A Self-Supervised Image Registration Approach for Measuring Local Response Patterns in Metastatic Ovarian Cancer

High-grade serous ovarian carcinoma (HGSOC) is characterised by significant spatial and temporal heterogeneity, typically manifesting at an advanced metastatic stage. A major challenge in treating advanced HGSOC is effectively monitoring localised change in tumour burden across multiple sites during neoadjuvant chemotherapy (NACT) and predicting long-term pathological response and overall patient survival. In this work, we propose a self-supervised deformable image registration algorithm that utilises a general-purpose image encoder for image feature extraction to co-register contrast-enhanced computerised tomography scan images acquired before and after neoadjuvant chemotherapy. This approach addresses challenges posed by highly complex tumour deformations and longitudinal lesion matching during treatment. Localised tumour changes are calculated using the Jacobian determinant maps of the registration deformation at multiple disease sites and their macroscopic areas, including hypo-dense (i.e., cystic/necrotic), hyper-dense (i.e., calcified), and intermediate density (i.e., soft tissue) portions. A series of experiments is conducted to understand the role of a general-purpose image encoder and its application in quantifying change in tumour burden during neoadjuvant chemotherapy in HGSOC. This work is the first to demonstrate the feasibility of a self-supervised image registration approach in quantifying NACT-induced localised tumour changes across the whole disease burden of patients with complex multi-site HGSOC, which could be used as a potential marker for ovarian cancer patient's long-term pathological response and survival.

DinoBloom: A Foundation Model for Generalizable Cell Embeddings in Hematology

In hematology, computational models offer significant potential to improve diagnostic accuracy, streamline workflows, and reduce the tedious work of analyzing single cells in peripheral blood or bone marrow smears. However, clinical adoption of computational models has been hampered by the lack of generalization due to large batch effects, small dataset sizes, and poor performance in transfer learning from natural images. To address these challenges, we introduce DinoBloom, the first foundation model for single cell images in hematology, utilizing a tailored DINOv2 pipeline. Our model is built upon an extensive collection of 13 diverse, publicly available datasets of peripheral blood and bone marrow smears, the most substantial open-source cohort in hematology so far, comprising over 380,000 white blood cell images. To assess its generalization capability, we evaluate it on an external dataset with a challenging domain shift. We show that our model outperforms existing medical and non-medical vision models in (i) linear probing and k-nearest neighbor evaluations for cell-type classification on blood and bone marrow smears and (ii) weakly supervised multiple instance learning for acute myeloid leukemia subtyping by a large margin. A family of four DinoBloom models (small, base, large, and giant) can be adapted for a wide range of downstream applications, be a strong baseline for classification problems, and facilitate the assessment of batch effects in new datasets. All models are available at github.com/marrlab/DinoBloom.

Towards Learning Contrast Kinetics with Multi-Condition Latent Diffusion Models

Contrast agents in dynamic contrast enhanced magnetic resonance imaging allow to localize tumors and observe their contrast kinetics, which is essential for cancer characterization and respective treatment decision-making. However, contrast agent administration is not only associated with adverse health risks, but also restricted for patients during pregnancy, and for those with kidney malfunction, or other adverse reactions. With contrast uptake as key biomarker for lesion malignancy, cancer recurrence risk, and treatment response, it becomes pivotal to reduce the dependency on intravenous contrast agent administration. To this end, we propose a multi-conditional latent diffusion model capable of acquisition time-conditioned image synthesis of DCE-MRI temporal sequences. To evaluate medical image synthesis, we additionally propose and validate the Fr\'echet radiomics distance as an image quality measure based on biomarker variability between synthetic and real imaging data. Our results demonstrate our method's ability to generate realistic multi-sequence fat-saturated breast DCE-MRI and uncover the emerging potential of deep learning based contrast kinetics simulation. We publicly share our accessible codebase at https://github.com/RichardObi/ccnet.

Sparse annotation strategies for segmentation of short axis cardiac MRI

Short axis cardiac MRI segmentation is a well-researched topic, with excellent results achieved by state-of-the-art models in a supervised setting. However, annotating MRI volumes is time-consuming and expensive. Many different approaches (e.g. transfer learning, data augmentation, few-shot learning, etc.) have emerged in an effort to use fewer annotated data and still achieve similar performance as a fully supervised model. Nevertheless, to the best of our knowledge, none of these works focus on which slices of MRI volumes are most important to annotate for yielding the best segmentation results. In this paper, we investigate the effects of training with sparse volumes, i.e. reducing the number of cases annotated, and sparse annotations, i.e. reducing the number of slices annotated per case. We evaluate the segmentation performance using the state-of-the-art nnU-Net model on two public datasets to identify which slices are the most important to annotate. We have shown that training on a significantly reduced dataset (48 annotated volumes) can give a Dice score greater than 0.85 and results comparable to using the full dataset (160 and 240 volumes for each dataset respectively). In general, training on more slice annotations provides more valuable information compared to training on more volumes. Further, annotating slices from the middle of volumes yields the most beneficial results in terms of segmentation performance, and the apical region the worst. When evaluating the trade-off between annotating volumes against slices, annotating as many slices as possible instead of annotating more volumes is a better strategy.

Is MC Dropout Bayesian?

MC Dropout is a mainstream "free lunch" method in medical imaging for approximate Bayesian computations (ABC). Its appeal is to solve out-of-the-box the daunting task of ABC and uncertainty quantification in Neural Networks (NNs); to fall within the variational inference (VI) framework; and to propose a highly multimodal, faithful predictive posterior. We question the properties of MC Dropout for approximate inference, as in fact MC Dropout changes the Bayesian model; its predictive posterior assigns $0$ probability to the true model on closed-form benchmarks; the multimodality of its predictive posterior is not a property of the true predictive posterior but a design artefact. To address the need for VI on arbitrary models, we share a generic VI engine within the pytorch framework. The code includes a carefully designed implementation of structured (diagonal plus low-rank) multivariate normal variational families, and mixtures thereof. It is intended as a go-to no-free-lunch approach, addressing shortcomings of mean-field VI with an adjustable trade-off between expressivity and computational complexity.

Bayesian analysis of the prevalence bias: learning and predicting from imbalanced data

Datasets are rarely a realistic approximation of the target population. Say, prevalence is misrepresented, image quality is above clinical standards, etc. This mismatch is known as sampling bias. Sampling biases are a major hindrance for machine learning models. They cause significant gaps between model performance in the lab and in the real world. Our work is a solution to prevalence bias. Prevalence bias is the discrepancy between the prevalence of a pathology and its sampling rate in the training dataset, introduced upon collecting data or due to the practioner rebalancing the training batches. This paper lays the theoretical and computational framework for training models, and for prediction, in the presence of prevalence bias. Concretely a bias-corrected loss function, as well as bias-corrected predictive rules, are derived under the principles of Bayesian risk minimization. The loss exhibits a direct connection to the information gain. It offers a principled alternative to heuristic training losses and complements test-time procedures based on selecting an operating point from summary curves. It integrates seamlessly in the current paradigm of (deep) learning using stochastic backpropagation and naturally with Bayesian models.

Weakly Supervised Estimation of Shadow Confidence Maps in Ultrasound Imaging

Detecting acoustic shadows in ultrasound images is important in many clinical and engineering applications. Real-time feedback of acoustic shadows can guide sonographers to a standardized diagnostic viewing plane with minimal artifacts and can provide additional information for other automatic image analysis algorithms. However, automatically detecting shadow regions is challenging because pixel-wise annotation of acoustic shadows is subjective and time consuming. In this paper we propose a weakly supervised method for automatic confidence estimation of acoustic shadow regions, which is able to generate a dense shadow-focused confidence map. During training, a multi-task module for shadow segmentation is built to learn general shadow features according based image-level annotations as well as a small number of coarse pixel-wise shadow annotations. A transfer function is then established to extend the binary shadow segmentation to a reference confidence map. In addition, a confidence estimation network is proposed to learn the mapping between input images and the reference confidence maps. This confidence estimation network is able to predict shadow confidence maps directly from input images during inference. We evaluate DICE, soft DICE, recall, precision, mean squared error and inter-class correlation to verify the effectiveness of our method. Our method outperforms the state-of-the-art qualitatively and quantitatively. We further demonstrate the applicability of our method by integrating shadow confidence maps into tasks such as ultrasound image classification, multi-view image fusion and automated biometric measurements.