Alceu Bissoto

Zahra Mirikharaji, Kumar Abhishek, Alceu Bissoto et al.

Skin cancer is a major public health problem that could benefit from computer-aided diagnosis to reduce the burden of this common disease. Skin lesion segmentation from images is an important step toward achieving this goal. However, the presence of natural and artificial artifacts (e.g., hair and air bubbles), intrinsic factors (e.g., lesion shape and contrast), and variations in image acquisition conditions make skin lesion segmentation a challenging task. Recently, various researchers have explored the applicability of deep learning models to skin lesion segmentation. In this survey, we cross-examine 177 research papers that deal with deep learning-based segmentation of skin lesions. We analyze these works along several dimensions, including input data (datasets, preprocessing, and synthetic data generation), model design (architecture, modules, and losses), and evaluation aspects (data annotation requirements and segmentation performance). We discuss these dimensions both from the viewpoint of select seminal works, and from a systematic viewpoint, examining how those choices have influenced current trends, and how their limitations should be addressed. To facilitate comparisons, we summarize all examined works in a comprehensive table as well as an interactive table available online at https://github.com/sfu-mial/skin-lesion-segmentation-survey.

Nourhan Bayasi, Jamil Fayyad, Alceu Bissoto et al.

Continual Learning (CL) is crucial for enabling networks to dynamically adapt as they learn new tasks sequentially, accommodating new data and classes without catastrophic forgetting. Diverging from conventional perspectives on CL, our paper introduces a new perspective wherein forgetting could actually benefit the sequential learning paradigm. Specifically, we present BiasPruner, a CL framework that intentionally forgets spurious correlations in the training data that could lead to shortcut learning. Utilizing a new bias score that measures the contribution of each unit in the network to learning spurious features, BiasPruner prunes those units with the highest bias scores to form a debiased subnetwork preserved for a given task. As BiasPruner learns a new task, it constructs a new debiased subnetwork, potentially incorporating units from previous subnetworks, which improves adaptation and performance on the new task. During inference, BiasPruner employs a simple task-agnostic approach to select the best debiased subnetwork for predictions. We conduct experiments on three medical datasets for skin lesion classification and chest X-Ray classification and demonstrate that BiasPruner consistently outperforms SOTA CL methods in terms of classification performance and fairness. Our code is available here.

Alceu Bissoto, Catarina Barata, Eduardo Valle et al.

Deep Learning failure cases are abundant, particularly in the medical area. Recent studies in out-of-distribution generalization have advanced considerably on well-controlled synthetic datasets, but they do not represent medical imaging contexts. We propose a pipeline that relies on artifacts annotation to enable generalization evaluation and debiasing for the challenging skin lesion analysis context. First, we partition the data into levels of increasingly higher biased training and test sets for better generalization assessment. Then, we create environments based on skin lesion artifacts to enable domain generalization methods. Finally, after robust training, we perform a test-time debiasing procedure, reducing spurious features in inference images. Our experiments show our pipeline improves performance metrics in biased cases, and avoids artifacts when using explanation methods. Still, when evaluating such models in out-of-distribution data, they did not prefer clinically-meaningful features. Instead, performance only improved in test sets that present similar artifacts from training, suggesting models learned to ignore the known set of artifacts. Our results raise a concern that debiasing models towards a single aspect may not be enough for fair skin lesion analysis.

Levy Chaves, Alceu Bissoto, Eduardo Valle et al.

Transfer learning boosts the performance of medical image analysis by enabling deep learning (DL) on small datasets through the knowledge acquired from large ones. As the number of DL architectures explodes, exhaustively attempting all candidates becomes unfeasible, motivating cheaper alternatives for choosing them. Transferability scoring methods emerge as an enticing solution, allowing to efficiently calculate a score that correlates with the architecture accuracy on any target dataset. However, since transferability scores have not been evaluated on medical datasets, their use in this context remains uncertain, preventing them from benefiting practitioners. We fill that gap in this work, thoroughly evaluating seven transferability scores in three medical applications, including out-of-distribution scenarios. Despite promising results in general-purpose datasets, our results show that no transferability score can reliably and consistently estimate target performance in medical contexts, inviting further work in that direction.

Alceu Bissoto, Catarina Barata, Eduardo Valle et al.

Skin lesion analysis models are biased by artifacts placed during image acquisition, which influence model predictions despite carrying no clinical information. Solutions that address this problem by regularizing models to prevent learning those spurious features achieve only partial success, and existing test-time debiasing techniques are inappropriate for skin lesion analysis due to either making unrealistic assumptions on the distribution of test data or requiring laborious annotation from medical practitioners. We propose TTS (Test-Time Selection), a human-in-the-loop method that leverages positive (e.g., lesion area) and negative (e.g., artifacts) keypoints in test samples. TTS effectively steers models away from exploiting spurious artifact-related correlations without retraining, and with less annotation requirements. Our solution is robust to a varying availability of annotations, and different levels of bias. We showcase on the ISIC2019 dataset (for which we release a subset of annotated images) how our model could be deployed in the real-world for mitigating bias.

Diogo J. Araújo, M. Rita Verdelho, Alceu Bissoto et al.

Deep learning models have revolutionized the field of medical image analysis, due to their outstanding performances. However, they are sensitive to spurious correlations, often taking advantage of dataset bias to improve results for in-domain data, but jeopardizing their generalization capabilities. In this paper, we propose to limit the amount of information these models use to reach the final classification, by using a multiple instance learning (MIL) framework. MIL forces the model to use only a (small) subset of patches in the image, identifying discriminative regions. This mimics the clinical procedures, where medical decisions are based on localized findings. We evaluate our framework on two medical applications: skin cancer diagnosis using dermoscopy and breast cancer diagnosis using mammography. Our results show that using only a subset of the patches does not compromise diagnostic performance for in-domain data, compared to the baseline approaches. However, our approach is more robust to shifts in patient demographics, while also providing more detailed explanations about which regions contributed to the decision. Code is available at: https://github.com/diogojpa99/MedicalMultiple-Instance-Learning.

Tiago Mota, M. Rita Verdelho, Alceu Bissoto et al.

The acquisition of different data modalities can enhance our knowledge and understanding of various diseases, paving the way for a more personalized healthcare. Thus, medicine is progressively moving towards the generation of massive amounts of multi-modal data (\emph{e.g,} molecular, radiology, and histopathology). While this may seem like an ideal environment to capitalize data-centric machine learning approaches, most methods still focus on exploring a single or a pair of modalities due to a variety of reasons: i) lack of ready to use curated datasets; ii) difficulty in identifying the best multi-modal fusion strategy; and iii) missing modalities across patients. In this paper we introduce a real world multi-modal dataset called MMIST-CCRCC that comprises 2 radiology modalities (CT and MRI), histopathology, genomics, and clinical data from 618 patients with clear cell renal cell carcinoma (ccRCC). We provide single and multi-modal (early and late fusion) benchmarks in the task of 12-month survival prediction in the challenging scenario of one or more missing modalities for each patient, with missing rates that range from 26$\%$ for genomics data to more than 90$\%$ for MRI. We show that even with such severe missing rates the fusion of modalities leads to improvements in the survival forecasting. Additionally, incorporating a strategy to generate the latent representations of the missing modalities given the available ones further improves the performance, highlighting a potential complementarity across modalities. Our dataset and code are available here: https://multi-modal-ist.github.io/datasets/ccRCC

Rosa Y. G. Paccotacya-Yanque, Alceu Bissoto, Sandra Avila

Deep Learning has shown outstanding results in computer vision tasks; healthcare is no exception. However, there is no straightforward way to expose the decision-making process of DL models. Good accuracy is not enough for skin cancer predictions. Understanding the model's behavior is crucial for clinical application and reliable outcomes. In this work, we identify desiderata for explanations in skin-lesion models. We analyzed seven methods, four based on pixel-attribution (Grad-CAM, Score-CAM, LIME, SHAP) and three on high-level concepts (ACE, ICE, CME), for a deep neural network trained on the International Skin Imaging Collaboration Archive. Our findings indicate that while these techniques reveal biases, there is room for improving the comprehensiveness of explanations to achieve transparency in skin-lesion models.

Miguel Correia, Alceu Bissoto, Carlos Santiago et al.

Skin cancer detection through dermoscopy image analysis is a critical task. However, existing models used for this purpose often lack interpretability and reliability, raising the concern of physicians due to their black-box nature. In this paper, we propose a novel approach for the diagnosis of melanoma using an interpretable prototypical-part model. We introduce a guided supervision based on non-expert feedback through the incorporation of: 1) binary masks, obtained automatically using a segmentation network; and 2) user-refined prototypes. These two distinct information pathways aim to ensure that the learned prototypes correspond to relevant areas within the skin lesion, excluding confounding factors beyond its boundaries. Experimental results demonstrate that, even without expert supervision, our approach achieves superior performance and generalization compared to non-interpretable models.

Tim Flühmann, Alceu Bissoto, Trung-Dung Hoang et al.

Performance monitoring is essential for safe clinical deployment of image classification models. However, because ground-truth labels are typically unavailable in the target dataset, direct assessment of real-world model performance is infeasible. State-of-the-art performance estimation methods address this by leveraging confidence scores to estimate the target accuracy. Despite being a promising direction, the established methods mainly estimate the model's accuracy and are rarely evaluated in a clinical domain, where strong class imbalances and dataset shifts are common. Our contributions are twofold: First, we introduce generalisations of existing performance prediction methods that directly estimate the full confusion matrix. Then, we benchmark their performance on chest x-ray data in real-world distribution shifts as well as simulated covariate and prevalence shifts. The proposed confusion matrix estimation methods reliably predicted clinically relevant counting metrics on medical images under distribution shifts. However, our simulated shift scenarios exposed important failure modes of current performance estimation techniques, calling for a better understanding of real-world deployment contexts when implementing these performance monitoring techniques for postmarket surveillance of medical AI models.

Trung-Dung Hoang, Alceu Bissoto, Vihangkumar V. Naik et al.

Accurately estimating parameters of physiological models is essential to achieving reliable digital twins. For Type 1 Diabetes, this is particularly challenging due to the complexity of glucose-insulin interactions. Traditional methods based on Markov Chain Monte Carlo struggle with high-dimensional parameter spaces and fit parameters from scratch at inference time, making them slow and computationally expensive. In this study, we propose a Simulation-Based Inference approach based on Neural Posterior Estimation to efficiently capture the complex relationships between meal intake, insulin, and glucose level, providing faster, amortized inference. Our experiments demonstrate that SBI not only outperforms traditional methods in parameter estimation but also generalizes better to unseen conditions, offering real-time posterior inference with reliable uncertainty quantification.

Alceu Bissoto, Trung-Dung Hoang, Tim Flühmann et al.

Machine learning (ML) models may suffer from significant performance disparities between patient groups. Identifying such disparities by monitoring performance at a granular level is crucial for safely deploying ML to each patient. Traditional subgroup analysis based on metadata can expose performance disparities only if the available metadata (e.g., patient sex) sufficiently reflects the main reasons for performance variability, which is not common. Subgroup discovery techniques that identify cohesive subgroups based on learned feature representations appear as a potential solution: They could expose hidden stratifications and provide more granular subgroup performance reports. However, subgroup discovery is challenging to evaluate even as a standalone task, as ground truth stratification labels do not exist in real data. Subgroup discovery has thus neither been applied nor evaluated for the application of subgroup performance monitoring. Here, we apply subgroup discovery for performance monitoring in chest x-ray and skin lesion classification. We propose novel evaluation strategies and show that a simplified subgroup discovery method without access to classification labels or metadata can expose larger performance disparities than traditional metadata-based subgroup analysis. We provide the first compelling evidence that subgroup discovery can serve as an important tool for comprehensive performance validation and monitoring of trustworthy AI in medicine.

Alceu Bissoto, Catarina Barata, Eduardo Valle et al.

Distribution shifts are common in real-world datasets and can affect the performance and reliability of deep learning models. In this paper, we study two types of distribution shifts: diversity shifts, which occur when test samples exhibit patterns unseen during training, and correlation shifts, which occur when test data present a different correlation between seen invariant and spurious features. We propose an integrated protocol to analyze both types of shifts using datasets where they co-exist in a controllable manner. Finally, we apply our approach to a real-world classification problem of skin cancer analysis, using out-of-distribution datasets and specialized bias annotations. Our protocol reveals three findings: 1) Models learn and propagate correlation shifts even with low-bias training; this poses a risk of accumulating and combining unaccountable weak biases; 2) Models learn robust features in high- and low-bias scenarios but use spurious ones if test samples have them; this suggests that spurious correlations do not impair the learning of robust features; 3) Diversity shift can reduce the reliance on spurious correlations; this is counter intuitive since we expect biased models to depend more on biases when invariant features are missing. Our work has implications for distribution shift research and practice, providing new insights into how models learn and rely on spurious correlations under different types of shifts.

Levy Chaves, Alceu Bissoto, Eduardo Valle et al.

Self-supervised pre-training appears as an advantageous alternative to supervised pre-trained for transfer learning. By synthesizing annotations on pretext tasks, self-supervision allows to pre-train models on large amounts of pseudo-labels before fine-tuning them on the target task. In this work, we assess self-supervision for the diagnosis of skin lesions, comparing three self-supervised pipelines to a challenging supervised baseline, on five test datasets comprising in- and out-of-distribution samples. Our results show that self-supervision is competitive both in improving accuracies and in reducing the variability of outcomes. Self-supervision proves particularly useful for low training data scenarios ($<1\,500$ and $<150$ samples), where its ability to stabilize the outcomes is essential to provide sound results.

Alceu Bissoto, Eduardo Valle, Sandra Avila

Despite the growing availability of high-quality public datasets, the lack of training samples is still one of the main challenges of deep-learning for skin lesion analysis. Generative Adversarial Networks (GANs) appear as an enticing alternative to alleviate the issue, by synthesizing samples indistinguishable from real images, with a plethora of works employing them for medical applications. Nevertheless, carefully designed experiments for skin-lesion diagnosis with GAN-based data augmentation show favorable results only on out-of-distribution test sets. For GAN-based data anonymization $-$ where the synthetic images replace the real ones $-$ favorable results also only appear for out-of-distribution test sets. Because of the costs and risks associated with GAN usage, those results suggest caution in their adoption for medical applications.

Alceu Bissoto, Eduardo Valle, Sandra Avila

Data-driven models are now deployed in a plethora of real-world applications - including automated diagnosis - but models learned from data risk learning biases from that same data. When models learn spurious correlations not found in real-world situations, their deployment for critical tasks, such as medical decisions, can be catastrophic. In this work we address this issue for skin-lesion classification models, with two objectives: finding out what are the spurious correlations exploited by biased networks, and debiasing the models by removing such spurious correlations from them. We perform a systematic integrated analysis of 7 visual artifacts (which are possible sources of biases exploitable by networks), employ a state-of-the-art technique to prevent the models from learning spurious correlations, and propose datasets to test models for the presence of bias. We find out that, despite interesting results that point to promising future research, current debiasing methods are not ready to solve the bias issue for skin-lesion models.

Alceu Bissoto, Eduardo Valle, Sandra Avila

Generative Adversarial Networks fostered a newfound interest in generative models, resulting in a swelling wave of new works that new-coming researchers may find formidable to surf. In this paper, we intend to help those researchers, by splitting that incoming wave into six "fronts": Architectural Contributions, Conditional Techniques, Normalization and Constraint Contributions, Loss Functions, Image-to-image Translations, and Validation Metrics. The division in fronts organizes literature into approachable blocks, ultimately communicating to the reader how the area is evolving. Previous surveys in the area, which this works also tabulates, focus on a few of those fronts, leaving a gap that we propose to fill with a more integrated, comprehensive overview. Here, instead of an exhaustive survey, we opt for a straightforward review: our target is to be an entry point to this vast literature, and also to be able to update experienced researchers to the newest techniques.

Alceu Bissoto, Michel Fornaciali, Eduardo Valle et al.

Melanoma is the deadliest form of skin cancer. Automated skin lesion analysis plays an important role for early detection. Nowadays, the ISIC Archive and the Atlas of Dermoscopy dataset are the most employed skin lesion sources to benchmark deep-learning based tools. However, all datasets contain biases, often unintentional, due to how they were acquired and annotated. Those biases distort the performance of machine-learning models, creating spurious correlations that the models can unfairly exploit, or, contrarily destroying cogent correlations that the models could learn. In this paper, we propose a set of experiments that reveal both types of biases, positive and negative, in existing skin lesion datasets. Our results show that models can correctly classify skin lesion images without clinically-meaningful information: disturbingly, the machine-learning model learned over images where no information about the lesion remains, presents an accuracy above the AI benchmark curated with dermatologists' performances. That strongly suggests spurious correlations guiding the models. We fed models with additional clinically meaningful information, which failed to improve the results even slightly, suggesting the destruction of cogent correlations. Our main findings raise awareness of the limitations of models trained and evaluated in small datasets such as the ones we evaluated, and may suggest future guidelines for models intended for real-world deployment.

Alceu Bissoto, Fábio Perez, Eduardo Valle et al.

Skin cancer is by far the most common type of cancer. Early detection is the key to increase the chances for successful treatment significantly. Currently, Deep Neural Networks are the state-of-the-art results on automated skin cancer classification. To push the results further, we need to address the lack of annotated data, which is expensive and require much effort from specialists. To bypass this problem, we propose using Generative Adversarial Networks for generating realistic synthetic skin lesion images. To the best of our knowledge, our results are the first to show visually-appealing synthetic images that comprise clinically-meaningful information.

Alceu Bissoto, Fábio Perez, Vinícius Ribeiro et al.

This extended abstract describes the participation of RECOD Titans in parts 1 to 3 of the ISIC Challenge 2018 "Skin Lesion Analysis Towards Melanoma Detection" (MICCAI 2018). Although our team has a long experience with melanoma classification and moderate experience with lesion segmentation, the ISIC Challenge 2018 was the very first time we worked on lesion attribute detection. For each task we submitted 3 different ensemble approaches, varying combinations of models and datasets. Our best results on the official testing set, regarding the official metric of each task, were: 0.728 (segmentation), 0.344 (attribute detection) and 0.803 (classification). Those submissions reached, respectively, the 56th, 14th and 9th places.