School of Art, Design and Architecture, Monash University, Melbourne, Australia
Abstract:While pathology foundation models have transformed cancer image analysis, they often lack integration with molecular data at single-cell resolution, limiting their utility for precision oncology. Here, we present PAST, a pan-cancer single-cell foundation model trained on 20 million paired histopathology images and single-cell transcriptomes spanning multiple tumor types and tissue contexts. By jointly encoding cellular morphology and gene expression, PAST learns unified cross-modal representations that capture both spatial and molecular heterogeneity at the cellular level. This approach enables accurate prediction of single-cell gene expression, virtual molecular staining, and multimodal survival analysis directly from routine pathology slides. Across diverse cancers and downstream tasks, PAST consistently exceeds the performance of existing approaches, demonstrating robust generalizability and scalability. Our work establishes a new paradigm for pathology foundation models, providing a versatile tool for high-resolution spatial omics, mechanistic discovery, and precision cancer research.
Abstract:3D medical image self-supervised learning (mSSL) holds great promise for medical analysis. Effectively supporting broader applications requires considering anatomical structure variations in location, scale, and morphology, which are crucial for capturing meaningful distinctions. However, previous mSSL methods partition images with fixed-size patches, often ignoring the structure variations. In this work, we introduce a novel perspective on 3D medical images with the goal of learning structure-aware representations. We assume that patches within the same structure share the same semantics (semantic consistency) while those from different structures exhibit distinct semantics (semantic discrepancy). Based on this assumption, we propose an mSSL framework named $S^2DC$, achieving Structure-aware Semantic Discrepancy and Consistency in two steps. First, $S^2DC$ enforces distinct representations for different patches to increase semantic discrepancy by leveraging an optimal transport strategy. Second, $S^2DC$ advances semantic consistency at the structural level based on neighborhood similarity distribution. By bridging patch-level and structure-level representations, $S^2DC$ achieves structure-aware representations. Thoroughly evaluated across 10 datasets, 4 tasks, and 3 modalities, our proposed method consistently outperforms the state-of-the-art methods in mSSL.
Abstract:We propose Network Automatic Relevance Determination (NARD), an extension of ARD for linearly probabilistic models, to simultaneously model sparse relationships between inputs $X \in \mathbb R^{d \times N}$ and outputs $Y \in \mathbb R^{m \times N}$, while capturing the correlation structure among the $Y$. NARD employs a matrix normal prior which contains a sparsity-inducing parameter to identify and discard irrelevant features, thereby promoting sparsity in the model. Algorithmically, it iteratively updates both the precision matrix and the relationship between $Y$ and the refined inputs. To mitigate the computational inefficiencies of the $\mathcal O(m^3 + d^3)$ cost per iteration, we introduce Sequential NARD, which evaluates features sequentially, and a Surrogate Function Method, leveraging an efficient approximation of the marginal likelihood and simplifying the calculation of determinant and inverse of an intermediate matrix. Combining the Sequential update with the Surrogate Function method further reduces computational costs. The computational complexity per iteration for these three methods is reduced to $\mathcal O(m^3+p^3)$, $\mathcal O(m^3 + d^2)$, $\mathcal O(m^3+p^2)$, respectively, where $p \ll d$ is the final number of features in the model. Our methods demonstrate significant improvements in computational efficiency with comparable performance on both synthetic and real-world datasets.
Abstract:Large language models (LLMs) have demonstrated significant advancements in reasoning capabilities, performing well on various challenging benchmarks. Techniques like Chain-of-Thought prompting have been introduced to further improve reasoning. However, these approaches frequently generate longer outputs, which in turn increase computational latency. Although some methods use reinforcement learning to shorten reasoning, they often apply uniform penalties without considering the problem's complexity, leading to suboptimal outcomes. In this study, we seek to enhance the efficiency of LLM reasoning by promoting conciseness for simpler problems while preserving sufficient reasoning for more complex ones for accuracy, thus improving the model's overall performance. Specifically, we manage the model's reasoning efficiency by dividing the reward function and including a novel penalty for output length. Our approach has yielded impressive outcomes in benchmark evaluations across three datasets: GSM8K, MATH500, and AIME2024. For the comparatively simpler datasets GSM8K and MATH500, our method has effectively shortened output lengths while preserving or enhancing accuracy. On the more demanding AIME2024 dataset, our approach has resulted in improved accuracy.
Abstract:Medical anomaly detection (AD) is crucial for early clinical intervention, yet it faces challenges due to limited access to high-quality medical imaging data, caused by privacy concerns and data silos. Few-shot learning has emerged as a promising approach to alleviate these limitations by leveraging the large-scale prior knowledge embedded in vision-language models (VLMs). Recent advancements in few-shot medical AD have treated normal and abnormal cases as a one-class classification problem, often overlooking the distinction among multiple anomaly categories. Thus, in this paper, we propose a framework tailored for few-shot medical anomaly detection in the scenario where the identification of multiple anomaly categories is required. To capture the detailed radiological signs of medical anomaly categories, our framework incorporates diverse textual descriptions for each category generated by a Large-Language model, under the assumption that different anomalies in medical images may share common radiological signs in each category. Specifically, we introduce SD-MAD, a two-stage Sign-Driven few-shot Multi-Anomaly Detection framework: (i) Radiological signs are aligned with anomaly categories by amplifying inter-anomaly discrepancy; (ii) Aligned signs are selected further to mitigate the effect of the under-fitting and uncertain-sample issue caused by limited medical data, employing an automatic sign selection strategy at inference. Moreover, we propose three protocols to comprehensively quantify the performance of multi-anomaly detection. Extensive experiments illustrate the effectiveness of our method.
Abstract:The advent of single-cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq) offers an innovative perspective for deciphering regulatory mechanisms by assembling a vast repository of single-cell chromatin accessibility data. While foundation models have achieved significant success in single-cell transcriptomics, there is currently no foundation model for scATAC-seq that supports zero-shot high-quality cell identification and comprehensive multi-omics analysis simultaneously. Key challenges lie in the high dimensionality and sparsity of scATAC-seq data, as well as the lack of a standardized schema for representing open chromatin regions (OCRs). Here, we present \textbf{ChromFound}, a foundation model tailored for scATAC-seq. ChromFound utilizes a hybrid architecture and genome-aware tokenization to effectively capture genome-wide long contexts and regulatory signals from dynamic chromatin landscapes. Pretrained on 1.97 million cells from 30 tissues and 6 disease conditions, ChromFound demonstrates broad applicability across 6 diverse tasks. Notably, it achieves robust zero-shot performance in generating universal cell representations and exhibits excellent transferability in cell type annotation and cross-omics prediction. By uncovering enhancer-gene links undetected by existing computational methods, ChromFound offers a promising framework for understanding disease risk variants in the noncoding genome.
Abstract:Deep learning-based medical image segmentation typically requires large amount of labeled data for training, making it less applicable in clinical settings due to high annotation cost. Semi-supervised learning (SSL) has emerged as an appealing strategy due to its less dependence on acquiring abundant annotations from experts compared to fully supervised methods. Beyond existing model-centric advancements of SSL by designing novel regularization strategies, we anticipate a paradigmatic shift due to the emergence of promptable segmentation foundation models with universal segmentation capabilities using positional prompts represented by Segment Anything Model (SAM). In this paper, we present SemiSAM+, a foundation model-driven SSL framework to efficiently learn from limited labeled data for medical image segmentation. SemiSAM+ consists of one or multiple promptable foundation models as generalist models, and a trainable task-specific segmentation model as specialist model. For a given new segmentation task, the training is based on the specialist-generalist collaborative learning procedure, where the trainable specialist model delivers positional prompts to interact with the frozen generalist models to acquire pseudo-labels, and then the generalist model output provides the specialist model with informative and efficient supervision which benefits the automatic segmentation and prompt generation in turn. Extensive experiments on two public datasets and one in-house clinical dataset demonstrate that SemiSAM+ achieves significant performance improvement, especially under extremely limited annotation scenarios, and shows strong efficiency as a plug-and-play strategy that can be easily adapted to different specialist and generalist models.
Abstract:Positron Emission Tomography (PET) imaging plays a crucial role in modern medical diagnostics by revealing the metabolic processes within a patient's body, which is essential for quantification of therapy response and monitoring treatment progress. However, the segmentation of PET images presents unique challenges due to their lower contrast and less distinct boundaries compared to other structural medical modalities. Recent developments in segmentation foundation models have shown superior versatility across diverse natural image segmentation tasks. Despite the efforts of medical adaptations, these works primarily focus on structural medical images with detailed physiological structural information and exhibit poor generalization ability when adapted to molecular PET imaging. In this paper, we collect and construct PETS-5k, the largest PET segmentation dataset to date, comprising 5,731 three-dimensional whole-body PET images and encompassing over 1.3M 2D images. Based on the established dataset, we develop SegAnyPET, a modality-specific 3D foundation model for universal promptable segmentation from PET images. To issue the challenge of discrepant annotation quality of PET images, we adopt a cross prompting confident learning (CPCL) strategy with an uncertainty-guided self-rectification process to robustly learn segmentation from high-quality labeled data and low-quality noisy labeled data. Experimental results demonstrate that SegAnyPET can correctly segment seen and unseen targets using only one or a few prompt points, outperforming state-of-the-art foundation models and task-specific fully supervised models with higher accuracy and strong generalization ability for universal segmentation. As the first foundation model for PET images, we believe that SegAnyPET will advance the applications to various downstream tasks for molecular imaging.
Abstract:Deep Neural Networks are increasingly leveraging sparsity to reduce the scaling up of model parameter size. However, reducing wall-clock time through sparsity and pruning remains challenging due to irregular memory access patterns, leading to frequent cache misses. In this paper, we present NPU Vector Runahead (NVR), a prefetching mechanism tailored for NPUs to address cache miss problems in sparse DNN workloads. Rather than optimising memory patterns with high overhead and poor portability, NVR adapts runahead execution to the unique architecture of NPUs. NVR provides a general micro-architectural solution for sparse DNN workloads without requiring compiler or algorithmic support, operating as a decoupled, speculative, lightweight hardware sub-thread alongside the NPU, with minimal hardware overhead (under 5%). NVR achieves an average 90% reduction in cache misses compared to SOTA prefetching in general-purpose processors, delivering 4x average speedup on sparse workloads versus NPUs without prefetching. Moreover, we investigate the advantages of incorporating a small cache (16KB) into the NPU combined with NVR. Our evaluation shows that expanding this modest cache delivers 5x higher performance benefits than increasing the L2 cache size by the same amount.
Abstract:Intracranial aneurysm (IA) is a common cerebrovascular disease that is usually asymptomatic but may cause severe subarachnoid hemorrhage (SAH) if ruptured. Although clinical practice is usually based on individual factors and morphological features of the aneurysm, its pathophysiology and hemodynamic mechanisms remain controversial. To address the limitations of current research, this study constructed a comprehensive hemodynamic dataset of intracranial aneurysms. The dataset is based on 466 real aneurysm models, and 10,000 synthetic models were generated by resection and deformation operations, including 466 aneurysm-free models and 9,534 deformed aneurysm models. The dataset also provides medical image-like segmentation mask files to support insightful analysis. In addition, the dataset contains hemodynamic data measured at eight steady-state flow rates (0.001 to 0.004 kg/s), including critical parameters such as flow velocity, pressure, and wall shear stress, providing a valuable resource for investigating aneurysm pathogenesis and clinical prediction. This dataset will help advance the understanding of the pathologic features and hemodynamic mechanisms of intracranial aneurysms and support in-depth research in related fields. Dataset hosted at https://github.com/Xigui-Li/Aneumo.