Yongheng Sun

Yongheng Sun, Fan Wang, Jun Shu et al.

Brain tissue segmentation is essential for neuroscience and clinical studies. However, segmentation on longitudinal data is challenging due to dynamic brain changes across the lifespan. Previous researches mainly focus on self-supervision with regularizations and will lose longitudinal generalization when fine-tuning on a specific age group. In this paper, we propose a dual meta-learning paradigm to learn longitudinally consistent representations and persist when fine-tuning. Specifically, we learn a plug-and-play feature extractor to extract longitudinal-consistent anatomical representations by meta-feature learning and a well-initialized task head for fine-tuning by meta-initialization learning. Besides, two class-aware regularizations are proposed to encourage longitudinal consistency. Experimental results on the iSeg2019 and ADNI datasets demonstrate the effectiveness of our method. Our code is available at https://github.com/ladderlab-xjtu/DuMeta.

Zehua Ren, Yongheng Sun, Miaomiao Wang et al.

Accurate segmentation of punctate white matter lesions (PWMLs) are fundamental for the timely diagnosis and treatment of related developmental disorders. Automated PWMLs segmentation from infant brain MR images is challenging, considering that the lesions are typically small and low-contrast, and the number of lesions may dramatically change across subjects. Existing learning-based methods directly apply general network architectures to this challenging task, which may fail to capture detailed positional information of PWMLs, potentially leading to severe under-segmentations. In this paper, we propose to leverage the idea of counterfactual reasoning coupled with the auxiliary task of brain tissue segmentation to learn fine-grained positional and morphological representations of PWMLs for accurate localization and segmentation. A simple and easy-to-implement deep-learning framework (i.e., DeepPWML) is accordingly designed. It combines the lesion counterfactual map with the tissue probability map to train a lightweight PWML segmentation network, demonstrating state-of-the-art performance on a real-clinical dataset of infant T1w MR images. The code is available at \href{https://github.com/ladderlab-xjtu/DeepPWML}{https://github.com/ladderlab-xjtu/DeepPWML}.

Yongheng Sun, Jun Shu, Jianhua Ma et al.

Accurate segmentation of brain tissues from MRI scans is critical for neuroscience and clinical applications, but achieving consistent performance across the human lifespan remains challenging due to dynamic, age-related changes in brain appearance and morphology. While prior work has sought to mitigate these shifts by using self-supervised regularization with paired longitudinal data, such data are often unavailable in practice. To address this, we propose \emph{DuMeta++}, a dual meta-learning framework that operates without paired longitudinal data. Our approach integrates: (1) meta-feature learning to extract age-agnostic semantic representations of spatiotemporally evolving brain structures, and (2) meta-initialization learning to enable data-efficient adaptation of the segmentation model. Furthermore, we propose a memory-bank-based class-aware regularization strategy to enforce longitudinal consistency without explicit longitudinal supervision. We theoretically prove the convergence of our DuMeta++, ensuring stability. Experiments on diverse datasets (iSeg-2019, IBIS, OASIS, ADNI) under few-shot settings demonstrate that DuMeta++ outperforms existing methods in cross-age generalization. Code will be available at https://github.com/ladderlab-xjtu/DuMeta++.

Minhui Yu, Yongheng Sun, David S. Lalush et al.

Multi-tracer positron emission tomography (PET) provides critical insights into diverse neuropathological processes such as tau accumulation, neuroinflammation, and $β$-amyloid deposition in the brain, making it indispensable for comprehensive neurological assessment. However, routine acquisition of multi-tracer PET is limited by high costs, radiation exposure, and restricted tracer availability. Recent efforts have explored deep learning approaches for synthesizing PET images from structural MRI. While some methods rely solely on T1-weighted MRI, others incorporate additional sequences such as T2-FLAIR to improve pathological sensitivity. However, existing methods often struggle to capture fine-grained anatomical and pathological details, resulting in artifacts and unrealistic outputs. To this end, we propose RelA-Diffusion, a Relativistic Adversarial Diffusion framework for multi-tracer PET synthesis from multi-sequence MRI. By leveraging both T1-weighted and T2-FLAIR scans as complementary inputs, RelA-Diffusion captures richer structural information to guide image generation. To improve synthesis fidelity, we introduce a gradient-penalized relativistic adversarial loss to the intermediate clean predictions of the diffusion model. This loss compares real and generated images in a relative manner, encouraging the synthesis of more realistic local structures. Both the relativistic formulation and the gradient penalty contribute to stabilizing the training, while adversarial feedback at each diffusion timestep enables consistent refinement throughout the generation process. Extensive experiments on two datasets demonstrate that RelA-Diffusion outperforms existing methods in both visual fidelity and quantitative metrics, highlighting its potential for accurate synthesis of multi-tracer PET.

Mengqi Wu, Yongheng Sun, Qianqian Wang et al.

Aggregating multi-site brain MRI data can enhance deep learning model training, but also introduces non-biological heterogeneity caused by site-specific variations (e.g., differences in scanner vendors, acquisition parameters, and imaging protocols) that can undermine generalizability. Recent retrospective MRI harmonization seeks to reduce such site effects by standardizing image style (e.g., intensity, contrast, noise patterns) while preserving anatomical content. However, existing methods often rely on limited paired traveling-subject data or fail to effectively disentangle style from anatomy. Furthermore, most current approaches address only single-sequence harmonization, restricting their use in real-world settings where multi-sequence MRI is routinely acquired. To this end, we introduce MMH, a unified framework for multi-site multi-sequence brain MRI harmonization that leverages biomedical semantic priors for sequence-aware style alignment. MMH operates in two stages: (1) a diffusion-based global harmonizer that maps MR images to a sequence-specific unified domain using style-agnostic gradient conditioning, and (2) a target-specific fine-tuner that adapts globally aligned images to desired target domains. A tri-planar attention BiomedCLIP encoder aggregates multi-view embeddings to characterize volumetric style information, allowing explicit disentanglement of image styles from anatomy without requiring paired data. Evaluations on 4,163 T1- and T2-weighted MRIs demonstrate MMH's superior harmonization over state-of-the-art methods in image feature clustering, voxel-level comparison, tissue segmentation, and downstream age and site classification.

Yuexi Gu, Mengqi Wu, Yongheng Sun et al.

Ultrasound is a non-invasive, real-time, and cost-effective imaging technique widely used in clinical diagnosis. However, its diagnostic efficacy is often compromised by inherent speckle noise that degrades image quality and obscures underlying anatomical structures. Existing speckle reduction methods tend to over-smooth tissue boundaries and generalize poorly to heterogeneous noise levels. To address these limitations, we propose a Noise-Aware Boundary-Enhanced Generative Learning (NBGL) framework for ultrasound speckle reduction, which simultaneously preserves annotated anatomical boundaries and adapts to varying noise levels. The NBGL framework consists of a speckle reduction branch and a boundary enhancement branch. The former leverages generative learning to suppress speckle noise, while the latter learns boundary-sensitive representations to preserve target anatomical structures. Furthermore, a noise-aware interaction weight generation (NIWG) module estimates the speckle noise level via 3D Laplacian filtering and a median absolute deviation estimator, and translates it into an adaptive interaction weight. This weight is incorporated into a weighted feature-wise linear modulation (wFiLM) module to adaptively modulate cross-branch feature coupling, thereby improving robustness to varying noise levels. Extensive evaluations on 141 3D transvaginal ultrasound volumes demonstrate that NBGL consistently outperforms state-of-the-art methods in speckle reduction and structural preservation across six noise levels, while maintaining consistency with annotated anatomical boundaries.

Yongheng Sun, Minhui Yu, Mengqi Wu et al.

While longitudinal brain PET imaging is the gold standard for quantifying the spatiotemporal accumulation of Beta-amyloid, its widespread clinical utility is constrained by high operational costs and cumulative radiation risks. Recent deep generative models show promise in longitudinal image synthesis; however, they often fail to capture subtle pathological progression due to identity drift and a persistent bias toward trivially replicating baseline signal intensities rather than modeling temporal transition. To this end, we propose Delta-Diffusion, a novel progression-aware framework that redefines longitudinal PET synthesis as a conditional Poisson Diffusion Bridge (PDB) process. Unlike standard diffusion models that start from Gaussian noise, our PDB formulation is mathematically anchored to the subject's baseline PET, effectively transforming the generative task into a conditional distribution transition of the amyloid trajectory. To handle heteroscedastic nature of PET imaging, we introduce a physically-grounded Poisson perturbation within a Diffusion Transformer (DiT). This architecture uses adaptive scale-shift modulation to precisely calibrate the synthesis with the elapsed clinical interval and structural MRI context. A volume-of-interest balanced objective is designed to emphasize sparse, high-risk regions of amyloid accumulation. Validated on two cohorts with 542 subjects, Delta-Diffusion demonstrates superior performance in capturing longitudinal variations in amyloid deposition compared to state-of-the-art methods, offering a robust computational framework for tracking disease progression.

Yongheng Sun, Mingxia Liu, Chunfeng Lian

Brain tumor segmentation is crucial for accurate diagnosisand treatment planning, but the small size and irregular shapeof tumors pose significant challenges. Existing methods of-ten fail to effectively incorporate medical domain knowledgesuch as tumor grade, which correlates with tumor aggres-siveness and morphology, providing critical insights for moreaccurate detection of tumor subregions during segmentation.We propose an Automated and Editable Prompt Learning(AEPL) framework that integrates tumor grade into the seg-mentation process by combining multi-task learning andprompt learning with automatic and editable prompt gen-eration. Specifically, AEPL employs an encoder to extractimage features for both tumor-grade prediction and segmen-tation mask generation. The predicted tumor grades serveas auto-generated prompts, guiding the decoder to produceprecise segmentation masks. This eliminates the need formanual prompts while allowing clinicians to manually editthe auto-generated prompts to fine-tune the segmentation,enhancing both flexibility and precision. The proposed AEPLachieves state-of-the-art performance on the BraTS 2018dataset, demonstrating its effectiveness and clinical potential.The source code can be accessed online.

Meimei Yang, Yongheng Sun, Qianqian Wang et al.

Multimodal neuroimages, such as diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI), offer complementary perspectives on brain activities by capturing structural or functional interactions among brain regions. While existing studies suggest that fusing these multimodal data helps detect abnormal brain activity caused by neurocognitive decline, they are generally implemented in Euclidean space and can't effectively capture intrinsic hierarchical organization of structural/functional brain networks. This paper presents a hyperbolic kernel graph fusion (HKGF) framework for neurocognitive decline analysis with multimodal neuroimages. It consists of a multimodal graph construction module, a graph representation learning module that encodes brain graphs in hyperbolic space through a family of hyperbolic kernel graph neural networks (HKGNNs), a cross-modality coupling module that enables effective multimodal data fusion, and a hyperbolic neural network for downstream predictions. Notably, HKGNNs represent graphs in hyperbolic space to capture both local and global dependencies among brain regions while preserving the hierarchical structure of brain networks. Extensive experiments involving over 4,000 subjects with DTI and/or fMRI data suggest the superiority of HKGF over state-of-the-art methods in two neurocognitive decline prediction tasks. HKGF is a general framework for multimodal data analysis, facilitating objective quantification of structural/functional brain connectivity changes associated with neurocognitive decline.