Zhuo Zhao

Hongxiao Wang, Yang Yang, Zhuo Zhao et al.

For predicting cancer survival outcomes, standard approaches in clinical research are often based on two main modalities: pathology images for observing cell morphology features, and genomic (e.g., bulk RNA-seq) for quantifying gene expressions. However, existing pathology-genomic multi-modal algorithms face significant challenges: (1) Valuable biological insights regarding genes and gene-gene interactions are frequently overlooked; (2) one modality often dominates the optimization process, causing inadequate training for the other modality. In this paper, we introduce a new multi-modal ``Path-GPTOmic" framework for cancer survival outcome prediction. First, to extract valuable biological insights, we regulate the embedding space of a foundation model, scGPT, initially trained on single-cell RNA-seq data, making it adaptable for bulk RNA-seq data. Second, to address the imbalance-between-modalities problem, we propose a gradient modulation mechanism tailored to the Cox partial likelihood loss for survival prediction. The contributions of the modalities are dynamically monitored and adjusted during the training process, encouraging that both modalities are sufficiently trained. Evaluated on two TCGA(The Cancer Genome Atlas) datasets, our model achieves substantially improved survival prediction accuracy.

Nishchal Sapkota, Yejia Zhang, Sirui Li et al.

Male infertility accounts for about one-third of global infertility cases. Manual assessment of sperm abnormalities through head morphology analysis encounters issues of observer variability and diagnostic discrepancies among experts. Its alternative, Computer-Assisted Semen Analysis (CASA), suffers from low-quality sperm images, small datasets, and noisy class labels. We propose a new approach for sperm head morphology classification, called SHMC-Net, which uses segmentation masks of sperm heads to guide the morphology classification of sperm images. SHMC-Net generates reliable segmentation masks using image priors, refines object boundaries with an efficient graph-based method, and trains an image network with sperm head crops and a mask network with the corresponding masks. In the intermediate stages of the networks, image and mask features are fused with a fusion scheme to better learn morphological features. To handle noisy class labels and regularize training on small datasets, SHMC-Net applies Soft Mixup to combine mixup augmentation and a loss function. We achieve state-of-the-art results on SCIAN and HuSHeM datasets, outperforming methods that use additional pre-training or costly ensembling techniques.

Peiran Quan, Zifan Gu, Zhuo Zhao et al.

Foundation models (FMs) have transformed computational pathology by providing powerful, general-purpose feature extractors. However, adapting and benchmarking individual FMs for specific diagnostic tasks is often time-consuming and resource-intensive, especially given their scale and diversity. To address this challenge, we introduce Group-Aggregative Selection Multi-Instance Learning (GAS-MIL), a flexible ensemble framework that seamlessly integrates features from multiple FMs, preserving their complementary strengths without requiring manual feature selection or extensive task-specific fine-tuning. Across classification tasks in three cancer datasets-prostate (PANDA), ovarian (UBC-OCEAN), and breast (TCGA-BrCa)-GAS-MIL consistently achieves superior or on-par performance relative to individual FMs and established MIL methods, demonstrating its robustness and generalizability. By enabling efficient integration of heterogeneous FMs, GAS-MIL streamlines model deployment for pathology and provides a scalable foundation for future multimodal and precision oncology applications.

Hao Zheng, Jun Han, Hongxiao Wang et al.

A large labeled dataset is a key to the success of supervised deep learning, but for medical image segmentation, it is highly challenging to obtain sufficient annotated images for model training. In many scenarios, unannotated images are abundant and easy to acquire. Self-supervised learning (SSL) has shown great potentials in exploiting raw data information and representation learning. In this paper, we propose Hierarchical Self-Supervised Learning (HSSL), a new self-supervised framework that boosts medical image segmentation by making good use of unannotated data. Unlike the current literature on task-specific self-supervised pretraining followed by supervised fine-tuning, we utilize SSL to learn task-agnostic knowledge from heterogeneous data for various medical image segmentation tasks. Specifically, we first aggregate a dataset from several medical challenges, then pre-train the network in a self-supervised manner, and finally fine-tune on labeled data. We develop a new loss function by combining contrastive loss and classification loss and pretrain an encoder-decoder architecture for segmentation tasks. Our extensive experiments show that multi-domain joint pre-training benefits downstream segmentation tasks and outperforms single-domain pre-training significantly. Compared to learning from scratch, our new method yields better performance on various tasks (e.g., +0.69% to +18.60% in Dice scores with 5% of annotated data). With limited amounts of training data, our method can substantially bridge the performance gap w.r.t. denser annotations (e.g., 10% vs.~100% of annotated data).

Hao Zheng, Yizhe Zhang, Lin Yang et al.

3D image segmentation plays an important role in biomedical image analysis. Many 2D and 3D deep learning models have achieved state-of-the-art segmentation performance on 3D biomedical image datasets. Yet, 2D and 3D models have their own strengths and weaknesses, and by unifying them together, one may be able to achieve more accurate results. In this paper, we propose a new ensemble learning framework for 3D biomedical image segmentation that combines the merits of 2D and 3D models. First, we develop a fully convolutional network based meta-learner to learn how to improve the results from 2D and 3D models (base-learners). Then, to minimize over-fitting for our sophisticated meta-learner, we devise a new training method that uses the results of the base-learners as multiple versions of "ground truths". Furthermore, since our new meta-learner training scheme does not depend on manual annotation, it can utilize abundant unlabeled 3D image data to further improve the model. Extensive experiments on two public datasets (the HVSMR 2016 Challenge dataset and the mouse piriform cortex dataset) show that our approach is effective under fully-supervised, semi-supervised, and transductive settings, and attains superior performance over state-of-the-art image segmentation methods.

Zhuo Zhao, Lin Yang, Hao Zheng et al.

Instance segmentation in 3D images is a fundamental task in biomedical image analysis. While deep learning models often work well for 2D instance segmentation, 3D instance segmentation still faces critical challenges, such as insufficient training data due to various annotation difficulties in 3D biomedical images. Common 3D annotation methods (e.g., full voxel annotation) incur high workloads and costs for labeling enough instances for training deep learning 3D instance segmentation models. In this paper, we propose a new weak annotation approach for training a fast deep learning 3D instance segmentation model without using full voxel mask annotation. Our approach needs only 3D bounding boxes for all instances and full voxel annotation for a small fraction of the instances, and uses a novel two-stage 3D instance segmentation model utilizing these two kinds of annotation, respectively. We evaluate our approach on several biomedical image datasets, and the experimental results show that (1) with full annotated boxes and a small amount of masks, our approach can achieve similar performance as the best known methods using full annotation, and (2) with similar annotation time, our approach outperforms the best known methods that use full annotation.

Lin Yang, Yizhe Zhang, Zhuo Zhao et al.

In recent years, deep learning (DL) methods have become powerful tools for biomedical image segmentation. However, high annotation efforts and costs are commonly needed to acquire sufficient biomedical training data for DL models. To alleviate the burden of manual annotation, in this paper, we propose a new weakly supervised DL approach for biomedical image segmentation using boxes only annotation. First, we develop a method to combine graph search (GS) and DL to generate fine object masks from box annotation, in which DL uses box annotation to compute a rough segmentation for GS and then GS is applied to locate the optimal object boundaries. During the mask generation process, we carefully utilize information from box annotation to filter out potential errors, and then use the generated masks to train an accurate DL segmentation network. Extensive experiments on gland segmentation in histology images, lymph node segmentation in ultrasound images, and fungus segmentation in electron microscopy images show that our approach attains superior performance over the best known state-of-the-art weakly supervised DL method and is able to achieve (1) nearly the same accuracy compared to fully supervised DL methods with far less annotation effort, (2) significantly better results with similar annotation time, and (3) robust performance in various applications.