Alzheimer's disease (AD) cannot be reversed, but early diagnosis will significantly benefit patients' medical treatment and care. In recent works, AD diagnosis has the primary assumption that all categories are known a prior -- a closed-set classification problem, which contrasts with the open-set recognition problem. This assumption hinders the application of the model in natural clinical settings. Although many open-set recognition technologies have been proposed in other fields, they are challenging to use for AD diagnosis directly since 1) AD is a degenerative disease of the nervous system with similar symptoms at each stage, and it is difficult to distinguish from its pre-state, and 2) diversified strategies for AD diagnosis are challenging to model uniformly. In this work, inspired by the concerns of clinicians during diagnosis, we propose an open-set recognition model, OpenAPMax, based on the anomaly pattern to address AD diagnosis in real-world settings. OpenAPMax first obtains the abnormal pattern of each patient relative to each known category through statistics or a literature search, clusters the patients' abnormal pattern, and finally, uses extreme value theory (EVT) to model the distance between each patient's abnormal pattern and the center of their category and modify the classification probability. We evaluate the performance of the proposed method with recent open-set recognition, where we obtain state-of-the-art results.
Medical image segmentation is a critical task that plays a vital role in diagnosis, treatment planning, and disease monitoring. Accurate segmentation of anatomical structures and abnormalities from medical images can aid in the early detection and treatment of various diseases. In this paper, we address the local feature deficiency of the Transformer model by carefully re-designing the self-attention map to produce accurate dense prediction in medical images. To this end, we first apply the wavelet transformation to decompose the input feature map into low-frequency (LF) and high-frequency (HF) subbands. The LF segment is associated with coarse-grained features while the HF components preserve fine-grained features such as texture and edge information. Next, we reformulate the self-attention operation using the efficient Transformer to perform both spatial and context attention on top of the frequency representation. Furthermore, to intensify the importance of the boundary information, we impose an additional attention map by creating a Gaussian pyramid on top of the HF components. Moreover, we propose a multi-scale context enhancement block within skip connections to adaptively model inter-scale dependencies to overcome the semantic gap among stages of the encoder and decoder modules. Throughout comprehensive experiments, we demonstrate the effectiveness of our strategy on multi-organ and skin lesion segmentation benchmarks. The implementation code will be available upon acceptance. \href{//github.com/mindflow-institue/WaveFormer}{GitHub}.
Alzheimer's disease (AD) is a heterogeneous, multifactorial neurodegenerative disorder characterized by beta-amyloid, pathologic tau, and neurodegeneration. There are no effective treatments for Alzheimer's disease at a late stage, urging for early intervention. However, existing statistical inference approaches of AD subtype identification ignore the pathological domain knowledge, which could lead to ill-posed results that are sometimes inconsistent with the essential neurological principles. Integrating systems biology modeling with machine learning, we propose a novel pathology steered stratification network (PSSN) that incorporates established domain knowledge in AD pathology through a reaction-diffusion model, where we consider non-linear interactions between major biomarkers and diffusion along brain structural network. Trained on longitudinal multimodal neuroimaging data, the biological model predicts long-term trajectories that capture individual progression pattern, filling in the gaps between sparse imaging data available. A deep predictive neural network is then built to exploit spatiotemporal dynamics, link neurological examinations with clinical profiles, and generate subtype assignment probability on an individual basis. We further identify an evolutionary disease graph to quantify subtype transition probabilities through extensive simulations. Our stratification achieves superior performance in both inter-cluster heterogeneity and intra-cluster homogeneity of various clinical scores. Applying our approach to enriched samples of aging populations, we identify six subtypes spanning AD spectrum, where each subtype exhibits a distinctive biomarker pattern that is consistent with its clinical outcome. PSSN provides insights into pre-symptomatic diagnosis and practical guidance on clinical treatments, which may be further generalized to other neurodegenerative diseases.
Whole slide image (WSI) analysis has become increasingly important in the medical imaging community, enabling automated and objective diagnosis, prognosis, and therapeutic-response prediction. However, in clinical practice, the ever-evolving environment hamper the utility of WSI analysis models. In this paper, we propose the FIRST continual learning framework for WSI analysis, named ConSlide, to tackle the challenges of enormous image size, utilization of hierarchical structure, and catastrophic forgetting by progressive model updating on multiple sequential datasets. Our framework contains three key components. The Hierarchical Interaction Transformer (HIT) is proposed to model and utilize the hierarchical structural knowledge of WSI. The Breakup-Reorganize (BuRo) rehearsal method is developed for WSI data replay with efficient region storing buffer and WSI reorganizing operation. The asynchronous updating mechanism is devised to encourage the network to learn generic and specific knowledge respectively during the replay stage, based on a nested cross-scale similarity learning (CSSL) module. We evaluated the proposed ConSlide on four public WSI datasets from TCGA projects. It performs best over other state-of-the-art methods with a fair WSI-based continual learning setting and achieves a better trade-off of the overall performance and forgetting on previous task
Echocardiography (echo) is an ultrasound imaging modality that is widely used for various cardiovascular diagnosis tasks. Due to inter-observer variability in echo-based diagnosis, which arises from the variability in echo image acquisition and the interpretation of echo images based on clinical experience, vision-based machine learning (ML) methods have gained popularity to act as secondary layers of verification. For such safety-critical applications, it is essential for any proposed ML method to present a level of explainability along with good accuracy. In addition, such methods must be able to process several echo videos obtained from various heart views and the interactions among them to properly produce predictions for a variety of cardiovascular measurements or interpretation tasks. Prior work lacks explainability or is limited in scope by focusing on a single cardiovascular task. To remedy this, we propose a General, Echo-based, Multi-Level Transformer (GEMTrans) framework that provides explainability, while simultaneously enabling multi-video training where the inter-play among echo image patches in the same frame, all frames in the same video, and inter-video relationships are captured based on a downstream task. We show the flexibility of our framework by considering two critical tasks including ejection fraction (EF) and aortic stenosis (AS) severity detection. Our model achieves mean absolute errors of 4.15 and 4.84 for single and dual-video EF estimation and an accuracy of 96.5 % for AS detection, while providing informative task-specific attention maps and prototypical explainability.
Accurate classification of white blood cells in peripheral blood is essential for diagnosing hematological diseases. Due to constantly evolving clinical settings, data sources, and disease classifications, it is necessary to update machine learning classification models regularly for practical real-world use. Such models significantly benefit from sequentially learning from incoming data streams without forgetting previously acquired knowledge. However, models can suffer from catastrophic forgetting, causing a drop in performance on previous tasks when fine-tuned on new data. Here, we propose a rehearsal-based continual learning approach for class incremental and domain incremental scenarios in white blood cell classification. To choose representative samples from previous tasks, we employ exemplar set selection based on the model's predictions. This involves selecting the most confident samples and the most challenging samples identified through uncertainty estimation of the model. We thoroughly evaluated our proposed approach on three white blood cell classification datasets that differ in color, resolution, and class composition, including scenarios where new domains or new classes are introduced to the model with every task. We also test a long class incremental experiment with both new domains and new classes. Our results demonstrate that our approach outperforms established baselines in continual learning, including existing iCaRL and EWC methods for classifying white blood cells in cross-domain environments.
Precision medicine fundamentally aims to establish causality between dysregulated biochemical mechanisms and cancer subtypes. Omics-based cancer subtyping has emerged as a revolutionary approach, as different level of omics records the biochemical products of multistep processes in cancers. This paper focuses on fully exploiting the potential of multi-omics data to improve cancer subtyping outcomes, and hence developed MoCLIM, a representation learning framework. MoCLIM independently extracts the informative features from distinct omics modalities. Using a unified representation informed by contrastive learning of different omics modalities, we can well-cluster the subtypes, given cancer, into a lower latent space. This contrast can be interpreted as a projection of inter-omics inference observed in biological networks. Experimental results on six cancer datasets demonstrate that our approach significantly improves data fit and subtyping performance in fewer high-dimensional cancer instances. Moreover, our framework incorporates various medical evaluations as the final component, providing high interpretability in medical analysis.
Learning-based methods have dominated the 3D human pose estimation (HPE) tasks with significantly better performance in most benchmarks than traditional optimization-based methods. Nonetheless, 3D HPE in the wild is still the biggest challenge of learning-based models, whether with 2D-3D lifting, image-to-3D, or diffusion-based methods, since the trained networks implicitly learn camera intrinsic parameters and domain-based 3D human pose distributions and estimate poses by statistical average. On the other hand, the optimization-based methods estimate results case-by-case, which can predict more diverse and sophisticated human poses in the wild. By combining the advantages of optimization-based and learning-based methods, we propose the Zero-shot Diffusion-based Optimization (ZeDO) pipeline for 3D HPE to solve the problem of cross-domain and in-the-wild 3D HPE. Our multi-hypothesis ZeDO achieves state-of-the-art (SOTA) performance on Human3.6M as minMPJPE $51.4$mm without training with any 2D-3D or image-3D pairs. Moreover, our single-hypothesis ZeDO achieves SOTA performance on 3DPW dataset with PA-MPJPE $42.6$mm on cross-dataset evaluation, which even outperforms learning-based methods trained on 3DPW.
Segmenting cells and tracking their motion over time is a common task in biomedical applications. However, predicting accurate instance-wise segmentation and cell motions from microscopy imagery remains a challenging task. Using microstructured environments for analyzing single cells in a constant flow of media adds additional complexity. While large-scale labeled microscopy datasets are available, we are not aware of any large-scale dataset, including both cells and microstructures. In this paper, we introduce the trapped yeast cell (TYC) dataset, a novel dataset for understanding instance-level semantics and motions of cells in microstructures. We release $105$ dense annotated high-resolution brightfield microscopy images, including about $19$k instance masks. We also release $261$ curated video clips composed of $1293$ high-resolution microscopy images to facilitate unsupervised understanding of cell motions and morphology. TYC offers ten times more instance annotations than the previously largest dataset, including cells and microstructures. Our effort also exceeds previous attempts in terms of microstructure variability, resolution, complexity, and capturing device (microscopy) variability. We facilitate a unified comparison on our novel dataset by introducing a standardized evaluation strategy. TYC and evaluation code are publicly available under CC BY 4.0 license.
Human doctors with well-structured medical knowledge can diagnose a disease merely via a few conversations with patients about symptoms. In contrast, existing knowledge-grounded dialogue systems often require a large number of dialogue instances to learn as they fail to capture the correlations between different diseases and neglect the diagnostic experience shared among them. To address this issue, we propose a more natural and practical paradigm, i.e., low-resource medical dialogue generation, which can transfer the diagnostic experience from source diseases to target ones with a handful of data for adaptation. It is capitalized on a commonsense knowledge graph to characterize the prior disease-symptom relations. Besides, we develop a Graph-Evolving Meta-Learning (GEML) framework that learns to evolve the commonsense graph for reasoning disease-symptom correlations in a new disease, which effectively alleviates the needs of a large number of dialogues. More importantly, by dynamically evolving disease-symptom graphs, GEML also well addresses the real-world challenges that the disease-symptom correlations of each disease may vary or evolve along with more diagnostic cases. Extensive experiment results on the CMDD dataset and our newly-collected Chunyu dataset testify the superiority of our approach over state-of-the-art approaches. Besides, our GEML can generate an enriched dialogue-sensitive knowledge graph in an online manner, which could benefit other tasks grounded on knowledge graph.
Applying artificial intelligence techniques in medical imaging is one of the most promising areas in medicine. However, most of the recent success in this area highly relies on large amounts of carefully annotated data, whereas annotating medical images is a costly process. In this paper, we propose a novel method, called FocalMix, which, to the best of our knowledge, is the first to leverage recent advances in semi-supervised learning (SSL) for 3D medical image detection. We conducted extensive experiments on two widely used datasets for lung nodule detection, LUNA16 and NLST. Results show that our proposed SSL methods can achieve a substantial improvement of up to 17.3% over state-of-the-art supervised learning approaches with 400 unlabeled CT scans.