Definitive cancer diagnosis and management depend upon the extraction of information from microscopy images by pathologists. These images contain complex information requiring time-consuming expert human interpretation that is prone to human bias. Supervised deep learning approaches have proven powerful for classification tasks, but they are inherently limited by the cost and quality of annotations used for training these models. To address this limitation of supervised methods, we developed Histomorphological Phenotype Learning (HPL), a fully blue{self-}supervised methodology that requires no expert labels or annotations and operates via the automatic discovery of discriminatory image features in small image tiles. Tiles are grouped into morphologically similar clusters which constitute a library of histomorphological phenotypes, revealing trajectories from benign to malignant tissue via inflammatory and reactive phenotypes. These clusters have distinct features which can be identified using orthogonal methods, linking histologic, molecular and clinical phenotypes. Applied to lung cancer tissues, we show that they align closely with patient survival, with histopathologically recognised tumor types and growth patterns, and with transcriptomic measures of immunophenotype. We then demonstrate that these properties are maintained in a multi-cancer study. These results show the clusters represent recurrent host responses and modes of tumor growth emerging under natural selection. Code, pre-trained models, learned embeddings, and documentation are available to the community at //github.com/AdalbertoCq/Histomorphological-Phenotype-Learning
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Physics-informed neural networks have emerged as a coherent framework for building predictive models that combine statistical patterns with domain knowledge. The underlying notion is to enrich the optimization loss function with known relationships to constrain the space of possible solutions. Hydrodynamic simulations are a core constituent of modern cosmology, while the required computations are both expensive and time-consuming. At the same time, the comparatively fast simulation of dark matter requires fewer resources, which has led to the emergence of machine learning algorithms for baryon inpainting as an active area of research; here, recreating the scatter found in hydrodynamic simulations is an ongoing challenge. This paper presents the first application of physics-informed neural networks to baryon inpainting by combining advances in neural network architectures with physical constraints, injecting theory on baryon conversion efficiency into the model loss function. We also introduce a punitive prediction comparison based on the Kullback-Leibler divergence, which enforces scatter reproduction. By simultaneously extracting the complete set of baryonic properties for the Simba suite of cosmological simulations, our results demonstrate improved accuracy of baryonic predictions based on dark matter halo properties, successful recovery of the fundamental metallicity relation, and retrieve scatter that traces the target simulation's distribution.
Alzheimer's disease is one of the most common types of neurodegenerative disease, characterized by the accumulation of amyloid-beta plaque and tau tangles. Recently, deep learning approaches have shown promise in Alzheimer's disease diagnosis. In this study, we propose a reproducible model that utilizes a 3D convolutional neural network with a dual attention module for Alzheimer's disease classification. We trained the model in the ADNI database and verified the generalizability of our method in two independent datasets (AIBL and OASIS1). Our method achieved state-of-the-art classification performance, with an accuracy of 91.94% for MCI progression classification and 96.30% for Alzheimer's disease classification on the ADNI dataset. Furthermore, the model demonstrated good generalizability, achieving an accuracy of 86.37% on the AIBL dataset and 83.42% on the OASIS1 dataset. These results indicate that our proposed approach has competitive performance and generalizability when compared to recent studies in the field.
Computer-assisted diagnostic and prognostic systems of the future should be capable of simultaneously processing multimodal data. Multimodal deep learning (MDL), which involves the integration of multiple sources of data, such as images and text, has the potential to revolutionize the analysis and interpretation of biomedical data. However, it only caught researchers' attention recently. To this end, there is a critical need to conduct a systematic review on this topic, identify the limitations of current work, and explore future directions. In this scoping review, we aim to provide a comprehensive overview of the current state of the field and identify key concepts, types of studies, and research gaps with a focus on biomedical images and texts joint learning, mainly because these two were the most commonly available data types in MDL research. This study reviewed the current uses of multimodal deep learning on five tasks: (1) Report generation, (2) Visual question answering, (3) Cross-modal retrieval, (4) Computer-aided diagnosis, and (5) Semantic segmentation. Our results highlight the diverse applications and potential of MDL and suggest directions for future research in the field. We hope our review will facilitate the collaboration of natural language processing (NLP) and medical imaging communities and support the next generation of decision-making and computer-assisted diagnostic system development.
A major interest in longitudinal neuroimaging studies involves investigating voxel-level neuroplasticity due to treatment and other factors across visits. However, traditional voxel-wise methods are beset with several pitfalls, which can compromise the accuracy of these approaches. We propose a novel Bayesian tensor response regression approach for longitudinal imaging data, which pools information across spatially-distributed voxels to infer significant changes while adjusting for covariates. The proposed method, which is implemented using Markov chain Monte Carlo (MCMC) sampling, utilizes low-rank decomposition to reduce dimensionality and preserve spatial configurations of voxels when estimating coefficients. It also enables feature selection via joint credible regions which respect the shape of the posterior distributions for more accurate inference. In addition to group level inferences, the method is able to infer individual-level neuroplasticity, allowing for examination of personalized disease or recovery trajectories. The advantages of the proposed approach in terms of prediction and feature selection over voxel-wise regression are highlighted via extensive simulation studies. Subsequently, we apply the approach to a longitudinal Aphasia dataset consisting of task functional MRI images from a group of subjects who were administered either a control intervention or intention treatment at baseline and were followed up over subsequent visits. Our analysis revealed that while the control therapy showed long-term increases in brain activity, the intention treatment produced predominantly short-term changes, both of which were concentrated in distinct localized regions. In contrast, the voxel-wise regression failed to detect any significant neuroplasticity after multiplicity adjustments, which is biologically implausible and implies lack of power.
Mental disorders impact the lives of millions of people globally, not only impeding their day-to-day lives but also markedly reducing life expectancy. This paper addresses the persistent challenge of predicting mortality in patients with mental diagnoses using predictive machine-learning models with electronic health records (EHR). Data from patients with mental disease diagnoses were extracted from the well-known clinical MIMIC-III data set utilizing demographic, prescription, and procedural information. Four machine learning algorithms (Logistic Regression, Random Forest, Support Vector Machine, and K-Nearest Neighbors) were used, with results indicating that Random Forest and Support Vector Machine models outperformed others, with AUC scores of 0.911. Feature importance analysis revealed that drug prescriptions, particularly Morphine Sulfate, play a pivotal role in prediction. We applied a variety of machine learning algorithms to predict 30-day mortality followed by feature importance analysis. This study can be used to assist hospital workers in identifying at-risk patients to reduce excess mortality.
Artificial intelligence has the potential to make valuable contributions to wildlife management through cost-effective methods for the collection and interpretation of wildlife data. Recent advances in remotely piloted aircraft systems (RPAS or ``drones'') and thermal imaging technology have created new approaches to collect wildlife data. These emerging technologies could provide promising alternatives to standard labourious field techniques as well as cover much larger areas. In this study, we conduct a comprehensive review and empirical study of drone-based wildlife detection. Specifically, we collect a realistic dataset of drone-derived wildlife thermal detections. Wildlife detections, including arboreal (for instance, koalas, phascolarctos cinereus) and ground dwelling species in our collected data are annotated via bounding boxes by experts. We then benchmark state-of-the-art object detection algorithms on our collected dataset. We use these experimental results to identify issues and discuss future directions in automatic animal monitoring using drones.
Histopathology plays a pivotal role in medical diagnostics. In contrast to preparing permanent sections for histopathology, a time-consuming process, preparing frozen sections is significantly faster and can be performed during surgery, where the sample scanning time should be optimized. Super-resolution techniques allow imaging the sample in lower magnification and sparing scanning time. In this paper, we present a new approach to super resolution for histopathological frozen sections, with focus on achieving better distortion measures, rather than pursuing photorealistic images that may compromise critical diagnostic information. Our deep-learning architecture focuses on learning the error between interpolated images and real images, thereby it generates high-resolution images while preserving critical image details, reducing the risk of diagnostic misinterpretation. This is done by leveraging the loss functions in the frequency domain, assigning higher weights to the reconstruction of complex, high-frequency components. In comparison to existing methods, we obtained significant improvements in terms of Structural Similarity Index (SSIM) and Peak Signal-to-Noise Ratio (PSNR), as well as indicated details that lost in the low-resolution frozen-section images, affecting the pathologist's clinical decisions. Our approach has a great potential in providing more-rapid frozen-section imaging, with less scanning, while preserving the high resolution in the imaged sample.
Biological organisms have acquired sophisticated body shapes for walking or climbing through million-year evolutionary processes. In contrast, the components of locomoting soft robots, such as legs and arms, are designed in trial-and-error loops guided by a priori knowledge and experience, which leaves considerable room for improvement. Here, we present optimized soft robots that performed a specific locomotion task without any a priori assumptions or knowledge of the layout and shapes of the limbs by fully exploiting the computational capabilities for topology optimization. The only requirements introduced were a design domain and a periodically acting pneumatic actuator. The freeform shape of a soft body was derived from iterative updates in a gradient-based topology optimization that incorporated complex physical phenomena, such as large deformations, contacts, material viscosity, and fluid-structure interactions, in transient problems. The locomotion tasks included a horizontal movement on flat ground (walking) and a vertical movement between two walls (climbing). Without any human intervention, optimized soft robots have limbs and exhibit locomotion similar to those of biological organisms. Linkage-like structures were formed for the climbing task to assign different movements to multiple legs with limited degrees of freedom in the actuator. We fabricated the optimized design using 3D printing and confirmed the performance of these robots. This study presents a new and efficient strategy for designing soft robots and other bioinspired systems, suggesting that a purely mathematical process can produce shapes reminiscent of nature's long-term evolution.
We hypothesize that due to the greedy nature of learning in multi-modal deep neural networks, these models tend to rely on just one modality while under-fitting the other modalities. Such behavior is counter-intuitive and hurts the models' generalization, as we observe empirically. To estimate the model's dependence on each modality, we compute the gain on the accuracy when the model has access to it in addition to another modality. We refer to this gain as the conditional utilization rate. In the experiments, we consistently observe an imbalance in conditional utilization rates between modalities, across multiple tasks and architectures. Since conditional utilization rate cannot be computed efficiently during training, we introduce a proxy for it based on the pace at which the model learns from each modality, which we refer to as the conditional learning speed. We propose an algorithm to balance the conditional learning speeds between modalities during training and demonstrate that it indeed addresses the issue of greedy learning. The proposed algorithm improves the model's generalization on three datasets: Colored MNIST, Princeton ModelNet40, and NVIDIA Dynamic Hand Gesture.
Breast cancer remains a global challenge, causing over 1 million deaths globally in 2018. To achieve earlier breast cancer detection, screening x-ray mammography is recommended by health organizations worldwide and has been estimated to decrease breast cancer mortality by 20-40%. Nevertheless, significant false positive and false negative rates, as well as high interpretation costs, leave opportunities for improving quality and access. To address these limitations, there has been much recent interest in applying deep learning to mammography; however, obtaining large amounts of annotated data poses a challenge for training deep learning models for this purpose, as does ensuring generalization beyond the populations represented in the training dataset. Here, we present an annotation-efficient deep learning approach that 1) achieves state-of-the-art performance in mammogram classification, 2) successfully extends to digital breast tomosynthesis (DBT; "3D mammography"), 3) detects cancers in clinically-negative prior mammograms of cancer patients, 4) generalizes well to a population with low screening rates, and 5) outperforms five-out-of-five full-time breast imaging specialists by improving absolute sensitivity by an average of 14%. Our results demonstrate promise towards software that can improve the accuracy of and access to screening mammography worldwide.
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