for the Alzheimer's Disease Neuroimaging Initiative
Abstract:Multiple Instance Learning (MIL) is a popular weakly-supervised method for various applications, with a particular interest in histological whole slide image (WSI) classification. Due to the gigapixel resolution of WSI, applications of MIL in WSI typically necessitate a two-stage training scheme: first, extract features from the pre-trained backbone and then perform MIL aggregation. However, it is well-known that this suboptimal training scheme suffers from "noisy" feature embeddings from the backbone and inherent weak supervision, hindering MIL from learning rich and generalizable features. However, the most commonly used technique (i.e., dropout) for mitigating this issue has yet to be explored in MIL. In this paper, we empirically explore how effective the dropout can be in MIL. Interestingly, we observe that dropping the top-k most important instances within a bag leads to better performance and generalization even under noise attack. Based on this key observation, we propose a novel MIL-specific dropout method, termed MIL-Dropout, which systematically determines which instances to drop. Experiments on five MIL benchmark datasets and two WSI datasets demonstrate that MIL-Dropout boosts the performance of current MIL methods with a negligible computational cost. The code is available at https://github.com/ChongQingNoSubway/MILDropout.
Abstract:High spatial and temporal resolution, coupled with a strong signal-to-noise ratio (SNR), has made BOLD 7 Tesla fMRI an invaluable tool for understanding how the brain processes visual stimuli. However, the limited availability of 7T MRI systems means that most research relies on 3T MRI systems, which offer lower spatial and temporal resolution and SNR. This naturally raises the question: Can we enhance the spatiotemporal resolution and SNR of 3T BOLD fMRI data to approximate 7T quality? In this study, we propose a novel framework that aligns 7T and 3T fMRI data from different subjects and datasets in a shared parametric domain. We then apply an unpaired Brain Disk Schr\"odinger Bridge diffusion model to enhance the spatiotemporal resolution and SNR of the 3T data. Our approach addresses the challenge of limited 7T data by improving the 3T scan quality. We demonstrate its effectiveness by testing it on two distinct fMRI retinotopy datasets (one 7T and one 3T), as well as synthetic data. The results show that our method significantly improves the SNR and goodness-of-fit of the population receptive field (pRF) model in the enhanced 3T data, making it comparable to 7T quality. The codes will be available at Github.
Abstract:Vision-language models (VLMs) such as CLIP demonstrate strong performance but struggle when adapted to downstream tasks. Prompt learning has emerged as an efficient and effective strategy to adapt VLMs while preserving their pre-trained knowledge. However, existing methods still lead to overfitting and degrade zero-shot generalization. To address this challenge, we propose an optimal transport (OT)-guided prompt learning framework that mitigates forgetting by preserving the structural consistency of feature distributions between pre-trained and fine-tuned models. Unlike conventional point-wise constraints, OT naturally captures cross-instance relationships and expands the feasible parameter space for prompt tuning, allowing a better trade-off between adaptation and generalization. Our approach enforces joint constraints on both vision and text representations, ensuring a holistic feature alignment. Extensive experiments on benchmark datasets demonstrate that our simple yet effective method can outperform existing prompt learning strategies in base-to-novel generalization, cross-dataset evaluation, and domain generalization without additional augmentation or ensemble techniques. The code is available at https://github.com/ChongQingNoSubway/Prompt-OT
Abstract:Alzheimer's disease (AD) is a major neurodegenerative condition that affects millions around the world. As one of the main biomarkers in the AD diagnosis procedure, brain amyloid positivity is typically identified by positron emission tomography (PET), which is costly and invasive. Brain structural magnetic resonance imaging (sMRI) may provide a safer and more convenient solution for the AD diagnosis. Recent advances in geometric deep learning have facilitated sMRI analysis and early diagnosis of AD. However, determining AD pathology, such as brain amyloid deposition, in preclinical stage remains challenging, as less significant morphological changes can be observed. As a result, few AD classification models are generalizable to the brain amyloid positivity classification task. Blood-based biomarkers (BBBMs), on the other hand, have recently achieved remarkable success in predicting brain amyloid positivity and identifying individuals with high risk of being brain amyloid positive. However, individuals in medium risk group still require gold standard tests such as Amyloid PET for further evaluation. Inspired by the recent success of transformer architectures, we propose a geometric deep learning model based on transformer that is both scalable and robust to variations in input volumetric mesh size. Our work introduced a novel tokenization scheme for tetrahedral meshes, incorporating anatomical landmarks generated by a pre-trained Gaussian process model. Our model achieved superior classification performance in AD classification task. In addition, we showed that the model was also generalizable to the brain amyloid positivity prediction with individuals in the medium risk class, where BM alone cannot achieve a clear classification. Our work may enrich geometric deep learning research and improve AD diagnosis accuracy without using expensive and invasive PET scans.
Abstract:Recently, Multimodal Large Language Models (MLLMs) have gained significant attention for their remarkable ability to process and analyze non-textual data, such as images, videos, and audio. Notably, several adaptations of general-domain MLLMs to the medical field have been explored, including LLaVA-Med. However, these medical adaptations remain insufficiently advanced in understanding and interpreting retinal images. In contrast, medical experts emphasize the importance of quantitative analyses for disease detection and interpretation. This underscores a gap between general-domain and medical-domain MLLMs: while general-domain MLLMs excel in broad applications, they lack the specialized knowledge necessary for precise diagnostic and interpretative tasks in the medical field. To address these challenges, we introduce \textit{RetinalGPT}, a multimodal conversational assistant for clinically preferred quantitative analysis of retinal images. Specifically, we achieve this by compiling a large retinal image dataset, developing a novel data pipeline, and employing customized visual instruction tuning to enhance both retinal analysis and enrich medical knowledge. In particular, RetinalGPT outperforms MLLM in the generic domain by a large margin in the diagnosis of retinal diseases in 8 benchmark retinal datasets. Beyond disease diagnosis, RetinalGPT features quantitative analyses and lesion localization, representing a pioneering step in leveraging LLMs for an interpretable and end-to-end clinical research framework. The code is available at https://github.com/Retinal-Research/RetinalGPT
Abstract:Over the past decade, generative models have achieved significant success in enhancement fundus images.However, the evaluation of these models still presents a considerable challenge. A comprehensive evaluation benchmark for fundus image enhancement is indispensable for three main reasons: 1) The existing denoising metrics (e.g., PSNR, SSIM) are hardly to extend to downstream real-world clinical research (e.g., Vessel morphology consistency). 2) There is a lack of comprehensive evaluation for both paired and unpaired enhancement methods, along with the need for expert protocols to accurately assess clinical value. 3) An ideal evaluation system should provide insights to inform future developments of fundus image enhancement. To this end, we propose a novel comprehensive benchmark, EyeBench, to provide insights that align enhancement models with clinical needs, offering a foundation for future work to improve the clinical relevance and applicability of generative models for fundus image enhancement. EyeBench has three appealing properties: 1) multi-dimensional clinical alignment downstream evaluation: In addition to evaluating the enhancement task, we provide several clinically significant downstream tasks for fundus images, including vessel segmentation, DR grading, denoising generalization, and lesion segmentation. 2) Medical expert-guided evaluation design: We introduce a novel dataset that promote comprehensive and fair comparisons between paired and unpaired methods and includes a manual evaluation protocol by medical experts. 3) Valuable insights: Our benchmark study provides a comprehensive and rigorous evaluation of existing methods across different downstream tasks, assisting medical experts in making informed choices. Additionally, we offer further analysis of the challenges faced by existing methods. The code is available at \url{https://github.com/Retinal-Research/EyeBench}
Abstract:Since its introduction, the transformer has shifted the development trajectory away from traditional models (e.g., RNN, MLP) in time series forecasting, which is attributed to its ability to capture global dependencies within temporal tokens. Follow-up studies have largely involved altering the tokenization and self-attention modules to better adapt Transformers for addressing special challenges like non-stationarity, channel-wise dependency, and variable correlation in time series. However, we found that the expressive capability of sequence representation is a key factor influencing Transformer performance in time forecasting after investigating several representative methods, where there is an almost linear relationship between sequence representation entropy and mean square error, with more diverse representations performing better. In this paper, we propose a novel attention mechanism with Sequence Complementors and prove feasible from an information theory perspective, where these learnable sequences are able to provide complementary information beyond current input to feed attention. We further enhance the Sequence Complementors via a diversification loss that is theoretically covered. The empirical evaluation of both long-term and short-term forecasting has confirmed its superiority over the recent state-of-the-art methods.
Abstract:Cross-modality translation between MRI and PET imaging is challenging due to the distinct mechanisms underlying these modalities. Blood-based biomarkers (BBBMs) are revolutionizing Alzheimer's disease (AD) detection by identifying patients and quantifying brain amyloid levels. However, the potential of BBBMs to enhance PET image synthesis remains unexplored. In this paper, we performed a thorough study on the effect of incorporating BBBM into deep generative models. By evaluating three widely used cross-modality translation models, we found that BBBMs integration consistently enhances the generative quality across all models. By visual inspection of the generated results, we observed that PET images generated by CycleGAN exhibit the best visual fidelity. Based on these findings, we propose Plasma-CycleGAN, a novel generative model based on CycleGAN, to synthesize PET images from MRI using BBBMs as conditions. This is the first approach to integrate BBBMs in conditional cross-modality translation between MRI and PET.
Abstract:Multiple signal modalities, such as vision and sounds, are naturally present in real-world phenomena. Recently, there has been growing interest in learning generative models, in particular variational autoencoder (VAE), to for multimodal representation learning especially in the case of missing modalities. The primary goal of these models is to learn a modality-invariant and modality-specific representation that characterizes information across multiple modalities. Previous attempts at multimodal VAEs approach this mainly through the lens of experts, aggregating unimodal inference distributions with a product of experts (PoE), a mixture of experts (MoE), or a combination of both. In this paper, we provide an alternative generic and theoretical formulation of multimodal VAE through the lens of barycenter. We first show that PoE and MoE are specific instances of barycenters, derived by minimizing the asymmetric weighted KL divergence to unimodal inference distributions. Our novel formulation extends these two barycenters to a more flexible choice by considering different types of divergences. In particular, we explore the Wasserstein barycenter defined by the 2-Wasserstein distance, which better preserves the geometry of unimodal distributions by capturing both modality-specific and modality-invariant representations compared to KL divergence. Empirical studies on three multimodal benchmarks demonstrated the effectiveness of the proposed method.
Abstract:In this work, we propose Many-MobileNet, an efficient model fusion strategy for retinal disease classification using lightweight CNN architecture. Our method addresses key challenges such as overfitting and limited dataset variability by training multiple models with distinct data augmentation strategies and different model complexities. Through this fusion technique, we achieved robust generalization in data-scarce domains while balancing computational efficiency with feature extraction capabilities.