Background and objective: Uncertainty quantification is a pivotal field that contributes to realizing reliable and robust systems. It becomes instrumental in fortifying safe decisions by providing complementary information, particularly within high-risk applications. existing studies have explored various methods that often operate under specific assumptions or necessitate substantial modifications to the network architecture to effectively account for uncertainties. The objective of this paper is to study Conformal Prediction, an emerging distribution-free uncertainty quantification technique, and provide a comprehensive understanding of the advantages and limitations inherent in various methods within the medical imaging field. Methods: In this study, we developed Conformal Prediction, Monte Carlo Dropout, and Evidential Deep Learning approaches to assess uncertainty quantification in deep neural networks. The effectiveness of these methods is evaluated using three public medical imaging datasets focused on detecting pigmented skin lesions and blood cell types. Results: The experimental results demonstrate a significant enhancement in uncertainty quantification with the utilization of the Conformal Prediction method, surpassing the performance of the other two methods. Furthermore, the results present insights into the effectiveness of each uncertainty method in handling Out-of-Distribution samples from domain-shifted datasets. Our code is available at: Conclusions: Our conclusion highlights a robust and consistent performance of conformal prediction across diverse testing conditions. This positions it as the preferred choice for decision-making in safety-critical applications.
Computer-aided diagnosis of skin diseases is an important tool. However, the interpretability of computer-aided diagnosis is currently poor. Dermatologists and patients cannot intuitively understand the learning and prediction process of neural networks, which will lead to a decrease in the credibility of computer-aided diagnosis. In addition, traditional methods need to be trained using negative samples in order to predict the presence or absence of a lesion, but medical data is often in short supply. In this paper, we propose a multiple high-order attention interaction model (MHA-UNet) for use in a highly explainable skin lesion segmentation task. MHA-UNet is able to obtain the presence or absence of a lesion by explainable reasoning without the need for training on negative samples. Specifically, we propose a high-order attention interaction mechanism that introduces squeeze attention to a higher level for feature attention. In addition, a multiple high-order attention interaction (MHAblock) module is proposed by combining the different features of different orders. For classifying the presence or absence of lesions, we conducted classification experiments on several publicly available datasets in the absence of negative samples, based on explainable reasoning about the interaction of 5 attention orders of MHAblock. The highest positive detection rate obtained from the experiments was 81.0% and the highest negative detection rate was 83.5%. For segmentation experiments, comparison experiments of the proposed method with 13 medical segmentation models and external validation experiments with 8 state-of-the-art models in three public datasets and our clinical dataset demonstrate the state-of-the-art performance of our model. The code is available from https://github.com/wurenkai/MHA-UNet.
Concept-based models naturally lend themselves to the development of inherently interpretable skin lesion diagnosis, as medical experts make decisions based on a set of visual patterns of the lesion. Nevertheless, the development of these models depends on the existence of concept-annotated datasets, whose availability is scarce due to the specialized knowledge and expertise required in the annotation process. In this work, we show that vision-language models can be used to alleviate the dependence on a large number of concept-annotated samples. In particular, we propose an embedding learning strategy to adapt CLIP to the downstream task of skin lesion classification using concept-based descriptions as textual embeddings. Our experiments reveal that vision-language models not only attain better accuracy when using concepts as textual embeddings, but also require a smaller number of concept-annotated samples to attain comparable performance to approaches specifically devised for automatic concept generation.
The clinical diagnosis of skin lesion involves the analysis of dermoscopic and clinical modalities. Dermoscopic images provide a detailed view of the surface structures whereas clinical images offer a complementary macroscopic information. The visual diagnosis of melanoma is also based on seven-point checklist which involves identifying different visual attributes. Recently, supervised learning approaches such as convolutional neural networks (CNNs) have shown great performances using both dermoscopic and clinical modalities (Multi-modality). The seven different visual attributes in the checklist are also used to further improve the the diagnosis. The performances of these approaches, however, are still reliant on the availability of large-scaled labeled data. The acquisition of annotated dataset is an expensive and time-consuming task, more so with annotating multi-attributes. To overcome this limitation, we propose a self-supervised learning (SSL) algorithm for multi-modality skin lesion classification. Our algorithm enables the multi-modality learning by maximizing the similarities between paired dermoscopic and clinical images from different views. In addition, we generate surrogate pseudo-multi-labels that represent seven attributes via clustering analysis. We also propose a label-relation-aware module to refine each pseudo-label embedding and capture the interrelationships between pseudo-multi-labels. We validated the effectiveness of our algorithm using well-benchmarked seven-point skin lesion dataset. Our results show that our algorithm achieved better performances than other state-of-the-art SSL counterparts.
Skin cancer is one of the deadliest diseases and has a high mortality rate if left untreated. The diagnosis generally starts with visual screening and is followed by a biopsy or histopathological examination. Early detection can aid in lowering mortality rates. Visual screening can be limited by the experience of the doctor. Due to the long tail distribution of dermatological datasets and significant intra-variability between classes, automatic classification utilizing computer-aided methods becomes challenging. In this work, we propose a multitask few-shot-based approach for skin lesions that generalizes well with few labelled data to address the small sample space challenge. The proposed approach comprises a fusion of a segmentation network that acts as an attention module and classification network. The output of the segmentation network helps to focus on the most discriminatory features while making a decision by the classification network. To further enhance the classification performance, we have combined segmentation and classification loss in a weighted manner. We have also included the visualization results that explain the decisions made by the algorithm. Three dermatological datasets are used to evaluate the proposed method thoroughly. We also conducted cross-database experiments to ensure that the proposed approach is generalizable across similar datasets. Experimental results demonstrate the efficacy of the proposed work.
The potential of deep neural networks in skin lesion classification has already been demonstrated to be on-par if not superior to the dermatologists diagnosis. However, the performance of these models usually deteriorates when the test data differs significantly from the training data (i.e. domain shift). This concerning limitation for models intended to be used in real-world skin lesion classification tasks poses a risk to patients. For example, different image acquisition systems or previously unseen anatomical sites on the patient can suffice to cause such domain shifts. Mitigating the negative effect of such shifts is therefore crucial, but developing effective methods to address domain shift has proven to be challenging. In this study, we carry out an in-depth analysis of eight different unsupervised domain adaptation methods to analyze their effectiveness in improving generalization for dermoscopic datasets. To ensure robustness of our findings, we test each method on a total of ten distinct datasets, thereby covering a variety of possible domain shifts. In addition, we investigated which factors in the domain shifted datasets have an impact on the effectiveness of domain adaptation methods. Our findings show that all of the eight domain adaptation methods result in improved AUPRC for the majority of analyzed datasets. Altogether, these results indicate that unsupervised domain adaptations generally lead to performance improvements for the binary melanoma-nevus classification task regardless of the nature of the domain shift. However, small or heavily imbalanced datasets lead to a reduced conformity of the results due to the influence of these factors on the methods performance.
Renal biopsies are the gold standard for the diagnosis of kidney diseases. Lesion scores made by renal pathologists are semi-quantitative and exhibit high inter-observer variability. Automating lesion classification within segmented anatomical structures can provide decision support in quantification analysis, thereby reducing inter-observer variability. Nevertheless, classifying lesions in regions-of-interest (ROIs) is clinically challenging due to (a) a large amount of densely packed anatomical objects, (b) class imbalance across different compartments (at least 3), (c) significant variation in size and shape of anatomical objects and (d) the presence of multi-label lesions per anatomical structure. Existing models cannot address these complexities in an efficient and generic manner. This paper presents an analysis for a \textbf{generalized solution} to datasets from various sources (pathology departments) with different types of lesions. Our approach utilizes two sub-networks: dense instance segmentation and lesion classification. We introduce \textbf{DiffRegFormer}, an end-to-end dense instance segmentation sub-network designed for multi-class, multi-scale objects within ROIs. Combining diffusion models, transformers, and RCNNs, DiffRegFormer {is a computational-friendly framework that can efficiently recognize over 500 objects across three anatomical classes, i.e., glomeruli, tubuli, and arteries, within ROIs.} In a dataset of 303 ROIs from 148 Jones' silver-stained renal Whole Slide Images (WSIs), our approach outperforms previous methods, achieving an Average Precision of 52.1\% (detection) and 46.8\% (segmentation). Moreover, our lesion classification sub-network achieves 89.2\% precision and 64.6\% recall on 21889 object patches out of the 303 ROIs. Lastly, our model demonstrates direct domain transfer to PAS-stained renal WSIs without fine-tuning.
An ugly duckling is an obviously different skin lesion from surrounding lesions of an individual, and the ugly duckling sign is a criterion used to aid in the diagnosis of cutaneous melanoma by differentiating between highly suspicious and benign lesions. However, the appearance of pigmented lesions, can change drastically from one patient to another, resulting in difficulties in visual separation of ugly ducklings. Hence, we propose DMT-Quadruplet - a deep metric learning network to learn lesion features at two tiers - patient-level and lesion-level. We introduce a patient-specific quadruplet mining approach together with a tiered quadruplet network, to drive the network to learn more contextual information both globally and locally between the two tiers. We further incorporate a dynamic margin within the patient-specific mining to allow more useful quadruplets to be mined within individuals. Comprehensive experiments show that our proposed method outperforms traditional classifiers, achieving 54% higher sensitivity than a baseline ResNet18 CNN and 37% higher than a naive triplet network in classifying ugly duckling lesions. Visualisation of the data manifold in the metric space further illustrates that DMT-Quadruplet is capable of classifying ugly duckling lesions in both patient-specific and patient-agnostic manner successfully.
Deployment of Deep Neural Networks in medical imaging is hindered by distribution shift between training data and data processed after deployment, causing performance degradation. Post-Deployment Adaptation (PDA) addresses this by tailoring a pre-trained, deployed model to the target data distribution using limited labelled or entirely unlabelled target data, while assuming no access to source training data as they cannot be deployed with the model due to privacy concerns and their large size. This makes reliable adaptation challenging due to limited learning signal. This paper challenges this assumption and introduces FedPDA, a novel adaptation framework that brings the utility of learning from remote data from Federated Learning into PDA. FedPDA enables a deployed model to obtain information from source data via remote gradient exchange, while aiming to optimize the model specifically for the target domain. Tailored for FedPDA, we introduce a novel optimization method StarAlign (Source-Target Remote Gradient Alignment) that aligns gradients between source-target domain pairs by maximizing their inner product, to facilitate learning a target-specific model. We demonstrate the method's effectiveness using multi-center databases for the tasks of cancer metastases detection and skin lesion classification, where our method compares favourably to previous work. Code is available at: https://github.com/FelixWag/StarAlign
Skin cancer is a treatable disease if discovered early. We provide a production-specific solution to the skin cancer classification problem that matches human performance in melanoma identification by training a vision transformer on melanoma medical images annotated by experts. Since inference cost, both time and memory wise is important in practice, we employ knowledge distillation to obtain a model that retains 98.33% of the teacher's balanced multi-class accuracy, at a fraction of the cost. Memory-wise, our model is 49.60% smaller than the teacher. Time-wise, our solution is 69.25% faster on GPU and 97.96% faster on CPU. By adding classification heads at each level of the transformer and employing a cascading distillation process, we improve the balanced multi-class accuracy of the base model by 2.1%, while creating a range of models of various sizes but comparable performance. We provide the code at https://github.com/Longman-Stan/SkinDistilVit.
Addressing fairness in lesion classification from dermatological images is crucial due to variations in how skin diseases manifest across skin tones. However, the absence of skin tone labels in public datasets hinders building a fair classifier. To date, such skin tone labels have been estimated prior to fairness analysis in independent studies using the Individual Typology Angle (ITA). Briefly, ITA calculates an angle based on pixels extracted from skin images taking into account the lightness and yellow-blue tints. These angles are then categorised into skin tones that are subsequently used to analyse fairness in skin cancer classification. In this work, we review and compare four ITA-based approaches of skin tone classification on the ISIC18 dataset, a common benchmark for assessing skin cancer classification fairness in the literature. Our analyses reveal a high disagreement among previously published studies demonstrating the risks of ITA-based skin tone estimation methods. Moreover, we investigate the causes of such large discrepancy among these approaches and find that the lack of diversity in the ISIC18 dataset limits its use as a testbed for fairness analysis. Finally, we recommend further research on robust ITA estimation and diverse dataset acquisition with skin tone annotation to facilitate conclusive fairness assessments of artificial intelligence tools in dermatology. Our code is available at https://github.com/tkalbl/RevisitingSkinToneFairness.
Skin image datasets often suffer from imbalanced data distribution, exacerbating the difficulty of computer-aided skin disease diagnosis. Some recent works exploit supervised contrastive learning (SCL) for this long-tailed challenge. Despite achieving significant performance, these SCL-based methods focus more on head classes, yet ignoring the utilization of information in tail classes. In this paper, we propose class-Enhancement Contrastive Learning (ECL), which enriches the information of minority classes and treats different classes equally. For information enhancement, we design a hybrid-proxy model to generate class-dependent proxies and propose a cycle update strategy for parameters optimization. A balanced-hybrid-proxy loss is designed to exploit relations between samples and proxies with different classes treated equally. Taking both "imbalanced data" and "imbalanced diagnosis difficulty" into account, we further present a balanced-weighted cross-entropy loss following curriculum learning schedule. Experimental results on the classification of imbalanced skin lesion data have demonstrated the superiority and effectiveness of our method.
Medical image classification is a challenging task due to the scarcity of labeled samples and class imbalance caused by the high variance in disease prevalence. Semi-supervised learning (SSL) methods can mitigate these challenges by leveraging both labeled and unlabeled data. However, SSL methods for medical image classification need to address two key challenges: (1) estimating reliable pseudo-labels for the images in the unlabeled dataset and (2) reducing biases caused by class imbalance. In this paper, we propose a novel SSL approach, SPLAL, that effectively addresses these challenges. SPLAL leverages class prototypes and a weighted combination of classifiers to predict reliable pseudo-labels over a subset of unlabeled images. Additionally, we introduce alignment loss to mitigate model biases toward majority classes. To evaluate the performance of our proposed approach, we conduct experiments on two publicly available medical image classification benchmark datasets: the skin lesion classification (ISIC 2018) and the blood cell classification dataset (BCCD). The experimental results empirically demonstrate that our approach outperforms several state-of-the-art SSL methods over various evaluation metrics. Specifically, our proposed approach achieves a significant improvement over the state-of-the-art approach on the ISIC 2018 dataset in both Accuracy and F1 score, with relative margins of 2.24\% and 11.40\%, respectively. Finally, we conduct extensive ablation experiments to examine the contribution of different components of our approach, validating its effectiveness.
The development of reliable and fair diagnostic systems is often constrained by the scarcity of labeled data. To address this challenge, our work explores the feasibility of unsupervised domain adaptation (UDA) to integrate large external datasets for developing reliable classifiers. The adoption of UDA with multiple sources can simultaneously enrich the training set and bridge the domain gap between different skin lesion datasets, which vary due to distinct acquisition protocols. Particularly, UDA shows practical promise for improving diagnostic reliability when training with a custom skin lesion dataset, where only limited labeled data are available from the target domain. In this study, we investigate three UDA training schemes based on source data utilization: single-source, combined-source, and multi-source UDA. Our findings demonstrate the effectiveness of applying UDA on multiple sources for binary and multi-class classification. A strong correlation between test error and label shift in multi-class tasks has been observed in the experiment. Crucially, our study shows that UDA can effectively mitigate bias against minority groups and enhance fairness in diagnostic systems, while maintaining superior classification performance. This is achieved even without directly implementing fairness-focused techniques. This success is potentially attributed to the increased and well-adapted demographic information obtained from multiple sources.
Trustworthy deployment of deep learning medical imaging models into real-world clinical practice requires that they be calibrated. However, models that are well calibrated overall can still be poorly calibrated for a sub-population, potentially resulting in a clinician unwittingly making poor decisions for this group based on the recommendations of the model. Although methods have been shown to successfully mitigate biases across subgroups in terms of model accuracy, this work focuses on the open problem of mitigating calibration biases in the context of medical image analysis. Our method does not require subgroup attributes during training, permitting the flexibility to mitigate biases for different choices of sensitive attributes without re-training. To this end, we propose a novel two-stage method: Cluster-Focal to first identify poorly calibrated samples, cluster them into groups, and then introduce group-wise focal loss to improve calibration bias. We evaluate our method on skin lesion classification with the public HAM10000 dataset, and on predicting future lesional activity for multiple sclerosis (MS) patients. In addition to considering traditional sensitive attributes (e.g. age, sex) with demographic subgroups, we also consider biases among groups with different image-derived attributes, such as lesion load, which are required in medical image analysis. Our results demonstrate that our method effectively controls calibration error in the worst-performing subgroups while preserving prediction performance, and outperforming recent baselines.
Many skin lesion analysis (SLA) methods recently focused on developing a multi-modal-based multi-label classification method due to two factors. The first is multi-modal data, i.e., clinical and dermoscopy images, which can provide complementary information to obtain more accurate results than single-modal data. The second one is that multi-label classification, i.e., seven-point checklist (SPC) criteria as an auxiliary classification task can not only boost the diagnostic accuracy of melanoma in the deep learning (DL) pipeline but also provide more useful functions to the clinical doctor as it is commonly used in clinical dermatologist's diagnosis. However, most methods only focus on designing a better module for multi-modal data fusion; few methods explore utilizing the label correlation between SPC and skin disease for performance improvement. This study fills the gap that introduces a Graph Convolution Network (GCN) to exploit prior co-occurrence between each category as a correlation matrix into the DL model for the multi-label classification. However, directly applying GCN degraded the performances in our experiments; we attribute this to the weak generalization ability of GCN in the scenario of insufficient statistical samples of medical data. We tackle this issue by proposing a Graph-Ensemble Learning Model (GELN) that views the prediction from GCN as complementary information of the predictions from the fusion model and adaptively fuses them by a weighted averaging scheme, which can utilize the valuable information from GCN while avoiding its negative influences as much as possible. To evaluate our method, we conduct experiments on public datasets. The results illustrate that our GELN can consistently improve the classification performance on different datasets and that the proposed method can achieve state-of-the-art performance in SPC and diagnosis classification.
Skin cancer, a deadly form of cancer, exhibits a 23\% survival rate in the USA with late diagnosis. Early detection can significantly increase the survival rate, and facilitate timely treatment. Accurate biomedical image classification is vital in medical analysis, aiding clinicians in disease diagnosis and treatment. Deep learning (DL) techniques, such as convolutional neural networks and transformers, have revolutionized clinical decision-making automation. However, computational cost and hardware constraints limit the implementation of state-of-the-art DL architectures. In this work, we explore a new type of neural network that does not need backpropagation (BP), namely the Forward-Forward Algorithm (FFA), for skin lesion classification. While FFA is claimed to use very low-power analog hardware, BP still tends to be superior in terms of classification accuracy. In addition, our experimental results suggest that the combination of FFA and BP can be a better alternative to achieve a more accurate prediction.
Chest radiographs are the most commonly performed radiological examinations for lesion detection. Recent advances in deep learning have led to encouraging results in various thoracic disease detection tasks. Particularly, the architecture with feature pyramid network performs the ability to recognise targets with different sizes. However, such networks are difficult to focus on lesion regions in chest X-rays due to their high resemblance in vision. In this paper, we propose a dual attention supervised module for multi-label lesion detection in chest radiographs, named DualAttNet. It efficiently fuses global and local lesion classification information based on an image-level attention block and a fine-grained disease attention algorithm. A binary cross entropy loss function is used to calculate the difference between the attention map and ground truth at image level. The generated gradient flow is leveraged to refine pyramid representations and highlight lesion-related features. We evaluate the proposed model on VinDr-CXR, ChestX-ray8 and COVID-19 datasets. The experimental results show that DualAttNet surpasses baselines by 0.6% to 2.7% mAP and 1.4% to 4.7% AP50 with different detection architectures. The code for our work and more technical details can be found at https://github.com/xq141839/DualAttNet.
Representational transfer from publicly available models is a promising technique for improving medical image classification, especially in long-tailed datasets with rare diseases. However, existing methods often overlook the frequency-dependent behavior of these models, thereby limiting their effectiveness in transferring representations and generalizations to rare diseases. In this paper, we propose FoPro-KD, a novel framework that leverages the power of frequency patterns learned from frozen pre-trained models to enhance their transferability and compression, presenting a few unique insights: 1) We demonstrate that leveraging representations from publicly available pre-trained models can substantially improve performance, specifically for rare classes, even when utilizing representations from a smaller pre-trained model. 2) We observe that pre-trained models exhibit frequency preferences, which we explore using our proposed Fourier Prompt Generator (FPG), allowing us to manipulate specific frequencies in the input image, enhancing the discriminative representational transfer. 3) By amplifying or diminishing these frequencies in the input image, we enable Effective Knowledge Distillation (EKD). EKD facilitates the transfer of knowledge from pre-trained models to smaller models. Through extensive experiments in long-tailed gastrointestinal image recognition and skin lesion classification, where rare diseases are prevalent, our FoPro-KD framework outperforms existing methods, enabling more accessible medical models for rare disease classification. Code is available at https://github.com/xmed-lab/FoPro-KD.
A lot of deep learning (DL) research these days is mainly focused on improving quantitative metrics regardless of other factors. In human-centered applications, like skin lesion classification in dermatology, DL-driven clinical decision support systems are still in their infancy due to the limited transparency of their decision-making process. Moreover, the lack of procedures that can explain the behavior of trained DL algorithms leads to almost no trust from clinical physicians. To diagnose skin lesions, dermatologists rely on visual assessment of the disease and the data gathered from the patient's anamnesis. Data-driven algorithms dealing with multi-modal data are limited by the separation of feature-level and decision-level fusion procedures required by convolutional architectures. To address this issue, we enable single-stage multi-modal data fusion via the attention mechanism of transformer-based architectures to aid in diagnosing skin diseases. Our method beats other state-of-the-art single- and multi-modal DL architectures in image-rich and patient-data-rich environments. Additionally, the choice of the architecture enables native interpretability support for the classification task both in the image and metadata domain with no additional modifications necessary.