology.

One of the goals of AI-based computational pathology is to generate compact representations of whole slide images (WSIs) that capture the essential information needed for diagnosis. While such approaches have been applied to histopathology, few applications have been reported in cytology. Bone marrow aspirate cytology is the basis for key clinical decisions in hematology. However, visual inspection of aspirate specimens is a tedious and complex process subject to variation in interpretation, and hematopathology expertise is scarce. The ability to generate a compact representation of an aspirate specimen may form the basis for clinical decision-support tools in hematology. In this study, we leverage our previously published end-to-end AI-based system for counting and classifying cells from bone marrow aspirate WSIs, which enables the direct use of individual cells as inputs rather than WSI patches. We then construct bags of individual cell features from each WSI, and apply multiple instance learning to extract their vector representations. To evaluate the quality of our representations, we conducted WSI retrieval and classification tasks. Our results show that we achieved a mAP@10 of 0.58 ±0.02 in WSI-level image retrieval, surpassing the random-retrieval baseline of 0.39 ±0.1. Furthermore, we predicted five diagnostic labels for individual aspirate WSIs with a weighted-average F1 score of 0.57 ±0.03 using a k-nearest-neighbors (k-NN) model, outperforming guessing using empirical class prior probabilities (0.26 ±0.02). We present the first example of exploring trainable mechanisms to generate compact, slide-level representations in bone marrow cytology with deep learning. This method has the potential to summarize complex semantic information in WSIs toward improved diagnostics in hematology, and may eventually support AI-assisted computational pathology approaches.

Cell projection plots: A novel visualization of bone marrow aspirate cytology.

Deep models for cell detection have demonstrated utility in bone marrow cytology, showing impressive results in terms of accuracy and computational efficiency. However, these models have yet to be implemented in the clinical diagnostic workflow. Additionally, the metrics used to evaluate cell detection models are not necessarily aligned with clinical goals and targets. In order to address these issues, we introduce novel, automatically generated visual summaries of bone marrow aspirate specimens called cell projection plots (CPPs). Encompassing relevant biological patterns such as neutrophil maturation, CPPs provide a compact summary of bone marrow aspirate cytology. To gauge clinical relevance, CPPs were inspected by 3 hematopathologists, who decided whether corresponding diagnostic synopses matched with generated CPPs. Pathologists were able to match CPPs to the correct synopsis with a matching degree of 85%. Our finding suggests CPPs can represent clinically relevant information from bone marrow aspirate specimens and may be used to efficiently summarize bone marrow cytology to pathologists. CPPs could be a step toward human-centered implementation of artificial intelligence (AI) in hematopathology, and a basis for a diagnostic-support tool for digital pathology workflows.

Applied machine learning in hematopathology.

An increasing number of machine learning applications are being developed and applied to digital pathology, including hematopathology. The goal of these modern computerized tools is often to support diagnostic workflows by extracting and summarizing information from multiple data sources, including digital images of human tissue. Hematopathology is inherently multimodal and can serve as an ideal case study for machine learning applications. However, hematopathology also poses unique challenges compared to other pathology subspecialities when applying machine learning approaches. By modeling the pathologist workflow and thinking process, machine learning algorithms may be designed to address practical and tangible problems in hematopathology. In this article, we discuss the current trends in machine learning in hematopathology. We review currently available machine learning enabled medical devices supporting hematopathology workflows. We then explore current machine learning research trends of the field with a focus on bone marrow cytology and histopathology, and how adoption of new machine learning tools may be enabled through the transition to digital pathology.

A radiomics model for predicting the response to methylprednisolone in brain necrosis after radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: Methylprednisolone is recommended as the front-line therapy for radiation-induced brain necrosis (RN) after radiotherapy for nasopharyngeal carcinoma. However, some patients fail to benefit from methylprednisolone or even progress. This study aimed to develop and validate a radiomic model to predict the response to methylprednisolone in RN. METHODS: Sixty-six patients receiving methylprednisolone were enrolled. In total, 961 radiomic features were extracted from the pre-treatment magnetic resonance imagings of the brain. Least absolute shrinkage and selection operator regression was then applied to construct the radiomics signature. Combined with independent clinical predictors, a radiomics model was built with multivariate logistic regression analysis. Discrimination, calibration and clinical usefulness of the model were assessed. The model was internally validated using 10-fold cross-validation. RESULTS: The radiomics signature consisted of 16 selected features and achieved favorable discrimination performance. The radiomics model incorporating the radiomics signature and the duration between radiotherapy and RN diagnosis, yielded an AUC of 0.966 and an optimism-corrected AUC of 0.967 via 10-fold cross-validation, which also revealed good discrimination. Calibration curves showed good agreement. Decision curve analysis confirmed the clinical utility of the model. CONCLUSIONS: The presented radiomics model can be conveniently used to facilitate individualized prediction of the response to methylprednisolone in patients with RN.

Automated bone marrow cytology using deep learning to generate a histogram of cell types.

Background: Bone marrow cytology is required to make a hematological diagnosis, influencing critical clinical decision points in hematology. However, bone marrow cytology is tedious, limited to experienced reference centers and associated with inter-observer variability. This may lead to a delayed or incorrect diagnosis, leaving an unmet need for innovative supporting technologies. Methods: We develop an end-to-end deep learning-based system for automated bone marrow cytology. Starting with a bone marrow aspirate digital whole slide image, our system rapidly and automatically detects suitable regions for cytology, and subsequently identifies and classifies all bone marrow cells in each region. This collective cytomorphological information is captured in a representation called Histogram of Cell Types (HCT) quantifying bone marrow cell class probability distribution and acting as a cytological patient fingerprint. Results: Our system achieves high accuracy in region detection (0.97 accuracy and 0.99 ROC AUC), and cell detection and cell classification (0.75 mean average precision, 0.78 average F1-score, Log-average miss rate of 0.31). Conclusions: HCT has potential to eventually support more efficient and accurate diagnosis in hematology, supporting AI-enabled computational pathology.

A BERT model generates diagnostically relevant semantic embeddings from pathology synopses with active learning.

Background: Pathology synopses consist of semi-structured or unstructured text summarizing visual information by observing human tissue. Experts write and interpret these synopses with high domain-specific knowledge to extract tissue semantics and formulate a diagnosis in the context of ancillary testing and clinical information. The limited number of specialists available to interpret pathology synopses restricts the utility of the inherent information. Deep learning offers a tool for information extraction and automatic feature generation from complex datasets. Methods: Using an active learning approach, we developed a set of semantic labels for bone marrow aspirate pathology synopses. We then trained a transformer-based deep-learning model to map these synopses to one or more semantic labels, and extracted learned embeddings (i.e., meaningful attributes) from the model's hidden layer. Results: Here we demonstrate that with a small amount of training data, a transformer-based natural language model can extract embeddings from pathology synopses that capture diagnostically relevant information. On average, these embeddings can be used to generate semantic labels mapping patients to probable diagnostic groups with a micro-average F1 score of 0.779 Â ± 0.025. Conclusions: We provide a generalizable deep learning model and approach to unlock the semantic information inherent in pathology synopses toward improved diagnostics, biodiscovery and AI-assisted computational pathology.