Mahdi Gilany, Paul Wilson, Andrea Perera-Ortega et al.
A large body of previous machine learning methods for ultrasound-based prostate cancer detection classify small regions of interest (ROIs) of ultrasound signals that lie within a larger needle trace corresponding to a prostate tissue biopsy (called biopsy core). These ROI-scale models suffer from weak labeling as histopathology results available for biopsy cores only approximate the distribution of cancer in the ROIs. ROI-scale models do not take advantage of contextual information that are normally considered by pathologists, i.e. they do not consider information about surrounding tissue and larger-scale trends when identifying cancer. We aim to improve cancer detection by taking a multi-scale, i.e. ROI-scale and biopsy core-scale, approach. Methods: Our multi-scale approach combines (i) an "ROI-scale" model trained using self-supervised learning to extract features from small ROIs and (ii) a "core-scale" transformer model that processes a collection of extracted features from multiple ROIs in the needle trace region to predict the tissue type of the corresponding core. Attention maps, as a byproduct, allow us to localize cancer at the ROI scale. We analyze this method using a dataset of micro-ultrasound acquired from 578 patients who underwent prostate biopsy, and compare our model to baseline models and other large-scale studies in the literature. Results and Conclusions: Our model shows consistent and substantial performance improvements compared to ROI-scale-only models. It achieves 80.3% AUROC, a statistically significant improvement over ROI-scale classification. We also compare our method to large studies on prostate cancer detection, using other imaging modalities. Our code is publicly available at www.github.com/med-i-lab/TRUSFormer
Fahimeh Fooladgar, Minh Nguyen Nhat To, Parvin Mousavi et al.
Deep neural networks have proven to be highly effective when large amounts of data with clean labels are available. However, their performance degrades when training data contains noisy labels, leading to poor generalization on the test set. Real-world datasets contain noisy label samples that either have similar visual semantics to other classes (in-distribution) or have no semantic relevance to any class (out-of-distribution) in the dataset. Most state-of-the-art methods leverage ID labeled noisy samples as unlabeled data for semi-supervised learning, but OOD labeled noisy samples cannot be used in this way because they do not belong to any class within the dataset. Hence, in this paper, we propose incorporating the information from all the training data by leveraging the benefits of self-supervised training. Our method aims to extract a meaningful and generalizable embedding space for each sample regardless of its label. Then, we employ a simple yet effective K-nearest neighbor method to remove portions of out-of-distribution samples. By discarding these samples, we propose an iterative "Manifold DivideMix" algorithm to find clean and noisy samples, and train our model in a semi-supervised way. In addition, we propose "MixEMatch", a new algorithm for the semi-supervised step that involves mixup augmentation at the input and final hidden representations of the model. This will extract better representations by interpolating both in the input and manifold spaces. Extensive experiments on multiple synthetic-noise image benchmarks and real-world web-crawled datasets demonstrate the effectiveness of our proposed framework. Code is available at https://github.com/Fahim-F/ManifoldDivideMix.
Prostate Cancer (PCa) is a prevalent disease among men, and multi-parametric MRIs offer a non-invasive method for its detection. While MRI-based deep learning solutions have shown promise in supporting PCa diagnosis, acquiring sufficient training data, particularly in local clinics remains challenging. One potential solution is to take advantage of publicly available datasets to pre-train deep models and fine-tune them on the local data, but multi-source MRIs can pose challenges due to cross-domain distribution differences. These limitations hinder the adoption of explainable and reliable deep-learning solutions in local clinics for PCa diagnosis. In this work, we present a novel approach for unpaired image-to-image translation of prostate multi-parametric MRIs and an uncertainty-aware training approach for classifying clinically significant PCa, to be applied in data-constrained settings such as local and small clinics. Our approach involves a novel pipeline for translating unpaired 3.0T multi-parametric prostate MRIs to 1.5T, thereby augmenting the available training data. Additionally, we introduce an evidential deep learning approach to estimate model uncertainty and employ dataset filtering techniques during training. Furthermore, we propose a simple, yet efficient Evidential Focal Loss, combining focal loss with evidential uncertainty, to train our model effectively. Our experiments demonstrate that the proposed method significantly improves the Area Under ROC Curve (AUC) by over 20% compared to the previous work. Our code is available at https://github.com/med-i-lab/DT_UE_PCa
Paul F. R. Wilson, Mahdi Gilany, Amoon Jamzad et al.
Deep learning-based analysis of high-frequency, high-resolution micro-ultrasound data shows great promise for prostate cancer detection. Previous approaches to analysis of ultrasound data largely follow a supervised learning paradigm. Ground truth labels for ultrasound images used for training deep networks often include coarse annotations generated from the histopathological analysis of tissue samples obtained via biopsy. This creates inherent limitations on the availability and quality of labeled data, posing major challenges to the success of supervised learning methods. On the other hand, unlabeled prostate ultrasound data are more abundant. In this work, we successfully apply self-supervised representation learning to micro-ultrasound data. Using ultrasound data from 1028 biopsy cores of 391 subjects obtained in two clinical centres, we demonstrate that feature representations learnt with this method can be used to classify cancer from non-cancer tissue, obtaining an AUROC score of 91% on an independent test set. To the best of our knowledge, this is the first successful end-to-end self-supervised learning approach for prostate cancer detection using ultrasound data. Our method outperforms baseline supervised learning approaches, generalizes well between different data centers, and scale well in performance as more unlabeled data are added, making it a promising approach for future research using large volumes of unlabeled data.
MOTIVATION: Detection of prostate cancer during transrectal ultrasound-guided biopsy is challenging. The highly heterogeneous appearance of cancer, presence of ultrasound artefacts, and noise all contribute to these difficulties. Recent advancements in high-frequency ultrasound imaging - micro-ultrasound - have drastically increased the capability of tissue imaging at high resolution. Our aim is to investigate the development of a robust deep learning model specifically for micro-ultrasound-guided prostate cancer biopsy. For the model to be clinically adopted, a key challenge is to design a solution that can confidently identify the cancer, while learning from coarse histopathology measurements of biopsy samples that introduce weak labels. METHODS: We use a dataset of micro-ultrasound images acquired from 194 patients, who underwent prostate biopsy. We train a deep model using a co-teaching paradigm to handle noise in labels, together with an evidential deep learning method for uncertainty estimation. We evaluate the performance of our model using the clinically relevant metric of accuracy vs. confidence. RESULTS: Our model achieves a well-calibrated estimation of predictive uncertainty with area under the curve of 88$\%$. The use of co-teaching and evidential deep learning in combination yields significantly better uncertainty estimation than either alone. We also provide a detailed comparison against state-of-the-art in uncertainty estimation.
Dilakshan Srikanthan, Amoon Jamzad, Paul Wilson et al.
Whether attention maps from pathology foundation models capture genuine biology remains unknown, yet this question is critical for clinical trust and regulatory approval. We propose a spatial transcriptomics-based framework for orthogonal, hypothesis-free evaluation of attention and apply it to five pathology foundation models (CONCH v1.5, UNI v2, Virchow2, GigaPath, H-Optimus-1) and a ResNet50 baseline. Using attention-based multiple instance learning, we train single-task and multi-task models to predict five molecular alterations in glioblastoma on the CPTAC cohort, validate on an independent TCGA cohort, and evaluate biological coherence of attention maps against 87 transcriptional signatures using co-registered Visium spatial transcriptomics data from 18 samples. Internally, no single encoder dominates across all tasks, and external validation inverts internal performance rankings. Attention maps show a five-fold enrichment gradient from pathways (Cohen's d=0.329) to individual genes (d=0.055), indicating that attention captures emergent multi-gene transcriptional programs rather than individual molecular events. Spatially smooth attention maps do not imply biological coherence, and different encoders attend to distinct biological compartments. Our framework provides objective, quantitative assessment of what foundation models learn from histopathology, moving the field beyond qualitative saliency map review.
Mahdi Gilany, Mohamed Harmanani, Paul Wilson et al.
High resolution micro-ultrasound has demonstrated promise in real-time prostate cancer detection, with deep learning becoming a prominent tool for learning complex tissue properties reflected on ultrasound. However, a significant roadblock to real-world deployment remains, which prior works often overlook: model performance suffers when applied to data from different clinical centers due to variations in data distribution. This distribution shift significantly impacts the model's robustness, posing major challenge to clinical deployment. Domain adaptation and specifically its test-time adaption (TTA) variant offer a promising solution to address this challenge. In a setting designed to reflect real-world conditions, we compare existing methods to state-of-the-art TTA approaches adopted for cancer detection, demonstrating the lack of robustness to distribution shifts in the former. We then propose Diverse Ensemble Entropy Minimization (DEnEM), questioning the effectiveness of current TTA methods on ultrasound data. We show that these methods, although outperforming baselines, are suboptimal due to relying on neural networks output probabilities, which could be uncalibrated, or relying on data augmentation, which is not straightforward to define on ultrasound data. Our results show a significant improvement of $5\%$ to $7\%$ in AUROC over the existing methods and $3\%$ to $5\%$ over TTA methods, demonstrating the advantage of DEnEM in addressing distribution shift. \keywords{Ultrasound Imaging \and Prostate Cancer \and Computer-aided Diagnosis \and Distribution Shift Robustness \and Test-time Adaptation.}
Faranak Akbarifar, Nooshin Maghsoodi, Sean P Dukelow et al.
Purpose: Visually Guided Reaching (VGR) on the Kinarm robot yields sensitive kinematic biomarkers but requires 40-64 reaches, imposing time and fatigue burdens. We evaluate whether time-series foundation models can replace unrecorded trials from an early subset of reaches while preserving the reliability of standard Kinarm parameters. Methods: We analyzed VGR speed signals from 461 stroke and 599 control participants across 4- and 8-target reaching protocols. We withheld all but the first 8 or 16 reaching trials and used ARIMA, MOMENT, and Chronos models, fine-tuned on 70 percent of subjects, to forecast synthetic trials. We recomputed four kinematic features of reaching (reaction time, movement time, posture speed, maximum speed) on combined recorded plus forecasted trials and compared them to full-length references using ICC(2,1). Results: Chronos forecasts restored ICC >= 0.90 for all parameters with only 8 recorded trials plus forecasts, matching the reliability of 24-28 recorded reaches (Delta ICC <= 0.07). MOMENT yielded intermediate gains, while ARIMA improvements were minimal. Across cohorts and protocols, synthetic trials replaced reaches without materially compromising feature reliability. Conclusion: Foundation-model forecasting can greatly shorten Kinarm VGR assessment time. For the most impaired stroke survivors, sessions drop from 4-5 minutes to about 1 minute while preserving kinematic precision. This forecast-augmented paradigm promises efficient robotic evaluations for assessing motor impairments following stroke.
Emma Willis, Tarek Elghareb, Paul F. R. Wilson et al.
Purpose: Non-invasive grading of prostate cancer (PCa) from micro-ultrasound (micro-US) could expedite triage and guide biopsies toward the most aggressive regions, yet current models struggle to infer tissue micro-structure at coarse imaging resolutions. Methods: We introduce an unpaired histopathology knowledge-distillation strategy that trains a micro-US encoder to emulate the embedding distribution of a pretrained histopathology foundation model, conditioned on International Society of Urological Pathology (ISUP) grades. Training requires no patient-level pairing or image registration, and histopathology inputs are not used at inference. Results: Compared to the current state of the art, our approach increases sensitivity to clinically significant PCa (csPCa) at 60% specificity by 3.5% and improves overall sensitivity at 60% specificity by 1.2%. Conclusion: By enabling earlier and more dependable cancer risk stratification solely from imaging, our method advances clinical feasibility. Source code will be publicly released upon publication.
Minh Nguyen Nhat To, Paul F RWilson, Viet Nguyen et al.
The subpopulationtion shift, characterized by a disparity in subpopulation distributibetween theween the training and target datasets, can significantly degrade the performance of machine learning models. Current solutions to subpopulation shift involve modifying empirical risk minimization with re-weighting strategies to improve generalization. This strategy relies on assumptions about the number and nature of subpopulations and annotations on group membership, which are unavailable for many real-world datasets. Instead, we propose using an ensemble of diverse classifiers to adaptively capture risk associated with subpopulations. Given a feature extractor network, we replace its standard linear classification layer with a mixture of prototypical classifiers, where each member is trained to classify the data while focusing on different features and samples from other members. In empirical evaluation on nine real-world datasets, covering diverse domains and kinds of subpopulation shift, our method of Diverse Prototypical Ensembles (DPEs) often outperforms the prior state-of-the-art in worst-group accuracy. The code is available at https://github.com/minhto2802/dpe4subpop
Mohamed Harmanani, Amoon Jamzad, Minh Nguyen Nhat To et al.
Prostate cancer (PCa) detection using deep learning (DL) models has shown potential for enhancing real-time guidance during biopsies. However, prostate ultrasound images lack pixel-level cancer annotations, introducing label noise. Current approaches often focus on limited regions of interest (ROIs), disregarding anatomical context necessary for accurate diagnosis. Foundation models can overcome this limitation by analyzing entire images to capture global spatial relationships; however, they still encounter challenges stemming from the weak labels associated with coarse pathology annotations in ultrasound data. We introduce Cinepro, a novel framework that strengthens foundation models' ability to localize PCa in ultrasound cineloops. Cinepro adapts robust training by integrating the proportion of cancer tissue reported by pathology in a biopsy core into its loss function to address label noise, providing a more nuanced supervision. Additionally, it leverages temporal data across multiple frames to apply robust augmentations, enhancing the model's ability to learn stable cancer-related features. Cinepro demonstrates superior performance on a multi-center prostate ultrasound dataset, achieving an AUROC of 77.1% and a balanced accuracy of 83.8%, surpassing current benchmarks. These findings underscore Cinepro's promise in advancing foundation models for weakly labeled ultrasound data.
Mohamed Harmanani, Paul F. R. Wilson, Fahimeh Fooladgar et al.
PURPOSE: Deep learning methods for classifying prostate cancer (PCa) in ultrasound images typically employ convolutional networks (CNNs) to detect cancer in small regions of interest (ROI) along a needle trace region. However, this approach suffers from weak labelling, since the ground-truth histopathology labels do not describe the properties of individual ROIs. Recently, multi-scale approaches have sought to mitigate this issue by combining the context awareness of transformers with a CNN feature extractor to detect cancer from multiple ROIs using multiple-instance learning (MIL). In this work, we present a detailed study of several image transformer architectures for both ROI-scale and multi-scale classification, and a comparison of the performance of CNNs and transformers for ultrasound-based prostate cancer classification. We also design a novel multi-objective learning strategy that combines both ROI and core predictions to further mitigate label noise. METHODS: We evaluate 3 image transformers on ROI-scale cancer classification, then use the strongest model to tune a multi-scale classifier with MIL. We train our MIL models using our novel multi-objective learning strategy and compare our results to existing baselines. RESULTS: We find that for both ROI-scale and multi-scale PCa detection, image transformer backbones lag behind their CNN counterparts. This deficit in performance is even more noticeable for larger models. When using multi-objective learning, we can improve performance of MIL, with a 77.9% AUROC, a sensitivity of 75.9%, and a specificity of 66.3%. CONCLUSION: Convolutional networks are better suited for modelling sparse datasets of prostate ultrasounds, producing more robust features than transformers in PCa detection. Multi-scale methods remain the best architecture for this task, with multi-objective learning presenting an effective way to improve performance.
Mohammad Farahmand, Amoon Jamzad, Fahimeh Fooladgar et al.
Purpose: Accurately classifying tissue margins during cancer surgeries is crucial for ensuring complete tumor removal. Rapid Evaporative Ionization Mass Spectrometry (REIMS), a tool for real-time intraoperative margin assessment, generates spectra that require machine learning models to support clinical decision-making. However, the scarcity of labeled data in surgical contexts presents a significant challenge. This study is the first to develop a foundation model tailored specifically for REIMS data, addressing this limitation and advancing real-time surgical margin assessment. Methods: We propose FACT, a Foundation model for Assessing Cancer Tissue margins. FACT is an adaptation of a foundation model originally designed for text-audio association, pretrained using our proposed supervised contrastive approach based on triplet loss. An ablation study is performed to compare our proposed model against other models and pretraining methods. Results: Our proposed model significantly improves the classification performance, achieving state-of-the-art performance with an AUROC of $82.4\% \pm 0.8$. The results demonstrate the advantage of our proposed pretraining method and selected backbone over the self-supervised and semi-supervised baselines and alternative models. Conclusion: Our findings demonstrate that foundation models, adapted and pretrained using our novel approach, can effectively classify REIMS data even with limited labeled examples. This highlights the viability of foundation models for enhancing real-time surgical margin assessment, particularly in data-scarce clinical environments.
Nooshin Maghsoodi, Sarah Nassar, Paul F R Wilson et al.
Objective: Electrocardiograms (ECGs) play a crucial role in diagnosing heart conditions; however, the effectiveness of artificial intelligence (AI)-based ECG analysis is often hindered by the limited availability of labeled data. Self-supervised learning (SSL) can address this by leveraging large-scale unlabeled data. We introduce PhysioCLR (Physiology-aware Contrastive Learning Representation for ECG), a physiology-aware contrastive learning framework that incorporates domain-specific priors to enhance the generalizability and clinical relevance of ECG-based arrhythmia classification. Methods: During pretraining, PhysioCLR learns to bring together embeddings of samples that share similar clinically relevant features while pushing apart those that are dissimilar. Unlike existing methods, our method integrates ECG physiological similarity cues into contrastive learning, promoting the learning of clinically meaningful representations. Additionally, we introduce ECG- specific augmentations that preserve the ECG category post augmentation and propose a hybrid loss function to further refine the quality of learned representations. Results: We evaluate PhysioCLR on two public ECG datasets, Chapman and Georgia, for multilabel ECG diagnoses, as well as a private ICU dataset labeled for binary classification. Across the Chapman, Georgia, and private cohorts, PhysioCLR boosts the mean AUROC by 12% relative to the strongest baseline, underscoring its robust cross-dataset generalization. Conclusion: By embedding physiological knowledge into contrastive learning, PhysioCLR enables the model to learn clinically meaningful and transferable ECG eatures. Significance: PhysioCLR demonstrates the potential of physiology-informed SSL to offer a promising path toward more effective and label-efficient ECG diagnostics.
Mohamed Harmanani, Paul F. R. Wilson, Minh Nguyen Nhat To et al.
While deep learning methods have shown great promise in improving the effectiveness of prostate cancer (PCa) diagnosis by detecting suspicious lesions from trans-rectal ultrasound (TRUS), they must overcome multiple simultaneous challenges. There is high heterogeneity in tissue appearance, significant class imbalance in favor of benign examples, and scarcity in the number and quality of ground truth annotations available to train models. Failure to address even a single one of these problems can result in unacceptable clinical outcomes.We propose TRUSWorthy, a carefully designed, tuned, and integrated system for reliable PCa detection. Our pipeline integrates self-supervised learning, multiple-instance learning aggregation using transformers, random-undersampled boosting and ensembling: these address label scarcity, weak labels, class imbalance, and overconfidence, respectively. We train and rigorously evaluate our method using a large, multi-center dataset of micro-ultrasound data. Our method outperforms previous state-of-the-art deep learning methods in terms of accuracy and uncertainty calibration, with AUROC and balanced accuracy scores of 79.9% and 71.5%, respectively. On the top 20% of predictions with the highest confidence, we can achieve a balanced accuracy of up to 91%. The success of TRUSWorthy demonstrates the potential of integrated deep learning solutions to meet clinical needs in a highly challenging deployment setting, and is a significant step towards creating a trustworthy system for computer-assisted PCa diagnosis.
This paper establishes an information theoretic framework for deep metric based image registration techniques. We show an exact equivalence between maximum profile likelihood and minimization of joint entropy, an important early information theoretic registration method. We further derive deep classifier-based metrics that can be used with iterated maximum likelihood to achieve Deep Information Theoretic Registration on patches rather than pixels. This alleviates a major shortcoming of previous information theoretic registration approaches, namely the implicit pixel-wise independence assumptions. Our proposed approach does not require well-registered training data; this brings previous fully supervised deep metric registration approaches to the realm of weak supervision. We evaluate our approach on several image registration tasks and show significantly better performance compared to mutual information, specifically when images have substantially different contrasts. This work enables general-purpose registration in applications where current methods are not successful.
Deep metrics have been shown effective as similarity measures in multi-modal image registration; however, the metrics are currently constructed from aligned image pairs in the training data. In this paper, we propose a strategy for learning such metrics from roughly aligned training data. Symmetrizing the data corrects bias in the metric that results from misalignment in the data (at the expense of increased variance), while random perturbations to the data, i.e. dithering, ensures that the metric has a single mode, and is amenable to registration by optimization. Evaluation is performed on the task of registration on separate unseen test image pairs. The results demonstrate the feasibility of learning a useful deep metric from substantially misaligned training data, in some cases the results are significantly better than from Mutual Information. Data augmentation via dithering is, therefore, an effective strategy for discharging the need for well-aligned training data; this brings deep metric registration from the realm of supervised to semi-supervised machine learning.