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
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
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
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
Anemia is a prevalent hematological disorder that requires frequent hemoglobin monitoring for early diagnosis and effective management. Conventional hemoglobin assessment relies on invasive blood sampling, limiting its suitability for large-scale or continuous screening. This paper presents a non-invasive framework for hemoglobin estimation and anemia screening using multichannel photoplethysmography (PPG) signals and explainable artificial intelligence. Four-wavelength PPG signals (660, 730, 850, and 940~nm) are processed to extract optical and cross-wavelength features, which are aggregated at the subject level to avoid data leakage. A gradient boosting regression model is employed to estimate hemoglobin concentration, followed by post-regression anemia screening using World Health Organization (WHO) thresholds. Model interpretability is achieved using SHapley Additive explanations (SHAP), enabling both global and subject-specific analysis of feature contributions. Experimental evaluation on a publicly available dataset demonstrates a mean absolute error of 8.50 plus minus 1.27 and a root mean squared error of 8.21~g/L on unseen test subjects, indicating the potential of the prop
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.
Microscopic evaluation of white blood cell morphology is central to leukemia diagnosis, yet current deep learning models often act as black boxes, limiting clinical trust and adoption. We introduce HemBLIP, a vision language model designed to generate interpretable, morphology aware descriptions of peripheral blood cells. Using a newly constructed dataset of 14k healthy and leukemic cells paired with expert-derived attribute captions, we adapt a general-purpose VLM via both full fine-tuning and LoRA based parameter efficient training, and benchmark against the biomedical foundation model MedGEMMA. HemBLIP achieves higher caption quality and morphological accuracy, while LoRA adaptation provides further gains with significantly reduced computational cost. These results highlight the promise of vision language models for transparent and scalable hematological diagnostics.
Label-free single-cell imaging offers a scalable, non-invasive alternative to fluorescence-based cytometry, yet inferring molecular phenotypes directly from bright-field morphology remains challenging. We present a unified Deep Learning (DL) framework that jointly performs White Blood Cell (WBC) classification and continuous protein-expression regression from label-free Differential Phase Contrast (DPC) images. Our model employs a Hybrid architecture that fuses convolutional fine-grained texture features with transformer-based global representations through a learnable cross-branch gating module, enabling robust morpho-molecular inference from DPC images. To support downstream interpretability, we further incorporate a Large Language Model (LLM) that generates concise, biologically grounded summaries of the predicted cell states. Experiments on the Berkeley Single Cell Computational Microscopy (BSCCM) and Blood Cells Image benchmarks demonstrate strong performance, achieving a 91.3% WBC classification accuracy and a 0.72 Pearson correlation for CD16 expression regression on BSCCM. These results underscore the promise of label-free single-cell imaging for cost-effective hematologica
Automated blood morphology analysis can support hematological diagnostics in low- and middle-income countries (LMICs) but remains sensitive to dataset shifts from staining variability, imaging differences, and rare morphologies. Building centralized datasets to capture this diversity is often infeasible due to privacy regulations and data-sharing restrictions. We introduce a federated learning framework for white blood cell morphology analysis that enables collaborative training across institutions without exchanging training data. Using blood films from multiple clinical sites, our federated models learn robust, domain-invariant representations while preserving complete data privacy. Evaluations across convolutional and transformer-based architectures show that federated training achieves strong cross-site performance and improved generalization to unseen institutions compared to centralized training. These findings highlight federated learning as a practical and privacy-preserving approach for developing equitable, scalable, and generalizable medical imaging AI in resource-limited healthcare environments.
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
Automated white blood cell (WBC) classification is essential for leukemia screening but remains challenged by extreme class imbalance, long-tail distributions, and domain shift, leading deep models to overfit dominant classes and fail on rare subtypes. We propose a hybrid framework for rare-class generalization that integrates a generative Pix2Pix-based restoration module for artifact removal, a Swin Transformer ensemble with MedSigLIP contrastive embeddings for robust representation learning, and a biologically-inspired refinement step using geometric spikiness and Mahalanobis-based morphological constraints to recover out-of-distribution predictions. Evaluated on the WBCBench 2026 challenge, our method achieves a Macro-F1 of 0.77139 on the private leaderboard, demonstrating strong performance under severe imbalance and highlighting the value of incorporating biological priors into deep learning for hematological image analysis. The code is available at https://github.com/trongduc-nguyen/WBCBench2026
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
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.
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
Biomedical datasets are often constrained by stringent privacy requirements and frequently suffer from severe class imbalance. These two aspects hinder the development of accurate machine learning models. While generative AI offers a promising solution, producing synthetic images of sufficient quality for training robust classifiers remains challenging. This work addresses the classification of individual white blood cells, a critical task in diagnosing hematological malignancies such as acute myeloid leukemia (AML). We introduce CytoDiff, a stable diffusion model fine-tuned with LoRA weights and guided by few-shot samples that generates high-fidelity synthetic white blood cell images. Our approach demonstrates substantial improvements in classifier performance when training data is limited. Using a small, highly imbalanced real dataset, the addition of 5,000 synthetic images per class improved ResNet classifier accuracy from 27\% to 78\% (+51\%). Similarly, CLIP-based classification accuracy increased from 62\% to 77\% (+15\%). These results establish synthetic image generation as a valuable tool for biomedical machine learning, enhancing data coverage and facilitating secure data
Medical imaging plays a vital role in early disease diagnosis and monitoring. Specifically, blood microscopy offers valuable insights into blood cell morphology and the detection of hematological disorders. In recent years, deep learning-based automated classification systems have demonstrated high potential in enhancing the accuracy and efficiency of blood image analysis. However, a detailed performance analysis of specific deep learning frameworks appears to be lacking. This paper compares the performance of three popular deep learning frameworks, TensorFlow with Keras, PyTorch, and JAX, in classifying blood cell images from the publicly available BloodMNIST dataset. The study primarily focuses on inference time differences, but also classification performance for different image sizes. The results reveal variations in performance across frameworks, influenced by factors such as image resolution and framework-specific optimizations. Classification accuracy for JAX and PyTorch was comparable to current benchmarks, showcasing the efficiency of these frameworks for medical image classification.
This paper presents a comprehensive methodology and comparative performance analysis for the automated classification and object detection of peripheral blood cells (PBCs) in microscopic images. Addressing the critical challenge of data scarcity and heterogeneity, robust data pipeline was first developed to standardize and merge four public datasets (PBC, BCCD, Chula, Sickle Cell) into a unified resource. Then employed a state-of-the-art Faster R-CNN object detection framework, leveraging a ResNet-50-FPN backbone. Comparative training rigorously evaluated a randomly initialized baseline model (Regimen 1) against a Transfer Learning Regimen (Regimen 2), initialized with weights pre-trained on the Microsoft COCO dataset. The results demonstrate that the Transfer Learning approach achieved significantly faster convergence and superior stability, culminating in a final validation loss of 0.08666, a substantial improvement over the baseline. This validated methodology establishes a robust foundation for building high-accuracy, deployable systems for automated hematological diagnosis.
Red blood cells (RBCs) are essential to human health, and their precise morphological analysis is important for diagnosing hematological disorders. Despite the promise of foundation models in medical diagnostics, comprehensive AI solutions for RBC analysis remain scarce. We present RedDino, a self-supervised foundation model designed for RBC image analysis. RedDino uses an RBC-specific adaptation of the DINOv2 self-supervised learning framework and is trained on a curated dataset of 1.25 million RBC images from diverse acquisition modalities and sources. Extensive evaluations show that RedDino outperforms existing state-of-the-art models on RBC shape classification. Through assessments including linear probing and nearest neighbor classification, we confirm its strong feature representations and generalization ability. Our main contributions are: (1) a foundation model tailored for RBC analysis, (2) ablation studies exploring DINOv2 configurations for RBC modeling, and (3) a detailed evaluation of generalization performance. RedDino addresses key challenges in computational hematology by capturing nuanced morphological features, advancing the development of reliable diagnostic tool
Acute lymphoblastic leukemia (ALL) is a prevalent hematological malignancy in both pediatric and adult populations. Early and accurate detection with precise subtyping is essential for guiding therapy. Conventional workflows are complex, time-consuming, and prone to human error. We present a deep learning framework for automated ALL diagnosis from bone marrow smear images. The method combines a robust preprocessing pipeline with convolutional neural networks (CNNs) to standardize image quality and improve inference efficiency. As a key design, we insert a multi-head self-attention (MHSA) block into a VGG19 backbone to model long-range dependencies and contextual relationships among cellular features. To mitigate class imbalance, we train with Focal Loss. Across evaluated architectures, the enhanced VGG19+MHSA trained with Focal Loss achieves 99.25% accuracy, surpassing a strong ResNet101 baseline (98.62%). These results indicate that attention-augmented CNNs, coupled with targeted loss optimization and preprocessing, yield more discriminative representations of leukemic cell morphology. Our approach offers a highly accurate and computationally efficient tool for automated ALL recog
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