Multimodal alignment of histopathology encoders with transcriptomic and genomic data has been shown to significantly improve performance in downstream diagnostic tasks. Hematological cytology is unique in that visual single-cell evaluation is often paired with cytogenetics and molecular genetics for blood cancer diagnosis. In this study, we present a framework to align single white blood cell images with chromosomal aberrations (karyotype) and somatic mutations from targeted gene panels. Our training strategy follows a two-stage approach: (i) self-supervised, vision-only pretraining of a transformer aggregator using an iBOT head on a cohort of over 1500 patients, and (ii) genetic alignment via supervised contrastive loss on acute myeloid leukemia patients. Our genetically aligned patient encoder improves hematological diagnostic tasks, outperforming slide-level histopathology foundation models. Additionally, the model provides off-the-shelf retrieval capabilities for diseases and genetic alterations. Incorporating genetic data into patient encoders increases the quality of patient representations, providing a framework that aligns with clinical diagnostic workflows and paves the wa
Hematologic toxicity (HT) is a major dose-limiting complication of pelvic radiotherapy for cervical cancer. Although radiomic and dosiomic features improve HT prediction beyond dosimetric metrics, their performance is highly sensitive to contour variability, limiting generalizability. We developed a cohort-aware representation-learning framework to address this challenge. We retrospectively analyzed 152 cervical cancer patients treated with pelvic radiotherapy without concurrent chemotherapy. Patients were divided into two cohorts based on the operators performing pelvic bone segmentation. HT prediction models were developed using cohort-specific training, pooled training, statistical harmonization, and a cohort-aware neural network (CANN) that learns shared and cohort-specific representations with contrastive regularization. Performance was evaluated using cross-validation and an independent test set. Cohort-specific models achieved test AUCs of 0.77 and 0.71, outperforming a dosimetry-only model (AUC=0.58). Directly pooling cohorts reduced performance (test AUC=0.64). Statistical harmonization provided limited benefit, while adversarial and correlation-based alignment further deg
Peripheral blood smears remain a cornerstone in the diagnosis of hematological neoplasms, offering rapid and valuable insights that inform subsequent diagnostic steps. However, since neoplastic transformations typically arise in the bone marrow, they may not manifest as detectable aberrations in peripheral blood, presenting a diagnostic challenge. In this paper, we introduce cAItomorph, an explainable transformer-based AI model, trained to classify hematological malignancies based on peripheral blood cytomorphology. Our data comprises peripheral blood single-cell images from 6115 patients with diagnoses confirmed by cytomorphology, cytogenetics, molecular genetics, and immunophenotyping from bone marrow samples, and 495 healthy controls, eight coarse classes. cAItomorph leverages the DinoBloom hematology foundation model and aggregates image encodings via a transformer-based architecture into a single vector. It achieves an overall accuracy of 0.72 in eight disease classification, with F1 scores of 0.76 for acute leukemia, 0.80 for myeloproliferative neoplasms and 0.94 for healthy cases. The overall accuracy increases to 0.87 in top-2 predictions. cAItomorph achieves high sensitivi
The dynamic environment of laboratories and clinics, with streams of data arriving on a daily basis, requires regular updates of trained machine learning models for consistent performance. Continual learning is supposed to help train models without catastrophic forgetting. However, state-of-the-art methods are ineffective for multiple instance learning (MIL), which is often used in single-cell-based hematologic disease diagnosis (e.g., leukemia detection). Here, we propose the first continual learning method tailored specifically to MIL. Our method is rehearsal-based over a selection of single instances from various bags. We use a combination of the instance attention score and distance from the bag mean and class mean vectors to carefully select which samples and instances to store in exemplary sets from previous tasks, preserving the diversity of the data. Using the real-world input of one month of data from a leukemia laboratory, we study the effectiveness of our approach in a class incremental scenario, comparing it to well-known continual learning methods. We show that our method considerably outperforms state-of-the-art methods, providing the first continual learning approach
In the realm of hematologic cell populations classification, the intricate patterns within flow cytometry data necessitate advanced analytical tools. This paper presents 'HemaGraph', a novel framework based on Graph Attention Networks (GATs) for single-cell multi-class classification of hematological cells from flow cytometry data. Harnessing the power of GATs, our method captures subtle cell relationships, offering highly accurate patient profiling. Based on evaluation of data from 30 patients, HemaGraph demonstrates classification performance across five different cell classes, outperforming traditional methodologies and state-of-the-art methods. Moreover, the uniqueness of this framework lies in the training and testing phase of HemaGraph, where it has been applied for extremely large graphs, containing up to hundreds of thousands of nodes and two million edges, to detect low frequency cell populations (e.g. 0.01% for one population), with accuracies reaching 98%. Our findings underscore the potential of HemaGraph in improving hematoligic multi-class classification, paving the way for patient-personalized interventions. To the best of our knowledge, this is the first effort to u
In the complex landscape of hematologic samples such as peripheral blood or bone marrow, cell classification, delineating diverse populations into a hierarchical structure, presents profound challenges. This study presents LeukoGraph, a recently developed framework designed explicitly for this purpose employing graph attention networks (GATs) to navigate hierarchical classification (HC) complexities. Notably, LeukoGraph stands as a pioneering effort, marking the application of graph neural networks (GNNs) for hierarchical inference on graphs, accommodating up to one million nodes and millions of edges, all derived from flow cytometry data. LeukoGraph intricately addresses a classification paradigm where for example four different cell populations undergo flat categorization, while a fifth diverges into two distinct child branches, exemplifying the nuanced hierarchical structure inherent in complex datasets. The technique is more general than this example. A hallmark achievement of LeukoGraph is its F-score of 98%, significantly outclassing prevailing state-of-the-art methodologies. Crucially, LeukoGraph's prowess extends beyond theoretical innovation, showcasing remarkable precisio
In the intricate field of medical diagnostics, capturing the subtle manifestations of diseases remains a challenge. Traditional methods, often binary in nature, may not encapsulate the nuanced variances that exist in real-world clinical scenarios. This paper introduces a novel approach by leveraging Fuzzy Logic Rules to derive disease classes based on expert domain knowledge from a medical practitioner. By recognizing that diseases do not always fit into neat categories, and that expert knowledge can guide the fuzzification of these boundaries, our methodology offers a more sophisticated and nuanced diagnostic tool. Using a dataset procured from a prominent hospital, containing detailed patient blood count records, we harness Fuzzy Logic Rules, a computational technique celebrated for its ability to handle ambiguity. This approach, moving through stages of fuzzification, rule application, inference, and ultimately defuzzification, produces refined diagnostic predictions. When combined with the Random Forest classifier, the system adeptly predicts hematological conditions using Complete Blood Count (CBC) parameters. Preliminary results showcase high accuracy levels, underscoring the
Although some pollutants emitted in vehicle exhaust, such as benzene, are known to cause leukemia in adults with high exposure levels, less is known about the relationship between traffic-related air pollution (TRAP) and childhood hematologic cancer. In the 1990s, the US EPA enacted the reformulated gasoline program in select areas of the US, which drastically reduced ambient TRAP in affected areas. This created an ideal quasi-experiment to study the effects of TRAP on childhood hematologic cancers. However, existing methods for quasi-experimental analyses can perform poorly when outcomes are rare and unstable, as with childhood cancer incidence. We develop Bayesian spatio-temporal matrix completion methods to conduct causal inference in quasi-experimental settings with rare outcomes. Selective information sharing across space and time enables stable estimation, and the Bayesian approach facilitates uncertainty quantification. We evaluate the methods through simulations and apply them to estimate the causal effects of TRAP on childhood leukemia and lymphoma.
Accurate morphological classification of white blood cells (WBCs) is an important step in the diagnosis of leukemia, a disease in which nonfunctional blast cells accumulate in the bone marrow. Recently, deep convolutional neural networks (CNNs) have been successfully used to classify leukocytes by training them on single-cell images from a specific domain. Most CNN models assume that the distributions of the training and test data are similar, i.e., the data are independently and identically distributed. Therefore, they are not robust to different staining procedures, magnifications, resolutions, scanners, or imaging protocols, as well as variations in clinical centers or patient cohorts. In addition, domain-specific data imbalances affect the generalization performance of classifiers. Here, we train a robust CNN for WBC classification by addressing cross-domain data imbalance and domain shifts. To this end, we use two loss functions and demonstrate their effectiveness in out-of-distribution (OOD) generalization. Our approach achieves the best F1 macro score compared to other existing methods and is able to consider rare cell types. This is the first demonstration of imbalanced dom
Traditional health authority approval for oncology drugs is based on a clinical benefit endpoint, or a valid surrogate. In 1992 the FDA created the Accelerated Approval pathway to allow for earlier approval of therapies in serious conditions with an unmet medical need. This is accomplished typically by granting accelerated approval based on a surrogate endpoint that can be measured earlier than a traditional approval endpoint. Minimal residual disease (MRD) is a sensitive measure of residual cancer cells in hematology oncology after treatment, and is increasingly considered as a secondary or exploratory endpoint due to its prognostic potential for traditional clinical trial endpoints such as progression-free survival (PFS) and overall survival (OS). This work aims to evaluate MRD's surrogacy potential across several hematologic cancer indications while keeping the focus on follicular lymphoma (FL), using data from published studies. We examine individual-level and trial-level correlations extracted from previously published studies to elucidate the potential role of MRD in accelerating the drug approval process in hematology oncology trials.
TNM staging is essential for lung cancer management, but patients within the same anatomic stage often show heterogeneous survival outcomes. We developed a multimodal adaptive risk score (AMRS) that integrates radiology-report semantics with routinely available clinical laboratory biomarkers. In a retrospective two-center cohort, 1129 patients diagnosed between December 2017 and February 2026 were screened; 574 patients were included after exclusion for short follow-up or missing imaging reports and were split into training (n = 459) and test (n = 115) cohorts. Radiology reports were encoded with a domain-adapted MC-BERT branch to capture imaging-derived semantic information, while clinical and laboratory variables were modeled after Mahalanobis-distance-based imputation using random survival forests. Weighted risk fusion generated the final patient-level score. AMRS achieved C-index values of 0.920 in training and 0.849 in testing, and separated survival trajectories across clinical subgroups and TNM-related strata. SHAP analysis identified hematologic, inflammatory, coagulation, nutritional, tumor-marker, organ-function, and age-related contributors. AMRS may complement TNM stagi
Background: More than 80% of U.S. cancer care is delivered in community settings, where survival remains worse than at academic centers. Clinicians must integrate genomics, staging, radiology, pathology, and changing guidelines, creating cognitive burden. We evaluated OncoBrain, an AI clinical reasoning platform for oncology treatment-plan generation, as an early step toward OGI. Methods: OncoBrain combines general-purpose LLMs with a cancer-specific graph retrieval-augmented generation layer, a gold-standard treatment-plan corpus as long-term memory, and a model-agnostic safety layer (CHECK) for hallucination detection and suppression. We evaluated clinician-enriched case summaries across gynecologic, genitourinary, neuro-oncology, gastrointestinal/hepatobiliary, and hematologic malignancies. Three clinician groups completed structured evaluations of 173 cases using a common 16-item instrument: subspecialist oncologists reviewed 50 cases, physician reviewers 78, and advanced practice providers 45. Results: Ratings were highest for scientific accuracy, evidence support, and safety, with lower but favorable scores for workflow integration and time savings. On a 5-point scale, mean a
Although the circulatory system functions as a continuous source of physiological data, contemporary diagnostics remain bound to intermittent, time-delayed assessments. To resolve this, we present a framework for ubiquitous hematological profiling driven by Integrated Sensing and Communication (ISAC). We demonstrate how electromagnetic signals can be exploited to monitor blood in real-time, effectively converting them into diagnostic tools. We analyze the biological foundations of blood, review existing Complete Blood Count (CBC) and sensing technologies, and detail a novel pipeline for continuous blood monitoring. Furthermore, we discuss the potential applications of deploying these devices to enable real-time CBC and biomarker detection, ultimately revolutionizing how we predict, detect, and manage individual and public health.
Mechanical properties of red blood cells (RBCs) are promising biomarkers for hematologic and systemic disease, motivating microfluidic assays that probe deformability at throughputs of $10^3$--$10^6$ cells per experiment. However, existing pipelines rely on supervised segmentation or hand-crafted kymographs and rarely encode the laminar Stokes-flow physics that governs RBC shape evolution. We introduce FlowMorph, a physics-consistent self-supervised framework that learns a label-free scalar mechanics proxy $k$ for each tracked RBC from short brightfield microfluidic videos. FlowMorph models each cell by a low-dimensional parametric contour, advances boundary points through a differentiable ''capsule-in-flow'' combining laminar advection and curvature-regularized elastic relaxation, and optimizes a loss coupling silhouette overlap, intra-cellular flow agreement, area conservation, wall constraints, and temporal smoothness, using only automatically derived silhouettes and optical flow. Across four public RBC microfluidic datasets, FlowMorph achieves a mean silhouette IoU of $0.905$ on physics-rich videos with provided velocity fields and markedly improves area conservation and wall v
This industrial Ph.D. project, carried out in collaboration between Radiometer Medical ApS and SDU Centre for Photonics Engineering at the University of Southern Denmark, explored the use of digital holographic microscopy (DHM) for the purposes of differential white blood cell counts (dWBCs) in point-of-care (PoC) devices for acute care settings. Two DHM prototypes were developed; an initial lens-based system serving as the foundation for algorithm development, and experimental validation of the approach, achieving 89.6% classification accuracy on a 3-part differential, and a subsequent lensless system for simplified design and increased field-of-view (FoV). Both prototypes employed convolutional neural networks (CNNs) for cell classification. With further optimizations, the lensless system achieved classification accuracies of 92.65% and 89.44% on the 3-part and 5-part differential, respectively. With the lensless system, the derivation of the monocyte distribution width (MDW), a biomarker for sepsis, was also demonstrated. Additionally, pixel super-resolution and multi-wavelength DHM approaches were investigated to enhance the obtained cell information. Finally, a proof-of-princi
White blood cell (WBC) classification is fundamental for hematology applications such as infection assessment, leukemia screening, and treatment monitoring. However, real-world WBC datasets present substantial appearance variations caused by staining and scanning conditions, as well as severe class imbalance in which common cell types dominate while rare but clinically important categories are underrepresented. To address these challenges, we propose a stain-normalized, decoupled training framework that first learns transferable representations using instance-balanced sampling, and then rebalances the classifier with class-aware sampling and a hybrid loss combining effective-number weighting and focal modulation. In inference stage, we further enhance robustness by ensembling various trained backbones with test-time augmentation. Our approach achieved the top rank on the leaderboard of the WBCBench 2026: Robust White Blood Cell Classification Challenge at ISBI 2026.
Accurate classification of Acute Lymphoblastic Leukemia (ALL) from peripheral blood smear images is essential for early diagnosis and effective treatment planning. This study investigates the use of transfer learning with pretrained convolutional neural networks (CNNs) to improve diagnostic performance. To address the class imbalance in the dataset of 3,631 Hematologic and 7,644 ALL images, we applied extensive data augmentation techniques to create a balanced training set of 10,000 images per class. We evaluated several models, including ResNet50, ResNet101, and EfficientNet variants B0, B1, and B3. EfficientNet-B3 achieved the best results, with an F1-score of 94.30%, accuracy of 92.02%, andAUCof94.79%,outperformingpreviouslyreported methods in the C-NMCChallenge. Thesefindings demonstrate the effectiveness of combining data augmentation with advanced transfer learning models, particularly EfficientNet-B3, in developing accurate and robust diagnostic tools for hematologic malignancy detection.
Understanding disease relationships through blood biomarkers offers a pathway toward data-driven taxonomy and precision medicine. In this study, we constructed a digital blood twin, a computational model derived from 103 disease signatures comprising longitudinal hematological and biochemical analytes. Profiles were standardized into a unified disease-analyte matrix, and pairwise Pearson correlations were computed to assess similarity across conditions. Hierarchical clustering revealed consistent grouping of hematopoietic disorders, while metabolic, endocrine, and respiratory diseases were more heterogeneous, reflecting weaker internal cohesion. To evaluate cluster structure, the tree was partitioned at a stringent distance threshold, yielding 16 groups. Enrichment analysis of the largest and most heterogeneous cluster demonstrated convergence on cytokine-signaling pathways, indicating shared inflammatory mechanisms that transcend conventional clinical boundaries. PCA and UMAP corroborated the correlation-based results, consistently separating hematological diseases as a distinct cluster. Random Forest feature selection identified neutrophils, mean corpuscular volume, red blood cel
Vision Language Models (VLMs) have shown promising capabilities in medical image analysis by jointly understanding visual and textual information for tasks such as Visual Question Answering. However, existing hematology vision-language resources remain predominantly English centric, limiting their applicability in multilingual healthcare environments. This challenge is releveant generally to South Asia and specifically to Pakistan, where Urdu is widely used despite healthcare information and digital medical systems being largely dependent on English. To investigate this gap, we conducted a survey among healthcare professionals, which revealed substantial language mismatches between clinical documentation and patient communication, emphasizing the need for multilingual healthcare technologies. To address this limitation, we introduce WBCMor VQA, a clinically validated bilingual English, Urdu morphology aware VQA benchmark for leukemia and normal white blood cell analysis. The benchmark is constructed using morphology-aware annotations from LeukemiaAttri and WBCAtt datasets and supported by a domain specific Urdu hematology dictionary to ensure linguistic consistency and clinical cor
Aplastic anemia is a rare, life-threatening hematologic disorder characterized by pancytopenia and bone marrow failure. ICU admission in these patients often signals critical complications or disease progression, making early risk assessment crucial for clinical decision-making and resource allocation. In this study, we used the MIMIC-IV database to identify ICU patients diagnosed with aplastic anemia and extracted clinical features from five domains: demographics, synthetic indicators, laboratory results, comorbidities, and medications. Over 400 variables were reduced to seven key predictors through machine learning-based feature selection. Logistic regression and Cox regression models were constructed to predict 7-, 14-, and 28-day mortality, and their performance was evaluated using AUROC. External validation was conducted using the eICU Collaborative Research Database to assess model generalizability. Among 1,662 included patients, the logistic regression model demonstrated superior performance, with AUROC values of 0.8227, 0.8311, and 0.8298 for 7-, 14-, and 28-day mortality, respectively, compared to the Cox model. External validation yielded AUROCs of 0.7391, 0.7119, and 0.7