Veeru Kasivisvanathan

Shiqi Huang, Yipei Wang, Natasha Thorley et al.

Foundation models leverage large-scale pretraining to capture extensive knowledge, demonstrating generalization in a wide range of language tasks. By comparison, vision foundation models (VFMs) often exhibit uneven improvements across downstream tasks, despite substantial computational investment. We postulate that this limitation arises from a mismatch between pretraining objectives and the demands of downstream vision-and-imaging tasks. Pretraining strategies like masked image reconstruction or contrastive learning shape representations for tasks such as recovery of generic visual patterns or global semantic structures, which may not align with the task-specific requirements of downstream applications including segmentation, classification, or image synthesis. To investigate this in a concrete real-world clinical area, we assess two VFMs, a reconstruction-focused MAE-based model (ProFound) and a contrastive-learning-based model (ProViCNet), on five prostate multiparametric MR imaging tasks, examining how such task alignment influences transfer performance, i.e., from pretraining to fine-tuning. Our findings indicate that better alignment between pretraining and downstream tasks, measured by simple divergence metrics such as maximum-mean-discrepancy (MMD) between the same features before and after fine-tuning, correlates with greater performance improvements and faster convergence, emphasizing the importance of designing and analyzing pretraining objectives with downstream applicability in mind.

Yipei Wang, Yinsong Xu, Weixi Yi et al.

Many diagnostic and therapeutic clinical tasks for prostate cancer increasingly rely on multi-parametric MRI. Automating these tasks is challenging because they necessitate expert interpretations, which are difficult to scale to capitalise on modern deep learning. Although modern automated systems achieve expert-level performance in isolated tasks, their general clinical utility remains limited by the requirement of large task-specific labelled datasets. In this paper, we present ProFound, a domain-specialised vision foundation model for volumetric prostate mpMRI. ProFound is pre-trained using several variants of self-supervised approaches on a diverse, multi-institutional collection of 5,000 patients, with a total of over 22,000 unique 3D MRI volumes (over 1,800,000 2D image slices). We conducted a systematic evaluation of ProFound across a broad spectrum of $11$ downstream clinical tasks on over 3,000 independent patients, including prostate cancer detection, Gleason grading, lesion localisation, gland volume estimation, zonal and surrounding structure segmentation. Experimental results demonstrate that finetuned ProFound consistently outperforms or remains competitive with state-of-the-art specialised models and existing medical vision foundation models trained/finetuned on the same data.

Weixi Yi, Yipei Wang, Natasha Thorley et al.

Current imaging-based prostate cancer diagnosis requires both MR T2-weighted (T2w) and diffusion-weighted imaging (DWI) sequences, with additional sequences for potentially greater accuracy improvement. However, measuring diffusion patterns in DWI sequences can be time-consuming, prone to artifacts and sensitive to imaging parameters. While machine learning (ML) models have demonstrated radiologist-level accuracy in detecting prostate cancer from these two sequences, this study investigates the potential of ML-enabled methods using only the T2w sequence as input during inference time. We first discuss the technical feasibility of such a T2-only approach, and then propose a novel ML formulation, where DWI sequences - readily available for training purposes - are only used to train a meta-learning model, which subsequently only uses T2w sequences at inference. Using multiple datasets from more than 3,000 prostate cancer patients, we report superior or comparable performance in localising radiologist-identified prostate cancer using our proposed T2-only models, compared with alternative models using T2-only or both sequences as input. Real patient cases are presented and discussed to demonstrate, for the first time, the exclusively true-positive cases from models with different input sequences.

Xiangcen Wu, Yipei Wang, Qianye Yang et al.

Prostate cancer diagnosis through MR imaging have currently relied on radiologists' interpretation, whilst modern AI-based methods have been developed to detect clinically significant cancers independent of radiologists. In this study, we propose to develop deep learning models that improve the overall cancer diagnostic accuracy, by classifying radiologist-identified patients or lesions (i.e. radiologist-positives), as opposed to the existing models that are trained to discriminate over all patients. We develop a single voxel-level classification model, with a simple percentage threshold to determine positive cases, at levels of lesions, Barzell-zones and patients. Based on the presented experiments from two clinical data sets, consisting of histopathology-labelled MR images from more than 800 and 500 patients in the respective UCLA and UCL PROMIS studies, we show that the proposed strategy can improve the diagnostic accuracy, by augmenting the radiologist reading of the MR imaging. Among varying definition of clinical significance, the proposed strategy, for example, achieved a specificity of 44.1% (with AI assistance) from 36.3% (by radiologists alone), at a controlled sensitivity of 80.0% on the publicly available UCLA data set. This provides measurable clinical values in a range of applications such as reducing unnecessary biopsies, lowering cost in cancer screening and quantifying risk in therapies.

Lynn Karam, Yipei Wang, Veeru Kasivisvanathan et al.

Automated segmentation of cancer on medical images can aid targeted diagnostic and therapeutic procedures. However, its adoption is limited by the high cost of expert annotations required for training and inter-observer variability in datasets. While weakly-supervised methods mitigate some challenges, using binary histology labels for training as opposed to requiring full segmentation, they require large paired datasets of histology and images, which are difficult to curate. Similarly, promptable segmentation aims to allow segmentation with no re-training for new tasks at inference, however, existing models perform poorly on pathological regions, again necessitating large datasets for training. In this work we propose a novel approach for promptable segmentation requiring only 24 fully-segmented images, supplemented by 8 weakly-labelled images, for training. Curating this minimal data to a high standard is relatively feasible and thus issues with the cost and variability of obtaining labels can be mitigated. By leveraging two classifiers, one weakly-supervised and one fully-supervised, our method refines segmentation through a guided search process initiated by a single-point prompt. Our approach outperforms existing promptable segmentation methods, and performs comparably with fully-supervised methods, for the task of prostate cancer segmentation, while using substantially less annotated data (up to 100X less). This enables promptable segmentation with very minimal labelled data, such that the labels can be curated to a very high standard.

Weixi Yi, Yipei Wang, Wen Yan et al.

Multiparametric MRI is increasingly recommended as a first-line noninvasive approach to detect and localize prostate cancer, requiring at minimum diffusion-weighted (DWI) and T2-weighted (T2w) MR sequences. Early machine learning attempts using only T2w images have shown promising diagnostic performance in segmenting radiologist-annotated lesions. Such uni-modal T2-only approaches deliver substantial clinical benefits by reducing costs and expertise required to acquire other sequences. This work investigates an arguably more challenging application using only T2w at inference, but to localize individual cancers based on independent histopathology labels. We formulate DWI images as a latent modality (readily available during training) to classify cancer presence at local Barzell zones, given only T2w images as input. In the resulting expectation-maximization algorithm, a latent modality generator (implemented using a flow matching-based generative model) approximates the latent DWI image posterior distribution in the E-steps, while in M-steps a cancer localizer is simultaneously optimized with the generative model to maximize the expected likelihood of cancer presence. The proposed approach provides a novel theoretical framework for learning from a privileged DWI modality, yielding superior cancer localization performance compared to approaches that lack training DWI images or existing frameworks for privileged learning and incomplete modalities. The proposed T2-only methods perform competitively or better than baseline methods using multiple input sequences (e.g., improving the patient-level F1 score by 14.4\% and zone-level QWK by 5.3\% over the T2w+DWI baseline). We present quantitative evaluations using internal and external datasets from 4,133 prostate cancer patients with histopathology-verified labels.

Yucheng Tang, Pawel Rajwa, Alexander Ng et al.

Foundation models in medical imaging have shown promising label efficiency, achieving high performance on downstream tasks using only a fraction of the annotated data otherwise required. In this study, we evaluate this potential in the context of prostate multiparametric MRI using ProFound, a recently developed domain-specific vision foundation model pretrained on large-scale prostate MRI datasets. We investigate the impact of variable image quality on the label-efficient finetuning, by quantifying the generalisability of the finetuned models. We conduct a comprehensive set of experiments by systematically varying the ratios of high- and low-quality images in the finetuning and evaluation sets. Our findings indicate that image quality distribution and its finetune-and-test mismatch significantly affect model performance. In particular: a) Varying the ratio of high- to low-quality images between finetuning and test sets leads to notable differences in downstream performance; and b) The presence of sufficient high-quality images in the finetuning set is critical for maintaining strong performance, whilst the importance of matched finetuning and testing distribution varies between different downstream tasks, such as automated radiology reporting and prostate cancer detection. Importantly, experimental results also show that, although finetuning requires significantly less labeled data compared to training from scratch when the quality ratio is consistent, this label efficiency is not independent of the image quality distribution. For example, we show cases that, without sufficient high-quality images in finetuning, finetuned models may fail to outperform those without pretraining.

Anindo Saha, Joeran S. Bosma, Jasper J. Twilt et al.

In this intercontinental, confirmatory study, we include a retrospective cohort of 22,481 MRI examinations (21,288 patients; 46 cities in 22 countries) to train and externally validate the PI-CAI-2B model, i.e., an efficient, next-generation iteration of the state-of-the-art AI system that was developed for detecting Gleason grade group $\geq$2 prostate cancer on MRI during the PI-CAI study. Of these examinations, 20,471 cases (19,278 patients; 26 cities in 14 countries) from two EU Horizon projects (ProCAncer-I, COMFORT) and 12 independent centers based in Europe, North America, Asia and Africa, are used for training and internal testing. Additionally, 2010 cases (2010 patients; 20 external cities in 12 countries) from population-based screening (STHLM3-MRI, IP1-PROSTAGRAM trials) and primary diagnostic settings (PRIME trial) based in Europe, North and South Americas, Asia and Australia, are used for external testing. Primary endpoint is the proportion of AI-based assessments in agreement with the standard of care diagnoses (i.e., clinical assessments made by expert uropathologists on histopathology, if available, or at least two expert urogenital radiologists in consensus; with access to patient history and peer consultation) in the detection of Gleason grade group $\geq$2 prostate cancer within the external testing cohorts. Our statistical analysis plan is prespecified with a hypothesis of diagnostic interchangeability to the standard of care at the PI-RADS $\geq$3 (primary diagnosis) or $\geq$4 (screening) cut-off, considering an absolute margin of 0.05 and reader estimates derived from the PI-CAI observer study (62 radiologists reading 400 cases). Secondary measures comprise the area under the receiver operating characteristic curve (AUROC) of the AI system stratified by imaging quality, patient age and patient ethnicity to identify underlying biases (if any).

Shaheer U. Saeed, Yipei Wang, Veeru Kasivisvanathan et al.

Reasoning is a hallmark of human intelligence, enabling adaptive decision-making in complex and unfamiliar scenarios. In contrast, machine intelligence remains bound to training data, lacking the ability to dynamically refine solutions at inference time. While some recent advances have explored reasoning in machines, these efforts are largely limited to verbal domains such as mathematical problem-solving, where explicit rules govern step-by-step reasoning. Other critical real-world tasks - including visual perception, spatial reasoning, and radiological diagnosis - require non-verbal reasoning, which remains an open challenge. Here we present a novel learning paradigm that enables machine reasoning in vision by allowing performance improvement with increasing thinking time (inference-time compute), even under conditions where labelled data is very limited. Inspired by dual-process theories of human cognition in psychology, our approach integrates a fast-thinking System I module for familiar tasks, with a slow-thinking System II module that iteratively refines solutions using self-play reinforcement learning. This paradigm mimics human reasoning by proposing, competing over, and refining solutions in data-scarce scenarios. We demonstrate superior performance through extended thinking time, compared not only to large-scale supervised learning but also foundation models and even human experts, in real-world vision tasks. These tasks include computer-vision benchmarks and cancer localisation on medical images across five organs, showcasing transformative potential for non-verbal machine reasoning.